Epstein-Barr Virus latent membrane protein 1 induces Snail and epithelial-mesenchymal transition in metastatic nasopharyngeal carcinoma.

BACKGROUND: Epstein-Barr Virus (EBV)-associated nasopharyngeal carcinoma (NPC) is distinctive among head-and-neck cancers in its undifferentiated histopathology and highly metastatic character. We have recently investigated the involvement of epithelial-mesenchymal transition (EMT) in NPC. In a previous study, we found a close association of expression of LMP1, the principal EBV oncoprotein, with expression of Twist and induction of EMT. METHODS: We analysed expression of Snail in 41 NPC tissues by immunohistochemistry. The role of Twist as well as Snail in EMT of NPC was investigated by using NP69SV40T human nasopharyngeal cells. RESULTS: In NPC tissues, overexpression of Snail is associated with expression of LMP1 in carcinomatous cells. In addition, expression of Snail positively correlated with metastasis and independently correlated inversely with expression of E-cadherin. Expression of Twist had no association with expression of E-cadherin. Further, in a human nasopharyngeal cell line, LMP1 induces EMT and its associated cellular motility and invasiveness. Expression of Snail is induced by LMP1 in these cells, and small hairpin RNA (shRNA) to Snail reversed the cellular changes. By contrast, Twist did not produce EMT in these nasopharyngeal cells. CONCLUSIONS: This study strengthens the association of EMT with the metastatic behaviour of NPC. These results suggest that induction of Snail by the EBV oncoprotein LMP1 has a pivotal role in EMT in NPC.

Invasive colorectal cancer detected up to 3 years after a colonoscopy negative for cancer.

BACKGROUND AND STUDY AIMS: Colonoscopy has replaced barium enema as the primary method for direct diagnosis of colorectal cancer, but detection may fail, and the reasons for this are not completely understood. PATIENTS AND METHODS: In order to analyze the accuracy of colonoscopy for detecting invasive colorectal cancer, 7365 colonoscopic examinations were matched with the most accurate local government population-based cancer registry in Japan. RESULTS: In 15 colonoscopic examinations, patients were not diagnosed as having invasive colorectal cancer, but disease of this type was detected within 3 years of the examinations (false-negative examinations). During the same period, 233 colonoscopies were identified as true-positive examinations. The false-negative rate for detecting invasive colorectal cancer with colonoscopy was 6% at 3 years. The false-negative rate was significantly higher in individuals between 60 and 69 years of age and in invasive cancers located to the right of the splenic flexure. CONCLUSIONS: Colonoscopists should receive adequate training in achieving easy cecal intubation, detecting small or flat lesions, and carrying out adequate biopsies.

Endoscopic surveillance for gastric remnant cancer after early cancer surgery.

BACKGROUND AND STUDY AIMS: The aims of this article were to clarify the incidence of gastric remnant cancer after surgery for early gastric cancer, and to develop surveillance programs for patients who have undergone partial gastrectomy in order to detect such lesions at an early stage. PATIENTS AND METHODS: A total of 642 patients with partial gastrectomy for early gastric cancer were enrolled in a surveillance program for gastric remnant cancer between 1985 and 1996. In 509 patients, the interval between endoscopic examinations was no more than 2 years. RESULTS: Among the 509 patients examined periodically, 15 patients were diagnosed as having gastric remnant cancer; in 12 patients, the cancers were detected at an early stage. All gastric remnant cancers were found distant from the site of the anastomosis, and in eight patients the cancers were located on the lesser curvature. The cumulative 5-year prevalence rate was estimated as 2.4 % and the 10-year prevalence rate as 6.1 %. The initial tumors in the patients with gastric remnant cancer were of the microscopically intestinal type, without exception. The interval between the preceding examination and diagnosis was shorter in the patients with early cancer than in those with advanced cancer ( P < 0.01). CONCLUSIONS: Periodical surveillance endoscopy for gastric remnant cancer is recommended after surgery for early gastric cancer, particularly in patients whose cancers are of the intestinal type. The examinations can be repeated at 2 - 3-year intervals, and special attention should be given to the lesser curvature away from the anastomotic site.

Detection of gastric cancer by repeat endoscopy within a short time after negative examination.

BACKGROUND AND STUDY AIMS: Although a large number of patients are examined using endoscopy in order to identify gastric cancer, it is unclear how individuals should be managed after they are not diagnosed as having gastric cancer at the time of their initial examinations. This study was conducted to identify the group at high risk for gastric cancer who should be examined by repeat endoscopy within a short time after obtaining negative results. PATIENTS AND METHODS: The study involved 3672 patients who were not diagnosed as having gastric cancer by endoscopy in 1993, but underwent re-examination by gastroscopy between January 1994 and December 1996. RESULTS: Among these participants, 32 patients (0.9%) were diagnosed as having gastric cancer. The incidence of gastric cancer was 2.0% in participants aged 60 to 69 and 2.7% in those with marked atrophy of the gastric mucosa. Multivariate analysis showed that the odds ratios (OR) for patients aged 60 to 69 and those with marked atrophy of the gastric mucosa were 3.092 and 3.255 (P < 0.01), respectively. Gastric cancer was detected in 17.2 % of patients who were previously diagnosed as having gastric adenoma and in 2.2% of those who were previously diagnosed as having gastric ulcer. The ORs for participants with these gastric lesions detected by the initial examination were 49.417 and 5.259 (P < 0.01), respectively. CONCLUSIONS: Groups at high risk for gastric cancer were identified by the initial endoscopy, when two findings (gastric lesions, atrophy) and age were combined. We emphasize the importance of repeat endoscopic examination for patients who are aged 60 to 69 or have marked atrophy of gastric mucosa, even if no lesions are detected on initial endoscopy. If gastric adenoma or ulcer are detected, endoscopic examination should be likewise repeated or these lesions should be treated by endoscopy or by other means.

