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Biomedical subjects

Y Tokusashi

Publications and source records attributed to Y Tokusashi.

At least 19 recordsLinked to original sources

[Basaloid-squamous carcinoma of the esophagus: report of a case].

We report herein the case of a 66-year-old man with basaloid squamous cell carcinoma (BSCC) of the esophagus. There are only 60 cases of BSCC of the esophagus previously reported in Japan. In our patient, endoscopic findings revealed a type 2 in the lower intrathoracic esophagus (Lt), and the tumor was intact with the aorta (T2). A biopsy suggested that it was adenosquamous cell carcinoma. An operation was done on June 11, 1996. With open thoracotomy, esophagectomy was performed with mediastinal lymphnode dissection by posterior mediastinal esophagogastrostomy. Histologically, the lesion of the tumor with ulceration was composed of BSCC, and other lesion was composed of typical squamous cell carcinoma (SCC). The immunohistochemical findings of the respected specimens led us to suspect that the basal-layer-type SCC had transformed into BSCC by undergoing differentiation and expansive proliferation. According to the prognosis, eventually the patient died of pneumonia due to methicillin resistant Staphylococcus aureus (MRSA) and candida 4 years and 9 months after the surgery.

Aged↗

Paravertebral neurinoma associated with aggressive intravertebral extension.

Neurinomas are relatively common benign tumors thought to arise from nerve sheath cells. Although intraosseous neurinomas may destroy the bone, extraosseous neurinomas with extensive destruction and invasion of bone are considered rare. We present two unusual cases of a benign extraosseous neurinoma that extensively invaded the vertebral body through the nutrient canal.

Adult↗

Prognostic significance of the labeling of Adnab-9 in pancreatic intraductal papillary mucinous neoplasms.

BACKGROUND: Pancreatic intraductal papillary mucinous neoplasms (IPMN), morphologically resembling colonic adenomas, often have an indefinable malignant potential. We used a monoclonal antibody (MAb) raised against colonic adenomas, Adnab-9, to identify patients with a better prognosis. METHODS: We assessed Adnab-9-labeled sections of these neoplasms from 50 patients, 13 pancreatic adenocarcinomas, and 32 colonic adenomas using standard immunohistochemical techniques. RESULTS: 26% of the IPMNs labeled with Adnab-9 as compared to 0% of pancreatic ductal cancers or surrounding benign tissues, (p < 0.001) and 53% of adenomas (p < 0.025). Labeling in IPMNs was usually seen in the noninvasive epithelium suggesting that Adnab-9 is a premalignant marker in these lesions. Labeling of invasive IPMN's identified a group of patients with a superior overall survival (p = 0.027). CONCLUSION: Adnab-9 labeling-characteristics appear similar for both IPMNs and adenomatous polyps, suggesting that they are analogous lesions. Adnab-9 labeling may also be a useful prognostic marker for invasive intraductal papillary mucinous neoplasms.

Adenocarcinoma, Mucinous↗

Protein-loss into retroperitoneal lymphangioma: demonstration by lymphoscintigraphy and blood-pool scintigraphy with Tc-99m-human serum albumin.

A rare, benign congenital lymphangioma has been reported to occur frequently in the neck and axilla, but rarely in the retroperitoneal space. We report a case of a retroperitoneal lymphangioma associated with hypoproteinemia caused by protein-loss into the tumor. In this case, lymphoscintigraphy with subcutaneously injected Tc-99m-human serum albumin (HSA) disclosed the communication between the tumor and the lymphatic system, and sequential abdominal scintigraphy with intravenously injected Tc-99m-HSA revealed the protein loss into the tumor. Abdominal scintigraphy with Tc-99m-HSA injected intravenously or subcutaneously is occasionally useful for determining the etiology of hypoproteinemia.

Adolescent↗

Genetic classification of combined hepatocellular-cholangiocarcinoma.

