Kazuyoshi Sakamoto

Pathology of hepatocellular carcinoma in Japan. 232 Consecutive cases autopsied in ten years.

The pathologic findings of 232 consecutive cases of hepatocellular carcinoma (HCC) autopsied during the past ten years at Kurume, Japan, were analyzed from the point of view of global epidemiology, in relation to clinical feature, and in regard to incidence, age, sex, etiologic factors, size of liver, changes in noncancer parenchyma, gross type of tumor, extrahepatic metastases, intravascular and intraductal growths, cancer cell histology, hepatitis B surface antigen (HBsAg) in hepatocytes and cancer cells, liver cell dysplasia, and frequency and clinicopathologic characteristics of minute HCC. Furthermore, postmortem hepatic arteriography and portography were done in 152 livers for comparison with gross anatomy and celiac angiograms. It was found that: (1) epidemiologicall), HCC in Japan is distinct from that in the West that it is frequently encapsulated, livers are generally small because of frequent and advanced cirrhosis and small cancer, minute HCC, is not uncommon at autopsy, cirrhosis most commonly associated is the one with thin stroma and medium size nodules, and micronodular cirrhosis is very rare despite frequent alcohol abuse; (2) HCC is increasing in incidence; (3) HBsAg is frequently found in parenchyma; (4) liver cell dysplasia is indirectly related to HBsAg with no evidence for premalignancy; (5) the lung is the most frequent site of metastasis but peritoneal dissemination is unusual; (6) intraportal tumor growth is very common and the hepatic vein is less frequently affected; (7) growth in the major bile duct is frequently associated with intraportal growth and clinically presents as obstructive jaundice; and (8) tumor is supplied solely by arteries and celiac arteriograms are closely correlated with gross pathologic findings.

Clinicopathologic features of encapsulated hepatocellular carcinoma. A study of 26 cases

The clinicopathologic features of 26 cases of hepatocellular carcinoma (HCC) surrounded by a grossly distinct capsule‐like fibrous tissue were studied. The frequency of this type was 10.3% among autopsy cases of HCC. The mean age of the patients was 64.1 years, which was significantly older compared with that of 143 cases of nonencapsulated HCC. Hepatitis‐B surface antigen in serum was positive in 18.7% of the cases studied, the positivity rate being lower than that of HCC in general. Histologically, the tumor was relatively well differentiated and the capsule was the product of slow expanding growth. Intravenous tumor invasion was less frequent compared with other types of HCC. Clinically, celiac angiography proves to be a most useful diagnostic method; a thick capsule may be demonstrated as a thin radiolucent rim around the mass. The clinical course from the early stage is protracted and, if detected early, this type of HCC may be removed surgically.

Angiographic demonstration of intrahepatic arterio-portal anastomoses in hepatocellular carcinoma.

Hepatic angiograms of 114 patients with hepatocellular carcinoma (HCC) were studied, particularly changes in the portal vein branches. Arterio-portal shunts of varying sizes, evidenced by opacification of intrahepatic portal branches, were seen in 72 cases (63.2%), with retrograde opacification of the portal vein trunk in 29 (25.4%). At least four types of shunts were found: (a) through a tumor thrombus in the portal branch, (b) in a retrograde direction via a peripheral tumor nodule, (c) through a small tumor invading or amputating an artery, and (d) through a tumor located near a major portal vein branch and supplied by a large, coiling artery. Postmortem angiography of the liver in 50 patients with HCC suggests that arterio-portal shunts are the result of the special vasculature in HCC and are highly diagnostic when accompanied by other angiographic changes.

Angiographic Assessment of Gross Anatomy of Hepatocellular Carcinoma: Comparison of Celiac Angiograms and Liver Pathology in 100 Cases1

Of 190 sets selective celiac and/or hepatic angiograms obtained in patients with hepatocellular carcinoma (HCC), comparison with gross anatomy of the liver was subsequently made by autopsy in 77 and by surgery in 23. It was found that the gross anatomy of HCC can be assessed with certain accuracy by careful interpretation of the angiograms, because tumor vasculature and vascular alterations in the noncancerous parenchyma are closely related to the mode of tumor growth, size of tumor nodules and their distribution. Even a fibrous capsule of the tumor may be discerned as a radiolucent zone around the tumor contour. Diagnosis of the gross anatomical type of HCC is important to the selection of therapeutic measure and assessment of prognosis.

Hepatocellular carcinoma arising in noncirrhotic and highly cirrhotic livers: A comparative study of histopathology and frequency of hepatitis B markers

