Search

Purpose: Obesity and its related severe comorbidities are increasing rapidly. The duodenal-jejunal bypass is an endoscopically implanted device (mimicking the Roux-en-Y gastric bypass) developed to support weight reduction and improve type 2 diabetes control., Materials and Methods: Retrospective data analysis of consecutive patients undergoing duodenal-jejunal bypass (EndoBarrier®, DJB) implantation between 2013 and 2017 was performed to evaluate safety as well as short- and long-term efficacy., Results: One hundred and twenty-one patients (mean BMI of 43.1 ± 7.2 kg/m 2 and weight of 138.2 ± 28.6 kg) underwent DJB implantation. The mean dwelling time was 15.5 months, the mean total body weight loss (%TBWL) after explantation was 10.3% ± 7.9% (14.2 kg, p < 0.0001), and the mean BMI was 39.5 ± 7.3 kg/m 2 (p < 0.0001). There was no significant weight gain 24 months after the explantation. Seventy-seven patients had type 2 diabetes mellitus (T2DM) with a mean HbA1c before implantation of 5.6% (n = 52). The mean HbA1c after explantation was 5.1% (p = 0.0001). Significant reductions in transaminase and lipid levels before and after explantation were observed. One complication occurred during implantation and another during explantation. In 16 patients, the device had to be extracted earlier than expected (7 for severe adverse events and 9 for adverse events; 13.2%)., Conclusion: Despite an evident rate of adverse events, the DJB shows promise as a weight-loss procedure. Our results show that some patients implanted with the device maintained reduced weight even 24 months after explantation, while many improved T2DM control., (© 2023. The Author(s).)

Background & Aims: Autoimmune pancreatitis (AIP) is an immune-mediated disease of the pancreas with distinct pathophysiology and manifestations. Our aims were to characterize type 1 AIP in a large pan-European cohort and study the effectiveness of current treatment regimens., Methods: We retrospectively analyzed adults diagnosed since 2005 with type 1 or not-otherwise-specified AIP in 42 European university hospitals. Type 1 AIP was uniformly diagnosed using specific diagnostic criteria. Patients with type 2 AIP and those who had undergone pancreatic surgery were excluded. The primary end point was complete remission, defined as the absence of clinical symptoms and resolution of the index radiologic pancreatic abnormalities attributed to AIP., Results: We included 735 individuals with AIP (69% male; median age, 57 years; 85% White). Steroid treatment was started in 634 patients, of whom 9 (1%) were lost to follow-up. The remaining 625 had a 79% (496/625) complete, 18% (111/625) partial, and 97% (607/625) cumulative remission rate, whereas 3% (18/625) did not achieve remission. No treatment was given in 95 patients, who had a 61% complete (58/95), 19% partial (18/95), and 80% cumulative (76/95) spontaneous remission rate. Higher (≥0.4 mg/kg/day) corticosteroid doses were no more effective than lower (<0.4 mg/kg/day) doses (odds ratio, 0.428; 95% confidence interval, 0.054-3.387) and neither was a starting dose duration >2 weeks (odds ratio, 0.908; 95% confidence interval, 0.818-1.009). Elevated IgG4 levels were independently associated with a decreased chance of complete remission (odds ratio, 0.639; 95% confidence interval, 0.427-0.955). Relapse occurred in 30% of patients. Relapses within 6 months of remission induction were independent of the steroid-tapering duration, induction treatment duration, and total cumulative dose., Conclusions: Patients with type 1 AIP and elevated IgG4 level may need closer monitoring. For remission induction, a starting dose of 0.4 mg/kg/day for 2 weeks followed by a short taper period seems effective. This study provides no evidence to support more aggressive regimens., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The European Society of Gastrointestinal Endoscopy (ESGE) has recognized the need to formalize and enhance training in diagnostic endoscopic ultrasound (EUS). This manuscript represents the outcome of a formal Delphi process resulting in an official Position Statement of the ESGE and provides a framework to develop and maintain skills in diagnostic EUS. This curriculum is set out in terms of the prerequisites prior to training; the recommended steps of training to a defined syllabus; the quality of training; and how competence should be defined and evidenced before independent practice. 1:  Trainees should have achieved competence in upper gastrointestinal endoscopy before training in diagnostic EUS. 2:  The development of diagnostic EUS skills by methods that do not involve patients is advisable, but not mandatory, prior to commencing formal training in diagnostic EUS. 3:  A trainee's principal trainer should be performing adequate volumes of diagnostic EUSs to demonstrate maintenance of their own competence. 4:  Training centers for diagnostic EUS should offer expertise, as well as a high volume of procedures per year, to ensure an optimal level of quality for training. Under these conditions, training centers should be able to provide trainees with a sufficient wealth of experience in diagnostic EUS for at least 12 months. 5:  Trainees should engage in formal training and supplement this with a range of learning resources for diagnostic EUS, including EUS-guided fine-needle aspiration and biopsy (FNA/FNB). 6:  EUS training should follow a structured syllabus to guide the learning program. 7:  A minimum procedure volume should be offered to trainees during diagnostic EUS training to ensure that they have the opportunity to achieve competence in the technique. To evaluate competence in diagnostic EUS, trainees should have completed a minimum of 250 supervised EUS procedures: 80 for luminal tumors, 20 for subepithelial lesions, and 150 for pancreaticobiliary lesions. At least 75 EUS-FNA/FNBs should be performed, including mostly pancreaticobiliary lesions. 8:  Competence assessment in diagnostic EUS should take into consideration not only technical skills, but also cognitive and integrative skills. A reliable valid assessment tool should be used regularly during diagnostic EUS training to track the acquisition of competence and to support trainee feedback. 9:  A period of supervised practice should follow the start of independent activity. Supervision can be delivered either on site if other colleagues are already practicing EUS or by maintaining contacts with the training center and/or other EUS experts. 10:  Key performance measures including the annual number of procedures, frequency of obtaining a diagnostic sample during EUS-FNA/FNB, and adverse events should be recorded within an electronic documentation system and evaluated., Competing Interests: A. Badaoui has received a consultancy from DEKRA Certification BV (2023). P. Fusaroli has participated in an advisory board for Olympus (2023). J.-W. Poley has received consultancy, travel, and speaker’s fees from Cook Endoscopy (2010 to 2022) and Boston Scientific (2012 to 2022), and consultancy and travel fees from Mediglobe GmbH (2022 to present). R. Gincul has provided EUS workshops for Ipsen (2022) and Olympus (2023) and has received sponsorship from Celltrion (2023) and Abbvie (2023). R. Sadik has received lecture fees from Cook Medical (2011 to present), Boston Scientific (2020 to present), and Olympus (2022 to present).L. Czako, A. Gines, T. Hucl, M. Kahaleh, E. Kalaitzakis, M.C. Petrone, L. Sosa Valencia, S. Teles de Campos, T. Tham, L. van Driel, and L. Vandeputte declare that they have no conflict of interest., (European Society of Gastrointestinal Endoscopy. All rights reserved.)

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

Background: Endoluminal radiofrequency ablation (RFA) has been promoted as palliative treatment for patients with cholangiocarcinoma (CCA) and pancreatic ductal adenocarcinoma (PDAC) in order to improve biliary drainage and eventually prolong survival. No high level evidence is, however, available on this technique., Design: In this randomised controlled study, we compared endoluminal RFA plus stenting with stenting alone (control group) in patients with malignant biliary obstruction; metal stents were primarily placed. Primary outcome was overall survival; secondary outcomes were stent patency, quality of life and adverse events. In a superiority design, survival was assumed to be doubled by RFA as compared with 6.4 months in the control group (n=280)., Results: A total of 161 patients (male:female 90:71, mean age 71±9 years) were randomised before recruitment was terminated for futility after an interim analysis. Eighty-five patients had CCA (73 hilar, 12 distal) and 76 had pancreatic cancer. There was no difference in survival in both subgroups: for patients with CCA, median survival was 10.5 months (95% CI 6.7 to 18.3) in the RFA group vs 10.6 months (95% CI 9.0 to 24.8), p=0.58)) in the control group. In the subgroup with pancreatic cancer, median survival was 6.4 months (95% CI 4.3 to 9.7) for the RFA vs 7.7 months (95% CI 5.6 to 11.3), p=0.73) for the control group. No benefit was seen in the RFA group with regard to stent patency (at 12 months 40% vs 36% in CCA and 66% vs 65% in PDAC), and quality of life was unchanged by either treatment and comparable between the groups. Adverse events occurred in seven patients in each groups., Conclusion: A combination of endoluminal RFA and stenting was not superior to stenting alone in prolonging survival or improving stent patency in patients with malignant biliary obstruction., Trial Registration Number: NCT03166436., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background & Aims: Fecal tests currently used for colorectal cancer (CRC) screening show limited accuracy in detecting early tumors or precancerous lesions. In this respect, we comprehensively evaluated stool microRNA (miRNA) profiles as biomarkers for noninvasive CRC diagnosis., Methods: A total of 1273 small RNA sequencing experiments were performed in multiple biospecimens. In a cross-sectional study, miRNA profiles were investigated in fecal samples from an Italian and a Czech cohort (155 CRCs, 87 adenomas, 96 other intestinal diseases, 141 colonoscopy-negative controls). A predictive miRNA signature for cancer detection was defined by a machine learning strategy and tested in additional fecal samples from 141 CRC patients and 80 healthy volunteers. miRNA profiles were compared with those of 132 tumors/adenomas paired with adjacent mucosa, 210 plasma extracellular vesicle samples, and 185 fecal immunochemical test leftover samples., Results: Twenty-five miRNAs showed altered levels in the stool of CRC patients in both cohorts (adjusted P < .05). A 5-miRNA signature, including miR-149-3p, miR-607-5p, miR-1246, miR-4488, and miR-6777-5p, distinguished patients from control individuals (area under the curve [AUC], 0.86; 95% confidence interval [CI], 0.79-0.94) and was validated in an independent cohort (AUC, 0.96; 95% CI, 0.92-1.00). The signature classified control individuals from patients with low-/high-stage tumors and advanced adenomas (AUC, 0.82; 95% CI, 0.71-0.97). Tissue miRNA profiles mirrored those of stool samples, and fecal profiles of different gastrointestinal diseases highlighted miRNAs specifically dysregulated in CRC. miRNA profiles in fecal immunochemical test leftover samples showed good correlation with those of stool collected in preservative buffer, and their alterations could be detected in adenoma or CRC patients., Conclusions: Our comprehensive fecal miRNome analysis identified a signature accurately discriminating cancer aimed at improving noninvasive diagnosis and screening strategies., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: The author declares that he has no conflict of interest.

