For Vol.70, No.5 pp405-408 A Multicenter, Prospective, Randomized Controlled Trial Evaluating the Efficacy of Rectal Diclofenac and Sublingual Nitrate as a Combined Prophylactic Treatment for Post-ERCP Pancreatitis

In the article by Tomoda T et al. entitled “A Multicenter, Prospective, Randomized Controlled Trial Evaluating the Efficacy of Rectal Diclofenac and Sublingual Nitroglycerin as a Combined Prophylactic Treatment for Post-ERCP Pancreatitis”, which appeared in the October 2016 issue, Vol. 70, No. 5, pp405-408, the word “nitroglycerin” should be corrected to “nitrate” throughout the manuscript

Bilateral verses bilateral with tri-segmental endoscopic drainage using metal stents for high-grade malignant hilar biliary obstructions: A multicenter, randomized controlled trial: BRAVE study (BRAVE study)

Introduction: Bilateral endoscopic drainage with self-expanding metallic stent (SEMS) can be used to manage hilar malignant biliary obstruction (HMBO) more effectively in comparison to unilateral drainage. An increased drainage area is predicted to prolong stent patency and patient survival. However, few reports have described the utility of trisegmental drainage and the benefits of using trisegmental drainage remain unknown. Thus, we launched a randomized clinical trial (RCT) to compare the clinical outcomes between bilateral and trisegmental drainage using SEMSs in patients with high-grade HMBO. Methods and analysis: This study was conducted as a multicenter randomized control trial (RCT) in 8 high-volume medical centers in Japan, and will prove the non-inferiority of bilateral drainage to trisegmental drainage. Patients with unresectable HMBO with Bismuth type IIIa or IV who pass the inclusion and exclusion criteria will be randomized to receive bilateral or trisegmental drainage at a 1:1 ratio. At each center, the on-site study investigators will obtain informed consent from the candidates, and will use an electronic data capture system (REDCap) to input necessary information, and register candidates with the registration secretariat. The primary endpoint is the rate of non-recurrent biliary obstruction (RBO) at 180 days after SEMSs placement. A -10% non-inferiority margin is assumed in the statistical analysis of the primary endpoint. Secondary endpoints include the rate of technical and clinical success, time to recurrent biliary obstruction (TRBO), causes of RBO, procedure-related adverse events (AEs), procedure time, TRBO with or without endoscopic sphincterotomy, overall survival, and the technical and clinical success rates at reintervention. Discussion: If the non-inferiority of bilateral drainage is demonstrated, it is predicted that the procedure time will be shortened and the medical cost will be reduced, which will be beneficial to the patient and the medical economy

Combination of Diclofenac and Sublingual Nitrates Is Superior to Diclofenac Alone in Preventing Pancreatitis After Endoscopic Retrograde Cholangiopancreatography

BACKGROUND & AIMS: Acute pancreatitis is a major adverse event of endoscopic retrograde cholangiopancreatography (ERCP). Rectal administration of nonsteroidal anti-inflammatory drugs (NSAIDs) decreases the incidence of post-ERCP pancreatitis (PEP). Little is known about the combined effects of sublingual nitrate and NSAIDs. We performed a randomized trial to assess whether the combination of NSAIDs and sublingual nitrate is more effective than NSAIDs alone in preventing PEP. METHODS: In a prospective superiority trial, eligible patients underwent ERCP at 12 endoscopic units in Japan, from March 2015 through May 2018. Patients were randomly assigned to groups given diclofenac suppositories (50 mg) within 15 minutes after the endoscopic procedure alone (diclofenac-alone group, n = 442) or in combination with sublingual isosorbide dinitrate (5 mg) 5 minutes before the endoscopic procedure (combination group, n = 444). The primary endpoint was the occurrence of PEP. RESULTS: PEP developed in 25 patients in the combination group (5.6%), and in 42 patients in the diclofenac-alone group (9.5%) (relative risk 0.59; 95% confidence interval 0.37-0.95; P = .03). Moderate to severe pancreatitis developed in 4 patients (0.9%) in the combination group, and 10 patients (2.3%) in the diclofenac-alone group (relative risk 0.12; 95% confidence interval 0.13-1.26; P = .12). There was no serious adverse event related to the additional administration of sublingual nitrate. CONCLUSIONS: In a randomized controlled trial, we found that prophylaxis with rectal diclofenac and sublingual nitrate significantly reduces the overall incidence of PEP compared with diclofenac suppository alone. ClinicalTrials.gov, no: UMIN 000016274

Efficacy and Safety of Endoscopic Ultrasound-guided Ethanol Ablation Therapy for Pancreatic Neuroendocrine Tumors

