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Background Biomarkers are urgently needed for pancreatic ductal adenocarcinoma (PDAC). Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is the cornerstone for diagnosing PDAC. We developed a method for discovery of PDAC biomarkers using the discarded EUS-FNA liquid. Methods This retrospective study included 58 patients with suspected pancreatic lesions who underwent EUS-FNA. Protein extracts from EUS-FNA liquid were analyzed by mass spectrometry. Proteomic and clinical data were modeled by supervised statistical learning to identify protein markers and clinical variables that distinguish PDAC. Results Statistical modeling revealed a protein signature for PDAC screening that achieved high sensitivity and specificity (0.92, 95 % confidence interval [CI] 0.79–0.98, and 0.85, 95 %CI 0.67–0.93, respectively). We also developed a protein signature score (PSS) to guide PDAC diagnosis. In combination with patient age, the PSS achieved 100 % certainty in correctly identifying PDAC patients > 54 years. In addition, 3 /4 inconclusive EUS-FNA biopsies were correctly identified using PSS. Conclusions EUS-FNA-derived fluid is a rich source of PDAC proteins with biomarker potential. The PSS requires further validation and verification of the feasibility of measuring these proteins in patient sera.

Peroral endoscopic myotomy (POEM) is a very effective treatment for achalasia. However, training remains non-standardized. We evaluated a training curriculum, including ex vivo cases, followed by patients' cases under expert supervision. The objective was to establish a learning curve of POEM.Four operators having completed advanced endoscopy fellowship were involved. They had already observed 30 cases performed by experts. They performed 30 POEMs standardized (tunnel and myotomy lengths) procedures on ex vivo porcine model. Procedural times, number/volume of injections, mucosal and serous perforations, and myotomy length were collected. The learning curve was assessed using dissection speed (DS) and a dedicated performance score (PS), including learning rate (LR) and learning plateau (LP).The operators completed all cases within 4 months (median of 3.5 cases/week). The mean procedural time was 43.3 min ± 14.4. Mean myotomy length was 70.0 mm ± 15.6 mm. Dissection speed averaged 1.78 mm/min ± 0.78. Using DS and PS as parameter, the LR was reached after 12.2 cases (DS = 2.0 mm/min) and 10.4 cases, respectively. When comparing the LP and the plateau phase, the DS was slower (1.3 ± 0.5 mm/min versus 2.1 ± 0.54 mm/min, p 0.005) and perforations were decreased: 0.35 ± 0.82 in LP vs. 0.16 ± 0.44 in PP. Following this training, all operators performed 10 supervised cases and are competent in POEM.The association of observed cases and supervised ex vivo model training is effective for starting POEM on patients. The learning curve is 12 cases to reach a plateau.

After 2 doses, the efficacy of anti-SARS-CoV-2 vaccination seems to be lower in solid organ transplant recipients than in the immunocompetent population. The objective of this study was to determine the humoral response rate after vaccination, including with a booster dose, and to identify risk factors for non-responsiveness in liver transplant recipients.We included all patients seen in consultation in two French liver transplant centres between January 1, 2021, and March 15, 2021.598 liver transplant recipients were enrolled and 327 were included for analysis. Sixteen patients received one dose, 63 patients two doses and 248 patients three doses. Anti-SARS-Cov-2 antibodies were detected in 242 out of 327 (74.0%) liver transplant patients after vaccination. Considering an optimal serologic response defined as an antibody titre260 BAU/ml, 172 patients (52.6%) were responders. Mycophenolate mofetil (MMF) treatment was an independent risk factor for a failure to develop anti-SARS-CoV-2 antibodies after vaccination (OR 0.458; 95%CI 0.258-0.813; p = .008). Conversely, male gender (OR 2.247, 95%CI 1.194-4.227; p = .012) and receiving an mRNA vaccine (vs a non-mRNA vaccine) (OR 4.107, 95%CI 1.145-14.731; p = .030) were independent predictive factors for developing an optimal humoral response after vaccination. None of the patients who received the vaccine experienced any serious adverse events.Even after a third booster dose, response rate to vaccination is decreased in liver transplant recipients. MMF appears to be a major determinant of seroconversion and optimal response to vaccination in these patients.

