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 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.

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.).

Impact of biliary stents on the diagnostic accuracy of EUS-guided fine-needle biopsy of solid pancreatic head lesions: A multicenter study.

BACKGROUND AND OBJECTIVES: There is no clear evidence of a negative impact of biliary stents on the diagnostic yield of EUS-guided fine-needle biopsy (EUS-FNB) for diagnosing pancreatic head lesions. We aimed to evaluate the association between the presence of biliary stents and the diagnostic accuracy of EUS-FNB. MATERIALS AND METHODS: A multicenter retrospective study including all jaundiced patients secondary to pancreatic head masses was performed. Patients were divided into two groups according to the presence of a biliary stent placed before EUS-FNB. Pathological results were classified according to the Papanicolaou classification and compared against the final diagnosis. Diagnostic measures in the two groups were compared. Multivariate logistic regression analyses including potential factors affecting EUS-FNB accuracy were performed. RESULTS: Overall, 842 patients were included, 495 (58.8%) without and 347 (41.2%) with biliary stent. A plastic or a metal stent was placed in 217 (62.5%) and 130 (37.5%) cases, respectively. Diagnostic sensitivity and accuracy were significantly higher in patients without biliary stent than in those with stent (91.9% and 92.1% vs. 85.9% and 86.4%, P = 0.010 At multivariate analyses, lesion size (odds ratio [OR]: 1.05, 95% confidence interval [CI]: 1.02-1.09, P = 0.01) and presence of biliary stent (OR: 0.51, 95% CI: 0.32-0.89, P = 0.01) were independently associated with diagnostic accuracy. In the subgroup of patients with biliary stent, the type of stent (plastic vs. metal) did not impact EUS-FNB yield, whereas the use of larger bore needles enhanced diagnostic accuracy (OR: 2.29, 95% CI: 1.28-4.12, P = 0.005). CONCLUSIONS: In this large retrospective study, an indwelling biliary stent negatively impacted the diagnostic accuracy of EUS-FNB. Preferably, EUS-FNB should precede endoscopic retrograde cholangiopancreatography, especially in the case of small tumors.

Stylet slow-pull vs. standard suction technique for endoscopic ultrasound-guided fine needle biopsy in pancreatic solid lesions using 20 Gauge Procore™ needle: A multicenter randomized trial.

BACKGROUND: Standard suction and slow-pull techniques have been utilized during endoscopic ultrasound-guided fine needle aspiration of pancreatic solid lesions, but the correct sampling technique remains unclear. New needles designed to obtain samples suitable for histological evaluation have become available. We performed a study comparing the two sampling methods during endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) in patients with pancreatic solid lesions. METHODS: We performed EUS-FNB with a 20 Gauge FNB needle using slow-pull or standard suction techniques in a prospective, randomized, multicenter study. The primary aim was bloodiness of the collected specimens. Secondary aims were technical success and performance of the two techniques. RESULTS: 110 patients were included (55 per group). No difference in blood contamination was observed (slow-pull 80% vs. suction 74%, p = 0.917). Technical success was 95% (96% vs. 94%, p = 0315). Sensitivity (96% vs. 93%), specificity (100% vs. 100%), positive likelihood ratio (NA), negative likelihood ratio (0.04 vs. 0.07), diagnostic accuracy (96 vs. 93%) did not differ between the two groups. CONCLUSION: EUS-FNB with slow-pull and standard suction techniques are comparable in terms of blood contamination providing similar high diagnostic sensitivity and accuracy in pancreatic solid lesions. The use of the new generation FNB needle allows to reach such high level of diagnostic adequacy regardless of the technique utilized.

Is Transient Elastography Needed for Noninvasive Assessment of High-Risk Varices? The REAL Experience.

