Daniele Balducci

Background & Aims: Post-ERCP pancreatitis (PEP) remains the most frequent adverse event after ERCP. Although rectal NSAIDs and aggressive intravenous hydration are guideline-endorsed, the incremental benefit of adding hydration to NSAIDs is uncertain. We performed a meta-analysis of randomized controlled trials (RCTs) comparing NSAIDs plus aggressive hydration versus NSAIDs alone for PEP prevention. Methods: A systematic search in MEDLINE, Scopus, and Cochrane Library databases was performed for RCTs comparing NSAIDs plus aggressive hydration versus NSAIDs alone in adults undergoing ERCP. For the primary outcome a random-effects meta-analysis was conducted to estimate the PEP pooled risk ratios (RRs) with 95% CIs. Supplementary analyses included pooled arm-specific PEP incidence, sensitivity analyses for few trials and sparse events, and trial sequential analysis (TSA). Results: Eight RCTs with a total of 1,903 patients were included. The pooled arm-specific incidence of PEP was 2.8% (95% CI 0.4%–6.7%) with NSAIDs plus aggressive hydration and 7.6% (95% CI 5.2%–10.4%) with NSAIDs alone.. The DerSimonian–Laird random-effects analysis suggested a directionally favorable but statistically inconclusive estimate with combination prophylaxis (RR 0.66, 95% CI 0.40–1.08; I²=18%),whereas the pooled risk difference was −3.8% (95% CI −6.3 to −1.4). . The REML/Hartung–Knapp analysis was also inconclusive (RR 0.73, 95% CI 0.45–1.18). Trial sequential analysis showed that the required information size (RIS) had not been reached. Conclusions: Compared with NSAIDs alone, the addition of aggressive hydration resulted in a directionally lower but statistically inconclusive relative risk of PEP. Although the pooled risk difference favored combination therapy, the small-sample-robust and trial-sequential analyses remained inconclusive. The available evidence therefore does not establish superiority.

Background and Aims: Upadacitinib is an oral selective JAK1 inhibitor approved for moderate‐to‐severe Crohn's disease (CD), but real‐world prospective multicentre data in advanced therapy–experienced (AT‐experienced) patients are limited. The UPGRADE‐CD study evaluated its effectiveness and safety. Methods: In this prospective, multicentre, observational study across 38 Italian centres, we enrolled consecutive AT‐experienced CD patients initiating upadacitinib. Effectiveness was assessed at weeks 12 and 24, including clinical response (HBI reduction ≥ 3) and remission (HBI ≤ 4), steroid‐free counterparts, biomarker normalisation, resolution of extraintestinal manifestations (EIMs) and endoscopic outcomes. Safety was assessed in all patients receiving ≥ 1 dose. Results: A total of 391 patients were included in the safety analysis and 323 in the efficacy analysis; 48% had failed more than two advanced therapies. Clinical remission reached 51.2% at Week 12 and 54.7% at Week 24 ( p = 0.07). Steroid‐free clinical response rose from 53.8% to 63.5% ( p = 0.09). Active EIMs, present in 39.9% at baseline, resolved completely in 65.7% by Week 24. Higher baseline HBI was the strongest predictor of failure to achieve remission. Discontinuation by Week 24 was 11.3%, mainly from treatment failure (7.2%) and adverse events (3.1%). No major cardiovascular, thromboembolic events or malignancies occurred. Conclusions: Upadacitinib was effective and well‐tolerated in AT‐experienced CD, including patients with active EIMs, with induction benefit maintained through 6 months without novel safety signals.

