Endoscopic internal drainage and low negative-pressure endoscopic vacuum therapy for anastomotic leaks after oncologic upper gastrointestinal surgery.

BACKGROUND: Endoscopic internal drainage (EID) with double-pigtail stents or low negative-pressure endoscopic vacuum therapy (EVT) are treatment options for leakage after upper gastrointestinal oncologic surgery. We aimed to compare the effectiveness of these techniques. METHODS: Between 2016 and 2019, patients treated with EID in five centers in France and with EVT in Göttingen, Germany were included and retrospectively analyzed using univariate analysis. Pigtail stents were changed every 4 weeks; EVT was repeated every 3-4 days until leak closure. RESULTS: 35 EID and 27 EVT patients were included, with a median (interquartile range [IQR]) leak size of 0.75 cm (0.5-1.5). Overall treatment success was 100 % (95 % confidence interval [CI] 90 %-100 %) for EID vs. 85.2 % (95 %CI 66.3 %-95.8 %) for EVT (P = 0.03). The median (IQR) number of endoscopic procedures was 2 (2-3) vs. 3 (2-6.5; P = 0.003) and the median (IQR) treatment duration was 42 days (28-60) vs. 17 days (7.5-28; P < 0.001), for EID vs. EVT, respectively. CONCLUSION: EID and EVT provide high closure rates for upper gastrointestinal anastomotic leaks. EVT provides a shorter treatment duration, at the cost of a higher number of procedures.

Per Oral Endoscopic Myotomy for Zenker's Diverticulum: A Novel and Superior Technique Compared With Septotomy?

INTRODUCTION: Endoscopic management of Zenker diverticuli (ZD) has traditionally been via septotomy technique. The recent development of tunneling technique has shown to be both efficacious and safe. The aim of this study is to evaluate the tunneling technique using per oral endoscopic myotomy (Z-POEM) versus septotomy. METHODS: Patients who underwent endoscopic management of ZD either by Z-POEM or septotomy from March 2017 until November 2020 from 9 international academic centers were included. Demographics, clinical data preprocedure and postprocedure, procedure time, adverse events, and hospital length of stay were analyzed. RESULTS: A total of 101 patients (mean age 74.9 y old, 55.4% male) were included: septotomy (n=49), Z-POEM (n=52). Preprocedure Functional Oral Intake Scale score and Eckardt score was 5.3 and 5.4 for the septotomy group and 5.9 and 5.15 for the Z-POEM group. Technical success was achieved in 98% of the Z-POEM group and 100% of the septotomy group. Clinical success was achieved in 84% and 92% in the septotomy versus Z-POEM groups. Adverse events occurred in 30.6% (n=15) in septotomy group versus 9.6% (n=5) in the Z-POEM group (P=0.017). Reintervention for ongoing symptoms occurred in 7 patients in the septotomy group and 3 patients in the Z-POEM group. Mean hospital length of stay was shorter for the Z-POEM group, at 1.5 versus 1.9 days. CONCLUSIONS: A tunneling technique via the Z-POEM procedure is an efficacious and safe endoscopic treatment for ZD. Z-POEM is a safer procedure with a statistically significant reduction in adverse events compared with traditional septotomy technique.

Comparative Efficacy of Anti-TNF Therapies For The Prevention of Postoperative Recurrence of Crohn's Disease: A Systematic Review and Network Meta-Analysis of Prospective Trials.

