Prognostic factors and status of hormone receptors and angiogenic factors in uterine carcinosarcoma.

AIM: To determine novel prognostic factors and treatment modalities for uterine carcinosarcoma (UCS). METHODS: We performed immunohistochemical staining of estrogen receptor (ER)-α, ER-ß, progesterone receptor, gonadotropin-releasing hormone receptor, vascular endothelial growth factor (VEGF), platelet-derived endothelial cell growth factor (PD-ECGF) and platelet-derived growth factor receptor (PDGFR)-ß in a clinicopathological study of 15 UCS patients. RESULTS: No significant differences were found between the sarcomatous and carcinomatous components with respect to expression of ER-α, ER-ß and progesterone receptor. However, VEGF was significantly more frequently expressed in the carcinomatous component, while PD-ECGF and PDGFR-ß were significantly more frequently expressed in the sarcomatous component. Only one patient showed gonadotropin-releasing hormone receptor expression in the sarcomatous component. Moreover, ER-ß expression in resected specimens, increased serum levels of carbohydrate antigen (CA)-125 and C-reactive protein (CRP), and thrombocytosis were determined as significant UCS prognostic factors. CONCLUSION: Combination of anti-VEGF therapy and anti-PD-ECGF or anti-PDGFR-ß therapy would be expected in advanced or recurrent UCS. Furthermore, careful monitoring for early detection of recurrence should be performed when UCS patients showed preoperative increase in serum CA-125 levels, CRP and platelet counts, and ER-ß expression in biopsied or surgically resected specimens.

Adenocarcinoma of the lower female genital tract in patients with Herlyn-Werner-Wunderlich syndrome.

We report 2 patients with Herlyn-Werner-Wunderlich syndrome, 1 with advanced endometrioid adenocarcinoma of the semiobstructed side of the uterine cervix and 1 with primary clear cell carcinoma of the obstructed side of the upper vagina.

Cutaneous metastasis from primary adenocarcinoma of the vagina: a case report.

Cutaneous metastasis in vaginal cancer is an extremely rare event and no cases of cutaneous metastasis from primary vaginal adenocarcinoma have been found. We report the clinicopathologic features, including cytopathologic findings, of the first case of cutaneous metastasis to the anterior chest wall from a sporadic-type advanced primary vaginal adenocarcinoma. Our present case suggested that cytopathologic examination should be performed as soon as possible when a patient exhibits multiple subcutaneous nodules or a painful cutaneous ulcer during treatment of advanced gynecologic cancer.

Primary adenomyoma of the fallopian tube mimicking tubal malignant tumor.

We report a rare case of adenomyoma localized only in the left fallopian tube mimicking tubal malignant tumor. A 45-year-old woman presented with mild pelvic pain, dysmenorrhea and left adnexal mass. Magnetic resonance imaging showed a solid tumor, suspected primary cancer of the fallopian tube, and serum carbohydrate antigen 125 was elevated to 72 U/mL (normal; 0-35). At surgery, the tumor was revealed as a left fallopian tube tumor without torsion. Postoperative histopathology showed that the tumor included bundle-like growing non-atypical leiomyoma cells and ectopic normal endometrium accompanied with endometrial stroma and we diagnosed primary adenomyoma of the left fallopian tube. Adenomyoma localized only in the fallopian tube is a rare entity and it can occur only in the fallopian tube.

Evaluation of parametrial spread in endometrial carcinoma.

OBJECTIVE: To evaluate the detailed clinicopathologic characteristics of parametrial spread in uterine endometrial cancer. METHODS: We retrospectively identified 334 individuals with uterine endometrial cancer who had undergone radical hysterectomy between 1988 and 2007. Parametrial spread was determined by histopathological analysis of surgically resected specimens. RESULTS: Twenty-eight (8.4%) individuals had histopathologically confirmed parametrial spread, and lymphatic or blood vessel invasion (22 cases) was the most frequently observed type of parametrial spread; direct invasion to parametrial connective tissue (five cases) or cardinal lymph node metastasis (four cases) were less frequently observed. Parametrial spread occurred not only in individuals with cervical involvement but also in individuals with more than half myometrial invasion, retroperitoneal (pelvic, paraaortic, or both), lymph node metastasis, ovarian metastasis, positive peritoneal cytology results, and lymphovascular space invasion. Twenty-six individuals (92.9%) with parametrial spread showed more than one of these histopathological factors (median number of factors 3, range 1-6); the other two individuals had lymphovascular space invasion alone. In 10 individuals with parametrial spread (35.7%), the condition recurred during the median follow-up period of 49 months, and initial recurrence was observed in the lung in six individuals (60.0%). Although the long-term prognosis for those with parametrial spread was significantly poorer than that of those without parametrial spread, both among all individuals (P<.001) and among individuals with International Federation of Gynecology and Obstetrics stage III (P<.05), multivariate analysis showed that parametrial spread was not an independent prognostic factor for uterine endometrial cancer. CONCLUSION: Parametrial spread cannot be predicted by cervical involvement alone but may be predicted by various lymphovascular space invasion-related histopathologic factors. Further, parametrial spread may not be an independent prognostic factor in individuals with uterine endometrial cancer. LEVEL OF EVIDENCE: III.

