Clinicopathologic characteristics of granulosa cell tumors of the ovary: a multicenter retrospective study / 부인종양

OBJECTIVE: To evaluate the clinicopathologic characteristics and prognostic factors of ovarian granulosa cell tumors. METHODS: Medical records of 113 patients presenting between January 1995 and December 2007 were retrospectively reviewed. RESULTS: One-hundred two patients had adult type disease, with a mean age of 46.2 years (range, 18 to 83 years) and a mean follow-up period of 54.7 months (range, 1 to 155 months). The distribution of FIGO stages was 86 patients at stage I, 11 at stage II, and 5 at stage III. During follow-up, ten patients recurred at a mean time of 48 months (range, 4 to 109 months). Among them, three patients died after a mean of 57 months (range, 25 to 103 months). In recurrence analysis, advanced stage (p=0.032) and presence of residual disease (p=0.012) were statistically significant, and age<40 years, premenopause and positive washing cytology were marginally significant (p<0.1). In multivariate analysis, stage was the only factor associated with recurrence; adjuvant chemotherapy and fertility-sparing surgery were not statistically significant. Among 36 patients with fertility-sparing operations, eight patients had nine pregnancies and delivered seven babies. Eleven patients had juvenile type tumors; the mean age was 20.0 years (range, 8 to 45 years) and the mean follow-up period was 69.8 months (range, 20 to 156 months). The distribution of FIGO stage was nine patients at stage I and two at stage III. There were no recurrences or deaths reported. Four patients had seven pregnancies and delivered six babies. CONCLUSION: Stage is the only factor associated with disease-free survival, and fertility-sparing surgery may be a treatment option for women with early-stage disease who want to retain fertility.

Erratum

No abstract available.

Vaccination with a Human Papillomavirus (HPV)-16/18 AS04-Adjuvanted Cervical Cancer Vaccine in Korean Girls Aged 10-14 Years

The human papillomavirus (HPV)-16/18 AS04-adjuvanted cervical cancer vaccine has been demonstrated to be highly efficacious and immunogenic with a favorable safety profile. This study assessed the immunogenicity and safety of the HPV-16/18 AS04-adjuvanted vaccine in healthy Korean girls aged 10-14 yr. This multi-center, observer-blind trial randomly assigned 321 healthy girls to receive three doses (0, 1, 6-month schedule) of HPV-16/18 AS04-adjuvanted vaccine or hepatitis A vaccine. Immunogenicity against vaccine antigens was assessed one month post-Dose 3. Solicited and unsolicited adverse events (AEs) and serious AEs (SAEs) were recorded. In the according-to-protocol analysis, all initially seronegative subjects vaccinated with the HPV-16/18 AS04-adjuvanted vaccine had seroconverted at Month 7, with a peak geometric mean titer (GMT) that was 600-fold higher than the natural infection titer of 29.8 EU/mL for HPV-16 and a peak GMT that was 400-fold higher than the natural infection titer of 22.6 EU/mL for HPV-18. The vaccine was well tolerated with no increase in reactogenicity with subsequent doses and no reports of vaccine-related SAEs. In conclusion, the HPV-16/18 AS04-adjuvanted vaccine is shown to be highly immunogenic and generally well-tolerated in Korean girls aged 10-14 yr.

Validation of a nomogram for predicting outcome of vulvar cancer patients, primarily treated by surgery, in Korean population: multicenter retrospective study through Korean Gynecologic Oncology Group (KGOG-1010) / 부인종양

