Endoscopic Diagnosis, Grading, and Treatment of Bleeding Peptic Ulcer Disease.

Peptic ulcer bleeding is a major cause for hospital admissions and has a significant mortality. Endoscopic interventions reduce the risk of rebleeding in high-risk patients and several options are available including injection therapies, thermal therapies, mechanical clips, hemostatic sprays, and endoscopic suturing. Proton-pump inhibitors and Helicobacter pylori treatment are important adjuncts to endoscopic therapy. Endoscopic therapy is indicated in Forrest 1a, 1b, and 2a lesions. Patients with Forrest 2b lesions may do well with proton-pump inhibitor therapy alone but can also be managed by removal of the clot and targeting endoscopic therapy to the underlying lesion.

Developments in Gastroesophageal Reflux Disease over the Last 40 Years.

BACKGROUND: The last 40 years have seen a remarkable change in our understanding of reflux disease. SUMMARY: These changes encompass disease definition and impact, pathophysiology, diagnostic testing, regulatory oversight of clinical trials, pharmacotherapy, endoscopic, and surgical treatment. We have also seen a number of promising therapies fail. KEY MESSAGES: The future holds the promise of further advances. Adaptive artificial intelligence will take over diagnostics in manometry and pH impedance testing and patient-driven outcomes may be changed by interactions with artificial intelligence rather than humans. Changes in chip technology will allow higher resolution chips to be carried on smaller devices making extra-esophageal areas where reflux may play a role more accessible to prolonged observation and testing.

Helicobacter pylori World Gastroenterology Organization Global Guideline.

Helicobacter pylori remains a major health problem worldwide, causing considerable morbidity and mortality due to peptic ulcer disease and gastric cancer. The burden of disease falls disproportionally on less well-resourced populations. As with most infectious diseases, the largest impact on reducing this burden comes from improvement in socioeconomic status, which interrupts transmission. This has been observed in many regions of the world, but the prevalence of infection remains high in many regions where improvements in living standards are slow to occur. Meanwhile, the optimal clinical management and treatment pathways remain unsettled and are evolving with changing antimicrobial resistance patterns. Despite decades of research and clinical practice, major challenges remain. The quest for the most effective, safe, and simple therapy remains the major issue for clinicians. The search for an effective vaccine appears to be elusive still. Clinical guidelines do not infrequently proffer discordant advice. A major challenge for guidelines is for relevance across a variety of populations with a varying spectrum of disease, antimicrobial resistance rates, and vastly different resources. As local factors are central to determining the impact and management strategies for H. pylori infection, it is important that pathways are based on the best available local knowledge rather than solely extrapolating from guidelines formulated in other regions, which may be less applicable. To this end, this revision of the World Gastroenterology Organisation (WGO) H. pylori guideline uses a "Cascades" approach that seeks to summarize the principles of management and offer advice for pragmatic, relevant and achievable diagnostic and treatment pathways based on established key treatment principles and using local knowledge and available resources to guide regional practice.

Environmental and health outcomes of single-use versus reusable duodenoscopes.

BACKGROUND AND AIMS: The large-scale effects of duodenoscopes on the environment and public health have not been quantified. Our aim was to perform an exploratory life cycle assessment comparing environmental and human health effects of single-use duodenoscopes (SDs) and reusable duodenoscopes (RDs). METHODS: We evaluated 3 duodenoscopes: conventional RDs, RDs with disposable endcaps, and SDs. The primary outcomes were impacts on climate change and human health, complemented by multiple environmental impacts. RESULTS: Performing ERCP with SDs releases between 36.3 and 71.5 kg of CO2 equivalent, which is 24 to 47 times greater than using an RD (1.53 kg CO2) or an RD with disposable endcaps (1.54 kg CO2). Most of the impact of SDs comes from its manufacturing, which accounts for 91% to 96% of its greenhouse gas emission. The human health impact of RDs becomes comparable with the SD lower bound if disposable endcaps or other design modifications can reduce serious infection rates below a target rate of 23 cases per year (.0046%). CONCLUSIONS: Although SDs may provide incremental public health benefit compared with RDs, it comes at a substantially higher cost to the environment. As infection rates continue to decrease from more regimented cleaning protocols and enhanced designs such as disposable endcaps to facilitate cleaning, the negative impact to human health from contaminated RDs could be comparable with SDs.

