Clinical Implications of Circulating Tumor DNA from Ascites and Serial Plasma in Ovarian Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The purpose of this study was to identify the clinical utility of circulating tumor DNA (ctDNA) from ascites and serial plasma samples from epithelial ovarian cancer (EOC) patients. @*Materials and Methods@#Using targeted next-generation sequencing, we analyzed a total of 55 EOC samples including ctDNA from ascites and serial plasma and gDNA from tumor tissues. Tumor tissues and ascites were collected during debulking surgeries and plasma samples were collected before and after the surgeries. Because one EOC patient underwent secondary debulking surgery, a total of 11 tumor tissues, 33 plasma samples, and 11 ascites samples were obtained from the 10 patients. @*Results@#Of the 10 patients, nine (90%) contained somatic mutations in both tumor tissues and ascites ctDNA. This mutational concordance was confirmed through correlation analysis. The mutational concordance between ascites and tumor tissues was valid in recurrent/progressive ovarian cancer. TP53 was the most frequently detected gene with mutations. ctDNA from serial plasma samples identified EOC progression/recurrence at a similar time or even more rapidly than cancer antigen 125, an established serum protein tumor marker for EOC. @*Conclusion@#Our data suggest that ascites ctDNA can be used to identify the mutational landscape of ovarian cancer for therapeutic strategy planning.

Risk factors for cytological progression in HPV 16 infected women with ASC-US or LSIL: The Korean HPV cohort

OBJECTIVE: This study was to identify the risk factors for cytological progression in women with atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesions (LSIL). METHODS: We analyzed data from women infected with the human papillomavirus (HPV) who participated in the Korean HPV cohort study. The cohort recruited women aged 20–60 years with abnormal cervical cytology (ASC-US or LSIL) from April 2010. All women were followed-up at every 6-month intervals with cervical cytology and HPV DNA testing. RESULTS: Of the 1,158 women included, 654 (56.5%) and 504 (43.5%) women showed ASC-US and LSIL, respectively. At the time of enrollment, 143 women tested positive for HPV 16 (85 single and 58 multiple infections). Cervical cytology performed in the HPV 16-positive women showed progression in 27%, no change in 23%, and regression in 50% of the women at the six-month follow-up. The progression rate associated with HPV 16 infection was higher than that with infection caused by other HPV types (relative risk [RR], 1.75; 95% confidence interval [CI], 1.08–2.84; P=0.028). The cytological progression rate in women with persistent HPV 16 infection was higher than that in women with incidental or cleared infections (P < 0.001). Logistic regression analysis showed a significant relationship between cigarette smoking and cytological progression (RR, 4.15; 95% CI, 1.01–17.00). CONCLUSION: The cytological progression rate in HPV 16-positive women with ASC-US or LSIL is higher than that in women infected with other HPV types. Additionally, cigarette smoking may play a role in cytological progression.

Can human papillomavirus (HPV) genotyping classify non-16/18 high-risk HPV infection by risk stratification? / 부인종양

OBJECTIVE: Infection with high-risk genotypes of human papillomavirus (HR-HPV) is the major cause of invasive cervical cancers. HPV-16 and HPV-18 are known to be responsible for two-thirds of all invasive cervical carcinomas, followed by HPV-45, -31, and -33. Current guidelines only differentiate HPV-16/18 (+) by recommending direct colposcopy for treatment. We tried to evaluate whether there are differences in risk among 12 non-16/18 HR-HPV genotypes in this study. METHODS: The pathology archive database records of 1,102 consecutive gynecologic patients, who had results for cervical cytology and histology and for HPV testing, as determined by HPV 9G DNA chip, were reviewed. RESULTS: Among the 1,102 patients, 346 were non-16/18 HR-HPV (+) and 231 were HPV-16/18 (+). We calculated the odds ratios for ≥cervical intraepithelial neoplasia 2 (CIN 2) of 14 groups of each HR-HPV genotype compared with a group of HR-HPV (–) patients. Based on the odds ratio of each genotype, we divided patients with non-16/18 HR-HPV genotypes (+) into two groups: HPV-31/33/35/45/52/58 (+) and HPV-39/51/56/59/66/68 (+). The age-adjusted odds ratios for ≥CIN 2 of the HPV-31/33/35/45/52/58 (+) and HPV-39/51/56/59/66/68 (+) groups compared with a HR-HPV (–) group were 11.9 (95% CI, 7.6 to 18.8; p<0.001) and 2.4 (95% CI, 1.4 to 4.3; p<0.001), respectively, while that of the HPV-16/18 (+) group was 18.1 (95% CI, 11.6 to 28.3; p=0.003). CONCLUSION: The 12 non-16/18 HR-HPV genotypes can be further categorized (HPV-31/33/35/45/52/58 vs. HPV-39/51/56/59/66/68) by risk stratification. The HPV-31/33/35/45/52/58 genotypes might need more aggressive action. Large scale clinical trials or cohort studies are necessary to confirm our suggestion.

