Therapeutic Advances in Gastroenterology最新文献

Background: Safety and usefulness of double-balloon enteroscopy (DBE) in patients with short bowel syndrome (SBS) are unknown. DBE could be effective in exploring the residual small bowel (SB) entirely, in monitoring patients receiving teduglutide (TED) treatment and, if necessary, could be operative.

Objective: This study aimed to assess the safety, feasibility, and efficacy of enteroscopy in SBS patients.

Design: Single center, retrospective.

Methods: We collected data on patients with SBS patients undergoing DBE from December 2019 to October 2023. We analyzed the technical success total enteroscopy rates, adverse events, diagnostic yield, and residual SB length measurement.

Results: A total of 12 SBS patients (8 females, median age at first enteroscopy, 66 years, interquartile range (IQR) 58-79) were included; among them, 10 received TED therapy (median interval from TED prescription to DBE surveillance 9.1 months (IQR 3.2-32.9)). Overall, 15 DBE procedures (3 retrograde) were performed, all of which were technically successful and completed without adverse events. The overall diagnostic yield was 60% for relevant findings, defined as conditions unknown before DBE. No SB malignancies were detected during the study period. In 80% of cases, a complete visualization of the SB was obtained with a reevaluation of the SB length. The median depth of maximal insertion was 85 cm (IQR 50-187).

Conclusion: DBE is feasible, safe, and effective in SBS patients. Total enteroscopy can be frequently achieved with a single approach in these patients, allowing easy diagnostic and oncologic surveillance for SB and colonic malignancy.

Background: Acute kidney injury (AKI) in cirrhotic patients is associated with high morbidity and mortality. Serum creatinine (sCr) has limited utility for early detection and etiological differentiation. Novel biomarkers and predictive models offer potential to address these limitations.

Objectives: To comprehensively evaluate the diagnostic performance of novel biomarkers and predictive models for the early detection and etiological differentiation of AKI in patients with liver cirrhosis.

Design: Systematic review conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Data sources and methods: A comprehensive literature search was performed in PubMed/Medline, EMBASE, and the Cochrane Library from inception to August 31, 2025. Studies evaluating biomarkers or models for AKI prediction or phenotyping in adult cirrhotic patients were included. Study selection, data extraction, and quality assessment (using Quality Assessment of Diagnostic Accuracy Studies-2, QUADAS-2) were performed independently by reviewers.

Results: A total of 33 studies were included. For the early prediction of AKI, serum cystatin C (Cys C) demonstrated superior performance to sCr, with an area under the receiver operating characteristic curve (AUROC) of up to 0.85. Urinary neutrophil gelatinase-associated lipocalin (NGAL) exhibited strong predictive capability and was most reliable in differentiating acute tubular necrosis from hepatorenal syndrome (HRS), achieving an AUROC up to 0.87. In contrast, kidney injury molecule-1, interleukin-18, and liver-type fatty acid binding protein, showed only moderate or inconsistent performance across most studies. Seven studies developed predictive models by integrating clinical variables with biomarkers, some of which employed machine learning techniques. However, the clinical applicability of these models is currently constrained by significant heterogeneity and limited external validation.

Conclusion: Serum Cys C and urinary NGAL offer distinct advantages over sCr in the early diagnosis and phenotypic differentiation of AKI. Although prediction models show promise, their routine clinical application requires further standardization and extensive external validation.

Trial registration: PROSPERO (CRD420251126410).

Background: Pancreatic neuroendocrine tumors (pNETs) are rare; however, they are increasingly being detected. Although surgical resection remains the standard treatment, its invasiveness has prompted interest in less invasive alternatives, particularly for small non-functional pNETs (NF-pNETs) and insulinomas.

Objectives: To evaluate the clinical efficacy and safety of endoscopic ultrasound-guided ethanol injection (EUS-EI) and radiofrequency ablation (EUS-RFA) for pNETs.

Design: A systematic review and meta-analysis.

Data sources and methods: A literature search of PubMed, MEDLINE, and Google Scholar was conducted (April 2005-April 2025). Studies were eligible if they reported clinical outcomes of EUS-EI or EUS-RFA in adult patients with insulinomas or NF-pNETs. The primary endpoints were clinical success (short-term symptom resolution or radiological response) and adverse event (AE) rates. Data were pooled using a random-effects model.

Results: Twenty-six studies were included in the meta-analysis. For insulinomas, the pooled clinical success rate was 77% (95% confidence interval (CI), 59-88) for EUS-EI and 95% (95% CI, 89-97) for EUS-RFA. The pooled incidence of total AEs was 32% (95% CI, 17-51) for EUS-EI and 25% (95% CI, 15-39) for EUS-RFA. For NF-pNETs, the pooled clinical success rates were 76% (95% CI, 54-90) for EUS-EI and 85% (95% CI, 74-92) for EUS-RFA, and the pooled incidence of total AEs was 27% (95% CI, 20-35) and 26% (95% CI, 17-38), respectively. The most common moderate or severe AEs were pancreatitis in 12 patients (7.6%) after EUS-EI, and pancreatic fluid collection in 4 patients (1.9%) and pancreatic duct stricture in 3 patients (1.4%) after EUS-RFA. One fatal case occurred in a 97-year-old patient following EUS-RFA.