OBJECTIVE: Regarding vulvar cancer, a nomogram has been suggested for the prediction of relapse-free survival (RFS). While the nomogram has been developed and validated in a Western study, there was no validation in Korean population. Thus, we have undertaken the study to assess the applicability of nomogram for predicting RFS in Korean patients with vulvar cancer. METHODS: A total of 204 cases newly diagnosed as vulvar cancer between 1982 and 2006 were identified. Among them 70 cases were not eligible due to inappropriate cell type (40 cases) and radiation as primary therapy (30 cases). Forty-four cases were not evaluable due to inadequate data and persistent disease. Finally a total of 90 patients primarily treated by surgery were included for analysis. Variables including age and the characteristics of primary tumor, nodal status, and surgical margin were collected for predicting RFS based on nomogram, which was compared with actual RFS. A calibration plot was drawn showing the actual versus predicted probability for 6 groups of patients segregated according to their predicted probabilities. In addition, discrimination of the nomogram was quantified with the concordance index. RESULTS: Patients' mean age was 58 years and mean follow-up period was 47.9 months. Observed 2y- and 5y-RFS rates were 81% and 68%, respectively, corresponding to 79% and 72% in the original cohort. The trend line in calibration plot showed comparable concordance with an ideal line, having a slope of 1.04 for 2y-RFS (R(2)=.35) and 0.98 for 5y-RFS (R2=.80), respectively. The concordance index was 0.79 in the KGOG data set, which was improved to 0.82 with the data set limited to squamous cell carcinoma. CONCLUSION: The nomogram provides the predictive capacity for relapse-free survival in Korean patients with vulvar cancer.

Expression of immunoreactive leptin and its receptor in epithelial ovarian cancer / 대한산부인과학회지

OBJECTIVE: Leptin, a secreted protein of the Ob gene by white adipose tissue, plays an important role in the regulation of food intake and energy consumption in the brain and acts as a potential growth stimulator in normal and neoplastic breast cancer cells. However, a potential role of leptin as an endocrine regulator is unknown in ovarian cancer. In the present study, we investigated the expression of leptin and its receptors in various histologic types of ovarian cancer and immortalized ovarian cancer cell lines to find out potential effect of leptin on the cell growth and activation of ovarian cancer cell line. METHODS: The ovarian cancer tissues, serous (n=18), mucinous (n=15), clear cell (n=12) and endometrioid type (n=14), were used for immuno-histochemical staining for leptin (Ob) and leptin-receptors (Ob -R). Ovrian cancer cell lines (non-mucinous: SNU-8, OVCAR-3, and SKOV-3) and mucinous: MUC) were used for RT-PCR, Western blot analysis, and [H3] thymidine incorporation assay for the cell growth and activation of mitogen-activated protein kinase. RESULTS: Both long (Ob-Rb) and short (Ob-Rt) isoforms of leptin receptors are expressed in non-mucinous type of ovarian cancer tissues (serous, clear cell carcinoma and endometrioid cell carcinoma) and in non-mucinous ovarian cancer cell lines (SNU-8, OVCAR-3 and SKOV-3 cells). However, leptin and its receptors are not found in mucinous cancer cells and mucinous cancer cell line (MUC). In immunohistochemical staining, the immunreactive leptin is expressed on the nuclei of the stratified cuboidal-to-columnar epithelial cells whereas its receptor was sparsely expressed on the innermost epithelial cell clusters and cytoplasm in non-mucinous tumor. However, there are no immunoreactive leptin and its receptor expressions in the mucinous tumor. In addition, treatment with leptin resulted in the growth stimulation of ovarian cancer cell line, an activation of ERK 1/2 and inhibition of constitutive phosphorylation of p38 Mitogen-activated protein kinase (MAPK). CONCLUSION: Taken together, our data demonstrates preliminary that the expression of leptin and its receptor is different according to the cell types of the ovarian cancer. Also it canbe thought that leptin immunolocalized on the nuclei in non-mucinous type but not in mucinous possibly acts as a nuclear transcription factor. Further studies are necessary to validate whether leptin may be a potential regulator for ovarian cancer.

