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M Nagino

Publications and source records attributed to M Nagino.

At least 19 recordsLinked to original sources
PubMed2007

CLCP1 interacts with semaphorin 4B and regulates motility of lung cancer cells.

We previously established a highly metastatic subline, LNM35, from the NCI-H460 lung cancer cell line, and demonstrated upregulation of a novel gene, CLCP1 (CUB, LCCL-homology, coagulation factor V/VIII homology domains protein), in LNM35 and lung cancer specimens. In this study, we focused on the potential roles of that gene in cancer metastasis. First, we established stable LNM35 RNAi clones, in which CLCP1 expression was suppressed by RNAi, and found that their motility was significantly reduced, although growth rates were not changed. Next, in vitro selection of a phage display library demonstrated that a phage clone displaying a peptide similar to a sequence within the Sema domain of semaphorin 4B (SEMA4B) interacted with LNM35. Immunoprecipitation experiments confirmed interaction of CLCP1 with SEMA4B, regulation of CLCP1 protein by ubiquitination and proteasome degradation enhanced in the presence of SEMA4B. These results are the first to indicate that CLCP1 plays a role in cell motility, whereas they also showed that at least one of its ligands is SEMA4B and that their interaction mediates proteasome degradation by CLCP1. Although the physiological role of the interaction between CLCP1 and SEMA4B remains to be investigated, this novel gene may become a target of therapy to inhibit metastasis of lung cancers.

Amino Acid Sequence↗
PubMed2007

Intrahepatic cholangiojejunostomy following hepatobiliary resection.

BACKGROUND: Although intrahepatic cholangiojejunostomy is technically difficult, with recent improvements in surgery it should be possible to perform the anastomosis safely. The aim of this study was to evaluate the incidence of anastomotic leak after intrahepatic cholangiojejunostomy and to identify risk factors for such leakage. METHODS: Intrahepatic cholangiojejunostomy was performed in 423 patients undergoing hepatobiliary resection between January 1991 and December 2005. Anastomotic leak was proven radiographically by leakage from the anastomosis of contrast medium introduced via a biliary drainage tube placed during surgery. RESULTS: Anastomotic leak occurred in 27 patients (6.4 per cent), and was not related to the number of bile ducts reconstructed. The leak rate decreased significantly from 9.5 per cent (19 of 199) in the first 10 years to 3.6 per cent (eight of 224) in the last 5 years. Anastomotic leak was often followed by infections such as wound infection, intra-abdominal abscess and bacteraemia. Multivariable analysis identified age and intraoperative blood loss as independent risk factors for anastomotic leak. All leaks were treated by maintaining a prophylactically placed drain near the cholangiojejunostomy; neither repeat laparotomy nor percutaneous transhepatic biliary drainage was required. CONCLUSION: Although demanding, intrahepatic cholangiojejunostomy can be performed successfully with a relatively low failure rate. Routine use of prophylactic drains and anastomotic stenting allows safe management of anastomotic leak with conservative therapy.

Aged↗
PubMed2007

Mechanisms of hepatic regeneration following portal vein embolization and partial hepatectomy: a review.

BACKGROUND: Portal vein embolization (PVE) improves outcome following major hepatectomy, and basic studies have presented evidence related to the mechanisms responsible for hepatic regeneration. Hemodynamic changes following PVE are similar to, but slightly different from, those of partial hepatectomy (PH) because arterial flow to the embolized lobe is preserved. However, the process of hepatic regeneration is essentially the same after both PVE and PH. A number of mediators are involved in PVE or PH-induced hepatic regeneration. These include inflammatory cytokines, vasoregulators, growth factors, eicosanoids, and various hormones. These mediators activate a complex network of signal transduction that promotes hepatic regeneration. A variety of conditions have been shown to modulate the function of these mediators and inhibit regeneration. These include biliary obstruction, diabetes, chronic ethanol consumption, malnutrition, gender, aging, and infection. CONCLUSION: Optimizing these factors, where possible, before PVE or PH, is essential to maximize hypertrophy of the liver. A fuller understanding of hepatic physiology and pathophysiology following PVE or PH may lead to greater functional capacity of the remaining liver and extend the indications for hepatectomy in patients who require large liver volume resection.

Embolization, Therapeutic↗
PubMed2006

Fundamental study of small interfering RNAs for ganglioside GD3 synthase gene as a therapeutic target of lung cancers.