Combined hepatocellular-cholangiocarcinoma (combined HCC/ CC) is a rare form of liver neoplasms showing both hepatocellular (HCC) and bile duct differentiation (CC). In an attempt to clarify the clonality and genetic/phenotypic relationships in the evolution of these neoplasms, we microdissected multiple HCC and CC foci and studied allelic status of chromosome arms 1p, 1q, 3p, 4q, 5q, 6q, 8p, 9p, 10q, 11q, 13q, 16q, 17p, 17q, 18q, and 22q. Overall, the highest frequency of loss of heterozygosity (LOH) was seen on 4q and 17p, followed by 8p and 16q. Of the 11 cases studied, 3 cases did not show any of the identical allelic losses between HCC and CC foci, indicating the biclonal nature. The remaining 8 cases showed multiple allelic losses shared between both components, strongly suggestive of a single clonal derivation. Moreover, 4 of the 8 cases showed additional or divergent allelic losses at more than 1 chromosomal locus only in HCC and/or CC foci. Thus, this heterogeneity was shown to affect the phenotypic diversity of the tumor. Summarizing the genetic patterns, combined HCC/CC could be classified into the following 3 possibilities: (1) collision tumor in which 2 independent neoplastic clones develop at close proximity; (2) single clonal tumor with homogeneous genetic background in both components--histological diversity is thus a manifestation of divergent differentiation potential of a single clone; (3) single clonal process in which genetic heterogeneity in the process of clonal evolution within the tumor parallels histologic diversity; therefore, the tumor in this category is mainly composed of mosaics of closely related subclones.

Aged↗

Successful treatment of a patient with nephrotic syndrome associated with chronic lymphocytic leukemia.

We report the case of a 62-year-old man with nephrotic syndrome associated with stage B chronic lymphocytic leukemia (CLL). Kappa Bence Jones proteinuria and the glomerular deposition of kappa-light chain were observed. Although treatment with cyclophosphamide and prednisolone tended to reduce the level of proteinuria, the administration of angiotensin-converting enzyme inhibitor, enalapril, resulted in complete remission of nephrotic syndrome.

Angiotensin-Converting Enzyme Inhibitors↗

Beta-catenin mutations are frequent in hepatocellular carcinomas but absent in adenomas induced by diethylnitrosamine in B6C3F1 mice.

Activating mutations in the region of the beta-catenin gene corresponding to the NH2-terminal phosphorylation sites of glycogen synthetase kinase 3beta have been causally implicated in carcinogenesis. In this study, the beta-catenin exon 3 was examined in hepatic lesions induced by diethylnitrosamine in B6C3F1 mice. PCR and DNA sequencing detected seven beta-catenin mutations in 13 samples dissected from hepatocellular carcinoma tissues, but none in 14 hepatic adenomas. All of the mutations were found in codon 41 encoding a threonine residue, one of the possible glycogen synthetase kinase-3beta phosphorylation sites. Although beta-catenin protein was immunohistochemically stained mainly on the cell membrane in preneoplastic hepatocytic foci and most adenomas, as observed in normal hepatocytes, it was detected in the cytoplasm and nuclei in addition to the cell membrane, indicating stabilization of the protein in HCCs. This shift in staining was observed not only in tumors with mutations, but also in examples lacking exon 3 mutations. Our data demonstrate that beta-catenin alterations may be important for malignant progression during multistep hepatic carcinogenesis in mice.

Adenoma↗

Metastatic seeding of bile duct carcinoma in the transhepatic catheter tract: report of a case.

We describe herein the case of a 51-year-old woman in whom metastatic tumor seeding of the percutanenous transhepatic biliary drainage tract occurred following a pancreatoduodenectomy for carcinoma of the distal common bile duct. An abdominal computed tomography scan done 6 months after the initial operation detected a hepatic lesion located at the site of the previous percutaneous transhepatic biliary drainage tract. Implantation of bile duct carcinoma in the drainage tract was diagnosed, and the recurrent tumor was successfully resected by performing a subsegmentectomy of segment 3 and removal of the adjacent abdominal wall. At present, 5 years and 4 months after the second resection, the patient is in good health without any signs of recurrence. This case report demonstrates that an aggressive surgical approach should be performed for tumor seeding of a transhepatic biliary catheter tract.

Carcinoma, Squamous Cell↗

Mucin-producing tumors of the pancreas: clinicopathological features, surgical treatment, and outcome.

