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Biomedical subjects

K Hirohashi

Publications and source records attributed to K Hirohashi.

At least 55 records · Page 3Linked to original sources
PubMed2000

Preoperative portal vein embolization improves prognosis after right hepatectomy for hepatocellular carcinoma in patients with impaired hepatic function.

BACKGROUND: Percutaneous transhepatic portal vein embolization (PTPE) increases the safety of subsequent major hepatectomy. The aim of this study was to determine the effect of PTPE on long-term prognosis after hepatectomy in patients with hepatocellular carcinoma (HCC). METHODS: Seventy-one patients with HCC underwent right hepatectomy between 1984 and 1998. Preoperative PTPE was performed in 33 patients (group 1) and was not used in 38 patients (group 2). Outcome after operation was compared between the groups. The patients were further divided according to the median tumour diameter (cut-off 6 cm) and indocyanine green retention rate at 15 min (ICGR15) (cut-off 13 per cent). RESULTS: The cumulative survival rate was significantly higher in group 1 than in group 2 in patients with an ICGR15 of at least 13 per cent. Tumour-free survival rates were similar in both groups. Of patients with tumour recurrence after right hepatectomy, those in group 1 were more frequently subjected to further treatment. CONCLUSION: Preoperative PTPE improves the prognosis after right hepatectomy for HCC in patients with impaired hepatic function, although it does not prevent tumour recurrence.

Adult↗
PubMed2000

Computed tomography during arteriography and arterial portography in small hepatocellular carcinoma and dysplastic nodule: a prospective study.

We studied the relationship between the findings of computed tomography during arteriography (CTA) and computed tomography during arterial portography (CTAP), and pathologic findings of 81 small nodular lesions (3 cm or less in diameter) in resected liver specimens. The 81 lesions consisted of 8 dysplastic nodule (DN) lesions, 23 well-differentiated hepatocellular carcinomas (early HCCs) and 50 moderately or poorly differentiated HCCs (advanced HCCs). We also performed standard computed tomography (CT), digital subtraction angiography (DSA), magnetic resonance imaging (MRI), and ultrasonography, and compared sensitivities with CTA, CTAP, or combination of CTA and CTAP with other imaging methods. Forty-four of the 50 advanced HCCs, 12 of the 23 early HCCs, and none of 8 DNs hyperattenuated with CTA and hypoattenuated with CTAP. The sensitivity for the early HCCs was significantly higher for CTA and CTAP in combination as compared with DSA or standard CT. The sensitivity for the advanced HCCs was significantly higher for CTA and CTAP in combination than with DSA. The sequential changes of the blood supply from the portal vein to the hepatic artery during the development of the HCCs were observed. Although CTA and CTAP in combination were useful for the distinction of advanced HCC from early HCC or DN, CTA and CTAP used in combination were not superior to CTA alone in the detection of such lesions.

Adult↗
PubMed2000

Factors influencing the outcome of Chiari pelvic osteotomy: a long-term follow-up.

We have reviewed 103 of 126 Chiari osteotomies carried out in our department between 1956 and 1987. The cases were graded radiologically, using the Japanese Orthopaedic Association (JOA) system, into a pre/early osteoarthritis (OA) group and an advanced OA group. In the pre/early group there were 86 hips. The mean follow-up was for 17.1 years (4 to 37). Preoperatively, 51 hips had an average JOA clinical score of 78.6+/-8.4 points and the final mean JOA clinical score was 89.4+/-12.5 points. Advanced degenerative change developed in 33.7% and one hip required a total replacement arthroplasty (TRA). Chiari osteotomy alone, without accompanying intertrochanteric osteotomy, was performed on 62 hips. For these the median survival time was 26.0+/-2.5 years, using as the endpoint progression to advanced OA. Differences in survivorship curves related significantly to the severity of the preoperative OA, the shape of the femoral head and the level of osteotomy. In the advanced OA group, we followed up 17 hips for a mean of 16.2 years (1 to 27). Before operation, the mean JOA clinical score in 13 hips was 63.2+/-7.9 points and the final score 84.0+/-12.0 points. TRA was eventually carried out on four hips. Our findings suggest that the Chiari osteotomy remains radiologically effective for about 25 years. The procedure is best suited to subluxated hips with round or flat femoral heads and early or no degenerative change. Intra-articular osteotomy can lead to osteonecrosis, and should be avoided. In hips with advanced OA, the Chiari procedure creates an acetabulum which facilitates later TRA, and may delay the need for this procedure in younger patients.

