Endoscopic ultrasonography-guided gastroenterostomy versus surgical gastrojejunostomy for palliation of malignant gastric outlet obstruction (ENDURO): study protocol for a randomized controlled trial.

BACKGROUND: Malignant gastric outlet obstruction (GOO) is a debilitating condition that frequently occurs in patients with malignancies of the distal stomach and (peri)ampullary region. The standard palliative treatment for patients with a reasonable life expectancy and adequate performance status is a laparoscopic surgical gastrojejunostomy (SGJ). Recently, endoscopic ultrasound-guided gastroenterostomy (EUS-GE) emerged as a promising alternative to the surgical approach. The present study aims to compare these treatment modalities in terms of efficacy, safety, and costs. METHODS: The ENDURO-study is a multicentre, open-label, parallel-group randomized controlled trial. In total, ninety-six patients with gastric outlet obstruction caused by an irresectable or metastasized malignancy will be 1:1 randomized to either SGJ or EUS-GE. The primary endpoint is time to tolerate at least soft solids. The co-primary endpoint is the proportion of patients with persisting or recurring symptoms of gastric outlet obstruction for which a reintervention is required. Secondary endpoints are technical and clinical success, quality of life, gastroenterostomy dysfunction, reinterventions, time to reintervention, adverse events, quality of life, time to start chemotherapy, length of hospital stay, readmissions, weight, survival, and costs. DISCUSSION: The ENDURO-study assesses whether EUS-GE, as compared to SGJ, results in a faster resumption of solid oral intake and is non-inferior regarding reinterventions for persistent or recurrent obstructive symptoms in patients with malignant GOO. This trial aims to guide future treatment strategies and to improve quality of life in a palliative setting. TRIAL REGISTRATION: International Clinical Trials Registry Platform (ICTRP): NL9592. Registered on 07 July 2021.

Clinical Outcomes of Biliary Drainage in Patients with Malignant Biliary Obstruction Caused by Colorectal Cancer Metastases.

BACKGROUND AND AIM: Malignant biliary obstruction is an ominous complication of metastatic colorectal cancer (mCRC) that is challenging to solve. Biliary drainage can be performed to relieve symptoms of jaundice, treat cholangitis, or enable palliative systemic therapy. The aim of this study is to evaluate clinical outcomes of biliary drainage of malignant biliary obstruction in mCRC patients. METHODS: Consecutive patients with malignant biliary obstruction due to mCRC who underwent endoscopic retrograde cholangiopancreatography or percutaneous transhepatic cholangiography were included. Patient, disease, and procedural characteristics and outcomes were retrospectively collected from electronic medical records. Radiological data were prospectively reassessed. Main outcome was functional success, i.e. achievement of the intended goal of biliary drainage. Prognostic factors for functional success and survival were assessed. RESULTS: Thirty-seven patients were included. Functional success was achieved in 18 (50%) patients. Seventeen (46%) patients experienced adverse events (suspected to be) related to the procedure. Median overall survival after biliary drainage was 61 days (IQR 31-113). No prognostic factors of functional success were identified. Performance status, presence of the primary tumor, ascites, ≥ 5 intrahepatic metastases, estimated hepatic invasion of > 50% and above-median levels of bilirubin and lactate dehydrogenase were significantly associated with poorer survival. Improved survival was seen in patients with technical, functional, or biochemical success, and with subsequent oncologic treatment. CONCLUSIONS: Functional successful biliary drainage was achieved in half of the patients. Adverse events also occurred in nearly half of the patients. We observed a significantly longer survival in whom biliary drainage allowed palliative oncologic therapy.

Digital single-operator cholangioscopy to guide selective cannulation of complex biliary strictures.

BACKGROUND: Selective cannulation and stenting of complex, tight, and/or angulated biliary strictures under endoscopic retrograde cholangiopancreaticography (ERCP) can be challenging. Digital single-operator cholangioscopy (SOC) may facilitate guidewire advancement through the stricture with endoscopic visual guidance. We aimed to describe a case series on clinical outcomes of this technique for selective cannulation, when used after failed conventional ERCP attempts. METHODS: Consecutive patients who underwent therapeutic digital SOC for selective cannulation of biliary strictures after failed conventional ERCP were retrospectively included. RESULTS: Ten patients with a malignant (n = 6) or benign (n = 4) biliary stricture were included. Digital SOC-assisted selective guidewire insertion and stent placement across the biliary stricture were technically successful in five (50%) patients. Bilirubin levels improved in all patients with technical success. One (10%) patient developed a post-ERCP pancreatitis. CONCLUSIONS: Technically successful cannulation of biliary strictures with digital SOC was achieved in half of patients in whom cannulation with conventional ERCP failed, sparing them more invasive interventions. Stricture opacification during the failed ERCP was seen in all technically successful SOCs.

Clinical outcomes of biliary drainage of malignant biliary obstruction due to colorectal cancer metastases: A systematic review.

