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Mitsuo Shimada

Publications and source records attributed to Mitsuo Shimada.

At least 55 records · Page 3Linked to original sources
PubMed2004

A simple and accurate formula to estimate left hepatic graft volume in living-donor adult liver transplantation.

BACKGROUND: In the field of living-donor adult liver transplantation, a small-for-size graft often occurs, particularly when using left-lobe grafts. This is because of the limited volumes associated with left-lobe grafts. The accurate preoperative evaluation of graft volumes is crucial to avoid this complication. The aim of this study is to clarify the usefulness of a new formula to estimate the left-lobe graft volume. METHOD: In 61 left-lobe grafts, a new formula was created with stepwise regression analysis using the following variables: height, weight, the thoracic and abdominal distance from anterior to posterior side (A-P), and distance from left to right side (L-R) of the initial 20 donors. With another 41 donors, the difference between the actual and estimated graft volume using the formula and two- and three-dimensional computed tomography was prospectively evaluated. RESULTS: On the basis of the results of the stepwise regression analysis, a new formula was created as follows: graft volume (ml) = 313.4 + 7.7 x weight (kg)-12.6 x thoracic L-R (cm). The difference between the actual and estimated graft volumes using the formula was significantly better (10.8 +/- 9.5%) than that of the volumetry using two-dimensional computed tomography (16.3 +/- 10.1%) (P < 0.05). CONCLUSIONS: In conclusion, the new formula can estimate the actual graft volume more accurately than conventional volumetry with two-dimensional computed tomography. The formula is useful to estimate the volume of left-lobe graft in living-donor adult liver transplantation.

Adult↗
PubMed2004

Role of expression of focal adhesion kinase in progression of hepatocellular carcinoma.

PURPOSE: Although hepatocellular carcinoma (HCC) is the most common cancer of the human liver, the mechanisms that regulate HCC development and progression remain unclear. The aim of this study was to investigate whether focal adhesion kinase (FAK) is involved in the progression of human HCC. EXPERIMENTAL DESIGN: Western blot analysis for FAK was performed on three HCC cell lines. We reviewed 64 consecutive patients who had undergone initial liver resection for HCC without preoperative treatment. Immunohistochemistry analysis for FAK was performed on paraffin-embedded tissues. FAK expression was confirmed by Western blot analysis in several clinical samples. We investigated the correlation between FAK expression and clinical outcome. RESULTS: FAK proteins were detected in all HCC cell lines. Hepatocytes in the normal liver and chronic hepatitis with or without cirrhosis were negative for immunohistochemical staining for FAK expression. Cytoplasmic FAK expression was observed in 18 of 64 patients (28.1%), and this positive staining was correlated with gender (P < 0.05), a lower level of serum albumin (P < 0.05), and portal venous invasion (P < 0.01). Positive staining for FAK was associated with significantly poorer survival (P < 0.05). In multivariate analysis, FAK overexpression was an independent factor in determining the prognosis of patients. CONCLUSIONS: These data suggest that FAK plays an important role in promoting tumor progression, especially vascular invasion, in HCC. FAK could play an important role in HCC progression and would be a novel target for HCC therapeutics as well as a prognostic marker.

Aged↗
PubMed2004

Sustained spatial disturbance of bile canalicular networks during regeneration of the steatotic rat liver.

BACKGROUND: Although it is generally considered that livers with moderate steatosis can be safely used in the setting of living-donor liver transplantation, the effect of the regenerative process of such a graft on postoperative liver function is incompletely understood. We assessed the morphologic and functional alterations during the regeneration of fatty liver, with special reference to the biliary system. METHODS: Wistar rats with normal or fatty livers induced by a choline-deficient diet were subjected to 70% partial hepatectomy (PH). The regenerated liver weight and serum parameters were compared. Furthermore, to assess the spatial alterations of bile canalicular networks, the distribution of AGp110, a fibronectin receptor that localizes on the apical (bile canalicular) membrane of the hepatocytes, was analyzed immunohistochemically. RESULTS: The serum albumin levels of the fatty-liver rats decreased significantly after 24 hours, and this continued until day 7. The increase in the total bile acid levels of the fatty-liver group was higher and more prolonged compared with that of the normal-liver group. At 24 hours after PH, discontinuity of the AGp110-positive canalicular network was evident in both groups. At 7 days after PH, the typical AGp110-positive canalicular network was almost restored in the normal-liver group. In contrast, the fatty-liver group showed sustained discontinuity of canalicular networks at the same time point. CONCLUSIONS: The livers with moderate steatosis are associated with prolonged cholestasis after 70% PH, and this was caused, in part, by sustained spatial disturbance of bile canalicular networks during the regenerative process.

