Recent Scientific Abstracts of Squamous Cell Carcinoma

Undifferentiated malignant neoplasms of the sinonasal tract. Wenig BM. Arch Pathol Lab Med. 2009 May;133(5):699-712.

CONTEXT: The most commonly encountered malignant neoplasms of the sinonasal tract
are the keratinizing and nonkeratinizing types of squamous cell carcinoma.
However, this complex anatomic region may represent the site of aggressive,
non-squamous cell epithelial and nonepithelial malignant neoplasms of varying
histogenesis, which are grouped under the term undifferentiated malignant
neoplasms. Frequently, these undifferentiated malignancies share clinical and
light microscopic features, which makes differentiation of one from the other
virtually impossible without the use of adjunct analyses (eg,
immunohistochemistry, electron microscopy, or molecular biologic studies). These
tumors often are clinically aggressive and usually fatal, despite all attempts at
controlling disease. Nevertheless, differentiating these tumors has clinical
import because advances in therapeutic intervention may increase survival with
good quality of life, and in some instances may achieve a cure. OBJECTIVE: To
compare and contrast the clinical, light microscopic, and immunohistochemical
features of sinonasal undifferentiated malignant neoplasms. DATA SOURCES:
Case-derived material and literature review. CONCLUSIONS: A variety of
undifferentiated malignant neoplasms occur in the sinonasal tract with
overlapping clinical and pathologic findings. In limited biopsy material,
differentiation of these tumor types can be challenging. The pathologist plays a
primary role in establishing the correct diagnosis, which often necessitates the
use of adjunct studies that allow for differentiating among these neoplasms.

Necrotizing sialometaplasia: a practical approach to the diagnosis. Carlson DL. Arch Pathol Lab Med. 2009 May;133(5):692-8.

CONTEXT: Necrotizing sialometaplasia is a benign, self-limited lesion of both
major and minor salivary glands, although more commonly the latter. It can
represent a diagnostic dilemma and may be mistaken for a malignant neoplasm, such
as mucoepidermoid carcinoma, as well as invasive squamous cell carcinoma. A major
causal relationship has been ascribed to ischemia. Bulimia, an eating disorder
with increasing prevalence in our society, may also be an underlying
underreported cause. OBJECTIVE: To discuss the potential pathogenesis, diagnostic
pitfalls, and the application of immunohistochemistry as an aid in the diagnosis
of necrotizing sialometaplasia. DATA SOURCES: This report uses a previously
published case history for illustrative purposes and a review of the current
literature. CONCLUSIONS: The diagnosis of necrotizing sialometaplasia may be
difficult and is reliant upon a well-oriented biopsy section and a complete
clinical history. Diagnosis may be further supplemented via immunohistochemistry,
demonstrating focal to absent immunoreactivity for p53, low immunoreactivity for
MIB1 (Ki-67), and the presence of 4A4/p63- and calponin-positive myoepithelial
cells. Interpreted in context collectively, these findings may be helpful
adjuncts in the diagnosis of necrotizing sialometaplasia; nonetheless, to date,
hematoxylin-eosin staining remains the gold standard.

Surgical monotherapy versus surgery plus adjuvant radiotherapy in high-risk cutaneous squamous cell carcinoma: a systematic review of outcomes. Jambusaria-Pahlajani A, Miller CJ, Quon H, Smith N, Klein RQ, Schmults CD. Dermatol Surg. 2009 Apr;35(4):574-85.

BACKGROUND: Adjuvant radiotherapy (ART) has been recommended for squamous cell
carcinoma(SCC) with a high risk of recurrence, particularly perineurally invasive
disease. The utility of ART is unknown. This study compares reported outcomes of
high-risk SCC treated with surgical monotherapy(SM) with those of surgery plus
ART (S + ART). METHODS: The Medline database was searched for reports of
high-risk SCC treated with SM or S + ART that reported outcomes of interest:
local recurrence, regional or distant metastasis, or disease-specific death.
RESULTS: There were no controlled trials. Of the 2,449 cases of high-risk SCC
included, 91 were treated with S + ART. Tumor stage and surgical margin status
before ART were generally unreported. In 74 cases of perineural invasion (PNI),
outcomes were statistically similar between SM and S + ART. In 943 high risk SCC
cases in which clear surgical margins were explicitly documented, risks of local
recurrence,regional metastasis, distant metastasis, and disease-specific death
were 5%, 5%, 1%, and 1%, respectively. CONCLUSIONS: High cure rates are achieved
in high-risk cutaneous SCC when clear surgical margins are obtained. Current data
are insufficient to identify high-risk features in which ART may be beneficial.
In cases of PNI, the extent of nerve involvement appears to affect outcomes, with
involvement of larger nerves imparting a worse prognosis.

Human papillomavirus and head and neck squamous cell carcinoma: recent evidence and clinical implications. Hennessey PT, Westra WH, Califano JA. J Dent Res. 2009 Apr;88(4):300-6.

Over the past 20 years, high-risk human papilloma-virus (HPV) infection has been
established as a risk factor for developing head and neck squamous cell
carcinoma, independent of tobacco and alcohol use. In particular, HPV is strongly
associated with the development of oropharyngeal cancer and a small minority of
oral cavity cancers. In this review, we summarize what is currently known about
the biology of HPV, the mechanisms by which it effects malignant transformation,
and the potential impact of HPV status on the clinical management of persons with
head and neck cancer.

Surveillance procedures for patients with cervical carcinoma: a review of the literature. Zanagnolo V, Ming L, Gadducci A, Maggino T, Sartori E, Zola P, Landoni F. Int J Gynecol Cancer. 2009 Feb;19(2):194-201.

Cervical cancer is still one of the most common malignancies in women. Treatment
of cervical cancer is very successful, especially in the early stage. However,
some patients will experience recurrence. The primary purpose of follow-up
programs is early detection of recurrence disease that should be more likely to
be amenable to treatment, thereby improving the clinical outcome. Although, in
the literature, most studies have shown that the surveillance programs did not
improve the clinical outcome of patients with diagnosis of recurrence, this
clinical practice is regarded as traditional management. The use of Papanicolaou
tests to detect recurrent cervical cancer is not sufficiently justified. The
assessment of tumor markers such as the squamous cell carcinoma antigen could be
useful. Imaging techniques are important for the detection and assessment of
recurrent disease. The role of chest x-rays in detecting asymptomatic recurrence
in patients treated for cervical carcinoma remains controversial. Detection of a
new abnormal mass or the changes in the size of a known lesion caused by cancer
growth and the determination of the extent of recurrence with computed tomography
and magnetic resonance imaging may provide clinical assistance in the selection
of optimal therapy. The fluoro-2-deoxy-glucose-positron emission tomography for
surveillance only show 80% of specificity and accuracy with negative predictive
value of 100%. Integrated fluoro-2-deoxy-glucose-positron emission
tomography/computed tomography provides precise anatomic localization of
suspicious areas and, therefore, a better diagnostic interpretation with a
possible impact on disease-free survival as well. In conclusion, our review
confirms the need for prospective studies to compare the effectiveness of
different follow-up regimens measuring overall survival and quality of life
parameters as outcomes.

[Epidemiology and risk factors of the esophageal squamous cell carcinoma] [Article in Polish] Szumiło J. Pol Merkur Lekarski. 2009 Jan;26(151):82-5.

Esophageal carcinoma is the eighth most common malignancy in the world. In most
countries, including Poland, the squamous cell carcinoma is a predominant
histological type. It is characterized by extreme diversity in geographical
distribution and incidence. High incidence is noted in regions located along with
so-called “Asian esophageal cancer belt” beginning from eastern Turkey through
Caspian littoral countries, northern Afghanistan to Central and Eastern Asia, as
well as in Japan, South Africa and some South American countries. In Western
Europe the highest incidence is observed in France, Portugal and northern Italy.
Poland belongs to low-incidence countries with the age-standardized annual
incidence exceeding 4.5 and 0.7/100,000, for men and women respectively. Etiology
of the cancer is multi-factorial. In western countries the most important risk
factors are tobacco smoking and alcohol consumption, and to a lesser extent, an
inappropriate diet. In other countries, a diet lacking of fresh vegetables and
fruits with vitamin and mineral deficiency and high level of sodium chloride,
carbohydrates and animal fats is a predominant factor. Furthermore, preserving
and processing food which facilitates accumulation of carcinogens, special
dietary habits and viral infections are also attributed to the development of
cancer. More recently, the significance of genetically determined increased
susceptibility of some individuals versus environmental factors has been
stressed. Previous studies proved the relationship between cancer susceptibility
and polymorphisms in genes encoding some important molecules engaged in
carcinogens metabolism or DNA repair.

[Natural compounds in chemoprevention of esophageal squamous cell tumors--experimental studies] [Article in Polish] Szumiło J. Pol Merkur Lekarski. 2009 Feb;26(152):156-61.

Chemoprevention refers to prevention of tumor formation due to administration of
nontoxic synthetic or natural compounds, which can block or weaken the influence
of carcinogens on target cells or even reverse previously formed lesions. In
esophageal squamous cell carcinoma–which belongs to the group of the most
aggressive tumors of digestive system with poor prognosis–an effective
prevention would be strongly expected. Chemopreventive properties of many complex
diets and pure natural compounds were evaluated until now. Most studies were
performed on rats exposed to chemical carcinogens, usually
N-nitroso-N-methylbenzylamine (NMBA). The best effects were achieved after
administration of diallyl sulfide and phenethyl isothiocyanate. Lyophilized black
raspberries, blackberries and strawberries, as well as products obtained from
leaves and buds of tea plant, elagic acid and resveratrol were also very
effective. Mechanisms of chemopreventive action were associated with, i.e.,
activity of enzymes involved in carcinogen metabolic activation (mostly
cytochrome P450 isoenzymes), inhibition of DNA adducts formation and modulation
of gene expression involved in regulation of proliferation, apoptosis and
angiogenesis. However, some agents e.g., perillyl alcohol, could enhance
development of proliferative lesions in esophageal epithelium.

Osteoclast-like giant cell reaction associated with cutaneous squamous cell carcinoma: a report of 2 cases and review of the literature. Wooff J, Werner D, Murphy J, Walsh N. Am J Dermatopathol. 2009 May;31(3):282-7.

The observation of osteoclast-like giant cells (O-LGCs) in intimate association
with visceral malignancies is an uncommon phenomenon that has been recognized for
over 40 years. Recently, the same observation has been made in relation to
cutaneous malignancies. In an article published in 2005, O-LGCs were documented
in association with 3 melanomas, and since then, there have been 3 separate case
reports recording the presence of these cells in cutaneous carcinomas. In the
context of both visceral and cutaneous malignancies, the exact nature of the
O-LGCs has been a source of controversy, with respect to whether they represent
modified tumor cells or an unusual host response to the neoplasm. We report here
2 additional cases of cutaneous squamous cell carcinoma associated with O-LGCs.
The morphological pattern of the giant cell proliferation differed between these
cases, taking the form of (1) a giant cell tumor-like nodule apposed to the
carcinoma in one and (2) scattered O-LGCs interspersed with tumor cells in the
other. Based on scrutiny of routine sections and the contrasting
immunohistochemical profiles of the O-LGCs versus the carcinomas, showing CD68
positivity on one hand and high-molecular weight keratin and p63 positivity on
the other, we concluded that in both instances, the O-LGC proliferation was a
reactive phenomenon. This theory is supported by most publications on the
subject. Clinical and histopathological details of the new cases are outlined and
integrated with those in the literature.

Clinicopathological features of eyelid skin tumors. A retrospective study of 5504 cases and review of literature. Deprez M, Uffer S. Am J Dermatopathol. 2009 May;31(3):256-62.

Eyelid tumors are the most common neoplasm in daily ophthalmology practice and
encompass a wide variety of benign and malignant tumors. In this retrospective
study, we report the clinical and histological features of 5504 eyelid skin
tumors diagnosed at the Laboratory of Ophthalmopathology of the Hôpital
Ophtalmique Jules Gonin, Lausanne, Switzerland, between January 1989 and December
2007. Benign tumors largely predominated over malignant ones, representing 84% of
cases in this series, and the 5 most frequent subtypes were squamous cell
papilloma (26%), seborrheic keratosis (21%), melanocytic nevus (20%),
hidrocystoma (8%), and xanthoma/xanthelasma (6%). Basal cell carcinoma was the
most frequent malignant tumor (86%), followed by squamous cell carcinoma (7%) and
sebaceous carcinoma (3%). For several tumor subtypes, there was a poor
correlation between clinical and histological diagnosis, stressing the numerous
pitfalls in the diagnosis of eyelid tumors. We further discuss our results with
reference to previously published series.

Colposcopy to evaluate abnormal cervical cytology in 2008. Chase DM, Kalouyan M, DiSaia PJ. Am J Obstet Gynecol. 2009 May;200(5):472-80.

The rates of cervical cancer in the United States are low in comparison with
developing nations. Whereas the Papanicolaou smear has performed well in terms of
detecting both precursors of squamous cell carcinoma and squamous cell carcinoma
of the cervix, this test has been less successful at identifying those women with
the highest-risk premalignant disease. The use of human papillomavirus testing
has also contributed to the improved sensitivity of screening for cervical
cancer. In light of this, the colposcopy clinic retains high referral rates yet
has poor diagnostic accuracy. Unfortunately, patients are triaged to follow-up
for abnormal Papanicolaou smears based on algorithms that rely on the less
evidence-based techniques of colposcopy. Therefore, the need to improve the
specificity of colposcopic-guided biopsy remains. The colposcopic procedure is
highlighted in this review and evaluated in terms of current literature on
technique, the colposcopic impression, cervical biopsy, and methods proposed to
enhance appreciation of the highest-risk lesions. By outlining certain flaws in
technique and discussing the proposal of new tests to supplement the current
standard of care, this review aimed to highlight the need for future research to
maintain sensitivity but improve the specificity of colposcopy.

The efficacy of combined treatment with cetuximab (erbitux) and radiation therapy in patients with head and neck cancer. Koukourakis G, Kouloulias V, Koukourakis M, Kouvaris J, Zacharias G, Gouliamos A. J BUON. 2009 Jan-Mar;14(1):19-25.

Squamous cell carcinoma of the head and neck (SCCHN) region is among the most
frequent human tumors due to the alcohol and tobacco abuse. Its management has
evolved gradually from surgery as the mainstay of therapy to irradiation as the
principal treatment. When radiation therapy is combined with chemotherapy,
additional benefit is obtained. The value of chemoradiotherapy (CRT) is, however,
counterbalanced by increased and often prohibitive toxicity, particularly among
patients with coexisting medical conditions and decreased performance status. A
member of the ErbB family of receptor tyrosine kinases known as the epidermal
growth factor receptor (EGFR) is abnormally activated in epithelial cancers,
including head and neck cancers. Overexpression of EGFR is a feature associated
with poor clinical outcome. It is observed that radiation increases the
expression of EGFR in cancer cells and the blockade of EGFR signaling sensitizes
cells to the effects of radiation. The cytotoxic effects of radiation therapy in
squamous cell carcinoma could be enhanced by cetuximab (erbitux), a monoclonal
antibody against the ligand-binding domain of EGFR. The major studies that focus
on the efficacy of adding cetuximab to radiotherapy in the treatment of patients
with head and neck cancer and its impact in quality of life are reviewed in this

Surgery versus radical endotherapies for early cancer and high grade dysplasia in Barrett’s oesophagus. Green S, Tawil A, Barr H, Bennett C, Bhandari P, Decaestecker J, Ragunath K,
Singh R, Jankowski J. Cochrane Database Syst Rev. 2009 Apr 15;(2):CD007334.

BACKGROUND: Barrett’s oesophagus is one of the most common premalignant lesions
in the world. Currently the mainstay of therapy is surgical management of
advanced cancer but this has improved the five-year survival very little in the
last 30 years. As a consequence, improved survival relies on early detection
through endoscopic surveillance programmes. Success of this strategy relies on
the fact that late stage premalignant lesions or very early cancers can be cured
by intervention. Currently there is considerable controversy over which method is
best: i.e. conventional open surgery or endotherapy (techniques involving
endoscopy). OBJECTIVES: We used data from randomised controlled trials to examine
the effectiveness of endotherapies compared with surgery, in people with
Barrett’s Oesophagus; those with early neoplasias (defined as high grade
dysplasia (HGD), and those with early cancer (defined as carcinoma in-situ,
superficially invasive, early cancer or superficial cancer T-1m (T1-a) and T-1sm
(T1-b)). SEARCH STRATEGY: We used the Cochrane highly sensitive search strategy
to identify randomized trials in MEDLINE, EMBASE, CENTRAL, ISI Web of Science,
EBMR, Controlled Trials mRCT and ISRCTN and LILACS, in July and August 2008.
SELECTION CRITERIA: Types of studies: randomised controlled trials comparing
endotherapies with surgery in the treatment of high grade dysplasia (HGD), or
early cancer. All cellular types of cancer were included (i.e. adenocarcinomas,
squamous cell carcinomas and more unusual types) but will be discussed
separately.Types of participants: patients of any age and either gender with a
histologically confirmed diagnosis of early neoplasia (HGD and early cancer) in
Barrett’s or squamous lined oesophagus.Types of interventions; endotherapies (the
intervention) compared with surgery (the control), all with curative intent. DATA
COLLECTION AND ANALYSIS: Reports of studies which meet the inclusion criteria for
this review would have been analysed using the methods detailed in Appendix 9.
MAIN RESULTS: We did not identify any studies which met the inclusion criteria.
AUTHORS’ CONCLUSIONS: This Cochrane review has indicated that there are no
randomised control trials to compare management options in this vital area,
therefore trials should be undertaken as a matter of urgency. The problems with
such randomised methods are standardising surgery and endotherapies in all sites;
standardising histopathology in all centres; assessing which patients are fit or
unfit for surgery; and making sure there are relevant outcomes for the study i.e.
no progression of high grade dysplasia or long term survival i.e. over five

[Diagnosis of laryngeal carcinoma] [Article in Serbian] Jovanović MB. Med Pregl. 2008 Nov-Dec;61(11-12):591-5.

prognostic serious disease associated with high mortality. Survival rates for
these tumors vary and depend on the presence of early symptoms, anatomic
accessibility and lymphatic supply. Despite advances in therapy and novel
surgical and non-surgical approaches, early diagnosis remains the best predictor
of survival. STRATEGY AND NOVEL DIAGNOSTICAL PROCEDURES: This article reviews the
diagnosis for laryngeal carcinoma in an effort to heighten the clinical and
endoscopic recognition of these lesions, providing also global overview of
clinical conventional and recent endoscopic diagnostic tools for squamous cell
type of carcinoma of the larynx. Screening of asymptomatic individuals would
detect tumors at an early enough stage to patients’ benefit. CONCLUSION: The
progress in the elucidation of the molecular genetic changes in these tumors
should soon bring novel diagnostic procedures into the clinical practise. The
review higlights the important advances of endoscopic, radilogical and molecular
methods in detection of the tumor which may help clinicians to diagnose tumors as
early as possible. TNM staging, biopsy and histopathological grading remain the
gold standard for diagnosis of laryngeal carcinoma. A great number of novel
endoscopical methods are only supplementary tools to microlaryngoscopy. Some of
the most significant biological markers might be integrated with the evaluation
of behavioural factors, clinical and histopathological examinations for a new
clinicomolecular approach to laryngeal cancer.

Skin cancer: new markers for better prevention. Greinert R. Pathobiology. 2009;76(2):64-81. Epub 2009 Apr 9.

Skin cancer is the most frequent cancer in the white population worldwide.
Incidence of basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and
malignant melanoma (MM) is still increasing. This trend can be counteracted by
means of primary and secondary prevention because the main risk factor for skin
cancer – UV-radiation – is known, and, early detected, skin cancer can be cured
successfully. For early detection of skin cancer suitable risk (group) markers
have to be used to identify persons at risk. In order to increase the sensitivity
and specificity of early detection efforts (screening programs) new molecular
markers or biomarkers should be used in the future in the field of molecular
epidemiology. In this review the skin cancer problem is summarized and the
possible use of new biomarkers for skin cancer development, progression,
metastasis and prognosis is discussed. The review focuses on results of gene
expression profiling using array techniques and the new possibilities for the use
of epigenetic biomarkers.

Verrucous carcinoma of the skin: case report with literature review. Simatos G, Savvanis G, Paraskevaides M, Vechinni G, Porfiris E, Arkoulis N, Tzerbinis H, Mastoraki S, Tsikkinis C, Ammari S, Nissiotis A. J BUON. 2009 Jan-Mar;14(1):139-41.

We present a case of verrucous carcinoma of the axilla with multiple recurrences
and we review the literature with regard to the optimal therapeutic approach for this rare entity.

Chemoprevention of lung cancer. Keith RL. Proc Am Thorac Soc. 2009 Apr 15;6(2):187-93.

Lung cancer is the leading cause of cancer death in the United States, and the
majority of diagnoses are made in former smokers. While avoidance of tobacco
abuse and smoking cessation clearly will have the greatest impact on lung cancer
development, effective chemoprevention could prove to be more effective than
treatment of established disease. Chemoprevention is the use of dietary or
pharmaceutical agents to reverse or inhibit the carcinogenic process and has been
successfully applied to common malignancies other than lung. Despite previous
studies in lung cancer chemoprevention failing to identify effective agents, our
ability to determine higher risk populations and the understanding of lung tumor
and pre-malignant biology continues to advance. Additional biomarkers of risk
continue to be investigated and validated. The World Health
Organization/International Association for the Study of Lung Cancer
classification for lung cancer now recognizes distinct histologic lesions that
can be reproducibly graded as precursors of non-small cell lung cancer. For
example, carcinogenesis in the bronchial epithelium starts with normal epithelium
and progresses through hyperplasia, metaplasia, dysplasia, and carcinoma in situ
to invasive squamous cell cancer. Similar precursor lesions exist for
adenocarcinoma, and these pre-malignant lesions are targeted by chemopreventive
agents in current and future trials. At this time, chemopreventive agents can
only be recommended as part of well-designed clinical trials, and multiple trials
are currently in progress and additional trials are in the planning stages. This
review will discuss the principles of chemoprevention, summarize the completed
trials, and discuss ongoing and potential future trials with a focus on targeted

Treatments for psoriasis and the risk of malignancy. Patel RV, Clark LN, Lebwohl M, Weinberg JM. J Am Acad Dermatol. 2009 Jun;60(6):1001-17. Epub 2009 Apr 2.

BACKGROUND: There are multiple therapeutic options for the treatment of moderate
to severe psoriasis. The process of choosing among potential treatment options
requires both the physician and the patient to weigh the benefits of individual
modalities against their potential risks. Traditional systemic therapies for
psoriasis, including methotrexate (MTX) and cyclosporine (CsA), have a
well-documented array of toxicities, particularly end-organ toxicities. Over the
past several years, the use of biologic therapies for the treatment of moderate
to severe psoriasis has been a major clinical and research focus. With the advent
of these novel immunosuppressive therapies, one of the central safety issues
surrounding these agents is their potential to increase the risk of malignancy.
OBJECTIVE: Our objective was to review the risk of malignancy associated with
therapies for moderate to severe psoriasis, including phototherapy, traditional
systemic therapies, and biologic therapies. We reviewed the existing body of
literature in order to define the known incidence of malignancy associated with
psoralen and ultraviolet A (PUVA), narrowband and broadband ultraviolet B (UVB),
MTX, CsA, mycophenolate mofetil (MMF), and biologic therapies, including
alefacept, efalizumab, infliximab, etanercept, adalimumab, and ustekinumab.
RESULTS: PUVA, when given long term, is associated with increased risks of
cutaneous squamous cell carcinoma and malignant melanoma. Reviews of studies on
UVB, both narrowband and broadband, do not indicate any increased risk of
nonmelanoma skin cancer or melanoma. The traditional systemic psoriasis
therapies-MTX, CsA, and MMF-may be associated with an increased risk of
lymphoproliferative disorders during treatment, demonstrated in clinical trials
in patients with rheumatoid arthritis and documented in case reports concerning
psoriasis patients. The risk of malignancy with biologic therapy is still
unclear. However, the majority of studies examining this carcinogenic risk
suggest that tumor necrosis factor-alpha inhibitors may cause a slightly
increased risk of cancer, including nonmelanoma skin cancer and hematologic
malignancies. LIMITATIONS: The majority of studies cited in this review lack the
power and randomization of large clinical trials, as well as the long-term
follow-up periods which would further substantiate the hypothetical link between
these antipsoriatic treatment regimens and the potential for malignancy. Because
of the substantial lack of clinical data, the majority of studies evaluated focus
on the treatment of patients with rheumatoid arthritis, which is a systemic
inflammatory disorder comparable to psoriasis. Additionally, the increased risk
of malignancy associated with psoriasis itself is a confounding factor.
CONCLUSION: Many of the therapies for moderate to severe psoriasis, including
PUVA, traditional systemic therapies, and some biologic therapies, may increase
the risk of malignancy. Appropriate patient counseling and selection, as well as
clinical follow-up, are necessary to maximize safety with these agents. Further
long-term study is necessary to more precisely quantify the risks associated with
biologic therapies.

Human papillomavirus vaccines and anal carcinoma. Franceschi S, De Vuyst H. International Agency for Research on Cancer, Lyon, France.

PURPOSE OF REVIEW: To explore the possible role of current prophylactic vaccines
against human papillomavirus (HPV) in the prevention of anal intraepithelial
neoplasia and squamous cell carcinoma of the anus (SCCA). RECENT FINDINGS: SCCA
incidence is increasing in several developed countries, particularly in
HIV-positive men who have sex with men (MSM). Antiretroviral treatments against
HIV do not seem to decrease SCCA risk. A meta-analysis of 955 SCCA showed that
HPV prevalence was 85%, i.e., similar to that in cervical carcinoma, with an even
stronger predominance of HPV16. In addition, more than 90% prevalence of HPV was
found in anal intraepithelial neoplasia. Trials of the bivalent and quadrivalent
vaccines against HPV16/18 have shown nearly 100% efficacy against high-grade
lesions of the cervix, vulva and vagina in uninfected women under 26 years of
age. The quadrivalent vaccine that includes HPV6/11/16/18 has also shown high
efficacy against anogenital warts. SUMMARY: Currently available HPV vaccines
could potentially prevent the vast majority of SCCA, but only if administered
before the onset of sexual activity. Answers to some still open questions,
notably vaccine efficacy in men and HIV-infected individuals and willingness to
expand vaccination programmes to both sexes, are essential to predict the
ultimate impact of HPV vaccines on the prevention of cancerous and precancerous
anal lesions.

Genetic polymorphisms of smoking-related carcinogen detoxifying enzymes and head and neck cancer susceptibility. Lacko M, Oude Ophuis MB, Peters WH, Manni JJ.Anticancer Res. 2009 Feb;29(2):753-61.

Smoking and the consumption of alcohol are the main risk factors for head and
neck cancer. However, interindividual variation in the activity of enzymes
involved in the detoxification of tobacco smoke (pro)carcinogens, such as
microsomal epoxide hydrolase (mEH), glutathione-S-transferases (GSTs) and uridine
5′-diphosphate (UDP)-glucuronosyltransferase (UGTs), may influence the process of
carcinogenesis. Genetic polymorphisms of these enzymes may alter their activity
and may thus modulate the risk for squamous cell carcinomas of the head and neck
(SCCHN). A literature review on the role of mEH, GSTs and UGTs polymorphisms in
relation to SCCHN was performed and the results summarized. For mEH
polymorphisms, some of the studies revealed a relationship between genetic
polymorphisms of these enzymes and an altered risk for SCCHN, whereas others did
not. The presence of null polymorphisms in GSTM1 or GSTT1 were associated with an
increased risk for SCCHN. For the UGTs, only variants in UGT1A7 and UGT1A10 have
been studied, both of which were associated with an altered risk for SCCHN.

Human papillomavirus and head and neck cancer: a growing concern. Gillespie MB, Smith J, Gibbs K, McRackan T, Rubinchik S, Day TA, Sutkowski N. J S C Med Assoc. 2008 Dec;104(8):247-51.

Head and neck cancer is increasing in incidence in patients without the usual
risk factors for the disease. Practitioners need to be aware that young,
non-smoking patients are also at risk for certain types of head and neck cancer.
Head and neck cancer in this patient group is likely due to infection of the
tonsil and tongue with high-risk strains of human papillomavirus (HPV). There is
strong epidemiological and laboratory evidence that HPV is a cause of head and
neck cancer. Therefore, any patient with persistent lesions, ulcers, swallowing
difficulty, change in voice, or neck mass needs prompt referral to an
otolaryngologist- head and neck surgeon.

Dilemmas in managing oral dysplasia: a case report and literature review. Jack H, Lee K, Polonowita A. N Z Med J. 2009 Mar 13;122(1291):89-98.

Oral epithelial dysplasia (OED) is a premalignant lesion which has an
unpredictable course of progression. Its management has remained controversial
due to a lack of high-quality prospective studies evaluating the different
treatment modalities.1 We present a patient with a long history of OED which
subsequently transformed into malignancy. The clinical features of OED and the
controversies surrounding its management, as they present in the current
literature, will also be reviewed and discussed.

The alcohol flushing response: an unrecognized risk factor for esophageal cancer from alcohol consumption. Brooks PJ, Enoch MA, Goldman D, Li TK, Yokoyama A. PLoS Med. 2009 Mar 24;6(3):e50.

[Impact of the HIV infection on skin cancers] [Article in French] Quatresooz P, Piérard-Franchimont C, Piérard GE. Rev Med Liege. 2009 Jan;64(1):37-40.

A series of skin cancers are more frequent or show a worse course and outcome in
HIV-treated patients. The leading neoplasms correspond to basal and squamous cell
carcinomas, some primary cutaneous lymphomas and malignant melanomas. In these
patients, early diagnosis and radical treatment on sight should be considered.

Photodynamic therapy for the treatment of cutaneous neoplasia, inflammatory disorders, and photoaging. Tierney E, Barker A, Ahdout J, Hanke CW, Moy RL, Kouba DJ. Dermatol Surg. 2009 May;35(5):725-46. Epub 2009 Mar 20.

BACKGROUND: Photodynamic therapy (PDT) has demonstrated high efficacy, minimal
side effects, and improved cosmetic outcome when used for the treatment of
actinic keratoses (AK), basal cell carcinoma (BCC), squamous cell carcinoma, and
photoaging. METHODS: To review the literature on the use of PDT in dermatologic
surgery using MEDLINE. RESULTS: Published clinical studies using PDT in the
treatment of AKs yield overall efficacy rates ranging from 50% to 71% with one
treatment to as high as 88% to 90% with two or more treatments. For superficial
BCC, initial clearance rates were 76% to 97%, and for Bowen’s disease, initial
clearance rates ranged from 72% to 94% overall. The use of PDT for
photorejuvenation is a relatively new application of this technology, which has
shown promise in improving the appearance of fine lines, pigmentary variation,
and telangiectasias. CONCLUSIONS: The advantages of photodynamic therapy include
the capacity for noninvasive targeted therapy through topical application of
aminolevulinic acid and methyl aminolevulinic acid, with outstanding cosmetic
results. Although the theory behind the use of chemical photosensitizers and
ultraviolet light to treat a wide variety of skin disorders is straightforward,
the practical application of this technology is evolving. Additional research
into the precise mechanisms of action for specific photosensitizers and optimal
light sources will be highly beneficial to the advancement of this technology.

Larynx preservation clinical trial design: key issues and recommendations-a consensus panel summary. Lefebvre JL, Ang KK; Larynx Preservation Consensus Panel. Int J Radiat Oncol Biol Phys. 2009 Apr 1;73(5):1293-303.

PURPOSE: To develop guidelines for the conduct of Phase III clinical trials of
larynx preservation in patients with locally advanced laryngeal and
hypopharyngeal cancer. METHODS AND MATERIALS: A multidisciplinary international
consensus panel developed recommendations after reviewing results from completed
Phase III randomized trials, meta-analyses, and published clinical reports with
updates available through November, 2007. The guidelines were reviewed and
approved by the panel. RESULTS: According to the recommendations, the trial
population should include patients with T2 or T3 laryngeal or hypopharyngeal
squamous cell carcinoma not considered for partial laryngectomy and exclude those
with laryngeal dysfunction or age greater than 70 years. Functional assessments
should include speech and swallowing. Voice should be routinely assessed with a
simple, validated instrument. The primary endpoint should capture survival and
function. The panel created a new endpoint: laryngo-esophageal dysfunction-free
survival. Events are death, local relapse, total or partial laryngectomy,
tracheotomy at 2 years or later, or feeding tube at 2 years or later. Recommended
secondary endpoints are overall survival, progression-free survival, locoregional
control, time to tracheotomy, time to laryngectomy, time to discontinuation of
feeding tube, and quality of life/patient-reported outcomes. Correlative
biomarker studies for near-term trials should include estimated glomerular
filtration rate, excision repair cross-complementary-1 gene, E-cadherin and
beta-catenin, epiregulin and amphiregulin, and TP53 mutation. CONCLUSIONS:
Revised trial designs in several key areas are needed to advance the study of
larynx preservation. With consistent methodologies, clinical trials can more
effectively evaluate and quantify the therapeutic benefit of novel treatment
options for patients with locally advanced laryngeal and hypopharyngeal cancer.

Photochemoprevention of cutaneous neoplasia through natural products. Filip A, Clichici S, Daicoviciu D, Adriana M, Postescu ID, Perde-Schrepler M, Olteanu D. Exp Oncol. 2009 Mar;31(1):9-15.

Non-melanoma skin cancers such as squamous cell carcinoma and basal cell
carcinoma are the most common types of human tumors, representing 30% of the new
cases of malignancies diagnosed each year. Ultraviolet radiation (UV) from the
sun is a major cause of non-melanoma skin cancer in humans. The prevention and
mainly the photochemoprevention with natural products represent a simple but very
effective strategy in the management of cutaneous neoplasia. Here we review the
progress in the research of new and existing agents developed to protect the skin
exposed to UV. We also discuss the current state of knowledge on their
photosuppression mechanism in humans as well as in animal models, and efficiency
in cancer prevention.

Diagnosis of hepatocellular carcinoma. Gomaa AI, Khan SA, Leen EL, Waked I, Taylor-Robinson SD. World J Gastroenterol. 2009 Mar 21;15(11):1301-14.

Hepatocellular carcinoma (HCC) is one of the commonest cancers worldwide,
particularly in parts of the developing world, and is increasing in incidence.
This article reviews the current modalities employed for the diagnosis of HCC,
including serum markers, radiological techniques and histological evaluation, and
summarises international guidelines for the diagnostic approach to HCC.

Toxicity of targeted therapy in non-small-cell lung cancer management. Ricciardi S, Tomao S, de Marinis F. Clin Lung Cancer. 2009 Jan;10(1):28-35.

Lung cancer is the leading cause of cancer-related death worldwide. Despite
several chemotherapeutic agents, a survival plateau has been reached, so new
treatment strategies are clearly needed. A strong interest is now focused on the
use of targeted therapies for the management of non-small-cell lung cancer.
Monoclonal antibodies against the epidermal growth factor receptor (EGFR;
cetuximab) or vascular endothelial growth factor receptor (VEGFR; bevacizumab)
and EGFR tyrosine kinase inhibitors (gefitinib, erlotinib) are generally well
tolerated and do not have the severe systemic side effects usually seen with
cytotoxic drugs. A considerable number of treated patients develop dermatologic
side effects, such as acneiform eruption, xerosis, and eczema, and unfortunately,
this is often one cause of negative impact on a patient’s quality of life. No
controlled clinical trials have been performed to manage rash, so it is necessary
to provide suggestions for managing this frequent side effect. The main problems
related to the class of angiogenesis inhibitors affecting VEGFRs are the
exclusion of patients with brain metastases and/or squamous histology, and
vascular adverse effects, such as hypertension, proteinuria, thrombosis, and
hemorrhage. There are other new agents in clinical development, such as
sorafenib, sunitinib, vorinostat, vandetanib, everolimus, panobinostat, and
ASA404. They are all associated with a spectrum of toxicities, often reversible
with interruption of dosing. Further research is required to clarify the role of
targeted therapies and toxicities management.

Concurrent chemotherapy and radiotherapy for head and neck cancer. Burri RJ, Lee NY. Expert Rev Anticancer Ther. 2009 Mar;9(3):293-302.

Head and neck cancer is best managed in a multidisciplinary setting. Surgery,
radiation therapy, chemotherapy and, more recently, biologic therapy are often
employed in various combinations in an attempt to eradicate both clinically
apparent and occult disease. The goals of treatment include maximizing tumor
control while maintaining function and quality of life. Most patients present
with locally advanced disease, and multimodality organ-conserving therapy is
often employed for these patients based on the results of multiple Phase III
clinical trials. This article focuses on the rationale and evidence supporting
the use of concurrent chemotherapy and radiation therapy in the management of
locally advanced head and neck cancers.

Intricacies of bevacizumab-induced toxicities and their management. Gressett SM, Shah SR. Ann Pharmacother. 2009 Mar;43(3):490-501. Epub 2009 Mar 3.

OBJECTIVE: To review the serious and common toxicities of bevacizumab and
describe their incidence, risk factors, presentation, pathophysiology, and
management. DATA SOURCES: Literature for this review article was collected from
PubMed, MEDLINE, and the proceedings of the American Society of Clinical Oncology
(2000-November 2008). The key terms used in the search were: bevacizumab,
vascular endothelial growth factor, angiogenesis inhibitors, toxicity, toxicity
management, and adverse event. STUDY SELECTION AND DATA EXTRACTION: Review
articles, preclinical studies, and all published Phase 1-3 clinical trials were
reviewed. The references listed in identified articles were examined for
additional publications. DATA SYNTHESIS: The biomedical literature from 2000 to
2008 confirms that bevacizumab carries serious and potentially life-threatening
toxicity risks and emphasizes the importance of early recognition, continuous
monitoring, and prompt management of these toxicities. Such toxicities include
hemorrhage/bleeding, wound healing complications, gastrointestinal perforation,
arterial thromboembolism, congestive heart failure, hypertension,
proteinuria/nephrotic syndrome, infusion-related hypersensitivity reactions, and
reversible posterior leukoencephalopathy syndrome. Patients at the highest risk
for these toxicities are individuals with a history of hypertension,
thromboembolism, bleeding, cardiovascular disease, or preexisting proteinuria, as
these conditions may be exacerbated by bevacizumab use. Additionally, particular
tumor types correlate with risk for individual toxicities; for example, patients
with squamous non-small-cell lung cancer or rectal cancer have a higher risk of
bleeding, those with renal cell carcinoma have a higher proteinuria risk, and
patients with colorectal cancer have a higher risk of gastrointestinal
perforation. Further investigation is warranted to develop effective management
strategies for these toxicities. CONCLUSIONS: As bevacizumab is becoming widely
used in general oncology practice, it is important to understand the toxicities
that can arise and to develop practice guidelines for their management.

Meningeal carcinomatosis and uterine carcinoma: three different clinical settings and review of the literature. Asensio N, Luis A, Costa I, Oliveira J, Vaz F. Int J Gynecol Cancer. 2009 Jan;19(1):168-72.

INTRODUCTION: Leptomeningeal carcinomatosis is a rare metastatic event in
gynecological neoplasias, and most cases occur in ovarian cancer. It is extremely
infrequent in cervical cancer, and so far, there are not any reports of this
complication in association with endometrial cancer. PATIENTS AND METHODS: We
report a case of leptomeningeal carcinomatosis secondary to endometrial carcinoma
and 2 complex cervix cancer cases. A MEDLINE search was done to review all
published cases of this complication in gynecological cancer to identify
predictive factors for this diagnosis. RESULTS AND DISCUSSION: Leptomeningeal
carcinomatosis is usually diagnosed late in the course of the disease, and most
reports concern ovarian cancer patients. The number of cases describing this
neurologic complication in cervix cancer is increasing. Gadolinium-enhanced
magnetic resonance imaging may be necessary for this diagnosis, because
cerebrospinal fluid analysis results may be negative. Most cervix cases had
squamous cell (8/14) or neuroendocrine histologic subtype (3/14), and when
reported, differentiation was usually poor. The case we report of endometrial
carcinoma, unique in the literature, is a serous adenocarcinoma. CONCLUSIONS: A
high index of suspicion is necessary, and leptomeningeal carcinomatosis should be
considered in patients with unexplained neurologic symptoms whose gynecologic
tumors are poorly undifferentiated or have a serous component.

[Molecular markers of carcinogenesis in the diagnostics of cervical cancer] [Article in Polish] Bedkowska GE, Ławicki S, Szmitkowski M. Postepy Hig Med Dosw (Online). 2009 Feb 27;63:99-105.

Cervical carcinoma is the most frequent disease of the reproductive organ and is
the second most common cancer in women after breast cancer. As it is
characterized by high mortality, new diagnostic methods are needed, for example
tumor markers, enabling earlier diagnosis and rapid detection of recurrence after
therapy. Different tumor markers may be useful in the diagnostics of cervical
cancer, for example squamous cell carcinoma antigen (SCC-Ag), tissue polypeptide
antigen (TPA), and CYFRA 21-1, as well as some cytokines such as vascular
endothelial growth factor (VEGF), granulocyte colony-stimulating factor, and
macrophage colony-stimulating factor (M-CSF). About 150 genes connected with the
carcinogenesis of cervical carcinoma have been identified. This paper is devoted
to evaluating the diagnostic usefulness of molecular markers of carcinogenesis,
especially P53, Bcl-2, Brn-3a, and MCM, and comparing the results with those of
typical tumor markers or cytokines useful in diagnosing this type of cancer. It
was shown that telomerase and Brn-3a proteins demonstrate usefulness in screening
examination, P53 in monitoring the effectiveness of therapy, and Bcl-2 as a
survival prognostic factor. In summary, it is evident that molecular makers of
carcinogenesis are helpful in the diagnostics of cervical cancer, but further
investigation and confirmation by a prospective study is necessary.

Thyroid gland management in total laryngectomy: meta-analysis and surgical recommendations. Mendelson AA, Al-Khatib TA, Julien M, Payne RJ, Black MJ, Hier MP. Otolaryngol Head Neck Surg. 2009 Mar;140(3):298-305.

OBJECTIVES: 1) Review the incidence of thyroid gland invasion by squamous cell
laryngeal carcinoma reported in the literature. 2) Assess the association between
thyroid gland invasion and anatomical characteristics of the laryngeal tumor.
DATA SOURCES: MEDLINE (1967-2007) and EMBASE (1980-2007). These databases were
supplemented with 61 patients from McGill University who underwent total
laryngectomy with hemi- or total thyroidectomy from 2001-2006. REVIEW METHODS:
Systematic review for series of laryngeal carcinoma that commented on thyroid
gland invasion according to tumor subsite and pathological characteristics. Total
laryngectomy specimens for primary laryngeal squamous cell carcinoma with
concomitant thyroid resection were included in the analysis. RESULTS: In total,
eight series (n = 399) were included in the meta-analysis. Thyroid gland invasion
was present in 33 laryngectomy specimens (8%); the principal method of invasion
of the gland was by direct extralaryngeal extension. Subglottic extension > 10 mm
(OR 7.22 [2.05 to 25.46]; P = 0.002), transglottic tumors (OR 3.23 [1.16 to
9.00]; P = 0.025), and subglottic subsite (OR 5.66 [1.34 to 23.87]; P = 0.018)
were all significantly associated with thyroid gland invasion. Cartilaginous
invasion by tumor was not a significant predictor of thyroid gland invasion (P >
0.05). CONCLUSIONS: Thyroid gland invasion is not a general feature of squamous
cell laryngeal carcinoma. When present, it is strongly associated with
anteroinferior spread of advanced laryngeal tumors. Thyroidectomy may only be
required during total laryngectomy for transglottic tumors, subglottic tumors,
and tumors with subglottic extension >10 mm.

Determinants of outcome following surgery for oral squamous cell carcinoma. Woolgar JA, Hall GL. Future Oncol. 2009 Feb;5(1):51-61.

The recent changes in incidence and prevalence of oral squamous cell carcinoma in
relation to gender and age mirror the changing patterns of exposure to tobacco
and alcohol, the main etiological agents. Most cases of oral cancer are managed
by surgery, often combined with radiotherapy. Histopathological assessment of the
resection specimen provides information vital for postoperative management and
prognosis. This review considers the full range of histological determinants of
outcome in relation to the primary oral tumor and any metastatic involvement of
the cervical lymphatic system, together with an outline of more general patient
factors that may also impact on morbidity and mortality rates.

Nonmelanoma skin cancer of the head and neck I: histopathology and clinical behavior. McGuire JF, Ge NN, Dyson S. Am J Otolaryngol. 2009 Mar-Apr;30(2):121-33. Epub 2008 Jul 22.

Non-Melanoma skin cancer (NMSC) is the most commonly encountered malignancy in
almost every area of practice, but the cases that present to an Otolaryngology
practice will be advanced in nature. The major subtypes of NMSC include basal
cell carcinoma, squamous cell carcinoma, dermatofibrosarcoma protuberans, merkel
cell carcinoma, and adnexal malignancies. In this review, we present the
epidemiology, histology, clinical presentation and management of these major
subtypes. Further, we present background on multimodality treatment for NMSC
lesions that have become metastatic from their primary site and an introduction
to the behavior and treatment of NMSC lesions in patients who have received organ
transplants. Understanding the clinical behavior of advanced NMSC is essential
knowledge for a general Otolaryngologist.

Chemotherapy and radiation therapy in the treatment of squamous cell carcinoma of the vulva: Are two therapies better than one? Moore DH. Gynecol Oncol. 2009 Jun;113(3):379-83. Epub 2009 Feb 20.

As gynecologic surgeons garnered a better understanding of various
clinical-pathological prognostic factors, there evolved a number of modifications
in the surgical approach allowing for more individualized therapy with less
morbidity, while still retaining the curative potential of the radical vulvectomy
operation. The incorporation of radiation therapy and eventually chemotherapy in
the primary treatment of vulva cancer also represents a slow evolution in
clinical management. The addition of chemotherapy concurrent to radiation therapy
for the treatment of vulvar carcinoma was heavily influenced by advances in the
treatment of cervical cancer, and squamous cell carcinoma of the anal canal. On
the basis of many good phase II studies but no randomized controlled trials in
the disease, chemoradiation therapy is now inherent to the clinical management of
vulvar carcinoma. The rarity of vulva cancer precludes prospective randomized
clinical trials in the absence of international collaboration. Nonetheless,
patients with locally advanced vulva cancer have derived considerable benefit
from chemoradiation studies in other related tumor sites, and will continue to do
so in the future.

Lobectomy of second primary cancer in survivor of small cell lung cancer with brain metastasis. Nakamura Y, Iwazaki M, Maitani F, Inoue Y, Hayashi Y, Hasegawa A, Inoue H. Ann Thorac Surg. 2009 Mar;87(3):952-4.

Resection of a second primary nonsmall cell lung carcinoma in a long-term
survivor of small cell lung carcinoma with brain metastasis is reported. The
patient had squamous cell carcinoma as the second primary tumor and underwent
lobectomy with node dissection. He was alive 79 months after the initial
diagnosis of the small cell carcinoma, 64 months after the diagnosis of the brain
metastasis, and 21 months after the curative pulmonary resection for his second
primary carcinoma.

[Risk factors for esophageal cancer, and possible genetic background] [Article in Hungarian] Hagymási K, Tulassay Z. Orv Hetil. 2009 Mar 1;150(9):407-13.

Esophageal cancer is the sixth most common cancer mortality, with increasing
incidence. 95% of the esophageal cancer is squamous cell carcinoma or
adenocarcinoma. Although they differ in histology and epidemiology, some of their
risk factors (smoking, dietary factors) and their pathogenesis are the same. More
than 90% of esophageal cancer is diagnosed in late stage. Despite the development
of diagnostic and therapeutic techniques, esophageal cancer has poor prognosis,
with 5-year survival rates between 10-13%. Understanding the exact pathogenesis
can help the prevention of this highly aggressive cancer, with the use of natural
substances and nonsteroid inflammatory drugs.

[Human papilloma virus infection and cervical cancer: a public health perspective] [Article in Spanish] Torres-Poveda KJ, Burguete A, Bermúdez-Morales VH, Madrid-Marina V. Rev Invest Clin. 2008 Sep-Oct;60(5):414-20.

Colon, rectal, and anal cancers. Wilkes G, Hartshorn K. Semin Oncol Nurs. 2009 Feb;25(1):32-47.

OBJECTIVES: To review the incidence, risk factors, staging, diagnosis, and
treatment of colon, rectal, and anal cancers, as well as nursing care associated
with managing patients diagnosed with these malignancies. DATA SOURCES: Published
research reports, epidemiologic data, published patient management guidelines,
and institution-based clinical tools. CONCLUSIONS: Significant advances in the
management of colon, rectal, and anal cancers in the past decade have extended
patient survival. Further clinical research will refine current therapeutic
strategies and treatment decision-making aids while minimizing symptoms of
disease and treatment. IMPLICATIONS FOR NURSING PRACTICE: Nurses need to be
familiar with risk factors, disease course, and current and emerging therapies to
assist patients with treatment decision-making, and to anticipate and intervene
in managing disease and treatment-induced problems. Early identification and
management of distressing symptoms can help to avoid life-threatening effects and
promote patient adherence to prescribed therapies; timely patient/family
education may minimize anxiety and promote self-management.

Immunotherapy of head and neck cancer using tumor antigen-specific monoclonal antibodies. Lee SC, López-Albaitero A, Ferris RL. Curr Oncol Rep. 2009 Mar;11(2):156-62.

Monoclonal antibodies (mAbs) are now commonly used therapeutic agents in cancer
patients. Since US Food and Drug Administration approval of cetuximab for head
and neck squamous cell carcinoma, it has been used increasingly in this disease.
Several other mAbs also are in development or in clinical -trials. Recently,
evidence has accumulated that mAbs induce activation of cellular immunity,
including natural killer and T cells and that this may contribute to clinical
response. mAbs have been shown to mediate antibody-dependent cellular
cytotoxicity, complement-dependent lysis, and activation of tumor
antigen-specific T cells. Various patient and tumor factors, such as
polymorphisms in Fcgamma receptors expressed by immune cells, activity of
T-regulatory cells, and tumor escape through downregulation of antigen-processing
machinery in tumor cells, are likely to modulate the immune activation mediated
by therapeutic mAbs. Understanding the interplay of these factors is likely to
improve the selection of the most appropriate candidates for mAb-based
immunotherapy, prediction of clinical response, and our understanding of
mechanisms of tumor escape from therapeutic mAbs.

Surgical salvage of cancer of the oropharynx after chemoradiation. Bumpous JM. Curr Oncol Rep. 2009 Mar;11(2):151-5.

Advanced oropharyngeal squamous cell carcinoma is treated primarily with
chemoradiation, with the goal of excellent disease control and preservation of
swallowing and articulation functions of the oropharynx. Disease control rates
generally are excellent; however, a significant number of patients do not achieve
locoregional control of disease. The importance of human papillomavirus
expression in predicting successful tumor response, locoregional control, and
survival following chemoradiation is increasingly confirmed. Emerging is a
clinical profile, viral expression, and genetic expression pattern that can
predict success of chemoradiation and indicate which patients are at higher risk
for locoregional failure necessitating surgical salvage. Successful surgical
salvage depends on restaging at the time of recurrence and the time interval from
chemoradiation to recurrence. Although surgical morbidity and mortality remain a
challenge in patients undergoing salvage surgery of the oropharynx after
radiation failure with or without chemotherapy, they may be mitigated by liberal
application of regional and microvascular free flap reconstruction techniques.

Telomerase-specific virotherapy for human squamous cell carcinoma. Fujiwara T. Expert Opin Biol Ther. 2009 Mar;9(3):321-9.

