EUS-Guided Choledocho-duodenostomy Using Lumen Apposing Stent Versus ERCP With Covered Metallic Stents in Patients With Unresectable Malignant Distal Biliary Obstruction: A Multicenter Randomized Controlled Trial (DRA-MBO Trial).

BACKGROUND & AIMS: Several studies have compared primary endoscopic ultrasound (EUS)-guided biliary drainage to endoscopic retrograde cholangiopancreatography (ERCP) with insertion of metal stents in unresectable malignant distal biliary obstruction (MDBO) and the results were conflicting. The aim of the current study was to compare the outcomes of the procedures in a large-scale study. METHODS: This was a multicenter international randomized controlled study. Consecutive patients admitted for obstructive jaundice due to unresectable MDBO were recruited. Patients were randomly allocated to receive EUS-guided choledocho-duodenostomy (ECDS) or ERCP for drainage. The primary outcome was the 1-year stent patency rate. Other outcomes included technical success, clinical success, adverse events, time to stent dysfunction, reintervention rates, and overall survival. RESULTS: Between January 2017 and February 2021, 155 patients were recruited (ECDS 79, ERCP 76). There were no significant differences in 1-year stent patency rates (ECDS 91.1% vs ERCP 88.1%, P = .52). The ECDS group had significantly higher technical success (ECDS 96.2% vs ERCP 76.3%, P < .001), whereas clinical success was similar (ECDS 93.7% vs ERCP 90.8%, P = .559). The median (interquartile range) procedural time was significantly shorter in the ECDS group (ECDS 10 [5.75-18] vs ERCP 25 [14-40] minutes, P < .001). The rate of 30-day adverse events (P = 1) and 30-day mortality (P = .53) were similar. CONCLUSION: Both procedures could be options for primary biliary drainage in unresectable MDBO. ECDS was associated with higher technical success and shorter procedural time then ERCP. Primary ECDS may be preferred when difficult ERCPs are anticipated. This study was registered to Clinicaltrials.gov NCT03000855.

Partially covered versus uncovered pyloro-duodenal stents for unresectable malignant gastric outlet obstruction: Randomized controlled study.

OBJECTIVES: The aim of the current study was to compare the efficacy of partially covered duodenal stent (PCDS) vs. uncovered duodenal stent (UCDS) in patients suffering from unresectable primary malignant gastric outlet obstruction (GOO). METHODS: This was a prospective international randomized controlled study conducted in 10 high-volume institutions. Consecutive patients suffering from malignant GOO were recruited. The primary outcome measurement was the reintervention rate. Secondary outcomes included technical and clinical success, 30-day adverse events, 30-day mortality, causes of stent dysfunction, and the duration of stent patency. RESULTS: Between March 2017 and October 2020, 115 patients (59 PCDS, 56 UCDS) were recruited. The 1-year reintervention was not significantly different (PCDS vs. UDCS = 12/59, 20.3% vs. 14/56, 25%, P = 0.84). There was a trend to fewer patients with tumor ingrowth in the PCDS group (6/59 [10.2%]) vs. 13/56 [23.2%], P = 0.07). There were no significant differences in the technical success (100% vs. 100%, P = 1), clinical success (91.5% vs. 98.2%, P = 0.21), procedural time (21.5 [interquartile range [IQR] 17-30] vs. 20.0 [IQR 15-34.75], P = 0.62), hospital stay (4 [IQR 3-12] vs. 5 [IQR 3-8] days, P = 0.81), 30-day adverse events (18.6% vs. 14.3%, P = 0.62), or 30-day mortality (6.8% vs. 5.2%, P = 1.00). CONCLUSION: The use of PCDS was associated with a lower risk of tumor ingrowth but did not improve on reintervention rates or stent patency. Both kinds of stents could be used in this group of patients.

90Y Radioembolization versus Drug-eluting Bead Chemoembolization for Unresectable Hepatocellular Carcinoma: Results from the TRACE Phase II Randomized Controlled Trial.

