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Biomedical subjects

Kenji Kashiwabara

Publications and source records attributed to Kenji Kashiwabara.

16 recordsLinked to original sources

Up-regulation of a BCL9-related beta-catenin-binding protein, B9L, in different stages of sporadic colorectal adenoma.

Aberrant activation of Wnt signaling is a critical event in the development of human colorectal tumors. The aim of this study was to elucidate the role of B9L and its association with beta-catenin in each stage of the adenoma-carcinoma sequence of human colorectal tumorigenesis. We investigated the expression levels of B9L in sporadic colorectal adenomas and carcinomas, categorized according to the Vienna classification, using real-time quantitative polymerase chain reaction (RTQ-PCR) and immunohistochemical analysis. B9L was expressed in the nuclei of non-neoplastic colonic mucosa cells and was overexpressed in the nuclei of neoplasias and invasive carcinoma cells. Immunoreactivity to B9L protein was correlated with the progressive grades of colorectal neoplasias, as was the expression of B9L mRNA. A high level of immunoreactivity to nuclear B9L was present in 27% of low-grade neoplasias and in more than 50% of high-grade neoplasias and invasive carcinomas, whereas a high level of nuclear B9L immunoreactivity was not observed in any of the non-neoplastic mucosa samples. The expression of B9L was dramatically increased in low-grade neoplasias compared with that in non-neoplastic mucosa. B9L may play an important role in tumorigenesis induced by aberrant activation of Wnt signaling and may act as a key protein in the progressive dysplasia of adenoma.

Adenocarcinoma↗

Methtrexate-associated lymphoproliferative disorders. A clinicopathological study of 13 Japanese cases.

We conducted clinicopathological and immunohistochemical analyses to investigate the prevalence of Epstein-Barr virus (EBV) among 13 cases with methotrexate (MTX)-associated lymphoproliferative disorder (LPD). The subjects of this study were four men and nine women ranging in age from 53 to 78 years (mean: 63 years). All 13 patients had received low dose MTX therapy for 1-13 years before the onset of LPD (mean: 5.8 years). LPDs were found at extranodal sites in six cases, and the disease stage was advanced in seven cases. The present study confirmed certain aspects of a previous observation made in the USA, including the following findings (i) the cases commonly showed diffuse large B-cell lymphomas (n=4) and Hodgkin lymphomas (HL) (n=3), (ii) EBV-encoded small RNA (EBER) + cells were identified in seven cases (60%), which is a much higher percentage than would be expected in lymphomas occurring in a general population, and (iii) three cases of polymorphous small lymphocytic or lymphoplasmacytic infiltrate achieved spontaneous remission of LPDs after MTX withdrawal. Of seven cases of EBER + in our series, three cases were PSLLPI, and two were HL. EBER + tumor cells were detected in only two (30%) of the seven cases with non-Hodgkin lymphomas. The present study suggests that EBV- associated non-Hodgkin lymphomas comprise only a portion of all non-Hodgkin lymphomas among MTX-associated LPDs.

Aged↗

Xanthogranulomatous cholangitis causing obstructive jaundice: a case report.

This article reports the case of a 34-year-old woman with xanthogranulomatous cholangitis who developed obstructive jaundice. Microscopically, the bile duct was surrounded and narrowed by a xanthogranulomatous lesion, but no xanthogranulomatous cholecystitis was seen. Although percutaneous cholangiograms done via the transhepatic biliary drainage showed smooth narrowing of the upper to middle bile duct, the cytology of bile was diagnosed as class V adenocarcinoma. Therefore, right extended hepatectomy and extrahepatic bile duct resection were performed. The differentiation of benign and malignant strictures at the hepatic hilum is often difficult. Xanthogranulomatous cholangitis is one possible diagnosis of a bile duct stricture. Precise review of all the preoperative information is required to make a correct diagnosis.

Adenocarcinoma↗

Spontaneous regression of hepatic inflammatory pseudotumor with primary biliary cirrhosis: case report and literature review.

Hepatic inflammatory pseudotumor (IPT) is a rare benign non-neoplastic lesion characterized by proliferating fibrous tissue infiltrated by inflammatory cells. The exact etiology of IPT remains unclear. Although the association of IPT with systemic inflammatory disorders has been well established, a specific relationship with cholangitis is distinctly rare. We report a case of spontaneous regression of hepatic IPT with primary biliary cirrhosis (PBC). To date, only two cases of IPT with PBC have been reported. In our case, however, IPT developed during the course of improvement of cholangitis of PBC induced by effective treatment, differing from two previously reported cases. Our case indicates that the development of IPT does not also relate to the activity of cholangitis and/or hyper gamma-globulinemia, since our case was confirmed radiologically to be free of IPT when biliary enzymes and immunoglobulins were much higher than the corresponding values on admission. Comparison of our case with the two previously reported cases suggests that IPT occurring with PBC does not represent the same disease entity or be a bystander for PBC.

