Hiroshi Obata

Natural history of hepatocellular carcinoma and prognosis in relation to treatment. Study of 850 patients

A total of 850 patients with hepatocellular carcinoma seen during the last 8 years were analyzed retrospectively for survival in relation to treatment and disease stage. A new staging scheme based on tumor size, ascites, jaundice and serum albumin was used. Clearly, the prognosis depended on disease stage. The median survival of 229 patients who received no specific treatment was 1.6 months, 0.7 month for Stage III patients, 2.0 months for Stage II, and 8.3 months for Stage I. The median survival of Stage I patients who had hepatic resection (n = 115) was 25.6 months and Stage II patients with resection (n = 42) was 12.2 months. In patients who had a small cancer (≤25% of liver area in size) the median survival was 29.0 months. Survival of the surgically treated patients, which represented a highly selected group, was better than that of medically treated patients of a comparable stage. Median survival of Stage I medically treated patients (n = 124) was 9.4 months, for Stage II (n = 290) 3.5 months, and for Stage III (n = 50) 1.6 months. Medical treatment prolonged survival in Stage II and III patients, but not in Stage I. Transcatheter arterial embolization gave a better survival compared with chemotherapy, whether intra‐arterial bolus administration of mitomycin C, systemic mitomycin C, or oral/rectal tegafur, in Stage II. Among various chemotherapeutic modalities, intra‐arterial bolus injection was superior to systemic chemotherapy in survival in Stage II. In Stage III, chemotherapy improved survival as compared with no specific treatment. The major causes of death were hepatic failure and gastrointestinal bleeding, probably due to the coexistent advanced cirrhosis. These results in survival are much improved over the past reports, and the differences are probably a result of earlier diagnosis and frequent hepatic resections.

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 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.

Evaluation of endoscopic ultrasonography for gastric tumors and presentation of three-dimensional display of endoscopic ultrasonography

SummaryWe have studied the usefulness of endoscopic ultrasonography (EUS) for: (1) differentiation between extragastric mural compression (EGMC) and submucosal tumors (SMT); (2) qualitative assessment of these lesions; (3) diagnosis of serosal invasion by malignant gastric tumors; (4) presentation of three-dimensional display of EUS findings. A total of 103 patients with submucosal lesions protruding into the gastric lumen on endoscopy were examined. Differentiation between EGMC and SMT could be made by EUS in all cases. Qualitative assessment of these lesions was made by observing their EUS findings, i.e. their internal and marginal echo pattern and their location in the gastric layers. The correct diagnosis was made in 88% (23/26) of EGMC. Of 50 patients with SMT, comprising myogenic tumor (32), aberrant pancreas (8), lipoma (3), gastric cyst (4) and malignant lymphoma (elevated type; 3), differentiation between malignant and benign myogenic tumors was impossible by EUS alone. In addition, 48 patients with advanced gastric cancer and malignant lymphoma were examined. Invasion to the serosal surface was diagnosed as interruption of the fifth layer of the gastric wall. Invasion to other organs was diagnosed by interruption and fusion of the fifth layer into the border of the adjacent structure. Serosal invasion was diagnosed accurately in 65% of 48 patients. Microscopic invasion was difficult to diagnose, and gastric stenosis by tumor was an obstacle to adequate scanning. EUS can be valuable in the differential diagnosis between EGMC and SMT and in the qualitative diagnosis of gastric lesions. It is also effective in detecting serosal invasion by gastric malignant tumors. Three-dimensional display of pathological lesions is new in EUS. With this method, it is easy to get the stereograph and to obtain a complete picture of the lesions. We present two cases in this report.

Hepatitis B Surface Antigenemia in Patients with Hepatocellular Carcinoma in Relation to Clinical Course and α-Fetoprotein

Hepatitis B surface antigen was determined in sera of 122 cases of hepatocellular carcinoma seen in Japan, using both the counterimmunoelectrophoresis and radioimmunoassay (RIA) techniques. It was positive in 49.2% of the patients with RIA, but the level of antigen in serum was relatively low since positivity rate by counterimmunoelectrophoresis was only 10.7%. The degree of antigenemia as assessed from the count relative to the cut-off value in RIA, was increased during the clinical course in 75% of the patients. The antigen tended to rise in concentration when the tumor grew at a rapid rate, when damage to liver parenchyma was extensive, or in patients receiving chemotherapy. There was also a tendency for less frequent positive antigen tests in patients with higher α-fetoprotein levels. Illustrative cases are presented with discussion on the possible explanation for the change in the degree of antigenemia.