Background: Peroral endoscopic myotomy (POEM) is nowadays a standard method for treatment of achalasia; nevertheless, it remains an invasive intervention with corresponding risk of adverse events (AEs). The classification and grading of AEs are still a matter of discussion. The aim of our retrospective study was to assess the occurrence of all "undesirable" events and "true" adverse events in patients undergoing POEM and to compare the outcomes when either Clavien-Dindo classification (CDC) or American Society of Gastrointestinal Endoscopy (ASGE) lexicon classification applied., Methods: This was a retrospective analysis of prospectively managed database of all patients who had undergone POEM between December 2012 and August 2018. We assessed the pre-, peri-, and early-postoperative (up to patient's discharge) undesirable events (including those not fulfilling criteria for AEs) and "true" AEs according the definition in either of the classifications., Results: A total of 231 patients have successfully undergone 244 POEM procedures (13 × re-POEM). Twenty-nine procedures (11.9%) passed uneventfully, while in 215 procedures (88.1%), a total of 440 undesirable events occurred. The CDC identified 27 AEs (17 minor, 10 major) occurring in 23/244 (9.4%) procedures. The ASGE lexicon identified identical 27 AEs (21 mild or moderate, 6 severe or fatal) resulting in the severity distribution of AEs being the only difference between the two classifications. Only the absence of previous treatment was found to be a risk factor [p = 0.047, OR with 95% CI: 4.55 (1.02; 20.25)] in the combined logistic regression model., Conclusion: Undesirable events are common in patients undergoing POEM but the incidence of true AEs is low according to both classifications. Severe adverse events are infrequent irrespective of the classification applied. CDC may be more appropriate than ASGE lexicon for classifying POEM-related AEs given a surgical nature of this procedure., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

BACKGROUND Acute pancreatitis (AP) is a relatively rare but serious complication that can occur after organ transplantation. MATERIAL AND METHODS The aim of this study was to evaluate the incidence, potential risk factors, and course of AP in patients following liver transplantation at a single large-volume transplant center. RESULTS Out of a total of 1850 transplanted patients, 49 (2.8%) were diagnosed with AP. Of this group, 37 (75.5%) had a mild form of AP and 12 (24.5%) had a severe form of AP. The mortality rate was 10% overall and 42% in the group of patients with severe AP. An early form of AP (<30 days from transplantation) occurred in 13 patients (26.5%), most of whom presented with severe AP (10 patients, 76.9%); 4 patients died (40%). A late form of AP was diagnosed in 36 patients (73.5%), most of whom had mild AP (34 patients, 94.4%); 1 of 2 patients with severe AP died. The most common AP etiologies were post-ERCP (38.8%), idiopathic (34.7%), and postoperative (18.4%). Chronic HBV infection was a risk factor for development of AP (P=0.01). CONCLUSIONS AP in liver transplant recipients was more frequent and more severe than in the general population. This unfavorable course was associated with the occurrence of AP in the early post-transplant period. Liver transplantation due to complications of HBV infection was a risk factor for the development of AP.

1: ESGE recommends that patients with compensated advanced chronic liver disease (ACLD; due to viruses, alcohol, and/or nonobese [BMI < 30 kg/m 2 ] nonalcoholic steatohepatitis) and clinically significant portal hypertension (hepatic venous pressure gradient [HVPG] > 10 mmHg and/or liver stiffness by transient elastography > 25 kPa) should receive, if no contraindications, nonselective beta blocker (NSBB) therapy (preferably carvedilol) to prevent the development of variceal bleeding.Strong recommendation, moderate quality evidence. 2: ESGE recommends that in those patients unable to receive NSBB therapy with a screening upper gastrointestinal (GI) endoscopy that demonstrates high risk esophageal varices, endoscopic band ligation (EBL) is the endoscopic prophylactic treatment of choice. EBL should be repeated every 2-4 weeks until variceal eradication is achieved. Thereafter, surveillance EGD should be performed every 3-6 months in the first year following eradication.Strong recommendation, moderate quality evidence. 3: ESGE recommends, in hemodynamically stable patients with acute upper GI hemorrhage (UGIH) and no history of cardiovascular disease, a restrictive red blood cell (RBC) transfusion strategy, with a hemoglobin threshold of ≤ 70 g/L prompting RBC transfusion. A post-transfusion target hemoglobin of 70-90 g/L is desired.Strong recommendation, moderate quality evidence. 4 : ESGE recommends that patients with ACLD presenting with suspected acute variceal bleeding be risk stratified according to the Child-Pugh score and MELD score, and by documentation of active/inactive bleeding at the time of upper GI endoscopy.Strong recommendation, high quality of evidence. 5 : ESGE recommends the vasoactive agents terlipressin, octreotide, or somatostatin be initiated at the time of presentation in patients with suspected acute variceal bleeding and be continued for a duration of up to 5 days.Strong recommendation, high quality evidence. 6 : ESGE recommends antibiotic prophylaxis using ceftriaxone 1 g/day for up to 7 days for all patients with ACLD presenting with acute variceal hemorrhage, or in accordance with local antibiotic resistance and patient allergies.Strong recommendation, high quality evidence. 7 : ESGE recommends, in the absence of contraindications, intravenous erythromycin 250 mg be given 30-120 minutes prior to upper GI endoscopy in patients with suspected acute variceal hemorrhage.Strong recommendation, high quality evidence. 8 : ESGE recommends that, in patients with suspected variceal hemorrhage, endoscopic evaluation should take place within 12 hours from the time of patient presentation provided the patient has been hemodynamically resuscitated.Strong recommendation, moderate quality evidence. 9 : ESGE recommends EBL for the treatment of acute esophageal variceal hemorrhage (EVH).Strong recommendation, high quality evidence. 10 : ESGE recommends that, in patients at high risk for recurrent esophageal variceal bleeding following successful endoscopic hemostasis (Child-Pugh C  ≤ 13 or Child-Pugh B > 7 with active EVH at the time of endoscopy despite vasoactive agents, or HVPG > 20 mmHg), pre-emptive transjugular intrahepatic portosystemic shunt (TIPS) within 72 hours (preferably within 24 hours) must be considered.Strong recommendation, high quality evidence. 11 : ESGE recommends that, for persistent esophageal variceal bleeding despite vasoactive pharmacological and endoscopic hemostasis therapy, urgent rescue TIPS should be considered (where available).Strong recommendation, moderate quality evidence. 12 : ESGE recommends endoscopic cyanoacrylate injection for acute gastric (cardiofundal) variceal (GOV2, IGV1) hemorrhage.Strong recommendation, high quality evidence. 13: ESGE recommends endoscopic cyanoacrylate injection or EBL in patients with GOV1-specific bleeding.Strong recommendations, moderate quality evidence. 14: ESGE suggests urgent rescue TIPS or balloon-occluded retrograde transvenous obliteration (BRTO) for gastric variceal bleeding when there is a failure of endoscopic hemostasis or early recurrent bleeding.Weak recommendation, low quality evidence. 15: ESGE recommends that patients who have undergone EBL for acute EVH should be scheduled for follow-up EBLs at 1- to 4-weekly intervals to eradicate esophageal varices (secondary prophylaxis).Strong recommendation, moderate quality evidence. 16: ESGE recommends the use of NSBBs (propranolol or carvedilol) in combination with endoscopic therapy for secondary prophylaxis in EVH in patients with ACLD.Strong recommendation, high quality evidence., Competing Interests: M.C. Duboc has provided consultancy to Boston Scientific (2017 to 2019), Cook Medical (2019), and AMBU (2021 to 2022); she has received payments from the journal HepatoGastroentérologie et Oncologie digestive. I.M. Gralnek has provided consultancy to and been on the advisory board of Motus GI, has provided consultancy to Boston Scientific, Clexio Biosciences, Medtronic, Neurogastrx, and Symbionix; he has received consultancy and speaker’s fees from Vifor Pharma, and speaker’s fees from 3-D Matrix; he has received research support from AstraZeneca and Check Cap. J.G. Karstensen has received lecture fees from Norgine (2020 to 2022) and provides consultancy to SNIPR BIOME and AMBU (2020 to present). H. Awadie, M.C. Burgmans. A. Ebigbo, L. Fuccio, J.C. Garcia-Pagan, V. Hernandez-Gea, T. Hucl, I. Jovanovic, I. Mostafa, R. Rosasco, M. Tantau, K. Triantafyllou, and J. Vlachogiannakos declare that they have no conflict of interest., (European Society of Gastrointestinal Endoscopy. All rights reserved.)

A colorectal adenoma, an aberrantly growing tissue, arises from the intestinal epithelium and is considered as precursor of colorectal cancer (CRC). In this study, we investigated structural and numerical chromosomal aberrations in adenomas, hypothesizing that chromosomal instability (CIN) occurs early in adenomas. We applied array comparative genomic hybridization (aCGH) to fresh frozen colorectal adenomas and their adjacent mucosa from 16 patients who underwent colonoscopy examination. In our study, histologically similar colorectal adenomas showed wide variability in chromosomal instability. Based on the obtained results, we further stratified patients into four distinct groups. The first group showed the gain of MALAT1 and TALAM1 , long non-coding RNAs (lncRNAs). The second group involved patients with numerous microdeletions. The third group consisted of patients with a disrupted karyotype. The fourth group of patients did not show any CIN in adenomas. Overall, we identified frequent losses in genes, such as TSC2 , COL1A1 , NOTCH1 , MIR4673 , and GNAS , and gene gain containing MALAT1 and TALAM1 . Since long non-coding RNA MALAT1 is associated with cancer cell metastasis and migration, its gene amplification represents an important event for adenoma development.

Radiofrequency ablation (RFA) is a mini-invasive loco-regional ablation technique that is increasingly being used as a palliative treatment for pancreatic cancer and cholangiocarcinoma. Ablation-triggered immune system stimulation has been proposed as a mechanism behind the systemic effects of RFA. The aim of our study was to investigate the immune response to endoluminal biliary RFA. Peripheral blood samples were collected from patients with pancreatic cancer and cholangiocarcinoma randomised to receive endoluminal biliary radiofrequency ablation + stent (19 patients) or stent only (21 patients). We observed an early increase in IL-6 levels and a delayed increase in CXCL1, CXCL5, and CXCL11 levels as well as an increase in CD8+ and NK cells. However, these changes were not specific to RFA treatment. Explicitly in response to RFA, we observed a delayed increase in serum CXCL1 levels and an early decrease in the number of anti-inflammatory CD206+ blood monocytes. Our study provides the first evidence of endoluminal biliary RFA-based regulation of the systemic immune response in patients with pancreatic cancer and cholangiocarcinoma. These changes were characterised by a general inflammatory response. RFA-specific activation of the adaptive immune system was not confirmed.

