Oxytocin (OT) is a 9-amine neuropeptide that plays an essential role in mammalian labor, lactation, maternal bonding, and social affiliation. OT has been reported to exert an analgesic effect in both humans and animals, and the results of certain animal experiments have shown that the analgesic effect of OT is partially blocked by opioid receptor antagonists. To investigate the relationship between OT and μ opioid receptor (MOR), we evaluated how OT affects MOR in vitro by performing an electrical impedance-based receptor biosensor assay (CellKey™ assay), an intracellular cAMP assay, and a competitive receptor-binding analysis by using cells stably expressing human MOR and OT receptor. In both the CellKey™ assay and the intracellular cAMP assay, OT alone exerted no direct agonistic effect on human MOR, but treatment with 10 M OT markedly enhanced the MOR signaling induced by 10 M endomorphin-1, β-endorphin, morphine, fentanyl, and DAMGO. Moreover, in the competitive receptor-binding assay, 10 M OT did not alter the affinity of endomorphin-1 or morphine for MOR. These results suggest that OT could function as a positive allosteric modulator that regulates the efficacy of MOR signaling, and thus OT might represent a previously unrecognized candidate analgesic agent.

A 54-year-old Japanese woman was referred with a gallbladder tumor. Based on the results of the computed tomography scan, endoscopic retrograde cholangiopancreatography, and magnetic resonance cholangiopancreatography, a mucin-producing neoplasm of the gallbladder associated with pancreaticobiliary maljunction was diagnosed. Extended cholecystectomy, extrahepatic bile duct resection, and choledochojejunostomy were performed, and she remains free of recurrence 24 months after resection. Histopathological examination revealed that the papillary component of the lesion was an intracystic papillary neoplasm with diverse characteristics of pancreaticobiliary epithelium and intestinal epithelium including mucin. In this component, most of the papillary lesion was a high-grade intraepithelial neoplasm, but also showed slight invasion into the muscular layer. The nodular component consisted of both poorly differentiated biliary type adenocarcinoma and large cell neuroendocrine carcinoma. We report a rare case of a mixed adenoneuroendocrine carcinoma arising from an intracystic papillary neoplasm associated with pancreaticobiliary maljunction. As for the histogenesis of this tumor, based on the histopathologic appearance, transdifferentiation from poorly differentiated biliary type adenocarcinoma to large cell neuroendocrine carcinoma is considered the most possible histogenesis of this tumor.

SCC components are derived from squamous metaplasia in a pre-existing adenocarcinoma. A gastric adenocarcinoma with SCC components is associated with various patterns of metastasis and both SCC and adenocarcinoma components have the potential for metastasis. Gastric cancer with SCC components is a clinically aggressive tumor.

We report a case of hepatic choriocarcinoma in a man diagnosed at autopsy after a rapid downhill clinical course. The patient was a 49-year-old man who presented with acute right-sided abdominal pain. There were no masses palpable on physical examination. Radiographic findings showed large multi-nodular tumors mainly in the right lobe of the liver. Fludeoxyglucose-positron emission tomography scan showed uptake only in the liver, and no uptake in the testes. We initially planned to perform a liver resection for the presumed diagnosis of intra-hepatic cholangiocarcinoma. However, the tumors grew rapidly and ruptured. Multiple lung metastases rapidly developed resulting in respiratory failure, preventing liver resection or even biopsy. He died 60 d after initial presentation with no pathological diagnosis. Postmortem studies included histopathological and immunohistological examinations which diagnosed a primary choriocarcinoma of the liver. Primary hepatic choriocarcinoma is very rare but should be considered in the differential diagnosis of a liver tumor in a middle aged man. Establishing this diagnosis may enable treatment of the choriocarcinoma. Liver biopsy and evaluation of serum human chorionic gonadotropin are recommended in these patients.

Oxytocin (OT) influences various physiological functions such as uterine contractions, maternal/social behavior, and analgesia. Opioid signaling pathways are involved in one of the analgesic mechanisms of OT. We previously showed that OT acts as a positive allosteric modulator (PAM) and enhances μ-opioid receptor (MOR) activity. In this study, which focused on other opioid receptor (OR) subtypes, we investigated whether OT influences opioid signaling pathways as a PAM for δ-OR (DOR) or κ-OR (KOR) using human embryonic kidney-293 cells expressing human DOR or KOR, respectively. The CellKeyTM results showed that OT enhanced impedance induced by endogenous/exogenous KOR agonists on KOR-expressing cells. OT did not affect DOR activity induced by endogenous/exogenous DOR agonists. OT potentiated the KOR agonist-induced Gi/o protein-mediated decrease in intracellular cAMP, but did not affect the increase in KOR internalization caused by the KOR agonists dynorphin A and (-)-U-50488 hydrochloride (U50488). OT did not bind to KOR orthosteric binding sites and did not affect the binding affinities of dynorphin A and U50488 for KOR. These results suggest that OT is a PAM of KOR and MOR and enhances G protein signaling without affecting β-arrestin signaling. Thus, OT has potential as a specific signaling-biased PAM of KOR.

