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Biomedical subjects

K Hirohashi

Publications and source records attributed to K Hirohashi.

At least 73 records · Page 4Linked to original sources
PubMed1998

Clinicopathological criteria for multicentricity of hepatocellular carcinoma and risk factors for such carcinogenesis.

Multicentric occurrence is an important characteristic of hepatocellular carcinoma. We evaluated clinicopathological criteria for multicentric hepatocellular carcinoma and identified risk factors for such carcinogenesis. Subjects were 251 consecutive patients undergoing liver resection for hepatocellular carcinoma. One kind of multicentric hepatocellular carcinoma had at least one tumor consisting of well-differentiated hepatocellular carcinoma, together with moderately or poorly differentiated hepatocellular carcinoma located in a separate region. The other kind had an area of well-differentiated component around hepatocellular carcinoma with less differentiation in all occurrences. The outcome of patients with tumors classified in this way was studied. Univariate and multivariate analyses were done to identify risk factors for multicentric hepatocellular carcinoma. The cumulative survival rate was significantly higher in patients with multicentric hepatocellular carcinoma than in patients with hepatocellular carcinoma associated with intrahepatic metastasis. Analysis by Cox's proportional hazard model showed that multicentricity was not a factor in the outcome. The risk of multicentric occurrence increases with progression of chronic liver disease. Univariate analysis showed hepatitis C virus marker and hepatitis B core antibody to be risk factors. By multivariate analysis, the odds ratio for multicentric occurrence in patients infected with hepatitis C virus and with serum hepatitis B virus core antibody compared with patients without either hepatitis C virus or hepatitis B virus was 10.86. This ratio in patients with hepatitis C virus alone was 4.30. These criteria for multicentric hepatocellular carcinoma seem to be clinically useful. Hepatitis C virus infection with or without former infection by hepatitis B virus is a strong risk factor for multicentric hepatocarcinogenesis.

Aged↗
PubMed1998

Hyperplastic foci in chronic liver disease: their proliferative activity assessed by nucleolar organizing region.

In the cirrhotic and precirrhotic liver, there may be small foci with increased cellularity and amphophilic cytoplasm. These are microscopic lesions that do not form macroscopically detectable nodules, which differ from the macroscopically apparent nodules of dysplastic nodules. In the present study, we assessed the proliferating activity of 12 hyperplastic foci in 11 patients with cirrhosis or chronic hepatitis, by staining for agyrophilic nucleolar organizing regions (AgNOR). The mean AgNOR count per nucleus in the hyperplastic foci ranged from 0.96 to 1.36 (mean, 1.13; SD 0.12), and from 0.81 to 1.06 (mean, 0.94; SD 0.08) in the controls. The AgNOR count in the hyperplastic foci was significantly higher than that in the controls (P < 0.01). Small hyperplastic foci show increased proliferative activity. Further study on these foci is required to clarify their relation to hepatocarcinogenesis.

Adult↗
PubMed1998

Serous cystadenoma of the pancreas with atypical cells. Case report.

CONCLUSION: Serous cystadenomas of the pancreas may have the biologic ability to undergo malignant transformation. BACKGROUND: It is generally recognized that: serous cystadenomas of the pancreas are benign and that their malignant potential is low. METHODS: A serous cystadenoma of the pancreas was resected from a 53-yr-old woman. In the central portion of the tumor, papillary structures were found on the cyst wall. Immunohistologic studies using antibodies to carbohydrate antigen 19-9, carcinoembryonic antigen, and proliferating cell nuclear antigen were performed to determine the malignant potential of this tumor. RESULTS: On histology, most tumor cells were positive for periodic acid-Schiff but were negative for periodic acid-Schiff after diastase digestion and Alcian blue, a staining pattern typical of serous cystadenomas. The cells found in the papillary structure of the cyst wall were mildly atypical. These cells were stained with antibodies to carbohydrate antigen 19-9, carcinoembryonic antigen, and proliferating cell nuclear antigen, indicating that the cells comprising the papillary structure were proliferating more rapidly than cells in other parts of the tumor and strongly suggesting that the cells are premalignant.

CA-19-9 Antigen↗
PubMed1998

Effect of alcohol abuse on polyamine metabolism in hepatocellular carcinoma and noncancerous hepatic tissue.