Background Transarterial chemoembolization (TACE) is the recommended treatment for intermediate hepatocellular carcinoma (HCC) according to the Barcelona Clinic Liver Cancer guidelines. Prospective uncontrolled studies suggest that yttrium 90 (90Y) transarterial radioembolization (TARE) is a safe and effective alternative. Purpose To compare the efficacy and safety of TARE with TACE for unresectable HCC. Materials and Methods In this single-center prospective randomized controlled trial (TRACE), 90Y glass TARE was compared with doxorubicin drug-eluting bead (DEB) TACE in participants with intermediate-stage HCC, extended to Eastern Cooperative Oncology Group performance status 1 and those with early-stage HCC not eligible for surgery or thermoablation. Participants were recruited between September 2011 and March 2018. The primary end point was time to overall tumor progression (TTP) (Kaplan-Meier analysis) in the intention-to-treat (ITT) and per-protocol (PP) groups. Results At interim analysis, 38 participants (median age, 67 years; IQR, 63-72 years; 33 men) were randomized to the TARE arm and 34 (median age, 68 years; IQR, 61-71 years; 30 men) to the DEB-TACE arm (ITT group). Median TTP was 17.1 months in the TARE arm versus 9.5 months in the DEB-TACE arm (ITT group hazard ratio [HR], 0.36; 95% CI: 0.18, 0.70; P = .002) (PP group, 32 and 34 participants, respectively, in each arm; HR, 0.29; 95% CI: 0.14, 0.60; P < .001). Median overall survival was 30.2 months after TARE and 15.6 months after DEB-TACE (ITT group HR, 0.48; 95% CI: 0.28, 0.82; P = .006). Serious adverse events grade 3 or higher (13 of 33 participants [39%] vs 19 of 36 [53%] after TARE and DEB-TACE, respectively; P = .47) and 30-day mortality (0 of 33 participants [0%] vs three of 36 [8.3%]; P = .24) were similar in the safety groups. At the interim, the HR for the primary end point, TTP, was less than 0.39, meeting the criteria to halt the study. Conclusion With similar safety profile, yttrium 90 radioembolization conferred superior tumor control and survival compared with chemoembolization using drug-eluting beads in selected participants with early or intermediate hepatocellular carcinoma. Clinical trial registration no. NCT01381211 © RSNA, 2022 Online supplemental material is available for this article.

Novel 15-mm-long lumen-apposing metal stent for endoscopic ultrasound-guided drainage of pancreatic fluid collections located ≥10 mm from the luminal wall.

BACKGROUND: Endoscopic ultrasound (EUS)-guided drainage of pancreatic fluid collections (PFCs) by cautery-enhanced lumen-apposing metal stents (LAMS) has largely been limited to collections located < 10 mm from the luminal wall. We present outcomes of the use of a novel 15-mm-long cautery-enhanced LAMS for drainage of PFCs located ≥ 10 mm away. METHODS: This international, multicenter study analyzed all adults with PFCs located ≥ 10 mm from the luminal wall who were treated by EUS-guided drainage using the 15-mm-long cautery-enhanced LAMS. The primary outcome was technical success. Secondary outcomes included clinical success (decrease in PFC size by ≥ 50 % at 30 days and resolution of clinical symptoms without surgical intervention), complications, and recurrence. RESULTS: 35 patients (median age 57 years; interquartile range [IQR] 47-64 years; 49 % male) underwent novel LAMS placement for drainage of PFCs (26 walled-off necrosis, 9 pseudocysts), measuring 85 mm (IQR 64-117) maximal diameter and located 11.8 mm (IQR 10-12.3; range 10-14) from the gastric/duodenal wall. Technical and clinical success were high (both 97 %), with recurrence in one patient (3 %) at a median follow-up of 123 days (58-236). Three complications occurred (9 %; one mild, two moderate). CONCLUSIONS: The 15-mm-long cautery-enhanced LAMS was feasible and safe for drainage of PFCs located 10-14 mm from the luminal wall.

The Evolution in Non-Alcoholic Fatty Liver Disease Patients' Profile and the Associated Sustainable Challenges: A Multidisciplinary Perspective.

