Explore the vast range of titles available.

Tobacco and alcohol use are established risk factors for esophageal squamous cell carcinoma (ESCC). We sought to determine whether these factors act synergistically to increase the risk of ESCC. We performed a systematic literature search in multiple electronic databases regardless of language. Eligible studies were population-based case-control or cohort studies of ESCC that assessed the effects of tobacco and/or alcohol. Departures from multiplicative effects were quantified by the synergy factor (SF); SF >1 indicates positive synergy. Meta-analyses were performed to estimate summary-adjusted odds ratios (ORs) and the summary crude SF using random-effect models. Heterogeneity was defined by Cochrane's Q P<0.10 and the inconsistency index. Systematic review identified 7,629 unique citations, of which 5 were eligible. Either tobacco or alcohol use was associated with a 20-30% increased risk for ESCC compared with nonuse, but the use of both was associated with an approximately threefold risk for ESCC; the summary-adjusted OR for combined alcohol and tobacco use was 3.28 (95% confidence interval (CI)=2.11, 508; Cochrane's Q P value=0.05; I(2)=55.3%). The summary SF for ever-use of both tobacco and alcohol was 1.85 (95% CI=1.45, 2.38; Cochrane's Q P value=0.49; I(2)=0.0%). There is a positive synergistic effect of alcohol and tobacco use for ESCC. The observed combined effect of the two factors is almost double if there were no synergy. Efforts for controlling the burden of ESCC should focus on individuals who use both alcohol and tobacco.

Little is known about how reports on the adverse effects of proton pump inhibitors (PPIs) impact patients' perceptions of these drugs and medication use. We sought to determine patients' level of concern about PPI adverse effects and its association with attempts to discontinue these drugs. This study is an online survey of US adults who use PPIs for gastroesophageal reflux disease. Topics included awareness of and concern about PPI adverse effects, prior discussion with providers, and attempts to stop PPI because of concern about adverse effects. For the primary analysis, we used logistic regression to identify associations between having attempted to stop PPI and concern about PPI-related adverse effects, a provider's recommendation to stop, risk of upper gastrointestinal bleeding (UGIB), age, and gender. Among 755 patient participants, mean age was 49 years (s.d. 16), 71% were women, and 24% were at high risk of UGIB. Twenty percent of patients were able to write in ≥1 reported adverse effect, and 46% endorsed awareness of ≥1 adverse effect when presented with a list, most commonly chronic kidney disease (17%). Thirty-three percent of patients were slightly concerned, 32% somewhat concerned, and 14% extremely concerned about adverse effects. Twenty-four percent of patients had discussed PPI risks and benefits with a provider, and 9% had been recommended to stop. Thirty-nine percent had attempted to stop their PPI, most (83%) without a provider recommendation. Factors associated with an attempt at stopping PPI included: (i) provider recommendation to stop (odds ratio [OR] 3.26 [1.82-5.83]); (ii) concern about adverse effects (OR 5.13 [2.77-9.51] for slightly, 12.0 [6.51-22.2] for somewhat, and 19.4 [9.75-38.7] for extremely concerned); and (iii) female gender (OR 1.64 [1.12-2.39]). Patients at high risk of UGIB were as likely to have attempted to stop as others (OR 0.98 [0.66-1.44]). Concern about PPIs is common and strongly associated with attempts at discontinuation, even without a provider's recommendation. Notably, individuals at high risk of UGIB, who benefit from PPIs, were equally likely to have tried stopping PPIs as others. Providers should proactively discuss the risks and benefits of PPIs with their patients, who may otherwise make unwise decisions about PPI management on their own.

