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Ovarian cancer spheroids constitute a metastatic niche for transcoelomic spread that also engenders drug resistance. Spheroid-forming cells express active STAT3 signaling and display stem cell–like properties that may contribute to ovarian tumor progression. In this study, we show that STAT3 is hyperactivated in ovarian cancer spheroids and that STAT3 disruption in this setting is sufficient to relieve chemoresistance. In an NSG murine model of human ovarian cancer, STAT3 signaling regulated spheroid formation and self-renewal properties, whereas STAT3 attenuation reduced tumorigenicity. Mechanistic investigations revealed that Wnt signaling was required for STAT3-mediated spheroid formation. Notably, the Wnt antagonist DKK1 was the most strikingly upregulated gene in response to STAT3 attenuation in ovarian cancer cells. STAT3 signaling maintained stemness and interconnected Wnt/β-catenin signaling via the miR-92a/DKK1–regulatory pathways. Targeting STAT3 in combination with paclitaxel synergistically reduced peritoneal seeding and prolonged survival in a murine model of intraperitoneal ovarian cancer. Overall, our findings define a STAT3–miR-92a–DKK1 pathway in the generation of cancer stem–like cells in ovarian tumors, with potential therapeutic applications in blocking their progression. Cancer Res; 77(8); 1955–67. ©2017 AACR.

Purpose: The Q-tip test is used to measure urethral hypermobility and can predict surgical outcomes. However, certain factors may affect the reliability of this test. Our aim was to identify independent clinical and urodynamic predictors of the results of the Q-tip test.Methods: Between January 2014 and June 2019, 176 consecutive women with lower urinary tract symptoms who underwent the Q-tip test and urodynamic studies were included in this retrospective study.Results: Multivariable regression analysis revealed that age (regression coefficient, -0.55), point Ba (regression coefficient, 4.1), urodynamic stress incontinence (regression coefficient, 9.9), maximum flow rate (Qmax) (regression coefficient, 0.13), pressure transmission ratio (PTR) at maximum urethral pressure (MUP) (regression coefficient, -0.14), and the score on the fifth question of the Incontinence Impact Questionnaire (IIQQ5; “Has urine leakage affected your participation in social activities outside your home?”; regression coefficient, -4.1) were independent predictors of the Q-tip angle, with a constant of 87.0. The following Spearman rank correlation coefficients were found between the Q-tip angle and the following variables: age, -0.38; point Ba, 0.34; urodynamic stress incontinence, 0.32; Qmax, 0.28; PTR at MUP, -0.28; and IIQQ5, -0.23. A receiver operating characteristic curve (ROC) analysis for the prediction of urodynamic stress incontinence found that the optimum cutoff for PTR at MUP was

Women who underwent vaginal pelvic reconstructive surgery with or without mesh consecutively between 2004 and 2018 were retrospectively analyzed to determine the learning curve in vaginal pelvic reconstructive surgery. With cumulative summation (CUSUM) analysis of surgical failure and operation time, we assessed the learning curve of vaginal pelvic reconstructive surgery, including sacrospinous ligament fixation, anterior colporrhaphy, posterior colporrhaphy, and optional vaginal hysterectomy with or without mesh placement. Two hundred and sixty-four women with stage III or IV pelvic organ prolapse underwent vaginal pelvic reconstructive surgery by surgeon A or B. The median follow-up time of 44 months ranged from 24 to 120 months. Surgical proficiency was achieved in 32-54 vaginal pelvic reconstructive surgery procedures without mesh and 37-61 procedures in the same surgery with mesh. The surgical success rates for surgeons A and B were 82.2% and 94.1%, with median follow-up times of 60 and 33 months, respectively. The learning phase of vaginal pelvic reconstructive surgery in advanced pelvic organ prolapse in this institutional cohort required 54 and 61 procedures, respectively. A higher number of procedures were required for the learning curve of vaginal pelvic reconstructive surgery with mesh. Having crossed the boundary of proficiency, the surgical success rate and operation time were improved.

