Intravenous Hemin, a potential heme oxygenase-1 activator, does not protect from post-ERCP acute pancreatitis in humans: Results of a randomized multicentric multinational placebo-controlled trial.

OBJECTIVE: Hemin, a heme oxygenase 1 activator has shown efficacy in the prevention and treatment of acute pancreatitis in mouse models. We conducted a randomized controlled trial (RCT) to assess the protective effect of Hemin administration to prevent post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in patients at risk. METHODS: In this multicenter, multinational, placebo-controlled, double-blind RCT, we assigned patients at risk for PEP to receive a single intravenous dose of Hemin (4 mg/kg) or placebo immediately after ERCP. Patients were considered to be at risk on the basis of validated patient- and/or procedure-related risk factors. Neither rectal NSAIDs nor pancreatic stent insertion were allowed in randomized patients. The primary outcome was the incidence of PEP. Secondary outcomes included lipase elevation, mortality, safety, and length of stay. RESULTS: A total of 282 of the 294 randomized patients had complete follow-up. Groups were similar in terms of clinical, laboratory, and technical risk factors for PEP. PEP occurred in 16 of 142 patients (11.3%) in the Hemin group and in 20 of 140 patients (14.3%) in the placebo group (p = 0.48). Incidence of severe PEP reached 0.7% and 4.3% in the Hemin and placebo groups, respectively (p = 0.07). Significant lipase elevation after ERCP did not differ between groups. Length of hospital stay, mortality and severe adverse events rates were similar between groups. CONCLUSION: We failed to detect large improvements in PEP rate among participants at risk for PEP who received IV hemin immediately after the procedure compared to placebo. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number, NCT01855841).

Endoscopic internal drainage of complex bilomas and biliary leaks by transmural or transpapillary/transfistulary access.

BACKGROUND AND AIMS: Bilomas most frequently result from postoperative bile leaks. The endoscopic conventional treatment is sphincterotomy ± stent placement. In complex cases, such as altered anatomy or failure of conventional treatment, transpapillary/transfistulary (TP/TF) drainage or EUS-guided transmural drainage (EUS-TD) may obviate additional biliary surgery. This study reports our experience with treating biloma secondary to refractory biliary leak with TP/TF drainage or EUS-TD and evaluates the safety and outcomes associated with this approach. METHODS: This observational study focused on consecutive patients managed for biliary leakage (diagnosis based on imaging and/or bile outflow from a surgical drain) at a tertiary care hospital (2007-2017). TP/TF drainage was performed by double-pigtail stent(s) placement to drain the biloma through the leak during ERCP. For EUS-TD, plastic stent(s) were placed under EUS control. Primary outcomes were a composite of clinical success (patient free of sepsis after percutaneous drain removal and, in patients with benign disease, removal of all endoscopically placed stents, without need for reintervention) and biloma regression (<3 cm) at last follow-up. RESULTS: Thirty patients (men, 57%; median age, 55 years) were included. Most biliary leaks resulted from cholecystectomy (27%) and hepatectomy (50%). Initial EUS-TD and TP/TF drainage were performed in 14 (47%) and 16 (53%) patients, respectively. At last follow-up (median, 33.2 months), clinical success and primary outcome were achieved in 70.4% of patients (EUS-TD, 75%; TP/TF, 67%). Additional surgery was necessary in 1 patient. Rate of serious adverse events was 23% (7/30), of which 13% (4/30) were procedure related. There were 4 deaths during the course of treatment, 2 of which were related to endoscopic interventions (hemorrhage and fibrillation). CONCLUSIONS: TP/TF drainage or EUS-TD is technically feasible with high clinical success and may avoid the need for additional surgery in complex cases or in patients with altered anatomy.

Biliary cast syndrome after liver transplantation: A cholangiographic evolution study.