DNA methylation in human papillomavirus-infected cervical cells is elevated in high-grade squamous intraepithelial lesions and cancer / 부인종양

OBJECTIVE: DNA methylation has been shown to be a potential biomarker for early cancer detection. The aim of this study was to evaluate DNA methylation profiles according to liquid-based Pap (LBP) test results and to assess their diagnostic value in a Korean population. METHODS: A total of 205 patients with various Papanicolaou test results were enrolled to this study (negative, 26; atypical squamous cells of undetermined significance, 39; low grade squamous intraepithelial lesion, 44; high grade squamous intraepithelial lesion (HSIL), 48; and cancer, 48). DNA methylation analysis of four genes, ADCYAP1, PAX1, MAL, and CADM1, was performed on residual cervical cells from LBP samples using a quantitative bisulfite pyrosequencing method. To evaluate the diagnostic performance of the four methylated genes for cancer detection, receiver operating characteristic (ROC) curves were drawn. Sensitivities and specificities were also tested at cutoffs determined from the ROC curves. RESULTS: Cervical cancer cells showed dramatically increased methylation levels for the four genes analyzed. ADCYAP1 and PAX1 also trended toward elevated methylation levels in HSIL samples, although the levels were much lower than those in cancer cells. The sensitivities of methylated ADCYAP1, PAX1, MAL, and CADM1 for the detection of cancer were 79.2%, 75.0%, 70.8%, and 52.1%, and the specificities were 92.0%, 94.0%, 94.7%, and 94.0%, respectively. Methylated ADCYAP1 and PAX1 demonstrated relatively better discriminatory ability than did methylated MAL and CADM1 (area under the curves 0.911 and 0.916 vs. 0.854 and 0.756, respectively). CONCLUSION: DNA methylation status, especially in the ADCYAP1 and PAX1 genes, showed relatively good specificity, ranging from 90% to 94%. The possible additive and complementary roles of DNA methylation testing with respect to conventional cervical cancer screening programs will need to be validated in prospective population-based studies.

Clinical Significance of an HPV DNA Chip Test with Emphasis on HPV-16 and/or HPV-18 Detection in Korean Gynecological Patients

BACKGROUND: Human papillomavirus (HPV) is a major risk factor for cervical cancer. METHODS: We evaluated the clinical significance of the HPV DNA chip genotyping assay (MyHPV chip, Mygene Co.) compared with the Hybrid Capture 2 (HC2) chemiluminescent nucleic acid hybridization kit (Digene Corp.) in 867 patients. RESULTS: The concordance rate between the MyHPV chip and HC2 was 79.4% (kappa coefficient, κ = 0.55). The sensitivity and specificity of both HPV tests were very similar (approximately 85% and 50%, respectively). The addition of HPV result (either MyHPV chip or HC2) to cytology improved the sensitivity (95%, each) but reduced the specificity (approximately 30%, each) compared with the HPV test or cytology alone. Based on the MyHPV chip results, the odds ratio (OR) for ≥ high-grade squamous intraepithelial lesions (HSILs) was 9.9 in the HPV-16/18 (+) group and 3.7 in the non-16/18 high-risk (HR)-HPV (+) group. Based on the HC2 results, the OR for ≥ HSILs was 5.9 in the HR-HPV (+) group. When considering only patients with cytological diagnoses of “negative for intraepithelial lesion or malignancy” and “atypical squamous cell or atypical glandular cell,” based on the MyHPV chip results, the ORs for ≥ HSILs were 6.8 and 11.7, respectively, in the HPV-16/18 (+) group. CONCLUSIONS: The sensitivity and specificity of the MyHPV chip test are similar to the HC2. Detecting HPV-16/18 with an HPV DNA chip test, which is commonly used in many Asian countries, is useful in assessing the risk of high-grade cervical lesions.

