Presentation of two patients with malignant granulosa cell tumors, with a review of the literature.

Granulosa cell tumors (GCTs) of the ovary account for 2 to 5 of ovarian malignancies. We present two patients with malignant ovarian adult GCT. In one patient, a combination of bleomycin, etoposide, and cisplatin was effective after initial surgery for malignant GCT. In the other, an aromatase inhibitor was effective for recurrent malignant GCT. We also review the literature for further management of this tumor. Because GCT of the ovary is rare, it will be necessary to elucidate the clinical phenotype and establish treatment protocols by accumulating and analyzing more patients.

A case of ovarian mucinous adenocarcinoma in a premenarcheal girl.

We report a case of a 12-year-old premenarcheal girl who developed ovarian mucinous adenocarcinoma. The tumor, which originated from the right ovary, weighed 1400 g, and had a smooth surface and thin capsule, was extirpated. The cut surface showed multilocular cysts of various sizes and yellowish gelatinous to solid parts that accounted for approximately 40% of the cut surface. The histological findings showed a continuous mixture of mucinous adenoma, mucinous borderline tumor, and mucinous adenocarcinoma with an expansile invasive pattern. It was assumed that an ovarian mass developed in an early period after birth or infancy, and the mutation of certain oncogens occurred in an early period, leading to cancer. While some etiological hypotheses concerning ovarian carcinogenesis have been suggested, we believe this case provides valuable information when considering a new onset mechanism of ovarian epithelial malignant tumors.

A Case of Ovarian Clear Cell Carcinoma Simultaneously Producing Parathyroid Hormone-related Protein and Granulocyte Colony-Stimulating Factor.

We describe the first report of an ovarian clear cell carcinoma simultaneously producing parathyroid hormone-related protein (PTHrP) and granulocyte colony-stimulating factor (G-CSF). A 64-year-old woman complained of general fatigue, loss of appetite, nausea, vomiting and constipation. The results of blood and biochemistry tests were white blood cell count of 21,060 /ml and calcium of 18.0 mg/dl, indicating an increase in the number of leukocytes and hypercalcemia. A computerized tomography scan showed a tumor in the lower abdomen with a maximum diameter of 16 cm and containing both cystic and solid parts. There was a remarkable elevation of the tumor marker CA 19-9, to 1611 IU/ml, and serum level of PTHrP was elevated to 25.9 pmol/ml. The PTH-intact level was 14 pg/ml, which was at the lower limit of the normal range. In addition, the G-CSF level was also elevated to 73 pg/ml (normal range: <38 pg/ml). Since hypercalcemia caused by tumor PTHrP production was suspected, and as this required elimination of the primary disease, extirpation of the tumor was carried out. Serum calcium levels promptly returned to 11.1 mg/ml on the first day following surgery, and PTHrP also dropped to its normal level on the same day. Histological and immunohistochemical examinations revealed that the tumor was clear cell adenocarcinoma which was partially positive for PTHrP and positive for G-CSF, indicating the tumor simultaneously producing PTHrP and G-CSF.

4-Methylumbelliferone inhibits hyaluronate synthesis in human uterine cervical fibroblasts.

AIM: Hyaluronate plays an important role in the regulation of cervical function during parturition. In our previous study we showed that 4-methylumbelliferone (MU) suppresses hyaluronate synthesis by cultured human skin fibroblasts. The present study investigated the effects of MU on fibroblasts obtained from the human uterine cervix and assessed the possibility of controlling cervical ripening with MU. METHODS: Human uterine cervical fibroblasts were collected from uterine cervices obtained from the uteri of three patients who had a total hysterectomy for uterine myoma at Hirosaki University Hospital. The fibroblasts were cultured in Dulbecco's modified Eagle's medium until confluence. They were then cultured in medium containing [3H]glucosamine (0.074 MBq/mL) with various MU doses. Hyaluronate synthesis was evaluated by assessing the incorporation of [3H]glucosamine into the soluble fraction of hyaluronate. Three independent studies were carried out on each specimen to clarify whether MU causes compositional changes or promotes hyaluronate degradation, whether the inhibitory effects of MU on hyaluronate synthesis are dose-dependent, and whether the effects of MU are reversible. RESULTS: MU added to the medium of the cultured cells reduced the synthesis of hyaluronate in a dose-dependent manner. After MU was removed from the medium, hyaluronate synthesis recommenced, and the amount of [3H]hyaluronate synthesized was similar to the control level. CONCLUSIONS: MU inhibits the synthesis of hyaluronate in human uterine cervical fibroblasts.

[Hormone replacement Up-to-date. Effect of estrogen therapy (EP) and estrogen-progestogen therapy (EPT) on the bone metabolism].

Estrogen depletion after menopause become involved with postmenopausal bone loss, therefore ET (estrogen therapy) and EPT (estrogen-progestogen therapy) have been considered as first-line therapy for postmenopausal osteopenia and osteoporosis. However, after WHI (Women's Health Initiative) reports, use of estrogen for treatment of osteopenia and osteoporosis is limited. Because estrogen plays indispensable roles in maintaining female physiological functions including bone metabolism, use of estrogens would elicit much benefits when administered properly.