Comparison of EsophyX2.0 and MUSE systems for transoral incisionless fundoplication: Technical aspects and outcomes up to 3 years.

OBJECTIVES: We compared the efficacy and safety of transoral incisionless fundoplication (TIF) with the EsophyX2.0 and MUSE systems for treatment of gastroesophageal reflux disease (GERD). METHODS: TIF outcomes from prospective protocols (Esophy2.0X: 2007-2012; MUSE: 2015-2019) were retrospectively compared regarding technical success, moderate/severe adverse events, morpho-functional findings up to 1 year, and clinical outcomes up to 3 years. Inclusion criteria were: (i) at least 6-month symptomatic GERD, full/partial response to proton pump inhibitors (PPI), esophagitis, and nonerosive reflux disease/hypersensitive esophagus (both protocols); (ii) hiatal hernia <3 cm (Esophy2.0X) and ≤2.5 cm (MUSE); and (iii) Barrett's esophagus <3 cm (MUSE). RESULTS: In the 50 EsophyX2.0 and 46 MUSE procedures, technical success and adverse event rates were similar, but MUSE-related adverse events (4.4%) were life-threatening. At 12 months, hiatal hernia recurred more frequently after EsophyX2.0 (P = 0.008). At 6 months, significantly fewer total and acid refluxes were reported after both TIF, but not more significantly at 1 year. Symptoms improved after both TIF up to 1 year (P < 0.0001), but to a greater extent in MUSE patients up to 3 years (P < 0.0001 vs. P < 0.01 for EsophyX2.0). The rates of 3-year off-PPI therapy patients were 73.5% in the MUSE and 53.3% in the EsophyX2.0 series (P = 0.069). CONCLUSION: Although no conclusion could be drawn from this limited study, the MUSE technique seemed more effective in the long term in patients with hiatal hernia; however, there were more severe adverse events than with EsophyX2.0.

Transoral incisionless fundoplication with Medigus ultrasonic surgical endostapler (MUSE) for the treatment of gastro-esophageal reflux disease: outcomes up to 3 years.

BACKGROUND: Transoral incisionless fundoplication (TIF) with Medigus Ultrasonic Surgical Endostapler (MUSE) is a new intervention for treatment of gastro-esophageal reflux disease (GERD). We aimed at assessing the clinical, functional, and endoscopic effects of TIF by MUSE. METHODS: Forty-six patients underwent TIF. Proton pump inhibitor (PPI) consumption, GERD-health-related quality of life (HRQL) and reflux symptom index (RSI) questionnaires, upper gastrointestinal (GI) endoscopy, esophageal 24-h pH-impedance recording, and high-resolution manometry (HRM) were done before TIF and scheduled 6 and 12 months later (HRM only at 6-month). PPI consumption and symptoms were then assessed yearly. Data up to 3 years are reported in this study (PP- and ITT-analysis). RESULTS: TIF was successfully performed in 45/46 patients; in one patient esophageal intubation was impossible. Perforation occurred in two cases. One patient required surgery within 6 months. Clinical follow-up was available for 42 patients at 6 months and 1 year, 35 patients at 2 years, and 31 patients at 3 years. At 1, 2, and 3 years, PPI consumption was stopped, respectively, in 64.3%, 62.9%, and 74.2% of cases (ITT-analysis: 58.7%, 56.4%, and 65.7%). GERD-HRQL and RSI scores decreased at least 50%, respectively, in 71.5% and 76.2%, 71.4% and 68.6%, and 67.7% of cases (ITT-analysis: 65.2% and 69.6%, 64.1% and 61.5%, and 60%). A significant improvement of both scores was observed up to 3 years. 6-month and 1-year functional follow-up were possible in 31 and 20 patients. HRM showed significant increase of the median lower esophageal sphincter length and rate of peristaltic waves. Esophageal pH-impedance recording found significantly fewer acid, proximal and total refluxes, and percentage of esophageal pH < 4 total time at 6 months, but not at 1 year. CONCLUSION: TIF by MUSE significantly improved symptoms and PPIs consumption up to 3 years. However, esophagitis still persisted in one-third of cases at 1 year and functional improvement at 6 months was not confirmed at 1 year. Severe complications requiring surgery occurred in two cases. CLINICALTRIALS: GOV: ID: NCT03669874.

