In primary care, second-line IBS therapy with amitriptyline vs. placebo reduced symptoms at 6 mo.

SOURCE CITATION: Ford AC, Wright-Hughes A, Alderson SL, et al; ATLANTIS trialists. Amitriptyline at low-dose and titrated for irritable bowel syndrome as second-line treatment in primary care (ATLANTIS): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023;402:1773-1785. 37858323.

In persons with constipation or IBS-C, kiwifruit vs. psyllium increased spontaneous bowel movements.

SOURCE CITATION: Gearry R, Fukudo S, Barbara G, et al. Consumption of 2 green kiwifruits daily improves constipation and abdominal comfort-results of an international multicenter randomized controlled trial. Am J Gastroenterol. 9 Jan 2023. [Epub ahead of print]. 36537785.

Review of the clinical development of fexuprazan for gastroesophageal reflux-related disease.

Proton pump inhibitors (PPIs) are a mainstay treatment for acid peptic disorders such as gastroesophageal reflux disease (GERD). Although PPIs are considered first-line medications for acid suppression, they have notable limitations such as requiring acid-mediated activation, short half-life and duration of action, and metabolic variability. Fexuprazan is a newly developed potassium-competitive acid blocker (P-CAB), which inhibits acid generation and secretion in a competitive and reversible manner. Fexuprazan, like other P-CABs, has significantly different pharmacodynamic and pharmacokinetic properties than PPIs with potential advantages including rapid, robust, and durable acid suppression, lack of CYP2C19 metabolism, independence from food intake, and no requirement for activation into an active form. Completed clinical trials of fexuprazan have demonstrated comparable efficacy to PPIs for the healing of erosive esophagitis and relief of GERD-related esophageal symptoms without concerning safety signals. Ongoing clinical trials are evaluating fexuprazan for the prevention of NSAID-induced peptic ulcer disease, non-erosive GERD, and acute and chronic gastritis, as well as healing efficacy and maintenance of erosive esophagitis (EE). Fexuprazan is approved in South Korea for the treatment of EE and at the time of this writing is being considered for regulatory approval in several other countries. In this article, we summarize and discuss the pharmacology, efficacy, and safety of fexuprazan.

Irritable Bowel Syndrome Is Not Associated with an Increased Risk of Polyps and Colorectal Cancer: A Systematic Review and Meta-Analysis.

OBJECTIVES: Colorectal cancer (CRC) is the third most common malignancy in the US. Several factors are associated with increased/decreased CRC risk and often linked to adenomatous colorectal polyps (CRP). Recent studies suggest a lower risk of neoplastic lesions among irritable bowel syndrome (IBS) patients. We aimed to systematically assess the occurrence of CRC and CRP in IBS patients. METHODS: Searches of the Medline, Cochrane, and EMBASE databases were performed, blindly and independently, by two investigators. Studies of CRC or CRP incidence in IBS patients (diagnosed by Rome or other symptom-based criteria) were eligible for inclusion. CRC and CRP effect estimates were pooled in meta-analyses using random models. RESULTS: Of 4941 non-duplicate studies, 14 were included, comprising 654,764 IBS patients and 2,277,195 controls in 8 cohort studies, and 26,641 IBS patients and 87,803 controls in 6 cross-sectional studies. Pooled analysis revealed a significantly decreased prevalence of CRP in IBS subjects vs. controls, with a pooled odds ratio (OR) of 0.29 (95% CI (0.15, 0.54)). There was significant heterogeneity between studies (I2 = 96%, p < 0.01). This finding persisted when studies which did not report pre-cancerous polyps separately were excluded (OR 0.23, 95% CI (0.15, 0.35), I2 = 85%, p < 0.01). CRC prevalence was lower in IBS subjects, but this did not reach statistical significance (OR 0.40, 95% CI (0.09, 1.77]). CONCLUSION: Our analyses reveal a decreased incidence of colorectal polyps in IBS, although CRC did not reach significance. Mechanistic studies with detailed genotypic analysis and clinical phenotyping are needed to better elucidate the potentially protective effect of IBS on CRC development.