Animal Nutritional Physiological Phenomena↗
PubMed2004

Graft-versus-host disease following living donor liver transplantation.

Graft-versus-host disease (GVHD) is the most common and well-known cause of morbidity and mortality following allogeneic bone marrow transplantation. Sporadic cases have been reported after cadaveric donor liver transplantation with usually fatal outcomes, however, the actual incidence and the characteristics of GVHD after living donor liver transplantation (LDLT) remain unknown. We herein report a person who developed fatal GVHD following LDLT and discuss the applicability of an HLA-homozygous donor to an HLA-haploidentical recipient. A 48-year-old male underwent LDLT for unresectable hepatocellular carcinoma with alcoholic liver cirrhosis. The donor was his 20-year-old son whose pretransplant HLA typing was homozygous at all loci. GVHD occurred 35 days after LDLT and was characterized by fever, diarrhea, maculopapular rash, and leukopenia, which led to the development of fatal pneumonia. We identified 4 cases of GVHD after LDLT in Japan and 1 in the United States, all associated with the use of an HLA-homozygous donor. The use of an HLA homozygous donor which results in a complete 1-way donor-recipient HLA match carries an extremely high risk of developing GVHD after LDLT. Therefore, it is possible that LDLT should be ruled out for such donors. A pretransplant work-up of the HLA type in both the donors and recipients is therefore imperative before determining the indications for LDLT.

Fatal Outcome↗
PubMed2004

Prognostic factors in node-negative intrahepatic cholangiocarcinoma with special reference to angiogenesis.

BACKGROUND: The aim of this study was to clarify prognostic factors and recurrence patterns in patients with node-negative intrahepatic cholangiocarcinoma (IHCC). METHODS: A retrospective study was performed to review prognostic factors and recurrence patterns (1) in 22 patients with node-negative IHCC after curative hepatic resection and (2) in 49 patients who underwent resection and lymph node dissection for IHCC. In addition to determining the clinicopathologic factors, the investigators also performed immunohistochemical examination of microvessel counts using antihuman CD-31 and antibody. RESULTS: The significant poor prognostic factors in node-negative IHCC were the presence of intrahepatic metastasis, portal vein invasion of cancer cells, and high microvessel counts. After multivariate analysis was conducted, the independent poor prognostic factors were the presence of intrahepatic metastases and high microvessel counts. Of 9 patients who had postoperative recurrence of their disease, intrahepatic recurrence was observed in 7 (78 %). CONCLUSIONS: The factors linked to poor prognosis in IHCC were tumor angiogenesis and the presence of intrahepatic metastasis. Because intrahepatic recurrence was common, regional and adjuvant chemotherapy to the liver may improve the outcome of patients with these risk factors and node-negative IHCC.

Bile Duct Neoplasms↗
PubMed2004

Clinicopathological correlates of aspartyl (asparaginyl) beta-hydroxylase over-expression in cholangiocarcinoma.

