Therapeutic Advances in Gastroenterology最新文献

Background: Refractory esophageal stricture is the common complication of extensive endoscopic submucosal dissection (ESD), without satisfactory endoscopic treatment strategies. We evaluated the efficacy, safety, and long-term patency of the modified endoscopic radial incision and selective cutting combined with short-term stenting (RISC-STS) for the treatment of refractory esophageal stenosis.

Methods: This was a retrospective study. Patients diagnosed with refractory esophageal stricture from June 2016 to June 2023 were enrolled. Efficacy, safety, and risk factors for dysphagia after RISC-STS operation were assessed.

Results: Compared with clinical symptoms before RISC-STS, there was no significant improvement in the times of stricture recurred (p = 0.75). However, the narrowest diameter of esophageal stenosis was significantly larger after RISC-STS treatment (p = 0.04). Corresponding dysphagia scores after RISC-STS were obviously lowered according to the Mellow-Pinkas grading scale (p = 0.002). More cases ((14 (60.87%) vs 5 (21.74%)) received valid symptom-relief periods after RISC-STS (p = 0.0004). The complications of RISC-STS include perforation (4.35%), fever (4.35%), and pain (30.43%). Univariate Cox analysis suggested that resection length >7 cm of scar tissue was a risk factor for refractory dysphagia after RISC-STS.

Conclusion: The present study revealed that RISC-STS is an effective and safe technique for refractory esophageal stricture with lower restenosis, higher valid symptom-relief rate, and fewer complications.

Colorectal cancer (CRC) is the third most prevalent cancer globally and poses a significant health threat, making early detection crucial. This review paper explored emerging detection methods for early screening of CRC, including gut microbiota, metabolites, genetic markers, and artificial intelligence (AI)-based technologies. Current screening methods have their respective advantages and limitations, particularly in detecting precursors. First, the importance of the gut microbiome in CRC progression is discussed, highlighting how specific microbial alterations can serve as biomarkers for early detection, potentially enhancing diagnostic accuracy when combined with traditional screening methods. Next, research on metabolic reprogramming illustrates the relationship between metabolic changes and CRC, with studies developing metabolite-based detection models that show good sensitivity for early diagnosis. In terms of genetic markers, methylated DNA markers like SEPTIN9 have demonstrated high sensitivity, although further validation across diverse populations is necessary. Lastly, AI technology has shown immense potential in improving adenoma detection rates, significantly enhancing the quality of colonoscopic examinations through image recognition techniques. This review aims to provide a comprehensive perspective on new strategies for CRC screening, emphasizing the potential of noninvasive detection technologies and the prospects of AI and genomics in clinical applications. Despite several challenges, this review advocates for future large-scale prospective studies to validate the effectiveness and cost-effectiveness of these new screening methods while promoting the implementation of screening protocols tailored to individual characteristics.

Background: Potassium-competitive acid blocker (P-CAB)-based therapies are emerging as promising alternatives for eradicating Helicobacter pylori infection. However, the comparative efficacy of P-CAB-based therapy versus proton-pump inhibitor (PPI)-based therapy in treating H. pylori infection remains uncertain.

Objectives: This meta-analysis evaluated the efficacy and safety of P-CAB-based therapies, including Vonoprazan (VPZ) and Tegoprazan (TPZ), compared to PPI-based therapies for H. pylori infection. Subgroup analysis assessed the influence of drug history, experimental drug, treatment duration, combination therapies, and geographic regions on treatment outcomes.

Design: Meta-analysis.

Data sources and methods: Comprehensive searches were conducted in major databases, including PubMed, Embase, the Cochrane Library, and Web of Science, up to January 1, 2024. The primary outcome was the eradication rate, analyzed by intention-to-treat (ITT). Secondary outcomes included adverse events. Heterogeneity among studies was assessed using the χ² test and the I ² test. I ² > 50% or p < 0.05 indicated significant heterogeneity.

