Takayuki Shiraki

Renoprotective effect of erythropoietin against ischaemia–reperfusion injury in a non-human primate model

BACKGROUND The renoprotective effect of erythropoietin (Epo) against ischaemia-reperfusion injury (IR/I) was evaluated in a non-human primate model. METHODS Crab-eating macaques were divided into two groups: Control (n = 10), treated with saline, and EPO (n = 10), treated with Epo. Epo was injected intravenously at a dose of 12,000 units, 5 min before clamping the renal pedicle and 5 min before declamping. Renal IR/I was created by clamping the left renal artery for 90 min following right nephrectomy. Haemoglobin (Hb), haematocrit (Ht), creatinine (Cr), blood urea nitrogen (BUN), cystatin C and interleukin-6 (IL-6) were measured before (Pre) and after (Day 0) the operation, and on post-operative days: Day 1, Day 3, Day 5 and Day 7. Apoptotic cells were counted on Day 1. RESULTS There were no differences in Hb and Ht between the two groups. Cr, BUN, cystatin C and IL-6 levels in the EPO group were lower than those in the Control group at most of the observation points. The number of apoptotic cells in the Control was significantly higher than that of and EPO group. CONCLUSIONS Epo significantly ameliorates renal IR/I in this non-human primate model. Our findings justify the clinical application of Epo, not only for acute renal failure, but also in transplantation.

Analysis of hepcidin expression: In situ hybridization and quantitative polymerase chain reaction from paraffin sections

AIM To establish methods for quantitative polymerase chain reaction (PCR) for hepcidin using RNAs isolated from paraffin-embedded sections and in situ hybridization of hepatocellular carcinoma (HCC). METHODS Total RNA from paraffin-embedded sections was isolated from 68 paraffin-embedded samples of HCC. Samples came from 54 male and 14 female patients with a mean age of 66.8 ± 7.8 years. Quantitative PCR was performed. Immunohistochemistry and in situ hybridization for hepcidin were also performed. RESULTS Quantitative PCR for hepcidin using RNAs isolated from paraffin-embedded sections of HCC was performed successfully. The expression level of hepcidin mRNA in cancer tissues was significantly higher than that in non-cancer tissues. A method of in situ hybridization for hepcidin was established successfully, and this demonstrated that hepcidin mRNA was expressed in non-cancerous tissue but absent in cancerous tissue. CONCLUSION We have established novel methods for quantitative PCR for hepcidin using RNAs isolated from paraffin-embedded sections and in situ hybridization of HCC.

Glycated albumin suppresses glucose-induced insulin secretion by impairing glucose metabolism in rat pancreatic β-cells

BackgroundGlycated albumin (GA) is an Amadori product used as a marker of hyperglycemia. In this study, we investigated the effect of GA on insulin secretion from pancreatic β cells.MethodsIslets were collected from male Wistar rats by collagenase digestion. Insulin secretion in the presence of non-glycated human albumin (HA) and GA was measured under three different glucose concentrations, 3 mM (G3), 7 mM (G7), and 15 mM (G15), with various stimulators. Insulin secretion was measured with antagonists of inducible nitric oxide synthetase (iNOS), and the expression of iNOS-mRNA was investigated by real-time PCR.ResultsInsulin secretion in the presence of HA and GA was 20.9 ± 3.9 and 21.6 ± 5.5 μU/3 islets/h for G3 (P = 0.920), and 154 ± 9.3 and 126.1 ± 7.3 μU/3 islets/h (P = 0.046), for G15, respectively. High extracellular potassium and 10 mM tolbutamide abrogated the inhibition of insulin secretion by GA. Glyceraldehyde, dihydroxyacetone, methylpyruvate, GLP-1, and forskolin, an activator of adenylate cyclase, did not abrogate the inhibition. Real-time PCR showed that GA did not induce iNOS-mRNA expression. Furthermore, an inhibitor of nitric oxide synthetase, aminoguanidine, and NG-nitro-L-arginine methyl ester did not abrogate the inhibition of insulin secretion.ConclusionGA suppresses glucose-induced insulin secretion from rat pancreatic β-cells through impairment of intracellular glucose metabolism.