1:  ESGE recommends a prolonged course of a prophylactic broad-spectrum antibiotic in patients with ascites who are undergoing therapeutic endoscopic ultrasound (EUS) procedures.Strong recommendation, low quality evidence. 2:  ESGE recommends placement of partially or fully covered self-expandable metal stents during EUS-guided hepaticogastrostomy for biliary drainage in malignant disease.Strong recommendation, moderate quality evidence. 3:  ESGE recommends EUS-guided pancreatic duct (PD) drainage should only be performed in high volume expert centers, owing to the complexity of this technique and the high risk of adverse events.Strong recommendation, low quality evidence. 4:  ESGE recommends a stepwise approach to EUS-guided PD drainage in patients with favorable anatomy, starting with rendezvous-assisted endoscopic retrograde pancreatography (RV-ERP), followed by antegrade or transmural drainage only when RV-ERP fails or is not feasible.Strong recommendation, low quality evidence. 5:  ESGE suggests performing transduodenal EUS-guided gallbladder drainage with a lumen-apposing metal stent (LAMS), rather than using the transgastric route, as this may reduce the risk of stent dysfunction.Weak recommendation, low quality evidence. 6:  ESGE recommends using saline instillation for small-bowel distension during EUS-guided gastroenterostomy.Strong recommendation, low quality evidence. 7:  ESGE recommends the use of saline instillation with a 19G needle and an electrocautery-enhanced LAMS for EUS-directed transgastric endoscopic retrograde cholangiopancreatography (EDGE) procedures.Strong recommendation, low quality evidence. 8:  ESGE recommends the use of either 15- or 20-mm LAMSs for EDGE, with a preference for 20-mm LAMSs when considering a same-session ERCP.Strong recommendation, low quality evidence., Competing Interests: M. Barthet has received a research grant from Boston Scientific (2015 to present). K.F. Binmoeller has received fees for training and education from Boston Scientific (2015 to present). M. Bronswijk has consultancy agreements with Prion Medical and Taewoong Medical (both ongoing). M.A. Khashab receives consultancy fees from BSCI, Medtronic, Olympus, Pentax, GI Supply, and Apollo (all ongoing). A. Larghi has received consultancy fees from Boston Scientific and Pentax Medical, and educational fees from Taewoong Medical; he receives research support from Medtronic. R. Law receives consultancy fees from Medtronic (2020 to present) and Conmed (2021). M. Perez-Miranda receives consultancy fees from Lumendi and Olympus (both 2020 to present) and consultancy and speaker's fees from Boston Scientific (2021). S. van der Merwe has received consultancy fees from Boston Scientific and Cook Endoscopy (both 2012 to present); he was the Boston Chair in Interventional Endoscopy (2018 to 2021) and is the Cook Chair in Portal Hypertension (2021). J.E. van Hooft has received lecture fees from Medtronics (2014, 2015, and 2019), Cook Medical (2019), and Abbivie (2021), and consultancy fees from Boston Scientific (2014 to 2017) and Olympus (2021); her department received research support from Abbott (2014 to 2017) and Cook Medical (2014 to 2019). P.G. Arcidiacono, A. Badaoui, S. Everett, T. Hucl, R. Kunda, S. Lakhtakia, M. Rimbas, and R.L.J. van Wanrooij declare that they have no conflict of interest., (European Society of Gastrointestinal Endoscopy. All rights reserved.)

1: ESGE recommends the use of endoscopic ultrasound-guided biliary drainage (EUS-BD) over percutaneous transhepatic biliary drainage (PTBD) after failed endoscopic retrograde cholangiopancreatography (ERCP) in malignant distal biliary obstruction when local expertise is available.Strong recommendation, moderate quality evidence. 2: ESGE suggests EUS-BD with hepaticogastrostomy only for malignant inoperable hilar biliary obstruction with a dilated left hepatic duct when inadequately drained by ERCP and/or PTBD in high volume expert centers.Weak recommendation, moderate quality evidence. 3: ESGE recommends that EUS-guided pancreatic duct (PD) drainage should only be considered in symptomatic patients with an obstructed PD when retrograde endoscopic intervention fails or is not possible.Strong recommendation, low quality evidence. 4: ESGE recommends rendezvous EUS techniques over transmural PD drainage in patients with favorable anatomy owing to its lower rate of adverse events.Strong recommendation, low quality evidence. 5: ESGE recommends that, in patients at high surgical risk, EUS-guided gallbladder drainage (GBD) should be favored over percutaneous gallbladder drainage where both techniques are available, owing to the lower rates of adverse events and need for re-interventions in EUS-GBD.Strong recommendation, high quality of evidence. 6: ESGE recommends EUS-guided gastroenterostomy (EUS-GE), in an expert setting, for malignant gastric outlet obstruction, as an alternative to enteral stenting or surgery.Strong recommendation, low quality evidence. 7: ESGE recommends that EUS-GE may be considered in the management of afferent loop syndrome, especially in the setting of malignancy or in poor surgical candidates. Strong recommendation, low quality evidence. 8: ESGE suggests that endoscopic ultrasound-directed transgastric ERCP (EDGE) can be offered, in expert centers, to patients with a Roux-en-Y gastric bypass following multidisciplinary decision-making, with the aim of overcoming the invasiveness of laparoscopy-assisted ERCP and the limitations of enteroscopy-assisted ERCP.Weak recommendation, low quality evidence., Competing Interests: M. Barthet has received a research grant from Boston Scientific (2015 to present). K.F. Binmoeller has received fees for training and education from Boston Scientific (2015 to present). M. Bronswijk has received consultancy fees from Prion Medical and Taewoong Medical (both 2021). M.A. Khashab receives consultancy fees from BSCI, Medtronic, Olympus, Pentax, GI Supply, and Apollo (all ongoing). A. Larghi has received consultancy fees from Boston Scientific and Pentax Medical, and educational fees from Taewoong Medical; he receives research support from Medtronic. R. Law receives consultancy fees from Medtronic (2020 to present) and Conmed (2021). M. Perez-Miranda receives consultancy fees from Lumendi and Olympus (both 2020 to present) and consultancy and speaker's fees from Boston Scientific (2021). S. van der Merwe has received consultancy fees from Boston Scientific and Cook Endoscopy (both 2012 to present); he was the Boston Chair in Interventional Endoscopy (2018 to 2021) and is the Cook Chair in Portal Hypertension (2021). J.E. van Hooft has received lecture fees from Medtronics (2014, 2015, and 2019), Cook Medical (2019), and Abbivie (2021), and consultancy fees from Boston Scientific (2014 to 2017) and Olympus (2021); her department received research support from Abbott (2014 to 2017) and Cook Medical (2014 to 2019). P.G. Arcidiacono, A. Badaoui, S. Everett, T. Hucl, R. Kunda, S. Lakhtakia, M. Rimbas, and R.L.J. van Wanrooij declare that they have no conflict of interest., (European Society of Gastrointestinal Endoscopy. All rights reserved.)

1: ESGE suggests performing segmental biopsies (at least two from each segment), which should be placed in different specimen containers (ileum, cecum, ascending, transverse, descending, and sigmoid colon, and rectum) in patients with clinical and endoscopic signs of colitis.Weak recommendation, low quality of evidence. 2: ESGE recommends taking two biopsies from the right hemicolon (ascending and transverse colon) and, in a separate container, two biopsies from the left hemicolon (descending and sigmoid colon) when microscopic colitis is suspected.Strong recommendation, low quality of evidence. 3: ESGE recommends pancolonic dye-based chromoendoscopy or virtual chromoendoscopy with targeted biopsies of any visible lesions during surveillance endoscopy in patients with inflammatory bowel disease. Strong recommendation, moderate quality of evidence. 4: ESGE suggests that, in high risk patients with a history of colonic neoplasia, tubular-appearing colon, strictures, ongoing therapy-refractory inflammation, or primary sclerosing cholangitis, chromoendoscopy with targeted biopsies can be combined with four-quadrant non-targeted biopsies every 10 cm along the colon. Weak recommendation, low quality of evidence. 5: ESGE recommends that, if pouch surveillance for dysplasia is performed, visible abnormalities should be biopsied, with at least two biopsies systematically taken from each of the afferent ileal loop, the efferent blind loop, the pouch, and the anorectal cuff.Strong recommendation, low quality of evidence. 6: ESGE recommends that, in patients with known ulcerative colitis and endoscopic signs of inflammation, at least two biopsies be obtained from the worst affected areas for the assessment of activity or the presence of cytomegalovirus; for those with no evident endoscopic signs of inflammation, advanced imaging technologies may be useful in identifying areas for targeted biopsies to assess histologic remission if this would have therapeutic consequences. Strong recommendation, low quality of evidence. 7: ESGE suggests not biopsying endoscopically visible inflammation or normal-appearing mucosa to assess disease activity in known Crohn's disease.Weak recommendation, low quality of evidence. 8: ESGE recommends that adequately assessed colorectal polyps that are judged to be premalignant should be fully excised rather than biopsied.Strong recommendation, low quality of evidence. 9: ESGE recommends that, where endoscopically feasible, potentially malignant colorectal polyps should be excised en bloc rather than being biopsied. If the endoscopist cannot confidently perform en bloc excision at that time, careful representative images (rather than biopsies) should be taken of the potential focus of cancer, and the patient should be rescheduled or referred to an expert center.Strong recommendation, low quality of evidence. 10: ESGE recommends that, in malignant lesions not amenable to endoscopic excision owing to deep invasion, six carefully targeted biopsies should be taken from the potential focus of cancer.Strong recommendation, low quality of evidence., Competing Interests: M. Barret has received consultancy fees from Medtronic (2018 to present) and Pentax (2019 to present). R. Bisschops has received consultancy and speaker’s fees from Fujifilm, Pentax, Medtronic (all 2015 to present), and Norgine (2016 to present), consultancy fees from Boston Scientific, Cook (both 2015 to present), CDx Diagnostics (2017 to present), and GI Supply (2018 to present), and speaker’s fees from Medivators (2017 to 2018) and Ipsen (2020 to present); his department has received research grants from Fujifilm, Pentax (both 2015 to present), Cook (2016 to 2019), and Medtronic (2018 to present). M. Dinis Ribeiro is co-editor-in-chief of Endoscopy; his department has received a research grant from Fujifilm (2020 to present) and an educational grant from Olympus (2020 to present). M. Iacucci has received research grant support from Pentax (2016 to present), Olympus (2018 to 2020), and Fujifilm (2019 to present). M.C.W. Spaander has received research support from Boston Scientific (2013 to present) and Cook Medical (2009 to 2013). J.E. van Hooft has received lecture fees from Medtronic (2014, 2015, and 2019) and Cook Medical (2019), and consultancy fees from Boston Scientific (2014 to 2017) and Olympus (2021); her department has received research grants from Abbot (2014 to 2017) and Cook Medical (2014 to 2019). K. Biermann, L. Czakó, K.B. Gecse, G. de Hertogh, T. Hucl, M. Jansen, R.E. Pouw, M. Rutter, E. Savarino, P.T. Schmidt, and M. Vieth declare that they have no conflict of interest., (European Society of Gastrointestinal Endoscopy. All rights reserved.)

