Therapeutic Advances in Gastroenterology最新文献

Stimulant laxatives are well established as first- or second-line treatments for constipation and although they have a reliable therapeutic effect, alleged safety concerns still exist, particularly with long-term use. The potential harmful effects on the gastrointestinal system (including carcinogenicity) of the long-term use of diphenylmethane [bisacodyl, sodium picosulfate (SPS)] and senna stimulant laxatives were assessed in a comprehensive review of the publications identified in literature searches performed in PubMed and Embase up to and including June 2023. We identified and reviewed 43 publications of interest. While stimulant laxatives at supratherapeutic doses have been shown to cause structural alterations to surface absorptive cells in animals and humans, these effects are reversible and not considered clinically relevant. No formal long-term studies have demonstrated morphological changes in enteric neural elements or intestinal smooth muscle with bisacodyl or SPS in humans. Furthermore, there is no convincing evidence that stimulant laxatives are associated with the development of colon cancer, and in fact, chronic constipation itself has been reported to potentially increase the risk of colon cancer, therefore, the use of stimulant laxatives might reduce this risk. Many studies suggesting a possible harmful effect from laxatives were limited by their failure to consider confounding factors such as concomitant neurological disease, metabolic disorders, and age. These findings highlight the lack of evidence for the harmful effects of laxatives on the colon, and thus, the benefits of treatment with stimulant laxatives, even in the long-term, should be reconsidered for the management of patients with constipation.

Background: Acute pancreatitis (AP) has a high incidence, and patients can develop recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) after AP.

Objectives: We aimed to estimate the pooled incidence rates (IRs), cumulative incidences, and proportions of RAP and CP after AP.

Design: A systematic review and meta-analysis of studies reporting the proportion of RAP and CP after AP.

Data sources and methods: The systematic search was conducted in three (PubMed, EMBASE, and CENTRAL) databases on 19 December 2023. Articles reporting the proportion of RAP or CP in patients after the first and multiple episodes of AP were eligible. The random effects model was used to calculate the pooled IR with 95% confidence intervals (CIs). The I ² value assessed heterogeneity. The risk of bias assessment was conducted with the Joanna Briggs Institute Critical Appraisal Tool.

Results: We included 119 articles in the quantitative synthesis and 29 in the IRs calculations. Our results showed that the IR of RAP in adult patients after AP was 5.26 per 100 person-years (CI: 3.99-6.94; I ² = 93%), while in children, it was 4.64 per 100 person-years (CI: 2.73-7.87; I ² = 88%). We also found that the IR of CP after AP was 1.4 per 100 person-years (CI: 0.9-2; I ² = 75%), while after RAP, it increased to 4.3 per 100 person-years (CI: 3.1-6.0; I ² = 76%). The risk of bias was moderate in the majority of the included studies.

Conclusion: Our results showed that RAP affects many patients with AP. Compared to patients with the first AP episode, RAP leads to a threefold higher IR for developing CP.

Trial registration: Our protocol was registered on PROSPERO (CRD42021283252).

Background: Colon capsule endoscopy (CCE) has gained momentum as an alternative modality for the investigation of the lower gastrointestinal tract. Of the few challenges that remain, the comparison and - eventually - matching of polyps at different timestamps leads to the potential for double reporting and can contribute to false-positive findings and inaccuracies. With the impending artificial intelligence integration, the risk of double reporting the same polyp due to the lack of information on spatial orientation underscores the necessity for establishing criteria for polyp matching.

Objectives: This RAND/University of California, Los Angeles (modified Delphi) process aims to identify the key factors or components used to match polyps within a CCE video. This involves exploring the attributes of each factor to create comprehensive polyp-matching criteria based on international expert consensus.

Design: A systematic qualitative study using surveys.

Methods: A panel of 11 international CCE experts convened to assess a survey comprised of 60 statements. Participants anonymously rated statement appropriateness on a 1-9 scale (1-3: inappropriate, 4-6: uncertain and 7-9: appropriate). Following a virtual group discussion of the Round 1 results, a Round 2 survey was developed and completed before the final analysis.

Results: The factors that were agreed to be essential for polyp matching include (1) timestamp, (2) polyp localization, (3) polyp vascular pattern, (4) polyp size, (5) time interval of the polyp appearance between the green and yellow camera, (6) surrounding tissue, (7) polyp morphology and (8) polyp surface and contour. When five or more factors are satisfied, it was agreed that the comparing polyps are likely the same polyp.

Conclusion: This study has established the first complete criteria for polyp matching in CCE. While it might not provide a definitive solution for matching difficult, small and common polyps, these criteria serve as a framework to guide and facilitate the process of polyp-matching.

