Yasuo Majima

The extracellular matrix in hepatocellular carcinoma shows different localization patterns depending on the differentiation and the histological pattern of tumors: immunohistochemical analysis

This study investigated cells producing type I, III, and IV collagens, laminin, and fibronectin, the major components of the extracellular matrix, and compared their localization patterns in relation to the grade of tumor differentiation and the histological pattern of hepatocellular carcinoma. Type I, III, and IV collagens, laminin, and fibronectin were produced by tumor, endothelial, and Ito cells. Regarding their localization pattern in relation to the histological pattern of tumors, although the extracellular matrix was present in the subendothelial spaces of sinusoids in every histological pattern, the localization of these components in the intercellular spaces of tumor cells was most marked in hepatocellular carcinoma with a compact pattern. These results suggest that the extracellular matrix produced by tumor, endothelial, and Ito cells is deposited in appropriate positions in hepatocellular carcinoma to sustain the tissue structure showing different histological patterns. In relation to the grade of tumor differentiation, in most cases, Type I, III, and IV collagens and fibronectin were present in the subendothelial spaces of sinusoids and the intercellular spaces of some tumor cells, while little laminin was observed in well-differentiated small hepatocellular carcinoma (less than 10 mm diameter). In undifferentiated hepatocellular carcinoma, little extracellular matrix was observed, except around vessels. These results suggest that sinusoidal capillarization may not yet have occurred in the early stage of hepatocarcinogenesis, although it develops as the tumors increase in size and the tumor cells dedifferentiate. In undifferentiated hepatocellular carcinoma, tumor cells are too atypical to produce each extracellular matrix component.

Arterial chemotherapy and transcatheter arterial embolization therapy for non-resectable hepatocellular carcinoma

SummaryAn assessment was made on the therapeutic effects of arterial chemotherapy and transcatheter arterial embolization (TAE) therapy on 378 cases with non-resectable hepatocellular carcinoma (HCC). For the 191 cases who had undergone arterial chemotherapy, 22% had a 1-year survival rate, 8.9% survived for 2 years, and 4.0% for 3 years. Of these, for the 128 cases who were compatible with our criteria for patient selection, the three survival rates were 31.4%, 12.2% and 5.9% respectively. However, for the other 63 cases, who were incompatible with our criteria, the 1-year survival rate was 1.6% and it was worse for the cases who had received supportive care alone. For the cases who had undergone arterial chemotherapy, the highest survival rates were obtained by the alternate administration of different anticancer agents, and the three survival rates were 39.0%, 13.1% and 4.9% respectively. For the 187 cases who had undergone TAE therapy, the 1-year survival rate was 66.2%, the 2-year survival rate 36.5%, and the 3-year survival rate 21.9%. For the 124 cases with a tumor progression rate of less than 20% in the liver (E1), the survival rates were 77.8%, 50.1% and 30.8% respectively. The peripheral venous drug concentrations of mitomycin C and adriamycin were lower, but were maintained for a longer period in TAE therapy than in arterial chemotherapy. These results suggest that consideration of the criteria for patient selection and the alternate administration of anticancer agents are necessary in arterial chemotherapy, and that the best therapeutic effects can be obtained by TAE therapy combined with chemotherapy for cases of non-resectable HCC because of the chemotherapeutic and ischemic effects on the tumors.

A patient with hepatocellular carcinoma who underwent resection of the primary lesion 10 years ago and resection of a giant adrenal metastasis 8 and a half years later.

SummaryA 56-year-old male consulted us because of a palpable mass and pain of the left flank 8 and a half years after resection of hepatocellular carcinoma of the left lobe about 3 cm in diameter. Ultrasound examination of the abdomen demonstrated a tumor about 10 cm in diameter showing a mosaic of hyperechoic and hypoechoic areas on the upper pole of the left kidney. By angiography, the tumor was found to be supplied mainly by the inferior adrenal artery. PIVKA-II was increased. Adrenal metastasis of hepatocellular carcinoma was suspected, and adrenalectomy was carried out. No intrahepatic metastasis was noted. The tumor was histopathologically identified as a pseudo-glandular type of moderately differentiated hepatocellular carcinoma with a trabecular pattern similar to the primary lesion. In this patient, a resectable giant metastasis was observed only in the left adrenal gland and no intrahepatic metastasis was demonstrated 8 and a half years after resection of hepatocellular carcinoma. The patient has survived 10 years after the first operation. This case is considered to be important for evaluation of the treatment for distant metastasis of hepatocellular carcinoma.

