The spread of tumor cells to regional lymph nodes is an early event of gastric cancer metastasis. In our study, we assessed the expression of lymphangiogenic factors and lymphatic endothelial markers in gastric carcinoma tissues and compared expression levels with the status of lymph node metastasis. We also examined the correlation between lymphatic vessel density (LVD) in primary tumors and lymph node metastasis. Paired biopsy samples (tumor and corresponding normal mucosa) of gastric tissue were obtained from 39 patients with gastric carcinoma. The expression of VEGF-C, VEGF-D, VEGFR-3 and podoplanin mRNAs was assessed by real-time quantitative PCR. The expression of VEGF-C (but not of VEGF-D) was significantly greater in patients with lymph node metastasis than in those without metastasis. The expression of lymphatic endothelial markers VEGFR-3 and podoplanin was also significantly greater in the node-positive group. LVD, as assessed by immunohistochemistry for podoplanin, was correlated with lymph node metastasis. These results indicate that quantitative analysis of lymphangiogenic markers in gastric biopsy specimens may be useful in predicting metastasis of gastric cancer to regional lymph nodes. ' 2005 Wiley-Liss, Inc.

The goal of this study was to investigate the association of mutations in the KIT gene and the plateletderived growth factor receptor • (PDGFRA) gene with clinicopathological features of patients with gastrointestinal stromal tumor (GIST) localized in the stomach. We evaluated 56 gastric GISTs for KIT and PDGFRA mutations. DNA was extracted from paraffin-embedded tumor specimens, and exons 9, 11, 13 and 17 of the KIT gene and exons 12 and 18 of the PDGFRA gene were amplified by polymerase chain reaction and sequenced. The genetic features were then compared with the clinicopathological features. Immunohistochemistry was performed for KIT, CD34, Ki-67 (as a marker of cell proliferation) and CD31 (as a marker of microvessel density), and apoptosis was assessed by in situ DNA nick-end labeling. Thirty-four (61%) of the 56 GISTs had a mutation in exon 11 of KIT, and 2 (4%) had a mutation in exon 13 of KIT. Deletions in exon 11 of KIT were the most common mutation encountered in the present study. No mutations were found in exon 9 or 17 of KIT. Six of the 20 GISTs lacking KIT mutations had a mutation in exon 18 of PDGFRA, and 1 had a mutation in exon 12 of PDGFRA. The KIT mutation-positive GISTs showed more frequent liver metastases and higher mortality than KIT mutation-negative GISTs. Our data indicate that KIT mutations, especially deletions in exon 11, are markers of poor prognosis for gastric GISTs.

Aim. Delayed bleeding after endoscopic submucosal dissection (ESD) for gastric epithelial neoplasms is a major complication. We investigated factors related to post-ESD bleeding to identify preventive measures. Methods. The study included 161 gastric epithelial neoplasms in 142 patients from June 2007 to September 2010. Post-ESD bleeding was defined as an ulcer with active bleeding or apparent exposed vessels diagnosed by an emergency endoscopy or a planned follow-up endoscopy. We analyzed associations between bleeding and the following factors: age, sex, morphology, pathology, tumor depth, ulcer presence/absence, location, size of the resected lesion, duration of the procedure, the number of times bleeding occurred during ESD, and the use of anticoagulants and/or antiplatelet drugs. Subsequently, we examined characteristics of bleeding cases. Results. Post-ESD bleeding occurred in 21 lesions. Univariate analysis of these cases showed that ulcer presence/absence (P < 0.001), middle or lower third lesions (P = 0.036), circumference (P = 0.014), and a post-ESD ulcer with an extended lesser curve (P = 0.009) were significant predictors of bleeding. Multivariate analysis showed that ulcer presence/absence (OR 9.73, 95% CI 2.28–41.53) was the only significant predictor. Conclusion. Ulcer presence/absence was considered the most significant predictor of post-ESD bleeding.

Coagulation plus artery-selective clipping (the 2C method) of post-ESD ulcers might effectively reduce the incidence of delayed bleeding after ESD for gastric neoplasms.

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Abstract. The goal of this study was to investigate differences in the clinicopathologic and genetic characteristics of gastric and extragastric gastrointestinal stromal tumors (GISTs). We evaluated 13 extragastric GISTs and compared them with 56 gastric GISTs, which were described previously. DNA was extracted from paraffin-embedded tumor specimens, and exons 9, 11, 13, and 17 of the KIT gene and exons 12 and 18 of the platelet-derived growth factor receptor · (PDGFRA) gene were amplified by polymerase chain reaction and sequenced. Immunohistochemistry was performed for KIT, CD34, Ki-67 (as a marker of cell proliferation), and CD31 (as a marker of microvessel density), and apoptosis was assessed by in situ DNA nick end-labeling. Of the 13 extragastric GISTs 7 (54%) had a mutation in exon 11 of KIT, and 2 (15%) had a mutation in exon 13 of KIT. Deletions in exon 11 of KIT were the most common mutation encountered in the extragastric GISTs. The extragastric GISTs, especially small intestinal GISTs, showed larger deletions, leading to deletions of amino acid residues in the KIT protein, and higher vascularity than did the gastric GISTs. These data suggest that extragastric GISTs differ from gastric GISTs with respect to associated mutations and angiogenic activity.

Backgrounds: Gastrointestinal (GI) toxicity is an undesirable effect of nonsteroidal anti-inflammatory drugs (NSAIDs). We conducted a multicenter study in Japan to clarify the GI risk grade in patients with NSAID-induced GI bleeding. Methods: Patients with emergent endoscopic hemostasis by nonvariceal bleeding were registered from 36 hospitals in Hiroshima. In cases with NSAID use, the GI risk grade (low, moderate, or high) was evaluated, and concomitant drugs were investigated. We asked 79 gastroenterologists and 234 orthopedists what concomitant drugs they would prescribe to 3 simulated patients. Results: A total of 1,350 patients were registered. NSAIDs were used in 278 cases (21%). Concerning the risk grade in each patient, the largest group was the moderate-risk group (203 patients; 73%), while the high-risk group comprised 10% of all NSAID users with bleeding. A proton pump inhibitor (PPI) or misoprostol was administrated to only 20 patients (7%). A small number of the gastroenterologists and orthopedists who responded to the questionnaire would prescribe PPI or misoprostol to simulated patients with short-term loxoprofen use. Conclusions: In NSAID users with GI bleeding, the moderate-risk group was the largest group for GI toxicity in Japan. In these cases, PPI or misoprostol was not commonly medicated in clinical practice.