BACKGROUND: Replication-selective tumor-specific viruses present a novel approach
for treatment of neoplastic disease. They are designed to induce lysis after
propagation within the tumor. Human telomerase is active in over 85% of primary
cancers and its activity correlates closely with human telomerase reverse
transcriptase (hTERT) expression. OBJECTIVES: Oncolytic viruses, Telomelysin and
TelomeScan, that combine the specificity of hTERT promoter-based expression
systems with the lytic efficacy of replicative viruses were developed. The goal
was to confirm the efficacy of the viruses for human squamous cell carcinoma.
RESULTS/CONCLUSION: Squamous cell carcinoma of the head and neck (SCCHN) is
characterized by locoregional spread, and is clinically accessible, making it an
attractive target for intratumoral virotherapy. The viruses replicated
efficiently and induced killing in a panel of human cancer cell lines including
SCCHN cells in vitro and in vivo. These results illustrate the potential of
telomerase-specific oncolytic viruses for treatment of human SCCHN.

Squamous intraepithelial neoplasia of the esophagus: past, present, and future. Shimizu M, Nagata K, Yamaguchi H, Kita H. J Gastroenterol. 2009;44(2):103-12. Epub 2009 Feb 13.

With regard to the esophagus, the term “squamous dysplasia” has been used in
European countries, the United States, and China, while its use is controversial
in Japan. Recently, “low-grade intraepithelial neoplasia” and “high-grade
intraepithelial neoplasia” have been used as inclusive terms for dysplasia and
carcinoma in situ in the World Health Organization classification.
Endoscopically, it is often difficult to identify squamous intraepithelial
neoplasia by conventional endoscopy, but application of iodine is useful for the
diagnosis of such a lesion. In addition, new types of endoscopic techniques,
including magnifying endoscopy, narrow-band imaging (NBI), and endocytoscopy are
helpful to detect squamous intraepithelial neoplasia. NBI is very useful for
identifying the intrapapillary capillary loop pattern. Regarding the pathological
criteria of squamous dysplasia and squamous cell carcinoma, the views of Japanese
and Western pathologists have differed significantly. Before the term
“intraepithelial neoplasia” was introduced, severe dysplasia as diagnosed by
Western pathologists was in fact the same as squamous cell carcinoma in situ or
noninvasive carcinoma as diagnosed by Japanese pathologists. This problem has
been solved by the introduction of the Vienna classification; however, there are
still some issues that need to be resolved. One of them is the presence of basal
layer type squamous cell carcinoma in situ, which is often underdiagnosed as
lowgrade intraepithelial neoplasia by Western pathologists. Endoscopic treatments
such as endoscopic mucosal resection and endoscopic submucosal dissection have
recently become possible choices for squamous intraepithelial neoplasia; however,
these techniques are not in widespread use in the West. We believe that a
consensus meeting between Japanese and Western pathologists as well as
endoscopists should be held promptly to reach a common ground for the

A review of the epidemiology of cancers at the University Teaching Hospital, Lusaka, Zambia. Bowa K, Wood C, Chao A, Chintu C, Mudenda V, Chikwenya M. Trop Doct. 2009 Jan;39(1):5-7.

This is a retrospective study based on pathology reports of specimens reviewed at
the University Teaching Hospital (UTH) pathology laboratory in Lusaka, Zambia,
from January 1997 to December 2005. UTH is the main reference hospital in Zambia
and has a catchment area covering 1.3 million people. The most common cancer
among men was Kaposi’s sarcoma followed by cancer of the eye, soft tissue
sarcomas and cancer of the prostate. The most common cancer among women was
cancer of the cervix, followed by cancer of the eye, cancer of the breast and
Kaposi’s sarcoma. Non-Hodgkin’s lymphoma is the fifth most common cancer in both
men and women. There has been a significant change in the pattern of malignancies
at the UTH over the last 20 years, with an increase in Kaposi’s sarcoma, cancer
of the cervix and cancer of the eye.

[Advanced esophageal carcinoma recanalization] [Article in Slovak] Molnárová A. Klin Onkol. 2008;21(5):309-12.

Advanced esophageal carcinoma has poor prognosis with 5-year survival of less
than 20%. This poor prognosis is the same for squamous cell carcinoma and
adenocarcinoma. Surgical therapy, external radiation and chemotherapy with
curative intent are usually impossible because of the advanced disease. Dysphagia
is the most frequent symptom affecting quality of life. Bougies or balloon
dilation improves dysphagia only short-term (few days). Nd-YAG laser, ACP and
photodynamic therapy all have mid-range effect and require repetition after few
weeks. Brachytherapy and esophageal self-expanding stent insertion have longer
benefit. Stent insertion provides fastest improvement of dysphagia; however,
complications in later setting occur in30% and require further endoscopic
treatment. Brachytherapy has slower onset of benefit but has fewer complications
and longer benefit. Brachytherapy is suitable for patients wit expected lifespan
more than 3 months. Most important contraindication of brachytherapy is
tracheo-esophageal fistula.

[Human papillomavirus and cancer of the oropharynx. Molecular interaction and clinical implications] [Article in German] Klussmann JP, Preuss SF, Speel EJ. HNO. 2009 Feb;57(2):113-22.

One-third of the cases of oropharyngeal squamous cell carcinoma (OSCC) contain
oncogenic human papillomavirus (HR-HPV). Epidemiologic and molecular evidence
underlines the causal role of HR-HPV in these tumors, which can be defined as
HPV-related OSCC. These tumors differ from chemical/toxin-induced OSCC in several
biological aspects, including specific molecular and genetic alterations. This
leads to a characteristic clinical profile of HPV-related OSCC. Sexual risk
factors play a role; however, the knowledge about natural infection and the rate
of persistence of HR-HPV in the oropharynx is marginal. It is shown that the
distinct biological behavior of the HPV-related subset of oropharyngeal tumors
results in a more favorable prognosis. This might be the result of a better
response to chemotherapy and radiotherapy. However, further studies are needed to
show whether it will be possible to reliably select patients for individualized
therapy depended on the HPV status of their tumors. Therefore, we think it will
be mandatory to consider and stratify HPV status in the design of prospective
clinical trials in the future.

Chest wall resection for lung cancer: indications and techniques. Stoelben E, Ludwig C. Eur J Cardiothorac Surg. 2009 Mar;35(3):450-6. Epub 2009 Feb 1.

Lung cancer invasion of the chest wall is not a common challenge and represents
only about 5% of all patients resected for lung cancer. In T3N0M0 tumours,
long-term survival reaches 40-50%, provided certain conditions are fulfilled. The
number of explorative thoracotomies and the rate of non-radical resections might
be high due to the local extension of an aggressive tumour. Mortality after
resection is as high as for pneumonectomy. For historical and anatomical reasons,
we have to divide the patients into two groups: infiltration of, and above, the
second rib (Pancoast) and tumours located caudally to the second rib. We have to
define the two entities. There is a problem concerning correct diagnosis: many
tumours reach the chest wall. If the lung is not adherent to the parietal pleura,
a standard lobectomy can be performed. However, in the case of adhesions, the
differentiation between tumour invasion and inflammation may be difficult. We do
not want to perform over-treatment since lung resection en bloc with the chest
wall has a higher morbidity and mortality than lobectomy. But we have to avoid
opening the tumour intraoperatively or perform a non-radical resection.
Therefore, we need a preoperative diagnostic tool answering the question of
extrapulmonary infiltration. In this context, we will discuss whether
extrapleural lung resection is acceptable in the case of pleural invasion without
chest wall involvement. The prognosis of patients with tumours invading the chest
wall and mediastinal lymph node metastasis is worse. But patients with
ipsilateral supraclavicular lymph node metastasis are not excluded. Thus, careful
clinical investigations are necessary. To achieve complete resection, the surgeon
should use anatomical knowledge to choose the best form of access to make radical
resection more feasible. The problem of pain after thoracotomy is accentuated
after chest wall resection, especially after paravertebral resection. The use of
modern pain treatment is very important.

Pulmonary preneoplasia–sequential molecular carcinogenetic events. Lantuéjoul S, Salameire D, Salon C, Brambilla E. Histopathology. 2009 Jan;54(1):43-54.

Bronchial and bronchioloalveolar carcinogenesis is a multicentric and multistep
process, leading to a sequential accumulation of molecular and genetic
abnormalities, mainly due to exposure to tobacco carcinogens. Concomitantly, a
series of morphological alterations of normal bronchial or bronchioloalveolar
epithelium occur, resulting in preneoplastic and then neoplastic lesions. The
three pulmonary preneoplastic changes recognized to date in the lung include
bronchial squamous dysplasia and in situ carcinoma, preceding invasive squamous
cell carcinoma and basaloid carcinoma, atypical adenomatous hyperplasia, a
preneoplastic condition of bronchioloalveolar carcinoma, and diffuse idiopathic
pulmonary neuroendocrine cell hyperplasia, a proposed precursor for carcinoid
tumours. Although the gradual accumulation of molecular alterations has been
widely investigated in bronchial carcinogenesis, with the aim of determining new
biomarkers for early lung cancer detection in high-risk patients and targeted
chemoprevention, lung adenocarcinoma pathogenesis has been only recently
highlighted, with the recent discovery of epidermal growth factor receptor
mutation pathway in non-smokers. This review focuses on the current status of
molecular pathology in lung cancer and pulmonary preneoplastic conditions.

Multidisciplinary approach to esophageal and gastric cancer. Quiros RM, Bui CL. Surg Clin North Am. 2009 Feb;89(1):79-96, viii.

The incidence of esophageal and gastric malignancies has increased over the last
decade. Historically, surgery has been considered the best treatment for these
cancers. However, long-term survival after surgery is fair at best, because of
the tendency of disease to recur locally and distantly. Presently, the management
of these cancers involves surgery, chemotherapy, and radiation therapy. This
article discusses various treatment strategies that employ these modalities
either alone or in combination, in an attempt to improve survival rates for
patients who have gastroesophageal malignancies.

Multimodal treatment for head and neck cancer. Lango MN. Surg Clin North Am. 2009 Feb;89(1):43-52, viii.

Head and neck cancers are relatively less common tumors, but with complex
anatomic and physiologic relationships to the structures from which they arise.
Multimodal management is required for advanced stage disease, while single
modality treatment is usually sufficient for early lesions. Treatment paradigms
have shifted toward more functional preservation of speech and swallowing, when
possible. Increased use of radiation, systemic/targeted therapies and
function-preserving surgical approaches have allowed for organ preservation
without compromising oncologic outcomes in properly selected patients.

[Squamous intraepithelial neoplasia (WHO 2005). Precancerous lesions of the head and neck region] [Article in German] Neid M, Tannapfel A. HNO. 2009 Feb;57(2):181-7; quiz 188.

The recent WHO classification 2005 applies the concept of intraepithelial
neoplasia to the head and neck region. Precursor lesions of the head and neck
mucosa are classified as squamous intraepithelial neoplasia (SIN) and are graded
as mild, moderate and severe (SIN 1-3). SIN 3 is equivalent to former carcinoma
in situ. Each precursor lesion is associated with an ascertained risk of
progression to carcinoma, which is important for further diagnostic or therapy.

Treatment for patients with unknown primary cancer and favorable prognostic factors. Hainsworth JD, Fizazi K. Semin Oncol. 2009 Feb;36(1):44-51.

Patients with carcinoma of unknown primary site are heterogeneous with respect to
clinical and pathologic features. Within this diverse group, specific clinical
and/or pathologic features can be used to define several subsets with favorable
prognoses. Specific subsets include women with peritoneal carcinomatosis, women
with isolated axillary lymph node metastases, adenocarcinoma presenting as a
single metastatic lesion, young men with features of extragonadal germ cell
tumor, squamous carcinoma involving cervical or inguinal lymph nodes, and
neuroendocrine carcinoma. Prospective identification of patients in these
favorable subgroups allows the most effective treatment to be selected. This
review summarizes current recommendations for the evaluation and treatment of
patients in each of these favorable prognostic subsets.

Pathologic evaluation of unknown primary cancer. Oien KA. Semin Oncol. 2009 Feb;36(1):8-37.

The pathologic approach to metastases of unknown primary cancer (UPC) is stepwise
and uses the clinical context, morphology, and, where necessary,
immunohistochemistry (IHC). This review covers the initial approach to a UPC
biopsy; the diagnosis of malignancy and broad tumor typing into carcinoma,
melanoma, lymphoma, or sarcoma; and further subtyping of carcinoma into germ cell
(broadly included), squamous, neuroendocrine, and solid organ including liver and
renal, and adenocarcinomas. Finally, for adenocarcinoma, the prediction of
primary tumor site, including lung, pancreas, stomach, colon, ovary, prostate,
and breast, is discussed. For each tumor type, the morphologic features are
presented alongside established useful IHC markers, with a description of their
staining patterns and common diagnostic dilemmas. Optimal tissue handling and IHC
interpretation, quality assurance, and limitations also are discussed. The target
readership is oncologists, but other clinicians and trainee pathologists also may
find the content of use.

Cisplatin: a review of toxicities and therapeutic applications. Barabas K, Milner R, Lurie D, Adin C. Vet Comp Oncol. 2008 Mar;6(1):1-18.

Cisplatin is a platinum chemotherapeutic used in a variety of malignancies. The
antineoplastic activity occurs from DNA cross-links and adducts, in addition to
the generation of superoxide radicals. Nephrotoxicity is the most well-known and
potentially most clinically significant toxicity. Unfortunately, the mechanism
for cisplatin nephrotoxicity has not been completely elucidated; however, many
theories have been developed. Other toxicities include gastrointestinal,
myelosuppression, ototoxicity and neurotoxicity. Saline diuresis is currently the
most accepted way to prevent cisplatin nephrotoxicity. Research has focused on
pharmaceuticals and enzyme/molecular alterations as alternatives to long-term
diuresis. No agents have currently been identified that can protect from all
toxicities. Cisplatin has shown activity against osteosarcoma, transitional cell
carcinoma, squamous cell carcinoma (SCC), melanoma, mesothelioma, carcinomatosis
and germinal cell tumours in the dog. In the cat, cisplatin cannot be utilized
because of fulminant pulmonary oedema that occurs at standard doses.
Intralesional cisplatin has been utilized in horses for the treatment of SCC and

Evaluation and management of the unknown primary carcinoma of the head and neck. Galer CE, Kies MS. J Natl Compr Canc Netw. 2008 Nov;6(10):1068-75.

Squamous cell carcinoma of unknown primary origin in the head and neck is
encountered as a recurring clinical problem in head and neck cancer clinics,
affecting 3% to 25% of patients. This article describes the clinical
presentation, appropriate evaluation, and treatment strategies for this important
subgroup. Treatment–best carried out with multidisciplinary teams of specialists
experienced in the care of head and neck cancer patients–is curative for most of
these patients.

A review of contusugene ladenovec (Advexin) p53 therapy. Senzer N, Nemunaitis J. Curr Opin Mol Ther. 2009 Feb;11(1):54-61.

Contusugene ladenovec (Advexin; INGN-201; Introgen Therapeutics Inc) is a
replication-impaired, non-integrating, serotype 5 adenoviral vector that carries
the p53 gene under the control of the CMV promoter. Deletion or mutation of the
p53 gene has been observed in approximately half of malignancies in patients with
cancer and p53 pathway dysfunction was observed in the majority of others,
thereby providing the rationale for p53 restoration in the treatment of cancer.
Advexin has demonstrated a consistent safety profile and clinical efficacy as a
monotherapy, as well as in combined modality regimens with chemotherapy and
radiation. Additive or synergistic effects have been observed in a variety of
tumor types, including NSCLC, squamous cell carcinoma of the head and neck,
hepatocellular carcinoma, glioma, and breast, prostate and colorectal cancers.
The identification of biomarkers may help direct research in tumor-specific

Marjolin ulcer arising within hidradenitis: a case report and literature review. Katz RD, Goldberg NH. Ann Plast Surg. 2009 Feb;62(2):173-4.

This is a report of a patient with squamous cell carcinoma discovered in a bed of
longstanding (>20 years) hidradenitis suppurativa. A literature search
demonstrates this to be an entity with potentially devastating sequelae if not
expediently diagnosed and treated. In light of the possibility of malignant
transformation, the hidradenitis specimen and any suspicious lesions in proximity
should be sent to pathology for thorough assessment.

Targeted therapies in squamous cell carcinoma of the head and neck. Gold KA, Lee HY, Kim ES. Cancer. 2009 Mar 1;115(5):922-35.

Head and neck cancer is a challenging disease that is expected to account for
greater than 500,000 new cases worldwide in 2008. Toxicity has impeded advances
in chemotherapy and radiation for head and neck cancer, and the prognosis for
patients with recurrent and/or metastatic disease remains poor. Over the past
decade, clinical research in head and neck cancer has focused on improving the
efficacy of current multimodal approaches by targeting cellular pathways
associated with carcinogenesis. Blocking the epidermal growth factor receptor
(EGFR) and the vascular endothelial growth factor receptor (VEGFR) have emerged
as primary strategies that account for the success of current targeted therapies
in cancer. Recent studies with cetuximab, a monoclonal antibody inhibitor of the
EGFR, have demonstrated survival benefits across the range of treatment settings
in advanced head and neck cancer, and it is the only targeted therapy approved
for use in this malignancy. In this review, the authors present the current
development status of targeted therapies, focusing on those that have potential
to impact the management of head and neck cancer in the near-term future. Trials
are ongoing in all stages of disease and with a variety of modalities and agents,
and those trials should provide critical insight into the best way to use these
agents to improve patient outcomes. (c) 2009 American Cancer Society.

Insulin-like growth factor 1 receptor targeted therapeutics: novel compounds and novel treatment strategies for cancer medicine. Hewish M, Chau I, Cunningham D. Recent Pat Anticancer Drug Discov. 2009 Jan;4(1):54-72.

The insulin-like growth factor 1 receptor (IGF-1R) and its associated signalling
system has provoked considerable interest over recent years as a novel
therapeutic target in cancer. A brief outline of the IGF-1R signalling system and
the rationale for its use in cancer medicine is given. This is followed by a
discussion of the different possible targets within the IGF-1R system, and drugs
developed to interact at each target. A systems-based approach is then used to
review the in vitro and in vivo data in the published literature of the following
compounds targeting IGF-1R components using specific examples: growth hormone
releasing hormone antagonists (e.g. JV-1-38), growth hormone receptor antagonists
(e.g. pegvisomant), IGF-1R antibodies (e.g. CP-751,871, AVE1642/EM164, IMC-A12,
SCH-717454, BIIB022, AMG 479, MK-0646/h7C10), and IGF-1R tyrosine kinase
inhibitors (e.g. BMS-536942, BMS-554417, NVP-AEW541, NVP-ADW742, AG1024, potent
quinolinyl-derived imidazo (1,5-a)pyrazine PQIP, picropodophyllin PPP,
Nordihydroguaiaretic acid Insm-18/NDGA). The following tumour types are
specifically discussed: lung, breast, colorectal, pancreatic, NETs, sarcoma,
prostate, leukaemia, multiple myeloma. Other tumour types are mentioned briefly:
squamous cell carcinoma of the head and neck, melanoma, glioblastoma, ovary,
gastric and mesothelioma. Results of early stage clinical trials, involving
recently patented drugs. are included where appropriate. We then outline the
current understanding of toxicity related to IGF-1R targeted therapy, and finally
outline areas for further research.

Unilateral submandibular gland aplasia masquerading as cancer nodal metastasis. Shipchandler TZ, Lorenz RR. Am J Otolaryngol. 2008 Nov-Dec;29(6):432-4. Epub 2008 Jun 16.

OBJECTIVE: Five reports have examined unilateral submandibular gland aplasia. The
purposes of this report are to demonstrate submandibular gland aplasia leading to
contralateral gland hypertrophy in the setting of oral cavity cancer and to
discuss the corresponding diagnostic and management challenges. STUDY DESIGN:
This study is a case report of a 60-year-old male who presented with pain on the
right side of the mobile tongue. METHOD: This report uses literature review.
RESULTS: A 60-year-old male presented with pain on the right side of the mobile
tongue. Subsequent results of punch biopsy revealed squamous cell carcinoma in
situ with foci of microinvasion of the tongue. Head and neck examination revealed
no abnormalities. The patient underwent a wide-local excision of the tongue
lesion. Postoperative computed tomographic (CT) scan showed an asymmetric mass on
the ipsilateral side of the cancer in the region of the submandibular gland. The
gland was noted to be abnormally large. A diagnosis of contralateral
submandibular gland aplasia was made. The patient is cancer-free at 2 years
postlocal excision. Salivary gland aplasia is an extremely rare disorder and is
often associated with various congenital syndromes. Unilateral submandibular
gland aplasia is even rarer with ours representing the sixth reported case.
Aplasia is believed to stem from a regional disturbance in early fetal
development. Common symptoms can include dysphagia, dry mouth, decreased taste,
and tooth decay. In the presence of a history of oral cavity cancer, unilateral
submandibular gland aplasia poses a challenge during postoperative cancer
follow-up. CONCLUSIONS: Unilateral submandibular gland aplasia in the setting of
oral cavity cancer poses a unique challenge for cancer follow-up. Hypertrophy of
the submandibular gland on the other side can masquerade as nodal metastasis.
Head and neck examination as well as CT scan can be inconclusive. Regular
confirmatory tests such as fine needle aspiration biopsy and positron emission
tomography/CT for cancer detection is extremely useful for detecting recurrence.

Pemetrexed disodium for the treatment of NSCLC: an update. Hsu JY, Wakelee H. Drugs Today (Barc). 2008 Sep;44(9):669-78.

Pemetrexed disodium is a multitargeted antifolate cytotoxic chemotherapy agent
approved by the U.S. Food and Drug Administration (FDA) initially for the
treatment of malignant pleural mesothelioma, and in August 2004 for second-line
treatment of non-small cell lung cancer (NSCLC). In September 2008, the FDA also
approved pemetrexed and cisplatin as first-line therapy for NSCLC. Pemetrexed is
also no longer recommended for treatment of NSCLC with squamous cell carcinoma
histology. Pemetrexed is currently being tested in clinical trials as part of
second-line combination, first-line, adjuvant and maintenance therapies.
Copyright 2008 Prous Science, S.A.U. or its licensors. All rights reserved.

The role of alcohol in oral carcinogenesis with particular reference to alcohol-containing mouthwashes. McCullough MJ, Farah CS. Aust Dent J. 2008 Dec;53(4):302-5.

Worldwide, oral cancer represents approximately 5 per cent of all malignant
lesions, with over 800 new intra-oral squamous cell carcinomas registered in
Australia each year. Despite recent advances in therapy, the five-year survival
rate remains around 50 per cent and the sequelae of treatment can be seriously
debilitating. It has been long established that smoking and alcohol consumption
are risk factors linked to the development of oral cancer. This review assesses
the epidemiological evidence, supportive in vitro studies and mechanism by which
alcohol is involved in the development of oral cancer. Further, we review the
literature that associates alcohol-containing mouthwashes and oral cancer. On the
basis of this review, we believe that there is now sufficient evidence to accept
the proposition that alcohol-containing mouthwashes contribute to the increased
risk of development of oral cancer and further feel that it is inadvisable for
oral healthcare professionals to recommend the long-term use of
alcohol-containing mouthwashes.

Qat and its health effects. El-Wajeh YA, Thornhill MH. Br Dent J. 2009 Jan 10;206(1):17-21.

In Southern Arabia and Eastern Africa, qat chewing is a widely practised
socio-cultural habit. It consists of placing the green-leaved plant into the
mucobuccal fold and chewing it for several hours, with subsequent release of
psychoactive agents. Qat chewing is often accompanied by smoking tobacco. The
reported prevalence of qat chewing in Europe and North America is on the increase
with global migration. Oral diseases reportedly associated with qat chewing
include periodontitis, oral leukoplakia and oral cancer. However, precise data on
the association of qat use with the development of oral cancer are sparse. The
aim of this review is to 1) Educate health clinicians about qat usage and related
oral/systemic health issues; and 2) Review the current literature regarding qat
use and its association with oral disease but more specifically review its link
with oral leukoplakia and oral squamous cell carcinoma (OSCC). To do this we
searched the literature (PubMed, Science Direct and Scopus) to identify all
relevant articles published over the last 20 years using a combination of terms
‘qat’, ‘khat’, ‘kat’, ‘cathinone’ and ‘cathaedulis’.

Urologic complications of HIV and AIDS. Heyns CF, Groeneveld AE, Sigarroa NB. Nat Clin Pract Urol. 2009 Jan;6(1):32-43.

In recent years the nature of HIV infection has been dramatically transformed
from an invariably fatal disease to a chronic disorder with a relatively benign
course. Disease progression from HIV to AIDS and HIV-related mortality can be
reduced effectively by several years of treatment with highly active
antiretroviral therapy (HAART). For patients who do not have access to HAART, HIV
infection continues to be a lethal disorder characterized by opportunistic
infection with uncommon organisms (e.g. mycobacteria, fungi, parasites and
viruses), as well as lethal malignancies such as Kaposi sarcoma, non-Hodgkin
lymphoma and squamous cell carcinoma of the penis or cervix. In patients
receiving HAART, urologic complications are likely to be caused by adverse
effects of antiretroviral medication (e.g. indinavir urolithiasis) or disorders
associated with aging, such as benign prostatic hyperplasia and prostate cancer.
Prospective clinical trials have shown that adult male circumcision can reduce
the rate of female to male HIV transmission by more than 50%; however, the
development of preventive or curative modalities with 100% efficacy remains

Early Barrett’s carcinoma of the esophagus. Hölscher AH, Vallböhmer D, Bollschweiler E. Ann Thorac Cardiovasc Surg. 2008 Dec;14(6):347-54.

Super competition as a possible mechanism to pioneer precancerous fields. Rhiner C, Moreno E. Carcinogenesis. 2009 May;30(5):723-8. Epub 2009 Jan 6.

Cancer is the result of sequential genetic changes over time that transform a
cell into a malignant and ultimately invasive entity. The insight that cancerous
cells arise from a series of mutations in oncogenes and tumor suppressors,
commonly known as multistep carcinogenesis, has been conceptually elaborated and
proven in the last 20 years. Although knowledge about late steps of
cancerogenesis and disease progression has greatly advanced, the initial
molecular events remain largely unknown. Basic research in Drosophila has started
the quest to find early markers that detect initial clonal expansion of
precancerous cells. These efforts were spurred by novel findings demonstrating
that certain mutations transform cells into super-competitors that expand at the
expense of the surrounding epithelial cells without inducing histological
changes. This mechanism, discovered as super competition in the fly, might also
lie at the heart of a clinical observation termed ‘field cancerization’. This
review aims to bring together current understanding from basic research on cell
competition and clinical studies that have analyzed field characteristics to
highlight parallels and possible connections.

Malignant transformation of penile lichen sclerosus: exactly how common is it? Ranjan N, Singh SK. Int J Dermatol. 2008 Dec;47(12):1308-9.

Squamous cell carcinoma of the eyelid and conjunctiva. Mehta M, Fay A.

Dealing with aberrant vessels in radial forearm flaps – report of a case and review of literature. Bhatt V, Green J, Grew N. J Craniomaxillofac Surg. 2009 Mar;37(2):87-90. Epub 2008 Dec 30.

INTRODUCTION: Anomalies of the radial artery are uncommon. A brief tabulated
review of the literature is presented. CASE REPORT: We report a rare anomaly of
the forearm vascular anatomy we encountered when elevating a radial forearm free
flap. This is a previously unreported anatomical variation. The radial artery
divided into medial and lateral branches (accompanied by their respective venae
commitantes) about 1.5 cm below the bifurcation of the brachial artery. The skin
paddle was predominantly supplied by the aberrant medial branch and was raised on
this branch along with its venae commitantes up to the point of division.
CONCLUSION: This case highlights the need for vigilance when raising free flaps
and the techniques employed to avoid compromising both limb and skin paddle

[Role of pemetrexed in the treatment of advanced non-small-cell lung cancer: news from ASCO, 2008] [Article in Italian] de Marinis F, Ricciardi S. Tumori. 2008 Sep-Oct;94(5):suppl 3-13.

[Chemoprevention of esophageal squamous cell carcinoma--clinical trials] [Article in Polish] Szumiło J. Pol Merkur Lekarski. 2008 Sep;25(147):280-3.

Esophageal squamous cell carcinoma is one of the most lethal malignances of
digestive tract. Epidemiological data confirmed influence of the diet especially
Mediterranean one that decreases the risk of cancer. High consumption of fresh
vegetables and fruits, mainly citrus and tea drinking, also has a beneficial
effect on decreasing incidence of the cancer. High intake of various antioxidants
and natural fibers found in the plant diet as well as prolonged administration of
cyclooxygenase-inhibitors, especially aspirin, plays also a protective role.
Results of sparse, prospective, randomized trials on chemoprevention of
esophageal squamous cell carcinoma are not so unequivocal. Supplementation of six
traditional Chinese herbs, retinamide and riboflavin provided the most promising
effects, but intake of multiple vitamins and minerals, including calcium and
decaffeinated green tea, was ineffective. However, the studies were performed on
small populations inhabiting select Chinese provinces known for their high
esophageal cancer incidence. Due to a number of limitations, the collected data
cannot be compared directly to other populations who are exposed to different
environmental factors and with different genetic predispositions.

Contemporary management of oropharyngeal cancer: anatomy and physiology of the oropharynx. Duvvuri U, Myers JN. Curr Probl Surg. 2009 Feb;46(2):119-84.

Risk factors and gene expression in esophageal cancer. Xu XC. Methods Mol Biol. 2009;471:335-60.

Esophageal cancer is a significant worldwide health problem because of its poor
prognosis and high incidence in certain parts of the world. Tobacco smoke and
alcohol consumption are significant risk factors for esophageal squamous cell
carcinoma, whereas frequent gastroesophageal reflux and subsequent inflammatory
reactions play a role in causing the adenocarcinoma. Esophageal carcinogenesis
involves multiple genetic alterations. A large body of knowledge has been
generated regarding molecular alterations associated with esophageal
carcinogenesis. These alterations include aberrant cell cycle control, DNA
repair, cellular enzymes, growth factor receptors, and nuclear receptors. This
chapter reviews the most frequent gene alterations and their correlation with
risk factors as well as the prevention strategies in esophageal cancer.

Basosquamous carcinoma. Garcia C, Poletti E, Crowson AN. J Am Acad Dermatol. 2009 Jan;60(1):137-43.

BACKGROUND: Basosquamous carcinoma is considered an aggressive type of basal cell
carcinoma (BCC) with an increased risk of recurrence and metastases. This concept
has been perpetuated in the literature in spite of confusing terminology, limited
scientific data, and the contradictory surgical experiences of some observers.
METHODS: This is a narrative review based on a MEDLINE search of articles in
English and a manual search of popular dermatology textbooks to define
basosquamous carcinoma, its incidence, clinical behavior, and treatment of
choice. RESULTS: There are no specific clinical features to distinguish
basosquamous carcinoma from other BCC types and the diagnosis is made only after
biopsy. There are several histologic definitions of basosquamous carcinoma
ranging from a characteristic combination of BCC and squamous cell carcinoma with
or without a transition zone, to any BCC with evidence of keratinization. The
authors confine the use of the term to an infiltrative growth BCC with areas of
keratinization and/or intercellular bridge formation in the setting of a
prototypic proliferative stromal reaction. The term “metatypical basal cell
carcinoma” is considered a synonym but its use is discouraged for the reasons
outlined. The reported incidence of basosquamous carcinoma ranges from 1.2% to
2.7%. Published recurrence rates are 12% to 51% for surgical excision and 4% for
Mohs micrographic surgery. The incidence of metastasis is at least 5%. The
aggressive biological behavior and clinical course distinguish basosquamous
carcinoma from other forms of BCC. LIMITATIONS: This study is a literature
review, contains a limited number of patients, and is mostly retrospective
studies. CONCLUSION: The terminology surrounding basosquamous carcinoma is
confusing and there is a need for more uniform language. Based on our review and
personal experience, we propose a more precise and specific definition. Data
regarding the incidence, recurrence, and metastasis rates of basosquamous
carcinoma are based mostly on retrospective series with a limited number of
cases. We conclude that although the incidence of basosquamous carcinoma is
unknown, there is a literature precedent suggesting more aggressive biological
behavior. We believe that complete surgical excision is the preferred approach,
and that basosquamous carcinoma is an ideal candidate lesion for Mohs
micrographic surgery.

Lichen sclerosis et atrophicus masquerading as tonsillar squamous cell carcinoma. Ajayi O, Stephens JC, Karim S, Daly N. J Laryngol Otol. 2009 Feb;123(2):e10. Epub 2008 Dec 23.

OBJECTIVE: We report a case of a 70-year-old man of Asian origin with lichen
sclerosus et atrophicus affecting the tonsil, which presented as a painful,
enlarging, exophytic lesion mimicking squamous cell carcinoma. METHOD: We present
a case report and a review of the world literature regarding lichen sclerosus et
atrophicus. RESULTS: Lichen sclerosus is a chronic, benign, inflammatory
dermatosis of the skin and mucous membranes which mostly affects the female
genitalia, presenting as white plaques with epidermal atrophy. The cause is
unknown, although a number of aetiologies have been proposed. The prevalence is
unknown. Women have been reported to be affected six to 10 times more than men,
and the condition has no known racial preference. CONCLUSION: Our patient
illustrates a rare case of the condition lichen sclerosus et atrophicus; to our
knowledge, this case represents the first report of tonsillar involvement of the
condition. The case presented a diagnostic challenge.

[Role of human papillomavirus in carcinogenesis of head and neck cancer] [Article in Czech] Nováková V, Laco J. Klin Onkol. 2008;21(4):141-8.

Head and neck squamous cell carcinomas develop predominantly in individuals over
40 years of age and more frequently in males. The strongest risk factors for this
disease are long-term abuse of tobacco products and alcohol. Recently, several
reports of increasing incidence of head and neck cancer in atypical population
groups of females or young adults have been published, often in patients with no
history of smoking or alcohol abuse. It seems highly probable that at least in a
part of these cases, human papillomavirus (HPV) played an important etiological
role. Some of the HPV types were proved to cause certain anogenital carcinomas,
particularly cervical carcinoma. It seems that in some cases these very HPV types
are also involved in head and neck carcinogenesis. Published data on the
prevalence of HPV infection in head and neck squamous cell carcinomas vary in
different studies. However, it is generally understood that the infection is more
commonly present in carcinomas of the oropharynx and palatine tonsils than in
oral cavity carcinomas. The hypothesis of sexual transmission of oncogenic HPV
types has yet to be confirmed. It is not clear whether current HPV vaccines could
possibly decrease the incidence of head and neck squamous carcinomas.

[Current treatment strategies for patients with cancers of the head and neck] [Article in Czech] Mechl Z, Smilek P, Cervená R. Klin Onkol. 2008;21(2):45-52.

Head and neck squamous cell cancer (HNSCC) management is evolving rapidly.
Approaches under exploration include induction chemotherapy, altered
fractionation radiation with chemotherapy, intensity modulated radiation therapy
(IMRT) and the use of biologically targeted drugs to enhance radiation. The goal
of the new methods is improving the effectivity without increasing the toxicity.
This article will focus maily on locally advanced HNSCC, which frequently remains
a clinical challenge, review state-of-the-art therapy and introduce promising
novel terapies. For the future the incorporation of new agents, the use of novel
biomarkers to accurately assess and individualize therapy, and expanded
supportive care approaches will play an increasingly important role.

Gingival squamous cell carcinoma in adolescence. Woo VL, Kelsch RD, Su L, Kim T, Zegarelli DJ. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009 Jan;107(1):92-9.

Squamous cell carcinoma (SCC) is a rare finding in the adolescent population,
with most cases occurring in patients with underlying heritable diseases or
immunologic conditions. Moreover, the incidence of oral SCC in this age group is
extremely low. While isolated cases of adolescent oral SCC have been documented,
most have been primary tongue or lip lesions. We report 4 cases of gingival SCC
occurring in otherwise healthy adolescent patients. The preliminary clinical
impressions ranged from factitial injury to inflammatory tissue. Microscopic
similarities, including overlap with pseudoepitheliomatous hyperplasia and
keratoacanthoma, were seen. Review of the literature indicates that adolescent
gingival SCC is extremely rare and a challenging diagnosis for the clinician and
pathologist alike. Diagnostic pitfalls, possible etiologic factors, and the
prognostic outlook of this condition are discussed.

Head and neck cancer in the elderly: an overview on the treatment modalities. Syrigos KN, Karachalios D, Karapanagiotou EM, Nutting CM, Manolopoulos L, Harrington KJ. Cancer Treat Rev. 2009 May;35(3):237-45. Epub 2008 Dec 18.

The percentage of elderly people with head and neck cancers (HNC) is rising due
to increasing average lifespan. As with younger patients, elderly patients
require a multidisciplinary approach in order to optimise treatment results. The
biological, not the chronological, age should be defined individually based on
co-morbidities and performance status. A comprehensive geriatric assessment
represents the first and essential step for selecting further treatment options.
Major improvements have been accomplished in surgical techniques and radiotherapy
delivery. Several chemotherapeutic agents and targeted therapies with different
toxicity profile are also available. However, the randomised studies that defined
the nature of these improvements included only a small proportion of patients
older than 65 years. In deciding which treatment strategy would be suitable for
an individual elderly patient, we review the literature regarding surgery,
radiotherapy, and chemotherapy or their various combinations.

[Galectins in squamous cell carcinomas of the head and neck cancers] [Article in Czech] Cada Z, Plzák J, Chovanec M, Dvoránková B, Lacina L, Szabó P, Smetana K Jr, Betka J. Cas Lek Cesk. 2008;147(11):559-63.

Cancers of head and neck represents about 5% of all tumors. 80 to 90% of these
tumors are constituted of squamous cell carcinomas. Despite a rapid progress in
diagnostics and therapy the overall 5-year survival of this type of cancer is
among the lowest of the major cancer types. This unfavourable situation needs the
extensive research to found new markers to better characterize biological
behavior of tumors as a rational background for more sophisticated therapeutic
modalities. Among the most promising markers are endogenous lectins called
galectins and their ligands. Especially galectin-1, -3 and -7 play a key role in
pathology of squamous cell carcinomas.

Glycemic index, glycemic load, and risk of digestive tract neoplasms: a systematic review and meta-analysis. Mulholland HG, Murray LJ, Cardwell CR, Cantwell MM. Am J Clin Nutr. 2009 Feb;89(2):568-76. Epub 2008 Dec 16.

BACKGROUND: Habitual consumption of diets with a high glycemic index (GI) and a
high glycemic load (GL) may influence cancer risk via hyperinsulinemia and the
insulin-like growth factor axis. OBJECTIVE: The objective was to conduct a
systematic review to assess the association between GI, GL, and risk of digestive
tract cancers. DESIGN: Medline and Embase were searched for relevant publications
from inception to July 2008. When possible, adjusted results from a comparison of
cancer risk of the highest compared with the lowest category of GI and GL intake
were combined by using random-effects meta-analyses. RESULTS: Cohort and
case-control studies that examined the risk between GI or GL intake and
colorectal cancer (n = 12) and adenomas (n = 2), pancreatic cancer (n = 6),
gastric cancer (n = 2), and squamous-cell esophageal carcinoma (n = 1) were
retrieved. Most case-control studies observed positive associations between GI
and GL intake and these cancers. However, pooled cohort study results showed no
associations between colorectal cancer risk and GI intake [relative risk (RR):
1.04; 95% CI: 0.92, 1.12; n = 7 studies] or GL intake (RR: 1.06; 95% CI: 0.95,
1.17; n = 8 studies). Furthermore, no significant associations were observed in
meta-analyses of cohort study results of colorectal cancer subsites and GI and GL
intake. Similarly, no significant associations emerged between pancreatic cancer
risk and GI intake (RR: 0.99; 95% CI: 0.83, 1.19; n = 5 studies) or GL intake
(RR: 1.01; 95% CI: 0.86, 1.19; n = 6 studies) in combined cohort studies.
CONCLUSIONS: The findings from our meta-analyses indicate that GI and GL intakes
are not associated with risk of colorectal or pancreatic cancers. There were
insufficient data available regarding other digestive tract cancers to make any
conclusions about GI or GL intake and risk.

Critical role of IkappaB kinase alpha in embryonic skin development and skin carcinogenesis. Zhu F, Park E, Liu B, Xia X, Fischer SM, Hu Y. Histol Histopathol. 2009 Feb;24(2):265-71.

IkappaB kinase alpha (IKKalpha), IKKbeta, and IKKgamma/NEMO form the IKK complex,
which is essential for NF-kappaB activation. However, genetic studies have shown
that the role of IKKalpha is distinct from that of IKKbeta or IKKgamma in the
development of the mouse embryonic skin. Loss of IKKalpha has been shown to cause
epidermal hyperplasia, prevent keratinocyte terminal differentiation, and impair
the formation of the skin, resulting in the deaths of IKKalpha-deficient
(Ikkalpha-/-) mice soon after birth. Recent experimental data from several
laboratories have revealed that IKKalpha functions as a tumor suppressor in human
squamous cell carcinomas (SCCs) of skin, lungs, and head and neck. Chemical
carcinogenesis studies using mice have shown that reduction in IKKalpha
expression increases the number and size of Ras-initiated skin tumors and
promotes their progression, indicating that reduced IKKalpha expression provides
a selective growth advantage that cooperates with Ras activity to promote skin
carcinogenesis. In this review, we will summarize these findings from our and
other studies on the role that IKKalpha plays in development of the mouse
embryonic skin and skin carcinogenesis.

Lacrimal fossa lesions: pictorial review of CT and MRI features. Vaidhyanath R, Kirke R, Brown L, Sampath R. Orbit. 2008;27(6):410-8.

A wide range of disease process involve the lacrimal gland/fossa. In this
pictorial review, we use histology-proven cases to illustrate conditions that
affect the lacrimal gland/fossa. CT and MRI features of neoplastic, inflammatory,
infiltrative, and developmental conditions are discussed.

Radiological-pathological correlation in intratumoural tissue components of solid lung tumours. [Article in English, Italian] Quaia E, Baratella E, Pizzolato R, Bussani R, Cova MA. Radiol Med. 2009 Mar;114(2):173-89. Epub 2008 Dec 11.

The aim of this paper is to describe the intratumoural tissue components of solid
lung tumours evidenced by macroscopic and/or microscopic examination of the
autopsy or surgical specimen and visible on computed tomography (CT) without and
with contrast material administration. Seven intratumoural tissue components can
be identified both at CT and at pathology: (1) solid component, (2) haemorrhagic
component, (3) coagulation necrosis, (4) liquefaction necrosis, (5) parenchymal
consolidation, (6) diffuse peripheral component and (7) fibrotic component.
Necrotic and haemorrhagic components are typically observed in malignant lesions,
whereas solid and fibrotic components may be seen both in solid lung malignancies
and in benign lesions.

Systematic review of human papillomavirus prevalence in invasive penile cancer. Backes DM, Kurman RJ, Pimenta JM, Smith JS. Cancer Causes Control. 2009 May;20(4):449-57. Epub 2008 Dec 11.

OBJECTIVE: Type-specific prevalence data of human papillomavirus (HPV) DNA in
penile carcinoma are needed to determine the potential impact of HPV prophylactic
vaccines, assuming demonstrated efficacy in men. METHODS: A review was conducted
using search terms including HPV and penile cancer. Studies using polymerase
chain reaction (PCR) assays for HPV DNA detection in invasive penile carcinoma
were included. RESULTS: A total of 1,266 squamous cell carcinoma (SCC) cases
contributed data from 30 studies. The number of SCC was similar in Europe
(28.2%), North America (27.6%), South America (23.9%) and Asia (20.4%). All SCC
were histologically confirmed with biopsies for DNA detection. Most commonly used
PCR primers were type-specific (35.2%), and combination PCR (18.2%). HPV
prevalence was 47.9%, ranging from 22.4% in verrucous SCC to 66.3% for the
basaloid/warty subtypes. HPV16 (30.8%), HPV6 (6.7%) and HPV18 (6.6%) were the
most prevalent types. HPV16 and/or HPV 18 prevalence was 36.7%. CONCLUSIONS: HPV
DNA was detected in half of SCC, with HPV16 being the most common type. If proven
efficacious in men, prophylactic vaccines targeting carcinogenic types HPV16 and
18 could potentially reduce approximately one-third of incident SCC.

Combined and sequential treatment of oral and maxillofacial malignancies: an evolving concept and clinical protocol. Zheng JW, Qiu WL, Zhang ZY. Chin Med J (Engl). 2008 Oct 5;121(19):1945-52.

OBJECTIVE: To introduce the concept and rational regimens and present the latest
development of combined treatment of oral and maxillofacial malignancies. Data
sources The related published literature was searched through the CNKI database
and MEDLINE using the terms of oral cancer, oral and maxillofacial malignancies,
combined and sequential therapy, multidisciplinary approach. Study selection The
available related literature was read and evaluated. Studies that met the
inclusion criteria were selected. RESULTS: The results show that oral and
maxillofacial malignancies diagnosed at an early stages (stages I and II) can be
well treated with surgery alone and/or radiotherapy with optimal outcome, but
advanced or recurrent diseases should be treated with rational combined and
sequential treatment modalities. The use of concomitant chemoradiotherapy,
taxane-containing, three-drug induction regimens and Cetuximab in combination
with chemotherapy or radiotherapy demonstrated favorable results in previously
untreated patients with head and neck squamous cell carcinoma. CONCLUSIONS: The
concept of combined and sequential treatment of advanced oral and maxillofacial
malignancies should be widely accepted, and the rational regimen for individual
and each type of entity should be determined based on the anatomical site and the
patient’s performance status.

Non-endometrioid adenocarcinoma of the uterine corpus: a review of selected histological subtypes. Mendivil A, Schuler KM, Gehrig PA. Cancer Control. 2009 Jan;16(1):46-52.

BACKGROUND: Understanding the etiology, presentation, evaluation, and management
of selected non-endometrioid endometrial adenocarcinomas of the uterine corpus is
needed to define optimal treatment regimens. METHODS: The pathology and treatment
of selected non-endometrioid endometrial adenocarcinomas of the uterus are
reviewed and summarized. RESULTS: The most common non-endometrioid histology is
papillary serous (10%), followed by clear cell (2% to 4%), mucinous (0.6% to 5%),
and squamous cell (0.1% to 0.5%). Some non-endometrioid endometrial carcinomas
behave more aggressively than the endometrioid cancers such that even women with
clinical stage I disease often have extrauterine metastasis at the time of
surgical evaluation. Therefore, when technically and medically feasible,
comprehensive surgical staging is helpful for women with non-endometrioid
endometrial cancer histology. Comprehensive surgical staging includes
hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic
lymphadenectomy, and cytological evaluation of the abdominal cavity. While whole
abdominal radiotherapy has a limited role in early-stage uterine papillary serous
carcinoma (UPSC) and clear cell carcinoma (CC), there may be a role for
postoperative chemotherapy and volume-directed radiotherapy in both early-stage
UPSC and CC. In the setting of optimally debulked advanced-stage disease, a
combination of radiation and chemotherapy may be indicated. In the setting of
recurrent disease or in women with residual disease after surgery, a
platinum-based regimen or enrollment in a clinical trial is recommended.
CONCLUSIONS: UPSC and CC are managed similarly since sufficient data to separate
treatment recommendations are lacking. Because both histologies are associated
with a high rate of recurrence, adjuvant therapy is recommended even in women
with early-stage disease. The remaining cell types should be treated similar to
endometrioid or other low-grade histologies.

Current use and future perspectives of diagnostic and therapeutic lasers in Oral Medicine. Maia AM, Barkokebas A, Pires AP, Barros LF, Carvalho AA, Leão JC. Minerva Stomatol. 2008 Oct;57(10):511-7.

Several diagnostic and therapeutic methods are based on the optical properties of
lasers. In therapeutic applications, laser light is absorbed in a specific
manner, whereas light is scattered, reflected, or transmitted from different
structures. Improvements in laser technology allow new procedures and broaden the
scope of applications for both diagnosis and therapy. The focus of laser
application in Oral Medicine diagnosis should be early detection of oral squamous
cell carcinoma. Novel modalities for the detection of oral malignancy are
urgently needed, while others must be continuously improved. Optical coherence
tomography and laser-induced fluorescence spectroscopy are currently being
studied. In addition to diagnosis of non-malignant lesions, laser therapy has
been used based upon the biological reactions and molecular wound healing
mechanisms as an alternative for the treatment of a variety of oral soft tissue
lesions. The aim of the present article is to review current knowledge and future
perspectives of lasers in Oral Medicine.

The Leser-Trélat sign is associated with nasopharyngeal carcinoma: case report and review of cases reported in China. Li M, Yang LJ, Zhu XH, Zhang YS, Sun H, Jiang PD, Zhang RR, Tang W, Cai Y. Clin Exp Dermatol. 2009 Jan;34(1):52-4.

The sign of Leser-Trélat (LT) is defined as the sudden eruption of multiple
seborrhoeic keratoses (SKs), or increase in the number and size of existing SKs,
associated with an underlying malignancy. A 75-year-old man was admitted to our
hospital with dyspnoea and multiple verrucous papules that had been developing
gradually over the previous 30 years. During the 3 months before presentation,
the number of SKs on his chest and back had increased rapidly. A diagnosis of
nasopharyngeal carcinoma was made based on results of computed tomography,
endoscopy and biopsy examinations. The patient is receiving radiotherapy at
present. To our knowledge, this is the first case of the Leser-Trélat sign
associated with nasopharyngeal carcinoma.

Ciliated hepatic foregut cyst: an increasingly diagnosed condition. Sharma S, Dean AG, Corn A, Kohli V, Wright HI, Sebastian A, Jabbour N. Hepatobiliary Pancreat Dis Int. 2008 Dec;7(6):581-9.

BACKGROUND: Ciliated foregut cysts of the liver are rare, with only 96 cases
diagnosed since the first description in 1857. They are being increasingly
diagnosed recently; the majority of the cases have been reported in the last 15
years. Although they bear a close resemblance to the simple cyst of the liver
which has essentially a benign course, ciliated hepatic foregut cysts (CHFCs) can
progress to malignancy with devastating consequences. It is imperative that this
group of conditions be diagnosed and treated adequately. DATA SOURCES: This
review includes discussion of the data from all the 96 reported cases from
English and non-English literature. Analysis of the incidence rates,
embryogenesis, growth, clinical features, risk of malignancy and the prognosis
are highlighted systematically. The roles of various diagnostic modalities
including ultrasound, CT, MRI, fine needle aspiration cytology (FNAC),
immunohistochemistry and surgery are further discussed. RESULTS: The mean age of
patients with CHFC was 48+/-12 years. The male/female ratio was 1.1:1. The
majority of patients with CHFC (62%) were asymptomatic, and the common mode of
presentation was right upper abdominal pain. The cysts occurred in the left lobe
in 51 patients, with sole location in segment IV in 44, and in the right lobe in
26. The average size of the cysts was 3.6+/-2.12 cm. The majority of the cysts
were unilocular, and only 7 cases were multilocular. Cyst contents were described
as viscous or mucinous in 73 patients, whereas bilious fluid was noted in 3.
Large cysts having squamous carcinoma were cited in 3 patients, and 2 had
extensive squamous metaplasia without malignancy. Others had benign
histopathology. CONCLUSIONS: Clinicians have become increasingly aware of CHFC.
Imaging alone is not diagnostic per se, but when considered in the context of the
global picture does provide important clues to the diagnosis. FNAC is diagnostic
by the presence of the ciliated columnar aspirate but lacks sensitivity.
Infantile presentation is usually accompanied by biliary communication and
mandates a different surgical approach. The demonstration of malignant
transformation in 3 cases and its fatal course emphasizes the need for surgical
resection in all cases once the diagnosis is made.

[HPV in non-gynecological tumors] [Article in German] Petersen I, Klein F. Pathologe. 2008 Nov;29 Suppl 2:118-22.

