A phase II trial of cytoreductive surgery combined with niraparib maintenance in platinum-sensitive, secondary recurrent ovarian cancer: SGOG SOC-3 study / 부인종양

Background@#In China, secondary cytoreductive surgery (SCR) has been widely used in ovarian cancer (OC) over the past two decades. Although Gynecologic Oncology Group-0213 trial did not show its overall survival benefit in first relapsed patients, the questions on patient selection and effect of subsequent targeting therapy are still open. The preliminary data from our pre-SOC1 phase II study showed that selected patients with second relapse who never received SCR at recurrence may still benefit from surgery. Moreover, poly(ADP-ribose) polymerase inhibitors (PARPi) maintenance now has been a standard care for platinum sensitive relapsed OC. To our knowledge, no published or ongoing trial is trying to answer the question if patient can benefit from a potentially complete resection combined with PARPi maintenance in OC patients with secondary recurrence. @*Methods@#SOC-3 is a multi-center, open, randomized, controlled, phase II trial of SCR followed by chemotherapy and niraparib maintenance vs chemotherapy and niraparib maintenance in patients with platinum-sensitive second relapsed OC who never received SCR at recurrence. To guarantee surgical quality, if the sites had no experience of participating in any OC-related surgical trials, the number of recurrent lesions evaluated by central-reviewed positron emission tomography–computed tomography image shouldn't be more than 3. Eligible patients are randomly assigned in a 1:1 ratio to receive either SCR followed by 6 cyclesof platinum-based chemotherapy and niraparib maintenance or 6 cycles of platinum-based chemotherapy and niraparib maintenance alone. Patients who undergo at least 4 cycles of chemotherapy and must be, in the opinion of the investigator, without disease progression, will be assigned niraparib maintenance. Major inclusion criteria are secondary relapsed OC with a platinum-free interval of no less than 6 months and a possibly complete resection. Major exclusion criteria are borderline tumors and non-epithelial ovarian malignancies, received debulking surgery at recurrence and impossible to complete resection. The sample size is 96 patients. Primary endpoint is 12-month non-progression rate.

Expressions of growth factor receptor binding protein 7 and human epidermal growth factor receptor 2 in endometrial carcinoma and their significances / 肿瘤研究与临床

Objective To investigate the expressions of growth factor receptor binding protein 7 (GRB7) and human epidermal growth factor receptor 2 (HER2) in endometrial carcinoma and their clinical significances. Methods Immunohistochemistry was used to detect the expressions of GRB7 and HER2 in 52 endometrial carcinoma tissues, 38 endometrial atypical hyperplasia tissues and 30 normal endometrial tissues collected from patients in the Sixth People's Hospital of Shanghai Jiao Tong University from May 2015 to September 2017. The relationship between the expressions of GRB7 and HER2 and clinicopathological features of endometrial carcinoma patients was analyzed. Results The positive expression rates of GRB7 in endometrial carcinoma, endometrial atypical hyperplasia and normal endometrial tissues were 71.2％ (37/52), 39.5％(15/38), and 13.3％(2/30), respectively, and the difference was statistically significant (χ2=35.14, P<0.05). The positive expression rates of HER2 in endometrial carcinoma, endometrial atypical hyperplasia and normal endometrial tissues were 67.3％ (35/52), 34.2％ (13/38), and 10.0％ (3/30), respectively, and the difference was statistically significant (χ2= 29.360, P< 0.05). The positive expression rates of GRB7 in endometrial carcinoma patients with different clinical stages, histological grades and pathological types were statistically significant (all P<0.05). The positive expression rates of HER2 in endometrial carcinoma patients with different clinical stages, histological grades, lymph nodes metastasis and myometrial invasion were statistically significant (all P< 0.05). The expression of GRB7 in endometrial carcinoma was positively correlated with the expression of HER2 (r=0.375, P<0.05). Conclusion The high expressions of GRB7 and HER2 in endometrial carcinoma are closely related to the malignant degree of endometrial carcinoma.

