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Masayuki Imamura

Publications and source records attributed to Masayuki Imamura.

125 records · Page 7Linked to original sources

Duct-to-mucosa pancreaticojejunostomy reduces the risk of pancreatic leakage after pancreatoduodenectomy.

The aim of this retrospective study was to analyze the risk factors for pancreatic anastomotic leakage after pancreatoduodenectomy (PD) and to determine whether duct-to-mucosa pancreaticojejunostomy is superior to the total external tube drainage technique. Between 1990 and 1999, 161 patients underwent PD with end-to-side pancreaticojejunostomy at our institution. Fourteen preoperative and ten intraoperative risk factors for pancreaticojejunal anastomotic leakage were analyzed. Pancreaticojejunal anastomotic leakage was identified in 11% (17/161) of the patients. No preoperative parameters were found to have a significant association with the risk of pancreatic leakage. Three intraoperative parameters were identified as significant by means of univariate analysis: anastomotic technique, pancreatic duct size and texture of the remnant pancreas. A duct-to-mucosa pancreaticojejunostomy with total external tube drainage (3% vs. 15%, p = 0.018). A pancreas without duct dilatation of soft pancreas was more likely to develop pancreatic leakage than one with duct dilatation or atrophy. A multivariate analysis revealed that only anastomotic technique turned out to be an independent risk factor (Odds ratio: 4.15, CI: 1.1-27.4). Sub-analysis of patients with soft pancreas and non-dilated pancreatic duct further supported the finding that the duct-to-mucosa pancreaticojejunostomy technique is safer for patients at high risk. Results indicate that the status of the remnant pancreas and the pancreaticojejunostomy technique are the substantial risk factors for pancreatic leakage after pancreatoduodenecomy. Duct-to-mucosa pancreaticojejunostomy might well be the procedure of choice.

Anastomosis, Surgical↗

Effects of preceding gastrectomy on the outcome of pancreatoduodenectomy.

It is a complicated task to perform pancreatoduodenectomy for patients who previously had undergone gastrectomy. This paper reviewed our experience of eight pancreatoduodenectomies in gastrectomized patients. The indications for gastrectomy included gastric cancer in 3 patients, duodenal ulcer in 1 patient, and gastric ulcer in 4 patients. The interval between the two operations ranged from 15-254 months (average: 103 months). All patients underwent pancreatoduodenectomy, and the reconstruction after pancreatoduodenectomy was performed by the Whipple method, the Child method, or other complex Roux-en-Y type methods. All the patients recovered and were discharged without gastrointestinal disorder. The results suggest that the secondary pancreatoduodenectomy does not increase the mortality rate, although we should use the jejunal limb with less tissue damage at the anastomotic site of which circulation is well maintained for choledochojejunostomy and pancreaticojejunostomy. Furthermore, the jejunal limb should be lined carefully to avoid intestinal kinking and excess tension to the anastomosis.

Adult↗

How to control blood glucose under continuous glucose challenge.

A newly improved method for controlling blood glucose was compared with the standard model predictive controller under continuous glucose infusion. Continuous intravenous glucose infusion at rates of 50 or 100 mg/kg/hour was conducted on pancreatectomized dogs. An improved blood glucose control method using a combination of the proportional controller in the initial stage and the model predictive controller in the later stage was compared with the simple model predictive controller. The parameters of the controller were determined by identifying individual responses to the infused insulin during the first 60 minutes. The parameters of the proportional controller were changed at 60, 90, and 120 minutes to reflect the response to the infused insulin. The simple model predictive controller was able to reach the target level in the usual manner under the low infusion rate of glucose. However, under glucose infusion rates of 100 mg/kg/hour and more, it was difficult to reach the target level within 8 hours. In contrast, the improved system could reach the target level within 5 to 8 hours even under continuous glucose challenge. Addition of the modified proportional controller to the model predictive controller can stabilize the blood glucose control even under continuous glucose infusion.

Animals↗

Paratracheal lymph node metastasis is associated with cervical lymph node metastasis in patients with thoracic esophageal squamous cell carcinoma.