Human papilloma viruses (HPVs) are the main tumor viruses in humans and have been
identified in gynecological malignancies, especially carcinomas of the uterine
cervix and their precursor lesions. In addition, they are frequently observed in
other anogenital tumors such as vulva/vagina, anal and penis carcinoma.
Furthermore, the potential association with head and neck cancer, in particular
tonsillar carcinoma, is now well documented. However, there are controversial
reports on the detection of HPV in various other tumors; these are summarized in
the present report. Data revealed that apart from the heart and the kidney, the
virus has been found in all other organs that have been analyzed so far, i.e.,
prostate, urinary bladder, oral cavity, larynx, esophagus, stomach, colon, liver,
vagina/vulva, endometrium, ovary, breast, penis, anus, skin, and lung. Some of
the detection rates are remarkable, e.g., colon cancer up to 97%, lung cancer
80%, and breast cancer 74%. They point to geographical differences in the
incidence of HPV in different populations, but also highlight the need for
validation of the results. HPV is nevertheless an important biomarker in
molecular tumor diagnostics. Firstly, it is useful for the differentiation of a
secondary squamous cell carcinoma from a metastasis. Secondly, HPV-positive
carcinomas not only have a distinct etiology but also a particular morphological
phenotype. Overall, they are characterized by different tumor biology, such as,
for example, increased sensitivity to radiotherapy.

Human papillomavirus vaccine and cervical cancer prevention. Oaknin A, Barretina MP. Clin Transl Oncol. 2008 Dec;10(12):804-11.

Cervical cancer is one of the most common types of cancer in women worldwide,
with the highest rates observed in underdeveloped countries. In the last decades,
its incidence has decreased after the implementation of screening programs,
mainly in developed countries. Infection with high-risk oncogenic HPV is
associated with precancerous lesions and cervical cancer. Advances in the
understanding of the role of HPV in the etiology of high-grade cervical lesions
(CIN 2/3) and cervical cancer have led to the development, evaluation and
recommendation of two prophylactic HPV vaccines. This review article provides a
summary of the studies related with their development and efficacy.

Cutaneous manifestation of myiasis in malignant wounds of the head and neck. Sesterhenn AM, Pfützner W, Braulke DM, Wiegand S, Werner JA, Taubert A. Eur J Dermatol. 2009 Jan-Feb;19(1):64-8. Epub 2008 Dec 5.

Parasitic infestation of the body by dipterous larvae belongs to the most
undesirable events in cancer patients with malignant cutaneous wounds. Human
myiasis is rare in developed countries of the northern hemisphere but occurs more
often in tropical and subtropical regions. Advanced age, poor hygiene, bad
housing conditions, vascular disease and diabetes seem to be predisposing factors
for myiasis. We report a case of myiasis in an extensive skin metastasis
resulting from a primary cancer located in the oropharynx. In the literature
there are few reports on myiasis in malignant wounds resulting from malignancies
of the head and neck area. Furthermore, guidelines or recommendations for
standard treatment options are not available. Therefore a review of the
literature with a focus on therapeutical aspects was performed. Conclusion: At
present the treatment of choice for human myiasis in malignant cutaneous wounds
comprises mechanical removal of maggots and, if possible, surgical excision of
the lesion. Most important in the treatment of malignant wounds is a thorough
rinsing procedure with antiseptic- and/or antibiotic solutions before consistent
dressing changes on a daily basis. Here, a complete covering of the wound is
indispensable, especially in the summer months.

Utility of methylation markers in cervical cancer early detection: appraisal of the state-of-the-science. Wentzensen N, Sherman ME, Schiffman M, Wang SS. Gynecol Oncol. 2009 Feb;112(2):293-9. Epub 2008 Dec 2.

OBJECTIVE: We wanted to identify the most promising methylation marker candidates
for cervical cancer early detection. METHODS: A systematic literature review was
performed in Medline and weighted average frequencies for methylated genes
stratified by tissue source and methods used were computed. RESULTS: 51 studies
were identified analyzing 68 different genes for methylation in 4376 specimens
across all stages of cervical carcinogenesis. 15 genes, DAPK1, RASSF1, CDH1,
have been analyzed in 5 or more studies. The published data on these genes is
highly heterogeneous; 7 genes (CDH1, FHIT, TERT, CDH13, MGMT, TIMP3, and HIC1)
had a reported range of methylation frequencies in cervical cancers of greater
than 60% between studies. Stratification by analysis method did not resolve the
heterogeneity. Three markers, DAPK1, CADM1, and RARB, showed elevated methylation
in cervical cancers consistently across studies. CONCLUSIONS: There is currently
no methylation marker that can be readily translated for use in cervical cancer
screening or triage settings. Large, well-conducted methylation profiling studies
of cervical carcinogenesis could yield new candidates that are more specific for
HPV-related carcinogenesis. New candidate markers need to be thoroughly validated
in highly standardized assays.

Focus on TILs: prognostic significance of tumor infiltrating lymphocytes in head and neck cancers. Uppaluri R, Dunn GP, Lewis JS Jr. Cancer Immun. 2008 Dec 4;8:16.

The expanding and established literature that correlates tumor infiltrating
lymphocytes (TILs) with outcomes of patients with solid tumors has contributed
greatly to the appreciation of the interaction between the host immune system
with neoplastic growth. This analysis has been limited to specific tumors, such
as melanoma and ovarian cancer, and our understanding of TILs in relation to many
other malignancies has yet to be explored. We review one less well studied
malignancy, head and neck squamous cell carcinoma (HNSCC), and the initial
attempts to examine the impact of TILs on outcomes of these patients. To provide
a context for the discussion of TILs and HNSCC, we first review the epidemiology,
relevant head and neck anatomy, immune responses and discuss the historical data
regarding the unique immunobiology of these tumors. Finally, with this
perspective, we describe our current understanding of tumor infiltrating
lymphocyte data for head and neck cancers.

Infection: is it a cause of bladder cancer? Abol-Enein H. Scand J Urol Nephrol Suppl. 2008 Sep;(218):79-84.

This article reviews the literature regarding the possible correlation between
infection and occurrence of bladder cancer. The PubMed literature database was
searched from inception to January 2008. Keywords of bladder, cancer, parasitic,
bacterial, viral and infection, were used. Forty studies were included in the
review. Several investigators support the idea that schistosomiasis is
aetiologically related to the development of bladder cancer in individuals
infected with Schistosoma haematobium. Approximately 70% of those with chronic
schistosomiasis who have bladder cancer develop squamous cell rather than
transitional cell carcinoma. Several investigators suggest that bacteria may play
a role in inducing bladder cancer. Clinically, researchers have linked the
development of infection, urinary stones and indwelling catheters with bladder
cancer. Nevertheless, to date, no prospective study has examined the association
between urinary tract infection and bladder cancer risk. The possibility that
infection by human papilloma virus (HPV) is a risk factor contributing to bladder
cancer has been investigated but no definite conclusions have been drawn. Thus,
the debate remains open as to whether there is any direct link between chronic
HPV infection and bladder cancer. Only 15 cases of vesical carcinoma have been
reported, to date, in the setting of human immunodeficiency virus (HIV). The rare
occurrence of bladder cancer during HIV infection and the lack of correlation
with the laboratory markers of HIV disease progression may suggest a trivial
association between two unrelated disorders. BK virus is oncogenic in newborn
hamsters and can transfer to mammalian cells in vitro, but there is little
consistent evidence of a link with human bladder cancer. Studies showed no
correlation between herpes simplex virus (HSV) and bladder cancer, but bladder
cancer becomes infected with HSV much more easily than non-neoplastic urothelium.
In conclusion, with the exception of chronic infection with S. haematobium, the
association between the occurrence of bladder cancer and chronic bacterial or
viral infections could not be confirmed. Prospective studies with large numbers
of patients and controls are required to confirm this issue.

Squamous-cell carcinoma in mature cystic teratoma of the ovary: systematic review and analysis of published data. Hackethal A, Brueggmann D, Bohlmann MK, Franke FE, Tinneberg HR, Münstedt K. Lancet Oncol. 2008 Dec;9(12):1173-80.

Up to a quarter of ovarian masses originate from germ cells, and many of these
are mature cystic teratomas. The secondary development of malignancy is a rare
but well-known phenomenon in patients with ovarian teratomas. Squamous-cell
carcinoma accounts for 80% of secondary malignant transformations of ovarian
teratomas. We aimed to do an up-to-date systematic review of this rare malignant
transformation. 64 suitable studies provided information on 277 patients.
Squamous-cell carcinoma in mature cystic teratoma was mainly found in women aged
more than 50 years, with high concentrations of squamous-cell-carcinoma antigen
and cancer antigen CA125, and with ovarian tumours more than 100 mm in size.
Patients with FIGO stage Ia tumours had better survival than those with more
advanced disease. Complete resection together with hysterectomy, bilateral
salpingo-oophorectomy and lymphadenectomy for patients with advanced disease,
followed by adjuvant chemotherapy with an alkylating drug was associated with
higher survival, radiotherapy was not. We make proposals for investigation and
treatment of this rare disorder.

Molecular target approaches in head and neck cancer: epidermal growth factor receptor and beyond. Harari PM, Wheeler DL, Grandis JR. Semin Radiat Oncol. 2009 Jan;19(1):63-8.

Approximately 50,000 new cases of head and neck squamous cell carcinoma (HNSCC)
will be diagnosed in the United States in 2009. Although the gradual decline in
smoking rates in the United States is a highly favorable trend, the future global
HNSCC incidence will likely reflect the increased marketing and penetration of
tobacco products across several of our most populous countries. Although modern
surgery, radiation, and conventional chemotherapy strategies for HNSCC continue
to provide gradual improvement in outcome, the first molecular targeting approach
to show a survival advantage for HNSCC patients has recently emerged in the
context of epidermal growth factor receptor biology. The scientific background
and current challenges accompanying this recent advance are described in this
article as are several additional promising molecular targets for HNSCC. There is
cautious anticipation that the logical advancement of molecular targeting agents
in conjunction with radiation may afford increased cure rates and diminished
normal tissue toxicity profiles for HNSCC patients over the years to come.

Integrating biologically targeted therapy in head and neck squamous cell carcinomas. Le QT, Raben D. Semin Radiat Oncol. 2009 Jan;19(1):53-62.

The integration of targeted therapies such as cetuximab to radiation therapy has
revolutionized the management of head and neck cancers in the last decade.
However, the use of targeted therapies raised several clinically relevant
questions that have yet to be answered. These questions include the optimal
patient and tumor profile for biologically targeted therapy, the optimal
radiation fractionation to use with targeted therapies, how to integrate them
into standard or new chemoradiation regimens, their schedule and duration of
administration, their toxicity, and which direction to consider for novel
targeted treatment. In this review, we highlight several of these important
issues, discuss the clinical trials that are designed to address these issues,
and introduce some novel targeted therapies that may contribute to the
improvement of the therapeutic ratio for head and neck cancer therapy.

Balancing risk and reward in target delineation for highly conformal radiotherapy in head and neck cancer. Eisbruch A, Gregoire V. Semin Radiat Oncol. 2009 Jan;19(1):43-52.

The therapeutic index of highly conformal radiotherapy (RT) depends on adequate
selection and delineation of the gross tumor volumes, the clinical target
volumes, and the tissues and organs whose sparing is likely to gain clinical
benefit. Decisions about target and tissue selection and delineation affect the
balance of reward and the risk of highly conformal RT. Some of these issues
relating to head and neck cancer, including target delineation after tumor
shrinkage by induction chemotherapy or at midradiotherapy, are discussed in this

Dysphagia in head and neck cancer patients treated with radiation: assessment, sequelae, and rehabilitation. Murphy BA, Gilbert J. Semin Radiat Oncol. 2009 Jan;19(1):35-42.

Dysphagia is commonly seen in patients undergoing radiation-based therapy for
locally advanced squamous carcinoma of the head and neck. Within 4 to 5 weeks of
starting therapy, patients develop mucositis, radiation dermatitis, and edema of
the soft tissues. Resulting pain, copious mucous production, xerostomia, and
tissue swelling contribute to acute dysphagia. As the acute effects resolve, late
effects including fibrosis, lymphedema, and damage to neural structures become
manifest. Both acute and late effects result in adverse sequelae including
aspiration, feeding tube dependence, and nutritional deficiencies. Early referral
for evaluation by speech-language pathologists is critical to (1) ensure adequate
assessment of swallow function, (2) determine whether further testing is needed
to diagnose or treat the swallowing disorder, (3) generate a treatment plan that
includes patient education and swallow therapy, (4) work with dieticians to
ensure adequate and safe nutrition, and (5) identify patients with clinically
significant aspiration.

Strategies for managing radiation-induced mucositis in head and neck cancer. Rosenthal DI, Trotti A. Semin Radiat Oncol. 2009 Jan;19(1):29-34.

Radiation-induced mucositis (RIM) is a common toxicity for head and neck cancer
(HNC) patients. The frequency has increased because of the use of more intensive
altered radiation fractionation and concurrent chemotherapy regimens. The extent
of the injury is directly related to the mucosal volume irradiated, anatomic
subsite exposed, treatment intensity, and individual patient predisposition. The
consequences of mucositis include pain, dysphagia including feeding tube
dependency, dehydration, micronutrient deficiencies, weight loss, and potentially
life-threatening aspiration. Currently, there is no Food and Drug
Administration-approved cytoprotective agent that reliably prevents RIM for HNC,
but several are under investigation. Strategies to limit the extent of mucositis
and to manage its symptoms include basic oral care and supportive medications.
Limiting the use of aggressive treatments to truly high-risk cancers and special
attention to radiation therapy planning techniques can also help restrict the
scope of the problem. This review focuses on mucositis recognition, patient
treatment selection, and RIM symptom-management strategies.

Controversies in surgical management of the node-positive neck after chemoradiation. Lango MN, Myers JN, Garden AS. Semin Radiat Oncol. 2009 Jan;19(1):24-8.

The addition of chemotherapy to radiation in the treatment of advanced-staged
head and neck cancer has improved local-regional control and increased complete
clinical and pathologic response rates in the neck. However, for those patients
with residual neck disease on a posttreatment computed tomography (CT) scan,
there remains significant controversy as to how to further assess the neck for
the presence of a viable tumor and when to perform a neck dissection. Recently,
investigators from Australia have assembled level I evidence to support the use
of positron-emission tomography (PET) scanning to assess treatment response and
have shown a very high negative predictive value for patients with a negative PET
at 12 weeks after the completion of therapy. These data support the practice of
observing PET-negative necks and intervening with neck dissection in PET-positive
necks. However, not all investigators, practitioners, and patients are
comfortable with delaying intervention for such a long time interval after
treatment. The authors favor assessment of the neck with a CT scan at 6 weeks
after the completion of chemoradiotherapy and recommend neck dissection for
patients with radiographic residual disease at this time point. One rationale is
that 6 weeks is an optimal window for operative intervention after acute
treatment effects have subsided and before extensive fibrosis and scarring, which
translates to less morbidity for the patient who is treated surgically. Another
rationale is that those who develop regional recurrence can be hard to salvage
surgically, and waiting an additional 6 weeks could allow for the expansion of
resistant clones. The significance of this is unclear, however, because patients
with residual disease are at a higher risk for local and distant as well as
regional failure. Thus, further prospective studies of the role of
postchemoradiotherapy PET scanning and neck dissection are needed.

Organ and function preservation: the role of surgery as the optimal primary modality or as salvage after chemoradiation failure. Scher RL, Esclamado RM. Semin Radiat Oncol. 2009 Jan;19(1):17-23.

The treatment for squamous cell carcinoma (SCC) of the head and neck has advanced
considerably with the use of multimodality therapy including radiation,
chemotherapy, and surgery. Efforts to achieve greater rates of disease control
and survival have been coupled with attempts to reduce acute and chronic toxicity
and preserve function. In the setting of advanced-stage disease, these goals have
typically been achieved via the use of combined radiation and chemotherapy.
Although very effective, (chemo)radiation does not always succeed and may not
offer benefits to the patient equal to those achieved with surgical resection and
reconstruction. This article discusses the issues involved in the selection of
surgical therapy both for the primary treatment of SCC of the head and neck and
for salvage of disease persistence or recurrence after chemoradiation.

Induction chemotherapy: to use or not to use? That is the question. Brizel DM, Vokes EE. Semin Radiat Oncol. 2009 Jan;19(1):11-6.

The intensification of radiation, induction chemotherapy, and concomitant
chemoradiotherapy has been extensively investigated over the past 2 decades for
the nonsurgical management of locally advanced, nonmetastatic squamous cell head
and neck cancer (HNC). Concurrent chemoradiation has emerged as the standard of
care, with the majority of its benefit resulting from improvements in
locoregional disease control. Distant failure has become a more prominent problem
in conjunction with these improvements. Concurrent chemotherapy provides
suboptimal adjuvant treatment for distant disease. Multiagent induction
chemotherapy holds more promise especially with the use of taxane-based regimens.
Induction chemotherapy followed by concurrent chemoradiation (sequential
chemoradiation) is now under investigation. The rationale and evidence supporting
the choice to use or not to use a sequential program are discussed.

Current state-of-the-art for concurrent chemoradiation. Bernier J. Semin Radiat Oncol. 2009 Jan;19(1):3-10.

Throughout the last 2 decades, great strides have been made in managing patients
with locally advanced head and neck squamous cell carcinoma. In many clinical
settings, they translated to significant advances in treatment efficacy and
improvements in disease prognosis. To achieve this, most strategies, ranging from
induction to postoperative treatments, are essentially based on multidisciplinary
approaches. Nowadays, the indication and sequencing of surgery, radiotherapy, and
systemic treatments are carefully weighted in the function of risk levels,
efficacy results, and quality of life. Along this track, the coadministration of
chemotherapy and radiotherapy was shown, as definitive or adjuvant treatment, to
improve the results of conventional radiotherapy alone. However, recent
prospective trials showed that the compliance of patients to aggressive
approaches is more of a concern for poor tolerability and reduced compliance
inevitably impact on treatment dose intensity, leading to the delivery of
suboptimal regimens. Therefore, further efforts to tailor novel,
multidisciplinary approaches based on drug-radiation interactions have been put
forth to optimize treatment outcomes in terms of both disease control and quality
of life. Because therapy is becoming more intense, a careful recording and
reporting of treatment-related morbidity is also a crucial element in estimating
the therapeutic gain from competing strategies.

Modern surgery for esophageal cancer. Dubecz A, Molena D, Peters JH. Gastroenterol Clin North Am. 2008 Dec;37(4):965-87, xi.

Primary treatment of carcinoma of the esophagus and cardia rests on surgical
resection. Although recent advances have shown the suitability of endoscopic
treatment in selected patients with very early cancers, and preliminary studies
have suggested that responders to primary chemoradiation may be equivalent to
resection in selected patients with squamous cell carcinoma, surgical resection
remains the mainstay of therapy, as it has for the past 50 years. Various changes
support highly individualized treatment decisions, in which each patient receives
the treatment with the best chance of eliminating all disease.

Advances in endoscopic imaging of the esophagus. Reddymasu SC, Sharma P. Gastroenterol Clin North Am. 2008 Dec;37(4):763-74, vii.

The introduction of flexible fiberoptic endoscopy in the 1960s was a major step
forward in the diagnosis and management of various esophageal disorders. Since
then, there has been steady progress in the development of novel gastrointestinal
endoscopy techniques. Magnification and high-resolution endoscopy,
chromoendoscopy, narrow-band imaging, autofluorescence imaging, and confocal
laser endomicroscopy are some of the recent advances that have shown promise in
the diagnosis of squamous cell carcinoma, gastroesophageal reflux disease,
Barrett’s esophagus, and adenocarcinoma of the esophagus. The purpose of this
review is to summarize the recent advances in endoscopic imaging of the esophagus
and their practical application for the gastroenterologist.

Survival outcomes of squamous cell carcinoma arising from sinonasal inverted papilloma: report of 6 cases with systematic review and pooled analysis. Tanvetyanon T, Qin D, Padhya T, Kapoor R, McCaffrey J, Trotti A. Am J Otolaryngol. 2009 Jan-Feb;30(1):38-43. Epub 2008 Jul 22.

BACKGROUND: Inverted papilloma (IP) is an uncommon sinonasal tumor. Squamous cell
carcinoma (SCC) is associated with IP in about 7% of cases. To date, there has
been no pooled analysis to formulate a survival outcome associated with this rare
condition. PATIENTS AND METHODS: We retrospectively reviewed the medical records
of patients with IP and SCC treated at our institution during 1999-2007.
Including our series, a systematic review of literature on Medline database and
pooled analysis were performed to establish a survival estimate. RESULTS: Six
patients were identified. Squamous cell carcinoma was metachronous to the initial
diagnosis of IP in 1 case and synchronous in 5 cases. Of 5 patients who had
completed therapy at the time of this report, only 1 remained disease-free at 74
months. The median overall survival in our series was 33 months. Three patients
developed distant metastases in brain, lung, bone, and liver. Literature review
and pooled survival analysis consisting of 76 cases indicated a median overall
survival of 126 months with 3- and 5-year survival rates of 63% and 61%,
respectively. CONCLUSION: Although the survival outcome of SCC arising from IP
seems comparable with sinonasal SCCs, some patients with this disease do have a
highly aggressive disease, including hematogenous distant metastasis. Overall,
about 40% of patients will die of the disease within the first 3 years.

Toll-like receptor modulation in head and neck cancer. Pries R, Wulff S, Wollenberg B. Crit Rev Immunol. 2008;28(3):201-13.

Toll-like receptors (TLRs) are the archetypal pattern recognition receptors that
have emerged as key mediators of immune functions. Activation of TLRs is a first
line of defense of the immune system, leading to the activation and recruitment
of different types of immune cells to sites of infection and malignant cell
growth. Cells of human cancers, such as head and neck squamous cell carcinoma
(HNSCC), are known to develop numerous molecular strategies to escape from
efficient antitumor immune responses. It is supposed that tumor production of
various immunosuppressive mediators contributes to impaired and altered immune
functions in cancer patients. The molecular mechanisms responsible for these
immunomodulatory processes and the biosynthesis of the immunosuppressive HNSCC
microenvironment remain mostly unknown. Recently, different studies have shown
that tumor cells are able to modulate the expression and function of TLR proteins
in different kinds of immune cells. In this review, we present recent progress in
these studies on the modulation of TLR expression and signaling through malignant
head and neck cancer.

Thyroid carcinomas found incidentally in the cervical lymph nodes: do they arise from heterotopic thyroid tissues? Yamamoto T, Tatemoto Y, Hibi Y, Ohno A, Osaki T. J Oral Maxillofac Surg. 2008 Dec;66(12):2566-76.

PURPOSE: Thyroid carcinomas have been found incidentally in the cervical lymph
nodes during surgery for head and neck squamous cell carcinoma (SCC). Such
carcinomas have been considered a metastatic focus for malignant transformation
of heterotopic thyroid tissue. We report on cases of so-called occult thyroid
carcinoma in the cervical lymph nodes, and review the relevant literature.
PATIENTS AND METHODS: We encountered 3 cases of incidental papillary carcinoma in
the cervical lymph nodes of patients with oral SCC, and consequently reviewed 75
previously reported cases. RESULTS: Among 148 patients with oral SCC who had
undergone cervical lymph node dissection, 3 were diagnosed with occult thyroid
carcinoma. Papillary carcinomas were found in 3, 10, and 3 lymph nodes in cases
1, 2, and 3, respectively. Computed tomography showed 2 tumor-like shadows and 1
calcified mass in the thyroid gland in cases 2 and 3, respectively. These shadows
did not enlarge during the 3 to 5 years of observation, and all patients are
alive, without any events related to the neck and thyroid gland. Among the
reviewed cases, approximately two fifths were histopathologically or clinically
free from thyroid carcinoma. Progressive thyroid carcinoma was not detected in
any patient. CONCLUSIONS: We propose the possibility that thyroid carcinoma in
the cervical lymph nodes is not necessarily metastatic, but may occasionally
arise from heterotopic thyroid tissue.

Current progress of immunostains in Mohs micrographic surgery: a review. Thosani MK, Marghoob A, Chen CS. Dermatol Surg. 2008 Dec;34(12):1621-36. Epub 2008 Oct 13.

Mohs micrographic surgery is often considered the treatment of choice for a
variety of skin malignancies. In recent years, the application of immunostaining
techniques has facilitated the successful removal of a number of common and less
common cutaneous malignancies, including basal cell carcinoma, squamous cell
carcinoma, malignant melanoma, dermatofibrosarcoma protuberans, microcystic
adnexal carcinoma, sebaceous carcinoma, atypical fibroxanthoma, extramammary
Paget’s disease, and even sarcomas. Immunostains highlight the tumor cells and
allow the Mohs surgeons to pinpoint and eliminate the residual tumor at the
surgical margin. It is especially helpful when a tumor presents with subtle or
nonspecific histologic features or when a tumor is masked in a pocket of dense
inflammation. However, the cost, the labor, and the time consumption are of
concern to many of our peers, as are the diversity of antigens, which may
overwhelm some. This article serves as a review of the literature on current uses
of immunostaining in Mohs micrographic surgery and as a summary of their
realistic applications in the dermatologic surgeon’s practice. We conclude that
immunohistochemical technique has played an important role in Mohs surgery
advancement. With greater use and more cost-effective staining methods, we
believe that the use of immunostains in a Mohs practice will become routine.

Management of head and neck tumours during pregnancy: case report and literature review. Chow VL, Chan JY, Ng RW, Wei WI. Asian J Surg. 2008 Oct;31(4):199-203.

Ethical dilemmas arise in managing head and neck cancers during pregnancy. The
timing of treatment is an important determinant on foetal wellbeing. Diagnostic
and treatment modalities may harm the foetus, while delaying or choosing
suboptimal treatment in order to preserve foetal health may worsen maternal
outcome. A multidisciplinary approach should be adopted to enable parents and
clinicians to make the best clinical decision. We report on two cases. Case 1 is
a 34-year-old female who presented with squamous cell carcinoma of the tongue at
29 weeks’ gestation. Partial glossectomy, selective neck dissection and posterior
tibial flap reconstruction was performed at 31 weeks. She underwent induction and
early delivery at 38 weeks prior to receiving radiotherapy. Case 2 is a
36-year-old female who presented with carcinoma of the cervical oesophagus
complicated by tracheal invasion, thyroid and cervical lymph node metastasis at
13 weeks’ gestation. Pregnancy was terminated at 16 weeks. She received a course
of neoadjuvant chemoirradiation.

Understanding the results of meta-analyses in the treatment of head and neck squamous cell cancer. Hotte SJ, Wright JR. Hematol Oncol Clin North Am. 2008 Dec;22(6):1257-66, x.

Clinical trials evaluating therapies in patients who have head and neck cancer
are often challenged by low power and competing clinical outcomes, which makes
interpretation difficult. Meta-analyses that combine the results of independent
trials have the potential to provide high-quality, evidence-based information on
what should be considered best practice beyond that of any one trial. In this
summary of published meta-analyses, the authors review the evidence supporting
the use of concurrent chemotherapy and fractionated radiotherapy for patients who
have locally advanced squamous cell carcinoma of the oral cavity, oropharynx,
hypopharynx, and larynx.

Evaluation of quality of life and organ function in head and neck squamous cell carcinoma. Martino R, Ringash J. Hematol Oncol Clin North Am. 2008 Dec;22(6):1239-56, x.

Common concerns of head and neck squamous cell cancer patients include concerns
about illness and their future, general physical and emotional well being,
speech, body image, and financial issues. Patients receiving radiotherapy report
high levels of problems with swallowing, eating, and dry mouth. This article
focuses on several of the most common and severe lasting issues for head and neck
squamous cell cancer patients: impairments of overall quality of life,
xerostomia, speech, and swallowing, focusing primarily on the tools and
techniques for measuring such effects.

Role of functional imaging in head and neck squamous cell carcinoma: fluorodeoxyglucose positron emission tomography and beyond. Porceddu SV, Burmeister BH, Hicks RJ. Hematol Oncol Clin North Am. 2008 Dec;22(6):1221-38, ix-x.

Positron emission tomography (PET) has emerged as an integral diagnostic tool in
the management of head and neck squamous cell carcinoma (HNSCC). This article
reviews the usefulness and ongoing dilemmas of fluorine-18 fluorodeoxyglucose
(18-F FDG) PET and FDG PET/CT in HNSCC. In addition, it examines the potential
role of novel markers and biologic characterization of disease, which in the
future may assist in targeted therapeutic strategies.

Molecularly targeted agents in the treatment of recurrent or metastatic squamous cell carcinomas of the head and neck. Le Tourneau C, Chen EX. Hematol Oncol Clin North Am. 2008 Dec;22(6):1209-20, ix.

Proof of principle that molecularly targeted therapy is a valid therapeutic
approach for squamous cell carcinoma of the head and neck (SCCHN) has emerged
with epidermal growth factor receptor targeting agents. Other interesting
targets, such as Src, insulin-like growth factor 1 receptor, and the proteasome,
have been shown in vitro to play key roles in SCCHN, and their inhibition is
currently being studied in phase II trials. Identification of predictive
biomarkers of resistance or sensitivity to these therapies remains one of the
main challenges in the optimal selection of patients most likely to benefit from
them. However, clinical trials with these novel agents need to be designed
rationally to improve the overall outcome of patients. Given the emerging
evidence that human papilloma virus-related SCCHN is a distinct disease, it
should be studied in specific trials.

Incorporation of molecularly targeted agents in the primary treatment of squamous cell carcinomas of the head and neck. Bernier J. Hematol Oncol Clin North Am. 2008 Dec;22(6):1193-208, ix.

Molecular markers will become increasingly important in directing treatment
approaches in locally advanced squamous cell carcinomas of the head and neck
(HNSCC). Several predictive markers have been identified that may be useful for
selecting tumors most likely to respond to radiotherapy or chemotherapy. However,
few markers have potential as therapeutic targets. The epidermal growth factor
receptor (EGFR) is the most extensively investigated of these targets in the
clinical setting. EGFR inhibitors have demonstrated activity in several studies
and the monoclonal antibody cetuximab is currently the only biologic agent
approved for the treatment of locally advanced HNSCC in combination with
radiotherapy. Another potentially promising approach is the inhibition of
vascular endothelial growth factor, alone or in combination with EGFR inhibition.

Human papillomavirus in HNSCC: a European epidemiologic perspective. Licitra L, Zigon G, Gatta G, Sánchez MJ, Berrino F; EUROCARE Working Group. Hematol Oncol Clin North Am. 2008 Dec;22(6):1143-53, vii-viii.

The aim of this study was to assess incidence and survival of human
papillomavirus-related and unrelated head and neck squamous cell carcinoma sites
from 15 European population-based cancer registries. This analysis was performed
on 29,265 adult (aged approximately 15 years) cancer patients diagnosed in the
period from 1988 to 2002. The human papillomavirus-unrelated cancer sites had an
age-standardized incidence higher than the human papillomavirus-related cancer
cases (3.8 versus 2.5/100,000 year). Incidence rates of head and neck squamous
cell carcinomas increased more for human papillomavirus-related than unrelated
cancer sites. Three-year survival rates improved more in human
papillomavirus-related than unrelated cancer sites, and women had better rates of
survival than men.

Human papillomavirus in HNSCC: recognition of a distinct disease type. Vidal L, Gillison ML. Hematol Oncol Clin North Am. 2008 Dec;22(6):1125-42, vii.

Strong epidemiologic and molecular data now support the conclusion that human
papillomavirus (HPV) infection is responsible for a distinct form of head and
neck squamous cell carcinoma (HNSCC), independent from the traditional risk
factors of tobacco and alcohol use. Patients with HPV-positive HNSCC have a
different clinical presentation and better clinical outcomes than those with
HPV-negative HNSCC. A diagnosis of HPV-positive HNSCC is associated not only with
therapeutic relevance, but also has important implications for future prevention
and screening strategies.

[Modern approaches to the organization of oncological care for patients with tumours of upper respiratory tract] [Article in Russian] Aliev DA, Rzaev RM. Vestn Otorinolaringol. 2008;(5):11-3.

Despite reports of successful treatment of oncological diseases of the upper
respiratory tract, many patients with this pathology still apply for medical aid
too late. Squamous cell carcinoma remains the predominant problem. Clinical
symptoms of metastases are absent in 60% of the lethal cases with locally
spreading tumours. The most common causes of death among these patients are
obstruction of the upper air passages, invasion of tumour cells into the brain,
local and systemic metastasis. It is concluded that the improvement of early
diagnosis of malignant neoplasms of the upper respiratory tract and organization
of specialized care for subjects with pre-tumor processes requires joint efforts
of oncologists and otorhinolaryngologists. The achievement of this goal would
enhance the effectiveness of the treatment of this pathology.

Vitamin D and skin cancer: a meta-analysis. Gandini S, Raimondi S, Gnagnarella P, Doré JF, Maisonneuve P, Testori A. Eur J Cancer. 2009 Mar;45(4):634-41. Epub 2008 Nov 12.

A comprehensive bibliographic search of the literature was conducted to identify
studies on Cutaneous Malignant Melanoma (CMM) and non-melanoma skin cancer
(NMSC), Vitamin D receptor (VDR) polymorphisms, Vitamin D intake and 25(OH)D
serum levels. Fully adjusted risk estimates were found and extracted for the two
polymorphisms FokI and BsmI and Vitamin D intake. Ten studies were included in
the meta-analysis, with a total of 6805 skin cancer cases. We found an
association with CMM for both polymorphisms. The summary relative risks (SRR) for
the studies on CMM were: 1.21 (1.03-1.42) and 1.21 (0.95-1.54) for the Ff and ff
versus wild-type of FokI, respectively. The SRR for ff versus wild-type became
significant with the inclusion of NMSC. The SRR for the studies on CMM were: 0.78
(0.65-0.92) and 0.75 (0.59-0.95) for the Bb and BB versus wild-type of BsmI,
respectively. There is also a slight indication of a role of dietary Vitamin D in
CMM development. In conclusion, this meta-analysis suggests a possible
significant role of VDR FokI and BsmI polymorphism in CMM and NMSC risk. The
association with Vitamin D intake is less clear and further studies could be
useful to clarify the role of diet.

The role of cetuximab for the treatment of squamous cell carcinoma of the head and neck. Mehra R, Cohen RB, Burtness BA. Clin Adv Hematol Oncol. 2008 Oct;6(10):742-50.

Squamous cell carcinoma of the head and neck (HNSCC), while curable in many cases
with surgery, radiation, and chemotherapy, remains a disease that is associated
with significant morbidity and mortality. Agents that target the epidermal growth
factor receptor (EGFR) have demonstrated beneficial effects in this disease. The
Food and Drug Administration approved cetuximab-a monoclonal antibody-in
conjunction with radiation, for locally advanced, potentially curable disease,
and also as a single agent for incurable recurrent/metastatic disease. In
addition, there are more recent data showing a survival benefit for patients with
recurrent/metastatic disease who were treated with a first-line regimen of
platinum, fluorouracil and cetuximab. These promising results have had a
significant impact on the standard of care for HNSCC, and have prompted further
research on the role of EGFR inhibitors in the treatment of HNSCC. In the
following review, we will discuss the history, mechanism, and clinical trials
that pertain to the role of cetuximab in the treatment of HNSCC.

[Bronchial carcinoma and intensive care] [Article in French] Toffart AC, Pluquet E, Timsit JF, Diab S, Moro-Sibilot D. Rev Pneumol Clin. 2008 Oct;64(5):250-6. Epub 2008 Oct 25.

INTRODUCTION: Lung cancer is a disease with a poor prognosis. Therapeutic
innovations in oncology and the optimisation of intensive care patient management
have improved the prognosis of lung cancer presenting with acute life-threatening
respiratory or cardiac emergencies. OBSERVATION: We reported on the case of a
patient with lung cancer presenting with mildly abundant haemoptysis, who was
hospitalised in intensive care. After multidisciplinary discussion, the patient
was intubated following recurrent haemorrhage that resulted in respiratory
failure. The outcome was favourable. Four months later, this patient was still
alive and autonomous. DISCUSSION: After years of pessimism, the medical
literature has revealed an improvement in lung cancer patients’ survival.
Respiratory failure and shock are the main reasons for admission to the intensive
care unit. The mortality risk factors depend more on acute conditions than on the
underlying lung cancer. The patient’s admission must be made before multiorgan
failure occurs, along with the implementation of non invasive therapies. The use
of intensive care as a bridge to overcome an acute event is a possible means of
caring for the patient. CONCLUSION: Consideration of the acute event is important
when deciding whether to hospitalise a patient with lung cancer in intensive
care. An early admission, if indicated, is desirable. The course in the first
72hours provides a good estimation of the patient’s prognosis and helps to
achieve better treatment.

Metatypical basal cell carcinoma: a clinical review. Tarallo M, Cigna E, Frati R, Delfino S, Innocenzi D, Fama U, Corbianco A, Scuderi N. J Exp Clin Cancer Res. 2008 Nov 7;27:65.

BACKGROUND: Metatypical cell carcinoma can be considered as a new entity of skin
cancer, being an intermediate typology between basal cell carcinomas and squamous
cell carcinomas. The behaviour of the metatypical cell carcinoma lies between
these two varieties of skin cancer. It is difficult to perform a differential
diagnosis based on morphological and clinical features – therefore it is only
possible by accurate histology. METHODS: The authors have retrospectively
analysed clinical records of 240 patients who were affected by metatypical skin
cancer and who were treated by surgery, radiotherapy and chemotherapy. RESULTS:
MTC affected more males than females (62.5% vs 37.5%) than males. The most
affected site was the cervicofacial area, 71.7%; then the trunk, 10%; the limbs,
9.6%; the scalp 3.7%; and other regions 5%. A recurrence occurred in 24 cases
(10%), mainly in head and neck area. CONCLUSION: In this manuscript, the authors
have emphasised the importance of conducting a differential diagnosis, and the
importance of the specific treatment for metatypical skin cancer, even though
more clinical studies and long-term follow-ups are required before establishing
specific guidelines.

[Massive pneumocephalus and cerebrospinal fluid fistula after thoracotomy] [Article in Spanish] Olarra J, Longarela A. Rev Esp Anestesiol Reanim. 2008 Oct;55(8):504-7.

We report the case of a 70-year-old man (ASA physical status 2) who developed
massive pneumocephalus caused by a fistula between the subarachnoid and pleural
spaces following a left pneumonectomy. After an uneventful immediate
postoperative period, the patient was readmitted to the recovery care unit with
dyspnea, intense headache, confusion, and diminished level of consciousness.
Computed tomography confirmed a cerebrospinal fluid fistula secondary to the
opening of the intradural space during tumor resection. Treatment was
conservative, consisting of rest in a slightly Trendelenburg position, antibiotic
prophylaxis to prevent meningitis, and a water seal on the thoracic drainage

Carcinoma of unknown primary (CUP). Pavlidis N, Fizazi K. Crit Rev Oncol Hematol. 2009 Mar;69(3):271-8. Epub 2008 Nov 1.

Carcinoma of unknown primary (CUP) is one of the 10 most frequent cancers
worldwide. It constitutes 3-5% of all human malignancies. Patients with CUP
present with metastases without an established primary site. CUP manifests as an
heterogeneous group of mainly epithelial cancers recognised by distinct
clinicopathological entities. The diagnostic work-up includes extensive
histopathology investigations and modern imaging technology. Nevertheless, the
primary tumour remains undetected most of the time. Molecular diagnosis with DNA
microarrays demonstrates high sensitivity, but its prognostic contribution is
still uncertain. Certain clinicopathological CUP entities are considered as
favourable sub-sets responding to systemic platinum-based chemotherapy or managed
by locoregional treatment. These sub-sets are: the poorly differentiated
carcinomas involving the mediastinal-retroperitoneal nodes, peritoneal papillary
serous adenocarcinomatosis in females, poorly differentiated neuroendocrine
carcinomas, isolated axillary node adenocarcinomas in females or cervical nodal
involvement by a squamous cell carcinoma. Patients who belong to the
non-favourable sub-sets have a worse prognosis.

Fine-needle aspiration diagnosis of squamous cell carcinoma in a lymph node involved with small lymphocytic lymphoma: case report and review of the literature. McElroy C, Velilla R, Chaudhary H, Al-Abbadi MA. Diagn Cytopathol. 2009 Jan;37(1):48-50.

Diagnosis of two distinct malignant entities existing concurrently and at the
same location (synchronous malignancy) by fine- needle aspiration (FNA) is
unusual but may occur. Small lymphocytic lymphoma/chronic lymphocytic leukemia
(SLL/CLL) in particular is associated with an increased incidence of secondary
tumor, likely due to associated immunodeficiency. Co-occurrence of some
carcinomas such as squamous cell carcinoma (SCC), may show especially aggressive
behavior. A 57-year-old Caucasian male presented with recurrent upper extremity
lymphedema and diffuse lymphadenopathy of the axillary and cervical regions. FNA
of a large cervical lymph node was diagnostic for both atypical lymphocytic
proliferation and SCC. Flow cytometric analysis showed the atypical lymphocytic
proliferation to be positive for CD5, CD23, CD19, CD20, HLA-DR, CD38, and the
population was kappa light chain restricted. These cells were negative for CD-10
and FMC-7 antigens, suggesting a phenotype of B-cell SLL/CLL. We report a rare
occurrence of metastatic SCC to a lymph node infiltrated by SLL/CLL. The
diagnosis was achieved by a combination of cytomorphologic examination of FNA
smears, immunohistochemical staining of cell block material, and flow cytometry
on the sample obtained by FNA. To the best of our knowledge, only three cases of
SCC metastasis to SLL/CLL diagnosed by FNA have been reported in the English
literature. Though rare, awareness of such a possibility and careful cytological
examination under the appropriate clinical conditions is warranted. (c) 2008
Wiley-Liss, Inc.

Prognosis and treatment of squamous cell carcinoma from a mature cystic teratoma of the ovary. Chen RJ, Chen KY, Chang TC, Sheu BC, Chow SN, Huang SC. J Formos Med Assoc. 2008 Nov;107(11):857-68.

BACKGROUND/PURPOSE: Squamous cell carcinoma (SCC) arising from a mature cystic
teratoma of the ovary is rare and only reported sporadically. Clinical
information on the disease is limited. This study assesses the clinical
characteristics, treatment, outcome and prognostic factors of reported cases.
METHODS: Two hundred and twenty cases from 1976 through to 2005 in MEDLINE were
analyzed for patient age, clinical and laboratory data, extent of disease, tumor
markers, treatment and survival rates. Only the 188 cases with surgical staging
were included in the survival analysis. RESULTS: The disease occurred most often
in elderly women (mean, 55.0 +/- 14.4 years) and cysts were large (mean, 13.7 +/-
5.7 cm). Abdominal pain (71.6%) was the most common symptom. Preoperative serum
SCC antigen level had a high positive rate (81.3%). Overall 5-year survival rate
for all stages was 48.4%. For Stage I, the 5-year survival rate was 75.7%; stage
II, 33.8%; stage III, 20.6%; and stage IV, 0% (p < 0.0001). Univariate analysis
revealed that tumor stage, patient age, tumor size, preoperative SCC antigen and
CA125 levels, and optimal debulking were significant prognostic factors. Further
investigation into treatments for all stages revealed that postoperative adjuvant
chemotherapy may produce a better survival rate for both stage III and stage IV
cases. However, postoperative radiotherapy did not show a similar effect.
Multivariate analysis indicated that stage and optimal debulking were significant
factors that influenced survival. CONCLUSION: A mature cystic teratoma should be
treated as early as possible. Tumor stage and optimal debulking are critical to
survival. Unlike SCCs of the uterine cervix, postoperative adjuvant chemotherapy
may produce a better result than adjuvant radiotherapy for advanced-stage cases.

Guidelines for topical photodynamic therapy: update. Morton CA, McKenna KE, Rhodes LE; British Association of Dermatologists Therapy Guidelines and Audit Subcommittee and the British Photodermatology Group. Br J Dermatol. 2008 Dec;159(6):1245-66. Epub 2008 Oct 13.

Multicentre randomized controlled studies now demonstrate high efficacy of
topical photodynamic therapy (PDT) for actinic keratoses, Bowen’s disease (BD)
and superficial basal cell carcinoma (BCC), and efficacy in thin nodular BCC,
while confirming the superiority of cosmetic outcome over standard therapies.
Long-term follow-up studies are also now available, indicating that PDT has
recurrence rates equivalent to other standard therapies in BD and superficial
BCC, but with lower sustained efficacy than surgery in nodular BCC. In contrast,
current evidence does not support the use of topical PDT for squamous cell
carcinoma. PDT can reduce the number of new lesions developing in patients at
high risk of skin cancer and may have a role as a preventive therapy. Case
reports and small series attest to the potential of PDT in a wide range of
inflammatory/infective dermatoses, although recent studies indicate insufficient
evidence to support its use in psoriasis. There is an accumulating evidence base
for the use of PDT in acne, while detailed study of an optimized protocol is
still required. In addition to high-quality treatment site cosmesis, several
studies observe improvements in aspects of photoageing. Management of
treatment-related pain/discomfort is a challenge in a minority of patients, and
the modality is otherwise well tolerated. Long-term studies provide reassurance
over the safety of repeated use of PDT.

HIV, human papillomavirus, and cervical neoplasia and cancer in the era of highly active antiretroviral therapy. De Vuyst H, Lillo F, Broutet N, Smith JS. Eur J Cancer Prev. 2008 Nov;17(6):545-54.

The objective of this study was to review the literature on the epidemiological
association between human papillomavirus (HPV), HIV, and cervical neoplasia, and
the impact of highly active antiretroviral therapy (HAART) on this association.
MEDLINE was searched using the terms ‘human papillomavirus’, ‘HPV’, ‘HIV’,
‘cervix’, ‘neoplasm’, and ‘antiretroviral’ to identify articles published before
December 2006. HIV-infection was strongly associated with a higher prevalence,
incidence, and persistence of HPV infection and correlated with prevalence,
incidence, persistence, and progression of squamous intraepithelial lesions. The
association between HIV and invasive cervical carcinoma has been more difficult
to establish, but is now fully recognized. HAART seems to have little, if any,
beneficial effect on the natural history of intraepithelial lesions in
HIV-positive women. Despite this fact, HAART, does increase the life expectancy
of HIV-positive women. Therefore, it remains important to closely monitor
HPV-related disease in women with HIV who are receiving HAART, particularly in
regions of the world where cervical screening is not available routinely.

Management of locally advanced or unresectable head and neck cancer. Culliney B, Birhan A, Young AV, Choi W, Shulimovich M, Blum RH. Oncology (Williston Park). 2008 Sep;22(10):1152-61; discussion 1162-6, 1171-2.

The treatment of patients with locoregionally advanced or unresectable squamous
cell carcinoma of the head and neck is complex and associated with significant
toxicities. During the past 30 years, there has been an ongoing shift in what is
perceived as the best treatment approach. Differing radiation techniques have
been employed, and chemotherapy has been incorporated in both sequential and
concomitant strategies. In this article, we will review the available data
regarding many of the advances that have been achieved. We will also discuss the
most relevant recent clinical trials, as well as ongoing trials that will
hopefully answer some of the questions that remain as we attempt to best treat
this patient population

Keratinizing squamous metaplasia of the bladder: a review. Ahmad I, Barnetson RJ, Krishna NS. Urol Int. 2008;81(3):247-51. Epub 2008 Oct 16.

AIMS: Keratinizing squamous metaplasia is infrequently found in bladder biopsies
and its clinical significance remains unclear, with studies linking it to the
development of invasive squamous cell carcinoma. Once diagnosed, there is a
dilemma how to treat and follow-up this group. METHODS: We reviewed the
literature on the topic with particular emphasis on natural history, management
and subsequent follow-up. RESULTS: Keratinizing squamous metaplasia of the
bladder is rare. Pathognomonic findings on biopsy are required to confirm the
diagnosis. Both synchronous diagnosis of urothelial tumour and subsequent tumour
development on follow-up has been identified. Risk of malignant transformation
increases in the presence of dysplasia as well as with extensive keratinization.
Lesions should be treated with local transurethral resection. Considering the
lack of evidence cystectomy cannot be justified for those with extensive lesions.
CONCLUSION: Currently there is not enough data to identify keratinizing squamous
metaplasia of the bladder as a pre-malignant condition; this term being reserved
for those with obvious histological dysplasia. However at present all patients
should undergo regular follow-up. 2008 S. Karger AG, Basel

Evaluation of potential human carcinogenicity of the synthetic monomer ethyl acrylate. Williams GM, Iatropoulos MJ. Regul Toxicol Pharmacol. 2009 Feb;53(1):6-15. Epub 2008 Oct 5.

Ethyl acrylate (EA) is an acrylic monomer used in the manufacture of a variety of
polymers and copolymers as components of many commercially important products.
Human exposure to EA occurs primarily in the workplace via inhalation or dermal
contact. In F344 rat and B6C3F(1) mouse studies of EA carcinogenicity conducted
by the National Toxicology Program [National Toxicology Program, NTP, 1986.
Carcinogenesis Studies of Ethyl Acrylate (CAS No. 140-88-5) in F344/N Rats and
B6C3F(1) Mice (Gavage Studies) (Tech. Rep. Ser. No. 259; NIH Publication No.
87-2515), Research Triangle Park, NC, USA], the only increased tumor incidences
was in squamous cell papillomas and carcinomas of the forestomach, when EA was
administered by gavage in corn oil at 100 or 200mg/kg/day (high dose; HD). The
neoplasms were preceded by forestomach irritation, inflammation, hyperkeratosis
and hyperplasia of the forestomach mucosa. In studies in which rats and mice were
exposed at comparable doses to EA in drinking water, by inhalation, or by dermal
application, no neoplasms in the forestomach or in any other tissue were
reported. EA exhibited clastogenicity and related mutagenicity in vitro, but was
non-genotoxic in vivo, including in the forestomach of treated rats. The in vitro
clastogenicity response correlates well with cellular toxicity, mediated by
non-protein sulfhydryl depletion and mitochondrial impairment. Thus, the
carcinogenicity in the forestomach can be ascribed to a non-genotoxic mode of
action (MOA). The forestomach mucosal hyperplastic and even dysplastic changes,
observed chronically, were reversible, provided the HD exposure was not longer
than 6months. This again supports a non-genotoxic MOA. In addition, the route and
rate of EA exposure in rodents for forestomach neoplasia are irrelevant to
potential human exposure, since humans do not have forestomach and are not
exposed to EA by oral bolus. Thus, the weight of evidence indicates that the
tumors produced in the rodent carcinogenicity studies arise from conditions that
are irrelevant for human risk assessment.

Desmoplastic fibroma of the hand: case report. Bernstein ML, Chung KC. J Hand Surg Am. 2008 Oct;33(8):1405-8.

Desmoplastic fibroma is a benign tumor of the soft tissue and rarely of the bone.
It typically presents in the trunk and proximal limbs, but it is quite rare in
the hands. We present a rare case of desmoplastic fibroma of the soft tissues of
the hand that presented as a slow-growing, painless, well-encapsulated mass.

Bovine papillomaviruses: their role in the aetiology of cutaneous tumours of bovids and equids. Nasir L, Campo MS. Vet Dermatol. 2008 Oct;19(5):243-54.

Bovine papillomavirus (BPV) is perhaps the most extensively studied animal
papillomavirus. In cattle BPVs induce benign tumours of cutaneous or mucosal
epithelia, called papillomas or warts. Cattle papillomas are benign tumours and
generally regress without eliciting any serious clinical problems in the host,
but occasionally persist and provide the focus for malignant transformation to
squamous cell carcinoma, as in the case of cancer of the urinary bladder and
cancer of the upper alimentary canal. BPV is the only papillomavirus that jumps
species: the virus also infects equids, and gives rise to fibroblastic tumours
called sarcoids. Sarcoids very rarely regress, more often they persist and can be
locally aggressive. These tumours are the most common dermatological tumour of
equids worldwide. The purpose of this review is to discuss the biology of BPV,
the biology of bovine tumours and equine sarcoids, and present the current
understanding of BPV in tumour pathogenesis in its natural host, cattle, and in
its heterologous host, equids. Finally, the use of anti-BPV vaccines as a therapy
for equine sarcoids will be discussed. Only limited information on the clinical
or pathological aspects of either bovine or equine tumours will be provided as
this subject has been extensively addressed previously.

Combined modality therapy of esophageal cancer. Juergens RA, Forastiere A. J Natl Compr Canc Netw. 2008 Oct;6(9):851-60; quiz 861.

