Prospective randomized controlled trial comparing a novel and dedicated device with conventional endoscopic techniques for the treatment of buried bumper syndrome (with video).

BACKGROUND AND AIMS: Buried bumper syndrome (BBS) is a rare adverse event of PEG tubes. This study compared the newly developed Flamingo device (Fujifilm Medwork GmbH, Höchstadt, Germany) with conventional endoscopic techniques for BBS treatment. METHODS: This prospective, randomized controlled trial compared the Flamingo set (study group) with other endoscopic techniques (control group) for BBS treatment in 6 German hospitals. The primary endpoint was procedure time. Further outcome parameters were technical success, adverse event rate, and number and cost of devices used in each group. RESULTS: Thirty-six patients (18 in each group; mean age, 73 years; 12 women) were included in this study between March 2018 and December 2022. Median time since placement of the feeding tube was 30 months. The bumper was located in the gastric corpus in 27 patients, and the internal bumper was completely overgrown in 31 patients. The duration of the removal procedure was 17 minutes (range, 3-72) in the study group compared with 38 minutes (range, 12-111) in the control group (P = .046). The primary technical success rate was 77.8% in the study group and 55.6% in the control group (P = .157), whereas the overall technical success rate was 100% compared with 83.3% (P = .070). Adverse events occurred in 4 patients (11.1%). CONCLUSIONS: Endoscopic removal of the buried bumper using the Flamingo device was significantly faster than that with other endoscopic techniques and showed a higher technical success rate. This device may become the endoscopic treatment of choice for BBS. (Clinical trial registration number: NCT03186066.).

GWAS meta-analysis of 16 790 patients with Barrett's oesophagus and oesophageal adenocarcinoma identifies 16 novel genetic risk loci and provides insights into disease aetiology beyond the single marker level.

OBJECTIVE: Oesophageal cancer (EC) is the sixth leading cause of cancer-related deaths. Oesophageal adenocarcinoma (EA), with Barrett's oesophagus (BE) as a precursor lesion, is the most prevalent EC subtype in the Western world. This study aims to contribute to better understand the genetic causes of BE/EA by leveraging genome wide association studies (GWAS), genetic correlation analyses and polygenic risk modelling. DESIGN: We combined data from previous GWAS with new cohorts, increasing the sample size to 16 790 BE/EA cases and 32 476 controls. We also carried out a transcriptome wide association study (TWAS) using expression data from disease-relevant tissues to identify BE/EA candidate genes. To investigate the relationship with reported BE/EA risk factors, a linkage disequilibrium score regression (LDSR) analysis was performed. BE/EA risk models were developed combining clinical/lifestyle risk factors with polygenic risk scores (PRS) derived from the GWAS meta-analysis. RESULTS: The GWAS meta-analysis identified 27 BE and/or EA risk loci, 11 of which were novel. The TWAS identified promising BE/EA candidate genes at seven GWAS loci and at five additional risk loci. The LDSR analysis led to the identification of novel genetic correlations and pointed to differences in BE and EA aetiology. Gastro-oesophageal reflux disease appeared to contribute stronger to the metaplastic BE transformation than to EA development. Finally, combining PRS with BE/EA risk factors improved the performance of the risk models. CONCLUSION: Our findings provide further insights into BE/EA aetiology and its relationship to risk factors. The results lay the foundation for future follow-up studies to identify underlying disease mechanisms and improving risk prediction.

Digital single-operator pancreatoscopy for the treatment of symptomatic pancreatic duct stones: a prospective multicenter cohort trial.

BACKGROUND: Digital single-operator pancreatoscopy (DSOP)-guided lithotripsy is a novel treatment modality for pancreatic endotherapy, with demonstrated technical success in retrospective series of between 88 % and 100 %. The aim of this prospective multicenter trial was to systematically evaluate DSOP in patients with chronic pancreatitis and symptomatic pancreatic duct stones. METHODS: Patients with symptomatic chronic pancreatitis and three or fewer stones ≥ 5mm in the main pancreatic duct (MPD) of the pancreatic head or body were included. The primary end point was complete stone clearance (CSC) in three or fewer treatment sessions with DSOP. Current guidelines recommend extracorporeal shock wave lithotripsy (ESWL) for MPD stones > 5 mm. A performance goal was developed to show that the CSC rate of MPD stones using DSOP was above what has been previously reported for ESWL. Secondary end points were pain relief measured with the Izbicki pain score (IPS), number of interventions, and serious adverse events (SAEs). RESULTS: 40 chronic pancreatitis patients were included. CSC was achieved in 90 % of patients (36/40) on intention-to-treat analysis, after a mean (SD) of 1.36 (0.64) interventions (53 procedures in total). The mean (SD) baseline IPS decreased from 55.3 (46.2) to 10.9 (18.3). Overall pain relief was achieved in 82.4 % (28/34) after 6 months of follow-up, with complete pain relief in 61.8 % (21/34) and partial pain relief in 20.6 % (7/34). SAEs occurred in 12.5 % of patients (5/40), with all treated conservatively. CONCLUSION: DSOP-guided endotherapy is effective and safe for the treatment of symptomatic MPD stones in highly selected patients with chronic pancreatitis. It significantly reduces pain and could be considered as an alternative to standard ERCP techniques for MPD stone treatment in these patients.

