Evaluation of pelvic floor muscle function (PFMF) in cervical cancer patients with Querleu-Morrow type C hysterectomy: a multicenter study.

INTRODUCTION: To evaluate the pelvic floor muscle function (PFMF) of cervical cancer patients after type QM-C hysterectomy and to explore the relationship between decreased PFMF and related factors. METHODS: This was a multi-centered retrospective cohort study. 181 cervical cancer patients who underwent type QM-C hysterectomy were enrolled from 9 tertiary hospitals. Strength of PFMF were measured using neuromuscular apparatus (Phenix U8, French). Risk factors contributing to decreased PFMF were analyzed by univariate and multivariate ordinal polytomous logistic regression. RESULTS: Totally 181 patients were investigated in this study. 0-3 level of type I muscle fibre strength (MFSI) was 52.6% (95/181), 0-3 level of type IIA muscle fibre strength (MFSIIA) was 50% (91/181). Subjective stress urinary incontinence was 46% (84/181), urinary retention was 27.3% (50/181), dyschezia was 41.5% (75/181), fecal incontinence was 9% (18/181). ① MFSI: Multivariate ordinal polytomous logistic regression shows that the follow-up time (p < 0.05), chemotherapy and radiotherapy (p = 0.038) are independent risk factors of MFSI's reduction after type QM-C hysterectomy. ② MFSIIA: multivariate ordinal polytomous logistic regression shows that the follow-up time (p < 0.05) are independent risk factors of MFSIIA's reduction after type QM-C hysterectomy. The pelvic floor muscle strength (PFMS) increased after 9 months than in 9 months after operation, which showed that the PFMS could be recovered after operation. CONCLUSIONS: We advocate for more attention and emphasis on the PFMF of Chinese female patients with cervical cancer postoperation. PEKING UNIVERSITY PEOPLE'S HOSPITAL: PFMF after QM-C hysterectomy has not been analyzed by current study. The contribution is that patients with radical hysterectomy should do pelvic floor rehabilitation exercises in 3 months after operation. Clinical Trails NCT number of this study is 02492542.

Association of pelvic floor function with postoperative urinary incontinence in cervical cancer patients after the radical hysterectomy.

AIMS: To assess the pelvic floor function in cervical cancer patients after radical hysterectomy and its relationship with urinary incontinence (UI). METHODS: Cervical cancer patients who underwent radical hysterectomy were recruited from 18 hospitals in China from January 2012 to March 2015. Pelvic floor examinations were conducted by measuring the pelvic floor muscle strength, fatigue of pelvic floor muscle fatigue, dynamic pressure of vaginal, nerve injury, A3 feedback, muscle potential, static tension, and dynamic tension. Postoperative urinary incontinence (UI) was identified using the International Consultation on Incontinence Questionnaire. Multivariable logistic regression analysis was used to assess the association of pelvic floor function examination results with postoperative UI. RESULTS: Totally 169 patients were included in this study. The prevalence of UI was 39.6% (67/169). The proportion of abnormal fatigue of Type I muscle (64% vs. 36%, p = .04) and abnormal A3 feedback (53.9% vs. 46.1%, p = .03) were higher among patients with postoperative UI compared to those without UI. In the multivariable analysis, abnormal fatigue of Type I muscle (odds ratio [OR] = 3.73, 95% confidence interval [CI]: 1.42-9.84), abnormal A3 feedback (OR = 2.40, 95% CI: 1.04-5.51), and length of resected vagina > 3 cm (OR = 3.44, 95% CI: 1.27-9.31) were associated with postoperative UI. Compared to laparoscopy, laparotomy was less likely to cause postoperative UI (OR = 0.12, 95% CI:0.04-0.33). CONCLUSIONS: The abnormal function of the pelvic floor muscle is related to postoperative UI. Early assessment among these patients is needed to prevent the development of pelvic floor disorder postoperatively.

Fertility preservation in patients with uterus didelphys and endometrial carcinoma: a case report.