Treatment with rapamycin can restore regulatory T-cell function in IPEX patients.

BACKGROUND: Immune-dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a lethal disease caused by mutations in a transcription factor critical for the function of thymus-derived regulatory T (Treg) cells (ie, FOXP3), resulting in impaired Treg function and autoimmunity. At present, hematopoietic stem cell transplantation is the therapy of choice for patients with IPEX syndrome. If not available, multiple immunosuppressive regimens have been used with poor disease-free survival at long-term follow-up. Rapamycin has been shown to suppress peripheral T cells while sparing Treg cells expressing wild-type FOXP3, thereby proving beneficial in the clinical setting of immune dysregulation. However, the mechanisms of immunosuppression selective to Treg cells in patients with IPEX syndrome are unclear. OBJECTIVE: We sought to determine the cellular and molecular basis of the clinical benefit observed under rapamycin treatment in 6 patients with IPEX syndrome with different FOXP3 mutations. METHODS: Phenotype and function of FOXP3-mutated Treg cells from rapamycin-treated patients with IPEX syndrome were tested by flow cytometry and in vitro suppression assays, and the gene expression profile of rapamycin-conditioned Treg cells by droplet-digital PCR. RESULTS: Clinical and histologic improvements in patients correlated with partially restored Treg function, independent of FOXP3 expression or Treg frequency. Expression of TNF-receptor-superfamily-member 18 (TNFRSF18, glucocorticoid-induced TNF-receptor-related) and EBV-induced-3 (EBI3, an IL-35 subunit) in patients' Treg cells increased during treatment as compared with that of Treg cells from untreated healthy subjects. Furthermore inhibition of glucocorticoid-induced TNF-receptor-related and Ebi3 partially reverted in vitro suppression by in vivo rapamycin-conditioned Treg cells. CONCLUSIONS: Rapamycin is able to affect Treg suppressive function via a FOXP3-independent mechanism, thus sustaining the clinical improvement observed in patients with IPEX syndrome under rapamycin treatment.

Transoral incisionless fundoplication with an ultrasonic surgical endostapler for the treatment of gastroesophageal reflux disease: 12-month outcomes.

BACKGROUND: Transoral incisionless fundoplication (TIF) with the Medigus ultrasonic surgical endostapler (MUSE) is a new intervention for the treatment of the gastroesophageal reflux disease (GERD). The aim of this study was to assess the 12-month clinical, functional, and endoscopic effects of TIF by MUSE. METHODS: Patients undergoing MUSE completed the GERD-Health Related Quality of Life (GERD-HRQL) and Reflux Symptom Index (RSI) questionnaires, and underwent endoscopy, esophageal 24-hour pH-impedance recording, and high resolution manometry (HRM) before the TIF procedure and 12 months later, or after 6 months for HRM. RESULTS: Among the 37 patients treated, esophageal intubation was not possible in one and esophageal perforation occurred in another. Clinical and endoscopic follow-up at 12 months was completed in 20 patients, with significant improvements in GERD-HRQL, RSI, heartburn, regurgitation scores, and proton pump inhibitor (PPI) consumption observed. One patient required surgery for persisting symptoms. Functional follow-up was possible in 13 patients and showed no significant improvements in the analyzed parameters. CONCLUSIONS: TIF with MUSE significantly improved symptoms at 1-year follow-up, allowing the consumption of PPIs to be stopped or halved in 90 % of patients.

G-EYE colonoscopy is superior to standard colonoscopy for increasing adenoma detection rate: an international randomized controlled trial (with videos).