Over-the-scope-clips versus standard treatment in high-risk patients with acute non-variceal upper gastrointestinal bleeding: a randomised controlled trial (STING-2).

OBJECTIVE: Acute non-variceal upper gastrointestinal bleeding (NVUGIB) is managed by standard endoscopic combination therapy, but a few cases remain difficult and carry a high risk of persistent or recurrent bleeding. The aim of our study was to compare first-line over-the-scope-clips (OTSC) therapy with standard endoscopic treatment in these selected patients. DESIGN: We conducted a prospective, randomised, controlled, multicentre study (NCT03331224). Patients with endoscopic evidence of acute NVUGIB and high risk of rebleeding (defined as complete Rockall Score ≥7) were included. Primary endpoint was clinical success defined as successful endoscopic haemostasis without evidence of recurrent bleeding. RESULTS: 246 patients were screened and 100 patients were finally randomised (mean of 5 cases/centre and year; 70% male, 30% female, mean age 78 years; OTSC group n=48, standard group n=52). All but one case in the standard group were treated with conventional clips. Clinical success was 91.7% (n=44) in the OTSC group compared with 73.1% (n=38) in the ST group (p=0.019), with persistent bleeding occurring in 0 vs 6 in the OTSC versus standard group (p=0.027), all of the latter being successfully managed by rescue therapy with OTSC. Recurrent bleeding was observed in four patients (8.3%) in the OTSC group and in eight patients (15.4%) in the standard group (p=0.362). CONCLUSION: OTSC therapy appears to be superior to standard treatment with clips when used by trained physicians for selected cases of primary therapy of NVUGIB with high risk of rebleeding. Further studies are necessary with regards to patient selection to identify subgroups benefiting most from OTSC haemostasis. TRIAL REGISTRATION NUMBER: NCT03331224.

Endoscopic Submucosal Dissection in Europe: Results of 1000 Neoplastic Lesions From the German Endoscopic Submucosal Dissection Registry.

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) enables the curative resection of early malignant lesions and is associated with reduced recurrence risk. Due to the lack of comprehensive ESD data in the West, the German ESD registry was set up to evaluate relevant outcomes of ESD. METHODS: The German ESD registry is a prospective uncontrolled multicenter study. During a 35-month period, 20 centers included 1000 ESDs of neoplastic lesions. The results were evaluated in terms of en bloc, R0, curative resection rates, and recurrence rate after a 3-month and 12-month follow-up. Additionally, participating centers were grouped into low-volume (≤20 ESDs/y), middle-volume (20-50/y), and high-volume centers (>50/y). A multivariate analysis investigating risk factors for noncurative resection was performed. RESULTS: Overall, en bloc, R0, and curative resection rates of 92.4% (95% confidence interval [CI], 0.90-0.94), 78.8% (95% CI, 0.76-0.81), and 72.3% (95% CI, 0.69-0.75) were achieved, respectively. The overall complication rate was 8.3% (95% CI, 0.067-0.102), whereas the recurrence rate after 12 months was 2.1%. High-volume centers had significantly higher en bloc, R0, curative resection rates, and recurrence rates and lower complication rates than middle- or low-volume centers. The lesion size, hybrid ESD, age, stage T1b carcinoma, and treatment outside high-volume centers were identified as risk factors for noncurative ESD. CONCLUSION: In Germany, ESD achieves excellent en bloc resection rates but only modest curative resection rates. ESD requires a high level of expertise, and results vary significantly depending on the center's yearly case volume.