Preeclampsia serum-induced collagen I expression and intracellular calcium levels in arterial smooth muscle cells are mediated by the PLC-gamma1 pathway

In women with preeclampsia (PE), endothelial cell (EC) dysfunction can lead to altered secretion of paracrine factors that induce peripheral vasoconstriction and proteinuria. This study examined the hypothesis that PE sera may directly or indirectly, through human umbilical vein ECs (HUVECs), stimulate phospholipase C-gamma1-1,4,5-trisphosphate (PLC-gamma1-IP3) signaling, thereby increasing protein kinase C-alpha (PKC-alpha) activity, collagen I expression and intracellular Ca2+ concentrations ([Ca2+]i) in human umbilical artery smooth muscle cells (HUASMCs). HUASMCs and HUVECs were cocultured with normal or PE sera before PLC-gamma1 silencing. Increased PLC-gamma1 and IP3 receptor (IP3R) phosphorylation was observed in cocultured HUASMCs stimulated with PE sera (P<0.05). In addition, PE serum significantly increased HUASMC viability and reduced their apoptosis (P<0.05); these effects were abrogated with PLC-gamma1 silencing. Compared with normal sera, PE sera increased [Ca2+]i in cocultured HUASMCs (P<0.05), which was inhibited by PLC-gamma1 and IP3R silencing. Finally, PE sera-induced PKC-alpha activity and collagen I expression was inhibited by PLC-gamma1 small interfering RNA (siRNA) (P<0.05). These results suggest that vasoactive substances in the PE serum may induce deposition in the extracellular matrix through the activation of PLC-gamma1, which may in turn result in thickening and hardening of the placental vascular wall, placental blood supply shortage, fetal hypoxia-ischemia and intrauterine growth retardation or intrauterine fetal death. PE sera increased [Ca2+]i and induced PKC-alpha activation and collagen I expression in cocultured HUASMCs via the PLC-gamma1 pathway.

Clinical value of hCG ratio of blood in peritoneal cavity versus venous blood in diagnosis of ectopic pregnancy / 中华妇产科杂志

Objective To study the value of hCG ratio of blood in peritoneal cavity versus venous blood (RPhCG/VhcG) in diagnosis of early ectopic pregnancy (EP).Methods From Mar.2009 to Oct.2012,268 cases with EP (EP group) and 53 women with intrauterine pregnancy with haemoperitoneum (hIUP) (hIUP group) from International Peace Maternity and Child Health Hospital of Shanghai Jiaotong University School of Medicine,Shanghai 6th People Hospital and Shanghai Jiangwan Hospital were enrolled in this prospective study.The HCG of all subjective were measured in blood in peritonea cavity and venous blood,then calculate the ratio of RPhCG/VhCG.Scatter point analysis and ROC were used to differentiate EP,determine threshold of hlUP and evaluate the sensitivity,specificity and accuracy in diagnosis EP preoperatively.Results The mean RPhCG/VhCG; of EP group was 4.35,which was significantly higher than 0.81 in hIUP group (P ＜ 0.01).Scatter point analysis showed that the threshold value of RPhCG/VhCG between ectopic pregnancy and hIUP was 1.0.The overall sensitivity of RPhCG/VhcG in the diagnosis of EP was 98％,the specificity was 100％,the positive predictive value was 100％ and the negtive predictive value was 93％.Conclusion RPhCG/VhCG ＞ 1.0 could be used to diagnose and differentiate EP from hIUP accurately.

Impact of bilateral ovariectomy on climacteric symptoms in post-menopausal women / 上海交通大学学报（医学版）

Objective To evaluate the impact of bilateral ovariectomy in post-menopausal women by comparison of climacteric symptoms before and after operation. Methods Post-menopausal women who received hysterectomy with concurrent bilateral ovariectomy on benign uterine indications were recruited.Climacteric symptoms before and after operation were accessed by a questionaire including modified Kupperman Index.Comparison was made after grouping the patients into early menopause group,whose menopausal period was no more than 5 years,and late menopause group,whose menopausal period was more than 5 years. Results Among a total of 95 individuals,8 had normal,46 had mild,34 had moderatc,and the other 7 had severe Kupperman Index scores before operation,while 5 had normal,28 had mild,48 had moderate,and the other 14 had severe Kupperman Index scores after operation,with more moderate and severe climacteric symptoms after operation than before operation(P<0.05).Women of early menopause group had higher total Kupperman Index scores and symptom scores of sweating,insomnia,depression,fatigue and headache than those of late menopause group before operation(P<0.05).Women of early menopause group had significantly higher Kupperman Index scores after operation than before operation(23.93±7.53 vs 17.63±8.07,P<0.05).However,there was no significant difference in total Kupperman Index scores in women of late menopause group before and after operation. Conclusion Bilateral ovariectomy may affect the climacteric symptoms in post-menopausal women,especially in early menopausal period.