BACKGROUND: Alcohol abuse is a risk factor for hepatocellular carcinoma (HCC) and the recurrence of HCC after resection. We therefore investigated polyamine metabolism, which is important in cell proliferation, HCC tissue, and noncancerous hepatic tissue. METHODS: In 30 patients who underwent liver resection for HCC, 13 patients had drunk 86 gm or more ethanol per day for at least 10 years (group 1), whereas the remaining 17 patients were nondrinkers or occasional drinkers (group 2). The control subjects were five patients who did not have liver disease or abuse alcohol. Tissue ornithine decarboxylase (ODC) activity and polyamine concentrations were measured. RESULTS: ODC activity in the HCC tissue was significantly higher in group 1 than in group 2. ODC activity in noncancerous tissue was significantly higher in group 1 than in group 2 and the control group. The ratio of spermidine/spermine in the HCC tissue was significantly higher in group 1 than in group 2. The ratio in noncancerous tissue was significantly higher in groups 1 and 2 than in the control group. CONCLUSIONS: Alcohol abuse affects polyamine metabolism, which influences the grade of malignancy of HCC. Hepatic tissue has greater potential for carcinogenesis in patients with chronic liver disease and alcohol abuse than in patients without them.

Aged↗
PubMed1998

[Percutaneous transhepatic portal vein embolization for hepatocellular carcinoma].

We report on the significance of percutaneous transhepatic portal vein embolization (PTPE) for hepatocellular carcinoma based on the results in 111 patients who underwent PTPE in our hospital. All patients tolerated the procedure without major complications, although transient elevations in serum transaminase levels were noted. Immediately after PTPE, the portal pressure increased. Portal venous flow at the main portal trunk decreased, but the flow in the nonembolized part of the liver increased. PTPE produced regenerative hypertrophy in the nonembolized part of the liver, which was mainly predicted by the volume of the embolized area and the morphological score of the hepatitis or cirrhosis. PTPE increased the safety of subsequent hepatectomy and expanded the indications for hepatectomy. PTPE is also useful as a type of multiplicative therapy for hepatocellular carcinoma.

Carcinoma, Hepatocellular↗
PubMed1998

Delayed hepatic resection for ruptured hepatocellular carcinoma.

BACKGROUND: Although transcatheter arterial embolization is advocated as initial therapy for ruptured hepatocellular carcinoma (HCC), hepatic resection is necessary for cure. The effectiveness of delayed hepatic resection for ruptured HCC was determined. METHODS: The records of 10 patients who underwent delayed hepatic resection for ruptured HCC were reviewed. RESULTS: All patients were men, and the mean age was 63 years. For hemostasis, transcatheter arterial embolization was performed in three patients, whereas in the other patients bleeding stopped without special procedures. Mean interval from rupture to hepatic resection was 74 days. Liver function test results before hepatic resection were almost normal. Trisegmentectomy in one and bisegmentectomy in four patients were performed, whereas minor hepatic resection was performed for four extrahepatic HCCs. There were no operative or hospital deaths. Four patients had cirrhosis. The mean tumor diameter was 7.5 cm. Of seven patients with recurrence, two with dissemination had tumors that ruptured on the inferior aspect of the liver. The 1- and 3-year survival rates were 77% and 48%, respectively. CONCLUSIONS: Because delayed hepatic resection for ruptured HCC was safe and compared similarly with that for other patients who underwent resection for HCC, it should be used. However, when HCC ruptures in an inferior location, recurrence of tumor as dissemination is likely.

Adult↗
PubMed1997

High malignancy of hepatocellular carcinoma in alcoholic patients with hepatitis C virus.