BACKGROUND AND AIMS: Colorectal cancer (CRC) is largely preventable with routine screening and surveillance colonoscopy; however, interval cancers arising from precancerous lesions missed by standard colonoscopy still occur. An increased adenoma detection rate (ADR) has been found to be inversely associated with interval cancers. The G-EYE device includes a reusable balloon integrated at the distal tip of a standard colonoscope, which flattens haustral folds, centralizes the colonoscope's optics, and reduces bowel slippage. The insufflated balloon also aims to enhance visualization of the colon during withdrawal, thereby increasing the ADR. METHODS: In this randomized, controlled, international, multicenter study (11 centers), patients (aged ≥50 years) referred to colonoscopy for screening, surveillance, or changes in bowel habits were randomized to undergo either balloon-assisted colonoscopy by using an insufflated balloon during withdrawal or standard high-definition colonoscopy. The primary endpoint was the ADR. RESULTS: One thousand patients were enrolled between May 2014 and September 2016 to undergo colonoscopy by experienced endoscopists; 803 were finally analyzed (standard colonoscopy n = 396; balloon-assisted colonoscopy n = 407). Baseline parameters were similar in both groups. Balloon-assisted colonoscopy provided a 48.0% ADR compared with 37.5% in the standard colonoscopy group (28% increase; P = .0027). Additionally, balloon-assisted colonoscopy provided for a significant increase in detection of advanced (P = .0033) flat adenomas (P < .0001) and sessile serrated adenomas/polyps (P = .0026). CONCLUSION: Balloon-assisted colonoscopy yielded a higher ADR and increased the detection of advanced, flat, and sessile serrated adenomas/polyps when compared with standard colonoscopy. Improved detection by the G-EYE device could impact the quality of CRC screening by reducing miss rates and consequently reducing interval cancer incidence. (Clinical trial registration number: NCT01917513.).

Common variants in the CLDN2-MORC4 and PRSS1-PRSS2 loci confer susceptibility to acute pancreatitis.

BACKGROUND/OBJECTIVES: Acute pancreatitis (AP) is one of the most common gastrointestinal disorders often requiring hospitalization. Frequent aetiologies are gallstones and alcohol abuse. In contrast to chronic pancreatitis (CP) few robust genetic associations have been described. Here we analysed whether common variants in the CLDN2-MORC4 and the PRSS1-PRSS2 locus that increase recurrent AP and CP risk associate with AP. METHODS: We screened 1462 AP patients and 3999 controls with melting curve analysis for SNPs rs10273639 (PRSS1-PRSS2), rs7057398 (RIPPLY), and rs12688220 (MORC4). Calculations were performed for the overall group, aetiology, and gender sub-groups. To examine genotype-phenotype relationships we performed several meta-analyses. RESULTS: Meta-analyses of all AP patients depicted significant (p-value < 0.05) associations for rs10273639 (odds ratio (OR) 0.88, 95% confidence interval (CI) 0.81-0.97, p-value 0.01), rs7057398 (OR 1.27, 95% CI 1.07-1.5, p-value 0.005), and rs12688220 (OR 1.32, 95% CI 1.12-1.56, p-value 0.001). For the different aetiology groups a significant association was shown for rs10273639 (OR 0.76, 95% CI 0.63-0.92, p-value 0.005), rs7057398 (OR 1.43, 95% CI 1.07-1.92, p-value 0.02), and rs12688220 (OR 1.44, 95% CI 1.07-1.93, p-value 0.02) in the alcoholic sub-group only. CONCLUSIONS: The association of CP risk variants with different AP aetiologies, which is strongest in the alcoholic AP group, might implicate common pathomechanisms most likely between alcoholic AP and CP.

Resection outcomes and recurrence rates of endoscopic submucosal dissection (ESD) and hybrid ESD for colorectal tumors in a single Italian center.