INTRODUCTION: The Baveno VI consensus guidelines and an expanded algorithm suggest that transient elastography (TE) and platelet (PLT) count can be used to identify patients with cirrhosis who can avoid esophagogastroduodenoscopy (EGD). The primary aims of this study were to assess the ability of a simple algorithm, which uses only laboratory parameters, to predict medium/large esophageal varices (EV) in patients with hepatitis C virus (HCV) and cirrhosis from the Rete Sicilia Selezione Terapia-HCV (RESIST-HCV) cohort and to compare the performance of the algorithm with Baveno VI and Expanded Baveno VI criteria. The secondary aim was to assess the role of TE in ruling out large EV. METHODS: In total, 1,381 patients with HCV-associated cirrhosis who had EGD and TE within 1 year of starting treatment with direct-acting antivirals were evaluated. Using multivariate logistic analysis, laboratory variables were selected to determine which were independently associated with medium/large EV to create the RESIST-HCV criteria. These criteria were tested in a training cohort with patients from a single center (Palermo) and validated with patients from the 21 other centers of the RESIST-HCV program (validation cohort). RESULTS: In the entire cohort, medium/large EV were identified in 5 of 216 patients (2.3%) using the Baveno VI criteria and 13 of 497 patients (2.6%) using the Expanded Baveno VI criteria. PLT count and albumin level were independently associated with medium/large EV. The best cut-off values were a PLT count greater than 120 × 10 cells/µL and serum albumin level greater than 3.6 g/dL; negative predictive values (NPVs) were 97.2% and 94.7%, respectively. In the training cohort of 326 patients, 119 (36.5%) met the RESIST-HCV criteria and the NPV was 99.2%. Among 1,055 patients in the validation cohort, 315 (30%) met the RESIST-HCV criteria and the NPV was 98.1%. Adding TE to the RESIST-HCV criteria reduced the avoided EGDs for approximately 25% of patients and the NPV was 98.2%. DISCUSSION: The "easy-to-use" RESIST-HCV algorithm avoids EGD for high-risk EV screening for more than 30% of patients and has the same performance criteria as TE. Using these criteria simplifies the diagnosis of portal hypertension.

Characterization of γδ T Cells in Intestinal Mucosa From Patients With Early-Onset or Long-Standing Inflammatory Bowel Disease and Their Correlation With Clinical Status.

BACKGROUND AND AIMS: Inflammatory bowel disease [IBD] is a complex chronic inflammatory disease of the human gut with no clear aetiology. Traditionally, dysregulated adaptive immune responses play an important role even though accumulating evidence suggests a role also for innate immunity. Because of the well-known plasticity of γδ T cells, we investigated their percentage occurrence, phenotypic features and effector functions in the intestinal mucosa of early-onset and long-standing IBD patients, as compared to healthy subjects. METHODS: Fresh biopsies from 30 Crohn's disease and ulcerative colitis patients were obtained and digested, and cells were analysed by flow cytometry. RESULTS: We found a reduced frequency of Vδ1 T cells in tissue from early and late IBD patients (2.24% and 1.95%, respectively, vs 5.44% in healthy tissue) but an increased frequency of Vδ2 T cells in the gut of late IBD patients (3.19% in late patients vs 1.5% in early patients and 1.65% in healthy tissue). The infiltrating Vδ2 T cells had predominant effector memory and terminally differentiated phenotypes and produced elevated levels of tumour necrosis factor-α [TNF-α] and interleukin-17 [IL-17]. The frequency of tissue Vδ2 T cells correlated with the extent of the inflammatory response and the severity of IBD. CONCLUSION: Our study shows that tissue Vδ1 T cells are decreased in IBD patients while Vδ2 T cells are increased in the gut of IBD patients and contribute to TNF-α production. Moreover, we identify an as yet unappreciated role of Vδ2 T cells in IL-17 production in the gut of long-standing IBD patients, suggesting that they also participate in the chronic inflammatory process.

Effects of Eradicating Hepatitis C Virus Infection in Patients With Cirrhosis Differ With Stage of Portal Hypertension.

