Day: 11/10/2010

Alcoholics show reduced telomere length in the esophagus

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Aida J et al. – The finding that telomeres in the oesophageal epithelium are shorter in alcoholics than in non-alcoholics indicates that telomere shortening may be associated with the frequent occurrence of squamous cell carcinoma in alcoholics.

Methods

  • Measured telomere lengths of basal and parabasal cells in comparison with those of non-alcoholics using Q-FISH and our original software, Tissue Telo
  • Assessed histologic inflammation

Results

  • Telomeres in basal cells significantly shorter in alcoholics than in age-matched normal controls
  • Prominent histologic findings of chronic inflammation not evident in either alcoholics or non-alcoholics

Gout Drug May Reduce Colorectal Cancer

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Nov. 8, 2010 — A small study suggests that taking allopurinol, a drug that has been used to treat gout for more than 20 years, may reduce colorectal tumor growth and lower the risk for colorectal cancer.

Italian researchers compared three treatment groups with precancerous colorectal polyps. For up to six weeks, patients took either a placebo, 100 milligrams of allopurinol, or 300 milligrams of allopurinol, an oral drug that reduces levels of uric acid in the body. To measure effectiveness, researchers looked at levels of a colorectal cancer biomarker called Ki67 in the tissue of colorectal polyps.  Among people who took a placebo, Ki67 levels increased by 70%, but they increased by 12% among people taking 300 milligrams of allopurinol and by 6% among people taking 100 milligrams of the drug.

Study researcher Andrea DeCensi, MD, director of the medical oncology unit at Galliera Hospital in Genoa, Italy, presented the study results at the Ninth Annual American Association for Cancer Research Frontiers in Cancer Prevention Research Conference held in Philadelphia.

“In the era of very expensive target therapy in oncology, it is important to search for cheap agents that could be active in cancer prevention and thus have huge public health implications,” DeCensi says in a statement.

Colorectal cancer tumors have high levels of reactive oxygen metabolites, which are critical for tumor growth. Allopurinol, sold under the brand names Lopurin and  Zyloprim, reduced reactive oxygen metabolite activity. Earlier research had also shown that gout patients taking allopurinol had a lowered risk for colorectal cancer, one of the most commonly diagnosed cancers among men and women in the U.S. According to 2010 statistics from the American Cancer Society, there were an estimated 102,900 new cases of colon cancer and 39,670 new cases of rectal cancer.

Allopurinol for Colorectal Cancer

DeCensi conducted a clinical trial involving 73 patients with colorectal polyps who were treated with allopurinol between 2006 and 2010. The researchers collected samples of normal and abnormal tissue samples from the patients to compare Ki67 levels. The research team reported that allopurinol is a very safe drug and that during the study only a few side effects were reported — three mild gastrointestinal events.

Even before the study was completed, an early analysis of normal tissue samples already showed differences between patients taking a placebo and those taking allopurinol. Among the first 13 patients treated in the study, the results showed that levels of Ki67 had doubled in normal tissue in patients taking a placebo, compared with only a 5% increase in patients taking either dose of allopurinol.

Although these preliminary findings suggest allopurinol could have potential as a cancer-fighting therapy, DeCensi said the findings need to be confirmed in larger clinical trials involving more patients.