BACKGROUND: Endoscopic submucosal dissection (ESD) and hybrid-ESD techniques are treatment modalities for colorectal neoplasia, although mostly used in the Eastern hemisphere. Only few data on ESD for colorectal neoplasia have been published in the West. We report the outcomes of colorectal ESD and hybrid ESD in a single Italian center. METHODS: We retrospectively evaluated the outcomes of all ESD and hybrid-ESD procedures for colorectal neoplasia performed over the first 2-year experience from a prospectively recorded database. Neuroendocrine tumors and adenocarcinoma with submucosal infiltration through the submucosal (SM) 2 layer or deeper were excluded. The primary outcome was the recurrence rate at the 6- to 12-month follow-up. RESULTS: Fifty-two patients were included in the study, of which 23 underwent ESD and 29 hybrid ESD. The mean lesion sizes for ESD and hybrid ESD were similar (25.8 vs. 25.4 mm, p = 0.940), while median procedure length was significantly longer for ESD (120 vs. 60 min, p < 0.001). ESD and hybrid ESD yielded similar en-bloc resection rate (82.6 vs. 82.8%) and R0 resection rate (34.8 vs. 31%). ESD had a lower neoplasia recurrence rate than hybrid ESD (11.7 vs. 20%) and a lower bleeding rate (0 vs. 8.7%). One perforation occurred in the hybrid-ESD cohort and two perforations in the ESD cohort, of which one required surgical intervention. Non-recurrence at follow-up was associated with R0 status, en-bloc resection, and lesion size ≤ 20 mm. CONCLUSION: Our outcomes are comparable with other studies in Western series. Studies addressing the cost effectiveness of ESD and comparing its long-term outcome with endoscopic mucosal resection in the West are needed.

Early precut sphincterotomy for difficult biliary access to reduce post-ERCP pancreatitis: a randomized trial.

BACKGROUND AND STUDY AIM: Precut sphincterotomy is a technique usually employed for difficult biliary cannulation during endoscopic retrograde cholangiopancreatography (ERCP) for the treatment of bile duct disease. It is a validated risk factor for post-ERCP pancreatitis (PEP), but it is not clear whether the risk is related to the technique itself or to the repeated biliary cannulation attempts preceding it. The primary aim of the study was to assess the incidence of PEP in early precut compared with the standard technique in patients with difficult biliary cannulation. Secondary aims were to compare complications and cannulation success. PATIENTS AND METHODS: In this prospective, multicenter, randomized, clinical trial, patients who were referred for therapeutic biliary ERCP and difficult biliary cannulation were randomized to early precut (Group A) or repeated papillary cannulation attempts followed, in cases of failure, by late precut (Group B). PEP was defined as the onset of upper abdominal pain associated with an elevation in serum pancreatic enzymes of at least three times the normal level at more than 24 hours after the procedure. No rectal indomethacin or diclofenac was used for prevention of PEP. RESULTS: A total of 375 patients were enrolled. PEP developed in 10 of the 185 patients (5.4 %) in Group A and 23 of the 190 (12.1 %) in Group B (odds ratio [OR] 0.35; 95 % confidence interval [CI] 0.16 - 0.78). The incidence of PEP was significantly lower in the early precut group (10/185, 5.4 %) than in the delayed precut subgroup (19/135 [14.1 %]; OR 0.42, 95 %CI 0.17 - 1.07). There were no differences in biliary cannulation success rates, bleeding, perforation, and cholangitis. CONCLUSIONS: In patients with difficult biliary cannulation, early precut is an effective technique and can significantly reduce the incidence of PEP. Repeated biliary cannulation attempts are a real risk factor for this complication.

Papillary cannulation and sphincterotomy techniques at ERCP: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline.