INTRODUCTION: There is a lack of studies on the optimal anti-tumor necrosis factor (anti-TNF) agent for postoperative prophylaxis of Crohn's disease (CD) recurrence. Therefore, we conducted a network meta-analysis (NMA) of prospective trials to compare the efficacy of anti-TNF agents in the prevention of postoperative endoscopic and clinical recurrence of CD following ileocolonic resection. METHODS: We searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and recent American gastroenterology association (AGA) meeting abstracts through August 2017. We selected prospective studies comparing anti-TNF agents among each other or to other agents in the setting of postoperative prevention of CD recurrence. We performed a NMA using a frequentist approach with generalized pairwise modeling and inverse variance heterogeneity method. RESULTS: We identified 9 studies, including 571 patients and 5 treatment agents, among which 2 anti-TNF drugs (adalimumab and infliximab). Compared with infliximab, our NMA yielded the following results for endoscopic recurrence: adalimumab [odds ratio (OR), 0.92; 95% confidence interval (CI), 0.18-4.75], thiopurines (OR, 4.11; 95% CI, 0.68-24.78), placebo (OR, 4.39; 95% CI, 0.70-27.68), and Mesalamine (OR, 37.84; 95% CI, 3.77-379.42). For clinical recurrence: adalimumab (OR, 1.03; 95% CI, 0.17-6.03), thiopurines (OR, 1.40; 95% CI, 0.20-10.02), placebo (OR, 1.77; 95% CI, 1.01-3.10), and mesalamine (OR, 16.54; 95% CI, 1.55-176.24). CONCLUSIONS: On the basis of a NMA combining direct and indirect evidence either adalimumab or infliximab may be used in the postoperative prophylaxis of CD recurrence. There is currently a lack of evidence on the use of other anti-TNF agents in this setting.

Endoscopic submucosal dissection versus endoscopic mucosal resection for early esophageal adenocarcinoma.

OBJECTIVES: Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) allow endoscopic resection of early esophageal adenocarcinoma. The choice between the two techniques takes into account the morphology of the lesion, and the experience of the endoscopist. The aim of this study was to compare EMR to ESD for the treatment of early esophageal adenocarcinoma. METHODS: Patients who underwent an endoscopic resection for esophageal adenocarcinomas between March 2015 and December 2019 were included. ESD was compared to EMR in terms of clinical, procedural, histologic, and oncologic outcomes. RESULTS: 85 patients were included: 57 ESD and 28 EMR. The median (IQR) diameter of the lesion was 20(15-25) mm in the ESD group, and 15(8-16) mm in the EMR group, p<0.01. ESD allowed en bloc resection in 100% of cases, and EMR in 39% of cases, p<0.001. The R0 and curative resection rate in the ESD group versus the EMR group were 88% and 67%, respectively, versus 21% and 11%, p<0.001. We recorded one severe adverse event, in the EMR group. After a median (IQR) follow-up of 27.5 (14.5-38.7) months, the local recurrence rate was 23% vs. 18% (p = 0.63), and the overall survival 89% vs. 86% (p = 0.72), in the ESD and EMR groups, respectively. CONCLUSION: ESD was as safe as EMR and allowed higher en bloc, R0 and curative resection rates. Although these results did not translate into long-term outcomes, these data prompt for a broader adoption of ESD for the resection of esophageal lesions suspected of harboring early esophageal adenocarcinoma.

Impact of Sarcopenia on Survival in Patients Treated with FOLFIRINOX in a First-Line Setting for Metastatic Pancreatic Carcinoma.

Sarcopenia, defined as decreased muscle mass and strength, can be evaluated by a computed tomography (CT) examination and might be associated with reduced survival in patients with carcinoma. The prognosis of patients with metastatic pancreatic carcinoma is poor. The FOLFIRINOX (a combination of 5-fluorouracil, irinotecan, and oxaliplatin) chemotherapy regimen is a validated first-line treatment option. We investigated the impact of sarcopenia on overall survival (OS) and progression-free survival (PFS) in patients with metastatic pancreatic carcinoma. Clinical data and CT examinations of patients treated with FOLFIRINOX were retrospectively reviewed. Sarcopenia was estimated using baseline CT examinations. Seventy-five patients were included. Forty-three (57.3%) were classified as sarcopenic. The median OS of non-sarcopenic and sarcopenic patients were 15.6 and 14.1 months, respectively (p = 0.36). The median PFS was 10.3 in non-sarcopenic patients and 9.3 in sarcopenic patients (p = 0.83). No differences in toxicity of FOLFIRINOX were observed. There was a trend towards a higher probability of short-term death (within 4 months of diagnosis) in sarcopenic patients. In this study, the detection of sarcopenia failed to predict a longer OS or PFS in selected patients deemed eligible by a physician for triplet chemotherapy and receiving the FOLFIRINOX regimen in a first-line setting, confirming the major importance of a comprehensive patient assessment by physicians in selecting the best treatment option.