Mucin-producing tumors (MPTs) of the pancreas are increasingly being recognized. To evaluate the appropriate surgical treatment and predict the prognosis of MPTs, we performed a retrospective clinicopathological study in 51 patients, 27 with benign tumors and 24 with borderline/malignant tumors. Three of the malignant tumors showed stromal invasion and lymph node metastasis on histological examination. Of the 24 patients with borderline/malignant tumors, 2 died of MPTs and 4 died of other diseases. At the last follow-up, 35 patients were alive and well. The 5-year postoperative survival rate was 90% for patients with benign tumors, and 78% of these with borderline/malignant tumors. Five of the patients with borderline/malignant tumors had multicentric tumors. Three of these patients underwent resection of the rest of the pancreas, 5, 6, and 8 years, respectively, after the first operation. Extended radical resection is required for malignant MPT with invasion of the pancreatic stroma. We prefer to perform pancreatogastrostomy or Imanaga's procedure to allow examination of the body and tail of the pancreas by endoscopic retrograde pancreatography after resection of the pancreatic head. Careful follow-up for a long period may be the most prudent approach for detecting multiple MPTs in the residual pancreas after surgical treatment.

Adenocarcinoma, Mucinous↗

Papillary adenoma of the distal common bile duct.

A 73-year-old man with a papillary adenoma located in the distal common bile duct is reported. He underwent pylorus-preserving pancreatoduodenectomy. The lesion in the common bile duct featured papillary proliferation of the epithelium and fibrous elements with diffuse infiltration by inflammatory cells. Positive staining for MIB-1 (Ki-67) and p53 was identified in the nuclei of the proliferative epithelium. These findings suggested the malignant potential of this lesion. Further progress in imaging diagnostic techniques should increase the frequency with which such lesions are discovered. Even now, if mural irregularities and defects are found in the extrahepatic biliary system, especially the distal common bile duct, the possibility of such borderline biliary adenoma should be taken into consideration when making a diagnosis.

Adenoma, Bile Duct↗

Morphology, proliferation and apoptosis of mouse liver epithelial cells cultured as spheroids.

The MLEC10 is an epithelial cell line derived from an untreated, normal C3H/HeN mouse liver. We previously demonstrated that tumorigenic variants from this cell line produced moderately differentiated hepatocellular carcinomas in nude mice. However, it has remained unclear whether the parental MLEC10 cells represent immortalized hepatocytes or so-called oval cells, both of which may serve as precursors for hepatocellular neoplasms. In this study, we performed 3-dimensional, spheroid culture of the MLEC100 cells in order to facilitate histological assessment of their lineage. Spheroidal aggregates were formalin-fixed and embedded in paraffin for routine light-microscopic observation of hematoxylin and eosin-stained sections. Histopathologically, the MLEC10 cells were indistinguishable from immature hepatocytes and distinct from oval cells. At the electron-microscopic level, their hepatocytic nature was evidenced by bile canaliculus structures and glycogen storage. Intriguingly, the spheroids contained fragmentary material reminiscent of Councilman bodies, implying apoptosis of the hepatocytes. Although the cells significantly proliferated during the first three days of culture, apoptotic death then resulted in a 75 % decrease in viable cell number. Thereafter, both apoptosis and cell division appeared silent, the numbers being unchanged. Expression of the p53 tumor suppressor gene became gradually elevated, correlating positively with growth arrest, but negatively with apoptosis, suggesting that the cell death occurred independently of p53. Our results indicate that at least some liver epithelial cell lines derived from untreated murine livers exhibit a hepatocytic morphology in spheroid culture. Also, the present culture system provides a useful tool for investigating biological phenomena, e.g. apoptosis, specifically involving liver cells, under 3-dimensional conditions.

Agar↗

[Apolipoprotein E immunoreactivities in normal human ovary and ovarian neoplasms].

An immunohistochemical study on localization of apoE in normal human ovary and various ovarian neoplasms was performed using polyclonal anti-human apoE antibody. In the normal tissues, apoE immunoreactivity was found in folliculus (theca interna and stratum granulosum), and most intensely in a corpus luteum. The stroma cells were not stained. Among various ovarian tumours, positive staining was found in granulosa cell tumour, teratoma and dysgerminoma. Close relationship between apoE and steroid synthesis was suggested by the distribution of apoE in the studied tissues. The present results show that an immunohistochemical study for apoE may be helpful for the diagnosis of steroid producing tumours.

