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Biomedical subjects

M Kojiro

Publications and source records attributed to M Kojiro.

At least 91 records · Page 5Linked to original sources

Clinicopathologic study on lymph node metastasis of hepatocellular carcinoma: a retrospective study of 660 consecutive autopsy cases.

There have been few reports in the literature concerning lymph node metastasis (LM) in hepatocellular carcinoma (HCC). Nowadays, hepatectomy has become one of the most popular treatments for HCC, and understanding LM in HCC is indispensable at surgery for improving the patient's prognosis. In the present study, the authors verified this using autopsy cases. The clinicopathologic characteristics of LM have been studied in 660 consecutive autopsy cases of HCC at Kurume University Hospital during the past 22 years. LM was noted in 168 (25.5%) of the 660 cases, and was most frequent (66.7%) in HCCs of the pedunculated type. The incidence of LM was significantly higher in the massive type of HCC (30.1%) than the nodular type (19.9%) (P < 0.05). The incidence of LM was also higher in non-cirrhotic (34.8%) than cirrhotic cases (23.5%) (P < 0.05). No metastasis was found in tumors less than 3 cm in diameter. The metastasis rate increased to 40% in tumors larger than 10 cm in diameter. The LM sites were peripancreatic, 13.6%; hepatic hilar, 13.5% and perigastric, 10.8%. The incidence of LM in the perigastric nodes was significantly higher in tumors located in the left hepatic lobe. LM was not found in well-differentiated HCCs but was frequently found in poorly-differentiated HCCs. Extensive LM was found in 60% of HCCs with sinusoidal tumor growth and in 57% of cases showing sarcomatous changes.

Aged↗

[A study on the distribution of metastases at autopsy in 70 patients with ovarian cancer].

A total of 6,457 autopsy protocols were reviewed to identify 70 women who died of ovarian cancer. 1. Epithelial tumors were the most common tumor (74%). Twenty% were germ cell tumors. There were two cases each of sarcoma and stromal cell tumors. 2. The patients with germ cell tumors were younger than those with epithelial tumors. The duration of the epithelial tumor disease was longer than that of germ cell tumor. 3. The most common mechanism of death was carcinomatosis (69%). Eight of 70 patients (11%) had respiratory failure. One case of subacute cor pulmonale was due to tumor embolization. One case had a rupture of the portal vein. 4. The peritoneum was most frequently involved in every tumor (87%). The liver was the second most frequent site (73%). Other frequent metastatic sites included the lungs (44%), and spleen (47%). Lymph nodes including the paraaortic, pelvic and mesenteric were also very frequent metastatic sites. 5. CDDP containing regimens were used in 33 cases (47%). FAMT regimen was the second most common treatment (15.7%). Another common treatment is whole abdominal radiotherapy (14%). The patients treated with the CDDP containing regimen had a significantly longer survival time (23.4 months) than those treated with FAMT (19.2 months) and others (13.6 months). 6. For metastasis to the lungs, spleen and mesenteric lymph nodes the patients treated with the CDDP containing regimen were more numerous than those treated without CDDP. For metastasis to the kidneys, the patients treated without CDDP were more numerous than those treated with CDDP containing regimens.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

The increasing prevalence of benign proliferative breast lesions in Japanese women.

BACKGROUND: Although the increasing incidence of breast cancer in Japan has been well-documented, the possibility that there also has been an increase in the frequency of benign proliferative breast disease in Japanese women has not been previously studied. METHODS: The authors compared the histologic findings in a series of 266 consecutive benign breast biopsy specimens from 1974 to 1975 (Group I) to those in a series of 266 similar biopsy specimens accessioned at the same institution in Japan one decade later (i.e., 1984 to 1985; Group II). The extent of sampling was similar in both groups. The specimens were categorized as showing nonproliferative lesions, proliferative lesions without atypia, or atypical hyperplasia using the criteria of Dupont and Page. RESULTS: Proliferative lesions without atypia were significantly more common in biopsy specimens from Group II than those from Group I (16.2% versus 9%; P = 0.01). Although atypical hyperplasias were twice as common in Group II as in Group I, these lesions were uncommon in both groups (2% in Group II versus 1% in Group I, p = NS). The differences in pathologic findings between the two groups were most evident in younger women. For patients younger than 40 years of age, the prevalence of proliferative lesions (with or without atypia) was 18% for Group II and 6% for Group I (P = 0.003). For patients 40 years of age or older, proliferative lesions were seen in 17% of patients in Group II and 13% in Group I (P value, not significant). CONCLUSIONS: The frequency of benign proliferative breast lesions in Japanese women, particularly among women younger than 40 years of age, is increasing. These observations are consistent with the results of previous studies in North America that have demonstrated a relationship between benign proliferative breast lesions and the development of breast cancer.