Impact of endobiliary radiofrequency ablation on biliary drainage in patients with malignant biliary strictures treated with uncovered self-expandable metal stents: a randomized controlled multicenter trial.

BACKGROUND AND AIMS: Endobiliary radiofrequency ablation (RFA), usually combined with endoscopic stent insertion, is a simple procedure with the potential to improve stent patency and patient survival for malignant biliary obstruction. We conducted this randomized multicenter trial to evaluate the impact of RFA on stent patency. METHODS: Eighty-six patients with malignant biliary obstruction and nonresectable tumors (pancreatic carcinoma, cholangiocarcinoma, or metastases) were included and randomly assigned to receive a self-expandable metal stent (SEMS) only (n = 44) or RFA followed by SEMS insertion (RFA+SEMS, n = 42). The primary outcome measure was stent patency after 3 and 6 months; secondary outcome measures were patient survival and early adverse events within 30 days. RESULTS: Technical success rates for RFA and stent insertion were 100% and 98.8%, respectively. Stent patency after 3 and 6 months did not differ significantly between groups (RFA+SEMS group, 73.1% and 33.3%, respectively; SEMS-only group, 81.8% and 52.4%, respectively; P = .6). Similarly, the addition of RFA did not impact overall survival (hazard ratio, .72; P = .389 for RFA+SEMS). The adverse event rate in the RFA+SEMS group was 10.5% compared with 2.3% in the SEMS-only group, without a statistically significant difference (P = .18). CONCLUSIONS: RFA as an addition to SEMS implantation had no positive impact on patency rate or survival. (Clinical trial registration number: DRKS00018993.).

Quantitative analysis of submucosal excision depth in endoscopic resection for early Barrett's cancer.

BACKGROUND : Following endoscopic resection of early-stage Barrett's esophageal adenocarcinoma (BEA), further oncologic management then fundamentally relies upon the accurate assessment of histopathologic risk criteria, which requires there to be sufficient amounts of submucosal tissue in the resection specimens. METHODS : In 1685 digitized tissue sections from endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) performed for 76 early BEA cases from three experienced centers, the submucosal thickness was determined, using software developed in-house. Neoplastic lesions were manually annotated. RESULTS : No submucosa was seen in about a third of the entire resection area (mean 33.8 % [SD 17.2 %]), as well as underneath cancers (33.3 % [28.3 %]), with similar results for both resection methods and with respect to submucosal thickness. ESD results showed a greater variability between centers than EMR. In T1b cancers, a higher rate of submucosal defects tended to correlate with R1 resections. CONCLUSION : The absence of submucosa underneath about one third of the tissue of endoscopically resected BEAs should be improved. Results were more center-dependent for ESD than for EMR. Submucosal defects can potentially serve as a parameter for standardized reports.

Sex-Specific Genetic Associations for Barrett's Esophagus and Esophageal Adenocarcinoma.

BACKGROUND & AIMS: Esophageal adenocarcinoma (EA) and its premalignant lesion, Barrett's esophagus (BE), are characterized by a strong and yet unexplained male predominance (with a male-to-female ratio in EA incidence of up to 6:1). Genome-wide association studies (GWAS) have identified more than 20 susceptibility loci for these conditions. However, potential sex differences in genetic associations with BE/EA remain largely unexplored. METHODS: Given strong genetic overlap, BE and EA cases were combined into a single case group for analysis. These were compared with population-based controls. We performed sex-specific GWAS of BE/EA in 3 separate studies and then used fixed-effects meta-analysis to provide summary estimates for >9 million variants for male and female individuals. A series of downstream analyses were conducted separately in male and female individuals to identify genes associated with BE/EA and the genetic correlations between BE/EA and other traits. RESULTS: We included 6758 male BE/EA cases, 7489 male controls, 1670 female BE/EA cases, and 6174 female controls. After Bonferroni correction, our meta-analysis of sex-specific GWAS identified 1 variant at chromosome 6q11.1 (rs112894788, KHDRBS2-MTRNR2L9, PBONF = .039) that was statistically significantly associated with BE/EA risk in male individuals only, and 1 variant at chromosome 8p23.1 (rs13259457, PRSS55-RP1L1, PBONF = 0.057) associated, at borderline significance, with BE/EA risk in female individuals only. We also observed strong genetic correlations of BE/EA with gastroesophageal reflux disease in male individuals and obesity in female individuals. CONCLUSIONS: The identified novel sex-specific variants associated with BE/EA could improve the understanding of the genetic architecture of the disease and the reasons for the male predominance.