A Clinicopathological Review of Pulmonary Metastasis from Uterine Cervical Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to investigate the clinicopathological features of pulmonary metastasis from cervical cancer. MATERIALS AND METHODS: We reviewed the medical records of 56 patients with cervical cancer who developed pulmonary metastasis after radical hysterectomy, postoperative concurrent chemoradiation or systemic chemotherapy between January 1990 and March 2014. RESULTS: Fifty-six patients were diagnosed with pulmonary metastasis from cervical cancer. The prevalence of pulmonary metastasis was 3.6%. The mean event-free duration was 12 months. Twelve patients underwent surgical removal of metastatic lesions. The overall survival (OS) of patients with 4 lesions (25 months, p=0.034). The OS of patients who underwent surgical resection was 53.8 months, longer than that of those who did not (p=0.006). In addition, the OS of patients with adjuvant platinum-based chemotherapy was 32.6 months (p=0.027). CONCLUSION: In this study, we found that the number of metastatic nodules, surgical resection, and postoperative platinum-based chemotherapy can influence clinical outcome. Further studies on prognostic factors and successful treatment modalities are warranted.

Establishment of a Korea HPV cohort study / 부인종양

We have designed a five-year multicentre prospective cohort study in women who are both human papillomavirus (HPV)-positive with either atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) of cervix. This study aimed to analyze the risk of developing a high-grade squamous intraepithelial lesion (HSIL) from either ASCUS or LSIL in HPV-positive women, so called 'progression' rate, to investigate differences in the progression rates according to HPV type-specific infection, and to evaluate the various factors associated with the persistence or clearance of HPV infection in the Korean population. At present, the study protocol composed of cervical cytology, HPV DNA testing, and questionnaire have been conducted actively since the first participant was enrolled in 2010. This study is the first nationwide Korea HPV cohort study. Our data will provide valuable information about not only the ambiguous cytology results of ASCUS and LSIL but also the effect of the specific HPV type and other various factors on the progression to HSIL. Finally, the results of our study will be helpful and applicable to determine the primary cervical cancer prevention strategies.

Practice guidelines for the early detection of cervical cancer in Korea: Korean Society of Gynecologic Oncology and the Korean Society for Cytopathology 2012 edition / 부인종양

The consensus guideline development committee of Korean Society of Gynecologic Oncology was reconvened in March 2012. The committee consisted of 36 experts representing 12 university hospitals and professional organizations. The objective of this committee was to develop standardized guidelines for cervical cancer screening tests for Korean women and to distribute these guidelines to every clinician, eventually improving the quality of medical care. Since the establishment of the consensus guideline development committee, evidence-based guidelines have either been developed de novo considering specific Korean situations or by adaptation of preexisting consensus guidelines from other countries. Recommendations for cervical cancer screening tests, management of atypical squamous and glandular cells, and management of low-grade and high-grade squamous intraepithelial lesions were developed. Additionally, recommendations for human papillomavirus DNA testing and recommendations for adolescent and pregnant women with abnormal cervical screening test results were also included.