UNLABELLED: Aspartyl (asparaginyl) beta-hydroxylase (AAH) expression in surgically resected intrahepatic cholangiocarcinoma significantly correlated with tumor size, growth type, differentiation, vascular invasion, and prognosis after surgery. AAH may have a role in regulating invasive or metastatic tumor cell growth of human intrahepatic cholangiocarcinoma. BACKGROUND: Recent studies demonstrated increased expression of the AAH gene in the majority of cholangiocarcinomas. The present study was undertaken to determine the relationship between high or low levels of AAH expression and the clinical course of intrahepatic cholangiocarcinoma (ICC). METHODS: AAH expression was examined in 50 surgically resected primary ICCs, 12 samples of normal liver, and 12 cases of primary sclerosing cholangitis (PSC). The sections were evaluated by immunohistochemical staining with the FB-50 monoclonal antibody to human AAH protein. The sections were examined under code and graded for relative levels of AAH immunoreactivity. The results were analyzed with respect to multiple clinical and histopathological variables to determine correlates of AAH expression in ICCs. RESULTS: Forty-six of the 50 (92%) ICCs had AAH immunoreactivity, whereas the 12 normal liver and 12 PSC specimens were AAH negative. In the ICC specimens, the highest levels of AAH immunoreactivity were detected at the infiltrating margins that interfaced with uninvolved liver tissue, and the lowest levels occurred in the central portions of the tumors. Multivariate analysis demonstrated that high levels of AAH expression were correlated with tumor size (P < 0.05), infiltrative growth pattern (P < 0.01), aggressive histological grade (P < 0.01), vascular invasion (P < 0.05), and poor prognosis (P < 0.05). CONCLUSIONS: These findings suggest that AAH has an important role in regulating invasive or metastatic tumor cell growth of human ICC, and that high levels of AAH expression correlate with poor prognosis.

Aged↗
PubMed2004

Aberrant expression of laminin gamma 2 chain and its prognostic significance in intrahepatic cholangiocarcinoma according to growth morphology.

Laminin gamma 2 chain is an extracellular matrix protein that plays an important role in cell migration and tumor invasion. We report altered expression and characteristic localization of this chain in a series of 105 cases of intrahepatic cholangiocarcinomas examined immunohistochemically. All tumors were grossly classified into the following three types: intraductal growth type (n=9), periductal infiltrating type (n=8) and mass-forming type (n=88). The tumors exhibited three distinct staining types: basement membrane staining, cytoplasmic staining and stromal staining. The basement membranous staining of laminin gamma 2 chain was more frequent in biliary dysplasia, intraductal growth and periductal infiltrating type than in mass-forming type. The cytoplasmic staining of carcinoma cells was observed especially at the cancer-stromal interface or at the invasive front of tumors. Stromal staining of laminin gamma 2 chain was essentially localized in the stroma around cancer cells at the invasive area, and the expression was significantly correlated with tumor aggressive factors and a poor prognosis in patients with intrahepatic cholangiocarcinoma. We conclude that laminin gamma 2 chain exhibits aberrant expression in a stepwise manner through different aggressive stages of tumor progression.

Aged↗
PubMed2004

Decreased expression of osteopontin is related to tumor aggressiveness and clinical outcome of intrahepatic cholangiocarcinoma.

BACKGROUND: Osteopontin (OPN) is known to be a secreted adhesive glycoprotein. Recent studies have reported that the overexpression of OPN is correlated with tumorigenesis, tumor aggressiveness, and poor prognosis in several types of human cancer. The aim of this study was to determine whether the expression of OPN in cases of intrahepatic cholangiocarcinoma (ICC) indicates the clinical outcome. METHODS: The expression of OPN protein was investigated immunohistochemically in surgically resected specimens from 73 patients, and the level of OPN mRNA was also examined by quantitative real-time reverse transcription-polymerase chain reaction (real-time RT-PCR) in nine samples of ICC. We examined the correlation between the expression of OPN and the clinicopathological factors, including overall survival, in patients with ICC. RESULTS: We detected the positive expression of OPN protein in 31 of 73 (42.5%) of the primary ICCs. Negative expression of OPN protein was significantly related to lymphatic permeation, perineural invasion, intrahepatic metastasis, and lymph node metastasis (P=0.0029, 0.0072, 0.0134, and 0.0101, respectively). Overall survival was significantly lower among the patients with a negative expression of OPN than it was among those with a positive expression of OPN. The negative expression of OPN protein and the lower levels of OPN mRNA were statistically significant (P=0.0139). CONCLUSIONS: Decreased expression of OPN is considered to be a reliable indicator of tumor aggressiveness and clinical outcome in patients with ICC.