The prevalence and incidence of NAFLD is rising due to the obesity pandemic, caused by the widespread availability of ultra-processed foods and the decrease of physical activity. Factors such as socioeconomic status (SES), ethnicity and geographical location are associated with NAFLD, with lower SES correlating with higher incidence, particularly in regions like America or Europe. Beside the quality of food, the quantity also plays a crucial role. The World Health Organization (WHO) recommends a Mediterranean diet with a balanced energy intake. Since no hard medical treatment is available for NAFLD, lifestyle adjustments are key. Patient empowerment by providing relevant information and co-ownership of the therapy will increase the implementation rate and enhance the quality of medical follow-up and medication adherence, as studies report a good adherence to medication among patients who are well-aware of the severity of their disease. Regarding sustainability, patients with NAFLD have a high load of ambulatory follow-up, which, since the COVID-19 pandemic, can be partially provided by teleconsulting. Both patients' lifestyle modifications and healthcare practitioners' therapeutical strategy can decrease the carbon footprint.

Endoscopic ultrasound-guided gastroenterostomy for the management of gastric outlet obstruction: A large comparative study with long-term follow-up.

Background and study aims Gastric outlet obstruction (GOO) is traditionally managed with surgical gastroenterostomy (surgical-GE) and enteral stenting (ES). Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) is now a third option. Large studies assessing their relative risks and benefits with adequate follow-up are lacking. We conducted a comparative analysis of patients who underwent EUS-GE, ES, or surgical-GE for GOO. Patients and methods In this retrospective comparative cohort study, consecutive patients presenting with GOO who underwent EUS-GE, ES, or surgical-GE at two academic institutions were reviewed and independently cross-edited to ensure accurate reporting. The primary outcome was need for reintervention. Secondary outcomes were technical and clinical success, length of hospital stay (LOS), and adverse events (AEs). Results A total of 436 patients (232 EUS-GE, 131 ES, 73 surgical-GE) were included. The median duration of follow-up of the entire cohort was 185.5 days (interquartile range 55.25-454.25 days). The rate of reintervention in the EUS-GE group was lower than in the ES and surgical-GE groups (0.9 %, 12.2 %, and 13.7 %, P  < 0.0001). Technical success was achieved in 98.3 %, 99.2 %, and 100 % ( P  = 0.58), and clinical success was achieved in 98.3 %, 91.6 %, and 90.4 % ( P  < 0.0001) in the EUS-GE, ES, and surgical-GE groups, respectively. The EUS-GE group had a shorter LOS (2 days vs. 3 days vs. 5 days, P  < 0.0001) and a lower AE rate than the ES and surgical-GE groups (8.6 % vs. 38.9 % vs. 27.4 %, P  < 0.0001). Conclusion This large cohort study demonstrates the safety and palliation durability of EUS-GE as an alternative strategy for GOO palliation in select patients.

Step-up approach in emphysematous hepatitis: A case report.

BACKGROUND: Emphysematous hepatitis (EH) is a rare, rapidly progressive fulminant gas-forming infection of the liver parenchyma. It is often fatal and mostly affects diabetes patients. CASE SUMMARY: We report a case of EH successfully managed by a step-up approach consisting of aggressive hemodynamic support, intravenous antibiotics, and percutaneous drainage, ultimately followed by laparoscopic deroofing. Of 11 documented cases worldwide, only 1 of the patients survived, treated by urgent laparotomy and surgical debridement. CONCLUSION: EH is a life-threatening infection. Its high mortality rate makes timely diagnosis essential, in order to navigate treatment accordingly.

Esophageal Findings in the Setting of a Novel Preventive Strategy to Avoid Thermal Lesions during Hybrid Thoracoscopic Radiofrequency Ablation for Atrial Fibrillation.

