Clinical and Translational Gastroenterology最新文献

Introduction: Current strategies for upper gastrointestinal (UGI) cancer screening primarily target cancer-specific risk, with the strongest focus on esophageal adenocarcinoma (EAC). However, all UGI cancers are amendable to screening and early detection with an upper endoscopic examination. This study assesses and explores incidence-based mortality (IBM) for cumulative UGI cancers, aiming to identify race-based or sex-based disparities.

Methods: We used Surveillance, Epidemiology, and End Results Research data to analyze patients diagnosed with EAC, esophageal squamous cell carcinoma, cardia gastric cancer, noncardia gastric cancer, or colorectal adenocarcinoma from 2000 to 2019. Age-adjusted IBM was calculated as a rate per 100,000 population and stratified by sex and race/ethnicity. We also compared UGI cancer IBM with that of colorectal cancer, a cancer with established population-wide endoscopic screening guidelines.

Results: Cumulative IBM for UGI cancers was 8.40 (95% confidence interval [CI] 8.34-8.46). The highest cancer-specific IBM rates were for EAC (2.26, 95% CI 2.23-2.29), followed by noncardia gastric cancer (2.07, 95% CI 2.04-2.10), cardia gastric cancer (1.60, 95% CI 1.57-1.62), esophageal squamous cell carcinoma (1.21, 95% CI 1.19-1.23), and miscellaneous UGI cancer (1.27, 95% CI 1.13-1.40). UGI cancer IBM was highest among Black men (16.43, 95% CI 15.97-16.89), American Indian/Alaska Native men (15.23, 95% CI 13.75-16.82), and Hispanic men (13.76, 95% CI 13.42-14.11). These rates are significantly greater than among White men (12.81, 95% CI 12.68-12.95).

Discussion: UGI cancers impose a significantly higher mortality burden on non-White population subgroups that are not currently targeted by any systematic screening approach.

Introduction: Little has been reported about the clinical relevance and trajectories of symptoms in end-stage liver disease (ESLD). The purpose of this prospective study was to identify trajectories of change in symptom burden over the course of 12 months in adults with ESLD.

Methods: Patients were recruited from hepatology clinics at 2 healthcare systems. Validated measures were used to assess physical and psychological symptoms. Latent growth mixture modeling and survival and growth modeling were used to analyze the survey data.

Results: Data were available for 192 patients (mean age 56.5 ± 11.1 years, 64.1% male, mean Model for ESLD (MELD) 3.0 19.2 ± 5.1, ethyl alcohol as primary etiology 33.9%, ascites 88.5%, encephalopathy 70.8%); there were 38 deaths and 39 liver transplantations over 12 months. Two symptom trajectories were identified: 62 patients (32.3%) had high and unmitigated symptoms, and 130 (67.7%) had lower and improving symptoms. Patients with high and unmitigated symptoms had twice the hazard of all-cause mortality (subhazard ratio 2.53, 95% confidence interval: 1.32-4.83) and had worse physical ( P < 0.001) and mental quality of life ( P = 0.012) compared with patients with lower and improving symptoms. Symptom trajectories were not associated with MELD 3.0 scores ( P = 0.395). Female sex, social support, and level of religiosity were significant predictors of symptom trajectories ( P < 0.05 for all).

Discussion: There seems to be 2 distinct phenotypes of symptom experience in patients with ESLD that is independent of disease severity and associated with sex, social support, religiosity, and mortality. Identifying patients with high symptom burden can help optimize their care.

Introduction: Early neoplastic progression of Barrett's esophagus (BE) is often treated with endoscopic therapy. Although effective, some patients are refractory to therapy or recur after apparent eradication of the BE. The goal of this study was to determine whether genomic alterations within the treated BE may be associated with persistent or recurrent disease.

Methods: We performed DNA sequencing on pre-treatment esophageal samples from 45 patients who were successfully treated by endoscopic therapy and did not recur as well as pre-treatment and post-treatment samples from 40 patients who had persistent neoplasia and 21 patients who had recurrent neoplasia. The genomic alterations were compared between groups.

