Coffee consumption and risk of liver cancer: a meta-analysis

BACKGROUND & AIMS: Mounting evidence indicates that coffee drinking may protect against liver injury and lower the risk of liver cancer. We quantitatively assessed the relation between coffee consumption and the risk of liver cancer in a meta-analysis of epidemiologic studies. METHODS: Relevant studies were identified by searching MEDLINE (from 1966 to February 2007) and the reference lists of retrieved articles. We included cohort and case-control studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) of primary liver cancer or hepatocellular carcinoma by quantitative categories of coffee consumption. Study-specific RRs were pooled using a random-effects model. RESULTS: Four cohort and 5 case-control studies, involving 2260 cases and 239,146 noncases, met the inclusion criteria. All studies observed an inverse relation between coffee consumption and risk of liver cancer, and in 6 studies the association was statistically significant. Overall, an increase in consumption of 2 cups of coffee per day was associated with a 43% reduced risk of liver cancer (RR, 0.57; 95% CI, 0.49-0.67). There was no statistically significant heterogeneity among studies (P = .17). In stratified analysis, the summary RRs of liver cancer for an increase in consumption of 2 cups of coffee per day were 0.69 (95% CI, 0.55-0.87) for persons without a history of liver disease and 0.56 (95% CI, 0.35-0.91) for those with a history of liver disease. CONCLUSIONS: Findings from this meta-analysis suggest that an increased consumption of coffee may reduce the risk of liver cancer.     

Chemoprevention of colorectal neoplasia: the potential for personalized medicine

CRC development is a multi-step process that spans 10 to 15 years, thereby providing an opportunity for early detection and even prevention. The poor survival rate of advanced CRC has prompted the emphasis on prevention of this disease. CRC screening and removal of adenomas is an effective intervention, and is the cornerstone of prevention. However, screening efforts have had limited impact due to less than optimal compliance with guidelines. Chemoprevention involves the long-term use of a variety of oral agents that can delay, prevent or even reverse the development of adenomas in the large bowel, thus interfering with the multi-step progessing from adenoma to carcinoma. This effect is of particular importance to individuals with a hereditary prediposition to colorectal neoplasia and to those who are especially susceptile to the environmental causes of CRC. NSAIDs have drawn the most attention as chemoprevention agents. Sulindac and celecoxib are effective in promoting poly regression in high risk individuals with Familial Adenomatous Polyposis (FAP). In the more common sporadic setting the APROVe (refecoxib), APC and PreSAP (Celecoxib) trials have shown a significant reduction in adenoma recurrence but important concerns exist regarding cardiovascular toxicity associated with selective COX-2 inhibitors. These landmark studies are very important, as they provide a proof of concept that we can prevent high risk adenomas that can lead to CRC development. The ideal chemopreventive agent remains to be discovered with great emphasis on need not to harm. Possibly, combinations of agents will maximize effectiveness while limiting drug toxicity. Finally, personalized approaches will include the ability to predict risk and toxicity.     

Folate intake, MTHFR polymorphisms, and risk of esophageal, gastric, and pancreatic cancer: a meta-analysis

BACKGROUND & AIMS: Increasing evidence suggests that a low folate intake and impaired folate metabolism may be implicated in the development of gastrointestinal cancers. We conducted a systematic review with meta-analysis of epidemiologic studies evaluating the association of folate intake or genetic polymorphisms in 5,10-methylenetetrahydrofolate reductase (MTHFR), a central enzyme in folate metabolism, with risk of esophageal, gastric, or pancreatic cancer. METHODS: A literature search was performed using MEDLINE for studies published through March 2006. Study-specific relative risks were weighted by the inverse of their variance to obtain random-effects summary estimates. RESULTS: The summary relative risks for the highest versus the lowest category of dietary folate intake were 0.66 (95% confidence interval [CI], 0.53-0.83) for esophageal squamous cell carcinoma (4 case-control), 0.50 (95% CI, 0.39-0.65) for esophageal adenocarcinoma (3 case-control), and 0.49 (95% CI, 0.35-0.67) for pancreatic cancer (1 case-control, 4 cohort); there was no heterogeneity among studies. Results on dietary folate intake and risk of gastric cancer (9 case-control, 2 cohort) were inconsistent. In most studies, the MTHFR 677TT (variant) genotype, which is associated with reduced enzyme activity, was associated with an increased risk of esophageal squamous cell carcinoma, gastric cardia adenocarcinoma, noncardia gastric cancer, gastric cancer (all subsites), and pancreatic cancer; all but one of 22 odds ratios were >1, of which 13 estimates were statistically significant. Studies of the MTHFR A1298C polymorphism were limited and inconsistent. CONCLUSIONS: These findings support the hypothesis that folate may play a role in carcinogenesis of the esophagus, stomach, and pancreas.     