Adolescent↗
PubMed2000

Portal vein stenting to treat portal vein tumor thrombus in hepatocellular carcinoma.

Tumor thrombus in the portal vein is refractory to therapy and a serious negative prognostic factor in hepatocellular carcinoma. We describe herein the case of a patient in whom an expandable metallic stent was successfully employed to treat portal vein tumor thrombus by restoring blood flow. An expandable metallic stent was implanted in a patient with severe main portal vein stenosis caused by tumor thrombus protruding from the left portal vein branch. Immediately after stent placement, the stenotic lesion was effectively dilated, the portal blood flow restored, and portal hypertension relieved. Angiography, computed tomography, and doppler ultrasonography done 2 months after the stent placement revealed continued patency of the portal vein. Thus, intraportal placement of an expandable metallic stent appears to be an effective treatment for major portal vein tumor

Aged↗
PubMed1999

Clinical significance of prior hepatitis B virus infection in patients with hepatitis C virus-related hepatocellular carcinoma.

BACKGROUND: The effect of prior hepatitis B virus (HBV) infection on the clinicopathologic findings for patients with hepatitis C virus (HCV) RNA and hepatocellular carcinoma (HCC) is still unclear. METHODS: Of 59 patients who underwent liver resection for HCV-related HCC (</=2.0 cm in greatest dimension) without metastases between 1990 and 1997, 38 patients had anti-HB core antibody (anti-HBc) and did not have HB surface antigen in their sera (Group 1). Their clinicopathologic findings and outcomes after surgery were compared with those of the remaining 22 patients without anti-HBc (Group 2). RESULTS: The proportion of well-differentiated HCC was significantly lower in Group 1 than in Group 2 (P = 0.0214). The percentage of patients with cirrhosis was significantly lower in Group 1 than in Group 2 (P = 0.0228). The cumulative survival rate was significantly lower in Group 1 than in Group 2 (P = 0.0224). The risk ratio of anti-HBc for shorter survival time was 3.817. CONCLUSIONS: HCC more often developed before cirrhosis in patients with HCV RNA and anti-HBc than in patients positive for HCV RNA alone. Prior HBV infection was a risk factor for poor outcome after liver resection for patients infected with HCV.

Aged↗
PubMed1999

Possible contribution to hepatocarcinogenesis of X transcript of hepatitis B virus in Japanese patients with hepatitis C virus.

Serological research suggests that hepatitis B virus (HBV) and hepatitis C virus (HCV) are associated with the development of hepatocellular carcinoma (HCC). It is unclear how genes of hepatitis viruses participate in hepatocarcinogenesis in patients infected with HCV. We investigated the expression of hepatitis virus-related RNAs in resected liver from 51 patients with HCV antibodies (Ab) and without hepatitis B surface antigen (HBsAg). mRNA transcripts of the genes HBx, HBc, HBs, nonstructural (NS) region 3 of HCV, the 5'-untranslated region (UTR) of HCV, and the 5'-UTR of hepatitis G virus (HGV) were amplified by reverse-transcription polymerase chain reaction (RT-PCR) with specific primers for each gene. The HBx transcript was detected in 19 (37%) tumors and in 8 (16%) specimens of noncancerous tissues (P =.014). The NS3 gene of HCV was detected in 35 (69%) tumors and 41 (80%) noncancerous tissues. HGV RNA was detected in 3 tumors (6%). Patients with HBx transcripts were younger than patients without HBx transcripts (P =.012). HBx transcripts were detected in 3 (33%) of 9 well-differentiated HCCs, in 8 (31%) of 26 moderately differentiated HCCs, and in 8 (50%) of 16 poorly differentiated HCCs. Codon 130 (AAG) and codon 131 (GTC) of HBx were changed to ATG and ATC, respectively, in all HCCs with HBx transcripts. In conclusion, we found that the HBx gene was expressed in many HCCs; the gene might promote hepatocarcinogenesis in patients with HCVAb and without HBsAg, but HGV is not closely related to hepatocarcinogenesis in such patients.