An Open-label, Multicenter Study to Assess the Efficacy and Safety of a Novel Probiotic Blend in Patients With Functional Gastrointestinal Symptoms.

GOAL: A novel 5-strain (Bl-04, Bi-07, HN019, NCFM, and Lpc-37) probiotic blend was developed and its safety and efficacy were evaluated in patients with functional gastrointestinal (GI) symptoms. BACKGROUND: These strains administered together have not previously been investigated. STUDY: Patients aged 18 to 75 years with functional GI symptoms were eligible for inclusion in a single-arm, open-label, multicenter study (NCT04155801). An oral capsule containing the novel probiotic blend was administered once daily for 30 days. The primary efficacy endpoint was patient-reported improvement in overall GI well-being at day 30. Secondary efficacy endpoints included changes in GI symptoms assessed using the GI Health Symptom Questionnaire. Incidence of treatment-emergent adverse events was recorded at all visits. RESULTS: Of 188 enrolled patients, 72.3% were female and mean (SD) age was 44.1 (13.4) years. At day 30, 85.1% of patients achieved the primary endpoint, a positive response signifying improvement in overall GI well-being. Improvements from baseline were reported at day 30 in diarrhea frequency (baseline frequency≥3 to 4 d/wk) and severity (baseline severity≥5/10) for 75.8% and 87.3% of patients, respectively. Over the same time period, constipation frequency (baseline frequency≥3 to 4 d/wk) and severity (baseline severity≥5/10) improved in 73.6% and 80.4% of patients, respectively. Most patients reported improvements at day 30 in frequency and severity of straining, urgency, abdominal pain/discomfort, bloating, and distention. Improvements reported at day 30 were generally observable at day 14. No safety signals were identified. CONCLUSION: A novel 5-strain probiotic blend improved functional GI symptoms and was safe.

Transient alterations in plasma sodium concentrations with NER1006 bowel preparation: an analysis of three phase III, randomized clinical trials.

BACKGROUND: This analysis characterized changes in sodium levels in patients receiving the 1 L polyethylene glycol-based preparation NER1006. METHODS: Data were pooled from three phase III, randomized clinical trials. A post hoc subanalysis included adults who received a 2-day split-dose (evening/morning) NER1006 regimen, a 1-day split-dose (morning only) regimen, or evening-before regimen and had an increase in sodium concentrations from normal to above the upper limit of normal (143-148 mmol/L) at ≥ 1 of three post-treatment visits. Blood samples were collected at baseline, day of colonoscopy (visit 2), 2 ± 1 days post-colonoscopy (visit 3), and 7 ± 1 days post-colonoscopy (visit 4). RESULTS: A total of 214 of 1028 patients were included. Of the 214 patients, sodium concentration increased from a mean baseline value of 141.8 mmol/L to a mean of 147.1 mmol/L (median increase from baseline of approximately 5 mmol/L). The mean sodium concentration was within normal range at visit 3 (142.3 mmol/L) and visit 4 (142.4 mmol/L), as was the median sodium concentration. Overall, ~ 90% of patients had a normal serum concentration at visits 3 and 4. Based on day of colonoscopy test results, there were four adverse events involving hypernatremia (0.4% of 1028), which were mild and did not require medical intervention; sodium levels returned to normal range by visit 3. CONCLUSION: NER1006 was associated with small, transient increases in sodium levels that were not considered clinically significant. Trial registration NOCT (ClinicalTrials.gov: NCT02254486 [registered October 2, 2014]), MORA (ClinTrials.gov: NCT02273167 [registered October 23, 2014]; EudraCT number: 2014-002185-78 [registered August 13, 2014]), DAYB (ClinicalTrials.gov: NCT02273141 [registered October 23, 2014]; EudraCT Number: 2014-002186-30 [registered August 12, 2014]).