Use of over-the-scope clips in the colon in clinical practice: results from a German administrative database.

BACKGROUND : The efficacy and safety of over-the-scope (OTS) clips in the colon is limited. This study aimed to evaluate OTS clip use in the colon in routine colonoscopy. METHODS: Using administrative data from a large health insurance company, patients with OTS clip placement during colonoscopy were identified and analyzed by specific administrative codes. Indication for OTS clipping was analyzed, and follow-up was evaluated for surgical and repeat endoscopic interventions. RESULTS: In 505 patients, indications for OTS clips were iatrogenic perforations (n = 80; Group A), polypectomy (n = 315; Group B), colonic bleeding (n = 51; Group C), and various underlying diseases (n = 59; Group D). In 11 Group A patients (13.8 %), surgical interventions occurred, mostly within 24 hours after clipping (n = 9), predominantly overstitching (n = 8). OTS clipping during polypectomy (Group B) was for complications (e. g. bleeding in 27 %) or was applied prophylactically. Only five patients required early surgery, three of whom had colorectal cancer. In four Group C patients (7.8 %), surgical resections were performed (persistent bleeding n = 1, colorectal cancer n = 2), while six patients underwent early repeat colonoscopy for recurrent bleeding. During further follow-up (days 11-30), 17 patients underwent resection for colonic neoplasms (n = 12) or persistent bleeding (n = 4), but only one case could be directly traced back to local OTS clip complication. CONCLUSION: Colonic OTS clipping appears safe and effective in selected indications and complications in clinical routine but must be anatomically and technically feasible, avoiding overuse.

No Association Between Vitamin D Status and Risk of Barrett's Esophagus or Esophageal Adenocarcinoma: A Mendelian Randomization Study.

BACKGROUND & AIMS: Epidemiology studies of circulating concentrations of 25 hydroxy vitamin D (25(OH)D) and risk of esophageal adenocarcinoma (EAC) have produced conflicting results. We conducted a Mendelian randomization study to determine the associations between circulating concentrations of 25(OH)D and risks of EAC and its precursor, Barrett's esophagus (BE). METHODS: We conducted a Mendelian randomization study using a 2-sample (summary data) approach. Six single-nucleotide polymorphisms (SNPs; rs3755967, rs10741657, rs12785878, rs10745742, rs8018720, and rs17216707) associated with circulating concentrations of 25(OH)D were used as instrumental variables. We collected data from 6167 patients with BE, 4112 patients with EAC, and 17,159 individuals without BE or EAC (controls) participating in the Barrett's and Esophageal Adenocarcinoma Consortium, as well as studies from Bonn, Germany, and Cambridge and Oxford, United Kingdom. Analyses were performed separately for BE and EAC. RESULTS: Overall, we found no evidence for an association between genetically estimated 25(OH)D concentration and risk of BE or EAC. The odds ratio per 20 nmol/L increase in genetically estimated 25(OH)D concentration for BE risk estimated by combining the individual SNP association using inverse variance weighting was 1.21 (95% CI, 0.77-1.92; P = .41). The odds ratio for EAC risk, estimated by combining the individual SNP association using inverse variance weighting, was 0.68 (95% CI, 0.39-1.19; P = .18). CONCLUSIONS: In a Mendelian randomization study, we found that low genetically estimated 25(OH)D concentrations were not associated with risk of BE or EAC.

Endoscopic full-thickness resection for early colorectal cancer.

BACKGROUND AND AIMS: Current international guidelines recommend endoscopic resection for T1 colorectal cancer (CRC) with low-risk histology features and oncologic resection for those at high risk of lymphatic metastasis. Exact risk stratification is therefore crucial to avoid under-treatment as well as over-treatment. Endoscopic full-thickness resection (EFTR) has shown to be effective for treatment of non-lifting benign lesions. In this multicenter, retrospective study we aimed to evaluate efficacy, safety, and clinical value of EFTR for early CRC. METHODS: Records of 1234 patients undergoing EFTR for various indications at 96 centers were screened for eligibility. A total of 156 patients with histologic evidence of adenocarcinoma were identified. This cohort included 64 cases undergoing EFTR after incomplete resection of a malignant polyp (group 1) and 92 non-lifting lesions (group 2). Endpoints of the study were: technical success, R0-resection, adverse events, and successful discrimination of high-risk versus low-risk tumors. RESULTS: Technical success was achieved in 144 out of 156 (92.3%). Mean procedural time was 42 minutes. R0 resection was achieved in 112 of 156 (71.8%). Subgroup analysis showed a R0 resection rate of 87.5% in Group 1 and 60.9% in Group 2 (P < .001). Severe procedure-related adverse events were recorded in 3.9% of patients. Discrimination between high-risk versus low-risk tumor was successful in 155 of 156 cases (99.3%). In Group 1, 84.1% were identified as low-risk lesions, whereas 16.3% in group 2 had low-risk features. In total, 53 patients (34%) underwent oncologic resection due to high-risk features whereas 98 patients (62%) were followed endoscopically. CONCLUSIONS: In early colorectal cancer, EFTR is technically feasible and safe. It allows exact histological risk stratification and can avoid surgery for low-risk lesions. Prospective studies are required to further define indications for EFTR in malignant colorectal lesions and to evaluate long-term outcome.

