A 14-year multi-institutional collaborative study of Chinese pelvic floor surgical procedures related to pelvic organ prolapse.

BACKGROUND: It has been a global trend that increasing complications related to pelvic floor surgeries have been reported over time. The current study aimed to outline the development of Chinese pelvic floor surgeries related to pelvic organ prolapse (POP) over the past 14 years and investigate the potential influence of enhanced monitoring conducted by the Chinese Association of Urogynecology since 2011. METHODS: A total of 44,594 women with POP who underwent pelvic floor surgeries between October 1, 2004 and September 30, 2018 were included from 22 tertiary academic medical centers. The data were reported voluntarily and obtained from a database. We compared the proportion of each procedure in the 7 years before and 7 years after September 30, 2011. The data were analyzed by performing Z test (one-sided). RESULTS: The number of different procedures during October 1, 2011-September 30, 2018 was more than twice that during October 1, 2004-September 30, 2011. Regarding pelvic floor surgeries related to POP, the rate of synthetic mesh procedures increased from 38.1% (5298/13,906) during October 1, 2004-September 30, 2011 to 46.0% (14,107/30,688) during October 1, 2011-September 30, 2018, whereas the rate of non-mesh procedures decreased from 61.9% (8608/13,906) to 54.0% (16,581/30,688) (Z = 15.53, P < 0.001). Regarding synthetic mesh surgeries related to POP, the rates of transvaginal placement of surgical mesh (TVM) procedures decreased from 94.1% (4983/5298) to 82.2% (11,603/14,107) (Z = 20.79, P < 0.001), but the rate of laparoscopic sacrocolpopexy (LSC) procedures increased from 5.9% (315/5298) to 17.8% (2504/14,107). CONCLUSIONS: The rate of synthetic mesh procedures increased while that of non-mesh procedures decreased significantly. The rate of TVM procedures decreased while the rate of LSC procedures increased significantly. TRIAL REGISTRATION NUMBER: NCT03620565, https://register.clinicaltrials.gov.

Periostin Secreted by Carcinoma-Associated Fibroblasts Promotes Ovarian Cancer Cell Platinum Resistance Through the PI3K/Akt Signaling Pathway.

Periostin (POSTN) is a protein secreted by mesenchymal cells. Periostin is upregulated in several cancer types and overexpression is associated with poor prognosis. However, the functional role and molecular underpinnings of periostin in epithelial ovarian cancer (EOC) is unknown. In the present study, periostin was found to be significantly upregulated in EOC stroma. Functional studies revealed that periostin could decrease cisplatin (DDP)-induced apoptosis in EOC. Periostin led to DDP resistance in EOC cells, potentially through the PI3K/Akt signaling pathway. We generated periostin-overexpressing fibroblasts and found that EOC cells were resistant to DDP when co-cultured with periostin-overexpressing fibroblasts. The findings of the present study indicated that periostin secreted by cancer-associated stromal cells may be a potential therapeutic target for EOC.

A systematic review on efficacy and safety of gasless laparoscopy in the management of uterine leiomyoma.

Uterine leiomyoma causes considerable morbidity in women. This study systematically reviewed the efficacy and safety of gasless laparoscopic myomectomy (GLM) in the management of uterine leiomyoma by comparing GLM with other minimally invasive procedures. Cochrane Library, Pub- Med, EMBASE, Web of Science, WANFANG database and China National Knowledge Infrastructure (CNKI) were searched for studies published in English or Chinese between January 1995 and May 2015, and related references were traced. Study outcomes from randomized controlled trials and retrospective cohort studies were presented as mean difference (MD) or odds ratio (OR) with a 95% confidence interval (CI). Seventeen studies (including 1862 patients) meeting the inclusion criteria, including 934 treated with GLM and 928 treated with other minimally invasive procedures were reviewed. The results of meta-analysis revealed that GLM resulted in significantly shorter operating time [MD=-10.34, 95% CI (-18.12,-2.56), P<0.00001], shorter hospital stay [MD=-0.47, 95% CI (-0.88,-0.06)], less time to flatus [MD=-2.04, 95% CI (-2.59,-1.48)], less postoperative complications [OR=0.20, 95% CI (0.06, 0.62)] and less blood loss [MD =-30.74, 95% CI (-47.50,-13.98)]. On the other hand, there were no significant differences in duration of post-operative fever [MD=-0.52, 95% CI (-1.46, 0.42)] between the two groups. Additionally, GLM was associated with lower febrile morbidity, lower postoperative abdominal pain, and higher postoperative hemoglobin than other minimally invasive procedures for the treatment of uterine leiomyoma. In conclusion, GLM and other minimally invasive procedures are feasible, safe, and reliable for uterine leiomyoma treatment. However, available studies show that GLM is more effective and safer than other minimally invasive approaches.