Gangliosides GD3 and GD2 are specifically expressed in neuro-ectoderm-derived tumors, and are considered to play roles in the malignant properties of those cells. We analysed effects of small interfering (si) RNAs against GD3 synthase gene on the expression of ganglioside GD2 and biological phenotypes of human lung cancer cells expressing GD2. An siRNA could suppress the mRNA level of GD3 synthase gene even by single transfection, whereas repeated transfection was required to suppress GD2 expression on the cell surface. Significant reduction in the cell growth and invasion activity was observed in both lung cancer cell lines examined, when repeatedly transfected with the siRNA twice a week. DNA ladder formation was observed after third transfection, indicating the potent induction of apoptosis. Stable transfection of an RNAi expression vector with H1 RNA promoter was also examined. Transfectant cells with the RNAi expression vector showed almost equivalent suppression of GD2 expression and tumor properties in vitro. Furthermore, the stable transfectant cells showed slower cell growth than the control cells in severe combined immunodeficiency mice. These results suggested that siRNAs and/or RNAi expression vectors to generate siRNAs are promising approach to overcome human lung cancers.

Apoptosis↗
PubMed2006

Hepatocyte morphology and kinetics after portal vein embolization.

BACKGROUND: Macroscopic volume changes after portal vein embolization (PVE) can be assessed accurately by computed tomography, but histological changes remain poorly understood. The aim of this study was to clarify hepatocyte morphology and kinetics after PVE. METHODS: The resected livers from 25 patients who underwent extended hepatectomy after PVE and five normal livers were examined using hepatocyte paraffin 1 staining for histomorphometric analysis of hepatocytes. Cell kinetics were determined by Ki-67 staining and terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick-end labelling assay. Kupffer cells were examined by CD68 immunostaining. RESULTS: The number of hepatocytes was similar in the embolized lobe, non-embolized lobe and normal liver, but hepatocyte volume was greater in the non-embolized lobe than in the embolized lobe (P = 0.017). The Ki-67 labelling index was higher in the non-embolized lobe (P < 0.001) whereas the apoptotic index was higher in the embolized lobe (P < 0.001). There were more Kupffer cells per unit area in the embolized lobe (P < 0.001). CONCLUSION: Hepatocyte hypertrophy and replication leads to volume enlargement of the non-embolized hepatic lobe, whereas hepatocyte atrophy and apoptosis causes a decrease in volume of the embolized lobe.

Adult↗
PubMed2003

Retrograde portography of the right caudate lobe via the middle hepatic vein.

Hepatobiliary resection with caudate lobectomy has been conducted in the surgical treatment of bile duct carcinoma of the hepatic hilus. However, insufficient attention has been paid to the anatomy of the right portion of the caudate lobe, and techniques to visualize the portal branches of the right caudate lobe (P1r) have not been reported. Contrast medium was injected into the dorso-caudal branches of the middle hepatic vein (MHV) and images were obtained by digital subtraction venography. Retrograde portography of the P1r was achieved in 64 (84%) out of 76 cases. The mean number of visualized branches was 2.1 (137 out of 64) and the P1r coursed beyond the trunk of the MHV in 36 (56%) out of the 64 cases. Contrast medium flowed into the right portal vein from 59 P1r branches in 32 cases and into the left portal vein in 20 cases. No complications were encountered. Retrograde portograms of the P1r may provide valuable information not previously available to surgeons operating on the caudate lobe.

Bile Ducts, Intrahepatic↗
PubMed2002

Extensive surgery for carcinoma of the gallbladder.

BACKGROUND: The purpose of this study was to clarify the efficacy of, and define the indications for, extensive surgery for gallbladder carcinoma. METHODS: Between 1979 and 1994, 116 patients with gallbladder carcinoma underwent operation. Radical resection was performed in 80 patients. RESULTS: In 68 patients with stage III or IV disease, extensive resection including extended right hepatectomy (n = 40), pancreaticoduodenectomy (n = 23) and/or portal vein resection (n = 23) was employed to achieve complete tumour excision. The hospital mortality rate was 18 per cent. The postoperative 3- and 5-year survival rates were 44 and 33 per cent respectively in the patients with stage III disease (n = 9), and 24 and 17 per cent respectively in patients with stage IV (M0) disease (n = 29). In contrast, the postoperative survival rate for the 30 patients with stage IV (M1) disease (7 per cent at 3 years and 3 per cent at 5 years) was worse than that for patients with stage III and stage IV (M0) disease (P = 0.009 and P = 0.062 respectively). CONCLUSION: Radical resection should be undertaken for stage III and stage IV (M0) gallbladder cancer. Although portal vein resection and/or pancreaticoduodenectomy did not contribute to long-term survival, better survival was obtained than that for the unresected patients.