Computed tomographic colonography without cathartic preparation for the detection of colorectal polyps

BACKGROUND AND AIMS: We prospectively compared the performance of low-dose multidetector computed tomographic colonography (CTC) without cathartic preparation with that of colonoscopy for the detection of colorectal polyps. METHODS: A total of 203 patients underwent low-dose CTC without cathartic preparation followed by colonoscopy. Before CTC, fecal tagging was achieved by adding diatrizoate meglumine and diatrizoate sodium to regular meals. No subtraction of tagged feces was performed. Colonoscopy was performed 3-7 days after CTC. Three readers interpreted the CTC examinations separately and independently using a primary 2-dimensional approach using multiplanar reconstructions and 3-dimensional images for further characterization. Colonoscopy with segmental unblinding was used as reference standard. The sensitivity of CTC was calculated both on a per-polyp and a per-patient basis. For the latter, specificity, positive predictive values, and negative predictive values were also calculated. RESULTS: CTC had an average sensitivity of 95.5% (95% confidence interval [CI], 92.1%-99%) for the identification of colorectal polyps > or =8 mm. With regard to per-patient analysis, CTC yielded an average sensitivity of 89.9% (95% CI, 86%-93.7%), an average specificity of 92.2% (95% CI, 89.5%-94.9%), an average positive predictive value of 88% (95% CI, 83.3%-91.5%), and an average negative predictive value of 93.5% (95% CI, 90.9%-96%). Interobserver agreement was high on a per-polyp basis (kappa statistic range, .61-.74) and high to excellent on a per-patient basis (kappa statistic range, .79-.91). CONCLUSIONS: Low-dose multidetector CTC without cathartic preparation compares favorably with colonoscopy for the detection of colorectal polyps.     

The efficacy of proton pump inhibitors in nonulcer dyspepsia: a systematic review and economic analysis

BACKGROUND AND AIMS: The evidence that proton pump inhibitor (PPI) therapy affects symptoms of nonulcer dyspepsia is conflicting. We conducted a systematic review to evaluate whether PPI therapy had any effect in nonulcer dyspepsia and constructed a health economic model to assess the cost-effectiveness of this approach. METHODS: Electronic searches were performed using the Cochrane Controlled Trials Register, MEDLINE, EMBASE, CINAHL, and SIGLE until September 2002. Dyspepsia outcomes were dichotomized into cured/improved versus same/worse. Results were incorporated into a Markov model comparing health service costs and benefits of PPI with antacid therapy over 1 year. RESULTS: Eight trials were identified that compared PPI therapy with placebo in 3293 patients. The relative risk of remaining dyspeptic with PPI therapy versus placebo was .86 (95% confidence interval, .78-.95; P = .003, random-effects model) with a number needed to treat of 9 (95% confidence interval, 5-25). There was statistically significant heterogeneity between trials (heterogeneity chi(2) = 30.05; df = 7; P < .001). The PPI strategy would cost an extra US dollar 278/month free from dyspepsia if the drug cost US dollar 90/month. If a generic price of US dollar 19.99 is used, then a PPI strategy costs an extra US dollar 57/month free from dyspepsia. A third-party payer would be 95% certain that PPI therapy would be cost-effective, provided they were willing to pay US dollar 94/month free from dyspepsia. CONCLUSIONS: PPI therapy may be a cost-effective therapy in nonulcer dyspepsia, provided generic prices are used.     