Results: The genomic landscape was similar between all groups. Patients with persistent disease were more likely to have pre-treatment alterations involving the receptor tyrosine kinase pathway ( P = 0.01), amplifications of oncogenes ( P = 0.01), and deletions of tumor suppressor genes ( P = 0.02). These associations were no longer significant after adjusting for patient age and BE length. More than half of patients with persistent (52.5%) or recurrent (57.2%) disease showed pre-treatment and post-treatment samples that shared at least 50% of their driver mutations.

Discussion: Pre-treatment samples were genomically similar between those who responded to endoscopic therapy and those who had persistent or recurrent disease, suggesting there is not a strong genomic component to treatment response. Although it was expected to find shared driver mutations in pre-treatment and post-treatment samples in patients with persistent disease, the finding that an equal number of patients with recurrent disease also showed this relation suggests that many recurrences represent undetected minimal residual disease.

Introduction: The impact of pregnancy on the development of pouchitis in women who have undergone total proctocolectomy with ileal pouch anal anastomosis for ulcerative colitis is poorly understood.

Methods: This was a retrospective study of women with ulcerative colitis who underwent total proctocolectomy with ileal pouch anal anastomosis and subsequently became pregnant at Mount Sinai Hospital. The primary outcome was acute pouchitis during pregnancy or the postpartum period defined as symptoms of increased stool frequency and urgency treated with antibiotics.

Results: A total of 44 women with 63 pregnancies and complete data were identified. Acute pouchitis occurred in 14 pregnancies (22.2%) in 12 women and in the postpartum period of 10 pregnancies (15.9%) in 9 women. Acute pouchitis occurred more frequently in women with a history of acute pouchitis immediately before, during, or after pregnancy.

Discussion: Acute pouchitis was common during pregnancy and the postpartum period, likely due to microbial shifts. Although not statistically significant, these results provide insight into the impact of pregnancy on the risk of pouchitis and establish the framework for preconception counseling that focuses on prevention and management of pouchitis during pregnancy.

Introduction: Several studies have reported the role of Helicobacter pylori eradication in gastric cancer (GC) prevention. However, for individuals with unsatisfactory management of their H. pylori infection status after eradication, the risk of GC remains unclear.

Methods: An exhaustive search strategy of the incidence of GC (including primary gastric cancer and metachronous gastric cancer) incidence in patients with unsuccessful eradication or H. pylori reinfection was implemented in the PubMed, Embase, Cochrane Library, and Web of Science. The hazard ratios (HRs) and cumulative incidence of total GC in patients with failed eradication or H. pylori reinfection (FE-Hp (+)) group were compared with that in patients with successful eradication and no H. pylori reinfection (SE-Hp (-)) group and patients with noneradication (NE) group.

Results: Seven eligible studies (including 8,767 patients with H. pylori infection) were identified. In the FE-Hp (+) group, the total GC risk was 1.86-fold of that in the SE-Hp (-) group (HR = 1.86, 95% confidence interval [CI]: 1.14-3.04, P = 0.013). The total GC risk in the NE group was also higher than that in the FE-Hp (+) group (HR = 1.98, 95% CI: 1.11-3.52, P = 0.002). On further analysis with different end points showed that the pooled GC risk increased over time (5-year follow-up: HR = 2.92, 1.34-6.34; 10-year follow-up: HR = 4.04, 2.56-6.37).

Discussion: Compared with the SE-Hp (-) group, the FE-Hp (+) group had a higher risk of gastric carcinoma. Long-term monitoring of H. pylori infection status could consolidate the benefit of eradicating H. pylori for preventing GC prevention in patients after eradication.

Introduction: Stricture is a common complication in Crohn's disease (CD). Accurate identification of strictures that poorly respond to biologic therapy is essential for making optimal therapeutic decisions. The aim of this study was to determine the association between ultrasound characteristics of strictures and their therapeutic outcomes.

