Hiroji Nishino

Inhibitory effect of a selective cyclooxygenase-2 inhibitor on liver metastasis of colon cancer.

COX‐2 overexpression is recognized in various cancers, but the role of COX‐2 in the progression of cancer, including the liver metastasis of colon cancer, is not clearly understood. We examined the role of COX‐2 in the mechanism of liver metastasis of colon cancer, using a highly metastasizable colon carcinoma cell line, LM‐H3. A COX‐2 inhibitor, JTE‐522, inhibited cell proliferation and invasion of LM‐H3 in vitro and clearly reduced the number of metastatic nodules on the surface of nude mouse livers in vivo. We also examined the effects of JTE‐522 on the production of growth factors and MMPs through the use of ELISA and gelatin zymography, respectively. JTE‐522 downregulated PDGF production by LM‐H3 but had no influence on VEGF production. JTE‐522 also inhibited MMP‐2 secretion by LM‐H3. JTE‐522 downregulated PGE2 production, but the associated changes in PGE2 did not affect PDGF and VEGF production by LM‐H3. We conclude that JTE‐522 downregulated the cell proliferation and invasive potential of LM‐H3 by reducing the production of PDGF and MMP‐2 and hypothesize that these inhibitory effects on the production of PDGF and MMP‐2 can lead to inhibition of liver metastasis of colon cancer. These data indicate that the COX‐2 inhibitor JTE‐522 has a high potential for use as a clinical agent for the treatment of liver metastasis of colon cancer.

Very low incidence of microsatellite instability in intraductal papillary-mucinous neoplasm of the pancreas

Intraductal papillary‐mucinous carcinoma (IPMC) of the pancreas, a new entity of pancreatic cancer with a favorable prognosis, has shown a gradual increase in the number of reported cases. Patients with high‐frequency microsatellite instability (MSI‐H) tumors have been shown to survive longer than those with low‐frequency MSI (MSI‐L) or microsatellite stable (MSS) tumors in colorectal and gastric cancer. We investigated whether MSI‐H in patients with IPMC can contribute to a good prognosis. The formalin‐fixed paraffin‐embedded tumors and surrounding normal pancreatic tissues from 10 patients with IPMCs and 16 with intraductal papillary‐mucinous adenomas (IPMAs) were provided for DNA extraction after microdissection. Polymerase chain reaction (PCR) was carried out using 8 microsatellite primer marker sets. The mixed PCR samples were analyzed using a genetic analyzer. MSI‐H was determined by assessment of microsatellite variations in 3 or more of the 8 tested markers. Immunohistochemical staining of the MSI‐responsible proteins hMLH1 and hMSH2 was conducted for both the IPMC and IPMA samples. Ten percent of IPMC harbored MSI‐H tumors, whereas no MSI‐H tumors were detected in the IPMAs. Thirty percent of IPMC tumors and 25% of IPMA tumors showed MSI‐L. All IPMCs and IPMAs showed normal expression of both hMLH1 and hMSH2. MSI‐H and loss of hMLH1 and hMSH2 are very rare events in both IPMCs and IPMAs. We conclude that a good prognosis for patients with IPMC is not associated with MSI‐H.

Primary leiomyosarcoma of the breast: report of a case.

Abstract.We describe herein a case of primary leiomyosarcoma of the breast in a 59-year-old woman. Preoperative clinical examination and cytology findings indicated a benign breast tumor, but intraoperative histopathological examination of the tumor revealed malignant spindle cells, and a modified radical mastectomy was performed. Immunohistochemical analysis subsequently confirmed a diagnosis of leiomyosarcoma. Primary leiomyosarcoma of the breast is extremely rare and difficult to diagnose before surgery because of the need for mitotic figures and immunohistochemical staining to confirm the diagnosis. When pre- and intraoperative examinations indicate the possibility of a leiomyosarcoma, an extended excision with sufficient margins should be performed to remove all of the affected tissue. A review of the literature on this unusual tumor of the breast is presented.

A case of osteoclast-type giant cell tumor of the pancreas with high-frequency microsatellite instability.

It has been reported that osteoclast-type giant cell tumor of the pancreas (OGTP) is rare, with a frequency of only 0.2% of the total reported pancreatic carcinomas. We report herein a rare case of OGTP in a 57-year-old Japanese man. Preoperative examinations showed a solid and cystic tumor, measuring 20 x 15 cm at the pancreas body. The resected specimen was a solid tumor with a giant cyst containing bloody contents. The tumor was composed of a proliferation of mononuclear cells admixed with osteoclast-type giant cells. The tumor cells were immunoreactive for vimentin, alpha1-antitrypsin, and EMA but not for CEA and cytokeratin. These findings indicated that this case was a malignant OGTP. The tumor cells showed microsatellite instability with high frequency (MSI-H). The present patient is alive 3 years after the operation, while OGTP has been reported to have a poor outcome. It has been reported that pancreatic carcinomas with MSI-H status have a favorable outcome. MSI-H might be one of the predictive markers for the long survival in OGTP.