BACKGROUND: We determined which lymph node metastases were associated with cervical lymph node metastases of thoracic esophageal squamous cell carcinoma. METHODS: A total of 6464 lymph nodes derived from 155 consecutive patients with thoracic esophageal squamous cell carcinoma were stained by immunohistochemistry (antibody: AE1/AE3). Lymph node metastases were mapped according to the mapping scheme of the American Thoracic Society, as modified by Casson et al. (Ann Thorac Surg 1994;58:1569-70). Patients were divided into two groups: those with and without cervical lymph node metastasis (CLNM). Mapping data were examined by uni- and multivariate analysis. RESULTS: Hematoxylin and eosin-positive and AE1/AE3-positive lymph node metastases were found in 59% and 77% of patients, respectively. Twenty-one (55%) of 38 patients in the CLNM(+) group and 30 (26%) of 117 patients in the CLNM(-) group had AE1/AE3-positive lymph node metastasis in the thoracic paratracheal lymph node. Paratracheal lymph node metastasis is only one independent factor for (CLNM), whereas upper thoracic paraesophageal lymph node and pulmonal hilar lymph node status were also significant in univariate analysis. Three (43%) of seven patients with cervical jumping metastasis from the thoracic esophagus had micrometastasis in the paratracheal lymph node. CONCLUSIONS: The paratracheal lymph node is most associated with (CLNM) of thoracic esophageal squamous cell carcinoma.

Aged↗

Successive cultures of mature hepatocytes for hepatocyte autotransplantation to assist liver function after liver resection for cancer.

We developed a method for the rapid successive cultures of adult rat mature hepatocytes on plastic dishes while avoiding viral transformation or co-culture with other cell lines. This method also allows for culturing adult human mature hepatocytes up to the secondary culture. These can be expected to provide a good source for hepatocyte autotransplantation, and, combined with the previously reported methods for the transplantation of hepatocytes into the spleen, a promising option for the support of liver function after liver resection for cancer without the need for immunosuppressive agents.

Adult↗

Altered expression of the receptor and ligand in the TGF beta signaling pathway in diffusely infiltrating colon carcinoma.

A diffusely infiltrating colorectal carcinoma (DICC) is a distinct clinicopathological entity demonstrating invasive growth with extensive matrix production and associated with an extremely poor prognosis. The factors producing these peculiar features, however, remain to be determined. Here we investigated the receptor and ligand of the transforming growth factor (TGF) beta signaling pathway in 32 DICCs and 60 common type colorectal carcinomas (CCCs). Immunohistochemical analysis revealed that the expression of TGF beta 1 was markedly increased in DICC, especially of the schirrous type, compared to CCC, whereas the expression of the TGF beta type II receptor (RII) was significantly decreased in DICC compared to CCC. The molecular basis for the reduced expression of RII was further investigated in 15 cases of DICC with a diminished RII expression. Two somatic mutations were found: one was a missense mutation in the kinase domain (Cys533Tyr), and the other was a G to C transition at the putative Sp1 binding site in the core promoter region. The latter mutation reduced the promoter activity, which may be due to a reduced affinity of the mutant sequence to the putative transcriptional regulator, which was neither Sp1 nor Sp3. No methylated cytosine was found at any CpG sites in the promoter region. These results suggested the presence of unidentified mechanisms for the diminished expression of RII in DICC cases.

Colonic Neoplasms↗

Expression of IL-6 receptor in pancreatic cancer: involvement in VEGF induction.