BACKGROUND: We investigated the relationships between alcohol consumption, the degree of malignancy evaluated histologically, and tumor-free survival rates. METHODS: In 80 male patients with the hepatitis C virus and small hepatocellular carcinomas (diameter of main tumor, 3.0 cm or less), 38 patients had drunk 86 gm or more of ethanol per day for at least 10 years until the detection of hepatocellular carcinoma (group 1), whereas the remaining 42 patients were nondrinkers or occasional drinkers (group 2). RESULTS: Differences in the results of liver function tests between the groups were not statistically significant. The operative methods used in the groups were comparable. The proportion of well-differentiated hepatocellular carcinoma was lower in group 1 than in group 2 (p < 0.0001). The prevalences of extracapsular invasion, portal tumor thrombi, and intrahepatic metastasis were higher in group 1 than in group 2 (p = 0.0085, p = 0.0319, and p = 0.0428, respectively). The tumor-free survival rate after operation was lower in group 1 than in group 2(p = 0.041 by the log-rank test; p = 0.032 by the generalized Wilcoxon test). CONCLUSIONS: These findings indicate that in group 1, even though tumors were small, the carcinomas were advanced and the outcomes after surgery were poor, suggesting that alcohol affects the grade of malignancy of this disease.

Aged↗
PubMed1997

Poor association of GBV-C viremia with hepatocellular carcinoma.

BACKGROUND/AIMS: The role of the hepatitis GB virus C in chronic liver disease is unclear. The clinical findings, results of laboratory tests, pathological findings, and outcome after liver resection for hepatocellular carcinoma in patients infected or not infected with GB virus C were compared. METHODS: Serum samples from 213 patients were tested for hepatitis B virus, hepatitis C virus, and GB virus C. Of the 213 patients, 159 had hepatitis C viral RNA or antibodies (group 1), seven had both hepatitis C viral RNA or antibodies and hepatitis B surface antigen (group 2), 25 had hepatitis B surface antigen (group 3), and 22 did not have hepatitis C viral RNA, hepatitis C antibodies, or hepatitis B surface antigen (group 4). RESULTS: GB virus C RNA was detected in 12 of the 213 patients. Of the 12 patients, 11 were in group 1 and one was in group 4. There were no patients with hepatocellular carcinoma associated with GB virus C RNA alone. In groups 1 and 4, there were no differences in clinical findings, results of laboratory tests, pathological findings, or outcome after surgery in patients with and without GB virus C RNA. CONCLUSIONS: These results indicate a poor association of GB virus C viremia with hepatocellular carcinoma. We did not find clinically significant interaction between hepatitis C virus and GB virus C.

Adult↗
PubMed1997

Analysis of hyperplastic foci in livers with hepatocellular carcinomas by flow cytometry and AgNOR staining.

The phase S ratio in cell cycles were analyzed in livers with hyperplastic foci (HPF) and in livers without HPF by nuclear DNA determinations using flow cytometry, and by staining with argyrophilic proteins of the nucleolar organizer region (AgNOR). Flow cytometric analysis was done on 50 fresh frozen specimens of livers resected from 50 patients with hepatocellular carcinoma (HCC). Paraffin sections from the same patients were analyzed using AgNOR staining. There were 25 cases each with and without HPF. We examined the stage of fibrosis and the grade of inflammatory activity according to the modified Scheuer and Desmet scale. The incidence of HCC recurrence among these patients was also studied. The average phase S ratio of the livers of the patients with HPF was 6.5 +/- 3.2%, and that of the livers of the patients without HPF was 4.0 +/- 2.5%. The ratio differed significantly between the two groups (P < 0.01). The average AgNOR score for HPF lesions of the HPF-positive cases was 1.60 +/- 0.34, that for non-HPF lesions in the HPF-positive cases was 1.29 +/- 0.12, and that for the HPF-negative cases was 1.19 +/- 0.14. Significant differences were found between the average AgNOR scores for HPF lesions of the HPF-positive cases and the non-HPF lesions of the HPF-positive cases (P < 0.01), as well as between the non-HPF lesions in the HPF-positive cases and the HPF-negative cases (P < 0.05). Severe fibrosis (stage 3) and cirrhosis (stage 4) were found in 76% of HPF-positive cases and 48% of HPF-negative cases. The livers of HPF-positive patients were significantly more cirrhotic than those of HPF-negative patients (P < 0.05). The association between HPF and the inflammatory grade was not significant (P > 0.05). The incidence of HCC recurrence among HPF-positive cases was significantly higher than that among the HPF-negative cases (P < 0.05). The average phase S ratio of the recurrent HPF-positive patients was 7.48 +/- 3.48%, significantly higher than that of HPF negative cases (5.57 +/- 3.06%, P < 0.05). Hyperplastic foci of the liver was shown to be a highly proliferative lesion. The proliferative activity of the non-HPF lesions in the HPF-positive patients was also higher than that of the HPF-negative patients. Hyperplastic foci tended to be present in cirrhotic livers, but it was not associated with the grade of inflammatory activity of the liver. Hyperplastic foci may represent an important predictor of recurrence after hepatic resection.