Adolescent↗

Induction of apoptosis by transforming growth factor-beta 1 in the rat hepatoma cell line McA-RH7777: a possible association with tissue transglutaminase expression.

We report here that transforming growth factor-beta 1 induces cell death in the Morris hepatoma cell line McA-RH7777. We assessed the type of cell death induced by transforming growth factor-beta 1 in this hepatoma cell line on the basis of morphological and biochemical characteristics. Dying cells, which detached from the cell monolayer, showed morphological characteristics of apoptosis (programmed cell death) such as chromatin condensation, nuclear disintegration and cellular fragmentation into clusters of eosinophilic globules. DNA isolated from these cells showed a ladder pattern consisting of multimers of 180 to 190 bp, indicating extensive DNA cleavage into oligonucleosomal units by an endogenous endonuclease. Treatment of the dead cells with detergents and chaotropic agents resulted in formation of insoluble shells, so-called apoptotic bodies, suggesting extensive cross-linking of cell proteins by tissue transglutaminase. Furthermore, increased amounts of cytosolic tissue transglutaminase, which has been recognized as a possible marker of apoptosis, and extensive cross-linking of cytokeratin polypeptides was demonstrated in TGF-beta 1-treated hepatoma cells on immunoblot analysis. These results provide strong evidence that the cell death induced by TGF-beta 1 in McA-RH7777 hepatoma cells is mainly apoptotic. It also suggests that a specific induction of the cytosolic tissue transglutaminase may be involved in the TGF-beta 1-induced pathways of apoptotic cell death in McA-RH7777 hepatoma cells.

Animals↗

Morphologic characteristics, proliferation, and tumor marker expression of two human ovarian carcinoma cell lines in three-dimensional culture.

Two cell lines derived from human serous ovarian adenocarcinoma (KOC-1S, KOC-2S) were cultured three-dimensionally in type I collagen gel, and their morphology, growth kinetics, and tumor marker expression were compared with those of cells grown on plastic dishes. KOC-1S cells were established from a well-differentiated adenocarcinoma and they formed three-dimensional round colonies and tubular structures in collagen gel culture. KOC-2S cells were established from a poorly differentiated serous adenocarcinoma and they proliferated diffusely in a solid pattern to form irregularly shaped colonies in collagen gel culture. The doubling times of both cell lines were longer in collagen gel culture, but the ratio of their doubling times was virtually the same in both culture systems. KOC-1S cells produced CA125 and TPA, while KOC-2S cells only produced TPA. For both cell lines, tumor marker secretion per 10(5) cells was greater in collagen gel that on plastic dishes. These results suggest that human ovarian carcinoma cell lines retain characteristics similar to those in vivo with regard to histologic type, degree of differentiation, and growth kinetics when they are cultured in collagen gel.

Antigens, Neoplasm↗

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.

A 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.

Adrenal Gland Neoplasms↗

Alveolar soft part sarcoma of the uterine cervix.

A rare case of an alveolar soft part sarcoma of the uterine cervix in an 8 year old girl is presented. The patient was admitted because of genital bleeding lasting for 7 months. A polypoid tumor, 2 x 1.5 cm in diameter, was found in her external uterine os and was surgically resected. Microscopically, the tumor consisted of a uniform sheet of tumor cells in the cytoplasm which contained granules and which were stained with periodic acid-Schiff, both before and after the diastase digestion. Alveolar arrangement of the tumor cells was manifested with reticulin silver impregnation. Dense, membrane bound granules were evident at an ultrastructural level in the cytoplasm of the tumor cells. An immunohistochemical examination demonstrated a positive reaction for anti-desmin, anti-myoglobin, anti-HHF35 and anti-neuron specific enolase in the cytoplasm.