Efficacy and safety of solifenacin succinate tablets versus solifenacin succinate tablets with local estrogen for the treatment of overactive bladder in postmenopausal women--a multicenter, randomized, open-label, controlled comparison study.

OBJECTIVE: The aim of the study was to compare the effectiveness and safety of solifenacin succinate tablets alone or combined with local estrogen for overactive bladder treatment in postmenopausal women. METHODS: This multicenter, randomized, open, parallel-controlled clinical trial enrolled 104 women between January 2012 and August 2013. Participants meeting the inclusion criteria were randomized 1:1 to 12 weeks of treatment with group A (solifenacin 5 mg qd + promestriene vaginal capsules intravaginally) or group B (solifenacin 5 mg qd). Before and after 12 weeks of treatment, symptoms (urinary urgency, frequency, and urge incontinence) were analyzed. Our primary outcome was the change from baseline to the end of treatment in the mean number of voids in 24 hours. Quality of life (QoL) was assessed using International Prostate Symptom Score and Overactive Bladder Symptom Score questionnaires and safety according to the incidence of adverse events. The t test or the Mann-Whitney U test was used to compare continuous variables, and the χ(2) test or Fisher's exact test was used to compare categorical variables. RESULTS: The median decreases in the mean number of voids in 24 hours in groups A and B were 5.2. and 4.3, respectively, which were not significantly different. The median decreases in urgency episodes in groups A and B were 2.0 and 2.5, respectively. In addition, the QoL scores significantly changed in both groups (both P < 0.05). The most common adverse event was dry mouth (19.2% in both groups). CONCLUSIONS: Solifenacin with or without local estrogen was effective and safe for overactive bladder treatment in postmenopausal women. The addition of local estrogen improved subjective feelings and QoL.

Laparoscopic repair of iatrogenic vesicovaginal and rectovaginal fistula.

OBJECTIVE: To investigate the clinical efficacy of laparoscopic repair of iatrogenic vesicovaginal fistulas (VVF) and rectovaginal fistulas. METHODS: Seventeen female patients with iatrogenic fistulas (11 cases of VVF and 6 cases of high rectovaginal fistulas) were included. All patients were hospitalized and underwent laparoscopic fistula repair in our hospital between 2008 and 2012. The mean age of the patients was 44.8 ± 9.1 years. The fistulas and scar tissue were completely excised by laparoscopy, orifices were tension-free closed using absorbable sutures, omental flaps were interposed between the vagina and the bladder or rectum, and drainage was kept after repair. RESULTS: Laparoscopic repair of fistulas was successful in all 17 patients. No complication was found during or after repair. No reoperation was needed after the repair. The operative time was 80.2 ± 30.0 minutes (range 50-140 minutes). The blood loss was 229.4 ± 101.6 ml (range 100-400 ml). The double J catheters were placed in 7 patients and removed 1-2 months after repair. Eight VVF patients underwent cystoscopy 3 months after laparoscopic repair and there were no abnormal findings. The follow-up time was 17.1 ± 6.5 months (range 8-29 months). CONCLUSION: Laparoscopic repair of VVF and rectovaginal fistulas is a safe and an effective minimally invasive procedure for treatment of iatrogenic fistula.

