Digestive Diseases and Sciences最新文献

Background and aim: Although long self-expandable metal stent (SEMS) with a sufficient intragastric portion is typically preferred for endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS), this design can complicate endoscopic re-intervention for recurrent biliary obstruction (RBO). We evaluated the efficacy and safety of endoscopic re-intervention for RBO through the stent after EUS-HGS using a novel partially covered SEMS with an anchoring flange.

Methods: The partially covered SEMS was designed with a intrahepatic uncovered portion measuring 1.5 cm in length and a resilient fold-back wide distal anchoring flange with a 2.0 cm diameter. Re-interventions were performed through the stent lumen while the stent was in situ. The primary outcomes were technical and clinical success, and secondary outcomes were procedure time, adverse events, and the median time to RBO after re-intervention.

Results: In total, 35 re-interventions were performed in 19 patients. Re-intervention was successfully conducted in 97.1% (34/35) of cases via the intragastric end of the stent in a retroflexed position. Technical and clinical success were 94.3% (33/35) and 88.6% (31/35). Re-intervention methods included stent cleaning (18.2%), additional HGS stent placement (33.3%), and antegrade stent placement (48.5%). Mild cholangitis occurred in 5.7% (2/35) of patients and was managed conservatively. The median time to RBO after re-intervention was 148 days.

Conclusion: Endoscopic re-interventions can be effectively and safely performed through the lumen of the novel partially covered SEMS with an anchoring flange.

Colorectal cancer (CRC) is ranked as the second leading cause of cancer-related deaths globally, necessitating urgent advancements in therapeutic approaches. The emergence of groundbreaking therapies, including chimeric antigen receptor-T (CAR-T) cell therapies, oncolytic viruses, and immune checkpoint inhibitors, marks a transformative era in oncology. These innovative modalities, tailored to individual genetic and molecular profiles, hold the promise of significantly enhancing patient outcomes. This comprehensive review explores the latest clinical trials and advancements, encompassing targeted molecular therapies, immunomodulatory agents, and cell-based therapies. By evaluating the strengths, limitations, and potential synergies of these approaches, this research aims to reshape the treatment landscape and improve clinical outcomes for CRC patients, offering new found hope for those who have exhausted conventional options. The culmination of this work is anticipated to pave the way for transformative clinical trials, ushering in a new era of personalized and effective CRC therapy.

Background: Therapeutic drug monitoring is important for optimizing anti-tumor necrosis factor-α (TNF-α) therapy in inflammatory bowel disease. However, the exposure-response relationship has never been assessed in pouchitis.

Aims: To explore associations between anti-TNF-α drug concentration and pouchitis disease activity in patients with a background of ulcerative colitis.

Methods: A retrospective, multicenter, cross-sectional study was conducted in adult patients with pouchitis requiring anti-TNF-α treatment. Rates of clinical and endoscopic remission were calculated, and drug concentrations during maintenance therapy were compared between remission and non-remission cohorts.

Results: Sixty-three patients were included: median age, 48 years (IQR 36-59) and median time since pouchitis diagnosis, 7 years (IQR 2-13). Patients received infliximab, n = 27 (43%), adalimumab, n = 29 (46%), or both n = 7 (11%). Thirty-two (51%) patients received concomitant immunomodulation. Median infliximab trough concentrations (mg/ml) were similar between patients in clinical remission (n = 21) vs non-remission (n = 11), 5.3 vs. 4.4, p = 0.73. For adalimumab, median drug concentrations did not significantly differ between remission/non-remission groups based on clinical (n = 18/18), 11.4 vs 7.6, p = 0.32, or endoscopic assessment, (n = 7/29), 9.0 vs. 7.8, p = 0.78. Four patients had positive anti-drug antibodies with undetectable drug concentration.

Conclusion: In a cohort of patients with pouchitis, higher anti-TNF-α drug concentrations were not associated with more clinical or endoscopic remission.