Comparison between L and E gene amplification analytical methods for human papillomavirus typing / 부인종양

OBJECTIVE: L and E6/E7 gene amplification analyses were compared to identify human papillomavirus (HPV) infection and verify the HPV type, with the intent to minimize HPV typing errors. METHODS: L1 gene verified HPV typing was accomplished via polymerase chain reaction (PCR) and membrane assays. Verification of HPV typing via E6/E7 genes was accomplished through nested multiplexed PCR. The results from 104 samples were compared. RESULTS: The rates of accordance and difference were 35% and 65%, respectively. For 29% of the analyses, nested multiplexed PCR was more diversified than the membrane assay. CONCLUSION: HPV can be classified into low-risk HPV and high-risk HPV groups. In parallel amplifications of the L and E genes is more efficient for accurate diagnosis in light of the different symptoms and attendant precautions of the risk groups.

Comparison between L and E gene amplification analytical methods for human papillomavirus typing / 부인종양

OBJECTIVE: L and E6/E7 gene amplification analyses were compared to identify human papillomavirus (HPV) infection and verify the HPV type, with the intent to minimize HPV typing errors. METHODS: L1 gene verified HPV typing was accomplished via polymerase chain reaction (PCR) and membrane assays. Verification of HPV typing via E6/E7 genes was accomplished through nested multiplexed PCR. The results from 104 samples were compared. RESULTS: The rates of accordance and difference were 35% and 65%, respectively. For 29% of the analyses, nested multiplexed PCR was more diversified than the membrane assay. CONCLUSION: HPV can be classified into low-risk HPV and high-risk HPV groups. In parallel amplifications of the L and E genes is more efficient for accurate diagnosis in light of the different symptoms and attendant precautions of the risk groups.

Expression analysis of mRNA and proteins related to angiogenesis following management with cytotoxic agents in gynecologic cancer cell lines / 대한산부인과학회지

OBJECTIVE: Angiogenesis is central role to both the proliferation and metastasis of malignant tumor. The intense interest in angiogenesis has also lead to a re-examination of the activity of established cytotoxic agents which are known to be an antiangiogenic effect anecdotally. In this study, anti-angiogenic effect of cisplatin, paclitaxel and thalidomide was evaluated in human ovarian cancer cell lines and cervical cancer cell line. METHODS: Human ovarian cancer cell line A2780, cisplatin resistant human ovarian cancer cell line A2780-CDDP, human breast cancer cell line MCF-7, and squamous cell uterine cervical carcinoma cell line SiHa were used to evaluate the level of mRNA and protein expression of VEGF, bFGF and TSP-1, 2 before and after the treatment with cisplatin, paclitaxel, and thalidomide using RT-PCR, protein extraction, and Western blot. The results were analyzed with Wilcoxon signed rank test in the SAS ver 8.1. RESULTS: Targeted mRNAs were synthesized as 212 bp VEGF, 238 bp bFGF, and 492 bp band sized except mRNA of TSP-2 via RT-PCR. The protein of VEGF and bFGF were appeared as 21KDa and 17 KDa size, however, the protein of TSP-1 was not appeared through western blot. No effect of cisplatin on protein expression was measured in these cell lines, but paclitaxel influenced the expression of bFGF in MCF-7 cell line and the expression of TSP-1 in MCF-7 and SiHa cell lines. TSP-1 expression was influenced by thalidomide in A2780 cell line. The protein expression of VEGF and bFGF were not influenced following treatment with cisplatin, paclitaxel, and thalidomide. CONCLUSION: These results were suggested that bFGF and TSP-1 will be used as a target gene for the assay of antiangiogenic effect of paclitaxel in breast and uterine cervical cancer tissue and TSP-1 will be used as that of thalidomide in ovarian cancer. Furthermore, thalidomide will be tried as an adjunctive agent for the improvement of the survival in the case of the patient with ovarian cancer.