The Safety of Long-Term Proton Pump Inhibitor Use on Cardiovascular Health: A Meta-Analysis.

Introduction: Proton pump inhibitors (PPIs) are one of the most prescribed classes of drugs worldwide as a first-line treatment of acid-related disorders. Although adverse effects are rare and rapidly reversible after a short exposure, concerns have been recently raised about a greater toxicity on cardiovascular health after a longer exposure, especially when combined with clopidogrel. We aimed to evaluate the safety of long-term PPI use on cardiovascular health in patients with known atheromatous cardiovascular disease. Methods: A literature search was conducted in the PubMed, Embase, and Cochrane Library databases and grey literature in April 2022. Articles published between 2014 and 2022 were considered relevant if they were designed as randomized controlled trials (RCTs) that included post hoc analyses or prospective observational studies and if they investigated clinical cardiovascular outcomes associated with PPI use for 6 months or more in patients suffering from cardiovascular disease requiring antiplatelet agent therapy and/or coronary angioplasty. Statistical analyses were performed using RevMan 5.4 software (Computer program, the Cochrane Collaboration, 2020, London, UK). The risk of bias was assessed using the Cochrane risk-of-bias tool for the RCTs and the Newcastle−Ottawa scale for the observational studies. Results: A total of 10 full-text articles involving 53,302 patients were included. Substantial heterogeneity was found among the 10 included studies. The primary analysis showed no significant differences between the PPI group and the control group for the risks of major adverse cardiovascular events (MACEs), all-cause death (ACD), or target vessel revascularization (TVR) using a random-effects model (OR 1.15, 95% CI 0.98−1.35, p = 0.08, I2 = 73%; OR 1.24, 95% CI 0.94−1.65, p = 0.13, I2 = 63%; and OR 1.19, 95% CI 0.76−1.87, p = 0.45, I2 = 61%, respectively). The primary analysis yielded similar results for the risks of myocardial infarction (MI), stroke, and cardiovascular death (CVD) using a fixed-effects model (OR 0.98, 95% CI 0.88−1.09, p = 0.66, I2 = 0%; OR 1.02, 95% CI 0.90−1.17, p = 0.73, I2 = 0%; and OR 1.04, 95% CI 0.94−1.16, p = 0.44, I2 = 35%, respectively). Likewise, a subgroup analysis based on eight randomized controlled trials failed to identify any association between PPI use and the risks of MACEs, MI, stroke, TVR, ACD, or CVD using a fixed-effects model (overall pooled OR 1.01, 95% CI 0.96−1.06; p = 0.66; I2 = 0%). The pulled data from the two included observational studies (OS) demonstrated a significantly increased risk of MACEs in the PPI group (OR 1.42, 95% CI [1.29−1.57], p <0.001; I2 = 0%). In another subgroup analysis, no evidence of an increased risk of adverse cardiovascular events in the co-therapy PPI/clopidogrel versus clopidogrel alone groups was found with the exception of the risk of ACD (OR 1.50, 95% CI 1.23−1.82, p = 0.001, I2 = 0%). Nevertheless, after performing a sensitivity analysis reaching heterogeneity I2 = 0%, the co-prescription of PPIs and clopidogrel was at increased risk of MACEs (p < 0.001), CVD (p = 0.008), and TVR (p < 0.001) but remained statistically non-significant for the risk of MI (p = 0.11). Conclusions: The overall results of this meta-analysis showed that long-term PPI use was not associated with an increased risk of adverse cardiovascular events. However, inconsistent results were found for combined PPI/clopidogrel therapy. These results should be considered with caution in light of the significant heterogeneity, the limited number of included studies, and the lack of adjustment for potential confounders.

Endoscopic management of non-ampullary duodenal adenomas.