1: ESGE recommends that, where there is a suspicion of eosinophilic esophagitis, at least six biopsies should be taken, two to four biopsies from the distal esophagus and two to four biopsies from the proximal esophagus, targeting areas with endoscopic mucosal abnormalities. Distal and proximal biopsies should be placed in separate containers.Strong recommendation, low quality of evidence. 2: ESGE recommends obtaining six biopsies, including from the base and edge of the esophageal ulcers, for histologic analysis in patients with suspected viral esophagitis.Strong recommendation, low quality of evidence. 3: ESGE recommends at least six biopsies are taken in cases of suspected advanced esophageal cancer and suspected advanced gastric cancer.Strong recommendation, moderate quality of evidence. 4: ESGE recommends taking only one to two targeted biopsies for lesions in the esophagus or stomach that are potentially amenable to endoscopic resection (Paris classification 0-I, 0-II) in order to confirm the diagnosis and not compromise subsequent endoscopic resection.Strong recommendation, low quality of evidence. 5: ESGE recommends obtaining two biopsies from the antrum and two from the corpus in patients with suspected Helicobacter pylori infection and for gastritis staging.Strong recommendation, low quality of evidence. 6: ESGE recommends biopsies from or, if endoscopically resectable, resection of gastric adenomas.Strong recommendation, moderate quality of evidence. 7: ESGE recommends fine-needle aspiration (FNA) and fine-needle biopsy (FNB) needles equally for sampling of solid pancreatic masses.Strong recommendation, high quality evidence. 8: ESGE suggests performing peroral cholangioscopy (POC) and/or endoscopic ultrasound (EUS)-guided tissue acquisition in indeterminate biliary strictures. For proximal and intrinsic strictures, POC is preferred. For distal and extrinsic strictures, EUS-guided sampling is preferred, with POC where this is not diagnostic.Weak recommendation, low quality evidence. 9: ESGE suggests obtaining possible non-neoplastic biopsies before sampling suspected malignant lesions to prevent intraluminal spread of malignant disease.Weak recommendation, low quality of evidence. 10: ESGE suggests dividing EUS-FNA material into smears (two per pass) and liquid-based cytology (LBC), or the whole of the EUS-FNA material can be processed as LBC, depending on local experience.Weak recommendation, low quality evidence., Competing Interests: M. Barret has received consultancy fees from Medtronic (2018 to present) and Pentax (2019 to present). R. Bisschops has received consultancy and speaker’s fees from Fujifilm, Pentax, Medtronic (all 2015 to present), and Norgine (2016 to present), consultancy fees from Boston Scientific, Cook (both 2015 to present), CDx Diagnostics (2017 to present), and GI Supply (2018 to present), and speaker’s fees from Medivators (2017 to 2018) and Ipsen (2020 to present); his department has received research grants from Fujifilm, Pentax (both 2015 to present), Cook (2016 to 2019), and Medtronic (2018 to present). M. Dinis Ribeiro is co-editor-in-chief of Endoscopy; his department has received a research grant from Fujifilm (2020 to present) and an educational grant from Olympus (2020 to present). M. Iacucci has received research grant support from Pentax (2016 to present), Olympus (2018 to 2020), and Fujifilm (2019 to present). M.C.W. Spaander has received research support from Boston Scientific (2013 to present) and Cook Medical (2009 to 2013). J.E. van Hooft has received lecture fees from Medtronic (2014, 2015, and 2019) and Cook Medical (2019), and consultancy fees from Boston Scientific (2014 to 2017) and Olympus (2021); her department has received research grants from Abbot (2014 to 2017) and Cook Medical (2014 to 2019). K. Biermann, L. Czakó, K.B. Gecse, G. de Hertogh, T. Hucl, M. Jansen, R.E. Pouw, M. Rutter, E. Savarino, P.T. Schmidt, and M. Vieth declare that they have no conflict of interest., (European Society of Gastrointestinal Endoscopy. All rights reserved.)

Cholangiocarcinoma and pancreatic cancer are the most common causes of malignant biliary obstruction. The majority of patients are diagnosed at a late stage when surgical resection is rarely possible. In these cases, palliative chemotherapy and radiotherapy provide only limited benefit and are associated with poor survival. Radiofrequency ablation (RFA) is a procedure for locoregional control of tumours, whereby a high-frequency alternating current turned into thermal energy causes coagulative necrosis of the tissue surrounding the catheter. The subsequent release of debris and tumour antigens by necrotic cells can stimulate local and systemic immunity. The development of endoluminal RFA catheters has led to the emergence of endoscopically delivered RFA, a treatment mainly used for malignant biliary strictures to prolong survival and/or stent patency. Other indications include recanalisation of occluded biliary stents and treatment of intraductal ampullary adenoma or benign biliary strictures. This article presents a comprehensive review of endobiliary RFA, mainly focusing on its use in patients with malignant biliary obstruction. The available data suggest that biliary RFA may be a promising modality, having positive impacts on survival and stent patency and boasting a reasonable safety profile. However, further studies with better characterised and stratified patient populations are needed before the method becomes accepted within routine clinical practice., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

The European Society of Gastrointestinal Endoscopy (ESGE) has recognized the need to formalize and enhance training in endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS). This manuscript represents the outcome of a formal Delphi process resulting in an official Position Statement of the ESGE and provides a framework to develop and maintain skills in ERCP and EUS. This curriculum is set out in terms of the prerequisites prior to training; recommended steps of training to a defined syllabus; the quality of training; and how competence should be defined and evidenced before independent practice. 1: Trainees should be competent in gastroscopy prior to commencing training. Formal training courses and the use of simulation in training are recommended. 2: Trainees should keep a contemporaneous logbook of their procedures, including key performance indicators and the degree of independence. Structured formative assessment is encouraged to enhance feedback. There should be a summative assessment process prior to commencing independent practice to ensure there is robust evidence of competence. This evidence should include a review of a trainee's procedure volume and current performance measures. A period of mentoring is strongly recommended in the early stages of independent practice. 3: Specifically for ERCP, all trainees should be competent up to Schutz level 2 complexity (management of distal biliary strictures and stones > 10 mm), with advanced ERCP requiring a further period of training. Prior to independent practice, ESGE recommends that a trainee can evidence a procedure volume of > 300 cases, a native papilla cannulation rate of ≥ 80 % (90 % after a period of mentored independent practice), complete stones clearance of ≥ 85 %, and successful stenting of distal biliary strictures of ≥ 90 % (90 % and 95 % respectively after a mentored period of independent practice). 4: The progression of EUS training and competence attainment should start from diagnostic EUS and then proceed to basic therapeutic EUS, and finally to advanced therapeutic EUS. Before independent practice, ESGE recommends that a trainee can evidence a procedure volume of > 250 cases (75 fine-needle aspirations/biopsies [FNA/FNBs]), satisfactory visualization of key anatomical landmarks in ≥ 90 % of cases, and an FNA/FNB accuracy rate of ≥ 85 %. ESGE recognizes the often inadequate quality of the evidence and the need for further studies pertaining to training in advanced endoscopy, particularly in relation to therapeutic EUS., Competing Interests: A. Anderloni has provided consultancy for Boston Scientific (2016 to present), Olympus (2018 to present), and Medtronic (2018–2019). M. Arvanitakis has received lecture fees from Olympus (2019–2020). R. Bisschops is supported by a grant from Flanders Research Foundation; he has received speaker’s and consultancy fees from Medtronic, Fujifilm, and Pentax (2015 to present), and consultancy fees from Boston Scientific and Cook (2015 to present); his department has received research grants from Pentax and Fujifilm (2015 to present), Cook (2016–2019), Medtronic (2018 to present), and Boston Scientific (2019 to present). M. Dinis-Ribeiro provided consultancy for Medtronic (2020); he is also co-editor in-chief of Endoscopy. I. Hritz was a consultant and trainer for Olympus and Pentax Medical (2017–2018). G. Johnson has received education consultancy fees from Boston Scientific (2014 to present), Pentax (2017–2018), and Olympus (2013 to present). J.-W. Poley has received consultancy and travel fees from Boston Scientific, Cook Endoscopy, and Pentax Medical (2015 to present). J.J. Vila has provided consultancy for Boston Scientific (2014 to present). G. Webster has received fees for invited lectures and advisory boards from Boston Scientific, Cook Endoscopy, and Pentax Medical (2010 to present) and has received support for endoscopy teaching courses from Boston Scientific, Cook Endoscopy, Pentax Medical, Olympus, Medtronic, and ERBE (2010 to present). U. Arnelo, A. Badaoui, N. Bekkali, I. Boskoski, S. Campos, D. Christodoulou, L. Czakó, S. Gölder, T. Hucl, E. Kalaitzakis, L. Kylänpää, I. Nedoluzhko, M.C. Petrone, T. Ponchon, C. Schlag, A. Seicean, and M.F.Y. Viesca declare that they have no conflict of interest., (European Society of Gastrointestinal Endoscopy. All rights reserved.)

Background: Chronic pancreatitis is a known risk factor of pancreatic cancer (PDAC). A similar association has been suggested but not demonstrated for autoimmune pancreatitis (AIP)., Objective: The aim of our study was to identify and analyse all published cases of AIP and PDAC co-occurrence, focusing on the interval between the diagnoses and the cancer site within the pancreas., Methods: Relevant studies were identified through automatic searches of the MEDLINE, EMBASE, Scopus, and Web of Science databases, and supplemented by manual checks of reference lists in all retrieved articles. Missing/unpublished data were obtained from the authors of relevant publications in the form of pre-prepared questionnaires., Results: A total of 45 cases of PDAC in AIP patients were identified, of which 12 were excluded from the analysis due to suspicions of duplicity or lack of sufficient data. Thirty-one patients (94%) had type 1 AIP. Synchronous occurrence of PDAC and AIP was reported in 11 patients (33%), metachronous in 22 patients (67%). In the metachronous group, the median period between diagnoses was 66.5 months (2-186) and a majority of cancers (86%) occurred more than two years after AIP diagnosis. In most patients (70%), the cancer originated in the part of the pancreas affected by AIP., Conclusions: In the literature, there are reports on numerous cases of PDAC in AIP patients. PDAC is more frequent in AIP type 1 patients, typically metachronous in character, and generally found in the part of the pancreas affected by AIP., (Copyright © 2021 IAP and EPC. All rights reserved.)

