Inhibiting the proton pump: mechanisms, benefits, harms, and questions

Inhibition of the H+/K+-adenosine triphosphatase (the proton pump) is the final common mechanistic pathway in reducing gastric acid secretion pharmacologically. Proton pump inhibitors are widely used in upper gastrointestinal diseases, including gastric and duodenal ulcers, eradication of Helicobacter pylori in combination with antibiotics, gastroesophageal reflux disease, Zollinger-Ellison syndrome, eosinophilic esophagitis, and prevention of non-steroidal anti-inflammatory drug-induced peptic ulceration. Reviewing their benefits and harms in BMC Medicine, Scarpignato et al. report effectiveness in these conditions, and harms that are generally mild and uncommon (1-3 %). Serious adverse reactions, such as tubulointerstitial nephritis, are rare. However, the risks of gastric and pancreatic cancer are unclear. Drug-drug interactions can occur through effects on P glycoprotein and cytochrome P450 (CYP) isoenzymes. Several questions remain. Do all proton pump inhibitors carry the same risks of serious adverse reactions? Which individuals are most susceptible? What are the time courses of individual reactions? What monitoring strategies are best? New drugs for the same indications continue to emerge, including potassium-competitive acid blockers, inhibitors of transient lower esophageal sphincter relaxation, serotonergic agents/prokinetics, mucosal protectants, histamine H3 receptor agonists, anti-gastrin agents, and esophageal pain modulators. Their benefit to harm balance remains to be discovered.Please see related article: https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-016-0718-z

A prognostic model for advanced colorectal neoplasia recurrence

Following colonoscopic polypectomy, US Multisociety Task Force (USMSTF) guidelines stratify patients based on risk of subsequent advanced neoplasia (AN) using number, size, and histology of resected polyps, but have only moderate sensitivity and specificity. We hypothesized that a state-of-the-art statistical prediction model might improve identification of patients at high risk of future AN and address these challenges. Data were pooled from seven prospective studies which had follow-up ascertainment of metachronous AN within 3-5 years of baseline polypectomy (combined n = 8,228). Pooled data were randomly split into training (n = 5,483) and validation (n = 2,745) sets. A prognostic model was developed using best practices. Two risk cut-points were identified in the training data which achieved a 10 percentage point improvement in sensitivity and specificity, respectively, over current USMSTF guidelines. Clinical benefit of USMSTF versus model-based risk stratification was then estimated using validation data. The final model included polyp location, prior polyp history, patient age, and number, size and histology of resected polyps. The first risk cut-point improved sensitivity but with loss of specificity. The second risk cut-point improved specificity without loss of sensitivity (specificity 46.2 % model vs. 42.1 % guidelines, p < 0.001; sensitivity 75.8 % model vs. 74.0 % guidelines, p = 0.64). Estimated AUC was 65 % (95 % CI: 62-69 %). This model-based approach allows flexibility in trading sensitivity and specificity, which can optimize colonoscopy over- versus underuse rates. Only modest improvements in prognostic power are possible using currently available clinical data. Research considering additional factors such as adenoma detection rate for risk prediction appears warranted.Public Health Service Grants from the National Cancer Institute [CA-41108, CA-23074, CA95060, CA37287, CA104869, CA23108, CA59005, CA26852, 5R01CA155293]; Cooperative Studies Program, Department of Veterans Affairs; UCSD Department of Family Medicine and Public Health; United States Department of Veterans Affairs Health Services Research and Development Service of the VA Office of Research and Development [1 I01 HX001574-01A1]Published online: 12 August 2016; 12 Month Embargo.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Recommendations for Post-Polypectomy Surveillance in Community Practice

BACKGROUND: After colon cancer screening, large numbers of persons discovered with colon polyps may receive post-polypectomy surveillance with multiple colonoscopy examinations over time. Decisions about surveillance interval are based in part on polyp size, histology, and number. AIMS: To learn physicians’ recommendations for post-polypectomy surveillance from physicians’ office charts. METHODS: Among 322 physicians performing colonoscopy in 126 practices in N. Carolina, offices of 152 physicians in 55 practices were visited to extract chart data, for each physician, on 125 consecutive persons having colonoscopy in 2003. Subjects included persons with first-time colonoscopy and no positive family history or other indication beyond colonoscopy findings that might affect postpolypectomy surveillance recommendations. Data were extracted about demographics, reason for colonoscopy, family history, symptoms, bowel prep, extent of examination, and features of each polyp including location, size, histology. Recommendations for post-polypectomy surveillance were noted. RESULTS: Among 10,089 first-time colonoscopy examinations, hyperplastic polyps were found in 4.5% of subjects, in whom follow-up by 4–6 years was recommended in 24%, sooner than recommended in guidelines. Of the 6.6% of persons with only small adenomas, 35% were recommended to return in 1–3 years (sooner than recommended in some guidelines) and 77% by 6 years. Surveillance interval tended to be shorter if colon prep was less than “excellent.” Prep quality was not reported for 32% of examinations. CONCLUSIONS: Surveillance intervals after polypectomy of low-risk polyps may be more aggressive than guidelines recommend. The quality of post-polypectomy surveillance might be improved by increased attention to guidelines, bowel prep, and reporting