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Background and Aims: The quality of a colonoscopy is heavily reliant on the effectiveness of bowel cleansing. Various cleansing solutions are currently available, but their comparative efficacy remains uncertain. This systematic review and network meta-analysis aims to compare the performance of different bowel preparations for colonoscopy., Methods: MEDLINE, Embase, Scopus, and the Cochrane Library were systematically searched for randomized controlled trials (RCTs) comparing the efficacy of different bowel preparations. The primary outcome was cleansing success (CS), and the secondary outcome was adenoma detection rate (ADR)., Results: On network meta-analysis for CS (22 RCTs, 7179 patients, 14 bowel preparations), 2 L PEG + simethicone (RR = 1.25 [95 %CI = 1.13-1.37]), 2 L PEG + lactulose (RR = 1.22 [95 %CI = 1.10-1.38]) and 1 L PEG + ascorbate (ASC) (RR = 1.03 [95 %CI = 1.01-1.06]) were significantly superior to 2 L PEG + ASC. Overall, 2 L PEG + lactulose resulted as the best product (SUCRA 0.94), followed by 2 L PEG + simethicone (SUCRA 0.93). On network meta-analysis for ADR (17 RCTs, 6639 patients, 11 bowel preparations), only 2 L PEG + simethicone (RR = 1.60 [95 %CI = 1.05-2.43]) resulted significantly superior to 2 L PEG + ASC., Conclusions: 2 L PEG + simethicone, 2 L PEG + lactulose, and 1 L PEG + ASC seemed to provide high rates of CS, albeit only 2 L PEG + simethicone was associated with significantly higher ADR. Consequently, these products should be preferred for bowel preparation of colonoscopy. Further randomized studies with adequate sample sizes are needed for a more accurate comparison of these products on ADR., Competing Interests: Declaration of competing interest RV and LF received consultation fees from AlfaSigma and Norgine. MM, RDM and AR received consultation fees from Norgine. Other authors have no proprietary, financial, professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of this manuscript., (Copyright © 2024 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Competing Interests: The authors declare that they have no conflict of interest.

Background: Real-world evidence is needed to determine the value of tofacitinib (TOFA) for the treatment of ulcerative colitis (UC)., Aim: To assess the safety and effectiveness of TOFA in clinical practice., Methods: TOFA-UC is a multicenter, observational study performed among the Sicilian Network for Inflammatory Bowel Disease (SN-IBD). All consecutive patients with UC starting TOFA from its introduction in Sicily (July 2021) to July 2022 were included., Results: 111 patients were included (mean follow-up: 31.7 ± 14.9 weeks; biologic-experienced: 92.8%). Nineteen adverse events were reported (17.1%; incidence rate: 28.2 per 100 patient years), including 11 cases of hypercholesterolemia and 3 infections (no cases of herpes zoster reactivation. At week 8, the rates of clinical response, steroid free clinical remission, and CRP normalization were 74.8%, 45.0%, and 56.9%, respectively, and 68.5%, 51.4%, and 65.2%, respectively, at the end of follow-up. Eighteen patients experienced a loss of response after successful induction (21.7%; incidence rate: 33.2 per 100 patient years). Twenty-six patients (23.4%) discontinued TOFA over time, of whom 3 due to AEs, and 23 to non response or loss of response., Conclusions: TOFA is safe and effective in patients with UC, including those with history of multiple failures to biological therapies., Competing Interests: Conflict of interest Fabio Salvatore Macaluso served as an advisory board member and/or received lecture grants from Biogen, Ferring, Galapagos, Janssen, MSD, Pfizer, Samsung Bioepis, and Takeda Pharmaceuticals. Walter Fries served as an advisory board member and/or received lecture grants from Abbvie, MSD, Takeda, Pfizer, Biogen, Sandoz, Zambon, Ferring Italia, Sofar. Anna Viola received lecture grants from Pfizer. Maria Cappello served as an advisory board member for AbbVie, MSD, Takeda Pharmaceuticals, and received lecture grants from AbbVie, MSD, Chiesi, and Takeda Pharmaceuticals. Filippo Mocciaro served as an advisory board member for Janssen and Galapagos, and received lecture grants from Takeda Pharmaceuticals. Antonino Carlo Privitera served as consultant to Mundipharma, Abbvie, MSD, Takeda, and Janssen, and received lecture fees from Abbvie, Sara Renna served as an advisory board member for AbbVie, Janssen, and MSD Pharmaceuticals, and received lecture grants from AbbVie, Janssen, MSD, Pfizer, and Takeda Pharmaceuticals. Ambrogio Orlando served as an advisory board member for AbbVie, Galapagos, MSD, Janssen, Pfizer, Samsung Bioepis, and Takeda Pharmaceuticals, and received lecture grants from AbbVie, Fresenius Kabi, Galapagos, MSD, Sofar, Chiesi, Janssen, Pfizer, and Takeda Pharmaceuticals., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Competing Interests: The authors declare that they have no conflict of interest.

