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Objective We analyzed a large number of stage I clear cell carcinoma of the ovary (CCC) patients to estimate the survival impact of the capsule status in stage I CCC patients, particularly in comparison with non-CCC patients. Methods Clinicopathologic data on 564 patients with stage I epithelial ovarian cancer (EOC) collected under the central pathological review system were subjected to uni- and multivariable analyses to evaluate the disease-free survival (DFS) and overall survival (OS). Results There was no significant difference in both the OS and DFS of CCC patients between IA and IC(ir) (intraoperative capsule rupture) {IA vs. IC(ir); OS: P =0.1402, DFS: P =0.2701}. In contrast, CCC patients at IC(non-ir) {IC excluding for IC(ir), such as preoperative capsule rupture, positive ascites/washing, and surface involvement} showed a poorer OS and DFS than those at IC(ir), or those at the corresponding stage in non-CCC. In multivariable analysis, the capsule status was an independent prognostic factor of a poor OS and DFS {OS: HR, 2.832; 95% CI 1.156–6.938; P =0.023; DFS: HR, 4.327; 95% CI, 1.937–9.667; P =0.0004)} {In contrast, non-CCC: N.S. (OS/DFS)}. Furthermore, in CCC patients, intraperitoneal recurrences were more frequently observed in IC(non-ir) CCC than IA or IC(ir) CCC ( P =0.0083) {In contrast, non-CCC: N.S. }. Conclusion This study suggests that CCC patients other than those with intraoperative capsule rupture show a considerable risk for mortality despite adjuvant chemotherapy.

The purpose of this study was to clarify the clinical outcome of patients with stage IA mucinous epithelial ovarian cancer (mEOC) treated with fertility-sparing surgery (FSS).After a central pathological review and search of the medical records from multiple institutions, a total of 148 stage I mEOC patients were retrospectively evaluated in the current study. All mEOC patients were divided into three groups: group A (FSS; age, 40≥); groups B and C {radical surgery; age, 40≥ (B); 40(C)}. Survival analysis was performed among these three groups using Kaplan-Meier methods.The median follow-up time of all mEOC patients was 71.6 (4.8-448.3) months. Among the 41 patients in group A, 27 patients (65.9%) had IA disease, and 14 (34.1%) had IC disease. Five-year overall survival (OS) and disease-free survival (DFS) rates of patients in the groups were as follows: group A, 97.3% (OS)/90.5% (DFS); group B, 94.4% (OS)/94.4% (DFS); group C; 97.3% (OS)/89.3% (DFS). Collectively, there was no significant difference in OS or DFS among these groups even though they were stratified to each substage (IA/IC) (OS, P=0.180; DFS, P=0.445, respectively). Furthermore, in multivariate analyses, the surgical procedure was not an independent prognostic factor for either OS or DFS (OS, HR: 0.340, 95% CI: 0.034-3.775, P=0.352; DFS, HR: 0.660, 95% CI: 0.142-3.070, P=0.596).Patients with stage I mEOC treated with FSS did not necessarily show a poorer prognosis than those receiving radical surgery.

Objective Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-catabolizing enzyme that induces immune tolerance. The purpose of the present study is to investigate IDO expression and its functional role in ovarian cancer cells in vitro and in vivo . Methods IDO expression was immunohistochemically scored in surgically-resected ovarian cancer tissues ( n =60), and its association with tumor-infiltrating lymphocyte (TIL) count or patient survival was analyzed. Next, IDO cDNA was transfected into the human ovarian carcinoma cell line SKOV3, establishing stable clones of IDO-overexpressing cells (SK-IDO). SK-IDO cells were characterized in vitro as well as in vivo using a nude mouse xenograft model. Results High IDO expression in tumor cells was found in 34 (56.7%) cases and was correlated with a reduced number of CD8+ TIL. Patients with high IDO expression had significantly impaired overall and progression-free survival compared to patients with no or low IDO expression. There were no significant differences in in vitro cell proliferation, migration, invasion, or chemosensitivity to paclitaxel between the SK-IDO and control vector-transfected (SK-pcDNA) cells. However, tumor peritoneal dissemination was significantly increased in SK-IDO-xenografted mice compared to SK-pcDNA-xenografted mice. This tumor-progressive effect in SK-IDO-xenografted mice was abrogated by oral administration of the IDO inhibitor 1-methyl-tryptophan (1-MT). Finally, treatment with weekly i.p. paclitaxel combined with daily administration of 1-MT significantly prolonged the survival of the SK-IDO-xenografted mice compared to treatment with paclitaxel alone. Conclusions These results suggest that IDO is involved in ovarian cancer progression in vivo and may be a promising therapeutic target for advanced ovarian cancer.

