Tadashi Furihata

Identification of genes differentially expressed in a newly isolated human metastasizing esophageal cancer cell line, T.Tn-AT1, by cDNA microarray

We isolated a metastasizing human esophageal squamous cell carcinoma (SCC) cell line, T.Tn‐AT1, from a parental non‐metastasizing cell line, T.Tn, by in vitro selection and by use of a nude mouse orthotopic inoculation model. Then, we compared the expression profiles of 9206 genes in T.Tn‐AT1 and T.Tn by cDNA microarray analysis. The gene expression profiles of T.Tn and T.Tn‐AT1 were very similar, and only 34 genes showed more than 3‐fold differential expression. Among the 34 genes, 29 genes were down‐regulated and only 5 genes were up‐regulated in T.Tn‐AT1 cells. Subsequently, we confirmed the expression levels of 14 of the 34 genes in T.Tn and T.Tn‐AT1 cells by means of reverse transcription‐polymerase chain reaction. The expression of 8 genes (KAL1, HPGD, NDN, REG1A, CXCR4, SPOCK, DIAPH2 and AIF1) was down‐regulated and that of one gene (VNN2) was up‐regulated in T.Tn‐AT1 cells. These 9 genes encoded proteins associated with metastatic processes, such as adhesion, migration, inflammation, proliferation, and differentiation. Thus, these genes might regulate the metastasis of esophageal SCC, and could be predictive markers for lymph node metastasis of esophageal SCC.

Biliary Papillomatosis Arising in a Congenital Choledochal Cyst: Report of a Case

Abstract.We report a rare case of biliary papillomatosis arising in a congenital choledochal cyst, with an anomalous junction of the pancreatobiliary ductal system (AJPBDS). A 50-year-old woman was admitted to our department with epigastralgia, and imaging studies showed two masses in the cystic common bile duct and an AJPBDS. We made a preoperative diagnosis of biliary tract cancer, considering the size of the masses and the presence of the AJPBDS, and performed a pylorus-preserving pancreatoduodenectomy. The resected specimen contained two papillary tumors, which were subsequently diagnosed as benign papillomas. Histopathological and oncological examinations indicated that the lesions were involved in the development and progression of carcinogenesis because a point mutation of the K-ras gene and overexpression of p53 protein were detected. These findings suggest that biliary papillomatosis is a precancerous lesion induced by an AJPBDS.

Evaluation of cell proliferation and apoptosis in Helicobacter pylori gastritis using an image analysis processor

Abstract.Background: Infection of the gastric mucosa by Helicobacter pylori is primarily responsible for gastritis, gastric ulcer, adenocarcinoma, and lymphoproliferative disorders. H. pylori appears to accelerate apoptosis and the proliferation of the gastric epithelium directly or indirectly. To precisely assess the proliferative and apoptotic profile of H. pylori-infected gastric mucosa, a quantitative imaging system is now required.Methods: Fifty-two patients with H. pylori gastritis were the subjects of the study. Biopsy materials were taken from at least two sites (usually three to five sites) including the antrum and corpus. The grade of gastritis was evaluated by the Updated Sydney System. The proliferative and apoptotic profile was examined by Ki-67 immunohistochemistry and by a terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling method. In addition, Ki-67-positive cells were quantitated by an image processor for analytical pathology (IPAP) system.Results:H. pylori density and polymorphonuclear neutrophil activity were significantly decreased after H. pylori eradication (P < 0.0001). Chronic inflammation (P < 0.0001) and lymphoid follicle numbers (P < 0.0005) were also significantly decreased after the eradication. Glandular atrophy and intestinal metaplasia were slightly decreased after eradication, but the decrease did not reach the significant level. The Ki-67 labeling index was significantly decreased after the eradication (P < 0.0001). The apoptosis index was also decreased after the eradication, but this decrease did not reach the significant level (P = 0.06).Conclusion: Our data suggest that the activation of proliferative cells and induction of apoptosis in the gastric mucosa is a response to H. pylori-induced mucosal damage. Moreover, IPAP may be a useful technology for evaluating the results of immunohistochemistry, and it could provide quantitative and reliable data for studying H. pylori gastritis.

Esophageal small cell carcinoma effectively treated by cisplatin and irinotecan

Small cell carcinoma of the esophagus (SSCE) is regarded as a relatively uncommon neoplasm. Because of its aggressive characteristics with early systemic dissemination and widespread metastasis, SCCE is often associated with a poor prognosis. We report a case of carcinoembryonic antigen-positive SCCE coexistent with squamous cell carcinoma, which was successfully treated with cisplatin (CDDP) and irinotecan (CPT-11). The present case showed no evidence of distant metastasis at the time of preoperative examination. Therefore, the surgical resection was selected as a primary treatment followed by adjuvant therapy (CDDP and 5-flourouracil). However, multiple liver metastases appeared 8 months after the surgery. We changed the chemotherapy to CPT-11 and CDDP, because the regimen is effective for small cell carcinoma of the lung. After six courses of this regimen, the metastatic lesions had dramatically disappeared. These facts suggest that surgical intervention followed by a new regimen consisting of CDDP and CPT-11 is an effective treatment for SCCE.