Limited data exist concerning the long-term efficiency of gastric peroral endoscopic myotomy (G-POEM) as a treatment of refractory gastroparesis. This study evaluated the 3-year results of G-POEM in patients with refractory gastroparesis.This was a prospective multicenter study of all G-POEM operations performed in 2 expert French centers for 46 patients with refractory gastroparesis with at least 3 years of follow-up.Clinical success was 65.2% at 36 months. There was significant improvement in symptom severity. Median Gastroparesis Cardinal Symptom Index decreased from 3.33 to 1.80 (P .0001), with improvement in all subscales. We created a predictive score concerning G-POEM success (G-POEM predictive score) to which points were assigned as follows: nausea subscale 2: predictive of success, 1 point; satiety subscale4: predictive of success, 1 point; bloating subscale3.5: predictive of success, 1 point; percentage of gastric retention at 4 hours on scintigraphy50%: 1 point. A threshold of 2 was identified by receiver operating characteristic curve analysis with an area under the curve of .825 that predicted clinical success with a sensitivity of 93.3% (95% confidence interval [CI], .77-.99), specificity of 56.3% (95% CI, .33-.77), positive predictive value of 80% (95% CI, .67-.93), negative predictive value of 81.8% (95% CI, .59-1.00), and accuracy of 80.4% (95% CI, .69-.92). Patients with a score ≥2 were significantly more likely to be responders at 3 years than were patients with a score 2 (80% and 18%, respectively; P = .0004).The clinical success of G-POEM for refractory gastroparesis was 65.2% at 36 months. Our predictive score offers an easy tool that needs to be confirmed in other studies.

Background and Objectives: Concomitant biliary and duodenal malignant obstruction are a severe condition mainly managed by duodenal and biliary stenting, which can be performed simultaneously (SAMETIME) or in two distinct procedures (TWO-TIMES). We conducted a single-center retrospective study to evaluate the feasibility of a SAMETIME procedure and the impact of endoscopic ultrasound (EUS)-hepaticogastrostomy in double malignant obstructions. Patients and Methods: From January 1, 2011, to January 1, 2018, patients with concomitant malignant bilioduodenal obstruction treated endoscopically were included. The primary endpoint was hospitalization duration. The secondary endpoints were bilioduodenal reintervention rates, adverse event rates, and overall survival. Patients were divided into groups for statistical analysis: (i) divided according to the timing of biliary drainage: SAMETIME vs. TWO-TIMES group, (ii) divided based on the biliary drainage method: EUS-HG group underwent hepaticogastrostomy, while DUODENAL ACCESS group underwent endoscopic retrograde cholangiopancreatography (ERCP), percutaneous transhepatic drainage (PCTD) or EUS-guided choledocoduodenostomy (EUS-CD). Results: Thirty-one patients were included (19 women, median age = 71 years). Stenosis was mainly related to pancreatic cancer (17 patients, 54.8%). Sixteen patients were in the SAMETIME group, and 15 were in the TWO-TIMES group. Biliary drainage was performed by EUS-HG in 11 (35.%) patients, PCTD in 11 (35.%), ERCP in 8 (25.8%) and choledoduodenostomy in 1. Thirty patients died during follow-up. The median survival was 77 days (9% confidence interval [37–140]). The mean hospitalization duration was lower in the SAMETIME group: 7.5 vs. 12.6 days, P = 0.04. SAMETIME group patients tended to have a lower complication than TWO-TIMES (26.7% vs. 56.3%, P = 0.10). The EUS-HG group tended to have a lower complication rate (5% vs. 18.2%, P = 0.07) and less biliary endoscopic revision (30% vs. 9.1%, P = 0.37) than DUODENAL ACCESS. Conclusions: SAMETIME drainage is associated with a lower hospital stay without increased morbidity. EUS-HG could provide better access because it did not exhibit a higher complication rate and showed a tendency toward better patency and fewer complications.