Esophageal cancer is a deadly disease. Only one third of patients with localized
disease experience long-term survival. Over the past 20 years, investigators have
evaluated neoadjuvant strategies to improve the outcomes of surgical management.
Chemotherapy and radiation have been evaluated individually and in combination
for preoperative management of patients with localized esophageal cancer. This
article provides a critical review of the data on multimodality approaches to the
management of esophageal cancer.

Controversies in the management of anal high-grade squamous intraepithelial lesions. Pineda CE, Welton ML. Minerva Chir. 2008 Oct;63(5):389-99.

Anal squamous dysplasia is recognized as a spectrum of disease that ranges from
low-grade intraepithelial lesions (LSIL) to high-grade squamous intraepithelial
lesions (HSIL) to invasive anal squamous cell carcinoma (SCC). Recent reports
have shown a significant increase in both the incidence and prevalence of both
HSIL and anal SCC, particularly in immunocompromised patients and in men who have
sex with men. These lesions are associated with chronic infection with the human
papillomavirus. The natural history is unknown, yet reports of untreated patients
have shown progression rates of up to 50% in high risk patients. There are
controversies as to the optimal management of patients with HSIL. However, there
is evidence that screening of high-risk patients with anal cytology is useful in
identifying those that require further evaluation. Examination of the anorectal
region is enhanced with the use of high resolution anoscopy. Treatment modalities
vary in terms of morbidity and success rates. Wide local excision is associated
with significant morbidity. Newer therapies such as topical immunomodulation,
photodynamic therapy and therapeutic vaccines have been proposed, but long-term
follow-up is unavailable. High resolution anoscopy can be used in the office or
in the operating room to direct therapy. Using a comprehensive approach of
cytology and office-based and/or operating room procedures directed with high
resolution anoscopy results in clearance of HSIL in up to 80% of patients,
malignant progression in 1%, and less morbidity than wide local excision.

The urokinase receptor and its structural homologue C4.4A in human cancer: expression, prognosis and pharmacological inhibition. Jacobsen B, Ploug M. Curr Med Chem. 2008;15(25):2559-73.

The urokinase-type plasminogen activator receptor (uPAR) and its structural
homologue C4.4A are multidomain members of the Ly6/uPAR/alpha-neurotoxin protein
domain family. Both are glycosylphosphatidylinositol-anchored membrane
glycoproteins encoded by neighbouring genes located on chromosome 19q13 in the
human genome. The structural relationship between the two proteins is, however,
not reflected at the functional level. Whereas uPAR has a well-established role
in regulating and focalizing uPA-mediated plasminogen activation to the surface
of those cells expressing the receptor, the biological function of C4.4A remains
elusive. Nonetheless, both uPAR and C4.4A have been implicated in human
pathologies such as wound healing and cancer. A large body of experimental
evidence thus demonstrates that high levels of uPAR in resected tumour tissue as
well as in plasma are associated with poor prognosis in a number of human cancers
including colon adenocarcinoma and pulmonary squamous cell carcinoma. Targeting
uPAR in experimental animal models has also provided promising results regarding
the interference with pathogenic plasminogen activation. In the case of C4.4A,
very recent data have demonstrated that high protein expression in tumour cells
of non-small cell pulmonary adenocarcinomas is associated with a particularly
severe disease progression. This review will evaluate structural-functional and
disease-related aspects of uPAR and C4.4A with a view to possible pharmacological
targeting strategies for therapy and for non-invasive bioimaging.

[The treatment of malignant tumors on venous leg ulcers. Case presentation and literature review] [Article in German] Lehnert W, Kohl K, Riebe H, Jünger M, Ladwig A. Hautarzt. 2008 Nov;59(11):912-6.

Malignant changes in persistent venous leg ulcers are a grave complication of
chronic impaired wound healing. In our case, a venous leg ulcer had persisted on
the right calf for 30 years. Exophytic tumors in the ulcer with frequent bleeding
prompted biopsies. A squamous cell carcinoma was found, but only in the second
biopsy. The surgical procedure was planned so that in a single session both the
tumor and the underlying causes of the chronic venous insufficiency in the leg
could be treated appropriately. Extirpation of the enlarged lymph nodes in the
groin was combined with crossectomy and removal of the long saphenous vein,
followed by circular radial excision of the ulcer scar fascia (fasciotomy). The
excised tissue was examined histologically. Muscle biopsies were taken from the
site of suspicious adhesions of the fascia to the calf muscle. The large,
circular defects on the lower leg were covered with the appropriate dressing to
condition the wound bed. After three weeks the well-granulated area was covered
with meshed split skin grafts. During the operation and in the post-operative
phase, machine-assisted and manual decongestion was performed, an established
therapy for lymphedema, chronic venous insufficiency and chronic venous ulcers.

[Radiochemotherapy for oesophageal cancer: a locoregional failure history] [Article in French] Créhange G, Maingon P, Bosset JF. Cancer Radiother. 2008 Nov;12(6-7):640-8. Epub 2008 Oct 8.

Esophageal cancer is characterized by various degrees of lymph node invasion and
metastasis, both of which are associated with a poor prognosis. Exclusive
concomitant radiochemotherapy (RCT) at a dose of 50 Gy delivered over 25
sessions, according to the RTOG 85-01 protocol, has led to improved five-year
survival in 25% of patients, whereas no patients survive for five years using
radiotherapy alone. Surgery, even when combined with preoperative RCT, also gives
disappointing results for locally advanced tumors, which casts serious doubts on
the usefulness of preoperative radiotherapy. By varying the fractionation
schedule, the length of treatment or the radiotherapy volumes, it has become
possible to obtain levels of locoregional relapse of around 35 to 45%. The
increasing incidence of adenocarcinoma, which differs from epidermoid cancer with
regard to the degree of lymph node invasion, has revived discussion on
radiotherapy volumes. Given this difference between these two histological forms,
we propose here a number of recommendations concerning radiotherapy volumes for
patients presenting with cancer of the esophagus. Finally, analysis of the
results for locoregional relapse according to the dose of radiation and the
recommended radiotherapy volumes, has led us to investigate why increasing the
dose of radiation has no impact in esophageal cancers.

Oral submucous fibrosis, a clinically benign but potentially malignant disease: report of 3 cases and review of the literature. Auluck A, Rosin MP, Zhang L, Sumanth KN. J Can Dent Assoc. 2008 Oct;74(8):735-40.

Oral submucous fibrosis (OSF) is a premalignant condition mainly associated with
the practice of chewing betel quid containing areca nut, a habit common among
South Asian people. It is characterized by inflammation, increased deposition of
submucosal collagen and formation of fibrotic bands in the oral and paraoral
tissues, which increasingly limit mouth opening. Recently, OSF has been reported
among South Asian immigrants in Canada, the United Kingdom and Germany. Dentists
in western countries should enhance their knowledge of this disease as it seems
to be increasing with population migration. In this paper, we review the
literature on OSF and present 3 cases representing different stages of the
disease to help dentists make an early diagnosis and reduce the morbidity and
mortality associated with this condition.

EGFR-targeted therapeutics: focus on SCCHN and NSCLC. Sattler M, Abidoye O, Salgia R. ScientificWorldJournal. 2008 Sep 21;8:909-19.

Cancers of the head and neck and of the lung are associated with high morbidity
and mortality rates that have remained relatively unchanged for more than 3
decades, despite advances in radiation therapies and chemotherapies over the same
time. It is generally believed that the efficacy of standard therapy regimens has
reached a plateau for these cancers. The discovery of specific aberrant molecular
signaling pathways in solid tumors has afforded promising new directions for
newer “targeted” cancer therapeutics. Among these, the epidermal growth factor
receptor (EGFR) shows promise as a therapeutic target. Clinical studies have
demonstrated that this targeted approach provides clinically meaningful benefit.
This article reviews EGFR-targeted therapies in use and in development, with a
focus on the role of EGFR in the pathophysiology of head and neck and lung
cancer, and new concepts being investigated to improve outcomes with these

Squamous differentiation in a sarcomatoid chromophobe renal cell carcinoma: an unusual case report with review of the literature. Viswanathan S, Desai SB, Prabhu SR, Amin MB. Arch Pathol Lab Med. 2008 Oct;132(10):1672-4.

We describe an extremely rare occurrence of a squamous differentiation in a
sarcomatoid chromophobe renal cell carcinoma in a 45-year-old woman with nodal
and lung metastasis at presentation. The tumor on histology showed all 3
components intimately admixed with each other, which to the best of our knowledge
is the first such case to be reported in the literature. The renal pelvis was
smooth walled and uninvolved. Kidney-specific cadherin was positive in the
chromophobe renal cell carcinoma areas and negative in the sarcomatoid and
squamous areas.

Drug Insight: cetuximab in the treatment of recurrent and metastatic squamous cell carcinoma of the head and neck. Bernier J. Nat Clin Pract Oncol. 2008 Dec;5(12):705-13. Epub 2008 Sep 30.

Patients with recurrent and/or metastatic squamous cell carcinoma of the head and
neck (SCCHN) have a poor prognosis, particularly those whose disease has
progressed on previous platinum-containing therapy. The epidermal growth factor
receptor (EGFR) is expressed at very high levels in SCCHN and is associated with
a poor prognosis. Several phase II-III studies have shown that the EGFR-targeting
monoclonal antibody, cetuximab, offers clinical benefit for patients with SCCHN.
Cetuximab monotherapy is active in patients whose cancer progresses on
platinum-containing therapy. Tumor response and patient survival are in excess of
what is achieved with commonly used therapies in this setting. Addition of a
platinum regimen to cetuximab in patients with disease that progresses on
platinum seems to confer no further benefit over cetuximab alone, either in terms
of response rate or survival. In the first-line setting, cetuximab plus platinum
and 5-fluorouracil significantly prolongs overall survival compared with platinum
and 5-fluorouracil alone. The superior survival observed with cetuximab compared
with platinum-based treatment demonstrates that cetuximab is the most active
treatment for recurrent and/or metastatic SCCHN, and is of particular clinical

Diffusion-weighted magnetic resonance imaging in neck lymph adenopathy. Vandecaveye V, De Keyzer F, Hermans R. Cancer Imaging. 2008 Sep 30;8:173-80.

In patients with head and neck squamous cell carcinoma (SCC), nodal metastases
are an adverse prognostic factor compromising long term patient survival.
Therefore, accurate detection of regional nodal metastases is required for
optimization of treatment. Computed tomography (CT) and magnetic resonance
imaging (MRI) remain the primary imaging modalities for locoregional staging of
head and neck SCC. Next to evaluation of the primary tumour, both modalities
facilitate detection of non-palpable lymph nodes (LN). However, both modalities
rely on size-related and morphological criteria to differentiate between benign
and malignant lymph nodes, decreasing the sensitivity for detection of small
metastases. Diffusion-weighted MRI (DW-MRI) measures differences in tissue
microstructure, based on the random displacement of water molecules. The
differences in water mobility are quantified using the apparent diffusion
coefficient (ADC), which has an inverse relationship with tissue cellularity. As
such the technique is able to differentiate between tumoral tissue and normal or
necrotic tissue. The added value of DW-MRI to conventional imaging for staging of
lymph nodes in head and neck cancer is discussed, before and after treatment. The
possible consequences regarding therapeutic management are outlined.

[Human papillomavirus infection. Pathology and molecular pathology] [Article in German] Sotlar K. Pathologe. 2008 Nov;29 Suppl 2:153-6.

Cervical cancer is the second most frequent female malignoma worldwide and
accounts for about 500,000 cases every year. The peak incidence lies between 35
and 55 years of age. Persistent infections with a group of 15 so-called high-risk
human papillomaviruses (HR-HPV) are the cause of cervical carcinogenesis of
squamous cell carcinomas and for most of the adenocarcinomas. The transforming
potential of HR-HPVs is based on the interaction of viral oncogene products E6
and E7 with the cellular tumor suppressor proteins p53 and pRB. The resulting
loss of cell cycle control sets the basis for additional, as yet only
incompletely discovered, genetic and epigenetic changes, finally leading to
invasive growth. Preneoplastic changes, cervical intraepithelial neoplasias, can
be identified morphologically, thus allowing for therapeutic interventions. Since
November 2007, the Ständige Impfkommission, the German standing committee on
immunizations, has recommended the prophylactic use of vaccines against the two
most frequent HR-HPV genotypes, HPV-16 and HPV-18, in women age 12-17 years
before first sexual intercourse. In addition to cervical cancer, HPV infections
are responsible for the development of genital warts (condyloma) and a number of
vaginal, vulvar, and anal intraepithelial neoplasias. HPV infections are usually
transmitted sexually.

IKKalpha, a critical regulator of epidermal differentiation and a suppressor of skin cancer. Descargues P, Sil AK, Karin M. EMBO J. 2008 Oct 22;27(20):2639-47. Epub 2008 Sep 25.

IkappaB kinase alpha (IKKalpha), one of the two catalytic subunits of the IKK
complex involved in nuclear factor kappaB (NF-kappaB) activation, also functions
as a molecular switch that controls epidermal differentiation. This unexpected
function requires IKKalpha nuclear translocation but does not depend on its
kinase activity, and is independent of NF-kappaB signalling. Ikkalpha(-/-) mice
present with a hyperproliferative and undifferentiated epidermis characterized by
complete absence of a granular layer and stratum corneum. Ikkalpha-deficient
keratinocytes do not express terminal differentiation markers and continue to
proliferate even when subjected to differentiation-inducing stimuli. This
antiproliferative function of IKKalpha is also important for the suppression of
squamous cell carcinogenesis. The exact mechanisms by which nuclear IKKalpha
controls keratinocyte proliferation and differentiation remained mysterious for
some time. Recent studies, however, have revealed that IKKalpha is a major
cofactor in a TGFbeta-Smad2/3 signalling pathway that is Smad4 independent. This
pathway controls cell cycle withdrawal during keratinocyte terminal
differentiation. Although these are not the only functions of nuclear IKKalpha,
this multifunctional protein is a key regulator of keratinocyte and epidermal
differentiation and a critical suppressor of skin cancer.

EGFR inhibition as a therapy for head and neck squamous cell carcinoma. Loeffler-Ragg J, Schwentner I, Sprinzl GM, Zwierzina H. Expert Opin Investig Drugs. 2008 Oct;17(10):1517-31.

BACKGROUND: Improved understanding of disease biology of head and neck squamous
cell carcinoma (HNSCC) with nearly universal expression of EGFR has led to the
introduction of targeted therapies to interrupt signalling of this negative
prognostic marker. OBJECTIVE: We performed a literature review on the mechanisms
and efficacy of anti-EGFR antibodies and EGFR tyrosine kinase inhibitors in
patients with locally advanced or recurrent/metastatic HNSCC. RESULTS/CONCLUSION:
Clinical trials in HNSCC have administered EGFR directed drugs as single agents,
in combination with chemotherapy or radiotherapy and demonstrated a good safety
profile with antitumour activity in a subgroup of patients. The biology of
responsiveness is still unclear, although there is growing evidence of an
association of skin toxicity or presence of shorter EGFR intron 1
cytosine-adenine repeats with positive outcome.

Skin cancers. Krueger H, McLean D, Williams D. Prog Exp Tumor Res. 2008;40:111-21.

Optimizing approaches to head and neck cancer. Metastatic head and neck cancer: new options. Licitra L, Locati LD, Bossi P. Ann Oncol. 2008 Sep;19 Suppl 7:vii200-3.

Diagnosis and management of anal cancer. Gervaz P, Buchs N, Morel P. Curr Gastroenterol Rep. 2008 Oct;10(5):502-6.

During the past three decades, anal cancer has served as a paradigm for the
successful application of chemoradiation to solid tumors. Since the early 1990s,
the increasing incidence of anal cancer in homosexual men has highlighted the
causative role of oncogenic human papilloma-virus infection. This review focuses
on significant trends and developments in the management of patients with
squamous cell carcinoma of the anal canal, emphasizing three major aspects of
diagnosis and treatment: routine screening and eradication of premalignant
lesions in high-risk individuals; outcome of chemoradiation therapy in
HIV-positive individuals in the era of highly active antiretroviral therapy; and
potential improvements in chemoradiation protocols through improved radiation
delivery technique and the combination of mitomycin with cisplatin in current
prospective randomized trials.

Head and neck cancer: an evolving treatment paradigm. Cognetti DM, Weber RS, Lai SY. Cancer. 2008 Oct 1;113(7 Suppl):1911-32.

Since the inception of this journal in 1948, the understanding of etiologic
factors that contribute to and the treatment of head and neck cancer has evolved
dramatically. Advances in surgery, radiation therapy, and chemotherapy have
improved locoregional control, survival, and quality of life. The outcomes of
these treatment modalities have shifted the focus of curative efforts from
radical ablation to preservation and restoration of function. This evolution has
been documented in the pages of Cancer for the past 6 decades. This review
focuses on the evolution of treatment approaches for head and neck cancer and
future directions while recognizing the historic contributions recorded within
this journal.

Rare and unusual histological variants of prostatic carcinoma: clinical significance. Mazzucchelli R, Lopez-Beltran A, Cheng L, Scarpelli M, Kirkali Z, Montironi R. BJU Int. 2008 Nov;102(10):1369-74. Epub 2008 Sep 12.

We review the clinicopathological features of the following unusual histological
variants of prostatic carcinoma: small cell carcinoma, ductal adenocarcinoma,
sarcomatoid (carcinosarcoma), basal cell, squamous cell and adenosquamous, and
urothelial carcinoma. These variants are rare and account for 5-10% of carcinomas
that originate in the prostate. Some develop from acinar adenocarcinoma after
hormonal or radiation therapy. They are usually aggressive tumours that often
present with secondary deposits. The outcome is generally poor. Only basal cell
carcinoma is seen as a low-grade carcinoma.

[Keratoacanthoma? Better to say "squamous cell carcinoma, keratoacanthoma type"][Article in French] Cribier B. Ann Dermatol Venereol. 2008 Aug-Sep;135(8-9):541-6.

Skin cancer in organ transplant recipients–where do we stand today? Ulrich C, Kanitakis J, Stockfleth E, Euvrard S. Am J Transplant. 2008 Nov;8(11):2192-8. Epub 2008 Sep 8.

Skin cancers are the most frequent malignancies in organ transplant recipients
(OTR), with 95% being nonmelanoma skin cancers (NMSC), especially squamous (SCC)
and basal cell carcinomas. Most OTR with a first SCC subsequently develop
multiple NMSC within 5 years, highlighting the concept of ‘field cancerization’,
and are also at high risk for noncutaneous cancers. In order to reduce the tumor
burden in these patients, their management requires an interdisciplinary approach
including revision of immunosuppression, new dermatological treatments and
adequate education about photoprotection in specialized dermatology clinics for
OTR. Whereas surgery remains the gold-standard therapy for NMSC, noninvasive
methods have shown promising results to treat superficial keratoses and
subclinical lesions on large body areas. Although the threshold of skin cancer
necessitating revision of immunosuppression is debated, this measure should be
envisaged at the occurrence of the first SCC, or in case of multiple non-SCC
NMSC. While the role of immunosuppressants in the occurrence of NMSC is widely
recognized, the best immunosuppressive strategies remain to be defined.
Presently, randomized prospective studies assess the burden of new skin tumors,
as well as graft and patient survival, in patients with one or several NMSC after
the introduction of mTOR (mammalian target of rapamycin) inhibitors.

Targeted therapies in head and neck cancer: past, present and future. Rapidis AD, Vermorken JB, Bourhis J. Rev Recent Clin Trials. 2008 Sep;3(3):156-66.

Head and neck cancers remain a significant health problem globally. The addition
of chemotherapy to radiotherapy for locoregionally advanced squamous cell
carcinoma of the head and neck (SCCHN) has led to improvements in locoregional
disease control and in survival, but is associated with substantial acute and
late toxicities. In recurrent and/or metastatic SCCHN, there have been no
improvements in survival, despite the manipulation of standard therapeutic
regimens and the introduction of newer cytotoxic agents. Over the last decade,
targeted therapies have been increasingly used in a range of solid tumor types.
This article discusses the clinical evidence for the use of a number of targeted
agents in the treatment of locoregionally advanced and recurrent and/or
metastatic SCCHN. The article focuses on the epidermal growth factor receptor
(EGFR) inhibitors, for which the majority of clinical information is available.
These include the monoclonal antibody (MAb) cetuximab and the tyrosine kinase
inhibitors, erlotinib and gefitinib. Clinical data for the vascular endothelial
growth factor (VEGF) inhibitor, bevacizumab, are also presented.

Epigenetic aberrations and targeted epigenetic therapy of esophageal cancer. Zhao R, Casson AG. Curr Cancer Drug Targets. 2008 Sep;8(6):509-21.

Squamous cell carcinoma of the esophagus is one of the ten most frequent
malignancies worldwide, characterized by a striking geographic variation in
incidence. In North America and Europe, there has recently been a marked change
in the epidemiology of this disease, where incidence rates for primary esophageal
adenocarcinoma have increased in excess of any other human solid tumor. Although
the reasons for this are largely unknown, several molecular genetic alterations
have been associated with esophageal tumor progression. In recent years,
epigenetic aberrations have been increasingly recognized as an important
alternative mechanism of carcinogenesis and it is anticipated that substantial
progress in the treatment of esophageal malignancy will likely only be made with
a clearer understanding of esophageal tumor biology. Whereas genetic mutations,
deletions, or allelic losses are fixed and irreversible, epigenetic abnormalities
can potentially be corrected without interfering with the fundamental sequence of
the target gene. Our current understanding of epigenetics in esophageal cancer,
and the potential for targeted epigenetic therapy, will be the subject of this

[Skin cancers after organ transplants] [Article in French] Euvrard S. Presse Med. 2008 Oct;37(10):1475-9. Epub 2008 Sep 4.

Squamous cell carcinoma and basal cell carcinoma are the most common cancers
after transplants, affecting more than half of all patients in the long term. In
the 5 years after a first squamous cell carcinoma, 90 to 100% of transplant
patients subsequently develop multiple skin carcinomas of various types and at
least 20% develop noncutaneous cancers. Management of these patients requires,
beyond the usual dermatologic treatments, a revision of their immunosuppression
regimen to reduce the tumor risk. New immunosuppressants that inhibit the m-TOR
protein (sirolimus and everolimus) appear to offer promising perspectives, and
patients treated with these drugs from the time of their transplantation have
fewer skin cancers than patients with the standard protocols. On the other hand,
the benefit of prescribing them later after the transplant remains to be shown,
because of the frequency of intolerance phenomena. Several prospective French
multicenter studies are currently assessing the effect of replacing
anticalcineurins by sirolimus or everolimus for secondary prevention of skin
cancers in renal or cardiac transplant patients who have already developed skin
cancer. Primary prevention requires that patients be educated about strict sun
protection from the transplant onwards and have a routine annual dermatologic
examination enabling early treatment of lesions.

[Carcinoma of the lips] [Article in French] Ben Slama L. Presse Med. 2008 Oct;37(10):1490-6. Epub 2008 Sep 6.

Epidermoid carcinoma, that is, squamous cell carcinoma of the skin, is the most
common malignant tumor of the lips. It occurs especially in men. Its primary
causes are sun exposure, smoking, and chronic irritation. Leukoplakia is the most
frequent precancerous lesion. Epidermoid carcinoma may appear clinically as a
scaly erosion or an ulceration. Standard treatment is surgical excision with

[Epidermoid (or squamous cell) carcinoma] [Article in French] Perrinaud A. Presse Med. 2008 Oct;37(10):1485-9. Epub 2008 Sep 3.

Cutaneous epidermoid carcinomas are common cancers that most often affect people
who are elderly or immunocompromised. They may occur anywhere but are found most
often on photoexposed areas because UV rays are a major risk factor for them.
They often develop on precancerous lesions of the skin (actinic keratosis) but
also of the mucous membranes (HPV-induced infections or lichen). Their particular
clinical presentation depends on their site and their cause. Prognosis is
generally good when surgical excision is performed early with a sufficient margin
of healthy tissue. Nonetheless, some advanced forms or with histologic criteria
indicating poor prognosis have a risk of lymph node or distant metastasis and may
require more intense treatment. Their prevention is based on photoprotection and
on dermatologic surveillance of at-risk subjects.

Head and neck tumour immunology: basic concepts and new clinical implications. Topping KP, Fletcher LM, Agada FO, Alhamarneh O, Stafford ND, Greenman J. J Laryngol Otol. 2009 Jan;123(1):9-18. Epub 2008 Sep 2.

An understanding of the immune system and its modes of action is fundamental to
understanding the causes, natural history, management and treatment of many
diseases. As such, a grasp of the principles of immunology is essential for every
physician.This paper represents a succinct overview of the immune system,
discussing the major components in turn, in respect of structure, function and
integrated organisation, in relation to head and neck cancer.

Immunotherapy in head and neck cancer: current practice and future possibilities. Agada FO, Alhamarneh O, Stafford ND, Greenman J. J Laryngol Otol. 2009 Jan;123(1):19-28. Epub 2008 Sep 2.

The survival of patients with head and neck squamous cell carcinoma has changed
little over the last 30 years. However, with recent advances in the fields of
cellular and molecular immunology, there is renewed optimism with regards to the
development of novel methods of early diagnosis, prognosis estimation and
treatment improvement for patients with head and neck squamous cell carcinoma.
Here, we present a critical review of the recent advances in tumour immunology,
and of the current efforts to apply new immunotherapeutic techniques in the
treatment of head and neck squamous cell carcinoma.

[Sentinel node biopsy in vulvar cancer] [Article in French] Douay-Hauser N, Akerman G, Tulpin L, Morel O, Malartic C, Desfeux P, Barranger E. Bull Cancer. 2008 Jul-Aug;95(7):701-6.

In vulvar cancer, lymph node status is a major prognostic factor. Currently, the
reference regarding nodal exploration is the groin lymphadenectomy responsible
for a significant morbidity. The sentinel node technique in breast cancer has
become a standard of care. This technique has been studied for fifteen years in
vulvar cancer, on small numbers because of its low incidence. There is not yet
consensus about its use in practice. This article is a focus on this technology,
its feasibility and the benefits of sentinel node detection applied to vulvar

Head and neck cancer in the betel quid chewing area: recent advances in molecular carcinogenesis. Chen YJ, Chang JT, Liao CT, Wang HM, Yen TC, Chiu CC, Lu YC, Li HF, Cheng AJ. Cancer Sci. 2008 Aug;99(8):1507-14.

Head and neck cancer (HNC) is one of the 10 most frequent cancers worldwide, with
an estimated over 500,000 new cases being diagnosed annually. The overall 5-year
survival rate in patients with HNC is one of the lowest among common malignant
neoplasms and has not significantly changed during the last two decades. Oral
cavity squamous cell carcinoma (OSCC) shares part of HNC and has been reported to
be increasing in the betel quid chewing area in recent years. During 2006, OSCC
has become the sixth most common type of cancer in Taiwan, and it is also the
fourth most common type of cancer among men. It follows that this type of cancer
wreaks a high social and personal cost. Environmental carcinogens such as betel
quid chewing, tobacco smoking and alcohol drinking have been identified as major
risk factors for head and neck cancer. There is growing interest in understanding
the relationship between genetic susceptibility and the prevalent environmental
carcinogens for HNC prevention. Within this review, we discuss the molecular and
cellular aspects of HNC carcinogenesis in Taiwan, an endemic betel quid chewing
area. Knowledge of molecular carcinogenesis of HNC may provide critical clues for
diagnosis, prognosis, individualization of therapy and molecular therapeutics.

Molecular pathology of head and neck cancer: implications for diagnosis, prognosis, and treatment. Pai SI, Westra WH. Annu Rev Pathol. 2009;4:49-70.

The prototypic head and neck squamous cell carcinoma (HNSCC) arises from the
mucosal lining of the upper aerodigestive tract, demonstrates squamous
differentiation microscopically, involves older men with a long history of
cigarette smoking and alcohol consumption, and is treated by multimodality
therapy. HNSCC has long been regarded as a uniform disease process requiring a
methodical and unwavering therapeutic approach. Divergence in epidemiologic
trends among HNSCCs arising from different anatomic sites has introduced a view
that, morphologic repetition aside, head and neck cancers form a heterogeneous
group. This view has been supported at the molecular genetic level. A more
complete understanding of the molecular genetics of head and neck cancer is
providing new insights into long-held but poorly comprehended concepts such as
field cancerization and is introducing various biomarkers with potential
application for diagnosing, staging, monitoring, and prognosticating HNSCC.

Tumors composed of malignant epithelial and melanocytic populations: a case series and review of the literature. Satter EK, Metcalf J, Lountzis N, Elston DM. J Cutan Pathol. 2009 Feb;36(2):211-9. Epub 2008 Aug 23.

Over the last 30 years, there have been approximately 49 case reports of tumors
composed of both malignant epithelial and malignant melanocytic populations.
Herein, we present four additional cases of combined tumors that consist of two
phenotypically distinct but intermingled populations of malignant cells. Each
tumor was composed of an invasive melanoma closely associated with either a basal
cell carcinoma or a squamous cell carcinoma. We review all previous case reports
in the English literature and attempt to clarify the terminology and summarize
what is currently known about these unique tumors.

Diagnostic problems in anal pathology. Longacre TA, Kong CS, Welton ML. Adv Anat Pathol. 2008 Sep;15(5):263-78.

Anal squamous cell carcinoma and its precursor lesions are increasing in
incidence in the United States and Europe. This trend predates human
immunodeficiency virus/acquired immune deficiency syndrome and has been
associated with persistent high-risk human papilloma virus (HPV) genotype
infection, previous lower genital tract dysplasia/carcinoma, high frequency
anoreceptive intercourse, heavy cigarette smoking, immunosuppression in solid
organ transplant and immune disorders, and human immunodeficiency virus
seropositivity. Screening protocols for at-risk patients are under active
investigation and pathologists are often asked to assess anal canal and perianal
biopsies for the presence of dysplasia and/or invasive carcinoma. Because
underdiagnosis and overdiagnosis of anal cancer and precancer may lead to
inappropriate treatment, it is important for the pathologist to be aware of
current screening strategies, specific risk lesions, and the role of pathology in
initial diagnosis and evaluation of anal biopsy and/or resection specimens.
Standardized histologic criteria and uniform terminology should be used for
reporting all anal canal and perianal squamous intraepithelial lesions. HPV
subtyping, anal cytology, and recently identified biomarkers, such as p16 and
Becton Dickinson ProEx C may provide additional information in problematic cases,
but it is important to be aware of the limitations of these assays. HPV has been
linked to all the major histologic subtypes of anal carcinoma (eg, basaloid,
cloacogenic, transitional, etc.) and this association is strongest for anal canal
lesions. With the possible exception of the microcystic pattern, histologic
subtype does not seem to predict prognosis; and anal squamous cell carcinomas
should be classified as either keratinizing or nonkeratinizing. Poorly
differentiated squamous cell carcinomas have a worse prognosis and should be
distinguished from poorly differentiated adenocarcinoma, melanoma, and
neuroendocrine tumors. Very well differentiated squamous cell carcinoma with
pushing margins (so-called giant condyloma of Buschke and Lowenstein) should be
classified as verrucous carcinoma; this tumor shows aggressive local infiltration
but does not metastasize. As all anal condylomata may harbor foci of high-grade
dysplasia or invasive carcinoma, careful sectioning and complete histologic
examination is required.

Clinical implication and prognostic significance of standardised uptake value of primary non-small cell lung cancer on positron emission tomography: analysis of 176 cases. Al-Sarraf N, Gately K, Lucey J, Aziz R, Doddakula K, Wilson L, McGovern E, Young V. Eur J Cardiothorac Surg. 2008 Oct;34(4):892-7. Epub 2008 Aug 21.

OBJECTIVE: We sought to assess the clinical implication and prognostic
significance of maximum standardised uptake value (SUV(max)) of primary non-small
cell lung cancer (NSCLC) staged by integrated PET-CT. METHODS: A retrospective
review was carried out on 176 consecutive patients with histologically proven
NSCLC who underwent staging with integrated PET-CT prior to curative intent
surgical resection. SUV(max) of primary NSCLC were measured and correlated with
tumour characteristics, lymph node involvement, surgical stage, type of surgical
resection and survival following resection. RESULTS: SUV(max) was significantly
higher in centrally located tumours, tumours > or =4.0 cm, squamous cell subtype,
poorly differentiated tumours, advanced T stage, advanced nodal stage, pleural
invasion, and patients requiring complex surgical resection. SUV(max) value of 15
was the best discriminative cut-off value for survival generated by log-rank
test. When patients were stratified based on this value, those with SUV(max) >15
were more likely to have centrally located tumours, squamous cell subtype,
advanced T stage, advanced nodal stage, advanced American Joint Committee on
Cancer (AJCC) stage, larger tumour size and required more advanced surgical
resections than a simple lobectomy. Overall survival was significantly longer for
patients with SUV(max) < or =15 than those with SUV(max) >15. Furthermore, nodal
stage specific survival following resection (i.e. non-N2 and N2) were
significantly better in patients with SUV(max) < or =15 than SUV(max) >15.
CONCLUSION: SUV(max) correlates with tumour characteristics, surgical stage and
prognosis following resection. SUV(max) may be a useful preoperative tool, in
addition to other known prognostic markers, in allocating patients with
potentially poor prognosis preoperatively to neoadjuvant chemotherapy prior to
resection in order to improve their overall survival. Prospective and randomised
trials are warranted.

Akt pathway as a target for therapeutic intervention in HNSCC. Moral M, Paramio JM. Histol Histopathol. 2008 Oct;23(10):1269-78.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common form of
cancer worldwide. One frequent alteration found in this type of cancer is
overactivation of the PI3K/PTEN/mTOR pathway, of which protein kinase B (PKB)/Akt
is a central key element, controlling important cellular processes such as
metabolism, cell size, proliferation and apoptosis, ultimately regulating cell
growth and survival. Thus, drugs that target Akt directly or elements of the
pathway are plausible candidates for cancer treatment. Accordingly, numerous
clinical trials in various phases are being performed for these drugs. In this
review, we discuss the tumorigenic capacity of Akt and focus on its role in
HNSCC, paying special attention to the current efforts in treating this cancer in
a more specific, Akt-targeted way, based on its primordial role in this type of

Anterior segment manifestations of human immunodeficiency virus/acquired immune deficiency syndrome. Biswas J, Sudharshan S. Indian J Ophthalmol. 2008 Sep-Oct;56(5):363-75.

Ocular complications are known to occur as a result of human immunodeficiency
virus (HIV) disease. They can be severe leading to ocular morbidity and visual
handicap. Cytomegalovirus (CMV) retinitis is the commonest ocular opportunistic
infection seen in acquired immune deficiency syndrome (AIDS). Though posterior
segment lesions can be more vision-threatening, there are varied anterior segment
manifestations which can also lead to ocular morbidity and more so can affect the
quality of life of a HIV-positive person. Effective antiretroviral therapy and
improved prophylaxis and treatment of opportunistic infections have led to an
increase in the survival of an individual afflicted with AIDS. This in turn has
led to an increase in the prevalence of anterior segment and adnexal disorders.
Common lesions include relatively benign conditions such as blepharitis and dry
eye, to infections such as herpes zoster ophthalmicus and molluscum contagiosum
and malignancies such as squamous cell carcinoma and Kaposi’s sarcoma. With the
advent of highly active antiretroviral therapy, a new phenomenon known as immune
recovery uveitis which presents with increased inflammation, has been noted to be
on the rise. Several drugs used in the management of AIDS such as nevirapine or
indinavir can themselves lead to severe inflammation in the anterior segment and
adnexa of the eye. This article is a comprehensive update of the important
anterior segment and adnexal manifestations in HIV-positive patients with special
reference to their prevalence in the Indian population.

Subungual squamous cell carcinoma of the toe: working toward a standardized therapeutic approach. Kelly KJ, Kalani AD, Storrs S, Montenegro G, Fan C, Lee MH, Wallack MK. J Surg Educ. 2008 Jul-Aug;65(4):297-301.

Subungual squamous cell carcinoma (SCC) is a rare malignancy with very few
reported cases that occur on the toe. The etiology of these lesions is not known,
and although this location is generally considered low risk for metastasis, cases
of inguinal lymph node metastasis after toe amputation have been reported.
Patients with subungual disease may meet criteria other than location that
increase their risk for metastasis. Currently, no standardized approach to
therapy for these patients has been established. In this article, we describe a
patient with SCC of the right fourth toe with no clinical evidence of lymph-node
metastasis. This patient underwent toe amputation and has done well for 2.5 years
with no evidence of recurrence. We discuss this case of subungual SCC of the toe
along with others in the literature to propose an optimal standardized approach
for therapy and follow-up. In so doing, we aim to advance medical knowledge of
subungual SCC and to improve patient care.

Concurrent chemoradiation for locally advanced squamous cell carcinoma of the vagina: case series and literature review. Nashiro T, Yagi C, Hirakawa M, Inamine M, Nagai Y, Sakumoto K, Tamaki W, Ogawa K, Toita T, Aoki Y. Int J Clin Oncol. 2008 Aug;13(4):335-9. Epub 2008 Aug 15.

BACKGROUND: We reviewed our experience with patients with primary squamous cell
carcinoma of the vagina who received concurrent chemoradiation therapy (CCRT).
METHODS: We retrospectively analyzed six patients (median age, 60 years) with
squamous cell carcinoma of the vagina who underwent CCRT between 2002 and 2005 at
the University of the Ryukyus Hospital. Two patients were in International
Federation of Obstetricians and Gynecologists (FIGO) stage II, one in stage III,
and three in stage IVA. All patients had an Eastern Cooperative Oncology Group
(ECOG) performance status of 2 or less. Tumor size ranged from 3.2 to 7.7 cm. All
patients were treated with true pelvic external-beam radiotherapy (EBRT) at 50
Gy. Then two of the six patients underwent intracavitary vaginal brachy-therapy.
The remaining four patients received boost EBRT with shrinking fields. Total
radiation dose to the vaginal tumor ranged from 60 to 66 Gy. All patients
received two or three concomitant cycles of cisplatin during EBRT. RESULTS: All
six patients completed their scheduled CCRT, and achieved a clinical complete
response. One stage II patient died of disease 24 months after treatment, and the
stage III patient had local failure at 12 months. The remaining four patients
were free of their disease at 18, 23, 33, and 55 months, respectively. One
patient with stage IVA developed a vesicovaginal fistula during CCRT.
Nevertheless, CCRT was well tolerated by all six patients, and no grade 3 or 4
late toxicity was observed, as evaluated by the Radiation Therapy Oncology Group
(RTOG) scoring system. CONCLUSION: CCRT is effective for primary squamous cell
carcinoma of the vagina and should be considered for treatment in patients with
high-risk disease having good performance status.

Multidisciplinary management of locally advanced SCCHN: optimizing treatment outcomes. Ang KK. Oncologist. 2008 Aug;13(8):899-910. Epub 2008 Aug 13.

The management of locally advanced squamous cell carcinoma of the head and neck
(LA-SCCHN) is highly complex. Data from recent clinical trials have altered the
treatment landscape by refining the use of existing therapies, such as radiation
therapy and chemotherapy, and providing new treatment options, such as cetuximab.
Selecting the most appropriate treatment for an individual patient requires a
multidisciplinary approach and careful assessment of the relative advantages and
disadvantages of each treatment approach. Surgery is highly effective but can
have debilitating long-term consequences. Chemoradiation and altered
fractionation radiation therapy are more effective than conventional radiation
therapy, but also more toxic; as a consequence of toxicity, suboptimal delivery
of radiation may diminish, in practice, the efficacy observed in clinical trials
of these strategies. Cetuximab plus radiation therapy is more effective than
radiation alone and does not substantially increase radiation-related toxicity,
or affect the delivery of planned radiotherapy. However, whether cetuximab plus
radiation therapy is similar in efficacy to chemoradiation is unknown at this
time. Ideally, multidisciplinary teams weigh all these factors when making
individual treatment decisions. Data from current trials will help further
optimize multimodality treatment for LA-SCCHN.

Radiation treatment breaks and ulcerative mucositis in head and neck cancer. Russo G, Haddad R, Posner M, Machtay M. Oncologist. 2008 Aug;13(8):886-98. Epub 2008 Aug 13.

Unplanned radiation treatment breaks and prolongation of the radiation treatment
time are associated with lower survival and locoregional control rates when
radiotherapy or concurrent chemoradiotherapy is used in the curative treatment of
head and neck cancer. Treatment of head and neck cancer is intense, involving
high-dose, continuous radiotherapy, and often adding chemotherapy to
radiotherapy. As the intensity of treatment regimens has escalated in recent
years, clinical outcomes generally have improved. However, more intensive therapy
also increases the incidence of treatment-related toxicities, particularly those
impacting the mucosal lining of the oral cavity, pharynx, and cervical esophagus,
and results in varying degrees of ulcerative mucositis. Ulcerative mucositis is a
root cause of unscheduled radiation treatment breaks, which prolongs the total
radiation treatment time. Alterations in radiotherapy and chemotherapy, including
the use of continuous (i.e., 7 days/week) radiotherapy to ensure constant
negative proliferative pressure, may improve efficacy outcomes. However, these
approaches also increase the incidence of ulcerative mucositis, thereby
increasing the incidence of unplanned radiation treatment breaks. Conversely, the
reduction of ulcerative mucositis to minimize unplanned breaks in radiotherapy
may enhance not only tolerability, but also efficacy outcomes. Several strategies
to prevent ulcerative mucositis in radiotherapy for head and neck cancer have
been evaluated, but none have demonstrated strong efficacy. Continued
investigation is needed to identify superior radiation treatment regimens,
technology, and supportive care that reduce unplanned radiation treatment breaks
with the goal of improving clinical outcomes in head and neck cancer.

Management of gingivobuccal complex cancer. Misra S, Chaturvedi A, Misra NC. Ann R Coll Surg Engl. 2008 Oct;90(7):546-53. Epub 2008 Aug 12.

INTRODUCTION: Squamous cell carcinoma of the oral cavity ranks as the 12th most
common cancer in the world and the 8th most frequent in males. It accounts for up
to one-third of all tobacco-related cancers in India. Cancer of the gingivobuccal
complex is especially common in Indians due to their tobacco habits. This review
focuses on the management of lower gingivobuccal complex cancers. PATIENTS AND
METHODS: References for this review were identified by search of Medline and
other bibliographic information available in the PubMed database. The search
terms carcinoma oral cavity, and cancer oral cavity, buccal mucosa, gingiva,
gingivobuccal complex, and alveolus cancer/carcinoma were used. References from
relevant articles and abstracts from international conferences were also
included. Only articles published in the English language were used. RESULTS:
Treatment of gingivobuccal complex cancer is primarily surgical. Radical neck
dissection, or its modification, is the standard treatment for the node-positive
neck. Supraomohyoid neck dissection is the accepted treatment for the
node-negative neck. Radiotherapy is usually not the preferred modality of
treatment for early gingivobuccal complex cancer. It is used either as
postoperative adjuvant treatment or as definitive treatment for advanced cancer
with or without chemotherapy. Chemotherapy has been used as neo-adjuvant,
adjuvant or palliative treatment. Advanced cancers are common and continue to
pose a challenge to the multidisciplinary team. CONCLUSIONS: Gingivobuccal
complex cancer remains a major public health problem despite being highly
preventable and easily detectable. Advanced cancers constitute a major proportion
of patients presenting for treatment. These patients are difficult to treat and
have a poor outcome.

[Tumor markers and biomarkers in squamous cell cancer of the head and neck] [Article in German] Lordick F, Krauss J, Jäger D. HNO. 2008 Sep;56(9):881-5.

The early detection of recurrences after surgical or radiation treatment of
squamous cancers of the head and neck is often difficult. A rise in circulating
tumor marker levels such as SCCA and CEA often precedes the clinical appearance
of recurrences by about several months. The combined analysis of SCCA and CEA can
facilitate the early detection of local relapse or distant recurrence and can
therefore accelerate specific diagnostic and/or therapeutic procedures.
Therefore, after primary therapy of locally advanced head and neck cancers, the
combined analysis of SCCA and CEA normally every 3-6 months can be recommended.
Molecular markers give increasing insight into tumor biology, prognosis and
response to chemotherapy, radiation and molecular targeted therapies. Biomarkers
require a careful validation before being implemented into clinical decision
making, but promising markers such as EGFR, p53 and HPV oncogene may become
important stratification factors for individualized tumor treatment algorithms.

Controversies in the management of oropharynx cancer. Worden FP, Ha H. J Natl Compr Canc Netw. 2008 Aug;6(7):707-14.

Squamous cell carcinomas of the oropharynx account for approximately 25% of all
head and neck squamous cell malignancies. Most patients present with locally
advanced tumors and require a multimodality approach to treatment, with input
from qualified surgeons and radiation and medical oncologists. For organ
preservation, concurrent chemoradiotherapy is usually preferred over surgery with
adjuvant radiotherapy. Controversies regarding management of particular
populations of locally advanced oropharyngeal tumors exist, including whether to
include induction chemotherapy before chemoradiation, the use of biologic agents
as radiation sensitizers, and how best to manage the neck after definitive
treatment. Additionally, infection with human papilloma virus (HPV), particularly
HPV-16, is now an established risk factor for head and neck cancer. Most cases
involve the oropharynx, and prognosis seems to be much better than for patients
with non-HPV- and tobacco-related tumors. Given the distinct differences between
these HPV and non-HPV-related cancers, controversy also exists regarding the
management of these patient populations, with the concern that HPV-related
malignancies may be overtreated. Unfortunately, these and other questions
concerning the management of locally advanced oropharyngeal cancers are
outstanding. Hence, it is critical that eligible patients are screened for and
encouraged to participate in clinical trials.

The role of inhibitors of the epidermal growth factor in management of head and neck cancer. Brockstein B, Lacouture M, Agulnik M. J Natl Compr Canc Netw. 2008 Aug;6(7):696-706.

Epidermal growth factor receptor (EGFR) is overexpressed in most head and neck
cancers and correlates with poor prognosis. In the past few years, numerous
clinical trials for head and neck cancer have tested monoclonal antibodies
against EGFRs and small molecule inhibitors of EGFR tyrosine kinase. Results led
to FDA approval of cetuximab with concomitant radiotherapy for treating locally
or regionally advanced squamous cell carcinoma of the head and neck (SCCHN), and
as a single agent in patients with recurrent or metastatic SCCHN for whom prior
platinum-based therapy failed. This article reviews the biology of EGFR as it
pertains to head and neck cancer, including the important clinical trials of EGFR
monoclonal antibodies and tyrosine kinase inhibitors in SCCHN, alone and with
concomitant radiotherapy. Molecular and clinical markers of response and outcome
are also discussed.

An unusual skin nodule. Over the past 2 months, the patient lost 20 pounds and noticed “bumps” on her body. Kasper DA, Saxena A. J Fam Pract. 2008 Aug;57(8):537-8.

Biomarkers in cervical precancer management: the new frontiers. Khan AM, Singer A. Future Oncol. 2008 Aug;4(4):515-24.

The major cause of cervical cancer and its pre-invasive lesions is persistent
infections with oncogenic human papillomavirus (HPV). Viral replication and
integration in the cervix depends on the ordered expression of viral gene
products, which can lead to overexpression of multiple molecular proteins or
biomarkers. These novel biomarkers allow the monitoring of essential molecular
events in histological or cytological specimens and are likely to improve the
detection of lesions that have a high risk of progression in both primary
screening and triage settings. This review focuses on these molecular markers and
their role in the diagnosis and management of cervical dysplasia and cancer.

Multimedia article. Laparoscopic ultralow anterior resection with colonic J-pouch-anal anastomosis. Selvindos PB, Ho YH. Dis Colon Rectum. 2008 Nov;51(11):1710-1. Epub 2008 Aug 5.

PURPOSE: Optimal treatment of mid to distal rectal cancers includes total
mesorectal excision for oncologic clearance and, where reanastomosis is feasible,
a colonic J-pouch-anal anastomosis improves bowel function. There is recent
interest in performing an ultralow anterior resection laparoscopically. A
technique is described that includes specimen extraction through the eventual
routine defunctioning colostomy or ileostomy site. METHODS: Consecutive
unselected patients who underwent laparoscopic ultralow anterior resection were
recruited. Patients with adenocarcinoma underwent preoperative endorectal
ultrasound to individualize for neoadjuvant chemoradiotherapy, based on local
extent and lymph nodes seen. The operative procedures were as shown in the video.
Posterior dissection along the “total mesorectal excision plane” included
incision of Waldeyer’s fascia. Bowel continuity was restored by an intracoporeal
double-cross stapled colonic J-pouch-anal anastomosis, but where not possible a
coloplasty with pull-through handsewn coloanal anastomosis was performed.
RESULTS: Laparoscopic ultralow anterior resection was performed on 55 patients
(35 men; median age, 63 (range, 33-90) years) from March 2004 to October 2006.
The median body mass index was 26.3 (19-38); 14 patients (25 percent) had a body
mass index >30. Ten patients (18 percent) had an American Society of
Anesthesiologists’ classification of III. The indications were adenocarcinoma (n
= 51), squamous-cell carcinoma of rectum (n = 1), dermoid tumor of mesorectum (n
= 1), large villous adenoma (n = 1), and carcinoid with local lymph node
metastases (n = 1). The adenocarcinomas were a median distance of 6 (3-12) cm
from the anal verge. Neoadjuvant radiotherapy was given in 12 patients (24
percent) who had preoperative endoanal ultrasound findings of tumor extension
beyond the muscularis propria and chemoradiotherapy in 7 (14 percent) of these
patients where the tumor was more bulky and fixed. Laparoscopic ultralow anterior
resection was completed at a median 180 (90-405) minutes, with 53.5 (2-2250) ml
of blood loss, and the specimen was extracted through a 4.5 (3.5-11) cm wound.
The latter included three cases (5 percent) that were converted. Significant
adhesiolysis was required in 29 patients (52.7 percent) because of previous
operations. The histologic grading or the adenocarcinoma patients were: Stage I,
n = 14; Stage II, n = 23; Stage III, n = 11; Stage IV, n = 3. Of those who
underwent curative resection (Stages I-III), the distal resection margin was 2.9
+/- 0.7 cm (mean +/- standard error) and the radial resection margins were at
least 2 mm in all patients. The level of the coloanal anastomosis was a median
3.5 (0-4.5) cm from the anal verge; a coloanal pull-through anastomosis was
required in one patient who had a distal cancer. The ileostomies functioned and
patients tolerated free fluids at a median of two (1-9) days, and the median
postoperative hospital stay was seven (3-22) days. At a median follow-up of 14
(2-33) months, none of the adenocarcinoma patients who had undergone curative
resection had recurrences. Four patients (8 percent) had postoperative
complications that required operative/invasive intervention (anatomotic leak n =
1, proximal bowel ischemia n = 1, port site hernia n = 1, pelvic collection n =
1). Four other patients had smaller pelvic collections that resolved with
antibiotics; pelvic collections were associated with advanced stage of cancer (P
= 0.047). Discharge was delayed by acute gastric distension in 11 patients; the
latter was associated with poorer American Society of Anesthesiologists’ risk
classification (P = 0.035). Erectile dysfunction occurred in ten men, and this
was associated with adjuvant chemoradiotherapy (P = 0.042). One patient (2
percent) had persistent urinary retention that required catheterization at latest
follow-up. The ileostomy had been closed in 50 patients, and at last follow-up,
the median stool frequency was two (1-8) bowel movements per day. CONCLUSIONS:
Laparoscopic ultralow anterior resection could be offered routinely and completed
safely in Western populations, where obesity and adhesions from previous
abdominal surgery is common. A laparoscopic technique readily allowed visual
identification of the autonomic nerves in the abdomen over the aorta, which could
then be followed down into the pelvis. If the pelvis was deep, inversion of the
30 degrees laparoscope in the “upside down” position fascilited incision of
Waldeyer’s fascia. This brought the rectum proximally and anteriorly, aiding with
the laparoscopic stapler transection of the distal rectum, especially if the
cancer was distal, the patient was obese, and the pelvis was narrow. Extraction
of the specimen at the eventual defunctioning stoma site reduced the incisions
required. Preoperative chemoradiotherapy may have a role in postoperative male
sexual dysfunction. Further randomized, controlled studies that include assessing
five-year cancer survival/recurrence, pelvic nerve dysfunction, and bowel
function are needed before laparoscopic ultralow anterior resection becomes
widely accepted.

