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Biomedical subjects

Toshio Morohoshi

Publications and source records attributed to Toshio Morohoshi.

At least 19 recordsLinked to original sources

Oncocytic non-functioning endocrine tumor of the pancreas.

Herein is presented the case of a malignant non-functioning endocrine tumor of the pancreas with oncocytic features, and a discussion on the high incidence of malignancy in oncocytic endocrine pancreatic tumors. The patient was a 65-year-old woman who showed no paraneoplastic symptoms produced by functioning pancreatic endocrine tumors. The primary tumor was located in the body and tail of the pancreas, and had metastasized to the liver. Tumor cells were arranged in a ribbon-like or trabecular pattern and had an abundant eosinophilic cytoplasm containing numerous mitochondria and neurosecretory granules. The cytoplasm of the tumor cells was intensely stained with an antimitochondrial antigen antibody. Most tumor cells stained positively with Grimelius stain and for chromogranin A. Some tumor cells also stained for synaptophysin. However, the tumor cells negatively stained for hormones such as insulin, glucagon, somatostatin, gastrin, vasoactive intestinal peptide and pancreatic polypeptide, for serotonin, and for pancreatic enzymes such as amylase and trypsin. Analysis of 18 oncocytic pancreatic endocrine tumors, consisting of those reported previously and that in the present case, suggests that the high incidence of malignancy in oncocytic endocrine tumors is associated with the high incidence of non-functioning endocrine tumors among them, most of which are malignant.

Adenoma, Oxyphilic↗

Right pleural effusion in Fitz-Hugh-Curtis syndrome.

Right pleural effusion was diagnosed in a 36-year-old woman with right upper quadrant pain and fever. Enhanced pelvic computed tomography performed because of irregular genital bleeding revealed the pelvic inflammatory disease. Upon further questioning, the patient confirmed that she had recently undergone therapy for Chlamydia trachomatis infection. Therefore she was given an injection of tetracycline because we suspected Fitz-Hugh-Curtis syndrome (FHCS), a pelvic inflammatory disease characterized by perihepatitis associated with chlamydial infection. A remarkable clinical response to antibiotics was noted. The right upper quadrant pain was due to perihepatitis, and the final diagnosis was FHCS. Right pleural effusion may be caused by inflammation of the diaphragm associated with perihepatitis. Once chlamydial infection reaches the subphrenic liver, conditions in the closed space between the liver and diaphragm due to inflammatory adhesion may be conductive to chlamydial proliferation. The possibility of FHCS should be considered in patients and carefully distinguished from other abdominal diseases.

Adult↗

Clinical significance of nuclear morphometry at the invasive front of T1 colorectal cancer and relation to expression of VEGF-A and VEGF-C.

OBJECTIVES: To better understand the metastatic potential of T1 colorectal cancer, we investigated variations in nuclear morphometry and expression of angiogenic factors in cancer cells at the invasive front. Sixty-five patients who had undergone curative resection were entered. METHODS: Nuclear shape factor, area, width, and proportion of cells with large nucleoli in all cells were determined in two high-power magnification areas at the invasive front of the tumor. We then performed the Ward method for cluster analysis. A dendrogram revealed that cases fell into two clusters: cluster A with high atypical nuclei and cluster B with low atypical nuclei. Expression of vascular endothelial growth factor-A (VEGF-A) and -C were evaluated immunohistochemically at the invasive front of the tumor. RESULTS: Nuclear atypia, and VEGF-C expression were associated significantly with lymph node metastasis by univariate analysis. Nuclear atypia was independently and significantly associated with lymph node metastasis by multivariate analysis. Whereas VEGF-A expression was associated with nuclear atypia, VEGF-C expression was not showed. Nuclear atypia, strong VEGF-A or -C expressions were not associated with the depth of invasion. CONCLUSION: Nuclear morphometry and expression of angiogenic factors at the invasive front are useful prognostic markers of lymph node metastasis, even cases with slight invasion.

Adult↗

Osteopontin expression in proliferated bile ductules: the correlation with liver damage in fulminant hepatitis.

