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Biomedical subjects

Mitsuo Shimada

Publications and source records attributed to Mitsuo Shimada.

At least 91 records · Page 5Linked to original sources
PubMed2002

Electroporation-mediated tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/Apo2L gene therapy for hepatocellular carcinoma.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/Apo2 ligand (Apo2L) has been identified as important in promoting programmed cell death in breast and colon cancer xenografts. More importantly, normal liver tissue appears not to be susceptible to the cytotoxic effects of TRAIL/Apo2L, although activation of the related Fas ligand receptor system is known to promote massive liver apoptosis terminating in fulminant hepatitis. In the present study, we investigated the therapeutic potential of TRAIL/Apo2L gene therapy in hepatocellular carcinoma (HCC) and evaluated its side effects in an immune-competent mouse model. Intratumoral administration of the TRAIL/Apo2L vector by electroporation elevated serum TRAIL/Apo2L through at least day 28 after gene therapy and significantly inhibited the growth not only of the HCC directly administered TRAIL/Apo2L vector, but also of distant subcutaneous HCC. In addition, intratumoral administration of the TRAIL/Apo2L vector inhibited spontaneous lung metastasis. Serum alanine aminotransferase was mildly elevated by TRAIL/Apo2L gene therapy, but without showing such histological signs as TUNEL staining. These results demonstrate that TRAIL/Apo2L gene therapy for HCC by electroporation in vivo is efficient without significant side effects, and is thus promising for use in future clinical trials.

Animals↗
PubMed2002

Characteristics of liver grafts in living-donor adult liver transplantation: comparison between right- and left-lobe grafts.

HYPOTHESIS: Few studies have investigated the results of research focused on living-donor adult liver transplantation. Different characteristics between right- and left-lobe grafts have not yet been clarified in living-donor adult liver transplantation. Left-lobe graft remains an important option, even in adult recipients. SETTING: A single liver transplantation center with a long history of hepatic resection. PATIENTS: Forty-five donors received left-lobe (n = 39) and right-lobe (n = 6) grafts. The clinicopathological data for the donor, graft, and recipient were compared. All left-lobe grafts were extended grafts that included the middle hepatic vein, and 24 of the 39 left-lobe grafts included the left caudate lobe. No right-lobe graft included a middle hepatic vein. RESULTS: The postoperative aspartate aminotransferase and total bilirubin values of the donor in the right-lobe graft group were higher, and the postoperative hospital stay was longer than in the left-lobe graft group. Graft weight in the left-lobe graft group was lighter than in the right-lobe graft group (median weight, 450 vs 675 g). The median graft weight divided by the standard liver volume in the left-lobe graft group was 41% (range, 21%-66%), compared with 52% (range, 47%-75%) in the right-lobe graft group. We found no difference in terms of the incidence of postoperative complications between groups. No difference in induced complications of small-for-size grafts such as intractable ascites and persistent hyperbilirubinemia was evident between groups. The survival rate for grafts at 18 months was 75.0% in the right-lobe graft group compared with 85.6% in the left-lobe group. In the right-lobe graft group, we found a few cases in which a marked poor-perfusion area in the anterior segment caused liver dysfunction. CONCLUSIONS: Left-lobe grafts are a feasible option for living-donor adult liver transplantation, and in the case of right-lobe grafts, hepatic venous drainage is one of the most critical problems.

Adult↗
PubMed2002

G protein gamma 7 expression as a new clinicopathological marker in patients with intrahepatic cholangiocarcinoma.

