Safety and effectiveness of tofacitinib in ulcerative colitis: Data from TOFA-UC, a SN-IBD study.

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.

EUS-guided gallbladder drainage using a lumen-apposing metal stent as rescue treatment for malignant distal biliary obstruction: a large multicenter experience.

BACKGROUND AND AIMS: EUS-guided gallbladder drainage (EUS-GBD) with lumen-apposing metal stents (LAMSs) has been reported as a rescue treatment with encouraging results for the relief of jaundice in patients with distal malignant biliary obstruction (DMBO) and after failure of both ERCP and EUS-guided choledochoduodenostomy. METHODS: This was a multicenter retrospective analysis of all cases of consecutive EUS-GBD with LAMSs used as a rescue treatment for patients with DMBO in 14 Italian centers from June 2015 to June 2020. Primary endpoints were technical and clinical success, whereas the secondary endpoint was the adverse event (AE) rate. RESULTS: Forty-eight patients (52.1% women) with a mean age of 74.3 ± 11.7 years were included in the study. Biliary stricture was related to pancreatic adenocarcinoma (85.4%), duodenal adenocarcinoma (2.1%), cholangiocarcinoma (4.2%), ampullary cancer (2.1%), colon cancer (4.2%), and metastatic breast cancer (2.1%). The mean diameter of the common bile duct was 13.3 ± 2.8 mm. LAMSs were placed transgastrically in 58.3% of cases and transduodenally in 41.7%. Technical success was 100%, whereas clinical success was 81.3%, with a mean total bilirubin reduction after 2 weeks of 66.5%. The mean procedure time was 26.4 minutes, and the mean hospital stay was 9.2 ± 8.2 days. AEs occurred in 5 patients (10.4%): 3 were classified as intraprocedural and 2 were classified as delayed because they occurred after >15 days. When the American Society for Gastrointestinal Endoscopy lexicon was used, 2 AEs were mild and 3 were moderate (2 buried LAMSs). The mean follow-up was 122 days. CONCLUSIONS: Our study shows that EUS-GBD with LAMSs used as a rescue treatment for patients affected by DMBO represents a valuable option in terms of technical and clinical success rates, with an acceptable AE rate. To the best of our knowledge, this is the largest study concerning the use of this procedure. (Clinical trial registration number: NCT03903523.).

Ustekinumab is a promising option for the treatment of postoperative recurrence of Crohn's disease.

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.

Wet-suction versus slow-pull technique for endoscopic ultrasound-guided fine-needle biopsy: a multicenter, randomized, crossover trial.

BACKGROUND : It is unknown whether there is an advantage to using the wet-suction or slow-pull technique during endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) with new-generation needles. We aimed to compare the performance of each technique in EUS-FNB. METHODS: This was a multicenter, randomized, single-blind, crossover trial including patients with solid lesions of ≥ 1 cm. Four needle passes with 22 G fork-tip or Franseen-type needles were performed, alternating the wet-suction and slow-pull techniques in a randomized order. The primary outcome was the histological yield (samples containing an intact piece of tissue of at least 550 µm). Secondary end points were sample quality (tissue integrity and blood contamination), diagnostic accuracy, and adequate tumor fraction. RESULTS: Overall, 210 patients with 146 pancreatic and 64 nonpancreatic lesions were analyzed. A tissue core was retrieved in 150 (71.4 %) and 129 (61.4 %) cases using the wet-suction and the slow-pull techniques, respectively (P = 0.03). The mean tissue integrity score was higher using wet suction (P = 0.02), as was the blood contamination of samples (P < 0.001). In the two subgroups of pancreatic and nonpancreatic lesions, tissue core rate and tissue integrity score were not statistically different using the two techniques, but blood contamination was higher with wet suction. Diagnostic accuracy and tumor fraction did not differ between the two techniques. CONCLUSION: Overall, the wet-suction technique in EUS-FNB resulted in a higher tissue core procurement rate compared with the slow-pull method. Diagnostic accuracy and the rate of samples with adequate tumor fraction were similar between the two techniques.