Methods: Consecutive CD patients with symptomatic strictures scheduled for biologic therapy were retrospectively recruited at a tertiary hospital. Baseline intestinal ultrasound was conducted to assess stricture characteristics, including bowel wall thickness, length, stratification, vascularity, and creeping fat wrapping angle. Patients were followed up for a minimum of 1 year, during which long-term outcomes including surgery, steroid-free clinical remission, and mucosal healing were recorded. Statistical analyses were performed.

Results: A total of 43 patients were enrolled. Strictures were located in the ileocecal region (39.5%), colon (37.2%), anastomosis (20.9%), and small intestine (2.3%). The median follow-up time was 17 months (interquartile range 7-25), with 27 patients (62.8%) undergoing surgery. On multivariant analysis, creeping fat wrapping angle > 180° (odds ratio: 6.2, 95% confidence interval [CI]: 1.1-41.1) and a high Limberg score (odds ratio: 2.3, 95% CI: 1.4-6.0) were independent predictors of surgery, with an area under the curve of 0.771 (95% CI: 0.602-0.940), accuracy of 83.7%, sensitivity of 96.3%, and specificity of 62.5%. On Cox survival analysis, creeping fat >180° was significantly associated with surgery (hazard ratio, 5.2; 95% CI: 1.2-21.8; P = 0.03). In addition, creeping fat was significantly associated with steroid-free clinical remission ( P = 0.015) and mucosal healing ( P = 0.06).

Discussion: Intestinal ultrasound characteristics can predict outcomes in patients with stricturing CD who undertook biologic therapy.

Introduction: Accurate early detection of ileocolonic lesions in patients with chronic lower gastrointestinal symptoms (LGISs) is often difficult due to the rarity of early-stage alarm signs. This study assesses the effectiveness of noninvasive blood and stool biomarkers in diagnosing ileocolonic lesions in patients with chronic LGISs undergoing colonoscopy.

Methods: We conducted a prospective study between April 2020 and July 2022 involving patients with LGISs lasting a month or more. Before colonoscopy, we gathered clinical data, blood samples for C-reactive protein (CRP) and stool samples for fecal immunochemical test (FIT) and fecal calprotectin (FC) analysis.

Results: Of 922 participants analyzed (average age 62 years, 37% male), 130 (14.1%) had significant colonoscopy findings, including cancer, advanced adenoma, and inflammatory conditions. Test effectiveness showed an area under the curve of 0.630 for alarm features, 0.643 for CRP, 0.781 for FIT, and 0.667 for FC. Combining stool tests with alarm features improved diagnostic precision. Those without alarm features had a high negative predictive value of 0.97 with low threshold FIT and FC, missing minimal significant lesions, and no cancer. For patients with alarm features, dual high-cutoff test positivity showed a positive predictive value of 0.67. Adding CRP to fecal tests did not enhance accuracy.

Discussion: FIT and FC are valuable in evaluating LGISs. Negative results at low cutoffs can delay colonoscopy in limited resource settings while positive results at dual high cutoffs substantiate the need for the procedure.

Introduction: Immune-related adverse events (irAE) secondary to immune checkpoint inhibitors (ICI) have gastrointestinal (GI) manifestations, including gastritis, enteritis, and/or colitis. The long-term sequelae of ICI-associated GI toxicities (GI-irAE), particularly the development of disorders of gut-brain interaction, are not well known. We characterized the incidence of persistent GI symptoms after GI-irAE.

Methods: This is a retrospective study of adults with melanoma treated with ICI and diagnosed with GI-irAE at our institution from 2013 to 2021. All patients had endoscopic and histologic evidence of GI-irAE. The primary outcome was incidence of persistent GI symptoms (diarrhea, abdominal pain, bloating, constipation, fecal incontinence, nausea, vomiting) after resolution of GI-irAE. Hazard ratios evaluated the association between parameters and time to persistent GI symptoms.