Background: The existing body of scientific literature offers inconclusive findings on the safety and therapeutic effectiveness of etrolizumab (ETR) for the treatment of ulcerative colitis (UC).

Objectives: The goal of this meta-analysis is to furnish a comprehensive synthesis of evidence that evaluates the safety and therapeutic effects of ETR in the management of UC.

Design: Meta-analysis.

Data sources and methods: PubMed, Embase, and Web of science were searched to collect relevant English studies, and the reference lists of eligible studies were manually searched to avoid missing any eligible studies. Outcome measures encompassed clinical response, incidence of adverse events, histological remission, endoscopic remission, endoscopic improvement, and antidrug antibodies. Relevant data were extracted by two independent investigators.

Results: The meta-analysis incorporated five eligible studies, involving a total of 1528 patients, with 1015 treated with ETR and 513 with placebo. The pooled analysis indicates that ETR is both effective and safe. The adverse event rates, endoscopic and histological response, as well as overall remission were comparable between the two groups. The monoclonal antibody group had a lower incidence rate of adverse reactions than the placebo group [odds ratio (OR): 0.81; 95% confidence interval (CI): 0.63-1.03; p = 0.09)]. Clinical response was higher in the ETR group than in the placebo group (OR: 1.56; 95% CI: 1.20-2.02; p = 0.0009), and endoscopic improvement was more favorable in the ETR group (OR: 1.88; 95% CI: 1.45-2,45; p < 0.00001). A higher rate of endoscopic remission was found in the ETR group than in the placebo group (OR: 2.48; 95% CI: 1.75-3.50; p < 0.00001); histological remission was significantly higher in the ETR group than in the placebo group (OR: 2.11; 95% CI: 1.55-2.86; p < 0.00001). The placebo group had a lower rate of positive antidrug antibodies (OR: 1.31; 95% CI: 0.79-2.17; p < 0.29), and the incidence of complications was significantly higher in the ETR group compared with the placebo group (OR: 2.05; 95% CI: 1.48-2.83; p < 0.0001).

Conclusion: Given the heterogeneity and potential biases in the included studies, gastroenterologists should cautiously tailor drug delivery strategies based on their clinical experience and the unique needs of individual patients.

Prospero registration: CRD42023396100.

Background: The symptoms of gastric outlet obstruction have traditionally been managed surgically or endoscopically. Enteral stenting (ES) is a less invasive endoscopic treatment strategy for this condition. Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) has recently become a potential alternative technique.

Objectives: We conducted a systematic review and meta-analysis of the effectiveness and safety profile of EUS-GE compared with ES.

Design: Meta-analysis and systematic review.

Data sources and methods: We searched multiple databases from inception to August 2023 to identify studies that reported the effectiveness and safety of EUS-GE compared with ES. The outcomes of technical success, clinical success, and adverse events (AEs) were evaluated. Pooled proportions were calculated using both fixed and random effects models.

Results: We included 13 studies with 1762 patients in our final analysis. The pooled rates of technical success for EUS-GE were 95.59% [95% confidence interval (CI), 94.01-97.44, I ² = 32] and 97.96% (95% CI, 96.06-99.25, I ² = 63) for ES. The pooled rate of clinical success for EUS-GE was 93.62% (95% CI, 90.76-95.98, I ² = 54) while for ES it was lower at 85.57% (95% CI, 79.63-90.63, I ² = 81). The pooled odds ratio (OR) of clinical success was higher for EUS-GE compared to ES at 2.71 (95% CI, 1.87-3.93). The pooled OR of clinical success for EUS-GE was higher compared to ES at 2.72 (95% CI, 1.86-3.97, I ² = 0). The pooled rates of re-intervention for EUS-GE were lower at 3.77% (95% CI, 1.77-6.46, I ² = 44) compared with ES, which was 25.13% (95% CI, 18.96-31.85, I ² = 69). The pooled OR of the rate of re-intervention in the ES group was higher at 7.96 (95% CI, 4.41-14.38, I ² = 13). Overall, the pooled rate for AEs for EUS-GE was 8.97% (95% CI, 6.88-11.30, I ² = 15), whereas that for ES was 19.63% (95% CI, 11.75-28.94, I ² = 89).

Conclusion: EUS-GE and ES are comparable in terms of their technical effectiveness. However, EUS-GE has demonstrated improved clinical effectiveness, a lower need for re-intervention, and a better safety profile compared to ES for palliation of gastric outlet obstruction.

Background: Esophageal gastrointestinal stromal tumors (E-GISTs) are highly uncommon and have not been thoroughly examined.

Objectives: The objective of this multi-center study was to assess the viability of endoscopic resection (ER) in the treatment of E-GISTs and to explore its clinical implications.