Gallbladder Neoplasms↗
PubMed2002

Perineural invasion has a negative impact on survival of patients with gallbladder carcinoma.

BACKGROUND: The clinical significance of perineural invasion of gallbladder carcinoma remains unclear. The aim of this study was to elucidate the incidence and mode of perineural invasion of gallbladder carcinoma and clarify its prognostic significance. METHODS: A clinicopathological study was conducted on 68 patients who underwent attempted curative resection for gallbladder carcinoma. According to the pathological tumour node metastasis (pTNM) classification of the Union Internacional Contra la Cancrum, there were five (7 per cent), nine (13 per cent), 20 (29 per cent) and 34 (50 per cent) patients with pT1, pT2, pT3 and pT4 disease respectively. Twenty patients (29 per cent) had pM1 disease, including involved para-aortic nodes, liver metastases and localized dissemination. RESULTS: The overall incidence of perineural invasion was 71 per cent (48 of 68 patients). Forty-four (96 per cent) of 46 patients with extrahepatic bile duct invasion had perineural invasion. Although several histological factors were associated with perineural invasion, multivariate analysis demonstrated that extrahepatic bile duct invasion was the only significant factor correlated with perineural invasion (odds ratio 99.0, P < 0.001). The perineural invasion index, defined as the ratio of the number of involved nerves to the total number of nerves examined, was significantly higher at the centre than in the proximal and distal parts of the tumour in the 46 patients with extrahepatic bile duct invasion (P < 0.001). The 5-year survival rate for patients with perineural invasion was significantly lower than that for patients with no invasion (7 versus 72 per cent; P < 0.001). Cox proportional hazard analysis identified perineural invasion (relative risk (RR) 5.3, P < 0.001) and lymph node metastasis (RR 2.5, P = 0.008) as significant independent prognostic factors. CONCLUSION: Perineural invasion is common in advanced gallbladder carcinoma and has a significant negative impact on patient survival.

Adult↗
PubMed2001

Bilirubin impairs bactericidal activity of neutrophils through an antioxidant mechanism in vitro.

BACKGROUND: Liver failure accompanied by hyperbilirubinemia after major hepatic resection is profoundly associated with septic complications. Although the immune dysfunction in cholestasis has been intensively investigated, the contribution of increased serum bilirubin to the impaired resistance to bacterial infection remains to be elucidated. Because bilirubin possesses an antioxidant activity, we hypothesized that bilirubin may scavenge reactive oxygen species (ROS) produced by neutrophils and consequently impair neutrophil bacterial killing. To address this, we evaluated the effects of bilirubin on the bactericidal activity of ROS or of neutrophils in vitro. MATERIALS AND METHODS: The antioxidant activity of bilirubin was determined using an ROS-sensitive fluorophore, dichlorofluorescin diacetate (DCFH-DA). Bilirubin concentration in the buffer solution was monitored spectorophotometrically after incubation with ROS. The effect of bilirubin on killing of Escherichia coli by ROS or by isolated human neutrophils was determined by counting the viable E. coli after incubation on nutrient agar. RESULTS: The bilirubin concentration in the buffer solution was decreased by the addition of hydrogen peroxide, especially in the presence of peroxidase or ferrous iron. DCFH-DA oxidation by ROS or activated neutrophils was inhibited by bilirubin in a dose-dependent manner. The bactericidal activity of ROS or of isolated neutrophils was significantly attenuated by bilirubin. CONCLUSIONS: Bilirubin impairs bactericidal activity of neutrophils through scavenging ROS. Increased levels of serum bilirubin may well be responsible for the impaired bacterial clearance in patients with hyperbilirubinemia.

Antioxidants↗
PubMed2001

An experimental study of selective intrahepatic biliary ablation with ethanol.