BACKGROUND: Endometrial cancer combining uterus didelphys is quite rare clinically which partially explains that there is no discussion about young patients' fertility preservation and follow up of tumor outcome. CASE PRESENTATION: In this article, we report a case of unilateral endometrial carcinoma found in a young patient with uterus didelphys who was treated with high-efficiency progesterone due to unfinished child-bearing. During the follow-up, the affected uterine endometrium was not reversed by progesterone. So, the patient underwent the abdominal surgery with the left uterus and left fallopian tube resection. We performed three consecutive immunohistochemical studies of the contralateral uterine endometrium to verify the safety of preserving the contralateral uterus and its appendages which preserved her fertility. CONCLUSIONS: Endometrial cancer occurring in patients with uterus didelphys is quite rare in child-bearing age. In this case report, we preserved the patient's contralateral uterus based on patient's strong needs and negative IHC analysis of the preserved side uterine endometrium. However, the tumor and fertility outcome require more follow-up.

Assessment of Pelvic Floor Function and Quality of Life in Patients Treated for Cervical Cancer: A Multicenter Retrospective Study.

OBJECTIVES: Our study aimed to evaluate the quality of life (QoL) and pelvic floor function of cervical cancer (CC) patients after treatment. DESIGN: This was a cross-sectional observational cohort study. PARTICIPANTS: The participants included in this study were CC patients who underwent radical hysterectomy (RH) from 2012 to 2018 at 18 medical centers across China. METHODS: The validated versions of the Pelvic floor Distress Inventory-Short Form 20, Overactive Bladder Symptom Score, and Euro Qol Five-Dimension questionnaires were used to evaluate postoperative pelvic floor dysfunction (PFD) and QoL. RESULTS: A total of 689 CC patients were enrolled. The incidence of stress urinary incontinence (SUI), incomplete urinary emptying, and constipation were 32.7, 27.7, and 28.6%, respectively. Multivariate analysis confirmed that laparoscopic RH (LRH) and vaginal wall resection greater than 3 cm were risk factors for lower urinary tract symptoms (LUTS). LRH and chemotherapy were risk factors for SUI. Chemoradiotherapy and LRH were risk factors for overactive bladder (OAB). A high body mass index and LRH were risk factors for more severe defecation symptoms. ARH and large amount of operative blood loss were risk factors for poor QoL. CONCLUSION: PFD is common in CC patients after treatment. LRH seems to increase the postoperative distress, including LUTS and defecation symptoms. Postoperative urinary incontinence and OAB are more bothersome for patients undergoing chemotherapy and radiotherapy. We recommend evaluating pelvic floor function as a standard assessment during follow-up.

[Expression of Notch1, Jagged1 and NICD in epithelial ovarian carcinomas and a preliminary study on the activity of gamma-secretase in epithelial ovarian carcinoma cell lines].

OBJECTIVE: To study the expression of Notch1, Jagged1 and Notch intracellular domain (NICD)in epithelial ovarian carcinoma tissues and analyze the clinical significance. To explore the activity of γ-secretase in epithelial ovarian carcinoma cell line SKOV3 and the effect of N-[N-(3, 5-dil uorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT), a γ-secretase inhibitor on the activity of γ-secretase in SKOV3. METHODS: Immunohistochemistry staining method was performed in 43 patients with epithelial ovarian carcinoma and 11 patients with benign epithelial ovarian tumor to detect the expression of Notch1, Jagged1 and NICD. The differences of expressionof Notch1, Jagged1 and NICD between malignant and benign ovarian tumors was compared and alsoanalyzed the correlation with clinicopathological parameters of ovarian carcinoma. Human serous ovarian cancer cell line SKOV3 and immortalized nontumorigenic ovarian epithelial cell line T29 were incubated in vitro. The activities of γ-secretase in SKOV3 and T29 with dimethyl sulfoxide (DMSO) and DAPT were detected respectively by Gal4-VP16/UAS and dual luciferase reporter assay system. RESULTS: (1) The immunohistochemical composite scores (ICS) of Notch1 in epithelial ovarian carcinoma (6.7 ± 2.2) were not significantly different with those in benign epithelial ovarian tumor (5.4 ± 2.7, P = 0.153), while the ICS of Jagged1 and NICD in epithelial ovarian carcinoma (5.3 ± 2.4, 5.3 ± 2.3)were higher than those in benign epithelial ovarian tumor (1.6 ± 1.4, 3.1 ± 1.7; all P < 0.01). The expression of Notch1, Jagged1 and NICD had no correlation with patients' aged, history of carcinoma, ascites, the level of serum CA125, maximum length of ovarian tumor, Federation International of Gynecology and Obstetrics (FIGO) stage, grade and pathology subtypes (all P > 0.05). The hazard ratio between the high expression of Notch1, Jagged1, or NICD and the moderate to low expression of Notch1, Jagged1, or NICD, and Jagged1 were 0.771, 1.648 and 1.316, respectively (all P > 0.05). The 5-year survival rate and median survival time between the high expression of Notch, Jagged1 or NICD in subgroup and moderate to low expression in subgroup were of no difference (all P > 0.05). The activity of γ-secretase in SKOV3 was significantly higher than that in T29([ 12.2 ± 1.4)%, P = 0.019]. (2) After DAPT treated, the relative activity of γ-secretase in SKOV3 (50 µmol/L) was declined from (100.0 ± 5.3)% to(6.6 ± 0.8)% (P = 0.001). CONCLUSIONS: Jagged1 and NICD in Notch1 pathway may play a key role in the occurrence of ovarian carcinoma. The activity of γ-secretase in epithelial ovarian carcinoma was higher than that in ovarian epithelial cell which suggest that DAPT, γ-secretase inhibitor, may become the target of ovarian carcinoma treatment.