Ultrastructural observation on hepatocellular carcinoma

In 31 cases of hepatocellular carcinoma, electron microscopic observation and morphometry on the cell organelles were carried out to evaluate the usefulness of electron microscopy for the diagnosis of well differentiated hepatocellular carcinoma. The cell organelles in well differentiated tumor cells were very similar to those in normal hepatocytes or hepatocytes with liver cirrhosis (LC). We found that in poorly differentiated tumor cells, the nuclear area, N/C ratio, nucleolar area, the amount of dispersed chromatin, and the number of free ribosomes had increased, but the cellular area, degree of nuclear roundness, and mitochondrial area had decreased. These results seem to indicate that electron microscopy is not as useful as light microscopy in the diagnosis of well differentiated hepatocellular carcinoma, but is useful in the study of poorly differentiated tumor cells, which indicated that the cell proliferation through mitoses was activated.

Involvement of arterial blood supply in the proliferation of hepatocellular carcinoma

Abstract The aim of this study was to clarify whether arterial blood supply by tumor vessels was involved in the proliferation of hepatocellular carcinoma. Proliferative activity was evaluated by the tumor volume doubling time determined on ultrasonography and the number of silver-staining nucleolar organizer regions in biopsy specimen. The degree of arterial blood supply to the tumor was evaluated based on the degree of contrast enhancement during the early phase on incremental dynamic computed tomography. The tumor volume doubling time negatively correlated with the number of silver-staining nucleolar organizer regions. The number of silver-staining nucleolar organizer regions in hepatocellular carcinoma cells was significantly increased with the increase of arterial blood supply. In well-differentiated hepatocellular carcinomas, the number of silver-staining nucleolar organizer regions in the group showing arterial blood supply on computed tomography was significantly increased compared with that in the group without arterial blood supply to the tumor. These findings suggest that the arterial blood supply is involved in the proliferation of hepatocellular carcinoma.

A case of laparoscopic microwave coagulo-necrotic therapy for small hepatocellular carcinoma.

肝後下区域(S6)の腹側表面に,癌腫の一部が露出し存在した22×21mmの小肝細胞癌に対して,新たに開発した手術機器を用いて,本邦で初めて,腹腔鏡下マイクロ波凝固壊死療法を行ったところ,本法は,小肝細胞癌に対する新しい治療法として,有用と考えられたので報告した.症例は63歳,男性.肝機能,および凝固系検査の術後推移をみると,術後1日目に,GOTは423K.U, GPTは241K.U, T. Bil.は2.1mg/100mlと上昇した.また,術後,凍結血漿をまったく使用しなかったため,HPTは42%, PTは48.3%に低下した.しかし,すべての検査値は,術後7日目には術前値に復した.胃管は,術翌日には抜去し,2日目より食事を開始した.術後3週目に撮影したCTでは,治療部は癌腫を含め,著しくlow density areaに陥り,まったくenhanceされず,治療効果も充分であると判断された.また,術後合併症はまったく認められなかった.

Abstracts of selected papers presented at the 30th Annual meeting of the Japanese Society of Gastroenterology

S OF SELECTED PAPERS PRESENTED AT THE 30TH ANNUAL MEETING OF THE JAPANESE SOCIETY OF GASTROENTEROLOGY October 20-22, 1988 -Kagoshima, Japan Chairman: Shuji HASHIMOTO, M.D.

Abstracts of selected papers presented at the 29th annual meeting of the japanese society of gastroenterology

S OF SELECTED PAPERS PRESENTED AT THE 29TH A N N U A L MEETING OF THE JAPANESE SOCIETY OF GASTROENTEROLOGY K0fu, Japan, November 5--7, 1987 Chairman: Katsuhiko SUGAHARA, M.D.

Clinical studies of hepatocellular carcinoma (HCC) in the aged patients.

老年人口の急速な増加に伴い,老年者肝細胞癌(以下肝癌)を診断,治療する機会も増えた.1973年から10年間に経験した肝癌379例を59歳以下,60～69歳,70歳以上の3群に分け,高齢者肝癌の特徴について検討した.70歳以上の高齢者肝癌は55例(14, 5%)で,1979年までは増加したが,その後減少した.男女比は加齢と共に低下し,高齢者では4.5:1であった.肝硬変を合併する肝癌は61%と少なく,大酒家も少数であった.HBs抗原,HBc抗体陽性率は加齢と共に低下したが,HBVマーカー陰性例には差がなかった.肝癌の自然発育速度は加齢と明確な関係はなかった.高齢者では手術可能例が少なく,動脈塞栓療法の予後は加齢と共に不良となった.動脈内注入化学療法は高齢者で骨髄抑制などの副作用の出現率が高いが,予後は若年者と差がないことから,これらに注意して積極的に施行すべきであると考えられた.死因は腫瘍破裂と腫瘍死が多く,肝不全は少なかった.