A novel duodenal-release formulation of caraway oil and L-menthol is a safe, effective and well tolerated therapy for functional dyspepsia.

BACKGROUND: A randomized, placebo-controlled clinical trial (FDREST) of a novel formulation of caraway oil and L-menthol (COLM-SST) demonstrated symptom relief in patients with functional dyspepsia (FD). Two follow-up studies were conducted to evaluate patient satisfaction, self-regulated dosing, and long-term safety data: FDACT, Functional Dyspepsia Adherence and Compliance Trial, and FDSU36, Functional Dyspepsia Safety Update at 36 months. METHODS: A patient reported outcomes (PRO) questionnaire was designed and distributed online to assess real-world satisfaction and dosing frequency of open-label COLM-SST in patients with FD. A separate study analyzing voluntary safety surveillance data evaluated the frequency and severity of reported adverse events (AEs). RESULTS: A total of 600 FD patients were enrolled in the PRO study. Ninety five percent of respondents reported a major or moderate improvement in their FD symptoms and 91.7% indicated a major or moderate improvement in quality of life (QOL) using COLM-SST. Between 1 and 4 capsules were consumed daily by 91.2% of respondents, with 56.2% taking them before meals. Symptom relief was rapid, with 86.4% of respondents indicating relief within 2 h of taking COLM-SST. Few adverse events (AEs) were reported (0.0187%) by patients using COLM-SST. No serious AEs were identified. CONCLUSION: COLM-SST is safe, well tolerated, and provides rapid relief of FD symptoms. These findings, demonstrated in the FDREST trial, were further supported by a large prospective PRO study evaluating self-regulated dosing frequency, symptom improvement, and QOL. COLM-SST was well-tolerated based on review of AE data at 36 months.

Multicentre, prospective, randomised study comparing the diagnostic yield of colon capsule endoscopy versus CT colonography in a screening population (the TOPAZ study).

OBJECTIVE: Colon capsule endoscopy (CCE) has shown promise for colorectal neoplasia detection compared with optical colonoscopy (OC), but has not been compared with other screening tests in average risk screening patients. DESIGN: Patients 50 to 75 years of age (African Americans, 45-75 years) were randomised to CCE or CT colonography (CTC) and subsequent blinded OC. The primary endpoint was diagnostic yield of polyps ≥6 mm with CCE or CTC. Secondary endpoints included accuracy for size and histology, examination completeness, number/proportion of subjects with polyps and adenomas ≥6 mm and ≥10 mm, subject satisfaction and safety. RESULTS: From 320 enrolled subjects, data from 286 (89.4%) were evaluable. The proportion of subjects with any polyp ≥6 mm confirmed by OC was 31.6% for CCE versus 8.6% for CTC (pPr non-inferiority and superiority=0.999). The diagnostic yield of polyps ≥10 mm was 13.5% with CCE versus 6.3% with CTC (pPr non-inferiority=0.9954). The sensitivity and specificity of CCE for polyps ≥6 mm was 79.2% and 96.3% while that of CTC was 26.8% and 98.9%. The sensitivity and specificity of CCE for polyps ≥10 mm was 85.7% and 98.2% compared with 50% and 99.1% for CTC. Both tests were well tolerated/safe. CONCLUSION: CCE was superior to CTC for detection of polyps ≥6 mm and non-inferior for identification of polyps ≥10 mm. CCE should be considered comparable or superior to CTC as a colorectal neoplasia screening test, although neither test is as effective as OC. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov no: NCT02754661.