Child↗

Cross-linked cytokeratin polypeptides in liver and hepatoma cells: possible association with the process of cell degeneration and death.

We investigated transglutaminase-induced cross-linking of cytokeratin polypeptides in liver and hepatoma cells. To overcome the difficulties in the biochemical analysis of highly cross-linked polymers and aggregates of cytokeratins, cross-linked cytokeratin dimers were analyzed by immunoblotting to evaluate the degree of cross-linking of cytokeratins. Covalently cross-linked cytokeratin dimers were not detectable in normal rat liver cells. However, cytokeratin dimers and high-molecular-weight cytokeratin polymers were detected in liver tissue with histological evidence of coagulative necrosis induced by ischemia or carbon tetrachloride. Treatment of cultured hepatoma cells with the Ca2+ ionophore A23187 showed a dose-dependent, time-dependent decrease of cell viability. The appearance of cytokeratin dimers was shown to be correlated with cell death. These results suggest that the transglutaminase-induced cross-linking of cytokeratin polypeptides in liver and hepatoma cells is closely associated with the process of cell degeneration and death.

Animals↗

Intrahepatic and extrahepatic biliary papillomatosis.

We report a case of biliary papillomatosis that occurred 8 years after resection of a bile duct tumor. In 1982, a 63-year-old man underwent a cholecystectomy because of cholelithiasis. At operation, a solitary tumor was found in the left intrahepatic bile duct, and a lateral hepatic segmentectomy was performed. The tumor was diagnosed as a benign papillary adenoma. In 1990, mild liver dysfunction was revealed in a routine medical examination. Ultrasonography and computed tomography showed a solid tumor measuring approximately 6 cm in diameter in the left hepatic duct. There was no appearance of jaundice during the course. In 1991, a partial hepatic resection and a bile duct resection were performed. At operation, two tumors were found and removed. These tumors were essentially the same as the bile duct tumor resected 8 years ago. They were diagnosed as biliary papillomatosis.

Bile Duct Neoplasms↗

Demonstration of extensive chromatin cleavage in transplanted Morris hepatoma 7777 tissue: apoptosis or necrosis?

Cell death may occur by either of two mechanisms: necrosis or apoptosis (programmed cell death). In this paper, we demonstrate extensive chromatin cleavage into oligonucleosome-length fragments (DNA ladder) in transplanted Morris hepatoma 7777 tissue, which is suggestive of the stimulation of an endogenous endonuclease activity previously found to be involved in the process of apoptosis. The existence of many apoptotic cells, which are morphologically characterized by condensed cytoplasm and basophilic nuclear fragments, were also seen in this tissue. In vivo and in vitro experiments were designed to further differentiate the morphological and biochemical features of necrosis and apoptosis in liver and hepatoma cells. Liver tissue undergoing ischemic necrosis showed a distinct DNA ladder pattern without demonstrating the morphology of apoptosis, indicating that chromatin cleavage into oligonucleosomal-length fragments is not confined to apoptotic cell death, at least in liver cells. In in vitro-cultured McA-RH7777 cells, however, DNA ladder pattern was detected only in cells showing characteristic morphology of apoptosis. From these two criteria (i.e., characteristic morphology and DNA ladder), it was strongly suggested that the apoptotic process is highly activated in the transplanted 7777 tissue. Based on the results obtained from in vitro experiments, it was suggested that tumor apoptosis may represent a residual attempt at autoregulation within the expanding tumor population and/or may result from mild cellular injuries such as hypoxia, nutrient deficiency, or other unknown noxious factor(s). We also showed evidence that apoptosis is inducible in hepatoma cells in vitro by a wide range of mild injuries or stimuli.

Animals↗

Establishment of two distinct human hepatocellular carcinoma cell lines from a single nodule showing clonal dedifferentiation of cancer cells.