This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). It provides practical advice on how to achieve successful cannulation and sphincterotomy at minimum risk to the patient. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was adopted to define the strength of recommendations and the quality of evidence. Main recommendations 1 ESGE suggests that difficult biliary cannulation is defined by the presence of one or more of the following: more than 5 contacts with the papilla whilst attempting to cannulate; more than 5 minutes spent attempting to cannulate following visualization of the papilla; more than one unintended pancreatic duct cannulation or opacification (low quality evidence, weak recommendation). 2 ESGE recommends the guidewire-assisted technique for primary biliary cannulation, since it reduces the risk of post-ERCP pancreatitis (moderate quality evidence, strong recommendation). 3 ESGE recommends using pancreatic guidewire (PGW)-assisted biliary cannulation in patients where biliary cannulation is difficult and repeated unintentional access to the main pancreatic duct occurs (moderate quality evidence, strong recommendation). ESGE recommends attempting prophylactic pancreatic stenting in all patients with PGW-assisted attempts at biliary cannulation (moderate quality evidence, strong recommendation). 4 ESGE recommends needle-knife fistulotomy as the preferred technique for precutting (moderate quality evidence, strong recommendation). ESGE suggests that precutting should be used only by endoscopists who achieve selective biliary cannulation in more than 80 % of cases using standard cannulation techniques (low quality evidence, weak recommendation). When access to the pancreatic duct is easy to obtain, ESGE suggests placement of a pancreatic stent prior to precutting (moderate quality evidence, weak recommendation). 5 ESGE recommends that in patients with a small papilla that is difficult to cannulate, transpancreatic biliary sphincterotomy should be considered if unintentional insertion of a guidewire into the pancreatic duct occurs (moderate quality evidence, strong recommendation).In patients who have had transpancreatic sphincterotomy, ESGE suggests prophylactic pancreatic stenting (moderate quality evidence, strong recommendation). 6 ESGE recommends that mixed current is used for sphincterotomy rather than pure cut current alone, as there is a decreased risk of mild bleeding with the former (moderate quality evidence, strong recommendation). 7 ESGE suggests endoscopic papillary balloon dilation (EPBD) as an alternative to endoscopic sphincterotomy (EST) for extracting CBD stones < 8 mm in patients without anatomical or clinical contraindications, especially in the presence of coagulopathy or altered anatomy (moderate quality evidence, strong recommendation). 8 ESGE does not recommend routine biliary sphincterotomy for patients undergoing pancreatic sphincterotomy, and suggests that it is reserved for patients in whom there is evidence of coexisting bile duct obstruction or biliary sphincter of Oddi dysfunction (moderate quality evidence, weak recommendation). 9 In patients with periampullary diverticulum (PAD) and difficult cannulation, ESGE suggests that pancreatic duct stent placement followed by precut sphincterotomy or needle-knife fistulotomy are suitable options to achieve cannulation (low quality evidence, weak recommendation).ESGE suggests that EST is safe in patients with PAD. In cases where EST is technically difficult to complete as a result of a PAD, large stone removal can be facilitated by a small EST combined with EPBD or use of EPBD alone (low quality evidence, weak recommendation). 10 For cannulation of the minor papilla, ESGE suggests using wire-guided cannulation, with or without contrast, and sphincterotomy with a pull-type sphincterotome or a needle-knife over a plastic stent (low quality evidence, weak recommendation).When cannulation of the minor papilla is difficult, ESGE suggests secretin injection, which can be preceded by methylene blue spray in the duodenum (low quality evidence, weak recommendation). 11 In patients with choledocholithiasis who are scheduled for elective cholecystectomy, ESGE suggests intraoperative ERCP with laparoendoscopic rendezvous (moderate quality evidence, weak recommendation). ESGE suggests that when biliary cannulation is unsuccessful with a standard retrograde approach, anterograde guidewire insertion either by a percutaneous or endoscopic ultrasound (EUS)-guided approach can be used to achieve biliary access (low quality evidence, weak recommendation). 12 ESGE suggests that in patients with Billroth II gastrectomy ERCP should be performed in referral centers, with the side-viewing endoscope as a first option; forward-viewing endoscopes are the second choice in cases of failure (low quality evidence, weak recommendation). A straight standard ERCP catheter or an inverted sphincterotome, with or without the guidewire, is recommended by ESGE for biliopancreatic cannulation in patients who have undergone Billroth II gastrectomy (low quality evidence, strong recommendation). Endoscopic papillary ballon dilation (EPBD) is suggested as an alternative to sphincterotomy for stone extraction in the setting of patients with Billroth II gastrectomy (low quality evidence, weak recommendation).In patients with complex post-surgical anatomy ESGE suggests referral to a center where device-assisted enteroscopy techniques are available (very low quality evidence, weak recommendation).

Long-term efficacy of transoral incisionless fundoplication with Esophyx (Tif 2.0) and factors affecting outcomes in GERD patients followed for up to 6 years: a prospective single-center study.