Clinical analysis of intra-operative frozen section proven borderline tumors of the ovary / 부인종양

OBJECTIVE: We have assessed the accuracy of frozen section diagnosis and the outcomes of misdiagnosis in borderline tumors of the ovary (BTO) according to frozen section. METHODS: All pathology reports with BTO in both frozen and permanent section analyses between 1994 and 2008 at Seoul St. Mary's Hospital were reviewed. Frozen section diagnosis and permanent section histology reports were compared. Logistic regression models were conducted to evaluate the correlation of patient and tumor characteristics with diagnostic accuracy. The clinical outcomes of misdiagnosis were evaluated. RESULTS: Agreement between frozen section diagnosis and permanent histology was observed in 63 of 101 patients (62.4%). Among the 76 patients with frozen section proven BTO, under-diagnosis and over-diagnosis occurred in 8 of 76 (10.5%) and 5 of 76 patients (6.6%), respectively. Mean diameter of under-diagnosed tumor was larger than matched BTO (21.0+/-11.4 vs. 13.7+/-7.1; p=0.021). Tumor size 20 cm was determined as the optimal cut-off for under-diagnosis (50% sensitivity, 87.3% specificity). Among 8 under-diagnosed patients, no patient relapsed. Among 5 over-diagnosed patients, 2 patients < 35 years of age had fertility-preserving surgery. CONCLUSION: Although frozen section diagnosis is an important and reliable tool in the clinical management of patients with ovarian tumors, over-diagnosis and under-diagnosis are relatively frequent in frozen proven BTO. Surgical decision-making for BTO based on frozen section diagnosis should be done carefully, especially in large tumors.

Epithelial ovarian cancer in patients under 20 years of age / 대한산부인과학회지

OBJECTIVE: Epithelial ovarian cancer is the most common cause of death due to gynecologic malignancies in adults, but is rare in children and adolescents. This is a report of series of such patients under 20 years of age documenting their presentation, histologic type, stage of disease, treatment, and outcome. METHODS: We collected data on 21 patients with epithelial ovarian cancer under 20 years of age between January 1990 and December 2005. Patient records and pathology were reviewed. RESULTS: Epithelial ovarian cancer under 20 years of age was 2.2% in overall ovarian cancer. Epithelial ovarian cancer was 42.0% among 50 patients under 20 years of age and the most common histologic type was germ cell tumors (54%). The median age at the time of diagnosis was 17.6 years (range, 13-20 years), and the median follow-up was 87 months (range, 4-175 months). There were seventeen (81.0%) mucinous tumors, four (19.0%) serous tumors. About thirty-eight percent were low malignant potential or borderline tumors. About Eighty-five percent (18 patients) of tumors were stage I disease and about fourteen percent (3 patients) were stage III disease at the time of diagnosis. Surgical treatment included conservative surgery in 18 patients (85.7%), total abdominal hysterectomy and bilateral salpingo- oophorectomy in 3 patients (14.3%). CONCLUSION: Epithelial ovarian cancers are rare in patients in children and adolescents. The majority of ovarian cancers in this age group are mucinous tumors, stage I at diagnosis and borderline ovarian tumor. Conservative management is feasible to achieve preservation of fertility.

Conservative treatment of endometrial adenocarcinoma in young women with hormone therapy / 대한산부인과학회지

Endometrial cancer is the ninth common cancer in women and the third common gynecologic cancer in Korea. Although it is primarily a disease of the postmenopausal female, 3-5% of patients are 40 years old or younger. Because of the particularly good prognosis for young women with early stage endometrial cancer, the limited myometrial invasion and high tumor differentiation, and because most of the women also suffer from subfertility, many attempts have been made to treat such cases conservatively with hormonal therapy rather than with surgery. This article discusses the current, available data about conservative management of endometrial cancer in young women. A comprehensive pretreatment evaluation including dilatation and curettage, pelvic ultrasound, abdominopelvic computed tomography, and pelvic magnetic resonance imaging is critical. Detailed counseling is essential. Multiple effective protocols exist for conservative treatment of endometrial cancer, and the initial response rates are as high as 57 to 75%. When the patient finishes her fertility plans, the option of hysterectomy should be considered. Most of studies have been based on retrospective case reports, and many questions still remain unanswered regarding the optimal treatment protocol or long-term surveillance for conservative management of these patients. Larger prospective clinical studies are warranted.