Results: One hundred four patients with melanoma (90% stage IV disease) and GI-irAE met inclusion criteria. Thirty-four percent received anti-cytotoxic T lymphocyte-associated protein-4 therapy, 33% anti-programmed death-1, and 34% dual therapy. Patients were treated for GI-irAE for an average of 9 ± 6 weeks. Twenty-eight (27%) patients developed persistent GI symptoms 1.6 ± 0.8 years after GI-irAE. The most common symptom was constipation (17%), followed by bloating (8%) and diarrhea (5%). Over 453 person-years, the incident rate was 6.2% per 100 person-years. Use of cytotoxic T lymphocyte-associated protein-4 single or dual therapy was associated with a 3.51× risk of persistent GI symptoms (95% confidence interval 1.20-10.23).

Discussion: In this cohort of melanoma patients who experienced GI-irAE, 26% developed persistent GI symptoms, most frequently constipation. Future studies should characterize the GI sequelae after GI-irAE, which may shed light on disorders of gut-brain interaction pathogenesis and improve the lives of cancer survivors.

Introduction: An association between female sex hormones and inflammatory bowel disease (IBD) has been reported in epidemiological studies. However, a solid causal relationship has not been established. Therefore, we performed a 2-sample Mendelian randomization (MR) study to explore the causal association between genetically predicted female sex hormone exposure, especially estrogen, and IBD.

Methods: Genetic variants for female sex hormone exposure (ovulatory function, reproductive function, oral contraceptive pills, and hormone replacement therapy) were obtained from genome-wide association studies. Summary statistics for IBD were derived from the International Inflammatory Bowel Disease Genetics Consortium. We applied inverse variance weighted (IVW), MR-Egger, and weighted median (WM) methods in this MR study. Heterogeneity, horizontal pleiotropy, and sensitivity analyses were conducted to confirm the accuracy and robustness of our results.

Results: Our study found that genetically predicted age at menarche was associated with an increased risk of Crohn's disease (odds ratio [OR] IVW 1.235, 95% confidence interval [CI] 1.028-1.484, P = 0.024), genetically predicted age of the last used hormone replacement therapy was associated with an increased risk of ulcerative colitis (OR WM 1.636, 95% CI 1.011-2.648, P = 0.045), and genetically predicted number of live births was related to a decreased risk of Crohn's disease (OR IVW 0.583, 95% CI 0.373-0.912, P = 0.018).

Discussion: This study provided evidence for a link between female sex hormone exposure, especially estrogen, and IBD. Further investigations are needed to explore the causal effect of estrogen on IBD activity and the underlying mechanism of estrogen in IBD.

Background and aims: Esophageal Lichen Planus (ELP) is a rare inflammatory disease most seen in middle-aged Caucasian women, manifested by sloughing mucosa, thick exudate, and proximal strictures. Most case reports and small series highlight using steroids and other immunosuppressants. To our knowledge, oral tablet tacrolimus has not been studied. We aimed to assess the change in ELP after oral tacrolimus treatment.

Methods: The primary outcome was the efficacy of tacrolimus objectively through our scoring system, ELPSS. All consecutive adults with ELP who underwent more than one EGD by two esophagologists and being treated with tacrolimus or other treatment were eligible for inclusion in this retrospective cohort study. Inflammation and fibrostenotic disease were graded using the novel ELP Severity Score (ELPSS).

Results: Twenty two patients met the inclusion criteria. Half (11) received tacrolimus (dose 1-2 mg BID) and half (11) received other therapy (i.e. cyclosporine, topical steroids, or none). Mean ELPSS on first EGD, extraesophageal manifestations of disease, presenting symptoms, and baseline characteristics were similar between groups. Among patients on Tac vs No-Tac, there was a statistically significant improvement in ELPSS (mean difference 1.8 pts; 95% CI 0.25-3.38; P=0.02). Response rate was 89% with Tac vs 30% with No-Tac (P=0.025). All 22 patients underwent bougie dilation safely with a mean diameter of 16 mm achieved. Patients on Tac also required less frequent dilation.

Conclusion: Oral tablet tacrolimus reduced the inflammatory and fibrostenotic components of ELP. Thus, low-dose oral tacrolimus is safe and should be considered in patients with more severe disease.