[Clinical application of perforator flap in extended radical vulvectomy of vulvar carcinoma].

OBJECTIVE: To evaluate the clinical application of perforator flap in extended radical vulvectomy of vulvar carcinoma. METHODS: Retrospectively, twelve cases of vulva carcinoma were treated by radical extensive excision, and the defects were repaired with perforator flap. RESULTS: All the flaps were survived and healed with first intention except one infection. The wound infection patient was treated with change of the dressing and antibiotics. The reconstructed vulvae were plump and elastic. It appeared like the normal vulvae and there was no contraction of the vagina. CONCLUSIONS: Vulvar reconstruction with the perforator flap after the radical vulvectomy could make the patients recover easily, which produces almost normal appearance and function of the vulvae, reduces the time of wound healing, the patient could get the next therapy more quickly and the quality of life improving. It has wide clinical application value.

Senaparib as first-line maintenance therapy in advanced ovarian cancer: a randomized phase 3 trial.

Poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors as maintenance therapy after first-line chemotherapy have improved progression-free survival in women with advanced ovarian cancer; however, not all PARP inhibitors can provide benefit for a biomarker-unselected population. Senaparib is a PARP inhibitor that demonstrated antitumor activity in patients with solid tumors, including ovarian cancer, in phase 1 studies. The multicenter, double-blind, phase 3 trial FLAMES randomized (2:1) 404 females with advanced ovarian cancer (International Federation of Gynecology and Obstetrics stage III-IV) and response to first-line platinum-based chemotherapy to senaparib 100 mg (n = 271) or placebo (n = 133) orally once daily for up to 2 years. The primary endpoint was progression-free survival assessed by blinded independent central review. At the prespecified interim analysis, the median progression-free survival was not reached with senaparib and was 13.6 months with placebo (hazard ratio 0.43, 95% confidence interval 0.32-0.58; P < 0.0001). The benefit with senaparib over placebo was consistent in the subgroups defined by BRCA1 and BRCA2 mutation or homologous recombination status. Grade ≥3 treatment-emergent adverse events occurred in 179 (66%) and 27 (20%) patients, respectively. Senaparib significantly improved progression-free survival versus placebo in patients with advanced ovarian cancer after response to first-line platinum-based chemotherapy, irrespective of BRCA1 and BRCA2 mutation status and with consistent benefits observed between homologous recombination subgroups, and was well tolerated. These results support senaparib as a maintenance treatment for patients with advanced ovarian cancer after a response to first-line chemotherapy. ClinicalTrials.gov identifier: NCT04169997 .

[Efficacy of postoperative simple chemotherapy and concurrent chemoradiotherapy in FIGO stage IB2-IIB cervical cancer].