International audience; Background and objectives: Concomitant biliary and duodenal malignant obstruction are a severe condition mainly managed by duodenal and biliary stenting, which can be performed simultaneously (SAMETIME) or in two distinct procedures (TWO-TIMES). We conducted a single-center retrospective study to evaluate the feasibility of a SAMETIME procedure and the impact of endoscopic ultrasound (EUS)-hepaticogastrostomy in double malignant obstructions.Patients and methods: From January 1, 2011, to January 1, 2018, patients with concomitant malignant bilioduodenal obstruction treated endoscopically were included. The primary endpoint was hospitalization duration. The secondary endpoints were bilioduodenal reintervention rates, adverse event rates, and overall survival. Patients were divided into groups for statistical analysis: (i) divided according to the timing of biliary drainage: SAMETIME vs. TWO-TIMES group, (ii) divided based on the biliary drainage method: EUS-HG group underwent hepaticogastrostomy, while DUODENAL ACCESS group underwent endoscopic retrograde cholangiopancreatography (ERCP), percutaneous transhepatic drainage (PCTD) or EUS-guided choledocoduodenostomy (EUS-CD).Results: Thirty-one patients were included (19 women, median age = 71 years). Stenosis was mainly related to pancreatic cancer (17 patients, 54.8%). Sixteen patients were in the SAMETIME group, and 15 were in the TWO-TIMES group. Biliary drainage was performed by EUS-HG in 11 (35.%) patients, PCTD in 11 (35.%), ERCP in 8 (25.8%) and choledoduodenostomy in 1. Thirty patients died during follow-up. The median survival was 77 days (9% confidence interval [37-140]). The mean hospitalization duration was lower in the SAMETIME group: 7.5 vs. 12.6 days, P = 0.04. SAMETIME group patients tended to have a lower complication than TWO-TIMES (26.7% vs. 56.3%, P = 0.10). The EUS-HG group tended to have a lower complication rate (5% vs. 18.2%, P = 0.07) and less biliary endoscopic revision (30% vs. 9.1%, P = 0.37) than DUODENAL ACCESS.Conclusions: SAMETIME drainage is associated with a lower hospital stay without increased morbidity. EUS-HG could provide better access because it did not exhibit a higher complication rate and showed a tendency toward better patency and fewer complications.

Background Nab-paclitaxel/gemcitabine (AG) and FOLFIRINOX (FFX) are promising drugs in metastatic pancreatic cancer (MPC). This study evaluated a new first-line sequential treatment (AG followed by FFX) in MPC that might overcome resistance to primary therapy and delay tumor progression. Patients and methods Patients with histologically/cytologically confirmed MPC were included in a multicentric trial receiving AG (day 1, 8 and 15) followed by FFX (day 29 and 43). In phase Ib, three dose-levels were tested for maximum tolerated dose (MTD) and recommended phase II dose. In phase II, the main outcome was the objective response rate (ORR) and secondarily safety, progression-free survival (PFS) and overall survival (OS). Results In phase Ib, we included 33 patients (31 assessable) of median age 61.0 years (range 42-75 years) and represented by 54.8% males. Five dose-limiting toxicities were reported without any death. The main grade 3/4 toxicities were neutropenia with spontaneous resolution (35.5%/32.3%), venous thromboembolism (grade 3: 22.6%) and thrombopenia (grade 3: 29.0%), while the MTD was not reached. In phase II, we included 58 patients of median age 60 years (range 34-72 years), 50% males and with Eastern Cooperative Oncology Group stage score 0 and 1 of 37.9% and 62.1%, respectively. They received a median of 4 (1-9) cycles in 8.5 months (0.5-19.8 months). The ORR was 64.9% [95% confidence interval (CI) 51.1% to 77.1%], and neurotoxicity was remarkably low. The main grade 3-4 toxicities were venous thromboembolism, thrombopenia, neutropenia/febrile neutropenia, nausea, diarrhea, weight loss and asthenia without any death. Tumor response was complete in 3.5% and partial in 61.4%, while disease was stable in 19.3% and progressive in 15.8% of patients. The median PFS was 10.5 months (95% CI 6.0-12.5 months) and median OS was 15.1 months (95% CI 10.6-20.1 months). Conclusion Sequential AG and FFX showed acceptable toxicity as first-line treatment with no limiting neurotoxicity, while high response rate and survival justify randomized trials., Highlights • AG and FFX are promising drugs in MPC. • We hypothesize that nab-paclitaxel by targeting tumor microenvironment would increase FFX access in sequential treatment. • Phase Ib-II trial with AG followed by FFX showed acceptable toxicity with no limiting neurotoxicity. • The high response rate and promising survival justify a further randomized trial.