BACKGROUND: Few attempts have been made to investigate the feasibility of selective intrahepatic biliary ablation with absolute ethanol. METHODS: Through a catheter cannulated into the bile duct of the left lateral and median lobes (70% of total liver weight), 0.2 mL of absolute ethanol was injected into rats. RESULTS: The weight of the infused lobes decreased to less than 50% of the entire liver weight 14 days after treatment, while the weight of the noninfused lobes increased to 1.6-fold of the original value. This increase was associated with a markedly elevated Ki-67 labeling index. Both bile flow and bile acid excretion in the noninfused lobes significantly increased to more than twice the original values on Day 14. Histologically, the interlobular bile ducts of the infused lobes were destroyed. Ethanol also soaked through Glisson's capsule and destroyed hepatocytes, which were replaced by fibrous tissue and proliferating bile ductules without necrosis by Day 14. The portal veins and hepatic arteries supplying the infused lobes were structurally well preserved throughout the study period. CONCLUSION: Selective biliary infusion of ethanol can be performed safely without serious complications, achieving lobar ablation with contralateral hypertrophy of the liver.

Animals↗
PubMed2001

Complications of hepatectomy for hilar cholangiocarcinoma.

We retrospectively reviewed postoperative complications in 105 patients with hilar cholangiocarcinoma who underwent hepatectomy at Nagoya University Hospital from January 1990 through March 1999. Of the 105 subjects, 97 (92.4%) underwent resection of two or more Healey's segments of the liver. Combined portal vein resection was performed in 33 (31.4%) patients and pancreatoduodenectomy in 10 (9.5%). Twenty (19.0%) patients had no postoperative complications, another 39 (37.1%) patients had minor complication(s) only, and the remaining 46 (43.8%) developed major complication(s). The morbidity rate reached as high as 81.0%. Major complications required relaparotomy in 11 (10.5%) patients. Of the 46 patients with major complication(s) 36 recovered; the remaining 10 patients died of liver failure with other organ failure(s) or of intraabdominal bleeding 12, 14, 18, 21, 57, 75, 75, 87, 93, or 134 days after surgery. Thus the 30-day mortality was 3.8% and the overall mortality 9.5%. Pleural effusion was the most frequent complication found in 66 (62.9%) patients, followed by wound sepsis in 39 (37.1%), and then liver failure in 29 (27.6%). Liver failure developed in 16.7% of 48 patients with less than 50% liver resection and in 36.8% of 57 patients with 50% or more resection (P < 0.05). Other organ failures, including renal, respiratory, gastrointestinal, and hematologic failures, developed as a sign of multiple organ failure following liver failure in most patients or preceding liver failure in a few patients. None of the six patients with four or more organ failures survived. Hepatectomy for hilar cholangiocarcinoma is risky owing to impaired hepatic functional reserve in jaundiced patients and the technical difficulty associated with hepatobiliary resection. Our goal is to reduce mortality to less than 5% while keeping a high resectability rate (above 80%).

Adult↗
PubMed2001

Five-year survivors after aggressive surgery for stage IV gallbladder cancer.

PURPOSE: To describe 5-year survivors after radical surgery for stage IV gallbladder cancer and to determine the characteristics leading to potential long-term survival. METHODS: Of 59 patients undergoing radical resection for stage IV disease between 1979 and 1994, 6 patients who have survived for more than 5 years were followed up. RESULTS: Three patients had developed obstructive jaundice due to involvement of the hepatic hilum, but the other three had not. The jaundiced patients had remarkable tumor spread over the bile duct and right hepatic artery within the hepatoduodenal ligament. However, the proper and left hepatic arteries and the portal trunk and its left branch were free from tumor involvement. The nonjaundiced patients had N1 or N2 lymph node metastasis. However, none underwent bile duct resection or pancreatoduodenectomy to establish radical lymphadenectomy. CONCLUSIONS: Selected patients with stage IV gallbladder cancer may be candidates for 5-year survival when the primary tumor is fairly localized even if it forms a large mass and involves neighboring organs including the hepatic duct, lymph node metastasis is limited to N1 and N2 except for the celiac and superior mesenteric nodes and is less infiltrative, and distant metastasis including that in the paraaortic area is absent.

Adult↗
PubMed2001

Advanced gallbladder carcinoma with biliobiliary fistula, resected by hepatopancreatoduodenectomy, in an aged patient.