OBJECTIVE: To evaluate the effectiveness of neoadjuvant chemotherapy (NAC) followed by radical hysterectomy plus postoperative chemotherapy but no radiotherapy for stage IB2-IIB cervical cancer. METHODS: Seventy-nine patients with stage IB2-IIB cervical cancer were treated with NAC followed by radical hysterectomy. According to different adjuvant therapies, patients were divided into postoperative chemotherapy group (47 cases) and postoperative radiotherapy/concurrent chemoradiotherapy group (32 cases). Regimens for NAC and postoperative chemotherapy were BIP (bleomycin+ ifosfamide+ cisplatin/carboplatin) or TP (paclitaxel+ cisplatin/carboplatin). An average of 1.1±0.3 cycles of NAC and 3.4±1.2 cycles of postoperative chemotherapy were prescribed. RESULTS: Toxicities due to chemotherapy were generally tolerable. Overall response rate of NAC was 88.6%. With a median follow-up period of 42 months, the three-year progression-free survival rates of the two groups were 88.5% and 84.3%, the total survival rates were 90.3% and 86.4%, respectively. There was no statistically significant difference. The recurrent rates were 10.6% and 21.8% in the two groups. In the absence of radiotherapy, pelvic recurrence was observed in two patients; the other three had distant metastases. CONCLUSION: The results indicate that NAC followed by surgery plus postoperative chemotherapy but no radiotherapy offers a viable option in the treatment of stage IB2-IIB cervical cancer. The patients can tolerate the side effects of chemotherapy with better efficacy.

[Results of different postoperative adjuvant therapies for stage Ib-IIa cervical carcinoma with risk factors].

OBJECTIVE: To investigate the effects of postoperative adjuvant chemotherapy (CT) and chemoradiotherapy (CRT) or radiotherapy(RT) for Ib-IIa cervical cancer with risk factors. METHODS: From March 1995 to June 2010, there were 137 patients underwent radical hysterectomy and systematic pelvic lymphadenectomy for stage Ib-IIa cervical cancer admitted at Peking University First Hospital. These patients had risk factors, intermediate risk factors including bulky tumor ( > 4 cm) , lymph vascular space invasion, deep stromal invasion; high risk factors including positive surgical margin, parametrial invasion, lymph node involvement. Of the all patients, 79 cases of them were treated with CT, 58 of them were treated with RT or CRT. The 5-year survival and prognosis factors were analyzed retrospectively, the prognosis was compared between two adjuvant therapy groups. RESULTS: The univariate analysis shown that types of pathology, different grade of risk factors, stroma invasion and lymph node involvement were prognostic factors of 5-year overall survival. Patients with squamous cell carcinoma, intermediate risk factors, no parametrial invasion, and no lymph node involvement had better prognosis(P < 0.05). Whether patients with high-risk factors or intermediate-risk factors, the 5-year overall survival and 3-year disease-free survival had no difference between CT and RCT or RT groups respectively. Cox regression multivariate analysis of survival indicated that clinical stages, types of histology, different grade of risk factors were independent prognostic indicator. Patients with early stage, squamous cell carcinoma, intermediate risk factors had better prognosis. Univariate and multivariate analysis indicated that different postoperative adjuvant therapies had no effects on the prognosis. The 5-year overall survival was 88.6% in patients treated with CT, and 89.7% in patients treated with RT or CRT (P = 0.455) . CONCLUSION: There are equivalent therapeutic results between CT and RT or CRT for patients with risk factors after radical surgery, CT may be as one choice of postoperative adjuvant therapy for stage Ib-IIa cervical carcinoma with risk factors.

[Clinical features and drug resistance characteristics of ovarian clear cell adenocarcinoma and analysis of its prognostic factors].