Design: This was a multi-center retrospective study. Consecutive patients referred to the four participating centers.

Methods: E-GISTs among the consecutive subepithelial tumors (SETs) treated by ER methods were enrolled from April 2019 to August 2022. Clinicopathological, endoscopic, and follow-up data were collected and analyzed.

Results: A total of 23 patients with E-GISTs were included for analysis, accounting for 1.9% of all the esophageal SETs (1243 patients). The average size of the tumor lesions was 2.3 cm (range 1.0-4.0 cm). We observed that tumors larger than 2.0 cm were more likely to grow deeper, with a statistically significant difference (p < 0.001). End bloc resection was achieved in all 23 patients. The mean operation time was 53.6 min (range 25-111 min). One patient experienced significant intraoperative bleeding, which was promptly managed endoscopically without necessitating surgery. The average hospital stay was 4.5 days (range 3-8 days). The overall median follow-up period was 31 months (range 13-47 months). No tumor recurrence, residual tumor, distal metastasis, or death was observed during the follow-up period.

Conclusion: Based on our limited data, our study indicates that ER may be a feasible and effective option for treating esophageal GISTs measuring 4 cm or less. We suggest submucosal tunnel endoscopic resection as the preferred approach, as all E-GISTs in our study were situated in the muscularis propria layer. Additionally, tumors larger than 2 cm were more prone to deeper growth or extraluminal extension.

Background: Given the growing problem of antibiotic resistance, it is crucial to improve Helicobacter pylori (H. pylori) treatment interventions or provide adjunctive therapy. The objective of this meta-analysis was to evaluate whether Lactobacillus reuteri (L. reuteri) could improve H. pylori eradication rate, reduce the incidence of adverse events (AEs), and alleviate gastrointestinal symptoms.

Design: A meta-analysis of randomized controlled trials (RCTs) comparing L. reuteri supplementation therapy with placebo was conducted.

Sources and methods: We retrieved relevant studies from PubMed, Embase, and the Cochrane Library. The primary outcome was H. pylori eradication rate, and the scores on the Gastrointestinal Symptom Rating Scale and AEs were secondary outcomes.

Results: Eight RCTs including 1087 patients were included in this analysis. The L. reuteri supplementation group showed significantly higher H. pylori eradication rates in both intention-to-treat (ITT) and per-protocol (PP) analysis [ITT: 80.0% versus 72.6%; p = 0.005, relative risk (RR): 1.10; 95% confidence interval (CI): 1.03-1.17; number needed to treat (NNT) = 14; PP: 81.8% versus 75.0%; p = 0.006, RR: 1.09; 95% CI: 1.03-1.16; NNT = 15]. Patients treated with L. reuteri showed greater improvements in gastrointestinal symptoms (pooled mean difference: -2.43, 95% CI: -4.56 to -0.29, p = 0.03). The incidence of AEs was significantly reduced in the L. reuteri supplementation group based on ITT and PP analysis (ITT: p < 0.00001, RR: 0.72, 95% CI: 0.67-0.78; PP: p < 0.00001, RR: 0.70, 95% CI: 0.65-0.77).

Conclusion: The present meta-analysis demonstrated that supplementation with L. reuteri was beneficial for improving the eradication rate of H. pylori, reducing the overall incidence of side effects, and relieving gastrointestinal symptoms in patients during treatment. The findings provide new insights into clinical decision-making.

Trial registration prospero: CRD42023424052.

Background: The transition from pediatric to adult healthcare in individuals with inflammatory bowel disease (IBD) poses significant challenges mainly due to the high burden of IBD during adolescence, a critical period of psychosocial development. So far, there are few longitudinal data linking transition readiness to long-term disease outcomes.

Objective: We aimed to assess patients' readiness to transition and its impact on clinical outcomes, quality of life, and adherence to therapy.

Design: An observational, prospective study was conducted in a tertiary adult and pediatric center, including adolescents aged ⩾17 years with a diagnosis of IBD, who underwent a 'structured transition' program including two joint adult-pediatric visits.

Methods: Transition readiness skills were assessed with the Transition Readiness Assessment Questionnaire (TRAQ). All patients completed the TRAQ at the time of recruitment, which occurred during the initial joint adult-pediatric visit, to determine those deemed ready for transition versus those not ready. The Morisky Medication Adherence Scale and the 36-Item Short Form Health Survey Questionnaire (SF-36) were also completed at baseline and after 12 months. Clinical outcomes were collected at the 12-month follow-up.