Duodenal polyps are found in 0.1 % to 0.8 % of all upper endoscopies. Duodenal adenomas account for 10 % to 20 % of these lesions. They can be sporadic or occur in the setting of a hereditary predisposition syndrome, mainly familial adenomatous polyposis. Endoscopy is the cornerstone of management of duodenal adenomas, allowing for diagnosis and treatment, primarily by endoscopic mucosal resection. The endoscopic treatment of duodenal adenomas has a high morbidity, reaching 15 % in a prospective study, consisting of bleeding and perforations, and should therefore be performed in expert centers. The local recurrence rate ranges from 9 % to 37 %, and is maximal for piecemeal resections of lesions > 20 mm. Surgical resection of the duodenum is flawed with major morbidity and considered a rescue procedure in cases of endoscopic treatment failures or severe endoscopic complications such as duodenal perforations. In this paper, we review the existing evidence on endoscopic diagnosis and treatment of non-ampullary duodenal adenomas.

A new system to prevent SARS-CoV-2 and microorganism air transmission through the air circulation system of endoscopes.

Background and study aims Evidence for the modes of transmission of SARS-CoV-2 remains controversial. Recently, the potential for airborne spread of SARS-CoV-2 has been stressed. Air circulation in gastrointestinal light source boxes and endoscopes could be implicated in airborne transmission of microorganisms. Methods The ENDOBOX SC is a 600 × 600 mm cube designed to contain any type of machine used during gastrointestinal endoscopy. It allows for a 100-mm space between a machine and the walls of the ENDOBOX SC. To use the ENDOBOX SC, it is connected to the medical air system and it provides positive flow from the box to the endoscopy room. The ENDOBOX SC uses medical air to inflate the digestive tract and to decrease the temperature induced by the microprocessors or by the lamp. ENDOBOX SC has been investigated in different environments. Results An endoscopic procedure performed without ventilation was interrupted after 40 minutes to prevent computer damage. During the first 30 minutes, the temperature increased from 18 °C to 31 °C with a LED system. The procedure with fans identified variations in temperature inside the ENDOBOX SC from 21 to 26 °C (±â€Š5 °C) 1 hour after the start of the procedure. The temperature was stable for the next 3 hours. Conclusions ENDOBOX SC prevents the increase in temperature induced by lamps and processors, allows access to all necessary connections into the endoscopic columns, and creates a sterile and positive pressure volume, which prevents potential contamination from microorganisms.

Outcomes of endoscopic mucosal resection for large superficial non-ampullary duodenal adenomas.

Endoscopic mucosal resection (EMR) is the recommended treatment for superficial non-ampullary duodenal epithelial tumors larger than 6 mm. This endoscopic technique carries a high risk of adverse events. Our aim was to identify the risk factors for adverse events following EMR for non-ampullary duodenal adenomatous lesions. We retrospectively analyzed a prospectively collected database of consecutive endoscopic resections for duodenal lesions at a tertiary referral center for therapeutic endoscopy. We analyzed patients with non-ampullary duodenal adenomatous lesions ≥ 10 mm resected by EMR, and searched for factors associated with adverse events after EMR. 167 duodenal adenomatous lesions, with a median size of 25 (25-40) mm, were resected by EMR between January 2015 and December 2020. Adverse events occurred in 37/167 (22.2%) after endoscopic resection, with 29/167 (17.4%) delayed bleeding, 4/167 (2.4%) immediate perforation and 4/167 (2.4%) delayed perforation. In logistic regression, the size of the lesion was the only associated risk factor of adverse events (OR = 2.81, 95% CI [1.27; 6.47], p = 0.012). Adverse events increased mean hospitalization time (7.7 ± 9 vs. 1.9 ± 1 days, p < 0.01). None of the currently recommended preventive methods, particularly clips, affected the adverse event rate. EMR of centimetric and supracentimetric duodenal adenomatous lesions carries a high risk of adverse events, increasing with the size of the lesion and with no benefit from any preventive method. These results suggest that these procedures should be performed in expert centers, and underline the need for novel endoscopic tools to limit the rate of adverse events.

Endoscopic ultrasound guided fine needle biopsy in patients with suspected gastric linitis plastica.