OBJECTIVE: To investigate the clinical features and factors involved in the drug resistance and prognosis of ovarian clear cell adenocarcinoma (OCCA). METHODS: Forty-seven OCCA patients and 53 ovarian serous cyst adenocarcinoma (OSCA) patients were included in this study. Their clinical characteristics, drug resistance, and prognostic factors were analyzed. RESULTS: The onset age of OCCA was (49.09 + 11.80) years old, and that of OSCA was (55.51 + 1.38) year old. There were 53.3% (24/45) of OCCA and 98.0% (50/51) of OSCA patients who had elevated CA125 levels. There were 46.8% (22/47) of OCCA patients and 7.5% (4/53) of OSCA patients who suffered from endometriosis (EMS). The percentage of early stage (stage I and stage II) OCCA was 80.9% (38/47), and that of OSCA was 11.3% (6/53). A statistically significant difference was observed on all these aspects (P < 0.05). The percentage of drug resistant OCCA was 26.1% (12/46), and that of OSCA was 24.0% (12/50), with a non-significant difference (P = 0.814).Among the patients with advanced stage disease, the percentage of drug resistance was 87.5% (7/8) for OCCA, while that of OSCA was 25.0% (11/44), showing a statistically significant difference (P = 0.003). Multiple logistic regression analysis revealed that OCCA (OR = 21.774, 95%CI: 2.438 to 194.431) and advanced stage (OR = 58.329, 95%CI: 5.750 to 591.703) were independent risk factors of drug resistance in ovarian epithelial cancers. For the advanced stage patients, the median overall survival time of OCCA and OSCA were 11 and 29 months, respectively, with a statistically significant difference (P = 0.000). Cox survival analysis showed that OCCA, advanced stage, suboptimal surgery, fewer than 6 cycles of chemotherapy and drug resistance were all risk factors of OS in ovarian cancer patients (P < 0.05). CONCLUSIONS: The age of onset in OCCA patients is younger than that of OSCA patients. The proportion of combination with endometriosis (EMS) is higher, and more early stage disease is observed in OCCA patients. The percentage of drug resistant in OCCA is higher, especially in advanced stage patients. The prognosis of advanced stage OCCA patients is poorer than that of OSCA patients in advanced stage.

Analysis of the Vulvar Skin Microbiota in Asymptomatic Women and Patients With Vulvar Lichen Sclerosus Based on 16S rRNA Sequencing.

Vulvar lichen sclerosus (VLS) is a chronic inflammatory skin disease that brings life-long and psychological distress to patients. It remains unclear whether this condition is related to changes in the skin microbial community. The aim of this study was to evaluate the compositional characteristics of the vulvar skin microbiota between VLS patients and asymptomatic postmenopausal women. We included 60 cases of postmenopausal patients in the outpatient vulvar clinic of Peking University First Hospital from August 2020 to October 2020. Thirty-one patients were diagnosed with VLS by vulvar skin biopsy (VLS group), while 29 women were asymptomatic volunteers (control group). DNA was extracted from vulvar skin swabs of the VLS and control groups. The V3-V4 fragments of 16S rRNA were targeted for high-throughput sequencing and gene sequence analysis. The sequencing results were analysed by α diversity, ß diversity, species composition, LEfSe analysis to compare the compositional differences of the vulvar skin microbiota between the two groups. Our study revealed that at the phylum level, patients with VLS had a lower relative abundance of Firmicutes (p < 0.0001) and a higher relative abundance of Proteobacteria than the control group (p < 0.0001). At the genus level, Lactobacillus spp. accounted for the largest proportion of the microflora in the asymptomatic controls, while the proportion of Prevotella spp. in the VLS group was the highest. In the VLS group, the relative abundance of Finegoldia spp., Ralstonia spp., Peptoniphilus spp., Anaerococcus spp., Campylobacter spp., Providencia spp. Kelbsiella spp., Ezakiella spp., and Escherichia-Shigella spp. was significantly increased compared with the control group. Although there was no significant difference in the α diversity of the vulvar skin microbiota, the ß diversity differed significantly between the two groups.

Long-Term Effect of Early Post-operative Transcutaneous Electrical Stimulation on Voiding Function After Radical Hysterectomy: A Multicenter, Randomized, Controlled Trial.