The BougieCap - a new method for endoscopic treatment of complex benign esophageal stenosis: results from a multicenter study.

BACKGROUND: A major limitation of current treatment strategies for nonmalignant upper gastrointestinal stenoses is the lack of either optical or haptic feedback during dilation. Wire guidance and fluoroscopy is often necessary to control the position. METHODS: A novel device for endoscopic dilation, the BougieCap (Ovesco Endoscopy AG, Tübingen, Germany) was evaluated in a prospective multicenter trial. Primary outcome was successful dilation of stenosis and secondary outcome was alteration in dysphagia symptoms in short-term follow-up.  RESULTS: 50 patients with benign esophageal strictures were included. Endoscopic bougienage was successful in 96 %. Bougienage failed in two cases because of high resistance. Symptoms of dysphagia decreased significantly after bougienage (59.0 points at Day 0 vs. 28.6 points at Day 14; P < 0.001). Adverse events were loss of BougieCap into the stomach in two cases; no severe adverse events were reported. CONCLUSIONS: Endoscopic treatment of benign stenoses using the BougieCap enabled direct visual control of the bougienage procedure. This might help to adapt treatment more precisely to the stricture. Symptoms of dysphagia were improved in short-term follow-up. Additional wire guidance may be used for selected cases (e. g. narrow lumen, pediatric scope).

Colonoscopic full-thickness resection using an over-the-scope device: a prospective multicentre study in various indications.

OBJECTIVE: Endoscopic full-thickness resection (EFTR) is a novel treatment of colorectal lesions not amenable to conventional endoscopic resection. The aim of this prospective multicentre study was to assess the efficacy and safety of the full-thickness resection device. DESIGN: 181 patients were recruited in 9 centres with the indication of difficult adenomas (non-lifting and/or at difficult locations), early cancers and subepithelial tumours (SET). Primary endpoint was complete en bloc and R0 resection. RESULTS: EFTR was technically successful in 89.5%, R0 resection rate was 76.9%. In 127 patients with difficult adenomas and benign histology, R0 resection rate was 77.7%. In 14 cases, lesions harboured unsuspected cancer, another 15 lesions were primarily known as cancers. Of these 29 cases, R0 resection was achieved in 72.4%; 8 further cases had deep submucosal infiltration >1000 µm. Therefore, curative resection could only be achieved in 13/29 (44.8%). In the subgroup with SET (n=23), R0 resection rate was 87.0%. In general, R0 resection rate was higher with lesions ≤2 cm vs >2 cm (81.2% vs 58.1%, p=0.0038). Adverse event rate was 9.9% with a 2.2% rate of emergency surgery. Three-month follow-up was available from 154 cases and recurrent/residual tumour was evident in 15.3%. CONCLUSION: EFTR has a reasonable technical efficacy especially in lesions ≤2 cm with acceptable complication rates. Curative resection rate for early cancers was too low to recommend its primary use in this indication. Further comparative studies have to show the clinical value and long-term outcome of EFTR in benign colorectal lesions. TRIAL REGISTRATION NUMBER: NCT02362126; Results.

Peroral endoscopic myotomy (POEM) is effective in treatment of noncardiac chest pain caused by hypercontractile esophageal motility disorders: results of the POEM-HYPE-Study.