Background and Aim: Postoperative recurrence (POR) following ileocolonic resection is a major concern in patients with Crohn's disease (CD). The role of ustekinumab (UST) in this setting is poorly known., Methods: All consecutive CD patients with a baseline colonoscopy at 6-12 months from ileocolonic resection showing POR (Rutgeerts score ≥ i2) who were treated with UST after the baseline colonoscopy and with an available post-treatment endoscopy, were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD). The primary outcome was endoscopic success, defined as reduction of at least one point of Rutgeerts score. The secondary outcome was clinical success, assessed at the end of follow-up. Reasons for clinical failure included mild clinical relapse (Harvey-Bradshaw index 5-7), clinically relevant relapse (Harvey-Bradshaw index > 7), and need for new resection., Results: Forty-four patients were included (mean follow-up: 17.8 ± 8.4 months). The baseline postoperative colonoscopy showed severe POR (Rutgeerts score i3 or i4) in 75.0% of patients. The post-treatment colonoscopy was performed after a mean of 14.5 ± 5.5 months following initiation of UST. Endoscopic success was reported in 22 out of 44 (50.0%) patients, of whom 12 (27.3%) achieved a Rutgeerts score i0 or i1. Clinical success at the end of follow-up was reported in 32 out of 44 patients (72.7%); none of the 12 patients with clinical failure had achieved endoscopic success at post-treatment colonoscopy., Conclusions: Ustekinumab could be a promising option for the treatment of POR of CD., (© 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Competing Interests: The authors declare that they have no conflict of interest.

Competing Interests: Dr. Roberto Di Mitri is consultant to Boston Scientific. The other authors have no conflicts of interest and disclosed no financial relationships relevant to this publication.

Competing Interests: Dr. Roberto Di Mitri is consultant of Boston Scientific; the other authors have no conflicts of interest.

