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

Impact of Surgical Resection and Reasons for Poor Prognosis of Pelvic Osteosarcoma Based on the Bone Tumor Registry in Japan

Pelvic osteosarcoma has a poor prognosis compared to osteosarcomas in other locations, and the reasons for this remain unknown. Surgical resection of pelvic osteosarcoma is technically demanding and often results in dysfunction and complications. In this study, we investigated the reasons underlying the poor prognosis of pelvic osteosarcoma by comparing it to femoral osteosarcoma using data from the Bone Tumor Registry in Japan. We used propensity score analysis to determine whether surgical resection of pelvic osteosarcoma improved its prognosis. We demonstrated that pelvic osteosarcoma had a poor prognosis because it occurred more often in the elderly, often had larger tumor size, and had metastasis at presentation more often in comparison to femoral osteosarcoma. These three factors were also associated with the non-surgical treatment of pelvic osteosarcoma, which also led to a poor outcome. The overall survival rate was only comparable in pelvic osteosarcoma and femoral osteosarcoma in cases treated with surgical resection. Propensity score analysis revealed that surgical treatment improved the prognosis of pelvic osteosarcoma. As such, we propose that surgical resection should be considered based on tumor stage and patient age in order to improve the prognosis of pelvic osteosarcoma

Phenotypic Characterization by Single-Cell Mass Cytometry of Human Intrahepatic and Peripheral NK Cells in Patients with Hepatocellular Carcinoma

Overall response rates of systemic therapies against advanced hepatocellular carcinoma (HCC) remain unsatisfactory. Thus, searching for new immunotherapy targets is indispensable. NK cells are crucial effectors and regulators in the tumor microenvironment and a determinant of responsiveness to checkpoint inhibitors. We revealed the landscape of NK cell phenotypes in HCC patients to find potential immunotherapy targets. Using single cell mass cytometry, we analyzed 32 surface markers on CD56dim and CD56bright NK cells, which included Sialic acid-binding immunoglobulin-type lectins (Siglecs). We compared peripheral NK cells between HCC patients and healthy volunteers. We also compared NK cells, in terms of their localizations, on an individual patient bases between peripheral and intrahepatic NK cells from cancerous and noncancerous liver tissues. In the HCC patient periphery, CD160+CD56dim NK cells that expressed Siglec-7, NKp46, and NKp30 were reduced, while CD49a+CD56dim NK cells that expressed Siglec-10 were increased. CD160 and CD49a on CD56dim NK cells were significantly correlated to other NK-related markers in HCC patients, which suggested that CD160 and CD49a were signature molecules. CD49a+ CX3CR1+ Siglec-10+ NK cells had accumulated in HCC tissues. Considering further functional analyses, CD160, CD49a, CX3CR1, and Siglec-10 on CD56dim NK cells may be targets for immunotherapies of HCC patients