Apolipoproteins E↗

Genetic progression and heterogeneity in intraductal papillary-mucinous neoplasms of the pancreas.

Intraductal papillary-mucinous neoplasms (IPMNs) of the pancreas are ideal neoplasms to study clonal progression and genetic diversity because of their large size and prominent intraductal component. We microdissected 55 histologically defined areas from 13 IPMNs, extracted the DNA from each, and performed polymerase chain reaction (PCR)-based microsatellite analysis to detect loss of heterozygosity on chromosome arms 1p, 3p, 6q, 8p, 9p, 17p, 18q, and 22q. LOH was identified at 1p in two cases, at 3p in four cases, at 6q in seven cases, at 8p in four cases, at 9p in eight cases, at 17p in five cases, at 18q in five cases, and at 22q in one of the IPMNs examined. In one of the IPMNs, the allelic losses were uniform throughout multiple microdissected areas, and in four of the IPMNs, there was evidence of clonal progression. In contrast, in three of the IPMNs, substantial allelic heterogeneity was seen. This remarkable heterogeneity may, in part, be due to the slow growth rate of these neoplasms.

Adenocarcinoma, Mucinous↗

[Multiple myeloma with a solitary osteosclerotic legion on seventh cervical vertebra].

The osseous manifestation of multiple myeloma is well known as the osteolytic or osteoporotic feature. On the other hand, there are rare cases of general osteosclerotic manifestation as myeloma variants. We report a case of multiple myeloma with solitary osteosclerotic legion in the cervical vertebra. A 60-year-old-man was admitted with paralysis of both arms. The cervical roentogenogram showed the osteosclerotic change of the seventh cervical vertebra. The pathological study of surgical bone biopsy from the vertebra revealed osseous and severe fibrotic change and accumulation of plasma cells in the residual bone marrow. Clusters of plasma cells were also observed in the bone marrow of ileac bone. In addition, IgG-lambda type M protein was seen in the serum. Therefore we diagnosed this case as the osteosclerotic multiple myeloma. We then analyzed the cytokines known to influence bone formation, and found that the bone marrow serum TGF-beta and PDGF levels were increased compared with normal control. These results may suggest that the preferential increase of osteosclerotic cytokines caused the osteosclerotic changes of bone marrow.

Cervical Vertebrae↗

Hepatocytic cells form bile duct-like structures within a three-dimensional collagen gel matrix.

It has been suggested that hepatocytes have the ability to form bile ductal structures during normal development and in various pathological conditions of the liver. In the present study, we attempted to establish an in vitro model of ductal morphogenesis of hepatocytic cells by combining an aggregate culture and a type I collagen gel culture. When spheroidal aggregates of rat or mouse primary hepatocytes were embedded within the collagen gel matrix and then cultured with a medium containing a fibroblast-conditioned medium, the aggregates extended many dendritic processes composed of a trabecular arrangement of cells. Dendritic morphogenesis was also seen in embedded aggregates of immortal liver epithelia] cell lines, which spontaneously emerged during long-term cultures of mouse primary hepatocytes. A similar morphogenesis was induced by the presence of insulin in the medium. Although epidermal growth factor (EGF) and hepatocyte growth factor (HGF) showed only a small effect on the morphogenesis of most of the hepatocytic cells when used alone, these factors, especially EGF, enhanced the morphogenetic effect of insulin. Electron microscopical observations revealed luminal structures lined by microvilli within these dendritic processes, indicating ductal differentiation. Immunocytochemically, the dendritic processes were positive for cytokeratin 19, a marker for bile duct cells. On the other hand, an H-ras-transformed mouse liver epithelial cell line and rat hepatocellular carcinoma cell lines did not demonstrate the organized morphogenesis. Our results indicate that hepatocytic cells can produce bile duct-like structures in the presence of the type I collagenous matrix and soluble morphogenetic factors.

Animals↗