BACKGROUND: Vascular endothelial growth factor (VEGF) is one of the most potent angiogenic growth factors and its expression is correlated with MVD (microvascular density) in malignant tumors, including pancreatic adenocarcinoma. On the other hand, serum interleukin-6 (IL-6) is elevated in many patients with pancreatic cancer in accordance with their disease progression. In this study, we examined whether IL-6 and its receptors have any involvement in the induction of VEGF in pancreatic cancer. MATERIALS AND METHODS: Two human pancreatic cancer cell lines were examined for the induction of VEGF after treatment with IL-6. Thirty-two pancreatic cancer surgical specimens were stained immunohistochemically with VEGF, IL-6 and IL-6 receptor antibodies. RESULTS: CFPAC-1 cells expressed IL-6 receptor whereas AsPC-1 cells rarely expressed it. IL-6 treatment induced VEGF expression significantly and dose-dependently in CFPAC-1 cells, while it did not change in AsPC-1 cells. The intensity of VEGF expression in CFPAC-1 also increased time-dependently with IL-6 treatment. In 32 surgical pancreatic cancer tissues, 19 (59%) stained positive for VEGF and 26 (87%) positive for IL-6 receptor beta subunit. The correlation between IL-6 receptors and VEGF was significant (p = 0.0002 and p = 0.0019) while less correlation was seen between IL-6 and VEGF (p = 0.1937). CONCLUSION: Our results suggest that IL-6 is likely to take part in VEGF expression in both paracrine and autocrine fashion in pancreatic cancer. Induction of VEGF seems to be regulated by the extent of the IL-6 receptor expression on cancer cells.

Aged↗

Promotion effects of hot water on N-nitrosomethylbenzylamine-induced esophageal tumorigenesis in F344 rats.

This study is to determine the effects of hot water on N-nitrosomethylbenzylamine (NMBA)-induced rat esophageal tumorigenesis model. F344 rats received one treatment of hot water 1 ml/kg and NMBA 1 mg/kg, or a combination treatment of NMBA 1 mg/kg pus hot water 1 ml/kg, or/and EGCG (epigallocatechin-3-gallate) 10 mg/kg. The experiment was concluded at the 20th week. Our results showed that the number of tumors and incidence of carcinomas were significantly increased by hot water (65 degrees C) (p<0.05, p<0.03, respectively), as compared with the group which received NMBA injections only. EGCG treatment did not significantly reduce the number or the size of tumours as the temperature of added hot water increased. In addition, PGE2 production was induced by NMBA, and further significantly increased by added hot water (p<0.05). On the other hand, EGCG slightly decreased the elevated PGE2 production, however, this effect of EGCG was offset by hot water. Our study further confirmed that the drinking of hot beverages increased the risk of esophageal carcinogenesis, and the drinking hot tea will abolish the inhibitory effects of EGCG on this disease.

Animals↗

Portal embolization in various types of liver: novel variables to predict hypertrophy.

BACKGROUND/AIMS: The aim of this study was to investigate the hypertrophic effect of portal embolization in various types of liver and clarify useful variables, for predicting efficacy of portal embolization. METHODOLOGY: Portal embolization was performed for 46 patients with hepatocellular carcinoma (n = 30), biliary tract cancer (n = 9), or metastatic liver tumors (n = 7). The hypertrophic effect of portal embolization in relation to diseases, clinical liver conditions, histological fibrosis, and liver function were examined. RESULTS: The hypertrophic effect of portal embolization was impaired in the patients with hepatocellular carcinoma, chronic hepatitis/cirrhotic liver, and advanced liver fibrosis. ICGR15 (indocyanine green dye retention rate at 15 minutes) was revealed to be an independent adverse predicting factor. Especially in hepatocellular carcinoma patients, platelet count was significantly correlated with the hypertrophy ratio. In patients who underwent major hepatectomy for hepatocellular carcinoma, not only the incidences of posthepatectomy liver failure but also survival rate were similar between patients with and without portal embolization, although patients with portal embolization originally had a limited liver function. CONCLUSIONS: Preoperative portal embolization made major hepatectomy possible in hepatocellular carcinoma patients, although portal embolization was less effective compared with other diseases. ICGR15 and platelet count may be novel variables to predict the hypertrophic effect of portal embolization in all and hepatocellular carcinoma patients, respectively.

Adult↗

High serum soluble E-selectin levels are associated with postoperative haematogenic recurrence in esophageal squamous cell carcinoma patients.