HYPOTHESIS: The signal alterations mediated by small G proteins such as Ras, Rho, and Rac have been reported in several cancers. The human G protein gamma 7 (G-gamma 7) gene, which is down-regulated in various digestive organ cancers, was recently identified and cloned. Thus, the G-gamma 7-coupled heterotrimeric G proteins may also contribute to carcinogenesis in human cancers. SETTING: University hospital and medical institute of bioregulation. PATIENTS AND METHODS: The clinicopathological significance of G-gamma 7 expression in 18 patients with intrahepatic cholangiocarcinoma (IHCC) was examined. The tumor-nontumor ratio of G-gamma 7 expression was determined using reverse transcription polymerase chain reaction analysis. To visualize the localization of G-gamma 7, an immunohistochemical study was performed. MAIN OUTCOME MEASURE: Clinicopathological significance of G-gamma 7 expression in human IHCC. RESULTS: Expression of G-gamma 7 messenger RNA was lower in tumor tissue than in the corresponding nontumor tissue in 17 (94%) of 18 patients with IHCC. The mean tumor-nontumor ratio was 0.54. Eleven patients with tumor-nontumor ratios less than 0.5 showed significantly poorer differentiated IHCC than 7 with tumor-nontumor ratios of 0.5 and greater (P<.01). Decreased expression of G-gamma 7 protein in the carcinoma tissue, especially in the poorly differentiated IHCC tissue, was confirmed using immunohistochemical staining. CONCLUSIONS: Reduced expression of G-gamma 7 is associated with the histological grade of IHCC and may therefore prove to be a useful marker for predicting the biological aggressiveness of human IHCC.

Adult↗
PubMed2002

Video-assisted thoracoscopic extirpation of a posterior mediastinal mass using the da Vinci computer enhanced surgical system.

A 28-year-old woman presented a left posterior mediastinal mass surrounded by the intercostal vein, hemiazygos vein, sympathetic nerve, and descending aorta. We successfully resected the mass, that was revealed to be a bronchogenic cyst, by a totally thoracoscopic procedure using the da Vinci computer-enhanced system (Intutive Surgical, Mountain View, CA) without injuring the neighboring structures or the capsule of the mass.

Adult↗
PubMed2002

Tie2 vascular endothelial receptor expression and function in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is generally characterized as a hypervascular tumor of rapid growth. We have previously reported that angiopoietin (Ang), a ligand for Tie2 vascular endothelial-specific receptor tyrosine kinase, may play a role in the progression of human HCC (J Clin Invest 1999;103:341-345) and matrix proteinase expression (Cancer Res 2001;61:2145-2153). However, the role of Tie2 receptor in hepatic oncogenesis is unknown. The Tie2 receptor protein was overexpressed in the neovascular endothelium of 31 of 39 (80%) human HCC tumors by immunohistochemical analysis with significant correlation to cell dedifferentiation and tumor size (P <.05). In vitro expression of a dominant-negative construct, containing a soluble Tie2 ectodomain (sTie2), led to Ang protein interaction, inhibition of endogenous Tie2 phosphorylation in vascular endothelial cells and matrix metalloproteinase 9 (MMP-9) suppression. In conclusion, tumorigenicity with neovascularization was suppressed by in vivo gene transfer and sTie2 expression in a murine HCC model, suggesting a possible role for Tie2 expression in the induction of HCC neovascularization and disease progression. Inhibition of the Ang/Tie2 signal transduction cascade is a promising approach for tumor treatment.

Angiopoietin-1↗
PubMed2002

Hepatic artery reconstruction and biliary stricture formation after living donor adult liver transplantation using the left lobe.

Biliary complications, including bile leak, biliary stricture, and cholangitis, are seen in 15% to 29% of all cases after living related liver transplantation. We investigate risk factors and discuss the management of biliary complications after living related liver transplantation in adults using left-lobe grafts. We studied 37 adult patients who underwent living related liver transplantation using left-lobe grafts. Perioperative variables were evaluated as risk factors for biliary strictures. The overall incidence of biliary complications was 43.2% (16 of 37 patients). Anastomotic strictures occurred in 8 patients, whereas bile leaks and cholangitis occurred in 9 and 8 patients, respectively. Anastomotic stricture was strongly related to a partial artery reconstruction (P <.02) and cholangitis (P <.01). Anastomotic biliary stricture was not associated with bile leak, acute cellular rejection, or infection. Our results suggest that an important risk factor for biliary anastomotic biliary strictures is a partial artery reconstruction. To minimize the risk for biliary anastomotic strictures, we will reconstruct both the middle and left hepatic artery.

Adult↗
PubMed2002

A 16-year experience in performing hepatic resection in 303 patients with hepatocellular carcinoma: 1985-2000.

