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Prognostic analysis of radical radiotherapy in stage Ⅰ b and Ⅱ a cervical carcinoma

Jing ZENG ; Rong ZHANG ; Manni HUANG ; Jusheng AN ; Lingying WU

Chinese Journal of Obstetrics and Gynecology.2013;48(9):644-648. doi:10.3760/cma.j.issn.0529-567x.2013.09.002

Objective To investigate the efficacy and prognostic factors in patients with stage Ⅰ b and Ⅱ a cervical carcinoma by radical radiotherapy.Methods Between January 1999 and January 2012,108 patients with stage Ⅰ b and Ⅱ a cervical carcinoma received radical radiotherapy in Cancer Hospital,Chinese Academy of Medical Sciences were included and analyzed retrospectively.Patients of stage Ⅰ b1,Ⅰ b2,Ⅱa1 and Ⅱa2 were 18 (16.7％,18/108),38 (35.2％,38/108),33 (30.6％,33/108) and 19 (17.6％,19/108),respectively.Results The 5-year overall survival rate was 76.2％ and the 5-year disease free survival rate was 75.6％.Totally 25 (23.1％,25/108) patients developed recurrent disease,16 of them (64％,16/25) had local recurrences,6 (24％,6/25) had distant metastases and 3 cases had both local recurrence and distant metastases.Among patients with recurrent disease,23 died and 2 survive with tumor.Totally 24 patients died,23 of them died due to tumor recurrence and the other one died of other reason.The univariate analysis showed that,lymph node metastasis,squamous cell carcinoma antigen (SCC) levels before treatment,SCC levels after treatment 1 month had relation with overall survival time in patients with stage Ⅰ b and Ⅱ a cervical carcinoma (all P ＜ 0.05).The multivariate analysis showed that,lymph node metastasis and SCC levels after treatment 1 month were the independent prognostic factors for overall survival time for the cervical squamous cell carcinoma (OR =2.5,4.4 ; all P ＜ 0.05).Conclusions By means of radical radiotherapy,stage Ⅰ b and Ⅱ a cervical carcinoma patients with lymph node metastasis and SCC levels≥ 1.5 mg/L after treatment one month have poor prognosis.While,stage Ⅰ b and Ⅱ a patients with concurrent chemoradiotherapy after neoadjuvant chemotherapy did not affect the prognosis.The 5-year survival rate with concurrent chemoradiotherapy was higher than that of radiotherapy.

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Extended-field intensity modulated radiation therapy and intra-cavitary brachytherapy combined with chemotherapy for stage Ⅰ b1-Ⅳ a cervical cancer with positive para-aortic lymph nodes

Guihao KE ; Xiao HUANG ; Xiaowei HUANG ; Suping LIU ; Xiaohua WU

Chinese Journal of Obstetrics and Gynecology.2013;48(9):649-653. doi:10.3760/cma.j.issn.0529-567x.2013.09.003

Objective To investigate the treatment effects and toxicities of extended-field intensity modulated radiation therapy (EF-IMRT) and intra-cavitary brachytherapy combined with chemotherapy for stage Ⅰ b1-Ⅳa cervical cancer with positive para-aortic lymph nodes.Methods A total of 46 stage Ⅰ b1-Ⅳa cervical cancer patients with positive para-aortic lymph nodes treated at Fudan University Shanghai Cancer Center between 2009 and 2011 were reviewed.Neoadjuvant,concomitant and adjuvant chemotherapy with paclitaxel and carboplatin were administrated for one cycle before radiation therapy,two cycles during radiation therapy or three cycles after radiation therapy.All patients received EF-IMRT and intra-cavitary brachytherapy.The positive lymph nodes received an additional boost dose.Results All patients received EF-IMRT to 50.4 Gy (1.8 Gy per fraction).Twenty-six patients was treated with boost dose of 6.0-8.0 Gy in 2.0 Gy per fraction to positive para-aortic lymph nodes.Thirty-seven patients received a positive paraaortic lymph nodes boost or(and) parametrial boost.All patient also received a high-dose-rate intra-cavitary brachytherapy at the point A dose of 20.0-30.0 Gy in 5.0 Gy per fraction.Total chemotherapy cycles were 189,and the average patient received 4.1 courses.Two cases (4％,2/46) experienced grade Ⅲ gastrointestinal toxicities,no patients suffered grade Ⅳ gastrointestinal toxicities.Fifteen cases (33％,15/46) experienced grade Ⅲ hematological toxicities,and 3 (7％,3/46) experienced grade Ⅳ hematological toxicities.Late grade Ⅲ-Ⅳ toxicity was seen in 3 cases (7％,3/46).The 3 year progressionfree survival rate was 46.2％,and the 3 years overall survival rate was 61.2％.Conclusion EF-IMRT and intra-cavitary brachytherapy combined with chemotherapy is safe and effective for stage Ⅰ b1-Ⅳa cervical cancer with positive para-aortic lymph nodes.