E-selectin has been reported to be associated with haematogenic metastasis in various cancer patients. In order to evaluate the risk of postoperative haematogenic recurrence of esophageal squamous cell carcinoma (SCC) patients, we examined the preoperative serum levels of soluble E-selectin and clinicopathological data of the patients. Preoperative serum was obtained from 135 esophageal SCC patients who received esophagectomies from 1990 to 1998. Serum soluble E-selectin levels were measured by means of enzyme linked immunoreactive synthesis assay (ELISA). The expression of sialyl Lewis A and X antigens were evaluated in 58 out of 135 patients. Thirty-five patients (25.9%) had haematogenic recurrence in their postoperative course. Serum soluble E-selectin levels of the haematogenic recurrence group (mean 55.6 ng/ml) were significantly higher than those of the non-haematogenic recurrence group (mean 41.1 ng/ml). When the cut-off level of soluble E-selectin was 56 ng/ml, the logistic regression analysis showed that high serum soluble E-selectin levels, lymph node metastasis and intraepithelial spread were associated with postoperative haematogenic recurrence of the esophageal SCC patients (OR 2.99, p=0.047, OR 4.94, p=0.009 and OR 5.0, p=0.019. respectively). Univariate analysis revealed that the patients with a high serum soluble E-selectin level tended to have poor survival (p=0.078) and Cox multivariate analysis revealed that a high serum soluble E-selectin level was a prognostic factor in esophageal SCC patients (RR 1.84, p=0.065). The patients with a high serum soluble E-selectin concomitant with expression of sialyl Lewis antigens had a significant risk of postoperative haematogenic recurrence (p=0.005). These results indicated that preoperative high serum soluble E-selectin was a risk factor in the development of postoperative haematogenic recurrence and was a prognostic factor in esophageal SCC patients.

Biomarkers, Tumor↗

Expressions of molecules associated with hepatocyte growth factor activation after hepatectomy in liver cirrhosis.

BACKGROUND/AIMS: The activation pathway of hepatocyte growth factor (HGF), including HGF activator (HGFA) and HGFA inhibitor-1, 2 (HAI-1, 2), has recently been clarified. The present study examined mRNA expressions of HGF, HGFA and HAI-1 following partial hepatectomy in normal and cirrhotic rats. METHODOLOGY: Liver cirrhosis was induced by intraperitoneal injections of dimethylnitrosamine. Two weeks after, the cirrhotic and normal rats underwent 70% hepatectomy and the liver regeneration rate, DNA synthesis of hepatocytes, plasma HGF level, and mRNA expressions of HGF, HGFA, and HAI-1 in the liver, spleen, and lung were examined at different times. RESULTS: Liver regeneration in the cirrhotic rats was deteriorated with a later peak of hepatocellular DNA synthesis. Hepatic HGF mRNA and splenic HAI-1 mRNA were upregulated and liver HGFA mRNA was downregulated in the cirrhotic rats. CONCLUSIONS: Insufficient HGF activation both by a reduced expression of hepatic HGFA and an increased expression of splenic HAI-1 may be one of the reasons for the impaired liver regeneration in cirrhosis.

Animals↗

Simultaneous transfer of vascular endothelial growth factor and hepatocyte growth factor genes effectively promotes liver regeneration after hepatectomy in cirrhotic rats.

BACKGROUND/AIMS: Liver regeneration in a cirrhotic liver is unsatisfactory. In the course of liver regeneration, non-parenchymal cells such as sinusoidal endothelial cells as well as hepatocytes increase in number while the liver structure and physiological functions are maintained. The aim of this study was to examine whether sufficient liver regeneration could be obtained by the simultaneous, preoperative injection of recombinant adenoviral vectors encoding human vascular endothelial growth factor (VEGF), a potent mitogen for sinusoidal endothelial cells, (pAxCAVEGF) and rat hepatocyte growth factor (HGF), a potent mitogen for hepatocytes, (pAxCAHGF) in 70% hepatectomized cirrhotic rats. METHODOLOGY: Forty-eight hours before 70% hepatectomy, dimethylnitrosamine-induced cirrhotic rats were infused intravenously with pAxCAVEGF or with pAxCAVEGF and pAxCAHGF, or with a control virus encoding Escherichia coli beta-galactosidase (pAxCALacZ). RESULTS: Strong VEGF mRNA expressions were shown in the livers of VEGF and VEGF/HGF-treated animals. The plasma HGF concentrations in the VEGF/HGF-treated rats were elevated compared with the other groups. Proliferating cell nuclear antigen immunostaining showed increased labeling indices of hepatocytes in the VEGF/HGF-treated rats at 24 and 48 h after hepatectomy. PCNA labeling indices of SECs were increased in the VEGF and VEGF/HGF-treated rats compared with the control animals at 24 and 48 h after hepatectomy. Moreover, the hepatic regeneration rate after hepatectomy was significantly augmented by the VEGF and VEGF/HGF treatment. CONCLUSIONS: Simultaneous preoperative injection of recombinant adenoviral vectors encoding VEGF and HGF effectively stimulates liver regeneration in cirrhotic rats.