Colorectal cancer in 18- to 49-year-olds: rising rates, presentation, and outcome in a large integrated health system.

BACKGROUND AND AIMS: Colorectal cancer (CRC) rates are increasing in young people, and new guidelines recommend screening should begin at age 45 years. We aimed to evaluate CRC detection rates in a large integrated healthcare system to assess treatment outcomes in younger CRC patients and to determine factors that could aid in identifying these individuals. METHODS: We analyzed confirmed cases of CRC using a cancer database spanning from 1985 to 2017 from a large integrated healthcare system composed of 15 hospitals, 150 outpatient clinics, and 20 outpatient oncology clinics. Three cohorts were evaluated (18-44 years, 45-49 years, and ≥50 years). RESULTS: Significant increases in CRC detection were seen in the cohort aged 18 to 44 (annual percentage change, 2.70%) and the cohort aged 45 to 49 (annual percentage change, 4.15%). A higher proportion of African American, Hispanic, and obese subjects were seen in the younger cohorts. A family history of CRC was found in 49% of patients aged 18 to 44 and 38% of patients aged 45 to 50. Patients younger than age 50 were more likely to have metastases at diagnosis (6.8%) versus the cohort over 50 (4.15%; P < .05). Survival was better in younger cohorts, and they were more likely to receive multimodality treatment (surgery with chemotherapy or radiation). Survival probability was similar in different ethnic groups. CONCLUSIONS: CRC is increasing at similar rates in young people aged 18 to 44 and 45 to 49, and they are more likely to present with advanced disease needing multimodality treatment. A family history identifies some patients <50 years. Young patients presenting with changes in bowel habit, rectal bleeding, anemia, and weight loss should undergo colonoscopy. Rectal and anal symptoms should prompt careful physical and endoscopic evaluation.

IW-3718 Reduces Heartburn Severity in Patients With Refractory Gastroesophageal Reflux Disease in a Randomized Trial.

BACKGROUND & AIMS: Refractory gastroesophageal reflux disease (GERD) reduces quality of life and creates significant financial burden on the health care system. Approximately 30% of patients with GERD who receive label-dose proton pump inhibitors (PPIs) still have symptoms. We performed a trial to evaluate the efficacy and safety of IW-3718, a bile acid sequestrant, as an adjunct to PPI therapy. METHODS: We performed a multicenter, double-blind, placebo-controlled trial, from March 2016 through April 2017, of 280 patients with confirmed GERD. The patients, stratified by esophagitis status, were randomly assigned (1:1:1:1) to groups given placebo or IW-3718 (500, 1000, or 1500 mg) twice daily, with ongoing label-dose PPI. The primary endpoint was percent change from baseline to week 8 in weekly heartburn severity score. We also analyzed percent change from baseline to week 8 in weekly regurgitation frequency score. RESULTS: Mean changes from baseline to week 8 in weekly heartburn severity scores were reductions of 46.0% in the placebo group, 49.0% in the 500 mg group, 55.1% in the 1000 mg group, and 58.0% in the 1500 mg IW-3718 group (dose-response P = .02). The treatment difference was 11.9% between the 1500 mg IW-3718 and placebo groups (P = .04, analysis of covariance). The mean change in weekly regurgitation frequency score from baseline to week 8 in the 1500 mg IW-3718 vs placebo groups was a reduction of 17.5% (95% confidence interval, reductions of 31.4% to 3.6%). The most common adverse event was constipation (in 8.1% of patients receiving IW-3718 and 7.1% of patients receiving placebo). There were no drug-related serious adverse events. CONCLUSIONS: In a randomized trial of patients with refractory GERD, adding 1500 mg IW-3718 to label-dose PPIs significantly reduced heartburn symptoms compared with adding placebo. Regurgitation symptoms also decreased. IW-3718 was well tolerated. (ClinicalTrials.gov, Number: NCT02637557).

Multitarget stool DNA testing for the prevention of colon cancer: outcomes in a large integrated healthcare system.