Women who underwent vaginal pelvic reconstructive surgery with or without mesh consecutively between 2004 and 2018 were retrospectively analyzed to determine the learning curve in vaginal pelvic reconstructive surgery. With cumulative summation (CUSUM) analysis of surgical failure and operation time, we assessed the learning curve of vaginal pelvic reconstructive surgery, including sacrospinous ligament fixation, anterior colporrhaphy, posterior colporrhaphy, and optional vaginal hysterectomy with or without mesh placement. The study is based on two individual surgeons who performed vaginal pelvic reconstructive surgery with or without mesh. Two hundred and sixty-four women with stage III or IV pelvic organ prolapse underwent vaginal pelvic reconstructive surgery by surgeons A or B. The median follow-up time of 44 months ranged from 24 to 120 months. Surgical proficiency was achieved in 32–33 vaginal pelvic reconstructive surgery procedures without mesh and 37–47 procedures in the same surgery with mesh. The total surgical success rates for surgeons A and B were 82.2% and 94.1%, with median follow-up times of 60 and 33 months, respectively. More procedures were needed for the learning curve of vaginal pelvic reconstructive surgery with mesh. Having crossed the proficiency boundary, the surgical success rate and operation time were improved.

In recent years, industrial control systems (ICS) are widely used in many occasions, which makes information security of ICS an important issue. This study discusses the communication and management on ICS to make ICS intelligent. We proposed a method to avoid attack of communication, and elaborated the means of our proposed communication in which all communication parties communicate with each other without transmitting IP information. Moreover, as an intelligent ICS, the transmission module we design can detect anomaly in the system and change the transmission rule based on our algorithm, also known as a type of moving target defense. Therefore, we proposed the scheme to improve the transmission security in ICS. The experimental results also show that our scheme can be feasible in ICS.

Single incision laparoscopic surgery (SILS) has emerged as least invasive interventions for gynecologic disease. However, SILS is slow to gain in popularity due to difficulties in triangulation and instrument crowding. Besides, the costly instruments may influence patients’ will to have this procedure, and limit other medical expense as well. To optimize outcome and reduce cost, the objective of this study is to evaluate the feasibility and safety for patients undergoing adnexal surgeries using conventional laparoscopic instruments with SILS (SILS-C), and to compare with those of patients subject to TP using conventional laparoscopic instruments (TP-C). This is a retrospective case–control study. The data dated from April 2011 to April 2018. Patients who received concomitant multiple surgeries, were diagnosed with suspected advanced stage ovarian malignancy, or required frozen sections for intraoperative pathologic diagnosis were excluded. Demographic data, including the age, body weight, height, previous abdominal surgery were obtained. The surgical outcomes were compared using conventional statistical methods. 259 patients received SILS-C. The operating time was 63.83 ± 25.31 min. Blood loss was 2.38 ± 6.09 c.c. 58 patients (24.38%) needed addition of port to complete surgery. 384 patients received TP-C. Compared with SILS-C, the operating time was shorter (57.32 ± 26.38 min, OR = 0.984, CI = 0.975–0.992). The patients were further divided into unilateral or bilateral adnexectomy, and unilateral or bilateral cystectomy. Other than the operating time in unilateral cystectomy (66.12 ± 19.5 vs. 58.27 ± 23.92 min, p = .002), no statistical differences were observed in the subgroup analysis. Single incision laparoscopic surgery using conventional laparoscopic instruments is feasible and safe as initial approach to adnexal lesions. In complex setting as unilateral cystectomy or pelvic adhesions, two-port access may be considered.

Sacrospinous ligament fixation (SSLF) is one of the most utilized surgeries in the management of pelvic organ prolapse (POP). We conducted a large-series study of SSLF in a tertiary center by an experienced urogynecologic team. The 453 women with POP who underwent SSLF at National Taiwan University Hospital in the period from 2002 to 2015 are reviewed. All patients received unilateral SSLF with Veronikis ligature carrier. Concomitant anterior colporrhaphy was performed in 75.3% of the cases and posterior colporrhaphy in 78.6%. The mean operation time was 92.3 ± 31.5 minutes. The intraoperative blood loss was 92.3 ± 91.4 ml. The objective cure rate was 82.5%, and 79 (17.5%) patients recurred. The Kaplan-Meier recurrence-free analysis showed a steep decline during the first postoperative year, and the yearly number of recurrent patients decreased as the follow-up period proceeded. A comparison of the site of recurrence found that anterior compartment prolapse was the most common with 57 cases (12.6%). Paravaginal repair is frequently implemented in the management of recurrent anterior prolapse. In conclusion, SSLF provides excellent support to the apex compartment, and our long-term results show that the anterior compartment is the most commonly encountered type of POP recurrence.