Introduction: Post-radical-hysterectomy (RH) patients suffer from a series of problems resulting from neurovascular injury, such as bladder dysfunction, which reduce their quality of life. We have designed this study to evaluate the efficacy of transcutaneous electrical stimulation (TENS) on patient rehabilitation after RH for early cervical cancer. Materials and methods: A total of 97 patients were enrolled in a randomized-controlled trial (from January 2015 to December 2019) involving 7 medical centers nationwide. Patients were assigned to either the intervention group (n = 46), or the control group (n = 51). TENS was given to patients in the intervention group from the 7th day after surgery for a total of 14-21 days. The control group received no TENS. Primary outcomes were measured for residual urine volume and recovery of urination function. Secondary outcomes were measures for urodynamics (UDS), pelvic floor electromyography function examination (PFEmF), and quality of life (QoL). Results: Residual urine volume and improvement in the rate of urination were found to show no significant differences on the 14th, 21st, and 28th days after surgery. The maximum flow rate (Qmax) in the intervention group was significantly higher than that in the control group on the 28th day, but there were no significant differences in average flow rate, voiding time, time to Qmax, muscle fiber strength, muscle fiber fatigue, and the abnormal rate of A3 reflection on the 28th day and the 3rd mo., as well as in the QoL at 3rd mo., 6th mo., and 12th mo. after surgery. Conclusion: Our study showed no sufficient evidence to prove that TENS under the trialed parameters could improve the subject's voiding function, PFEmF, and QOL after RH. This has provided valuable data for rehabilitation after RH. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02492542.

[Expression of Notch3 and Notch intracellular domain in ovarian carcinoma and effect of N-[N-(3,5-difluorophenyl) acetyl-L-alanyl]-S-phenyl glycine t-butyl ester on ovarian carcinoma cell].

OBJECTIVE: To study the expression and clinical significance of Notch3 and Notch intracellular domain (NICD) in ovarian carcinoma and the effects of N-[N-(3,5-difluorophenyl) acetyl-L-alanyl]-S-phenyl glycine t-butyl ester (DAPT), a γ-secretase inhibitor on the proliferation and apoptosis in OVCAR3, A2780 ovarian carcinoma cell lines. METHODS: Western blot was used to detect the expression of NICD in the tissues from 58 ovarian carcinomas patients and 21 normal ovarie, who were admitted in Peking University First Hospital from July 2006 to June 2009.Immunohistochemistry was also used to detect the expression of Notch3 in these tissues. The relationship with clinical features of ovarian carcinoma was also analyzed. Proliferation of OVCAR3 and A2780 ovarian cancer cells was determined by methyl thiazolyl tetrazolium (MTT) assay, cell cycles and apoptosis and index of proliferation were detected by flow cytometry method. The expression of NICD in OVCAR3 and A2780 cells incubated with DAPT was detected by western blot. RESULTS: (1) The expression level of NICD in ovarian carcinomas was significantly higher than that in normal ovarian tissues (1.64 ± 0.19 vs. 0.98 ± 0.20; P < 0.05). The NICD expression was higher in ovarian cancers with low grade or advanced stage than those in high-middle grade or early stage, respectively (1.90 ± 0.22 vs. 1.25 ± 0.21, 1.80 ± 0.21 vs. 1.21 ± 0.15; all P < 0.05). The Notch3 protein was stained positively in cytoplasm, nuclear and cell membrane. The expression of Notch3 was higher in ovarian carcinomas than that in normal ovaries [78% (45/58) vs. 24% (5/21); P < 0.01]. While, there were no stasistical difference in different pathological types, stages, differentiation of ovarian carcinoma. There was no difference between the patients with adjuvant chemotherapy or not. (2) After OVCAR3 and A2780 cells incubated with DAPT 24, 48, 72 hours, NICD expression was significantly lower than that in control group (P < 0.05). The effects of DAPT inhibited the proliferation and prompted the apoptosis of OVCAR3 and A2780 cells were depended on the concentrations and times. CONCLUSIONS: Notch3 and NICD may play a key role in the occurrence and progress of ovarian carcinoma. The mechanism of DAPT inhibited the proliferation and prompted the apoptosis of OVCAR3 and A2780 cells may be due to decreased the formation of NICD.

Urodynamic assessment of bladder storage function after radical hysterectomy for cervical cancer.