We read with interest the article by Schuitenmaker et al 1 that evaluated oesophageal pneumatic dilation (PD) for persistent dysphagia after antireflux surgery (ARS). The authors concluded that PD is not more effective than sham procedure in patients with persistent dysphagia after laparoscopic fundoplication. The therapeutic target of PD is the esogastric junction (EGJ) and its effect is theoretically explained by mechanical forces applied on an EGJ obstacle, being either cardial muscular in achalasia or extrinsic valve after antireflux fundoplication. But most of the patients included in the study (76%) did not have an EGJ outflow obstruction (EGJOO). The realisation of an antireflux valve can lead to the development of inefficient oesophageal motility in nearly 20% of cases2 and the study of Schuitenmake et al reinforces the idea that post-ARS dysphagia is not necessarily related …

International audience; Laparoscopic sleeve gastrectomy has become the most commonly used bariatric surgery worldwide. However, there are a proportion of patients who present with a refractory GERD after this procedure. In these patients, when surgical conversion to RYGPB is not possible or declined, we propose to describe the results of an endoscopic antireflux mucosectomy band (ARM-b) technique in 6 LSG patients with refractory GERD. The technical feasibility was 100%; 5 out of 6 patients had a clinical response with a reduction of the GERD-HRQL score of > 50%. Two patients had adverse events: one esophageal stricture and one benign bleeding. ARM-b is feasible and potentially effective to treat patients with refractory GERD after LSG.

A 49-year-old woman attended our unit with progressive abdominal pain that progressively worsened over a period of several months, accompanied by chronic diarrhea with 3–4 stools per day, without rectal bleeding. She had no personal or family history of digestive disease and she had travelled to Vietnam and to India 3 and 10 years ago, respectively. Blood testing revealed moderate biological inflammatory syndrome (C-reactive protein levels ranging from 10 to 15 mg/L). Bacterologic stool examinations, Clostridium difficile testing and parasitological stool examinations were all negative for 3 days in a row.

Nonmalignant esophago-respiratory fistulas (ERF) are frightening clinical situations, involving surgery with high morbi-mortality rate. We described the endoscopic management of benign ERF. The aim of the study was to describe outcomes of endoscopic treatment of nonmalignant ERF and to analyze factors associated with its success. This is a retrospective study involving patients managed for benign ERF in our center between 2012 and 2016. The ERFs were classified into three groups of sizes: (I) punctiform, (II) medium, and (III) large. The primary aim was to document the endoscopic success (= fistula’s healing after 6 months). The secondary objectives were characteristics of endoscopic treatment, the functional success and death, and identifying factors associated with success and death. 22 patients were included. The etiologies of ERF were surgery in 12 patients, esophageal dilatation in 3, invasive ventilation in 3, radiation therapy in 2, and tracheostomy in 2. Ninety-three procedures were performed (mean of number: 4.2 ± 4.5/patient). Twenty-one patients had stent placement, eight over-the-scope clips (OTSC), and seven a combined therapy. The endoscopic success rate was 45.5% (n = 10; 67% in punctiform, 50% in medium, and 14% in large ERF), and the functional success was 55% (n = 12). Serious adverse events occurred in 9 patients (40.9%). Six patients died (27%). The persistence of the orifice after 6 months of endoscopic treatment was associated with failure (OR 44; IC95: 3.38–573.4; p = 0.004 multivariate analysis). The orifice’s size was associated with mortality [71% of death if large fistulas (p = 0.001) univariate analysis]. Endoscopic treatment of ERF leads to 45.5% of successful endoscopic closure and 55.5% of functional success, depending on fistula’s orifice size. After 6 months without healing, the chances for success dramatically decrease.

Venous thromboembolism (VTE; defined by deep-vein thrombosis, central venous catheter-related thrombosis or pulmonary embolism) is a major therapeutic issue in cancer patients. VTE is reported in 15-20% of patients with cancer and is an independent prognostic factor and a leading cause of death. In this population, low-molecular-weight heparins have been shown to be superior to vitamin K antagonists. The Italian Association of Medical Oncology, the National Comprehensive Cancer Network, the American Society of Clinical Oncology, the French 'Institut National du Cancer', the European Society of Medical Oncology and the American College of Chest Physicians have all published specific guidelines, but their implementation is still low in clinical practice. Methodological assessment of these guidelines was performed using the Appraisal of Guidelines Research & Evaluation Instrument. None of the guidelines on thrombosis and cancer have sought for patients' preferences, nor were they tested among target users. VTE in cancer patients requires a multidisciplinary approach but downstream of the guidelines publication, the potential organisational barriers in applying the recommendations have not been discussed. Tolerance and cost-effectiveness of long-term use of low-molecular-weight heparin may account for the large heterogeneity seen in daily clinical practice. Homogenization of guidelines in international consensus working groups followed by educational and active implementation strategies would be very valuable in order to improve the care of VTE in cancer patients.