Results: The analysis totally included 28 randomized controlled trials (RCTs) comprising 37 studies and 8818 patients diagnosed with H. pylori infection. Of these, 14 RCTs, including 20 studies and 4286 patients, compared P-CAB-based therapy with 14-day bismuth-based quadruple therapy (BQT). P-CAB-based therapy exhibited superior eradication rates compared to both 14-day BQT and PPI-based therapy (ITT analysis: 87.0% vs 79.8%, risk ratio (RR) = 1.08, 95% CI: 1.04-1.12, p < 0.0001; and 85.6% vs 77.8%, RR = 1.09, 95% CI: 1.05-1.12, p < 0.00001, respectively). This enhanced efficacy was particularly pronounced in patients with clarithromycin-resistant infections (73.7% vs 41.5%, RR = 1.53, 95% CI: 1.07-2.20, p = 0.02). Subgroup analysis demonstrated higher eradication rates with P-CAB-based therapy in treatment-naïve participants, VPZ recipients, and those receiving 7- or 14-day regimens (dual, triple, or quadruple therapy). However, no significant differences were observed in treatment-experienced subgroups, TPZ recipients, or those on 10-day regimens. In addition, P-CAB-based therapy showed a lower incidence of adverse events than PPI-based treatments (RR = 0.73, 95% CI: 0.63-0.86, p < 0.0001).

Conclusion: P-CAB-based therapies are more effective than traditional PPI-based treatments for eradicating H. pylori infection, with a reduced incidence of adverse events.

Prospero registration: CRD42024503665.

Last decades led to a revolution in the management of ulcerative colitis (UC), due to the development of novel advanced therapies and the identification of increasingly ambitious therapeutic goals. Nevertheless, a subset of patients, refractory to available therapies, still requires proctocolectomy with ileal pouch-anal anastomosis (IPAA). Pouchitis, an inflammatory condition of the ileal pouch, is the most common long-term complication of IPAA, affecting almost one-half of patients in the first 10 years after surgery. Symptoms of pouchitis include increased stool frequency, urgency, and abdominal discomfort, significantly affecting patients' quality of life. Traditionally the mainstay treatment of acute pouchitis involves the use of antibiotics, but one-fifth of patients develop chronic pouchitis (CP), which may be dependent or resistant to antibiotics, posing significant challenges in the management of this condition. Currently, there is still no consensus on the optimal management for CP, though recent progress in understanding the pathophysiology of pouchitis has paved the way for innovative therapeutic approaches, based on biological therapies and small molecules. This review aims to discuss the recent advanced therapies available for pouchitis and provide a comprehensive review on the topic to guide physicians in their clinical practice.

Background: Alkaline phosphatase (ALP) is a potential cancer biomarker. However, its prognostic value in patients with colorectal liver metastasis remains unclear.

Objectives: This study aimed to investigate the association between ALP levels and mortality risk in patients with colorectal liver metastases (CRLM), providing insights for enhancing prognostic assessments.

Design: Retrospective cohort study.

Methods: This study included 195 patients with CRLM from a single centre in China. ALP level was the primary exposure variable, with demographic, clinical and pathological factors serving as covariates. Multivariate Cox regression analyses were used to evaluate the impact of ALP on mortality over a 4-year follow-up period. Covariates included the number of liver metastases, T stage, N stage, chemotherapy, tumour location, primary surgery, topical treatment, apolipoprotein A1, targeted therapy, tumour type, CA-199 levels, metastatic surgery, sex, Karnofsky Performance Status and age.

Results: Of 195 enrolled patients, 134 (68.72%) were male, and 61 (31.28%) were female, with ages ranging from January 2008 to December 2019. A total of 147 patients (76.96%) were diagnosed with left hemicolon cancer and 44 (23.04%) with right hemicolon cancer. After adjusting for the covariates, elevated ALP levels were significantly associated with an increased risk of mortality (hazard ratio = 1.24, 95% confidence interval: 1.08-1.43, p = 0.0029). Sensitivity analyses confirmed the robustness of these findings, reinforcing the association across different analytical approaches.

