Namiko Yada-Hashimoto

Metastatic ovarian tumors: a review of 64 cases

OBJECTIVE The goal was to review cases of metastatic ovarian tumor with respect to their clinical features. METHODS Sixty-four patients with pathologically confirmed metastatic ovarian carcinoma, who were treated between 1978 and 2002 at Osaka Medical Center for Cancer and Cardiovascular Diseases (OMCC), were reviewed and the clinical features examined. RESULTS We found that metastatic tumors accounted for 21.1% (64/304) of malignant ovarian tumors. Of 64 metastatic ovarian tumors, 26 originated from gynecologic organs, and 38, from nongynecologic organs. Gynecologic primary sites were the uterine body (23%), uterine cervix (14%), and fallopian tube (3%). Eight of nine cervical cancers with ovarian metastases were adenocarcinomas. Adenocarcinoma of the uterine cervix metastasized to the ovaries more frequently than squamous cell carcinoma (5.6% vs 0.1%, respectively; P < 0.01). Among 38 cases of metastatic ovarian tumors from nongynecologic organs, Krukenberg tumors, pathologically characterized by the presence of typical signet-ring cells, were found in 11 patients (29%). Most (8/11) had originated in the stomach. Half (19/38) were preoperatively diagnosed as metastases. The 5-year survival rate after resection of metastatic ovarian tumors from gynecologic organs was significantly higher than the rate after resection of such tumors from nongynecologic organs (47% vs 19%, respectively; P = 0.026). CONCLUSIONS Metastatic ovarian tumors are likely to be relatively common in Japan because of the high incidence of gastric cancer. In cases of pelvic tumor, metastatic ovarian tumor should always be included in the differential diagnoses. As the 5-year survival after resection of metastatic ovarian tumor is 19%, even for tumors from nongynecologic organs, it seems worthwhile to consider tumorectomy as the second cytoreduction.

Inhibition of inhibitor of nuclear factor-κB phosphorylation increases the efficacy of paclitaxel in in vitro and in vivo ovarian cancer models

We investigated whether inhibition of nuclear factor-κB (NFκB) increases the efficacy of paclitaxel in in vitro and in vivo ovarian cancer models. Treatment of paclitaxel-sensitive Caov-3 cells with paclitaxel transiently activated the phosphorylation of Akt, the phosphorylation of IκB kinase (IKK), and the phosphorylation of inhibitor of NFκB (IκBα). Paclitaxel also caused a transient increase in NFκB activity, followed by a decrease in NFκB activity. We show an association between Akt and IKK and show that the phosphorylation of IKK induced by paclitaxel is blocked by treatment with a phosphatidylinositol 3-kinase inhibitor (wortmannin or LY294002). Furthermore, interference of the Akt signaling cascade inhibits the transient induction of IκBα phosphorylation and NFκB activity by paclitaxel. Inhibition of NFκB activity by treatment with an IκBα phosphorylation inhibitor (BAY 11-7085) attenuated both basal and transient induction of IκBα phosphorylation by paclitaxel. Treatment with BAY 11-7085 also enhanced the inhibition of NFκB activity by paclitaxel for up to 24 hours. In addition, treatment with BAY 11-7085 decreased the viability of cells treated with paclitaxel. Moreover, treatment with BAY 11-7085 increased the efficacy of paclitaxel-induced inhibition of intraabdominal dissemination and production of ascites in athymic nude mice inoculated intraperitoneally with Caov-3 cells. These results suggest that paclitaxel transiently induces NFκB activity via the phosphatidylinositol 3-kinase/Akt cascade and that combination therapy with paclitaxel and an NFκB inhibitor would increase the therapeutic efficacy of paclitaxel.

Concurrent Weekly Nedaplatin, External Beam Radiotherapy and High-Dose-Rate Brachytherapy in Patients with FIGO Stage IIIb Cervical Cancer: A Comparison with a Cohort Treated by Radiotherapy Alone

Objectives: The aim of this study was to evaluate whether nedaplatin-based concurrent chemoradiotherapy (CCRT) using high-dose-rate intracavitary brachytherapy (HDR-ICBT) is superior to radiotherapy (RT) alone in patients with FIGO stage IIIb cervical cancer. Methods: The records of 41 consecutive women treated either with nedaplatin-based CCRT using HDR-ICBT (n = 20) or RT alone (nonrandomized control group, n = 21) for stage IIIb cervical cancer were retrospectively reviewed. The activity and toxicity were compared between the two treatment groups. Progression-free survival (PFS) and overall survival (OS) were the main endpoints. Results: The 5-year overall survival rates in the CCRT and RT groups were 65 and 33.3%, respectively. The median OS of the CCRT and RT groups were 60 and 29 months, respectively. CCRT was significantly superior to RT alone with regard to PFS (p = 0.0015) and OS (p = 0.0364). The frequency of acute grade 3–4 toxicity was significantly higher in the CCRT group than in the RT group. However, no statistically significant difference was observed with regard to severe late toxicity. Conclusions: Nedaplatin-based concurrent chemoradiotherapy was safely performed and significantly improved the prognosis of patients with FIGO stage IIIb cervical cancer. This treatment can be considered as an alternative to cisplatin-based chemoradiotherapy in this patient population.