Adult↗
PubMed2004

The role of heat shock protein 27 expression in hepatocellular carcinoma in Japan: special reference to the difference between hepatitis B and C.

BACKGROUND: A recent report showed that heat shock protein (HSP)-27 expression was related to histological grade and survival of patients with hepatocellular carcinoma (HCC). AIMS: The aim of this study was to examine the effect of expression of HSP-27 on clinicopathological variables in Japanese patients with HCC. METHODS: An immunohistochemical study for HSP-27 was performed on 60 HCC cases using a monoclonal anti-HSP-27 antibody. We divided 60 patients into two groups, patients with a low expression of HSP-27 (n = 34) and those with a high expression of HSP-27 (n = 26). Forty patients tested positive for the hepatitis C virus (HCV) antibody and 20 tested positive for the hepatitis B surface antigen. RESULTS: There appeared to be no relationship between HSP expression and clinicopathologic factors and no differences were observed between the high expression group and the low expression group. In the hepatitis B virus (HBV) group (n = 20), HSP-27 expression correlated significantly with prognosis, disease-free survival (DFS) and overall survival. High expression was significantly associated with poor prognosis in the HBV group. In contrast, patients with a high expression tended to have a good prognosis in the HCV group (n = 40): DFS and overall survival. CONCLUSIONS: This study showed the possibility that HSP-27 plays different roles in HBV- and HCV-associated HCCs.

Adult↗
PubMed2004

Effect of dietary conjugated linoleic acid on liver regeneration after a partial hepatectomy in rats.

We examined the effect of dietary conjugated linoleic acid (CLA) on liver regeneration after a partial hepatectomy (PH) in Sprague-Dawley rats. PH was performed on rats fed a 0 or 1 wt.% CLA diet for 3 wk. Average liver weight in the CLA fed rat population was heavier than the control rat population at the time of PH and 1-d after PH. Conversely. CLA fed rats' liver weight was significantly lower than control rats at 7-d after PH. This suggests that dietary CLA reduced liver weight gain after PH. Dietary CLA did not affect serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) activities. However. CLA significantly reduced serum albumin levels at 1-d but not at 7-d after PH. 5-Bromo- and 5-iododeoxyuridine incorporation into hepatocytes 1-d post PH was lower in the CLA group. In conclusion, the data suggests that dietary CLA inhibits DNA synthesis after PH, which results in hepatocyte proliferation inhibition.

Alanine Transaminase↗
PubMed2004

cDNA microarray analysis in hepatocyte differentiation in Huh 7 cells.

The risk of xenozoonosis infections poses the greatest obstacle against the clinical application of a hybrid artificial liver support system (HALSS). Primary human hepatocytes are an ideal source for HALSS, but the shortage of human livers available for hepatocyte isolation limits this modality. To resolve this issue, we previously demonstrated the upregulation of hepatocyte-specific function by spheroid formation in polyurethane foam and by culturing with the histone deacetylase inhibitor, trichostatin A (TSA), in a human hepatoma cell line (Huh 7). In this article we analyze the gene expression profile using cDNA microarray (1281 genes) in spheroid formation or culturing with TSA in Huh 7 to determine the target genes in hepatocyte differentiation. In both the spheroid formation and in the culture with TSA, the Oct-3/4 transcription factor was upregulated more thantwofold, while the early growth response-1 (EGR-1) transactivator was downregulated less than 0.5-fold. These results indicate that expressions of Oct-3/4 and EGR-1 may be key factors in the induction of hepatocyte differentiation in Huh 7.

Cell Culture Techniques↗
PubMed2004

[Novel molecularly targeted peptides interfering the specific signal transduction of cancer metastasis].

