Modal variety of microsatellite instability in human endometrial carcinomas.

PURPOSE: Microsatellite instability (MSI) in human endometrial cancer (EC) was analysed using a unique fluorescent technique. MSI is associated with various human neoplasms. However, the reported frequency of MSI differs widely in each malignancy. Methodological difficulties have in fact been pointed out in its assay techniques. METHODS: We previously established a sensitive fluorescent technique in which the major methodological problems are overcome. Application of this technique has revealed two distinct modes of microsatellite alterations, i.e. Type A and Type B. In the present study, we have applied this technique to 94 ECs. RESULTS: Significant microsatellite alterations were observed in 38 (40.4%) tumours of the panel. The two modes, Type A and Type B, were indeed observed in this malignancy. More importantly, we found that the modes more closely correlated with the molecular and clinicopathological backgrounds of the tumours than the established and widely used MSI grades, MSI-H and MSI-L. Type B MSI widely correlated with family history of hereditary non-polyposis colorectal cancer-associated cancers, whereas MSI-H only did with that of colorectal cancer. Furthermore, mutation in the KRAS oncogene, which has been regarded as generally infrequent in microsatellite-unstable tumours, was clearly associated with Type A MSI. CONCLUSIONS: Our observations may suggest a biological relevance and a potential utility of the modal classification of MSI and, furthermore, added complexities to genomic instability underlying tumourigenesis in human endometrium.

Secondary leukemia after chemotherapy and/or radiotherapy for gynecologic neoplasia.

OBJECTIVE: Secondary leukemia is a known complication of chemotherapy and radiotherapy. It was generally recognized that leukemia secondary to chemotherapy was due to the use of alkylating agents in the treatment of ovarian cancer. Recently, many types of chemotherapeutic agents have been used in the treatment of gynecologic malignancies in addition to ovarian cancer. We analyzed the clinical characteristics and outcome of patients with recent onset of secondary leukemia after the treatment of gynecologic cancer to consider the diagnosis and management of secondary leukemia. MATERIALS AND METHODS: We reviewed the clinical charts and follow-up data of patients with gynecologic malignancies treated in the past 20 years. During this period, 2482 newly diagnosed invasive gynecologic cancers were treated in our institution. All patients with secondary leukemia were analyzed for clinical background, latency period (interval between the diagnosis of primary carcinoma and the development of leukemia), treatment, and outcome. We also reviewed the literature for secondary leukemia under gynecology using the PubMed. RESULTS: Four patients were found to have developed secondary leukemia after the treatment of gynecologic malignancies during this period. The cumulative risk of secondary leukemia was approximately 0.38%. All patients received platinum-based chemotherapy. Two patients received combination chemotherapy and/or bone marrow transplantation, and 1 of these 2 patients lived more than 6 years but died of recurrent ovarian cancer. CONCLUSIONS: Long survival time might be expected in patients who show complete response to bone marrow transplantation and/or combination chemotherapy for secondary leukemia. In recent years, we have aggressively used various types of anticancer drugs for the treatment of not only ovarian cancer but also uterine cervical cancer and endometrial cancer. Physicians need to keep in mind the risk of secondary leukemia in the follow-up of long-term survivors after several courses of chemotherapy and radiotherapy.

The safety and efficacy of cisplatin plus gemcitabine in recurrent ovarian cancer.

BACKGROUND: The activity and synergy for the combination treatment of cisplatin and gemcitabine has been identified in a variety of human tumor cells, including ovarian cancer cells, and has been widely approved for the treatment of non-small cell lung cancer, pancreatic cancer and biliary tract cancer. As the gastrointestinal symptoms with cisplatin therapy are commonly considered to negatively affect the quality of life of patients more than those experienced with carboplatin therapy, carboplatin is generally preferred over cisplatin in combination therapy. This study evaluated the safety and efficacy of cisplatin plus gemcitabine in patients with recurrent ovarian cancer. METHODS: Patients with recurrent ovarian, peritoneal or fallopian tube cancer, who had failed with multiple other chemotherapy agents, including platinum, received cisplatin (30 mg/m(2)) plus gemcitabine (750 mg/m(2)) on days 1 and 8 of every 28 days for between 1 and 4 cycles. RESULTS: In total, 18 patients were treated with cisplatin and gemcitabine between 2006 and 2011. There were 1 complete and 5 partial responses, producing an overall response rate of 33.4 %. Median overall survival was 11.0 months. Grade 4 neutropenia and thrombocytopenia were seen in 11.1 and 22.2 % of patients, respectively. Non-hematological toxicity was less than Grade 1. CONCLUSIONS: Non-hematological toxicity with combined cisplatin and gemcitabine therapy was considered tolerable and did not impede patient quality of life. However, this drug combination should be monitored for hematologic toxicity.

Status of treatment for the overall population of patients with stage IVb endometrial cancer, and evaluation of the role of preoperative chemotherapy: a retrospective multi-institutional study of 426 patients in Japan.