Induction of apoptosis by the kinase inhibitor flavopiridol in human ovarian cancer cell lines / 부인종양

OBJECTIVE: Flavopiridol that inhibits cyclin-dependent kinase, can cause cell cycle arrest, induce apoptosis in human tumor cell lines. In the present study, we investigated apoptotic effects of flavopiridol and the underlying molecular mechanisms in human ovarian cancer cell lines. METHODS: We used TOV-21G and TOV-112D cell lines. The cell viability was tested by MTT assay and apoptosis was assessed by TUNEL assay and annexin-V binding. Western blot was used to examine apoptosis related protein levels. MAP kinase activity was analyzed by non-radioactive MAP kinase assay kit. RESULTS: Treatment of TOV-21G and TOV-112D cells with flavopiridol (50 nM to 1000 nM) led to a dose- and time-dependent inhibition of cell growth and survival. Dose-related induction of apoptosis was also observed in these cell lines. Flavopiridol (500 nM) induced striking decreases in the levels of the antiapoptic proteins Mcl-1, Bcl-X(L), and XIAP in both cell lines. In contrast, expression of Bax, Bcl-2, and AIF was not significantly influenced by flavopiridol. Although flavopiridol resulted in accumulation of p53 in both cells, flavopiridol mediated apoptosis was p53 independent because it occurred to the same degree in TOV-112D cells in which p53 was inactivated by mutation. Flavopiridol treatment resulted in enhanced cleavage of pro-caspase 9 and activation of caspase 3. Apoptosis was associated with suppression of ERK activity. CONCLUSION: Although the precise mechanisms of flavopiridol mediated cytotoxicity have not been fully defined, these data suggest that flavopiridol has activity against ovarian cancers in vitro and is worthy of continued clinical development in the treatment of ovarian cancer.

A case of choledochal cyst diagnosed and conservatively treated during pregnancy / 대한산부인과학회지

Choledocal cyst are cystic dilatations of the biliary tree varying in location from the ampulla of vater to the intrahepatic bile ducts. The majority of the cases are diagnosed during the first decade of the life but in 20% of patients with choledochal cysts, the diagnosis is not made until adulthood. Although these cysts occur frequently in females, presentation in pregnancy or the postpartum period is rare. Choledochal cysts presenting during pregnancy an increased risk to both the mother and developing fetus. The clinical presentation is often nonspecific, and physical and radiologic examination are limited during pregnancy because of the presence of the gravid uterus. We experienced one case of choledochal cyst during pregnancy and report our experience.

A case of inguinal lymph node squamous cell carcinoma of unknown origin, accompanied with carcinoma in situ of cervix / 부인종양

Metastatic Cancer of Unknown Primary Site (CUP) accounts for approximately 3-5% of all malignant neoplasms. CUP represents a heterogeneous group of metastatic tumors for which no primary site can be detected following a thorough medical history, careful clinical examination, and extensive diagnostic work-up. Several authors have reported poor prognosis of this malignancy, because there is no consensus on diagnostic guidelines and optimal therapy. Historically, chemotherapy has been the cornerstone of treatment for patients with CUP. We experienced a case of inguinal lymph node squamous cell carcinoma of unknown origin, accompanied with carcinoma in situ of the cervix. We report this case with a brief review of the literatures.

A case of chemoresistant placental site trophoblastic tumor in a patient who wants to remain fertile / 부인종양

Placental site trophoblastic tumor (PSTT) is a rare form of gestational trophoblastic tumor (GTT) that has different behavior in disease process. The hysterectomy is general for PSTT, but hysterectomy is undesirable for patients who wish to remain fertile. We planned to preserve fertility of a young patient by first administering EMA/CO (Etoposide, methotrexate, actinomycin D/cyclophosphamide, vincristine) chemotherapy and then performing an open uterine surgery to remove residual tumor. The patient who attempted primary chemotherapy for PSTT must be undergone a hysterectomy because this conservative regimen showed sign of chemoresistance. We report a case of chemoresistant PSTT with trial to preserve fertility with a brief review of literatures.