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Pregnancy outcomes of 103 women with pulmonary arterial hypertension

Bin LI ; Xiaoyuan SUN ; Kefang WANG

Chinese Journal of Obstetrics and Gynecology.2013;48(9):659-662. doi:10.3760/cma.j.issn.0529-567x.2013.09.005

Objective To evaluate the pregnancy outcome of women with pulmonary arterial hypertension (PAH).Methods The medical records of 103 pregnant women with PAH admitted to Beijing Anzhen Hospital from January 2007 to March 2011 were studied retrospectively.Results (1) Degree of PAH and cardiac function.Among the 103 PAH,92 cases were patients with congenital heart disease and 13 cases were with rheumatic heart disease.They were divided by color doppler ultrasound into mild PAH group (34 cases),moderate PAH group (22 cases) and severe PAH group (47 cases).Per heart function classification,21 cases (20.4％,21/103) were class Ⅰ,44 cases (42.7％,44/103) were class Ⅱ,27 cases (26.2％,27/103) were class Ⅲ and 11 cases (10.7％,11/103) were class Ⅳ.More patients were class Ⅲ and Ⅳcardiac function in the severe PAH group than in the mild and moderate PAH groups,with statistically significant difference (P ＜ 0.05).(2) Delivery mode.There were 44 term delivery and 23 preterm birth in the 103 PAH patients.Sixty-three cases (94％,63/67) received cesarean section and 4 cases had vaginal delivery.There were 36 iatrogenic abortion (35.0％,36/103).The iatrogenic abortion rate in the severe PAH group was significantly higher than those in the mild and moderate PAH groups (P ＜ 0.05).(3) Perinatal outcomes.The full-term delivery rates in the mild and moderate PAH groups [80％ (20/25) and 14/17] were significantly higher than the severe PAH group (40％,10/25),respectively (P ＜ 0.05).And the premature birth rate of the severe PAH group(60％,15/25) was significantly higher than the mild and moderate PAH group [20％ (5/25)and 3/17,P ＜ 0.05].There were 4 neonatal asphyxia.The birth weight of mild,moderate and severe PAH groups were (3071 ± 443),(2910 ± 619) and (2381 ±589) g,respectively.The birth weight in the severe PAH group was significantly lower than the mild and moderate PAH groups (P ＜ 0.05).(4) Mortality.Nine cases naternal death happened,with a mortality of 8.7％ (9/103).All of them were severe pulmonary hypertension patients.Conclusions PAH is a serious complication during pregnancy.Women with mild PAH and normal cardiac function could continue pregnancy to full-term.Women with moderate PAH might continue pregnancy to 32 weeks under intensive care,cesarean delivery is preferable.Pregnant women with severe PAH should terminate pregnancy because of the high mortality.

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Clinical study of 67 cases of endometriosis coexisting with genital tract anomalies

Shu WANG ; Jinghe LANG ; Lan ZHU

Chinese Journal of Obstetrics and Gynecology.2013;48(9):663-666. doi:10.3760/cma.j.issn.0529-567x.2013.09.006

