Inactivation of O6-methyguanine-DNA methyltransferase by promoter hypermethylation: association of epithelial ovarian carcinogenesis in specific histological types.

AIM: The aim of this study was to evaluate O6-methyguanine-DNA methyltransferase (MGMT) promoter hypermethylation, MGMT expression and microsatellite instability (MSI), as well as to elucidate their correlation with clinical and pathological parameters in epithelial ovarian cancer. METHODS: Ovarian cancer tissue specimens (n = 86) were obtained after a staging operation. The MGMT gene was investigated by methylation-specific polymerase chain reaction (MSP) and MGMT expression status was analyzed using immunohistochemistry. MSI status was examined by the fluorescence-based PCR using five National Cancer Institute markers. RESULTS: Negative MGMT expression was detected in 12 of 86 (14.0%) epithelial ovarian cancers. In 34 cases where MSP results were available, MGMT promoter hypermethylation was detected in five cases (14.7%) with mucinous or clear cell carcinomas, but not in any of other histological types (P = 0.031). Five out of six cases with negative MGMT expression showed MGMT promoter hypermethylation, whereas all of the 28 cases that retained expression of MGMT were unmethylated at the MGMT CpG island (P < 0.001). In 41 cases of MSI results available, seven (17.1%) cases showed MSI-H-phenotyped. Both MGMT promoter hypermethylation and negative MGMT expression were noted only in cases of mucinous or clear cell carcinoma in which MSI status were mostly MSS-phenotyped; however, no significant correlation was found between MSI status and clinicopathological parameters. CONCLUSIONS: Negative MGMT expression was significantly correlated with MGMT promoter hypermethylation in MSS-phenotyped tumors of mucinous or clear cell carcinoma. The results suggest that MGMT promoter hypermethylation might be associated with epithelial ovarian carcinogenesis in specific histological types.

Hepatic resection as part of secondary cytoreductive surgery for recurrent ovarian cancer involving the liver.

PURPOSE: The aims of this study were to assess the surgical outcomes and to also determine the prognostic factors in patients with surgically resectable liver metastases for recurrent ovarian cancer. METHODS: Between 1991 and 2008, 18 patients with recurrent ovarian cancer who underwent hepatic resection as part of secondary cytoreductive surgery were identified from the tumor registry pathology database. Parameters for safety, efficacy, and survival data were considered as primary endpoints. RESULTS: Hepatic resections included wedge resection (n = 4), unisegmentectomy (n = 13), and bisegmentectomy (n = 1). There were no surgery-related deaths. Only one patient (5.6%) had postoperative major complications. The median postoperative hospitalization was 15.5 days (range 11-46 days). The prognostic factors associated with improved survival were less abdominal than pelvic disease (38 vs. 11 months, P = 0.032), optimal cytoreduction (40 vs. 9 months, P = 0.0004), and negative margin status of the hepatic resection (40 vs. 9 months, P = 0.0196). The overall median survival after hepatic resection was 38 months (range 3-78 months). CONCLUSION: Hepatic resection for recurrent ovarian cancer is safe and is associated with a favorable outcome. Parenchymal liver metastases should not exclude attempts at optimal secondary cytoreductive surgery, and especially, patients with solitary liver metastases should be considered for hepatic resection.

Efficacy of taxane and platinum-based chemotherapy guided by extreme drug resistance assay in patients with epithelial ovarian cancer.

OBJECTIVE: To evaluate the efficacy of taxane and platinum-based chemotherapy guided by extreme drug resistance assay (EDRA) in patients with epithelial ovarian cancer. METHODS: Thirty-nine patients were enrolled, who were diagnosed as epithelial ovarian cancer, tubal cancer or primary peritoneal carcinoma and received both debulking surgery and EDRA in Asan Medical Center between August 2004 and August 2006. Another thirty-nine patients were enrolled, who did not receive EDRA as control. Paclitaxel 175 mg/m(2) and carboplatin AUC 5 were administered as primary combination chemotherapy to both EDRA group and the control group. In the EDRA group, paclitaxel was replaced by docetaxel 75 mg/m(2) if a patient showed extreme drug resistance (EDR) to paclitaxel and not to docetaxel. Carboplatin was replaced by cisplatin 75 mg/m(2) if a patient showed EDR to carboplatin and not to cisplatin. If only one drug showed low drug resistance (LDR), it was allowed to add another drug which showed LDR such as gemcitabine 1,000 mg/m(2). CT scan was performed every three cycles and CA-125 was checked at each cycle. RESULTS: There was no significant difference in overall response rate between EDRA group and the control group (84.5% vs. 71.8%, p=0.107). However, 93.8% of patients in EDRA group did not show EDR to at least one drug and its response rate was significantly higher than that of the control group (93.3% vs. 71.8%, p=0.023). CONCLUSION: we could choose a combination of taxane and platinum which did not show EDR and could obtain a good response in the patients with ovarian cancer.

Prenatally diagnosed ectrodactyly at 16 weeks' gestation by 2- and 3-dimensional ultrasonography: a case report.

OBJECTIVE: Ectrodactyly is a rare malformation with various presentations. The current report describes a case of ectrodactyly detected using 2-dimensional (2D) and 3-dimensional (3D) ultrasonography at 16 weeks' gestation. METHODS AND RESULTS: The 2D ultrasonographic findings were ectrodactyly in the right hand and monodactyly in the left hand, and these results were confirmed and further clarified using 3D imaging. The postmortem X-ray findings were consistent with the ultrasonography. CONCLUSION: We conclude that 3D ultrasonography can assist in clarifying 2D ultrasonography findings of hand malformations during the second trimester of pregnancy.

Comparative study of laparoscopico-vaginal radical hysterectomy and abdominal radical hysterectomy in patients with early cervical cancer.

OBJECTIVE: The objective of this study was to compare the outcomes of patients treated by laparoscopico-vaginal (modified) radical hysterectomy (LVMRH) to those of patients treated by abdominal radical hysterectomy (RH). METHODS: From 1997 to 2002, we performed 37 cases of LVMRH + pelvic lymph node dissection (PLND) and 47 cases of laparoscopico-vaginal radical hysterectomy (LVRH) with paraaortic lymph node sampling + PLND. Inclusion criteria for the laparoscopic surgery were patients with FIGO stage IA1 to IB1, for exocervical mass of grossly less than 2 cm. As a control, we selected 46 cases for MRH group and 96 cases for RH group. RESULTS: Operating time, the number of lymph nodes obtained and the rate of complications were similar in both groups. The hospital stay was significantly shorter in laparoscopic group. Four (8.5%) of 47 LVRH patients and 2 (2.1%) of 96 RH patients had recurrences. Recurrence-free survival in RH group was significantly higher than LVRH group (P = 0.0194). In LVRH group, patients with large tumor volume (>or=4.2 cm(3)) had significantly higher recurrence rate of 42.9% (3/7) than those with small volume (1/40) (P = 0.0021). The 3-year progression-free survivals were 97.1% in LVRH group (<4.2 cm(3)) and 98.9% in RH group. CONCLUSION: Laparoscopic surgery for the treatment of early cervical cancer is a safe and effective alternative to conventional RH. Considering the higher recurrence rate in patients with large tumor volume, it would be better if laparoscopic surgery is limited to patients with small volume disease (tumor diameter <2 cm or volume <4.2 cm(3)).