Base Sequence↗
PubMed1999

Changes in erythrocyte deformability after liver resection for hepatocellular carcinoma associated with chronic liver disease.

Erythrocyte deformability is an important factor in the microcirculation. The deformability in patients with chronic liver disease is less than normal. We studied changes in erythrocyte deformability in 32 patients undergoing liver resection for hepatocellular carcinoma with underlying chronic liver disease to investigate whether the measurement of deformability gives information useful for postoperative management. We measured erythrocyte deformability as erythrocyte transit time (ETT) before and after resection, as well as the erythrocyte adenosine triphosphate level, mean corpuscular volume, mean corpuscular hemoglobin concentration, and indices of liver function. The 15-minute indocyanine green retention rate (ICGR15) was measured before resection. Correlations between the change in deformability and these values were evaluated, as was correlation with the scale of the operation and with the occurrence of postoperative complications. Mean ETT was higher in the patients before resection than in healthy volunteers. ETT was correlated with serum high density lipoprotein-cholesterol (p < 0.05). The incidence of postoperative complications was higher (p = 0.001) in the patients (group A) with ETT increased during the first 3 postoperative days by >/=1 SD of the mean of the preoperative value than in patients (group B) with less change. Of the 12 patients whose ICGR15 value was >/=20%, all 9 patients in group A had postoperative complications. The increase in ETT (decrease in erythrocyte deformability) is associated with the development of postoperative complications. The measurement of erythrocyte deformability gives information useful for postoperative management, and special monitoring for postoperative complications is necessary in patients with the increase soon after liver resection.

Adenosine Triphosphate↗
PubMed1999

Influence of histological inflammatory activity on regenerative capacity of liver after percutaneous transhepatic portal vein embolization.

Percutaneous transhepatic portal vein embolization (PTPE) produces regenerative hypertrophy in the nonembolized part of the liver, but the regenerative capacity after PTPE in patients with chronic hepatitis is unknown. We studied 34 patients with hepatocellular carcinoma and chronic hepatitis who underwent PTPE at the right portal vein. Hepatic lobular volumes were calculated by computed tomography before and 2 weeks after PTPE. The increase in left lobular volume was analyzed using a stepwise multiple regression method incorporating 11 factors: age; portal venous pressure; proportional volume of the right lobe; indocyanine green retention test; platelet count; serum levels of aspartate transaminase, alanine transaminase, total bilirubin, and albumin; and histological inflammatory grade and stage of fibrosis, according to the criteria of the International Association for the Study of the Liver recommended at their 1994 meeting. The median volume of the left lobe had increased from 405 to 554 cm3 (P < 0.0001) by 2 weeks after PTPE. Inflammatory grade was the only independent factor predicting regenerative hypertrophy (regeneration ratio (%) = 80.3 - 20.1 x grade; standard correlation coefficient = -0.566; P = 0.0014). Histological inflammatory activity was the essential factor regulating liver regeneration after PTPE in patients with chronic hepatitis.

Aged↗
PubMed1999

Hepatic cytochrome P450 is directly inactivated by nitric oxide, not by inflammatory cytokines, in the early phase of endotoxemia.