BACKGROUND AND AIM: The aim of this study is to describe the cholangiographic features and endoscopic management of biliary cast syndrome (BCS), a rare specific ischemic cholangiopathy following liver transplantation. METHODS: Patients with biliary complications were identified from prospectively collected database records of patients who underwent liver transplantation at the Erasme Hospital from January 2005 to December 2014. After excluding patients with hepatico-jejunostomy or no suspicion of stricture, cholangiograms obtained during endoscopic retrograde cholangiopancreatography (ERCP) and magnetic resonance imaging were systematically reviewed. Biliary complications were categorized as anastomotic (AS) and non-AS strictures, and patients with BCS were identified. Clinical, radiological, and endoscopic data were reviewed. RESULTS: Out of 311 liver transplantations, 14 cases were identified with BCS (4.5%) and treated with ERCP. Intraductal hyperintense signal on T1-weighted magnetic resonance and a "duct-in-a-duct" image were the most frequent features of BCS on magnetic resonance imaging. On initial ERCP, 57% of patients had no stricture. Complete cast extraction was achieved in 12/14, and one of these had cast recurrence. On follow-up, 85% of the patients developed biliary strictures that were treated with multiple plastic stents reaching 60% complete stricture resolution, but 40% of them had recurrence. After a median follow-up of 58 months, BCS patients had lower overall and graft survival (42.9% and 42.9%) compared with non-AS (68.8% and 56.3%) and AS (83.3% and 80.6%), respectively. CONCLUSIONS: Particular magnetic resonance-cholangiographic and ERCP-cholangiographic features of BCS have been identified. Outcomes for BCS are characterized by high complete cast extraction rates, high incidence of secondary strictures, and poorer prognosis.

Trans-fistulary endoscopic drainage for post-bariatric abdominal collections communicating with the upper gastrointestinal tract.

BACKGROUND AND STUDY AIMS: Diverse endoscopic methods, such as placement of temporary self-expandable stents, have proven effective for the treatment of post-bariatric surgery leaks. However, some patients do not respond to the usual endoscopic treatment. This study tested the efficacy of an alternative treatment strategy based on trans-fistulary drainage with double-pigtail plastic stents. PATIENTS AND METHODS: We performed a retrospective analysis of patients with abdominal collections following bariatric surgery who were treated by trans-fistulary stenting between May 2007 and February 2015. Clinical success was defined as a sustained (> 4 months) clinical resolution (patient discharged from the hospital without antibiotics and able to resume a normal diet) and radiological response. Patient records, radiological images, and the hospital endoscopy database were reviewed. RESULTS: A total of 33 patients (26 women/7 men, mean age 42 years [SD 11.2]) were included. Collections occurred after sleeve gastrectomy (n = 28) or after gastric bypass (n = 5). Fourteen patients were treated by trans-fistulary stenting as primary treatment, and 19 patients had undergone previous unsuccessful endoscopic treatment. No serious complication occurred during the drainage procedure. Clinical success was achieved in 26 patients (78.8 %). In two successfully treated patients, stents are still in place. Spontaneous stent migration occurred in 12 patients. In 12 patients, the stents were removed, either electively (n = 5) or because of complications (ulcerations n = 3, upper gastrointestinal symptoms n = 3, splenic hematoma n = 1). CONCLUSIONS: Trans-fistulary drainage of post-bariatric abdominal collections is safe and associated with high success rates. This technique can be considered in previously untreated patients, when a collection is not properly drained percutaneously, or after failure of other endoscopic treatments.

European Society of Gastrointestinal Endoscopy - Establishing the key unanswered research questions within gastrointestinal endoscopy.

