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.).

Outcomes of rescue procedures in the management of locally recurrent ampullary tumors: A Pancreas 2000/EPC study.

BACKGROUND: Ampullary lesions are rare and can be locally treated either with endoscopic papillectomy or transduodenal surgical ampullectomy. Management of local recurrence after a first-line treatment has been poorly studied. METHODS: Patients with a local recurrence of an ampullary lesion initially treated with endoscopic papillectomy or transduodenal surgical ampullectomy were retrospectively included from a multi-institutional database (58 centers) between 2005 and 2018. RESULTS: A total of 103 patients were included, 21 (20.4%) treated with redo endoscopic papillectomy, 14 (13.6%) with transduodenal surgical ampullectomy, and 68 (66%) with pancreaticoduodenectomy. Redo endoscopic papillectomy had low morbidity with 4.8% (n = 1) severe to fatal complications and a R0 rate of 81% (n = 17). Transduodenal surgical ampullectomy and pancreaticoduodenectomy after a first procedure had a higher morbidity with Clavien III and more complications, respectively, 28.6% (n = 4) and 25% (n = 17); R0 resection rates were 85.7% (n = 12) and 92.6% (n = 63), both without statistically significant difference compared to endoscopic papillectomy (P = .1 and 0.2). Pancreaticoduodenectomy had 4.4% (n = 2) mortality. No deaths were registered after transduodenal surgical ampullectomy or endoscopic papillectomy. Recurrences treated with pancreaticoduodenectomy were more likely to be adenocarcinomas (79.4%, n = 54 vs 21.4%, n = 3 for transduodenal surgical ampullectomy and 4.8%, n = 1 for endoscopic papillectomy, P < .0001). Three-year overall survival and disease-free survival were comparable. CONCLUSION: Endoscopy is appropriate for noninvasive recurrences, with resection rate and survival outcomes comparable to surgery. Surgery applies more to invasive recurrences, with transduodenal surgical ampullectomy rather for carcinoma in situ and early cancers and pancreaticoduodenectomy for more advanced tumors.

A Phase II Study of Nab-Paclitaxel and Gemcitabine as First-Line Therapy in Patients with Cholangiocarcinoma Ineligible for Cisplatin-Based Chemotherapy (NACHO).

INTRODUCTION: Gemcitabine and cisplatin is the standard first-line systemic treatment in patients with advanced cholangiocarcinoma (CCA). However, a substantial number of patients do not qualify for cisplatin due to comorbidities or poor performance status. The phase II pilot study NACHO evaluated the efficacy of nab-paclitaxel (125 mg/m2) and gemcitabine (1000 mg/m2) given on days 1, 8, and 15 every 4 weeks as first-line therapy in patients with advanced CCA ineligible for cisplatin-based chemotherapy. METHODS: Patients with any comorbidity precluding cisplatin therapy, such as renal impairment, impaired hearing, increased risk or history for thromboembolic events, intolerance of extensive hydration, or significant cardiovascular disease were eligible. Primary endpoint was overall response rate (ORR) per RECIST 1.1. Secondary endpoints were progression-free survival (PFS), overall survival (OS), safety, and patient reported outcome. RESULTS: From December 2016 to July 2017, 10 patients were prospectively enrolled and treated. The ORR with nab-paclitaxel/gemcitabine was 50%, the disease control rate (DCR) was 90%. Median PFS was 5.7 months (95% CI: 5.3-6.1), and median OS was 7.8 months (95% CI: 5.4-10.2). In total, 13 SAEs were documented without any new safety signals. There were 14 grade 3-4 treatment-related adverse events (TRAEs) in 10 patients of the ITT population. Exploratory subgroup analyses including known prognostic markers were performed. CONCLUSIONS: The NACHO trial supports safety and efficacy of nab-paclitaxel and gemcitabine in patients with advanced CCA ineligible for cisplatin-based therapy and should be further evaluated in a larger prospective trial.

Clinical Outcome and Treatment Sequences of Patients with Advanced Pancreatic Cancer Treated with Contemporary Chemotherapy Protocols.