Esophageal cancer: epidemiology, pathogenesis and prevention. [No authors listed] Nat Clin Pract Gastroenterol Hepatol. 2008 Sep;5(9):517-26.

Esophageal cancer is highly aggressive and is a common cancer both worldwide and
in the US. In the past two decades, the incidence and mortality of esophageal
cancer in the US have both increased, where as the incidence and mortality of
other cancers have decreased. Although esophageal squamous cell carcinoma and
esophageal adenocarcinoma differ in their histology and epidemiologic
distribution, some of their risk factors (e.g. dietary deficiencies and tobacco)
and underlying mechanisms of carcinogenesis are the same. Intensive research into
risk factors combined with the ability to identify precursor lesions
(e.g.squamous dysplasia in esophageal squamous cell carcinoma and Barrett’s
esophagus in esophageal adenocarcinoma) has paved the way for studies of
chemoprevention for esophageal cancer, some of which have shown promising

An imaging-based tumour growth and treatment response model: investigating the effect of tumour oxygenation on radiation therapy response. Titz B, Jeraj R. Phys Med Biol. 2008 Sep 7;53(17):4471-88. Epub 2008 Aug 1.

A multiscale tumour simulation model employing cell-line-specific biological
parameters and functional information derived from pre-therapy PET/CT imaging
data was developed to investigate effects of different oxygenation levels on the
response to radiation therapy. For each tumour voxel, stochastic simulations were
performed to model cellular growth and therapeutic response. Model parameters
were fitted to published preclinical experiments of head and neck squamous cell
carcinoma (HNSCC). Using the obtained parameters, the model was applied to a
human HNSCC case to investigate effects of different uniform and non-uniform
oxygenation levels and results were compared for treatment efficacy. Simulations
of the preclinical studies showed excellent agreement with published data and
underlined the model’s ability to quantitatively reproduce tumour behaviour
within experimental uncertainties. When using a simplified transformation to
derive non-uniform oxygenation levels from molecular imaging data, simulations of
the clinical case showed heterogeneous tumour response and variability in
radioresistance with decreasing oxygen levels. Once clinically validated, this
model could be used to transform patient-specific data into voxel-based
biological objectives for treatment planning and to investigate biologically
optimized dose prescriptions.

The biological properties of cetuximab. Vincenzi B, Schiavon G, Silletta M, Santini D, Tonini G. Crit Rev Oncol Hematol. 2008 Nov;68(2):93-106. Epub 2008 Aug 3.

Cetuximab is a recombinant chimeric human murine immunoglobulin G1 antibody that
binds to the extra-cellular domain of epidermal growth factor receptor with a
higher affinity than either endogenous ligand. This binding inhibits receptor
phosphorylation and activation and it leads to receptor internalization and
degradation. Several studies have shown that cetuximab is able to inhibit growth
of epidermal growth factor receptor (EGFR)-expressing tumour cells in vitro.
Moreover, treatment with cetuximab results in a marked inhibition of tumour
growth in nude mice bearing xenografts of human cancer cell lines. These results
are linked to cetuximab biological effects as inhibition of cell cycle, tumour
progression, neo-angiogenesis, invasion and metastatization, as well as increase
and activation of pro-apoptotic molecules. Additionally, cetuximab potentiates,
in combination, the effects of chemotherapy and radiation therapy in eradicating
well-established tumours in nude mice and it may even reverse the resistance to
some cytotoxic agents in these xenografts. Moreover, numerous clinical trials
demonstrated cetuximab efficacy in different tumour types. It has been approved
by Food and Drugs Administration in the treatment of metastatic colorectal cancer
as single agent or in combination with chemotherapy, in locally and regionally
advanced head and neck squamous cell carcinoma in combination with radiation, and
as monotherapy for recurrent and metastatic head and neck squamous cell carcinoma
after failing platinum-based chemotherapy. This paper will overview all the
experimental and pre-clinical data on the biological properties of cetuximab.

Lymph node metastases from auricular squamous cell carcinoma. A systematic review and meta-analysis. Clark RR, Soutar DS. J Plast Reconstr Aesthet Surg. 2008 Oct;61(10):1140-7.

INTRODUCTION: Squamous cell carcinoma arising on the auricle is believed to
metastasise to the regional lymph nodes more frequently than comparable tumours
at other sites. Metastatic spread of these tumours is associated with a poor
outcome but there is no clear consensus of opinion on how to identify patients at
risk of metastatic spread and treat them. MATERIALS AND METHODS: A systematic
review database search of Medline and Embase was conducted with cross referencing
of articles. RESULTS: The metastatic rate is 11.2% with spread to the parotid and
upper deep cervical chain most common. Eighty-five per cent of metastases develop
within 12 months and 98% within 24 months, although follow up was limited to 12
to 36 months in most cases. Death occurs in 6.2% of cases (about half of the
patients who develop metastases) usually due to failure of loco-regional control.
Depth of invasion, tumour size, degree of cellular differentiation and incomplete
primary excision margins may be useful in identifying lesions most at risk of
metastasising but there is insufficient evidence at present to allow targeted
neck dissections.

Narrow-band imaging: a new tool for evaluation of head and neck squamous cell carcinomas. Review of the literature. Piazza C, Dessouky O, Peretti G, Cocco D, De Benedetto L, Nicolai P. Acta Otorhinolaryngol Ital. 2008 Apr;28(2):49-54.

Head and neck squamous cell carcinoma of the upper aerodigestive tract is well
known for its frequently late presentation and diagnosis at an advanced stage. In
addition, it is well recognized that it may arise in multiple sites, either
synchronously or metachronously. Thus it should be imperative to endoscopically
screen the upper aerodigestive tract of patients at risk for head and neck
squamous cell carcinoma with a new diagnostic tool, especially due to the fact
that early lesions are very difficult to detect even by multiple passes with a
standard endoscopy, if they are < or = 1 cm in diameter. Lugol chromoendoscopy,
which is mainly used in the oesophagus, is not suitable for the head and neck
region due to severe mucosal irritation. Herein, narrow-band imaging is
described, a diagnostic tool already proved as a useful screening method in other
endoscopic fields, and its application in the early detection of head and neck
squamous cell carcinoma is reviewed, as reported by previous studies in the
otolaryngologic literature. Narrow-band imaging relies on the principle of depth
of penetration of light, with the narrow-band blue light having a short
wavelength (415 nm) penetrating into the mucosa and highlighting the superficial
vasculature. Furthermore, the blue filter is designed to correspond to the peak
absorption spectrum of haemoglobin to enhance the image of capillary vessels on
surface mucosa. Thus, superficial mucosal lesions that would be missed by regular
white light endoscopy, are identified, in view of their neoangiogenetic pattern
of vasculature, using the blue light of the narrow-band imaging. Narrow-band
imaging has been used extensively in the lower aerodigestive system, yet there
are only 2 reports of applications in the region of the head and neck,
specifically the oropharynx and the hypopharynx. However, these are not the only
sites that can benefit from narrow-band imaging. Herewith, the uses and
importance are highlighted of narrow-band imaging as a future diagnostic tool in
otolaryngology, in the pre-, intra- and post-operative settings.

One-week treatment with once-daily fluorouracil cream 0.5% in participants with actinic keratoses. Menter A, Vamvakias G, Jorizzo J. Cutis. 2008 Jun;81(6):509-16.

Actinic keratoses (AKs) are common in fair-skinned individuals with a history of
chronic and excessive sun exposure and may progress to squamous cell carcinoma
(SCC). Topical fluorouracil is an effective therapeutic option for patients with
AKs, but it is associated with substantial skin irritation. The efficacy and
tolerability of 1-week treatment using microsponge-based fluorouracil cream 0.5%
were analyzed in 356 participants with AK lesions. One-week treatment with
once-daily fluorouracil cream 0.5% was significantly more effective than vehicle
control in reducing AK lesions and in achieving complete clearance (P<.001). No
serious treatment-related adverse events occurred. The most frequent
treatment-related adverse events were facial and eye irritations, which were
predominantly mild to moderate in severity. No participants in the fluorouracil
cream 0.5% treatment group discontinued the study because of treatment-related
adverse events. One-week treatment with once-daily fluorouracil cream 0.5% is an
effective well-tolerated therapy for AKs. Using this short treatment duration
period in combination with cryosurgery may prove beneficial in clinical practice.
Extending treatment for up to 4 weeks will further improve AK lesion clearance

Pictorial review: Unusual tumours involving the prostate: radiological-pathological findings. Chang JM, Lee HJ, Lee SE, Byun SS, Choe GY, Kim SH, Seong CK, Kim SH. Br J Radiol. 2008 Nov;81(971):907-15. Epub 2008 Jul 28.

The appearance of several unusual tumours in the prostate has resulted in
questions being raised concerning their histogenesis; moreover, some of these
tumours have prognoses that are quite unlike those of prostatic adenocarcinoma.
Unusual neoplasms involving the prostate have been described in recent years,
including mucinous cystadenocarcinoma, neuroendocrine cancer, lymphoma, spindle
cell neoplasm, squamous cell carcinoma and transitional cell carcinoma.
Radiological findings can overlap, and play limited roles in the diagnoses of
these entities. However, knowledge of the radiological findings in these
conditions can be helpful in making differential diagnoses. Images of prostate
lesions using several imaging modalities, including transrectal ultrasound, MRI
and CT, as well as available pathological images of such lesions, are presented
in this article.

Biochemical changes of extracellular proteoglycans in squamous cell laryngeal carcinoma. Vynios DH, Theocharis DA, Papageorgakopoulou N, Papadas TA, Mastronikolis NS, Goumas PD, Stylianou M, Skandalis SS. Connect Tissue Res. 2008;49(3):239-43.

Larynx is a complicated organ with peculiar properties, having a noticeable
impact in vocal and respiratory physiology. In squamous cell laryngeal carcinoma,
the extracellular matrix components underwent significant modifications
concerning their fine chemical structure. Degradation of aggrecan is observed,
whereas versican and decorin amounts are increased. The expression of aggrecan is
almost totally ceased in later cancer stages, whereas decorin is expressed in
normal and cancerous samples. But its expression is increased in cancer, being
related to cancer stage. However, the expression of versican seems to be
characteristic of the tumor, since none or traces expression is observed in
normal samples. Chondroitin/dermatan sulfate is the major glycosaminoglycan, but
its sulfation shows a shift from C6 position of galactosamine in normal samples
to C4 in malignancy. Dermatan sulfate represents minor amounts in normal samples
but increases in proportion up to one-fourth of total sulfated glycosaminoglycans
in malignancy. In addition, an increase in the amounts of hyaluronan is also
observed in malignant samples. Accumulated data demonstrate that tumor
progression is closely related to the alteration of the expression and
biochemical composition of specific extracellular constituents that describes the
mild aggressive phenotype of squamous cell laryngeal carcinoma.

Lower-extremity burn reconstruction in the child. Barbour JR, Schweppe M, O SJ. J Craniofac Surg. 2008 Jul;19(4):976-88.

Lower-extremity burns in a pediatric patient require special consideration. The
management of burn reconstruction in pediatric patients is often complex,
requiring multiple reconstructive operations, and the primary intention of the
surgeon is to prevent burn scar deformities. Timely management of the burn wound
and postburn scars has decreased the incidence of burn scar deformities and
contractures of the lower extremity in recent years. We present an overview of
the principles of reconstruction techniques using skin grafting and biologic skin
substitutes to restore the important barrier lost secondary to burns. In
addition, we address methods of repairing scar contracture, a common occurrence
in burn patients, at specific locations on the lower extremity. Finally, special
scenarios such as burns associated with fractures, burn injury in insensate
children, and Marjolin ulcer are discussed.

DNA copy number variation and loss of heterozygosity in relation to recurrence of and survival from head and neck squamous cell carcinoma: a review. Chen Y, Chen C. Head Neck. 2008 Oct;30(10):1361-83.

Genetic aberrations, such as DNA copy number variation (CNV) and loss of
heterozygosity (LOH), have been implicated in head and neck squamous cell
carcinoma (HNSCC) initiation and progression. This review examines CNV and LOH as
predictors of HNSCC recurrence and mortality. We searched PubMed for relevant
publications and compared and discussed results from the articles. Certain CNV
and LOH events have consistently been associated with HNSCC recurrence and
survival. The recent high-resolution single nucleotide polymorphism (SNP) arrays
have the potential to identify many more genetic changes and concurrent
genome-wide CNV, copy-neutral and/or allelic imbalance LOH in HNSCC that may bear
on prognosis. Our review confirms that outcome in HNSCC can be predicted to a
considerable extent by the presence of tumor cell genetic aberrations. It points
out the limitations of some methodologies that were used in the past and
discusses the advantages and challenges of using genome-wide SNP arrays.
Copyright (c) 2008 Wiley Periodicals, Inc. Head Neck 2008.

State of head and neck surgical oncology research–a review and critical appraisal of landmark studies. Higgins KM, Wang JR. Head Neck. 2008 Dec;30(12):1636-42.

Surgical literature has been criticized for the lack of high-quality research.
The present review examines methodological quality of literature published in
head and neck surgical oncology. We focus on landmark studies published on topics
of best practice controversy, namely (1) the role of chemotherapy and
organ-preservation protocols in the management of head and neck mucosal
malignancies; (2) the role of selective neck dissection versus radical neck
dissection; and (3) the role of laser microsurgery in the management of larynx
cancer. Similar flaws were evident in selected landmark studies with the major
issue being multiplicity in the form of multiple outcome analysis, comparison of
multiple treatment groups, repeated measures over time, planned interim analyses,
and subgroup analyses. The open nonrandomized controlled trial may be a feasible
option in head and neck surgical research allowing for standardization,
uniformity, consistency, and blinded outcome assessment. (c) 2008 Wiley
Periodicals, Inc.

Pseudoaneurysm of the external carotid artery–review of literature. Nadig S, Barnwell S, Wax MK. Head Neck. 2009 Jan;31(1):136-9.

BACKGROUND: Pseudoneurysms of the carotid artery are rarely encountered in
clinical practice. When encountered they are most likely secondary to acute neck
trauma, and involve the internal carotid. External carotid artery involvement is
very rare. METHODS: We report a case of an external carotid aneurysm following a
neck dissection review the literature and discuss the investigation and
management of these unusual lesions. RESULTS: Incidence is 0.07%, but mortality
can be as high as 30%. Clinical features include swelling and neurological
complications. Diagnosis is with a high index of suspicion and imaging with
duplex ultrasonography and CT angiography. Management options include
observation, anticoagulation, ligation of the carotid artery with or without a
bypass procedure, and arterial reconstruction. CONCLUSION: Early management with
appropriate imaging and treatment to prevent significant mortality and morbidity
is recommended. (c) 2008 Wiley Periodicals, Inc. Head Neck, 2009.

[Brachytherapy of head and neck cancer] [Article in Hungarian] Takácsi Nagy Z, Kásler M. Magy Onkol. 2008 Jun;52(2):145-50.

In the non-surgical treatment of head and neck tumours, the “organ preserving”
modalities have become more and more important. At present radiotherapy is the
most important means of this kind of treatment. In the radiotherapy of head and
neck cancer local dose escalation is an important factor in increasing local
tumour control. However, with sole external beam irradiation it is difficult to
spare adjacent normal tissues. Interstitial brachytherapy (BT) is ideally suited
to deliver a high dose limited to the volume of the primary tumour, thus
maximizing tumour control while minimizing complications. Low-dose-rate (LDR) BT,
which has been applied for a long time in the treatment of these tumours, is now
challenged by high-dose-rate (HDR) and pulsed-dose-rate (PDR) BT. The purpose of
this work is to show the role and the indications of BT in tumours of the head
and neck region and to offer general and site-specific recommendations based upon
the available information from the literature.

[Mitochondrial DNA mutations in the pathogenesis in the head and neck squamous cell carcinoma] [Article in Polish] Pietka G, Kukwa W, Bartnik E, Scińska A, Czarnecka AM. Otolaryngol Pol. 2008;62(2):158-64.

Data reported until today suggested a pivotal role of nuclear DNA mutations in
the process of carcinogenesis. Recently more and more authors claim that
disruption of mitochondrial DNA should not be excluded from this analysis. mtDNA
have been reported in many cancers of head and neck region. Mitochondrial D-loop
has been proven to be mutation hot – spot with majority of mutations in the
positions 303 to 315 of poly-C tract. Data show that 37% of patients with
premalignant lesions and 62% with carcinoma in situ are positive for mtDNA
mutations. Moreover mutations in genes encoding ND2, ND5, COIII, CYTB, and ATP6
were observed in 17% of patients. Mutations in mitochondrial rRNA genes occured
in similar number of cases. Neoplastic cells undifferentiation and disease
progression is accompanied by multiplication of mtDNA number and increased mtDNA
content. mtDNA content corellates with the stage of the disease. mtDNA mutations
faciliate cell proliferation and inhibit apoptosis by increasing the production
of ractive oxygen species (ROS). Cells harbouring mutated mtDNA have increased
proliferation rate, as increased ROS concentration may act as an endogenous
growth factor.

Contemporary Mohs surgery applications. Minton TJ. Curr Opin Otolaryngol Head Neck Surg. 2008 Aug;16(4):376-80.

PURPOSE OF REVIEW: The incidence of cutaneous malignancies continues to rise and
it is likely that the majority of skin cancers referred to otolaryngologists will
have characteristics that necessitate a more complex and aggressive approach.
Mohs micrographic surgery is a tissue-sparing technique that allows for excision
of cancers under complete microscopic control and thus boasts high cure rates.
This paper reviews the Mohs technique and discusses the current indications for
Mohs surgery in the head and neck. RECENT FINDINGS: For high-risk basal cell and
squamous cell carcinomas, studies continue to report superior cure rates with
Mohs surgery compared with non-Mohs modalities such as standard surgical
excision. Despite several supporting studies, Mohs surgery for melanoma continues
to be controversial in the literature, as histological identification of melanoma
with frozen sections remains challenging despite advances. Other means of margin
control remain popular among non-Mohs surgeons, including frozen section analysis
and, more recently, photodynamic delineation. SUMMARY: For cutaneous malignancies
of the head and neck, Mohs surgery offers the distinct advantages of complete
microscopic margin control coupled with tissue conservation and thus boasts of
high cure rates. It is important for otolaryngologists to understand the
technique and current indications for Mohs surgery.

MicroRNA and oral cancer: future perspectives. Gomes CC, Gomez RS. Oral Oncol. 2008 Oct;44(10):910-4. Epub 2008 Jul 11.

MicroRNAs (miRNAs) are small non-coding RNAs that mediate gene expression at the
post-transcriptional level by degrading or repressing target messenger RNAs
(mRNA). They are about 22 nucleotides in length and regulate mRNA translation by
base pairing to partially complementary sites, predominantly in the 3′
untranslated region (3′ UTR) of mRNA. In this review, we discuss miRNA biogenesis
and function, together with its possible involvement in oral cancer. Despite its
great importance in normal cell development and diseases, a small number of
studies have attempted to investigate miRNA in oral cancer. Overexpression of
oncogenic miRNA may reduce protein products of tumor-suppressor genes. On the
other hand, loss of tumor-suppressor miRNA expression may cause elevated levels
of oncogenic protein. One or both of these alterations could represent new
targets for cancer diagnosis and treatment in the future. Many researchers have
focused on genetic and epigenetic alterations in oral squamous cell carcinoma
cells. The emergence of miRNA knowledge, and its potential interactive action
with such alterations, therefore creates a new understanding of cell

[Topical Mitomycin C as a therapy of conjunctival tumours] [Article in German] Schallenberg M, Niederdräing N, Steuhl KP, Meller D. Ophthalmologe. 2008 Aug;105(8):777-84.

Surgical excision with tumour free margins is the gold standard for squamous cell
and melanocytic tumours of the conjunctiva. In cases of diffuse and extensive
tumours a complete surgical excision is sometimes not possible. Therefore,
alternative or adjuvant therapies are required. Topical chemotherapy with
mitomycin C (MMC) is increasingly finding use in clinical practice. MMC has
several advantages such as good tolerability and mild side effects. Present
studies have shown that mitomycin C is a good option in squamous cell neoplasia
of the conjunctiva. However, further multi-centre studies and long-term follow-up
are needed.The results in treating melanocytic tumours of the conjunctiva with
MMC are less convincing. MMC seems to be an option for the treatment of primary
acquired melanosis (PAM); but, if the tumour is suspicious for melanoma primary
chemotherapy with MMC is obsolete. In these cases MMC can only be used as an
adjuvant therapy, otherwise tumour control is not assured. However, prospective
randomized controlled trials are necessary for a final evaluation of MMC therapy
in melanocytic tumours of the conjunctiva.

Pulmonary preneoplasia. Dacic S. Arch Pathol Lab Med. 2008 Jul;132(7):1073-8.

CONTEXT: Improved screening techniques for lung cancer have resulted in detection
of lesions that are considered to represent precursors of invasive lung
carcinomas. These lesions may cause a diagnostic dilemma particularly on small
biopsy or cytology specimens. Ancillary studies are usually not helpful, and
diagnosis is based on morphology alone. Recognition of these lesions is very
important to prevent potential diagnostic mistakes that may result in inadequate
patient management. Future molecular studies may provide clinically useful
diagnostic and prognostic gene markers. OBJECTIVE: To review currently proposed
morphologic criteria for precursor lesions of non-small cell lung carcinomas
including squamous dysplasias, atypical adenomatous hyperplasia, and diffuse
idiopathic neuroendocrine cell hyperplasia. Major molecular abnormalities are
briefly discussed. DATA SOURCES: Published literature and recent World Health
Organization classification of lung tumors. CONCLUSIONS: Practicing surgical
pathologists must be familiar with morphology of recognized pulmonary
preneoplastic lesions that are more frequently detected radiographically and
subjected to diagnostic procedures. Future understanding of underlying molecular
abnormalities associated with progression of these lesions into invasive lung
carcinoma may result in a development of molecular assays with potential
diagnostic and prognostic importance.

Management of the N0 neck in oral squamous cell carcinoma. Cheng A, Schmidt BL. Oral Maxillofac Surg Clin North Am. 2008 Aug;20(3):477-97.

Oral squamous cell carcinoma (SCC) has an unpredictable capacity to metastasize
to the neck, an event that dramatically worsens prognosis. Metastasis occurs even
in earlier stages when no neck lymph node involvement is clinically detectable
(N0). Management of the N0 neck, namely when and how to electively treat, has
been debated extensively. This article presents the controversies surrounding
management of the N0 neck, and the benefits and pitfalls of different approaches
used in evaluation and treatment. As current methods of assessing the risk for
occult metastasis are insufficiently accurate and prone to underestimation of
actual risk, and because selective neck dissection (SND) is an effective
treatment and has minimal long-term detriment to quality of life, the authors
believe that all patients who have oral SCC, excluding lip SCC, should be
prescribed elective treatment of the neck lymphatics. However, this opinion
remains controversial. Because of the morbidity of radiation therapy and because
treatment of the primary tumor is surgical, elective neck dissection is the
preferred treatment. In deciding the extent of the neck dissection, several
retrospective studies and one randomized clinical trial have shown SND of levels
I through III to be highly efficacious.

[New tumour markers useful in diagnostics and monitoring of cervical cancer] [Article in Polish] Bedkowska GE, Lawicki S, Szmitkowski M. Przegl Lek. 2007;64(12):1022-7.

Cervical carcinoma is the most frequent disease of the female reproductive
organs. The tumour markers may be helpful: in early diagnosis of cervical cancer,
the initial assesment of the extent of the disease, monitoring of tumour growth
or tumour volume reduction, recurrence of cancer, and have been used for
monitoring of the clinical course of chemotherapy and radiotherapy. In this paper
we have focused on the role of new tumour markers, especially cytokines (for
example G-CSF, VEGF) and molecular markers of carcinogenesis (for example Bcl-2
and p53), in comparison to typical tumour markers useful in diagnostic of
cervical cancer such as CA 125, SCC-Ag, TPA, TPS, CYFRA 21-1.

Stage 1B cervical cancer in a pregnant woman at 25 weeks of gestation. González Bosquet E, Castillo A, Medina M, Suñol M, Capdevila A, Lailla JM. Eur J Gynaecol Oncol. 2008;29(3):276-9.

Cervical cancer associated with pregnancy is rare (0.05%), although it is the
most frequently diagnosed malignancy in pregnant women. We present the case of a
28-year-old woman at 25 weeks of gestation diagnosed with Stage 1B cervical
cancer. Treatment was delayed until fetal maturity, and an elective cesarean
section was performed at 33 weeks’ gestation, followed by a total hysterectomy
preserving the ovaries, and a pelvic lymphadenectomy. A review of the literature
on the treatment of cervical cancer during pregnancy relevant to the case
described is also presented.

Cervical cancer associated with genital prolapse–a brief review of the literature and long-term results of successful treatment with radiochemotherapy and surgery in a very frail patient. Reimer D, Sztankay A, Steppan I, Abfalter E, Lunzer H, Marth C, Zeimet AG. Eur J Gynaecol Oncol. 2008;29(3):272-5

BACKGROUND: A case of cervical cancer associated with irreducible procidentia
successfully treated with external beam radiation and extracorporeal HDR-AL with
concomitant chemotherapy followed by obliterative vaginal surgery is reported for
the first time. CASE: A 73-year-old woman presented in frail condition suffering
from a huge, irreducible uterovaginal procidentia combined with a squamous cell
carcinoma of the cervix in FIGO Stage IIa. Successful treatment consisted of
sequential application of combined radiotherapy with concurrent cisplatin
chemotherapy followed by total vaginal hysterectomy and partial colpectomy with
colpocleisis according to the Labhardt method. The five-year follow-up documents
the excellent long-term results with regard to cervical cancer and pelvic floor
stability. CONCLUSION: Especially in patients ineligible for extended surgery,
radiochemotherapy followed by an obliterative surgical approach is feasible
without aberrant wound healing and constitutes a suitable and efficient option
for treating carcinomas of the cervix associated with irreducible genital

Hemolytic uremic syndrome. Camp-Sorrell D. Oncol Nurs Forum. 2008 Jul;35(4):593-6.

Docetaxel in the management of patients with head and neck squamous cell carcinoma. Bernier J, Vrieling C. Expert Rev Anticancer Ther. 2008 Jul;8(7):1023-32.

The taxanes play a significant role in the treatment of various solid tumors of
epithelial origin. Docetaxel is the most extensively studied taxane in
prospective head and neck cancer trials and has been investigated as induction
chemotherapy or in combination with radiotherapy in locally advanced squamous
cell carcinomas of the head and neck (HNSCC) and as palliation in recurrent or
metastatic disease. The data in locally advanced disease are particularly
compelling. Three recently reported randomized trials, carried out in patients
with locally advanced disease who were receiving induction chemotherapy followed
by radiotherapy or chemoradiotherapy, demonstrated that adding docetaxel to the
standard induction regimen of cisplatin/5-fluorouracil (PF) significantly
improved survival compared with PF alone, without significantly increasing
toxicity. On the basis of these trials, docetaxel/PF (TPF) has become the current
standard induction regimen and TPF-based sequential therapy can be considered a
standard treatment alternative to chemoradiotherapy alone in patients with
locally advanced HNSCC. This review article discusses the current developments of
docetaxel-based chemotherapy and the optimal use of this agent in patients with

A practical approach to intraoperative consultation in gynecological pathology. Baker P, Oliva E. Int J Gynecol Pathol. 2008 Jul;27(3):353-65.

The use of frozen section in gynecological pathology has not been emphasized in
the literature to the same degree as in other surgical fields. This review
focuses on the indications, contraindications, and limitations of frozen-section
diagnosis specific to the female genital tract. An intraoperative consultation in
gynecological pathology is indicated (a) to ensure that the tissue sampled is
adequate for diagnosis, (b) to determine the nature of a disease process, (c) to
plan for appropriate ancillary studies, (d) to determine tumor spread, and (e) to
assess the margins. In the ovary, mucinous tumors in particular may present a
challenge and potential for misdiagnosis at the time of frozen section. It is
important to determine the nature of the ovarian involvement, as tumor size
greater than 10 cm or bilateral involvement strongly suggests a metastatic
process. Also, the distinction between ovarian carcinoma and tumors of borderline
malignancy may be difficult in a limited sampling. In the germ cell category, an
important distinction is that of a dysgerminoma from a large cell lymphoma, due
to different treatment regimes. Pregnant and postpartum women present a unique
challenge as the effects of high levels of pregnancy-related hormones may result
in lesions that closely mimic malignancy. Although intraoperative frozen section
should be discouraged as a primary diagnostic procedure for endometrial
carcinoma, it can be very helpful to identify those patients who are at risk for
extrauterine spread and who may require lymphadenectomy. Analysis of a cone
biopsy of the cervix by frozen section may be warranted particularly if the
previous biopsy showed equivocal stromal invasion, an uncertain depth of
invasion, there are issues related to fertility; however, the process is time
consuming and may compromise the permanent sections if the lesion is very small.
Frozen-section diagnosis in squamous cell carcinoma and in Paget disease of the
vulva is infrequently requested as these entities are multifocal resulting in an
inaccurate frozen-section diagnosis. Lastly, intraoperative evaluation of lymph
nodes including the role of sentinel lymph nodes is discussed.

Nuclear E-cadherin immunoexpression: from biology to potential applications in diagnostic pathology. Chetty R, Serra S. Adv Anat Pathol. 2008 Jul;15(4):234-40.

E-cadherin is a well-recognized molecule that is important in cell adhesion. Its
abrogation has been linked to increased invasiveness in several malignancies. The
normal immunohistochemical localization of E-cadherin is the cell membrane,
however, both cytoplasmic and nuclear immunostaining has been reported. Loss of
membrane staining and/or nuclear staining for E-cadherin is seen in 100% of cases
of solid pseudopapillary tumors (SPTs) of the pancreas. In the context of SPT,
E-cadherin staining is of diagnostic use. Nuclear staining has been seen in cases
of pancreatic neuroendocrine tumors, Merkel cell carcinomas, clear cell renal
cell carcinoma, esophageal squamous carcinoma, colorectal and gastric cancer, and
synovial sarcoma. The difference in the staining patterns seen (complete loss vs.
nuclear staining) is due to the type of E-cadherin antibody used. Antibodies
recognizing the extracellular domain show loss of E-cadherin staining in SPT,
whereas the antibody to the cytoplasmic domain results in nuclear staining in all
cases of SPT. Therefore, E-cadherin staining is of diagnostic use in the
immunohistochemical work-up of SPT. Nuclear E-cadherin staining of pancreatic
neuroendocrine tumors identified a subset of cases with more aggressive
potential, whereas nuclear staining of clear cell renal cancers identified a
subset of tumors with a better prognosis. The exact mechanism by which E-cadherin
enters the nucleus is not known but it is likely that it is closely related to
several partner molecules such as beta-catenin, p120, and presenilin-1.

The tyrosine kinase inhibitor cediranib for non-small cell lung cancer and other thoracic malignancies. Nikolinakos P, Heymach JV. J Thorac Oncol. 2008 Jun;3(6 Suppl 2):S131-4.

Cediranib (AZD2171; Recentin, AstraZeneca, Wilmington, Delaware) is a once-daily
oral tyrosine kinase inhibitor that targets vascular endothelial growth factor
receptors 1, 2, and 3, c-KIT, and platelet-derived growth factor receptors. In
preclinical testing it inhibits tumor angiogenesis and inhibits tumor growth in a
wide range of tumor models. Phase 1 studies show cediranib to be generally well
tolerated as monotherapy at doses of 45 mg/d or less, with a pharmacokinetic
profile that supports once-daily oral administration and toxic effects consistent
with those seen in other agents that target the vascular endothelial growth
factor pathway. Encouraging results from phase 1 studies as monotherapy or in
combination with chemotherapy have prompted further investigation in several
thoracic malignancies, including ongoing trials in malignant mesothelioma, small
cell lung cancer, and an ongoing phase 2/3 trial in non-small cell lung cancer
(NSCLC) in combination with chemotherapy. The NSCLC trials include patients with
squamous cell histologic features and treated brain metastases, populations for
which bevacizumab is currently not indicated. These trials will determine whether
cediranib will join the growing armamentarium of therapeutic options for thoracic
malignancies and broaden the number of patients with NSCLC who could potentially
benefit from antiangiogenic therapy.

Free flap transfer in cranio-maxillofacial surgery: a review of the current data. Thorwarth M, Eulzer C, Bader R, Wolf C, Schmidt M, Schultze-Mosgau S. Oral Maxillofac Surg. 2008 Sep;12(3):113-24.

BACKGROUND: The advances of cranio-maxillofacilal surgery are considerably driven
by the evolution of microsurgical techniques. At present, these methods continue
to provide new therapeutic options to the field. Especially, free flap transfer
has evolved to become an integral part of current treatment protocols for head
and neck malignancies. It ensures uneventful wound healing even after previous
radiotherapy and can often preserve form and function. For many patients, this
may lead to a significant improvement in their quality of life. OBJECTIVES: This
review summarizes aspects of tumor therapy, the impact of radiation, and
discusses different techniques of microvascular tissue transfer. DISCUSSION:
Specific advantages in different anatomical sites of the head and neck region are
highlighted in contrast to existing alternatives. Selected cases exemplify the
use of popular transplants. SUMMARY: While planning reconstructions, it is
important to consider both the functional and aesthetic aspects. The best
individual outcome is based on a thoughtful match of available methods to a given
defect and the patient’s condition.

The role of infectious agents in the etiology of ocular adnexal neoplasia. Verma V, Shen D, Sieving PC, Chan CC. Surv Ophthalmol. 2008 Jul-Aug;53(4):312-31.

Given the fact that infectious agents contribute to around 18% of human cancers
worldwide, it would seem prudent to explore their role in neoplasms of the ocular
adnexa: primary malignancies of the conjunctiva, lacrimal glands, eyelids, and
orbit. By elucidating the mechanisms by which infectious agents contribute to
oncogenesis, the management, treatment, and prevention of these neoplasms may one
day parallel what is already in place for cancers such as cervical cancer,
hepatocellular carcinoma, gastric mucosa-associated lymphoid tissue lymphoma and
gastric adenocarcinoma. Antibiotic treatment and vaccines against infectious
agents may herald a future with a curtailed role for traditional therapies of
surgery, radiation, and chemotherapy. Unlike other malignancies for which large
epidemiological studies are available, analyzing ocular adnexal neoplasms is
challenging as they are relatively rare. Additionally, putative infectious agents
seemingly display an immense geographic variation that has led to much debate
regarding the relative importance of one organism versus another. This review
discusses the pathogenetic role of several microorganisms in different ocular
adnexal malignancies, including human papilloma virus in conjunctival papilloma
and squamous cell carcinoma, human immunodeficiency virus in conjunctival
squamous carcinoma, Kaposi sarcoma-associated herpes virus or human herpes
simplex virus-8 (KSHV/HHV-8) in conjunctival Kaposi sarcoma, Helicobacter pylori
(H. pylori,), Chlamydia, and hepatitis C virus in ocular adnexal
mucosa-associated lymphoid tissue lymphomas. Unlike cervical cancer where a
single infectious agent, human papilloma virus, is found in greater than 99% of
lesions, multiple organisms may play a role in the etiology of certain ocular
adnexal neoplasms by acting through similar mechanisms of oncogenesis, including
chronic antigenic stimulation and the action of infectious oncogenes. However,
similar to other human malignancies, ultimately the role of infectious agents in
ocular adnexal neoplasms is most likely as a cofactor to genetic and
environmental risk factors.

Radiotherapeutic management of laryngeal carcinoma. Hristov B, Bajaj GK. Otolaryngol Clin North Am. 2008 Aug;41(4):715-40, vi.

Authors discuss laryngeal lesions, metastases, and relevant anatomy. Outcome of
surgical and radiotherapy in terms of voice preservation is discussed. Radiation
techniques and outcomes for laryngeal cancer are presented along with discussion
of interdisciplinary treatment. Authors review studies and quality of life
outcomes of surviving laryngeal cancer patients.

Laryngeal cancer: diagnosis and preoperative work-up. Chu EA, Kim YJ. Otolaryngol Clin North Am. 2008 Aug;41(4):673-95, v.

Laryngeal carcinoma is the eleventh-most common form of cancer among men
worldwide and is the second-most common malignancy of the head and neck. The
primary functions of the larynx involve phonation, respiration, and deglutition
but it also contributes to taste and smell by allowing the movement of air over
the special sense organs. Thus, loss of laryngeal function affects speech and
swallowing and some of the senses that allow us to enjoy the world. Moreover,
total laryngectomy bypasses the critical humidification function of the upper
aerodigestive tract that renders pulmonary toiletry problematic for these
patients. With relatively little change in mortality since the 1970s, recent
research has focused not only on improving survival but on laryngeal preservation

The molecular genetics of laryngeal cancer. Loyo M, Pai SI. Otolaryngol Clin North Am. 2008 Aug;41(4):657-72, v.

The authors present the clinical relevance of molecular genetics to laryngeal
cancer in terms of helping to develop novel diagnostic, prognostic, and
therapeutic strategies. They discuss how molecular diagnostics can detect
abnormalities in lesions not yet appreciated histologically, and thus detect
early recurrences. Patient management with novel targeted therapies for head and
neck squamous cell carcinoma in the clinical arena is presented, with treatment
options tailored to the individual patient and his or her cancer among them, with
the goal of improving clinical outcomes.

Genetic and environmental factors in head and neck cancer genesis. Báez A. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2008 Apr-Jun;26(2):174-200.

Head and neck squamous cell carcinoma (HNSCC) include squamous cell carcinomas of
the oral cavity, pharynx, and larynx. Epidemiologic data suggest that the
etiology and pathogenesis of HNSCC are influenced by environmental and
lifestyle-related factors, such as tobacco use, ethanol consumption, papilloma
virus infection, dietary factors and exposure to toxic substances. DNA repair
systems and carcinogen-metabolizing enzymes can increase the risk for HNSCC but
no definite causal mechanism has been demonstrated. There are several
well-characterized entities that are associated with risk and prognosis of head
and neck cancer, including Lynch-II syndrome, Bloom syndrome, Fanconi’s anemia,
xeroderma pigmentosum, ataxia telangiectasia, and Li-Fraumeni syndrome. This
review aims to present the current status in our understanding of HNSCC and
highlight controversies relating to the role of several factors in the genesis of
the cancer.

Protein alterations in ESCC and clinical implications: a review. Lin DC, Du XL, Wang MR. Dis Esophagus. 2009;22(1):9-20. Epub 2008 Jun 17.

Esophageal squamous cell carcinoma (ESCC) is the predominant histological subtype
of esophageal cancer in Asia, characterized by high incidence and mortality rate.
Although significant progress has been made in surgery and adjuvant
chemoradiotherapy, the prognosis of the patients with this cancer still remains
poor. Investigation into protein alterations that occurred in tumors can provide
clues to discover new biomarkers for improving diagnosis and guiding targeted
therapy. Hundreds of papers have appeared over the past several decades
concerning protein alterations in ESCC. This review summarizes all the
dysregulated proteins investigated in the disease from 187 published papers and
analyzes their contributions to tumor development and progression. We document
protein alterations associated with tumor metastasis and the transition from
normal esophageal epithelia to dysplasia in order to reveal the most useful
markers for prediction of clinical outcome, early detection, and identification
of high-risk patients for targeted therapies. In particular, we discuss the
largest and most rigorous studies on prognostic implications of proteins in ESCC,
in which cyclin D1, p53, E-cadherin and VEGF appeared to have the strongest
evidence as independent predictors of patient outcome.

[Organ sparing treatment modalities - which type of treatment for which carcinoma?] [Article in German] Kornek GV, Selzer E. Wien Med Wochenschr. 2008;158(9-10):264-9.

Radical surgery followed by postoperative radiotherapy is still the most
effective treatment option for advanced resectable head and neck cancer. It is
therefore of utmost importance to determine the resectability before start of the
treatment. For those patients who suffer from unresectable cancer or refuse to
undergo surgery, alternatives, such as induction-chemotherapy or radiotherapy
plus chemotherapy alone may be offered. Historical studies investigating
alternative treatment protocols were conducted almost 20 years ago. These studies
demonstrated that in approximately 2/3 of all patients with laryngeal and
hypopharyngeal cancer undergoing induction-chemotherapy according to the
PF-protocol (cisplatin plus 5-FU as a continuous infusion) and subsequent
radiotherapy, larynx preservation without negative impact on overall survival
could be achieved. At least three randomized studies have shown a clinical
advantage for a treatment combination consisting of docetaxel or paclitaxel plus
CDDP/5-FU over a historical control regimen containing CDDP/5-FU alone. This
novel combination therefore is currently regarded as the gold-standard for
induction-chemotherapy in advanced head and neck cancer patients. A further
significant addition to the therapeutic armamentarium for the head and neck
radiation oncologist is the recently introduced monoclonal antibody cetuximab. It
was found in a randomized landmark study that addition of cetuximab to
radiotherapy significantly improves local control as well as overall survival of
advanced stage head and neck cancer patients. In light of these recent
developments this review discusses the role of organ sparing treatment protocols
and different levels of evidence with special consideration of tumor

[Surgical treatment options in oropharyngeal cancer] [Article in German] Swoboda H. Wien Med Wochenschr. 2008;158(9-10):249-54.

Therapy of oropharyngeal squamous cell cancer traditionally has been
radiation-based, with surgery mainly in reserve. With increasing depth of local
infiltration and volume of regional metastases the role of surgery in
safeguarding curative chances increases. However, after failed chemoradiation of
oropharynx cancer, few patients are cured by salvage surgery. Thus, primary
surgery with postoperative radiotherapy may be contemplated if circumtances are
favorable. The oropharynx can be approached by transoral, transmandibular or
transcervical routes. Primary surgery is increasingly valuable when resultant
morbidity is decreased as in the case of more elaborated transoral approaches.
Classical approaches also have improved with increasing use of midline
mandibulotomy, marginal mandibulectomy, reconstructive surgery, selective neck
dissection (ND), and rehabilitation. Elective ND is restricted to levels I or II
to III or IV, therapeutic ND is comprehensive (classic or modified radical
depending on capsular integrity), and salvage ND is individualized. Surgery, most
often followed by radiotherapy, in selected cases of oropharynx cancer is an
interesting alternative to chemoradiation, and in advanced disease a facultative
but essential part of multimodal therapy.

[Surgical treatment options for squamous cell carcinoma of the oral cavity] [Article in German] Rasse M. Wien Med Wochenschr. 2008;158(9-10):243-8.

The squamous cell carcinoma of the oral cavity comprises 3% of all new cancer
cases. 10% have a hereditary component. Smokers stand at a 3-fold higher risk
with alcohol as an additive factor. 6 to 10 independent genetic events are
expected to take place until invasive carcinoma occurs. Chromosomal deletion may
also be detected in premalignant lesions. Staging is performed with inspection
including endoscopy, CT- and MR-Scans and biopsy for the primary tumour and
chest-X-ray, CT, Ultrasound and Scintigraphy for the N and M stage routinely.
Therapeutic options that are proven best are radiation or/and surgery for T1 and
T2 stages with a 5-year survival rate between 80% and 100%. Multimodal therapies,
also including chemotherapy for higher stages result in 5-year survival rates
between 55% and 62%. Since recurrence and metastasis have very poor prognosis
sufficient and radical primary therapy is crucial. Palliative chemotherapy may be
applied for functional improvement and pain release without statistical prove for
increased survival rates.

A systematic review and meta-analysis of the role of positron emission tomography in the follow up of head and neck squamous cell carcinoma following radiotherapy or chemoradiotherapy. Isles MG, McConkey C, Mehanna HM. Clin Otolaryngol. 2008 Jun;33(3):210-22.

OBJECTIVES: This review examines the effectiveness of positron emission
tomography (PET) in the detection of recurrent or persistent head and neck
squamous cell carcinoma after radiotherapy or chemoradiotherapy. DESIGN: A
systematic review and meta-analysis of trials of PET for detecting
residual/recurrent head and neck squamous cell carcinoma treated by radiotherapy
or chemoradiotherapy. Trials were quality assessed using the Quality Assessment
of Diagnostic Accuracy Studies tool for assessing diagnostic accuracy studies.
Quantitative data were extracted and a bivariate random effects model used to
calculate pooled sensitivity and specificity. SETTING: Tertiary referral head and
neck centre. PARTICIPANTS: Prospective and retrospective studies, excluding
reviews, which included patients with head and neck squamous cell carcinoma who
had fluorodeoxyglucose PET in the post-treatment phase following primary
treatment by radiotherapy or chemoradiotherapy. MAIN OUTCOMES MEASURES: Quality
assessment, sensitivity, specificity, false positive rates, false negative rates,
positive and negative predictive values. RESULTS: Twenty-seven of 1871 identified
studies were eligible for inclusion. The pooled sensitivity and specificity of
PET for detecting residual or recurrent head and neck squamous cell carcinoma
were 94% [95% confidence interval (CI), 87-97%] and 82% (95% CI, 76-86%)
respectively. Positive and negative predictive values were 75% (95% CI, 68-82%),
and 95% (95% CI, 92-97%) respectively. Sensitivity was greater for scans
performed 10 weeks or more after treatment. CONCLUSIONS: Positron emission
tomography is highly accurate in this role. However it is less sensitive early
after treatment and has poor anatomical detail. PET may reduce the requirement
for check endoscopies and planned neck dissections. A protocol for its use in
post-treatment surveillance is proposed.

HPV in oral squamous cell carcinoma vs head and neck squamous cell carcinoma biopsies: a meta-analysis (1988-2007). Termine N, Panzarella V, Falaschini S, Russo A, Matranga D, Lo Muzio L, Campisi G. Ann Oncol. 2008 Oct;19(10):1681-90. Epub 2008 Jun 16.

INTRODUCTION: In the literature, there exists a wide range of human
papillomavirus (HPV) DNA prevalence for head and neck squamous cell carcinoma
(HNSCC), especially in relation to methods of viral detection and the lesion
site. We estimated the pooled prevalence of HPV DNA in biopsies of HNSCC
generically grouped versus oral squamous cell carcinoma (OSCC) in relation to the
method of viral DNA detection, with the primary end point of verifying if these
two variables (specification of tumour site and method of HPV DNA identification)
influence the datum on HPV assay. METHODS: By means of MEDLINE/PubMED/Ovid
databases, we selected studies examining paraffin-embedded (PE) biopsies of HNSCC
and OSCC. According to the inclusion criteria, 62 studies were analyzed. The
following data were abstracted: sample size, HPV DNA prevalence, methods of
detection [PCR and in situ hybridization (ISH)] and HPV genotypes. After testing
the heterogeneity of the studies by the Cochran Q test, metanalysis was performed
using the random effects model. RESULTS: The pooled prevalence of HPV DNA in the
overall samples (Sigma: 4852) was 34.5%, in OSCC it was 38.1% and in the not
site-specific HNSCC was 24.1%. With regard to the detection method, PCR-based
studies reported a higher prevalence rate than ISH-based rates (34.8, versus
32.9%) especially in the OSCC subgroup (OSCC PCR based: 39.9%). CONCLUSION: These
findings support the assumption that a correct distinction of HNSCC by site,
together with the use of more sensitive HPV DNA detection methods, should be
considered as essential prerogatives in designing future investigations into
viral prevalence in head and neck tumors.

Screening for and diagnosis of oral premalignant lesions and oropharyngeal squamous cell carcinoma: role of primary care physicians. Epstein JB, Gorsky M, Cabay RJ, Day T, Gonsalves W. Can Fam Physician. 2008 Jun;54(6):870-5.

OBJECTIVE; To describe the role that primary care physicians can play in early
recognition of oral and oropharyngeal squamous cell carcinomas (OOSCCs) and to
review the risk factors for OOSCCs, the nature of oral premalignant lesions, and
the technique and aids for clinical examination. QUALITY OF EVIDENCE: MEDLINE and
CANCERLIT literature searches were conducted using the following terms: oral
cancer and risk factors, pre-malignant oral lesions, clinical evaluation of
abnormal oral lesions, and cancer screening. Additional articles were identified
from key references within articles. The articles contained level I, II, and III
evidence and included controlled trials and systematic reviews. MAIN MESSAGE:
Most OOSCCs are in advanced stages at diagnosis, and treatment does not improve
survival rates. Early recognition and diagnosis of OOSCCs might improve patient
survival and reduce treatment-related morbidity. Comprehensive head and neck
examinations should be part of all medical and dental examinations. The head and
neck should be inspected and palpated to evaluate for OOSCCs, particularly in
high-risk patients and when symptoms are identified. A neck mass or mouth lesion
combined with regional pain might suggest a malignant or premalignant process.
CONCLUSION: Primary care physicians are well suited to providing head and neck
examinations, and to screening for the presence of suspicious oral lesions.
Referral for biopsy might be indicated, depending on the experience of examining

SLNB and the importance of micrometastases in vulvar squamous cell carcinoma. Knopp S, Nesland JM, Tropé C. Surg Oncol. 2008 Sep;17(3):219-25. Epub 2008 Jun 16.

With the exception of patients with tumors smaller than 2 cm and infiltration
less than 1mm, standard treatment for squamous cell carcinomas of the vulva
includes ipsi- or bilateral inguinofemoral lymph node dissection. However, with
only 20% of early stage patients presenting with lymph node metastases in the
groin, the majority of these patients do not gain from the procedure, but are at
risk of its complications and detriments. The sentinel lymph node biopsy (SLNB)
method targets the lymph nodes most likely to contain metastasis and has proven
high accuracy in predicting the absence of metastasis in non-sentinel lymph nodes
when found negative on pathologic examination. The SLNB further provides for a
more thorough examination of the harvested lymph nodes and hence increases the
detection of micrometastases. Although the clinical significance of
micrometastases is controversial, reports on patients with micrometastasis
suffering recurrence emerge, making the importance of detecting micrometastases
in the pathologic examination of the sentinel lymph nodes evident. Appreciating
its limitations, the sentinel lymph node procedure shows evidence of evolving
into a feasible and safe procedure in the hands of experienced surgeons,
pathologists and nuclear medicine physicians in early stage vulvar carcinoma
patients. Still, larger multicenter trials are needed to assess its accuracy and

[Anal and anal margin tumors] [Article in French] Chatelain D, Mokrani N, Fléjou JF. Ann Pathol. 2007 Dec;27(6):459-75.

Tumors of the anal canal and anal margin are rare. They may raise specific
problems for the pathologist. Benign tumors mainly consist of condylomas,
cloacogenic polyps and fibro-epithelial polyps. Cancers are infrequent and
consisted of well-differentiated squamous cell carcinoma, or poorly
differentiated basaloid squamous cell carcinoma. The other malignant tumors are
very rare.

Pseudoepitheliomatous, keratotic, and micaceous balanitis: case report and review of the literature. Perry D, Lynch PJ, Fazel N. Dermatol Nurs. 2008 Apr;20(2):117-20.

Pseudoepitheliomatous, keratotic, and micaceous balanitis is a rare condition
involving the skin of the glans penis that occurs in older men, most circumcised
late in life. This condition is of uncertain malignant potential, and has been
associated with progression to verrucous carcinoma and squamous cell carcinoma.
The etiology of this condition is unknown. Treatment depends on severity, and may
range from topical treatment to surgical excision.

Targeting epidermal growth factor receptor and SRC pathways in head and neck cancer. Egloff AM, Grandis JR. Semin Oncol. 2008 Jun;35(3):286-97.

