Statin use is associated with reduced risk of histologic subtypes of esophageal cancer: a nested case-control analysis.

BACKGROUND & AIMS: Most patients with esophageal adenocarcinoma (EAC) or squamous cell cancer (ESCC) present with advanced, incurable disease. Statins have reported anti-carcinogenic effects and may be chemoprotective. We investigated the association between regular use of statins and the main histologic subtypes of esophageal malignancy (EAC, esophagogastric junctional adenocarcinoma, and ESCC) in the UK general population. METHODS: We identified all individuals in the UK General Practice Research Database diagnosed with esophageal cancer from 2000 through 2009. Patients were linked to the National Cancer Registry to confirm histologic subtypes. Each patient was matched with up to 4 controls for age, sex, and practice. We performed a nested case-control analysis using conditional logistic regression to estimate the risk of each subtype with regular statin use, adjusted for body mass index, smoking, alcohol intake, and concomitant use of medications. RESULTS: In total, 581 participants with EAC, 213 with esophagogastric junctional adenocarcinoma, and 332 with ESCC were matched to 2167, 783, and 1242 controls, respectively. Regular statin use was inversely associated with development of EAC (odds ratio = 0.58; 95% confidence interval: 0.39-0.87) (with significant dose and duration responses) and esophagogastric junctional adenocarcinoma (odds ratio = 0.29; 95% confidence interval: 0.09-0.92) (with high-dose use only). Statin use for 1-4 years was inversely associated with ESCC (odds ratio = 0.51; 95% confidence interval: 0.27-0.98). CONCLUSIONS: In a nested case-control analysis of a UK population-based cohort, statin use was inversely associated with histologic subtypes of esophageal cancer. Randomized controlled trials are warranted to determine whether statins have chemopreventive effects in high-risk groups.

Capecitabine to reduce nonmelanoma skin carcinoma burden in solid organ transplant recipients.

BACKGROUND: Solidorgan transplant recipients (SOTRs) are at greater risk of nonmelanoma skin cancer (NMSC) than the general population, in large part because of their immunosuppression. Select individual SOTRs demonstrate a rate of tumor development at the upper end of their cohort. Capecitabine, a prodrug converted in the body to 5-fluorouracil (5-FU), may alter the risk for development of NMSC in an individual SOTR with a high rate of tumor development. OBJECTIVE: To report observations of a series of 10 SOTRs treated with capecitabine as adjuvant prevention for high-incidence NMSC. METHODS: Ten SOTRs were administered cycles of low-dose oral capecitabine (0.5-1.5 g/m(2) per day) for days 1 to 14 of a 21-day treatment cycle. Measurements (skin screenings, laboratory and toxicity monitoring) were performed every 1 to 3 months. Incidence rates of squamous cell carcinoma (SCC) before and during treatment were determined and compared using the Wilcoxon signed-rank test. RESULTS: The average incidence rate (mean ± SD) of SCC before treatment (0.56 ± 0.28 SCCs/month, range 0.17-1.17 SCCs/month) declined to 0.16 ± 0.11 SCCs/month (range 0-0.33 SCCs/month) during the first 12 months of treatment (mean reduction 68 ± 30.0%, range 0-100%, p < .005). Reduction in actinic keratosis was observed. Common side effects included fatigue, nausea, hand-and-foot syndrome, gout, and poor renal function. Seven of 10 participants required dose adjustment, and two of these were discontinued from the study drug because of side effects. LIMITATIONS: Case series design, small observational population. CONCLUSIONS: SOTRs experienced a clinically and statistically significant decline in incident SCCs during treatment with low-dose oral capecitabine, with varying degrees of side effects. Larger randomized trials will determine the dose and efficacy of capecitabine for adjuvant treatment of NMSC in SOTRs.

A miR-centric view of head and neck cancers.