BACKGROUND/AIMS: Although the activity of the liver in metabolizing and eliminating various drugs decreases in endotoxemia, the mechanism remains to be elucidated. The generation of nitric oxide by the inducible type of nitric oxide synthase increases in endotoxemia. Nitric oxide readily reacts with heme proteins such as cytochrome P450 that metabolize various compounds, including steroids and eicosanoids. The purpose of this study was to determine the effect of nitric oxide on the function of hepatic cytochrome P450 in endotoxemic rats. METHODS: To determine the dynamic aspects of nitric oxide metabolism, hepatic levels of the inducible type of nitric oxide synthase and heme-iron nitrosyl complexes, and plasma levels of nitrite and nitrate were determined in rats before and after intravenous administration of lipopolysaccharide. Changes in the levels of P450 isoforms and testosterone hydroxylation activity in hepatic microsomes were also determined. To evaluate in vivo CYP3A2 activity, midazolam sleep time was measured. RESULTS: When lipopolysaccharide increased the hepatic inducible type of nitric oxide synthase and plasma levels of nitric oxide metabolites, the intensity of low-spin signal of electron spin resonance responsible for the ferric form of P450 decreased with a concomitant increase in heme-iron nitrosyl complexes in the liver. Lipopolysaccharide-related nitric oxide generation is followed by an early decrease in the levels of cytochrome P450 and of testosterone hydroxylation activity in liver microsomes. Midazolam sleep time was prolonged by lipopolysaccharide. All these early changes were prevented by the inhibitor of nitric oxide synthase, N(G)-iminoethyl-L-ornithine. Moreover, lipopolysaccharide suppressed the gene expression of CYP2C11 and CYP3A2. Decreases in levels of cytochrome P450 and their mRNAs were more pronounced at 24 h after LPS administration, but apparently they are NO-independent. CONCLUSIONS: These results suggest that lipopolysaccharide-induced modulation of cytochrome P450 may occur via the interplay of two different mechanisms and that, especially in the early phase, nitric oxide-dependent inhibition is more important.

Animals↗
PubMed1999

Relationship between multicentric occurrence of hepatocellular carcinoma and histology of noncancerous hepatic tissue in patients with chronic hepatitis C.

The relationship between multicentric occurrence of hepatocellular carcinoma (HCC) and the histology of noncancerous hepatic tissue was investigated in 252 patients infected with hepatitis C virus (HCV) and surgically treated for HCC. One type of multicentric HCC had at least one tumor consisting of well-differentiated HCC, together with moderately or poorly differentiated HCC located in a separate region. The other type had an area of well-differentiated component around HCC with less differentiation in all occurrences. Noncancerous hepatic tissues were assessed using a histologic activity index score. Serum alanine aminotransferase (ALT) activity, the concentration of type 4 collagen, the grading score (severity of active hepatitis), and the staging score (degree of fibrosis) were significantly higher in patients with multicentric HCCs than in those without them. Platelet count was significantly lower in patients with multicentric HCCs. The prevalence of multicentric HCCs increased as the grading score and staging score increased. On univariate analysis, a low platelet count and high grading and staging scores were risk factors for multicentric HCCs. A high ALT activity and a high concentration of type 4 collagen tended to be risk factors. On multivariate analysis, high grading score and high staging score were independent risk factors. These findings indicate that active hepatitis and extensive fibrosis are responsible for the development of multicentric HCCs. Measurement of platelet count, ALT activity, and the concentration of type 4 collagen, and histologic assessment of noncancerous hepatic tissue provide information useful for estimation of the potential for multicentric carcinogenesis.

Alanine Transaminase↗
PubMed1999

Correlation of clinicopathologic features of resected hepatocellular carcinoma with hepatitis C virus genotype.

Clinicopathologic findings in patients with hepatocellular carcinoma complicating hepatitis C virus and outcomes after liver resection were compared between different viral genotypes. One hundred and forty-seven patients with both anti-hepatitis C virus antibody and hepatitis C virus RNA in their sera underwent curative resection for hepatocellular carcinoma in our department between 1991 and 1997. Of these patients, 115 were infected with hepatitis C virus genotype 1b (group 1), and 32 were infected with 2a or 2b (group 2). Clinicopathologic findings and outcomes after operation were compared between the two groups. Alanine aminotransferase activity was significantly higher in group 2 than in group 1. Genotypes did not differ concomitantly with histopathologic features of the carcinoma or adjacent hepatic tissue. Although the tumor-free survival rate did not differ significantly between the two groups, recurrence was not detected during the period beyond 3 years following operation in group 2, while recurrences arose during that period in 16 group 1 patients, most of whom continued to manifest active hepatitis. In 7 of these 16 patients, the recurrent tumors were histologically multicentric in origin. The cumulative survival rate was significantly lower in group 1 than 2. Multivariate analysis indicated that genotype 1b was an independent risk factor for short survival. Patients infected with genotype 1b may have a relatively high risk of ongoing hepatocarcinogenesis and more aggressive progression of associated liver dysfunction, resulting in a poorer outcome than with other genotypes.