BACKGROUND: Hepatic resection is an accepted therapeutic modality for hepatocellular carcinoma (HCC). Over the past 2 decades, liver surgery has evolved to a refined and deliberate operation. In the present study surgical results are analyzed with an aim toward further improving the treatment of HCC. METHODS: We studied 303 patients with HCC who underwent a hepatic resection at 2 university hospitals from 1985 through 2000. Living-related liver transplantation was a procedure of choice in 1 patient with early staged HCC. Fifty-five percent of the patients had associated cirrhosis. Before the operation, the liver function was mainly evaluated with the indocyanine green retention test. RESULTS: The mortality rate within 30 days after the operation was 1.6%. One-, 3-, 5-, 10-, and 15-year cumulative survival rates were 84%, 67%, 51%, 20%, and 11%, respectively. The tumor stage I and II groups showed superior survival rates to those of the tumor stage III and IV groups, respectively, and the difference was statistically significant. The disease-free survival curves, however, showed the rate to be 27% at 5 years and 11% at 10 years. CONCLUSIONS: Although the surgical results have greatly improved in the treatment of HCC, the recurrence rate is still high. In carefully screened patients with poor liver function and small HCC, liver transplantation enhances the possibility of cure.

Aged↗
PubMed2002

Intrahepatic cholangiocarcinoma: its mode of spreading and therapeutic modalities.

Intrahepatic cholangiocarcinoma (IHCC) is a primary adenocarcinoma of the liver, arising from the intrahepatic bile ducts. The prognosis is generally poor because locoregional extension is usually advanced at the time of diagnosis. Even after a resection, the outcome for patients with advanced IHCC is extremely poor, and the presence of lymph node metastasis has been reported in most previous studies to be the worst prognostic factor after a resection. There are no clear guidelines on lymph node dissection with IHCC. In this article, we review the mode of invasion and the therapeutic modalities: hepatic resection, lymph node dissection, liver transplantation, radiation, and chemotherapy for IHCC.

Adenocarcinoma↗
PubMed2002

Living-donor liver transplantation for fulminant hepatic failure in adult patients with a left-lobe graft.

BACKGROUND: Living donors are practically the only source of organs in countries where the availability of cadaveric donors is severely restricted, such as Japan. A left-lobe graft, in which one third of the liver is donated, is therefore used for adult-to-adult living-donor liver transplantation (LDLT) in patients with fulminant hepatic failure (FHF). METHODS: Fifteen adult patients with FHF, ranging from 22 to 59 years of age, were treated with LDLT with a left-lobe graft. Preoperative encephalopathy was grade II in 2 patients, grade III in 4 patients, and grade IV in 9 patients. The graft volume (GV) ranged from 260 to 570 mL, thus corresponding to 23% to 54% of the recipients' standard liver volume (SLV). The patients were divided into 2 groups according to their GV/SLV: a medium-size graft group (GV/SLV > or =30%; group M, n = 11) and a small-size graft group (GV/SLV <30%; group S, n = 4). The effects of GV/SLV on graft function and survival were compared. Postoperative neurologic complications were also evaluated. RESULTS: The donors are all doing well. Twelve (80%) of the 15 recipients are still alive, with a follow-up period of from 3 to 43 months. No statistically significant differences were observed in the postoperative serum levels of bilirubin and alanine aminotransferase, prothrombin time, or frequency of postoperative complications between the 2 groups. The graft and patient survival rates were 75% (3/4) and 75% (3/4) in group S and 73% (8/11) and 82% (9/11) in group M, respectively. All patients who survived the perioperative period recovered without any neurologic sequelae. CONCLUSIONS: The high success rate and low donor risk of LDLT may therefore justify its use for adult patients with FHF using a left-lobe graft.

Adult↗
PubMed2002

Perioperative management and complications in donors related to living-donor liver transplantation.