INTRODUCTION: Systemic therapy is firmly established in patients with advanced or metastatic pancreatic ductal adenocarcinoma (PDAC). Clinical efficacy is still modest and options are limited. Combination therapy protocols such as FOLFIRINOX and gemcitabine/nab-paclitaxel (Gem/NP) define standard-of-care. Patients may receive a sequence of both regimens as first- and second-line palliative treatment. However, there is no guidance regarding a preferred order. METHODS: This is a retrospective analysis of clinical characteristics, treatment trajectories, and outcomes of patients with advanced PDAC treated at the West German Cancer Center Essen from 2014 to 2020 to inform treatment decisions with respect to predictive factors, impact of chemotherapy regimen sequence, and maintenance treatment. RESULTS: We identified 170 patients with available follow-up. Of those, 160 (94.1%) patients received palliative CTX for primary metastatic, locally advanced, or recurrent PDAC. Median progression-free survival (PFS) upon first palliative chemotherapy was 4.1 (3.1-5.9) months. First-line FOLFIRINOX was associated with superior PFS (median 6.3 months) and OS (9.7 months, HR 0.7, p = 0.03) as compared to Gem/NP or other regimens (PFS 3.0, OS 6.9 months). However, OS benefit of first-line FOLFIRINOX was lost in patients who received at least two treatment lines (median OS 12.1 vs. 13.1 months, p = 0.43). A landmark analysis of patients with clinical benefit (defined as CR/PR/SD for at least 20 weeks) upon first-line therapy revealed improved OS (HR 0.53, p = 0.02) for patients receiving continued deescalated maintenance therapy. Second-line regimens resulted in similar PFS (overall log-rank p = 0.92, median PFS upon second-line therapy 2.3 [1.8-2.9], per-regimen median between 1.8 and 3.9 months). A previously established systemic inflammation score proved to be strongly prognostic and allowed identification of a patient subgroup with dismal prognosis (OS 2.9 vs. 11.4 months, HR 5.23, p < 0.001), independent of other prognostic factors and with no relevant interaction with the choice of first-line regimen. CONCLUSION: In this real-world population of PDAC patients treated with contemporary combination chemotherapies, a positive impact of first-line FOLFIRINOX was only observed when no second or further line treatment was administered. Intensity-reduced maintenance therapy may lead to superior survival.

Deep learning-based assessment of body composition and liver tumour burden for survival modelling in advanced colorectal cancer.

BACKGROUND: Personalized therapy planning remains a significant challenge in advanced colorectal cancer care, despite extensive research on prognostic and predictive markers. A strong correlation of sarcopenia or overall body composition and survival has been described. Here, we explore whether automated assessment of body composition and liver metastases from standard of care CT images can add to clinical parameters in personalized survival risk prognostication. METHODS: We retrospectively analysed clinical imaging data from 85 patients (50.6% female, mean age 58.9 SD 12.2 years) with colorectal cancer and synchronous liver metastases. Pretrained deep learning models were used to assess body composition and liver metastasis geometry from abdominal CT images before the initiation of systemic treatment. Abdominal muscle-to-bone ratio (MBR) was calculated by dividing abdominal muscle volume by abdominal bone volume. MBR was compared with body mass index (BMI), abdominal muscle volume, and abdominal muscle volume divided by height squared. Differences in overall survival based on body composition and liver metastasis parameters were compared using Kaplan-Meier survival curves. Results were correlated with clinical and biomarker data to develop a machine learning model for survival risk prognostication. RESULTS: The MBR, unlike abdominal muscle volume or BMI, was significantly associated with overall survival (HR 0.39, 95% CI: 0.19-0.80, P = 0.009). The MBR (P = 0.022), liver metastasis surface area (P = 0.01) and primary tumour sidedness (P = 0.007) were independently associated with overall survival in multivariate analysis. Body composition parameters did not correlate with KRAS mutational status or primary tumour sidedness. A prediction model based on MBR, liver metastasis surface area and primary tumour sidedness achieved a concordance index of 0.69. CONCLUSIONS: Automated segmentation enables to extract prognostic parameters from routine imaging data for personalized survival modelling in advanced colorectal cancer patients.

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.

Identification of a new prognostic score for patients with high-grade metastatic GEP-NEN treated with palliative chemotherapy.