Effects of preeclampsia serum on activity and invasive ability of cultured cytotrophoblasts of first trimester of pregnancy / 上海交通大学学报（医学版）

Objective To investigate the effects of preeclampsia serum on activity and invasive ability of cultured cytotrophoblasts of first trimester of pregnancy. Methods Cytotrophoblasts of normal 6 to 8-week pregnancy were cultured by tissue explants adherent method,and were incubated with serum of women with normal pregnancy(normal group)and preeclampsia(preeclampsia group),respectively for 24 h.The activity of cytotrophoblasts was examined by CCK-8,invasive ability was determined by Transwell invasion assay,and expression of MMP-2,MMP-9 and PAI-1 mRNA was detected by reverse transcription-polymerase chain reaction(RT-PCR). Results The activity and invasive ability of cytotrophoblasts in preeclampsia group were lower than those in normal group(P<0.05,P<0.01).Compared with normal group,the expression of MMP-2 and MMP-9 mRNA of cytotrophoblasts was significantly lower(P<0.01),and the expression of PAI-1 mRNA was significantly higher(P<0.01).In both groups,the expression of MMP-2 mRNA was negatively related to that of PAI-1 mRNA(r=-0.985,P<0.01;r=-0.933,P<0.05),while there was no correlationship between the expression of MMP-9 mRNA and that of PAI-1 mRNA. Conclusion The preeclampsia serum may affect the invasive ability of cytotrophoblasts by regulating the expression of MMP-2,MMP-9 and PAI-1.

Effects of ethinylestradiol and cyproterone acetate on endocrine metabolism in non-obese women with polycystic ovary syndrome / 上海交通大学学报（医学版）

Objective To investigate the effects of ethinylestradiol and cyproterone acetate tablets(Diane-35)on endocrine metabolism in non-obese women with polycystic ovary syndrome(PCOS). Methods Fifty-three non-obese patients with PCOS were assigned to the 6-month treatment with Diane-35.Body mass index(BMI),waist to hip ratio(WHR),F-G score and acne score were recorded before treatment and at the end of the third and sixth cycle after treatment.Serum total testosterone,follicle stimulating hormone(FSH),luteinizing hormone(LH),LH/FSH,fast plasma glucose,fast insulin and insulin resistance index(HOMA-IR)were obtained at early follicular phase and at the end of the third and sixth month.Results There was no significant change in BMI and WHR after treatment.Compared with those before treatment.F-G score,acne score,serum total testosterone,LH and LH/FSH were significantly decreased at two time points after treatment (P<0.05).BMI and HOMA-IR in patients with insulin resistance were significantly higher at the end of the sixth cycle after treatment than those before treatment(P<0.05). Conclusion Diane-35 can improve hyperandrogenism in non-obese patients with PCOS.However,Diane-35 may aggravate insulin resistance in those with insulin resistance.

Characteristics of pelvic diaphragm hiatus in pregnant women with stress urinary incontinence detected by transperineal three-dimensional ultrasound / 中华妇产科杂志

