Takao Shinozuka

Malignant transformation of atypical endometrial hyperplasia after progesterone therapy showing germ-cell tumor-like differentiation

A 31‐year‐old woman was treated for atypical endometrial hyperplasia (AEH) with high‐dose medroxyprogesterone acetate (MPA) therapy to preserve fertility. The AEH was found by repeated cytologic and histologic examinations to have completely disappeared with the therapy, but 3 years after her last follow up she required emergency surgery to treat severe genital bleeding. The hysterectomied uterus consisted mostly of poorly differentiated adenocarcinoma, G3 endometrioid type. Minor AEH was present in the exophytic area, in which some glands were cystically dilated. Part of the AEH had transformed into other histologic features with germ‐cell‐like differentiation, demonstrated by immunohistochemical positive reaction of placental alkaline phosphatase, alpha‐fetoprotein, and human chorionic gonadotrophin. Recurrent AEH had undergone malignant transformation, resulting in the development of well‐ and poorly differentiated adenocarcinoma and tumor exhibiting germ‐cell‐like differentiation. The patient died of a massive tumor extension 7 months after surgery. The AEH before MPA therapy and the recurrent tumors had genetically different characteristics based on evidence of a loss of heterozygosity, detected at D8S1132 (chromosomal locus, 8q22.1) in the latter but not in the former, by analysis of genetic alterations using microsatellite markers.

Cytologic Study of Ascites and the Endometrium in Ovarian Carcinoma

OBJECTIVE To ascertain the usefulness of endometrial cytology with ovarian cancers when examining extension of the disease and to analyze significant factors associated with migration of ovarian cancer cells into the uterine cavity. STUDY DESIGN Cytologic results on ascites and the endometrium were analyzed in 87 patients with primary ovarian cancer in the absence of metastasis to the endometrium or cervicovagina. RESULTS Positive results for cytology were found in 62/87 of ascites cases (71.3%) and in 20/87 endometrium cases (23.0%). The 15 cases (15/62 or 24.2%) positive for ascitic and endometrial cytology, divided clinically into stage III (6 cases) and stage IV (9 cases), were classified histologically as serous, 7 cases; mucinous, 2 cases; clear cell, 4 cases; endometrioid, 1 case; and unclassified, 1 case. Half the clear cell carcinomas (4/8 or 50.0%) were positive in the ascites and endometrium. The ascitic volume at surgery exceeded 500 mL in 9/15 cases (60.0%). CONCLUSION Papillae with basement membrane material in the cores may be structurally associated with migration of ovarian cancer cells into the uterine cavity, especially in clear cell carcinomas. Cytologic positivity of the endometrium and ascites significantly correlated with ascitic volume.

Subcellular organelle analysis applying confocal laser scanning microscopy to the steroid‐producing epithelial ovarian tumor: A technical note

An epithelial ovarian tumor with steroid production was examined in a 70‐year‐old postmenopausal female. The stromal cells of this tumor were rather dense and occasionally characterized by tuteinization or hyperthecosis, which has been associated with steroidogenesis. Subcellular visualization using confocal laser scanning microscopy (CLSM) successfully led to the identification of 3β‐hydroxysteroid dehydrogenase (HSD) in both mitochondria‐like small particles and endoplasmic reticulum‐like linear profiles, and P450‐aromatase also in endoplasmic reticulum‐like linear profiles, on the three‐dimensional images.

Treatment Strategy for Recurrent and Refractory Epithelial Ovarian Cancer: Efficacy of High-Dose Chemotherapy with Hematopoietic Stem Cell Transplantation

According to population statistics in Japan, approximately 3,800 women die of ovarian cancer annually, and approximately 6,000 are affected by this disease. Ovarian cancer is referred to as a “silent tumor”, since patients have few subjective symptoms and by the time symptoms are observed, the cancer has progressed to Stage III or IV in about half of the patients. The basic treatment for advanced epithelial ovarian cancer is to remove as much of the tumor as possible, and subsequently to perform anticancer therapy using drugs such as cisplatin, carboplatin and paclitaxel, all of which have been shown to be effective for epithelial ovarian cancer. However, the 5-year survival rate in advanced ovarian cancer patients is still only about 20%, and a treatment that leads to long-term survival has yet to be developed. Here, we review the available treatments for ovarian cancer, and present the results of high-dose chemotherapy (HDC) performed in our hospital for recurrent and refractory ovarian cancer.

Long-term results and prognostic analysis in advanced and recurrent/refractory epithelial ovarian cancer treated by high-dose cyclophosphamide, adriamycin, and cisplatin with autologous bone marrow transplantation

AbstractBackground. The efficacy of high-dose chemotherapy (HDC) with autologous bone marrow transplantation (ABMT) was evaluated in patients with advanced or recurrent/refractory (r/r) epithelial ovarian cancer in terms of long-term results and prognostic analysis. Methods. Between 1984 and 1991, 47 patients were prescribed two courses of HDC, consisting of cyclophosphamide (1600–2400 mg/m2), adriamycin (80–100 mg/m2), and cisplatin (100–150 mg/m2) after maximal cytoreductive surgery. Prior to HDC, platinum-based chemotherapy was administered for optimal cytoreduction. Results. The 5- and 8-year overall survival (OS) rates (%) of the 47 patients were 44.7% and 40.4%, and the 5- and 8-year disease-free survival (DFS) rates (%) were 29.8% and 27.7%, respectively. The 5- and 8-year OS rates (%) by stage were: stage III, 60.0% and 52.0%; stage IV, 33.3% and 33.3%; and r/r, 20.0% and 20.0%. The 5- and 8-year DFS rates (%) by stage were: stage III, 40.0% and 36.0%; stage IV, 25.0% and 25.0%; and r/r, 10.0% and 10.0%, respectively. Significantly better long-term survival (P < 0.01) was obtained in the group with no residual disease or residual disease <0.5 cm than in the groups with residual disease of 0.5–2 cm and >2 cm. In the 32 stage III/IV patients, the group given two courses of 150 mg/m2 cisplatin (n = 18) showed significantly better long-term survival (P < 0.05) than another group given two courses of 100 or 120 mg/m2 cisplatin (n = 14). Conclusions. Administration of two courses of HDC con-taining 2400 mg/m2 cyclophosphamide, 100 mg/m2 adriamycin, and 150 mg/m2 cisplatin per course followed by ABMT appears to be a promising procedure for achieving long-term survival in patients with chemosensitive advanced or r/r epithelial ovarian cancers with no or minimal residual disease.