Noboru Yokoyama

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.

Delorme’s Procedure for Rectal Prolapse

AbstractPURPOSE: Clinical and physiological results of Delorme’s procedure were assessed retrospectively in patients undergoing this procedure for rectal prolapse. METHODS: A consecutive series of 31 patients (7 males, 24 females; age, 14–93, mean 70 years) with full-thickness, rectal prolapse were treated by Delorme’s procedure between 1994 and 2002. Median follow-up was 39 (range, 6–96) months. RESULTS: Good results were achieved in 27 patients (87 percent), prolapse recurrence was observed in 4 (13 percent), and mean recurrence time was 14 (range, 3–25) months. There were no postoperative deaths. Minor complications occurred in four patients. The median changes in preoperative and postoperative physiologic patterns in 16 patients were as follows: resting pressure from 21.0 (range, 5–48) to 23.5 (range, 12–76) cm H2O (P = 0.030), squeeze pressure from 64.0 (range, 27–248) to 108.0 (range, 32–264) cm H2O (P = 0.041), volume at first sensation from 100 (range, 70–180) to 70 (range, 40–130) ml (P = 0.002), maximum tolerated volume from 260 (range, 120–400) to 160 (range, 70–400) ml (P = 0.001). Incontinence improved in 63 percent. No patient became constipated, and 38 percent of those constipated preoperatively improved. The preoperative incontinence score improved from 11.5 (range, 1–20) to 6.0 (range, 0–20) after operation (P < 0.0001). CONCLUSION: Delorme’s procedure had a low morbidity, did not lead to constipation, improved anal continence, and had a reasonably low recurrence rate. Improved anal sphincter and rectal sensation were associated with a reduced incidence of defecatory problems after Delorme’s procedure.

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.

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.