Purpose: The performance of endoscopic evaluation of ulcerative colitis (UC) using conventional scoring, including Mayo endoscopic subscore (MES) and ulcerative colitis endoscopic index of severity (UCEIS), is not satisfactory. Recently, the usefulness of novel image-enhanced endoscopy (IEE) such as texture and color enhancement imaging (TXI) and red dichromatic imaging (RDI) has been reported in the endoscopic evaluation of UC. We evaluated the performance of IEEs in UC, particularly focusing on the correlation with MES and UCEIS, and prediction of relapse.

Methods: This is a prospective, observational study. UC patients in clinical remission who underwent colonoscopy with evaluation of IEEs and follow-up for > 3 months were analyzed. TXI and RDI were evaluated using the previously reported scoring system (TXI 0-2 and RDI 1-4). The IEE scores were compared with the conventional scoring, fecal calprotectin levels, and histological findings using Geboes score, and patient's clinical relapse rate stratified by each IEE score was examined.

Results: Both TXI and RDI scores were well-correlated with MES and UCEIS (both p < 0.001), fecal calprotectin levels (p = 0.015 and p = 0.006), and histology evaluated with Geboes score. In the Geboes subscore, the subscore 2B (neutrophil infiltration in lamina propria) was the most correlated with each endoscopic scoring. RDI 3-4 was significantly correlated with subsequent relapse (hazard ratio 3.56, 95% confidence interval 1.13-11.24), but TXI scoring did not predict relapse significantly.

Conclusion: The assessment using RDI could be a convenient and useful endoscopic evaluation method for predicting the prognosis of UC.

Background: This two-stage individual patient data meta-analysis (IPD-MA) compared the efficacy of a shorter duration (≤ 2 days) of vasoactive (VA) drug therapy to standard duration (3-5 days) after acute variceal bleeding (AVB) in patients with liver cirrhosis.

Patients and methods: Randomized clinical trials on patients with cirrhosis and AVB undergoing endoscopic band ligation which compared a short duration versus the standard duration of VA therapy were included. The primary outcome was 5-day rebleeding rate. Secondary outcomes included 5-day and 42-day mortality, 42-day rebleeding rate, and length of hospital stay in patients receiving short duration of therapy as compared to those receiving standard duration. Aggregate data meta-analysis and IPD-MA of trials were performed for these outcomes and comparisons in patients with different severities of liver disease.

Results: Out of 11 eligible trials, 542 IPD data sets were available from 6 trials. Two hundred and seventy-nine patients received short duration and 263 received standard duration VA therapy. Two-stage IPD-MA revealed no significant differences in the 5-day rebleeding rate (HR = 0.59, 95%CI: 0.19-1.81, p = 0.66), 5-day mortality (HR = 1.12, 95%CI: 0.18-6.63, p = 0.44), 42-day rebleeding rate (HR = 0.95, 95%CI: 0.47-1.90, p = 0.90) and 42-day mortality (HR = 1.05, 95% CI: 0.43-2.56, p = 0.34) between the two groups. One-stage IPD-MA revealed no significant differences in the outcomes across Child-Pugh classes, with shorter hospital stay in short duration group.

Conclusions: Short duration VA therapy has similar outcomes to standard duration in patients with liver cirrhosis presenting with AVB, irrespective of severity of liver disease.

Background and aim: Stent placement for biliary drainage in patients with malignant hilar biliary obstruction (MHBO) has been a topic of long-standing debate, and the best approach remains controversial. Therefore, we aimed to evaluate the efficacy, safety, and removability of multi-hole fully covered self-expandable metal stents (MH-FCSEMSs) in a preclinical experiment using swine hilar bile duct obstruction (HBDO) models and to assess the feasibility and safety of stent placement in patients with MHBO.