Background: EUS-guided biliary drainage (EUS-BD) with Lumen Apposing Metal Stent (LAMS) is a mini-invasive approach for jaundice palliation in distal malignant biliary obstruction (D-MBO) not amenable to ERCP, with good efficacy and not exiguous adverse events., Aims and Methods: From January 2015 to December 2019, we retrospectively enrolled all the EUS-BD with electrocautery-enhanced LAMS for biliary decompression in unresectable D-MBO and failed ERCP. Primary study aims were to evaluate technical/clinical success and AEs rate. In case of maldeployment, we estimated the efficacy of an intra-operative rescue therapy. Secondary aims were to assess the jaundice recurrence and gastric outlet obstruction symptoms., Results: Thirty-six EUS-BD were enrolled over a cohort of 738 patients (ERCP cannulation failure rate was 2.6%): 31 choledocho-duodenostomy and 5 cholecystogastrostomy. A pre-loaded guidewire through the LAMS was systematically used in case of common bile duct ≤ 15 mm or scope instability for a safe/preventive biliary entryway in case of intra-procedural complications. Technical success was 80.6% (29/36 patients). Seven cases of LAMS maldeployment during EUS-guided choledocho-duodenostomy were successfully treated with RT by an over-the-wire fully-covered Self-Expandable Metal Stent (FC-SEMS). The FC-SEMS was released through the novel fistula tract in endoscopic fashion in 5/7 cases and transpapillary in percutaneous-transhepatic-endoscopic rendezvous (1/7) and laparoscopic-endoscopic rendezvous (1/7) in the two remaining cases. The total efficacy of rescue therapy was 100%. Same-session duodenal SEMS was placed in 17 patients with optimal gastric outlet obstruction management. Final clinical success was 100% and no other late adverse events or FC-SEMS migration were observed., Conclusion: EUS-BD with LAMS is effective for jaundice palliation after ERCP failure but with considerable adverse events. Maldeployment remains a serious complication with fatal evolution if not correctly recognized/managed. Rescue therapy must be promptly applied especially in tertiary-care centers with highly skilled endoscopists, interventional radiologist and dedicated surgeon., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The role of Vedolizumab (VDZ) as therapeutic option for the postoperative recurrence of Crohn's disease (CD) following ileocolonic resection is unknown., Aims: To assess the effectiveness of VDZ in this setting., Methods: All consecutive CD patients with a baseline colonoscopy at 6-12 months from the ileocolonic resection showing postoperative recurrence (Rutgeerts score ≥i2) and treated with VDZ after the baseline colonoscopy were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD). The primary outcome was endoscopic success, assessed at the first colonoscopy following initiation of VDZ and defined as reduction of at least one point of Rutgeerts score. The secondary outcome was clinical failure, assessed at one year and at the end of follow-up., Results: Fifty-eight patients were included (mean follow-up: 24.8 ± 13.1 months). Endoscopic success was reported in 47.6% of patients. Clinical failure was reported in 19.0% of patients at one year, and in 32.8% of patients at the end of follow-up. A new resection was required in 7 patients (12.1%)., Conclusions: VDZ may be an effective option for the treatment of postoperative recurrence of CD., Competing Interests: Conflict of Interest None declared., (Copyright © 2021 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Adalimumab is used to treat ulcerative colitis, but additional effectiveness and safety data are needed., Patients and Methods: This retrospective study considered adults with ulcerative colitis treated with adalimumab at 19 hospitals. Clinical data were collected from the start of treatment, after 2, 6 and 12 months, and at the last visit. Outcome measures of effectiveness were treatment duration, reasons for discontinuation and colectomy., Results: We studied 381 patients treated with adalimumab for a median of 12.1 months. Disease activity at the start of treatment was moderate to severe in 262 cases (68.8%) and endoscopic activity was moderate to severe in 339 cases (89.0%). At week 8, clinical responses were observed in 177 cases (46.5%) and clinical remission in 136 cases (35.7%). At 12 months, remission was observed in 128 cases (33.6%). Overall, 44 patients required colectomy, and 170 patients (44.6%) were still taking adalimumab when data were collected. Variables associated with adalimumab discontinuation were concomitant steroid treatment, severe clinical-endoscopic activity at baseline, need for adalimumab intensification and drug-related adverse events. Variables associated with colectomy were concomitant steroid treatment and high baseline C-reactive protein., Conclusion: Adalimumab is safe and effective for the treatment of ulcerative colitis., Competing Interests: Conflict of Interest None declared., (Copyright © 2021. Published by Elsevier Ltd.)