Purpose The development of an atrio-esophageal fistula, a rare yet potentially lethal complication of ablation for atrial fibrillation, could be related to direct tissue heat transfer during and immediately after the ablation. We therefore studied the postoperative esophageal findings by esophagogastroduodenoscopy in patients that underwent a hybrid ablation procedure using a novel preventive strategy to avoid thermal lesions. Methods Thirty-four patients (28 males; 65 years ± 9 years) were retrospectively included. All underwent a hybrid ablation in our center between April 2015 and November 2019 and agreed to an esophagogastroduodenoscopy within 0-14 days (mean: 5 days) following the ablation. To reduce the incidence of thermal lesions three procedural preventive strategies were introduced: (i) videoscopic intrathoracic transesophageal echocardiographic probe visualization to understand the relationship between posterior left atrial wall and esophagus, with probe retraction before ablation; (ii) lifting the cardiac tissue away from the esophagus during energy application; and (iii) a 30-s cool-off period after energy delivery with irrigation of the device, the ablated tissue, and the surrounding tissues. Results No esophageal thermal lesions were observed. One third of patients were diagnosed with incidental esophageal findings unrelated to the ablation procedure (11; 32.4%). Conclusion Novel preventive strategies by visualization and by avoiding contact between the ablation catheter or ablated tissue and the pericardium, seems to eliminate the potential risk of esophageal thermal lesions in the setting of hybrid ablation. Since one third of patients had preexisting esophageal disease, a more comprehensive pre-operative screening could be important to reduce the risk.

A Bitter Pill to Swallow: Pseudoachalasia Secondary to Oesophageal Deviation Resulting from Mediastinal Shift and Left Atrial Enlargement after Left Lower Lobectomy.

Pseudoachalasia, also known as secondary achalasia, is a rare clinical condition mimicking idiopathic achalasia but unrelated to primary loss of nitrergic innervation. It has mostly been attributed to malignancy infiltrating the oesophageal wall, but several other benign underlying pathologies have been reported. Because of similar manometric appearance, high-resolution manometry (HRM) of the oesophagus alone cannot distinguish between idiopathic achalasia and pseudoachalasia. Misdiagnosis can result in ineffective treatment by dilatation or even more invasive therapy. This is the first case-report of pseudoachalasia secondary to oesophageal deviation resulting from mediastinal shift and left atrial enlargement following prior left lower lobectomy. HRM, the gold standard for the diagnosis of achalasia, confirmed the incomplete relaxation of the lower oesophageal sphincter (LES) in absence of normal oesophageal peristalsis. However, additional workup with CAT scan and cardiac ultrasound identified an anatomical shift by the extrinsic mass effect resulting from the atrial enlargement, but without contrast retention at the LES.

Cetuximab with hepatic arterial infusion of chemotherapy for the treatment of colorectal cancer liver metastases.

BACKGROUND: Both hepatic arterial infusion (HAI) of chemotherapy and cetuximab (CET) have interesting activity for the treatment of colorectal cancer liver metastases (CRC-LM). PATIENTS AND METHODS: Intravenous CET with HAI oxaliplatin (OXA) or i.v. Irinotecan (IRI) followed by HAI of infusion of folic acid modulated 5-fluorouracil 5-FU/l-FA was administered to patients (pts) with CRC-LM who had failed at least one line of prior chemotherapy. RESULTS: Eight pts received i.v. CET with HAI-OXA (5 pts) and i.v.-IRI (3 pts) and HAI-5-FU/l-FA. Adverse events: repeated grade 3 skin toxicity (1 pt), abdominal pain with elevated liver enzymes and asthenia (2 pts), duodenal ulcer (2 pts) with catheter migration and intestinal bleeding (1 pt), reversible interstitial pneumonitis (1 pt), and cystic bile duct dilatation (2 pts) with arteriobiliary fistulisation (1 pt). A partial response was documented in 5 pts (62%). The median time to progression was 8.7 months (95% confidence interval 8-14 months). CONCLUSION: Intravenous administration of CET with HAI of chemotherapy is feasible and has promising activity but is associated with specific toxicity.

Disease Control on Lanreotide Autogel® 120 mg in a Patient with Metastatic Gastrinoma: A Case Report.