Reduction in colorectal cancer mortality by fecal occult blood screening in a French controlled study

BACKGROUND & AIMS: Several randomized population-based studies have shown that screening for colorectal cancer (CRC) by fecal occult blood tests (FOBTs) can reduce CRC mortality. The aim of this French population-based study was to assess whether a similar benefit could be obtained in countries characterized by high performances in the diagnosis and management of CRC. METHODS: Small-sized geographic areas, including 91,199 individuals aged 45-74 years, were allocated to either FOBT screening or no screening. Six screening rounds were performed. The FOBT was performed without diet restriction and was sent to a central analysis center and processed without rehydration. Screening group participants who had a positive test result were offered a full colonoscopy. The entire population was followed up for 11 years after study entry. RESULTS: Acceptability of the test was 52.8% at the first screening round and varied between 53.8% and 58.3% in the successive rounds. Positivity rates were 2.1% initially and 1.4% on average in the successive rounds. CRC mortality was significantly lower in the screening population compared with the control population (mortality ratio, 0.84; 95% confidence interval, 0.71-0.99). The reduction in CRC mortality was more pronounced in those who participated at least once (mortality ratio, 0.67; 95% confidence interval, 0.56-0.81). CONCLUSIONS: Our findings, together with the results of other trials, suggest that biennial screening by FOBTs can reduce CRC mortality regardless of the quality of the health system and support attempts to introduce large-scale screening programs into the general population.     

Endoscopic therapy versus medical therapy for bleeding peptic ulcer with adherent clot: a meta-analysis

BACKGROUND & AIMS: The optimal management of bleeding peptic ulcer with adherent clot is controversial and may include endoscopic therapy or medical therapy. METHODS: We searched MEDLINE, BIOSIS, EMBASE, and the Cochrane Library to identify all randomized controlled trials comparing the 2 interventions. Outcomes evaluated in the meta-analysis were recurrent bleeding, need for surgical intervention, length of hospitalization, transfusion requirement, and mortality. RESULTS: Six studies were identified that included 240 patients from the United States, Hong Kong, South Korea, and Spain. Patients in the endoscopic therapy group underwent endoscopic clot removal and treatment of the underlying lesion with thermal energy, electrocoagulation, and/or injection of sclerosants. Rebleeding occurred in 5 of 61 (8.2%) patients in the endoscopic therapy group, compared with 21 of 85 (24.7%) in the medical therapy group (P = .01), for a pooled relative risk of 0.35 (95% confidence interval, 0.14-0.83; number needed to treat, 6.3). There was no difference between endoscopic therapy and medical therapy in length of hospital stay (mean, 6.8 vs 5.6 days; P = .27), transfusion requirement (mean, 3.0 vs 2.8 units of packed red blood cells; P = .75), or mortality (9.8% vs 7%; P = .54). Patients in the endoscopic therapy group were less likely to undergo surgery (pooled relative risk, 0.43; 95% confidence interval, 0.19-0.98; number needed to treat, 13.3); however, this outcome became nonsignificant when only peer-reviewed studies were considered. CONCLUSIONS: Endoscopic therapy is superior to medical therapy for preventing recurrent hemorrhage in patients with bleeding peptic ulcers and adherent clots. The interventions are comparable with respect to the need for surgical intervention, length of hospital stay, transfusion requirement, and mortality.     

Vitamin B6 intake, alcohol consumption, and colorectal cancer: a longitudinal population-based cohort of women

BACKGROUND & AIMS: Vitamin B6 has a crucial role in 1-carbon metabolism, which involves DNA synthesis and DNA methylation. Aberrations in these processes have been implicated in colorectal carcinogenesis. We examined the association between long-term dietary vitamin B6 intake and risk of colorectal cancer and whether this association is modified by consumption of alcohol, which may disrupt 1-carbon metabolism. METHODS: Our study population comprised 61,433 women in the population-based Swedish Mammography Cohort. The women were aged 40 to 76 years, had no history of cancer, and completed a food-frequency questionnaire at baseline in 1987-1990. Dietary information was updated in 1997. During a mean follow-up of 14.8 years, 805 incident colorectal cancer cases were diagnosed. RESULTS: After controlling for age and other potential confounders, long-term intake of dietary vitamin B6 was significantly inversely associated with risk of colorectal cancer (P value for trend = .002). Compared with women in the lowest quintile of vitamin B6 intake, those in the highest quintile had a 34% lower risk (multivariate rate ratio, 0.66; 95% confidence interval, 0.50-0.86). The association was most pronounced among women with moderate to high alcohol consumption. The multivariate rate ratio of colorectal cancer comparing extreme quintiles of vitamin B6 intake was 0.28 (95% confidence interval, 0.13-0.59) among women who consumed > or = 30 g/wk of alcohol (approximately equivalent to 2 drinks per week). CONCLUSIONS: Findings of this study suggest that vitamin B6 may play a role in the prevention of colorectal cancer, particularly among women who drink alcohol.