A new surgery for recurrent or persist stress urinary incontinence in females after primary mid-urethral slings.

OBJECTIVE: To retrospectively evaluate the efficacy of a new complementary mid-urethral sling surgery (Tong's hammock anterior, THA) in treatment of recurrent or persist stress urinary incontinence (SUI) in females after primary synthetic mid-urethral slings (MUSs). METHODS: THA was performed in 27 females with recurrent or persist SUI after primary MUSs from June 2005 and July 2010. These patients were followed up for one year, and clinical data including main complaints, operation duration, blood loss, efficacy and complications were reviewed. RESULTS: All 27 SUI patients were treated with THA surgery, a trans-vaginal mid-urethral sling on the descending pubic ramus. The average operation time was 39 min (range: 25-70 min), average blood loss was 70 ml (range: 20-120 ml). After urinary catheter removal, all patients could micturate and their average residual urine was 25.2 ml (range: 0-80 ml). The average hospital stay was 4.7 days (rage: 3-7 days). SUI symptom was persistent in 2 patients after THA surgery and the effective rate reached 92.5%. At 3 months, 6 months and 1 year after surgery, the effective rate was 92.5% (25/27), 92% (23/25) and 87.5% (21/24), respectively. 6 months after THA surgery, 2 were lost to follow up; 1 had recurrent SUI at 1 year and 1 had mesh erosion, 1 died of other diseases, and operative complications were absent after surgery. CONCLUSIONS: THA surgery is an effective method for treating recurrent or persistent SUI after primary MUSs. It is cheap, efficient, and easy to handle.

Expression of aryl hydrocarbon receptor in relation to p53 status and clinicopathological parameters in breast cancer.

The aryl hydrocarbon receptor (AhR) is a ligand activated transcription factor implicated in multiple cellular processes and its expression has been shown to play a critical role in tumorigenesis. However, the role of AhR in tumorigenesis of breast cancer remains unclear. In the current study, we investigated the expression levels of AhR in breast lesions and assessing the correlation between AhR expression and clinicopathological variables using breast cancer tissue microarray. Meanwhile, 10 paired of fresh breast cancer and corresponding non-cancer samples were detected for AhR and p53 expression by Western blot, respectively. Results showed that AhR expression levels in breast cancer tissues were significantly higher than that in the non-cancer tissues. AhR expression was associated with the pathological type and P53 status, but not patients age, tumor grade and TNM, as well as ER, PR, C-erbB2, Ki-67, AR, EGFR status. Moreover, Western blot data suggested a negative correlation between p53 protein and AhR protein expression levels. The results suggest that high levels of AhR were expressed in the majority of breast cancer tissues and closely associated with P53 status and histological types of breast cancer. AHR and its abnormal expression may play an important role in multiple stages of breast cancer progression.

Clinical observation of a modified surgical method: posterior vaginal mesh suspension of female rectocele with intractable constipation.

STUDY OBJECTIVE: To explore the feasibility and effectiveness of a modified posterior vaginal mesh suspension method in treating female rectocele with intractable constipation. DESIGN: Descriptive study (Canadian Task Force classification II-3). SETTING: The study was performed in the Study Center for Female Pelvic Dysfunction Disease, Department of Obstetrics and Gynecology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China. The Study Center includes 15 physicians, most of whom have received advanced training in pelvic floor dysfunctional disease and can skillfully perform many types of operations in patients with such disease. Almost 1500 operations to treat pelvic floor dysfunctional disease are performed every year at the center. PATIENTS: Thirty-six women with rectocele with intractable constipation. INTERVENTION: Posterior vaginal mesh suspension. MEASUREMENTS AND MAIN RESULTS: All patients were followed up for 15 to 36 months. In 29 patients, the condition was cured completely; in 5 patients it had improved; and in 2 patients, the intervention had no effect. Insofar as recovery and improved results, the overall effectiveness rate was 94.4%. CONCLUSION: Posterior vaginal mesh suspension is an effective, harmless, and convenient method for treatment of female rectocele with intractable constipation. It has positive short-term curative effects, with few complications and sequelae. However, the long-term effects of posterior vaginal mesh suspension should be evaluated.

