Capsules (8 x 30 mm) of technetium-99m pertechnetate were designed for measurement of portal blood flow. Most of the radionuclide entered the superior mesenteric vein. The capsule was taken orally and monitored with a collimator for scintigraphy until it reached the small intestine, when a magnetic field completed an electrical circuit in a sensor, burning a thread, releasing a spring, and discharging the preparation. A study in crab-eating monkeys (Macaca fascicularis) showed that the radionuclide in the small intestine circulated through the superior mesenteric vein to the portal vein and liver. Portal scintigraphy through the small intestine could be analysed in the same way as per-rectal portal scintigraphy, in which blood flow mostly from the inferior mesenteric vein is evaluated. A study of four volunteers showed that, after the radionuclide was released, it circulated through the superior mesenteric vein to the portal vein and liver. Use of a capsule enclosing a radioisotope was possible, and the procedure seemed to be safe. The use of the per-small intestine method plus the per-rectal method should give more accurate results than either method used alone, because the haemodynamics of both the superior and inferior mesenteric vein would be reflected.

Administration, Oral↗

PubMedDate not supplied

Significance of blood flow in the inferior and superior mesenteric veins for the formation of oesophageal varices.

The degree of involvement of blood flow in the superior mesenteric vein and inferior mesenteric vein in the formation of oesophageal varices is not known. We have developed a method by which the contributions of these veins to portal blood flow can be evaluated simultaneously in a relatively non-invasive way. An enteric-coated capsule containing [123I]iodoamphetamine (IMP) is given by mouth and 3 h later [123I]IMP is instilled into the rectum. The data obtained are treated by computer to calculate the portal shunt index via the inferior and superior mesenteric veins. In chronic hepatitis and cirrhosis, when varices were absent, the difference in these indices was not significant. In the presence of varices, the portal shunt index via the inferior mesenteric vein was significantly higher than that via the superior mesenteric vein. It was suggested that the contribution of blood flow in the inferior mesenteric vein the portal/splenic axis is important in the formation of varices.

Amphetamines↗

PubMedDate not supplied

Effect of drinking on the outcome of cirrhosis in patients with hepatitis B or C.

Survival rates were calculated for 251 patients with cirrhosis of the liver but without hepatocellular carcinoma, primary biliary cirrhosis, or autoimmune cirrhosis who underwent laparoscopy during the past 21 years at the authors' hospital. The survival rates were calculated by the Kaplan-Meier method. Stored serum was assayed for hepatitis B surface antigen (HBsAg) and antibodies to the hepatitis C virus (HCV). Patients with alcoholic cirrhosis had significantly better survival rates than patients with HBsAg, HCV, or both. Differences in survival rates between patients with hepatitis B and C were insignificant. In both groups, habitual drinkers had a significantly lower survival rate. The results suggested that alcohol accelerates liver damage in subjects with viral hepatitis.

Adult↗

PubMedDate not supplied

Detection of the preneoplastic lesions of small hepatocellular carcinoma in cirrhotic livers.

To identify the preneoplastic lesions of hepatocellular carcinoma and the fine structure of preneoplastic hepatocytes, we studied proliferative conditions in cirrhosis of the liver. In all, 46 foci of cellular alteration (FCA), three regions of adenomatous hyperplasia (ADH), and 21 small hepatocellular carcinomas (sHCC) were studied by published criteria for sHCC and by the proliferative activity of the lesions as examined with monoclonal antibodies against DNA polymerase alpha and proliferating cell nuclear antigen. The four patients with FCA composed of basophilic hepatocytes were classified by the criteria as having sHCC; cells had features similar to those of sHCC. Two of these four patients with FCA were found to have HCC several years later. The number of hepatocytes stained for proliferating cell nuclear antigen was 72 and 81 per 1000 hepatocyte nuclei in the two patients who developed HCC. In one of the three patients with ADH, a sHCC was found 1 year later, and dysplastic hepatocytes from the region of ADH in this patient had features similar to those of HCC cells by light and electron microscopy. In this patient, the number of hepatocytes stained for DNA polymerase alpha was 452 per 1000 nuclei. Therefore, FCA and ADH might be preneoplastic lesions of sHCC in cirrhosis of the liver. Preneoplastic hepatocytes seem to be small cells with basophilic cytoplasm, with a large nucleus to cytoplasm ratio, finely indented nuclei with a smaller amount of condensed chromatin than normal, and poorly to moderately developed organelles.

Aged↗

PubMedDate not supplied

Relationship between endotoxin antibody levels and portal systemic shunt evaluated by per-rectal portal scintigraphy.