Methods: Three minipigs underwent endoscopic retrograde cholangiopancreatography (ERCP)-guided endobiliary-radio frequency ablation (EB-RFA) to establish Bismuth type II hilar bile duct stenosis models. Four weeks after EB-RFA, 10-mm diameter and 4-cm length MH-FCSEMSs were endoscopically inserted into the left intrahepatic bile duct of the models. Stent patency and migration, as well as adverse events including cholangitis and endoscopic stent removability, were assessed three months after stent placement. Additionally, clinical applications of MH-FCSEMS were performed in two patients with MHBO to determine feasibility, safety, and stent patency.

Results: MH-FCSEMSs were successfully inserted into the left main intrahepatic bile duct and common hepatic duct of the models under ERCP in all three animals without any technical difficulties. Cholangiograms performed 12 weeks after MH-FCSEMS placement showed no stent migration, and all were successfully removed from the animal models. The functional success rate, defined as a decrease in serum total bilirubin level of more than 50% at 12 weeks after stent placement, was 100%. Moreover, MH-FCSEMSs were successfully inserted in two patients with hilar cholangiocarcinoma. The procedures were technically feasible, and no major periprocedural complications were noted.

Conclusion: The preliminary long-term results of both preclinical and clinical pilot studies suggest that endoscopic biliary drainage using MH-FCSEMS may be a safe and effective treatment option for stenting and stent revision in the management of HBDO. Further studies comparing clinical outcomes to those of MH-FCSEMS without multi-hole in malignant hilar biliary obstruction will be needed to verify the clinical benefits.

Background: Fecal lipocalin-2 (LCN2) is a biomarker of neutrophil activation, which is elevated in patients with inflammatory bowel disease (IBD); however, its dynamic changes during pregnancy and early life are largely unknown. We characterized LCN2 levels by maternal IBD diagnosis, offspring feeding behavior, and gut microbiota composition.

Methods: In the prospective MECONIUM (Exploring Mechanisms of Disease Transmission In Utero through the Microbiome) study, we analyzed 559 fecal samples from 91 pregnant women with IBD, 78 healthy controls, and their 147 offspring for LCN2 levels at each trimester of pregnancy and multiple time points during early life using linear mixed-effects model and multiple logistic regression analyses. Gut microbiota community compositions were evaluated following 16S rRNA gene sequencing.

Results: IBD cases had higher LCN2 levels throughout pregnancy compared to controls. In offspring, significantly higher LCN2 was found in babies born to mothers with IBD, compared to those without IBD, at 3 months, 1 year, and 4 years (all p < 0.03), with offspring LCN2 levels being predictive of maternal IBD case status with > 85% accuracy at ages 1 and 4. We also detected correlations between LCN2 levels and certain IBD-associated bacterial taxa in both mothers and babies. Exclusively breastfed babies had lower LCN2 in the first weeks of life compared to formula or mixed-fed counterparts.

Conclusions: Babies born to mother with IBD had significantly higher LCN2 during early life compared to controls with exclusive breastfeeding impacting LCN2 levels early on. LCN2 levels correlated with IBD-associated microbial taxa in both mothers and babies. Future studies should identify the biological drivers and health-related consequences of elevated LCN2 during early childhood.

Like all interventions in health care, novel non-invasive tests for colorectal cancer should be properly evaluated before they can be recommended. Such evaluations should be performed in well-designed studies, of which the results can serve as the evidence base for recommendations. While the methods for evaluating novel tests have been slower to develop, there is now a solid base for developing suggestions and even strong recommendations for their assessment. These include advice for study design, analysis of results, and clear and informative reporting. These considerations should be guided by the intended use of the new test and its role in the testing pathway. We distinguish between tests proposed as a replacement for an existing test, as a triage test, before an existing test, or as an add-on test, after an existing test. We recommend the definition of explicit, a priori defined, minimally acceptable performance criteria for the intended use of the new test and rigorous statistical hypothesis testing, to prevent "spin" in the interpretation of the findings.