Conclusion: Both EUS-EI and EUS-RFA are effective, relatively safe, and minimally invasive treatment options for pNETs. However, severe AE can occur, and careful patient selection and treatment indication are essential.

Trial registration: Not registered.

Background: Infliximab (IFX) is widely used for the treatment of Crohn's disease (CD), yet up to 40% patients experience primary non-response (PNR). Visceral adipose tissue (VAT) and intestinal ultrasound (IUS) could be used as noninvasive tools to predict treatment efficacy with limited value, respectively.

Objectives: This study aims to investigate the value of IUS combined with VAT in predicting PNR in CD patients.

Design: This was a single-center, prospective, and observational study.

Methods: Consecutive patients with active CD initiating regular IFX therapy were prospectively included. Patients underwent IUS at baseline (T0), week 2-4 (T1), and week 14 (T2), and CT at T0 to collected visceral fat area (VFA). Multivariable analyses and logistic regression analysis were used to identify predictors based on the efficacy at T2, regardless of prior biologic exposure.

Results: Of 100 patients, 31 (31%) experienced PNR. Multivariable analysis identified baseline bowel wall thickness [BWT_T0; odds ratio (OR), 2.082; 95% confidence interval (CI), 1.038-4.176; p < 0.05], VFA (VFA_T0; OR, 1.030; 95% CI, 1.008-1.052; p < 0.01), the decrease of BWT (△BWT; OR, 2.717; 95% CI, 1.349-5.472; p < 0.01) and the International Bowel Ultrasound Segmental Activity Score (△IBUS-SAS; OR, 1.082; 95% CI, 1.007-1.163; p < 0.05) from baseline to T1 were independent predictors of PNR. The △BWT combined with VFA_T0 can accurately predict PNR with a receiver operating characteristic (ROC) of 0.841 (95% CI, 0.756-0.926), superior to BWT_T0 combined with VFA_T0 (ROC, 0.832; 95% CI, 0.754-0.909) and △IBUS-SAS combined with VFA_T0 (ROC, 0.830; 95% CI, 0.753-0.917).

Conclusion: Early change in BWT on IUS combined with baseline VFA is highly predictive of PNR to IFX in CD patients, allowing stratification of patients beneficial from treatment initiation and guiding individualized clinical practice.

Background: Endoscopic resection (ER) is increasingly utilized for ulcerative colitis-associated neoplasias (UCANs); however, these lesions demonstrate higher rates of local residuals and recurrences compared with sporadic neoplasias. This may be partly explained by challenges in accurately delineating lesion borders preoperatively, though their clinicopathologic features remain incompletely understood.

Objectives: This study aimed to characterize the endoscopic and histologic features associated with local residuals and recurrences following ER for UCAN.

Design: A retrospective observational study.

Methods: Patients diagnosed with UCAN exhibiting a p53 mutation pattern between 2005 and 2024 and suspected of having local residual or recurrent lesions after ER were included. Endoscopic and histologic features were evaluated.

Results: Of 122 UCAN patients, 13 (6 underwent initial ER at our institution before 2018, and 7 underwent initial ER elsewhere) were identified with suspected local residuals or recurrences. Prior to initial ER, p53 immunostaining was not performed in eight cases (five without biopsy and three with biopsy specimens not stained), and only two patients underwent biopsy of the surrounding tissue. Ten tumors had positive or potentially positive horizontal margins (HMs) that were not identified endoscopically at the time of ER. All local recurrences were associated with suspected positive HMs, with a median time to recurrence of 16.5 (8.5-23.8) months. At recurrence, 50% of the lesions appeared flat, while the remaining 50% were superficial elevated lesions with adjacent flat dysplasia.

Conclusion: Inadequate preoperative assessment of the horizontal extent of UCANs may contribute to residual or recurrent disease after ER. Comprehensive evaluation-including p53 immunostaining and careful inspection for surrounding flat dysplasia-may improve curative outcomes in UCAN management.

Acute esophagogastric variceal bleeding (AEGVB) represents one of the most critical complications encountered in patients with decompensated liver cirrhosis. Endoscopic techniques, characterized by their dual benefits of direct diagnosis and immediate therapeutic intervention, have emerged as the primary modalities for the diagnosis and management of AEGVB. These endoscopic interventions are effective in controlling acute hemorrhage and in reducing or obliterating varices. Recent advancements in endoscopic therapy have increasingly focused on precision and the integration of intelligent technologies. This article aims to review the current status and advancements in endoscopic treatments for AEGVB in the context of liver cirrhosis, assist endoscopists in developing individualized endoscopic intervention strategies for patients with AEGVB, ultimately optimizing therapeutic outcomes and enhancing patient prognosis.

Background: In patients with irritable bowel syndrome with constipation (IBS-C), rapid, sustained relief from constipation and abdominal symptoms, such as pain, discomfort, and bloating, can improve quality of life.