Objective To identify the morphological characteristics of pelvic diaphragm hiatus in pregnant women with stress urinary incontinence ( SUI) by transperineal three-dimensional (3-D) ultrasound.Methods From Oct.2008 to Mar.2009,145 pregnant women (third trimester group) at 37-41 weeks of gestation underwent transperineal 3-D ultrasound investigation at Department of Obstetrics and Gynecology,the Sixth People's Hospital,Shanghai Jiaotong University,including 38 pregnant women with stress urinary incontinence (SUI) and the other 107 non SUI pregnant women.In the mean time,50 normal nulliparous healthy women were chosen as control group.The morphological characteristics of pelvic diaphragm hiatus,the diameter of pelvic diaphragm hiatus,pubovisceral muscle thickness and genitohiatal and levator ani angle were measured at rest,on maximum Valsalva and maximum pelvic floor contraction by 3-D ultrasound,respectively.Results Loosen connective tissue and pubococcygeus avulsion were observed in some pregnant women at third trimester.The area of pelvic diaphragm hiatus were (15.2 ±1.9),(16.4 ± 2.0) and (13.6±1.9) cm2,pubovisceral muscle thickness were (0.72 ±0.11),(0.68 ±0.14) and(0.77 ±0.11) cm,levator ani angle were (60 ±8) °,(57±10) ° and (64 ± 14)° at rest,on maximum Valsalva and maximum pelvic floor contraction respectively.These parameters were significantly increased than those in control group[(11.2 ±2.6),(14.5 ±4.5) and (9.2 ±2.6) cm2; (0.66 ±0.10),(0.67 ± 0.14) and (0.71 ±0.14) cm; (50 ±4) °,(51 ±5) ° and (46 ±5)°]at three maneuvers,respectively ( P <0.05).And those parameters of the anteroposterior hiatal diameter,lateral hiatal diameter,perimeter of pelvic diaphragm hiatus and area of pelvic diaphragm hiatus in SUI pregnant women were increased than those in non SUI pregnant women at three maneuvers,respectively (P < 0.05 ).Pubovisceral muscle thickness in SUI pregnant women was significantly lower than that in non SUI pregnant women at maximum pelvic floor contraction (P < 0.05 ),but there were not significant difference between SUI and non SUI pregnant women at rest and on maximum Valsalva in pubovisceral muscle thickness and genitohiatal and levator ani angle (P >0.05).Conclusions Pelvic floor anatomic remodeling is identified in late pregnant women.When compared with non pregnant women,the loosen pelvic floor connective tissue and the bigger diameters of pelvic diaphragm are observed in late pregnant women.It is observed that the increased diameters of pelvic diaphragm and decreased thickness of pubovisceral muscle in later pregnant SUI women than those in non SUI pregnant women.

Levels of soluble endoglin in peripheral blood and intervillous space blood of patients with preeclampsia / 上海交通大学学报（医学版）

Objective To study the levels of soluble endoglin (sEng) in peripheral blood and intervillous space blood of patients with preeclampsia, and analyse the correlation between levels of sEng and clinical performance. Methods Levels of sEng in peripheral blood and intervillous space blood of 22 patients with preeclampsia (preeclampsia group, 12 cases of severe preeclampsia and 10 cases of mild preeclampsia) were detected by ELISA, and the correlation between levels of sEng and blood pressure, 24 h urine protein and fetal birth weight was analysed. Twenty-two normal pregnant women were served as control group. Results The sEng levels in peripheral blood and intervillous space blood of preeclampsia group were significantly higher than those of control group [ (31.89 ± 8.80) ng/mL vs (5.24 ± 1.60) ng/mL, P < 0.01; ( 37.74 ± 7.12) ng/mL vs (6.63 ±1.76) ng/mL, P < 0.01]. In preeclampsia group, the sEng levels in peripheral blood and intervillous space blood of severe preeclampsia were significantly higher than those of mild preeclampsia (P <0.01). In preeclampsia group, the sEng level in peripheral blood was significantly correlated with that in intervillous space blood of preeclampsia group (r = 0.876, P < 0.01) , neither was significantly correlated with blood pressure (P > 0.05), both were significantly correlated with 24 h urine protein (r = 0.729, P < 0.01; r = 0.743, P < 0.01) , and both were significantly correlated with fetal birth weight (r = - 0.736, P < 0.01; r = - 0.707, P < 0.01). Conclusion Levels of sEng in peripheral blood and intervillous space blood of patients with preeclampsia are significantly higher than those of normal pregnant women, and the levels of sEng are significantly correlated with the clinical performance of preeclampsia.