Background/aims: Several studies have reported partial recovery of peristalsis in patients with achalasia after myotomy. The aim of our study is to analyze esophageal motility patterns after peroral endoscopic myotomy (POEM) and to assess the potential predictors and clinical impact of peristaltic recovery., Methods: We performed a retrospective analysis of prospectively collected data of consecutive patients with achalasia undergoing POEM at a tertiary center. High-resolution manometry (HRM) studies prior to and after POEM were reviewed and the Chicago classification was applied., Results: A total of 237 patients were analyzed. The initial HRM diagnoses were achalasia type I, 42 (17.7%); type II, 173 (73.0%); and type III, 22 (9.3%). Before POEM, peristaltic fragments were present in 23 (9.7%) patients. After POEM the Chicago classification diagnoses were: 112 absent contractility, 42 type I achalasia, 15 type II, 11 type III, 26 ineffective esophageal motility, 18 esophagogastric junction outflow obstruction, 10 fragmented peristalsis, and 3 distal esophageal spasm. Altogether 68 patients (28.7%) had signs of contractile activity, but the contractions newly appeared in 47 patients (47/214, 22.0%). Type II achalasia showed a trend for appearance of contractions ( P = 0.097). Logistic regression analysis did not identify any predictors of peristaltic recovery. The post-POEM Eckardt score did not differ between patients with and without contractions nor did the parameters of timed barium esophagogram., Conclusions: More than 20% of achalasia patients have signs of partial recovery of esophageal peristalsis after POEM. It occurs predominantly in type II achalasia but the clinical relevance seems to be negligible.

IgG4-related disease is a recently defined clinical entity that can manifest itself in any organ. The most common gastrointestinal manifestations are diseases of the pancreas (autoimmune pancreatitis type 1) and biliary tree (IgG4-associated cholangitis); involvement of liver parenchyma is uncommon and the affection of tubular organs is very rare. IgG4-related pancreatitis and cholangitis can mimic malignancies in their clinical presentation. Diagnosis is often difficult and requires careful evaluation of the combination of symptoms, serology and imaging findings, while adhering to the established diagnostic criteria. The first line of treatment is the administration of corticoids and the remission is achieved in the vast majority of patients. In case of contraindication, intolerance or failure of corticotherapy, patients should receive B cell depletion therapy (rituximab). Based on the available knowledge, monotherapy with other immunosuppressants is not considered to be sufficiently effective. Some patients may benefit from maintenance treatment to prevent relapse, which is otherwise common in both IgG4-related pancreatitis and cholangitis. Recognized IgG4-related disease has a good prognosis, but some patients develop irreversible fibrotic changes in the affected organ with consequent dysfunction; the possible association of the disease with a higher risk of malignancy has not yet been reliably elucidated.

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

Colorectal cancer (CRC) is a malignant disease with an incidence of over 1.8 million new cases per year worldwide. CRC outcome is closely related to the respective stage of CRC and is more favorable at less advanced stages. Detection of early colorectal adenomas is the key to survival. In spite of implemented screening programs showing efficiency in the detection of early precancerous lesions and CRC in asymptomatic patients, a significant number of patients are still diagnosed in advanced stages. Research on CRC accomplished during the last decade has improved our understanding of the etiology and development of colorectal adenomas and revealed weaknesses in the general approach to their detection and elimination. Recent studies seek to find a reliable non-invasive biomarker detectable even in the blood. New candidate biomarkers could be selected on the basis of so-called liquid biopsy, such as long non-coding RNA, microRNA, circulating cell-free DNA, circulating tumor cells, and inflammatory factors released from the adenoma into circulation. In this work, we focused on both genetic and epigenetic changes associated with the development of colorectal adenomas into colorectal carcinoma and we also discuss new possible biomarkers that are detectable even in adenomas prior to cancer development.

Introduction: An accurate histopathological diagnosis of indeterminate biliary strictures and pancreatic lesions is challenging because of insufficient quali-ty of tissue specimen taken during ERCP (brush cytology), cholangioscopy (biopsies) or endosonography (EUS, FNAB). Confocal laser endomicroscopy (CLE) allows virtual histopathological diagnosis with the potential to either replace or increase the diagnostic yield of standard histopathological diagnosis in patients presenting with biliary strictures and pancreatic lesions. The aims of our prospective pilot study were to: 1. Assess the diagnostic yield of standard histopathology compared to CLE in patients referred for cholangioscopy or for EUS of the pancreas; 2. Evaluate the cost of CLE in these indications., Methods: CLE was performed (during cholangioscopy or EUS), followed by standard tissue sampling. CLE-based diagnosis was compared with standard histopathology/cytology. CLE probe was introduced through the working channel of the cholangioscope or through the FNAB needle., Results: A total of 23 patients were enrolled (12 women, mean age 61 years); 13 patients underwent cholangioscopy and 10 patients underwent EUS. Cholangioscopy: CLE diagnosed correctly all 4 malignant strictures (histology 2 of them only as 2 patients had insufficient quality of the tissue specimen). Agreement between standard histopathology and CLE was achieved in 85 %. EUS: All 3 cases of pancreatic cancer were correctly diagnosed by both CLE and FNAB. All remaining (premalignant and benign) lesions were also correctly diagnosed by both methods. The cost of CLE examination is higher compared to FNAB but comparable with tissue sampling during digital cholangioscopy., Conclusion: CLE demonstrated sufficient diagnostic accuracy in patients with indeterminate biliary strictures or pancreatic lesions and, therefore, might improve diagnostic accuracy or even replace standard histopathology in these indications.

Cancers of the biliary tract include intra- and extrahepatic cholangiocarcinomas and gallbladder cancer. Biliary tract cancers are diseases with unfavorable prognoses. In recent years, several lesions have been described as precursors that precede biliary cancers. They include flat and microscopic lesions known as biliary intraepithelial neoplasia, macroscopic and tumor-forming intraductal papillary biliary neoplasia, intraductal tubular neoplasia, and mucinous cystic neoplasm of the bile duct. These conditions are rarely diagnosed, while their natural history and progression to cancer have yet to be adequately characterized. This review examines the epidemiology, pathology, molecular biology, diagnosis, and therapy of these various precursors. Further research is required if we are to better understand this evolving field and improve the prevention and early detection of bile duct cancer., Competing Interests: There is no conflict of interest regarding the publication of this paper., (Copyright © 2019 Tomas Hucl.)

The first-line chemotherapy of colorectal cancer (CRC), besides surgery, comprises administration of 5-Fluorouracil (5FU). Apart from cytotoxic effect on cancer cells, 5FU may also cause adverse side effects. Ganoderma Lucidum (GLC) is a mushroom used in Traditional Eastern Medicine. We propose that natural compounds, particularly GLC extracts, may sensitize cancer cells to conventional chemotherapeutics. This combination therapy could lead to more selective cancer cell death and may improve the response to the therapy and diminish the adverse effects of anticancer drugs. Here we demonstrate that GLC induced oxidative DNA damage selectively in colorectal cancer cell lines, whereas it protected non-malignant cells from the accumulation of reactive oxygen species. Accumulation of DNA damage caused sensitization of cancer cells to 5FU resulting in improved anticancer effect of 5FU. The results obtained in colorectal cell lines were confirmed in in vivo study: GLC co-treatment with 5FU increased the survival of treated mice and reduced the tumor volume in comparison with group treated with 5FU alone. Combination of conventional chemotherapeutics and natural compounds is a promising approach, which may reduce the effective curative dose of anticancer drugs, suppress their adverse effects and ultimately lead to better quality of life of CRC patients., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Heterozygous germline BRCA2 mutations predispose to breast, ovarian, pancreatic and other types of cancer. The presence of a pathogenic mutation in patients or their family members warrants close surveillance or prophylactic surgery. Besides clearly pathogenic mutations, variants leading only to a single amino acid substitution are often identified. The influence of such variants on cancer risk is often unknown, making their presence a major clinical problem. When genetic methods are insufficient to classify these variants, functional assays with various cellular models are performed. We developed and applied a new syngeneic model of human cancer cells to test all variants of unknown significance in exon 18 identified by genetic testing of high-risk cancer patients in the Czech Republic, via introduction of constructs containing each of these variants into the wild-type allele of BRCA2-heterozygous DLD1 cells (BRCA2 wt/Δex11 ). We found unaffected DNA repair function of BRCA2 in cell lines BRCA2 7997G>C/Δex11 , BRCA2 8111C>T/Δex11 , BRCA2 8149G>T/Δex11 , BRCA2 8182G>A/Δex11 , and BRCA2 8182G>T/Δex11 , whereas the cell line BRCA2 8168A>G/Δex11 and the nonsense mutation carrying line BRCA2 8305G>T/ Δex11 did affect protein function. Targeting the BRCA2 wild-type allele with a construct carrying the variant c.7988A> G resulted in incorporation exclusively into the already defective allele in all viable clones, strongly suggesting a detrimental phenotype. Our model thus offers a valuable tool for the functional evaluation of unclassified variants in the BRCA2 gene and provides a stable and distributable cellular resource for further research.

Esophageal cancer is a common disease with poor survival rates. The treatment and prognosis of patients with esophageal cancer depend on the stage of the disease. Accurate clinical staging is critical for stratifying patients for treatment. While advanced cancers are generally treated by neoadjuvant chemoradiotherapy and surgery, early cancers may be amendable to endoluminal, minimally invasive treatments, thus saving patients from unnecessary surgery. Endoscopic ultrasonography has a major role in loco-regional staging of esophageal cancer and should be performed in all patients after excluding significant comorbidities and distant metastases. However, the role of endosonography seems to be limited in early cancer, since it does not determine the depth of invasion with sufficient accuracy. This can prove decisive for treatment planning. Despite substantial efforts, its main role in early cancer is still confined to ruling out the deeper involvement or lymph node metastasis. A preferable treatment is for patients to undergo a diagnostic endoscopic resection, which facilitates correct pathological staging and final treatment decision.