Recommendation guideline of Korean Society of Gynecologic Oncology and Colposcopy for quadrivalent human papillomavirus vaccine / 부인종양

Genital HPV infection is the most common sexually transmitted infection, but the majority of infections are self-limited. However, persistent infection with high-risk types can cause cervical cancer in women, which is the most common female genital cancer in Korea. In addition, HPV infection is the cause of genital warts and is associated with other anogenital cancers. The HPV vaccine is composed of the HPV L1 protein, the major capsid protein of HPV. Expression of the L1 protein in yeast using recombinant DNA technology produces noninfectious virus-like particles (VLP) that resemble HPV virions. The quadrivalent HPV vaccine is a mixture of four HPV type-specific VLPs prepared from the L1 proteins of HPV 6, 11, 16, and 18 combined with an aluminum adjuvant. Clinical trials indicate that the vaccine has high efficacy in preventing persistent HPV infection, cervical cancer precursor lesions, vaginal and vulvar cancer precursor lesions, and genital warts caused by HPV types 6, 11, 16, or 18 among females who have not already been infected with the respective HPV type. The recommended age for primary vaccination of Korean females is 15-17 years, considering sexual debut and duration of protection of the vaccine. Vaccine can be administered as young as age 9 years. Catch-up vaccination is recommended for females aged 18-26 years who have not been previously vaccinated. Vaccination is not a substitute for routine cervical cancer screening, and vaccinated females should have cervical cancer screening as recommended.

Analysis of HLA-G expression in preeclampsia and intrauterine growth restriction / 대한산부인과학회지

OBJECTIVE: To determine whether soluble HLA-G protein levels in plasma and/or HLA-G protein in placental tissues differ between women with gestational complications (preeclampsia and/or intrauterine growth restriction, IUGR) and women with normal pregnancies. METHODS: A sandwich enzyme-linked immunosorbent assay was used to investigate the HLA-G expression level in 11 cases of preeclampsia, 8 cases of preeclampsia with IUGR, 18 cases of IUGR, and 10 normal control subjects. RESULTS: Plasma HLA-G levels were decreased significantly in the preeclampsia group (median, 0.072 microgram/mL), the preeclampsia with IUGR group (median, 0.086 microgram/mL), and the IUGR group (median, 0.081 microgram/mL), in comparison with normal pregnant women (median, 0.360 microgram/mL) (P=0.002, P=0.049, and P=0.003, respectively). Also, Placental HLA-G levels were decreased significantly in the preeclampsia group (median, 0.016 microgram/mg), the preeclampsia with IUGR group (median, 0.015 microgram/mg), and the IUGR group (median, 0.021 microgram/mg), in comparison with normal pregnant women (median, 0.091 microgram/mg) (P<0.001, P=0.002, and P=0.001, respectively). There was a significant correlation between plasma and placental HLA-G levels (r=0.807, P<0.001). CONCLUSION: Our results indicate that the attenuated expression of placental HLA-G and reduced release of this protein into the maternal circulation in gestational complications, such as preeclampsia and IUGR may alter the maternal-fetal immune relationship, and thus could be at play in the pathophysiology of these diseases. This suggests that assessment of levels of HLA-G proteins may be useful in predicting development of preeclampsia and IUGR.