Intraductal papillary neoplasm of the bile duct developing in a patient with primary sclerosing cholangitis: a case report.

We report a case of intraductal papillary neoplasm of the bile duct (IPNB) that developed in a patient with primary sclerosing cholangitis. A 46-year-old woman was admitted to our hospital with obstructive jaundice. The liver function tests demonstrated increased serum liver enzyme levels. Computed tomography showed dilatation of the intrahepatic bile ducts. Abdominal ultrasonography revealed a highly echoic protruding lesion in the posterior bile duct near the right lobe of the liver. The lesion was suspected to be IPNB, but we were unable to confirm whether it was a carcinoma. A right hepatectomy was performed, and this showed that the dilated bile duct was filled with mucin and contained several yellowish papillary tumors. Histologically, the neoplastic biliary epithelium showed papillary growth in the dilated lumen. The tumor was diagnosed as IPNB, high-grade intraepithelial neoplasia secreting abundant mucin. No recurrence has been detected 3 years after surgery.

The preoperative globulin-to-albumin ratio, a novel inflammation-based prognostic system, predicts survival after potentially curative liver resection for patients with hepatocellular carcinoma

Although the globulin‐to‐albumin ratio (GAR) is useful for prognostication of patients with various cancers, its relationship with hepatocellular carcinoma (HCC) remains unclear. The study aims to investigate the relationship between GAR and postoperative survival among patients with HCC undergoing potentially curative liver resection (LR).

Intraoperative frozen section diagnosis of bile duct margin for extrahepatic cholangiocarcinoma

AIM To evaluate the usefulness of frozen section diagnosis (FSD) of bile duct margins during surgery for extrahepatic cholangiocarcinoma (CCA). METHODS We retrospectively analyzed 74 consecutive patients who underwent surgery for extrahepatic CCA from 2012 to 2017, during which FSD of bile duct margins was performed. They consisted of 40 distant and 34 perihilar CCAs (45 and 55 bile duct margins, respectively). The diagnosis was classified into three categories: negative, borderline (biliary intraepithelial neoplasia-1 and 2, and indefinite for neoplasia), or positive. FSD in the epithelial layer, subepithelial layer, and total layer was compared with corresponding permanent section diagnosis (PSD) postoperatively. Then, association between FSD and local recurrence was analyzed with special reference to borderline. RESULTS Analysis of 100 duct margins revealed that concordance rate between FSD and PSD was 68.0% in the total layer, 69.0% in the epithelial layer, and 98.0% in the subepithelial layer. The extent of remaining biliary epithelium was comparable between FSD and PSD, and more than half of the margins lost > 50% of the entire epithelium, suggesting low quality of the samples. In FSD, the rate of negative margins decreased and that of borderline and positive margins increased according to the extent of the remaining epithelium. Diagnostic discordance between FSD and PSD was observed in 31 epithelial layers and two subepithelial layers. Alteration from borderline to negative was the most frequent (20 of the 31 epithelial layers). Patients with positive margin in the total and epithelial layers by FSD demonstrated a significantly worse local recurrence-free survival (RFS) compared with patients with borderline and negative margins, which revealed comparable local RFS. Patients with borderline and negative margins in the epithelial layer by PSD also revealed comparable local RFS. These results suggested that epithelial borderline might be regarded substantially as negative. When classifying the status of the epithelial layer either as negative or positive, concordance rates between FSD and PSD in the total, epithelial, and subepithelial layers were 95.0%, 93.0%, and 98.0%, respectively. CONCLUSION During intraoperative assessment of bile duct margin, borderline in the epithelial layer can be substantially regarded as negative, under which condition FSD is comparable to PSD.