1:  ESGE suggests using contrast-enhanced computed tomography (CT) as the first-line imaging modality on admission when indicated and up to the 4th week from onset in the absence of contraindications. Magnetic resonance imaging (MRI) may be used instead of CT in patients with contraindications to contrast-enhanced CT, and after the 4th week from onset when invasive intervention is considered because the contents (liquid vs. solid) of pancreatic collections are better characterized by MRI and evaluation of pancreatic duct integrity is possible. Weak recommendation, low quality evidence. 2:  ESGE recommends against routine percutaneous fine needle aspiration (FNA) of (peri)pancreatic collections. Strong recommendation, moderate quality evidence. FNA should be performed only if there is suspicion of infection and clinical/imaging signs are unclear. Weak recommendation, low quality evidence. 3:  ESGE recommends initial goal-directed intravenous fluid therapy with Ringer's lactate (e. g. 5 - 10 mL/kg/h) at onset. Fluid requirements should be patient-tailored and reassessed at frequent intervals. Strong recommendation, moderate quality evidence. 4:  ESGE recommends against antibiotic or probiotic prophylaxis of infectious complications in acute necrotizing pancreatitis. Strong recommendation, high quality evidence. 5:  ESGE recommends invasive intervention for patients with acute necrotizing pancreatitis and clinically suspected or proven infected necrosis. Strong recommendation, low quality evidence.ESGE suggests that the first intervention for infected necrosis should be delayed for 4 weeks if tolerated by the patient. Weak recommendation, low quality evidence. 6:  ESGE recommends performing endoscopic or percutaneous drainage of (suspected) infected walled-off necrosis as the first interventional method, taking into account the location of the walled-off necrosis and local expertise. Strong recommendation, moderate quality evidence. 7:  ESGE suggests that, in the absence of improvement following endoscopic transmural drainage of walled-off necrosis, endoscopic necrosectomy or minimally invasive surgery (if percutaneous drainage has already been performed) is to be preferred over open surgery as the next therapeutic step, taking into account the location of the walled-off necrosis and local expertise. Weak recommendation, low quality evidence. 8:  ESGE recommends long-term indwelling of transluminal plastic stents in patients with disconnected pancreatic duct syndrome. Strong recommendation, low quality evidence. Lumen-apposing metal stents should be retrieved within 4 weeks to avoid stent-related adverse effects.Strong recommendation, low quality evidence., Competing Interests: J. Albert has received speaker’s honoraria from Fujifilm (2015 – 2016), Falk foundation, and Covidien/Medtronic (2015 – 2017), and both research and speaker’s honoraria from Olympus Europe (2015 – 2017). A. Badaoui received a travel grant from Boston Scientific (2016). M. Barthet is a consultant for and receives research support from Boston Scientific (2016 to present). J. Devière has received research support from Cook Medical (until 2016) and from Boston Scientific (ongoing); his department is receiving research support from Olympus (ongoing). I. Hritz is a consultant (speaker/tutor) for Olympus Europe (ongoing). I. Papanikolaou is co-editor for social media with the Endoscopy journal. J.-W. Poley has received consultancy, travel, and speaker’s fees from Cook Endoscopy and Boston Scientific (ongoing). S. Seewald has received consultancy fees from Boston Scientific (until 2016), and from Olympus and Cook Medical (ongoing). J. van Hooft received lecture fees from Medtronics (2014 – 2015) and a consultancy fee from Boston Scientific (2014 – 2016); her department received research grants from Cook Medical and Abbott (2014 – 2017). K. van Lienden is receiving consultancy and speaker’s fees from Cook Medical (ongoing). M. Arvanitakis, M. A. Bali, M. Besselink, M. Delhaye, J.-M. Dumonceau, A. Ferreira, T. Gyökeres, T. Hucl, M. Milashka, H. van Santvoort, G. Vanbiervliet, and R. Voermans have no competing interests., (© Georg Thieme Verlag KG Stuttgart · New York.)

Aim: To assess the occurrence of autoimmune pancreatitis (AIP) in pancreatic resections performed for focal pancreatic enlargement., Methods: We performed a retrospective analysis of medical records of all patients who underwent pancreatic resection for a focal pancreatic enlargement at our tertiary center from January 2000 to July 2013. The indication for surgery was suspicion of a tumor based on clinical presentation, imaging findings and laboratory evaluations. The diagnosis of AIP was based on histology findings. An experienced pathologist specialized in pancreatic disease reviewed all the cases and confirmed the diagnosis in pancreatic resection specimens suggestive of AIP. The histological diagnosis of AIP was set according to the international consensus diagnostic criteria., Results: Two hundred ninety-five pancreatic resections were performed in 201 men and 94 women. AIP was diagnosed in 15 patients (5.1%, 12 men and 3 women) based on histology of the resected specimen. Six of them had AIP type 1, nine were diagnosed with AIP type 2. Pancreatic adenocarcinoma (PC) was also present in six patients with AIP (40%), all six were men. Patients with AIP + PC were significantly older (60.5 vs 49 years of age, P = 0.045), more likely to have been recently diagnosed with diabetes (67% vs 11%, P = 0.09), and had experienced greater weight loss (15.5 kg vs 8.5 kg, P = 0.03) than AIP patients without PC. AIP was not diagnosed in any patients prior to surgery; however, the diagnostic algorithm was not fully completed in every case., Conclusion: The possible co-occurrence of PC and AIP suggests that preoperative diagnosis of AIP does not rule out simultaneous presence of PC., Competing Interests: Conflict-of-interest statement: We have no financial relationship to disclose.

Percutaneous endoscopic gastrostomy (PEG) has become the method of choice for mid-to long-term enteral feeding. The majority of complications that occur are minor, but the rare major complications may be life threatening. Some complications occur soon after tube placement, others develop later, when the gastrostomy tract has matured. Older patients with comorbidities and infections appear to be at a greater risk of developing complications. Apart from being aware of indications and contraindications, proper technique of PEG placement, including correct positioning of the external fixation device, and daily tube care are important preventive measures. Adequate management of anticoagulation and antithrombotic agents is important to prevent bleeding, and administration of broad spectrum antibiotics prior to the procedure helps prevent infectious complications. Early recognition of complications enables prompt diagnosis and effective therapy., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

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., (© Georg Thieme Verlag KG Stuttgart · New York.)

The tetrahydroisoquinoline trabectedin is a marine compound with approved activity against human soft-tissue sarcoma. It exerts antiproliferative activity mainly by specific binding to the DNA and inducing DNA double-strand breaks (DSB). As homologous recombination repair (HRR)-deficient tumors are more susceptible to trabectedin, hyperthermia-mediated on-demand induction of HRR deficiency represents a novel and promising strategy to boost trabectedin treatment. For the first time, we demonstrate enhancement of trabectedin effectiveness in human sarcoma cell lines by heat and characterize cellular events and molecular mechanisms related to heat-induced effects. Hyperthermic temperatures (41.8 or 43°C) enhanced significantly trabectedin-related clonogenic cell death and G2/M cell cycle arrest followed by cell type-dependent induction of apoptosis or senescence. Heat combination increased accumulation of γH2AX foci as key marker of DSBs. Expression of BRCA2 protein, an integral protein of the HRR machinery, was significantly decreased by heat. Consequently, recruitment of downstream RAD51 to γH2AX-positive repair foci was almost abolished indicating relevant impairment of HRR by heat. Accordingly, enhancement of trabectedin effectiveness was significantly augmented in BRCA2-proficient cells by hyperthermia and alleviated in BRCA2 knockout or siRNA-transfected BRCA2 knockdown cells. In peripheral blood mononuclear cells isolated from sarcoma patients, increased numbers of nuclear γH2AX foci were detected after systemic treatment with trabectedin and hyperthermia of the tumor region. The findings establish BRCA2 degradation by heat as a key factor for a novel treatment strategy that allows targeted chemosensitization to trabectedin and other DNA damaging antitumor drugs by on-demand induction of HRR deficiency., (© 2016 UICC.)

This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). It addresses the removal of foreign bodies in the upper gastrointestinal tract in adults. Recommendations Nonendoscopic measures 1 ESGE recommends diagnostic evaluation based on the patient's history and symptoms. ESGE recommends a physical examination focused on the patient's general condition and to assess signs of any complications (strong recommendation, low quality evidence). 2 ESGE does not recommend radiological evaluation for patients with nonbony food bolus impaction without complications. We recommend plain radiography to assess the presence, location, size, configuration, and number of ingested foreign bodies if ingestion of radiopaque objects is suspected or type of object is unknown (strong recommendation, low quality evidence). 3 ESGE recommends computed tomography (CT) scan in all patients with suspected perforation or other complication that may require surgery (strong recommendation, low quality evidence). 4 ESGE does not recommend barium swallow, because of the risk of aspiration and worsening of the endoscopic visualization (strong recommendation, low quality evidence). 5 ESGE recommends clinical observation without the need for endoscopic removal for management of asymptomatic patients with ingestion of blunt and small objects (except batteries and magnets). If feasible, outpatient management is appropriate (strong recommendation, low quality evidence). 6 ESGE recommends close observation in asymptomatic individuals who have concealed packets of drugs by swallowing ("body packing"). We recommend against endoscopic retrieval. We recommend surgical referral in cases of suspected packet rupture, failure of packets to progress, or intestinal obstruction (strong recommendation, low quality evidence). Endoscopic measures 7 ESGE recommends emergent (preferably within 2 hours, but at the latest within 6 hours) therapeutic esophagogastroduodenoscopy for foreign bodies inducing complete esophageal obstruction, and for sharp-pointed objects or batteries in the esophagus. We recommend urgent (within 24 hours) therapeutic esophagogastroduodenoscopy for other esophageal foreign bodies without complete obstruction (strong recommendation, low quality evidence). 8 ESGE suggests treatment of food bolus impaction in the esophagus by gently pushing the bolus into the stomach. If this procedure is not successful, retrieval should be considered (weak recommendation, low quality evidence). The effectiveness of medical treatment of esophageal food bolus impaction is debated. It is therefore recommended, that medical treatment should not delay endoscopy (strong recommendation, low quality evidence). 9 In cases of food bolus impaction, ESGE recommends a diagnostic work-up for potential underlying disease, including histological evaluation, in addition to therapeutic endoscopy (strong recommendation, low quality evidence). 10 ESGE recommends urgent (within 24 hours) therapeutic esophagogastroduodenoscopy for foreign bodies in the stomach such as sharp-pointed objects, magnets, batteries and large/long objects. We suggest nonurgent (within 72 hours) therapeutic esophagogastroduodenoscopy for medium-sized blunt foreign bodies in the stomach (strong recommendation, low quality evidence). 11 ESGE recommends the use of a protective device in order to avoid esophagogastric/pharyngeal damage and aspiration during endoscopic extraction of sharp-pointed foreign bodies. Endotracheal intubation should be considered in the case of high risk of aspiration (strong recommendation, low quality evidence). 12 ESGE suggests the use of suitable extraction devices according to the type and location of the ingested foreign body (weak recommendation, low quality evidence). 13 After successful and uncomplicated endoscopic removal of ingested foreign bodies, ESGE suggests that the patient may be discharged. If foreign bodies are not or cannot be removed, a case-by-case approach depending on the size and type of the foreign body is suggested (weak recommendation, low quality evidence)., (© Georg Thieme Verlag KG Stuttgart · New York.)