There have been many reports about the severity of hepatic necrosis caused by fulminant hepatitis; however, the relation between proliferated bile ductules and osteopontin (OPN) expression in inflamed areas in each of the clinical forms of fulminant hepatitis has not been described. To analyze the mechanism in the onset of fulminant hepatitis, we classified not only 16 autopsy cases of fulminant hepatitis into two clinical forms--acute and subacute--but also 3 autopsy cases of late-onset hepatic failure (LOHF) associated with fulminant hepatitis, and examined liver specimens by light microscopy and immunohistochemistry and also serum transaminase levels. Histopathologic study revealed that some of the proliferated bile ductules were associated directly with deteriorating hepatocytes and that bile plugs were present in the proliferated bile ductules. The value of the proliferative cell nuclear antigen labeling index (PCNA-L I) for proliferated bile ductules was very high during the acute form of fulminant hepatitis. Immunohistochemical analysis revealed that OPN expression was higher in the proliferated bile ductules of acute-form fulminant hepatitis than in cirrhotic and normal liver bile ducts. Transaminase levels in acute-form fulminant hepatitis were significantly elevated in comparison with levels in the other forms of the disease. Comparison of acute form fulminant hepatitis with the subacute form and LOHF showed OPN expression in proliferated bile ductules and serum aspartate aminotransferase (ALT)max to be decreased in the subacute form of fulminant hepatitis. OPN expression is an important marker of the degree of liver inflammation, and its regulation mechanism is very important to understanding the pathophysiology of fulminant hepatitis.

Acute Disease↗

Intraductal tubular neoplasms of the pancreas: histogenesis and differentiation.

OBJECTIVES: Intraductal neoplasms of the pancreas are generally referred to as intraductal papillary mucin-producing neoplasms (IPMNs), according to the WHO classification system. Herein, we report that morphologic and immunohistochemical features of intraductal tubular carcinoma (ITC) are quite different from those of intraductal papillary mucinous carcinoma (IPMC). METHODS: We analyzed histogenesis and differentiation of ITC by light microscopy and immunohistochemistry. RESULTS: Histologically, ITC was characterized as an intraductal nodular appearances with a monotonous tubular growth pattern without papillary projection. ITC showed de novo-like appearance without sequential progression usually observed in IPMC, suggesting that ITC is a homogeneous neoplasm. Cuboidal tumor cells in ITC resembled normal pancreatic duct epithelia, and the characteristic growth pattern of ITC replaced that of normal pancreatic duct epithelium. Immunohistochemically, ITC cells were positive for MUC-1 on the apical side of the cell membrane. In contrast to ITC cells, IPMC cells were negative for MUC-1, and ductal adenocarcinoma cells were strongly positive for MUC-1, as was the stroma around the cancer. The immunohistochemical staining pattern of DUPAN-2 resembled that of MUC-1. Interestingly, localization of MUC-1 and DUPAN-2 staining in ITC cells was similar to that in normal pancreatic ductules. ITC cells were negative for MUC-2 and MUC-5AC. In contrast, most IPMC cells were positive for MUC-2 and MUC-5AC. CONCLUSION: Based on our histologic and immunohistochemical findings, the intraductal pancreatic neoplasm (IPN) can be classified into 2 groups: IPN with gastrointestinal differentiation and IPN with pancreatic duct differentiation. Our present data indicated that ITC cells may arise directly from duct epithelia without progression and possessed pancreatic duct differentiation. On the basis of our data, we suggest that classification of pancreatic neoplasms in the WHO and The Armed Forces Institute of Pathology (AFIP) systems should be reconsidered.

Adenocarcinoma↗

Pathological assessment of pancreatic endocrine tumors for metastatic potential and clinical prognosis.

The prognostic significance of several pathological factors (tumor size, mitotic index, Ki-67 labeling index, and vascular invasion) and expression of exocrine markers (CA19-9, CEA, AFP, and trypsin) in pancreatic endocrine tumors was studied. A total of 20 specimens of metastasizing (n = 10) and non-metastasizing (n = 10) tumors were subjected to histological and immunohistochemical examination. The metastasizing tumors showed significantly larger size, higher Ki-67 labeling index, increased number of mitotic cells, and more frequent vascular invasion in comparison with the non-metastasizing tumors. It was difficult to determine the effect of individual factors on clinical outcome because of slow disease progression in almost all cases. Numerous mitotic cells and widespread necrosis, however, were thought to indicate a poor prognosis, and tumors with these characteristics were regarded as high-grade malignant endocrine carcinomas. In one case, one-third of the tumor tissue comprised trypsin-positive cells, the outcome was comparatively poor, and the behavior of the tumor resembled that of mixed acinar-endocrine carcinoma. A simple multifactorial approach may be effective for the identification of tumors at increased risk of metastasis, but it remains difficult to determine clinical prognosis. It is essential to at least distinguish high-grade endocrine carcinomas from the more common endocrine tumors.

Adult↗

Prognostic significance of the maspin tumor suppressor gene in pulmonary adenocarcinoma.

