SMAD2 and the relationship of colorectal cancer to inflammatory bowel disease.

Inflammatory bowel diseases (IBDs) affecting the colon [Crohn's disease (CD) and ulcerative colitis (UC)] are associated with an increased risk of colorectal cancer (CRC). Our previous work using oligonucleotide array data indicated that SMAD2 was significantly underexpressed in UC dysplastic tissue compared to benign UC. The aim of this current study was to determine whether single nucleotide polymorphisms (SNPs) within the SMAD2 gene are associated with IBD dysplasia/cancer. We performed an SNP haplotype-based case-control association study. Leukocyte DNA was obtained from 489 unrelated Caucasians (158 UC, 175 CD, 71 CRC, 85 controls). Eleven SNPs were genotyped. All 11 SNPs were in Hardy-Weinberg equilibrium in the control population. Strong linkage disequilibrium was observed among nearly all SMAD2 SNPs. There were no significant associations between SMAD2 allele or haplotype frequencies. Power calculations indicated good power for single-marker analysis (>0.8) and reasonably good power against effects of 0.1-0.15 for haplotype analysis. SMAD2 SNPs were not associated with the development of IBD dysplasia/cancer. This incongruity between our previous microarray data and the findings from this genotype study may be attributed to mechanisms such as alternative splicing of pre-mRNA SMAD2 and/or cross talk with other cellular pathways.

Assessment of publication bias for the surgeon scientist.

BACKGROUND: Publication bias occurs when statistically non-significant (negative) findings are not published. It can profoundly affect the results of systematic reviews and meta-analyses. METHODS: Qualitative and quantitative methods of detecting publication bias are described, including their advantages and disadvantages. RESULTS AND CONCLUSION: Accepted quality standards for the reporting of meta-analyses recommend assessment of publication bias, but currently there is no uniform standard for reporting. Quantitative methods are being used with increasing frequency. Authors should take steps to minimize publication bias, and use both qualitative and quantitative assessment methods to determine whether it is present.

Meta-analysis: antibiotic prophylaxis to prevent peristomal infection following percutaneous endoscopic gastrostomy.

BACKGROUND: Despite numerous guidelines recommending prophylactic antibiotics prior to percutaneous endoscopic gastrostomy, their use remains controversial. AIM: To conduct a systematic literature review and performed meta-analyses to determine the benefit of antibiotic prophylaxis for percutaneous endoscopic gastrostomy placement. METHODS: We performed a systematic literature review by searching healthcare databases and grey literature for randomized-controlled trials of antibiotic prophylaxis against wound infection after percutaneous endoscopic gastrostomy. Relative risks were calculated for individual trials and data pooled using fixed-effects model. Relative risk reduction, absolute risk reduction and number needed to treat were calculated and are reported with 95% confidence intervals. RESULTS: Ten randomized-controlled trials met the inclusion criteria and 1059 cases were pooled. Overall findings indicated that antibiotic prophylaxis resulted in a relative risk reduction of 64% and an absolute risk reduction of 15%. Number needed to treat to prevent one wound infection was 8. Cephalosporin prophylaxis was associated with a relative risk reduction of 64%, absolute risk reduction of 10% and number needed to treat of 10, whereas penicillin-based prophylaxis was associated with a relative risk reduction of 62%, absolute risk reduction of 13% and number needed to treat of 8. CONCLUSIONS: Antibiotic prophylaxis prior to percutaneous endoscopic gastrostomy is effective in reducing the incidence of percutaneous endoscopic gastrostomy site wound infection. Based on sensitivity analyses, penicillin-based prophylaxis should be the prophylaxis of choice.

Systematic reviews and meta-analysis for the surgeon scientist.

BACKGROUND: Understanding of data-reporting methods is imperative for correct interpretation of the medical literature as well as for proper performance of future clinical research. Recent developments in biostatistics have greatly changed the types of statistical analyses used and the minimum quality standards that must be maintained. METHOD: Different types of review are described, including systematic review with and without meta-analysis. Minimum reporting standards, sources of bias, both quantitative and qualitative, and references are discussed. RESULTS AND CONCLUSION: Meta-analysis has become a clearly defined technique, with reporting standards for both randomized controlled trials and observational studies. It is assuming a wider role in the surgical literature. Although many sources of bias exist, there are clear reporting standards and readers should be aware of these when studying the literature.