Background: Risankizumab (RZB) is an anti-interleukin 23 (anti-IL-23) approved for the treatment of Crohn disease (CD). Study question: We aimed to evaluate the effectiveness and safety of RZB in the treatment of CD in real-world settings. Study design: We performed a retrospective review of a multicentre consortium of patients with CD treated with RZB. Measures and Outcomes: Coprimary outcomes were clinical remission at week 12, 24, and 52 (Harvey–Bradshaw Index score of ≤4), and safety. Secondary outcomes included steroid-free clinical remission, clinical response, and endoscopic remission at 52 weeks. Results: A total of 487 patients were included. The median follow-up was 24 (interquartile range: 16–38) weeks. A total of 372 (76.4%) patients achieved clinical remission at maximal follow-up. According to the treatment line in which RZB was administered, clinical remission occurred in 115/134 (85.8%) patients on second-line therapy, 112/153 (73.2%) on third-line therapy, and 145/200 (72.5%) on fourth-line therapy, with a significant difference ( P = 0.010). Adverse events occurred in 60 patients (12.6%) during follow-up; most of them were mild (50/60, 83.3%). Regarding the secondary outcomes: steroid-free clinical remission was achieved in 342 (71.8%) patients, and clinical response was observed in 443 (91.0%) patients. Six (1.2%) patients underwent surgery during follow-up. Mucosal healing was achieved in 34/67 (50.7%) patients. Conclusions: In this extensive, real-world study, RZB was effective and well tolerated in an advanced-therapy–exposed population of patients with CD and associated with favorable clinical and endoscopic outcomes.

Background: Inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are chronic conditions that affect the gastrointestinal tract. Since the initial approval of infliximab (IFX), a monoclonal antibody targeting TNF-α, numerous novel therapeutic targets have been identified, and many new therapies have been approved for the treatment of IBD. Methods: We conducted a narrative review of the literature using major biomedical databases, including EMBASE, Scopus, PubMed, CENTRAL, and ClinicalTrials.gov (last search date: 10 December 2025). Results: This review summarizes the current evidence on therapies approved for IBD (both CD and UC) and provides an overview of investigational agents currently being evaluated in ongoing phase II and III clinical trials. Conclusions: Moderate optimism arises from the expanding array of therapeutic targets under investigation and from emerging treatment strategies. However, only through a deeper understanding of the pathophysiological mechanisms underlying IBD will substantial improvements in treatment outcomes be achieved for conditions that continue to impose a significant burden on patients’ quality of life.

Unresectable extrahepatic cholangiocarcinoma remains a challenging malignancy with limited therapeutic options and poor prognosis. In this setting, effective and durable biliary drainage is crucial to prevent cholangitis, allow timely initiation and maintenance of systemic therapy, and ultimately improve survival. Endobiliary radiofrequency ablation (RFA) has emerged as a promising adjunct to biliary stenting, aimed at delaying tumor ingrowth and prolonging stent patency through localized thermal ablation of malignant tissue. Several studies have reported longer stent patency and, in some cases, improved survival with RFA plus stenting compared with stenting alone. However, the literature remains heterogeneous, and recent high-quality trials have yielded conflicting results, highlighting the need for further standardization of technique and patient selection. This narrative review summarizes the current evidence on the role of endobiliary RFA in unresectable cholangiocarcinoma, with particular emphasis on mechanism of action, endoscopic technique and oncologic outcomes.

Endobiliary radiofrequency ablation (RFA) has emerged as a promising adjunct to biliary stenting in the palliative management of unresectable extrahepatic cholangiocarcinoma. By generating localized thermal injury through a high-frequency alternating current (400–500 kHz) delivered via an intraductal electrode, RFA induces coagulative necrosis of malignant tissue, aiming to delay tumor ingrowth, maintain ductal patency, and improve quality of life. The procedure can be performed during endoscopic retrograde cholangiopancreatography or percutaneously, using bipolar probes advanced over a guidewire under fluoroscopic control. Technical success depends on adequate positioning of the electrodes within the stricture, correct energy settings (7–10 W for 60–120 s), and appropriate stent selection. Preclinical studies demonstrated controlled necrosis extending through the bile-duct wall, while clinical investigations have evaluated its impact on outcomes. Early retrospective series and several randomized controlled trials showed that RFA combined with stenting prolongs stent patency and, in selected subgroups, improves survival compared with stenting alone, without increasing the overall rate of complications. Meta-analyses have confirmed a consistent benefit in stent function and a moderate survival advantage, particularly in distal malignant strictures, although results remain heterogeneous due to differences in technique, patient selection, and stent type. The most frequent adverse events are cholangitis, pancreatitis, and acute cholecystitis. Overall, endobiliary RFA is a safe, technically feasible, and clinically relevant option to enhance biliary drainage in advanced cholangiocarcinoma. Standardization of procedural parameters and prospective trials are still needed to better define its therapeutic role and identify patients most likely to benefit.