Animals↗

Interleukin-6 augments hepatocyte growth factor-induced liver regeneration; involvement of STAT3 activation.

BACKGROUND/AIMS: In liver regeneration, quiescent hepatocytes need to be primed before they can fully respond to growth factors such as hepatocyte growth factor (HGF). Recently, interleukin-6 (IL-6) has been shown to play an important role in initiating liver regeneration via activating signal transducer and activator of transcription 3 (STAT3). We therefore investigated the effect of IL-6 on liver regeneration and examined STAT3 activation following IL-6 and/or HGF treatment in rats. METHODOLOGY: The animals underwent portal branch ligation (PBL) of the left lateral and median branches. They were intravenously treated with either IL-6 (500 microg/kg), HGF (50 microg/kg), both, or vehicle alone on and every 12 h after PBL. The degree of compensatory hypertrophy in unoccluded lobes was examined by measuring the wet weight ratios of the unoccluded lobes to the whole liver and the 5-bromo-2'-deoxyuridine labeling index of hepatocytes in each group. STAT3 expression in regenerating liver was examined by Western blotting and immunohistochemistry. RESULTS: Coadministration of IL-6 and HGF most effectively increased both the wet weight of the unoccluded lobes and the hepatocellular DNA synthesis. HGF as well as IL-6-treated animals showed moderate STAT3 activation in hepatocytes throughout the experiment. CONCLUSIONS: IL-6 augmented HGF-induced liver regeneration and hepatocellular replication. Liver regeneration stimulated by HGF treatment may be closely involved with STAT3 activation in a different manner induced by IL-6 treatment.

Animals↗

Unresectable hilar cholangiocarcinoma completely reduced by external radiation therapy.

A 68-year-old woman was referred to our hospital with liver dysfunction. Abdominal ultrasonography showed an isoechoic mass in the hepatic hilum. Abdominal computed tomography (CT) disclosed a homogenous mass adjacent to the portal bifurcation, and endoscopic retrograde choledocho-pancreatography (ERCP) revealed complete obstruction from the common hepatic duct to the hepatic duct confluence. After insertion of the endoscopic nasobiliary drainage (ENBD) tube, laparotomy was performed, revealing an approximately 5x6-cm elastic hard mass at the hepatic hilum, mainly spreading to the left hepatic duct, and involving surrounding vascular structures such as the portal vein and right and left hepatic arteries. Therefore, she was treated by external radiation therapy (ERT) of 60 Gy in 30 sessions after insertion of endoscopic retrograde biliary drainage (ERBD) tubes to bilateral hepatic ducts to replace the ENBD tube. After the completion of ERT, she was discharged from the hospital in good health. Three months later, she was readmitted for cholangitis and received antibiotic treatment. Surprisingly, abdominal CT disclosed complete remission of the tumor. ERCP revealed patency of the common hepatic duct and hepatic duct confluence. Therefore, the ERBD tubes were removed. Specimens from the hepatic duct confluence, and bilateral hepatic ducts showed no malignancy histologically. She is doing well without recurrence more than 4 years after surgery.

Aged↗

Tissue factor is a useful prognostic factor of recurrence in hepatocellular carcinoma in 5-year survivors.