The comparison of an inexpensive-modified transobturator vaginal tape versus TVT-O procedure for the surgical treatment of female stress urinary incontinence.

OBJECTIVE: To compare the safety and efficacy of an inexpensive-modified transobturator vaginal tape procedure with the transobturator tension-free vaginal tape (TVT-O) procedure for the surgical treatment of female stress urinary incontinence (SUI). MATERIALS AND METHODS: Patients with SUI were randomly allocated to either the test group receiving the inexpensive-modified transobturator vaginal tape procedure or the control group receiving the GYNECARE TVT-O procedure. Treatment outcomes and Quality-of-life scores were recorded and analyzed between two groups. RESULTS: A total of 156 patients were enrolled in this trial. Eighty patients underwent the modified transobturator vaginal tape procedure. Among them 75(93.8%) were cured and 5(6.2%) were improved. The rest of the 76 patients underwent the GYNECARE TVT-O procedure with a 92% (70 of 76) cure rate and an 8% (6 of 76) improvement rate. No inefficient or aggravated cases occurred in both groups. The success rates between groups had no significant statistic difference (p > 0.05). The operative time, blood loss, hospital stay, and medical cost were significantly lower in the test group (p < 0.01); the increases in Quality-of-life scores were comparable between groups. CONCLUSIONS: The modified transobturator vaginal tape procedure is an efficacious and economic surgical treatment for female SUI.

Endometriosis and regional lymph node involvement in a rat model.

OBJECTIVE(S): To establish an experimental bowel endometriosis model in the rat and to investigate regional lymph node involvement. STUDY DESIGN: Twenty Sprague-Dawley rats were subjected to autologous transplantation of endometrial tissue to the ileocecum by laparotomy. After two months, endometriotic lesions and mesenteric lymph nodes were harvested by repeat laparotomy subjected to histologic assessment regarding the histologically verified presence of endometriosis in the ileocecum and in mesenteric lymph nodes. RESULT(S): A total of 20 rats were subjected to autologous transplantation of endometrial tissue to the ileocecum. Ileocecal endometriosis was successfully induced in 19/20 (95%) rats. In 18/20 animals, the mesenteric lymph node was identified and resected. Regional lymph node involvement by endometriosis was identified in 0/18 mesenteric lymph nodes. CONCLUSION(S): Endometriosis can be successfully induced in a rat model by autologous transplantation of endometrial tissue. In this experimental rodent endometriosis model, regional mesenteric lymph node involvement by endometriosis was not identified.

Expression levels of hnRNP G and hTra2-beta1 correlate with opposite outcomes in endometrial cancer biology.

HnRNP G is a member of heterogeneous nuclear ribonucleoprotein (hnRNP) family with potent tumor suppressive activities. Human transformer-2-beta1 (hTra2-beta1) belongs to the arginine-serine rich like proteins and is found over-expressed in various human cancers. It was recently shown that hnRNP G and hTra2-beta1 exert antagonistic effects on alternative splicing. In our study we explored the impact of these two factors in tumor biology of endometrial cancer (EC). EC tissues (n = 139) were tested for hnRNP G and hTra2-beta1 expression on mRNA level by real time PCR and on protein level by immunohistochemistry. HTra2-beta1 mRNA level was found being induced in advanced International Federation of Gynecology and Obstetrics (FIGO) stages (p = 0.016). HnRNP G protein nuclear expression was found more prominent in patients without distant organ metastases (p = 0.033) and in FIGO Stages I/II group (p < 0.001). HTra2-beta1 protein nuclear levels were elevated in poorly differentiated (p = 0.044) and lymph node metastases (p = 0.003) cancers. Kaplan-Meier survival curves revealed that elevated hnRNP G mRNA (p = 0.029) and protein (p = 0.022) levels were associated with a favorable patient outcome. Multivariate Cox-regression analyses identified nuclear hnRNP G level [hazard ratio (HR) 0.468, p = 0.026) as well as hTra2-beta1 level (hazard ratio 5.760, p = 0.004) as independent prognostic factors for EC progression-free survival. Our results indicate that the antagonistic functional effects of hnRNP G and hTra2-beta1 on alternative splicing correlate directly to their opposite clinical effects on EC patient outcome.