BACKGROUND: Noncardiac chest pain (NCCP) is recurrent angina pectoris-like pain without evidence of coronary heart disease in conventional diagnostic evaluation. In gastroenterology, managing of patients with NCCP is ambiguous to detect gastroesophageal reflux and hypercontractile esophageal motility disorders. Recently, peroral endoscopic myotomy (POEM) was established as treatment option in achalasia. However, limited data exist on the effectivity of POEM in NCCP with hypercontractile esophageal motility disorders. MATERIAL AND METHODS: In this prospective study (POEM-HYPE), we evaluated 14 patients with NCCP and hypercontractile esophageal motility disorders (type III achalasia, n = 7; hypercontractile esophagus, n = 6; distal esophageal spasm, n = 1). All patients underwent standardized diagnostic work-up including esophagogastroduodenoscopy with esophageal biopsies, high-resolution esophageal manometry, and combined intraluminal impedance and pH testing before and 3 weeks after POEM. A standardized symptom questionnaire was disposed before POEM, 3 weeks after, and every 6 months after the POEM. RESULTS: After POEM, 12 patients showed significant symptom relief (pre-Eckardt score: 7.78 ±â€Š1.47, 3 weeks post: 1.64 ± 1.44, 6 months: 2.0 ±â€Š1.84 and 1.86 ±â€Š1.89 after 15.0 ±â€Š10.0 months post-intervention). High-resolution manometry showed significant reduction in integrated relaxation pressure (pre-POEM: 24.74 ±â€Š18.9 mm Hg, post-POEM: 13.8 ±â€Š16.5 mm Hg) and distal contractile integral (pre-POEM: 2880 ±â€Š3700 mmHg*s*cm, post-POEM: 1109 ±â€Š1042 mmHg*s*cm). One lesion of the submucosal tunnel occurred as a moderate adverse event and was handled endoscopically. The long-term clinical success rate was 85.7 %. No severe gastroesophageal reflux occurred after interventions. Two patients required secondary therapy with injection of botulinum toxin in the tubular esophagus and balloon dilation. CONCLUSION: The results suggest that POEM is an effective and safe therapeutic option for patients with NCCP and hypercontractile esophageal motility disorders.

A randomised trial of endoscopic submucosal dissection versus endoscopic mucosal resection for early Barrett's neoplasia.

BACKGROUND: For endoscopic resection of early GI neoplasia, endoscopic submucosal dissection (ESD) achieves higher rates of complete resection (R0) than endoscopic mucosal resection (EMR). However, ESD is technically more difficult and evidence from randomised trial is missing. OBJECTIVE: We compared the efficacy and safety of ESD and EMR in patients with neoplastic Barrett's oesophagus (BO). DESIGN: BO patients with a focal lesion of high-grade intraepithelial neoplasia (HGIN) or early adenocarcinoma (EAC) ≤3 cm were randomised to either ESD or EMR. Primary outcome was R0 resection; secondary outcomes were complete remission from neoplasia, recurrences and adverse events (AEs). RESULTS: There were no significant differences in patient and lesion characteristics between the groups randomised to ESD (n=20) or EMR (n=20). Histology of the resected specimen showed HGIN or EAC in all but six cases. Although R0 resection defined as margins free of HGIN/EAC was achieved more frequently with ESD (10/17 vs 2/17, p=0.01), there was no difference in complete remission from neoplasia at 3 months (ESD 15/16 vs EMR 16/17, p=1.0). During a mean follow-up period of 23.1±6.4 months, recurrent EAC was observed in one case in the ESD group. Elective surgery was performed in four and three cases after ESD and EMR, respectively (p=1.0). Two severe AEs were recorded for ESD and none for EMR (p=0.49). CONCLUSIONS: In terms of need for surgery, neoplasia remission and recurrence, ESD and EMR are both highly effective for endoscopic resection of early BO neoplasia. ESD achieves a higher R0 resection rate, but for most BO patients this bears little clinical relevance. ESD is, however, more time consuming and may cause severe AE. TRIAL REGISTRATION NUMBER: NCT1871636.

[The revised version of standard terminology in gastroenterological endoscopy - result of a consensus project of the german society for gastroenterology, digestive and metabolic diseases]. / Neufassung der Standard-Terminologie in der gastroenterologischen Endoskopie ­ Ergebnis eines Konsensusprojekts der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten.

A uniform and comprehensive terminology is essential in the correct documentation of diagnostic or therapeutic endoscopic procedure. In the German-speaking world, the standard terminology available so far is based on a previous version published in 1999. Therefore, the German Society for Gastroenterology, Digestive and Metabolic Diseases (DGVS) has undergone a comprehensive revision and re-structuring of the terminology. This appeared mandatory due to various changes, new diagnoses and new endoscopic procedures. The suggestions drawn up by individual working groups were approved by consensus and are now available as an online document (https://doi.org/10.1055/s-0043-121167) for modifying current software systems. In order to ensure an up-to-date documentation in the future, it was decided that annual updates will be performed by the DGVS to check respective software packages for modifications and new contents.