Hepatocellular carcinomas often contain tumor cells of more than one histological grade. The clonal relationship and biological behavior of hepatocellular carcinoma cells in histologically heterogeneous areas have not been fully explored. We established two distinct human hepatocellular carcinoma cell lines (HAK-1A and 1B) from a single nodule showing a three-layered structure with a different histological grade in each layer. Morphologically, HAK-1A and 1B resembled well-differentiated hepatocellular carcinoma cells in the outer layer of the original tumor and poorly differentiated ones in the inner layer, respectively. HAK-1B appeared less differentiated morphologically and more aggressive biologically than HAK-1A; HAK-1B had a shorter doubling time, higher tumorigenicity and an aneuploid DNA index. Chromosome analysis revealed many different abnormalities in the two cell lines, in which, however, two identical structural abnormalities (2q+ and 17p+) were identified. Moreover, sequence analysis of the p53 gene showed identical mutations at codon 242 in both cell lines. These findings suggest that the two cell lines are of clonal origin and that hepatocellular carcinomas consisting of cancerous tissues of more than one histological grade may reflect clonal dedifferentiation in the tumor. Furthermore, we predict that a clonal, morphologically less differentiated subpopulation such as HAK-1B is more aggressive in proliferation and may be closely related to subsequent tumor progression in hepatocellular carcinoma.

Base Sequence↗

Infantile cholestasis due to cytomegalovirus infection of the liver. A possible cause of paucity of interlobular bile ducts.

We report a neonatal case of hepatic cytomegalovirus (CMV) infection associated with paucity of interlobular bile ducts. The premature infant developed severe jaundice, and died of disseminated CMV infection. The diagnosis of CMV infection was based on detection of pathognomonic inclusions in the liver and on a high titer of CMV antibody in the serum. The hepatic histologic findings in this infant included severe cholestasis, complete absence of interlobular bile ducts in the majority of the portal tracts, and CMV inclusions in the duct epithelium. Interestingly, the CMV inclusions were localized in the bile duct, but not in the parenchyma. We postulate that the paucity of interlobular bile ducts may have been a sequela of CMV infection of the liver arising from destruction of the bile ducts, leading to severe cholestasis.

Bile Duct Diseases↗

Apocrine adenocarcinoma arising in cystic teratoma of the ovary.

We present a rare case of an apocrine adenocarcinoma arising in a mature cystic teratoma of the ovary. The patient, a 41-year-old woman, was admitted to the hospital with low back pain and hypermenorrhea. A unilocular cystic tumor, measuring 5.5 x 5.0 cm in diameter, was found in her right ovary, and was removed. The tumor contained a mural nodule, measuring 8 x 7 mm in diameter. Microscopically, the unilocular cystic tumor was a teratoma consisting of mature cutaneous tissue with numerous hairs. The mural nodule was composed mostly of cords of epithelial cells with an infiltrative fashion and anastomosing tubular structures, which were lined partly by cells with eosinophilic cytoplasm and decapitation secretion. The cytoplasm contained iron granules as well as granules that were stained with periodic acid-Schiff, with and without diastase digestion.

Adenocarcinoma↗

The morphologic transition in hepatocellular carcinoma. A comparison of the individual histologic features disclosed by ultrasound-guided fine-needle biopsy with those of autopsy.

In hepatocellular carcinoma (HCC), it has been strongly suggested that as the tumor increases in size, foci of less-differentiated malignant tissues arise in the well-differentiated tumor and increase until they replace the well-differentiated tumor tissues. It has also been suggested that tumor growth is attributed to such dedifferentiation. In the current study, the individual histologic features of ultrasound-guided fine-needle biopsy specimens, taken from 12 small HCC in an early stage, were compared with those of autopsy to confirm the dedifferentiation of HCC. In all 12 cases, autopsy was performed 6 months or more after the initial biopsy. Dedifferentiation was demonstrated in 9 of 12 cases (75.0%). Most of the biopsy specimens from minute HCC were well-differentiated. All tumors that had been well-differentiated when evaluated by biopsy were found to have become moderately differentiated at autopsy. This comparative study confirmed the dedifferentiation of HCC with tumor growth.

Aged↗

A cholangiocellular carcinoma nude mouse strain showing histologic alteration from adenocarcinoma to squamous cell carcinoma.