P21 and p53 expression in patients with epithelial ovarian carcinoma / 대한산부인과학회지

OBJECTIVE: Mutations in p53 are the most common genetic alterations in human malignancies. Expression of its protein product has been linked to decreased survival rate in ovarian carcinoma. P53 is well known as a pro-apoptotic tumor suppressor gene, but less is known about the importance of p21 expression in patients with epithelial ovarian malignancies. The purpose of this study was to investigate the different expression levels of p53 and p21 in various cell type of epithelial ovarian carcinomas and to determine their clinical significances. METHODS: Fifty eight patients (serous (n=18), mucinous (n=14), clear cell (n=12), endometrioid (n=14) carcinoma) with epithelial ovarian carcinoma were studied using paraffin-embedded tissue specimens. Immunohistochemical staining utilizing monoclonal antibody against p21 and p53 were performed. Amount of their proteins were quantified using western blotting. RESULTS: Mean age was 49.2 years old and advanced stage (III and IV) of cancer were 26 (44.8%). Recurrence rate and death rate were 20.7%, 22.4% respectively. With immunohistochemical staining for p21 and p53, p53 were significantly strongly stained in almost all epithelial ovarian carcinomas. However, p21 expressions were found in 10% of patients with serous carcinoma, 14% of patients with mucinous carcinoma, 38% of patients with endometrioid carcinoma, but 100% of patients with clear cell carcinoma. Among the patients whose tumors showed p21 staining, over expression were found in all clear cell typein western blot. But positive staining for p21 was below 10% in each slides of serous, mucinous and endometrioid type of ovarian carcinoma except clear cell type. This finding suggest that P21 expression was independent pathway in cell cycle regulation and apoptosis to the expression of p53 in serous, mucinous, and endometrioid type of ovarian carcinoma, but showed strongly positive correlation P21 and p53 expression in clear cell carcinoma. CONCLUSION: P21 may be used as a marker for confirmation of diagnosis of clear cell carcinoma due to its unique expressions of p21.

Expression and biologic significance of human estrogen receptor-alpha and -beta, progesterone receptor A and B, androgen receptor in benign, borderline, and malignant epithelial ovarian tumors / 대한산부인과학회지

OBJECTIVE: The object of this study was to provide a better understanding of the roles played by sex hormones in ovarian carcinogenesis. METHODS: 1) The expressions of estrogen receptor-alpha and -beta, progesterone receptor A and B, androgen receptor in normal ovarian tissue, benign, borderline, and malignant ovarian tumor were analyzed using immunohistochemical stains. 2) Expression of mRNA of sex hormone receptors of cell lines from postmenopausal normal surface epithelial cells, ovarian cancer, and breast cancer were studied using real time quantitative PCR methods. 3) Expression of PR isoforms after treatment with estradiol, expression of AR after treatment with testosterone were analyzed using RT-PCR and immunoblotting methods. 4) Apoptosis after treatment with levonorgestrel in cell lines from ovarian cancer were analyzed using flowcytometry. RESULTS: There was no significant difference in results shown by immunohistochemical staining between sex hormonal receptors of normal ovarian tissue (n=8), benign tumor (n=10), borderline tumor (n=8) and malignant tumor (n=24) according to malignant change. But, PRA was significantly reduced in epithelial ovarian cancer. 1) Expressions of ER-alpha and ER-beta, PRA, PRB and AR mRNA were seen in normal ovarian epithelial cells. 2) Deletion of exons of ER-alpha, ER-alpha wild type and variant, ER-beta variant were seen in many cell lines. 3) Down regulation of PR mRNA isoforms (especially PRA) in cell lines of ovarian cancer. 4) Flowcytometry showed that apoptotic cells markedly increased during exposure of progestins in ovarian cancer cell lines. CONCLUSION: These results suggest that down-regulation of ER-alpha and PRA is associated with the development of ovarian epithelial carcinoma. Progestins can activate the apoptotic pathway in the ovarian epithelium for protection of normal tissue from neoplastic transformation suggests that progestins deserve further evaluation as potential ovarian cancer preventive agents.

