Allelotype study of primary hepatocellular carcinoma.

Accumulation of mutations in oncogenes and tumor suppressor genes transforms a normal cell to a malignant cell by allowing it to escape from normal control of growth. In order to learn (a) how many tumor suppressor genes are involved in the tumor progression of hepatocellular carcinoma, (b) whether there is any association among allelic losses of chromosomes, or (c) whether integration of hepatitis B virus into host DNA influences any particular chromosomal losses, we have examined loss of heterozygosity with 44 restriction fragment length polymorphism markers in 46 cases of hepatocellular carcinoma. The markers represented all chromosomal arms except 5p, 8p, 9p, 18p, and acrocentric chromosomes. Allelic losses in tumors indicated that five tumor suppressor genes, located on chromosomes 5q, 10q, 11p, 16q, and 17p, may be involved in this cancer. However, no significant associations were observed among the various allelic losses or between the integration of hepatitis B virus and chromosomal losses. Furthermore, a deletion map for chromosome 16q indicated the localization of a tumor suppressor gene between q22 and q24 and that for chromosome 17p suggested the existence of a second tumor suppressor gene in addition to the p53 gene.

Intrahepatic metastases in hepatocellular carcinoma: the role of the portal vein as an efferent vessel.

The mechanism and pathogenesis of the high frequency of intrahepatic metastasis in hepatocellular carcinoma (HCC) has not yet been elucidated. Two hundred and thirty one tumors (< or = 5 cm in diameter) of resected specimens of HCC were examined for the relationship between mode of tumor spread and tumor size. Efferent vessels in HCC were identified by direct injection of radiopaque material into the tumor in 23 resected liver specimens selected at random from the 231 tumors. The most frequent site for tumor spread in HCC was capsular invasion followed by extracapsular invasion, vascular invasion, and finally intrahepatic metastasis. There was a strong statistical correlation between the presence of intrahepatic metastasis and the frequency of vascular invasion (correlation coefficient = 0.998). Radiopaque material injected directly into 23 resected tumors entered only the portal vein in 17 tumors and into both the portal and hepatic veins in six tumors. In all eight patients with unresectable lesions, radiopaque media injected percutaneously into tumor nodules flowed only into the portal vein. These findings suggest that tumor spread in HCC progresses from capsular invasion to intrahepatic invasion and that the portal vein may act as an efferent tumor vessel.

Histological findings of esophageal injury induced by intracavitary irradiation.

The histological findings of esophageal injury induced by intracavitary irradiation are reported. In the portion irradiated intracavitarily, denudation and regeneration were found in the epithelium, degenerative changes of small vessels and fibrotic changes were found in the submucosa, and fibrotic changes were also found in the muscle layers. Our data suggest that these characteristic changes correlate with the additional dosage given by intracavitary irradiation following external irradiation.

[Nuclear DNA analysis of hepatocellular carcinoma].

Retrospective DNA ploidy studies of paraffin-embedded blocks were performed by flow cytometry on 212 surgically resected hepatocellular carcinoma. One hundred and sixty-four of 212 specimens yielded evaluable DNA histograms. Eighty-three cases showed a DNA diploid pattern and 81 a DNA non-diploid pattern. The incidence of non-diploid pattern increased with the tumor size. (2cm; 15.4%, 2-5; 42.3%, 5-10; 70.8% greater than 10; 73.3%). The DNA pattern correlated with the backgrounds, the degree of vascular invasion, intrahepatic metastasis and serum AFP levels. Survival of patients with non-diploid pattern was significantly less than those with diploid patients in any different stage. Of thirty who survived three years with disease free condition, 20 patients showed diploid patterns. Though remaining 10 patients were non-diploid patterns, 9 were high DNA index more than 1.5. It is concluded that flow cytometric DNA ploidy study had prognostic value for patients with surgically resected hepatocellular carcinoma.

Intrahepatic metastases in hepatocellular carcinoma: evidence for spread via the portal vein as an efferent vessel.

BACKGROUND: The mechanism and pathogenesis of the high frequency of intrahepatic metastasis in hepatocellular carcinoma (HCC) has not yet been elucidated. METHODS: Two hundred thirty-one tumors ( < or = 5 cm in diameter) of resected specimens of HCC were examined for the relationship between mode of tumor spread and tumor size. Efferent vessels in HCC were identified by direct injection of radiopaque material into the tumor in 23 resected liver specimens selected from the 231 tumors. RESULTS: The most frequent site for tumor spread in HCC was capsular invasion followed by extracapsular invasion, vascular invasion, and finally intrahepatic metastasis. Radiopaque material injected directly into 23 resected tumors entered the portal vein in only 17 tumors and entered into both the portal and hepatic veins in six tumors. CONCLUSIONS: These findings suggest that tumor spread in HCC progresses from capsular invasion to intrahepatic invasion and that the portal vein may act as an efferent tumor vessel.

Pathologic and radiographic studies of intrahepatic metastasis in hepatocellular carcinoma; the role of efferent vessels.