BACKGROUND: Adenosquamous carcinoma and squamous cell carcinoma (SCC) occur rarely in the liver compared with adenocarcinoma, and the histogenesis and biologic behaviors of these tumors remain unknown. The authors addressed these issues in the current article. METHODS: A specimen aseptically obtained from the surgically resected cholangiocellular carcinoma (CCC) was cut into pieces and inoculated into the back of a nude mouse, bilaterally. The developed tumors were resected and serially transplanted into nude mice. The morphologic features and growth kinetics of the nude mouse tumors at different passages were compared. RESULTS: The authors established a new human CCC nude mouse strain, designated nuKMC-2, from a 64-year-old woman. The original tumor of the patient showed the features of moderately differentiated tubular adenocarcinoma with small sheet-like arrangement of polygonal cells. The initial tumor developed in a nude mouse showed morphologic features similar to the original tumor. With the serial transplantation to nude mice, the components of tubular adenocarcinoma diminished, and all of the nuKMC-2 was replaced by SCC. Doubling times of nuKMC-2 at the 5th and 11th passages were 9.9 and 7.4 days, respectively, which suggested that the tumor with squamous components were more aggressive biologically than the adenocarcinoma. CONCLUSIONS: The results suggested that adenosquamous carcinoma might be a transitional form from adenocarcinoma to SCC and that some of the primary hepatic SCC might originate from adenocarcinomas.

Adenocarcinoma↗

Establishment and characterization of a new human extrahepatic bile duct carcinoma cell line (KMBC).

A new human extrahepatic bile duct carcinoma cell line (KMBC) was established from a serially transplanted tumor in nude mice that originated from a surgically resected tumor from a 73-year-old Japanese man; the cell line has been maintained for 5 five years. KMBC cells proliferate in a monolayered sheet with a population doubling time of 30 hours. Chromosome number was distributed in a range from 37 to 44, with modal numbers of 40 and 41. KMBC cells and the reconstituted tumor in a nude mouse showed moderately to poorly differentiated adenocarcinoma and possessed various functional characteristics of extrahepatic bile duct carcinoma. KMBC cells secreted carbohydrate antigen 19-9, tissue polypeptide antigen, carcinoembryonic antigen, ferritin, beta 2-microglobulin, fibronectin, and alpha 2-macroglobulin and produced glutamic oxaloacetic transaminase and alkaline phosphatase. KMBC is the second established cell line that originated from a human extrahepatic bile duct carcinoma in the world literature, and it will be applicable to various experiments.

Adenoma, Bile Duct↗

Adenomatous hyperplasia in the vicinity of small hepatocellular carcinoma.

The nodular lesions seen in the noncancerous areas of the 80 consecutively resected small hepatocellular carcinoma associated with cirrhosis were pathomorphologically studied. A total of 51 nodular lesions were found, and they were classified into the following four groups: large regenerative nodule (30 nodules), adenomatous hyperplasia (12 nodules), atypical adenomatous hyperplasia (4 nodules) and adenomatous hyperplasia containing cancerous foci (5 nodules). Grossly, all large regenerative nodules were well demarcated, but some of the adenomatous hyperplasia group were vaguely nodular. Atypical adenomatous hyperplasia and adenomatous hyperplasia containing cancerous foci accounted for 43% of the adenomatous hyperplasia group found in the vicinity of the 16 resected hepatocellular carcinoma (20%) out of 80 cases. The mean size (+/- S.D.) of the adenomatous hyperplasias containing cancerous foci, 15.8 +/- 2.2 mm, was significantly larger than 10.1 +/- 2.6 mm of the adenomatous hyperplasias p less than 0.01). All adenomatous hyperplasias containing cancerous foci and 75% of the atypical adenomatous hyperplasias demonstrated a marked fatty change, but none of the large regenerative nodules were accompanied by any fatty changes. This study demonstrated the morphological transition from adenomatous hyperplasia to hepatocellular carcinoma that was suggestive of multistep hepatocarcinogenesis. As a result, it is predicted that approximately 20% of all hepatocellular carcinomas may have the potential for being of multicentric origin and that approximately 40% of adenomatous hyperplasias may undergo malignant transformation, but it is difficult to estimate the exact number of incidences. The presence of varying degrees of fatty change may be one of the significant morphological markers for a malignant transformation from adenomatous hyperplasia to hepatocellular carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