Background and study aim: Gastrointestinal endoscopy is a rapidly evolving research field. The European Society of Gastrointestinal Endoscopy (ESGE) plays a key role in shaping opinion and endoscopy activity throughout Europe and further afield. Establishing key unanswered questions within the field of endoscopy and prioritizing those that are important enables researchers and funders to appropriately allocate resources. Methods: Over 2 years, the ESGE Research Committee gathered information on research priorities and refined them through a modified Delphi approach. Consultations were held with the ESGE Governing Board and Quality Improvement Committee to identify important unanswered questions. Research workshops were held at the 21st United European Gastroenterology Week. Research questions were refined by the ESGE Research Committee and Governing Board, compiled into an online survey, and distributed to all ESGE members, who were invited to rank each question by priority. Results: The final questionnaire yielded 291 responses from over 60 countries. The three countries with the highest response rates were Spain, Italy, and United Kingdom. Most responders were from teaching hospitals (62 %) and were specialist endoscopists (51 %). Responses were analyzed with weighted rankings, resulting in prioritization of 26 key unanswered questions. The top ranked generic questions were: 1) How do we define the correct surveillance interval following endoscopic diagnosis? 2) How do we correctly utilize advanced endoscopic imaging? 3) What are the best markers of endoscopy quality? Conclusion: Following this comprehensive process, the ESGE has identified and ranked the key unanswered questions within the field of gastrointestinal endoscopy. Researchers, funders, and journals should prioritize studies that seek to answer these important questions.

The ST2 pathway is involved in acute pancreatitis: a translational study in humans and mice.

Acute pancreatitis (AP) is an inflammatory disease in which the regulatory pathways are not clearly elucidated. Activation of interleukin 1ß (IL-1ß) and immunomodulation via MyD88, the first signaling molecule in the ST2 pathway, seem to be involved. Because IL-33, the ST2 ligand, is an IL-1 family member and acts as an alarmin, we explored the ST2 pathway in human and mouse AP. Soluble ST2 was assayed by enzyme-linked immunosorbent assay (ELISA) in plasma of 44 patients admitted for AP. The levels of soluble ST2 increased early during AP and correlated with parameters of severity. Under two different experimental models of AP (ie, choline-deficient-ethionine-supplemented diet and cerulein injections), ST2-deficient mice (Il1rl1(-/-)) presented with more severe disease than wild-type mice, with increased activation of mast cells. In vitro, Il1rl1(-/-) bone-marrow-derived mast cells exhibited exacerbated degranulation, compared with the wild type. Flow cytometry identified mast cells as the main peritoneal population expressing ST2. Using immunohistochemistry and ELISA, we showed constitutive expression of IL-33 in murine pancreas and its release during experimental AP. Correlated with AP severity, increased soluble ST2 levels evoke involvement of the ST2 pathway in human AP. Furthermore, our experimental data suggest a protective role for ST2 during AP, highlighting the potential regulatory role of mast cells and the possibility of the ST2 pathway as a new therapeutic target in AP.

Endoscopic treatment for Zenker's diverticulum: long-term results (with video).

BACKGROUND: Diverticulotomy is a standard treatment for Zenker's diverticulum (ZD). This technique was adapted to flexible endoscopy. OBJECTIVE: We report our long-term results of ZD treatment by using flexible endoscopy assisted by a soft diverticuloscope. DESIGN: Follow-up study. SETTING: Academic hospital. Tertiary-care referral center. PATIENTS: A total of 150 patients with ZD were treated with the same technique from July 2002 to June 2011. INTERVENTION: The procedure was performed by using a soft diverticuloscope to expose the septum, which was then cut with a needle-knife, and the procedure was completed by use of endoclip placement at the bottom of the section. MAIN OUTCOME MEASUREMENTS: Symptoms were compared before and after the procedure, 1 month later, and at the end of follow-up. RESULTS: The median size of the ZD was 3 cm (range 1-8 cm). The endoscopic incision was performed in one session (range 1-3 sessions). Clinical success at 1 month was 90.3%. Four adverse events (2.2%) occurred and were managed conservatively. Symptom evaluation at 1 month and at the end of follow-up was obtained in 103 and 134 patients, respectively. The dysphagia score dropped from 1.88 to 0.29 (P < .01) and 0.34 (P < .05) at 1 month and at the end of follow-up, respectively (median 43 months, range 13-121 months). Regurgitations and chronic cough dropped from 73% and 27% to 11% and 2% at the end of follow-up, respectively. Symptom recurrence occurred in 31 patients (23.1%); among them 23 had a second treatment, and only 5 required a third one. LIMITATIONS: Retrospective study, single center. CONCLUSION: Endoscopic incision of ZD by using a soft diverticuloscope and completed by endoclips is safe and efficient at short term and long term.