Head and Neck Squamous Cell Carcinomas (HNSCCs) constitute the sixth most common cancer worldwide with an average 5-year survival rate of around 50%. Several microRNAs, small non-coding RNAs involved in post-transcriptional gene regulation, have been linked to HNSCC based on their differential expression in tumors. Here, we present a compilation of multiple types of information on each HNSCC linked miRNA including their expression status in tumors, their molecular targets relevant to cancer, results of gene manipulation studies and association with clinical outcome. Further, we use this information to devise a new scheme for classifying them into causal and non-causal miRNAs in HNSCC. We also discuss the possibility of using miRNAs as prognostic and diagnostic biomarkers for HNSCC, based on existing literature. Finally, we present available evidence that shows how altered expression of specific miRNAs can contribute to various "hallmarks of cancer" phenotypes such as limitless replicative potential owing to abnormal cell cycle regulation, evasion of apoptosis, reduced response to anti-growth signals, and Epithelial-Mesechymal transition (EMT).

Emerging strategies for the early detection and prevention of head and neck squamous cell cancer.

Despite significant improvements in therapeutic protocols, head and neck squamous cell carcinoma (HNSCC) remains a major health problem worldwide. The 5-year post-therapeutic survival rate is among the lowest of the major cancers with loco-regional relapse being the main cause of death. Moreover, in most instances, the quality of life of the afflicted patient is severely compromised. The poor prognosis for HNSCC is primarily due to disease detection at advanced stages. Accordingly, development of early detection and preventive strategies are essential. Recent advances in our understanding of the molecular biology and etiology of HNSCC should facilitate development of improved intervention and therapeutic approaches. The present review discusses the potential role of such factors for developing preventive and early diagnostic strategies for HNSCC management.

The role of human papillomavirus infection in head and neck cancers.

The link between head and neck squamous cell cancer (HNSCC), especially oropharyngeal cancer, and HPV has become established. HPV16 is the most common genotype in these tumours but HPV6 and HPV11 can also be found in a minority of these cancers, implying that these low-risk HPV types are not entirely benign in the head and neck region. HPV status is also associated with p16 expression and HPV+ tumours are less likely to harbour p53 mutations. HPV DNA is closely associated with poorly differentiated cancers, positive lymph nodes and late-stage disease, which all indicate poor prognosis. Contradictory to this, patients with HPV+ HNSCC seem to have significantly improved response to chemotherapy and radiotherapy as compared with HPV-negative tumours. Interestingly, the risk factors of HNSCC are the same as for HPV, including the number of sexual partners, younger age at first sexual intercourse, practice of oral sex, history of genital warts and younger age.

Skin cancer prevention education for kidney transplant recipients: a systematic evaluation of Internet sites.

CONTEXT: Repeated patient education about skin cancer prevention is important to self-care after transplant. OBJECTIVE: Examine educational materials for kidney transplant recipients available on the Internet that address sun protection and skin self-examination for early detection of squamous cell carcinoma. DESIGN: Systematic review of Web sites for kidney transplant recipients endorsed by transplant physicians and dermatologists. PARTICIPANTS: An expert panel of 8 dermatologists providing care for kidney transplant recipients and 1 research medical anthropologist. MAIN OUTCOME MEASURES: Reading grade level, inclusion of people with skin of color, sufficient content to support effective sun protection, and description of 4 sun-protection strategies and skin self-examination. Results-Of the 40 sites identified, 11 contained information about sun protection or increased risk of any type of cancer. The Web sites had a ninth-grade median reading level (range, seventh grade to college senior). Interrater reliability for the 25-item assessment tool was assessed by Fleiss' kappa (kappa = 0.87). Skin cancer risk was presented as relevant to those with fair skin. Sites recommended regular use of sunscreen with sun-protection factor of 15 or greater (n=3) to reduce the risk of skin cancer (n=4). Few sites recommended using protective clothing (n=5), seeking shade (n=4), and avoiding deliberate tanning with indoor or outdoor light (n=1). Five sites recommended skin self-examination. CONCLUSION: Because many patients seek self-management information from the Internet, Web sites must provide more thorough educational information about skin cancer prevention and health promotion at a lower reading grade level.

