Effectiveness of endoscopic ultrasound (EUS)-guided choledochoduodenostomy vs. EUS-guided gallbladder drainage for jaundice in patients with malignant distal biliary obstruction after failed endoscopic retrograde cholangiopancreatography: Retrospective, multicenter study (GALLBLADEUS Study).

OBJECTIVES: The aim of this study was to compare endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) vs. EUS-gallbladder drainage (EUS-GBD) in cases of failed endoscopic retrograde cholangiopancreatography (ERCP) for jaundice resulting from malignant distal biliary obstruction (MDBO). METHODS: This multicenter retrospective study included patients with obstructive jaundice secondary to MDBO who underwent EUS-GBD or EUS-CDS with lumen-apposing metal stents after failed ERCP. The primary end-point was clinical success rate. Secondary end-points were technical success, periprocedural adverse events rate (<24 h), late adverse events rate (>24 h), overall survival, and time to recurrent biliary obstruction. RESULTS: A total of 78 patients were included: 41 underwent EUS-GBD and 37 underwent EUS-CDS. MDBO was mainly the result of pancreatic cancer (n = 63/78, 80.7%). Clinical success rate was similar for both procedures: 87.8% for EUS-GBD and 89.2% for EUS-CDS (P = 0.8). Technical success rate was 100% for EUS-GBD and 94.6% for EUS-CDS (P = 0.132). Periprocedural morbidity (<24 h) rates were similar between both groups: 4/41 (9.8%) for EUS-GBD and 5/37 (13.5%) for EUS-CDS (P = 0.368). There was a significantly higher rate of late morbidity (>24 h) among patients in the EUS-CDS group (8/37 [21.6%]) than in the EUS-GBD group (3/41 [7.3%]) (P = 0.042). The median follow-up duration was 4.7 months. Overall survival and time to recurrent biliary obstruction did not significantly differ between the groups. DISCUSSION: After failed ERCP for MDBO, EUS-GBD and EUS-CDS show comparable clinical success rates and technical success. EUS-GBD appears to be a promising alternative for MDBO, even as a second-line treatment after failed ERCP. Further studies are needed to validate these findings and compare the long-term outcomes of EUS-GBD and EUS-CDS.

Gastric peroral endoscopic myotomy versus botulinum toxin injection for the treatment of refractory gastroparesis: results of a double-blind randomized controlled study.

INTRODUCTION: Gastric peroral endoscopic myotomy (G-POEM) is a promising technique for treating refractory gastroparesis. We present the first double-blind randomized study comparing the clinical efficacy of G-POEM versus pyloric botulinum toxin injection (BTI). METHODS: This randomized study, conducted in two expert centers, enrolled patients with refractory gastroparesis, medically managed for >6 months and confirmed by gastric emptying scintigraphy (GES), into two groups, G-POEM versus BTI, with follow-up of 1 year. The primary end point was the 3-month clinical efficacy, defined as a >1-point decrease in the mean Gastroparesis Cardinal Symptom Index (GCSI) score. Secondary end points were: 1-year efficacy, GES evolution, adverse events, and quality of life. RESULTS: 40 patients (22 women; mean age 48.1 [SD 17.4]), with mean symptom duration of 5.8 (SD 5.7) years, were randomized. Etiologies included idiopathic (n=18), diabetes (n=11), postoperative (n=6), and mixed (n=4). G-POEM showed a higher 3-month clinical success than BTI (65% vs. 40%, respectively; P=0.10), along with non-significantly higher 1-year clinical success (60% vs. 40%, respectively) on intention-to-treat analysis. The GCSI decreased in both groups at 3 months and 1 year. Only three minor adverse events occurred in the G-POEM group. The GES improvement rate was 72% in the G-POEM group versus 50% in the BTI group (non-significant). CONCLUSION: G-POEM seems to have a higher clinically relevant success rate than BTI, but this was not statistically demonstrated. This study confirms the interest in treatments targeting the pylorus, either mechanically or chemically, for managing refractory gastroparesis.

Training in esophageal peroral endoscopic myotomy (POEM) on an ex vivo porcine model: learning curve study and training strategy.

BACKGROUND: 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. MATERIALS AND METHODS: 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). RESULTS: 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. CONCLUSION: 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.

Detection of soluble biomarkers of pancreatic cancer in endoscopic ultrasound-guided fine-needle aspiration samples.

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.

Endoscopic management of concomitant biliary and duodenal malignant obstruction: Impact of the timing of drainage for one vs. two procedures and the modalities of biliary drainage.

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.

Identification of factors associated with aggressive end-of-life antitumour treatment: retrospective study of 1282 patients with cancer.

OBJECTIVE: Antitumour treatment in the last 2 weeks of death (ATT-W2) and a new regimen of ATT within 30 days of death (NATT-M1) are considered as aggressive end-of-life (EOL) care. We aimed to assess factors associated with inappropriate use of antitumour treatment (ATT) at EOL. METHODS: Data of patients with cancer who died in 2013, 2015, 2017 and 2019 in a single for-profit cancer centre were retrospectively analysed. ATT was divided into chemotherapy (CT), oral targeted therapy (OTT), hormonotherapy and immunotherapy (IMT). RESULTS: A total of 1282 patients were included. NATT-M1 was given to 197 (15.37%) patients, and 167 (13.03%) had an ATT-W2. Patients with a performance status of <2 and treated with CT had more both ATT- W2 (OR=2.45, 95% CI 1.65 to 3.65, and OR=10.29, 95% CI 4.70 to 22.6, respectively) and NATT-M1 (OR=2.01, 95% CI 1.40 to 2.90, and OR=8.41, 95% CI 4.46 to 15.86). Predictive factors of a higher rate of ATT-W2 were treatment with OTT (OR=19.08, 95% CI 7.12 to 51.07), follow-up by a medical oncologist (OR=1.49, 95% CI 1.03 to 2.17), miscellaneous cancer (OR=3.50, 95% CI 1.13 to 10.85) and length of hospital stay before death of <13 days (OR=1.92, 95% CI 1.32 to 2.79). Urinary tract and male genital cancers received less ATT-W2 (OR=0.38, 95% CI 0.16 to 0.89, and OR=0.40, 95% CI 0.16 to 0.99) and patients treated by IMT or with age <69 years more NATT-M1 (OR=19.21, 95% CI 7.55 to 48.8, and OR=1.69, 95% CI 1.20 to 2.37). Patients followed up by the palliative care team (PCT) had fewer ATT-W2 and NATT-M1 (OR=0.49, 95% CI 0.35 to 0.71, and OR=0.42, 95% CI 0.30 to 0.58). CONCLUSIONS: Most recent ATT and access to a PCT follow-up are the two most important potentially modifiable factors associated with aggressive EOL in patients with cancer. Early integrated palliative oncology care could help to decrease futile ATT at EOL.

Antireflux Mucosectomy Band (ARM-b) in Treatment of Refractory Gastroesophageal Reflux Disease After Bariatric Surgery.

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.

Endoscopic treatment of nonmalignant tracheoesophageal and bronchoesophageal fistula: results and prognostic factors for its success.

BACKGROUND: 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. METHODS: 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. RESULTS: 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]. CONCLUSION: 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.

How to improve the implementation of guidelines on cancer-related thrombosis.

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.