We report a 78-year-old man with a gallbladder carcinoma and biliobiliary fistula, diagnosed by percutaneous transhepatic cholangioscopic biopsy through the fistula. The impacted stones in the common hepatic duct were crushed, and then selective cholangiography under percutaneous transhepatic cholangioscopy (PTCS) revealed a biliobiliary fistula. Cholangioscopic biopsy tissues taken from the gallbladder revealed adenocarcinoma, but biopsies taken from the fistula revealed no evidence of malignancy. Further investigations indicated that the gallbladder carcinoma involved the duodenum and the distal common bile duct. A hepatopancreatoduodenectomy, including both an extended right hepatic lobectomy with resection of the caudate lobe and a pancreatoduodenectomy, was performed. Despite the patient's advanced age, he made an unremarkable postoperative recovery and was able to enjoy an active social life for 8 months after the surgery. We discuss biliobiliary fistula associated with gallbladder carcinomas and the use of hepatopancreatoduodenectomy for advanced biliary cancer in aged patients.

Aged↗
PubMed2001

Liver regeneration after major hepatectomy for biliary cancer.

BACKGROUND: The aim of this study was to evaluate serial changes in liver volume after major hepatectomy for biliary cancer and to elucidate clinical factors influencing liver regeneration. METHODS: Serial changes in liver volume were determined, using computed tomography, in 81 patients with biliary cancer who underwent right hepatic lobectomy or more extensive liver resection with or without portal vein resection and/or pancreatoduodenectomy. Possible factors influencing liver regeneration were evaluated by univariate and multivariate analyses. RESULTS: The remnant mean(s.d.) liver volume was 41(8) per cent straight after hepatectomy. This increased rapidly to 59(9) per cent within 2 weeks, then increased more slowly, finally reaching a plateau at 74(12) per cent about 1 year after hepatectomy. The regeneration rate within the first 2 weeks was 16(8) cm3/day and was not related to the extent of posthepatectomy liver dysfunction. On multivariate analysis, the extent of liver resection (P < 0.001), body surface area (P = 0.02), combined portal vein resection (P = 0.024) and preoperative portal vein embolization (P = 0.047) were significantly associated with the liver regeneration rate within the first 2 weeks. In addition, body surface area (P < 0.001) and liver function expressed as plasma clearance rate of indocyanine green (P = 0.01) were significant determinants of final liver volume 1 year after hepatectomy. CONCLUSION: The liver regenerates rapidly in the first 2 weeks after major hepatectomy for biliary cancer. This early regeneration is influenced by four clinical factors. Thereafter, liver regeneration progresses slowly and stops when the liver is three-quarters of its original volume, approximately 6 months to 1 year after hepatectomy.

Adult↗
PubMed2001

Percutaneous cholangioscopic bilioenterostomy for unreconstructed segmental bile duct after hepatobiliary resection for hilar cholangiocarcinoma.

During a major hepatectomy, inadvertent ligation of the major segmental bile-duct branch of the liver remnant is a serious complication. We experienced this serious complication of inadvertent ligation of the bile-duct branch, which should be anastomosed to the jejunal loop, during a left hepatic trisegmentectomy with total caudate lobectomy for a hilar cholangiocarcinoma. A percutaneous transhepatic bilioenteric connection was then created, modifying an endoscopic ureteroneocystostomy technique, between the ligated segmental bile duct and the jejunal loop. In this procedure, we used two cholangioscopes; one was introduced through the percutaneous transhepatic drainage route, the other was introduced through an enterostomy which was made during the surgery for postoperative enteral feeding; we also used a transjugular intrahepatic portosystemic shunt (TIPS) kit under fluoroscopic guidance. We present here our technique of percutaneous transhepatic bilioenterostomy.

Bile Duct Neoplasms↗
PubMed2001

Aggressive preoperative management and extended surgery for inflammatory pseudotumor involving the hepatic hilum in a child.

Inflammatory pseudotumors involving the hepatic hilum are rare. Only 14 cases have been reported (Table). Liver transplantation has been required when the pseudotumor has invaded extensively into the right and left lobes. (1,2) However, transplantation is associated with the lifelong use of immunosuppressants. This is particularly problematic in children. we report a case of a 6-year-old boy with an inflammatory pseudotumor extensively invading the hepatic hilum who was treated with aggressive surgical excision using the techniques devised for the treatment of hilar cholangiocarcinoma. (3)

Child↗