BACKGROUND AND AIMS: Multitarget stool DNA (MT-sDNA) testing is used in primary care as a screening test for colon cancer. Test effectiveness and patient compliance were examined in clinical practice. METHODS: We assessed outcomes of MT-sDNA testing in a cohort study conducted in a large integrated healthcare system comprising 15 hospitals and 150 outpatient clinics using advanced electronic data capture (Clarity2 [Epic, Verona, Wisc, USA] and REDCap [Encinitas, Calif, USA]) followed by manual chart review to confirm MT-sDNA test results and to monitor the outcomes of subsequent colonoscopy. RESULTS: A total of 6835 MT-sDNA tests were performed over 1 year between 2017 and 2018. Of 1242 patients (18%) who tested positive, 1109 (89%) were referred for colonoscopy, and 905 of them (73%) underwent colonoscopy. Eleven patients (<1%) with a positive test had colorectal cancer, 215 (17%) had advanced adenomas, 110 (9%) had serrated adenomas, and 546 (60%) patients had an adenoma. Of the 6835 patients tested, adenoma or cancer was found in 557 patients (8%). An advanced adenoma or cancer was found in 226 of 1242 patients with a positive test (18%). Nonadherence with colonoscopy after a positive test was high (21%), and the cost to detect 1 advanced adenoma or cancer was $38,849. CONCLUSIONS: The frequency of adenoma detection by an MT-sDNA screening strategy is low, and many positive tests are not associated with significant findings at colonoscopy. Failure to follow a positive test with colonoscopy is a significant problem that needs to be considered when this screening strategy is adopted.

Dietary Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols (FODMAPs) and Gastrointestinal Disease.

FODMAP is an acronym for fermentable oligosaccharides, disaccharides, monosaccharides, and polyols. Dietary modification of FODMAPs has been shown to have significant effects on the physiology of the gastrointestinal tract and improves symptoms of abdominal pain, distention, and bloating in patients with irritable bowel syndrome. Structured withdrawal and reintroduction of FODMAPs supervised by a dietitian is the optimal practice for dietary FODMAP modification in irritable bowel syndrome. FODMAPs are present in enteral feeding formulas and may have a role in diarrhea and bloating in tube-fed patients. Emerging areas of research include the effects of dietary modification of FODMAPs on the microbiome, micronutrient absorption, and caloric intake. FODMAP dietary modification is an emerging area in other gastrointestinal disorders and is of relevance to all practicing dietitians.

Rifabutin Triple Therapy is Effective in Patients With Multidrug-resistant Strains of Helicobacter pylori.

INTRODUCTION: Eradicating Helicobacter pylori continues to be a challenge, and no treatment regimen is uniformly successful in all treated patients. Triple therapy with rifabutin and amoxicillin is a successful rescue therapy after consecutive treatment failures. We designed this study to test the efficacy of 12-day rifabutin-based triple therapy in patients infected with multidrug-resistant strains. METHODS: Consecutive patients with dyspeptic symptoms after at least 1 antibiotic therapy course for H. pylori infection harboring triple-resistant (clarithromycin, metronidazole, levofloxacin) strains were enrolled. They received triple therapy with esomeprazole 40 mg bid, amoxicillin 1 g bid, and rifabutin 150 mg od for 12 days. Patients who failed rifabutin therapy were treated empirically on the basis of the judgment of the treating physician. RESULTS: A total of 254 out of 756 tested patients were found to be infected with a triple-resistant H. pylori strains after at least 1 antibiotic therapy course. Overall, the infection was eradicated in 213 patients, corresponding to a cure rate of 82.9% (95% CI, 78.3-87.5) by intention-to-treat analysis and 88.7% (95% CI, 84.7-92.7) at per-protocol analysis. In multivariate analysis, no factor was identified as an independent predictor of bacterial eradication. CONCLUSIONS: There is no current standard for the growing population of patients with multidrug-resistant strains of H. pylori. The 12-day low-dose rifabutin/high-dose proton pump inhibitor regimen is a safe and reliable option for patients infected with triple-resistant strains.

ACG and CAG Clinical Guideline: Management of Dyspepsia.