BACKGROUND & AIMS: Clearance of hepatitis C virus (HCV) via antiviral treatment changes the course of liver disease. We evaluated the benefit of sustained virologic response (SVR) in patients with HCV and cirrhosis without (stage 1) and with (stage 2) esophageal varices (EV). METHODS: We performed a prospective cohort study of 444 patients with HCV and compensated cirrhosis (218 with stage 1 and 226 with stage 2 disease) treated with peg-interferon and ribavirin from June 2001 through December 2009 at the University of Palermo, Italy and followed for a median of 7.6 years (range, 1-12.6 years). We used Cox regression analysis to identify variables associated with appearance or progression of EVs, development of hepatocellular carcinoma (HCC), liver decompensation, and overall survival. RESULTS: In the intention-to-treat analysis, 67 patients with stage 1 disease (30.7%) and 41 patients with stage 2 disease (18.1%) achieved an SVR (P = .003). Patients with stage 1 disease and an SVR were less likely to develop EVs than stage 1 patients without an SVR (hazard ratio [HR], 0.23; 95% confidence interval [CI], 0.11-0.48; P < .001). However, SVR did not affect whether patients with stage 2 disease developed further EVs (HR, 1.58; 95% CI, 0.33-1.03; P = .07, by log-rank test). An SVR was associated with lower risk for HCC (HR, 0.25; 95% CI, 0.12-0.55; P < .001). Patients with stage 2 disease, regardless of SVR, were at greater risk than patients with stage 1 disease for liver decompensation (HR, 2.82; 95% CI, 1.73-4.59; P < .001) or death (HR, 1.77; 95% CI, 1.12-2.80; P = .015). A lower proportion of patients with stage 1 disease and an SVR died from HCC (2.9%), compared with those without an SVR (11.9%) (P = .03) or developed liver decompensation (none vs 7.1% without an SVR; P = .009). A lower proportion of patients with stage 2 disease and an SVR died from causes secondary to HCC (2.0%) compared with those without an SVR (18.4%) (P = .003). Death from causes secondary to liver decompensation did not differ significantly between patients with stage 2 disease with or without an SVR (12.1% vs 25.4%; P = .15). CONCLUSIONS: In a prospective study of 444 patients with HCV and compensated cirrhosis, HCV eradication reduced risk for liver decompensation, HCC, and death, regardless of whether the patients had EVs.

Fibrosis evaluation by transient elastography in patients with long-term sustained HCV clearance.

BACKGROUND: Reversibility of advanced fibrosis after HCV-clearance is an important goal of therapy. OBJECTIVES: Measuring liver stiffness (LS) by transient elastography (TE) might be helpful in this setting. PATIENTS AND METHODS: We evaluated 104 patients with biopsy-proven chronic hepatitis C (CHC) and sustained virological response (SVR) after Peg-Interferon (IFN) plus ribavirin since at least 18 months. HCV-eradication was confirmed searching for serum HCV-RNA (TMA® sensitivity > 5-10 IU/ml). Data from literature reported the best LS cut-off values for different stages of liver fibrosis were 7.1 kPa for Metavir stage 2 (F2), 9.5 kPa for F3 and 12.5 for cirrhosis (F4). RESULTS: TE was not reliable in four SVR obese patients. Metavir-stage of biopsy was F0-1 in 28, F2 in 47, F3 in 17 and F4 in eight patients. The median interval elapsed since achieving SVR was 36 months (range: 18-77, SD¬¬:18). Stratifying patients according to the histological stage assessed before treatment, a clear-cut gradient of LS values was observed from F0-1: median: 3.8 kPa (range: 3.5-4.9) to F2: 4.6 kPa (3.8-6.0), F3: 6.2 kPa (4.8-8.6) and F4: 8.4 kPa (6.2-9.2) (P = 0.001). Overall, 86 patients had lower values of LS than the expected LS values according to Metavir-stage. At multivariate logistic analysis γ-GT and histological steatosis were independently associated with persistence of higher values of LS. CONCLUSION: Long term responders to IFN-based therapies have lower LS values than those who are untreated and still viraemic. High levels of γ-GT and liver steatosis, all markers of insulin resistance, may hamper reduction of liver stiffness after HCV-clearance.