Gastrinomas are functionally active pancreatic neuroendocrine tumors (NETs) secreting gastrin and are associated with local or regional metastases in 60% of the cases. Somatostatin analogs (SSAs) are currently recommended as a first-line treatment for the symptomatic treatment of NETs. Although antiproliferative activity of SSAs has been demonstrated in various cancer types in several in vivo and in vitro studies, clinical benefits with SSAs have been only achieved in a small proportion of patients. We report a disease control on a long-acting SSA lanreotide in a patient with metastatic gastrinoma. A 60-year-old man, who had previously undergone a surgical resection of metastatic pancreatic gastrinoma, presented with abdominal bloating, edema in the lower limbs, fatigue, and weight loss. The gastrinoma relapse with additional metastases in the pancreas, duodenum, and liver was confirmed by positron emission tomography-computed tomography (PET-CT) scan; the patient's blood gastrin level was >5,000 ng/L. Treatment with the SSA octreotide long-acting release was initiated to treat the gastrinoma relapse. On the CT scan done in September 2011, the liver metastases were still identifiable. In December 2011, the treatment was switched to lanreotide Autogel® (120 mg every 2 weeks). Following the treatment, the gastrin levels were reduced to <1,200 ng/L in September 2013, and 812 ng/L in July 2016. Since November 2012, the gastrinoma lesions were no longer visible in abdominal CT. At the time of this report, the patient's gastrinoma was under control with lanreotide Autogel®. This case report supports the use of lanreotide Autogel® as effective treatment for metastatic gastrinoma.

Hepatic arterial infusion of oxaliplatin and L-folinic acid-modulated 5-fluorouracil for colorectal cancer liver metastases.

BACKGROUND: Despite the progress made in the treatment of metastatic colorectal cancer (CRC), the results of second-line chemotherapy remain poor. PATIENTS AND METHODS: The feasibility of hepatic arterial infusion (HAI) of oxaliplatin (100 mg/m2 over 6 h) followed by l-folinic acid (L-FA) (400 mg over 2 h i.v.)-modulated continuous HAI of 5-Fluorouracil (5-FU) (60 mg/kg over 42 h; q2w) as second-line chemotherapy for metastatic CRC limited to the liver was investigated. RESULTS: A median of 9 treatment cycles were administered (range 4-14). Treatment-limiting toxicity consisted of: abdominal pain (3 patients), elevated liver enzymes accompanied by fatigue (3), elevated bilirubin (2), neutropenia (2), thrombocytopenia (3) and hypersensitivity to oxaliplatin (1). Normalization for >4 weeks of the carcinoembryonic antigen (CEA) level was documented in 3 patients and a decline of >50% for >4 weeks in 5 patients. A confirmed partial response (PR) was documented in 5, stable disease (SD) in 1 and progressive disease (PD) in 3 patients. In the latter 3 patients, lung metastases developed while a PR was observed in the liver metastases. A pathological complete response (CR) was documented in 2 patients. The median time to progression was 7.2 months (95% CI 1.3-13) and the median overall survival 18.3 months (95% CI 16.3-20.3). CONCLUSION: HAI of oxaliplatin plus CI5-FU/LV is feasible and merits further evaluation.

Current status and perspectives of immune-based therapies for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a frequent cancer with a high mortality. For early stage cancer there are potentially curative treatments including local ablation, resection and liver transplantation. However, for more advanced stage disease, there is no optimal treatment available. Even in the case of a "curative" treatment, recurrence or development of a new cancer in the precancerous liver is common. Thus, there is an urgent need for novel and effective (adjuvant) therapies to treat HCC and to prevent recurrence after local treatment in patients with HCC. The unique immune response in the liver favors tolerance, which remains a genuine challenge for conventional immunotherapy in patients with HCC. However, even in this "immunotolerant" organ, spontaneous immune responses against tumor antigens have been detected, although they are insufficient to achieve significant tumor death. Local ablation therapy leads to immunogenic tumor cell death by inducing the release of massive amounts of antigens, which enhances spontaneous immune response. New immune therapies such as dendritic cell vaccination and immune checkpoint inhibition are under investigation. Immunotherapy for cancer has made huge progress in the last few years and clinical trials examining the use of immunotherapy to treat hepatocellular carcinoma have shown some success. In this review, we discuss the current status of and offer some perspectives on immunotherapy for hepatocellular carcinoma, which could change disease progression in the near future.