Epidermal growth factor receptor (EGFR), a member of the ErbB family of receptor
tyrosine kinases (RTKs), is highly expressed in head and neck squamous cell
carcinoma (HNSCC) where increased EGFR expression levels in tumors are associated
with decreased survival. HNSCC patient responses to EGFR-targeted monotherapies
in clinical trials, though significant, have been limited. Tumor signaling
pathway components that work in cooperation with EGFR or provide compensation for
the loss of EGFR-initiated signaling will be ideal targets for therapies to be
used in combination with EGFR-targeted agents. Based on the current understanding
of molecular signaling pathways and available agents, ErbB family-targeted and
Src family-targeted agents represent strategies for further exploration. Here, we
discuss agents targeting ErbB and Src family kinases in clinical development,
provide an overview of completed and ongoing clinical trials, and outline a
molecular rationale for combining ErbB- and Src-targeted therapeutics.

Novel imaging approaches to head and neck cancer. Krohn KA, Yeuh B. Semin Oncol. 2008 Jun;35(3):262-73.

An inadequate supply of oxygen, hypoxia, is an important factor contributing to
resistance to treatment in a number of tumor types, including head and neck
cancer. Novel imaging methods have been applied to studies of this important
prognostic factor. Mammalian cells need oxygen to live but O2 also participates
in the cytotoxic effects of ionizing radiation. Hypoxia is often the result of
abnormal blood vessels supplying the tumor, increased diffusion distances to
tumor cells, and reduced O2 transport capacity of the blood. Its consequences are
mediated by a series of hypoxia-initiated genomic changes activating
angiogenesis, glycolysis, and other processes that enable tumor cells to survive
or escape the O2-deficient environment. Hypoxia has been shown to be important in
overall diminished therapeutic response, malignant progression, increased
probability of recurrence, locoregional spread, and distant metastases.
Strategies are being developed to surmount the cure-limiting consequences of
hypoxia, but methods are needed to select patients most likely to benefit from
these new treatments. Even though hypoxia is a common tumor phenotype, it is by
no means universal and is often heterogeneous within an individual patient. This
review considers the biology of hypoxia, its consequences with respect to
treatment, methods for measuring oxygenation in tissues, modern techniques for
imaging of regional hypoxia, and how information about the oxygenation status of
tumors might impact treatment.

New developments in radiation therapy for head and neck cancer: intensity-modulated radiation therapy and hypoxia targeting. Lee NY, Le QT. Semin Oncol. 2008 Jun;35(3):236-50.

Intensity-modulated radiation therapy (IMRT) has revolutionized radiation
treatment for head and neck cancers (HNCs). When compared to the traditional
techniques, IMRT has the unique ability to minimize the dose delivered to normal
tissues without compromising tumor coverage. As a result, side effects from
high-dose radiation have decreased and patient quality of life has improved. In
addition to toxicity reduction, excellent clinical outcomes have been reported
for IMRT. The first part of this review will focus on clinical results of IMRT
for HNC. Tumor hypoxia, or the condition of low oxygen, is a key factor for tumor
progression and treatment resistance. Hypoxia develops in solid tumors due to
aberrant blood vessel formation, fluctuation in blood flow, and increasing oxygen
demands for tumor growth. Because hypoxic tumor cells are more resistant to
ionizing radiation, hypoxia has been a focus of clinical research in radiation
therapy for half a decade. Interest for targeting tumor hypoxia has waxed and
waned as promising treatments emerged from the laboratory, only to fail in the
clinics. However, with the development of new technologies, the prospect of
targeting tumor hypoxia is more tangible. The second half of the review will
focus on approaches for assessing tumor hypoxia and on the strategies for
targeting this important microenvironmental factor in HNC.

Update on molecular diagnostic tests in head and neck cancer. Palka KT, Slebos RJ, Chung CH. Semin Oncol. 2008 Jun;35(3):198-210.

Head and neck cancers (HNCs) include several cancers originating in the upper
airways that represent a variety of histologies. The most common type of HNC is
squamous cell carcinoma (SCC), which is linked to tobacco and alcohol use and to
human papilloma virus (HPV). At present, there are no standard molecular tests
that are routinely used in clinics. This overview will discuss the current
knowledge on molecular markers with the potential to be developed as diagnostic
tests for cancer risk assessment, early detection, clinical response prediction
to specific therapies, and prognosis. These markers are usually based on recent
findings in tumor biology and genetic defects in HNC, and provide information
both independently and in combination with currently available clinical
parameters. In practice, many potential markers are difficult to measure due to
assay variability, lack of standards for the interpretation of assay results, and
incomplete knowledge of the effects on disease biology and response to treatment.
However, there is great enthusiasm for the general concept of using molecular
knowledge for the clinical management of HNC. Although it will be a great
challenge to develop robust and reliable molecular diagnostic tests, the
development of promising assays fueled by advances in science and technology will
continue and will ultimately reach the goal of improving the care of HNC

[Urethral cancer: report of three cases and review of the literature] [Article in French] Thibault F, Mouton A, Sibony M, Cussenot O, Sebe P, Gattegno B, Thibault P, Haab F. Prog Urol. 2008 May;18(5):318-22. Epub 2008 Apr 10.

OBJECTIVE: To review the various clinical forms of female urethral cancer in the
light of three clinical cases with a review of the corresponding treatment
guidelines. METHOD: The authors report three cases of female urethral cancer.
Case 1 consisted of squamous cell carcinoma in a 56-year-old woman with no
particular history. Case 2 was a urothelial tumour arising in a urethral
diverticulum in a 60-year-old smoker. Case 3 was a 69-year-old woman patient with
invasive urothelial carcinoma. RESULTS: Case 1 was treated by segmental
urethrectomy with no adjuvant therapy and a favourable course. Case 2 was treated
by anterior pelvic exenteration with no adjuvant therapy. This patient relapsed
in the form of peritoneal carcinomatosis two years later and died. Case 3 was
initially treated by anterior pelvic exenteration followed by a chemoradiotherapy
combination after local recurrence with a favourable course. CONCLUSION: There
are many clinical presentations and histological forms of female urethral cancer.
Localized distal lesions can be treated by simple circumferential resection. The
treatment of other lesions comprises anterior pelvic exenteration and platinum-
or M-VAC-based chemoradiotherapy. The main prognostic factors for these tumours
are their size, histological type, site and the presence of pelvic lymph node

Cetuximab: its use in combination with radiation therapy and chemo-therapy in the multimodality treatment of head and neck cancer. Wagner TD, Yang GY. Recent Pat Anticancer Drug Discov. 2008 Jun;3(2):76-83.

Dimerization of epidermal growth factor receptor (EGFR) on the cell membrane of
tumor cells has been implicated in triggering a complex signal cascade that leads
to increased tumor proliferation and survival. Cetuximab is a human-murine
chimeric monoclonal antibody designed to target EGFR and competitively inhibit
dimerization by circulating ligands. By this mechanism, it works to prevent this
signal cascade thus hindering tumor proliferation. Cetuximab has been shown in a
randomized phase III clinical trial to significantly increase overall survival
when it is added to radiation therapy in the treatment of locally advanced
squamous cell carcinoma of the head and neck. In this manuscript, the mechanism
of cetuximab with its associated patents is reviewed, with its role with
chemotherapy and radiation in the management of head and neck cancer along with
future directions of this targeted cancer therapy.

Bevacizumab as first-line treatment for advanced non-small cell lung cancer. Socinski MA. Drugs Today (Barc). 2008 Apr;44(4):293-301.

Bevacizumab is a humanized monoclonal antibody (mAb) to vascular endothelial
growth factor (VEGF), a major proangiogenic factor in advanced solid tumors.
Phase I and II trial results suggested that this agent was well tolerated and
could be combined with standard regimens in various solid tumors. An initial
randomized phase II trial in advanced non-small cell lung cancer (NSCLC) yielded
positive results regarding the potential efficacy of this agent in combination
with carboplatin and paclitaxel (CbP). It also identified a safety signal in
patients with squamous histology, who appear to have a higher rate of serious and
potentially life-threatening pulmonary hemorrhage. Because of this observation,
patients with predominantly squamous histology were excluded from the pivotal
phase III trials, as were patients with brain metastases and a history of
significant hemoptysis. Two phase III trials comparing a standard platinum-based
doublet with or without bevacizumab have been reported in advanced NSCLC, both of
which met their primary endpoints. The trial reported by the Eastern Cooperative
Oncology Group (ECOG 4599) was the first to show an overall survival benefit, as
well as a benefit in response rates and progression-free survival resulting from
the addition of bevacizumab to CbP. Certain toxicities were increased when
bevacizumab was added to CbP, including neutropenia, febrile neutropenia,
thrombocytopenia, bleeding (including pulmonary hemorrhage), hypertension and
proteinuria. Bevacizumab is the first targeted therapeutic agent to improve
survival in advanced NSCLC when added to standard chemotherapeutic regimens.

Current aspects of targeted therapy in head and neck tumors. Dietz A, Boehm A, Mozet C, Wichmann G, Giannis A. Eur Arch Otorhinolaryngol. 2008 Jul;265 Suppl 1:S3-12.

This review focuses on the current and upcoming options of targeted therapy
(biologicals) in head and neck squamous cell carcinoma (HNSCC) with special
regard to conceptual integration in future strategies. Epidermal growth factor
receptor (EGFR) is the most prominent candidate for therapeutic targeting because
of its more than 90% expression rate in HNSCC and influence on the regulation of
proliferation, apoptosis, metastasis, angiogenesis and cell differentiation. The
point of view of head and neck surgeons is mainly adjusted to reach a balance
between targeted, minimal ablative surgery and the evidence-based demand of
oncologic accurate surgery with clear margins and, if needed, adjuvant or primary
systemic chemoradiation. Therefore, the long-term effects of chemoradiation
regimens, such as dysphagia, aspiration and laryngeal immobility caused by
fibrosis, are just beginning to be studied and are becoming one of the major
problems in the ongoing treatment of HNSCC. In this context, molecular targeting
biologicals with a different toxicity profile and hopefully less late damage to
functionally important tissues may open new strategies in primary and adjuvant
treatment of HNSCC. Besides cetuximab and other EGFR targeting mAbs, this review
focuses on receptor and non-receptor tyrosine kinase inhibitors, which further
might play a role in the future treatment of HNSCC. To complete the current
picture, the problem of multi drug resistance in cancer progenitor cells,
targeting members of several relevant pathways and novel agents like pemetrexed
and enzastaurin, are discussed in a broader sense of targeted therapy.

Cancer of the esophagus and stomach. Khushalani N. Mayo Clin Proc. 2008 Jun;83(6):712-22.

Upper gastrointestinal tumors involving the esophagus and the stomach are a
serious public health problem worldwide. The West has seen a dramatic increase in
the incidence of gastroesophageal cancers in the past 2 decades. Although Barrett
esophagus has been well characterized, the exact pathway to developing frank
malignancy remains undefined. Current treatments for locoregional disease include
surgery, chemotherapy, radiation therapy, or some combination thereof. Clinical
trials are currently investigating biologic agents that target signaling pathways
in carcinogenesis. Whether this research translates into an improved therapeutic
index remains to be seen. This review provides a comprehensive update to
physicians and residents who contribute to the care of these patients. Studies in
the English language were identified searching PubMed (January 1, 1980, through
February 29, 2008) using the terms esophagus, gastric, carcinoma, adenocarcinoma,
squamous cell, radiation, chemotherapy, surgery, esophagectomy, and targeted

Detection of lymph node micrometastases in patients with squamous carcinoma of the head and neck. Ferlito A, Rinaldo A, Devaney KO, Nakashiro K, Hamakawa H. Eur Arch Otorhinolaryngol. 2008 Oct;265(10):1147-53. Epub 2008 Jun 4.

While the significance of large cervical node metastases in patients with head
and neck squamous carcinomas is well established, the import of a finding of
regional nodal micrometastases (where a micrometastasis is defined as a
metastatic deposit greater than 0.2 mm and not greater than 2.0 mm in greatest
dimension) or isolated tumor cells in those patients is less clearly understood.
Some earlier investigators have suggested that finding micrometastases does not
have an impact on prognosis; some later investigators, however, have taken issue
with this position, arguing that finding either micrometastases or isolated tumor
cells might portend a poorer prognosis for head and neck cancer patients. At this
juncture, it is difficult to advance a single recommendation for handling a
finding of micrometastases or isolated tumor cells. It would be helpful if two
courses of action were followed: first, while the detection of micrometastases
and isolated tumor cells remains an investigatory practice, data should be
collected and analyzed with an eye to discerning whether such findings are indeed
of significance to the individual head and neck cancer patient. Second, rigorous
definitions of micrometastases and isolated tumor cells (such as the definitions
suggested here) should be developed and widely employed so as to permit ready
comparison between the results as they are reported by different investigators.

Recessive dystrophic epidermolysis bullosa. Part 2: care of the adult patient. Abercrombie EM, Mather CA, Hon J, Graham-King P, Pillay E. Br J Nurs. 2008 Mar 27-Apr 9;17(6):S6, S8, S10 passim.

[Treatment and prognosis of oral cancer] [Article in Dutch] de Visscher JG. Ned Tijdschr Tandheelkd. 2008 Apr;115(4):192-8.

Squamous cell carcinoma is the most common variety of malignant oral tumour. Most
commonly oral carcinomas occur at the lateral tongue surfaces and at the anterior
part of the floor of the mouth. If oral cancer is suspected, a dentist will refer
the patient to an oral and maxillofacial surgeon who will perform a biopsy. When
the diagnosis squamous cell carcinoma is established, the patient will be
referred to a multidisciplinary head and neck oncological centre for additional
diagnostics and treatment. Depending upon size, location and extent of the tumour
and the presence or absence of regional metastases, the management may include
surgical excision, radiotherapy or a combination of surgery and radiotherapy. The
prognosis is mainly determined by the size of the tumour and regional lymph node
involvement. Therefore, early detection is of utmost importance.

[Epidemiology, aetiology, and clinical aspects of oral cancer and premalignant lesions] [Article in Dutch] van der Meij EH. Ned Tijdschr Tandheelkd. 2008 Apr;115(4):186-91.

Since oral cancer can be considered to be a relatively rare disease, dental
practitioners will only rarely be confronted with it. Nevertheless, dental
practitioners have a key role to play in the early diagnosis and referral to an
oral and maxillofacial surgeon. The major part of oral cancers are squamous cell
carcinomas, recognizable during routine oral inspection. Early referral is
essential since treatment of small, not yet metastasized cancers have the best
chance of long-term disease-free survival. Moreover, oral carcinoma is often
preceded by white and/or red pre-malignant lesions of the salivary glands. These
can similarly be detected by routine inspection. Here too, dentists play an
important role in recognizing such diseases and referring patients to an oral and
maxillofacial surgeon.

Cancer stem cells as targets for cancer therapy: selected cancers as examples. Hombach-Klonisch S, Paranjothy T, Wiechec E, Pocar P, Mustafa T, Seifert A, Zahl C, Gerlach KL, Biermann K, Steger K, Hoang-Vu C, Schulze-Osthoff K, Los M. Arch Immunol Ther Exp (Warsz). 2008 May-Jun;56(3):165-80. Epub 2008 May 30.

It is becoming increasingly evident that cancer constitutes a group of diseases
involving altered stem-cell maturation/differentiation and the disturbance of
regenerative processes. The observed malignant transformation is merely a symptom
of normal differentiation processes gone astray rather than the primary event.
This review focuses on the role of cancer stem cells (CSCs) in three common but
also relatively under-investigated cancers: head and neck, ovarian, and
testicular cancer. For didactic purpose, the physiology of stem cells is first
introduced using hematopoietic and mesenchymal stem cells as examples. This is
followed by a discussion of the (possible) role of CSCs in head and neck,
ovarian, and testicular cancer. Aside from basic information about the
pathophysiology of these cancers, current research results focused on the
discovery of molecular markers specific to these cancers are also discussed. The
last part of the review is largely dedicated to signaling pathways active within
various normal and CSC types (e.g. Nanog, Nestin, Notch1, Notch2, Oct3 and 4,
Wnt). Different elements of these pathways are also discussed in the context of
therapeutic opportunities for the development of targeted therapies aimed at
CSCs. Finally, alternative targeted anticancer therapies arising from recently
identified molecules with cancer-(semi-)selective capabilities (e.g. apoptin,
Brevinin-2R) are considered.

Immunostimulatory virotherapy using recombinant Sendai virus as a new cancer therapeutic regimen. Yonemitsu Y, Ueda Y, Kinoh H, Hasegawa M. Front Biosci. 2008 May 1;13:4953-9.

The utility of recombinant Sendai virus (rSeV) has been considerably examined
over the last decade as a potent gene transfer candidate in a cytoplasmic gene
expression system. Such risks as excessive immune responses associated with this
virus administration in vivo however have limited its applicability in clinical
settings as is the case with other viral vectors including adenoviruses. In
consequence of extensive assessment on the mechanisms of immune responses against
SeV, we found that ex vivo infection of immature dendritic cells (DCs) with SeV
demonstrates their spontaneous maturation and activation. We applied this result
to create a unique, representative, and powerful agent to activate DCs, namely
rSeV-modified DCs (rSeV/DCs), for use in cancer immunotherapy. Use of this system
in vivo resulted in the induction of efficient antitumor immunity against
vascularized rodent tumors, including melanoma, hepatocellular carcinoma,
neuroblastoma, squamous cell carcinoma, and prostatic cancer, and it even
frequently associated with elimination of those tumors. These results indicate
that rSeV could be a powerful immune booster for DC-based cancer immunotherapy
that is worth investigating further. We propose a conceptual term
“immunostimulatory virotherapy” to describe this new method of cancer therapy
using the rSeV/DCs system.

[Risk factors for cancers of the oral cavity, pharynx (cavity excluded) and larynx] [Article in French] Righini CA, Karkas A, Morel N, Soriano E, Reyt E. Presse Med. 2008 Sep;37(9):1229-40. Epub 2008 May 27.

OBJECTIVE: To review the risk factors for squamous cell carcinoma of the oral
cavity, pharynx, and larynx. METHODS: Review of the literature using the Medline
digital database (1980-2007). Previously published studies or studies not found
in the database were included if relevant. Four types of studies were selected:
(1) epidemiological, (2) toxicologic, (3) clinical, and (4) fundamental research.
Publications concerning cancer of the nasopharynx were excluded. This work is
based upon the ANAES guide for analysis of the literature and rating of
guidelines, published in January 2000. RESULTS: The principal risk factors are
tobacco and alcohol. Other risk factors, particularly infectious (viral) or
environmental (nutritional and occupational), are also involved. From this
analysis we conclude that: (1) most clinical and fundamental publications concern
smoking and alcohol use; (2) studies of other risk factors are relatively old,
especially those concerning nutritional and occupational factors; (3) most
publications have a low level of scientific proof (grade C, levels 3 and 4).
These 3 points explain the delay in the analysis of risk factors for upper
aerodigestive tract (UADT) cancers. CONCLUSIONS: We must make up for this delay
by prospective studies that include very large samples and use thorough and
multivariate statistical analyses to estimate the impact of various toxic
substances on the incidence of UADT cancer. This demands: (1) awareness on the
part of all physicians who manage this type of cancer of the need to ask
questions about exposure to risk factors besides than tobacco and alcohol; (2)
collaboration between these physicians as well as with general practitioners,
epidemiologists, nutritionists, and occupational physicians.

Targeted therapy in advanced non-small-cell lung cancer. Gettinger S. Semin Respir Crit Care Med. 2008 Jun;29(3):291-301.

Molecularly targeted therapies have recently expanded the options available for
patients with advanced non-small-cell lung cancer (NSCLC). Two cancer cell
pathways in particular have been exploited, the epidermal growth factor receptor
(EGFR) and the vascular endothelial growth factor (VEGF) pathway. The former has
emerged as a key regulator of cancer cell proliferation and invasion, and several
EGFR inhibitors have been developed. Erlotinib, a small-molecule inhibitor of the
EGFR intracellular tyrosine kinase, has been found to improve survival compared
with placebo in previously treated patients with advanced NSCLC and is Food and
Drug Administration (FDA)-approved in this setting. Clinical and molecular
predictors of response to erlotinib, such as a history of never smoking and EGFR
gene mutation or amplification, are presently being evaluated to select patients
for earlier therapy with erlotinib. Additional EGFR inhibitors are also being
examined in randomized trials. The VEGF pathway, a key mediator of angiogenesis,
has become an attractive target in multiple malignancies, including lung cancer.
Bevacizumab, a monoclonal antibody to VEGF, received FDA approval for use in
advanced non-squamous-cell NSCLC in 2006 after a phase III trial reported a
significant survival advantage when bevacizumab was added to standard first-line
chemotherapy. Small-molecule inhibitors of the VEGF receptor tyrosine kinase,
such as sunitinib and sorafenib, have also shown promise in phase II trials and
are being further investigated in phase III studies. Because preclinical data
suggest a synergistic effect when VEGF and EGFR inhibitors are combined, the
concurrent use of erlotinib and bevacizumab has additionally been evaluated in a
phase II trial, with encouraging early results suggesting at least equivalent
activity to standard salvage chemotherapy, with less toxicity. Several other
novel agents are being examined, including inhibitors of histone deacteylases and
the 26S proteosome. Research efforts are currently focusing on tailoring such
therapies according to predictive clinical and molecular markers.

[Thyroid carcinoma with thymus-like differentiation (CASTLE): case report and review of the literature] [Article in Portuguese] Rodrigues TA, Quintela AG, Luz RM, López D. Arq Bras Endocrinol Metabol. 2008 Apr;52(3):550-5.

Carcinoma with thymus-like differentiation (CASTLE) is a rare malignant
epithelial tumor which arises on soft tissue of the neck or thyroid gland. It is
important to differentiate CASTLE from primary or metastatic squamous cell
carcinoma of head and neck, and from squamous cell thyroid carcinoma, because it
has a different prognosis. CD5 immunoreactivity might be helpful in CASTLE
diagnosis. CASTLE behaves generally in an indolent fashion, even though it has a
high relapse rate, while the other have a dismal prognosis due its high
dissemination rate. Treatment includes surgical excision and radiotherapy.
Chemotherapy can be offered, although its efficacy is not clear. Authors present
a case of a 52 year-old male that complaints with cough, disphony, asthenia, and
thyroid mass. Thyroidectomy was performed and the pathology revealed a CASTLE.
After radiotherapy and chemotherapy, minimal response was obtained. The authors
intend to discuss the differential pathologic diagnosis and the best therapy of
this indolent but recurrent neoplasm, that demands strict long term follow-up.

Skin cancer in skins of color. Gohara MA. J Drugs Dermatol. 2008 May;7(5):441-5.

Lymph node classification of esophageal squamous cell carcinoma and adenocarcinoma. Tachibana M, Kinugasa S, Hirahara N, Yoshimura H. Eur J Cardiothorac Surg. 2008 Aug;34(2):427-31. Epub 2008 May 23.

The lymphatic channels of the esophagus run vertically along the axis of the
esophagus and some of them drain into the cervical lymph glands upwards and into
the abdominal glands downwards, and the pattern of lymph node metastasis of
esophageal carcinoma is widespread. In various classifications of pattern of
lymphatic spread, four classifications were proposed; location, number, ratio,
and size. No definite survival advantage of aggressive lymph node dissection
during esophagectomy has been proved compared with less dissection. Stage
migration, micrometastasis, and sentinel lymph node concept all make it possible
to individualize surgical management of esophageal carcinoma as a part of various
multimodal treatments. Early diagnosis, standardization of surgery including
routine lymph node dissection, and perioperative management of patients have all
led to better survival rates of esophageal carcinoma.

Fertility preservation in patients with early cervical cancer: radical trachelectomy. Ramirez PT, Schmeler KM, Soliman PT, Frumovitz M. Gynecol Oncol. 2008 Sep;110(3 Suppl 2):S25-8. Epub 2008 May 23.

OBJECTIVES: The goal of this review is to summarize the latest literature on the
subject of radical trachelectomy and fertility outcomes in patients with
early-stage cervical cancer. METHODS: We analyzed the published literature in
search of all articles addressing surgical techniques, intraoperative and
perioperative outcomes, and obstetrical results in patient undergoing radical
trachelectomy for cervical cancer. RESULTS: It is estimated that 43% of all cases
of cervical cancer in the United States are diagnosed in women younger than 45
years of age. As of 2007, a total of 520 patients had been reported to have
undergone a radical vaginal trachelectomy. The majority of patients (60%) had a
diagnosis of squamous cell carcinoma; adenocarcinoma was the second most common
histologic subtype (40%). Data on outcomes after radical abdominal trachelectomy
are less extensive-only approximately 50 cases have been reported worldwide.
Approximately 43% of patients who undergo a radical trachelectomy subsequently
attempt to become pregnant. Seventy percent of these women are successful at
achieving a pregnancy. CONCLUSIONS: Radical trachelectomy is safe and feasible
and pregnancy outcomes are very favorable. All patients interested in future
fertility who are diagnosed with cervical cancer are encouraged to discuss
radical trachelectomy with their physician.

Imaging of the larynx and hypopharynx. Becker M, Burkhardt K, Dulguerov P, Allal A. Eur J Radiol. 2008 Jun;66(3):460-79. Epub 2008 May 20.

The purpose of this article is to review currently used imaging protocols for the
evaluation of pathologic conditions of the larynx and hypopharynx, to describe
key anatomic structures in the larynx and hypopharynx that are relevant to tumor
spread and to discuss the clinical role of Computed Tomography (CT), Magnetic
Resonance Imaging (MRI) and PET CT in the pretherapeutic workup and
posttherapeutic follow-up of patients with squamous cell carcinoma of this
region. A detailed discussion of the characteristic neoplastic submucosal
invasion patterns, including extension to the preepiglottic space, paraglottic
space and laryngeal cartilages and the implications of imaging for tumor staging
and treatment planning is provided. The present article also reviews less common
tumors of this region, such as chondrosarcoma, lymphoma, minor salivary gland
tumors and lipoma. As the majority of non-neoplastic conditions do not require
imaging the role of CT and MRI is discussed in some particular situations, such
as to delineate cysts and laryngoceles, abscess formation in inflammatory
conditions, to evaluate laryngeal and hypopharyngeal involvement in granulomatous
and autoimmune diseases, and to evaluate the extent of laryngeal fractures due to
severe blunt trauma.

New directions in head and neck imaging. Shah GV, Wesolowski JR, Ansari SA, Mukherji SK. J Surg Oncol. 2008 Jun 15;97(8):644-8.

Computerized tomography (CT) and magnetic resonance imaging (MRI), positron
emission tomography (PET) and the hybrid modality of PET/CT are sensitive and
reliable tools for detection and staging of head and neck cancers. This article
describes the role of PET/CT in initial staging of head and neck squamous cell
carcinoma, the utility of CT/MR perfusion imaging in qualitative analysis of
tumor tissue, and the usefulness of diffusion weighted MR and dynamic
contrast-enhanced MR imaging in head and neck oncological imaging. Copyright (c)
2008 Wiley-Liss, Inc.

Current status of biomarkers in head and neck cancer. Chang SS, Califano J. J Surg Oncol. 2008 Jun 15;97(8):640-3.

As our understanding of HNSCC increases so has biomarker development. HPV16
integration is a significant marker of favorable prognosis and response to
therapy for HNSCC. EGFR-amplification and overexpression is a poor-prognostic
indicator. For premalignant lesions, LOH of 3p&9p21 loci confers an elevated risk
of malignant transformation. As molecular targets are identified, these will be
candidates for biomarkers for detection, diagnosis, prognosis, and therapy.
Validation of these biomarkers requires demonstration of independence of
significance beyond known biomarkers. Copyright (c) 2008 Wiley-Liss, Inc.

Chemotherapy in the treatment of locally advanced head and neck cancer. Forastiere AA. J Surg Oncol. 2008 Jun 15;97(8):701-7.

Three decades of collaborative research have led to the integration of
platinum-based chemotherapy into the curative management of squamous cell
carcinoma of the head and neck and gains in local-regional control, organ
preservation and survival endpoints. Concomitant cisplatin-based chemotherapy and
radiotherapy is the strategy that has proven most effective for organ
preservation for larynx and oropharynx cancers, the treatment of unresectable
disease, nasopharyngeal cancer and the post-operative adjuvant treatment of
patients at high risk of recurrence. The evolution of current indications for
this multimodality approach is reviewed and current areas of investigation
discussed. Nearly all patients with locally advanced head and neck cancer receive
chemotherapy as part of initial curative treatment. The focus of future trials
should be on survival improvement, toxicity reduction and risk stratification for
treatment decision making. Copyright (c) 2008 Wiley-Liss, Inc.

Sentinel node biopsy for squamous cell carcinoma of the head and neck. Civantos F Jr, Zitsch R, Bared A, Amin A. J Surg Oncol. 2008 Jun 15;97(8):683-90.

The clinical utility of sentinel node biopsy for melanoma has led multiple
investigators to apply this approach to other cutaneous malignancies as well as
to early cancers of the upper aerodigestive tract. Data are most extensive for
oral cancer. A multi-institutional pathologic validation trial for selected oral
cancers provided negative predictive values of 96%. Subsequent trials should
document clinical follow-up. This technique may ultimately play a wider role in
the management of mucosal cancers. Copyright (c) 2008 Wiley-Liss, Inc.

[Recent advances in molecular-targeted drugs in head and neck cancer] [Article in Japanese] Tahara M. Gan To Kagaku Ryoho. 2008 May;35(5):745-52.

Recently, the integration of radiotherapy and chemotherapy has advanced the
treatment of locally advanced squamous cell carcinoma of the head and neck
(SCCHN), allowing functional organ preservation while improving locoregional
control and overall survival compared with radiotherapy alone. However, as
recurrences remain inevitable, there is an absolute need for alternative modes of
therapeutic intervention. Moreover, the use of chemotherapy and radiotherapy also
increases the incidence of toxicities such as mucositis, myelosuppression,
xerostomia, and dysphasia. More recently, the use of molecular-targeted drugs,
which minimally adds to the existing toxicities, along with cytotoxic drugs and
radiotherapy has been intensively investigated. Cetuximab is a chimeric IgG1
monoclonal antibody that specifically blocks the epidermal growth factor
receptor. In a randomized trial of radiotherapy with or without cetuximab for
locally advanced SCCHN, the addition of cetuximab significantly improved the
locoregional control and overall survival without an increase in adverse events.
Furthermore, a randomized trial of 5-FU and cisplatin with or without cetuximab
for recurrent/metastatic SCCHN demonstrated a significant survival benefit for
cetuximab combination arms compared with 5-FU and cisplatin arms alone. Based on
these findings, many molecular-targeted drugs have been investigated in the
treatment of the head and neck cancer to ensure better clinical outcomes in the
near future.

[Non-small-cell lung cancer] [Article in Japanese] Akita H, Kinoshita I. Gan To Kagaku Ryoho. 2008 May;35(5):720-4.

Molecular targeted therapy in combination with chemotherapy or thoracic
radiotherapy has been studied in clinical trials. Gefitinib or erlotinib in
combination with standard chemotherapy did not improve efficacy on survival over
standard chemotherapy alone in chemotherapy-naive patients with advanced NSCLC.
On the other hand, bevacizumab in combination with standard chemotherapy improved
survival in chemotherapy-naive patients with advanced NSCLC, excluding squamous
cell carcinoma. Multi-target tyrosine kinase inhibitors in combination with
standard chemotherapy, and anti-EGFR antibodies and EGFR tyrosine kinase
inhibitors in combination with thoracic radiotherapy, are under clinical trials.

Case report. Isolated intrathyroid metastasis from undifferentiated and squamous carcinoma of the head and neck: the case for surgery and re-irradiation. Jankowska P, Teoh EM, Fisher C, Rhys Evans P, Nutting CM, Harrington KJ. Br J Radiol. 2008 Jun;81(966):e154-61.

Metastasis to the thyroid gland is rare, with fewer than 450 cases reported in
the literature. Furthermore, intrathyroid metastasis from head and neck squamous
cell carcinoma (HNSCC) is even more unusual, with only nine previously documented
cases. This study details the cases of three patients (from one centre) who
presented with intrathyroid metastasis from HNSCC and who were treated with a
combination of surgery and radiotherapy. Although previous reports have suggested
that this pattern of spread is associated with a poor outcome, we are able to
show that appropriately selected patients benefit from a combination of both
radical surgery and adjuvant radiation therapy, even when this entails some areas
of re-irradiation.

Squamous cell carcinoma of the lower lip. Hasson O. J Oral Maxillofac Surg. 2008 Jun;66(6):1259-62.

Department of Oral and Maxillofacial Surgery, Kaplan Medical Center, Rehovot,

Head and neck cancer. Argiris A, Karamouzis MV, Raben D, Ferris RL. Lancet. 2008 May 17;371(9625):1695-709.

Most head and neck cancers are squamous cell carcinomas that develop in the upper
aerodigestive epithelium after exposure to carcinogens such as tobacco and
alcohol. Human papillomavirus has also been strongly implicated as a causative
agent in a subset of these cancers. The complex anatomy and vital physiological
role of the tumour-involved structures dictate that the goals of treatment are
not only to improve survival outcomes but also to preserve organ function. Major
improvements have been accomplished in surgical techniques and radiotherapy
delivery. Moreover, systemic therapy including chemotherapy and molecularly
targeted agents–namely, the epidermal growth factor receptor inhibitors–has
been successfully integrated into potentially curative treatment of locally
advanced squamous-cell carcinoma of the head and neck. In deciding which
treatment strategy would be suitable for an individual patient, important
considerations include expected functional outcomes, ability to tolerate
treatment, and comorbid illnesses. The collaboration of many specialties is the
key for optimum assessment and decision making. We review the epidemiology,
molecular pathogenesis, diagnosis and staging, and the latest multimodal
management of squamous cell carcinoma of the head and neck.

TGF-beta and tumors–an ill-fated alliance. Moutsopoulos NM, Wen J, Wahl SM. Curr Opin Immunol. 2008 Apr;20(2):234-40. Epub 2008 May 15.

Mechanisms of host defense can form an unwitting alliance with tumor cells to
promote tumor progression, invasion, and dissemination to distant sites. By
secreting TGF-beta, an immunoregulatory molecule designated for both promoting
inflammation and dampening immune responses, the tumor tricks the host into
supporting its expansion and survival. TGF-beta not only recruits leukocytes to
secrete chemokines, growth factors, cytokines, and proteases in support of a
tumor-friendly niche but also in a context-specific manner, incapacitates the
emergent immune response. As a profound immunosuppressant, TGF-beta, both
directly and through the generation of regulatory T cells, blunts immune
surveillance, favoring tumor escape. Collectively, the ability of the tumor to
hijack these host defense pathways can tip the balance in favor of the tumor.

[Epigenetic aspects in carcinomas of the head and neck] [Article in German] Schmezer P, Plass C. HNO. 2008 Jun;56(6):594-602.

For years, head and neck squamous cell carcinomas (HNSCC) have been among the
leading cancers worldwide. Despite considerable efforts, the 5-year survival rate
for HNSCC has not changed significantly. To improve this situation, it is
necessary to understand the fundamental biological processes leading to the
disease and its progression. In addition to known genetic changes in HNSCC,
molecular cytogenetic investigations have identified chromosomal regions of gains
and losses, but many of the responsible candidate genes have yet to be
identified. Furthermore, recent results indicate the importance of epigenetic
modifications in HNSCC, such as DNA methylation. Several genes, including the
tumor suppressor CDKN2A and other candidates such as DAPK1, MGMT, TIMP3, TCF21,
and C/EBPalpha, have been found to harbor hypermethylated regulatory sequences
that lead to reduced expression or gene silencing. Hypermethylation in such genes
could be used not only as biomarkers for the early detection of HNSCC but also to
improve prevention strategies and therapy outcomes.

Persistent human papillomavirus infection and cervical neoplasia: a systematic review and meta-analysis. Koshiol J, Lindsay L, Pimenta JM, Poole C, Jenkins D, Smith JS. Am J Epidemiol. 2008 Jul 15;168(2):123-37. Epub 2008 May 15.

Detection of persistent cervical carcinogenic human papillomavirus (HPV) DNA is
used as a marker for cervical cancer risk in clinical trials. The authors
performed a systematic review and meta-analysis of the association between
persistent HPV DNA and high-grade cervical intraepithelial neoplasia (CIN2-3),
high-grade squamous intraepithelial lesions (HSIL), and invasive cervical cancer
(together designated CIN2-3/HSIL+) to evaluate the robustness of HPV persistence
for clinical use. MEDLINE and Current Contents were searched through January 30,
2006. Relative risks (RRs) were stratified by HPV comparison group. Of 2,035
abstracts, 41 studies were eligible for inclusion in the meta-analysis. Over
22,500 women were included in calculation of RRs for persistent HPV DNA detection
and cervical neoplasia. RRs ranged from 1.3 (95% confidence interval: 1.1, 1.5)
to 813.0 (95% confidence interval: 168.2, 3,229.2) for CIN2-3/HSIL+ versus
months), wider testing intervals, CIN2-3/HSIL+, and use of an HPV-negative
reference group were consistently associated with higher RRs. Thus, HPV
persistence was consistently and strongly associated with CIN2-3/HSIL+, despite
wide variation in definitions and study methods. The magnitude of association
varied by duration of persistence and testing interval. Precise definition and
standardization of HPV testing, sampling procedure, and test interval are needed
for reliable clinical testing. These findings validate HPV persistence as a
clinical marker and endpoint.

The important role of radiotherapy in patients with non-melanoma skin cancer and other cutaneous entities. Veness MJ. J Med Imaging Radiat Oncol. 2008 Jun;52(3):278-86.

Non-melanoma skin cancer is the commonest malignancy worldwide and a significant
public health issue. Although most non-melanoma skin cancers are small and easily
excised or ablated, a recommendation of definitive radiotherapy is often made in
patients where the outcome (cosmetic and/or functional) will probably be better
with radiotherapy compared to surgery. The aim of adjuvant radiotherapy is to
reduce the risk of loco-regional recurrence and the role of palliative
radiotherapy is important in improving the quality of life in patients with
advanced and/or incurable disease. The aim of this review article is to broadly
discuss the various clinical settings in which a recommendation of radiotherapy
may be made and also includes a discussion on less frequently encountered
cutaneous entities (e.g. in situ squamous cell carcinoma, keratocanthoma, lentigo
maligna, cutaneous lymphomas and malignant fibrous tumours).

T4 endonuclease V: review and application to dermatology. Cafardi JA, Elmets CA. Expert Opin Biol Ther. 2008 Jun;8(6):829-38.

BACKGROUND: T4 endonuclease V was originally isolated from Escherichia coli
infected with T4 bacteriophage. It has been shown to repair ultraviolet
(UV)-induced cyclobutane pyrimidine dimers in DNA, which, when unrepaired,
contribute to mutations that result in actinic keratoses and non-melanoma skin
cancers (NMSC). This is a particular concern in patients with genetic defects in
their DNA repair systems, especially those with xeroderma pigmentosum (XP). When
packaged in liposomes and applied topically, T4 endonuclease V can traverse the
stratum corneum and become incorporated within the cytoplasm and nucleus of
epidermal keratinocytes and Langerhans cells. OBJECTIVE: To review all major
studies evaluating the efficacy of T4 endonuclease V in animals and humans, the
toxicity and safety profile of the topical medication and its potential clinical
uses. METHODS: A literature search was performed through PubMed/Medline, using
the keywords ‘T4N5′, ‘T4 endonuclease V’ and ‘dimericine’. Papers found in the
bibliographies of those identified in the initial search and deemed relevant were
also included. CONCLUSION: This enzyme increases the repair of UV-damaged DNA and
produces other beneficial effects on UV-damaged cells. In clinical trials in XP
patients, topical application of liposome-encapsulated T4 endonuclease V reduced
the incidence of basal cell carcinomas by 30% and of actinic keratoses by > 68%.
Adverse effects were minimal, and there was no evidence of allergic or irritant
contact dermatitis. Although the photoprotective effect of T4N5 has been
investigated only in XP patients, the possibility exists that it may benefit
others likely to develop premalignant keratoses and NMSC, such as organ
transplant recipients receiving immunosuppressive therapy and individuals who
have had numerous psoralen plus UVA photochemotherapy treatments. It may be also
be effective for normal individuals.

Images in HIV/AIDS. The changing face of anal cancer. Romassi M, Nagle D. AIDS Read. 2008 Apr;18(4):185-7.

The use of hyperbaric oxygen therapy to treat chronic wounds: A review. Thackham JA, McElwain DL, Long RJ. Wound Repair Regen. 2008 May-Jun;16(3):321-30.

Chronic wounds, defined as those wounds which fail to proceed through an orderly
process to produce anatomic and functional integrity, are a significant
socioeconomic problem. A wound may fail to heal for a variety of reasons
including the use of corticosteroids, formation of squamous cell carcinoma,
persistent infection, unrelieved pressure, and underlying hypoxia within the
wound bed. Hypoxia appears to inhibit the wound healing process by blocking
fibroblast proliferation, collagen production, and capillary angiogenesis and to
increase the risk of infection. Hyperbaric oxygen therapy (HBOT) has been shown
to aid the healing of ulcerated wounds and demonstrated to reduce the risk of
amputation in diabetic patients. However, the causal reasons for the response of
the underlying biological processes of wound repair to HBOT, such as the
up-regulation of angiogenesis and collagen synthesis are unclear and,
consequently, current protocols remain empirical. Here we review chronic wound
healing and the use of hyperbaric oxygen as an adjunctive treatment for
nonhealing wounds. Databases including PubMed, ScienceDirect, Blackwell Synergy,
and The Cochrane Library were searched for relevant phrases including HBOT,
HBO/HBOT, wound healing, and chronic/nonhealing wounds/ulcers.

Molecular mechanisms of head and neck cancer. Deshpande AM, Wong DT. Expert Rev Anticancer Ther. 2008 May;8(5):799-809.

Despite advances in understanding the underlying genetics, squamous cell
carcinoma of the head and neck (SCCHN) remains a major health risk and one of the
leading causes of mortality in the world. Current standards of treatment have
significantly improved long-term survival rates of patients, but second tumors
and metastases still remain the most frequent cause of high mortality in SCCHN
patients. A better understanding of the underlying genetic mechanisms of SCCHN
tumorigenesis will help in developing better diagnostics and, hence, better
cures. In this article we will briefly outline the current state of diagnostics
and treatment and our understanding of the molecular causes of SCCHN.

Invadopodia: at the cutting edge of tumour invasion. Stylli SS, Kaye AH, Lock P. J Clin Neurosci. 2008 Jul;15(7):725-37. Epub 2008 May 12.

Invasion of tissues by malignant tumours is facilitated by tumour cell migration
and degradation of extracellular matrix (ECM) barriers. Several invasive
neoplasms, including head and neck squamous cell carcinoma, breast carcinoma,
melanoma and glioma, contain tumour cells that can form actin-rich protrusions
with ECM proteolytic activity called invadopodia. These dynamic organelle-like
structures adhere to, and digest, collagens, laminins and fibronectin.
Invadopodia are dependent on multiple transmembrane, cytoplasmic and secreted
proteins engaged in cell adhesion, signal transduction, actin assembly, membrane
regulation and ECM proteolysis. Strategies aimed at disrupting invadopodia could
form the basis of novel anti-invasive therapies for treating patients. Here we
review the molecular basis of invadopodia formation with particular emphasis on
the intracellular signaling networks that are essential for invadopodia activity
and examine the potential role of these structures in glioma invasion.

Perineural tumor spread. Maroldi R, Farina D, Borghesi A, Marconi A, Gatti E. Neuroimaging Clin N Am. 2008 May;18(2):413-29, xi.

Perineural spread (PNS) refers to the extent of tumor cells or other
nonneoplastic lesions along the tissues of the nerve sheath, its overall
incidence ranges from 2.5% to 5%. PNS is more frequently associated with
carcinoma arising from minor or major salivary glands (more often adenoid cystic
carcinoma), mucosal or cutaneous squamous cell carcinoma, basal cell carcinoma,
melanoma, lymphoma, and sarcoma. Although PNS was previously associated with
worsening prognosis, increasing evidence shows that cure is possible. Therefore,
radiologists must be aware of the relevant cranial nerve anatomy and thoroughly
scrutinize not only the nerves close to the primary tumor site but also the whole
neural pathways that can be accessed by PNS. Equally critical is knowledge of the
radiologic appearance of perineural tumor extension and the best imaging
strategies to detect PNS.

Curcumin and cancer: an “old-age” disease with an “age-old” solution. Anand P, Sundaram C, Jhurani S, Kunnumakkara AB, Aggarwal BB. Cancer Lett. 2008 Aug 18;267(1):133-64. Epub 2008 May 6.

Cancer is primarily a disease of old age, and that life style plays a major role
in the development of most cancers is now well recognized. While plant-based
formulations have been used to treat cancer for centuries, current treatments
usually involve poisonous mustard gas, chemotherapy, radiation, and targeted
therapies. While traditional plant-derived medicines are safe, what are the
active principles in them and how do they mediate their effects against cancer is
perhaps best illustrated by curcumin, a derivative of turmeric used for centuries
to treat a wide variety of inflammatory conditions. Curcumin is a
diferuloylmethane derived from the Indian spice, turmeric (popularly called
“curry powder”) that has been shown to interfere with multiple cell signaling
pathways, including cell cycle (cyclin D1 and cyclin E), apoptosis (activation of
caspases and down-regulation of antiapoptotic gene products), proliferation
(HER-2, EGFR, and AP-1), survival (PI3K/AKT pathway), invasion (MMP-9 and
adhesion molecules), angiogenesis (VEGF), metastasis (CXCR-4) and inflammation
(NF-kappaB, TNF, IL-6, IL-1, COX-2, and 5-LOX). The activity of curcumin reported
against leukemia and lymphoma, gastrointestinal cancers, genitourinary cancers,
breast cancer, ovarian cancer, head and neck squamous cell carcinoma, lung
cancer, melanoma, neurological cancers, and sarcoma reflects its ability to
affect multiple targets. Thus an “old-age” disease such as cancer requires an
“age-old” treatment.

Chemo-radiotherapy: an alternative to surgery for squamous cell carcinoma of the rectum–report of six patients and literature review. Rasheed S, Yap T, Zia A, McDonald PJ, Glynne-Jones R. Colorectal Dis. 2009 Feb;11(2):191-7. Epub 2008 May 3.

PURPOSE: Since 1943 [1], only 45 patients of squamous cancer of the rectum have
been reported in the published reports and the largest series to date consists of
12 patients. Reports suggest that the primary treatment is surgical resection
but, in the light of nonsurgical advances in the treatment of anal squamous cell
carcinoma (SCC), we present a review of the literature and report six patients
treated by chemoradiation therapy (CRT). METHOD: A literature search was
undertaken using the keywords squamous cell, epidermoid, basaloid and cloacagenic
and cancer of rectum and colon to provide evidence for this discussion from
studies of surgery, radiation therapy and CRT in rectal SCC. A prospective
database of the Mount Vernon Cancer Centre, UK was searched from 1995 to 2005 for
patients diagnosed with pure SCC of the rectum. RESULTS: Six patients with
histologically confirmed primary SCC of the rectum were treated with primary
combination chemo-radiotherapy according to protocols used for SCC of the anal
canal over a 15-year period. Surgery was avoided in four, and they remain
disease-free on follow-up. CONCLUSIONS: Primary CRT, as currently utilized in
anal cancer, can be extended to primary SCC of the rectum.

Oral and oropharyngeal tumors. Beil CM, Keberle M. Eur J Radiol. 2008 Jun;66(3):448-59. Epub 2008 May 23.

There is a large variability of tumors and tumor-like lesions, which are located
in the oral cavity and oropharynx. But more than 90% of all tumors in this area
are squamous cell carcinomas (SCCs). Other malignancies in this location are
rare. About 10% of all oral and oropharyngeal tumors are benign. Congenital
lesions, like vascular malformations, lingual thyroid or (epi-)dermoid cyst,
usually become present in youth or childhood. Acquired lesions can be
inflammatory (abscess) or neoplastic (pleomorphic adenoma and hemangioma).
Preferred imaging in childhood are ultrasound and magnetic resonance imaging
(MRI), while in adults usually computed tomography (CT) and MRI are more
frequently used.

Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA. Mayo Clin Proc. 2008 May;83(5):584-94.

Lung cancer is the leading cause of cancer-related mortality not only in the
United States but also around the world. In North America, lung cancer has become
more predominant among former than current smokers. Yet in some countries, such
as China, which has experienced a dramatic increase in the cigarette smoking rate
during the past 2 decades, a peak in lung cancer incidence is still expected.
Approximately two-thirds of adult Chinese men are smokers, representing one-third
of all smokers worldwide. Non-small cell lung cancer accounts for 85% of all lung
cancer cases in the United States. After the initial diagnosis, accurate staging
of non-small cell lung cancer using computed tomography or positron emission
tomography is crucial for determining appropriate therapy. When feasible,
surgical resection remains the single most consistent and successful option for
cure. However, close to 70% of patients with lung cancer present with locally
advanced or metastatic disease at the time of diagnosis. Chemotherapy is
beneficial for patients with metastatic disease, and the administration of
concurrent chemotherapy and radiation is indicated for stage III lung cancer. The
introduction of angiogenesis, epidermal growth factor receptor inhibitors, and
other new anti-cancer agents is changing the present and future of this disease
and will certainly increase the number of lung cancer survivors. We identified
studies for this review by searching the MEDLINE and PubMed databases for
English-language articles published from January 1, 1980, through January 31,
2008. Key terms used for this search included non-small cell lung cancer,
adenocarcinoma, squamous cell carcinoma, bronchioalveolar cell carcinoma, large
cell carcinoma, lung cancer epidemiology, genetics, survivorship, surgery,
radiation therapy, chemotherapy, targeted therapy, bevacizumab, erlotinib, and
epidermal growth factor receptor.

Nasopharyngeal carcinoma–review of the molecular mechanisms of tumorigenesis. Chou J, Lin YC, Kim J, You L, Xu Z, He B, Jablons DM. Head Neck. 2008 Jul;30(7):946-63.

Nasopharyngeal carcinoma (NPC) is a head and neck cancer rare throughout most of
the world but common in certain geographic areas, such as southern Asia. While
environmental factors and genetic susceptibility play important roles in NPC
pathogenesis, the Epstein-Barr virus in particular has been implicated in the
molecular abnormalities leading to NPC. There is upregulation of cellular
proliferation pathways such as the Akt pathway, mitogen-activated protein
kinases, and the Wnt pathway. Cell adhesion is compromised due to abnormal
E-cadherin and beta-catenin function. Aberrations in cell cycle are due to
dysregulation of factors such as p16, cyclin D1, and cyclin E. Anti-apoptotic
mechanisms are also upregulated. There are multiple abnormalities unique to NPC
that are potential targets for novel treatments.

Diagnostic utility of p16INK4a: a reappraisal of its use in cervical biopsies. Mulvany NJ, Allen DG, Wilson SM. Pathology. 2008 Jun;40(4):335-44.

p16(INK4a), an indirect marker of cell cycle dysregulation, is commonly expressed
in cervical dysplasias and carcinomas associated with high risk human
papillomavirus (HR-HPV) infections. Although p16(INK4a) immunohistology is
routinely used as a cost effective surrogate marker, many of the published
articles are confusing and contradictory. The discrepancies can be ascribed to a
multitude of factors operating at the molecular, technical and interpretative
levels. In the first place, our simplistic model of viral mediated oncogenesis is
speculative and fails to account for all the known biomolecular changes.
Unresolved technical issues include the variables of tissue fixation, antibody
dilution, antibody isotype and clone, and the sensitivity of the particular
detection method. Within any controlled staining method, strong diffuse or
‘block’ immunoreactivity in squamous cells may be found in moderate/severe
dysplasia (CIN 2/3) and invasive squamous carcinoma. In contrast, focal or
multifocal reactivity in squamous cells may be artefactual, related to low risk
or HR-HPV. p16(INK4a) is less reliable when dealing with glandular lesions since
considerable overlap exists between reactive and dysplastic lesions. In addition
not all glandular dysplasias/carcinomas are HR-HPV related, nor are all
p16(INK4a) immunoreactive lesions associated with HR-HPV. We conclude that
p16(INK4a) immunoperoxidase shows greater specificity than sensitivity for
squamous lesions; in comparison, glandular dysplasias/carcinomas show reduced
specificity and sensitivity. Like all cell cycle regulatory proteins, the future
diagnostic role of p16(INK4a) is limited. The ideal diagnostic molecular test for
cervical dysplasias will detect a HR-HPV related product after, but not before,
cell transformation and will reliably predict those cases yet to experience
disease progression.