Objective: This post hoc analysis evaluates the time to constipation and abdominal symptom relief achieved with tenapanor.

Design: Post hoc analysis of data pooled from three randomized placebo-controlled studies (phase IIb, T3MPO-1, and T3MPO-2) of tenapanor 50 mg twice daily in patients with IBS-C.

Methods: The time to first response for complete spontaneous bowel movement (CSBM) frequency, abdominal pain, discomfort, bloating, and 3-item abdominal score (AS3) were assessed. The AS3 was derived as the average of the weekly scores for abdominal pain, discomfort, and bloating. Cumulative incidences of response over time were estimated using the Kaplan-Meier method. A Cox proportional hazards model was used to assess the effect of baseline and demographic characteristics on the time to first response.

Results: Among 1372 patients with IBS-C (684 tenapanor; 688 placebo), median time to first CSBM response was 2 weeks, and median time to abdominal pain, discomfort, bloating, or AS3 response was 4-5 weeks in those treated with tenapanor, with 67.8%-76.7% achieving first response in CSBM frequency and abdominal symptoms by week 12. These time frames were shorter than those observed with the placebo (4 weeks for CSBM and 6-8 weeks for pain, discomfort, bloating, and AS3), of whom 59.1%-69.4% achieved the first response in CSBM and abdominal symptoms by week 12. Higher weekly response rates were observed with tenapanor than with placebo for all endpoints in each week of the 12-week treatment period.

Conclusion: This novel post hoc analysis demonstrates that, compared with placebo, tenapanor reduces the time to first response in CSBM frequency and abdominal symptoms and consistently increases the weekly response rate during 12 weeks of treatment.

Trial registration: NCT01923428; NCT02621892; NCT02686138.

Vedolizumab (VED) is a gut-selective monoclonal antibody and an effective biological agent for many patients with inflammatory bowel disease (IBD). Therapeutic drug monitoring has been used to optimise treatment with other biological agents; however, the clinical applicability of measuring vedolizumab trough concentrations is unclear. Initial registration trial data demonstrated a positive exposure-efficacy relationship of vedolizumab in IBD. However, there is conflicting data in more recent studies, with no definitive benefit of vedolizumab dose-escalation and no consistent target vedolizumab trough concentration identified. Also, unlike with anti-tumour necrosis factor agents, the clinical benefit of immunomodulator co-therapy with vedolizumab is uncertain. Although initial research suggested no clinical advantage of combining vedolizumab with an immunomodulator, more recent studies have shown potential benefit. This narrative review aims to explore current evidence on vedolizumab pharmacokinetics and whether immunomodulator co-therapy should be considered with vedolizumab.

Network meta-analysis (NMA) has seen an exponential rise in use over the past two decades, with publications in gastroenterology increasingly using this approach to inform guidelines, such as for colorectal cancer surveillance and inflammatory bowel disease management. However, alongside this growth comes a parallel risk: that methodological complexity and statistical misinterpretation may lead to misuse of the findings. As this paper outlines, NMAs can unintentionally mislead when clinical certainty is obscured by statistical hierarchy. To address these limitations, we present the promise of NMAs and a novel way of presenting NMA results, the GORDON Plot (Grade Of Results Diagram Of Network meta-analysis).

Background: Isolated gastric varices type 1 (IGV1) with spontaneous shunts carry a high risk of bleeding and ectopic embolization following cyanoacrylate injection.

Objectives: This study aimed to compare the efficacy and safety of endoscopic ultrasonography-guided cyanoacrylate injection (EUS-CYA) versus direct endoscopic injection of cyanoacrylate (DEI-CYA) in patients with IGV1 and spontaneous shunts.

Design: A prospective randomized controlled trial (RCT).

Methods: This prospective RCT enrolled patients with cirrhosis complicated by IGV1 and spontaneous portosystemic shunts. Eligible patients were randomly assigned to either the EUS-CYA group or the DEI-CYA group. The primary outcome was the rebleeding rate, while the secondary outcomes included technical success rate, gastric varices occlusion rate, cumulative non-bleeding rate, mortality rate, and incidence of ectopic embolization.

Results: A total of 96 patients were randomized to either the EUS-CYA (n = 47) or DEI-CYA (n = 49) group, both achieving 100% technical success. The rebleeding rate was significantly lower in the EUS-CYA group compared to the DEI-CYA group (19.15% vs 42.86%, p = 0.012), particularly for late rebleeding (17.02% vs 36.73%, p = 0.03). Kaplan-Meier analysis showed that the cumulative non-bleeding rates at 6, 12, 18, and 24 months were higher in the EUS-CYA group compared to the DEI-CYA group (p = 0.042). Mortality rates were similar between the groups (12.77% vs 16.33%, p = 0.621). No ectopic embolization occurred in the EUS-CYA group, while one case of pulmonary embolism was observed in the DEI-CYA group.

Conclusion: EUS-CYA demonstrates a higher gastric varices occlusion rate and a lower rebleeding rate for IGV1 with spontaneous shunts compared to DEI-CYA.

Trial registration: Chinese Clinical Trial Registry, ChiCTR2200058888.