Hydrochlorothiazide treatment and risk of non-melanoma skin cancer: Review of the literature. / Terapêutica com hidroclorotiazida e risco de cancro cutâneo não melanoma: revisão da literatura.

Non-melanoma skin cancer is the most prevalent malignancy in fair-skinned people and its incidence is increasing. Recently, studies have suggested that antihypertensive drugs may increase the risk of these tumors, particularly hydrochlorothiazide, due to its photosensitizing properties. The Portuguese National Authority for Medicines and Health Products, INFARMED, has issued an alert to healthcare professionals concerning the increased risk of non-melanoma skin cancer in patients exposed to cumulative doses of this drug. However, study results have been heterogeneous and sometimes conflicting. The high incidence of non-melanoma skin cancer and the large number of patients under chronic hydrochlorothiazide therapy may thus have important public health consequences. In this article, the authors review the published evidence and conclude that there may be an association between hydrochlorothiazide use and the risk of non-melanoma skin cancer, but also point out some limitations of the studies in the literature. It is important to promote preventive strategies against sun exposure, regular skin examinations, and individual assessment of the benefits of hydrochlorothiazide use, particularly in patients with previous skin cancer.

Photodynamic therapy: treatment of choice for actinic cheilitis?

The major therapeutic approaches (5-fluorouracil, imiquimod, vermilionectomy, and CO(2) Laser ablation) for actinic cheilitis are aimed at avoiding and preventing a malignant transformation into invasive squamous cell carcinoma via destruction/removal of the damaged epithelium. Recently, photodynamic therapy (PDT) has been introduced as a therapeutic modality for epithelial skin tumors, with good efficacy/safety profile and good cosmetic results. Regarding actinic cheilitis, PDT could be considered a new therapeutic option? The target of our study was to evaluate the efficacy and tolerability of PDT in actinic cheilitis, using a methyl-ester of aminolevulinic acid (MAL) as topical photosensitizing agent and controlled the effects of the therapy for a 30-month follow-up period. MAL-PDT seems to be the ideal treatment for actinic cheilitis and other actinic keratosis, especially on exposed parts such as the face, joining tolerability and clinical efficacy with an excellent cosmetic outcome.

[Prevalence of epithelial squamous cell abnormalities and associated factors in women of a rural town of Colombia]. / Prevalencia de anormalidades de células epiteliales y factoresasociados en mujeres de un municipio rural colombiano.

INTRODUCTION: In spite of implementation of cytology-based cervical cancer screening in Colombia, mortality rates remain stable. The description of factors associated to cervical pre-neoplasic lesions is needed to establish strategies for mortality prevention. OBJECTIVE: The prevalence of epithelial squamous cell abnormalities was determined to explore the association of cytology abnormalities with described risk factors. MATERIALS AND METHODS: This population-based, cross-sectional study included 739 women randomly selected by age. A validated face-to-face questionnaire and conventional cervical cytology were used to collect the information. To establish the association between cervical abnormalities and some qualitative variables, the independent chi squared test was used. We also calculated prevalence ratio with their 95% confidence intervals. A logistic regression model was used to explore variables that potentially explain cytology abnormalities. RESULTS: The prevalence of squamous cell abnormality was 15.8%. Among women with abnormal cytology, 10% presented atypical squamous cells of undetermined significance, 3.9% low grade squamous intra-epithelial lesion and 1.9% high grade squamous intra-epithelial lesion. The adjusted logistical regression analysis showed that history of sexual transmitted disease, two or more sexual partners during entire life and previous abnormal cytology were associated with cytology abnormalities. CONCLUSION: The relation of epithelial squamous cell abnormalities with sexual behavior history reflexes the link between human papiloma virus infection and cervical cancer pre-neoplasic lesions. The frequency of use and knowledge about the purpose of cytology were factors that suggested other diagnostic limitations such as quality of cervical cytology or barriers to access health care. These latter factors may be the underlying basis for the high cervical cancer mortality rates.