Targeted therapy in head and neck cancer: state of the art 2007 and review of clinical applications. Langer CJ.Cancer. 2008 Jun 15;112(12):2635-45.

In patients with squamous cell carcinoma of the head and neck (SCCHN), tumor
recurrence, secondary tumors, and comorbidities contribute to therapy failure,
and treatment approaches often are limited by their toxicity. With the
incorporation of targeted therapies, the number of options available for patients
with SCCHN is growing. The epidermal growth factor receptor (EGFR) is involved in
the development and progression of SCCHN and is associated with a poor prognosis.
The anti-EGFR monoclonal antibody (MoAb) cetuximab is the first targeted therapy
to be developed for SCCHN. Recent data confirmed a survival advantage and
enhanced locoregional control of SCCHN with cetuximab plus radiotherapy (RT) in
patients with locally advanced (LA) SCCHN. Single-agent cetuximab conferred
clinical benefits for patients with platinum-refractory metastatic disease, and a
recent phase 3 trial demonstrated a survival benefit with cetuximab and standard
platinum-based therapy in the front-line treatment of recurrent/metastatic
disease. Cetuximab has a toxicity profile milder than that of cytoxic agents and
does not exacerbate RT toxicity when it is used in combination. Small-molecule
EGFR-tyrosine kinase inhibitors also have shown promise in combination with
chemoradiotherapy or as single agents, although they are in earlier stages of
developmental. Other targeted approaches (eg, antiangiogenics) are also under
investigation. Ongoing clinical trials will further define targeted treatment
roles in all stages of SCCHN. Copyright (c) 2008 American Cancer Society.

Cutaneous ultraviolet exposure and its relationship to the development of skin cancer. Rigel DS. J Am Acad Dermatol. 2008 May;58(5 Suppl 2):S129-32.

Skin cancer is becoming an increasingly important public health problem. Multiple
studies have now demonstrated a relationship between ultraviolet exposure and
increased risk of developing skin cancer. However, the specifics of that
association are somewhat different for malignant melanoma, basal cell carcinoma,
and squamous cell carcinoma. A better understanding of the mechanisms that allow
cutaneous ultraviolet radiation to induce neoplasia will result in the
development of better future sun-protection agents and strategies.

Basic evidence of molecular targeted therapy for oral cancer and salivary gland cancer. Hamakawa H, Nakashiro K, Sumida T, Shintani S, Myers JN, Takes RP, Rinaldo A, Ferlito A. Head Neck. 2008 Jun;30(6):800-9.

BACKGROUND: Recently, attention has been focused on molecular targeted cancer
therapy in various tumors. Although there is no single consistent molecular
target specific for oral squamous cell carcinoma (OSCC) and salivary gland cancer
(SGC), there are a number of promising candidate proteins. The aim of this review
is to introduce the basic evidences to support the molecular targeting for OSCC
and SGC. METHODS: We focused on the 4 molecules, epidermal growth factor receptor
(EGFR), cyclooxygenase-2 (COX-2), peroxisome proliferator-activated receptor
gamma (PPARgamma), and progesterone receptor, that are, respectively, associated
with the proliferation and the differentiation of OSCC and SGC. RESULTS:
Gefitinib (“Iressa,” ZD1839), a small molecule EGFR tyrosine kinase inhibitor,
can inhibit the proliferation of OSCC cell lines in a dose- and time-dependent
manner and lead to cell cycle arrest with accumulation of cells in the G1 phase,
and a decrease of cells in S phase. The agent suppressed tumor metastasis in the
animal model. Furthermore, a cooperative antiproliferative effect was obtained
when cancer cells were treated with radiation followed by gefitinib. While
radiation alone did not significantly affect p38 mitogen-activated protein kinase
and MAP kinase kinase (MEK)1/2 autophosphorylation, the combination of gefitinib
and radiation completely inhibited the downstream signaling of EGFR. Gefitinib
enhanced tumor radioresponsiveness by multiple mechanisms, including the growth
inhibition and effects on DNA repair after exposure to radiation. Next, the level
of COX-2 expression correlated inversely with increased tumor radiation
sensitivity. Treatment with celecoxib, a COX-2 selective inhibitor, enhanced the
radioresponsiveness of HSC-2 cells, which constitutively expressed COX-2. Another
promising molecular target is the PPARgamma, which is a member of the nuclear
receptor superfamily of ligand-activated transcription factors. Recent studies
have demonstrated that PPARgamma ligands induce cellular differentiation and
inhibit cell growth in carcinomas of various types. These data suggest that
synthetic PPARgamma ligands may be useful for molecular targeting of oral cancer.
Finally, the possibility of using molecular targeted therapy directed at hormone
receptors in the treatment of advanced SGCs was described. CONCLUSION: The basic
data strongly suggested the possibility of tumor suppression by targeting these
molecules. Studies of different targeted agents alone or with more conventional
treatment modalities are needed to fully determine what role the targeted therapy
will play in the management of patients with OSCC and SGC.

Squamous cell carcinoma of the nasal vestibule: a 20-year case series and literature review. Dowley A, Hoskison E, Allibone R, Jones NS. J Laryngol Otol. 2008 Oct;122(10):1019-23. Epub 2008 Apr 21.

Squamous cell carcinoma of the nasal vestibule is a rare disease with significant
morbidity and mortality, and a five-year recurrence-free survival rate of between
42 and 92 per cent. There are several staging systems: the American Joint
Committee on Cancer (AJCC) skin and nasoethmoid complex system, the Union
International Centre Cancer (UICC) nasal fossa system, and Wang’s system.
Treatment options include radiotherapy or surgery for early lesions, but more
advanced cases require radical surgery with post-operative radiotherapy. We
present a case series spanning the last 20 years in one centre, and we compare
this series with cases reported in the literature, paying particular attention to
staging, treatment and outcome. We found that patients with tumours staged T2 or
T3 (Wang system) who received radiotherapy alone did poorly in comparison with
those who received surgery or surgery and radiotherapy.

[Resectable adenocarcinoma of the oesophagogastric junction care: which perioperative treatment?] [Article in French] Créhange G, Bonnetain F, Chauffert B, Rat P, Bedenne L, Maingon P. Cancer Radiother. 2008 Sep;12(5):365-73. Epub 2008 Apr 16.

Adenocarcinoma of the oesophagogastric junction has an ominous prognosis. Until
now, oesophageal adenocarcima care was close to the squamous cell cancer one
whereas adenocarcinoma of the cardia was mixed with gastric cancers. Results from
randomised studies mixed them without making distinctions. Nevertheless, context,
natural history and clinical outcome differ. Five-year survival rate is around 40
%, all stages included. Results from several phase-III studies or meta-analysis
allowed to define three therapeutic strategies applicable to adenocarcinoma of
the oesophagus and the oesophagogastric junction. In Europe, in the case of a
resectable tumour, preoperative chemotherapy became a standard treatment since
results from the Magic trial. In the United States, post-operative
radiochemotherapy according to the “Macdonald” scheme is used in case of a
resected tumour with a R0 surgery. Actually, modern techniques of irradiation
could reduce the rate of gastro-intestinal toxicities. The survival benefit from
preoperative radiochemotherapy is still very controversial with high rates of
postoperative morbidity and mortality. We have performed a review of the
literature with a methodological analysis of data with a high level of evidence
in order to advise perioperative treatment guidelines for patients with a
resectable adenocarcinoma of the lower oesophagus or gastro-oesophageal junction.
Results from pre- or postoperative strategies and the role of radiotherapy will
need to be analysed in the future through a randomised study.

An IFN-associated cytotoxic cellular immune response against viral, self-, or tumor antigens is a common pathogenetic feature in “interface dermatitis”. Wenzel J, Tüting T. J Invest Dermatol. 2008 Oct;128(10):2392-402. Epub 2008 Apr 17.

The term “interface dermatitis” (ID) involves a specific histological
inflammatory pattern that is characterized by a cytotoxic lymphocytic
infiltration and a hydropic degeneration of the basal epidermal layer. ID is
typically seen in autoimmune skin disorders such as lichen planus (LP), cutaneous
lupus erythematosus (CLE), and may also appear during immune reactions against
drugs, viruses, and tumors. Recent studies have shown that the type-I IFN system
is involved in cutaneous autoimmune diseases characterized by ID. IFNs induce the
expression of proinflammatory cytokines and chemokines, which support the
cellular immune response. The role of IFNs in ID is supported by a close
morphological association between the expression pattern of IFN-inducible
proteins and the distribution of CXCR3+ lymphocytes. The IFN-inducible chemokine
CXCL10 is expressed in exactly those areas where cytotoxic lymphocytes invade the
basal epidermis and cause keratinocyte death. A similar picture can be found in
early herpes simplex viral skin lesions and viral warts, but also in “lichenoid”
actinic keratosis and invasive squamous cell carcinoma. These data suggest that
ID morphologically reflects a common IFN-driven cytotoxic attack affecting the
basal keratinocytes under different conditions, which is important for antiviral
and antitumor immune response, but is inappropriately activated in autoimmune
skin disorders.

Bevacizumab in non-small cell lung cancer. Di Costanzo F, Mazzoni F, Micol Mela M, Antonuzzo L, Checcacci D, Saggese M, Di Costanzo F. Drugs. 2008;68(6):737-46.

Lung cancer continues to be the leading cause of cancer death in Western
countries. The median survival time for advanced non-small cell lung cancer
(NSCLC) remains poor and chemotherapy is the treatment of choice for most
patients with metastatic NSCLC. Platinum-based chemotherapy has long been the
standard of care for advanced NSCLC. The formation of new blood vessels
(angiogenesis) is needed for the growth and invasiveness of primary tumours, and
plays an important role in metastatic growth. Vascular endothelial growth factor
(VEGF) has emerged as a key potential target for the pharmacological inhibition
of tumour angiogenesis. This review discusses current data and the future
potential of bevacizumab, a recombinant humanized monoclonal antibody that binds
VEGF, in the treatment of NSCLC. Results from a phase II study showed that the
addition of bevacizumab to the first-line chemotherapy with paclitaxel and
carboplatin (CP) may increase the overall survival (OS) and the time to
progression in advanced NSCLC. Based on these promising results, a randomized
phase III trial compared the combination of bevacizumab with CP versus CP alone
in the treatment of advanced non-squamous NSCLC. The combination of CP plus
bevacizumab led to a statistically significant increase in median OS and
progression-free survival (PFS) compared with CP alone, with a response rate (RR)
in the CP arm of 15% compared with 35% in the bevacizumab plus CP arm (p <
0.001). More recently, the randomized AVAIL (Avastin in Lung Cancer) study, which
evaluated cisplatin with gemcitabine plus bevacizumab in two different dosages
versus chemotherapy alone in 1043 patients with recurrent or advanced
non-squamous NSCLC, reported a significant increase of PFS, RR and duration of
response for both of the bevacizumab-containing arms. Bevacizumab has also been
investigated in combination with erlitonib as second-line treatment in two small
early phase trials, with interesting results. Bevacizumab was generally well
tolerated in clinical trials; the main treatment-associated adverse events were
neutropenia and haemorrhage, especially in the lung, but also at other sites.
Several trials that incorporate bevacizumab in combination with new active drugs
in NSCLC are ongoing and should further help to define the place of bevacizumab
in the therapy of NSCLC.

[Photodynamic therapy using m-THPC (Foscan). Treatment of head and neck squamous cell carcinoma] [Article in German] Naim R. HNO. 2008 May;56(5):490-2.

Epidermolysis bullosa. Part 1: causes, presentation and complications. Pillay E. Br J Nurs. 2008 Mar 13-26;17(5):292-6.

This article is the first in a series of three focusing on the causes, clinical
presentation, complications and care of adult patients affected by epidermolysis
bullosa (EB), a group of rare genetic skin fragility disorders. Although the
condition is rare, in some cases it presents extreme challenges both to those
affected and those involved in the care of the EB patient; therefore, these
articles may have relevance for other long-term disorders. While there is a
wealth of information regarding the ‘science’ of EB there is dearth of
information regarding the care of the adult EB patient, and this series of
articles will endeavour to fill that gap. This article focuses mainly on those
patients affected with the most severe form of EB found in the adult group,
recessive dystrophic epidermolysis bullosa; with the part two looking at the care
of the adult with EB from the nursing perspective, including wound management,
and the experiences of a specialist EB psychotherapist being presented in the
final article of the series. Readers will thus have an opportunity to gain an
overall view of this difficult condition.

Actinic keratosis: an occupational and environmental disorder. Schwartz RA, Bridges TM, Butani AK, Ehrlich A. J Eur Acad Dermatol Venereol. 2008 May;22(5):606-15.

Solar ultraviolet light electromagnetic waves are a known environmental
carcinogenic agent closely associated with the development of skin cancer in
light-complexioned individuals. Outdoor workers have higher annual exposure to
ultraviolet light. We will review the topic of actinic keratoses among these
individuals as this common rudimentary form of superficial cutaneous squamous
cell carcinoma is explored in greater detail.

Anal intraepithelial neoplasia in HIV infection. [Article in English, German] Kreuter A, Brockmeyer NH, Altmeyer P, Wieland U; German Competence Network HIV/AIDS.

Human papillomavirus (HPV) infections belong to the most common sexually
transmitted infections worldwide. While the immune system eliminates most HPV
infections over time in immunocompetent individuals, HPV infections tend to
persist in immunodeficient individuals. In HIV-infected men who have sex with men
(MSM), anal HPV prevalence is more than 90% and infections with multiple HPV
types are common. Consequently, HPV-associated anogenital malignancies occur with
high frequency in patients with HIV infection. Anal intraepithelial neoplasia
(AIN) is a potential precursor lesion of squamous cell carcinoma of the anus.
Like its cervical counterpart, cervical intraepithelial neoplasia (CIN), AIN is
causally linked to persistent infections with high-risk HPV types such as HPV16
or HPV18. As AIN and CIN share distinct biological similar-ities, AIN screenings
analogous to Pap smear programs for CIN have been recommended in high-risk
populations to reduce the incidence of anal carcinoma. These screenings include
cytological analysis followed by high resolution anoscopy in case of anal
dysplasia. Treatment guidelines for AIN are not yet available. Therapeutic
strategies can be divided into topical (e.g. trichloroacetic acid,
podophyllotoxin, imiquimod, photodynamic therapy) and ablative (e. g. surgical
excision, laser ablation, infrared coagulation, electrocautery) measures.
However, controlled studies on AIN treatment have not been performed. The impact
of HPV vaccination on AIN development will also need to be assessed. Long-term
follow-up of these patients is essential to gain more insight into the natural
history of anogenital HPV infection in HIV-positive MSM.

Review of squamous premalignant vulvar lesions. van de Nieuwenhof HP, van der Avoort IA, de Hullu JA. Crit Rev Oncol Hematol. 2008 Nov;68(2):131-56. Epub 2008 Apr 11.

Vulvar squamous cell carcinoma (SCC) develops following two different pathways,
which have their own premalignant lesions. In the absence of human papilloma
virus (HPV), vulvar SCC can develop in a background of lichen sclerosus (LS),
differentiated vulvar intraepithelial neoplasia (VIN) or both. The other pathway
leading to vulvar SCC is associated with HPV and the HPV-associated premalignancy
is usual VIN. In this review we will discuss the history, epidemiology,
aetiology, histology, clinical characteristics, treatment options, malignant
potential and prevention strategies of the three squamous premalignant vulvar

Pigmented oral squamous cell carcinoma: a case report and brief review of the literature. Lisboa Castro J, Cazal C, Gomes Henriques AC, Carneiro Leão J, de Vasconcelos Carvalho M, de Carvalho Dourado HT, Carvalho AA. Int J Surg Pathol. 2009 Apr;17(2):153-7. Epub 2008 Apr 7.

Melanin impregnation in squamous cell carcinoma (SCC) is an uncommon histological
finding. Rare nonmelanocytic entities were previously described as having
melanocyte colonization. A 57-year-old Brazilian woman was referred with a
pigmented lesion in the lower lip and alveolar ridge with a prior clinical
diagnosis of melanoma. The incisional biopsy of the tumor revealed an SCC with
strong colonization of melanocytes in the stroma. The authors report a case of an
unusual SCC variant and a brief review of the literature.

Long-term survival following salvage reirradiation with concurrent chemotherapy for recurrent head and neck cancer. Watkins JM, Stuart RK, Davis BK, Day TA, Chaudharry UB, Sharma AK. J S C Med Assoc. 2008 Feb;104(2):36-9.

Endoscopic mucosal resection in the upper gastrointestinal tract. Ahmadi A, Draganov P. World J Gastroenterol. 2008 Apr 7;14(13):1984-9.

Endoscopic mucosal resection (EMR) is a technique used to locally excise lesions
confined to the mucosa. Its main role is the treatment of advanced dysplasia and
early gastrointestinal cancers. EMR was originally described as a therapy for
early gastric cancer. Recently its use has expanded as a therapeutic option for
ampullary masses, colorectal cancer, and large colorectal polyps. In the Western
world, the predominant indication for EMR in the upper gastrointestinal tract is
the staging and treatment of advance dysplasia and early neoplasia in Barrett’s
esophagus. This review will describe the basis, indications, techniques, and
complications of EMR, and its role in the management of Barrett’s esophagus.

Topical therapy for actinic keratoses: current and evolving therapies. Weinberg JM. Rev Recent Clin Trials. 2006 Jan;1(1):53-60.

Actinic keratoses (AKs) are evolving malignant cutaneous neoplasms. They are also
known as solar keratosis, squamous cell carcinoma in situ-solar keratotic type,
or keratinocytic intraepidermal neoplasia. Actinic keratoses can be treated by
two general methods: by physical/destructive methods and with topical therapies.
This article will review current and evolving topical therapeutic options for
AKs. Several topical treatment options have been shown to offer some significant
benefit in the alleviation of these lesions. The therapies include
5-fluorouracil, imiquimod, diclofenac, colchicine and retinoids.

Molecular-targeted therapies in the treatment of squamous cell carcinomas of the head and neck. Le Tourneau C, Siu LL. Curr Opin Oncol. 2008 May;20(3):256-63.

PURPOSE OF REVIEW: The present study reviews recent developments of
molecular-targeted therapies in the treatment of recurrent and/or metastatic head
and neck squamous cell carcinoma. It also highlights ongoing research regarding
predictive markers of sensitivity or resistance to anti-epidermal growth factor
receptor agents and discusses some promising novel targets in head and neck
squamous cell carcinoma, as well as clinical trial design challenges. RECENT
FINDINGS: Phase III randomized studies have brought the proof that cetuximab, an
anti-epidermal growth factor receptor agent, is able to improve survival, either
in combination with radiation therapy or in first-line treatment for recurrent
and/or metastatic head and neck squamous cell carcinoma. In addition, promising
results have been obtained with antiangiogenic therapies in phase II trials. Some
clinical and molecular markers of resistance to anti-epidermal growth factor
receptor agents have been identified, but they have not yet been validated for
clinical practice. Other interesting targets, such as insulin-like growth factor
1R or the PI3K/AKT/mTOR pathway, have been shown in vitro to play key roles in
head and neck squamous cell carcinoma, and their inhibition warrants further
evaluations. SUMMARY: Proof of the concept that molecular-targeted therapy is a
valid therapeutic approach for head and neck squamous cell carcinoma has emerged
with anti-epidermal growth factor receptor agents. Nevertheless, identification
of predictive biomarkers of resistance or sensitivity to these therapies remains
the main challenge in the optimal selection of patients most likely to benefit
from them.

A multidisciplinary approach to squamous cell carcinomas of the head and neck: an update. Bernier J. Curr Opin Oncol. 2008 May;20(3):249-55.

PURPOSE OF REVIEW: The treatment of locally advanced squamous cell carcinoma of
the head and neck has improved with the addition of chemotherapy to radiotherapy.
Other approaches are being investigated to improve the clinical benefit at an
acceptable level of toxicity. RECENT FINDINGS: The present review summarizes
recently published data on the treatment of locally advanced squamous cell
carcinoma of the head and neck. Altered radiation fractionation regimens have
been shown to increase efficacy, and induction chemotherapy may offer clinical
benefits. One of the most important advances in this setting has been the
demonstration that addition of the epidermal growth factor receptor-targeted
monoclonal antibody, cetuximab, to radiotherapy improves locoregional control and
overall survival compared with radiotherapy alone. The survival benefit of this
combination appears to be of at least the same magnitude as that seen with
chemoradiotherapy, but the combination is not associated with the high level of
toxicity that characterizes chemoradiotherapy. The use of more sensitive
instruments for adverse event recording may provide a better picture of the
toxicity burden. SUMMARY: Although the further modification of radiotherapy and
chemotherapy within chemoradiotherapy regimens is unlikely to offer major
clinical benefits, it is likely that any significant advances will be made with
the incorporation of novel agents into treatment regimens. The combination of
cetuximab and radiotherapy forms a new standard for the treatment of locally
advanced squamous cell carcinoma of the head and neck.

Review article: relationship of human papillomavirus with papillary squamous cell carcinoma of the upper aerodigestive tract: a review. Cobo F, Talavera P, Concha A. Int J Surg Pathol. 2008 Apr;16(2):127-36. Epub 2008 Apr 2.

The purpose of this review is to evaluate case reports of papillary squamous cell
carcinoma (PSCC) of the upper aerodigestive tract (UADT) to assess its
relationship with human papillomavirus (HPV). The medical literature was searched
for case reports of this condition. A total of 115 cases of PSCC were found that
described the condition in sufficient detail. HPV detection was performed in only
22 of the 115 cases of PSCC (19%), and 11 of the 22 cases (50%) are related to
this virus. The majority of cases related to HPV are produced by low-risk HPV
type 6 followed by high-risk HPV type 16. Today, the association of HPV with
PSCCs seems unclear because in the majority of patients tests were not performed
for the detection of the HPV. This association should be clearly established to
make a correct diagnosis and propose the best therapeutic strategies, such as new

Neoplastic transformation of oral lichen: case report and review of the literature. Abbate G, Foscolo AM, Gallotti M, Lancella A, Mingo F. Acta Otorhinolaryngol Ital. 2006 Feb;26(1):47-52.

Aim of the present investigation was to analyse the possible malignant
transformation of oral lichen planus to carcinoma, especially in the atrophic
erosive forms and those displaying plaques involving the top of the tongue. A
review has been made of the literature, from 1986 to the present day. This search
outlines the relationship between oral lichen planus, hepatitis C virus
infection, Epstein-Barr virus infection and the importance of periodic follow-up
in all patients with oral lichen planus. The case is described of malignant
transformation of oral lichen planus to oral cancer in a female presenting
asymptomatic hepatitis C virus infection. The clinical history confirms the most
important aspects of the relationship between oral lichen planus and oral cancer.
Oral lichen planus should be considered as a precancerous lesion, particularly in
patients presenting hepatitis C virus infection, requiring follow-up, at close
intervals, starting from 3 months after diagnosis.

Emerging perspectives in epidermal growth factor receptor targeting in head and neck cancer. Kim S, Grandis JR, Rinaldo A, Takes RP, Ferlito A. Head Neck. 2008 May;30(5):667-74.

The epidermal growth factor receptor (EGFR) has been shown to be a promising
therapeutic target in head and neck cancer. Cetuximab, a monoclonal antibody
against EGFR, has been approved in the United States for use with radiotherapy
for head and neck squamous cell carcinoma. However, the role of EGFR targeting
agents in other therapeutic modalities, such as combined chemoradiotherapy or
induction chemotherapy, remains to be defined. Although results from several
clinical trials have demonstrated the therapeutic potentials of EGFR targeting
agents in these settings, further studies are necessary before definitive
conclusions can be made. The concurrent targeting of EGFR along with other
pathways important in carcinogenesis may hold significant therapeutic potential.
In particular, several clinical trials are studying the effects of combining
agents that target the vascular endothelial growth factor with EGFR inhibitors.
Last, studies are ongoing to elucidate the predictive and correlative biomarkers
in anti-EGFR therapy to allow for proper patient selection. In the case of
cetuximab, these correlative biomarkers may include elements of the immune system
in addition to the signal transduction proteins involved in EGFR pathway.

Head and neck cancer: changing epidemiology, diagnosis, and treatment. Marur S, Forastiere AA. Mayo Clin Proc. 2008 Apr;83(4):489-501.

Head and neck cancers account for less than 5% of all cancers and for less than
3% of all cancer deaths in the United States. The populations at risk for head
and neck cancers are those who have a long-standing history of smoking and
alcohol use. More recently, the incidence of oropharyngeal cancer in younger
populations has been increasing and is associated with exposure to the human
papillomavirus. This subset of patients appears to have a better overall
prognosis and to respond better to treatment. This review is limited to head and
neck cancers of squamous cell histology, which constitute more than 90% of head
and neck cancers. Because treatment of head and neck cancers is complex and
involves multiple modalities, a multidisciplinary approach is needed. This review
focuses on the goal of organ preservation and postoperative treatment of
high-risk patients with the concurrent use of chemotherapy and radiation therapy.
This review also highlights recent advances in treatment using molecularly
targeted therapies, specifically the role of inhibitors of the epidermal growth
factor receptor in locally advanced and recurrent/metastatic squamous cell cancer
of the head and neck. Studies in the English language were identified by
searching the MEDLINE, EMBASE database (1980-2007) using the search terms head
and neck, squamous cell, carcinoma, chemotherapy, radiation, human
papillomavirus, epidermal growth factor receptor, and targeted therapy.

EGFR inhibitors for the treatment of squamous cell carcinoma of the head and neck. Mehra R, Cohen RB, Harari PM. Curr Oncol Rep. 2008 Mar;10(2):176-84.

Squamous cell carcinoma of the head and neck (SCCHN) continues to be a source of
significant morbidity and mortality. Agents that target the epidermal growth
factor receptor (EGFR), including monoclonal antibodies and small molecule
tyrosine kinase inhibitors, have demonstrated activity in this disease. The US
Food and Drug Administration has approved the monoclonal antibody cetuximab in
conjunction with radiation for locally advanced disease, and as a single agent
for recurrent/metastatic disease. In addition, recent data have shown a survival
benefit for patients with recurrent/metastatic disease who are treated with
platinum, fluorouracil, and cetuximab. These promising results have prompted
further study of EGFR inhibitors with radiation and cytotoxic chemotherapy to
further increase the benefit of treatment for SCCHN.

Head and neck cancer immunotherapy: clinical evaluation. Leibowitz MS, Nayak JV, Ferris RL. Curr Oncol Rep. 2008 Mar;10(2):162-9.

Overall survival for patients with squamous cell carcinoma of the head and neck
(SCCHN) has not improved appreciably over the past few decades. Because standard
treatments have not controlled this disease with sufficiently high success rates,
novel therapeutic approaches, such as immunotherapy, are under investigation.
Cancer immunotherapy involves various techniques used to expand and activate the
immune system to control tumor growth in vivo; to date, clinical evaluation has
demonstrated low toxicity. An emerging form of SCCHN immunotherapy involves the
use of antibodies that target growth factor receptors (where immune activation
appears to enhance tumor lysis), resulting in improved clinical outcome. So far,
immunotherapy appears to have the most applicability after other therapeutic
interventions; however, its vast potential clinical value has yet to be fully
explored. This article reviews immunotherapeutic strategies currently in clinical
trials or under development for patients with SCCHN.

Will vaccination against human papillomavirus prevent eye disease? A review of the evidence. Hughes DS, Powell N, Fiander AN. Br J Ophthalmol. 2008 Apr;92(4):460-5.

The role of human papillomavirus (HPV) infection in eye disease is controversial.
However, a recent case illustrates the possible role of HPV in conjunctival
squamous carcinoma and the potentially devastating effects of this disease. The
development of two vaccines to prevent infection with HPV types most commonly
associated with anogenital cancers has led to debate about the pros and cons of a
national immunisation programme to prevent cervical cancer. The introduction of
such a vaccination programme may have an additional beneficial effect on the
occurrence of some head and neck, including ocular, cancers. This review
discusses the nature of papillomaviruses, mechanisms of infection and
carcinogenesis, the possible role of HPV in eye disease, and finally the likely
impact of the new prophylactic vaccines.

The impact of variant histology on the outcome of bladder cancer treated with curative intent. Black PC, Brown GA, Dinney CP. Urol Oncol. 2009 Jan-Feb;27(1):3-7. Epub 2008 Jan 14.

Patient risk stratification is essential for optimal management of patients with
bladder cancer. Risk status determines the application and timing of therapeutic
interventions such as repeat transurethral resection, intravesical chemo- and
immunotherapy, systemic chemotherapy, and radical cystectomy. One key factor in
such risk stratification appears to be the presence of variant histologic
patterns in the bladder tumor. More than 90% of tumors are conventional
urothelial carcinoma, and the rest consist of urothelial carcinoma with aberrant
differentiation (squamous/glandular differentiation, small cell carcinoma,
sarcomatoid carcinoma, and micropapillary carcinoma) or nonurothelial carcinoma
(squamous cell carcinoma and adenocarcinoma). In this review, we focus on the
implications of aberrant differentiation on the management of patients with
bladder cancer. All of the variant histologies portend a worse prognosis than
pure urothelial carcinoma. Although radical cystectomy remains the mainstay of
treatment in all forms of bladder cancer, we highlight the use of neoadjuvant
chemotherapy in patients with subtypes responsive to such therapy.

Recurrent head and neck cancer: current treatment and future prospects. Specenier PM, Vermorken JB. Expert Rev Anticancer Ther. 2008 Mar;8(3):375-91.

Recurrent and metastatic squamous cell carcinoma of the head and neck still
carries a poor prognosis. Response rates with combination chemotherapy regimens
are generally higher than those observed with single-agent chemotherapy. However,
this did not translate into an overall survival benefit, not in even a single
randomized trial. As none of the combination chemotherapy regimens demonstrated
an overall survival benefit when compared with single-agent methotrexate,
cisplatin or 5-fluorouracil, the use of combination chemotherapy outside clinical
trials is usually restricted to younger patients with a good performance status
and with symptomatic disease who require prompt symptom relief. After decades
without real progress, a recent randomized trial showed that adding cetuximab,
the first clinically available EGF receptor-directed monoclonal antibody, to a
standard chemotherapy regimen (platinum/5-fluorouracil), led to an important
survival benefit. In addition, the response rate nearly doubled with this
approach, which has great promise for the treatment of symptomatic disease. There
is now a plethora of targeted therapies in various stages of preclinical and
clinical development. The next challenge will be to sort out which of them have a
clinically meaningful activity and find out how to incorporate them into existing
treatment regimens.

[Current role for induction chemotherapy in head and neck tumors] [Article in German] Dietz A, Keilholz U, Werner J, Hagen R, Flentje M, Iro H. Laryngorhinootologie. 2008 Apr;87(4):237-43; discussion 244.

According to recent publications in the New England Journal of Medicine (TAX323,
TAX324) of the study groups around Jan Vermorken and Marshall Posner induction
chemotherapy in squamous cell carcinomas of the head-neck area (in the closer:
Oro-hypopharynx, oral cavity and larynx) currently seems to generate a worldwide
renaissance. Renaissance, because in the last few decades, induction chemo
therapy in this group of tumors after lack of survival improvement in the vast
majority of studies was again abandoned. The new data raise the question for
which entities induction chemo therapy can be recommended (actually, a
combination of docetaxel, cisplatin and 5-fluorouracil; TPF)? The unbroken high
value of primary surgery with adjuvant radiation or chemo radiation was
complementary to primary radio chemotherapy for non resectable tumors until today
worldwide. Running studies are sorting out the role of induction chemotherapy in
the current context of clarifying optimal multimodal treatment.

An unusual composite pilomatrix carcinoma with intralesional melanocytes: differential diagnosis, immunohistochemical evaluation, and review of the literature. Jani P, Chetty R, Ghazarian DM. Am J Dermatopathol. 2008 Apr;30(2):174-7.

We report a case of an extremely rare histologic combination of pilomatrix or
pilomatrical carcinoma with admixed melanocytes within the same tumor mass.
Pilomatrix carcinoma is a neoplasm of low-grade malignancy that is characterized
by a tendency for recurrence but low risk of metastasis. A 77-year-old male
presented with a nodule on the bridge of the nose that was excised.
Histologically, it was typified by asymmetry and poor circumscription, the
presence of several variably sized and shaped basaloid aggregations, and surface
ulceration. The tumors were composed of pleomorphic basaloid cells with prominent
nucleoli and frequent mitoses (some of which were atypical) accompanied by
central areas with keratotic material, shadow cells, and foci of necrosis. In
addition, intermingled with the pilomatrix carcinoma, several easily identified
pigmented cells with dendritic processes were present singly and as small
aggregates. There was no atypia associated with the melanocytic component.
Immunohistochemistry revealed the CK14 to be positive mainly within the
keratinizing and the squamous epithelial elements of the tumor. The melanocytic
component was strongly immunoreactive for S100, melanoma cocktail (HMB45 and
Melan-A), and microphthalmia transcription factor. Pilomatrix carcinoma with
melanocytes should be distinguished from the conventional pilomatrixoma with
pigmentation, melanocytic matricoma, melanoma, and pigmented basal cell carcinoma
with matrical differentiation. Clinicians and pathologists should be aware of the
occurrence of pilomatrix carcinoma with melanocytes because of its potential for
diagnosis as melanoma. This peculiar lesion recapitulates the intimate
relationship existing between matrical epithelium and melanocytes in the
embryonal hair follicle or in the anagen stage of the hair cycle. It is possible
that sun damage played a role in stimulating migration of melanocytes among
matrical cells in this case.

Keratoacanthoma and infundibulocystic squamous cell carcinoma. Kossard S, Tan KB, Choy C. Am J Dermatopathol. 2008 Apr;30(2):127-34.

One of the major controversies in dermatopathology is the relationship of
keratoacanthoma to squamous cell carcinoma. Leaders in the field remain polarized
in their views. Carcinomas with distinct follicular pattern of differentiation
have been described in reference to the isthmus as trichilemmal carcinomas, to
the follicular bulb as pilomatricomal carcinomas, and to the stem cell or rapidly
amplifying cell compartment as basal cell carcinomas (trichoblastic carcinomas).
We have employed the term infundibulocystic or infundibular squamous cell
carcinoma to identify a subset of squamous cell carcinomas that demonstrate this
pattern of differentiation. The recognition of infundibular squamous cell
carcinoma is important in that well-differentiated examples are likely to have
been diagnosed as keratoacanthoma, whereas moderately or poorly differentiated
tumors would be more often reported as squamous cell carcinomas, leading to
underrecognition of these infundibular variants of squamous cell carcinoma. The
descriptive term infundibulocystic or infundibular squamous cell carcinoma may
help to better define an alternative follicular-based pathway to squamous cell
carcinoma distinct from the more common evolution from solar keratoses and also
refine the classification of keratoacanthoma.

[Smoking and the skin] [Article in Spanish] Just-Sarobé M. Actas Dermosifiliogr. 2008 Apr;99(3):173-84.

Smoking is the main modifiable cause of disease and death in the developed world.
Tobacco consumption is directly linked to cardiovascular disease, chronic
bronchitis, and many malignant diseases. Tobacco also has many cutaneous effects,
most of which are harmful. Smoking is closely associated with several
dermatologic diseases such as psoriasis, pustulosis palmoplantaris,
hidrosadenitis suppurativa, and systemic and discoid lupus erythematosus, as well
as cancers such as those of the lip, oral cavity, and anogenital region. A more
debatable relationship exists with melanoma, squamous cell carcinoma of the skin,
basal cell carcinoma, and acne. In contrast, smoking seems to protect against
mouth sores, rosacea, labial herpes simplex, pemphigus vulgaris, and dermatitis
herpetiformis. In addition to the influence of smoking on dermatologic diseases,
tobacco consumption is also directly responsible for certain dermatoses such as
nicotine stomatitis, black hairy tongue, periodontal disease, and some types of
urticaria and contact dermatitis. Furthermore, we should not forget that smoking
has cosmetic repercussions such as yellow fingers and fingernails, changes in
tooth color, taste and smell disorders, halitosis and hypersalivation, and early
development of facial wrinkles.

Oral maxillary squamous cell carcinoma: management of the clinically negative neck. Montes DM, Schmidt BL. J Oral Maxillofac Surg. 2008 Apr;66(4):762-6.

PURPOSE: Squamous cell carcinomas of the hard palate, maxillary gingiva, and
maxillary alveolus occur at relatively low rates compared with squamous cell
carcinomas in other oral sites. There is little within the surgical literature to
guide treatment for maxillary squamous cell carcinoma. To date, only 1 other
group has addressed neck management in the oral maxillary squamous cell carcinoma
patient presenting with a clinically negative neck. Adequate characterization of
maxillary gingival carcinoma behavior with respect to regional cervical
metastasis is wanting. PATIENTS AND METHODS: We present a retrospective review of
our own clinical experience as well as a review of the existing literature.
RESULTS: In our University of California San Francisco patient group, cervical
disease was detected in 20% of those individuals with maxillary squamous cell
carcinoma presenting for initial consultation. After ablative surgery, those
individuals who presented with clinically negative necks had a 21.4% rate of
regional node metastasis. Ultimately, 50% of our patients with squamous cell
carcinomas of the palate, maxillary gingiva, and maxillary alveolus developed
regional or metastatic distant disease; 42.9% of the patients manifested disease
to the cervical lymph nodes alone. CONCLUSIONS: The cases of oral maxillary
squamous cell carcinomas reviewed herein exhibit aggressive regional metastatic
behavior comparable to that of such carcinomas of the tongue, floor of the mouth,
and mandibular gingiva. Based on the findings presented herein, we recommend
selective neck dissection in the setting of a clinically negative neck as a
primary management strategy for patients with oral maxillary squamous cell
carcinomas involving the palate, maxillary gingiva, and maxillary alveolus.

Adult laryngeal rhabdomyosarcoma: report of a case and literature review. Shayah A, Agada FO, Karsai L, Stafford N. Ann Afr Med. 2007 Dec;6(4):190-3.

Rhabdomyosarcoma is relatively seen in the pediatric age group with the head and
neck region as the commonest site. To the best of our knowledge, few cases of
laryngeal involvement in adult have been described in the literature.
Biologically, rhabdomyosarcoma is different from squamous cell carcinoma, which
is the commonest tumor of the larynx. A previously healthy non-smoker 77-year-old
lady presented to the ENT outpatient with a six weeks history of intermittent
alteration of voice quality. She had no history of sore throat, or any symptoms
suggesting laryngo-pharyngeal reflux. Examination showed asymmetry of the left
arytenoid cartilage and aryepiglottic fold. She subsequently had a direct
laryngoscopy and biopsy. Histology and immunohistochemistry examination suggested
the diagnosis of mesenchymal neoplasm. Following discussion at MDT she
subsequently had a total laryngectomy. Histology confirmed a completely excised
laryngeal rhabdomyosarcoma. Rhabdomyosarcoma of larynx in adult is a rare
disease. Surgical treatment with or without adjuvant radiotherapy is currently
the treatment of choice for this disease.

Sinonasal undifferentiated carcinoma: a review of the literature. Smullen JL, Amedee RG. J La State Med Soc. 2001 Oct;153(10):487-90.

Sinonasal undifferentiated carcinoma is a relatively rare and aggressive
malignancy of the nose and paranasal sinuses. It is often difficult to
distinguish from other poorly differentiated sinonasal malignancies. Since it was
first described in 1986, advances have been made in the understanding of the
histology and immunohistochemical markers of sinonasal undifferentiated
carcinoma, but the treatment options and prognosis remain poor. Presenting signs
and symptoms, patient demographics, risk factors as well as immunohistochemical
findings are reviewed. While no treatment is standard for sinonasal
undifferentiated carcinoma, several modalities and combinations including
chemotherapy, radiation, and surgery have been used with varied success. The
several case series reported are examined and future directions of therapy

Treatment of melanoma and nonmelanoma skin cancer. Rass K, Tilgen W. Adv Exp Med Biol. 2008;624:296-318.

The incidence of skin cancer is increasing in Caucasian populations worldwide.
Treatment approaches for Nonmelanoma skin cancer (NMSC) are predominantly
curative and surgery can be regarded as standard of care. Nevertheless, novel and
less invasive topical therapy modalities like photodynamic therapy or local
immune modifiers are in progress. In contrast to NMSC, the mortality of melanoma
has not changed considerably over the last years and decades. Melanoma survival
mainly depends on primary tumor thickness underlining the importance of primary
and secondary prevention by avoidance or early detection of the disease. The
chance to cure melanoma patients is steadily decreasing with tumor stage. As the
prognosis in distant metastatic disease is still poor, except for single
situations therapy approaches are palliative and accompanied by an optimal
supportive care of the patients concerned. Albeit removal of localized metastases
is currently the most effective approach in metastatic melanoma, chemo- and
chemoimmunotherapy has to be regarded as standard treatment in most of the cases.
Novel and promising therapeutic options accrue from growing insights in tumor
biology and immunology. Not only in melanoma, development and application of
targeted therapies currently attract the most attention in the treatment of
advanced tumors. First clinical experiences with those antiproliferative,
antiangiogenic and proapoptotic agents reveal only moderate antitumoral activity
in melanoma, so that future efforts aim at defining more effective combination
strategies using chemo-, targeted and vaccination therapy approaches.

Apoptosis and pathogenesis of melanoma and nonmelanoma skin cancer. Erb P, Ji J, Kump E, Mielgo A, Wernli M. Adv Exp Med Biol. 2008;624:283-95.

Skin cancers, i.e., basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and
melanoma, belong to the most frequent tumors. Their formation is based on
constitutional and/or inherited factors usually combined with environmental
factors, mainly UV-irradiation through long term sun exposure. UV-light can
randomly induce DNA damage in keratinocytes, but it can also mutate genes
essential for control and surveillance in the skin epidermis. Various repair and
safety mechanisms exist to maintain the integrity of the skin epidermis. For
example, UV-light damaged DNA is repaired and if this is not possible, the DNA
damaged cells are eliminated by apoptosis (sunburn cells). This occurs under the
control of the p53 suppressor gene. Fas-ligand (FasL), a member of the tumor
necrosis superfamily, which is preferentially expressed in the basal layer of the
skin epidermis, is a key surveillance molecule involved in the elimination of
sunburn cells, but also in the prevention of cell transformation. However, UV
light exposure downregulates FasL expression in keratinocytes and melanocytes
leading to the loss of its sensor function. This increases the risk that
transformed cells are not eliminated anymore. Moreover, important control and
surveillance genes can also be directly affected by UV-light. Mutation in the p53
gene is the starting point for the formation of SCC and some forms of BCC. Other
BCCs originate through UV light mediated mutations of genes of the hedgehog
signaling pathway which are essential for the maintainance of cell growth and
differentiation. The transcription factor Gli2 plays a key role within this
pathway, indeed, Gli2 is responsible for the marked apoptosis resistance of the
BCCs. The formation of malignant melanoma is very complex. Melanocytes form nevi
and from the nevi melanoma can develop through mutations in various genes. Once
the keratinocytes or melanocytes have been transformed they re-express FasL which
may allow the expanding tumor to evade the attack of immune effector cells. FasL
which is involved in immune evasion or genes which govern the apoptosis
resistance, e.g., Gli2 could therefore be prime targets to prevent tumor
formation and growth. Attempts to silence these genes by RNA interference using
gene specific short interfering RNAs (siRNAs) or short hairpin RNAs (shRNAs) have
been functionally successful not only in tissue cultures and tumor tissues, but
also in a mouse model. Thus, siRNAs and/or shRNAs may become a novel and
promising approach to treat skin cancers at an early stage.

P53 protein and pathogenesis of melanoma and nonmelanoma skin cancer. Benjamin CL, Melnikova VO, Ananthaswamy HN. Adv Exp Med Biol. 2008;624:265-82.

The p53 tumor suppressor gene and gene product are among the most diverse and
complex been shown to have a direct correlation with cancer development and have
been shown to occur in nearly 50% of all cancers. p53 mutations are particularly
common in skin cancers and UV irradiation has been shown to be a primary cause of
specific ‘signature’ mutations that can result in oncogenic transformation. There
are certain ‘hot-spots’ in the p53 gene where mutations are commonly found that
result in a mutated dipyrimidine site. This review discusses the role of p53 from
normal function and its dysfunction in precancerous lesions, nonmelanoma and
melanoma skin cancers. Additionally, molecules that associate with p53 and alter
its function to produce neoplastic conditions are also explored in this chapter.

Molecular biology of basal and squamous cell carcinomas. Xie J. Adv Exp Med Biol. 2008;624:241-51.

Basal cell carcinomas and Squamous cell carcinomas are the two most common human
cancers. The incidence of these two types of cancer is estimated to double within
20 years. Identification of the key molecular events is critical in helping us
design novel strategies to treat and to prevent these cancers. For example,
identification of hedgehog signaling activation has opened up many opportunities
for targeted therapy and prevention of basal cell carcinomas. Significant
progress has also been made in our understanding of squamous cell carcinomas of
the skin. In this chapter, we will focus on major recent developments in our
understanding of basal cell carcinomas and squamous cell carcinomas at the
molecular levels and their clinical implications.

Cytogenetics of melanoma and nonmelanoma skin cancer. Carless MA, Griffiths LR. Adv Exp Med Biol. 2008;624:227-40.

Cytogenetic analysis of melanoma and nonmelanoma skin cancers has revealed
recurrent aberrations, the frequency of which is reflective of malignant
potential. Highly aberrant karyotypes are seen in melanoma, squamous cell
carcinoma, solar keratosis and Merkel cell carcinoma with more stable karyotypes
seen in basal cell carcinoma, keratoacanthoma, Bowen’s disease,
dermatofibrosarcoma protuberans and cutaneous lymphomas. Some aberrations were
common amongst a number of skin cancer types including rearrangements and
numerical abnormalities of chromosome 1, -3p, +3q, partial or entire trisomy 6,
trisomy 7, +8q, -9p, +9q, partial or entire loss of chromosome 10, -17p, +17q and
partial or entire gain of chromosome 20. Combination of cytogenetic analysis with
other molecular genetic techniques has enabled the identification of not only
aberrant chromosomal regions, but also the genes that contribute to a malignant
phenotype. This review provides a comprehensive summary of the pertinent
cytogenetic aberrations associated with a variety of melanoma and nonmelanoma
skin cancers.

Histology of melanoma and nonmelanoma skin cancer. Mueller CS, Reichrath J. Adv Exp Med Biol. 2008;624:215-26.

Solar UV-radiation, vitamin D and skin cancer surveillance in organ transplant recipients (OTRs). Reichrath J, Nürnberg B. Adv Exp Med Biol. 2008;624:203-14.

The introduction of organ transplantation in clinical medicine has resulted in a
constantly increasing, large population of patients that are chronically on
immunosuppressive medication. It is well known that skin cancer, especially SCC,
in this population has higher incidence rates, behaves more aggressively and has
higher rates of metastasis. OTRs who have been treated for many years with
immunosuppressive medication are at the highest risk for developing malignant
skin tumors. Therefore, the intensity of surveillance for cutaneous lesions is of
high importance in OTRs. A full-body skin exam at least once a year and more
frequently if skin cancer or precancerous cutaneous lesions develop is
recommended. Clinicians should not hesitate to biopsy or to surgically excise any
suspicious skin lesion. Of high importance is also the education of OTRs about
their increased risk. Protection against solar and artificial UV-radiation and
monthly self-examinations are good ways to prevent and to recognize any new
suspicious skin lesions. Patients are advised to always wear solar UV-radiation
protection (e.g., clothing, sunscreen) before going outdoors. However,
investigations have revealed that solar UV-B-exposure and serum 25(OH)D levels
positively correlate with decreased risk for various internal malignancies (e.g.,
breast, colon, prostate and ovarian cancer) and other severe diseases. As we have
shown previously, renal transplant recipients are at high risk of vitamin D
deficiency. A sunscreen with a sun protection factor (SPF)-8 reduces the skin’s
production of vitamin D by 95%. Clothing completely blocks all solar
UVB-radiation and this prevents any vitamin D production. Therefore, it is
important to detect and treat vitamin D deficiency in solid organ transplant
recipients. Optimal management of these patients requires communication between
the transplant teams and the treating dermatologist and other clinicians. For
advanced or metastatic disease, collaboration between clinicians of different
disciplines, including the transplant team, dermatologists and radiation
oncologists is also essential. In the future, dermatology clinics that are
integrated into transplant centers may make it easier to manage and to treat
OTRs, may make an interdisciplinary approach more effective and may thereby
improve the clinical outcome in OTRs.

Melanoma and nonmelanoma skin cancers and the immune system. Domingo DS, Baron ED. Adv Exp Med Biol. 2008;624:187-202.

UV damage and DNA repair in malignant melanoma and nonmelanoma skin cancer. Rass K, Reichrath J. Adv Exp Med Biol. 2008;624:162-78.

Exposition of the skin with solar ultraviolet radiation (UV) is the main cause of
skin cancer development. The consistently increasing incidences of melanocytic
and nonmelanocytic skin tumors are believed to be at least in part associated
with recreational sun exposure. Epidemiological data indicate that excessive or
cumulative sunlight exposition takes place years and decades before the resulting
malignancies arise. The most important defense mechanisms that protect human skin
against UV radiation involve melanin synthesis and active repair mechanisms. DNA
is the major target of direct or indirect UV-induced cellular damage. Low
pigmentation capacity in white Caucasians and rare congenital defects in DNA
repair are mainly responsible for protection failures. The important function of
nucleotide excision DNA repair (NER) to protect against skin cancer becomes
obvious by the rare genetic disease xeroderma pigmentosum, in which diverse NER
genes are mutated. In animal models, it has been demonstrated that UVB is more
effective to induce skin cancer than UVA. UV-induced DNA photoproducts are able
to cause specific mutations (UV-signature) in susceptible genes for squamous cell
carcinoma (SCC) and basal cell carcinoma (BCC). In SCC development, UV-signature
mutations in the p513 tumor suppressor gene are the most common event, as
precancerous lesions reveal approximately 80% and SCCs > 90% UV-specific p53
mutations. Mutations in Hedgehog pathway related genes, especially PTCH1, are
well known to represent the most significant pathogenic event in BCC. However,
specific UV-induced mutations can be found only in approximately 50% of sporadic
BCCs. Thus, cumulative UVB radiation can not be considered to be the single
etiologic risk factor for BCC development. During the last decades, experimental
animal models, including genetically engineered mice, the Xiphophorus hybrid
fish, the south american oppossum and human skin xenografts, have further
elucidated the important role of the DNA repair system in the multi-step process
of UV-induced melanomagenesis. An increasing body of evidence now indicates that
nucleotide excision repair is not the only DNA repair pathway that is involved in
UV-induced tumorigenesis of melanoma and nonmelanoma skin cancer. An interesting
new perspective in DNA damage and repair research lies in the participation of
mammalian mismatch repair (MMR) in UV damage correction. As MMR enzyme hMSH2
displays a p53 target gene, is induced by UVB radiation and is involved in NER
pathways, studies have now been initiated to elucidate the physiological and
pathophysiological role of MMR in malignant melanoma and nonmelanoma skin cancer

Solar UV exposure and mortality from skin tumors. Berwick M, Lachiewicz A, Pestak C, Thomas N. Adv Exp Med Biol. 2008;624:117-24.

Solar ultraviolet radiation (UVR) exposure is clearly associated with increased
mortality from nonmelanoma skin cancer–usually squamous cell carcinoma. However,
the association with cutaneous melanoma is unclear from the evidence in ecologic
studies and the few analytic studies show that high levels of intermittent UV
exposure prior to diagnosis are somehow associated with improved survival from
melanoma. Understanding this conundrum is critical to present coherent public
health messages and to improve the mortality rates from melanoma.

Ultraviolet radiation and malignant melanoma. Moan J, Porojnicu AC, Dahlback A. Adv Exp Med Biol. 2008;624:104-16.