PURPOSE: High-grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN G3) are rare and heterogeneous malignancies with poor prognosis. Aim of this study was to develop prognosticators identifying those patients that derive the most benefit from currently available systemic therapies. METHODS: This retrospective analysis included 78 patients with metastatic GEP-NEN G3. For patients with imaging data available (n = 52), the overall response rate (ORR) and disease control rate (DCR) were evaluated according to the Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1). A Cox proportional hazard model was used to analyze the prognostic value of selected clinical and blood-based biomarkers. The impact of palliative chemotherapy regimens on time-to-treatment-failure (TTF) and overall survival (OS) was assessed. RESULTS: Median OS of the study cohort was 9.0 months (95% CI 7.0-11.1). The majority of patients received first-line treatment with platinum plus etoposide (83.3%). The ORR and DCR of the RECIST-evaluable subgroup were 34.6% and 76.9%. Median TTF upon first-line treatment was 4.9 months (95% CI 3.4-6.4). Multivariate analysis identified the Eastern Cooperative Oncology Group performance status (ECOG PS), lactate dehydrogenase (LDH) and absolute lymphocyte count as independent prognostic factors. A prognostic score based on these parameters discriminated patients with favorable and unfavorable outcomes. CONCLUSION: Outcomes of patients with GEP-NEN G3 are still limited. A new prognostic score identifying those patients benefitting from current platinum/etoposide-based chemotherapy protocols may help as stratification factor in future trial design.

Safety of transesophageal echocardiography during transcatheter edge-to-edge tricuspid valve repair: A single-center experience.

Objectives: We aimed to determine transesophageal echocardiography (TEE) related complications during Transcatheter edge-to-edge tricuspid valve repair (TTVR). Background: Transesophageal echocardiography is essential to guide structural heart disease (SHD) interventions. TTVR has become an evolving procedure for high-risk patients not suitable for surgery. Whether this complex procedure is associated with TEE related complications is not known so far. Methods: We retrospectively analyzed 64 consecutive patients undergoing TTVR between 2019 and 2021 with the TriClip system (Abbott, Chicago, IL, USA) at our center. All procedures were performed under general anesthesia (GA). TEE related complications were classified as major and minor complications. Results: Transesophageal echocardiography related complications were observed in two patients (3.1%) with one major complication (1.6%) and one minor complication (1.6%). In one patient perforation of the esophageal mucosa requiring red blood cell transfusion was observed, the other patient had hematemesis due to minor esophageal and gastric lesions without the need for blood transfusion. Both patients recovered during hospital stay with no persistent symptoms at discharge. Conclusions: Transesophageal echocardiography related complications during TTVR are clinically relevant occurring in 3.1% of the patients. Further investigations are needed to identify potential risk factors and patients at high risk to develop a TEE related complication in the course of TTVR.

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.).

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.

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.

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.

Direct endoscopic necrosectomy in infected pancreatic necrosis using lumen-apposing metal stents: Early intervention does not compromise outcome.

Background and study aims Infection of pancreatic necrosis is a dreaded complication requiring an intervention. Nevertheless, the optimal timing of the first intervention is unclear, and consensus data are sparse. This retrospective two-center study evaluated direct endoscopic necrosectomy using lumen apposing metal stents in case of proven or suspected infected pancreatic necrosis in an early stage of the disease. Patients and methods Forty-nine patients with infected pancreatic necrosis were included. Sequent direct endoscopic necrosectomies after lumen apposing metal stent insertion (LAMS) were performed until the resolution of necrosis. In all patients, the first endoscopic intervention was performed within the first 30 days after first proof of pancreatic necrosis. Primary outcome parameters were inflammatory activity, days spent in the Intensive Care Unit (ICU), and mortality. Results The patient cohort received median 4 necrosectomies (3-5) after a median of 7 days (3-11) after first proof of pancreatic necrosis. Technical and clinical success were achieved in 98.3 % and 87.8 %, respectively; the mortality rate was 8.2 %. The median C-reactive protein level decreased from 241 mg/L (182.9-288.9) before the intervention to a median of 23.3 mg/L (18-60) after therapy. The median time period in the ICU was 5 days (3-9). Conclusions Early endoscopic therapy in the form of direct endoscopic necrosectomy after LAMS placement within the first 30 days after proof of pancreatic necrosis is effective and does not result in poor outcome. Our retrospective data suggest that early intervention before walled-off necrosis is formed is tenable when it is essential due to the patient's clinical deterioration.

Upper gastrointestinal stenting during the SARS-CoV-2 outbreak: impact of mitigation measures and risk of contamination for patients and staff.