BACKGROUND: Living-donor liver transplantation has become a legitimate alternative to cadaveric liver transplantation. However, information on the perioperative management of donors is still scarce. METHODS: Between October 1996 and May 2001, 52 consecutive living-donor liver transplantations have been performed at the authors' institution. The preoperative and postoperative management of donors, operative technique, and complications are herein described. RESULTS: All donors were discharged from the hospital alive and well, and all returned to their normal lifestyle without any significant adverse sequelae after a mean hospital stay of 13 days after the operation. Overall, 24 complications occurred, all of which could be managed conservatively, except for one case of hepatic duct stricture that required a relaparotomy. A learning curve has been observed in terms of blood loss during donor hepatectomy. CONCLUSIONS: These results indicate that our approach toward the selection and management of donors was appropriate. Because of the use of meticulous operative techniques, blood loss could also be minimized.

Adult↗
PubMed2002

Hepatic artery reconstruction in living-donor liver transplantation: a review of its techniques and complications.

BACKGROUND: Hepatic arterial reconstruction is one of the most difficult procedures in living-donor liver transplantation (LDLT) because the artery used is generally small in diameter and has a short stalk. If hepatic artery thrombosis (HAT) occurs, the recipient clinical course will be unstable. The introduction of microvascular hepatic arterial reconstruction has significantly decreased the incidence of HAT. METHODS: Fifty-two cases of LDLT were performed from October 1995 to May 2001 in our institution. Hepatic arterial reconstruction was performed under microscopic guidance. RESULTS: HATs were recognized in 2 cases (3.8%), both of which needed reoperation. CONCLUSIONS: Surgeons who perform hepatic arterial reconstruction in LDLT should be highly trained in microvascular techniques to decrease the incidence of HAT. This commentary reviews the surgical techniques of hepatic arterial reconstruction and possible complications that may arise in a reconstructed hepatic artery.

Hepatic Artery↗
PubMed2002

Auxiliary partial orthotopic liver transplantation from living donors.

Auxiliary liver transplantation was originally started in Western countries in the form of heterotopic auxiliary liver transplantation for end-stage liver disease. It thereafter developed into the form of auxiliary partial orthotopic liver transplantation for acute liver failure. In Japan, where living-donor liver transplantation is the main mode of liver transplantation, auxiliary partial orthotopic liver transplantation was initially used for patients with metabolic liver diseases and has since developed into an effective solution for small-for-size living donor grafts. Although there has been a reported case of successful auxiliary partial orthotopic liver transplantation from a living donor for the treatment of acute liver failure, wide application of this technique is made difficult at present by such unsolved problems as functional competition, small graft size, severe clinical status, and toxic liver syndrome. Auxiliary partial orthotopic liver transplantation from a living donor is an established procedure for small-for-size living-donor grafts and metabolic liver diseases, and the future establishment of its successful application to cases of acute liver failure is anticipated.

Adolescent↗
PubMed2002

Minimally invasive hepatectomy: modulation of systemic reactions to operation or laparoscopic approach?

BACKGROUND: A new concept of surgical stress has been proposed that consists of both aggressiveness of operation and systemic reactions to an operation. METHODS AND RESULTS: We have investigated a possible modulation of such systemic reactions to operation and have demonstrated the following 3 points: (1) coagulation and fibrinolytic systems are independently activated during hepatectomy and such activation can be modulated by protease inhibitors such as nafamostat mesilate and antithrombin III; (2) elevated thromboxane A2 during hepatectomy is characterized in the prostanoid system, the elevation of thromboxane A2 is inhibited by thromboxane A2 synthetase inhibitor, and postoperative liver injury is reduced; (3) cytokine response induced by hepatectomy is modulated by preoperative administration of methylprednisolone, leading to possible prevention of bacterial translocation. Therefore, modulating systemic reactions to hepatectomy may be important for successful minimally invasive hepatectomy. Another important option for minimally invasive hepatectomy is the use of operative procedures such as laparoscope or thoracoscope. We have investigated the usefulness of a laparoscopic hepatectomy from the standpoints of early and long-term outcome after hepatectomy. Laparoscopic hepatectomy, which is a difficult and dangerous procedure, can be a feasible option and can result in better short-term outcome and a similar long-term outcome after hepatectomy when compared with conventional open hepatectomy. Therefore, the laparoscopic approach is also a viable option for minimally invasive hepatectomy. CONCLUSIONS: Modulation of systemic reactions to the operation itself and laparoscopic hepatectomy may be new strategies for performing minimally invasive hepatectomy.