In the above-mentioned article the values in the last paragraph under the heading ‘Recurrence’ have been corrected. Correct is: Subgroup analyses revealed recurrence rates for adenomas of 25.8% (95%CI 20.9%-31.3%) for CSP and 11.7% (95%CI 8.3%–15.7%) for H-EMR, with an RR of 1.97 (95%CI 0.58–6.74; P = 0.14) and substantial heterogeneity (I2=57.7%). This was corrected in the online version on July 22, 2025. Article published online: 22 July 2025 © 2025. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

This meta-analysis of randomized controlled trials (RCTs) aimed to compare the risk of recurrence and adverse events (AEs) between cold snare polypectomy (CSP) and hot endoscopic mucosal resection (H-EMR) for large nonpedunculated colorectal polyps (LNPCPs).A systematic search of Medline, Embase, and Cochrane Library databases until August 2024 was performed for studies comparing recurrence, bleeding, and perforation rates between CSP and H-EMR for LNPCPs ≥15 mm. A random-effects meta-analysis, with heterogeneity measured with I2, was conducted to generate pooled risk ratios (RRs) with 95%CIs.Four RCTs comprising 1516 LNPCPs (766 CSP and 750 H-EMR) in 1442 patients were included in the quantitative analysis. CSP demonstrated a higher recurrence risk at first surveillance colonoscopy than H-EMR in the pooled analysis (22.6% vs. 10.8%; RR 1.98; 95%CI 1.22–3.21; P = 0.02; moderate certainty evidence), corresponding to a number needed to harm of 9. Regarding AEs, CSP demonstrated a 67% reduced risk of delayed bleeding (1.2% vs. 3.9%; RR 0.33; 95%CI 0.12–0.89; P = 0.03; high certainty evidence), corresponding to a number needed to treat of 37. Although CSP appeared to reduce the risk of intraprocedural bleeding (10.0% vs. 19.8%; RR 0.30, 95%CI 0–52 256, P = 0.42), the wide confidence interval from the random-effects model included 1. There were no intraprocedural or delayed perforations in the CSP group.CSP has nearly double the recurrence risk of H-EMR for LNPCPs; however, its superior safety profile may make it a preferable option for patients where procedural safety is prioritized over radicality, such as those with extensive co-morbidities.

Background: Ustekinumab (UST) is an interleukin-12/interleukin-23 receptor antagonist approved for the treatment of Crohn’s disease (CD). Only limited real-life data on the long-term outcomes of CD patients treated with UST are available. This study assessed UST’s long-term effectiveness and safety in a large population-based cohort of moderate to severe CD patients. Methods: This was a multicenter, retrospective, observational cohort study that included both naïve and biologic-experienced patients treated with UST who achieved clinical remission or clinical response after at least one year of treatment. Clinical activity was scored according to the Harvey–Bradshaw Index (HBI). The primary endpoints were the maintenance or achievement of clinical remission after a further 12-month period of treatment, defined as an HBI of ≤5, and safety. Other endpoints included steroid-free remission, mucosal healing (MH), steroid discontinuation, and the need for treatment optimization during the follow-up. Results: Out of 562 CD patients, after an overall 24-month follow-up, clinical remission was present in 450 (80.0%) patients, and at 12 months, clinical remission was observed in 417/437 (95.4%) patients; 33/125 (26.4%) showed clinical response at 12 months (p = 0.000). A total of 38/103 (36.9%) patients achieved MH. Only 2.1% (12/562), 3% (17/562), and 1.1% (6/562) of patients required surgery, optimization, and re-induction, respectively. Adverse events occurred in eight patients (1.42%). According to a multivariate analysis, the only predictor of long-term remission was the presence of remission at the 12-month follow-up (p = 0.000). Conclusions: Long-term treatment with UST presents good efficacy and safety profiles in CD patients, especially for patients who achieve remission after one year.