BACKGROUND: Transoral incisionless fundoplication (TIF) with the EsophyX™ device creates an antireflux valve with good functional results in patients with gastro-esophageal reflux disease (GERD). The aim of this study was to assess the long-term effect of TIF 2.0 on pathological reflux and symptoms in GERD patients with daily dependence on proton pump inhibitors (PPI). METHODS: Fifty patients underwent TIF. All underwent GERD-HRQL and GERD-QUAL questionnaires, upper GI endoscopy, esophageal manometry, and 24-h pH-impedance before and 6, 12, and 24 months after TIF, and subsequent yearly clinical re-evaluation. RESULTS: Patients were followed for up to six years (mean 52.7 ± 19.7 months). In all, 83.7, 79.6, 87.8, and 84.4% of patients stopped or halved the PPI therapy 6, 12, 24, and 36 months after TIF. Three-year figure remained stable up to 6 years. Symptom scores off PPI were significantly lower at 6, 12, 24, and 36 months. At 6 months, Hill's grade I of the newly created valve persisted in all pre-procedure Hill's grade I patients, in 66.7% of grade II and 58.3% of grade III. This figure remained substantially unchanged at 12 and 24 months, too. Impedance monitoring indicated significantly fewer total and acid refluxes after treatment (p = 0.01). Factors predicting good outcomes were pre-procedure Hill's grade I-II, no hiatal hernia or hernia ≤2 cm (p = 0.03), absence of ineffective esophageal motility (p < 0.0001), and number of fasteners deployed (p = 0.01). CONCLUSIONS: TIF by the EsophyX achieved lasting elimination of daily dependence on PPI in 75-80% of patients for up to 6 years. TIF seems an effective therapy for selected symptomatic GERD patients.

Pancreatic abnormalities detected by endoscopic ultrasound (EUS) in patients without clinical signs of pancreatic disease: any difference between standard and Rosemont classification scoring?

BACKGROUND: The prevalence of nine EUS features of chronic pancreatitis (CP) according to the standard Wiersema classification has been investigated in 489 patients undergoing EUS for an indication not related to pancreatico-biliary disease. We showed that 82 subjects (16.8%) had at least one ductular or parenchymal abnormality. Among them, 18 (3.7% of study population) had ≥3 Wiersema criteria suggestive of CP. Recently, a new classification (Rosemont) of EUS findings consistent, suggestive or indeterminate for CP has been proposed. AIM: To stratify healthy subjects into different subgroups on the basis of EUS features of CP according to the Wiersema and Rosemont classifications and to evaluate the agreement in the diagnosis of CP with the two scoring systems. Weighted kappa statistics was computed to evaluate the strength of agreement between the two scoring systems. Univariate and multivariate analysis between any EUS abnormality and habits were performed. RESULTS: Eighty-two EUS videos were reviewed. Using the Wiersema classification, 18 subjects showed ≥3 EUS features suggestive of CP. The EUS diagnosis of CP in these 18 subjects was considered as consistent in only one patient, according to Rosemont classification. Weighted Kappa statistics was 0.34 showing that the strength of agreement was 'fair'. Alcohol use and smoking were identified as risk factors for having pancreatic abnormalities on EUS. CONCLUSIONS: The prevalence of EUS features consistent or suggestive of CP in healthy subjects according to the Rosemont classification is lower than that assessed by Wiersema criteria. In that regard the Rosemont classification seems to be more accurate in excluding clinically relevant CP. Overall agreement between the two classifications is fair.

pH-Impedance Findings and proton pump inhibitors-responsiveness in patients with typical gastroesophageal reflux disease symptoms in a large single-center Italian series.

INTRODUCTION: A multicenter study with a limited sample size found that absence of esophagitis, presence of functional digestive disorders, and overweight were associated with proton pump inhibitors (PPI) failure. AIM: To assess clinical and reflux patterns associated with PPI-responsiveness. MATERIALS AND METHODS: Patients with typical gastroesophageal reflux disease (GORD) symptoms had 24 hours pH-impedance monitoring off therapy. Responders had <2 days of symptoms per week while on standard-dose/double-dose PPI. Clinical and reflux parameters were considered for analysis. RESULTS: A total of 514 patients were included (267 women), 185 patients were considered PPI responders, and 329 were considered nonresponders. In the whole population, the only significant factor in the prediction of responsiveness to PPI at the multivariate analysis was the presence of esophagitis (P=0.028). The factors identified as significant in patients with a pathologic acid exposure (142 patients) in the prediction of responsiveness to PPI were overweight (body mass index >25 kg/m(2)) and the presence of esophagitis (P=0.019 and 0.043, respectively). CONCLUSIONS: We confirm that no reflux pattern demonstrated by 24 hours pH-impedance monitoring is associated to PPI response in GORD patients. Presence of esophagitis in the whole population and overweight in patients with pathologic GORD, but not dyspepsia, are strongly associated with PPI-responsiveness.