Risk of malignancy index in the preoperative evaluation of ovarian masses / 부인종양

OBJECTIVE: To assess the ability of risk of malignancy index (RMI) based on ultrasound findings, serum levels of CA 125, and menopausal status to discriminate between benign and malignant ovarian masses for preoperative screening. METHODS: A retrospective study was conducted of 255 women with ovarian masses admitted for operation at the Department of Obstetrics and Gynecology, Hanyang University Hospital between 1999 and 2003. The sensitivity and specificity of serum levels of CA 125, ultrasound findings, and menopausal status were calculated both separately and combined into a RMI to diagnose malignancy. RESULTS: There were significant preoperative differences of ultrasound findings, serum CA 125 level, serum CA 19-9 level, platelet count and menopausal status between benign and malignant ovarian masses (P<0.05). Using a cut-off value of 100 to indicate malignancy, the RMI gave a sensitivity of 81.7%, specificity of 81.9%. The RMI was more accurate in predicting malignancy than each one of its components measured individually. CONCLUSION: The RMI is able to correctly discriminate between malignant and benign ovarian masses. This preoperative evaluation of women with ovarian masses is anticipated to help plan their management.

Biological significance of progesterone receptor isoforms A and B in the normal ovary, and in benign, borderline, and malignant ovarian tumors / 대한산부인과학회지

OBJECTIVE: The differential expression patterns of the two progesterone receptor (PR) isoforms, PRA and PRB were examined using immunohistochemistry and real time quantitative RT-PCR in normal and neoplastic ovarian tissues, and in cell lines derived from epithelial ovarian cancer and breast cancer as a positive control in order to further elucidate the possible involvement of progesterone in the development of ovarian neoplasia. METHODS: Breast cancer cell line MCF-7 and ovarian cancer cell line SNU-8 were seeded to 24-well plate with 5 X 10(5) cell/well and incubated overnight. Those cell lines were treated with 17-beta-estradiol and incubated for another 24 hrs. RNA were purified for RT-PCR and whole cell prepared total proteins were subject to immunoblot with DAB-staining. DNA ladder pattern and flowcytometry were studied to evaluate progestins induced apoptosis in the ovarian epithelium. RESULTS: The median H-scores for PR isoforms in normal (n=8), benign (n=10), borderline (n=8) and malignant (n=24) ovarian tissues were as follows; PRA: 194.0, 171.0, 49.5, 0.0 (P<0.05), and PRB: 175.0, 180.5, 251.5, 168.5, respectively. In ovarian cancer cell line (SNU-8), PRB/PRAB mRNA ratio was not increased by 17-beta-estradiol, but that ratio was increased by 17-beta-estradiol in breast cancer cell line (MCF 7). Immunoblotting analysis demonstrated that PRB protein expression was markedly up- regulated in SNU-8, whereas the PRA and PRB isoforms both appeared to be increased in MCF-7. DNA ladder pattern was increased in dose and time related exposure of progestins and apoptotic cells were markedly increased during exposure progestins in ovarian cancer cell line were found by flowcytometry. CONCLUSION: These results suggest that down-regulation of PRA is associated with the development of ovarian epithelial carcinoma. Progestins can activate the apoptotic pathway in the ovarian epithelium for protection of normal tissues from neoplatic transformation suggests that progestins deserve further evaluation as potential ovarian cancer preventive agents.

A comparison of criteria of gestational diabetes using 100 gm oral glucose tolerance test in Korean women / 대한산부인과학회지

