Kouji Shimizu

Gastric and Intestinal Phenotypic Marker Expression in Gastric Carcinomas and Its Prognostic Significance: Immunohistochemical Analysis of 136 Lesions

Objective: It is well known that both gastric and intestinal phenotypic cell markers are expressed in gastric carcinomas, irrespective of their histologic type. However, the clinicopathologic significance of these expressions has not yet been clarified. Methods: We analyzed the correlations among gastric and intestinal phenotypic marker expression patterns of the tumor, clinicopathologic findings and the patient’s outcome in 136 advanced gastric carcinomas. Results: Phenotypic marker expression was immunohistochemically evaluated using the monoclonal antibodies 45M1 (anti-human gastric mucin; HGM), CLH5 (anti-MUC6), Ccp58 (anti-MUC2) and 56C6 (anti-CD10). All tumors were classified as gastric (G), gastric and intestinal mixed (GI), intestinal (I) or unclassified (UC) phenotype. Of the 136 gastric carcinomas, 50 (36.8%), 56 (41.2%), 21 (15.4%) and 9 (6.6%) were classified as G, GI, I and UC phenotype, respectively. The G-phenotype tumors were associated with a higher rate of undifferentiated-type and infiltrative histology as compared with the I-phenotype tumors (p < 0.05 and p < 0.001, respectively). Furthermore, both univariate and multivariate analysis of survival revealed the G-phenotype tumor to be associated with a significantly poorer outcome than the I-phenotype tumor (p < 0.05). Conclusion: Our present results indicate that the gastric and intestinal phenotypic marker expression pattern of tumors, determined by the combination of HGM, MUC6, MUC2 and CD10 expression, is prognostically useful for patients with gastric carcinoma.

Peritoneal metastasis in gastric cancer with particular reference to lymphatic advancement; Extranodal invasion is a significant risk factor for peritoneal metastasis

We investigated the relationship between peritoneal metastasis and lymphatic involvement in gastric cancer by examining resected specimens.

Questionnaire survey regarding the current status and controversial issues concerning reconstruction after gastrectomy in Japan

The Japanese Society for the Study of Postoperative Morbidity after Gastrectomy conducted a nationwide questionnaire survey to clarify the current status of reconstruction after gastrectomy. One hundred and forty-five institutions (66%) responded to the survey. The questionnaire dealt with the reconstruction after a distal gastrectomy, pylorus-preserving gastrectomy (PPG), total gastrectomy, and proximal gastrectomy. The most common method of reconstruction after distal gastrectomy was Billroth I in 112 institutions (74%), and Roux-en-Y (RY) in 30 (21%). Seventy-seven institutions (53%) responded to the PPG questions. The lengths of the antral cuff were widely distributed among the institutions. Segmental gastrectomy was performed by 23 institutions for limited cases. The most common method of reconstruction after total gastrectomy was RY in 138 institutions (95%). Reconstruction with a pouch after total gastrectomy was done in 26 institutions (18%). The most common reconstructions after proximal gastrectomy were esophagogastrostomy in 69 institutions (48%), jejunal interposition in 41 (28%), double tract in 19 (13%) and pouch reconstruction in 6 (7%). Although most Japanese surgeons are concerned about the revised methods of reconstruction and quality of life after gastrectomy, surgeons have not yet reached a full consensus on these issues.

Multiple Carcinomata Associated with Anomalous Arrangement of the Biliary and Pancreatic Duct System

Two rare cases of multiple neoplasms occurring in association with anomalous arrangement of the pancreatobiliary duct system (PBD) are reported. Ultrasonography, computed tomography and endoscopic retrograde cholangiopancreatography revealed cholecystic tumor in the first case, and multiple choledochocholecystic tumors in the second case. In the first case, pancreatic tumor was discovered two years after cholecystectomy. In the second case, a pancreatic tumor was discovered incidentally in the removed pancreatic head after the operation. The histology of all of these biliary and pancreatic tumors revealed papillary adenocarcinoma in both patients, and additionally small pancreatic endocrine tumors were found in the first case. Postoperative prognosis was comfortably favorable in both patients. In a literature survey, two other cases of double carcinomata associated with anomalous PBD were found, in which the tumors showed the same histology of papillary adenocarcinoma and the postoperative prognoses were also good. These mutual clinicopathological features appear to suggest that this abnormal condition acts as a carcinogenetic risk factor in the pancreatic duct and the biliary duct system, and may finally cause multiple carcinomata in the PBD. Acta Pathol Jpn 40: 755‐763, 1990.

Association of gastric and intestinal phenotypic marker expression of gastric carcinomas with tumor thymidylate synthase expression and response to postoperative chemotherapy with 5-fluorouracil