Background and study aims The impact of COVID-19 mitigation measures on stent placement procedures has not yet been reported. The aim of this study was to assess the impact of COVID-19 mitigation measures on upper stenting during SARS-CoV-2 outbreak, as well as the use of personal protection equipment (PPE) and risk of contamination for patients and staff. Patients and methods This was a multicenter, retrospective study of consecutive patients who underwent stent placement for upper gastrointestinal obstruction during the second half of SARS-CoV-2 outbreak period in comparison to same period one year before. Results A total of 29 stents were placed for upper gastrointestinal obstruction during the study period, corresponding to an increase of 241 % comparing to the same period in 2019 (n = 12). No significant major differences were found between the two time periods regarding patients' baseline characteristics, post-stenting management and number of staff involved in stent placement. Fellows' involvement was significantly lower in 2020 compared to 2019 (21 % vs 67 %; P  = 0.01). The majority of procedures were performed using FFP2 /FFP3 mask (76 %), protective eyewear (86 %), two pairs of gloves (65 %), hairnet (76 %) and full disposable gowns (90 %). One patient tested positive for SARS-CoV-2 after the procedure. None of the medical staff involved in stenting procedures developed COVID-19 14 days after procedure. Conclusion Upper gastrointestinal stenting increased during the SARS-CoV-2 outbreak period, which could be related to yearly variation on the number of procedures or reflect a change of oncologic treatment practice during COVID times.

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.

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.

Endoscopic full-thickness resection and its treatment alternatives in difficult-to-treat lesions of the lower gastrointestinal tract: a cost-effectiveness analysis.

OBJECTIVE: Endoscopic full-thickness resection (EFTR) has shown efficacy and safety in the colorectum. The aim of this analysis was to investigate whether EFTR is cost-effective in comparison with surgical and endoscopic treatment alternatives. DESIGN: Real data from the study cohort of the prospective, single-arm WALL RESECT study were used. A simulated comparison arm was created based on a survey that included suggested treatment alternatives to EFTR of the respective lesions. Treatment costs and reimbursement were calculated in euro according to the coding rules of 2017 and 2019 (EFTR). R0 resection rate was used as a measure of effectiveness. To assess cost-effectiveness, the average cost-effectiveness ratio (ACER) and the incremental cost-effectiveness ratio (ICER) were determined. Calculations were made both from the perspective of the care provider as well as of the payer. RESULTS: The cost per case was €2852.20 for the EFTR group, €1712 for the standard endoscopic resection (SER) group, €8895 for the surgical resection group and €5828 for the pooled alternative treatment to EFTR. From the perspective of the care provider, the ACER (mean cost per R0 resection) was €3708.98 for EFTR, €3115.10 for SER, €8924.05 for surgical treatment and €7169.30 for all pooled and weighted alternatives to EFTR. The ICER (additional cost per R0 resection compared with EFTR) was €5196.47 for SER, €26 533.13 for surgical resection and €67 768.62 for the pooled rate of alternatives. Results from the perspective of the payer were similar. CONCLUSION: EFTR is cost-effective in comparison with surgical and endoscopic treatment alternatives in the colorectum.

Biweekly Cetuximab Plus FOLFOX6 as First-Line Therapy in Patients With RAS Wild-Type Metastatic Colorectal Cancer: The CEBIFOX Trial.

BACKGROUND: The multicenter, single-arm, phase II study CEBIFOX evaluated the efficacy of a biweekly cetuximab administration in combination with FOLFOX6 as first-line therapy in KRAS (exon 2) wild-type (wt) metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Patients received FOLFOX6 with cetuximab (500 mg/m2) every second week. Primary endpoint was objective response rate (ORR), among others secondary endpoints were safety, progression-free survival (PFS), overall survival (OS), and patient-reported outcome (PRO). The impact on the treatment efficacy was evaluated in explorative subgroup analyses, including extended molecular profiling and primary tumor location. RESULTS: In total, 57 were included in the intention-to-treat (ITT) analyses. New RAS mutations were detected in 14.0% by post hoc next-generation sequencing analysis in 43 patients. The ORR in the all RASwt population was 70.3% with a median PFS and OS of 10.9 (95% confidence interval [CI], 9.0-12.9) and 33.8 (95% CI, 21.1-45.5) months. Grade 3-5 adverse events occurred in 66.7% of the ITT, without significant impact on the PRO. Patients with right-sided primary tumors had a reduced ORR (54.5%), and median PFS and OS (10.1 and 23.8 months). BRAF mutations were detected in 11.3%. These patients had a significantly lower ORR, and median PFS and OS. Patients with RASwt/BRAFwt tumors had a notably high median PFS and OS of 14.3 and 38.9 months. CONCLUSIONS: This study supports the efficacy and safety of biweekly cetuximab given in combination with FOLFOX6 in patients with RASwt/BRAFwt mCRC with left-sided primary tumor. CEBIFOX is the first trial reporting the complete dataset, including extended molecular profiling and tumor location of a biweekly administered cetuximab/FOLFOX6 in mCRC. Clinical trial number: NCT01051167.