PURPOSE: Maspin is a member of the serpin family and has tumor suppressor activity. We evaluated maspin expression in pulmonary adenocarcinoma in relation to a number of clinicopathological features. METHODS: Maspin expression was examined immunohistochemically in a series of 78 pulmonary adenocarcinomas by the EnVision ChemMate method. RESULTS: . Thirty-seven of 78 cases (47%) showed distinct maspin expression (maspin-positive group) and 41 (53%) did not (maspin-negative group). Maspin expression was not associated significantly with most clinicopathological variables including sex, age, tumor size, primary tumor, lymph node metastasis, visceral pleural invasion, pulmonary metastasis, and disease stage. However, the maspin-positive group had a better 5-year survival rate (62%) than did the maspin-negative group (42%). The difference in the 5-year survival rate was greatest in stage II patients (maspin-positive group, 69%; maspin-negative group, 17%; P = 0.048). CONCLUSION: Our data indicate that maspin has prognostic significance for pulmonary adenocarcinoma. A better understanding of the role of maspin in tumor suppression may be helpful for development of novel chemotherapies for patients with this deadly tumor.

Adenocarcinoma↗

Mucinous cystadenoma of the pancreas 17 years after excision of gallbladder because of a choledochal cyst.

A 56-year-old woman who had undergone excision of the gallbladder because of a choledochal cyst had a tumorous lesion of the pancreas identified by upper abdominal ultrasonography, but an operation was not carried out, because there was no apparent increase in the cystic mass and no elevation of serum tumor markers. In October 2001, she was admitted to our hospital to check for malignancy because of elevated levels of the tumor marker Dupan-2. Abdominal enhanced computed tomography and upper abdominal ultrasonography revealed a large multilocular cystic mass in the body to tail of the pancreas. Endoscopic retrograde cholangiopancreatography showed elongation of the common duct that communicates with the common bile duct and the main pancreatic duct, indicating an anomalous arrangement of the biliary and pancreatic duct system. No apparent communications between the cystic mass and the main pancreatic duct were observed. In January 2002, the patient underwent a spleen-preserving distal pancreatectomy, and histopathological and immunohistochemical examinations led to the diagnosis of pancreatic mucinous cystadenoma with ovarian-like stroma. The mucinous cystadenoma was detected 17 years after the operation for the choledochal cyst. To the best of our knowledge, no documented case reports of mucinous cystadenoma of the pancreas associated with a choledocal cyst have been reported to date. We present here the first case report of pancreatic mucinous cystadenoma occurring in the body to tail of the pancreas, associated with a choledocal cyst.

Cholangiopancreatography, Endoscopic Retrograde↗

Relation of E-cadherin and beta-catenin expression to pit pattern in colorectal cancer.

To investigate the usefulness of pit pattern to estimate depth of submucosal invasion and the mechanism of change in pit pattern by tumor character in colorectal cancer, we investigated the relation between pit pattern and immuno-histochemical E-cadherin and beta-catenin expression. Fifty-seven colorectal tumors including 37 submucosal invasive carcinomas, 10 high-grade adenomas and 10 cases of advanced carcinomas invading into the muscularis propria were divided into a non-VN and VN group according to a modification of the Kudo classification system. In addition, distance between the invasive front and muscularis mucosae was measured, and histological and immunohistochemical expression of E-cadherin and beta-catenin in the superficial portion and invasive portion were examined. Many tumors with deep invasion were classified in the VN group. Among the submucosal invasive carcinomas in the VN group, there was a significantly higher number with deep invasion than with slight invasion. All submucosal invasive cancers with lymphatic invasion also had deep submucosal invasion. Immunohistochemical analysis revealed significant loss of normal membrano-cytoplasmic beta-catenin expression in the superficial area of cancers in the VN group. Submucosal carcinoma with deep invasion also had significant loss of membrano-cytoplasmic expression of beta-catenin in the superficial area. Pit pattern is useful not only to predict tumor character but also to estimate depth of invasion. Change in pit pattern may be associated with abnormality of beta-catenin expression.

Adenoma↗

Clinicopathological significance and molecular regulation of maspin expression in ductal adenocarcinoma of the pancreas.