Adult↗
PubMed1997

Magnetic resonance cholangiography in hepatolithiasis.

OBJECTIVES: Our objective was to examine the usefulness of magnetic resonance cholangiography in hepatolithiasis. METHODS: Ten patients with hepatolithiasis were studied by ultrasonography, computed tomography, direct cholangiography, and magnetic resonance cholangiography to detect stones and to determine the morphological features of the bile ducts. In nine patients who underwent surgery, dilation and stenosis of the bile ducts were confirmed by intraoperative cholangioscopy, pathology, or both. RESULTS: Stones were demonstrated in seven patients by ultrasonography, in eight by computed tomography, in seven by direct cholangiography, and in all by magnetic resonance cholangiography. The locations of stones were identified in four patients by ultrasonography, in seven by computed tomography, in six by direct cholangiography, and in nine by magnetic resonance cholangiography. Among nine patients with dilation of the bile ducts, the dilation was shown by ultrasonography in seven, by computed tomography in eight, by direct cholangiography in six, and by magnetic resonance cholangiography in eight. Among seven patients with stenosis of the bile ducts, this stenosis was shown by direct cholangiography in four and by magnetic resonance cholangiography in six. Ultrasonography and computed tomography did not show the stenosis. Sensitivity for detection of biliary stenosis was significantly higher in magnetic resonance cholangiography. CONCLUSIONS: This study shows that magnetic resonance cholangiography not only detects stones, but can also delineate detailed information on the bile ducts, which is useful in the planning of treatment for hepatolithiasis.

Adult↗
PubMed1997

Concentrations of bile and serum endotoxin and serum cytokines after biliary drainage for acute cholangitis.

Endotoxin contributes to cholangitis. We measured concentrations of bile and serum endotoxin and serum cytokines after biliary drainage for obstructive jaundice with or without acute cholangitis. Patients who underwent percutaneous transhepatic cholangiodrainage (PTCD) in 1995 were classified as having acute cholangitis (group A; n = 11), having a history of acute cholangitis (group B; n = 5), or not having a history of acute cholangitis (group C; n = 13). Bile endotoxin was positive (above the cut-off value) in all patients in groups A and B, and in five patients in group C. The mean concentration of bile endotoxin was significantly higher in groups A and B than in group C. After PTCD, the bile endotoxin level decreased more slowly in group A than in the other groups. Before PTCD, the mean serum levels of IL-1 receptor antagonist (IL-1ra), IL-6, and IL-8 were higher in group A than the other groups. The serum levels of IL-1ra and IL-6 before PTCD were significantly higher when the acute cholangitis was more severe. The mean serum levels of cytokines increased just after PTCD and then decreased. In group A, the serum level of IL-6 at 5 h after PTCD was significantly correlated to the endotoxin level in bile at this time. Increases in cytokines may participate in the pathophysiological changes of acute cholangitis. Biliary drainage for acute cholangitis causes improvement by decreasing the bile endotoxin level addition to decreasing bile-duct pressure, thereby preventing excess production of inflammatory cytokines.

Acute Disease↗
PubMed1996

Analysis of 69 patients with amebic liver abscess.

All 69 patients with amebic liver abscess that we treated in 1981-1992 were studied retrospectively. Men predominated by a 10:1 ratio. Of our 227 patients with amebiasis, some 30% yearly had liver involvement. The incidence peaked in 1988, decreasing later but increasing again in 1992. Most patients were 30-50 years old, the overall mean age being 45 years (range, 22-79), and decreasing with time. Patients with the related factors of travel abroad, positive results of a test for Treponema pallidum hemagglutination, and homosexuality have increased in number in recent years. Fever, abdominal pain, and hepatomegaly were the most frequent findings, and 39 patients had neither bloody stools nor diarrhea. Only 8 patients had had amebiasis previously. A solitary abscess in the right lobe of the liver was found in 40 patients. Entamoeba histolytica was found in the stool of 31 patients and in the pus of 39 patients. Sixty-one patients had positive results for an amebic serological test(s). The abscesses ruptured into the peritoneal cavity in 4 patients. All patients received metronidazole. Percutaneous or surgical drainage (or both) was done in 62 patients. The outcome was good, with 1 exception, and only 2 patients had recurrences.