Interobserver agreement among pathologists regarding core tissue specimens obtained with a new endoscopic ultrasound histology needle; a prospective multicentre study in 50 cases.

AIM: To evaluate the interobserver agreement among pathologists in grading the quality of specimens obtained with a new 19-gauge endoscopic ultrasound histology needle. METHODS AND RESULTS: This multicentre prospective study involved 50 slides prepared using material obtained with the new needle. Five experienced pathologists independently reviewed all of the samples, and made assessments of the following features: the presence of a core, the adequacy of the specimen, the interpretability of the specimen, and the possibility of performing additional analyses using the material. Interobserver agreement, determined by Fleiss' kappa statistic and 95% confidence intervals (CIs), was used as the primary outcome measure. Overall, the presence of a core was reported in 88% of cases with good agreement among the pathologists (κ = 0.61; 95% CI 0.52-0.70). The specimens were adequate in 91.2% of cases, and Fleiss' κ was 0.73 (95% CI 0.61-0.81). The interpretation of the specimens was reported to be 'easy' in approximately 87% of cases, with moderate agreement among the pathologists (κ = 0.44; 95% CI 0.35-0.53). The possibility of performing additional analyses from the same sample was rated as positive in approximately 91%, with good agreement (κ = 0.66; 95% CI 0.58-0.75). CONCLUSIONS: There was excellent interobserver agreement among pathologists in the assessment of the histological material, especially with regard to sample adequacy.

Cost-effectiveness Analysis of Radiofrequency Ablation in Patients With Barrett Esophagus and High-grade Dysplasia or Low-grade Dysplasia.

PURPOSE: Clinical guidelines recommend radiofrequency ablation (RFA) for eradication of Barrett esophagus in patients with low-grade dysplasia (LGD) and high-grade dysplasia (HGD), but evidence on whether RFA provides good value for money is still sparse. This study evaluates the cost-effectiveness of RFA in Italy. METHODS: A Markov model was used to estimate lifelong costs and consequences of disease progression with different treatments. RFA was compared with esophagectomy in the HGD group or endoscopic surveillance in the LGD group. Clinical and quality-of-life parameters were derived from a review of the literature and expert opinions, whereas Italian national tariffs were used as a proxy for costs. FINDINGS: RFA dominated esophagectomy in patients with HGD with a probability of 83%. For patients with LGD, RFA was more effective and more costly than active surveillance (incremental cost-effectiveness ratio, €6276 per quality-adjusted life-year). At a cost-effectiveness threshold of €15,272, the probability of RFA being the optimal strategy in this population was close to 100%. Model results were sensitive to the cost of the interventions and utility weights used in the different disease states. IMPLICATIONS: RFA is likely to be the optimal choice for patients with LGD and HGD in Italy. Italy is discussing the implementation of a national program for the health technology assessment of medical devices, requiring more studies to prove value for money of emerging technologies.

An Italian prospective multicenter study on colonoscopy practice and quality: What has changed in the last 10 years.

BACKGROUND: A relevant number of adenomas can be missed during colonoscopy. AIMS: Assess the current status of colonoscopy procedures in Italian centers. METHODS: A prospective observational study involving 17 hospitals (34 endoscopists) included consecutive patients undergoing standard colonoscopy. In the first phase, endoscopists performed consecutive colonoscopies. In the second phase, retraining via an online learning platform was planned, while in the third phase data were collected analogously to phase 1. RESULTS: A total of 3,504 patients were enrolled. Overall, a BBPS score ≥6 was obtained in 95.6% of cases (94.8% and 96.9% in the pre- and post-training phases, respectively). 88.4% of colonoscopies had a withdrawal time ≥6 min (88.2% and 88.7% in the pre- and post-training phases). Median adenoma detection rate (ADR) was 39.1%, with no significant differences between the pre- and post-training phases (40.1% vs 36.9%; P = 0.83). In total, 81% of endoscopists had a ADR performance above the 25% threshold. CONCLUSION: High colonoscopy quality standards are achieved by the Italian hospitals involved. Quality improvement initiatives and repeated module-based colonoscopy-training have been promoted in Italy during the last decade, which appear to have had a significant impact on quality colonoscopy metrics together with the activation of colorectal cancer screening programs.