OBJECTIVE: We previously reported on the role of cytoreduction in 248 patients with surgical stage IVb endometrial cancer (EMCA). This study aimed to evaluate the clinical characteristics, prognosis according to initial treatment, and impact of preoperative chemotherapy in the overall population of patients with clinical and surgical stage IVb EMCA. METHODS: A multi-institutional retrospective analysis was performed in 426 patients diagnosed with clinical and surgical stage IVb EMCA from 1996 to 2005. Factors associated with overall survival (OS) were identified using univariate and multivariate analyses. RESULTS: The median OS for all 426 patients was 14 months. Patients were divided into three groups according to their initial treatment: primary surgery group (n=279), primary chemotherapy group (n=125), and palliative care group (n=22). The median OS times for these groups were 21, 12, and 1 month, respectively (p<0.0001). Patients in the primary surgery group had better performance status (PS) and lower numbers of extra-abdominal metastases than those in the primary chemotherapy group. Multivariate analysis identified good PS, endometrioid histology, absence of clinical intra-abdominal stage IVb metastasis, hysterectomy, and chemotherapy as independent predictors of OS. In the primary chemotherapy group, 59 patients subsequently underwent surgery, and these patients had similar OS to those in the primary surgery group. CONCLUSIONS: Hysterectomy and chemotherapy may prolong OS in selected patients with stage IVb EMCA. Our data suggest that primary chemotherapy followed by surgery may be a useful treatment choice in patients not suitable for primary surgery.

Clinicopathological prognostic factors and the role of cytoreduction in surgical stage IVb endometrial cancer: a retrospective multi-institutional analysis of 248 patients in Japan.

OBJECTIVE: To evaluate clinicopathological prognostic factors and the impact of cytoreduction in patients with surgical stage IVb endometrial cancer (EMCA). METHODS: The records of 248 patients with stage IVb EMCA who underwent primary surgery including hysterectomy at multiple institutions from 1996 to 2005 were retrospectively analyzed. Data regarding disease distribution, surgical procedures, adjuvant therapy, and survival times were collected. Univariate and multivariate analyses were performed to identify factors associated with overall survival (OS). RESULTS: The median OS was 24 months. The most common histological types were endometrioid (grade 1: 15%, grade 2: 20%, grade 3: 24%) and serous (17%). The most common sites of intra-abdominal metastases were pelvis (65%), ovaries (58%), omentum (58%), retroperitoneal lymph nodes (52%), and upper abdominal peritoneum (44%). In 93 patients with extra-abdominal metastases, the most common site was the lung (n=49). Complete resection of extra-abdominal metastases was achieved in only 13 patients. Complete resection of intra-abdominal metastases was achieved in 101 patients, 52 had ≤1 cm residual disease, and 95 had >1cm residual disease; the median OS times in these groups were 48, 23, and 14 months, respectively (p<0.0001). Multivariate analysis showed that performance status, histology/grade, adjuvant treatment, and intra-abdominal residual disease were independent prognostic factors. Intra-abdominal residual disease was an independent prognostic factor in patients with and without extra-abdominal metastases. CONCLUSIONS: Cytoreductive surgery and adjuvant therapy may improve survival in stage IVb EMCA, particularly in patients with favorable prognostic factors, even in the presence of extra-abdominal metastases.

Dedifferentiated chondrosarcoma arising in a mature cystic teratoma of the ovary: a case report and review of the literature.

Malignant transformation of a mature cystic teratoma of the ovary is rare, occurring in approximately 2% of all cases. The most common malignancy arising in mature cystic teratoma is squamous cell carcinoma. Much less frequently, the malignant transformation is represented by sarcomas. Dedifferentiated chondrosarcoma usually develops in bone. There has been no case of a dedifferentiated chondrosarcoma arising in mature cystic teratoma of the ovary since the establishment of this diagnostic entity. This is a report of a definitive dedifferentiated chondrosarcoma arising in a mature cystic teratoma of the ovary, presenting clinicopathologic features.

Reassessment of the utility of frozen sections in endometrial cancer surgery using tumor diameter as an additional factor.

OBJECTIVE: The purpose of this study was to improve the reliability of frozen section with the use of tumor diameter (TD) as an additional factor and intraoperatively to identify a subgroup of early endometrial cancers that would not require lymphadenectomy. STUDY DESIGN: Data for 228 patients who underwent surgery with frozen section were analyzed retrospectively. Lymphadenectomy was performed in 86% of patients; the nodes were positive in 8%. RESULTS: The accuracy of frozen section for myometrial invasion, grade, and low-risk prediction significantly increased with decreasing TD (P = .036) and was 98%, 95%, and 95%, respectively, when the TD was ≤3 cm. Patients with a TD of ≤2 cm and patients with a TD of 2-3 cm who had low-risk predictors had no nodal metastasis; patients with a TD of 2-3 cm who had intermediate-high risk predictors and a TD of >3 cm with any level of risk predictors were at risk of nodal metastases. CONCLUSION: When the TD was ≤3 cm, the low-risk group that is defined by frozen section can be predicted accurately and safely to remain lymph-node metastasis free.