We have updated both the American College of Gastroenterology (ACG) and the Canadian Association of Gastroenterology (CAG) guidelines on dyspepsia in a joint ACG/CAG dyspepsia guideline. We suggest that patients ≥60 years of age presenting with dyspepsia are investigated with upper gastrointestinal endoscopy to exclude organic pathology. This is a conditional recommendation and patients at higher risk of malignancy (such as spending their childhood in a high risk gastric cancer country or having a positive family history) could be offered an endoscopy at a younger age. Alarm features should not automatically precipitate endoscopy in younger patients but this should be considered on a case-by-case basis. We recommend patients <60 years of age have a non-invasive test Helicobacter pylori and treatment if positive. Those that are negative or do not respond to this approach should be given a trial of proton pump inhibitor (PPI) therapy. If these are ineffective tricyclic antidepressants (TCA) or prokinetic therapies can be tried. Patients that have an endoscopy where no pathology is found are defined as having functional dyspepsia (FD). H. pylori eradication should be offered in these patients if they are infected. We recommend PPI, TCA and prokinetic therapy (in that order) in those that fail therapy or are H. pylori negative. We do not recommend routine upper gastrointestinal (GI) motility testing but it may be useful in selected patients.

White Paper AGA: Functional Dyspepsia.

Functional dyspepsia remains a major challenge for clinicians with no approved drugs available in the Western World. In October 2016, a meeting was held in Washington, DC, sponsored by the American Gastroenterological Association's Center for Diagnostics and Therapeutics, which included members of the Food and Drug Administration (FDA) and the pharmaceutical industry, experts in FD, and representatives of patient organizations. This white paper summarizes our current status, progress with a validated patient reported outcome instrument in functional dyspepsia, future directions and needs.

Mortality and complications following surgery for diverticulitis: Systematic review and meta-analysis.

BACKGROUND: The surgical treatment of diverticulitis is in a state of evolution. Clinicians across many disciplines need to counsel patients regarding surgical choices. OBJECTIVES: A systematic review and meta-analysis was conducted to determine the mortality and complication rates following surgery for diverticulitis in both the emergent and elective setting. METHODS: We searched PubMed, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) for relevant articles published from 1980 to 2012. The primary outcome of interest was the point estimate of mortality, following surgery for diverticulitis. RESULTS: Of the 289 citations reviewed, we included 59 studies. Overall, the point estimate for mortality was 3.05%, with a 95% confidence intereval (CI) of 1.73-5.32 and p < 0.001. Mortality following emergent surgery was 10.64% (95% CI 7.95-14.11; p < 0.001), versus 0.50% (95% CI 0.46-0.54; p < 0.001) following elective operations. A laparoscopic approach had an estimated mortality of 0.75% (95% CI 0.35-1.58; p < 0.001), compared to an open surgical approach, which had a mortality of 4.69% (95% CI 2.29-9.36, p < 0.001). The mortality following a resection with primary anastomosis was 1.96% (95% CI 1.22-3.13; p < 0.001) and for the Hartmann's procedure was 14.18% (95% CI 9.83-20.03; p < 0.001). A comparative analysis found that the risk of post-operative mortality was significantly higher following emergent surgery, compared to elective surgery (odds ratio (OR): 6.12 with 95% CI 1.62-23.10; p = 0.008; Q = 2.56, p = 0.46 and I2 = 0); the open approach, compared to a laparoscopic approach (OR: 36.43 with 95% CI 9.94-133.6; p = 0.13; and Q = 2.79, p = 0.25 and I2 = 28.26); and for Hartmann's procedure, compared to primary anastomosis without diversion (OR: 25.45 with 95% CI 15.13-42.81, p < 0.001; and Q = 23.34, p = 0.14 and I2 = 27.16). The overall reported post-operative complication rate was 32.64% (95% CI 27.43-38.32; p < 0.00). The overall surgical and medical complication rates were 18.96% and 13.93%, respectively. CONCLUSIONS: Urgent surgical treatment of diverticulitis has a significant complication rate. Even elective surgery has a significant complication rate that needs to be considered when doing the clinical decision-making for recurrent diverticulitis.