Aged↗
PubMed1999

Effects of continuous hepatitis with persistent hepatitis C viremia on outcome after resection of hepatocellular carcinoma.

The effect of persistent hepatitis C viremia on the outcome after resection of hepatocellular carcinoma (HCC) was investigated in 59 consecutive patients with a single small HCC (< or = 3.0 cm in diameter). The presence of serum hepatitis C virus (HCV) RNA was evaluated using a reverse transcription polymerase chain reaction method as well as a branched DNA probe method. Clinicopathologic findings were compared between patients with and without viremia and the risk factors for poor outcome were evaluated. Hepatitis C virus (HCV) RNA was not detected in the sera from 7 patients (group 1), but was detected in the sera from the other 52 patients (group 2). Alanine aminotransferase (ALT) activity was significantly higher in group 2 than in group 1. The proportion of patients with active hepatitis was significantly higher in group 2. In group 2, new HCC often developed after the operation and four patients died of liver dysfunction. HCV viremia, high ALT activity, high concentration of total bilirubin, and liver cirrhosis were related to recurrence after the operation. Multivariate analysis indicated that HCV viremia and high ALT activity were independent risk factors for recurrence of HCC. Continuous hepatitis with persistent HCV viremia worsened the outcome after the resection of HCC by causing new development of HCC and deterioration of liver function. In patients with HCV-related HCC, but without HCV viremia, satisfactory results can be expected after liver resection.

Aged↗
PubMed1999

A pancreatic anaplastic carcinoma of spindle-cell form.

A 56-yr-old man with complaint of abdominal pain and body weight loss was admitted to our hospital. Contrast-enhanced computed tomography on admission revealed a pancreatic tumor. Contrast-enhanced computed tomography 1 m.o. after admission revealed rapid growth of this tumor. We performed exploratory laparotomy with only a needle biopsy of the unresectable tumor because of extensive spread, including liver metastases. Further histological and immunohistochemical examination revealed that both the pancreatic tumor and the hepatic metastases featured malignant spindle-shaped cells. Despite radiotherapy, the patient died 40 d after laparotomy.

Biopsy, Needle↗
PubMed1999

Phenotypical and morphological alterations to rat sinusoidal endothelial cells in arterialized livers after portal branch ligation.

The hepatic sinusoids are preferentially supplied with portal venous blood and equipped with fenestrated endothelial cells that are distinct from capillary endothelial cells. We previously observed in rats that sinusoidal capillarization proceeded concurrently with arterial blood supply during hepatocarcinogenesis. This study aimed to clarify the inducing role of arterialization in sinusoidal capillarization by investigating phenotypical, morphological and functional alterations to sinusoidal endothelial cells (SECs) in arterialized rat livers induced by portal branch ligation. At one week, after massive hepatic necrosis following ligation, the livers were restored to their normal architecture without causing post-necrotic fibrosis. At 12-21 weeks, they exhibited a normal histology except for mild pericellular fibrosis which developed along sinusoids or between adjacent hepatocytes. SECs expressed factor VIII-related antigen and showed a decrease in the number of fenestrae and porosity, still lacking any basement membrane but further retaining the functional capacity for carmine dye uptake. Stellate cells, while occasionally associated with large amounts of collagen bundles, contained many lipid droplets and expressed no alpha-smooth muscle actin, indicating a quiescent property. Kupffer cells were commonly found within the sinusoids. The present results indicate that arterialization of the liver induces a partial (but not complete) transition of SECs into capillary-type endothelial cells, suggesting that arterialization might be one of the factors which induce sinusoidal capillarization in the development of hepatocellular carcinoma.