The reasons for the high frequency of endotoxaemia in cirrhosis, whether poor liver function or abnormal portal circulation, are not known. Accurate measurement of endotoxin itself is difficult. Instead, in this study an enzyme-linked immunosorbent assay was used to measure levels of IgA, IgG and IgM antibodies to endotoxin in patients with chronic liver disease and underlying hepatic viral infection. The relationships between the results and clinical symptoms or the presence of a portal systemic shunt were investigated. The median level of IgA antibodies was not different in patients with chronic hepatitis and those with cirrhosis, and the same was found for IgM, but the median level of IgG antibodies was significantly higher in the patients with cirrhosis. When patients with cirrhosis were grouped by the presence or absence of ascites or hepatocellular carcinoma, no significant difference was observed in any of these antibody levels. However, in cirrhotic patients with varices, the level of IgG antibodies to endotoxin was significantly higher than in patients without varices. For evaluation of the portal systemic shunt, the per-rectal portal shunt index was calculated. There was a significant correlation (R = 0.431, P < 0.001) between the per-rectal portal shunt index and the level of IgG antibodies to endotoxin. That is, the degree of abnormality in the portal haemodynamics was correlated with the level of IgG antibodies to endotoxin in patients with liver disease.

Antibodies, Bacterial↗

PubMedDate not supplied

Relationship of polyamine metabolism to degree of malignancy of human hepatocellular carcinoma.

We investigated polyamine metabolism in hepatocellular carcinoma (HCC) with respect to tumor volume doubling time, degree of differentiation, and prevalence of portal invasion and intrahepatic metastasis. Ornithine decarboxylase (ODC) activity and the spermidine/spermine ratio were correlated with tumor volume doubling time. ODC activity was higher in moderately and poorly differentiated HCC than in well-differentiated HCC. The prevalence of portal invasion and intrehapatic metastasis was higher in patients with high ODC activities. We conclude that polyamine metabolism in HCC estimates the degree of malignancy.

Adult↗

PubMedDate not supplied

High prevalence of infection with hepatitis B and C viruses in patients with hepatocellular carcinoma in Japan.

BACKGROUND/AIMS: Hepatitis B and C viruses are closely associated with hepatocellular carcinoma. We studied the prevalence of infection with either virus in patients with this cancer by examination of sera and tumor tissue. METHODOLOGY: Serum samples obtained before treatment from 330 patients with hepatocellular carcinoma were assayed for antibodies against hepatitis C virus and against hepatitis B surface and core antigen. Tumor tissues from 65 patients were examined for hepatitis B virus RNA. RESULTS: Of the 330 patients, 87 had anti-hepatitis C alone; 161 had anti-hepatitis C and anti-hepatitis B (core); 13 had anti-hepatitis C and anti-hepatitis B (surface); 39 had anti-hepatitis B (surface) alone; and, 19 had anti-hepatitis B (core) alone. Eleven patients had none of these. Hepatitis B virus genes were detected in tumor tissue in all 13 patients with anti-surface antibody, in 21 of 30 patients with anti-core antibody, and in 9 of 22 patients without hepatitis B antibodies. Viral genes were detected in tumor tissue in 5 of 11 patients with neither B nor C virus markers in their sera; viral markers were found in either serum or tumor tissue in 324 of 330 patients (98.2%). CONCLUSIONS: The prevalence of hepatitis B or C virus infection in patients with hepatocellular carcinoma in Japan is extremely high. The prevalence of co-infection with both viruses is also high.

Carcinoma, Hepatocellular↗

PubMedDate not supplied

Relationship between ornithine decarboxylase gene abnormalities and human hepatocarcinogenesis.

BACKGROUND/AIMS: Ornithine decarboxylase is essential for cell growth. Its activity was high in human hepatocellular carcinoma tissues and was highest in poorly differentiated tumors. METHODOLOGY: To find if there are tumor-specific ornithine decarboxylases, we examined the ornithine decarboxylase cDNA sequences of 91 clones prepared from hepatoma tissue and non-cancerous tissue of resected liver specimens from 15 patients with hepatocellular carcinoma. RESULTS: Ornithine decarboxylase gene mutations were more frequently detected in the hepatoma tissue. The incidence of mutation in hepatoma tissue was related to dedifferentiation. Mutation in regions rich in proline, glutamic acid, serine, and threonine were detected in moderately and poorly differentiated hepatocellular carcinoma only. CONCLUSIONS: Our findings suggested that the sequence of ornithine decarboxylase in hepatocellular carcinoma often is different from that in normal liver and that mutation of its gene is related to the progression of hepatocellular carcinoma.

Adult↗

PubMedDate not supplied

Homeless patients with hepatocellular carcinoma in Osaka City, Japan.