Multimodality endoscopic eradication for neoplastic Barrett oesophagus: results of an European multicentre study (EURO-II).

OBJECTIVE: Focal endoscopic resection (ER) followed by radiofrequency ablation (RFA) safely and effectively eradicates Barrett's oesophagus (BO) containing high-grade dysplasia (HGD) and/or early cancer (EC) in smaller studies with limited follow-up. Herein, we report long-term outcomes of combined ER and RFA for BO (HGD and/or EC) from a single-arm multicentre interventional study. DESIGN: In 13 European centres, patients with BO ≤ 12 cm with HGD and/or EC on 2 separate endoscopies were eligible for inclusion. Visible lesions (<2 cm length; <50% circumference) were removed with ER, followed by serial RFA every 3 months (max 5 sessions). Follow-up endoscopy was scheduled at 6 months after the first negative post-treatment endoscopic control and annually thereafter. OUTCOMES: complete eradication of neoplasia (CE-neo) and intestinal metaplasia (CE-IM); durability of CE-neo and CE-IM (once achieved) during follow-up. Biopsy and resection specimens underwent centralised pathology review. RESULTS: 132 patients with median BO length C3M6 were included. After entry-ER in 119 patients (90%) and a median of 3 RFA (IQR 3-4) treatments, CE-neo was achieved in 121/132 (92%) and CE-IM in 115/132 patients (87%), per intention-to-treat analysis. Per-protocol analysis, CE-neo and CE-IM were achieved in 98% and 93%, respectively. After a median of 27 months following the first negative post-treatment endoscopic control, neoplasia and IM recurred in 4% and 8%, respectively. Mild-to-moderate adverse events occurred in 25 patients (19%); all managed conservatively or endoscopically. CONCLUSIONS: In patients with early Barrett's neoplasia, intensive multimodality endotherapy consisting of ER combined with RFA is safe and highly effective, and the treatment effect appears to be durable during mid-term follow-up. TRIAL REGISTRATION NUMBER: NTR 1211, http://www.trialregister.nl.

Genome-wide association studies in oesophageal adenocarcinoma and Barrett's oesophagus: a large-scale meta-analysis.

BACKGROUND: Oesophageal adenocarcinoma represents one of the fastest rising cancers in high-income countries. Barrett's oesophagus is the premalignant precursor of oesophageal adenocarcinoma. However, only a few patients with Barrett's oesophagus develop adenocarcinoma, which complicates clinical management in the absence of valid predictors. Within an international consortium investigating the genetics of Barrett's oesophagus and oesophageal adenocarcinoma, we aimed to identify novel genetic risk variants for the development of Barrett's oesophagus and oesophageal adenocarcinoma. METHODS: We did a meta-analysis of all genome-wide association studies of Barrett's oesophagus and oesophageal adenocarcinoma available in PubMed up to Feb 29, 2016; all patients were of European ancestry and disease was confirmed histopathologically. All participants were from four separate studies within Europe, North America, and Australia and were genotyped on high-density single nucleotide polymorphism (SNP) arrays. Meta-analysis was done with a fixed-effects inverse variance-weighting approach and with a standard genome-wide significance threshold (p<5 × 10-8). We also did an association analysis after reweighting of loci with an approach that investigates annotation enrichment among genome-wide significant loci. Furthermore, the entire dataset was analysed with bioinformatics approaches-including functional annotation databases and gene-based and pathway-based methods-to identify pathophysiologically relevant cellular mechanisms. FINDINGS: Our sample comprised 6167 patients with Barrett's oesophagus and 4112 individuals with oesophageal adenocarcinoma, in addition to 17 159 representative controls from four genome-wide association studies in Europe, North America, and Australia. We identified eight new risk loci associated with either Barrett's oesophagus or oesophageal adenocarcinoma, within or near the genes CFTR (rs17451754; p=4·8 × 10-10), MSRA (rs17749155; p=5·2 × 10-10), LINC00208 and BLK (rs10108511; p=2·1 × 10-9), KHDRBS2 (rs62423175; p=3·0 × 10-9), TPPP and CEP72 (rs9918259; p=3·2 × 10-9), TMOD1 (rs7852462; p=1·5 × 10-8), SATB2 (rs139606545; p=2·0 × 10-8), and HTR3C and ABCC5 (rs9823696; p=1·6 × 10-8). The locus identified near HTR3C and ABCC5 (rs9823696) was associated specifically with oesophageal adenocarcinoma (p=1·6 × 10-8) and was independent of Barrett's oesophagus development (p=0·45). A ninth novel risk locus was identified within the gene LPA (rs12207195; posterior probability 0·925) after reweighting with significantly enriched annotations. The strongest disease pathways identified (p<10-6) belonged to muscle cell differentiation and to mesenchyme development and differentiation. INTERPRETATION: Our meta-analysis of genome-wide association studies doubled the number of known risk loci for Barrett's oesophagus and oesophageal adenocarcinoma and revealed new insights into causes of these diseases. Furthermore, the specific association between oesophageal adenocarcinoma and the locus near HTR3C and ABCC5 might constitute a novel genetic marker for prediction of the transition from Barrett's oesophagus to oesophageal adenocarcinoma. Fine-mapping and functional studies of new risk loci could lead to identification of key molecules in the development of Barrett's oesophagus and oesophageal adenocarcinoma, which might encourage development of advanced prevention and intervention strategies. FUNDING: US National Cancer Institute, US National Institutes of Health, National Health and Medical Research Council of Australia, Swedish Cancer Society, Medical Research Council UK, Cambridge NIHR Biomedical Research Centre, Cambridge Experimental Cancer Medicine Centre, Else Kröner Fresenius Stiftung, Wellcome Trust, Cancer Research UK, AstraZeneca UK, University Hospitals of Leicester, University of Oxford, Australian Research Council.