Colorectal cancer (CRC) risk is increased in Inflammatory Bowel Disease (IBD) and surveillance needs to be tailored according to individual risk. The open issues include the role of the characteristics of IBD and CRC in determining the long-term outcome. These issues were assessed in our multicenter study, including a cohort of 56 IBD patients with incident CRC. The clinical and histopathological features of IBD patients and of CRC were recorded. Incident CRC in IBD occurred at a young age (≤40 years) in 25% of patients (median age 55.5 (22-76)). Mucinous signet-ring carcinoma was detected in 6 out of the 56 (10.7%) patients, including 4 with Ulcerative Colitis (UC) and 2 with Crohn's disease (CD). CRC was more frequently diagnosed by colonoscopy in UC (85.4% vs. 50%; p = 0.01) and by imaging in Crohn's Disease CD (5.8% vs. 31.8%; p = 0.02). At onset, CRC-related symptoms occurred in 29 (51.9%) IBD patients. The time interval from the diagnosis of IBD to CRC was shorter in UC and CD patients with >40 years ( p = 0.002; p = 0.01). CRC-related death occurred in 10 (29.4%) UC and in 6 (27.2%) CD patients ( p = 0.89), with a short time interval from CRC to death (UC vs. CD: 6.5 (1-68) vs. 14.5 (8-40); p = 0.85; IBD: 12 months (1-68)). CRC occurring at a young age, a short time interval from the diagnosis of IBD to CRC-related death in the elderly, CRC-symptoms often mimicking IBD relapse and the observed high mortality rate may support the need of closer surveillance intervals in subgroups of patients.

Objective: There is a growing need for biomarkers to predict therapeutic outcome in Crohn's disease (CD)., Main Outcome Measures: The aim was to evaluate whether NLR (neutrophil-to-lymphocyte ratio), PLR (platelet-to-lymphocyte ratio), ELR (eosinophil-to-lymphocyte ratio), and ENLR (eosinophil*neutrophil-to-lymphocyte ratio), could be prognostic biomarkers of endoscopic response (ER) when starting biologics., Research Design and Methods: Patients with CD who started biologics were enrolled. Multivariate analysis was used to evaluate whether NLR, PLR, ELR and ENLR at baseline and at w12 could predict ER (Simple Endoscopic Score for Crohn's disease [SES-CD] ≤2 or SES-CD≤2 and Rutgeerts i0-i1) after 52 weeks of treatment. Area under the curve (AUC) was calculated to find the cutoffs., Results: 107 patients were included. Patients who achieved ER had significantly lower baseline NLR (p = 0.025), ELR (p = 0.013), and ENLR (p = 0.020) compared with those without ER; results after 12 weeks of treatment for ELR (p = 0.006) and ENLR (p = 0.003). AUC was 0.64 (p = 0.003), 0.67 (p = 0.006) and 0.65 (p = 0.014) for NLR, ELR and ENLR., Conclusions: Low NLR, ELR and ENLR can predict ER and could be used in clinical practice for a better management of CD patients.

Competing Interests: The authors declare that they have no conflict of interest.

Background and Aim: Ustekinumab is approved in Europe for the treatment of moderate to severe Crohn's disease (CD). Italian real-life data are scarce, so the aim of this study was to assess the effectiveness and safety of ustekinumab in an Italian cohort of CD patients., Methods: Data of patients with CD who started using ustekinumab were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Disease. Primary end-points were steroid-free clinical remission at 8, 24, and 52 weeks of therapy and reduction of C-reactive protein. Secondary end-points were treatment response, treatment persistence at 12 months, and safety., Results: A total of 131 patients (males 56%; mean age 46 years ± 15) were included. All patients were biologics experienced except for one. At 24 and 52 weeks, 40% and 43% of patients achieved steroid-free clinical remission, and 64% and 62% had clinical response, respectively. At the end of follow-up, there was a significant reduction of steroid use ( P = 0.012) and of the Harvey-Bradshaw Index ( P = 0.001). The probability of persistence in therapy with ustekinumab after 12 months of treatment was 89%. The only factor associated with discontinuation was older age., Conclusions: Data from our real-life cohort of treatment-refractory CD patients suggest the satisfactory effectiveness and safety profile of ustekinumab., (© 2021 The Authors. JGH Open: An open access journal of gastroenterology and hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)