Risk factors for Barrett's esophagus include gastroesophageal reflux disease (GERD) symptoms, age, abdominal obesity, and tobacco use. We aimed to develop a tool using these factors to predict the presence of Barrett's esophagus. Male colorectal cancer (CRC) screenees were recruited to undergo upper endoscopy, identifying newly diagnosed cases of Barrett's esophagus. Logistic regression models predicting Barrett's esophagus using GERD symptoms alone and together with abdominal obesity, tobacco use, and age were compared. Barrett's esophagus was found in 70 (8.5%) of 822 CRC screenees. Mutually adjusting for other covariates, Barrett's esophagus was associated with weekly GERD (odds ratio (OR)=2.33, 95% confidence interval (CI)=1.34, 4.05), age (OR per 10 years=1.53, 95% CI=1.05, 2.25), waist-to-hip ratio (OR per 0.10=1.44, 95% CI=0.898, 2.32) and pack-years of cigarette use (OR per 10 pack-years=1.09, 95% CI=1.04, 1.14). A model including those four factors had a greater area under the receiver operating characteristics curve than did a model based on GERD frequency and duration alone (0.72 vs. 0.61, P<0.001), and it had a net reclassification improvement index of 19-25%. The prevalence of Barrett's esophagus was substantial in our population of older overweight men. A model based on GERD, age, abdominal obesity, and cigarette use more accurately classified the presence of Barrett's esophagus than did a model based on GERD alone. Following validation of the tool in another population, its use in clinical practice might improve the efficiency of screening for Barrett's esophagus.

Shift work has been associated with gastrointestinal symptoms such as abdominal pain, constipation, and diarrhea. These symptoms overlap with those reported by patients with functional bowel disorders. Because shift work will lead to misalignment between the endogenous circadian timing system and the external 24 h environment, we hypothesized that nurses participating in shift work will have a higher prevalence of functional bowel disorders when compared with nurses participating in day shifts. Nurses engaged in patient care were invited to complete Rome III, irritable bowel syndrome-quality of life measure (IBS-QOL) and modified Sleep-50 questionnaires. Respondents were classified as working day, night, or rotating shifts. The prevalence of IBS, functional constipation, functional diarrhea, and individual gastrointestinal symptoms was determined. Data were available for 399 nurses (214 day shift, 110 night shift, and 75 rotating shift workers). Rotating shift nurses had a significantly higher prevalence of IBS compared to day shift nurses (48% vs. 31%, P<0.01). Multivariable logistic regression correcting for age, gender, and sleep quality proved this association robust. IBS-QOL scores among groups were similar. Prevalence of functional constipation and functional diarrhea was similar between groups. Rotating shift nurses had a significantly higher prevalence of abdominal pain compared to day shift (81% vs. 54%, P<0.0001) and night shift workers (61%, P=0.003). Participation in shift work, especially rotating shift work, is associated with the development of IBS and abdominal pain that is independent of sleep quality. Circadian rhythm disturbances may have a function in the pathogenesis of IBS and abdominal pain.

Gastroesophageal reflux disease (GERD) is key in the pathogenesis of Barrett's esophagus and esophageal adenocarcinoma (EAC). Endoscopic screening of select individuals with GERD symptoms for Barrett's esophagus and EAC has been recommended, but the great majority of patients with EAC had never undergone prior screening, despite over a million esophagogastroduodenoscopies (EGDs) performed annually in the United States among individuals with GERD symptoms. This is likely due to a conflation among providers regarding diagnostic EGD in those with refractory symptoms and screening EGD. An alternative approach is needed that de-emphasizes GERD to avoid confusion and increase uptake of appropriate screening.

ObjectiveBarrett’s oesophagus (BE) is a known precursor to oesophageal adenocarcinoma (OAC) but current clinical data have not been consolidated to address whether BE is the origin of all incident OAC, which would reinforce evidence for BE screening efforts. We aimed to answer whether all expected prevalent BE, diagnosed and undiagnosed, could account for all incident OACs in the US cancer registry data.DesignWe used a multiscale computational model of OAC that includes the evolutionary process from normal oesophagus through BE in individuals from the US population. The model was previously calibrated to fit Surveillance, Epidemiology and End Results cancer incidence curves. Here, we also utilised age-specific and sex-specific US census data for numbers at-risk. The primary outcome for model validation was the expected number of OAC cases for a given calendar year. Secondary outcomes included the comparisons of resulting model-predicted prevalence of BE and BE-to-OAC progression to the observed prevalence and progression rates.ResultsThe model estimated the total number of OAC cases from BE in 2010 was 9970 (95% CI: 9140 to 11 980), which recapitulates nearly all OAC cases from population data. The model simultaneously predicted 8%–9% BE prevalence in high-risk males age 45–55, and 0.1%–0.2% non-dysplastic BE-to-OAC annual progression in males, consistent with clinical studies.ConclusionThere are likely few additional OAC cases arising in the US population outside those expected from individuals with BE. Effective screening of high-risk patients could capture the majority of population destined for OAC progression and potentially decrease mortality through early detection and curative removal of small (pre)cancers during surveillance.