Objective To investigate the pathogenesis of endometriosis by studying endometriosis coexisting with variable genital tract anomalies and analysis the association between obstructive or nonobstructive anomalies with endometriosis.Methods From January 2000 to April 2010,a total of 67 cases of endometriosis coexisting with genital tract anomalies undergoing treatment in Peking Union Medical College Hospital were studied retrospectively.Results According to subtypes of concurrent genital tract anomalies,67 cases were divided into 19 cases in obstructive group and 48 cases in non-obstructive group.(1) Age and symptoms:the mean age were (22 ± 8) years in obstructive group and (32 ± 7) years in non-obstructive group,which reached statistical difference (P ＜ 0.05).The major symptoms were dysmenorrheal or chronic pelvic pain (14/19) and amenorrhea (8/19) in obstructive group.However,in non-obstructive group,the major symptoms were dysmenorrheal or chronic pelvic pain (31％,15/48) and infertility (35％,17/48) and abortion (21％,10/48).(2) Degree and incidence of endometriosis:the moderate or severe endometriosis was 11/19 in obstructive group and 40％ (19/48) in non-obstructive group,which did not show statistical difference (P ＞ 0.05).The incidence of peritoneal endometriosis,ovarian endometriosis,adenomyosis did not show significant difference between two groups (all P ＞ 0.05).The rate of moderate or severe endometriosis coexisting with duplex uterus,uterus bicornis and uterus septus did not show significant difference in non-obstructive group (P ＞ 0.05).Conclusions The severity of endometriosis showed no association with obstructive anomalies.The results implied that there might be other factors involved in pathogenesis of endometriosis.

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Application of oxytocin antagonists in thaw embryo transfer

Xueru SONG ; Xiaohui ZHAO ; Xiaohong BAI ; Yonghuan Lü ; Huijuan ZHANG ; Yanxia WANG ; Rui Lü

Chinese Journal of Obstetrics and Gynecology.2013;48(9):667-670. doi:10.3760/cma.j.issn.0529-567x.2013.09.007

Objective To study the effects of oxytocin antagonists-atosiban on pregnancy outcome after thaw embryo transfer (TET).Methods Between Jul.and Dec.2012,a total of 120 women undergoing TET in Reproductive Medical Center,General Hospital of Tianjin Medical University were randomly allocated into atosiban and control group.They were all transferred 2 or 3 top quality embryos at phase of 7-8 cells.Patients in atosiban group were administered by intravenous administration of atosiban before 30 minutes of embryo transfer with a total administered dose of 37.5 mg.In the control group,no special treatment was given before embryo transfer.All patients in 2 groups underwent progesterone luteal support regularly after embryo transfer,then the clinical rate of pregnancy,implantation and early abortion was compared.Results The clinical pregnancy rate per cycle and implantation rate per transfer were 60％(36/60) and 30.0％ (48/160) in the atosiban group,which were higher than 42％ (25/60) and 20.3％ (31/153) in the control group (all P ＜ 0.05).Early abortion rate was 6％ (2/36)in the atosiban group,which was no statistical difference comapring with control group [16％ (4/25),P ＞ 0.05].Conclusion It was suggested that atosiban treatment before embryo transfer can improve the outcome of pregnancy,and increase clinical pregnancy rate and implantation rate after TET.

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Biological effects of upregulated expression of transfected FOLR1 gene on SKOV3 cell lines acted by cisplatin

Mingju HUANG ; Wei ZHANG ; Qi WANG ; Zuai CAI ; Li LI

Chinese Journal of Obstetrics and Gynecology.2013;48(9):676-682. doi:10.3760/cma.j.issn.0529-567x.2013.09.009