BACKGROUND/AIMS: Although the number of homeless persons is increasing worldwide, studies delineating the health status of these persons according to various medical perspectives, including hepatology, are limited. However, such studies are important for understanding the pathogenesis of diseases and their prevention. METHODOLOGY: Thirty homeless patients with hepatocellular carcinoma (HCC) and 15 with liver cirrhosis (LC) who were admitted to the Osaka Socio Medical center Hospital during the past 6 years were analyzed clinicopathologically. All were from the Airin district of Osaka City. RESULTS: The patients with HCC had a history of long stay (mean: 25 years) in the district and many infectious opportunities and most of them were malnourished. The main causes of liver disease in the patients with HCC were hepatitis C virus (HCV) (77%), alcohol abuse (73%), and the combination of HCV and alcohol abuse (50%). Serum HCV RNA concentration was 10(5.8 +/- 0.9) copies/50 microliters in the 21 HCC patients and 10(6.5 +/- 0.7) copies/50 microliters in the 14 LC patients (p < 0.02). Six HCC patients (20%) were positive for the GB virus C/Hepatitis G virus (GBV-C/HGV) RNA in association with HCV or hepatitis B virus (HBV). Only 2 patients with HCC underwent the curative operations and most of the HCC cases were in progressed stages. CONCLUSIONS: A long stay in a hygiene-poor environment increases the opportunity for infection in homeless people. The causative agents in the HCC and LC patients were mostly HCV, alcohol abuse, and a combination of the two. Since the quantification of HCV-RNA in the HCC patients was lower, the high level of HCV-RNA may not be a risk factor for the development of HCC. GBV-C/HGV may not also. The reversion to former healthy living conditions and reduction in alcohol consumption as soon as possible may contribute to low incidence of HCC and save the tax dollar expenditures among homeless people.

Biopsy, Needle↗

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Resected cases of hepatocellular carcinoma detected after interferon therapy for chronic hepatitis C.

BACKGROUND/AIMS: Interferon therapy decreases the incidence of hepatocellular carcinoma in patients infected with hepatitis C virus. However, hepatocellular carcinoma was detected after interferon therapy in some patients. METHODOLOGY: Of the 167 patients who underwent liver resection for hepatitis C virus-related hepatocellular carcinoma between 1993 and September 1998, the carcinoma was detected after interferon therapy in 11 patients. The clinicopathologic findings in these 11 patients were studied. RESULTS: The response to interferon was complete (n = 4), partial (n = 4), or no response (n = 3). Hepatocellular carcinoma was detected 2 months to 3 years 9 months, after interferon therapy. The interval period from the end of interferon therapy to the detection of the carcinoma were significantly correlated with the longest diameter of the main tumor (P = 0.0043), indicating that most carcinomas have already developed before the end of interferon therapy. In one non-responder, multicentric carcinogenesis occurred after liver resection for primary hepatocellular carcinoma. Another patient with advanced hepatocellular carcinoma died of the recurrence. CONCLUSIONS: Surveillance for hepatocellular carcinoma must be performed even in patients successfully treated with interferon because occult carcinoma may have developed before or during the therapy.

Alanine Transaminase↗

PubMedDate not supplied

Case of small hepatocellular carcinoma in the caudate lobe detected after interferon caused disappearance of hepatitis C virus.

The high prevalence of antibodies to hepatitis C virus (HCV) in patients with hepatocellular carcinoma (HCC) in Japan suggests that the virus has a close relationship to hepatocarcinogenesis (1-4). HCV causes chronic inflammation of the human liver and HCC may finally develop, by way of an unknown mechanism. Interferon (IFN), which has an antiviral effect, is widely used for treatment of chronic hepatitis C infection (5). In Japan, about 40% of such patients have been cured of the infection by IFN therapy (6). The most suitable criteria for identification of a complete response to IFN are the most rigorous: both the disappearance of HCV RNA, verified by the polymerase chain reaction (PCR), and alanine aminotransferase activity in the normal range for at least six months after the end of the therapy. In the cured patients, the liver disorder and hepatocarcinogenesis are thought to stop progressing. However, few such patients have been monitored for years following the treatment (7-8). In this article, we describe a patient with small HCC in the caudate lobe after complete response to IFN therapy for chronic hepatitis. We suggest the necessity for regular liver checks for patients from whom HCV is eliminated by IFN therapy.

Antiviral Agents↗

PubMedDate not supplied

GB virus C infection by blood transfusion during and following liver surgery.

BACKGROUND/AIMS: GB virus C has been associated with some cases of fulminant hepatitis and post-transfusion hepatitis. We examined transfusion-related infection with this virus. METHODOLOGY: Of 150 patients undergoing liver resection, 108 received a homologous blood transfusion. Serum samples before and after surgery were examined for GB virus C RNA by a nested polymerase chain reaction with reverse transcription. We also studied the post-operative course of patients infected with GB virus C by blood transfusion. RESULTS: Viral RNA was detected in sera taken after transfusion in 4 (4%) patients receiving homologous transfusions. Viral RNA was not detected after surgery in the 42 patients given autologous transfusions or not receiving homologous blood. Post-operative courses in the 4 infected patients were uneventful. CONCLUSIONS: As 4% of homologous transfusions resulted in GB virus C infection in our small surgical study, autologous transfusion is recommended when circumstances permit.

Blood Transfusion↗