Feasibility study of oral cyclophosphamide salvage therapy for the treatment of heavily pretreated patients with recurrent epithelial ovarian cancer.

BACKGROUND: In patients with relapsed ovarian cancer, the objectives of salvage therapy are considered to be maintenance of quality of life and prolongation of patient survival. Chemotherapy using oral agents could be a good choice for salvage therapy. We reassessed the usefulness of oral cyclophosphamide (CPA) salvage therapy for heavily pretreated patients with recurrent epithelial ovarian cancer. METHODS: We evaluated the effects and toxicities of 100 mg oral dose (50 mg twice a day) of CPA for 14 patients who had undergone an average of 3 chemotherapy treatments before enrolling in our study. RESULTS: One patient showed partial response and 8 developed stable diseases. Median time to progression was 3 months (range 1-13 months) and median survival was 7 months (range 2-28 months). Common Terminology Criteria for Adverse Events (CTCAE) grade 3/4 adverse effects were leukopenia (7.1%), neutropenia (14.3%), thrombocytopenia (7.1%), and nausea/vomiting (21.4%). CONCLUSION: Although moderate gastrointestinal toxicity was observed, oral CPA therapy contributed to improving the survival of heavily pretreated patients with recurrent epithelial ovarian cancer. A well-designed phase II trial in this regard is awaited.

Feasibility study of docetaxel and nedaplatin for recurrent squamous cell carcinoma of the uterine cervix.

BACKGROUND: To determine a new taxane plus platinum treatment regimen for squamous cell carcinoma of the uterine cervix (CSCC), a phase I feasibility study of docetaxel (DTX) plus nedaplatin (CDGP) combination therapy was conducted. PATIENTS AND METHODS: Twenty consecutive patients were enrolled into the study. The starting dose of DTX/CDGP was 60 mg/m2 / 80 mg/m2, every 4 weeks for at least three courses and the dose was escalated to 70 mg/m2 / 100 mg/m2. DTX 60 mg/m2 / CDGP 100 mg/m2 was also evaluated as an extra dose level. RESULTS: Dose-limiting toxicity was granulocytopenia and the maximum tolerated dose was determined as 70 mg/m2 / 100 mg/m2. All 20 patients had measurable disease and a partial response was achieved in 8 (40.0%) patients. CONCLUSION: DTX/CDGP therapy appears to be a tolerable regimen for cervical squamous cell carcinoma, even in patients previously treated by cisplatin concurrent chemoradiotherapy. The recommended doses of DTX and CDGP were determined to be 60 mg/m2 and 100 mg/m2, respectively.

Phase II study of single-agent gemcitabine in heavily pretreated Japanese patients with recurrent ovarian cancer.

BACKGROUND: Gemcitabine has been recommended as an active agent for salvage chemotherapy in patients with recurrent epithelial ovarian cancer, but no clinical study of this agent has been conducted for Japanese women with ovarian cancer. To evaluate the efficacy and feasibility of gemcitabine for heavily pretreated Japanese patients with recurrent epithelial ovarian cancer, we conducted a single-institute phase II clinical trial. METHODS: All patients had received a minimum of two previous chemotherapy regimens, In this study, gemcitabine was administered at 1000 mg/m(2) on days 1, 8, and 15 of a 28-day cycle. RESULTS: A total of 28 patients participated in this study. Although 5 patients (17.9%) needed dose reduction to 800 mg/m(2) because of thrombocytopenia and granulocytopenia, all patients completed an average of 6.7 courses (range, 2-24 courses). The overall response rate, including five partial responses, was 17.9% (95% confidence interval [C I], 6.0-36.9). The median time to progression was 8.8 months and the median survival period was 11.2 months. Grade 3/4 hematological toxicities included leucopenia, 35.7%; granulocytopenia, 39.3%; anemia, 46.4%; and thrombocytopenia, 10.7%. However, no grade 3/4 nonhematological toxicity was observed. The mean delay in treatment was 5.0 +/- 7.7 days (range, 0-15 days) in a total of 562 cycles. CONCLUSION: Single-agent gemcitabine is an effective salvage chemotherapy regimen in heavily pretreated Japanese patients with recurrent epithelial ovarian cancer.

A change in promoter methylation of hMLH1 is a cause of acquired resistance to platinum-based chemotherapy in epithelial ovarian cancer.

BACKGROUND: Acquired resistance to platinum-based chemotherapy (Pt-chemo) is a major problem for improving the prognosis for patients with advanced epithelial ovarian cancer (EOC). However, the molecular mechanism of acquired resistance to Pt-chemo is not well understood. MATERIALS AND METHODS: hMLH1 promoter methylation (hMLH1 MET) and hMLH1 protein expression was examined in 36 paired samples of primary and secondary resected tumors by methylation-specific polymerase chain reaction (PCR). RESULTS: No primary tumors exhibited hMLH1 MET, while 56.3% of secondary tumors showed hMLH1 MET. Moreover, no significant correlation was observed between hMLH1 MET and histological subtype, while hMLH1 MET was significantly greater (p < 0.001) in partially responsive secondary tumors compared with no change or progressive disease, and hMLH1 MET also occurred more frequently (p = 0.059) in tumors treated with four or more courses of Pt-chemo. CONCLUSION: A change in hMLH1 MET is a major molecular cause of acquired resistance to Pt-chemo in EOC.