Objective To explore biological effects of up-regulated expression of transfected FOLR1 gene on SKOV3 cell lines following action by cisplatin(DDP).Methods Three groups of cells originated from the same SKOV3 cell line were used in this research,including the SKOV3 cell line (blank control),the cell line transfected with lentiviral pWPI plasmid (no-load control) and the cell line transfected with FOLR1 gene via lentiviral pWPI plasmid (experimental group).Next,the mRNA and protein expression of FOLR1 gene in the three groups were detected by reverse transcription (RT)-PCR and western blot,respectively.Methyl thiazolyl tetrazolium (MTT) assay was used to analysis cells growth curve and identify their sensitivity to cisplatin,and their half inhibition concentration (IC5o) values were calculated.Based on the IC50 value (3.6 μg/ml) in the experimental group,different levels of cisplatin concentration (0.5 × IC50,1 × IC50,2 × IC50,respectively) were administered to the three groups of cells,and the inhibition rates,apoptosis rates as well as apoptosis proportion of each group after 24,48,72 hours were further recorded.Finally,the residual cisplatin concentrations in the three group cells acted successively by 1 × IC50 cisplatin for 48 hours were measured by high performance liquid chromatography(HPLC).P value less than 0.05 were defined as statistically significant.Results RT-PCR and western blot detection showed that stable mRNA and protein expression of the FOLR1 gene in the experimental group while the other two groups were not.MTT assay demonstrated that higher cell growth rate,sensitivity to cisplatin(IC50 =3.6 μg/ml) and inhibition rate in the experimental group compared with those in the other two groups (P ＜ 0.05),which showed no significance in intergroup comparison(P ＞ 0.05).Flow cytometry showed apoptosis rates among three groups increased with higher cisplatin concentrations and longer action duration in dosage-time dependent manner (P ＜ 0.05),and the proportion of S phase cells increased with higher cisplatin concentration in dosage-dependent manner (P ＜ 0.05) ; for the same concentration and duration,the experimental group showed significantly different apoptosis rates and S phase cells compared with the other two groups,which demonstrated no significance in intergroup comparison (P ＞ 0.05).After action by cisplatin(3.6 μg/ml) for 48 hours,HPLC showed significantly higher residual cisplatin concentration (2.60±0.21) μg/106 cell counts in experimental group than those in no-load control group (1.49 ±0.12) μg/106 cell counts and blank control group (1.54 ± 0.11)xg/106 cell counts,respectively (P ＜0.05),and the comparison within the latter two groups showed no significance (P ＞ 0.05).Conclusion Up-regulated expression of the transfected FOLR1 gene in SKOV3 cells may be associated with higher sensitivity to cisplatin,residual cisplatin concentration and higher proportion of S phase cells,and tended to inhibit cancer cells growth and induce apoptosis.

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Survey on epidemiologic factors associated with the age of natural menopause and menopausal symptoms in Jiangsu women

Lin LI ; Jie WU ; Xiaoqing JIANG ; Danhua PU ; Yang ZHAO

Chinese Journal of Obstetrics and Gynecology.2013;48(10):728-733. doi:10.3760/cma.j.issn.0529-567x.2013.10.003

Objective To investigate the epidemiologic factors associated with the age of natural menopause and menopausal symptoms in a large population at age of 40 to 65 years in Jiangsu Province.Methods From May 2010 to Oct.2011,a total of 20 275 women (40 to 65 years) attending health examination in Jiangsu Province were enrolled in this cross-sectional study.A structured questionnaire was used to collect data of demographics,menopausal status,chronic diseases,reproductive history.Also the menopausal symptoms were evaluated by Kupperman menopause index (KMI).Cox proportional hazards regression model and Logistic regression were performed to identify risk factors for earlier age of natural menopause and menopausal symptoms,respectively.Results The overall median age at natural menopause in Jiangsu women was 50 years.Lower educational level,poor economic status,lower body mass index (BMI),age at menarche less than 14 years,nulliparity and smoking were associated with earlier onset of natural menopause (P ＜ 0.05).The most frequently symptoms in perimenopausal women were fatigue (46.84％,1880/4014),insomnia (44.67％,1793/4014) and muscle/joint pain (43.80％,1758/ 4014),while sexual problems (57.06％,3463/6070),muscle/joint pain (53.30％,3235/6070) and insomnia (51.03％,3097/6070) were predominant symptoms in postmenopausal women.After adjusting for confounding factors,it was revealed that women with poor educational background,low income,divorce,higher BMI,higher parity,and smoking presented positive correlation with menopausal symptoms (P ＜ 0.05).Conclusions The study suggested that an estimate of median age at natural menopause were 50 years in Jiangsu women.The main factors contributing to earlier onset of menopause and menopausal symptoms were lower educational level,poor economic status,and smoking.Moreover,there were different menopausal symptoms between perimenopausal and postmenopausal women,which provided the important insights for physicians to prevent and treat menopause symptoms in their clinical practice.