Aged↗

Preoperative tegafur suppositories for resectable rectal cancer: phase II trial.

PURPOSE: Preoperative radiochemotherapy for rectal cancer causes a high rate of moderate-to-severe toxicities and is associated with only moderate survival benefits. A simpler, safer, and more convenient treatment would be preferable. Preoperative tegafur suppositories (1,500 mg/day) for at least 14 days were piloted. METHODS: A total of 129 patients with resectable rectal cancer were enrolled. The primary end points were pathologic response, adverse events, rate of sphincter-sparing surgery, recurrence, and survival. RESULTS: The total dose of tegafur ranged from 21 to 78 (mean, 32) g. The anal sphincter was preserved in 60.5 percent with microscopic no residual tumor (R0). The overall morbidity rate was 32 percent. Wound infection occurred in 13.2 percent of cases and anastomotic leakage in 9 percent of cases. Pathologic responses were observed in 70 percent of patients, with a complete necrosis occurring in 3.9 percent, two-thirds or more necrosis in 6.2 percent, one-third or more but less than two-thirds necrosis in 18.6 percent, and less than one-third necrosis in 41.9 percent. The mean total dose that patients showing complete or two-thirds or more necrosis received was 42.8 +/- 6.4 g (P = 0.01) compared with 31.6 +/- 1.2 g administered to patients showing less than two-thirds necrosis. Adverse events were observed in 15.6 percent of patients overall, and Grade III or IV events were observed in 2.3 percent of patients. During a median follow-up of 48 months, distant metastasis occurred in 14.7 percent of patients and local recurrence occurred in 6.2 percent of patients. The four-year, disease-free and overall survival rates were 67.6 and 80.1 percent, respectively. CONCLUSIONS: Preoperative tegafur suppositories are associated with low toxicity and may lead to anal sphincter-sparing surgery with acceptable postoperative complications and favorable local and distal control.

Adult↗

[A recurrent endocrine cell cancer of the stomach showing almost complete remission after chemotherapy for 1 year].

We report a recurrent case of gastric endocrine cell cancer that showed a remarkable response to systemic chemotherapy. A 70-year-old male who underwent gastroscopy at our hospital showed a 0-IIa-like lesion, but no abnormal CT findings. He was diagnosed with gastric cancer, and underwent a proximal gastrectomy. The resected specimen showed endocrine cell cancer. The tumor was Grimelius-positive histologically and chromogranin A-and NSE-positive immunohistochemically. About 2 years after surgery, liver, lymph node, and bone metastases were detected. Systemic chemotherapy with TS-1 and CDDP was started, and the lesions progressed. Then, by approximately 1 year after CDDP and CPT-11 treatments, the recurrent lesions had diminished remarkably and were no longer seen on CT or FDG-PET.

Adenocarcinoma↗

Support adapter for radiofrequency ablation probe: experimental study.

BACKGROUND: The purpose of the present study was to experimentally evaluate a new support adapter, which was created in order to insure a more complete contact between the ablation probe and a beating heart. METHODS: Support sleeve adapters for the Cobra Cooled probe were fashioned using a semi-rigid plastic. Forty epicardial radiofrequency ablation (RFA) lesions were created on both atria under the condition of a beating heart in six pigs weighing 26-30 kg. A Cobra Cooled surgical probe was used with continuous internal irrigation of a saline solution (500 mL/h). The ablation temperature was fixed at 80 degrees C and the duration of the RFA in each case was 20, 30 and 60 s. RESULTS: A support adapter ensured a more complete epicardial contact between the probe and a beating heart. An RFA probe supported by the adapter delivered greater power to the tissue. The histopathological transmural coagulation was obtained in 82% and 72% in RFA lesions with and without the adaptor, respectively. CONCLUSION: A new adapter was effective in the epicardial RFA under the condition of a beating heart.

Animals↗

Epicardial radiofrequency ablation on a beating heart: an experimental study.