BACKGROUND/AIMS: Tissue factor (TF) is a transmembrane glycoprotein involved in initiating blood coagulation. TF has recently been reported to play an important role in tumor metastasis. The aim of this study was to evaluate the role and the prognostic value of TF in hepatocellular carcinoma (HCC) in long-term survivors. METHODOLOGY: Among 275 patients who underwent curative hepatectomy for HCC, 62 patients who survived more than 5 years after surgery were retrospectively studied. TF expression was immunohistochemically examined. RESULTS: TF was positive in 39 of the 62 patients. In patients with TF expression, the serum albumin level was significantly lower and capsular infiltration, tumor thrombus in the portal vein, and intrahepatic metastasis were more frequently shown than those without TF expression. The recurrence-free rate was significantly higher in the patients whose tissue stained negative for TF than in those whose tissue stained positive for TF. Multivariate analysis showed TF expression to be a significant and independent risk factor for recurrence. Concerning the recurrence pattern, all 23 patients with intrahepatic metastasis were TF-positive, whereas 3 out of 5 patients with multicentric carcinogenesis were TF-positive. CONCLUSIONS: TF expression is closely associated with the tumor invasion and metastasis, and may serve as a useful prognostic factor of recurrence in HCC in 5-year survivors.

Carcinoma, Hepatocellular↗

Hepatocyte growth factor as well as vascular endothelial growth factor gene induction effectively promotes liver regeneration after hepatectomy in Solt-Farber rats.

BACKGROUND/AIMS: Hepatic oval cells play an important role in liver regeneration when proliferation of mature hepatocytes is inhibited. The aim of this study was to examine the effect of hepatocyte growth factor (HGF), or vascular endothelial growth factor (VEGF) on proliferation of oval cells in the Solt-Farber rat model. METHODOLOGY: One hour after 70% partial hepatectomy, 2-acetyl-aminofluorene-induced damaged rats were infected intravenously with recombinant adenoviral vectors, encoding rat HGF or human VEGF, or Escherichia coli beta-galactosidase as a control. RESULTS: The plasma HGF concentrations in the HGF-transferred rats were elevated compared with the other groups at 4 and 7 days after hepatectomy. Oval cells were confirmed by positive staining of both cytokeratin-19 and alpha-fetoprotein. Oval cells around the portal tracts in the HGF or VEGF-transferred rats increased in number compared with the control rats at 7 and 9 days after hepatectomy. The proliferating cell nuclear antigen labeling indices of oval cells and the hepatic regeneration rate after hepatectomy were significantly augmented by the HGF or VEGF treatment. Moreover, cyclin E expression was elevated in the HGF-treated rats. CONCLUSIONS: In the Solt-Farber rat model, HGF or VEGF gene injection effectively promoted liver regeneration after hepatectomy mainly with increased proliferation of hepatic oval cells.

Adenoviridae↗

Predictive factors affecting early recurrence after hepatectomy for hepatocellular carcinoma in 5-year survivors.

BACKGROUND/AIMS: This study was undertaken to establish a therapeutic strategy for long-term recurrence-free survival in hepatocellular carcinoma (HCC) patients treated by hepatectomy by determining the factors that predict intrahepatic recurrence. METHODOLOGY: This study included 72 patients who survived more than 5 years after hepatectomy for HCC. Based on the interval between hepatectomy and intrahepatic recurrence, they were classified into 3 groups: those with early recurrence within 2 years after surgery (n=15), those with recurrence between 2 and 5 years (n=18), and those without recurrence within 5 years (n=39). Twenty-six parameters concerning host-related, tumor-related, treatment-related factors, and postoperative levels of serum transaminases were evaluated. RESULTS: Among host-related and tumor-related factors, serum albumin level, serum levels of transaminases, indocyanine green retention rate at 15 minutes, tumor number, intrahepatic metastasis and TNM stage were determined to be significantly different between the patients with recurrence within 5 years and those without recurrence. Among treatment-related factors, curability was highly associated with recurrence. The period until increase in the levels of transaminases after surgery was significantly shorter in patients with recurrence compared to the patients without recurrence. CONCLUSIONS: Curative operation minimizing intrahepatic metastasis and postoperative anti-inflammatory treatment lowering the occurrence of multicentric carcinogenesis are useful therapeutic strategies for achieving long-term recurrence-free survival for HCC patients treated with surgery.

Alanine Transaminase↗