Estrogen and raloxifene inhibit the monocytic chemoattractant protein-1-induced migration of human monocytic cells via nongenomic estrogen receptor alpha.

Objective: To investigate the effects of estradiol (E2) and raloxifene on the migration of human monocytic THP-1 cells to endothelium. Design: A prospective comparative study. THP-1 cells, a human acute monocytic leukemia cell line, were used for the study. Migration assays were performed using transwell inserts. THP-1 cells were exposed to E2 or raloxifene in the presence of monocytic chemoattractant protein-1 (MCP-1), a major chemoattractant for monocytes. The cells were transfected with small interfering RNA (siRNA) against estrogen receptor (ER) &agr; and ER&bgr; for gene silencing. ER expression was evaluated by Western blot analysis. Results: MCP-1 induced the migration of the cells for 90 minutes. The addition of E2 or raloxifene significantly inhibited the MCP-1-induced migration for 90 minutes. Preincubation of THP-1 cells with an ER antagonist, ICI 182780, significantly attenuated the inhibitory effects of E2 and raloxifene. Whereas transfection with siRNA of ER&agr; significantly attenuated the inhibition by E2 of MCP-1-induced monocyte migration, transfection with control siRNA or siRNA of ER&bgr; had no effect on the rapid inhibitory action of E2. Moreover, preincubation of THP-1 cells with a transcriptional inhibitor, actinomycin D, had no effect on the rapid inhibitory action of E2. Conclusions: Our findings suggest that both E2 and raloxifene inhibited the MCP-1-induced monocyte migration through nongenomic ER&agr;. This result may explain one of the antiatherosclerotic effects of E2 and raloxifene on vasculature.

Unexpected diagnosis of stage IIA dysgerminoma in streak gonad in a patient with Swyer syndrome: a case report

Abstract Patients with Swyer syndrome, which is also known as 46,XY pure gonadal dysgenesis, are at an increased risk of gonadoblastoma and germ cell tumor. Prophylactic gonadectomy is recommended for these patients. We report a case of stage IIA dysgerminoma arising in a streak gonad in a patient with Swyer syndrome, which was not diagnosable preoperatively and intraoperatively. The patient was primarily amenorrheic and identified as female phenotypically. She underwent gonadectomy at 27 years of age. Preoperative image analysis showed a relatively small uterus without adnexal masses. Laparoscopic findings showed bilateral streak gonads. Postoperatively, histopathological examination revealed that the patient had dysgerminoma in her left streak gonad. Preoperative and intraoperative diagnosis of dysgerminoma in normal size ovaries is thought to be difficult. Although it is rare, considering the occurrence of dysgerminoma in streak gonad with extension to the mesosalpinx, prompt prophylactic gonadectomy is strongly recommended for these patients regardless of the size of the ovaries.

Ovarian insufficiency following allogeneic hematopoietic stem cell transplantation

Abstract Ovarian insufficiency is a serious complication for young women who undergo hematopoietic stem cell transplantation (HSCT). Reduced-intensity conditioning (RIC) has been utilized more widely due to its reduced toxicity; however, there is a lack of data concerning ovarian function after HSCT with RIC. We investigated the ovarian function in patients who received HSCT with RIC, compared to those who received myeloablative conditioning (MAC). The records of 69 female patients who received allogeneic HSCT at the institution under 40 years of age at transplantation from 1991 to 2012 were retrospectively analyzed. Prevalence of ovarian insufficiency was significantly lower in patients conditioned with RIC than in those conditioned with MAC (4/27 = 14.8% for RIC and 36/42 = 85.7% for MAC, p < 0.0001). A younger age at HSCT was associated with a lower risk of ovarian insufficiency. Among the 40 patients with ovarian insufficiency, four patients recovered ovarian function, and two conceived following hormone-replacement therapy (HRT). A higher serum E2 level prior to HRT was a significant predictor for the restoration of ovarian function (p = 0.0028). In conclusion, RIC was significantly less toxic to ovarian function compared with MAC. HSCT-associated ovarian insufficiency is not irreversible, and a higher E2 level may predict the restoration of ovarian function.

Contents Vol. 69, 2010

M.A. Belfort, Provo, Utah J. Bornstein, Nahariya H.L. Brown, Durham, N.C. C. Chapron, Paris J. de Haan, Maastricht G.A. Dekker, Adelaide J.A. Deprest, Leuven K. Hecher, Hamburg S. Kahhale, São Paulo H. Kliman, New Haven, Conn. T.F. Kruger, Tygerberg J.A. Kuller, Raleigh, N.C. M.J. Kupferminc, Tel Aviv H. Minkoff , Brooklyn, N.Y. J. Moodley, Congella J.M. Mwenda, Nairobi H. Odendaal, Tygerberg J.T. Repke, Hershey, Pa. Founded 1895 as ‘Monatsschrift für Geburtshilfe und Gynäkologie’, continued 1946–1969 as ‘Gynaecologia’ and 1970–1977 as ‘Gynecologic Investigation’