Perforation of the sigmoid colon with ischemic change due to polyarteritis nodosa.

A 60-year-old man who developed a perforation of the sigmoid colon with ischemic change due to polyarteritis nodosa is described. Histological examination of the resected colon led to the diagnosis of polyarteritis nodosa. Although the gastrointestinal tract is frequently involved with polyarteritis nodosa, it is extremely rare for polyarteritis nodosa to be accompanied by a perforation of the colon, particularly at the initial presentation.

Telomerase activity in gastrointestinal stromal tumors.

BACKGROUND: Telomerase activity has been observed in 80-90% of carcinomas derived from various organs. However, to the authors' knowledge this report is the first assessment of telomerase activity in gastrointestinal stromal tumors (GISTs). METHODS: Telomerase activity was analyzed by the telomerase repeat amplification protocol assay in 29 tumors from 26 patients (23 primary tumors from 22 patients, 1 pair of primary and metastatic tumors from 1 patient, and 4 metastatic tumors from 3 patients). Phenotypes, tumor cell proliferation, and overexpression of p53 protein were evaluated immunohistochemically. RESULTS: Seven of 24 primary tumors (29%) and 5 of 5 metastatic tumors (100%) showed telomerase activity. Telomerase activity positive (+) GISTs were significantly larger (P < 0.05) and showed a significantly higher rate of proliferation than telomerase activity negative (-) tumors (P < 0.0001). All telomerase activity (+) GISTs were classified histologically as high risk tumors. Conversely, 15 of the 17 telomerase (-) GISTs were classified histologically as low risk tumors (P < 0.0001). With regard to p53 immunoreactivity, two and seven telomerase activity (+) tumors showed diffuse and sporadic positivity, respectively, whereas only five telomerase activity (-) tumors showed only focal or sporadic positivity. Telomerase activity was correlated significantly with poor prognosis (P < 0.05) in the patients in whom the primary GISTs were evaluated (n = 23). CONCLUSIONS: Telomerase activity may be a useful marker for evaluating the malignant potential of GIST. A distinct subgroup of GISTs is a target for therapy with a telomerase inhibitor.

Gastric neuroendocrine carcinoma associated with chronic atrophic gastritis type A.

We report a case of gastric neuroendocrine (NE) carcinoma associated with chronic atrophic gastritis type A (CAG/A) or reversed atrophic type gastritis. A 9 x 6 cm tumor was resected from the stomach to control pain in a 55-year-old Japanese woman with peritoneal dissemination and metastatic tumors of the liver and ovary. Histologically, the tumor was NE carcinoma which showed an organoid structure, but consisted of NE cells with overt cytological atypia and frequent mitotic activity. Multiple microcarcinoids and NE cell micronests (NECMs) were also observed in the atrophic non-neoplastic mucosa of the gastric body. CEA immunoreactivity and a high Ki-67 labeling index were characteristic features of the neoplastic NE cells of the carcinoma. Although most NE tumors arising from CAG/A are typical carcinoid tumors, the present case illustrates that a high-grade NE carcinoma can develop from diverse NE cell proliferation in association with CAG/A.

[State of art: Epstein Barr virus-associated gastric carcinoma].

Epstein Barr virus(EBV)-associated gastric carcinoma (EBVaGC), comprising 10% of gastric carcinoma, is the most frequent EBV-associated neoplasm in Japan. EBVaGC is a distinct type of gastric carcinoma, which is marked by the monoclonal EBV, and its morphogenesis seems to be different from that of other gastric carcinomas. Future studies are necessary to disclose precise timing of EBV infection to the epithelial cells of the stomach, status and mechanism of EBV-infection in the non-neoplastic gastric mucosa, molecular mechanism of the development of EBVaGC, and role of EBV in the maintenance of EBVaGC. Development of new therapeutic approach specific to EBVaGC will also facilitate the recognition of this entity in clinical medicine.

[Study of early gastric carcinomas with a pyloric stenosis].

From 1969 to 1989, 1106 cases of early gastric carcinomas were treated in our hospital, and 9 cases (0.8%) of an early gastric carcinoma with a pyloric stenosis were found among them. Five of these cases involved males and 4 cases females. The average age of these patients was 57.1 years. An accurate preoperative diagnosis was very difficult and 7 cases had been considered to be advanced gastric carcinoma preoperatively. In all these cases the lesions were found located on the pyloric ring or in the antral region. Further, all cases evidenced a submucosal infiltration and/or ulceration in the lesion. Most of the stenotic cases had lesions greater than 3.1 cm in diameter, with diameters of over 1.1 cm in the ulceration and the submucosal infiltration. Some early gastric carcinomas in the antral region with no pyloric stenosis also had lesions that were over this size.