Hepatocellular carcinoma (HCC) associated with cirrhosis and HCC developing in a noncirrhotic liver may have differing pathogeneses. To study this possibility, 426 autopsied cases of HCC were investigated. Of these, 45 livers were not cirrhotic, 50 were highly cirrhotic (liver weight less than 99 g), and the remaining 331 were cirrhotic but not so highly. The average age was significantly older in the highly cirrhotic group, suggesting a longer premalignant period of chronic liver disease. The liver weight in the noncirrhotic group was about 3.5 times that in the highly cirrhotic group. Hepatitis B surface antigen was positive in serum in only 9.3% and in liver tissue in 10% in the noncirrhotic cases, the positivity rate being much lower compared with other groups (P < 0.005–0.01), yet antibody to HB core was positive in 90%. The antibody titers were low, however, indicating that these noncirrhotic patients had in the past had HB virus (HBV) infection with no residual chronic B hepatitis. Analysis of the grades of anaplasia of cancer tissue demonstrated an inverse correlation between the degree of fibrosis and grade of anaplasia, i.e., the more advanced the fibrosis, the less anaplastic the cancer. These data suggest that HCC arising in highly cirrhotic livers and in noncirrhotic livers have different pathogenetic backgrounds, and that HBV infection, even though transient, has a certain role in hepatocarcinogenesis. The generally held conjecture that HCC in a noncirrhotic liver is caused by nonviral carcinogens and HCC arising on the ground of cirrhosis is due to HBV seems untenable in such a simple concept.

Serum glutamic oxalacetic transaminase/glutamic pyruvic transaminase ratios in hepatocellular carcinoma.

Serum enzyme activities were studied in 131 cases of hepatocellular carcinoma (HCC), 76 cases of metastatic liver carcinomas (MLC) and 234 cases of hepatic cirrhosis. SGOT was elevated above SGPT in most of the time in these patients, SGOT/SGPT was greater in HCC compared with other groups, and that this ratio increased during the preterminal period more markedly in patients with HCC because of the significant increase of SGOT in the face of relatively stable SGPT. Preterminal rises of alkaline phosphatase and LDH activities were more pronounced in MLC. Leucine aminopeptidase activity exhibited no characteristic feature of diagnostic value. Of the five enzymes, SGOT changes were more closely correlated with the growth of HCC; SGPT reflected more of the liver parenchymal damage while SGOT was probably accounted for in part by tumor‐derived GOT. Other clinical and pathological implications are discussed. Cancer 40:319–324, 1977.

Localized submassive liver cell necrosis as a terminal event of liver carcinoma.

Six cases of hepatocellular carcinoma (HCC) and one case of metastatic liver carcinoma in which SGOT, SGPT, and SLDH were suddenly and markedly elevated immediately before death are described. All had a large blood loss and systemic hypotension in the preterminal period; autopsy disclosed irregularly shaped, patchy necrotic areas or infarcts, often clearly demarcated by hemorrhagic rims, in the noncancerous liver parenchyma. Tumor growths in the intrahepatic portal branches were extensive in all six cases with HCC; in the metastatic case, invasion and narrowing of the portal branches were extensive. The incidence of this terminal catastrophe was 3.3% (6 of 184 cases) for HCC and 1.15% (1 of 87) for metastatic carcinoma. The terminal liver necrosis was probably a result of sudden reduction in portal perfusion which had been inadequate because of tumor thrombosis, combined with hypotension of hepatic arteries.

A minute hepato cellular carcinoma found in a liver with clonorchis sinensis infection. Report of two cases

Two cases of minute hepatocellular carcinoma (HCC) found in a liver infested with Clonorchis sinensis are described. One had mild infestation with hepatic changes suggestive of posthepatitic cirrhosis, and the other heavy infestation exhibiting secondary biliary cirrhosis with dilated intrahepatic bile ducts and periductal fibrosis. None had evidence of hepatitis B infection. The tumor nodule was solitary, measuring 5 × 7 mm and 10 × 11 mm, respectively, and the cells were differentiated to be classified as Grade I of Edmondson‐Steiners scale of anaplasia. It is not clear whether or not clonorchiasis was etiologically related to HCC, but it was of interest that in both cases the tumor nodule was very small representing the primary lesion without metastasis.

Direct observation of the portal vein interior by intra‐operative angioscopy in the dog and man

The purpose of this study was to develop the technique of intra‐operative portal angioscopy using a portal angioscope, and to demonstrate its potential use in the therapy for patients with hepatocellular carcinoma (HCC) bearing a portal thrombus. Portal angioscopes, Olympus BF3C10 and CHFP10 of a diameter of 3.5 mm and 4.8 mm, respectively, were used during operation in five dogs, two patients with hepatic metastasis from colon cancer and three patients with HCC having a portal tumour thrombus. The portal vein and hepatic artery were ligated simultaneously, and the angioscope was immediately introduced under direct vision through a small portal venotomy. Blood in the portal vein was almost fully diverted by infusion of heparinized saline through a channel of the angioscope at a rate of 3 mL/min in dogs and 5 mL/min in patients with hepatic metastasis. Rates of 6 mL/min and 10 mL/min in dogs and patients, respectively, were adequate to clear completely the portal vein of blood. In patients with HCC, portal tumour thrombectomy was performed with a Fogarty balloon catheter by suctioning thrombi through a channel of the fibrescope after visual study of the portal thrombus.

The Use of Operative Ultrasonography for Esophageal Cancer

Recent advances in various imaging techniques such as double-contrast X-ray, computed tomography, whole-body and endoscopic ultrasound, and magnetic resonance imaging have significantly improved the diagnosis of esophageal cancer. However, the extent of local tumor invasion and lymph node or distant organ metastasis are not always accurately assessed by these preoperative studies.