The efferent vessel of hepatocellular carcinoma (HCC) and the mechanism and pathogenesis of the high frequency of intrahepatic metastasis in HCC has not yet been clarified. Three hundred ninety-three resected specimens of HCC were examined for tumor thrombosis in the portal vein and the hepatic vein: 231 tumors < or = 5 cm in diameter were examined for the relationship between mode of tumor spread and tumor size. Efferent vessels in HCC were identified by direct injection of radiopaque material into the tumor in 23 resected liver specimens and by percutaneous infusion of radiopaque media into tumor nodules in 8 patients. The mode of tumor spread in HCC progressed from capsular invasion to extracapsular invasion, then to vascular invasion, and finally to intrahepatic metastasis. There was a strong statistical correlation between the presence of intrahepatic metastasis and portal vein thrombosis (p < 0.05, R = 0.998). Radiopaque material injected directly into 23 resected tumors entered only the portal vein in 17 tumors and into both the portal and hepatic veins in 6 tumors. In all 8 patients with unresectable lesions, radiopaque media injected percutaneously into tumor nodules flowed only into the portal vein. These findings suggest that intrahepatic invasion by HCC may occur through the portal vein as an efferent tumor vessel.

Flow cytometric DNA analysis of hepatocellular carcinoma.

The prognostic value of nuclear DNA content was studied retrospectively using flow cytometry in 203 cases of resected hepatocellular carcinoma. The occurrence of DNA aneuploidy, which was detected in 50% of patients, correlated significantly with tumor size and the presence of vascular invasion or intrahepatic metastasis. Overall, patients with DNA aneuploid tumors had a significantly worse prognosis than those with DNA diploid tumors (P less than 0.001) and, also in subdivided groups by tumor size (P less than 0.01). Among DNA aneuploid patients, the survival times were significantly shorter for patients with a low DNA index (less than 1.5) than for those with a high DNA index (greater than or equal to 1.5) (P less than 0.05). In a Cox multivariate analysis, nuclear DNA content provided significant prognostic value (P = 0.008), as did vascular invasion (P = 0.001) and intrahepatic metastasis (P = 0.005). These results indicated that nuclear DNA content has an important prognostic value in hepatocellular carcinoma.

Malignant pheochromocytoma with ACTH production.

An autopsy case of a 54-year-old woman with malignant pheochromocytoma and ectopic ACTH production was reported. Noradrenaline was increased in 24 hour urine and in the blood sample from the left adrenal vein. Hormone assay studies of the tumor tissue and plasma revealed abnormally high levels of ACTH. Formaldehyde fume induced fluorescence method demonstrated biogenic amine in the tumor cytoplasm. Electron microscopic examinations also disclosed numerous neurosecretory granules in the tumor cytoplasm. These findings confirmed that this pleomorphic carcinoma of the left adrenal gland was one of the APUDoma originating from the adrenal medulla, so-called pheochromocytoma.

Malignant histiocytosis in the oropharynx.

Malignant histiocytosis is characterized by systemic, progressive, and invasive proliferation of malignant histiocytes. The disorder is typically accompanied by fever, general fatigue, lymphadenopathy, and hepatosplenomegaly. A case of a 21-year-old woman with primary malignant histiocytosis of the oropharynx is reported. Histologic diagnosis from the biopsy specimen was confused by infiltration of normal-appearing histiocytes and inflammatory cells. The titers of Epstein-Barr virus and the Paul-Bunnell test were elevated without atypical lymphocytes. The patient died 3.5 months after the onset of symptoms. Autopsy revealed systemic neoplastic proliferation of malignant histiocytes. A review of literature on this subject revealed no cases of malignant histiocytosis primarily involving the oropharynx.

A primary lung carcinoma producing alpha-fetoprotein, carcinoembryonic antigen, and human chorionic gonadotropin. Immunohistochemical and biochemical studies.

This article documents a patient with lung carcinoma that produced three oncofetal antigens including alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), and human chorionic gonadotropin (hCG). Serum AFP, CEA, and hCG-beta-subunit were extremely high--118,000 ng/ml, 133 ng/ml and 0.9 ng/ml, respectively. Immunohistochemical staining of these tumor markers revealed that these proteins were present in different cells. The pattern of lectin affinity electrophoresis of AFP resembled that of hepatocellular carcinoma. Also investigated was the reactivity of serum CEA to monoclonal antibodies against peptide or sugar moieties. Serum CEA values measured by antipeptide monoclonal antibodies were higher than those measured by antisugar monoclonal antibodies. The demonstration of AFP, CEA, and hCG in different tumor cells suggests that three genomes were not reactivated together in a cell, and the lung carcinoma probably consisted of at least three clones of cancer cells with different phenotypes.

Do the tumor cells of hepatocellular carcinomas dislodge into the portal venous stream during hepatic resection?

BACKGROUND: The current study was undertaken to investigate whether or not tumor cells are dislodged into the portal venous stream during hepatic resection for hepatocellular carcinomas. METHODS: A catheter was placed using echo guidance into the portal branch through the mesenteric vein in 31 patients. Cytologic examinations were done on multiple blood samples at various operative stages. RESULTS: Tumor cells were recovered in 7 of 31 patients in whom the tumor sizes were more than 5 cm and portal invasions were found microscopically and/or macroscopically. By contrast, the remaining 24 tumors were less than 5 cm in size and showed negative portal invasions. Recovery of the tumor cells was found, not during the earlier operative stage of mobilization or rotation of the hepatic lobe, but during the later stages of hilar dissection or hepatic parenchymal dissection. CONCLUSIONS: The portal pedicles should be divided before hepatic dissection in segmentectomy and lobectomy to lessen the chance of dissemination of intravasated tumor cells.