Risk-adjusted scoring systems in colorectal surgery

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Consequent to recent advances in surgical techniques and management, survival rate has increased substantially over the last 25 years, particularly in colorectal cancer patients. However, postoperative morbidity and mortality from colorectal cancer vary widely across the country. Therefore, standardised outcome measures are emphasised not only for professional accountability, but also for comparison between treatment units and regions. In a heterogeneous population, the use of crude mortality as an outcome measure for patients undergoing surgery is simply misleading. Meaningful comparisons, however, require accurate risk stratification of patients being analysed before conclusions can be reached regarding the outcomes recorded. Sub-specialised colorectal surgical units usually dedicated to more complex and high risk operations. The need for accurate risk prediction is necessary in these units as both mortality and morbidity often are tools to justify the practice of high-risk surgery.The Acute Physiology And Chronic Health Evaluation (APACHE) is a system for classifying patients in the intensive care unit. However, APACHE score was considered too complex for general surgical use. The American Society of Anaesthesiologists (ASA) grade has been considered useful as an adjunct to informed consent and for monitoring surgical performance through time. ASA grade is simple but too subjective. The Physiological & Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) and its variant Portsmouth POSSUM (P-POSSUM) were devised to predict outcomes in surgical patients in general, taking into account of the variables in the case-mix. POSSUM has 2 parts, which include assessment of physiological parameters and operative scores. There are 12 physiological parameters and 6 operative measures. The physiological parameters are taken at the time of surgery. Each physiological parameter or operative variable is sub-divided into 3 or 4 levels with an exponentially increasing score. However, POSSUM and P-POSSUM over-predict mortality in patients who have had colorectal surgery. Discrepancies in these models have led to the introduction of a specialty-specific POSSUM: the ColoRectal POSSUM (CR-POSSUM). CR-POSSUM only uses 6 physiological parameters and 4 operative measures for prediction of mortality. It is much simplified to allow ease of use Critics have suggested that CR-POSSUM might be too non-specific for prediction of mortality in patients with colorectal cancer because the original POSSUM models are used to predict various different clinical conditions, including benign and malignant disease. In 2003, the Association of Coloproctology of Great Britain and Ireland (ACPGBI) devised a scoring system for use specifically in surgical patients with colorectal cancer. The model uses multilevel regression analysis to adjust for multiple risk factors, their interactions, and the clustering of adverse outcomes in hospitals. The system was found to be simpler to use than the three POSSUM models. The ACPGBI score assesses only five operative variables: age, cancer resection, ASA grade; Dukes’ stage and operative urgency. Both CR-POSSUM and ACPGBI score have recently been validated as accurate predictor of mortality in colorectal cancer patients in a recent series.

source: science direct

Biologically Active Vitamin B12, Homocysteine, and Alzheimer Disease

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Baseline serum levels of homocysteine correlated positively and holotranscobalamin levels correlated negatively with AD risk in a population-based, 7-year cohort study.

Studies of the associations among the components of the vitamin B12 cascade and dementia have had inconsistent results (Eur J Neurol 2009; 16:808, Am J Clin Nutr 2007; 85:511, and Neurology 2004; 62:1972). In this study, researchers examined three of the cascade components — homocysteine, holotranscobalamin (holoTC, the biologically active fraction of vitamin B12), and folate — and subsequent risk for Alzheimer disease (AD). Participants were 271 initially nondemented older adults (baseline age range, 65–79) selected from a larger cohort based on the availability of baseline serum samples of these components. After a mean follow-up of 7.4 years, participants underwent a multistep AD screening process.

In a multiple logistic regression model adjusted for known cerebrovascular risk factors (including history of stroke, blood pressure, body-mass index, and smoking) and AD risk factors (including age, education, APOE {varepsilon}4, and Mini-Mental State Exam score), the odds ratios for AD were 1.16 per increase of 1 µmol/L of Hcy and 0.980 per increase of 1 pmol/L of holoTC. Of note, 95% confidence intervals for both calculations did not include 1. The authors report an attenuated link between Hcy and AD when adjusting for holoTC; however, the reported 95% confidence interval for this association included 1 (0.96–1.25). Folate levels were not associated with AD. The authors conclude that further study is needed, in light of the established associations of elevated Hcy with vascular disease and of vitamin B12 deficiency with neurological illness.

Comment: The authors acknowledge the obvious limitations of the study (e.g., the small sample size and one-time Hcy and holoTC measurements). A more universal challenge arises in determining the most sensitive marker of vitamin B12 deficiency (e.g., total serum vitamin B12, holoTC, or methylmalonic acid) and the true range of normal values. Nonetheless, these findings are provocative and suggest that simple supplementation with vitamin B12 in an aging population might be beneficial.

— Brandy R. Matthews, MD

Published in Journal Watch Neurology November 9, 2010