OBJECTIVE: The purpose of this study was to compare the National Diabetes Data Group (NDDG) with the American Diabetes Association (ADA) criteria proposed by Carpenter and Coustan for determining gestational diabetes using the 100 gm oral glucose tolerance test (GTT) in Korean women. METHODS: Seventeen-hundred pregnant women who underwent a 50 g oral GTT and delivered in the department of Ob/Gyn, Hanyang Univ Guri Hospital, between March, 1999 and February, 2004 were the subjects of this study. The women were categorized into A through D groups as follows: euglycemic control subjects (A), subjects with non gestational diabetes diagnosed by the NDDG and ADA criteria (B), subjects with gestational diabetes diagnosed by only the ADA criteria but not the NDDG criteria (C) and subjects with gestational diabetes diagnosed by only the NDDG criteria (D). The general characteristic and pregnancy outcomes were compared for each groups. The effectiveness of the ADA criteria was determinined by macrosomia and preeclampsia after controlling for confounding risk factors by logistic regression modeling. RESULTS: Of the 1700 pregnant women, 1420 women were classified in group A, 184 women were in group B, 28 women were in group C and 68 women were in group D. The group D showed more obese and less gestational weeks at delivery than the other groups. In pregnancy outcomes, groups B, C, and D showed more weighted average birth weight and higher frequency of macrosomia of the fetus than in group A. No differences existed among the 4 groups regarding intrauterine growth restriction, preeclampsia, and cesarean section. The risk factors of macrosomia were groups B, C, and D that shows glucose intolerance, obesity and more higher weight gain during pregnancy. Even after controlling for confounding risk factors by logistic regression modeling, groups B, C, and D were risk factors for macrosomia. Especially, the odds ratio for group C has shown a higher risk factor at 7.6 as compared to group D at 5.3. Glucose intolerance was not shown to be a risk factor of preeclampsia. CONCLUSION: Because glucose intolerance as shown in abnormal 50 g oral GTT is a risk factor for macrosomia and more weighted average birth weight of the fetus in Korean women, the diagnostic standards for Korean women are more suited to the ADA criteria compared to the NDDG criteria.

A case of pelvic splenosis after splenectomy: A cause of pelvic pain / 대한산부인과학회지

Splenosis represents the autotransplantation of splenic tissue, after splenic trauma or surgery. These splenic implants may be located anywhere in the abdominal cavity. These implants may misinterpreted as endometriosis or malignancy. We present a case of multiple pelvic splenic implants after a splenectomy.

The effectiveness of Lysophosphatic acid (LPA) as a biological marker in gynecologic cancer patients / 대한산부인과학회잡지

OBJECTIVE: LPAs are suggested as useful biological markers in early detection of ovarian carcinoma and other gynecological malignancies except breast and hematologic malignancy. We assessed the possible diagnostic role of serum LPA level in cervical, ovarian and the uterine corpus in Korean women. METHODS: The patients were enrolled in Hanyang University Hospital, Department of OB/GYN from Jan. 1999 to Jun. 2001. There were 19 ovarian carcinomas including 2 metastatic carcinomas, and 1 primary peritoneal carcinoma, 10 cervical carcinomas, 6 uterine carcinomas, 15 benign tumor as the study group and 5 healthy nulliparous women as the control group. Plasma was obtained following the centrifuge of whole blood, LPA was extracted from the plasma and the level was assessed by tandem mass spectrometry in multiple reaction mode. The quantity was measured by ratio of level of LPA and standard material, C14:0 LPA, in chromatogram compared with standard. The level of LPA were compared among control group, benign disease and gynecological malignancies, and also with conventional tumor markers. The statistical significance was analyzed by unpaired student-T test and McNemar test. RESULTS: The mean level of LPA and standard deviation were 7.1698 nmol/mL, 1.70 in malignancies, 4.5357 nmol/mL, 1.10 in benign disease and 5.2812 nmol/mL, 0.88 in healthy control. The level of LPA was significantly higher than in benign and control groups (p0.05). But, in cervical cancer, LPA level is more sensitive than CEA (p=0.039). CONCLUSION: The levels of LPA in cervical cancer, uterine cancer, ovarian carcinoma were significantly higher than in benign disease. Thus LPA is considered as an useful tumor marker in diagnosis and follow-up after treatment, especially in recurrent cervical carcinoma and uterine carcinoma which have no sensitive tumor markers. But further study with large number of casesfor a long period is required for clinical application in the future.

