Tatsuro Sakata

Serum amino acid levels in patients with hepatocellular carcinoma.

Serum amino acid concentrations in cirrhotic patients with and without hepatocellular carcinoma (HCC) were investigated. Elevation of serum aromatic amino acids (AAA) and methionine levels observed in cirrhotic patients without malignancy was not apparent in cirrhotic cases with HCC, and thus the ratio of branched chain amino acids (BCAA) to AAA was not so diminished in the latter cases. Development of hepatic encephalopathy in cirrhotic patients with HCC led to only a slight change in the serum aminogram characteristic of hepatic failure. In patients who underwent operations, tissue amino acid compositions of hepatocellular, gastric, and colon cancers were compared with each other and their respective surrounding epithelia. Amino acid contents in the tumor tissue were generally higher than those in the respective nontumorous parts, especially in the case of HCC. The methionine, tyrosine, and phenylalanine contents in HCC were much higher than in cirrhotic or normal liver. Serum aminograms in rats with ethionine‐induced HCC were similar to those in cirrhotic patients with HCC. Amino acid contents in HCC were higher than those in the surrounding cirrhotic liver tissue of rats. Serum and liver tyrosine and isoleucine contents rose significantly in rats 5 to 6 weeks after the initiation of a 0.25% ethionine‐containing diet. After the 20th week of the experiment, by which time well‐differentiated HCC had developed, liver tyrosine and isoleucine contents increased whereas serum isoleucine concentrations decreased. The results suggest that the serum amino acid patterns characteristic of cirrhotic patients with HCC may result from the increased consumption of amino acids by HCC. Determinations of the amino acid levels are also useful for estimating the prognosis and discovering imminent hepatic encephalopathy in cirrhotic patients with HCC.

Glutamic acid and glutamine levels in serum and cerebrospinal fluid in hepatic encephalopathy

Significant elevation of glutamic acid and glutamine concentrations in CSF was observed in hepatic encephalopathic patients with fulminant hepatitis and liver cirrhosis. However, the ratios of CSF glutamic acid to CSF glutamine levels and of CSF to serum glutamic acid and glutamine levels were significantly higher only in cirrhotic patients with hepatic encephalopathy. CSF glutamine levels were positively correlated with blood ammonia and CSF tyrosine levels in cirrhotic patients. The results indicate that CSF glutamic acid and glutamine levels are important tools in diagnosing hepatic encephalopathy in severe liver disease.

Mucosa‐associated lymphoid tissue lymphoma of the rectum that regressed spontaneously

We report a case of mucosa‐associated lymphoid tissue (MALT) lymphoma of the rectum that regressed spontaneously. A 76‐year‐old man visited our hospital because of positive faecal occult blood testing. Colonoscopic examination revealed a slightly yellowish protruded lesion with a grooved depression in the lower rectum and two flat elevations in the upper rectum. Microscopic and immunohistological studies led to a diagnosis of MALT lymphoma. As the patient exhibited severe renal dysfunction and angina pectoris, the lesions were left untreated. Three months later, the protruded lesion became flat and the other lesions became unclear. He was followed up closely with endoscopy, but no relapse of these lesions was detected 19 months after the diagnosis.

Characteristic change in serum amino acid levels in different types of hepatic encephalopathy

SummarySerum amino acid patterns in patients with different types of hepatic encephalopathy were investigated. Marked elevations in most of serum amino acids observed in untreated patients with acute type of fulminant hepatitis were not remarkable in the patients who have already treated; particularly branched chain amino acids (BCAA), phenylalanine and tyrosine were much lower in the latter group. However, elevation of serum methionine levels and lower ratio of BCAA/(phenylalanine + tyrosine) were similarly observed in both groups. In encephalopathic patients with decompensated cirrhosis, many amino acids such as phenylalanine, tyrosine and methionine were elevated with a slight depressed levels of serum BCAA. Highly significant decrease in serum BCAA levels and no elevation of phenylalanine and methionine with a minimal increase of typosine were observed in patients with chronic type of hepatic encephalopathy; other amino acids except for glutamine and arginine were much lower as compared to those in decompensated cirrhotics and even to the control values.

Evaluation of endoscopic injection sclerotherapy with and without simultaneous ligation for the treatment of esophageal varices.

Abstract: For more effective and simple endoscopic injection sclerotherapy (EIS) for esophageal varices, we developed an EIS procedure with ligation (EISL) that is non-invasive, in which EIS and endoscopic variceal ligation (EVL) are performed simultaneously. In this study, we compared EISL and EIS in a randomlized sample of patients (n = 14 for each procedure). For EISL, EVL was performed, including the injection site, after the injection of 5% ethanolamine oleate with iopamidol (EOI) into a varix. The mean number of treatment sessions required for eradication of esophageal varices was 2.3 ± 0.5 for EISL and 3.9 ± 0.8 for EIS (P < 0.001); the mean number of treatment sites was 6.2 ± 2.2 for EISL and 14.0 ± 5.0 for EIS (P < 0.001); the mean total amount of EOI used was 13.8 ± 5.2 ml for EISL and 26.3 ± 9.8 ml for EIS (P < 0.001). There were no significant differences in rates of recurrence of varices or in bleeding between the two groups. For EISL, fewer treatment sessions and less sclerosant were sufficient, probably because the sclerosants were more effective due to the blockage of variceal blood flow by the ligation. This method should provide a novel modification of EIS.