Digital single-operator cholangioscopy in diagnostic and therapeutic bilio-pancreatic diseases: A prospective, multicenter study.

BACKGROUND AND AIM: Digital single-operator cholangioscopy (D-SOC) is an endoscopic procedure that is increasingly used for the management of bilio-pancreatic diseases. We aimed to investigate the efficacy and safety of D-SOC for diagnostic and therapeutic indications. METHODS: This is a multicenter, prospective study(January 2016-June 2019) across eighteen tertiary centers. The primary outcome was procedural success of D-SOC. Secondary outcomes were: D-SOC visual assessment and diagnostic yield of SpyBite biopsy in cases of biliary strictures, stone clearance rate in cases of difficult biliary stones, rate of adverse events(AEs) for all indications. RESULTS: D-SOC was performed in 369 patients (201(54,5%) diagnostic and 168(45,5%)therapeutic). Overall, procedural success rate was achieved in 360(97,6%) patients. The sensitivity, specificity, PPV, NPV and accuracy in biliary strictures were: 88,5%, 77,3%, 83,3%, 84,1% and 83,6% for D-SOC visual impression; 80,2%, 92,6%, 95,1%, 72,5% and 84,7% for the SpyBite biopsy, respectively. For difficult biliary stones, complete duct clearance was obtained in 92,1% patients (82,1% in a single session). Overall, AEs occurred in 37(10%) cases.The grade of AEs was mild or moderate for all cases, except one which was fatal. CONCLUSION: D-SOC is effective for diagnostic and therapeutic indications.Most of the AEs were minor and managed conservatively, even though a fatal event has happened that is not negligible and should be considered before using D-SOC.

EUS-guided choledochoduodenostomy for malignant distal biliary obstruction after failed ERCP: a retrospective nationwide analysis.

BACKGROUND AND AIMS: EUS-guided choledochoduodenostomy (EUS-CDS) with a lumen-apposing metal stent (LAMS) has been proposed as an alternative procedure in patients with distal malignant biliary obstruction (DMBO) and failed ERCP. METHODS: This multicenter, retrospective analysis included all cases of EUS-CDS with LAMS performed in patients with DMBO and failed ERCP in 23 Italian centers from January 2016 to July 2020. Primary endpoints were technical and clinical success. Secondary endpoints were the assessment of the adverse event (AE) rate and variables associated with technical success. RESULTS: Two hundred fifty-six patients (44.9% women) with a mean age of 73.9 ± 12.6 years were included in the study. The most common etiology of DMBO was pancreatic adenocarcinoma (75%), followed by ampullary cancer (8.6%) and cholangiocarcinoma (6.6%). The common bile duct median diameter was 17.3 ± 3.9 mm. Technical and clinical success were achieved in 239 of 256 (93.3%), and 230 of 239 (96.2%) patients, respectively. The mean follow-up was 151 ± 162 days. Twenty-seven AEs occurred in 25 of 239 patients (10.5%) (3 mild, 21 moderate, and 3 severe). No fatal AEs occurred. Reinterventions to manage AEs with endoscopic or radiologic procedures occurred in 22 patients (9.2%). CONCLUSIONS: The results of our study show that EUS-CDS with LAMSs in patients with DMBO and failed ERCP represent a viable alternative in terms of effectiveness and safety with acceptable AE rates. (Clinical trial registration number: NCT03903523.).

EUS-guided biliary drainage with LAMS for distal malignant biliary obstruction when ERCP fails: single-center retrospective study and maldeployment management.

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.

Vedolizumab may be an effective option for the treatment of postoperative recurrence of Crohn's disease.

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.

Common bile duct size in malignant distal obstruction and lumen-apposing metal stents: a multicenter prospective study.