Evidence for benefits from treating cervical ectopy: literature review.

CONTEXT AND PURPOSE: Uterine cervical ectopy (cervical erosion) is today considered to be a physiological condition, but there still seems to be a strong tendency towards treating it. The purpose of this study was to review the medical literature for evidence regarding benefits from treating cervical ectopy. METHODS: The following databases were reviewed: Medical Literature Analysis and Retrieval System Online (Medline), Excerpta Medica Database (Embase), Literatura Latino-Americana e do Caribe em Ciências da Saúde (Lilacs) and Cochrane Library databases. In addition, six medical textbooks were consulted. RESULTS: The review showed that: 1) there is probably an association between ectopy and higher risk of Chlamydia trachomatis, human papillomavirus and human immunodeficiency virus infection; 4) there is probably an association between ectopy and cervical intraepithelial neoplasia; 5) there is an association between ectopy and mucous discharge and nocturia; and 6) there is no evidence of an association between ectopy and cervical cancer, or of protection against cervical cancer associated with ectopy treatment. CONCLUSIONS: 1) No data were found in the medical literature to support routine treatment for ectopy; 2) Treatment could be recommended for symptom relief, but more symptoms are attributed to ectopy than could be demonstrated in a controlled study; 3) Further studies to test the hypothesis of protection against cervical cancer associated with treatment are necessary.

The multidisciplinary management of gastrointestinal cancer. Epidemiology of oesophagogastric cancer.

Oesophagogastric cancer occurs in the oesophagus, the oesophagogastric region and the stomach, including the proximal and distal stomach. In 2005, the worldwide burden of oesophagogastric cancer was estimated to be 1,500,000 new cases (500,000 oesophagus and 1,000,000 stomach). Squamous cell cancer is linked with alcohol and tobacco consumption in Western countries. Its incidence is much higher in regions of Asia with a low-socio-economic status, nutritional deficiencies, poor oral status, carcinogens absorbed with smoked meat, fat-cooked foodstuffs, vegetables containing toxic alkaloids or mycotoxins, and water containing nitrites, nitrates and nitrosamines. Adenocarcinoma develops in the columnar lined oesophagus. Its incidence is still low but there is an increasing trend. The incidence of stomach cancer is decreasing worldwide, but is still high in Japan. Causal factors include Helicobacter pylori infection with atrophic gastritis and a diet poor in fruit and vegetables. Preneoplastic conditions of the oesophagogastric mucosa include erosive oesophagitis in alcoholics, columnar lined oesophagus as a complication of gastro-oesophageal reflux disease, and atrophic gastritis following H. pylori infection.

The role of topical cyclo-oxygenase-2 inhibitors in skin cancer: treatment and prevention.

Cyclo-oxygenases (COXs) are rate-limiting enzymes in arachidonic acid metabolism and prostaglandin production. COX-2 is the main UV-responsive COX isoform in human skin and is involved in UV-induced skin inflammation and apoptosis. The topical NSAID diclofenac works as a nonspecific COX inhibitor and is an effective and well tolerated treatment for actinic keratosis, which is a principal precursor of cutaneous squamous cell carcinoma. Oral and topical COX-2 inhibitors have chemopreventive activity against chemically and UV light-induced skin cancer in animal models. The mechanism of action of COX inhibitors in skin tumorigenesis is complex and not completely understood. Clinical trials to evaluate whether topical administration of NSAIDs or specific COX-2 inhibitors can prevent skin cancer in high-risk patients are warranted.

Human papillomavirus molecular biology.

Human papillomaviruses are small DNA viruses with a tropism for squamous epithelia. A unique aspect of human papillomavirus molecular biology involves dependence on the differentiation status of the host epithelial cell to complete the viral lifecycle. A small group of these viruses are the etiologic agents of several types of human cancers, including oral and anogenital tract carcinomas. This review focuses on the basic molecular biology of human papillomaviruses.