Recently, endoscopic ultrasonography (EUS)-guided ethanol ablation for small pancreatic neuroendocrine tumors (p-NETs) has been reported. However, the efficacy and safety of the technique remain unclear. We have launched a prospective pilot study of EUS-guided ethanol ablation for p-NETs. The major eligibility criteria are the presence of a pathologically diagnosed grade (G) 1 or G2 p-NET, a tumor size of 2cm, and being a poor candidate for surgery. A total of 5 patients will be treated. The primary endpoint will be the complete ablation rate at 1 month after treatment

A Multicenter, Prospective, Randomized Controlled Trial Evaluating the Efficacy of Rectal Diclofenac and Sublingual Nitroglycerin as a Combined Prophylactic Treatment for Post-ERCP Pancreatitis

Acute pancreatitis is the major complication of endoscopic retrograde cholangiopancreatography (ERCP). A preliminary research suggested that the administration of nonsteroidal anti-inflammatory drugs (NSAIDs) with nitroglycerin might reduce the incidence of post-ERCP pancreatitis (PEP) more effectively than NSAIDs alone. We conduct a two-arm, multicenter, prospective, randomized, superiority trial to evaluate the additional effect of nitroglycerin for prevention of PEP. A total of 900 patients randomly receive 50 mg diclofenac suppository either alone or with 5 mg isosorbide dinitrate sublingual tablet. The primary endpoint is the occurrence of PEP. This study will clarify whether NSAIDs plus nitroglycerin can prevent PEP

Diagnosing Pancreatic Tumors Using Contrast-enhanced Harmonic Endoscopic Ultrasonography with Sonazoid

Contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) with contrast agent enabled us to assess the hemodynamics closely, despite limited data in pancreatic tumors. We have initiated a prospective, single arm, and non-randomized study to clarify the accuracy and safety of CH-EUS with Sonazoid and time-intensity curve (TIC) analysis for diagnosing benign or malignant pancreatic tumors. A total of 200 patients will undergo CH-EUS and TIC analysis. Receiver operating characteristic (ROC) analysis will be used to determine the optimal parameter cutoff values for TIC analysis. This will clarify whether CH-EUS and TIC can further improve the diagnosis of pancreatic tumors over conventional EUS

A Prospective Randomized Controlled Study Comparing EUS Sonopsy CY(R) and 22-gauge Biopsy Needles for Endoscopic Ultrasound-guided Fine-Needle Aspiration of Solid Pancreatic Mass Lesions

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is a standard procedure for precise histological diagnosis of pancreas tumors, but it is sometimes difficult to obtain adequate specimens. EUS Sonopsy CY® is a newly designed needle with original features. This randomized study will compare the tissue collection rate of EUS Sonopsy CY® to that of a conventional needle in EUS-FNA. The major eligibility criteria are as follows: Patients with a pancreatic mass referred for EUSFNA; age ≥20 years, and performance status＜4. The primary outcome is the tissue collection rate. This study will elucidate the efficacy of EUS Sonopsy CY®

Dynamic computed tomography is useful for prediction of pathological grade in pancreatic neuroendocrine neoplasm

BACKGROUND AND AIM: Pathological grading is important in defining the therapeutic strategy in pancreatic neuroendocrine neoplasm (PNEN) but is difficult for unresectable cases. Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) is useful in the diagnosis of PNEN, but its usefulness for pathological grading is not well established. No studies have examined the diagnostic ability of dynamic computed tomography (CT) for pathological grading of PNEN. We investigated the usefulness of EUS-FNA and dynamic CT in the diagnosis and pathological grading of PNEN. METHODS: In this retrospective study, 39 PNEN patients finally diagnosed via EUS-FNA and/or surgical resection underwent dynamic CT. Pathological samples were diagnosed based on WHO2010; staging was based on the European Neuroendocrine Tumor Society classification. The proportion of the quantification value in the tumor to the pancreatic parenchyma in arterial phase was defined as the CT ratio. Immunohistochemical staining with CD31 was performed to evaluate microvessel density (MVD). We evaluated the relationship between pathological grade, CT ratio, and MVD. RESULTS: By using EUS-FNA, 35 of 39 (90%) cases were diagnosed as PNEN. As for pathological grade, 15 of 35 (43%) cases could be identified correctly. CT ratio could predict pathological Grade 3 disease. The sensitivity, specificity, and diagnostic accuracy were 100%, 94%, and 95%. MVD was significantly correlated with CT ratio (r = 0.83, P < 0.0001) and pathological grade (P = 0.0074). CONCLUSIONS: Computed tomography ratio has a relationship with pathological grade in PNEN, which would help decide therapeutic strategy in unresectable cases and cases in which pathological grading is difficult