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Background. Gastrointestinal stromal tumors (GISTs) are usually refractory to standard chemotherapeutic agents. We successfully treated a patient with a tyrosine kinase inhibitor (STI571) for GIST with peritoneal dissemination and liver metastases. Methods. In a 32-year-old man presenting with abdominal pain from diffuse peritonitis, a GIST and associated perforated small intestine were resected. Multiple liver metastases were present. After therapies with microwave coagulation, ethanol injection, and local and systemic antineoplastic drugs (fluorouracil, cisplatin, tegafur-uracil, and tegafur) failed, investigational treatment with a tyrosine kinase inhibitor was initiated (STI571, 300 mg, p.o. daily). Results. Anorexia and abdominal fullness resolved within a few days. At 24 days after initiation, positron emission tomography showed a remarkable decrease in the abdominal uptake of [18F] fluorodeoxyglucose. Adverse effects of STI571, including mild alopecia and anemia, were minimal. Conclusions. The tyrosine kinase inhibitor STI571 may be effective against GISTs.

A 65-year-old Japanese man underwent radiofrequency ablation (RFA) therapy of a hepatocellular carcinoma. Hemobilia from the intrahepatic bile ducts adjacent to the tumor developed on the fifth day after the RFA therapy. Ultrasonograms and computed tomograms showed swelling of the gallbladder, which was filled with a clot, suggesting the diagnosis of hemocholecyst. The hemobilia resolved with conservative therapy, but a cholecystectomy was performed to manage postprandial abdominal pain. The resected gallbladder was filled with a clot, but injury or ulceration of the gallbladder was absent, suggesting that the hemocholecyst developed secondary to the hemobilia. Secondary hemocholecyst is a rare complication of RFA therapy. The number of cases of secondary hemocholecyst is likely to increase as hepatocentestic therapy becomes more common. Cholecystectomy is indicated for hemocholecyst because spontaneous liquefication and drainage of a clot in the gallbladder usually does not occur.

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.

The Japan integrated staging (JIS) score is recognized to be useful in managing hepatocellular carcinoma (HCC). We evaluated the effects of the causative virus in patients stratified by this system.We compared clinicopathologic features, cumulative and tumor-free survival rates, and causes of death between 301 hepatitis C virus-positive patients (HCV group) and 60 hepatitis B virus-positive patients (HBV group).Among patients with low JIS scores (0 or 1), the proportions of patients with high aspartate and alanine aminotranferase activities, moderate-to-severe active hepatitis, and with cirrhosis were significantly higher in the HCV than in the HBV group. Among patients with high JIS scores (2 to 4), the proportion with moderate-to-severe active hepatitis was also significantly higher in the HCV group. In patients with low JIS scores, those in the HCV group had significantly lower tumor-free and cumulative survival rates than those in the HBV group. Although no patient in the HBV group died of causes other than liver disease (HCC or hepatic failure), some patients in the HCV group died of causes other than liver disease. The proportion of patients who died because of HCC recurrence tended to be higher among patients with high JIS scores than among patients with a low JIS score.The effects of viral status on survival outcomes are greatest in patients with JIS scores of 0 or 1.

Mitochondrial DNA (mtDNA) mutations are found in many kinds of human cancer. The aim of this study was to evaluate the relationship between mtDNA mutations in the liver and human hepatocarcinogenesis.Direct sequencing of mtDNA was done in 54 hepatocellular carcinomas (HCCs) and 47 surrounding liver tissue samples, obtained from 54 patients with HCC, and in 5 liver samples without inflammation, obtained from 5 patients with metastatic liver tumors. We also examined p53 mutations in the 54 HCCs to examine the correlation between nuclear DNA mutations and mtDNA mutations.Mutations of mtDNA in the D-loop region were found in both HCC and noncancerous liver tissue. In normal liver without chronic inflammation, no mtDNA mutation was detected. In every case, the number of mtDNA mutations in HCC correlated with that in noncancerous liver tissue. Twelve of 52 mutation sites in the D-loop region of mtDNA were specific for HCC. The mean number of mtDNA mutations was 1.7 in well-differentiated HCC, as compared with 4.5 in moderately differentiated HCC and 4.6 in poorly differentiated HCC. The frequency of mtDNA mutations was thus higher in less differentiated HCC. We detected p53 mutations in 15 (28%) of 54 HCCs. The mean number of mtDNA mutations was 5.3 in HCC with p53 mutations and 3.8 in HCC with wild-type p53 (P = 0.024).A higher frequency of mtDNA mutations was found in less differentiated HCCs, and it is also possible that mtDNA mutations are related to nuclear DNA mutations in HCC. The accumulation of mtDNA mutations is a useful predictor of hepatocarcinogenesis.

Background. The clinicopathologic features of cystic neoplasms of the liver, such as cystadenoma and cystadenocarcinoma, are poorly defined because these lesions are extremely rare. Methods. Clinicopathologic findings in six patients who underwent surgery for a cystic hepatic neoplasm were reviewed retrospectively to determine the best surgical strategy to treat this condition. Results. Five patients had a multilocular cyst or elevated lesions detected on preoperative imaging studies. The remaining patient had elevated serum concentrations of carcinoembryonic antigen and carbohydrate antigen 19-9, even though preoperative imaging studies of the hepatic cystic lesion revealed no imaging features of cystadenocarcinoma. Cytology failed to detect malignant cells in the cyst contents of any patient. One patient underwent palliative resection because pleural dissemination was present, and five patients underwent curative resection. Three patients had cystadenoma diagnosed in the surgical specimen. One patient with cystadenocarcinoma has survived for more than 8 years after a curative resection that was limited to the cyst wall, and another patient died of recurrence 13 months after surgery. Conclusions. When a cystic neoplasm is suspected of being cystadenocarcinoma, hepatic resection should be considered, because reliable criteria for distinguishing cystadenoma from cystadenocarcinoma clinically do not exist.

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 × 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.