Malignant T-cell lymphoma of the pancreas.

A case of malignant T-cell lymphoma of the pancreas is presented. Previously reported histological data confirming this disease are reviewed to elucidate features that may suggest this disease and how to differentiate between T- and B-cell lymphoma of the pancreas.

Prognostic predictive value of endoscopic ultrasound findings for invasive ductal carcinomas of pancreatic head.

Objectives: Accurate preoperative prediction of the prognosis of patients with invasive ductal carcinoma of pancreatic head (pancreatic head cancer) is important for selecting treatment methods. We retrospectively examined the prognostic predictive values of endoscopic ultrasound (EUS) findings for patients with this disease. Methods: The subjects were 66 patients with pancreatic head cancer who had undergone EUS. We examined each EUS finding as a possible prognostic predictor, including heterogeneity of internal echo, irregularity of peripheral echo, clarity of boundary echo, dilatation of the main pancreatic duct (MPD), dilatation of the common bile duct, lymph node swelling, vessel invasion, and the presence of ascites, by univariate and multivariate analysis for survival. Results: Irregular peripheral echo, portal vein invasion, superior mesenteric artery/celiac artery invasion, and the presence of ascites were significant predictors of a poorer prognosis by univariate analysis for survival. In resectable cases, EUS findings of MPD dilatation and portal invasion were significant prognostic predictors by univariate analysis, and MPD dilatation was an independent prognostic predictor by multivariate analysis. Conclusion: EUS may be useful for predicting the prognosis of patients with pancreatic head cancer, based on the accuracy it provides in evaluating locoregional spreading.

Transpyloric prolapse of a pedunculated polypoid gastric carcinoma

SummaryA patient with transpyloric prolapse of a pedunculated polypoid gastric carcinoma is reported. Only three previous cases have been reported in the international literatures. However, in Japan, 33 cases of prolapsed gastric carcinoma have been reported during the past 30 years. Prolapsed gastric carcinoma should be included in the differential diagnosis of localized intraluminal filling defects in the duodenal bulb. Endoscopy and biopsy are essential for correct diagnosis.

PREDICTION OF RECURRENCE AFTER ENDOSCOPIC TREATMENT FOR ESOPHAGEAL VARICES: WITH SPECIAL REFERENCE TO ESOPHAGEAL VARICEAL PRESSURE

Background: We investigated the factors influencing esophageal variceal recurrence after endoscopic treatment on the basis of 25 variceal patients who were measured for esophageal variceal pressure, which had been reported to have a close relationship to variceal rupture.

Contribution of Colon Cancer Cells to Mesenchymal Cells in the Formation of Hepatic Metastasis

Proliferations of cancer cells and mesenchymal cells are necessary for the formation of hepatic metastasis. Endothelial cells and hepatic stellate cells (HSCs), which exist in the extrasinusoidal space and produce extracellular matrix, are present in hepatic lobules as mesenchymal cells. In this study we investigated the contribution of colon cancer cells to endothelial cells and HSCs in the formation of hepatic metastasis. We collected serum-free conditioned medium (SFCM) of LM-H cells, which are highly liver metastatic colon cancer cells. The SFCM of LM-H cells significantly enhanced proliferation and migration of human umbilical vein endothelial cells (HUVECs) and enhanced the proliferation and migration of HSCs derived from rats. On investigating the growth factors in the SFCM of LM-H cells, we found vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF). The proliferation of HUVECs was inhibited by anti-VEGF antibody, and that of HSCs was inhibited by anti-PDGF antibody. The angiogenesis inhibitor TNP-470 significantly decreased the number of hepatic metastases of LM-H cells in nude mice. In conclusion, the VEGF and PDGF that colon cancer cells produce are important factors in the structural reorganization of hepatic metastasis. The angiogenesis inhibitor TNP-470 seems to be a potent agent for inhibiting hepatic metastasis of colon cancer.

External Pancreatic Juice Drainage Through a Percutaneous Endoscopic Drainage Tube for the Patient with a Postoperative Pancreatic Juice Leakage

Percutaneous endoscopic gastrostomy (PEG) has been widely accepted for patients who have no swallowing ability but have an intact gut. Its clinical application is mainly for nutritional support and decompression of the intestine in patients with bowel obstruction. In this paper, we report external pancreatic juice drainage through a percutaneous endoscopic drainage tube in a patient with postoperative pancreatic juice leakage. Soon after this procedure, pancreatic juice leakage subsided. This procedure was minimally invasive for the patient and may be a new application of PEG to maintain the good quality of life (QOL) in a patient with pancreatic juice leakage.