Kras mutation rate precisely orchestrates ductal derived pancreatic intraepithelial neoplasia and pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related death in the United States. Despite the high prevalence of Kras mutations in pancreatic cancer patients, murine models expressing the oncogenic mutant Kras (Krasmut) in mature pancreatic cells develop PDAC at a low frequency. Independent of cell of origin, a second genetic hit (loss of tumor suppressor TP53 or PTEN) is important for development of PDAC in mice. We hypothesized ectopic expression and elevated levels of oncogenic mutant Kras would promote PanIN arising in pancreatic ducts. To test our hypothesis, the significance of elevating levels of K-Ras and Ras activity has been explored by expression of a CAG driven LGSL-KrasG12V allele (cKras) in pancreatic ducts, which promotes ectopic Kras expression. We predicted expression of cKras in pancreatic ducts would generate neoplasia and PDAC. To test our hypothesis, we employed tamoxifen dependent CreERT2 mediated recombination. Hnf1b:CreERT2;KrasG12V (cKrasHnf1b/+) mice received 1 (Low), 5 (Mod) or 10 (High) mg per 20 g body weight to recombine cKras in low (cKrasLow), moderate (cKrasMod), and high (cKrasHigh) percentages of pancreatic ducts. Our histologic analysis revealed poorly differentiated aggressive tumors in cKrasHigh mice. cKrasMod mice had grades of Pancreatic Intraepithelial Neoplasia (PanIN), recapitulating early and advanced PanIN observed in human PDAC. Proteomics analysis revealed significant differences in PTEN/AKT and MAPK pathways between wild type, cKrasLow, cKrasMod, and cKrasHigh mice. In conclusion, in this study, we provide evidence that ectopic expression of oncogenic mutant K-Ras in pancreatic ducts generates early and late PanIN as well as PDAC. This Ras rheostat model provides evidence that AKT signaling is an important early driver of invasive ductal derived PDAC.

Low Risk of Progression of Barrett's Esophagus to Neoplasia in Women.

BACKGROUND AND AIMS: Men are at a higher risk for Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC), but little is known about BE progression to dysplasia and EAC in women. We performed a retrospective, multicenter cohort study to assess risk of BE progression to dysplasia and EAC in women compared with men. We also investigated comorbidities, medication use, and endoscopic features that contribute to sex differences in risk of BE progression. METHODS: We collected data from large cohort of patients with BE seen at 6 centers in the United States and Europe, followed for a median 5.7 years. We obtained demographic information (age, sex, ethnicity), clinical history (tobacco use, body mass index, comorbidities), endoscopy results (procedure date, BE segment length), and histopathology findings. Neoplasia was graded as low-grade dysplasia, high-grade dysplasia (HGD), or EAC. Rates of disease progression between women and men were compared using χ2 analysis and the Student t test. Multivariable logistic regression was used to assess the association between sex and disease progression after adjusting for possible confounding variables. RESULTS: Of the total 4263 patients in the cohort, 2145 met the inclusion criteria, including 324 (15%) women. There was a total of 34 (1.6%) incident EACs, with an overall annual incidence of 0.3% (95% confidence interval: 0.2%-0.4%). We found significant differences between women and men in annual incidence rates of EAC (0.05% for women vs. 0.3% in men; P=0.04) and in the combined endpoint of HGD or EAC (0.1% for women vs. 1.1% for men; P<0.001). Female gender was an independent predictor for reduced progression to HGD or EAC when rates of progression were adjusted for body mass index, smoking history, race, use of aspirin, nonsteroidal anti-inflammatory drugs, proton-pump inhibitors, or statins, hypertriglyceridemia, BE length, and histology findings at baseline (hazard ratio: 0.11; 95% confidence interval: 0.03-0.45; P=0.002). CONCLUSIONS: In a multicenter study of men versus women with BE, we found a significantly lower risk of disease progression to cancer and HGD in women. The extremely low risk of EAC in women with BE (0.05%/y) indicates that surveillance endoscopy may not be necessary for this subgroup of patients with BE.

Patient experience with NER1006 as a bowel preparation for colonoscopy: a prospective, multicenter US survey.