Factors influencing the presence of potentially explosive gases during colonoscopy: Results of the SATISFACTION study.

This study tested the hypothesis that bowel preparation with mannitol should not affect the colonic concentration of H2 and CH4 . Therefore, the SATISFACTION study, an international, multicenter, randomized, parallel-group phase II-III study investigated this issue. The phase II dose-finding part of the study evaluated H2 , CH4 , and O2 concentrations in 179 patients randomized to treatment with 50 g, 100 g, or 150 g mannitol. Phase III of the study compared the presence of intestinal gases in 680 patients randomized (1:1) to receive mannitol 100 g in single dose or a standard split-dose 2 L polyethylene glycol (PEG)-Asc preparation (2 L PEG-Asc). Phase II results showed that mannitol did not influence the concentration of intestinal gases. During phase III, no patient in either group had H2 or CH4 concentrations above the critical thresholds. In patients with H2 and/or CH4 levels above detectable concentrations, the mean values were below the risk thresholds by at least one order of magnitude. The results also highlighted the effectiveness of standard washing and insufflation maneuvers in removing residual intestinal gases. In conclusion, bowel cleansing with mannitol was safe as the concentrations of H2 and CH4 were the same as those found in patients prepared with 2 L PEG-Asc. In both groups, the concentrations of gases were influenced more by the degree of cleansing achieved and the insufflation and washing maneuvers performed than by the preparation used for bowel cleansing. The trial protocol was registered with ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT04759885) and with EudraCT (eudract_number: 2019-002856-18).

Guidewire biliary cannulation does not reduce post-ERCP pancreatitis compared with the contrast injection technique in low-risk and high-risk patients.

BACKGROUND: Guidewire (GW) cannulation can reduce the risk of post-ERCP pancreatitis (PEP) by avoiding the opacification of the main pancreatic duct. OBJECTIVE: To compare the effects of conventional contrast ERCP and GW cannulation of the common bile duct on the rate of PEP in low- and high-risk patients. DESIGN: Prospective, comparative-intervention single-center study. SETTING: Tertiary referral center. PATIENTS: Patients with biliary disease with an intact papilla were prospectively examined by ERCP. INTERVENTIONS: Biliary cannulation using a sphincterotome with contrast injection (ConI) or a hydrophilic GW without contrast injection. MAIN OUTCOME MEASUREMENTS: Pancreatitis rate in the GW group and the contrast injection (ConI) group. RESULTS: PEP occurred in 60 of 1249 patients (4.8%), 35 of 678 (5.2%) in the GW group and 25 of 571 (4.4%) in the ConI group (not significant). The overall rate of PEP was significantly higher in high-risk patients (12.2%) than in low-risk patients (3.5%) (P < .001), but was similar for the 2 techniques within each of these 2 groups. In patients with unintended main pancreatic duct (MPD) cannulation or opacification, the rate of PEP was not significantly different with the GW (15.2%) and ConI (8.4%) techniques but was associated with a significantly higher rate of pancreatitis (11.9%) than in patients in whom the contrast medium or GW did not enter the MPD (3.5%) (P < .001). Multivariate analysis indicated that more than 10 papillary cannulation attempts, MPD cannulation or opacification, suspected sphincter of Oddi dysfunction, and precut methods were significant risk factors independently associated with PEP. LIMITATIONS: Lack of randomization. CONCLUSIONS: For selective cannulation of the CBD, the risk of inducing PEP is similar with the ConI and GW techniques in high-risk and low-risk patients. Any manipulation of the MPD must be considered a high-risk factor for PEP, such as multiple attempts on the papilla or use of the precut method.