A 41-year-old woman was admitted with upper abdominal pain, vomiting and fever. Abdominal CT scan showed a colo-duodenal fistula with inflammatory thickening of the transverse colon. The patient's general health was poor because of hypoalbuminemia and coagulopathy. Endoscopy showed a fistula at the lower duodenal angle and the stomach was filled with refluxed stool. Ileostomy and percutaneous endoscopic gastrostomy were performed at that time and a double lumen gastro-jejunostomy inserted through the gastrostomy to allow both gastric drainage and distal enteral feeding. Nutrition support was gradually converted from parenteral to enteral feeding. Colonoscopy showed stenosis of the transverse colon with a colo-colonic fistula near the stenosis. Two months later, right hemi-colectomy and closure of the colo-duodenal fistula were performed. The resected specimen showed stenosis and a fistula in the transverse colon due to Crohn's disease. The colo-colonic fistula was present and the colo-duodenal fistula had almost closed due to fibrosis. The postoperative course was uneventful and the patient was discharged after administration of infliximab. Use of a double lumen gastro-jejunostomy tube was effective in improving the patient's general condition. This therapeutic strategy allowed the safe conduct of major resection in a high-risk patient.

BACKGROUND Estimation of the functional reserve of the remnant liver is important to reduce morbidity and mortality. AIM To estimate the functional reserve of the remnant liver in patients with hepatocellular carcinoma (HCC). METHODS We reviewed the medical records of 199 patients who underwent resection of HCC. Hepatic clearance of the remnant liver was calculated using fusion images of 99m Tc-labelled galactosyl-human serum albumin liver scintigraphy and computed tomography. Posthepatectomy liver failure (PHLF) was classified according to the International Study Group of Liver Surgery. Complications was classified according to Clavien–Dindo classification. We analyzed by the risk factors for PHLF, morbidity and mortality with multivariate analysis. RESULTS Twenty-seven (30%) patients had major complications and 23 (12%) developed PHLF. The incidence of major complications increased with increasing albumin–bilirubin (ALBI) grade. The area under the curve values for hepatic clearance of the remnant liver, liver to heart-plus-liver radioactivity at 15 min (LHL15), and ALBI score predicting PHLF were 0.868, 0.629, and 0.655, respectively. The area under the curve for hepatic clearance of the remnant liver, LHL15, and ALBI score predicting major complications were 0.758, 0.594, and 0.647, respectively. The risk factors for PHLF and major complications were hepatic clearance of the remnant liver and intraoperative bleeding. CONCLUSION The measurement of hepatic clearance may predict PHLF and major complications for patients undergoing resection of HCC.

Background: Osteopenia is defined as low bone mineral density (BMD) and has been shown to be associated with outcomes of patients with various cancers. The association between osteopenia and perihilar cholangiocarcinoma is unknown. The aim of this study was to evaluate osteopenia as a prognostic factor in patients with perihilar cholangiocarcinoma. Methods: A total of 58 patients who underwent surgery for perihilar cholangiocarcinoma were retrospectively analyzed. The BMD at the 11th thoracic vertebra was measured using computed tomography scan within one month of surgery. Patients with a BMD < 160 HU were considered to have osteopenia and b BMD ≥ 160 did not have osteopenia. The log-rank test was performed for survival using the Kaplan–Meier method. After adjusting for confounding factors, overall survival was assessed by Cox′s proportional-hazards model. Results: The osteopenia group had 27 (47%) more females than the non-osteopenia group (p = 0.036). Median survival in the osteopenia group was 37 months and in the non-osteopenia group was 61 months (p = 0.034). In multivariable analysis, osteopenia was a significant independent risk factor associated with overall survival in patients with perihilar cholangiocarcinoma (hazard ratio 3.54, 95% confidence interval 1.09–11.54, p = 0.036), along with primary tumor stage. Conclusions: Osteopenia is associated with significantly shorter survival in patients with perihilar cholangiocarcinoma.