Conclusion: ALP level is a valuable prognostic indicator in patients with CRLM. Integrating ALP measurement into clinical practice may enhance risk stratification and patient management. Future research should explore the role of ALP in broader populations and explore its implications for treatment strategies.

Background: Efficacy of eradication regimens in Helicobacter pylori (Hp) infection is commonly reported with proton pump inhibitors (PPIs). In patients with corpus atrophic gastritis, characterized by impaired acid secretion, PPI treatment is questionable.

Objectives: The current study aimed to assess in clinical practice the tolerability and eradication rate of modified eradication regimens without PPI as first-line treatment in patients with histologically Hp-positive corpus atrophic gastritis.

Design: Real-life longitudinal observational study.

Methods: Overall, 76 patients (77.6% females, age 58.5 (26-88) years) with histologically Hp-positive corpus atrophic gastritis were consecutively diagnosed (2001-2022). First-line eradication treatment was prescribed without PPIs: concomitant or sequential amoxicillin-based therapy (ABT) until 2016 (n = 30), then single-pill bismuth treatment (SPBT; n = 46). Treatment adherence and adverse events were clinically evaluated and treatment efficacy was assessed by histopathology (updated Sydney system) at 6 ± 3 months after treatment.

Results: Only mild adverse events not requiring medical treatment were observed in four patients treated with SPBT without PPIs (vomiting, self-limiting diarrhoea, nausea, abdominal discomfort) and in two treated with ABT without PPIs (vomiting and abdominal discomfort). Overall, 71/76 (93.4%) corpus atrophic gastritis patients completed the treatment: 43/46 (93.5%) SPBT without PPIs and 28/30 (93.3%) ABT without PPIs. Successful cure of Hp was observed in 64/71 patients: overall eradication rate 90.1%, 95%CI 69.4%-115.1%. 42/43 corpus atrophic gastritis patients treated with SPBT without PPIs were successfully cured against 22/28 of those treated with ABT without PPIs. The eradication rate was higher for SPBT than ABT: 97.7%, 95%CI 70.4%-132.0% vs 78.6%, 95%CI 49.2%-118.9%, p = 0.013.

Conclusion: In clinical practice, Hp cure can be achieved without PPIs as first-line treatment in about 90% of patients with corpus atrophic gastritis.

Background: Medically intractable ascites causes substantial distress in patients with palliative disease. Tunneled peritoneal catheters have been established as a feasible treatment option allowing patient-controlled paracentesis in a homecare setting. However, while a range of complications is associated with these drainages, risk factors for complications have not been identified so far.

Objectives: To explore potential risk factors associated with complications of tunneled peritoneal catheters.

Design: Retrospective observational cohort study.

Methods: Single-center cohort comprising 49 patients with palliative disease receiving 57 tunneled peritoneal catheters at a tertiary care hospital.

Results: Catheter placement was successful in all patients and associated with low numbers of severe complications. Our data suggest a higher risk for severe late complications in patients with benign disease, with drainage replacement, and when performed by less experienced physicians.

Conclusion: Tunneled peritoneal catheters are an effective and safe option to treat symptomatic ascites in patients with end-stage palliative disease. The indication should be carefully considered in patients with benign disease and after removal or dislocation of a previous catheter.

Background: Inflammatory bowel disease (IBD) occurs in up to 70%-80% of patients with primary sclerosing cholangitis (PSC). Oral vancomycin therapy (OVT) has been reported to be effective in the treatment of IBD associated with PSC (IBD-PSC).

Objectives: To examine the effectiveness and safety of OVT in the treatment of IBD-PSC by performing a systematic review and pooled analysis of the literature.

Design: We performed a systematic review and pooled analysis of studies reporting IBD clinical response to OVT in IBD-PSC.

Data sources and methods: A systematic search was conducted in Cochrane Library, Embase, Google Scholar, Medline, PubMed, Scopus, and Web of Science from database inception to June 3, 2024. We included adult and pediatric studies that reported on clinical response (defined as any improvement in IBD-related clinical symptoms) of IBD-PSC patients treated with OVT (including pre- and post-liver transplantation cohorts). Pooled analyses of OVT response and safety were performed.