BACKGROUND: NER1006 (Plenvu®, Salix Pharmaceuticals, Bridgewater, NJ) is a 1 L polyethylene glycol bowel preparation indicated for colonoscopy in adults. A US online survey assessed real-world ease of use and treatment satisfaction in individuals who received NER1006. METHODS: Adults were recruited from 444 US community gastrointestinal practices and provided a kit number for enrollment into an online survey to be completed within 2 weeks. Survey questions evaluated colonoscopy history and prior bowel preparation(s) prescribed, patient experience during NER1006 administration, and patient satisfaction with the bowel preparation process. A 9-point predefined grading scale was used to evaluate ease of NER1006 preparation and consumption (range, 1 "very difficult" to 9 "very easy"); the perceived importance of volume requirement and clear liquid options (range, 1 "not important at all" to 9 "very important"); and patient satisfaction (range, 1 "not satisfied at all" to 9 "very satisfied"). RESULTS: 1630 patients were enrolled, 1606 underwent colonoscopy, and 1598 completed the survey between September 15, 2018 and February 28, 2019. Among 1606 patients who had a colonoscopy, 62.5% were female, and the mean patient age was 54.4 years (range 18-89 years). Most patients (74.7%) did not report a family history of colon cancer, 62.6% had undergone prior colonoscopy, and 64.8% were undergoing colonoscopy for routine colorectal cancer screening. A majority (76.1%) of patients who completed the survey reported that NER1006 was very easy to prepare and take, and 89.9% were very or moderately satisfied with NER1006 overall. Most (97.6%) patients reported consuming all or most of the bowel preparation. Among 1005 patients with previous bowel preparation use, 84.7% indicated that their experience with NER1006 was much better or better (65.3%) or about the same (19.4%) compared with previously used bowel preparations, while only 15.3% rated NER1006 as worse or much worse. CONCLUSIONS: In this first real-world, US multicenter survey, patient-reported experience with NER1006 as a bowel preparation for colonoscopy was favorable and adherence was high. The majority of patients were very or moderately satisfied with the overall experience and found it much better/better than previously used bowel preparations. TRIAL REGISTRATION: Not applicable.

Development and Validation of a Model to Determine Risk of Progression of Barrett's Esophagus to Neoplasia.

BACKGROUND & AIMS: A system is needed to determine the risk of patients with Barrett's esophagus for progression to high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC). We developed and validated a model to determine of progression to HGD or EAC in patients with BE, based on demographic data and endoscopic and histologic findings at the time of index endoscopy. METHODS: We performed a longitudinal study of patients with BE at 5 centers in United States and 1 center in Netherlands enrolled in the Barrett's Esophagus Study database from 1985 through 2014. Patients were excluded from the analysis if they had less than 1 year of follow-up, were diagnosed with HGD or EAC within the past year, were missing baseline histologic data, or had no intestinal metaplasia. Seventy percent of the patients were used to derive the model and 30% were used for the validation study. The primary outcome was development of HGD or EAC during the follow-up period (median, 5.9 years). Survival analysis was performed using the Kaplan-Meier method. We assigned a specific number of points to each BE risk factor, and point totals (scores) were used to create categories of low, intermediate, and high risk. We used Cox regression to compute hazard ratios and 95% confidence intervals to determine associations between risk of progression and scores. RESULTS: Of 4584 patients in the database, 2697 were included in our analysis (84.1% men; 87.6% Caucasian; mean age, 55.4 ± 20.1 years; mean body mass index, 27.9 ± 5.5 kg/m2; mean length of BE, 3.7 ± 3.2 cm). During the follow-up period, 154 patients (5.7%) developed HGD or EAC, with an annual rate of progression of 0.95%. Male sex, smoking, length of BE, and baseline-confirmed low-grade dysplasia were significantly associated with progression. Scores assigned identified patients with BE that progressed to HGD or EAC with a c-statistic of 0.76 (95% confidence interval, 0.72-0.80; P < .001). The calibration slope was 0.9966 (P = .99), determined from the validation cohort. CONCLUSIONS: We developed a scoring system (Progression in Barrett's Esophagus score) based on male sex, smoking, length of BE, and baseline low-grade dysplasia that identified patients with BE at low, intermediate, and high risk for HGD or EAC. This scoring system might be used in management of patients.