Adult↗
PubMed1996

Characteristic histologic features of human hepatocellular carcinoma with mutant p53 protein.

To characterize hepatocellular carcinoma (HCC) cells with mutant (m) p53 protein histologically, we examined 68 main nodules and 20 accessory lesions of 72 patients with HCC who underwent hepatic resection between October 1990 and September 1993. Some sections were fixed in periodate-lysine-paraformaldehyde, embedded in OCT compound, and stained with the mouse monoclonal antibody PAb1801 to m-p53 protein by the immunoperoxidase technique with avidin-biotin complexes. Other sections were fixed in 20% buffered formalin, embedded in paraffin, and stained with the mouse monoclonal antibody DO-1 to m-p53 protein in the same way. Lesions in which cells had nuclei stained for m-p53 protein were defined as being positive for the protein; 25 of the 68 main nodules and 14 of the 20 accessory lesions were positive. Large main nodules were more likely to be positive than small ones. Microscopic examination showed that a larger proportion of poorly differentiated main nodules than well differentiated nodules were positive. Larger proportions of main nodules with extracapsular invasion, septa, portal thrombi, or intrahepatic metastases were positive than main nodules without these features. Accessory lesions that seemed to be metastatic were almost all positive, but few accessory lesions that seemed to be of multicentric occurrence were positive. Our results suggest that lesions with m-p53 protein had a high grade of malignancy and metastasized readily.

Adult↗
PubMed1996

Sinusoidal capillarization and arterial blood supply continuously proceed with the advance of the stages of hepatocarcinogenesis in the rat.

Hepatocellular carcinoma (HCC) is supplied only with arterial blood and has capillaries instead of sinusoids, unlike the normal hepatic tissue. In order to reveal the sequential changes of sinusoidal structure and blood supply during hepatocarcinogenesis, we examined hyperplastic nodules (HPN), atypical hyperplastic nodules (AHPN) and HCC in F344 rats fed with 2-acetylaminofluorene for 25-35 weeks. The extent of arterial blood supply and the degree of sinusoidal capillarization were assessed by the staining of hepatic nodules with arterially infused ink and by immunohistochemical and ultrastructural analyses of the sinusoids, respectively. The proportion of arterialized nodules was 47% in HPN, 57% in AHPN and 85% in HCC, which indicates that arterialization begins at the stage of HPN and a few HCC still receive portal venous blood. The proportion of Factor-VIII-related antigen (F-VIII)-positive nodules was 25% in HPN, 40% in AHPN and 100% in HCC. Non-arterialized nodules did not express F-VIII, while some F-VIII-negative nodules were already arterialized. Electron microscopically, non-arterialized HPN exhibited normal features of sinusoids, while arterialized HPN showed disappearance of Kupffer cells and partial defenestration of sinusoidal endothelial cells. In non-arterialized and arterialized AHPN, basement membrane became continuous and lipid droplet-containing stellate cells were no longer seen. In HCC, endothelial fenestrae were diminished and basement membrane became thick. The present study has demonstrated that sinusoids are altered in the following order as hepatocarcinogenesis advances from HPN to HCC; onset of arterialization and decrease of endothelial fenestrae, expression of F-VIII by endothelial cells, disappearance of Kupffer cells, diminution of lipid droplets in stellate cells and thickening of basement membrane.

Animals↗
PubMed1996

Immunohistochemistry and angiography in adenomatous hyperplasia and small hepatocellular carcinomas.

The sinusoidal structure and blood supply of 38 liver nodules less than 2 cm in diameter were investigated. There were 18 cases of adenomatous hyperplasia (AH) and 20 cases of hepatocellular carcinoma (HCC). Growth pattern, encapsulation and vascularity were examined, and immunohistochemistry performed for factor VIII related antigen (factor VIII), type IV collagen (collagen IV), laminin and CD68. There were significant differences between AH and small HCC, except for the expression of CD68. There were differences in tumor size, vascularity and the components of the basement membrane between AH and small, well differentiated HCC. The cases of AH were supplied by the portal system and maintained the sinusoidal structure, but small well-differentiated' HCC were supplied by a mixture of portal and arterial vessels. In spite of their small size, moderately and poorly differentiated HCC had capillary and were supplied by branches of the hepatic artery.