BACKGROUND AND AIMS: Malignant biliary obstruction is an ominous complication of metastatic colorectal cancer (mCRC). Biliary drainage is frequently performed to relieve symptoms of jaundice or enable palliative systemic therapy, but effective drainage can be difficult to accomplish. The aim of this study is to summarize literature on clinical outcomes of biliary drainage in mCRC patients with malignant biliary obstruction. METHODS: We searched Medline and EMBASE for studies that included patients with malignant biliary obstruction secondary to mCRC, treated with endoscopic and/or percutaneous biliary drainage. We summarized available data on technical success, clinical success, adverse events, systemic therapy administration and survival after biliary drainage. RESULTS: After screening 3584 references and assessing 509 full-text articles, seven cohort studies were included. In these studies, rates of technical success, clinical success and adverse events varied between 63%-94%, 42%-81%, and 19%-39%, respectively. Subsequent chemotherapy was administered in 17%-56% of patients. Overall survival varied between 40 and 122 days across studies (278-365 days in patients who received subsequent chemotherapy, 42-61 days in patients who did not). CONCLUSIONS: Successful biliary drainage in mCRC patients can be challenging to achieve and is frequently associated with adverse events. Overall survival after biliary drainage is limited, but is significantly longer in patients treated with subsequent systemic therapy. Expected benefits of biliary drainage should be carefully weighed against its risks.

Early Lumen-Apposing Metal Stent Dysfunction Complicating Endoscopic Ultrasound-Guided Gastroenterostomy: A Report of Two Cases.

Endoscopic ultrasonography-guided gastroenterostomy using a lumen-apposing metal stent has emerged as a novel technique in the palliative treatment of malignant gastric outlet obstruction. Endoscopic ultrasonography-guided gastroenterostomy seems to have the potential to provide long-lasting patency in a minimally invasive manner. Low reintervention rates have been described. We report two cases with early lumen-apposing metal stent dysfunction, compromising patency. One case showed food impaction after three weeks, and hyperplastic tissue overgrowth with a buried distal flange six weeks after stent placement. The latter was successfully treated by argon plasma coagulation, stent removal, and deployment of a larger-diameter lumen-apposing metal stent. The second case showed a narrowed luminal diameter of the stent and jejunal pressure ulcerations after three weeks. The narrowing was successfully treated by balloon dilation. Eight weeks later, hyperplastic tissue overgrowth at the distal flange of the stent and a gastro-colonic fistula were diagnosed, followed by extensive reconstructive surgery.

Patency of endoscopic ultrasound-guided gastroenterostomy in the treatment of malignant gastric outlet obstruction.

Background and study aims Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) with a lumen-apposing metal stent (LAMS) is a novel, minimally invasive technique in the palliative treatment of malignant gastric outlet obstruction (GOO). Several studies have demonstrated feasibility and safety of EUS-GE, but evidence on long-term durability is limited. The aim of this study was to evaluate patency of EUS-GE in treatment of malignant GOO. Patients and Methods An international multicenter study was performed in seven centers in four European countries. Patients who underwent EUS-GE with a LAMS between March 2015 and March 2019 for palliative treatment of symptomatic malignant GOO were included retrospectively. Our main outcome was recurrent obstruction due to LAMS dysfunction; other outcomes of interest were technical success, clinical success, adverse events (AEs), and survival. Results A total of 45 patients (mean age 69.9 ±â€Š12.3 years and 48.9 % male) were included. Median duration of follow-up was 59 days (interquartile range [IQR] 41-128). Recurrent obstruction occurred in two patients (6.1 %), after 33 and 283 days of follow-up. Technical success was achieved in 39 patients (86.7 %). Clinical success was achieved in 33 patients (73.3 %). AEs occurred in 12 patients (26.7 %), of which five were fatal. Median overall survival was 57 days (IQR 32-114). Conclusions EUS-GE showed a low rate of recurrent obstruction. The relatively high number of fatal AEs underscores the importance of careful implementation of EUS-GE in clinical practice.

The dynamics of the pulmonary microbiome during mechanical ventilation in the intensive care unit and the association with occurrence of pneumonia.

RATIONALE: Ventilator-associated pneumonia (VAP) is the most common nosocomial infections in patients admitted to the ICU. The adapted island model predicts several changes in the respiratory microbiome during intubation and mechanical ventilation. OBJECTIVES: We hypothesised that mechanical ventilation and antibiotic administration decrease the diversity of the respiratory microbiome and that these changes are more profound in patients who develop VAP. METHODS: Intubated and mechanically ventilated ICU-patients were included. Tracheal aspirates were obtained three times a week. 16S rRNA gene sequencing with the Roche 454 platform was used to measure the composition of the respiratory microbiome. Associations were tested with linear mixed model analysis and principal coordinate analysis. MEASUREMENTS AND MAIN RESULTS: 111 tracheal aspirates were obtained from 35 patients; 11 had VAP, 18 did not have VAP. Six additional patients developed pneumonia within the first 48 hours after intubation. Duration of mechanical ventilation was associated with a decrease in α diversity (Shannon index; fixed-effect regression coefficient (ß): -0.03 (95% CI -0.05 to -0.005)), but the administration of antibiotic therapy was not (fixed-effect ß: 0.06; 95% CI -0.17 to 0.30). There was a significant difference in change of ß diversity between patients who developed VAP and control patients for Bray-Curtis distances (p=0.03) and for Manhattan distances (p=0.04). Burkholderia, Bacillales and, to a lesser extent, Pseudomonadales positively correlated with the change in ß diversity. CONCLUSION: Mechanical ventilation, but not antibiotic administration, was associated with changes in the respiratory microbiome. Dysbiosis of microbial communities in the respiratory tract was most profound in patients who developed VAP.