Metastatic spread of tumor cells is one of the major risk factors affecting clinical prognosis. There are several sequential steps in this process including cell migration into the surrounding host tissue, infiltration and penetration into vessels for dissemination, attachment to capillary beds of distant organs, cell extravasation and subsequent growth in tissues. Some of the mechanisms involving normal cell migration observed during development are believed to be closely associated with the properties of tumor cell invasion. Thus, the so-called 'cell migration genes' may be frequently utilized by cancer cells to allow for metastatic spread of disease. We have isolated one of the candidate genes homologous to a C. elegans cell migration gene, that overexpressed specially in clinical cancer tissues. Based on in vitro analysis of the signal transduction, a novel peptide interfering the signals provides an attractive target for therapeutic intervention against the cancer invasion and metastasis.

Animals↗
PubMed2004

Muscle-targeted interleukin-12 gene therapy of orthotopic hepatocellular carcinoma in mice using in vivo electrosonoporation.

We developed a new potent nonviral gene transfer method into mouse muscles in vivo named "electrosonoporation." We tried in this report to treat murine orthotopic hepatocellular carcinoma (HCC) by muscle-targeted mouse interleukin-12 (mIL-12) gene transfer using in vivo electrosonoporation. I.m. administration of the mIL-12 gene with electrosonoporation elevated serum IL-12 and IFN-gamma and significantly prolonged the survival periods with both growth inhibition of orthotopic HCC and inhibition of spontaneous lung metastasis. The IL-12 gene therapy reduced the number of microvessels and induced more Mac-1-positive cells into HCC. These results show that muscle-targeted mIL-12 gene therapy for orthotopic HCC using in vivo electrosonoporation is very efficient and is thus promising for further clinical trial.

Animals↗
PubMed2004

[Pathophysiology and strategy for small-for-size graft syndrome after living-donor liver transplantation].

Small-for-size (SFS) graft syndrome is an important problem after living-donor liver transplantation in adults. Hemodynamic change is thought to be the main cause of graft injury. Excessive portal flow is associated with hepatic sinusoidal injury, and reduction of portal flow improves postoperative liver function. Increased venous outflow due to hepatic venoplasty or reconstruction of the middle hepatic vein decrease the risk of graft congestion. However, the intragraft acute-phase response remains unclear. Recent studies have revealed that downregulation of heat shock protein (HSP) may account for SFS graft injury, and induction of HSP may prevent SFS syndrome. On the other hand, derangement in the regulation of liver regeneration is recognized as another important factor. Further investigation of the regulatory mechanisms of liver regeneration in SFS grafts may suggest a strategy for the prevention and treatment of SFS syndrome. Successful transplantation of marginal-size liver grafts would improve outcome for recipients and increase the margin of safety for living donors.

Activins↗
PubMed2004

[Evaluation of acute hepatic failure treated at the Department of Medicine III, Kyushu University Hospital: indications for living-donor liver transplantation].

To evaluate indications for living-donor liver transplantation (LDLT), we examined 25 consecutive patients with acute hepatic failure admitted to the Department of Medicine III, Kyushu University Hospital between November 2001 and July 2004. These cases were diagnosed as fluminant hepatitis (n=13), severe-type acute hepatitis (n=11), or late-onset hepatic failure (n=1). Nine patients (36%) improved with conservative treatment (conservative treatment group), and the other 16 patients (64%) needed LDLT (LDLT indicated group). In the LDLT indicated group, 11 patients received LDLT, and 4 died because of lack of LDLT donors (n=3), or renal failure (n=1). The LDLT survival rate was 82% (9/11); two patients died due to hepatic infarction and brain edema, respectively. It is very important to predict whether a patient with acute hepatic failure belongs to the conservative treatment group or the LDLT indicated group on admission. Therefore, we analyzed variables that could influence prognosis, including, parameters of hepatic function and platelet counts on admission, and relative hepatic volume (%), which represents the ratio of hepatic volume measured by CT relative to standard hepatic volume calculated with body surface area. Univariate logistic analysis showed that relative hepatic volume, gammaglutamyl transpeptidase (gamma-GTP), alkaline phosphatase (ALP), and the ratio of direct bilirubin to total bilirubin (DB/TB) were significant predictors of survival (p < 0.05). Using these factors plus prothrombin time (PT) and total cholesterol, both of which were relatively significant predictors of survival (p < 0.2), we proposed a model for predicting the probability of survival by the stepwise method. Consequently, we proposed a model using four parameters: ALP, GGTP, PT, and relative hepatic volume (Volume) as shown below: p(%) = 1/(1+exp (-(-36.2375 + ALP x 0.0251 + gamma-GTP x 0.0102 + PT x 0.2558 + Volume 21.2158))) x 100. This model showed a significant correlation between prediction and consequence of survival (r2 = 0.7388, p = 0.0003). In conclusion, LDLT is an effective treatment for acute hepatic failure. The results of this study suggested that our model can adequately predict prognosis in the early phase of acute hepatic failure.