BACKGROUND: Gastric linitis plastica (GLP) is a diffuse infiltrating type of gastric adenocarcinoma. It is associated with a poor prognosis and a five-year survival of 3-10%. The infiltrating profile of this tumor explains the low yield of the superficial mucosal biospies. The objective of this study was to investigate the role of endoscopic ultrasound-fine needle biopsy (EUS-FNB) in the diagnosis of GLP. METHODS: We performed a retrospective analysis including all patients who had an EUS-FNB, at a tertiary referral center, over the last 3 years. The primary outcome was the sensitivity of EUS-FNB in patients with suspected GLP. RESULTS: Between January 2017 and December 2020, 34 patients had an EUS-FNB for suspected GLP. Ten patients had a diagnostic of GLP. This diagnosis was obtained by EUS-FNB in 90% (9/10) of the cases. Eight patients had at least one previous esophagogastroduodenoscopy (EGD) with negative mucosal biopsies. Gastric EUS-FNB helped diagnose other serious conditions in 47% (16/34) of cases with inconclusive mucosal biopsies. CONCLUSION: Gastric EUS-FNB in patients with suspected GLP and normal endoscopic mucosal biopsies may lead to a positive diagnosis of GLP in 90% of cases without notable adverse events. This technique should be considered as a second step in the setting of suspicion of GLP after inconclusive mucosal biopsies.

Air circulation in a gastrointestinal light source box and endoscope in the era of SARS-CoV-2 and airborne transmission of microorganisms.

Background and study aims The role that air circulation through a gastrointestinal endoscopy system plays in airborne transmission of microorganisms has never been investigated. The aim of this study was to explore the potential risk of transmission and potential improvements in the system. Methods We investigated and described air circulation into gastrointestinal endoscopes from Fujifilm, Olympus, and Pentax. Results The light source box contains a lamp, either Xenon or LED. The temperature of the light is high and is regulated by a forced-air cooling system to maintain a stable temperature in the middle of the box. The air used by the forced-air cooling system is sucked from the closed environment of the patient through an aeration port, located close to the light source and evacuated out of the box by one or two ventilators. No filter exists to avoid dispersion of particles outside the processor box. The light source box also contains an insufflation air pump. The air is sucked from the light source box through one or two holes in the air pump and pushed from the air pump into the air pipe of the endoscope through a plastic tube. Because the air pump does not have a dedicated HEPA filter, transmission of microorganisms cannot be excluded. Conclusions Changes are necessary to prevent airborne transmission. Exclusive use of an external CO 2 pump and wrapping the endoscope platform with a plastic film will limit scatter of microorganisms. In the era of pandemic virus with airborne transmission, improvements in gastrointestinal ventilation systems are necessary to avoid contamination of patients and health care workers.

Immuno-oncology: a narrative review of gastrointestinal and hepatic toxicities.

Vaccines, cytokines, and adoptive cellular therapies (ACT) represent immuno-therapeutic modalities with great development potential, and they are currently approved for the treatment of a limited number of advanced malignancies. The most up-to-date knowledge on the regulation of the anti-cancer immune response has recently led to the development and approval of inhibitors of immune checkpoints, which have produced unprecedented clinical activity in several hard to treat solid malignancies. However, severe adverse events (AEs) represent a limitation to the use of these drugs. Currently approved checkpoint inhibitors block cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death protein (PD-1) and its ligand (PD-L1), resulted in increased survival of patients with several solid and hematologic malignancies. The most common treatment AEs associated with these drugs are fatigue, rash, and auto-immune/inflammatory reactions. Many of the immune-related AEs are reversible and the strategies for their management include supportive care either with or without treatment withdrawal; nevertheless, in severe cases, hospitalization and treatment with immune suppressants, and/or immunomodulators may be required. Steroid therapy is a critical component of the treatment algorithm; nevertheless, the associated immunosuppression may compromise the antitumor response. This article provides a comprehensive and narrative review of luminal gastrointestinal and hepatic complications, including recommendations for their investigation and management.

Outcomes of endoscopic submucosal dissection for early esophageal and gastric cardia adenocarcinomas.