Alveolar stability under different combinations of positive end-expiratory pressure and tidal volume: alveolar microscopy in isolated injured rat lungs.

BACKGROUND: High positive end-expiratory pressure (PEEP) and low tidal volume (VT) ventilation is thought to be a protective ventilation strategy. It is hypothesized that the stabilization of collapsible alveoli during expiration contributes to lung protection. However, this hypothesis came from analysis of indirect indices like the analysis of the pressure-volume curve of the lung. The purpose of this study was to investigate isolated healthy and injured rat lungs by means of alveolar microscopy, in which combination of PEEP and VT is beneficial with respect to alveolar stability (I-E%). METHODS: Alveolar stability was investigated in isolated, non-perfused mechanically ventilated rat lungs. Injured lungs were compared with normal lungs. For both groups three PEEP settings (5, 10, 20 cmH2O) were combined with three VT settings (6, 10, 15 ml/kg) resulting in nine PEEP-VT combinations per group. Analysis was performed by alveolar microscopy. RESULTS: In normal lungs alveolar stability persisted in all PEEP-VT combinations (I-E% (3.2 +/- 11.0)%). There was no significant difference using different settings (P > 0.01). In contrast, alveoli in injured lungs were extremely instable at PEEP levels of 5 cmH2O (mean I-E% 100%) and 10 cmH2O (mean I-E% (30.7 +/- 16.8)%); only at a PEEP of 20 cmH2O were alveoli stabilized (mean I-E% of (0.2 +/- 9.3)%). CONCLUSIONS: In isolated healthy lungs alveolar stability is almost unaffected by different settings of PEEP and VT. In isolated injured lungs only a high PEEP level of 20 cmH2O resulted in stabilized alveoli whereas lower PEEP levels are associated with alveolar instability.

[Clinical research of a butterfly shaped mesh in the treatment of stress urinary incontinence].

OBJECTIVE: To investigate the effect of a butterfly shaped mesh in treatment of stress urinary incontinence (SUI). METHODS: From July 2003 to January 2004, 82 patients with SUI were treated with a butterfly shaped mesh. All patients were followed up at 1st, 3rd, 6th month after operation. According to their complaints, the cure standard of urinary incontinence is that the patient can control micturate by herself. The improved is that the times and volume of urinary incontinence is less than before. The inefficacy is that the patients' symptoms is not improved even more than before. RESULTS: All patients were operated under local anesthesia. Mean operation time was (27 +/- 9) min, and mean blood loss was (21 +/- 6) ml. Seventy two patients were able to micturate spontaneously at 2nd hour after operation and the volume of residual urine was less than 100 ml after 24 hour behind operation. They were discharged on the next day. 10 patients, an in-dwelling catheter had been used for 48 hours because the volume of residual urine was more than 100 ml. Seventy eight of 82 patients had no signs of stress incontinence. The remaining 4 patients with apoplexy history showed leakage of urine slightly. But their signs were improved obviously after a month. Seventy six patients had been followed up for from 1 to 6 month: 74 patients were completely cured, and the other 2 patients were improved. No urine retention, infection or bladder dysfunction were observed. CONCLUSION: A butterfly shaped mesh is effective, simple and safe procedure to treat stress urinary incontinence.

[Clinical application of a modified posterior vaginal wall hammock in female pelvic floor reconstruction].