Efficacy of endoscopic closure of acute perforations of the gastrointestinal tract.

BACKGROUND & AIMS: Acute perforations of the gastrointestinal tract are rare, severe complications of endoscopy that usually require surgical repair. Endoscopic repair of perforations would reduce the need for surgeries; we evaluated the efficacy and safety of endoscopic closure of acute perforations of the gastrointestinal tract by using a new clip device. METHODS: We conducted a prospective, international, multicenter study of 36 consecutive patients (15 male) with acute iatrogenic perforations (5 esophageal, 6 gastric, 12 duodenal, and 13 colonic perforation). Endoscopic repair was performed by using the Over-the-Scope-Clip according to a standardized operating procedure. Primary end point was successful closure, which was determined as endoscopic successful closure without leakage (detected by water-soluble contrast x-ray analysis), and absence of adverse events within 30 days after the procedure. RESULTS: Immediate closure was endoscopically successful in 33 patients (92%). One patient developed an esophageal perforation while the cap was introduced, and in 2 patients the perforations did not close; these 3 patients were successfully treated with surgery. None of the patients had leakage of soluble contrast on the basis of contrast x-ray. One patient with a closed colonic perforation deteriorated clinically within 6 hours after the procedure. Despite surgery, the patient died within 36 hours. The remaining 32 patients had successful endoluminal closures; the overall success rate was 89% (95% confidence interval, 75%-96%). The mean endoscopic closure time was 5 minutes 44 seconds ± 4 minutes 15 seconds. CONCLUSIONS: The Over-the-Scope-Clip is effective for endoluminal closure of acute iatrogenic perforations. It allows patients to avoid surgery, and 89% of patients had successful closures without adverse events.

Common polymorphism in the PNPLA3/adiponutrin gene confers higher risk of cirrhosis and liver damage in alcoholic liver disease.

BACKGROUND & AIMS: A recent genome-wide association study identified genetic polymorphism (rs738409 C>G) in the PNPLA3/adiponutrin gene associated with liver steatosis. This variant has also been linked to increased risk of alcoholic liver disease (ALD) and cirrhosis in Mestizo Mexicans with excessive alcohol intake. Our aim was to study the influence of this polymorphism on European Caucasian patients with histologically suggestive ALD. METHODS: Three-hundred-and-twenty-eight healthy controls and 330 ALD patients, among whom 265 had cirrhosis, were genotyped for the rs738409 polymorphism. We studied the impact of rs738409 on clinical and biological parameters, together with histological staging of steatosis and fibrosis. PNPLA3 messenger RNA (mRNA) levels were measured by quantitative real-time PCR according to the patient's phenotype. RESULTS: The G-allele was significantly more frequent in ALD patients than in controls (odds ratio [OR] = 1.54, 95% confidence interval [CI] = 1.12-2.11 p = 0.008) and was, among ALD patients, significantly associated with steatosis (p = 0.048), fibrosis (p = 0.001), and greater risk of cirrhosis (p = 0.001). In multivariate analysis, rs738409 remained the strongest independent factor associated with risk of cirrhosis (OR = 2.08; 95% CI = 1.15-3.77; p = 0.02). Furthermore, the PNPLA3 mRNA liver expression level was significantly lower in patients with more advanced fibrosis (p = 0.03) and negatively correlated with the hepatic venous pressure gradient (r = -0.41, p = 0.006). CONCLUSIONS: In European Caucasians, the rs738409 variant is associated with increased risk of ALD, liver damage, and cirrhosis. Further prospective studies are required to confirm these results and to evaluate the potential of PNPLA3 as both a predictor and a therapeutic target in ALD.

Self-expandable metal stents for the treatment of benign upper GI leaks and perforations.