PURPOSE: The effect of epicardial radiofrequency ablation (RFA) during normal heart beating was experimentally studied in order to establish safe and effective procedures for RFA. METHODS: Seven pigs weighing approximately 30 to 50 kg were used in this study. Fifty-one epicardial RFA lesions were created on both atria using a Cobra Cooled probe with continuous internal irrigation of a saline solution. The ablation temperature was fixed at 80 degrees C and the duration of the RFA in each case was 20, 30, 60 and 120 seconds. RESULTS: There was significant positive correlation between the right and left atria in wall thickness. Transmural coagulation was obtained in 69% of the total specimens, which decreased according to the increase of wall thickness especially over 3 mm. Transmural coagulation was seen in 64% of the specimens after RFA of less than 30 seconds, and 86% after ablation of >or=60 seconds. Occurence of 90% or deeper coagulation was higher in the right atrium than in the left one (97% vs. 78%). Right atrial rupture occurred in a region of 1 mm in thickness after ablation of 60 seconds. CONCLUSION: Further technical improvements associated with new instruments are indispensable to complete epicardial RFA procedures on a beating heart.

Animals↗

Fatal pneumonia caused by Burkholderia cepacia 9 months after resection of aspergilloma.

A 69-year-old man developed an episode of severe community-acquired pneumonia 9 months after resection of aspergilloma. Although Aspergillus fumigatus was also isolated in the pleural cavity, it did not invade the remaining lung parenchyma. The patient developed progressive bilateral pneumonia leading to death from respiratory failure. Burkholderia cepacia was considered as prime pathogen, as it was repeatedly cultured from sputum and tracheal secretions, as well as the autopsy lung. B. cepacia is resistant to most antibiotics, and seldom causes pneumonia in patients without cystic fibrosis or chronic granulomatous disease. The precise reason that this apparently immunocompetent patient developed B. cepacia pneumonia remains unknown.

Aged↗

Synergistic decline in expressions of p73 and p21 with invasion in esophageal cancers.

The significance of the p73 gene, a homologue of the p53 gene, in esophageal cancers is not fully understood. In order to clarify the role of p73 expression in esophageal cancers, p73 expression was immunohistochemically investigated in 106 surgically resected esophageal cancers and the results were compared with various clinicopathological factors. In normal esophageal epithelium, the expression of p73 was observed only in the nuclei of basal cells. In esophageal cancers, p73 immunoreactivity was observed in all intraepithelial lesions except one cancer, and was reduced with cancer invasion, to 78% and 64% at superficial invasion and deep invasion sites, respectively. However, p73 expression was not correlated with any other clinicopathological factor. The expressions of p53 and p21 were also investigated in esophageal cancer. To evaluate the status of the p53 gene mutation immunohistochemically, two monoclonal antibodies (DO7 and PAb240) were used. There seemed to be an inverse correlation between p73 expression and p53 mutation. Moreover, the expression of p21 was highly correlated with p73 expression irrespective of the p53 mutation status. In human esophageal cancers, p73 expression decreased with increasing degree of tumor invasion, and its decreased expression in local advanced tumor caused down-regulation of p21 expression, which might reflect tumor progression.

DNA-Binding Proteins↗

Aberrant expression of pRb, p16, p14ARF, MDM2, p21 and p53 in stage I adenocarcinomas of the lung.

Cancers are always associated with cell cycle abnormalities. To clarify the cell cycle abnormalities present in lung adenocarcinomas, various cell cycle regulatory proteins of both the pRb and p53 pathways were studied immunohistochemically in 50 cases of stage I adenocarcinoma of the lung. In regard to the pRb pathway, most adenocarcinomas showed frequent expression of both p16 and pRb proteins, and aberrant expression in the pRb pathway was observed in about one-quarter of stage I adenocarcinomas. In regard to the p53 pathway, the frequency of immunohistochemical positivity was 8% for p14ARF, 64% for MDM2, 20% for p53 and 24% for p21. In this pathway, the immunohistochemical profile of p14ARF-negative/MDM2-positive/p53-negative is characteristic of stage I adenocarcinoma of the lung. An inverse relationship was found between MDM2 and p53 protein and was associated with the differentiation status of stage I adenocarcinoma of the lung. Our results suggest that the disruption of the pRb and p53 pathways is frequently observed in the early stages of lung adenocarcinoma and might play an important role in the growth and differentiation of adenocarcinoma of the lung.

Adenocarcinoma↗

Mucosa-associated lymphoid tissue lymphoma of the extrahepatic bile duct.