Pleomorphism of hepatic regeneration

SummaryThe pleomorphism of hepatic regeneration was studied in acute liver injury and partial hepatectomy of rats. Increases in3H-thymidine incorporation into the liver DNA fraction and in liver ornithine decarboxylase (ODC) activity were observed similarly in acute liver injury and following a two-thirds partial hepatectomy in normal rats. However, the increase in serum AFP levels was significant only in carbon tetrachloride (CCl4)-treated rats, and the portal-peripheral vein difference in plasma glucagon concentrations was great only in rats that underwent a partial hepatectomy. The weight of the remaining liver increased rapidly following a 67% hepatectomy in normal rats, but not in cirrhotic rats, of which three of five died within 6 days. Increases in liver prostaglandin E levels,14C-orotate incorporation into the liver RNA fraction and hepatic ODC activity were observed up to 10 h following a partial hepatectomy of normal liver but not after similar removal of cirrhotic liver. Three kinds of hepatic regeneration, i.e., normal and pathologic regeneration following surgical removal of either normal or injured liver and repair of liver damage following chemically induced liver deficiency, were proposed from the observations.

EFFECT OF AZATHIOPRINE AND CARBON TETRACHLORIDE ON INDUCTION OF HYPERPLASTIC LIVER NODULE AND HEPATOCELLULAR CARCINOMA BY DIETHYLNITROSAMINE AND N‐2‐FLUORENYLACETAMIDE IN RATS

The enhancing or inhibitory action of the hepatotoxic agents, carbon tetrachloride (CCl4) and azathioprine (AZP), on the evolution of hyperplastic liver nodule (HN) and hepatocellular carcinoma (HCC) in diethylnitrosamine (DEN)- and N-2-fluorenylacetamide (FAA)-treated rats (control group) was tested. The area of gamma-glutamyl transpeptidase(gamma-GTP)-positive HN and/or foci in the eighth week was remarkably small in rats fed on a diet containing FAA and AZP (the AZP group), but was quite large in rats fed a diet containing FAA in addition to repeated CCl4 injections (the CCl4 group). HCC was first detected in the 21st week and the incidence of HCC within the 36 weeks of the experiment was very high in the CCl4 group. However, no tumor, including HCC, was detected in the AZP group during this observation period. No essential differences in the biochemical characteristics of HCC between the control group and the CCl4 group were observed with respect to several enzyme activities. The increased activity of liver aniline hydroxylase observed 12 hr after the administration of FAA, AZP, or DEN decreased when AZP was administered simultaneously with FAA to rats treated with DEN in advance. The mechanisms of the enhancing of inhibitory effect observed are discussed with special reference to the drug-drug interactions.

Chronic liver injury in rats by carbon tetrachloride inhalation.

Chronic liver injury is commonly induced in rats by repeated carbon tetrachloride (CCl/sub 4/) injection. There have been several investigations of CCl/sub 4/ hepatotoxicity by its inhalation, although only a few reports on chronic liver injury is available. The present study was thus carried out to determine whether or not the inhalation method can replace the ordinary injection method for inducing chronic liver injury

Alterations in neutral amino acid transport across the blood-brain barrier in hepatic failure

SummaryThe accelerated transport of the blood neutral amino acids into the brain in encephalopathic patients with fulminant hepatitis and advanced liver cirrhosis was demonstrated not only by determining the cerebrospinal fluid (CSF) aminogram but also by calculating the predicted velocity of the amino acid transport through the blood-brain barrier. Significant elevation in CSF aromatic amino acid (AAA) and methionine levels was observed in the encephalopathic patients. Arousal from hepatic encephalopathy by drip infusion of a branched chain amino acid (BCAA)-enriched solution was obtained coincidentally with the elevated BCAA levels and diminished concentrations of AAA and methionine in CSF. These clinical observations were confirmed experimentally in rats treated with carbon tetrachloride (CCl4) andd-galactosamine by obtaining the elevation of neutral amino acid contents in the brain and the slight increase in the brain uptake index (BUI) of a radiolabeled amino acid.

Hepatocellular Carcinoma of Small Size

Clinicopathological features of hepatocellular carcinoma (HCC) of small size, not larger than 5.0 cm in diameter, were studied in 11 patients with underlying cirrhosis. The presence of tumor was detected and confirmed by computed tomography (CT) and ultrasonography (US) during periodic imaging re-examinations of cirrhotic patients. The HCCs grew slowly up to a certain stage and formed satellite tumors that could not be visualized on CT image. Therefore, infusion hepatic angiography and/or transcatheter arterial embolization (TAE) are essential before undertaking a major operation.