BACKGROUND: Self-expandable metal stents (SEMSs) have been suggested for the treatment of benign upper GI leaks and perforations. Nevertheless, uncomplicated removal remains difficult. Placement of a self-expandable plastic stent (SEPS) into an SEMS can facilitate retrieval. OBJECTIVES: This study reviews our experience with sequential SEMS/SEPS placement in patients with benign upper GI leaks or perforations. DESIGN: A retrospective review of the chart of each patient who underwent SEMS placement for benign upper GI leaks or perforations, including (1) fistula after bariatric surgery, (2) other postoperative fistulae, (3) Boerhaave syndrome, (4) iatrogenic perforations, and (5) other perforations. SETTING: Single, tertiary center. PATIENTS: Eighty-eight patients (37 male, average age 51.6 years, range 18-89 years). INTERVENTIONS: SEMS placement and removal, with or without SEPS placement. MAIN OUTCOME MEASUREMENTS: Feasibility of SEMS removal and successful treatment of lesions and short-term and long-term complications. RESULTS: A total of 153 SEMSs were placed in 88 patients; all placements were successful. Six patients died (not SEMS-related deaths) and 6 patients were lost to follow-up with SEMSs still in place. Seventy-three of the remaining 76 patients had successful SEMS removal (96.1%). The rate of successful SEMS removal per stent was 97.8% (132/135). Resolution of leaks and perforations was achieved in 59 patients (77.6%) with standard endoscopic treatment, and in 64 patients (84.2%) after prolonged, repeated endoscopic treatment. Spontaneous migration occurred in 11.1% of stents, and there were minor complications (dysphagia, hyperplasia, rupture of coating) in 20.9% and major complications (bleeding, perforation, tracheal compression) in 5.9%. LIMITATIONS: Retrospective design and highly selected patient population. CONCLUSIONS: Use of SEMSs for the treatment of benign upper GI leaks and perforations is feasible, relatively safe, and effective, and SEMSs can be easily removed 1 to 3 weeks after SEPS insertion. Leaks and perforations were closed in 77.6% of cases.

Transoral gastroplasty for morbid obesity: a multicenter trial with a 1-year outcome.

BACKGROUND: Bariatric surgery is associated with specific complications and mortality. Transoral gastroplasty (TOGA) is a transoral restrictive bariatric procedure that might offer the benefits of surgery with a reduced complication rate. OBJECTIVE: To evaluate the safety and efficacy of TOGA at 12-month follow-up. DESIGN: Prospective, multicenter, single-arm trial. SETTING: Two tertiary-care referral medical centers. PATIENTS: This study involved 67 patients (average age 41.0 years, 47 women, baseline body mass index [BMI] 41.5 kg/m(2); 20 patients with BMI <40). INTERVENTION: The TOGA procedures were performed by using 2 stapling devices that were used to create a small, restrictive pouch along the lesser gastric curvature. The pouch is designed to give the patient a sustained feeling of satiety after small meals. MAIN OUTCOME MEASUREMENTS: Excess weight loss, excess BMI loss, safety, and improvements in quality of life, obesity-related comorbidities, and medication use. RESULTS: Fifty-three patients were available at the 12-month follow-up. Excess BMI loss was 33.9%, 42.6%, and 44.8% at 3, 6, and 12 months, respectively. At 12 months, excess BMI loss was 52.2% for patients with a baseline BMI of <40.0 and 41.3% for patients with a baseline BMI of ≥ 40.0 (P < .05). At 12 months, hemoglobin A(1c) levels decreased from 7.0% at baseline to 5.7% (P = .01); triglyceride levels decreased from 142.9 mg/dL to 98 mg/dL (P < .0001); high-density lipoprotein levels increased from 47.0 mg/dL to 57.5 mg/dL (P < .0001). Two complications occurred: a case of respiratory insufficiency and an asymptomatic pneumoperitoneum treated conservatively. LIMITATIONS: Small number of patients. Short-term follow-up. Twenty-one percent of patients were not available for the 12-month follow-up. CONCLUSION: The TOGA procedure allowed a substantial weight loss 1 year after the operation without severe complications. A long-term evaluation is needed before definitive conclusions can be drawn.