Results: In all, 80 patients were enrolled who had transitioned through a structured transition clinic and completed 12 months of follow-up. In total, 54 patients were ready for the transition, with a mean TRAQ = 3.2 ± 0.5. The number of clinical relapses and hospitalizations at 12 months was lower in ready compared to not-ready patients (p = 0.004 and p = 0.04, respectively). SF-36 did not differ between ready and not-ready patients and pre- and post-transition clinics (p > 0.05). Based on the receiver operating characteristic curve, a TRAQ cutoff ⩾3.16 could predict medication adherence with a sensibility of 77%, a specificity of 82%, and an AUC of 0.81 (0.71-0.91; p < 0.001).

Conclusion: Patients ready for transition had better outcomes at 12 months compared to those who were not ready. Therefore, readiness assessment tools should be integrated into transition management to ensure that interventions are targeted, patient-centered, and responsive to individuals' changing needs.

Background: Despite the continuously rising rate of pediatric-onset inflammatory bowel diseases (PIBD), there are no consensus transitional guidelines or standardized practices.

Objectives: We aimed to examine: (1) the determinants of a successful transfer, (2) the effects of the transfer versus transition on the disease course and patient compliance, (3) the unique characteristics of PIBD patients, that need special attention in adult care.

Design: Longitudinal, follow-up, controlled study conducted between 2001 and 2022, with retrospective data collection until 2018, thence prospective.

Methods: Three hundred fifty-one PIBD patients enrolled in the study, of whom 152 were moved to adult care, with a mean post-transfer follow-up time of 3 years. Seventy-three patients took part in structured transition, whereas 79 self-transferred to adult care. The main outcome measures were disease activity (defined by PCDAI, PUCAI, CDAI, and Mayo-scores) and course, hospitalizations, surgeries, IBD-related complications, including anthropometry and bone density, patient compliance, medication adherence, and continuation of medical care.

Results: Patients who underwent structured transition spent significantly more time in remission (83.6% ± 28.5% versus 77.5% ± 29.7%, p = 0.0339) and had better adherence to their medications (31.9% versus 16.4% non-adherence rate, p = 0.0455) in adult care, with self-transferred patients having a 1.59-fold increased risk of discontinuing their medical care and a 1.88-fold increased risk of experiencing a relapse. Post-transfer the compliance of patients deteriorated (38.5% versus 29%, p = 0.0002), with the highest lost-to-follow-up rate during the changing period between the healthcare systems (12.7%), in which female gender was a risk factor (p = 0.010). PIBD patients had experienced IBD-related complications (23.4%) and former surgeries (15%) upon arriving at adult care, with high rates of malnutrition, growth impairment, and poor bone health.

Conclusion: Structured transition plays a key role in ensuring the best disease course and lowering the lost-to-follow-up rate among PIBD patients.

Brief summary: Structured transition plays a key role in ensuring the best disease outcome among PIBD patients, as in our study it was associated with lower disease activity, fewer relapses, better medication adherence, and lower lost-to-follow-up rate as opposed to self-transfer.

Background: Anti-tumor necrosis factor (TNF) monoclonal antibodies, especially infliximab (IFX) and adalimumab (ADA), are considered the first-line treatment for active Crohn's disease (CD). However, the predictive role of therapeutic drug monitoring (TDM) of serum anti-TNF in monitoring the treatment of inflammatory bowel disease (IBD) remains controversial.

Objectives: To explore the correlation between serum anti-TNF levels and early endoscopic response in active CD using a TDM-based nomogram.

Design: Cross-sectional study.

Methods: The simplified endoscopic activity score for CD (SES-CD), Crohn's disease activity index (CDAI), laboratory parameters, and the serum trough levels of IFX and ADA were assessed.

Results: The trough levels of IFX or ADA were significantly higher in patients with endoscopic response compared to non-responders in the development cohort (p < 0.001). The IFX and ADA levels showed a weak but significantly negative correlation with SES-CD (p < 0.001), CDAI (p < 0.001), and C-reactive protein (CRP) (p < 0.001) at week 14 post-IFX therapy in the development cohort. Furthermore, the receiver operating characteristic curve revealed that an optimal level of IFX (4.80 μg/mL) and ADA (8.80 μg/mL) exhibited the best performance in predicting endoscopic response. Concomitantly, we developed a novel nomogram prediction model based on the results of multivariate logistic regression analysis, which consisted of CRP, albumin (Alb), and anti-TNF trough levels at week 14. The nomogram showed significant discrimination and calibration for both IFX and ADA in the development cohort and performed well in the external validation cohort.

Conclusion: This study demonstrates a robust association between serum concentrations of IFX, ADA, Alb, and CRP and primary endoscopic response in active CD patients. Importantly, the TDM- and laboratory marker-based nomogram may be used to evaluate the primary endoscopic response to anti-TNF therapy, especially for optimizing treatment strategies and switching therapy in CD patients.