Lower Annual Rate of Progression of Short-Segment vs Long-Segment Barrett's Esophagus to Esophageal Adenocarcinoma.

BACKGROUND & AIMS: European guidelines recommend different surveillance intervals of non-dysplastic Barrett's esophagus (NDBE) based on segment length, as opposed to guidelines in the United States, which do recommend surveillance intervals based on BE length. We studied rates of progression of NDBE to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) in patients with short-segment BE using the definition of BE in the latest guidelines (length ≥1 cm). METHODS: We collected demographic, clinical, endoscopy, and histopathology data from 1883 patients with endoscopic evidence of NDBE (mean age, 57.3 years; 83.5% male; 88.1% Caucasians) seen at 7 tertiary referral centers. Patients were followed for a median 6.4 years. Cases of dysplasia or EAC detected within 1 year of index endoscopy were considered prevalent and were excluded. Unadjusted rates of progression to HGD or EAC were compared between patients with short (≥1 and <3) and long (≥3) BE lengths using log-rank tests. A subgroup analysis was performed on patients with a documented Prague C&M classification. We used a multivariable proportional hazards model to evaluate the association between BE length and progression. Adjusted hazards ratios were calculated after adjusting for variables associated with progression. RESULTS: We found 822 patients to have a short-segment BE (SSBE) and 1061 to have long segment BE (LSBE). We found patients with SSBE to have a significantly lower annual rate of progression to EAC (0.07%) than of patients with LSBE (0.25%) (P = .001). For the combined endpoint of HGD or EAC, annual progression rates were significantly lower among patients with SSBE (0.29%) compared to compared to LSBE (0.91%) (P < .001). This effect persisted in multivariable analysis (hazard ratio, 0.32; 95% CI, 0.18-0.57; P < .001). CONCLUSION: We analyzed progression of BE (length ≥1 cm) to HGD or EAC in a large cohort of patients seen at multiple centers and followed for a median 6.4 years. We found a lower annual rate of progression of SSBE to EAC (0.07%/year) than of LSBE (0.25%/year). We propose lengthening current surveillance intervals for patients with SSBE.

Efficacy and Safety of Eluxadoline in Patients With Irritable Bowel Syndrome With Diarrhea Who Report Inadequate Symptom Control With Loperamide: RELIEF Phase 4 Study.

OBJECTIVES: Irritable bowel syndrome with diarrhea (IBS-D) is a functional gastrointestinal disorder with limited effective treatment options. We evaluated the efficacy and safety of eluxadoline in patients with IBS-D who reported inadequate symptom control with prior loperamide. METHODS: Three hundred forty-six adults with IBS-D (Rome III criteria) were randomly assigned to placebo or eluxadoline 100 mg twice daily for 12 weeks. Patients recorded daily IBS-D symptoms, including worst abdominal pain (WAP) and stool consistency (through Bristol Stool Scale). The primary endpoint was proportion of composite responders, defined as patients who met daily composite response criteria (≥40% WAP improvement and <5 Bristol Stool Scale score) for at least 50% of treatment days, and recorded ≥60 days of diary entries over the 12-week period. RESULTS: Over 12 weeks, a significantly greater proportion of eluxadoline patients achieved the primary composite responder endpoint compared to placebo (22.7% vs 10.3%, P = 0.002), and component endpoints of improvements in stool consistency (27.9% vs 16.7%, P = 0.01) and WAP (43.6% vs 31.0%, P = 0.02). Additionally, a greater proportion of eluxadoline patients met the composite responder endpoint assessed at monthly intervals compared to placebo (weeks 1-4: 14.0% vs 6.9%, P = 0.03; weeks 5-8: 26.7% vs 14.9%, P = 0.006; weeks 9-12: 30.8% vs 16.7%, P = 0.002). Rates of adverse events were comparable in both groups (37.4% vs 35.3%); no treatment-related serious adverse event, cases of sphincter of Oddi spasm, or pancreatitis were reported. DISCUSSION: Eluxadoline appears safe and effective for treating IBS-D symptoms in patients with an intact gallbladder reporting inadequate relief with prior loperamide use.