Steatosis occurs frequently after liver transplantation (LT). We aimed to determine the prevalence of steatosis in adult LT recipients, to determine the effects of significant (>33%; grades 2-3) steatosis on patient survival, and to identify risk factors for the development of significant steatosis and its effect on fibrosis progression. We retrospectively examined 2360 posttransplant biopsies of 548 LT recipients. Survival was compared between patients with significant steatosis and those with grades 0-1 steatosis. Patients with significant steatosis were compared to controls without steatosis (grade 0) for clinical and laboratory factors and fibrosis progression. Steatosis was found in 309 (56.4%) patients, including 93 (17.0%) patients with significant steatosis. Steatohepatitis (nonalcoholic fatty liver disease activity score ≥ 5) was diagnosed in 57 (10.4%) patients. The prevalence of steatosis increased from 30.3% at 1 year to 47.6% at 10 years after LT (P < 0.001). Survival times did not differ between groups (P = 0.29). On multivariate analysis of pretransplant factors and initial immunosuppression (IS), alcohol-induced cirrhosis (P < 0.001) and high body mass index (BMI; P = 0.002) were associated with the development of significant steatosis, whereas increased levels of alkaline phosphatase (P = 0.01) and mycophenolate mofetil given initially (P = 0.009) appeared to protect against significant steatosis. On multivariate analysis of posttransplant factors, high BMI (P < 0.001), serum triglycerides (P < 0.001), alcohol consumption (P = 0.005), and type 2 diabetes mellitus (P = 0.048) were associated with significant steatosis, whereas high creatinine (P = 0.02) appeared to protect against significant steatosis. Significant steatosis was not associated with a higher fibrosis stage (P = 0.62). Posttransplant steatosis affects 56.4% of LT recipients, and the prevalence increases with time after LT. Recipient factors and types of IS affect the risk for significant steatosis, which is not associated with a higher fibrosis stage or worse patient survival. Liver Transplantation 22 644-655 2016 AASLD., (© 2015 American Association for the Study of Liver Diseases.)

Purpose: DNA repair defects due to detrimental BRCA2-mutations confer increased susceptibility towards DNA interstrand-crosslinking (ICL) agents and define patient subpopulations for individualized genotype-based cancer therapy. However, due to the side effects of these drugs, there is a need to identify additional agents, which could be used alone or in combination with ICL-agents. Therefore, we investigated whether BRCA2-mutations might also increase the sensitivity towards TRAIL-receptors (TRAIL-R)-targeting compounds., Experimental Design: Two independent model systems were applied: a BRCA2 gene knockout and a BRCA2 gene complementation model. The effects of TRAIL-R-targeting compounds and ICL-agents on cell viability, apoptosis and cell cycle distribution were compared in BRCA2-proficient versus-deficient cancer cells in vitro. In addition, the effects of the TRAIL-R2-targeting antibody LBY135 were assessed in vivo using a murine tumor xenograft model., Results: BRCA2-deficient cancer cells displayed an increased sensitivity towards TRAIL-R-targeting agents. These effects exceeded and were mechanistically distinguishable from the well-established effects of ICL-agents. In vitro, ICL-agents expectedly induced an early cell cycle arrest followed by delayed apoptosis, whereas TRAIL-R-targeting compounds caused early apoptosis without prior cell cycle arrest. In vivo, treatment with LBY135 significantly reduced the tumor growth of BRCA2-deficient cancer cells in a xenograft model., Conclusions: BRCA2 mutations strongly increase the in vitro- and in vivo-sensitivity of cancer cells towards TRAIL-R-mediated apoptosis. This effect is mechanistically distinguishable from the well-established ICL-hypersensitivity of BRCA2-deficient cells. Our study thus defines a new genetic subpopulation of cancers susceptible towards TRAIL-R-targeting compounds, which could facilitate novel therapeutic approaches for patients with BRCA2-deficient tumors.

The European Society of Gastrointestinal Endoscopy (ESGE) and United European Gastroenterology (UEG) have a vision to create a thriving community of endoscopy services across Europe, collaborating with each other to provide high quality, safe, accurate, patient-centered and accessible endoscopic care. Whilst the boundaries of what can be achieved by advanced endoscopy are continually expanding, we believe that one of the most fundamental steps to achieving our goal is to raise the quality of everyday endoscopy. The development of robust, consensus- and evidence-based key performance measures is the first step in this vision. ESGE and UEG have identified quality of endoscopy as a major priority. This paper explains the rationale behind the ESGE Quality Improvement Initiative and describes the processes that were followed. We recommend that all units develop mechanisms for audit and feedback of endoscopist and service performance using the ESGE performance measures that will be published in future issues of this journal over the next year. We urge all endoscopists and endoscopy services to prioritize quality and to ensure that these performance measures are implemented and monitored at a local level, so that we can provide the highest possible care for our patients.

Aims. The aim of our study was to determine the physiologic impact of NOTES and to compare the transgastric and transcolonic approaches. Methods. Thirty pigs were randomized to transgastric, transcolonic, or laparoscopic peritoneoscopy. Blood was drawn and analyzed for C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin- (IL-) 1β, IL-6, WBCs, and platelets. Results. Endoscopic closure with an OTSC was successful in all 20 animals. The postoperative course was uneventful in all animals. CRP values rose on day 1 in all animals and slowly declined to baseline levels on day 14 with no differences between the groups (P > 0.05, NS). The levels of TNF-α were significantly increased in the transcolonic group (P < 0.01); however this difference was already present prior to the procedure and remained unchanged. No differences were observed in IL1-β and IL-6 values. There was a temporary rise of WBC on day 1 and of platelets on day 7 in all groups (P > 0.05, NS). Conclusions. Transgastric, transcolonic, and laparoscopic peritoneoscopy resulted in similar changes in systemic inflammatory markers. Our findings do not support the assumption that NOTES is less invasive than laparoscopy.

Pancreatic cancer and cholangiocarcinoma are the most common causes of malignant biliary obstruction. They are diseases of increasing incidence and unfavorable prognosis. Only patients with localized disease indicated for surgery have a chance of long-term survival. These patients represent less than 20 % of all patients, despite the progress in our diagnostic abilities.Locally advanced and metastatic tumors are treated with palliative chemotherapy or chemoradiotherapy; the results of such treatments are unsatisfactory. The average survival of patients with unresectable disease is 6 months and only 5-10 % of patients survive 5 years.Biliary drainage is an integral part of palliative treatment. Endoscopically or percutaneosly placed stents improve quality of life, decrease cholestasis and pruritus, but do not significantly improve survival. Biliary stents get occluded over time, possibly resulting in acute cholangitis and require repeated replacement.Photodynamic therapy and radiofrequency ablation, locally active endoscopic methods, have been increasingly used in recent years in palliative treatment of patients with malignant biliary obstruction. In photodynamic therapy, photosensitizer accumulates in tumor tissue and is activated 48 hours later by light of a specific wave length. Application of low voltage high frequency current during radiofrequency ablation results in tissue destruction by heat. Local ablation techniques can have a significant impact in a large group of patients with malignant biliary obstruction, leading to improved prognosis, quality of life and stent patency.

This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). It addresses the diagnosis and management of nonvariceal upper gastrointestinal hemorrhage (NVUGIH). Main Recommendations MR1. ESGE recommends immediate assessment of hemodynamic status in patients who present with acute upper gastrointestinal hemorrhage (UGIH), with prompt intravascular volume replacement initially using crystalloid fluids if hemodynamic instability exists (strong recommendation, moderate quality evidence). MR2. ESGE recommends a restrictive red blood cell transfusion strategy that aims for a target hemoglobin between 7 g/dL and 9 g/dL. A higher target hemoglobin should be considered in patients with significant co-morbidity (e. g., ischemic cardiovascular disease) (strong recommendation, moderate quality evidence). MR3. ESGE recommends the use of the Glasgow-Blatchford Score (GBS) for pre-endoscopy risk stratification. Outpatients determined to be at very low risk, based upon a GBS score of 0 - 1, do not require early endoscopy nor hospital admission. Discharged patients should be informed of the risk of recurrent bleeding and be advised to maintain contact with the discharging hospital (strong recommendation, moderate quality evidence). MR4. ESGE recommends initiating high dose intravenous proton pump inhibitors (PPI), intravenous bolus followed by continuous infusion (80 mg then 8 mg/hour), in patients presenting with acute UGIH awaiting upper endoscopy. However, PPI infusion should not delay the performance of early endoscopy (strong recommendation, high quality evidence). MR5. ESGE does not recommend the routine use of nasogastric or orogastric aspiration/lavage in patients presenting with acute UGIH (strong recommendation, moderate quality evidence). MR6. ESGE recommends intravenous erythromycin (single dose, 250 mg given 30 - 120 minutes prior to upper gastrointestinal [GI] endoscopy) in patients with clinically severe or ongoing active UGIH. In selected patients, pre-endoscopic infusion of erythromycin significantly improves endoscopic visualization, reduces the need for second-look endoscopy, decreases the number of units of blood transfused, and reduces duration of hospital stay (strong recommendation, high quality evidence). MR7. Following hemodynamic resuscitation, ESGE recommends early (≤ 24 hours) upper GI endoscopy. Very early (< 12 hours) upper GI endoscopy may be considered in patients with high risk clinical features, namely: hemodynamic instability (tachycardia, hypotension) that persists despite ongoing attempts at volume resuscitation; in-hospital bloody emesis/nasogastric aspirate; or contraindication to the interruption of anticoagulation (strong recommendation, moderate quality evidence). MR8. ESGE recommends that peptic ulcers with spurting or oozing bleeding (Forrest classification Ia and Ib, respectively) or with a nonbleeding visible vessel (Forrest classification IIa) receive endoscopic hemostasis because these lesions are at high risk for persistent bleeding or rebleeding (strong recommendation, high quality evidence). MR9. ESGE recommends that peptic ulcers with an adherent clot (Forrest classification IIb) be considered for endoscopic clot removal. Once the clot is removed, any identified underlying active bleeding (Forrest classification Ia or Ib) or nonbleeding visible vessel (Forrest classification IIa) should receive endoscopic hemostasis (weak recommendation, moderate quality evidence). MR10. In patients with peptic ulcers having a flat pigmented spot (Forrest classification IIc) or clean base (Forrest classification III), ESGE does not recommend endoscopic hemostasis as these stigmata present a low risk of recurrent bleeding. In selected clinical settings, these patients may be discharged to home on standard PPI therapy, e. g., oral PPI once-daily (strong recommendation, moderate quality evidence). MR11. ESGE recommends that epinephrine injection therapy not be used as endoscopic monotherapy. If used, it should be combined with a second endoscopic hemostasis modality (strong recommendation, high quality evidence). MR12. ESGE recommends PPI therapy for patients who receive endoscopic hemostasis and for patients with adherent clot not receiving endoscopic hemostasis. PPI therapy should be high dose and administered as an intravenous bolus followed by continuous infusion (80 mg then 8 mg/hour) for 72 hours post endoscopy (strong recommendation, high quality evidence). MR13. ESGE does not recommend routine second-look endoscopy as part of the management of nonvariceal upper gastrointestinal hemorrhage (NVUGIH). However, in patients with clinical evidence of rebleeding following successful initial endoscopic hemostasis, ESGE recommends repeat upper endoscopy with hemostasis if indicated. In the case of failure of this second attempt at hemostasis, transcatheter angiographic embolization (TAE) or surgery should be considered (strong recommendation, high quality evidence). MR14. In patients with NVUGIH secondary to peptic ulcer, ESGE recommends investigating for the presence of Helicobacter pylori in the acute setting with initiation of appropriate antibiotic therapy when H. pylori is detected. Re-testing for H. pylori should be performed in those patients with a negative test in the acute setting. Documentation of successful H. pylori eradication is recommended (strong recommendation, high quality evidence). MR15. In patients receiving low dose aspirin for secondary cardiovascular prophylaxis who develop peptic ulcer bleeding, ESGE recommends aspirin be resumed immediately following index endoscopy if the risk of rebleeding is low (e. g., FIIc, FIII). In patients with high risk peptic ulcer (FIa, FIb, FIIa, FIIb), early reintroduction of aspirin by day 3 after index endoscopy is recommended, provided that adequate hemostasis has been established (strong recommendation, moderate quality evidence)., (© Georg Thieme Verlag KG Stuttgart · New York.)