The Relationship of Maternal Physical Characteristic Change and Neonatal Weights: the Comparison between 1989 and 1999 / 대한산부인과학회잡지

OBJECTIVE: This study was organized to find out whether there are differences between pregravid weight, body mass index, weight gain during pregnancy and birth weight in 1989 and 1999. Also it was designed to find out the factors which influenced the birth weight changes. METHODS: A total of 725 (313 in 1989, 412 in 1999) pregnant women who had term delivery in the department of Obstetrics and Gynecology, Hanyang University Hospital were recruited for the study. Pregravid weight, body mass index, weight gain during pregnancy, body weight at the time of delivery and birth weight were examined through medical records retrospectively. RESULTS: Pregnant women in 1999 were older (29.7 +/- 3.7 yr vs 28.3 +/- 3.2 yr, p=0.0001), pregravid weight (54.0 +/- 7.5 kg vs 50.7 +/- 5.5 kg, p=0.0001), height (159.6 +/- 4.8 cm vs 158.5 +/- 4.7 cm, p=0.002), body mass index (21.2 +/- 2.8 kg/m2 vs 20.2 +/- 2.1 kg/m2, p=0.0001), weight gain during pregnancy (13.6 +/- 4.8 kg vs 12.8 +/- 4.6 kg, p=0.016) and birth weight (3103 +/- 652 gm vs 2993 +/- 843 gm, p=0.025) compared with those in 1989. The frequency of overweight (BMI>26) in pregravid was significantly higher in 1999 (9.4%) than in 1989 (1.9%) (p=0.0001). Weight gain during pregnancy were lower in over-weight pregravid than in normal or under-weight pregravid in both year, but birth weight was not different according to pregravid weight in both years. Compared to the weight gain during pregnancy less than 16 kg, women who gained weight more than 16 kg during pregnancy were significantly taller and weighed more at the time of delivery, and showed increased birth weight than those who gained weight during pregnancy less than 16 kg in both years. Weight gain during pregnancy was higher in over-weight pregravid than normal or under-weight pregravid in 1999 (p=0.012). The gain of body weight at the time of delivery in 1999 compared to those in 1989 is the most important factor for the birth weight change between two years. The increased pregravid weight, greater weight gain during pregnancy, and increased BMI also had an impact on the increasing birth weight in 1999. CONCLUSION: It is considered that physical characteristics of pregnant women in 1999 have been changed compared to those in 1989, and this change might be responsible for a birth weight increase.

A Significance of Thrombocytosis as a Prognostic Factor in Patient with Epithelial Ovarian Cancer / 대한산부인과학회잡지

OBJECTIVE: We tried to determine the relevance of thrombocytosis as a possible prognostic factor in patient with epithelial ovarian cancer. METHODS: One hundred and eighty-three (183) patients with epithelial ovarian cancer had been surgically treated in our hospital between January 1984 and December 2001. Uni- and multivariate analyses were performed of 9 clinical variables including age, FIGO stage, histologic subtype, grade, volume of residual tumor, presence of ascites, pretreatment levels of hemoglobin, platelet, and tumor marker (CA 125). The Kaplan-Meier method and log-rank test were used for univariate analysis and a multiple regression analysis based on the Cox proportional hazards model was done to find the independent prognostic variables. RESULTS: Prevalence of thrombocytosis was 20.8% and significantly correlated with FIGO stage (p=0.015), tumor grade (p=0.029), presence of ascites (p=0.001) and volume of residual tumor (p=0.032). Significant difference in survival between patients with or without thrombocytosis was found (p=0.006). Multivariate analysis model was used and only volume of residual tumor (p=0.004) was significant independent prognostic variable. Thrombocytosis (p=0.041) was significant independent prognostic variable in patients with early FIGO stage of disease. CONCLUSION: Thrombocytosis is a useful prognostic factor in epithelial ovarian cancer and significantly independent prognostic factor in patients with early FIGO stage of disease.