BACKGROUND: After radical hysterectomy for cervical cancer, the most common complication is lower urinary tract symptoms. Post-operatively, bladder capacity can alter bladder function for a prolonged period. This study aimed to identify factors affecting bladder storage function. METHODS: A multicenter, retrospective cohort study was conducted. Information of patients with stages IA2 to IIB cervical cancer with urodynamic study results were retrospectively collected from nine hospitals between June 2013 and June 2018 according to the inclusion criteria. Demographic, surgical, and oncological data were collected. The univariate and multivariate logistic regression was used to identify clinical factors associated with bladder storage function. RESULTS: Two hundred and three patients with cervical cancer had urodynamic testing post-operatively. Ninety-five (46.8%) patients were diagnosed with stress urinary incontinence (SUI). The incidence of low bladder compliance (LBC) was 23.2%. Twenty-seven (13.3%) patients showed detrusor overactivity (DO). Fifty-seven patients (28.1%) presented with a decreased maximum cystometric capacity (DMCC). The probability of composite bladder storage dysfunction was 68.0%. Multivariate analysis confirmed that laparoscopy represents a protective factor for SUI with an odds ratio of 0.498 (P = 0.034). Patients who underwent a nerve-sparing procedure were less odds to experience SUI (P = 0.014). A significant positive correlation between LBC and DO was observed (P < 0.001). A greater length of the resected vagina and chemoradiotherapy were common risk factors for LBC and DO, while radiotherapy exerted a stronger effect than chemotherapy. Additionally, patients who received chemoradiotherapy frequently developed a DMCC. The follow-up time was not correlated with bladder storage function. CONCLUSION: A nerve-sparing procedure without longer resected vagina is recommended for protecting the bladder storage function.

[Effects of postoperative chemotherapy on the prognosis of patients with high-risk early stage endometrial cancer].

OBJECTIVE: To investigate the effects of adjuvant chemotherapy for patients with high-risk stage I and II (early stage) endometrial cancer. METHODS: From Jan. 1994 to Jun. 2007, 106 cases with early stage high-risk endometrial cancer were treated in Peking University First Hospital and were divided into two groups based with postoperative adjuvant chemotherapy (ACT group, 66 cases) and without adjuvant chemotherapy (control group, 40 cases). The 5-year survival rates was calculated by Kaplan-Meier method. Prognosis factors were further determined by univariate analysis and Cox proportional hazards models. RESULTS: The 5-year survival rate in the ACT group was significantly higher than that in control group (94% and 81%, P<0.05). On the univariate analysis, the 5-year survival rate of patients received four or more cycles combined chemotherapy was higher than that of cases less than four cycles chemotherapy (100% and 86%, P<0.05). While, it were not significant difference in age, stage, histology, grade, radiotherapy alone, chemotherapy combined radiotherapy or progestin hormonal therapy (P>0.05). On the multivariate analysis, adjuvant chemotherapy was found to affect independent prognostic covariates on early stage cases (P<0.05). CONCLUSION: Postoperative adjuvant chemotherapy maybe improve the prognosis of patients with high-risk early stage endometrial cancer, which need to be further study by prospective randomized trials.

[Expression of Notch intracellular domain in cervical cancer and effect of DAPT on cervical cancer cell].

OBJECTIVE: To study the expression and clinical significance of Notch intracellular domain (NICD) in cervical cancer and the effects of N-[N-(3,5-difluorophenyl)acetyl-L-alanyl]-S-phenyl glycine t-butyl ester (DAPT), a gamma-secretase inhibitor on the proliferation and apoptosis of cervical cancer cell lines. METHODS: Western blot was used to detect the expression of NICD in the tissues of 40 cervical cancers and 21 normal cervix and its relationship with clinical features of cervical cancer was also analyzed. Proliferation of SiHa and HeLa cervical cells was determined by methyl thiazolyl tetrazolium (MTT) assay, cell cycles and apoptosis and index of proliferation were detected by flow cytometry method. The expression of NICD in SiHa and HeLa cells incubated with DAPT was detected by western blot. RESULTS: The expression level of NICD in cervical cancers was significantly higher than that of normal cervical tissues (1.237 +/- 0.353 vs 0.938 +/- 0.105, P < 0.05). The NICD expression was higher in cervical cancers with high grade, lymph node involvement and parametrial invasion than that with low-middle grade (1.496 +/- 0.540 vs 1.150 +/- 0.216), without lymph node involvement (1.419 +/- 0.532 vs 1.159 +/- 0.210) and no parametrial invasion (1.718 +/- 0.710 vs 1.183 +/- 0.258), respectively (all P < 0.05). The expression of NICD in cervical adenocarcinoma was higher than that of squamous cell cancer (1.463 +/- 0.395 vs 1.162 +/- 0.187, P < 0.05). After SiHa and HeLa cells were incubated with DAPT, NICD expression was significantly lower than that in control (P < 0.05). The effects of DAPT inhibited the proliferation and prompted the apoptosis of SiHa and HeLa cells was depended on its concentrations and times. CONCLUSIONS: NICD may play a key role in the occurrence and progress of cervical cancer. The mechanism of DAPT inhibited the proliferation and prompted the apoptosis of SiHa and HeLa cells may be due to decreased the formation of NICD.