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Study on risk factors of cardiovascular disease and the status of bone mineral density in women with hypoestrogenism

Fang ZHAO ; Xuetao GUO ; Yun CHENG ; Zifen YANG ; Huiping LIU

Chinese Journal of Obstetrics and Gynecology.2013;48(10):734-739. doi:10.3760/cma.j.issn.0529-567x.2013.10.004

Objective To study risk factors of cardiovascular disease (CVD) and status of bone mineral density (BMD) in women with hypoestrogenism.Methods From Jul 2011 to April 2013,a total of 256 women with hypoestrogenism in the First Affiliated Hospital of Shanxi Medical University were enrolled in this retrospective study,which were divided into four groups:133 women in ppausal group,25 women in premature ovarian failure (POF) group,67 women in menopausal transition group and 31 women in premature ovarian failure transition group.General statue,CVD risk factors and BMD were compared among four groups.General statue include menopausal period,menopausal symptoms (Kupperman Index),CVD risk factors include body mass index,blood pressure,waist circumference,waist-hip ratio,blood lipids and glucose,BMD include left hip,lumbar spine bone mineral density and T or Z value.Results (1) The median menopausal period were 3.4 years in postmenopausal group and 3.6 years in premature ovarian failure group,which did not show no statistical difference (P ＞ 0.05).Kupperman Index in four groups were 12 in postmenopausal group,9 in POF group,9 in menopausal transition group and 8 in premature ovarian failure transition group,which reached statistical difference (P ＜ 0.05).(2) The difference of body mass index (BMI),waist circumference,waist-hip ratio,diastolic blood pressure were no statistically significant among four groups(P ＞ 0.05) ; the systolic blood pressure in four groups were 120,110,110,110 mm Hg (1 mm Hg =0.133 kPa),their differences were statistically significance (P ＜ 0.05); the high-density lipoprotein (HDL-C) was 1.6 mmol/L in postmenopausal group,and 1.3 mmol/L in premature ovarian failure transition group,their differences were all statistically significance (P ＜ 0.05) ; the difference of the fasting plasma glucose (FPG) was not statistically different in 4 groups (P ＞0.05).(3) The abnormal rate of lower bone mass in lumbar spine were 57％ (46/81) postmenopausal group,8/15 in POF group,32％ (9/28) in menopausal transition group,12/19 in premature ovarian failure transition group,and osteoporosis was 9％ (7/81),3/15,1％ (3/28)and 0 respectively,their differences were statistically different (P ＜ 0.05) ; the abnormal rate of BMD of left hip and lumbar spine of 11/15 and 12/16 in POF group was higher than 65％ (53/81) in postmenopausal group.In the mean time,the abnormal rate of BMD of left hip and lumbar spine were,12/19 and 10/20 in premature ovarian failure transition group,which were significantly higher than 43％ (12/28) and 39％ (12/31) in the menopausal transition group.Conclusions The menopausal symptoms resulting from hypoestrogenism in natural postmenopausal women are mostly remarkable.The decrease of BMD in lumbar spine is more significant than that of left hip among postmenopausal women.Women with earlier menopause was prone to cause the changes of blood fat and abnormal of BMD,especially HDL-C decreased significantly compared with those natural postmenopause,it is more likely to cause CVD and osteoporosis.

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Study on relationship between endogenous androgens and insulin resistance at the different stages of postmenopause

Yuankui CAO ; Shaofen ZHANG ; Shien ZOU ; Xian XIA ; Linna XU

Chinese Journal of Obstetrics and Gynecology.2013;48(10):740-744. doi:10.3760/cma.j.issn.0529-567x.2013.10.005

