Therapeutic Advances in Gastroenterology最新文献

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.

Background: Diverticular disease (DD) represents a common gastrointestinal condition that poses a heavy burden on healthcare systems worldwide. A high degree of uncertainty surrounds the therapeutic approaches for the control of symptoms in patients with symptomatic uncomplicated diverticular disease (SUDD) and primary and secondary prevention of diverticulitis and its consequences.

Objectives: To review the current knowledge and discuss the unmet needs regarding the management of SUDD and the prevention of acute diverticulitis.

Eligibility criteria: Randomized trials, observational studies, and systematic reviews on lifestyle/dietary interventions and medical treatment (rifaximin, mesalazine, and probiotics) of SUDD or prevention of acute diverticulitis.

Sources of evidence: The literature search was performed from inception to April 2023, without language restriction, following the modified Preferred Reporting Items for Systematic review and Meta-Analyses (PRISMA) reporting guidelines. References of the papers selected were checked to identify additional papers of potential interest. The final list of references was evaluated by a panel of experts, who were asked to check for any lack of relevant studies.

Charting methods: Information on patient population, study design, intervention, control group, duration of the observation, and outcomes assessed was collected by two authors independently.

Results: The review shows a high degree of uncertainty about therapeutic interventions, both dietary/lifestyle and pharmacological, in patients with SUDD, because of the scarcity and weakness of existing evidence. Available studies are generally of low quality, heterogeneous, and outdated, precluding the possibility to draw robust conclusions. Similarly, acute diverticulitis prevention has been seldom investigated, and there is a substantial lack of evidence supporting the role of dietary/lifestyle or pharmacological approaches to reduce the risk of diverticulitis.

Conclusion: The lack of robust evidence regarding therapeutic options for gastrointestinal symptoms in SUDD patients and for primary and secondary prevention of acute diverticulitis remains an important unmet need in the management of DD.

Restorative proctocolectomy with ileal pouch-anal anastomosis is a treatment option for patients with refractory ulcerative colitis. Pouchitis is the most common complication, representing a spectrum of diseases ranging from acute antibiotic-responsive type to chronic antibiotic-refractory. Early accurate diagnosis using a combined assessment of symptoms, endoscopy and histology is important for both treatment and prognostication. Most patients respond well to antibiotic therapy; however, management of chronic antibiotic-refractory pouchitis remains a challenge, and treatment options are based on small studies. Pouchitis is thought to be driven by the interaction between genetics, the immune system and the environment but as yet a causal relationship has yet to be identified. Further longitudinal assessment of the pouch integrating new technologies may help us understand the factors driving pouchitis. This review outlines the currently understood risk factors and aetiology of pouchitis.

Background: Gastrointestinal (GI) angiodysplasias is a potential cause of life-threatening bleeding. Thalidomide may have a certain effect on the treatment.

Objectives: We aim to evaluate the efficacy and safety of thalidomide and used trial sequential analysis (TSA) to assess the need for further randomized controlled trials (RCTs).

Design: Meta-analysis of RCTs.

Data sources and methods: We systematically searched Cochrane Central Register of Controlled Trials (CENTRAL), Medical Literature Analysis and Retrieval System Online (MEDLINE), Embase, WanFang, and China National Knowledge Infrastructure databases for RCTs evaluating thalidomide in GI angiodysplasias without language restrictions. We used a random-effects model to obtain pool data and followed Grading of Recommendations Assessment, Development and Evaluation framework. TSA was employed to control the risk of random errors and to evaluate the validity of our conclusions.

Results: Three RCTs were included involving 279 patients with the proportion of small intestinal angiodysplasias of 87.1%. Thalidomide led to improved mean change of hemoglobin level [mean difference (MD): 3.06, 95% confidence interval: 2.66-3.46] without severe adverse effects occurring. Other secondary endpoints, including effective response rate, cessation of bleeding after treatment, hospitalization rate because of bleeding, change in duration of hospital stays for bleeding, transfused red cell requirements, and overall adverse effects, also showed significantly better outcomes in the thalidomide group compared to the control group. TSA for all outcomes exceeded required information sizes, and cumulative Z curve all traverse trial sequential monitoring boundary.

Conclusion: Almost all of the evidence was of moderate quality, suggesting that thalidomide holds promise for treating GI angiodysplasias, with favorable safety profiles. TSA suggests that conducting large-scale real-world research is recommended over relying solely on RCTs conducted within the same population and trial design.

Trial registration: This meta-analysis protocol was registered on PROSPERO (CRD42023480621).