Masashi Nishiya

A clinical and pathologic study on para‐aortic lymph node metastasis in endometrial carcinoma

Recent studies have shown that poor survival for patients with early endometrial cancer was related to the extrapelvic spread of the cancer. The purpose of this study was to evaluate the correlation between para‐aortic lymph node (PAN) metastasis and histopathologic findings and to assess the clinical utility of identifying PAN metastasis of endometrial carcinoma.

First-line intraperitoneal carboplatin-based chemotherapy for 165 patients with epithelial ovarian carcinoma: results of long-term follow-up.

OBJECTIVE Currently, no long-term follow-up data are available on intraperitoneal (IP) carboplatin-based chemotherapy for ovarian carcinoma. In this study we evaluated retrospectively the survival and recurrence of a retrospective cohort of patients with epithelial ovarian cancer treated with first-line IP carboplatin-based therapy. METHODS Records were reviewed of 174 patients with epithelial ovarian cancer who received IP carboplatin-based therapy between 1990 and 2000. All patients underwent surgical staging, and implantable port systems were placed regardless of residual tumor size. The pathological slides were submitted and reviewed, and then nine patients were excluded because of borderline malignancies (n = 8), and wrong histology (n = 1). Therefore, the records of 165 patients were analyzed for survival. Tumor grade was determined by the Universal grading system. Statistical analysis included tests for association between potential prognostic factors, and between prognostic factors and survival. Survival probabilities were estimated by Kaplan-Meier methods, and prognostic factors for survival were evaluated by a Cox regression model. RESULTS The mean age of the patients was 53.7 years (range 21-83). The median follow-up was 41 months. The distribution by stage and histology was as follows: high risk (grade 2/3, clear cell, capsule rupture) stage I, 54; II, 21; III, 72; IV, 18; and serous, 75; clear cell, 30; mucinous, 27; endometrioid, 20; others, 13. The chemotherapy regimen was either carboplatin alone (n = 22) or in combination with cyclophosphamide (n = 116) or paclitaxel (n = 27). Catheter-related complications occurred in 16 (9.7%) cases. The chemotherapeutic response in 54 patients with measurable disease was 66.4%. The 5-year survival was 94.4% for stage I, and 87.9% for stage II. The median survival for optimal and suboptimal stage III/IV patients was 51 months and 34 months, respectively. The median survival of patients with stage III/IV disease was 51 months with carboplatin doses of 400 mg/m(2) or more, but it was only 25 months with carboplatin doses smaller than 400 mg/m(2). Poor prognostic factors, determined by Cox regression multivariate analysis, were clear cell histology (P < 0.001) and a carboplatin dose smaller than 400 mg/m(2) (P = 0.002). CONCLUSIONS Survival of patients who underwent carboplatin-based IP chemotherapy was excellent when the dose of carboplatin was higher than 400 mg/m(2). A prospective evaluation of IP carboplatin therapy with modern combination is warranted.

Cox multivariate regression models for estimating prognosis of patients with endometrioid adenocarcinoma of the uterine corpus who underwent thorough surgical staging

The International Federation of Gynecology and Obstetrics (FIGO) adopted surgical staging criteria in 1988. Many studies have shown that histologic grade, nuclear grade, lymph‐vascular space invasion and cell type are also important predictors of survival. It has not been clarified, however, how to integrate these histopathologic variables into the process of estimating individual prognosis. We performed Cox multivariate regression analysis to create models that incorporate various histopathologic factors for estimating the prognoses of patients with endometrioid adenocarcinoma of the uterine corpus. Our study was based on data from 206 patients who underwent complete surgical staging, including systematic pelvic and para‐aortic lymph node dissection. Two models resulted: one included depth of myometrial invasion, para‐aortic node metastasis and the number of sites involved by the tumor among the cervix, ovary and pelvic lymph nodes (which we designated as extracorporeal spread score, ECS) and the other incorporated nuclear grade and lymph‐vascular space invasion as variables. These 2 models enabled the prognosis for patients with endometrioid adenocarcinoma to be stratified into several levels according to hazard ratio. Comprehensive integration of the histopathologic prognostic factors, categorized into those relating to tumor extent and those relating to tumor virulence, should facilitate the estimation of individual prognosis more accurately than FIGO staging alone. Int. J. Cancer (Pred. Oncol.) 79:521–525, 1998.© 1998 Wiley‐Liss, Inc.

Bcl-2 expression and apoptosis in human trophoblast

Summary The function of Bcl-2 in the differentiation and proliferation of human trophoblast cells is not yet elucidated. The expression of Bcl-2 in human placenta was examined immunohistochemically using a monoclonal antibody to Bcl-2 and apoptosis of trophoblast cells was investigated by the 3′-end labeling method to detect fragmented DNA. Bcl-2 protein was localized in syncytiotrophoblast and its amount seemed to increase as pregnancy advanced. The proliferation of trophoblast cells decreased by term, and apoptotic cell death was found less frequently in the placenta at term. This suggests that the higher expression of Bcl-2 protein in late pregnancy may prolong the life of trophoblast cells so that the placental mass is maintained although proliferative activity of trophoblast cells has decreased. Combined with our previous result that there is an inverse relation between p53 protein expression and Bcl-2 protein expression, apoptotic death of trophoblast cells may be under the control of p53 and Bcl-2 proteins.