Hisatake Ishikawa

Squamous cell carcinoma arising from mature cystic teratoma of the ovary: A clinicopathologic analysis

Objective There have been few studies concerning the clinical pathology of squamous cell carcinoma arising from ovarian mature cystic teratoma. Thus, the objective of this study is to determine clinicopathologic factors affecting survival in this rare tumor. Methods From September 1979 to June 1996, 37 patients with squamous cell carcinoma arising from ovarian mature cystic teratoma were treated by the Tokai Ovarian Tumor Study Group. A restrospective clinicopathologic and survival analysis of these patients was performed. The mode of infiltration was classified into expansive, moderately diffused, and diffused patterns. Results Although the 5-year survival rate was 94.7% and 80.0% for stage I and II patients, respectively, 12 and 13 patients with stage III died within 20 months (P = .0001). A significant difference was also observed between the survival of the groups with and without residual tumor at surgery (P = .0001). Pathologic features, grade, mode of infiltration, and vascular involvement were significant factors by univariate analysis. Multivariate analysis showed significant differences in survival related to grade (P = .0154) and mode of infiltration (P = .0053). The preoperative squamous cell carcinoma antigen level was significantly higher in the patients with squamous cell carcinoma arising from mature custic teratoma than in patients with mature cystic teratoma (P < .0001). Conclusion This study suggests that pathologic factors, grade, and mode of infiltration can provide valuable information for predicting the survival of patients with squamous cell carcinoma arising from mature cystic teratoma. In addition, squamous cell carcinoma antigen may be a useful marker to detect this disease preoperatively.

Characterization of extracellular matrix-degrading proteinase and its inhibitor in gynecologic cancer tissues with clinically different metastatic form

Background. The authors conducted a comparison study of matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase‐1 (TIMP‐1) activities in clinically different metastatic types of ovarian cancer, cervical cancer, and endometrial cancer tissues.

Randomised study of immunotherapy with OK-432 in uterine cervical carcinoma

OK-432, a streptococcal preparation, was administered to patients with stage Ib and II cervical carcinoma except for adeno- and adenosquamous carcinomas. To evaluate the efficacy of OK-432 precisely, 177 patients were stratified by clinical stage, radiotherapy, and lymph node metastasis after complete radical hysterectomy and pelvic lymphadenectomy. Within each stratum, patients were divided randomly into OK-432 and control groups. 85 patients received OK-432 and 92 patients did not. No significant difference was observed in overall 5-year disease free rates between the OK-432 and the control groups, although the mean diameter of erythema on SU-polysaccharide (SU-PS) skin test was larger in the OK-432 group than in the control group. In stage IIb, a significant difference was observed between the OK-432 and control groups. This difference, however, could be attributed in part to the different incidence of the lymph node metastasis. In stage II without lymph node metastasis, 5-year disease free rate was significantly higher in the OK-432 group.

Clinical value of a new serum tumor marker, CA125 II, in gynecologic disease : comparison with CA125

CA125 II, an improved version of the conventional CA125 was compared with CA125 as to which was more useful in gynecologic disease. In the diagnosis of tumors around the adnexal field (primary epithelial ovarian cancer, metastatic ovarian cancer, benign ovarian tumor and endometrial cyst), CA125 II showed the same sensitivity and specificity as CA125. CA125 II also has high simultaneous reproducibility in the low concentration area. The examination by the receiver operating characteristic curve revealed that CA125 II has higher precision than that of CA125 when it is used for the screening test. In conclusion, CA125 II is a better tumor marker than conventional CA125.

Recurrence of epithelial ovarian carcinoma after clinical remission.

One hundred and eighty-eight patients with epithelial ovarian carcinoma were treated with primary cytoreductive surgery and subsequent combination chemotherapy. The first recurrent findings such as sites and disease-free interval were analyzed in 141 patients who were clinically remitted 6 months after operation or chemotherapy. Fifty-seven cases had a recurrence. Five-year disease-free survival rates were 75, 72, 29, and 0% in stage I, II, III, and IV, respectively. Twenty-one of 22 patients with > 2 cm maximum residual tumor died, although they once achieved clinical remission. Significant differences were observed between histologic types, and the disease-free survival rate was lowest for serous cystadenocarcinoma. Nine of 15 stage IV patients with serous histology experienced remission, but none of the 8 in stage IV with other histologies did so, suggesting that serous adenocarcinoma is sensitive to chemotherapy and conducive to clinical remission. However, all stage IV patients in remission encountered a recurrence. Intra-abdominal cavity and lymph node were frequently the initial recurrent sites (38 and 27%, respectively). On the other hand, the incidence of distant recurrence was as high as 27%, and 8 of 16 cases with distant recurrence were stage I. Survival time after recurrence was not different among initial sites of recurrence and mean survival time was 15 months.