Animals↗
PubMed1998

Hepatocellular carcinoma with chondrosarcomatous variation: case report with immunohistochemical findings, and review of the literature.

Hepatocellular carcinoma with chondrosarcomatous variation is very rare. We report a case with the results of pathology examination, and review the literature. The patient, a 72-year-old may had a very large tumor in the liver revealed during follow-up for diabetes mellitus. The liver mass, which was 14 cm in diameter, was diagnosed as hepatocellular carcinoma by abdominal ultrasonography. Anterior segmentectomy and partial liver resection were performed. Histopathology examination revealed that the tumor consisted of two different components: the major one was hepatocellular carcinoma (HCC), which occupied most of the tumor; and a sarcomatous component, which occupied a smaller area, and included spindle-shaped cells with chondroscarcomatous variation. Intrahepatic metastases and tumor thrombi of HCC were also found in portal and hepatic veins. Investigations of the immunohistochemical localization of keratin (KRT), vimentin (VMT), and S-100 protein (S 100) were performed by the avidin-biotin complex method. Some of the spindle cells were immunohistochemically positive for both KRT and VMT, and the chondrosarcomatous cells were positive for S 100. These results strongly suggested that the sarcomatous lesion resulted from a sarcomatous change of HCC.

Aged↗
PubMed1998

Changes and results of surgical strategies for hepatocellular carcinoma: results of a 15-year study on 452 consecutive patients.

In an attempt to define better surgical strategies for patients with hepatocellular carcinoma (HCC), we conducted a retrospective analysis of 452 patients who underwent hepatic resection at our institute during a period of 15 years. The patients were divided into two groups: group A, comprising 188 patients who underwent hepatic resection before 1988, and group B, comprising 264 patients after 1989. These groups were compared clinicopathologically. The percentage of patients with Child's A disease but without cirrhosis, in group A was lower. The diameter of the resected tumor was larger in group A, and major hepatic resections and curative operations were more frequently performed in group A. In group B, there was less blood loss, the specimen weighed less, and the hospital mortality was lower. Although the tumor-free survival rates were similar between the two groups, the survival rate in group B was significantly better. While even minor hepatic resection accompanied by a lower rate of surgical margin-free surgery has contributed to making hepatic resection safer, it has not improved the tumor-free survival rate. Conversely, recent advances in imaging modalities used during follow-up for the early detection of recurrence and for planning multimodality treatment have contributed to increasing the survival rate.

Carcinoma, Hepatocellular↗
PubMed1998

Suppressive effect of the angiogenesis inhibitor TNP-470 on the development of carcinogen-induced hepatic nodules in rats.

Tumor metastasis can be prevented by inhibiting angiogenesis. In the present study, we have demonstrated that the angiogenesis inhibitor TNP-470 also suppresses the development of primary hepatic nodules. Hepatocarcinogenesis was performed by the feeding of 2-acetylaminofluorene to hepatectomized rats during 8-14 weeks of age. Predominantly arterial-to-portal circulation and sinusoidal capillarization were determined by the staining of nodules with arterially infused ink and immunostaining for factor VIII-related antigen, respectively. Intraperitoneal administration of 30 mg/kg b.w. of TNP-470 twice a week significantly reduced the number of hepatic nodules. Among the nodules, hyperplastic nodules stained with ink, atypical hyperplastic nodules and hepatocellular carcinoma, all of which possess structurally altered sinusoidal endothelial cells or capillary-type endothelial cells, were dramatically decreased in number. Suppression was observed equally in nodules of all sizes. TNP-470 was more effective when administered during 8-20 weeks than during 14-26 weeks. In contrast, ink-non-stained hyperplastic nodules, which have normal sinusoidal endothelial cells, were not affected at all. The present results indicate that TNP-470 suppresses the development of primary hepatic nodules whose microvessels are capillaries or transitional forms from sinusoids to capillaries.

2-Acetylaminofluorene↗