Sexual behavior of Korean young women: preliminary study for the introducing of HPV prophylactic vaccine / 부인종양

OBJECTIVE: The decision of optimal age for administration of recently approved prophylactic human papillomavirus (HPV) vaccines in the world depend on the basis of the sexual behavior of each countries. The aim of the study was to survey the age-specific sexual behavior including the sexual debut time and sexual experience in the Korean young women to design the tailored HPV vaccination. METHODS: This study was conducted by the Synovate Healthcare in the 6 city of Korea e.g. Seoul, Pusan, Daegu, Incheon, Kwangju and Daejon. By a stratified sampling methods 2,400 women aged 12-29 years old were included. The measures of sexual behavior presented in this report were collected by a Computer-Assisted Self-Interviewing (ACASI), in which the respondent enters her own answers into a computer without telling them to an interviewer. RESULTS: Among women 12-29 years of age, 39 percent of women (934 persons in 2,400 women) and 33 percent of single women (724 persons in 2,190 women) have had vaginal intercourse; 8 percent of women under 19 years old single women (79 persons in 1,045) and 56 percent of single women with 20-29 years old (645 persons in 1,145). Number of sexual partner was 2.8 person and 54 percent of women had more than 2 partners. Age of the first sexual activity (sexual debut) was 21 years old. The age of partner at the sexual debut was 23.2 years old. Sexual experience before 15 years old was only 2%. About the condom, 41% did not use or rarely use. CONCLUSION: Our data demonstrate that the sexual debut time of young Korean women differ from other countries in which the prophylactic HPV vaccine had already used. We conclude that the optimal age for HPV vaccination in Korea would be determined at 15-17 years old by this situation.

Association study of 5-HTT gene polymorphism with fear during childbirth / 대한산부인과학회지

The fear and anxiety in the biological processes of childbirth have been of clinical interest, but the studies addressing this subject are rare, particularly where the outcome of the pregnancy has been favourable. In this study, single nucleotide polymorphisms were studied for understanding the fear during childbirth in 534 Korean pregnant women. The frequencies of each SNP were 5-HTT -15375 insdel (44 bp) 0.24, -1002A>C 0.10, -922A>C 0.11, +18784A>C 0.073 in Korean pregnant women (n=534). No polymorphisms was found in 5-HTT +3746G>C The relationship between the fear during childbirth and genetic polymorphisms was investigated by multiple regression analysis adjusting for parity in 293 women who gave birth to a child vaginally and made a reply to Delivery Fear Scale (DFS) which was the measuring instrument for the fear during childbirth among 534 Korean pregnant women. There was no genetic association between the 5-HTT gene polymorphism and fear during childbirth. The results of this study show that the psychological, social, environmental factors play the major role in the fear during childbirth whereas this gene (5-HTT) most likely has only a minor effect in its etiology. And other genes and the interactions between them have been thought to make complex effects. In order to identify the fear during childbirth, further studies will have to be focused on the comprehensive research of the social, psychological, environmental factors and the interaction of the connected genes.

The significance of maternal serum and umbilical cord blood leptin concentration with intrauterine fetal growth restriction and/or preeclampsia / 대한산부인과학회지

OBJECTIVE: To ascertain whether fetal growth restriction with or without preeclampsia is associated with alteration of leptin concentration in maternal and umbilical cord serum. METHODS: Maternal serum and umbilical cord blood leptin concentrations were determined by ELISA assay in 25 women with singletone pregnancies complicated by fetal growth restriction without preeclampsia (IUGR), in 11 women with singletone pregnancies complicated by fetal growth restriction with preeclampsia (IUGR+PE), in 9 women with singletone pregnancies complicated by preeclampsia without fetal growth restriction (PE), and in 13 women with uncomplicated singletone pregnancies (Control). RESULTS: Maternal weight and BMI before pregnancy and in delivery were significantly different among groups. The lowest weight and BMI before pregnancy and in delivery was group IUGR. Neonatal birth weight was significantly different among groups. The lowest birth weight was group IUGR+PE. Maternal serum leptin concentration and umbilical cord leptin concentration were not significantly different among groups. Maternal serum leptin levels were not significantly correlated with maternal BMI or with neonatal birth weight. Umbilical cord blood leptin levels were significantly correlated with neonatal birth weight. CONCLUSION: Maternal serum leptin concentration and umbilical cord blood leptin levels were independent of presence of preeclampsia and/or IUGR. Umbilical cord blood leptin reflects neonatal birth weight.