A case of obstructive jaundice due to early carcinoma of the cystic duct protruding into the common bile duct

Highlights • An extremely rare early cystic duct carcinoma.• The protruding part was the cause of jaundice.• There is a significant interesting macro findings in the removed sample.• The only small part of the invasive part which reach fibro-muscular layer is revealed by the pathological findings.

Hepatic myomatous angiomyolipoma diagnosedpreoperatively from specific imaging features: A case report

Highlights • An extremely rare case report of hepatic myomatous angiomyolipoma.• Including specific imaging features to diagnose with hepatic angiomyolipoma.• There is a significant interesting imaging findings of hepatic myomatous angiomyolipoma.• Previous reports only revealed the pathological findings and a few imaging findings, however we show two specific features of imaging with rare pathological findings.

A Case of Intracystic Papillary Neoplasm With an Associated Invasive Adenocarcinoma

Intracystic papillary neoplasm (ICPN) is a preinvasive neoplasm of the gallbladder. Preoperative discrimination between ICPN and gallbladder cancer (GC) is difficult. The standard surgical strategy for ICPN has not yet been established. Herein, we report a case of ICPN with an associated invasive adenocarcinoma. A gallbladder tumor was detected by abdominal ultrasonography in an asymptomatic 69-year-old man, and he was referred to our hospital. Although computed tomography (CT), endoscopic ultrasonography, and magnetic resonance imaging findings in the present case were similar to those for GC, positron emission tomography-CT revealed that fluorodeoxyglucose (FDG) did not accumulate within the tumor. These imaging features suggested that patient was suspected to have GC with serosal invasion, and he underwent extended cholecystectomy and D2 lymph node dissection. He did not develop any postoperative complications, and he was discharged on postoperative day 7. There was no evidence of recurrence for 20 mon...

Preoperative neutrophil-to-lymphocyte ratio for prognostication of patients with distal bile duct carcinomas undergoing surgery.

BACKGROUND Surgical resection continues to be the current standard treatment for distal bile duct carcinoma (DBC), as no effective alternative treatment exists. However, even after resection, the long-term prognosis is poor. Simple biomarkers that can predict response or toxicity, and which are applicable to all community oncology settings worldwide, have not been identified. Differential white-cell counts, such as the neutrophil-to-lymphocyte ratio (NLR), as markers of inflammation, may be simple and readily available biomarkers. This study aimed to determine whether the NLR can be used as a predictor of surgical outcome in patients with DBC. MATERIALS AND METHODS We enrolled 91 DBC patients who had undergone pancreatoduodenectomy (PD) at a single institution between April 2000 and December 2013. Blood was sampled on admission for determination of NLR. An NLR of ≥5 was selected as the cut-off value for validation. RESULTS Seventeen patients had an NLR of ≥5 (Group 1; 18.7%), while 74 had an NLR of <5 (Group 2; 81.3%). The 1-, 3- and 5-year survival rates for Group 1 patients were 75.9, 34.5 and 34.5%, respectively, while those for Group 2 patients were 94.8, 55.2 and 46.6%, respectively (p = 0.02). There were no significant inter-group differences in clinicolaboratory background factors such as the mean operation time, bleeding volume, tumor size, CRP, neutrophil count and lactate dehydrogenase (LDH) level. On the other hand, there were significant inter-group differences for albumin level (p = 0.011), lymphocyte count (p = 0.001) and NLR (p < 0.001). Multivariate analyses were performed for factors such as gender, age, maximum tumor diameter, drainage method, operation time, bleeding volume, pathology, albumin, CRP, neutrophil count, lymphocyte count, LDH and NLR. The results revealed that NLR (odds ratio, 2.032; 95% CI, 0.999-4.134; p = 0.040) was associated with postoperative overall survival. CONCLUSIONS An NLR of ≥5 predicts a poor outcome in patients undergoing PD for DBC. NLR is an independent indicator of overall survival for such patients.