Excluding inflammatory bowel disease in the irritable bowel syndrome patient: how far to go?

PURPOSE OF REVIEW: Irritable bowel syndrome (IBS) is among the most commonly encountered conditions in primary care and gastroenterology. There is ample evidence that an IBS diagnosis based on symptom-based criteria and exclusion of alarm features that would otherwise support diagnostic testing is accurate and durable. For many clinicians, however, IBS remains a diagnosis of exclusion because of concern surrounding missed diagnoses of inflammatory bowel disease (IBD) or other organic gastrointestinal diseases. Using blood and/or fecal biomarker tests to shift the precolonoscopy probability of IBD in patients with symptoms mimicking IBS is becoming an increasingly reasonable practice with improvement in 'preliminary' tests. RECENT FINDINGS: Fecal calprotectin (FCP) testing appears to be the most sensitive preliminary test for discriminating IBD from IBS. Although both fecal lactoferrin and FCP were superior to serum C-reactive peptide (CRP) in their diagnostic accuracy, FCP is superior to fecal lactoferrin based on available literature. SUMMARY: In patients with IBS with diarrhea who have not undergone previous extensive evaluation, the ability of screening tests to detect colonic inflammation is improving. FCP and fecal lactoferrin are reliable predictors of colonic inflammation and should be considered for standard testing in patients with IBS-D symptoms to help identify those who would benefit most from colonoscopy. Although predictive, there currently are no fecal or serum tests that can definitively identify or subtype IBD.

Increasing prevalence of high-grade dysplasia and adenocarcinoma on index endoscopy in Barrett's esophagus over the past 2 decades: data from a multicenter U.S. consortium.

INTRODUCTION: Data on time trends of dysplasia and esophageal adenocarcinoma (EAC) in Barrett's esophagus (BE) during the index endoscopy (ie, prevalent cases) are limited. Our aim was to determine the prevalence patterns of BE-associated dysplasia on index endoscopy over the past 25 years. METHODS: The Barrett's Esophagus Study is a multicenter outcome project of a large cohort of patients with BE. Proportions of patients with index endoscopy findings of no dysplasia (NDBE), low-grade dysplasia (LGD), high-grade dysplasia (HGD), and EAC were extracted per year of index endoscopy, and 5-yearly patient cohorts were tabulated over years 1990 to 2010+ (2010-current). Prevalent dysplasia and endoscopic findings were trended over the past 25 years using percentage dysplasia (LGD, HGD, EAC, and HGD/EAC) to assess changes in detection of BE-associated dysplasia over the last 25 years. Statistical analysis was done using SAS version 9.4 software (SAS, Cary, NC). RESULTS: A total of 3643 patients were included in the analysis with index endoscopy showing NDBE in 2513 (70.1%), LGD in 412 (11.5%), HGD in 193 (5.4%), and EAC in 181 (5.1%). Over time, there was an increase in the mean age of patients with BE (51.7 ± 29 years vs 62.6 ± 11.3 years) and the proportion of males (84% vs 92.6%) diagnosed with BE but a decrease in the mean BE length (4.4±4.3 cm vs 2.9±3.0 cm) as time progressed (1990-1994 to 2010-2016 time periods). The presence of LGD on index endoscopy remained stable over 1990 to 2016. However, a significant increase (148% in HGD and 112% in EAC) in the diagnosis of HGD, EAC, and HGD/EAC was noted on index endoscopy over the last 25 years (P < .001). There was also a significant increase in the detection of visible lesions on index endoscopy (1990-1994, 5.1%; to 2005-2009, 6.3%; and 2010+, 16.3%) during the same period. CONCLUSION: Our results suggest that the prevalence of HGD and EAC has significantly increased over the past 25 years despite a decrease in BE length during the same period. This increase parallels an increase in the detection of visible lesions, suggesting that a careful examination at the index examination is crucial.