Expression of Genes Related to Multidrug Resistance and Apoptosis in Human Ovarian Cancer Cell Lines, Sensitive and Resistant to Cisplatin / 대한산부인과학회잡지

OBJECTIVE: The resistance mechanisms of tumor cells to chemotherapeutic drugs are known as the followings; the alterations in the drug transport and activation, the enhanced expression of the DNA repair and replication and the decreased apoptosis. The aim of this study is to examine a relative difference on the level of the mRNA expression of the multidrug resistance (MDR)-related and the apoptosis-associated genes between cisplastin-sensitive and cisplatin-resistant human ovarian cancer cell line. METHODS: MDR-associated genes (lrp, mdr1/p-glycoprotein, mrp) and PKC isozymes (alpha, beta1, beta2, epsilon, eta, theta), DNA mismatch repair (MMR) genes (hMLH1, hMSH2, hMSH3, hMSH6), DNA topology-related genes (topoisomerase IIalpha and beta) and apoptosis-related genes (p53, p21, mdm2, fas (Apo-1), trail (Apo-2L) were analyzed in cisplatin-sensitive ovarian cancer cell line A2780 and -resistant cell line A2780cp by complementary DNA polymerase chain reaction. RESULTS: The mdr1 and PKC eta in mRNA level were expressed in A2780cp, but not in A2780. The mRNA expressions of lrp, p21 and mdm2 were more increased in A2780cp than drug sensitive variant A2780, but not significantly correlated. In contrast mRNA expression of hMLH1, a kind of DNA MMR gene, was remarkably decreased and mRNA expression of hMSH2 was slightly decrease in A2780cp. However, the levels of mrp, topo II alpha and beta, hMSH3, hMSH6, p53, fas and trail were not affected. CONCLUSION: These results showed that mdr1/p-gp expression may be an important determinant of MDR phenotype in resistant cell line to chemotherapeutic agents, and PKC isozymes and DNA MMR genes may be responsible for cisplatin resistant in ovarian cancer.

A Clinical Significance of Second-look Laparotomy in Patients with Epithelial Ovarian Cancer / 대한산부인과학회잡지

OBJECTIVE: To evaluate pathological complete remission rate (pCR), survival rate, recurrence rate, 91 patients who had clinical complete remission with epithelial ovarian cancer were studied. METHODS: From 1983 to 2002, 91 consecutive patients with epithelial ovarian cancer underwent surgical cytoreduction followed by platinum-based chemotherapy at the Department of Obstetrics and Gynecology, Hanyang University Hospital. At the conclusion of chemotherapy, all patients who were clinically disease free and whose CA 125 was 2 cm with advanced stage at primary surgery and negative second-look findings should be the focus of future protocols for consolidation chemotherapy.

A Study of Ovarian Dysfunction after Chemotherapy in Cancer Survivals / 대한산부인과학회잡지

OBJECTIVE: We analysed the duration of ovarian dysfunction, amenorrhea and pregnancy rate of the patients who underwent the fertility preserving surgery and adjuvant chemotherapy at the reproductive age to identify the contributing factors of ovarian dysfunction and premature menopause. METHODS: We select the 25 patients (<40 years old at diagnosis) among the 270 patients with malignant ovarian tumor who undergone conservative surgery and platinum-based adjuvant chemotherapy between the year 1985 and 2001. All patient was disease free state. Method used for follow up were physical exam, tumor markers and ultrasonography. We analysed age at diagnosis, amenorrheic period, recovery of ovarian function whether hormonal agent was used or not, times of pregnancy, times of successful pregnancy, and times of pregnancy outcome with anomaly. RESULTS: In 25 cases, patients who became pregnant had a shorter period of amenorrhea of 2.55 months compared to 20.47 months of the rest. Total times (Kur) of chemotherapy shows no difference between two groups (6.45 vs 6.33). Average age show no differences between two groups (22.43 years vs 22.9 years), but amenorrheic period increased in proportion to age at treatment and times of chemotheapy, so we can guess that ovarian dysfunction is more serious with higher age at diagnosis and many times of chemotherapy. In the group who had been pregnant, successful outcome were 7 of 9 total times of pregnancy (abortion rate was 22%), and no baby had gross anomaly. CONCLUSION: So we can guess that ovarian dysfunction is more serious with higher age at diagnosis and more times of chemotherapy.