PurposeIt is well known that both gastric and intestinal phenotypic markers are expressed in gastric carcinomas, irrespective of their histological type. In the present study, the associations among phenotypic marker expression of gastric carcinomas, tumor thymidylate synthase (TS) expression, and the chemotherapeutic response to 5-fluorouracil (5-FU) were examined.MethodsThe gastric and intestinal phenotypic marker expression of the tumor was determined by the combination of the expression of human gastric mucin (HGM), MUC6, MUC2, and CD10, and was evaluated in comparison with tumor TS expression in 137 advanced gastric carcinomas in 137 patients (75 with postoperative chemotherapy with 5-FU and 62 without postoperative chemotherapy). Tumors were classified into the gastric- (G-), gastric and intestinal mixed- (GI-), intestinal- (I-), or unclassified- (UC-) phenotype according to the immunopositivity of HGM, MUC6, MUC2, and CD10 stainings. The associations among the gastric and intestinal phenotypic marker expression of the tumor, tumor TS expression, effect of postoperative chemotherapy with 5-FU, and the patient’s prognosis were examined.ResultsOf the 137 gastric carcinomas, 48 (35.0%), 58 (42.3%), 23 (16.8%), and 8 (5.8%)were classified as the G-, GI-, I- and UC-phenotype, respectively. The high TS expression of more than 25% tumor cell positivity was found in 25 (52.1%) of the 48 G-phenotype tumors, 39 (67.2%) of the 58 GI-phenotype tumors, 18 (78.3%) of the 23 I-phenotype tumors, and 4 (50.0%) of the 8 UC-phenotype tumors. The I-phenotype tumors were significantly correlated with the higher rate of the high TS expression as compared with the G-phenotype tumors (P<0.05). Among 48 patients with the G-phenotype tumor, the 5-year survival rate in patients with and without postoperative chemotherapy was 39.7 and 27.8%, respectively. The patients with postoperative chemotherapy had a significantly better prognosis than those without postoperative chemotherapy (P<0.05). Conversely, there were no significant correlations between the presence of postoperative chemotherapy and the patient’s prognosis among patients with GI-, I-, and UC-phenotype tumors.ConclusionsThese results indicate that postoperative chemotherapy with 5-FU could be effective for patients with the G-phenotype tumor, since the incidence of intratumoral expression of TS, the target enzyme of 5-FU, is significantly low in G-phenotype tumors.

Gastrointestinal cancer metastasis and lymphatic advancement

The role of angiogenesis in the growth of solid tumors is well established, but the role of lymphatic vessels and the relationship between lymphangiogenesis and tumor spread are less clear. Recently, the molecular pathway that signals lymphangiogenesis and specific markers for lymphatic endothelium have been discovered; however, the lymphatic pathway of cancer metastasis is only partly clarified. Several investigators from the mid 20th century indicated the existence of lymphatico-venous communications, and some observed the retrograde filling of lymph flow and lymphatico-venous communication in obstructive lymphopathy. In the 1960s Burn reported the importance of lymphovenous communication in his clinical and animal experimental data. Thus, the role of potential peripheral lymphatico-venous communication must be considered in the mechanism of cancer metastasis. We observed the lymphatico-venous (portal) communication, as well as lymph retention and reflux, in a rat model of mesenteric lymph vessel obstruction. Based on the phenomenon of lymphatico-venous communication and lymph flow reflux by lymphatic obstruction, we speculate that tumor cell obstruction in the lymph system will lead to the establishment of liver and/or peritoneal metastasis. Clinically, we observed extranodal cancer invasion in a model of lymphatic obstruction, and noted a strong relationship between extranodal invasion and liver or peritoneal metastasis. Thus, the existence of peritoneal and liver metastasis via a lymphatic pathway should be considered.

Anticancer Effects ofPreoperative Chemotherapy onColorectal Carcinoma

This study was designed to evaluate the efficacy of preoperative chemotherapy and to investigate the relationship between the histopathologic response and prognosis in patients with colorectal carcinoma. Thirty-six previously untreated patients with advanced colorectal carcinoma were consecutively enrolled in this study and received preoperative N-(2-tetrahydrofuryl-5-fluorouracil (FT-207) by suppository. The histopathologic response was investigated. Histopathologically, 14 patients had no response, 19 responded slightly, 2 moderately and 1 had a complete response to the chemotherapy. The extent of the histopathologic response to chemotherapy was greater in the deeper layers of the invaded tissue. There was no relation between the location of the tumor and the extent of the histopathologic response. Based on clinical cancer staging, the overall 5-year survival rate was 100% in patients with Duke’s A and Duke’s B cancer and 45% in patients with Duke’s C cancer; the 3-year survival rate was 25% in patients with Duke’s D cancer. The 5-year survival rate for those with a positive histopathologic response to chemotherapy was 71%, whereas that for the nonresponders was 79%. Mild chemotherapy in the form of FT-207 suppositories was found to be effective histopathologically. However, no relationship was seen between the histopathologic response and survival rate.

CASE OF A MINUTE SESSILE LESION OF THE SIGMOID COLON WITH MASSIVE CANCER INVOLVEMENT IN THE SUBMUCOSAL LAYER

A 53‐year‐old man was referred to our hospital because of the appearance of a positive fecal occult immunological reaction. We found a domed lesion 0.4 cm in diameter in the sigmoid colon. Bleeding spots were observed on the surface of the lesion on endoscopy. We performed endoscopic mucosal resection of the lesion, which was found to contain well‐differentiated adeno‐carcinoma and cancer cells infiltrating to the cut‐end of resected specimen. Laparoscopy‐assisted sigmoidectomy was then performed with dissection of the lymph nodes. The dissected lesion was diagnosed as adenocarcinoma with moderate fibrosis and massive cancerous involvement. The patient died of recurrent cancer 3 years after the operation. In the minute sessile lesion, bleeding spots on the surface may suggest invasive cancer with massive cancer involvement within the submucosal layer.