Background In epithelial ovarian cancer (EOC), fertility-sparing surgery (FSS) has mainly been chosen for stage IA disease. The purpose of this study was to clarify the clinical outcome of patients with clear-cell carcinoma of the ovary (CCC) who would usually undergo radical surgery. Cases After a central pathological review and search of the medical records from multiple institutions between 1988 and 2005, a total of 10 CCC patients treated with FSS were retrospectively evaluated in the current study. The mean age was 35.9 years (range: 32–39 years). The median follow-up time was 35.4 months (range: 21.7–153.2 months). The stage was IA in 4 patients, and IC in 6 patients {IC(b) in 5 patients, and IC(2) in one}. Nine patients received adjuvant chemotherapy. Nine patients were alive and one patient with stage IC(2) died of the disease at a follow-up time of 36.8 months. Five pregnancies were observed in 4 patients. Conclusions Although there is no worldwide criterion for FSS in CCC patients at present, it seems that, in selected patients, this surgical approach could be adopted. This should be investigated by additional studies in a larger series.

Seventy-one cases of ovarian epithelial tumor of borderline malignancy have been surveyed from a clinicopathologic viewpoint. The majority of the borderline tumors (73.2%) were of the mucinous type, versus only 16.9% of the serous type. The other types--endometrioid (2.8%), Brenner (1.4%), and mixed type (5.6%)--were much rarer. Patients with mucinous tumors were significantly younger (mean age 42.6) than those with serous tumors (mean age 57.5) (P less than 0.01). Of patients with mucinous tumors, 64.2% were of reproductive age (15-45 years), compared with 17% of patients with serous tumors. Some 78.8% of mucinous and 83.3% of serous borderline tumors were FIGO stage I. Serous tumors were more frequently bilateral (66.7%) than mucinous tumors (9.8%). In mucinous borderline tumors, the extent of tumor spread at the first laparotomy had an intimate relationship to the prognosis, but in serous borderline tumors, it was insignificant. The survival rate of patients with mucinous borderline tumors was 69.3% at 5 years and 62.4% at 10 years (Kaplan-Meier method). Most patients with pseudomyxoma peritonei classified as borderline at the time of discovery died within 5 years of the operation. The prognosis of the serous type was extremely favorable. Criteria for borderline tumors of various cell types and differences in the clinicopathologic data of ovarian borderline tumors between Japan and other countries were discussed.

Background Although Cushing’s syndrome arises from various neuroendocrine tumors secreting adrenocorticotropin (ACTH) ectopically, ovarian carcinoma rarely causes this syndrome. Case A 66-year-old woman presented with facial swelling and skin pigmentation. She manifested hypercortisolemia, high plasma ACTH, and lack of dexamethasone suppression. MRI showed a solid ovarian tumor and resection of the tumor led to normalization of ACTH and cortisol levels. In addition, elevated serum vasopressin (ADH) and α-fetoprotein (AFP) were found, which were also normalized after removal of tumors. Pathological diagnosis was serous adenocarcinoma with neuroendocrine and hepatoid features. Immunohistochemistry detected immunoreactivity of chromogranin A, ACTH, ADH, and AFP in tumor cells. Conclusion This is a very rare case of successful treatment of Cushing’s syndrome arising from an ovarian adenocarcinoma secreting multiple endocrine substances.

The relative frequency and the age distribution of ovarian tumors (873 primary and 47 secondary tumors) encountered over 23 years at Nagoya University Hospital were examined with respect to histological type and grade of malignancy. Of the primary neoplasms, common epithelial tumors accounted for 56.6%, sex cord-stromal tumors for 7.3%, and germ cell tumors for 39.5%. Among 296 cases with primary malignant neoplasms, common epithelial type accounted for 75.6%, sex cord-stromal tumors for 4.7%, and germ cell tumors for 19.6%. A review of the literature from Western countries indicated that in Japan, the relative frequency of common epithelial tumors is lower but that of germ cell tumors, especially malignant germ cell tumors, is higher. The difference in the incidence of germ cell tumors between Japan and Western countries is not considered significant, and the incidence of common epithelial tumors is considered to be much lower in Japan.