Kenji Shiomori

Involvement of three or more lymph nodes predicts poor prognosis in submucosal gastric carcinoma

Background. Multivariate analyses has shown that the status of lymph node metastasis and the depth of tumor penetration through the gastric wall are the most important prognostic factors in patients with advanced gastric carcinoma after curative operation. A clinicopathological study was carried out to clarify a simple and optimal prognostic indicator for early gastric cancer.Methods. Retrospective analyses of 982 patients with early gastric cancer (562 with mucosal [M] and 420 with submucosal [SM] tumor) treated by gastrectomy with D2 lymph node dissection were performed.Results. The incidence of lymph node metastasis from M and SM tumors was 2.5% (14/562) and 20.2% (85/420), respectively. There were no apparent prognostic indicators in patients with M tumors. In patients with SM tumors, the cancer-specific 5-year survival of those with lymph node metastasis was significantly lower than that of those without such metastasis (77.6% vs 98.2%; P < 0.001). An sharp decrease in survival was seen between patients with two positive nodes and those with three positive nodes, and the cancer-specific 5-year survival rate of patients with three or more metastatic lymph nodes was significantly lower than that of those with one or two nodes (P < 0.001; univariate analysis). Multivariate analysis revealed that the involvement of three or more lymph nodes was the sole independent prognostic determinant (P = 0.016); the level of nodal metastasis was not an independent prognostic factor (P = 0.384). All patients with N2 lymph node echelons (according to the Japanese Research Society for Gastric Cancer classification of the draining lymph nodes of the stomach) in the group with one or two positive nodes survived for more than 5 years.Conclusion. The sole independent prognostic factor in SM gastric cancer is the involvement of three or more metastatic lymph nodes. We suggest that this simple prognostic indicator for the follow-up of early gastric cancer, and this could lead to potentially effective adjuvant chemotherapy.

A New Procedure of Percutaneous Microwave Coagulation Therapy Under Artificial Hydrothorax for Patients with Liver Tumors in the Hepatic Dome

Abstract Percutaneous microwave coagulation therapy (PMCT) has been widely used as an effective minimal invasive therapy for small liver tumors. The occurrence of a sonographic masked space due to the presence of the lung, however, has become a major obstacle to visualizing the whole tumor in the hepatic dome. To facilitate the use of PMCT for liver tumors in the hepatic dome, we developed PMCT in combination with the artificial hydrothorax method (percutaneous transdiaphragmatic MCT: PTD-MCT). Our new approach for PMCT to the hepatic tumors located in Couinauds segments VIII or VII just under the diaphragm resulted in a successful treatment. The separation of the lung from the diaphragm by the infusion of saline into the pleural cavity enabled us not only to visualize the whole tumor in the hepatic dome to accurately target the tumor, but also helped us to avoid injuring the lung. PTD-MCT is therefore strongly recommended for the treatment of liver tumors in the hepatic dome.

Gastric and intestinal phenotypes of gastric carcinoma with reference to expression of brain (fetal)-type glycogen phosphorylase

Purpose. Although reports have suggested that differentiated gastric carcinomas have different phenotypes, i.e., gastric and intestinal type, this classification is complicated and can be confusing. Our previous studies have demonstrated a close relationship between carcinogenesis in differentiated-type gastric cancer and the expression of brain (fetal)-type glycogen phosphorylase (BGP). The purpose of this study was to investigate the relationship between the mucin phenotype of gastric carcinoma and BGP expression. Methods. Ninety-six specimens of gastric carcinoma were studied using specific anti-BGP antibody. Correlation of BGP expression with intestinal and gastric phenotypes was determined with the anti-mucin antibodies, HGM, CD10, and MUC2. Results. BGP was expressed in 82.6% (38/46) of differentiated type and in 24.0% (12/50) of undifferentiated type carcinomas. The incidence of BGP positivity was significantly greater in the differentiated-type carcinoma than in the undifferentiated type (P < 0.001). The proportions of gastric, mixed and intestinal types in differentiated and undifferentiated gastric carcinomas were 13.0%, 47.8%, and 39.2%, and 56.0%, 32.0%, and 12.0%, respectively. In both differentiated and undifferentiated types, the phenotype of gastric and intestinal mucin expression corresponded very well with BGP expression, that is, more than 90% of carcinomas with gastric type did not express BGP, whereas approximately 90% of carcinomas with intestinal type did express BGP. Conclusions. The classification of gastric and intestinal phenotypes of gastric carcinoma in terms of BGP expression was simpler and clearer than such classification in terms of mucin immunohistochemistry. It is suggested that BGP is a useful biomarker for the classification of intestinal and gastric type carcinoma of the human stomach, including classification from the carcinogenetic point of view.