Immunohistochemical detection of proliferating cell nuclear antigen in hepatocellular carcinoma: relationship to histological grade.

Proliferating cell nuclear antigen (PCNA), also known as cyclin, is an auxiliary protein of DNA polymerase‐δ and is found only in the nuclei of proliferating cells in the late G1 and S phases. The proliferation of hepatocellular carcinoma (HCC) by immunohistochemical staining for PCNA using paraffin sections of 20 surgically resected HCC specimens was analysed. The mean percentage of PCNA‐positive nuclei in the HCC tissue was 10.3% in grade I of Edmondson and Steiners classification, 25.5% in grade II, 28.4% in grade III and 41.5% in grade IV. In early HCC, we observed only a few PCNA‐positive tumour cells. However, PCNA‐positive nuclei were numerous in the tumour thrombi found in portal vein branches, in regions of extracapsular tumour growth, and in the inner nodules of tumours with a nodule‐in‐nodule formation. Proliferating cell nuclear antigen positivity was correlated with an increase of the nucleocytoplasmic ratio of tumour cells as determined by image analysis. Our findings showed that PCNA positivity was correlated with the histological grade and invasiveness of HCC, suggesting that this antigen may be used as an indicator to predict tumour invasion in patients with HCC.

The Capability of Three Dimensional Display during Endoscopic Ultrasonography

Abstract: Endoscopic ultrasonography (EUS) has been found to be useful in determining the depth of invasion of gastric cancer, the diagnosis of submucosal tumors and extramural compressions. A problem with this procedure is that it is difficult to determine stereoscopically the relative position of the lesion as a whole, even though EUS may be an excellent diagnostic tool for determining tomographies. In this paper, we made three‐dimensional displays of EUS images using a personal computer to facilitate understanding of the relative anatomical positions of the lesions. During EUS examination, the distance from the incisors was acccurately measured, and the EUS image was recorded on U‐matic tape. To measure the distance from the incisors, we devised a new instrument for measuring the endoscopic insertion length. The recorded tape was edited for input into the computer. The soft‐ware for the three‐dimensional display program was made by Photoron. Inc. A patient with esophageal cancer, a patient with a common bile duct stone and a patient with pancreatic cancer are presented as examples for definition of the relationship with the surrounding organs. A patient with a gastric ulcer is used as an example to clarify the pathological structure of the lesions. Using our method on these patients, it was easy to obtain a stereograph and to obtain complete images of the lesions. EUS was available for three ‐dimensional displays of the lesions in the gastrointestinal tract and in the surrounding area, and this has clinical significance.

Significance of serum sialic acid in patients with Crohn’s disease

SummarySerum sialic acid was measured to evaluate the activity of Crohn’s disease. The sialic acid levels of patients with Crohn’s disease in remission (CRP 0.0 mg/dl) were significantly higher than those of healthy subjects and postoperative patients with Crohn’s disease. In patients in remission, serum sialic acid was significantly correlated with hemoglobin, hematocrit, platelet, and rapid turnover protein. Correlations with platelet, retinol-binding protein, and prealbumin were especially strong. From these findings, it was concluded that serum sialic acid level provides a useful index of the activity of Crohn’s disease.

Hepatitis viruses in southern taiwan—mass survey of 2985 inhabitants

SummaryA survey of 2985 apparently healthy Taiwanese in southern Taiwan revealed a high prevalence (18.2%) of hepatitis B surface antigen (HBsAg). It was significantly higher in males (22.3%) than in females (13.6%), but no correlation with family origin, socioeconomic status or residence was established. About one-third of the breeding female HBsAg carriers were HBeAg-positive, and these may be an important source in the spread of HBV. Subtyping of HBsAg in 63 subjects showed adw to be dominant in this area, and 8 subjects with suspicious results had overlapping heterotypic HBV’s (7 adwr and 1 adyw) in addition to 2 subjects in which coexistence of HBsAg and anti-HBs was recognized. The association between HBsAg positivity and serum transaminase elevation was significant, especially in the older groups who had a higher abnormal rate. Hepatitis A virus infection was serious too, with nearly 100% of people above 20 years of age being anti-HA antibody positive.