Blueberry inhibits invasion and angiogenesis in 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral squamous cell carcinogenesis in hamsters via suppression of TGF-ß and NF-κB signaling pathways.

Aberrant activation of oncogenic signaling pathways plays a pivotal role in tumor initiation and progression. The purpose of the present study was to investigate the chemopreventive and therapeutic efficacy of blueberry in the hamster buccal pouch (HBP) carcinogenesis model based on its ability to target TGF-ß, PI3K/Akt, MAPK and NF-κB signaling and its impact on invasion and angiogenesis. Squamous cell carcinomas were induced in the HBP by 7,12-dimethylbenz[a]anthracene (DMBA). The effect of blueberry on the oncogenic signaling pathways and downstream events was analyzed by quantitative real-time PCR and immunoblotting. Experiments with the ECV304 cell line were performed to explore the mechanism by which blueberry regulates angiogenesis. Blueberry supplementation inhibited the development and progression of HBP carcinomas by abrogating TGF-ß and PI3K/Akt pathways. Although blueberry failed to influence MAPK, it suppressed NF-κB activation by preventing nuclear translocation of NF-κB p65. Blueberry also modulated the expression of the oncomiR miR-21 and the tumor suppressor let-7. Collectively, these changes induced a shift to an anti-invasive and anti-angiogenic phenotype as evidenced by downregulating matrix metalloproteinases and vascular endothelial growth factor. Blueberry also inhibited angiogenesis in ECV304 cells by suppressing migration and tube formation. The results of the present study suggest that targeting oncogenic signaling pathways that influence acquisition of cancer hallmarks is an effective strategy for chemointervention. Identification of modulatory effects on phosphorylation, intracellular localization of oncogenic transcription factors and microRNAs unraveled by the present study as key mechanisms of action of blueberry is critical from a therapeutic perspective.

Technologic advances for evaluation of cervical cytology: is newer better?

Among those women who have cervical cancer and have been screened, 14% to 33% of the cases represent failure to detect abnormalities that existed at the time of screening. New technologies intended to improve detection of cytologic abnormalities include liquid-based, thin-layer cytology (ThinPrep, AutoCyte), computerized rescreening (PAPNET), and algorithm-based computer rescreening (AutoPap). This report combines evidence reviews conducted for the U.S. Preventive Services Task Force and the Agency for Healthcare Research and Quality, in which we systematically identified articles on cervical neoplasia, cervical dysplasia, and screening published between January 1966 and March 2001. We note the challenges for improving screening methods, providing an overview of methods for collecting and evaluating cytologic samples, and examining the evidence about the diagnostic performance of new technologies for detecting cervical lesions. Using standard criteria for evaluation of the diagnostic tests, we determined that knowledge about the sensitivity, specificity, and predictive values of new technologies is meager. Only one study of liquid-based cytology used a reference standard of colposcopy, with histology as indicated, to assess participants with normal screening results. Lack of an adequate reference standard is the overwhelming reason that test characteristics cannot be properly assessed or compared. Most publications compare results of screening using the new technology with expert panel review of the cytologic specimen. In that case, the tests are not independent measures and do nothing to relate the screening test findings to the true status of the cervix, making determination of false-negatives, and thus sensitivity, specificity, and negative predictive value, impossible. We did not identify any literature about health outcomes or cost effectiveness of using these tools in a system of screening. For the purposes of guiding decision making about choice of screening tools, the current evidence is inadequate to gauge whether new technologies are "better" than conventional cytology..

Routine use of ultrasound and flexible cystoscopy in the control of benign bladder tumours.