Background and study aims Feasibility of EUS-guided choledochoduodenostomy (EUS-CDS) using available lumen-apposing stents (LAMS) is limited by the size of the common bile duct (CBD) (≤ 12 mm, cut-off for experts; 15 mm, cut-off for non-experts). We aimed to assess the prevalence and predictive factors associated with CBD size ≥ 12 and 15 mm in naïve patients with malignant distal biliary obstruction (MDBO). Patients and methods This was a prospective cohort study involving 22 centers with assessment of CBD diameter and subjective feasibility of the EUS-CDS performance in naïve jaundiced patients undergoing EUS evaluation for MDBO. Results A total of 491 patients (mean age 69 ±â€Š12 years) with mean serum bilirubin of 12.7 ±â€Š6.6 mg/dL entered the final analysis. Dilation of the CBD ≥ 12 and 15 mm was detected in 78.8 % and 51.9 % of cases, respectively. Subjective feasibility of EUS-CDS was expressed by endosonographers in 91.2 % for a CBD ≥ 12 mm and in 96.5 % for a CBD ≥ 15 mm. On multivariate analysis, age ( P  < 0.01) and bilirubin level ( P  ≤ 0.001) were the only factors associated with both CBD dilation ≥ 12 and ≥ 15 mm. These variables were poorly associated with the extent of duct dilation; however, based on them a prediction model could be constructed that satisfactorily predicted CBD size ≥ 12 mm in patients at least 70 years and a bilirubin level ≥ 7 mg/dL. Conclusions Our study showed that at presentation in a large cohort of patients with MDBO, EUS-CDS can be potentially performed in three quarters to half of cases by expert and less experienced endosonographers, respectively. Dedicated stents or devices with different designs able to overcome the limitations of existing electrocautery-enhanced LAMS for EUS-CDS are needed.

Endoscopic Ultrasound-guided Fine-needle Biopsy With or Without Rapid On-site Evaluation for Diagnosis of Solid Pancreatic Lesions: A Randomized Controlled Non-Inferiority Trial.

BACKGROUND AND AIMS: The benefit of rapid on-site evaluation (ROSE) on the diagnostic accuracy of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) has never been evaluated in a randomized study. This trial aimed to test the hypothesis that in solid pancreatic lesions (SPLs), diagnostic accuracy of EUS-FNB without ROSE was not inferior to that of EUS-FNB with ROSE. METHODS: A noninferiority study (noninferiority margin, 5%) was conducted at 14 centers in 8 countries. Patients with SPLs requiring tissue sampling were randomly assigned (1:1) to undergo EUS-FNB with or without ROSE using new-generation FNB needles. The touch-imprint cytology technique was used to perform ROSE. The primary endpoint was diagnostic accuracy, and secondary endpoints were safety, tissue core procurement, specimen quality, and sampling procedural time. RESULTS: Eight hundred patients were randomized over an 18-month period, and 771 were analyzed (385 with ROSE and 386 without). Comparable diagnostic accuracies were obtained in both arms (96.4% with ROSE and 97.4% without ROSE, P = .396). Noninferiority of EUS-FNB without ROSE was confirmed with an absolute risk difference of 1.0% (1-sided 90% confidence interval, -1.1% to 3.1%; noninferiority P < .001). Safety and sample quality of histologic specimens were similar in both groups. A significantly higher tissue core rate was obtained by EUS-FNB without ROSE (70.7% vs. 78.0%, P = .021), with a significantly shorter mean sampling procedural time (17.9 ± 8.8 vs 11.7 ± 6.0 minutes, P < .0001). CONCLUSIONS: EUS-FNB demonstrated high diagnostic accuracy in evaluating SPLs independently on execution of ROSE. When new-generation FNB needles are used, ROSE should not be routinely recommended. (ClinicalTrial.gov number NCT03322592.).

Blood-based prognostic biomarkers in Crohn's Disease patients on biologics: a promising tool to predict endoscopic outcomes.

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.