Essential features of the epidemiology and photobiology of cutaneous malignant
melanoma (CMM) in Norway were studied in comparison with data from countries at
lower latitudes. Arguments for and against a relationship between ultraviolet
radiation (UV) from sun and sun beds are discussed. Our data indicate that UV is
a carcinogen for CMM and that intermittent exposures are notably melanomagenic.
This hypothesis was supported both by latitude gradients, by time trends and by
changing patterns of tumor density on different body localizations. However, even
though UV radiation generates CMM, it may also have a protective action and/or an
action that improves prognosis. The same may be true for a number of internal
cancers. There appears to be no, or even an inverse latitude gradient for CMM
arising on non-UV exposed body localizations (uveal melanoma). Furthermore, CMM
prognosis was gradually improved over all years of increasing incidence (up to
1990), but during the last 10 to 15 years, incidence rates decreased and
prognosis was not further improved. While CMM incidence rates are twice as high
in South Norway as in North Norway, the ratios of death rates to incidence rates
are higher in the North, where the annual UV fluences are lower. Death- and
incidence rates in Australia and New Zealand fully support this. Comparisons of
skin cancer data from Norway and Australia/New Zealand indicate that squamous
cell carcinoma and basal cell carcinoma are mainly related to annual solar UVB
fluences, while UVA fluences play a larger role for CMM.

Epidemiology of melanoma and nonmelanoma skin cancer–the role of sunlight. Leiter U, Garbe C. Adv Exp Med Biol. 2008;624:89-103.

Melanoma and nonmelanoma skin cancer (NMSC) are now the most common types of
cancer in white populations. Both tumor entities show an increasing incidence
rate worldwide but a stable or decreasing mortality rate. The rising incidence
rates of NMSC are probably caused by a combination of increased sun exposure or
exposure to ultraviolet (UV) light, increased outdoor activities, changes in
clothing style, increased longevity, ozone depletion, genetics and in some cases,
immune suppression. A dose-dependent increase in the risk of squamous cell
carcinoma (SCC) of the skin was found associated with exposure to Psoralen and
UVA irradiation. An intensive UV exposure in childhood and adolescence was
causative for the development of basal cell carcinoma (BCC) whereas for the
aetiology of SCC a chronic UV exposure in the earlier decades was accused.
Cutaneous malignant melanoma is the most rapidly increasing cancer in white
populations. The frequency of its occurrence is closely associated with the
constitutive colour of the skin and depends on the geographical zone. The highest
incidence rates have been reported from Queensland, Australia with 56 new cases
per year per 100,000 for men and 43 for women. Mortality rates of melanoma show a
stabilisation in the USA, Australia and also in European countries. The tumor
thickness is the most important prognostic factor in primary melanoma. There is
an ongoing trend towards thin melanoma since the last two decades.
Epidemiological studies have confirmed the hypothesis that the majority of all
melanoma cases are caused, at least in part, by excessive exposure to sunlight.
In contrast to squamous cell carcinoma, melanoma risk seems not to be associated
with cumulative, but intermittent exposure to sunlight. Therefore campaigns for
prevention and early detection are necessary.

[Brachytherapy in combination with function-preserving surgery. An interdisciplinary challenge] [Article in German] Meyer JE, Brocks C, Gehrking E, Kovács G, Neppert B, Gliemroth J, Wollenberg B.
HNO. 2008 Apr;56(4):471-8.

A multimodal, interdisciplinary approach known as intensity-modified
brachytherapy is a promising alternative for patients with advanced head and neck
cancer infiltrating the orbita and skull base. An 87-year-old man presented with
a recurrence of squamous cell carcinoma of the medial corner of the left eye that
had been locally resected and irradiated by external beam radiotherapy multiple
times. The cancer was resected with preservation of the eye with close margins,
implantation of afterloading catheters, and reconstruction of the defect with a
median forehead flap. The patient was irradiated with a total radiation dose of
30 Gy IMBT. After 1 year, there was no evidence of locoregional recurrence. The
background of this therapeutic process and analysis of the current literature
regarding this interdisciplinary treatment of head and neck cancer infiltrating
the orbita and skull base are discussed based on this case report.

Multiple cutaneous neoplasms in a patient with Rothmund-Thomson syndrome: case report and published work review. Stinco G, Governatori G, Mattighello P, Patrone P. J Dermatol. 2008 Mar;35(3):154-61.

Rothmund-Thomson syndrome (RTS) is a rare genodermatosis characterized by early
poikilodermatous skin lesions, often combined with juvenile cataracts,
photosensitivity and bone defects. Data in the published work indicate that there
is an increased risk of RTS patients developing malignant tumors. Herein, we
report the multiple skin carcinomas observed in a case of RTS and review the
published work on the occurrence of malignant tumors in these patients. We report
the case of a 63-year-old male with RTS who developed multiple cutaneous
neoplasms (three basal cell carcinomas, three squamous cell carcinomas and
Bowen’s disease) over the previous 15 years. A published work review confirmed
that RTS is a genetic condition that predisposes subjects to the development of
bone tumors, especially at an early age, and skin tumors at an adult age.
Therefore, alongside careful osteoarticular monitoring to identify a bone tumor
quickly, during the life of a patient suffering from the syndrome, it is just as
important to take appropriate preventive action and monitor the possible onset of
skin tumors.

[Breast metastasis from vulvar carcinoma: case report and review of literature] [Article in French] Khouchani M, Benchakroun N, Tahri A, Tawfiq N, Jouhadi H, Acharki A, Sahraoui S, Belaabidia B, Benider A. Cancer Radiother. 2008 Mar;12(2):120-5. Epub 2008 Mar 17.

The breast metastases resulting of vulvar carcinoma are very rare, and represent
exceptionally the first manifestation of the disease. We report the case of a 42
year-old patient who underwent a treatment because of vulvar epidermoid
carcinoma, right away metastatic at the level of the inguinal ganglia. The
treatment consisted in a total vulvectomy with bilateral ganglial curretage,
followed by external radiotherapy about the perineum and the inguinal ganglia.
Three months after the end of her treatment, the patient presented with a nodula
on the left outer breast with features of malignancy noticed by clinic and
mammographic examination. The histologic study of the mammary biopsy showed
epidermoid carcinoma of likely metastatic origin. A left Patey has been realized
and confirmed the metastatic localization of epidermoid carcinoma with axillary
ganglial metastasis (2N+/-7). Besides, this patient presented a right cervical
ganglial parcel that the biopsy showed a metastatic localization of a vulvar
carcinoma. A palliative chemotherapy type cyclophosphamid, adriblastin,
cisplatine (CAP) has been admistrated during three cycles spaced out three weeks.
The patient died 11 months after the supervene of the cerebral metastasis. We
present this case because its rarety and to show the possibility of metastasis at
the level of breast due to vulvar cancer. The clinicians must remember this
possible tropism of the vulvar cancer for the breast, not only during the
supervision and the complete examination as regards the disease spreading but
also when the affection revealed unknown primary tumor. The diagnostic
orientation is based on the mammography and the mammary biopsy. In this stage,
the treatment is unfortunately palliative, the survival until a year is not more
than 20%.

Indications and outcome of salvage surgery for oesophageal cancer. D’Journo XB, Michelet P, Dahan L, Doddoli C, Seitz JF, Giudicelli R, Fuentes PA, Thomas PA. Eur J Cardiothorac Surg. 2008 Jun;33(6):1117-23. Epub 2008 Mar 14.

OBJECTIVE: Some patients with localised oesophageal cancer are treated with
definitive chemoradiotherapy (CRT) rather than surgery. A subset of these
patients experiences local failure, relapse or treatment-related complication
without distant metastases, with no other curative treatment option but salvage
oesophagectomy. The aim of this study was to assess the benefit/risk ratio of
surgery in such context. METHODS: Review of a single institution experience with
24 patients: 18 men and 6 women, with a mean age of 59 years (+/-9). Histology
was squamous cell carcinoma in 18 cases and adenocarcinoma in 6. Initial stages
were cIIA (n=5), cIIB (n=1) and cIII (n=18). CRT consisted of 2-6 sessions of the
association 5-fluorouracil/cisplatin concomitantly with a 50-75 Gy radiation
therapy. Salvage oesophagectomy was considered for the following reasons: relapse
of the disease with conclusive (n=11) or inconclusive biopsies (n=7), intractable
stenosis (n=3), and perforation or severe oesophagitis (n=3), at a mean delay of
74 days (14-240 days) following completion of CRT. RESULTS: All patients
underwent a transthoracic en-bloc oesophagectomy with 2-field lymphadenectomy.
Thirty-day and 90-day mortality rates were 21% and 25%, respectively. Anastomotic
leakage (p=0.05), cardiac failure (p=0.05), length of stay (p=0.03) and the
number of packed red blood cells (p=0.02) were more frequent in patients who
received more than 55 Gy, leading to a doubled in-hospital mortality when
compared to that of patients having received lower doses. A R0 resection was
achieved in 21 patients (87.5%). A complete pathological response (ypT0N0) was
observed in 3 patients (12.5%). Overall and disease-free 5-year survival rates
were 35% and 21%, respectively. There was no long-term survivor following R1-R2
resections. Functional results were good in more than 80% of the long-term
survivors. CONCLUSION: Salvage surgery is a highly invasive and morbid operation
after a volume dose of radiation exceeding 55 Gy. The indication must be
carefully considered, with care taken to avoid incomplete resections. Given that
long-term survival with a fair quality of life can be achieved, such high-risk
surgery should be considered in selected patients at an experienced centre.

EGFR antagonists in cancer treatment. Ciardiello F, Tortora G. N Engl J Med. 2008 Mar 13;358(11):1160-74.

Tissue biomarkers for diagnosis & management of oral squamous cell carcinoma. D’Silva NJ, Ward BB. Alpha Omegan. 2007;100(4):182-9.

Squamous cell carcinoma (SCC) accounts for more than 90% of malignancies of the
oral cavity and oropharynx. Globally, SCC is one of the top ten cancers with a
predilection for older males. In the U.S., SCC accounts for more deaths annually
than cervical cancer, malignant melanoma or Hodgkin’s lymphoma and costs about 2
billion dollars in treatment expenses. The 5-year survival rate is less than 50%,
a prognosis that is poorer than that of breast cancer or melanoma.2 Significant
numbers of patients develop local recurrence, second primary tumors and distant
metastases. Patients presenting with late stage disease resulting in poor
survival, are common; in part due to inadequate screening protocols and access to
care issues. In the following review article, the risk factors, current screening
protocols, treatment options and biomarkers for diagnosis and prognosis of SCC,
will be discussed.

Management of clinically negative neck for the patients with head and neck squamous cell carcinomas in the modern era. Ad VB, Chalian A. Oral Oncol. 2008 Sep;44(9):817-22. Epub 2008 Mar 6.

Management of the cervical metastases is of paramount importance in the treatment
of patients with head and neck squamous cell carcinoma (HNSCC). Head and neck
oncologists continue to debate the appropriate approach of the clinically
negative neck among patients with HNSCC. There are three management options: (A)
Observation, reserving therapeutic neck dissection for only those patients who
subsequently develop metastatic disease in the neck. (B) Staging with reserving
definitive treatment for those who are found to have subclinical disease in the
neck. Staging may require the use of imaging techniques or “staging” neck
dissection. In the latter case a selective neck dissection (SND) is usually
recommended, but it is still controversial if this surgical procedure for
clinically negative neck is a staging or a therapeutic approach. (C) Elective
treatment of the neck using neck dissection, radiation therapy or both. All these
strategies may be appropriate, depending on the clinical circumstances and will
be discussed in this review.

Posttreatment imaging in head and neck cancer. Hermans R. Eur J Radiol. 2008 Jun;66(3):501-11. Epub 2008 Mar 6.

Posttreatment imaging is done when a recurrent tumour is suspected, to confirm
the presence of such a lesion and to determine its extent. The extent of a
recurrent cancer is important information for determining the possibility of
salvage therapy. Imaging may also be used to monitor tumour response and to try
to detect recurrent or persistent disease before it becomes clinically evident,
possibly with a better chance for successful salvage. This article reviews the
expected imaging findings after treatment of head and neck squamous cell cancer,
and how to differentiate these from persistent or recurrent cancer. The relative
value of anatomical and biological imaging modalities, including newer techniques
such as diffusion-weighted magnetic resonance imaging, is addressed. The imaging
findings in treatment-induced complications, such as tissue necrosis, sometimes
difficult to differentiate from cancer, are explained.

Bladder and bowel dysfunction in Parkinson’s disease. Sakakibara R, Uchiyama T, Yamanishi T, Shirai K, Hattori T. J Neural Transm. 2008;115(3):443-60. Epub 2008 Mar 10.

Bladder dysfunction (urinary urgency/frequency) and bowel dysfunction
(constipation) are common non-motor disorders in Parkinson’s disease (PD). In
contrast to motor disorder, the pelvic autonomic dysfunction is often
non-responsive to levodopa treatment. Brain pathology mostly accounts for the
bladder dysfunction (appearance of overactivity) via altered dopamine-basal
ganglia circuit, which normally suppresses the micturition reflex. In contrast,
peripheral enteric pathology mostly accounts for the bowel dysfunction (slow
transit and decreased phasic contraction) via altered dopamine-enteric nervous
system circuit, which normally promotes the peristaltic reflex. In addition, weak
strain and paradoxical anal contraction might be the results of brain pathology.
Pathophysiology of the pelvic organ dysfunction in PD differs from that in
multiple system atrophy; therefore it might aid the differential diagnosis. Drugs
to treat bladder dysfunction in PD include anticholinergic agents. Drugs to treat
bowel dysfunction in PD include dietary fibers, peripheral dopaminergic
antagonists, and selective serotonergic agonists. These treatments might be
beneficial not only in maximizing patients’ quality of life, but also in
promoting intestinal absorption of levodopa and avoiding gastrointestinal

Should there be more molecular staging of head and neck cancer to improve the choice of treatments and thereby improve survival? Almadori G, Bussu F, Paludetti G. Curr Opin Otolaryngol Head Neck Surg. 2008 Apr;16(2):117-26.

PURPOSE OF REVIEW: Overall survival of head and neck squamous cell carcinoma
patients on the whole has not dramatically improved in the last 30 years. One of
the reasons is that tumour, node, metastasis classification is probably in some
cases inadequate, since similar cases under a clinico-pathological point of view,
may differ widely in prognosis. The most important reason for this is probably
the extreme biological heterogeneity, which leads to a lack of consistency in
treatment planning. The aim of the present review is to delineate the advances
and the perspectives of clinical use of molecular characterization, which is an
attempt to break through such molecular heterogeneity and to define, together
with tumour, node, metastasis classification, homogeneous groups of patients for
prognostic stratification and treatment selection. RECENT FINDINGS: Among the
markers evaluated in the last years, some have revealed particular promise.
Epidermal growth factor receptor is probably the most reliable molecular marker
at present, retaining its prognostic value independently from primary treatment.
The p53 gene, the p53 protein being the main effector of DNA damage induced
apoptosis, is probably the best predictor of radio/chemosensitivity. SUMMARY:
Even if clinical tumour, node, metastasis classification will probably retain its
significance, it is now becoming possible, by molecular markers, to acquire
biological information about host and tumour, to break through the above-cited
molecular heterogeneity and eventually to optimize the choice of treatment.

Modern methods to predict costs for the treatment and management of head and neck cancer patients: examples of methods used in the current literature. Wineland AM, Stack BC Jr. Curr Opin Otolaryngol Head Neck Surg. 2008 Apr;16(2):113-6.

PURPOSE OF REVIEW: In the last year, several groups have used various methods to
calculate economic costs to patients with early- and late-stage head and neck
cancer, cost comparisons of palliative treatments, patient time costs associated
with cancer care, and the impact of new diagnostic technologies which need formal
cost-effectiveness assessment to determine their value. RECENT FINDINGS:
Late-stage oral and oropharyngeal cancer treatment is more expensive than
early-stage. Photodynamic therapy is cost-effective for esophageal cancer. Head
and neck cancer patients spend more time receiving care than control cancer.
Multimodal therapy for oropharynx cancer has a higher inpatient utilization than
a radio (chemo) approach. Positron emission tomography in combination with
computed tomography has a high accuracy, positive predictive value, and ability
to find unknown primaries. Soluble CD44 and methylation status are highly
sensitive and specific for detecting head and neck cancer. The Washington
University head and neck cancer comorbidity index was successful at predicting
5-year costs of head and neck cancer. SUMMARY: Evidence-based studies to inform
head and neck cancer care providers are limited. As this available literature
proliferates, it should inform providers and policy makers about optimizing the
quality and cost of healthcare expenses.

Current overview of the role of Akt in cancer studies via applied immunohistochemistry. Shtilbans V, Wu M, Burstein DE. Ann Diagn Pathol. 2008 Apr;12(2):153-60.

The family of AKT kinases, AKT-1, 2, and 3, collectively play a crucial role in
key processes, as well as pathologic processes such as oncogenesis. The numerous
AKT phosphorylation targets include proteins essential to the regulation of cell
cycling, protein translation, suppression of programmed cell death, all of which,
upon activation via AKT-mediated phosphorylation, promote tumor growth, survival,
and aggressiveness. Activation of the AKT pathway can be immunohistochemically
detected with antibodies that specifically react with phosphorylated or
nonphosphorylated forms of AKT. The following review summarizes the use of
phospho-AKT immunohistochemistry as a potentially valuable tool in cancer
prognostication in a wide spectrum of common and uncommon malignancies, including
squamous carcinoma of cervix and of head and neck; adenocarcinoma of endometrium,
ovarian, breast, prostate, kidney, colon, and pancreas; carcinomas of lung and
thyroid; and hematopoietic, soft tissue, and central nervous system neoplasms. To
date, the findings overall suggest that the major use of p-AKT
immunohistochemical staining lies in prognostication and possibly in
individualization of therapy rather than in differential diagnosis.

Actin cytoskeletal mediators of motility and invasion amplified and overexpressed in head and neck cancer. Kelley LC, Shahab S, Weed SA. Clin Exp Metastasis. 2008;25(4):289-304. Epub 2008 Mar 7.

Coordinated regulation of the actin cytoskeleton is central to cell motility,
invasion and metastasis. Head and neck squamous cell carcinoma (HNSCC) is a
highly invasive disease displaying frequent lymph node metastasis, compounding
patient management. HNSCC progression is characterized by frequent amplification
of chromosome segments 3q26-29, 8q23-24 and 11q13, events that are associated
with poor patient outcome. The relative frequency of these amplification events
and correlation with invasive disease raises the potential that these regions
harbor actin regulatory genes important in facilitating reorganization of the
actin cytoskeleton to promote tumor invasion. Identification of the actin
cytoskeletal regulatory genes located within the 3q26-29, 8q23-24 and 11q13
amplicons will provide an important first step towards the comprehensive
understanding of the molecular events that govern invasion and metastasis in
HNSCC and other tumors containing these amplifications. We utilized Ensembl
MartView to conduct a gene mining analysis within chromosome segments 3q26-29,
8q23-24 and 11q13 to identify known and predicted regulators of actin-based cell
movement, tumor invasion and metastasis. All examined chromosomal regions contain
genes known that regulate the actin cytoskeleton, with several (PI3-kinase alpha,
focal adhesion kinase (FAK) and cortactin) known to promote invasion in HNSCC and
other carcinomas. Additional genes known to regulate motility and invasion were
also identified. Amplification of chromosome 3q26-29, 8q23-24 and 11q13 therefore
results in known or predicted overexpression of several key mediators that can
act alone or potentially act in concert to promote actin-based cell invasion in
HNSCC and other cancer types.

10 derm mistakes you don’t want to make. Fox GN. J Fam Pract. 2008 Mar;57(3):162-9.

Application of immunohistochemistry to the diagnosis of malignant mesothelioma. Marchevsky AM. Arch Pathol Lab Med. 2008 Mar;132(3):397-401.

CONTEXT: The diagnosis of malignant mesothelioma (MM) is rendered with the aid of
immunohistochemistry to demonstrate the presence of “mesothelial,” “epithelial,”
or “sarcomatous” differentiation. Antibody panels that have been proposed for the
distinction between MM and other neoplasms usually include 2 or more epithelial
markers used to exclude the diagnosis of a carcinoma, such as monoclonal and
polyclonal carcinoembryonic antigen, Ber-EP4, B72.3, CD15, MOC-31, thyroid
transcription factor 1, BG8, and others, and 2 or more mesothelial markers used
to confirm the diagnosis of MM, such as cytokeratin 5/6, calretinin, HBME-1,
thrombomodulin, WT-1, mesothelin, D2-40, and podoplanin. In general, most
antibody panels provide excellent sensitivity and specificity for the
differential diagnosis between MM epithelial variant and adenocarcinoma,
particularly of lung origin. However, the accuracy of these markers is lower for
the diagnosis of sarcomatous MM and for the differential diagnosis between MM and
squamous cell carcinoma and carcinomas of renal, ovarian, and other origin.
OBJECTIVE: To identify optimal antibody panels for the diagnosis of MM. DATA
SOURCES: Literature review to determine how many and which mesothelial and
epithelial markers need to be included in differential diagnosis antibody panels.
CONCLUSIONS: Various antibody panels have been recommended for the diagnosis of
MM, with no overall consensus about how many and which markers should be used. A
recent study with Bayesian statistics has demonstrated that the use of many
markers does not provide higher diagnostic accuracy than the use of selected
single antibodies or various combinations of only 2 markers. There is a need for
the development of evidence-based or consensus-based guidelines for the diagnosis
of MM in different differential diagnosis situations.

Adenoid squamous carcinoma (pseudoangiosarcomatous carcinoma) of the vulva: a rare but highly aggressive variant of squamous cell carcinoma-report of a case and review of the literature. Horn LC, Liebert UG, Edelmann J, Höckel M, Einenkel J. Int J Gynecol Pathol. 2008 Apr;27(2):288-91.

Pseudoangiosarcomatous squamous cell carcinoma is an unusual but aggressive
variant of acantholytic squamous cell carcinoma of the vulva that mimics
angiosarcoma on histology. We present a case of a 57-year-old woman with
bilateral inguinal metastatic disease at the time of diagnosis, who died 4 months
later because of distant metastatic disease to the lungs. Molecular analysis did
not reveal any human papillomavirus infection. Because of the positive p53
immunostaining and the association to lichen sclerosus and simple type of
high-grade vulvar intraepithelial neoplasia, alteration of p53 tumor suppressor
gene might be involved in the pathogenesis of vulvar pseudoangiosarcomatous
squamous cell carcinoma. However, further molecular studies are required.

[Problem areas of tumour classifications--thyroid carcinomas] [Article in German] Schmid KW. Verh Dtsch Ges Pathol. 2007;91:57-65.

Thyroid carcinoma has been traditionally subdivided into the four major groups
papillary, follicular, medullary, and anaplastic carcinoma. The WHO
classification of thyroid tumours, published in 2004, has added to these four
tumour groups the entity of poorly differentiated carcinoma as well as a broad
variety of rare thyroid malignancies. Another important change concerns the
histological hallmarks of papillary carcinoma, the diagnosis of which is now
exclusively dependent on characteristic nuclear features. The aim of the present
paper is to highlight diagnostic problems particularly caused by the alteration
introduced onto the WHO classification, This includes a proposal of a more
systematic thyroid carcinoma classification based on the histogenetic
differentiation (follicular cell differentiation. C cell differentiation, rare
carcinomas) and tumour grading of carcinomas with follicular cell differentiation
(differentiated, poorly differentiated and anaplastic carcinomas) as well as
commentaries on the diagnosis of papillary carcinoma, poorly differentiated
carcinoma, and rare types of thyroid carcinoma (squamous cell carcinoma,
mucoepidermoid carcinoma, sclerosing mucoepidermoid carcinoma with eosinophilia,
mucinous carcinoma, SETTLE, and CASTLE).

Spindle cell carcinoma of the palatine tonsil: report of a diagnostic pitfall and literature review. Minami SB, Shinden S, Yamashita T. Am J Otolaryngol. 2008 Mar-Apr;29(2):123-5.

Spindle cell carcinomas of the tonsil are very rare tumors. We present an
additional case that occurred in a 58-year-old woman. She presented with a tumor
of the right tonsil. Histologic sections of tonsillar biopsies suggested that
this tumor was a squamous cell carcinoma. She underwent a transoral resection of
the right oropharynx. The final diagnosis was spindle cell carcinoma. We
emphasize the difficulties in diagnosing this type of tumor and discuss
therapeutic approaches to this rare tumor, which shows little response to
radiotherapy; the literature is reviewed. We offer this case study in an effort
to increase awareness of this rare malignancy.

Terameprocol, a novel site-specific transcription inhibitor with anticancer activity. Smolewski P. IDrugs. 2008 Mar;11(3):204-14.

Terameprocol, a novel, semisynthetic derivative of a naturally occurring plant
lignan, is under development by Erimos Pharmaceuticals LLC for the potential
treatment of cancer. The antitumor activity of terameprocol is based on the
selective inhibition of specificity protein 1 (Sp1)-regulated proteins, including
cyclin-dependent kinase 1, survivin and VEGF. With this mechanism of action,
terameprocol potentially inhibits the cell cycle, triggers apoptosis and
decreases angiogenesis. Several preclinical studies have demonstrated the potent
anticancer activity of terameprocol in tumor cell lines and animal models. In
addition, terameprocol prevented the proliferation of HIV, HSV and HPV by a
deactivation of viral Sp1-dependent promoters in preclinical studies. In a phase
I clinical trial in patients (25 evaluable) with solid tumors administered
intravenous terameprocol, 8 patients exhibited stable disease and 17 had
progressive disease; the drug was generally well tolerated. A good safety and
efficacy profile has also been observed with the intratumoral and intravaginal
administration of terameprocol in patients with head and neck or squamous cell
carcinoma and in patients with cervical dysplasia, respectively. At the time of
publication, terameprocol was in phase I or I/II clinical development for the
treatment of glioma, treatment-refractory solid tumors and cervical dysplasia; a
phase I clinical trial was also planned in patients with hematological cancers.
Thus, the favorable tolerability and efficacy profile demonstrated for
terameprocol to date suggests that the further investigation of this drug is

Activation of the PI3-K/AKT pathway and implications for radioresistance mechanisms in head and neck cancer. Bussink J, van der Kogel AJ, Kaanders JH. Lancet Oncol. 2008 Mar;9(3):288-96.

Activation of the phosphatidylinositol-3-kinase (PI3-K)/protein kinase B (AKT)
pathway is associated with three major radioresistance mechanisms: intrinsic
radioresistance; tumour-cell proliferation; and hypoxia. Monitoring and
manipulation of this signal-transduction pathway can have important implications
for the management of head and neck cancer, because activation of the PI3-K/AKT
pathway is a frequent event in these tumours. PI3-K/AKT signalling regulates
cellular processes, including proliferation, invasion, apoptosis, and the
upregulation of hypoxia-related proteins. Activation of this pathway can be
caused by stimulation of receptor tyrosine kinases, such as epidermal growth
factor receptor (EGFR). In clinical trials, a strong and independent association
has been noted between expression of activated AKT and treatment outcome.
Therefore, the search for molecular predictors of sensitivity to EGFR-directed
treatment should be extended to markers of PI3-K/AKT activation. Another strategy
might be the direct targeting and inhibition of this pathway. Such inhibition
will enhance the efficacy of radiotherapy, by antagonising radiation-induced
cellular defense mechanisms, especially in tumours that have activated the
PI3-K/AKT cascade. Thus, the activation status of this pathway might be a key
element for the prediction of treatment response and for therapeutic targeting in
head and neck cancer.

Bladder cancer in Africa. Heyns CF, van der Merwe A. Can J Urol. 2008 Feb;15(1):3899-908.

Accurate epidemiological data about the incidence and mortality of bladder cancer
are unavailable for most African countries. Transitional cell carcinoma (TCC) of
the bladder is probably less common in rural African regions than in
industrialized countries, due to lower levels of exposure to carcinogenic
chemicals. In areas with endemic schistosomiasis (bilharzia) caused by parasitic
schistosomes (blood flukes), most bladder cancer cases are comprised of squamous
cell carcinoma (SCC). However, with increased urbanization, industrialization,
and cigarette smoking in many African countries, there is an increasing incidence
of TCC relative to SCC of the bladder. SCC of the bladder presents in patients
who are on average 10 to 20 years younger than those with TCC. In Egypt and other
North African countries, SCC is more common in men (the male to female ratio
ranges from 3:1 to 5:1), probably because boys and men performing agricultural
work are more exposed to schistosomiasis-infested water. In some sub-Saharan
countries, SCC of the bladder is equally common in men and women, probably due to
equal schistosomiasis exposure of girls and boys, and because women obtain
household water and perform most agricultural tasks. Although SCC of the bladder
often presents at a locally advanced stage, the tumors are usually well
differentiated, with a relatively low incidence of lymphatic and hematogenous
metastases. Patients with localized SCC are ideal candidates for cystectomy and
orthotopic neobladder construction, because they are relatively young and
healthy, and there is no risk of urethral recurrence, unlike with TCC.
Unfortunately, many patients in Africa still present with advanced and inoperable
bladder cancer, and many do not have access to healthcare facilities that can
provide a cure and a good quality of life by means of radical cystectomy and
neobladder construction.

Antiangiogenic therapy in nonsmall cell lung cancer. Gutierrez M, Giaccone G. Curr Opin Oncol. 2008 Mar;20(2):176-82.

PURPOSE OF REVIEW: The use of targeted therapies, particularly those against the
key mediator of angiogenesis, vascular endothelial growth factor, has the
potential to improve outcomes for nonsmall cell lung cancer (NSCLC) patients.
This review summarizes recent findings on targeting mediators of angiogenesis,
treatment options and molecular targets in development. RECENT FINDINGS:
Bevacizumab, a recombinant humanized monoclonal antivascular endothelial growth
factor antibody, in a phase III study, showed significantly improved overall and
progression-free survival when used in combination with standard first-line
chemotherapy in patients with advanced NSCLC and was generally well tolerated.
Adverse events, including tumor-related bleeding, have been noted in some
patients, predominantly those with squamous cell histology or centrally located
tumors. SUMMARY: Several small-molecule vascular endothelial growth factor
receptor tyrosine kinase inhibitors have also shown promise in phase I and II
trials in NSCLC. This review summarizes the most important findings on
angiogenesis inhibitors in NSCLC and discusses the potential for the use of these
novel agents in different settings.

Neuroendocrine tumors of the lung. García-Yuste M, Matilla JM, González-Aragoneses F. Curr Opin Oncol. 2008 Mar;20(2):148-54.

PURPOSE OF REVIEW: The aim of this article is to answering different questions
related to the treatment and prognosis of neuroendocrine lung tumors. RECENT
FINDINGS: In neuroendocrine lung tumors, regardless of the grade of tumoral
malignancy, the general growth during the past years of the nodal involvement
percentage detected in lung neuroendocrine tumors might be explained by accepting
surgical treatment as the norm and a complete mediastinal nodal dissection. Among
non-small-cell carcinomas, large cell neuroendocrine carcinoma is the tumor with
the worst prognosis. Nodal invasion clearly decreases the possibility of
long-term survival in these patients, confirming the importance of preoperative
and perioperative staging. A definitive survival advantage for postoperative
adjuvant therapy has yet to be reported; tumoral genetics studies may contribute
to specifying its indication. The importance of neuroendocrine differentiation in
non-small-cell lung carcinomas for the treatment and prognosis of these tumors is
a reason to intensify research. SUMMARY: In the surgical treatment of lung
neuroendocrine carcinomas, nodal mediastinal dissection should always be
performed. In the large neuroendocrine carcinoma, experience confirms the
possibility of surgical treatment in early stages; in all cases, adjuvant
treatment should always be established. The presence of synaptophysin in squamous
carcinoma tumors and adenocarcinoma tumors in stage I seems to be associated with
a worse prognosis.

Non-neoplastic epithelial disorders of the vulva. O’Connell TX, Nathan LS, Satmary WA, Goldstein AT. Am Fam Physician. 2008 Feb 1;77(3):321-6.

Lichen sclerosus, lichen planus, and lichen simplex chronicus are three of the
most common non-neoplastic epithelial disorders of the vulva. Lichen sclerosus is
characterized by intense vulvar itching and can affect men and women of all ages,
but it manifests most commonly in postmenopausal women. Patients with lichen
sclerosus have an increased risk of developing squamous cell carcinoma, and they
should be monitored for malignancy. Lichen planus is an inflammatory autoimmune
disorder that can affect the vulva and the vagina; it peaks in incidence between
ages 30 and 60. There are three clinical variants of lichen planus affecting the
vulva: erosive, papulosquamous, and hypertrophic. Lichen simplex chronicus is
caused by persistent itching and scratching of the vulvar skin, which results in
a thickened, leathery appearance. It is thought to be an atopic disorder in many
cases and may arise in normal skin as a result of psychological stress or
environmental factors. Definitive diagnosis of non-neoplastic disorders depends
on the histology of biopsied tissue. All three disorders are treated with topical
corticosteroid ointments of varying potency. Lichen sclerosus and lichen planus
are not routinely treated with surgery, which is necessary only in patients who
have a malignancy or advanced scarring that causes dyspareunia or clitoral
phimosis. Educational counseling teaches patients that even though these chronic
disorders cannot be cured, they can be effectively managed.

From cancer genomics to thoracic oncology: discovery of new biomarkers and therapeutic targets for lung and esophageal carcinoma. Daigo Y, Nakamura Y. Gen Thorac Cardiovasc Surg. 2008 Feb;56(2):43-53. Epub 2008 Feb 24.

Over the last decade, many genetic and epigenetic alterations involved in the
development and progression of lung and esophageal cancers have been reported,
but their precise molecular mechanisms have remained unclear. Although novel
drugs targeting some of these molecular targets have been developed, they provide
limited survival benefits to only a small subset of cancer patients, and only a
small number of practically useful biomarkers are presently available. To
identify the molecules involved in lung and esophageal carcinogenesis and those
applicable as novel tumor biomarkers and for the development of new molecular
therapies, we performed gene expression profile analysis of 101 archived lung
cancers and 19 esophageal squamous cell carcinomas whose tumor cells were
purified by laser microdissection. Through a subsequent systematic approach using
tissue microarray, RNA interference, and high throughput enzyme-linked
immunosorbent assay techniques as well as bioinformatics, we have identified a
set of molecules that fall into the category of oncoantigens. These molecules are
potentially promising candidates for the development of novel diagnostic
biomarkers, therapeutic drugs, and/or immunotherapy; there is also a small subset
of biomarkers for predicting the presence of lymph node metastasis in surgically
treated patients.In this article, we introduce our sophisticated and integrated
cancer genomics strategy for improving the treatment of cancer patients.

A novel approach to the management of acute tracheal tear. Creagh-Brown B, Sheth A, Crerar-Gilbert A, Madden BP. J Laryngol Otol. 2008 Dec;122(12):1392-3. Epub 2008 Feb 21.

OBJECTIVE: We describe the emergency use of a covered, expandable, removable
tracheal stent in a patient who developed a large posterior tracheal tear
complicating endobronchial therapy for large airway obstruction. METHOD: Case
report and review of the literature concerning management of acute tracheal tear.
RESULTS AND CONCLUSION: Our patient demonstrates that endotracheal stenting is an
option for managing acute large airway tear. Moreover, the use of a removable
stent allows not only for rapid closure of the defect but also removal once the
defect has healed, thus avoiding long-term complications of stent deployment.

Neck dissection: present and future? Ferlito A, Silver CE, Rinaldo A. Eur Arch Otorhinolaryngol. 2008 Jun;265(6):621-6.

A number of issues are at the forefront of current considerations in surgical
treatment of the neck in head and neck cancer. These include proposed new
definitions of lymph node levels that will lend themselves to clinical and
radiographic examination, the possibility of employing molecular studies to
supply information on the metastatic potential of the primary tumor in the
clinically negative neck, and the results of multi-institutional prospective
pathologic studies of neck dissection specimens examining the early distribution
of lymph node metastases from various primary sites, to design more effective and
efficient surgical procedures for treatment. The pertinent current literature was
reviewed, and appropriate data extracted. Various new landmarks have been defined
to distinguish the boundaries between sublevels IB and IIA, the lateral borders
of level VI, and the boundaries of level VII. These landmarks are more readily
distinguishable on physical and radiographic examination than the definitions
currently in use. Numerous molecular studies have been employed to detect
subclinical metastatic deposits in the neck, but none have been found
sufficiently reliable for practical application. Multi-institutional studies have
shown that sublevels IIB and level IV are rarely within the first level of
lymphatic drainage routes for most primary squamous cell cancers of the head and
neck. Therefore, elective selective neck dissections may be further modified to
reduce morbidity and operating time. Various new issues in the treatment of
cervical metastatic disease are discussed in an effort to improve the accuracy of
pretreatment staging, identification of occult disease, and modification of
surgical treatment to optimize efficiency and reduce morbidity.

Basic and clinical aspects of non-neuronal acetylcholine: expression of non-neuronal acetylcholine in lung cancer provides a new target for cancer therapy. Song P, Spindel ER. J Pharmacol Sci. 2008 Feb;106(2):180-5. Epub 2008 Feb 16.

Lung cancer is the leading cause of cancer death worldwide and new treatment
strategies are clearly needed. The recent discovery that lung and other cancers
synthesize and secrete acetylcholine (ACh) which acts as an autocrine growth
factor suggests that this cholinergic autocrine loop may present new therapeutic
targets. In normal bronchial epithelium, small airway epithelium and pulmonary
neuroendocrine cells synthesize Ach; and in squamous cell lung carcinoma,
adenocarcinoma, and small cell lung carcinoma, the respective lung cancers that
derive from those cell types similarly synthesize ACh. ACh secreted by those
cancers stimulates growth of the tumors by binding to nicotinic and muscarinic
receptors expressed on lung cancers. Thus antagonists to nicotinic and muscarinic
receptors can inhibit lung cancer growth. The muscarinic receptor (mAChR) subtype
utilized for cell proliferation is the M(3) subtype and consistent with this M(3)
mAChR antagonists inhibit growth of SCLC and squamous cell carcinomas. This is
significant as M(3) mAChR antagonists have low toxicity and are in wide clinical
use. As multiple other cancer types besides lung carcinomas express both M(3)
mAChR and acetylcholine, other cancer types besides lung carcinoma may respond to
M(3) mAChR antagonists.

Outdoor sports and skin cancer. Moehrle M. Clin Dermatol. 2008 Jan-Feb;26(1):12-5.

Ultraviolet radiation is estimated to be one of the most important risk factors
for nonmelanoma and melanoma skin cancers. Athletes practicing outdoor sports
receive considerable UV doses because of training and competition schedules with
high sun exposure, and in alpine sports, by altitude-related increase of UV
radiation and reflection from snow- and ice-covered surfaces. Extreme UV exposure
in outdoor sports such as skiing, mountaineering, cycling, or triathlon has been
documented in a series of dosimetric studies. Sweating because of physical
exercise may contribute to UV-related skin damage as it increases the individual
photosensitivity of the skin, facilitating the risk of sunburns. Large
epidemiological studies showed that recreational activities such as sun exposure
on the beach or during water sports were associated with an increased risk of
basal cell carcinoma, whereas skiing has been shown to be at increased risk for
squamous cell carcinoma. Risk factors of cutaneous melanoma such as the number of
melanocytic nevi and solar lentigines have been found to be more frequent in
subjects practicing endurance outdoor sports. An increased risk for cutaneous
melanoma may be assumed for these athletes. In addition to the important sun
exposure, exercise-induced immunosuppression may increase the risk for
nonmelanoma skin cancer and cutaneous melanoma in athletes. Frequently, athletes
seem to know little about the risk of sun exposure. Protective means such as
avoiding training and competition with considerable sun exposure, choosing
adequate clothing, and applying water-resistant sunscreen still need to be
propagated in the community of outdoor sportsmen.

Activated leukocyte cell adhesion molecule: a new paradox in cancer. Ofori-Acquah SF, King JA. Transl Res. 2008 Mar;151(3):122-8. Epub 2007 Oct 23.

The activated leukocyte cell adhesion molecule [ALCAM/CD166/melanoma metastasis
clone D (MEMD)] is an immunoglobulin superfamily cell adhesion molecule. It is
expressed developmentally in cells of all 3 embryonic lineages. The ALCAM
expression is limited to subsets of cells in most adult tissues. ALCAM is
localized at intercellular junctions in epithelium presumably as part of the
adhesive complex that maintains tissue architecture. Over the past decade,
alterations in expression of ALCAM have been reported in several human tumors
(melanoma, prostate cancer, breast cancer, colorectal carcinoma, bladder cancer,
and esophageal squamous cell carcinoma). This review summarizes the current
knowledge of the role of ALCAM in malignancies.

Cyclooxygenase-2 in cervical neoplasia: a review. Young JL, Jazaeri AA, Darus CJ, Modesitt SC. Gynecol Oncol. 2008 Apr;109(1):140-5. Epub 2008 Feb 13.

OBJECTIVE: Previous data demonstrate an association between cyclooxygenase
activity and development of cervical cancer. This review investigates the role of
cyclooxygenase-2 (COX-2) in the development of cervical cancer and potential
therapeutic options targeting this pathway. METHODS: A literature search was
conducted using MEDLINE 1997-2007 utilizing the terms inflammation, cervical
cancer, cyclooxygenase, COX-2, indomethacin, cervical intraepithelial neoplasia,
and squamous cell cancer. Articles were included based on the quality of the
study and pertinence to the topic. Other sources were culled from the references
of the articles identified. RESULTS: Over 150 abstracts were reviewed for
inclusion. Studies in vivo and in vitro confirm the role of COX-2 in the
development of cervical cancer. In addition, COX-2 overexpression is associated
with an increase in angiogenesis markers. Clinical correlation found that COX-2
overexpression in cervical cancer patients is a poor prognostic marker associated
with increased risk for recurrent or metastatic disease. Despite early promise,
two phase II trials in use of specific COX-2 inhibitors as radio-sensitizers in
locally advanced cervical cancer demonstrated increased toxicity with no change
in therapeutic effect. Results of studies using COX-2 inhibitors in pre-invasive
cervical disease are encouraging. CONCLUSIONS: Treatment of cervical
intraepithelial neoplasia with cyclooxygenase inhibitors may provide a medical
alternative to surgical therapy.

Squamous cell carcinoma arising within a choledochal cyst. Price L, Kozarek R, Agoff N. Dig Dis Sci. 2008 Oct;53(10):2822-5. Epub 2008 Feb 15.

Choledochal cysts are rare congenital or acquired cystic dilatations of the
intra- or extrahepatic bile ducts. Their exact pathophysiology remains unclear.
Extensive complications exist with untreated cysts, including biliary stasis and
inflammation, with resultant stricture and stone formation, cholangitis,
pancreatitis, and malignant degeneration. Most commonly reported malignancies
include cholangiocarcinoma, adenocarcinoma, and gallbladder cancer. We report the
case of a 41-year-old female with a history of chronic calcific pancreatitis,
choledocholithiasis, and a large type I choledochal cyst, who presented with
flu-like symptoms followed by painless jaundice and weight loss. Endoscopic
retrograde cholangiopancreatography and direct cholangioscopy revealed a mass at
the biliary bifurcation, a 4-cm choledochal cyst with multiple calculi, absence
of anomalous pancreaticobiliary ductal union, and multiple calcifications in the
pancreatic head. Pathology demonstrated a synchronous choledochal cyst and
squamous cell carcinoma, an infrequently reported phenomenon. We report the
associated rare finding of chronic calcific pancreatitis, without anomaly of the
pancreatic biliary junction. This suggests that the formation of calculi within
the choledochal cyst may contribute to chronic calcific pancreatitis, possibly by
virtue of papillary stenosis.

Non-melanoma skin cancer: importance of gender, immunosuppressive status and vitamin D. Oberyszyn TM. Cancer Lett. 2008 Mar 18;261(2):127-36. Epub 2008 Feb 11.

Ultraviolet light B (UVB) is responsible for the majority of cutaneous damage and
is believed to be the single most important etiologic agent in the development of
non-melanoma skin cancers (NMSC). These skin tumors are by far the most common
form of cancer in humans, with over 1 million new cases identified in the United
States each year. Several risk factors exist, which increase the chance of a
patient developing NMSC including gender, immunosuppressive status and more
controversially vitamin D levels. The present review provides an overview of each
of these areas.

Cervical cancer. Greer BE, Koh WJ, Abu-Rustum N, Bookman MA, Bristow RE, Campos S, Cho KR, Copeland L, Eifel P, Huh WK, Jaggernauth W, Kapp DS, Kavanagh J, Lipscomb GH, Lurain JR 3rd, Morgan M, Morgan RJ Jr, Powell CB, Remmenga SW, Reynolds RK, Secord AA, Small W Jr, Teng N, National Comprehensive Cancer Network. J Natl Compr Canc Netw. 2008 Jan;6(1):14-36.

Recent advances in Oral Oncology 2007: imaging, treatment and treatment outcomes. Scully C, Bagan JV. Oral Oncol. 2008 Mar;44(3):211-5. Epub 2008 Feb 7.

This paper provides a synopsis of the main papers on imaging, treatment and
treatment outcomes in patients with oral and oropharyngeal squamous cell
carcinoma (OSCC) and head and neck SCC (HNSCC) published in 2007 in Oral Oncology
- an international interdisciplinary journal which publishes high quality
original research, clinical trials and review articles, and all other scientific
articles relating to the aetiopathogenesis, epidemiology, prevention, clinical
features, diagnosis, treatment and management of patients with neoplasms in the
head and neck, and orofacial disease in patients with malignant disease.

Indications for PET/CT in the head and neck. Agarwal V, Branstetter BF 4th, Johnson JT. Otolaryngol Clin North Am. 2008 Feb;41(1):23-49, v.

PET/CT has revolutionized the evaluation of patients with head and neck cancer by
allowing more accurate staging, more focused treatment modalities, earlier
detection of recurrent disease, and identification of incurable disease. In some
clinical scenarios, PET/CT is clearly useful, while in others the cost may not be
warranted. In this chapter, the authors review the literature on the use of
PET/CT in head and neck cancers (in particular squamous cell carcinoma) and
provide an evidence-based approach to the use of PET/CT for staging, treatment
planning, monitoring of treatment response, and surveillance of treated patients
with squamous cell carcinoma. They also briefly address the use of PET/CT for
thyroid cancer, lymphoma, and melanoma. At the end of each section, key points
are summarized in a box for quick reference.

[Strategy of combined treatment in patient with cancer of paranasal sinuses] [Article in Polish] Kiprian D. Otolaryngol Pol. 2007;61(4):527-30.

Cancers of pranasal sinuses are rare neoplasms in humans. In 2003, in Poland
there were 132 new patients diagnosed for this disease. Squamous cell cancer is
the most frequent one in this region. Other types of cancer in this region are
adenocarcinoma (about 30%), carcinoma adenoides cysticum or neoplasms such as
rhabdosarcoma, chondrosarcoma, lymphoma or melanoma malignum. There is a very
rare neoplasm as a olfactory neuroblastoma in this localization. Cancer of the
paranasal sinuses infiltrates only locoregionally. Metastases to the lymph nodes
are seldom–below 30%; this is why elective lymphangiectomy or irradiation are
not obligatory treatment in this case. The most important is histopathological
verification performed by biopsy. For clinical staging it is obligatory to
perform endoscopy, CT or MR examination. The treatment of cancers of paranasal
sinuses is always surgery with adjuvant irradiation. The modern radiotherapy
techniques provide the possibility to spare healthy tissues and organs at risk.
The organs at risk in this localization are optical nerves and chiasm, and
parotid glands. The conformal radiotherapy is used most frequently. In case of
the tumour being of complex shape and located in the vicinity of the organs at
risk the IMRT technique is used. The radiation treatment combined with
chemotherapy is applied in cases of not radical surgery in the region of
ethmoides sinuses.

Institutional and comprehensive review of laryngeal leukoplakia. Isenberg JS, Crozier DL, Dailey SH. Ann Otol Rhinol Laryngol. 2008 Jan;117(1):74-9.

OBJECTIVES: The nature and interpretation of vocal fold leukoplakia has been
limited by small study sizes. The present study reviewed institutional data and
the published literature to better characterize vocal fold leukoplakia. METHODS:
At our institution, the histopathology, age, and malignant conversion rates of
136 patients (208 biopsies) with vocal fold leukoplakia from 1990 to 2005 were
reviewed. RESULTS: No dysplasia (ND), mild and/or moderate dysplasia (MM), and
severe dysplasia and/or squamous cell carcinoma in situ (SS) was identified in,
respectively, 110 of 208 (53%), 38 of 208 (18%), and 31 of 208 (15%) biopsies.
After 30 months (range, 1 to 134 months), malignant transformation was observed
in 8 patients on subsequent biopsies. Additionally, a literature search was
performed from 1960 to 2005 for the medical subject headings (MeSH) premalignant
laryngeal lesions, laryngeal dysplasia, laryngeal leukoplakia, vocal cord
dysplasia, and hyperkeratosis of the larynx. Fifteen reports were included for
review. When these were combined with our institutional data, 1,173 of 2,188
biopsies (53.6%) revealed ND. Mild and/or moderate dysplasia and SS were present
in 717 of 2,140 (33.5%) and 375 of 2,471 (15.2%) biopsies, respectively. Squamous
cell carcinoma developed in 52 of 1,388 (3.7%), 83 of 824 (10.1%), and 56 of 310
(18.1%) patients whose initial biopsies demonstrated ND, MM, or SS. CONCLUSIONS:
More than half of the reported leukoplakia lesions with biopsies showed ND.
However, even lesions characterized as ND were associated with an increased risk
of development of squamous cell carcinoma. Importantly, the risk of developing
malignancy appears to correlate with the severity of dysplasia present on initial
biopsy. Because clinical examination does not accurately predict the risk of
malignancy, future studies, including genomic evaluation of this lesion, may be
necessary to further characterize its biologic behavior.

Recent advances in Oral Oncology 2007: epidemiology, aetiopathogenesis, diagnosis and prognostication. Bagan JV, Scully C. Oral Oncol. 2008 Feb;44(2):103-8.

This paper provides a synopsis of the main papers on epidemiology, diagnosis and
prognosis of oral and oropharyngeal squamous cell carcinoma (OSCC) and head and
neck SCC (HNSCC) published in 2007 in Oral Oncology – an international
interdisciplinary journal which publishes high quality original research,
clinical trials and review articles, and all other scientific articles relating
to the aetiopathogenesis, epidemiology, prevention, clinical features, diagnosis,
treatment and management of patients with neoplasms in the head and neck, and
orofacial disease in patients with malignant disease.

Tissue microarray – a high-throughput molecular analysis in head and neck cancer. Radhakrishnan R, Solomon M, Satyamoorthy K, Martin LE, Lingen MW. J Oral Pathol Med. 2008 Mar;37(3):166-76.

With the identification of a number of novel markers having diagnostic,
prognostic, and therapeutic significance, the application of tissue microarray
(TMA) has become a valuable tool for validating candidate markers in cancer
research. The TMA is a high-throughput technique, which allows large-scale
analyses of hundreds of archival clinical tissue samples using the ‘array’
approach. This paper highlights briefly its robust technology, technical aspects
of its construction, and the validity of the TMA results for oral pathology
diagnostics by reviewing data from recent literature particularly with reference
to head and neck cancer.

Oral epithelial dysplasia classification systems: predictive value, utility, weaknesses and scope for improvement. Warnakulasuriya S, Reibel J, Bouquot J, Dabelsteen E. J Oral Pathol Med. 2008 Mar;37(3):127-33.

At a workshop coordinated by the WHO Collaborating Centre for Oral Cancer and
Precancer in the United Kingdom issues related to potentially malignant disorders
of the oral cavity were discussed by an expert group. The consensus views of the
Working Group are presented in a series of papers. In this report, we review the
oral epithelial dysplasia classification systems. The three classification
schemes [oral epithelial dysplasia scoring system, squamous intraepithelial
neoplasia and Ljubljana classifica