During the period 1987-1992, 99 patients with benign bladder tumours were followed regularly with transabdominal ultrasound of the bladder and out-patient flexible cystoscopy. Thirty-five patients had recurrent bladder tumours, but in only one case was there progression to invasive tumour. Seventy-six per cent of the recurrences were diagnosed by flexible cystoscopy while 22% were found by ultrasound. Compared to conventional follow-up programs with in-patient rigid cystoscopy the combination of ultrasound and flexible cystoscopy proved to be safe, highly acceptable by the patients and cost-effective.

[Smoking and lung cancer]. / Roken en longkanker.

Since fifty years it is clear now that smoking of tobacco products is responsible for the lung cancer epidemic that is currently in progress worldwide. Although in the Western world a small decrease of lung cancer in males is found, the number of female patients is steadily increasing. Changes in tobacco production have resulted in exposition of smokers to other carcinogens. This is probably the cause of the change in the histological pattern with an increase of adenocarcinoma and stabilisation of squamous cell lung cancer. Despite the bad prognosis there is some hope that with improvement of early detection methods more patients can be cured. However, for a real change it is necessary to discourage smoking by all means.

A validation study of the FocalPoint GS imaging system for gynecologic cytology screening.

BACKGROUND: Studies of the performance of the automated FocalPoint Guided Screening (FPGS) imaging system in gynecologic cytology screening relative to manual screening have yielded conflicting results. In view of this uncertainty, a validation study of the FPGS was conducted before its potential adoption in 2 large laboratories in Ontario. METHODS: After an intense period of laboratory training, a cohort of 10,233 current and seeded abnormal slides were classified initially by FPGS. Manual screening and reclassification blinded to the FPGS results were then performed. Any adequacy and/or cytodiagnostic discrepancy between the 2 screening methods subsequently was resolved through a consensus process (truth). The performance of each method's adequacy and cytodiagnosis vis-a-vis the truth was established. The sensitivity and specificity of each method at 4 cytodiagnostic thresholds (atypical squamous cells of undetermined significance or worse [ASC-US+], low-grade squamous intraepithelial lesion or worse [LSIL+], high-grade squamous intraepithelial lesion or worse [HSIL+], and carcinoma) were compared. The false-negative rate for each cytodiagnosis was determined. RESULTS: The performance of FPGS in detecting carcinoma, HSIL+, and LSIL+ was no different from the performance of manual screening, but the false-negative rates for LSIL and ASC-US were higher with FPGS than with manual screening. CONCLUSIONS: The results from this validation study in the authors' laboratory environment provided no evidence that FPGS has diagnostic performance that differs from manual screening in detecting LSIL+, HSIL+, or carcinoma.

Implementation of FocalPoint GS location-guided imaging system: experience in a clinical setting.

BACKGROUND: Recently, the Food and Drug Administration approved the use of the location-guided imaging system FocalPoint GS (FPGS), on SurePath Papanicolaou (Pap) tests for primary screening. The objective of the current study was to evaluate the impact of FPGS on the following: distribution of diagnostic categories; rate of high-risk human papillomavirus (HR-HPV)-positive ASC-US cases; and quality control (QC) data before and after FPGS implementation. METHODS: A search of the laboratory information system was performed to identify all SurePath Pap tests processed in our laboratory for the first 19 months after FPGS implementation. We also retrieved all SurePath specimens from a 16-month period prior to FPGS implementation to serve as the control. During the period from Janaury 2008 to April 2009, the FocalPoint Slide Profiler was used. RESULTS: Implementation of FPGS resulted in a significantly higher percentage of LSIL and ASC-US interpretations, as well as a significant increase in the detection of candidiasis and bacterial vaginosis. The ASC-to-SIL ratio was 1.4 and 1.9 before and after FPGS implementation, respectively. There was a decrease in the HR-HPV positive rate in ASC-US cases, and a decrease in the estimated false-negative fraction after FPGS implementation. CONCLUSIONS: In conclusion, our study seems to demonstrate a favorable performance of FPGS in the routine clinical setting. FPGS may have the potential to be a promising screening tool for gynecologic cytology in a low-risk patient population.