Esophageal stenting for benign and malignant disease: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline.

This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE), endorsed by the European Society for Radiotherapy and Oncology (ESTRO), the European Society of Digestive Endoscopy (ESDO), and the European Society for Clinical Nutrition and Metabolism (ESPEN). The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was adopted to define the strength of recommendations and the quality of evidence. Main recommendations for malignant disease 1 ESGE recommends placement of partially or fully covered self-expandable metal stents (SEMSs) for palliative treatment of malignant dysphagia over laser therapy, photodynamic therapy, and esophageal bypass (strong recommendation, high quality evidence). 2 For patients with longer life expectancy, ESGE recommends brachytherapy as a valid alternative or in addition to stenting in esophageal cancer patients with malignant dysphagia. Brachytherapy may provide a survival advantage and possibly a better quality of life compared to SEMS placement alone. (Strong recommendation, high quality evidence.) 3 ESGE recommends esophageal SEMS placement as the preferred treatment for sealing malignant tracheoesophageal or bronchoesophageal fistula (strong recommendation, low quality evidence). 4 ESGE does not recommend the use of concurrent external radiotherapy and esophageal stent treatment. SEMS placement is also not recommended as a bridge to surgery or prior to preoperative chemoradiotherapy. It is associated with a high incidence of adverse events and alternative satisfactory options such as placement of a feeding tube are available. (Strong recommendation, low quality evidence.) Main recommendations for benign disease 1 ESGE recommends against the use of self-expandable stents (SEMSs) as first-line therapy for the management of benign esophageal strictures because of the potential for adverse events, the availability of alternative therapies, and costs (strong recommendation, low quality evidence). 2 ESGE suggests consideration of temporary placement of SEMSs as therapy for refractory benign esophageal strictures (weak recommendation, moderate evidence). Stents should usually be removed at a maximum of 3 months (strong recommendation, weak quality evidence). 3 ESGE suggests that fully covered SEMSs be preferred over partially covered SEMSs for the treatment of refractory benign esophageal strictures, because of their lack of embedment and ease of removability (weak recommendation, low quality evidence). 4 For the removal of partially covered esophageal SEMSs that are embedded, ESGE recommends the stent-in-stent technique (strong recommendation, low quality evidence). 5 ESGE recommends that temporary stent placement can be considered for treating esophageal leaks, fistulas, and perforations. The optimal stenting duration remains unclear and should be individualized. (Strong recommendation, low quality evidence.) 6 ESGE recommends placement of a SEMS for the treatment of esophageal variceal bleeding refractory to medical, endoscopic, and/or radiological therapy, or as initial therapy for patients with massive esophageal variceal bleeding (strong recommendation, moderate quality evidence).