Acute gastrointestinal obstruction occurs when the normal flow of intestinal contents is interrupted. The blockage can occur at any level throughout the gastrointestinal tract. The clinical symptoms depend on the level and extent of obstruction. Various benign and malignant processes can produce acute gastrointestinal obstruction, which often represents a medical emergency because of the potential for bowel ischemia leading to perforation and peritonitis. Early recognition and appropriate treatment are thus essential. The typical clinical symptoms associated with obstruction include nausea, vomiting, dysphagia, abdominal pain and failure to pass bowel movements. Abdominal distention, tympany due to an air-filled stomach and high-pitched bowel sounds suggest the diagnosis. The diagnostic process involves imaging including radiography, ultrasonography, contrast fluoroscopy and computer tomography in less certain cases. In patients with uncomplicated obstruction, management is conservative, including fluid resuscitation, electrolyte replacement, intestinal decompression and bowel rest. In many cases, endoscopy may aid in both the diagnostic process and in therapy. Endoscopy can be used for bowel decompression, dilation of strictures or placement of self-expandable metal stents to restore the luminal flow either as a final treatment or to allow for a delay until elective surgical therapy. When gastrointestinal obstruction results in ischemia, perforation or peritonitis, emergency surgery is required., (Copyright © 2013. Published by Elsevier Ltd.)

Background and Study Aims: Histological examination of core tissue samples may have advantages over cytology in endoscopic ultrasound (EUS)-guided sampling. We aimed to evaluate the feasibility and efficiency of a new 22G core biopsy needle., Patients and Methods: Consecutive patients with a pancreatic mass lesion or peri-intestinal lymphadenopathy sequentially underwent fine needle biopsy with both a newly developed 22G core needle (the FNB needle) and a standard 22G fine needle aspiration (FNA) needle, in randomized order., Results: In 144 patients, mean age 48 years (± standard deviation [SD] 14; range 18 - 82), with 145 lesions (mean lesion size 39 ± 15 mm, range 15 - 99), EUS-guided sampling was technically feasible with both needles in all patients. Mean number of passes to obtain sufficient tissue was 1.2 ± 0.5 with the core needle vs. 2.5 ± 0.9 with the standard needle (P < 0.001). FNB specimens were adequate for evaluation in 125 (86.2 %) vs. 127 (87.6 %) with FNA (P = 0.72). Among 139 patients available for follow-up, FNB provided a correct diagnosis in 110 (79.1 %) and FNA in 112 (80.6 %) (P = 0.73). Sensitivity, specificity, positive and negative predictive values, and accuracy for diagnosis of malignancy were 90 %, 100 %, 100 %, 93 %, 96 % for FNB and 77 %, 100 %, 100 %, 85 %, 92 % for FNA, respectively (P > 0.05)., Conclusion: FNB with the new 22G core needle was technically feasible, efficient and comparable to FNA with a standard needle. The core needle required fewer passes to provide an adequate sample, offering potentially shorter procedure time., (© Georg Thieme Verlag KG Stuttgart · New York.)

Aim: To evaluate the expression of epithelial markers of colorectal carcinogenesis in patients with long-term ulcerative colitis (UC) and primary sclerosing cholangitis (PSC) before and after transplantation., Methods: Eight patients with UC and PSC prior to liver transplantation (PSC-UC), 22 patients with UC after liver transplantation for PSC (OLT), 9 patients with active ulcerative colitis without PSC (UCA), 7 patients with UC in remission (UCR) and 10 controls (N) underwent colonoscopy with multiple biopsies. Specimens were analysed histologically and semi-quantitatively immunohistochemically for p53, Bcl-2 and cyclooxygenase-2 (COX-2) markers. Statistical analysis was performed by Kruskal-Wallis and Fisher's exact tests., Results: PSC-UC had a statistically significantly higher expression of p53 in the nondysplastic mucosa as compared to OLT, UCA, UCR and N (P < 0.05). We also found a statistically significant positive correlation between the incidence of PSC and the expression of p53 (P < 0.001). UCA had a higher p53 expression as compared to UCR. OLT had a significantly lower expression of p53 as compared with PSC-UC (P < 0.001). Bcl-2 had a significant higher bcl-2 expression as compared with controls. No difference in COX-2 expression between PSC-UC, UCR and UCA was found. UCA had higher COX-2 expression as compared to UCR. We also found a statistically significant positive correlation between the expression of COX-2 and p53. Patients after liver transplantation for PSC had a statistically significantly lower expression of the p53 compared with PSC-UC (P < 0.001). PSC-UC had the same inflammatory endoscopic activity as OLT and UCR when evaluated with the Mayo score., Conclusion: Our study shows that the nondysplatic mucosa of UC patients with PSC is characterised by a higher expression of the tumour suppressor gene p53, suggesting a higher susceptibility of cancer. This p53 overexpression correlates with the presence of PSC whilst it is not present in patients with UC after liver transplantation for PSC.

Aim: To investigate perception of natural orifice transluminal endoscopic surgery (NOTES) as a potential technique for appendectomy., Methods: One hundred patients undergoing endoscopy and 100 physicians were given a questionnaire describing in detail the techniques of NOTES and laparoscopic appendectomy. They were asked about the reasons for their preference, choice of orifice, and extent of complication risk they were willing to accept., Results: Fifty patients (50%) and only 21 physicians (21%) preferred NOTES (P < 0.001). Patients had previously heard of NOTES less frequently (7% vs 73%, P < 0.001) and had undergone endoscopy more frequently (88% vs 36%, P < 0.001) than physicians. Absence of hernia was the most common reason for NOTES preference in physicians (80% vs 44%, P = 0.003), whereas reduced pain was the most common reason in patients (66% vs 52%). Physicians were more likely to refuse NOTES as a novel and unsure technique (P < 0.001) and having an increased risk of infection (P < 0.001). The preferred access site in both groups was colon followed by stomach, with vagina being rarely preferred. In multivariable modeling, those with high-school education [odds ratio (OR): 2.68, 95% confidence interval (CI): 1.23-5.83] and prior colonoscopy (OR: 2.10, 95% CI: 1.05-4.19) were more likely to prefer NOTES over laparoscopic appendectomy. There was a steep decline in NOTES preference with increased rate of procedural complications. Male patients were more likely to consent to their wives vaginal NOTES appendectomy than male physicians (P = 0.02)., Conclusion: The preference of NOTES for appendectomy was greater in patients than physicians and was related to reduced pain and absence of hernia rather than lack of scarring.

Unlabelled: INTRODUCTION, STUDY AIM: Colorectal carcinoma is one of the most frequent malignancies. Most frequently, neoplasms, including malignant precursors, are in the form of polyps, although these might be of a non-tumour origin. The aim of this prospective multicentre study was to provide an overview of coloscopic identification and biological nature of polyps., Results: 3,400 consecutive coloscopies performed between 2009 and 2010 were analyzed. At different centres, the top of the cecum was reached in 89% to 93% and terminal ileum in 73% to 87% of cases. In the above 40 age group, 26.6% were screening coloscopies. The mean age of the above 40 patients was 56 years. The incidence of potential neoplastic lesions (polyps, carcinomas), advanced adenomas and carcinomas were: 7.8 %, 0.8 % and 0.16 %, respectively, in the above 40 age group, 41.5 %, 9.8 % and 1.6 %, respectively, in the 40-50 years age group and 70.5 %, 31.3 % and 6.8 %, respectively, in the above 50 age group. The incidence of tubular adenoma and hyperplastic polyps was 23.9% and 66.2%, respectively, in the below 40 age group and 53.1% and 26.1% in the above 50 age group. 57.8% of advances neoplasms were located in the rectosigmoid a descendent colon. The incidence ratio for adenomas and hyperplastic polyps was 76.6% and 14%, respectively, for rectosigmoid colon, 63.6 and 17.4 %, respectively, for descendent colon, 63.6 and 11.4 % for traverse colon and 63,4 a 17,9 %, respectively, for cecum and ascendant colon. The incidence of tubulovillous adenomas and hyperplastic polyps in pedunculated polyps larger than 1 cm was 19.4 % and 20.4 %, respectively, and 34.2 % and 13.1 %, respectively, in other polyps. The incidence of potential lesions (polyps and carcinomas), advanced adenomas, carcinomas and advanced neoplasms was 66.7 %, 23.1 %, 5.8 % and 28.9 %, respectively, in women and 63.1 %, 30.0 %, 5.7 % and 34.7 %, respectively, in men., Conclusion: The top of the cecum was reached in a higher proportion of cases than required, although this was lower than in the majority of other recent studies. Terminal ileum was reached in high number of cases. The incidence of polyps and neoplasms rose sharply from 40 years of age. Therefore, the screening threshold should be extended to the below 50 age group. Hyperplastic polyps predominated in younger age and adenomas in the above 40 age group. Histological profile was similar and did not suggest importantly different pathogenesis with respect to localization. There were relatively fewer adenomas and more hyperplastic polyps in pedunculated polyps and vice verse in other types of polyps, suggesting a higher risk associated with non-pedunculated lesions. Both sexes differed less than suggested based on epidemiological statistics.