OBJECTIVES: Adenocarcinomas of the esophagus and of the gastric cardia are regarded as a same clinical entity in oncology. For endoscopic resection however, endoscopic mucosal resection is recommended for esophageal adenocarcinoma, while endoscopic submucosal dissection (ESD) is advocated for gastric adenocarcinomas. Our aim was to compare the outcomes of ESD in both types of esophagogastric junction adenocarcinomas. METHODS: Between March 2015 and December 2019, we included all patients who underwent an ESD for early adenocarcinoma of the esophagogastric junction at a French tertiary referral center. Esophageal and gastric cardia adenocarcinomas were compared in terms of clinical, procedural and histological outcomes. RESULTS: 57 esophageal and 19 gastric cardia adenocarcinomas were included in the analysis, for a total of 76 patients. The median (IQR) size of the resections was 40 (40-57.5) and 50 (35-55)mm, p=0.96, respectively. En bloc resection was achieved in 100% and 89% for adenocarcinomas of the esophagus and the gastric cardia, p=0.06. Late adverse events occurred in 14% and 5.3%, respectively, p=0.44, with no severe adverse event. Curative resection rates were 67% and 63% for adenocarcinomas of the esophagus and the gastric cardia, respectively, p=0.89. CONCLUSION: ESD is a safe treatment for T1 adenocarcinomas of the esophagogastric junction, curative in two thirds of the patients, in tumors arising from the esophagus or from the stomach. ESD should be considered for the routine resection of esophageal adenocarcinomas.

Amplatzer occluders for refractory esophago-respiratory fistulas: a case series.

Background and study aims Endoscopic management of esophagorespiratory fistulas (ERF) is challenging and currently available options (stents, double pigtail, endoscopic vacuum therapy) are not very effective. We report the feasibility and efficacy of endoscopic placement of Amplatzer cardiovascular occluders for this indication. Patients and methods This was a single-center, prospective study (June 2019 to September 2020) of all patients with non-malignant ERF persistent after conventional management with esophageal and/or tracheal stents. The primary outcome was the technical feasibility of Amplatzer placement. Secondary outcomes were clinical success defined by effective ERF occlusion and resolution of respiratory symptoms allowing oral food intake. Results Endoscopic placement of Amplatzer occluders was feasible in 83 % of patients (5/6), with a 50 % (3/6) clinical success rate at 9 months. The mortality rate was 33 % (2/6). Conclusions An Amplatzer cardiac or vascular occluder is a feasible and safe treatment option for refractory ERF, with a 50 % short-term clinical success.

Clinical impact of routine CT esophagogram after peroral endoscopic myotomy (POEM) for esophageal motility disorders.

Background and study aims Per oral endoscopic myotomy (POEM) of the lower esophageal sphincter has become a major treatment for esophageal motility disorders, especially achalasia. POEM can result in esophageal bleeding or perforation and pleural and mediastinal effusion. Early routine computed tomography (CT) esophagogram is frequently performed to assess these adverse events (AEs) before resuming oral food intake. We sought to evaluate the value of routine CT esophagogram on postoperative day (POD) 1 after POEM. Patients and methods This single-center retrospective study was performed in a tertiary referral center for interventional digestive endoscopy. We included consecutive patients with POEM and routine CT esophagogram on POD 1 between July 2018 and July 2019. Results Fifty-eight patients were included in the study, 79 % of whom had achalasia. Twenty patients (34 %) presented post-endoscopic AEs, including two patients with severe AEs requiring intensive care admission (one compressive pneumothorax and one mediastinitis); no deaths occurred. Of the 58 CT esophagograms performed, only one was normal. The 57 others (98 %) showed at least one abnormal finding: pneumoperitoneum or retroperitoneal air (91 %), pneumomediastinum (78 %), pleural effusion (34 %), pneumothorax (14 %), pneumonia (7 %), pericardial effusion (2 %), and mediastinal collection (2 %). CT esophagograms revealed AEs and modified therapeutic management in eight patients of 58 (14 %), all of whom had clinical symptoms prior to CT. Conclusions POD 1 CT esophagogram after POEM for esophageal motility disorders diagnosed clinically meaningful AEs in 14 % of patients, all associated with persistent clinical symptoms. Routine use of CT esophagogram after POEM in asymptomatic patients is questionable.