OBJECTIVE: To explore the feasibility and effectiveness of a modified posterior vaginal wall hammock (PVWH) in the treatment of female pelvic organ prolapse without removal of uterus. METHODS: Thirty-two patients with different defects of pelvic organ prolapse underwent a modified PVWH. The procedures included restoring the position of prolapsed uterus by suturing polypropylene mesh to bilateral sacro-spinous ligaments, strengthening utero-sacral ligament by intra-vaginal slingplasty (Tyco Healthcare Group), forming a new recto-vaginal fascia and strengthening levator ani muscle. RESULTS: The average operating time was 55 minutes and hemorrhage was 150 ml respectively. Recovery of uterine prolapse was achieved in all cases. After an average follow up of seven months, no vagina distortion, shortening and dyspareunia were observed. One patient had uterine cervix elongation three months after operation. The relieving rate of subjective symptoms was more than 50%. CONCLUSIONS: Female uterine prolapse could be cured by the modified PVWH and the uterus could be successfully reserved during pelvic floor reconstruction with promising short-term results. More clinical trials are needed to evaluate its effectiveness, safety and long-term outcome.

A germline variation in the progesterone receptor gene increases transcriptional activity and may modify ovarian cancer risk.

Recently, we and others have detected a haplotype of the human progesterone receptor gene (PR). This haplotype consists of a 320-bp insertion in intron G together with point mutations in exons 4 and 5 and was named PROGINS. Whereas the exon 5 mutation is silent, the mutation in exon 4 results in a V660L substitution. Interestingly, this genetic polymorphism was seen to cosegregate with an increased risk of sporadic ovarian cancer in different ethnic groups. Our data provide evidence for the existence of an epidemiological link between a mutated progesterone receptor allele and ovarian cancer (odds ratio, 3.02; 95% confidence interval, 1.86-4.91). Functional characterization of the mutated receptor protein revealed a greater transcriptional activity compared with the wild-type receptor. By contrast, hormone binding and hormone dissociation rates were similar in both receptor proteins. We found that the increased transcriptional activity was due to increased stability resulting in higher expression of the mutant protein. Thus, the long-lasting hyperactivation of progesterone receptor-driven genes secondary to the increased transcriptional activity of the mutated progesterone receptor may participate in ovarian carcinogenesis. This is of special interest, because only a few genetic markers are available for the majority of women diagnosed with sporadic ovarian cancer.

Intraperitoneal adenovirus-mediated suicide gene therapy in combination with either topotecan or paclitaxel in nude mice with human ovarian cancer.

A mouse model of human ovarian cancer was used to investigate the effect of adenovirus-mediated thymidine kinase gene therapy (gt) in combination with chemotherapy. One hundred sixty female CD-1 nu/nu mice were injected intraperitoneally with Ov-ca-2774 cells. Onset of intraperitoneal treatment with either topotecan (6 or 12 mg/kg) or paclitaxel (18 or 36 mg/kg) was on day 4 or 8 and was repeated once after 4 days. Animals scheduled for gt received intraperitoneal application of adv/rsv-tk 1 day prior to chemotherapy and were subsequently treated with ganciclovir (gcv; 10 mg/kg, every 12 hours for 6 days). Survival was chosen as study endpoint. Whereas tumor burden had hardly any effect on survival, the lower dose of either cytotoxic agent was seen to be more effective than the higher one. In the topotecan group, an interaction between topotecan and gt was present. Survival was best for animals treated with low dose of topotecan only, the addition of gt reduced survival time significantly. With the higher dose, gt did not affect survival time. With paclitaxel, only slight effects of gt on the survival times were seen. Due to treatment toxicity, this animal model may be problematic for the evaluation of gt and chemotherapy combinations. The effect of dose varied strongly with time. Mice treated with high-dose chemotherapy had a substantially increased risk of dying in the time period following application, whereas this advantage of the lower dose disappeared later.