Blood Coagulation↗
PubMed2002

Hybrid-artificial liver support system.

We originally developed a multi-capillary polyurethane foam packed-bed module as a hybrid-artificial liver support system (HALSS) and have applied for the permission of the clinical application to our institutional ethical committee. We summarized here the history, recent obstacles in clinical applications, and future prospects of HALSS, including our own.

Animals↗
PubMed2002

The utility of keratin 903 as a new prognostic marker in mass-forming-type intrahepatic cholangiocarcinoma.

The cytokeratins phenotype is largely preserved during neoplastic transformation and tumor development. We evaluated the immunoreactivity of biliary epithelial markers keratin 903 and cytokeratin 7 and 19 for intrahepatic cholangiocarcinoma, and compared the results with those for biliary dysplasia and hepatocellular carcinoma. Reactivity with keratin 903 was weakly expressed and increased after the expression of cytokeratin 7 and 19 during human intrahepatic bile duct development. More than 80% of cases of biliary dysplasia showed positive reactivity with keratin 903. Of the 30 cases of hepatocellular carcinoma, 3 (10%), 6 (20%), and 1 (3%) showed positive reactivity with Keratin 903 and cytokeratin 7 and 19, respectively. Among the 73 cases of intrahepatic cholangiocarcinoma, 54 (74%), 66 (90%), and 61 (84%) showed positive reactivity with keratin 903 and cytokeratin 7 and 19, respectively. On clinicopathologic examination of intrahepatic cholangiocarcinomas, reduced keratin 903 reactivity was significantly higher in tumors with an expansive growth pattern (P <.0001), in those with medullary-type stromal reaction (P =.0327), in those without perineural invasion (P =.0001), and in those without lymph node metastasis (P =.0015). In addition, the reactivity with Keratin 903 was directly correlated with expression of cytokeratin 7 and 19 (P =.0153 and P <.0001, respectively). Cases showing reduced keratin 903 reactivity were characterized by a distinctive morphology indicating an hepatocellular carcinoma-like pattern. Multivariate analysis of overall survival revealed that keratin 903 reactivity was a significantly independent prognostic factor. In conclusion, patients with intrahepatic cholangiocarcinoma showing reduced keratin 903 reactivity had a favorable prognosis. Remarkably, the cytokeratin phenotype of intrahepatic cholangiocarcinoma was correlated with the morphologic appearance of intrahepatic cholangiocarcinoma.

Aged↗
PubMed2002

The role of thymidine phosphorylase and thrombospondin-1 in angiogenesis and progression of intrahepatic cholangiocarcinoma.

Thymidine phosphorylase (TP), an important regulator of angiogenesis, is correlated with progression, metastasis, and prognosis in various types of tumor. In contrast, both positive and negative effects of thrombospondin-1 (TSP-1) on angiogenesis have been reported. In the present study, we examined the expression of TP and TSP-1 in carcinoma cells in 67 primary intrahepatic cholangiocarcinomas (ICCs) immunohistochemically and its correlation with angiogenesis, clinicopathological features, and prognosis. Twenty-six (38.8%) cases were classified as exhibiting positive TP expression. TP expression showed a significant correlation with vascular invasion, lymphatic permeation, perineural invasion, and lymph node metastasis. Thirty-four (50.7%) cases were classified as exhibiting positive TSP-1 expression. TSP-1 expression was significantly correlated with only lymphatic permeation. The microvessel count in positive TP expression cases was significantly higher than that in negative cases. In contrast, the microvessel count in negative TSP-1 expression cases was significantly higher than that in positive cases. Survival in patients who were positive for both TP and TSP-1 expression was significantly poor. Our results suggest that the increased TP expression and decreased TSP-1 expression contribute to angiogenesis, but that the role of angiogenesis in ICC is not closely related to tumor aggressiveness. The TP and TSP-1 expression in ICC may enhance tumor aggressiveness.

Bile Duct Neoplasms↗