Patients with inflammatory bowel disease(IBD) are frequently exposed to computed tomography (CT). Each CT exposes patients to radiation that cumulatively could increase the risk of malignancy, particularly in younger patients. We aim to study the effect of age on CT use in IBD patients seen in the Emergency Department (ED) or the hospital. We conducted a retrospective cohort study of IBD patients identified in Truven Health Marketscan databases between 2009-2013. The main outcome was use of CT during an ED or inpatient visit. Effect of age on CT use was characterized using logistic regression accounting for important covariables. There were 66,731 patients with IBD with 144,147 ED or inpatient visits in this cohort with a diagnosis code of IBD. At first visit, 5.8% percent were below age 18. CT was utilized in 26.6% of visits. In multivariable analysis, adjusting for medications, recent surgery, and gender, patients 18-35 were more likely to undergo CT (OR 2.35, 95%CI: 2.20-2.52) compared to those <18. Examining patients only between 16 and 19, the odds of an 18 or 19-year-old undergoing CT is significantly higher than a 16 or 17-year-old (OR 1.96, 95%CI: 1.71-2.24). Patients with IBD undergo CT more than a quarter of the time in the ED or inpatient setting. Pediatric providers limit radiation exposure among those <18 while adult providers are not as cautious with radiation exposure for the young adult population. Increased awareness of the risks of cumulative radiation exposure in the young adult population is needed.

The gut and local esophageal microbiome progressively shift from healthy commensal bacteria to inflammation-linked pathogenic bacteria in patients with gastroesophageal reflux disease, Barrett's esophagus, and esophageal adenocarcinoma (EAC). However, mechanisms by which microbial communities and metabolites contribute to reflux-driven EAC remain incompletely understood and challenging to target. Herein, we utilized a rat reflux-induced EAC model to investigate targeting the gut microbiome-esophageal metabolome axis with cranberry proanthocyanidins (C-PAC) to inhibit EAC progression. Sprague-Dawley rats, with or without reflux induction, received water or C-PAC ad libitum (700 μg/rat/day) for 25 or 40 weeks. C-PAC exerted prebiotic activity abrogating reflux-induced dysbiosis and mitigating bile acid metabolism and transport, culminating in significant inhibition of EAC through TLR/NF-κB/TP53 signaling cascades. At the species level, C-PAC mitigated reflux-induced pathogenic bacteria (Streptococcus parasanguinis, Escherichia coli, and Proteus mirabilis). C-PAC specifically reversed reflux-induced bacterial, inflammatory, and immune-implicated proteins and genes, including Ccl4, Cd14, Crp, Cxcl1, Il6, Il1b, Lbp, Lcn2, Myd88, Nfkb1, Tlr2, and Tlr4, aligning with changes in human EAC progression, as confirmed through public databases. C-PAC is a safe, promising dietary constituent that may be utilized alone or potentially as an adjuvant to current therapies to prevent EAC progression through ameliorating reflux-induced dysbiosis, inflammation, and cellular damage.

INTRODUCTION:Dupilumab, the first US Food and Drug Administration-approved treatment for eosinophilic esophagitis (EoE), lacks real-world data on use and effectiveness.METHODS:We conducted a retrospective cohort study of 70 patients with EoE prescribed dupilumab, comparing prescriber type, indication, follow-up, and response.RESULTS:Indications varied with gastroenterologists commonly prescribing for treatment-refractory cases and allergists as first-line therapy. Endoscopic assessment was lacking in 25.9%, but those with follow-up showed high histologic remission (92.3% first-line and 85% previous treatment failure).DISCUSSION:Dupilumab demonstrates effectiveness across EoE severity, including milder disease without previous treatment failure. Improving follow-up and assessing cost-effectiveness will help clarify its role in the treatment algorithm.