Inhibition of gamma-secretase in Notch1 signaling pathway as a novel treatment for ovarian cancer.

Epithelial ovarian cancer (EOC) is the leading cause of death for gynecological cancer. Most patients are not diagnosed until the cancer is at an advanced stage with poor prognosis. Notch1 signaling pathway plays an oncogenic role in EOC. There have been few studies on enzymatic activity of γ-secretase and the mechanism of how γ-secretase inhibitor works on cancer cell. Here, we show that Jagged1 and NICD were highly expressed in ovarian carcinoma. The expressions of Notch1, Jagged1 and NICD in Notch1 pathway did not correlate with outcome in ovarian cancer. The enzymatic activity of γ-secretase in ovarian cancer cell lines SKOV3, CAOV3 and ES2 is significantly higher than in normal ovarian epithelial cell line T29. DAPT (a γ-secretase inhibitor) reduced the enzymatic activity of γ-secretase, inhibited the proliferation, and increased the apoptosis in ovarian cancer cell lines. Hence, γ-secretase inhibitor may become a highly promising novel therapeutic strategy against ovarian cancer in the field of precision medicine.

[Effect of pelvic lymphadenectomy on prognosis of endometrial carcinoma].

OBJECTIVE: To study the associated factors with pelvic lymph node metastasis of endometrial carcinoma and the effect of pelvic lymphadenectomy on prognosis of the disease. METHODS: Totally 102 patients with endometrial carcinoma who underwent pelvic lymphadenectomy (90 patients) or lymph node biopsy (12 patients) in our hospital from Jan 1981 to Dec 2002 were recruited. The relationship between various clinicopathologic factors and pelvic lymph node metastasis was analyzed. Prognosis of ninety patients with pelvic lymphadenectomy was compared with 90 patients without pelvic lymphadenectomy (control group) in the same period. The 5-year survival was calculated by life table method. RESULTS: The incidence of pelvic lymph node metastasis increased in patients with low grade (46%), deep myometrium invasion (42%), cervical involvement (44%), positive peritoneal cytology (52%), adenexal metastasis (75%) and distant spread (100%). The 5-year survival was lower in patients with lymph node metastasis (37%) than that without lymph node metastasis (89%, P < 0.05). Univariate and COX regression analysis demonstrated that pelvic lymphadenectomy did not improve patients' prognosis. The 5-year survival in patients undergoing lymphadenectomy was 78%, and it was 72% in patients without lymphadenectomy. CONCLUSIONS: The high risk factors for pelvic lymph node metastasis in endometrial carcinoma include low grade differentiation deep myometrium invasion, cervical involvement, positive peritoneal cytology, adenexal metastasis and distant spread. The prognosis is poorer in patients with pelvic lymph node metastasis. Pelvic lymphadenectomy could not improve the prognosis of patients with endometrial carcinoma.

A type IV osteogenesis imperfecta family and pregnancy: a case report and literature review.

Osteogenesis imperfecta is a group of inherited connective-tissue disorders in which synthesis or structure of type I collagen is defective and causes osseous fragility. Type IV osteogenesis imperfecta is dominant inheritance. Here, we report a case of type IV osteogenesis imperfecta family and their female member's pregnancy. Abnormal sonographic findings (marked bowing and shortening of long bones) and family history made the diagnosis of fetus with osteogenesis imperfecta. The parents decided to give up rescuing the infant and a caesarean section at 27 weeks of gestation was implemented. In conclusion, it is possible to make a prenatal diagnosis of osteogenesis imperfecta by ultrasound. For the pregnant women with osteogenesis imperfecta, management decision should be made on an individual basis.