Performance measures for small-bowel endoscopy: a European Society of Gastrointestinal Endoscopy (ESGE) Quality Improvement Initiative.

The European Society of Gastrointestinal Endoscopy (ESGE) together with the United European Gastroenterology (UEG) recently developed a short list of performance measures for small-bowel endoscopy (i. e. small-bowel capsule endoscopy and device-assisted enteroscopy) with the final goal of providing endoscopy services across Europe with a tool for quality improvement. Six key performance measures for both small-bowel capsule endoscopy and for device-assisted enteroscopy were selected for inclusion, with the intention being that practice at both a service and endoscopist level should be evaluated against them. Other performance measures were considered to be less relevant, based on an assessment of their overall importance, scientific acceptability, and feasibility. Unlike lower and upper gastrointestinal endoscopy, where performance measures had already been identified, this is the first time that small-bowel endoscopy quality measures have been proposed.

Update on Pharmacotherapy for Irritable Bowel Syndrome.

PURPOSE OF REVIEW: Irritable bowel syndrome (IBS) is a functional GI disorder that affects a large percentage of the population and presents a significant socio-economic burden on the society. In this article, we reviewed the evidence supporting various pharmacological treatment options for IBS. RECENT FINDINGS: Rifaximin, eluxadoline, and alosetron have demonstrated that they reduce symptom severity improving quality of life in patients with IBS-diarrhea. Ramosetron is a promising agent in development. Peppermint oil has also demonstrated a positive impact on some symptoms of IBS. For IBS with constipation, traditional laxatives have failed to demonstrate significant benefit. However, lubiprostone, linaclotide, and plecanatide have demonstrated improvement of IBS with constipation in large, placebo-controlled trials. Tenapanor, a sodium/hydrogen exchanger 3 inhibitor, appears to be a promising treatment option in the pipeline. There are multiple pharmacologic agents with a variety of mechanisms that have demonstrated efficacy in IBS with diarrhea and constipation. There are no established pharmacologic agents for IBS with a mixed bowel pattern. There is a promising pipeline for additional novel therapies for IBS.

Low Risk of High-Grade Dysplasia or Esophageal Adenocarcinoma Among Patients With Barrett's Esophagus Less Than 1 cm (Irregular Z Line) Within 5 Years of Index Endoscopy.

BACKGROUND & AIMS: Many patients with a < 1 cm segment of columnar metaplasia in the distal esophagus, also called an irregular Z line, are encountered. These patients, often referred to as patients with Barrett's esophagus (BE), are enrolled in surveillance programs. However, little is known about their risk of high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC). We aimed to determine the incidence of HGD and EAC in patients with irregular Z line with intestinal metaplasia. METHODS: We performed a prospective, multicenter cohort study of patients who underwent endoscopic examination for BE at tertiary care referral centers in the United States and Europe. We analyzed data from 1791 patients (mean age, 56 ± 17 years) found to have non-dysplastic BE at the index endoscopy and after 1 year or more of follow-up. Patients were followed for a median of 5.9 years (interquartile range, 3.1-8.3 years). We calculated rates of progression to HGD or EAC between groups of patients with irregular Z line (n = 167) and those with BE of ≥ 1 cm (n = 1624). RESULTS: A higher proportion of patients in the irregular Z-line group were female (26.3%) than in the BE group (14.8% female BE) (P <.001). A lower proportion of patients in the irregular Z-line group were smokers (33.5%) than in the BE group (52.6% smokers). None of the patients with irregular Z line developed HGD or EAC during a median follow-up period of 4.8 years (interquartile range, 3.2-8.3 years). All 71 incident cases of HGD or EAC developed in patients with BE of ≥1 cm in length. On multivariate analysis, patients with irregular Z line and patients with BE of ≥ 1 cm did not differ significantly in age, race, or duration of follow-up. CONCLUSIONS: In a prospective, multicenter cohort study, we found that patients with irregular Z line do not develop HGD or esophageal cancer within 5 years after index endoscopy.