Aged↗
PubMed1996

Mechanism that regulates nitric oxide production by lipopolysaccharide-stimulated rat Kupffer cells.

Mechanism that regulates nitric oxide (NO) production by stimulated Kupffer cells was studied. Lipopolysaccharide (LPS) stimulated NO production by primary-cultured Kupffer cells in a time- and dose-dependent manner. Twenty-four h after incubation with 1 microgram/ml of LPS, the nitrite concentration in the culture medium increased from 2.87 +/- 1.4 to 73.6 +/- 6.9 nmol/ml. NO production started to increase around 6 h after adding LPS and reached a maximum within 24 h. NO production was inhibited by 0.3 mM of NG-monomethyl-L-arginine and was reversed by adding 3 mM of L-arginine. When incubated with 1 microgram/ml of LPS for 24 h, NO synthase activity in Kupffer cells increased from 0.164 +/- 0.035 to 3.16 +/- 0.11 nmol/min/mg protein. Dexamethasone and prednisolone significantly inhibited the induction of NO synthase and NO production in Kupffer cells. Expression of mRNA for inducible type of NO synthase (iNOS) started to increase around 4 h after adding LPS (1 microgram/ml) and reached a maximum by about 20 h. The enhanced expression of iNOS mRNA was also suppressed by 1 microM dexamethasone. On the other hand, calcium ionophore A23187 significantly enhanced the induction of NO synthase and iNOS mRNA expression in LPS-stimulated Kupffer cells. In addition, a tyrosine kinase inhibitor, genistein (100 microM), significantly inhibited NO production by LPS-stimulated Kupffer cells. Neither phorbol 12-myristate 13-acetate, dibutyryl cAMP, indomethacin nor a protein kinase C inhibitor H-7 affected NO production by Kupffer cells. These results suggested that iNOS mRNA expression, NO synthase activity and NO production increased in LPS-stimulated Kupffer cells by a glucocorticoid-inhibitable mechanism and that Ca2+ and tyrosine phosphorylation might play important roles in LPS-dependent induction of NO synthase.

Animals↗
PubMed1995

The ultrastructure, kinetics and intralobular distribution of apoptotic hepatocytes after portal branch ligation with special reference to their relationship to necrotic hepatocytes.

Apoptosis was originally defined as shrinkage necrosis, as a distinct mode of cellular death from coagulative necrosis in the rat liver lobes after portal branch ligation. To reveal the functional role of the apoptosis of hepatocytes in the volume reduction and recovery of normal hepatic architecture in portal-deprived liver lobes, we ligated the portal vein branch supplying the left and median liver lobes in Wistar rats. The liver lobes were perfusion-fixed with glutaraldehyde solution via the proximal site of the ligated portion of the portal vein on Days 1, 2, 4, 7 and 14 after operation and examined light and electron microscopically. On Day 2 after ligation, massive necrosis of hepatocytes occurred in the central to intermediate zones of the liver lobule, and apoptotic hepatocytes were observed in the boundary region between necrotic and normal areas. Such necrotic area-associated apoptosis of hepatocytes was most frequent on Day 2, declining thereafter. The sequential changes of the cell organelles in apoptotic hepatocytes were distinct from those in necrotic hepatocytes. On Day 7, when necrotic areas had almost disappeared the apoptosis of hepatocytes occurred mostly between intact hepatocytes in the "combined hepatic cell cords" which included no obvious sinusoidal lumen between hepatic cell cords. Such necrotic area-nonassociated apoptosis began to increase in frequency on Day 4, reached a peak on Day 7 and was gone by Day 14, when normal hepatic architecture was recovered. The present study suggests that both necrotic area-associated and non-associated apoptosis of hepatocytes may be induced by mild ischemia and contribute in part to the volume reduction of ligated liver lobes. It further reveals that the necrotic area-non-associated apoptosis of hepatocytes plays a role in reconstructing the architecture of hepatic cell cords after necrotic hepatocytes have undergone dissolution in the liver lobule.

Animals↗