We evaluated the biological relevance of maspin expression in pancreatic ductal adenocarcinoma and studied regulatory mechanisms of maspin gene activation in pancreatic carcinoma cell lines. Maspin expression was immunohistochemically detected in a series of 57 pancreatic ductal adenocarcinomas, 51 (90%) of which were classified as high-expressers. In lymph node metastases, maspin expression was somewhat decreasingly found in 39/49 (80%). Maspin high-expressers showed predominantly a low histological grade (p=0.013). Moreover, maspin expression was found in two mixed ductal-endocrine carcinomas, but not in 10 endocrine tumors and the surrounding normal pancreatic tissues. Using a luciferase reporter system, maspin promoter activity was induced in the maspin-positive pancreatic cancer cell lines as well as maspin-negative PANC-1 cells. Additionally, treatment with the DNA methyltransferase inhibitor, 5-aza-2' deoxycytidine, and histone deacetylase inhibitor, trichostatin A, led to re-expression of maspin mRNA in PANC-1 cells. Our results indicate that maspin expression is up-regulated in most if not all pancreatic ductal adenocarcinomas and may be related to the development and differentiation, and that DNA methylation and histone deacetylation may suppress maspin gene activation in pancreatic cancer cells.

Acetylation↗

Arteriovenous fistula and bone healing: experimental study in the rat.

The incidence of fractures is greater in patients with hemodialysis than in the general population. Surgically created arteriovenous fistulas are widely used in end-stage renal failure patients for the vascular access of hemodialysis. Despite occurrence of fracture at the fistula site in the forearm, bone mineral density is similar in both arms. The effects of arteriovenous fistulas on fracture healing have not been widely studied. The goal of this study was to test the hypothesis that a fracture distal to a surgically-created arteriovenous fistula has negative effects in a rat osteotomy model. The tibial bones were fractured in a monocortical fashion bilaterally. No fixation method was used. The right side was used as control. On the left side of the rat, a side-to-side arteriovenous anastomosis was done between the common femoral vessels proximal to the fracture line under magnification with the operating microscope. Three weeks later, bone segments, including the monocortical osteotomy line, were removed and examined histopathologically. Although the gross appearance of callus formation was not different in both groups, histopathologically, there were more dead medullary bone and less cartilage cells around the osteotomy line in the bone associated with the arteriovenous fistula. But with short-term evaluation of the fracture sites after opening an arteriovenous connection proximal to the fracture site, no real difference was noted related to fracture healing.

Anastomosis, Surgical↗

Immunohistochemical evaluation of tissue-specific proteolytic enzymes in adenomas containing foci of early carcinoma: correlations with cathepsin D expression and other malignant features.

BACKGROUND: Cathepsin D (CD) is an aspartyl lysosomal protease, and the prognostic value of CD expression has been studied in a variety of tumors, however, its role in early adenocarcinomas remains unclear. AIM OF THE STUDY: We evaluated the expression of CD in a series of colorectal adenomas with severe dysplasia containing foci of early carcinoma and compared the results to several histopathological and immunohistochemical features. METHODS: Adenomas were obtained by endoscopic polypectomy from 33 patients. Twenty-four of the 33 adenomas contained well-differentiated adenocarcinomas and nine adenomas contained moderately differentiated adenocarcinomas. RESULTS: Positive CD expressions were observed in 25% of well-differentiated adenocarcinomas and in 66.7% of moderately differentiated adenocarcinomas (p < 0.05). Of the 12 adenocarcinomas with positive CD expression, four had positive CD expression in their adenomas (p < 0.01), 6 showed positive Ki-67 expression in their adenomas (NS), and 10 had positive p53 expression in their adenomas (p < 0.05). No significant association was seen between the level of CD expression and adenoma size. CONCLUSIONS: The expression of CD in adenocarcinoma correlated significantly with differentiation, and with the levels of CD and p53 expression in the adenomas of the polyp.

Adenocarcinoma↗

Secondary transplantation following a period of isografting: experimental study in rats.

The authors describe a study in which groin flaps from 20 Wistar rats were transplanted to another group of 20 Wistar rats and, after various time intervals, the groin flaps were re-transplanted back to the original animals. The goal of the first transfers was to preserve the flap in the second group of animals (isopreservation). During the isopreservation period, the second rat (the preserver) was treated with steroids or FK506 for immunosuppression. Thirty-three free groin flap transfers were performed between 40 rats. If possible, the same flap was transferred twice between two animals, one as an isograft, and other as an autograft following an isopreservation period in 13 pairs of animals. (A second transfer was not possible in seven pairs of animals.) The period for isopreservation varied between 2 days and 1 week. The survival of the flap was observed by visual inspection, laser Doppler flowmeter measurements, and was correlated with serial histopathologic examinations of skin and vessel biopsy specimens, including the anastomosis site. The severity of histopathologic signs that might be related to developing rejection was increased by the preservation time, and was more noticeable after the second transfer. The authors showed that successful secondary transplantation of the rat groin flap with a 1-week follow-up could be achieved, following isopreservation of at least up to 5 days.

Anastomosis, Surgical↗