Prognostic factors of secondary ovarian carcinoma.

Objective: Although the ovaries are common sites of metastases from a variety of primary neoplasms excluding carcinomas of the genital tract, there were few reports concerning survival and prognostic factors. The objective of this study was to assess the clinical factors affecting survival. Methods: Fifty-three secondary ovarian carcinomas excluding metastases from genital tract carcinoma were registered by the Tokai Ovarian Tumor Study Group from 1989 to 1999. FIGO staging was set without considering the pathologic findings of the lymph nodes and the primary tumors. Results: Twenty-four patients were stage I, 11 were stage II, 16 were stage III, and 2 were stage IV. There were significant differences in the survival curves between the early stages (I and II) and advanced stages (III and IV). The 5-year survival rate for patients without residual tumors was 39.9%, while all patients with residual tumors after surgery died within 33 months. The most frequent primary tumor was large intestinal carcinoma, and the second was gastric carcinoma. The 5-year survival rate for patients with large intestinal primary tumors was significantly better than that with stomach tumors. Multivariate analysis demonstrated that tumor stage and primary tumor sites were significant prognostic factors. Conclusion: FIGO staging without considering lymph node involvement and the primary tumor was a significant prognostic factor, and prognostic factors for primary ovarian carcinomas can be applied to secondary ovarian carcinomas. Furthermore, the primary tumor site was also an important prognostic factor for survival.

Distribution of platinum in human gynecologic tissues and pelvic lymph nodes after administration of cisplatin

BACKGROUND Defining tissue accumulation of platinum may be of importance, since it may provide a pharmacological explanation for organ-specific cisplatin activity. This study was conducted to evaluate the efficacy of cisplatin at the tissue level in different gynecologic organs. The doses administered were equivalent to those used in neoadjuvant chemotherapy regimens. STUDY DESIGN Cisplatin was administered intravenously to patients with cervical or endometrial cancer 1 h before operation, and platinum accumulations in tissues were assayed by the atomic absorption method. RESULTS Platinum accumulation was highest in the cervix and next highest in the myometrium in both cancers. Platinum accumulation in ovary and lymph node was only 0.58 and 0.57 times that in the myometrium, respectively. In patients with cervical cancer, the platinum accumulations in the myometrium and cervix were significantly higher than in the ovary and lymph node. Platinum accumulation in cervical cancer tissue was lower than in the myometrium and cervix, suggesting that delivery of cisplatin to a cervical cancer is somewhat more difficult than to the normal cervix. In patients with endometrial cancer, there was significantly more accumulation in the cervix than in the ovary and lymph node. CONCLUSIONS These data indicated that cisplatin was easily distributed to the cervix and myometrium, but not to the ovary, lymph node, and cancer tissues.

Sensitisation of human ovarian carcinoma cells to cis-diamminedichloroplatinum (II) by amphotericin B in vitro and in vivo

Human ovarian carcinoma cells (HRA) were sensitised to cis-diamminedichloroplatinum (II) (CDDP) 2.7-, 5.5- and 12.1-fold by treatment with amphotericin B (AMB) at concentrations of 2.1, 5.4 and 10.8 microM, respectively. Moreover, intracellular accumulation of platinum after a 2-h exposure to CDDP was increased significantly with AMB treatment. We prepared HRA cell-inoculated nude mice as an experimental therapeutic model for human advanced ovarian carcinoma. Ascites was evident after 7 to 9 days of intra-peritoneal (i.p.) inoculation of HRA cells, and mice died due to intra-abdominal carcinomatosis after 11 to 14 days [mean survival time (MST): 12.4 +/- 1.1 days]. Treatment with AMB (2.0 mg/kg) alone 4 days after inoculation increased MST by only 1.4 days. Simultaneous treatment with CDDP (1.0 to 2.0 mg/kg) and AMB (0.5 to 2.0 mg/kg) produced a significant increase in MST compared to treatment with CDDP alone. Maximal MST (30.1 days) was observed by treatment with 2.0 mg/kg CDDP plus 2.0 mg/kg AMB, whereas MST with 2.0 mg/kg CDDP alone was 16.4 days. A further drug accumulation study demonstrated that platinum accumulation in tumour tissues in nude mice treated with CDDP and AMB increased significantly compared to treatment with CDDP alone. These results indicate that intraperitoneal combination chemotherapy with CDDP and AMB is effective in an experimental animal model of advanced ovarian carcinoma.