Mucosa-associated lymphoid tissue lymphoma of the extrahepatic bile duct has not yet been reported. Much more common than this is secondary involvement of the extrahepatic bile duct in cases of disseminated lymphoma. A 59-year-old man manifesting jaundice was referred to our hospital. PTC revealed an extrahepatic bile duct stenosis from the hilum to the lower part of the choledochus. On the operative specimen, we examined L26/CD20, Bcl-2, UCHL-1/CD45RO, cyclin D1 and p53. Histologically, follicular colonization, centrocyte-like cells and lymphoepithelial lesion was observed. Tumor cells were positive for L26/CD20 and Bcl-2 and were negative for intracytoplasmic immunoglobulins, UCHL-1/CD45RO, cyclin D1 and p53. Pathological diagnosis was mucosa-associated lymphoid tissue lymphoma of the extrahepatic bile duct. The authors present herein the first case of mucosa-associated lymphoid tissue lymphoma of the extrahepatic bile duct. It was very difficult to distinguish from hilar cholangiocarcinoma clinically. Only incomplete stenosis of the bile duct and 18-F fluoro-2-deoxyglucose positron emission tomography (FDG-PET) could suggest this unusual clinical entity.

Antigens, CD20↗

Ampullary carcinoma associated with protein-losing gastropathy due to diffuse varioliform gastritis.

Protein-losing gastropathy due to diffuse varioliform gastritis is a rare condition, and its occurrence accompanying ampullary carcinoma is particularly rare. We report here a case of ampullary carcinoma accompanied with protein-losing gastroenteropathy due to diffuse varioliform gastritis. A 39-year-old Japanese woman was admitted to our hospital because of general fatigue and generalized edema. Her total protein level was 3.1g/dL, with an albumin level of 1.4g/dL, and hemoglobin level of 6.9g/dL. Upper gastrointestinal endoscopic examination showed diffuse varioliform gastritis and carcinoma of the papilla of Vater. A diagnosis of protein-losing gastropathy was made based on the results of scintigraphy using technetium 99m-labeled human albumin. Continuous bleeding from ampullary carcinoma caused anemia and deteriorated hypoproteinemia. Pancreaticoduodenectomy was performed for ampullary carcinoma prior to Helicobacter pylori eradication. The tumor was a papillary adenocarcinoma, which had invaded the lamina muscularis propria over the sphincter of Oddi; the resected stomach revealed typical hyperplastic lymphocytic gastritis. H. pylori were detected on microscopic analysis. Scintigraphy after surgery showed no accumulation of the tracer in the bowel. Anemia, hypoalbuminemia and diffuse varioliform gastritis are improved 6 months after surgery and H. pylori eradication, and the patient is currently free from disease.

Adenocarcinoma, Papillary↗

Alcoholic chronic pancreatitis with simultaneous multiple severe complications--extrahepatic portal obliteration, obstructive jaundice and duodenal stricture.

The major complications of chronic pancreatitis are malabsorption, diabetes mellitus, pancreatic calcification and pseudocysts. Sinistral portal hypertension due to splenic vein thrombosis, obstructive jaundice and duodenal stricture have also been reported as complications of chronic pancreatitis. However, a case having all these three complications at the same time is relatively rare. We present a case of chronic alcoholic pancreatitis complicated with simultaneous multiple severe complications. Although biliary drainage is usually a useful treatment for reducing the bilirubin level in the patients with obstructive jaundice, jaundice was hardly improved by the percutaneous transhepatic cholangio-drainage (PTCD) in this case. We discussed the cause of the failure in reducing the jaundice and reviewed the previous reports of complications of pancreatitis.

Adult↗

Immunohistochemical expression of 14-3-3 sigma protein in intraductal papillary-mucinous tumor and invasive ductal carcinoma of the pancreas.

BACKGROUND: 14-3-3 sigma (sigma) has been shown to be overexpressed in pancreatic cancers by a c-DNA microarray technique. However, the expression of 14-3-3 sigma in intraductal papillary-mucinous tumor (IPMT) of the pancreas remains unclear. MATERIALS AND METHODS: To evaluate the biological importance of 14-3-3 sigma expression in pancreatic carcinogenesis, immunohistochemistry for 14-3-3 sigma, CDX2, MUC1, MUC2, p53, p16 and Ki-67 was carried out on 33 IPMTs and the results were compared with those for 14 invasive ductal carcinomas (IDCs). RESULTS: The frequency of 14-3-3 sigma immunoreactivity was 70% and 100% in IPMT and IDC, respectively. The frequency of MUCI and Ki-67 immunoreactivity was significantly higher in IDC than IPMT. In IPMT, dark columnar cell types prevailed over clear columnar cell types in terms of the frequency of the Ki-67 labeling index. CONCLUSION: The overexpression of 14-3-3 sigma was confirmed in both IDC and IPMT. Therefore, this overexpression might occur in the early stages of pancreatic carcinogenesis. Moreover, IPMT composed of dark columnar cells might be a potentially more advanced form than that made up of clear columnar cells.

14-3-3 Proteins↗