Results: A total of 21 (open-label, non-controlled) studies including 290 patients with IBD-PSC treated with OVT were included. The median duration of OVT to treat IBD-PSC was 32.5 weeks (interquartile range (IQR): 19-83 weeks). The total daily dose of OVT ranged from 250 to 1500 mg. Concomitant treatment included the following: mesalamine in 14.5% (n = 42), advanced therapies in 10.7% (n = 31), and immunosuppressive agents in 14.1% (n = 41). Clinical response was noted in 47.6% (138/290) and clinical remission in 43.5% (100/230). The biochemical remission rate post-OVT was 68.8% (55/80) and endoscopic remission was 39.4% (80/203). Three studies (n = 11) reported no episodes of acute cholangitis while on OVT. Five studies (n = 69) reported an incidence rate of 8.7% of vancomycin-resistant enterococci post-OVT to treat IBD-PSC.

Conclusion: OVT was associated with clinical response/remission in almost half of patients with IBD-PSC with a favorable side effect profile. Further prospective randomized trials are needed to confirm the dosing, efficacy, treatment duration, and long-term safety of OVT for the treatment of IBD-PSC.

Trial registration: The study protocol was registered with PROSPERO a priori (no. CRD42023438341).

Acute infectious diarrhea (AID) represents an important clinical entity both regarding morbidity and mortality rates, even in industrialized countries, and it leads to one of the major public health burdens, among gastroenterological diseases, with significant healthcare costs. Oral rehydration solution is the cornerstone of the therapy, but despite its proven efficacy in avoiding dehydration, it is still underused as it does not reduce the duration of diarrhea; hence, it is perceived as ineffective by caregivers. In this narrative review, we collected literature regarding the use of racecadotril, deeply discussing its role in the treatment of AID in both adults and children. Racecadotril has been studied in wide populations of patients, in many countries, and in different clinical settings. Its effectiveness in reducing the stool output and the duration of diarrhea has been proven, not only in the early phase of the disease. Racecadotril has been shown to increase the likelihood of home management of AID, to reduce hospitalizations and parenteral rehydration needs resulting in healthcare costs reduction. The current new formulations require only two-daily doses for adults and the pediatric syrup should simplify its use.

Background: Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), can affect the hepatobiliary system and pancreas, substantially impacting the life quality of patients.

Objectives: To evaluate the quality of evidence and comprehensively assess the validity of associations of IBD with hepatobiliary and pancreatic diseases.

Design: We performed an umbrella review of existing meta-analyses in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) recommendations.

Data sources and methods: We systematically searched PubMed, Embase, and Web of Science from inception to April 2024, to identify and appraise meta-analyses examining IBD and risk of hepatobiliary and pancreatic manifestations. Methodologic quality was assessed with A Measurement Tool to Assess Systematic Reviews (AMSTAR 2) and the strength of evidence was graded according to prespecified criteria.

Results: A total of 14 meta-analyses of observational studies were included. The strongest-validity evidence suggested the significant associations between IBD and risk of gallstones (odds ratio (OR) = 1.72; 95% confidence interval (CI) = 1.40-2.12) and acute pancreatitis (OR = 3.11; 95% CI = 2.93-3.30). Highly suggestive evidence indicated a significantly increased risk of hepatobiliary cancer in UC (incidence rate ratio (IRR) = 2.05; 95% CI = 1.52-2.76) and CD (IRR = 2.31; 95% CI = 1.25-4.28). In addition, highly suggestive evidence indicated that IBD was associated with portal venous system thrombosis. Suggestive evidence showed a significantly higher prevalence of primary sclerosing cholangitis, non-alcoholic fatty liver disease, autoimmune hepatitis, and autoimmune pancreatitis in IBD patients than in the general population.

Conclusion: The associations between IBD and multiple hepatobiliary and pancreatic disorders showed varying levels of evidence and magnitude of risk. Further high-quality primary studies are needed to identify IBD patients who are more at risk and would benefit the most from screening and prevention programs.

Trial registration prospero: CRD42023451461.