Overexpression of TSC-22 (transforming growth factor- β-stimulated clone-22) causes marked obesity, splenic abnormality and B cell lymphoma in transgenic mice

In this study, we generated transgenic (Tg) mice, which overexpressed transforming growth factor (TGF)-β stimulated clone-22 (TSC-22), and investigate the functional role of TSC-22 on their development and pathogenesis. We obtained 13 Tg-founders (two mice from C57BL6/J and 11 mice from BDF1). Three of 13 Tg-founders were sterile, and the remaining Tg-founders also could generate only a limited number of the F1 generation. We obtained 32 Tg-F1 mice. Most of the Tg-mice showed marked obesity. Histopathological examination could be performed on 31 Tg-mice; seventeen mice died by some disease in their entire life and 14 mice were killed for examination. Most of the Tg-mice examined showed splenic abnormality, in which marked increase of the megakaryocytes, unclearness of the margin of the red pulp and the white pulp, and the enlargement of the white pulp was observed. B cell lymphoma was developed in 10 (71%) of 14 disease-died F1 mice. These results indicate that constitutive over-expression of TSC-22 might disturb the normal embryogenesis and the normal lipid metabolism, and induce the oncogenic differentiation of hematopoietic cells.

A Giant Lymphatic Cyst of the Adrenal Gland: Report of a Rare Case and Review of the Literature

Lymphatic type of adrenal cysts is most common; however, this type of endothelial cyst is quite rare in excessively large adrenal cysts. A 37-year-old Japanese woman was admitted to our institution with distension of her left flank and the upper quadrant of her abdomen. Abdominal ultrasonography revealed a cystic lesion with a homogenous anechoic texture, and measuring 21 cm in diameter. Computed tomography and magnetic resonance imaging displayed a giant cystic lesion adjacent to the liver, pancreas, kidney, and spleen. The origin of the cyst was not identified. We were not able to make a preoperative diagnosis; therefore, the patient underwent resection of the mass by open laparotomy for therapeutic diagnosis. Intraoperatively, the mass was identified to be cystic and adhered to the left adrenal gland. It was filled with more than 2000 mL of serous brown-red fluid. The content of the cyst contained no atypical cells on cytological examination. The wall of the cyst was composed of a lining of a single layer of lymphatic vessel-derived cells, and the cyst was pathologically classified as a true cyst. No abdominal symptoms were observed and a postoperative radiological work-up showed no evidence of recurrence during a 6-year follow-up period. We describe a case of a patient with a giant lymphatic cyst of the adrenal gland. The preset data suggest that surgeons should decide treatment strategy for large adrenal cysts in consideration of hormonal function, degree of size, and possibility of malignancy.

Does massive intraabdominal free gas require surgical intervention

We describe a rare case of an 81-year-old man who presented with severe epigastralgia. A chest radiograph showed massive free gas bilaterally in the diaphragmatic spaces. Computed tomography (CT) scan also showed massive free gas in the peritoneal cavity with portal venous gas. We used a wait-and-see approach and carefully considered surgery again when the time was appropriate. The patient received conservative therapy with fasting, an intravenous infusion of antibiotics, and nasogastric intubation. The patient soon recovered and was able to start eating meals 4 d after treatment; thus, surgical intervention was avoided. Thereafter, colonoscopy examination showed pneumatosis cystoides intestinalis in the ascending colon. On retrospective review, CT scan demonstrated sporadic air-filled cysts in the ascending colon. The present case taught us a lesson: the presence of massive intraabdominal free gas with portal venous gas does not necessarily require surgical intervention. Pneumatosis cystoides intestinalis should be considered as a potential causative factor of free gas with portal venous gas when making the differential diagnosis.

Repeated Duodenal Stump Perforation Using a Stapling Device Following Subtotal Gastrectomy With Roux-en-Y Reconstruction for Advanced Gastric Cancer: Lessons From a Rare Case

Closure of the duodenal stump using a stapling device is commonly applied in Roux-en-Y reconstruction after gastrectomy. However, serious and possibly fatal duodenal stump perforation can develop in extremely rare cases. We describe a case of subtotal gastrectomy with Roux-en-Y reconstruction followed by repeated duodenal stump perforations. A 79-year-old man with a long history of diabetes and hypertension was admitted to our institution with epigastralgia and right hypochondralgia. Computed tomography and an upper gastrointestinal imaging series revealed remarkable wall thickening of the gastric antrum and corpus. Upper endoscopy also showed a giant ulcerative lesion in the same area. The lesion was confirmed by histology to be poorly differentiated adenocarcinoma. The patient underwent open subtotal gastrectomy with Roux-en-Y reconstruction. However, duodenal stump perforation occurred repeatedly on postoperative days 1, 3, and 19, which caused peritonitis. The patient was kept alive through duodenal stump repair, an additional resection using a stapling device, and repeated drainage treatments; but he suffered considerable morbidity due to these complications. We report a case of a life-threatening duodenal stump perforation after subtotal gastrectomy, highlighting lessons learned from the profile and clinical course. Abdominal surgeons should be aware of the possibility of this serious complication of duodenal stump perforation, and be able to perform immediate interventions, including life-saving reoperation.