Adult↗
PubMed2003

Use of steatotic graft in living-donor liver transplantation.

BACKGROUND: The degree of fatty infiltration in hepatic grafts is known to be an important risk factor for primary graft nonfunction in cadaveric liver transplantation. However, the effect of hepatic steatosis in living-donor liver transplantation (LDLT) has not yet been well defined. In this study, we evaluated the impact that the degree of hepatic graft steatosis has on the outcome of LDLT. METHODS: Sixty consecutive donors and recipients who underwent LDLT between October 1996 and August 2001 at Kyushu University Hospital were the subjects of this study. The pathologic findings of the prereperfusion biopsy of the graft were classified into the following three groups according to the degree of macrovesicular steatosis: None (n=23), 0% steatosis; Mild (n=23), 0% to 20% steatosis; and Moderate (n=6), 20% to 50% steatosis. Liver function tests including total bilirubin (at postoperative day [POD] 7), the peak alanine aminotransferase (ALT) and prothrombin time (at POD 3), and both patient and graft survival were compared among the groups. Furthermore, we also compared the donor parameters including the peak ALT and total bilirubin (at POD 3) and the operative time, blood loss, and length of hospital stay after surgery. RESULTS: The 1-year patient and graft survival were comparable among the groups. The peak ALT was significantly higher in the Moderate group (606+/-641 IU/L) than in the None (290+/-190 IU/L) and Mild (376+/-296 IU/L) groups. Total bilirubin (POD 7) and prothrombin time (POD 3) were comparable among the groups. The donor parameters were comparable among the groups except for the fact that the donor body weight of the Mild and Moderate groups were significantly heavier (P<0.0001) than that of the None group. CONCLUSIONS: In conclusion, the use of a fatty liver graft up to the moderate level can be justified in LDLT, even though ischemia-reperfusion injury tends to be severe in such grafts.

Adult↗
PubMed2003

Hepatocyte growth factor and transforming growth factor beta1 contribute to regeneration of small-for-size liver graft immediately after transplantation.

Although the ability of the liver to regenerate to a predetermined size after resection made adult-to-adult living donor liver transplantation (LDLT) possible, there is little information regarding the growth regulatory mechanism for a small-for-size graft. Forty-one cases of LDLT were divided into two groups by graft volume to standard liver volume ratio (GV/SLV); small graft group (Group S, GV/SLV<40%, n=16) and non-small graft group (Group NS, GV/SLV>40%, n=25). The regeneration rate (GV at 1 week/harvested GV) and serum levels of hepatocyte growth factor (HGF), transforming growth factor-alpha (TGF-alpha) and transforming growth factor-beta1 (TGF-beta1) were compared between two groups. The regeneration rates in Group S were significantly higher than that of Group NS (217+/-12% and 178+/-10%, respectively, P<0.01). The serum HGF levels of Group S were significantly higher than those of Group NS on POD 1. The TGF-beta1 levels of Group S were significantly higher than those of Group NS on POD 3 and 5. The TGF-alpha levels were not different at any time points studied. These results indicate that a small-for-size graft retains the capacity to regenerate faster by modulation of expression pattern of HGF and TGF-beta1 immediately after LDLT. After the acceleration of the regenerative response by HGF, subsequent elevation of TGF-beta1 synergistically controls graft size, regulating uncontrolled proliferation of hepatocytes.

Adult↗