Association between Functional Inhibitors of Acid Sphingomyelinase (FIASMAs) and Reduced Risk of Death in COVID-19 Patients: A Retrospective Cohort Study.

Given the current scarcity of curative treatment of COVID-19, the search for an effective treatment modality among all available medications has become a priority. This study aimed at investigating the role of functional inhibitors of acid sphingomyelinase (FIASMAs) on in-hospital COVID-19 mortality. In this retrospective cohort study, we included adult in-patients with laboratory-confirmed COVID-19 between 1 March 2020 and 31 August 2020 with definite outcomes (discharged hospital or deceased) from Erasme Hospital (Brussels, Belgium). We used univariate and multivariate logistic regression models to explore the risk factors associated with in-hospital mortality. We included 350 patients (205 males, 145 females) with a mean age of 63.24 years (SD = 17.4, range: 21-96 years). Seventy-two patients died in the hospital and 278 were discharged. The four most common comorbidities were hypertension (184, 52.6%), chronic cardiac disease (110, 31.4%), obesity (96, 27.8%) and diabetes (95, 27.1%). Ninety-three participants (26.6%) received a long-term prescription for FIASMAs. Among these, 60 (64.5%) received amlodipine. For FIASMAs status, multivariable regression showed increasing odds ratio (OR) for in-hospital deaths associated with older age (OR 1.05, 95% CI: 1.02-1.07; p = 0.00015), and higher prevalence of malignant neoplasm (OR 2.09, 95% CI: 1.03-4.22; p = 0.039). Nonsignificant decreasing OR (0.53, 95% CI: 0.27-1.04; p = 0.064) was reported for FIASMA status. For amlodipine status, multivariable regression revealed increasing OR of in-hospital deaths associated with older age (OR 1.04, 95% CI: 1.02-1.07; p = 0.0009), higher prevalence of hypertension (OR 2.78, 95% CI: 1.33-5.79; p = 0.0062) and higher prevalence of malignant neoplasm (OR 2.71, 95% CI: 1.23-5.97; p = 0.013), then secondarily decreasing OR of in-hospital death associated with long-term treatment with amlodipine (OR 0.24, 95% CI: 0.09-0.62; p = 0.0031). Chronic treatment with amlodipine could be significantly associated with low mortality of COVID-19 in-patients.

Implementation of colonoscopy quality monitoring in a Belgian university hospital with integrated computer-based extraction of adenoma detection rate.

Background and study aims Quality in colonoscopy has been promoted in last decade with definition of different quality indicators (QI) as benchmarks. Currently, automatized monitoring systems are lacking, especially for merging pathologic and endoscopic data, which limits quality monitoring implementation in daily practice. We describe an adapted endoscopy reporting system that allows continuous QI recording, with automatic pathological data inclusion. Material and methods We locally adapted a reporting system for colonoscopy by adding and structuring in a dedicated tab selected key QI. Endoscopic data from a reporting system and pathological results were extracted and merged in a separate database. During the initial period of use, performing physicians were encouraged to complete the dedicated tab on a voluntary basis. In a second stage, completing of the tab was made mandatory. The completeness of QI recording was evaluated across both periods. Performance measures for all endoscopists were compared to global results for the department and published targets. Results During the second semester of 2017, a total of 1827 colonoscopies were performed with a QI tab completed in 100 % of cases. Among key QI, the cecal intubation rate was 93.8 %, the rate of colonoscopies with adequate preparation was 90.7 %, and the adenoma detection rate was 29.8 % considering all colonoscopies, irrespective of indication; 28.8 % considering screening procedures; and 36.6 % in colonoscopies performed in people older than age 50 years. Conclusion This study shows that quality monitoring for colonoscopy can be easily implemented with limited human resources by adapting a reporting system and linking it to a pathology database.

Enteral nutrition with or without N-acetylcysteine in the treatment of severe acute alcoholic hepatitis: a randomized multicenter controlled trial.