BGP expression in gastric biopsies may predict the development of new lesions after local treatment for early gastric cancer

Abstract.Background: Our previous studies have demonstrated the significant role of the generative cells of intestinal metaplasia (IM) expressing brain (fetal)-type glycogen phosphorylase (BGP) (BGP-IM) as a premalignant lesion of intestinal-type adenocarcinoma. The aims of the present study were to investigate the incidence of BGP-IM in gastric biopsy specimens and to establish BGP-IM as a predictor of the coexistence of accessory carcinoma and/or metachronous cancers before and after local treatment for early gastric carcinoma. Methods: We studied the incidence of BGP-IM in eight endoscopic biopsy specimens of methylene blue-positive mucosa of the stomach obtained from patients with multiple gastric carcinomas (n = 14), a single carcinoma (n = 25), and atrophic gastritis (n = 20). Results: BGP positivity was 93.3% in the multiple carcinomas and 80.0% in the single carcinomas. The incidences of BGP-IM (mean percentage ± SD) in the stomachs with multiple carcinomas, single carcinoma, and atrophic gastritis were 83.2% ± 22.8%, 36.5% ± 41.3%, and 7.1% ± 18.0%, respectively. The incidence was significantly higher in the stomachs with multiple carcinomas than in those with a single carcinoma or those with atrophic gastritis (P < 0.001). Conclusion: It is suggested that the frequent appearance of BGP-IM reflects the high potential of carcinogenesis of intestinal-type gastric cancer, and that the involvement of BGP-IM in more than 50% of the eight biopsies may be a predictor of the coexistence of accessory and/or metachronous carcinoma before and after local treatment for early gastric carcinoma.

Peritoneal metastasis after operation for non-serosa-invasive gastric carcinoma and a prophylactic strategy for peritoneal dissemination

Abstract The established ultra-rapid quantitative RT-PCR system for intraoperative detection of intraperitoneal free cancer cells, the elucidated cause of peritoneal recurrence after curative operation for patients with non-serosa-invasive gastric cancer, and the extensive intraperitoneal lavage (EIPL) therapy for the prophylaxis of peritoneal recurrence from the results of evaluation using the ultra-rapid quantitative RT-PCR system were reviewed. We established ultra-rapid RT-PCR protocol that enables diagnosis of intraperitoneal cancer spread about 70 min, using LightCycler method in combination with automated mRNA extractor. Both the carcinoembryonic antigen (CEA) and cytokeratin (CK)20 messenger RNA (mRNA) in intraperitoneal lavages after lymph node dissection were identified in three (14.2%) and four (26.7%) patients with submucosal (SM) and muscularis propria (MP) tumors, respectively. Although peritoneal metastasis occurs in some patients with early gastric carcinoma, the reasons have not been fully established. These results clarified that peritoneal metastasis after operation for non-serosal-invasive gastric cancer was caused by opening lymphatic channels during lymph node dissection allowing the spread of viable cancer cells into the peritoneal cavity. Furthermore, EIPL method was performed in five cases with serosa-invasive (SE) gastric carcinoma, and its efficacy was evaluated by the quantitative RT-PCR. The quantitative RT-PCR demonstrated that EIPL reduced free cancer cells from 3.8×10 5 ±1.4×10 5 to 2.8±1.5 cells/100 ml of lavage by from six to eight washes, and they disappeared after the seventh to ninth wash. In conclusion, an ultra-rapid quantitative RT-PCR system for intraoperative detection of intraperitoneal free cancer cells was established for clinical use. It is suggested that the combination with the novel rapid detection system with the intraoperative therapy of EIPL can be a useful prophylactic strategy for peritoneal metastasis from gastric carcinoma.

Proposal of genetic pathways of de novo colorectal carcinomas

Abstract Our recent study has demonstrated that brain (fetal)-type glycogen phosphorylase (BGP) positive foci (BGP foci) have a vital role in the de novo colorectal carcinogenesis. This paper reviewed the investigation on the genetic alternations in the BGP foci and the clarification of the mechanisms of de novo colorectal carcinogenesis. De novo colorectal carcinomas with invasion into submucosa or superficial muscularis propria were selected from resected specimens. Investigations of the p53, K-ras and APC mutations were performed in the BGP foci, BGP negative colorectal mucosa and de novo colorectal carcinoma. No K-ras mutation was observed in all of the cases. Mutations of p53 and APC were 14 (50.0%) and 9 (32.1%) in de novo colorectal carcinomas, and 11 (39.3%) and 1 (3.6%) in BGP foci, respectively. Both p53 and APC mutations were detected in 8 and 1, p53 mutation alone in 6 and 10, APC mutation alone in 1 and 0 out of 28 de novo colorectal carcinomas and BGP foci, respectively. Our sequential studies propose that the two major pathways, i.e., the p53–APC pathway and the p53 alone pathway in the de novo colorectal carcinogenesis.