Objective To investigate the relationship between insulin resistance and endogenous androgens at early and late phase of postmenopause.Methods A total of 105 women with early postmenopause (≤5 years since menopause) and 107 women with late postmenopause (≥ 10 years since menopause) were enrolled in this study.In the mean time,those women were classified into normal weight [body mass index (BMI),BMI ＜24 kg/m2] group and overweight (BMI≥24 kg/m2) group.Sex hormonebinding globulin (SHBG),testosterone (T),dehydroepiandrosterone-sulfate (DHEA-S),fasting blood glucose(FBG),fasting insulin (FINS)levels were measured and then calculated free androgen index(FAI) and homeostatic model assessment of insulin resistance (HOMA-IR).The relationship between sex hormones and insulin resistance was analyzed by partial correlation and multiple linear regression analyses.Results Compared to early postmenopausal women,late postmenopausal women had higher FINS [(7.9 ± 6.6) mU/L versus (6.6 ±4.0) mU/L] and HOMA-IR(2.1 ± 1.9 versus 1.7 ± 1.1),but they had lower DHEA-S [(0.9 ± 0.5) mg/L versus (1.1 ± 0.5) mg/L,all P ＜ 0.05)].Both in early postmenopausal and late postmenopausal groups,overweight women had higher HOMA-IR (early group,2.2 ± 1.0 versus 1.2 ±0.9 ; late group,2.8 ± 2.6 versus 1.6±1.1)and FINS early group[(6.9±2.9) mU/L versus (4.6±2.0) mU/L] ;late group [(10.2 ± 9.3) mU/L versus (6.4 ± 3.6) mU/L] than those at women with normal weight group(all P ＜ 0.05).In early postmenopausal group,overweight women had lower SHBG [(52 ±37) nmol/L versus (71 ±37) nmol/L] and higher FAI(2.5 ±2.1) versus (1.3 ± 1.1) than those at normal weight women group(all P ＜ 0.05).In late postmenopausal group,overweight women had higher DHEA-S (1.0 ± 0.5) mg/L versus (0.8 ± 0.4) mg/L (P ＜ 0.05).The analyses suggested that in early postmenopausal group,SHBG was correlated negatively with FINS and HOMA-IR (β =-0.386,P ＜ 0.05 ;β =-0.553,P ＜0.05),DHEA-S was correlated positively with FBG (β =0.348,P ＜ 0.05) in early postmenopausal group.FAI was correlated positively with FBG in late postmenopausal group (β =0.505,P ＜ 0.05).Conclusions The increased androgenic activities are associated with insulin resistance after of menopause.These correlations are different at different stages of postmenopause,which SHBG levels correlate with high risk of insulin resistance and DHEA-S levels correlates with high blood glucose levels at early postmenopause and FAI correlates with high blood glucose levels at late postmenopause.

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Protective effects of caloric restriction on ovarian function

Liangyan SHI ; Aiyue LUO ; Yong TIAN ; Zhiwen LAI ; Jinjin ZHANG ; Shixuan WANG

Chinese Journal of Obstetrics and Gynecology.2013;48(10):745-749. doi:10.3760/cma.j.issn.0529-567x.2013.10.006

Objective To study the protective effects on ovarian function by caloric restriction (CR) and its mechanism.Methods Thirty female C57BL/6 mice of 8 weeks old were randomly divided into two groups,including ad libitum (AL) group and caloric restriction (CR) group.The general situation and ovarian function of those mice were compared and evaluated.Ovarian follicles were counted by hematoxylin-eosin staining.Anti-Miillerian Hormone(AMH) mRNA expression of the ovary were detected by using real-time PCR.The concentrations of serum estradiol,progesterone of the mice were measured by ELISA.And the fertility of mice by mating trials were evaluated,SIRT3,Hypoxia inducible factor 1α (HIF-1α) and catalase (CAT) mRNA expression of the mice ovaries were detected by Real-Time PCR.Results The total follicles were 546 in CR mice and 286 in AL mice.The proportion of primordial follicles were 38.6％ (211/546)in ovaries of CR mice and 29.4％ (84/286)in ovaries of AL mice,which reached statistical difference.The proportion of atretic follicles 5.3％ (29/546) in ovaries of CR mice,compared with 16.8％ (48/286) in AL mice,was significantly decreased (P ＜ 0.05).The AMH mRNA expression in CR mice ovaries was 3.37 times of that of AL mice (P ＜ 0.05).The serum concentration of estradiol in CR mice was up to (5.3 ± 1.6) pmol/L,which was much higher than (3.6 ± 1.6) pmol/L in AL mice.While,the progesterone concentration of (0.4 ±0.3) nmol/L in CR mice was lower than (1.4 ± 0.8) nmol/L in AL mice (P ＜ 0.05).Fertility and survival of offsprings were both improved in CR mice.The expression level of SIRT3 mRNA in CR mice ovary was 1.39 times,CAT was 1.55 times and HIF-1 α was 0.31 times of those in AL mice (P ＜ 0.05).Conclusions Caloric restriction can delay the ovary aging process through reduce follicle depletion by suppressing follicle recruitment and ovulation.The function of ovarian reserve and reproductive endocrine was effectively protected.Caloric restriction can reduce the incidence of follicular atresia,its mechanism might be associated with anti-oxidative stress.

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