BACKGROUND & AIMS: Severe acute alcoholic hepatitis is associated with a high mortality rate. Oxidative stress is involved in the pathogenesis of acute alcoholic hepatitis. Previous findings had also suggested that enteral nutritional support might increase survival in patients with severe acute alcoholic hepatitis. Therefore, the aim of the present study was to evaluate the efficacy of N-acetylcysteine in combination with adequate nutritional support in patients with severe acute alcoholic hepatitis. METHODS: Patients with biopsy-proven acute alcoholic hepatitis and mDF ≥32 were randomized to receive N-acetylcysteine intravenously or a placebo perfusion along with adequate nutritional support for 14 days. The primary endpoint was 6-month survival; secondary endpoints were biological parameter evolution and infection rate. RESULTS: Fifty-two patients were randomized in the study (28 into the N-acetylcysteine arm, 24 into the control arm), and among them, five were excluded from the analysis for protocol violation. The two groups did not differ in baseline characteristics. Survival rates at 1 and 6 months in N-acetylcysteine and control groups were 70.2 vs. 83.8% (p=0.26) and 62.4 vs. 67.1% (p=0.60), respectively. Early biological changes, documented infection rate at 1 month, and incidence of hepatorenal syndrome did not differ between the two groups. CONCLUSIONS: In this study, high doses of intravenous N-acetylcysteine therapy for 14 days conferred neither survival benefits nor early biological improvement in severe acute alcoholic hepatitis patients with adequate nutritional support. However, these results must be viewed with caution, since the study suffered from a lack of power.

The interleukin-17 pathway is involved in human alcoholic liver disease.

UNLABELLED: Immune dysregulations in alcoholic liver diseases are still unclear, especially regarding alcoholic hepatitis inflammatory burst. Interleukin-17 (IL-17) is known to enhance neutrophil recruitment. We studied the IL-17 pathway in alcoholic cirrhosis and alcoholic hepatitis. Patients with alcoholic liver disease were compared with patients with chronic hepatitis C virus (HCV) infection or autoimmune liver disease and with healthy controls. IL-17 plasma levels and peripheral blood mononuclear cell secretion were assessed by enzyme-linked immunosorbent assay (ELISA) and T cell phenotype by flow cytometry. IL-17 staining and co-staining with CD3 and myeloperoxidase were performed on liver biopsy specimens. IL-17 receptor expression was studied on liver biopsies and in human hepatic stellate cells as well as their response to recombinant IL-17 by chemotaxis assays. IL-17 plasma levels were dramatically increased in alcoholic liver disease patients. Peripheral blood mononuclear cells of patients with alcoholic liver disease produced higher amounts of IL-17, and their CD4(+) T lymphocytes disclosed an IL-17-secreting phenotype. In the liver, IL-17-secreting cells contributed to inflammatory infiltrates in alcoholic cirrhosis, and alcoholic hepatitis foci disclosed many IL-17(+) cells, including T lymphocytes and neutrophils. In alcoholic liver disease, liver IL-17(+) cells infiltrates correlated to model for end-stage liver disease score, and in alcoholic hepatitis to modified discriminant function. IL-17 receptor was expressed in alcoholic liver disease by hepatic stellate cells, and these cells recruited neutrophils after IL-17 stimulation in a dose-dependent manner through IL-8 and growth related oncogen alpha (GRO-alpha) secretion in vitro. CONCLUSION: Human alcoholic liver disease is characterized by the activation of the IL-17 pathway. In alcoholic hepatitis, liver infiltration with IL-17-secreting cell infiltrates is a key feature that might contribute to liver neutrophil recruitment. (Clinical trials number NCT00610597).

Endoscopic removal of dysfunctioning bands or rings after restrictive bariatric procedures.

BACKGROUND: Intragastric band migrations or dysfunctions are common long-term complications of both vertical banded gastroplasty (VBG) and laparoscopic adjustable gastric banding (Lap-Band) that classically require surgical treatment. OBJECTIVE: In this series, we describe the endoscopic removal of partially eroded Lap-Bands or Silastic rings and noneroded dysfunctioning rings after VBG. DESIGN: Case series. SETTING: A European, tertiary-care academic center. PATIENTS: This study involved 13 patients--3 with eroded Lap-Bands, 4 with eroded Silastic rings, and 6 with refractory outlet stoma stenosis after VBG. INTERVENTION: Endoscopic removal was performed within 1 or 2 sessions, according to the presence and extent of band erosion at presentation, including optional placement of a self-expandable plastic stent across the band, followed about 6 to 8 weeks later by extraction with transsection, if needed, by using a wire-cutting system. MAIN OUTCOME MEASUREMENTS: Technical success and safety. RESULTS: One failure was caused by huge adhesion formation around a Lap-Band on the lesser curvature of the stomach and the left liver lobe. Twelve of 13 endoscopic removals were successful in 1 (n = 2) and 2 (n = 10) sessions. LIMITATIONS: Highly selected patients (tertiary-case academic center). CONCLUSION: Endoscopic removal of dysfunctioning bands or rings is safe and feasible by the use of a 1- or 2-step endoscopic procedure.

Endoscopic magnetic gastroenteric anastomosis for palliation of malignant gastric outlet obstruction: a prospective multicenter study.

BACKGROUND: Palliation of malignant gastric outlet obstruction remains challenging. Although there are 2 established treatment options, ie, surgical gastrojejunostomy and endoscopic duodenal stent insertion, there is an ongoing search for a technique that would combine the safety and rapid effect of duodenal stent placement with the long-term efficacy and low reintervention rate of a surgical gastrojejunostomy. OBJECTIVE: To investigate the safety and success rate of endoscopic creation of a gastroenteric anastomosis formed by magnetic compression and stent placement. DESIGN: Prospective, multicenter cohort study. SETTING: Four referral centers. PATIENTS: The expected number of patients with symptomatic malignant gastric outlet obstruction to be included at the participating hospitals during a year was 40. Because of a serious adverse device event, the study was terminated after inclusion of 18 patients. INTERVENTION: Creation of an endoscopic gastroenteric anastomosis by using the Cook Magnetic Anastomosis Device with transanastomotic deployment of a self-expandable stent. MAIN OUTCOME MEASUREMENTS: Primary endpoints were safety and success rate associated with the creation of an endoscopic gastrojejunostomy by using a magnetic anastomotic device with transanastomotic deployment of a self-expandable stent. RESULTS: Because of a serious adverse event, the study was terminated prematurely. A success rate of 66.7% (12 of 18 patients) was achieved; 1 serious adverse event (stent perforation) occurred leading to the death of the patient. Three patients (25%) experienced an adverse device effect (stent migration). LIMITATIONS: Small sample size, lack of a control group. CONCLUSION: Endoscopic creation of a gastroenteric anastomosis by magnetic compression is feasible and safe; however, the necessity of a stent led to serious morbidity and even mortality in this study. The current system can therefore not be recommended for clinical use.

Artificial Intelligence in Medicine: Today and Tomorrow.

Artificial intelligence-powered medical technologies are rapidly evolving into applicable solutions for clinical practice. Deep learning algorithms can deal with increasing amounts of data provided by wearables, smartphones, and other mobile monitoring sensors in different areas of medicine. Currently, only very specific settings in clinical practice benefit from the application of artificial intelligence, such as the detection of atrial fibrillation, epilepsy seizures, and hypoglycemia, or the diagnosis of disease based on histopathological examination or medical imaging. The implementation of augmented medicine is long-awaited by patients because it allows for a greater autonomy and a more personalized treatment, however, it is met with resistance from physicians which were not prepared for such an evolution of clinical practice. This phenomenon also creates the need to validate these modern tools with traditional clinical trials, debate the educational upgrade of the medical curriculum in light of digital medicine as well as ethical consideration of the ongoing connected monitoring. The aim of this paper is to discuss recent scientific literature and provide a perspective on the benefits, future opportunities and risks of established artificial intelligence applications in clinical practice on physicians, healthcare institutions, medical education, and bioethics.