Objective Radical trachelectomy (RT) is an alternative treatment for preserving fertility in patients with cervical cancer. Because women with operable cervical cancer opting for fertility preservation are scarce, few cases have been reported in Taiwan. Here we report our cases series. Materials and Methods We retrospectively evaluated seven patients who underwent vaginal RT and three patients who underwent abdominal RT in a single medical institute for a median follow-up period of 5 years. Results The oncological outcome was highly satisfactory. All patients survived and are currently disease-free, except for two who had recurrence and received additional concurrent chemoradiation therapy. Other complications included urinary tract infection, cervical stenosis, and unilateral hydronephrosis. All complications were manageable with little long-term effects. However, no pregnancy was observed during the 5-year follow-up period. Conclusion RT is considered a complicated surgical procedure among gynecological operations. Here we review the literature and describe several factors associated with higher pregnancy rates.

Epithelial ovarian cancer (EOC) is the most lethal of all gynecologic malignancies. Despite advances in surgical and chemotherapeutic options, most patients with advanced EOC have a relapse within three years of diagnosis. Unfortunately, recurrent disease is generally not curable. Recent advances in maintenance therapy with anti-angiogenic agents or Poly ADP-ribose polymerase (PARP) inhibitors provided a substantial benefit concerning progression-free survival among certain women with advanced EOC. However, effective treatment options remain limited in most recurrent cases. Therefore, validated novel molecular therapeutic targets remain urgently needed in the management of EOC. Signal transducer and activator of transcription-3 (STAT3) and STAT5 are aberrantly activated through tyrosine phosphorylation in a wide variety of cancer types, including EOC. Extrinsic tumor microenvironmental factors in EOC, such as inflammatory cytokines, growth factors, hormones, and oxidative stress, can activate STAT3 and STAT5 through different mechanisms. Persistently activated STAT3 and, to some extent, STAT5 increase EOC tumor cell proliferation, survival, self-renewal, angiogenesis, metastasis, and chemoresistance while suppressing anti-tumor immunity. By doing so, the STAT3 and STAT5 activation in EOC controls properties of both tumor cells and their microenvironment, driving multiple distinct functions during EOC progression. Clinically, increasing evidence indicates that the activation of the STAT3/STAT5 pathway has significant correlation with reduced survival of recurrent EOC, suggesting the importance of STAT3/STAT5 as potential therapeutic targets for cancer therapy. This review summarizes the distinct role of STAT3 and STAT5 activities in the progression of EOC and discusses the emerging therapies specifically targeting STAT3 and STAT5 signaling in this disease setting.

Objective To report a case of isolated omental peritoneal carcinoma without peritoneal carcinomatosis. Case report A 60-year-old female with abdominal distention was found to have a pelvic mass. Under the impression of ovarian cancer, laparotomy was performed only to show one isolated mass over omentum. Serial examination and pathology study including immunochemical staining indicated primary peritoneal serous carcinoma. Conclusion Isolated omental peritoneal carcinoma without peritoneal carcinomatosis and ascites is rare, and whether this represented a unique entity with different chemotherapy response and treatment outcome from the disseminated form of primary peritoneal carcinoma needs to be reviewed in the future.

Ovarian cancer spheroids constitute a metastatic niche for transcoelomic spread that also engenders drug resistance. Spheroid-forming cells express active STAT3 signaling and display stem cell–like properties that may contribute to ovarian tumor progression. In this study, we show that STAT3 is hyperactivated in ovarian cancer spheroids and that STAT3 disruption in this setting is sufficient to relieve chemoresistance. In an NSG murine model of human ovarian cancer, STAT3 signaling regulated spheroid formation and self-renewal properties, whereas STAT3 attenuation reduced tumorigenicity. Mechanistic investigations revealed that Wnt signaling was required for STAT3-mediated spheroid formation. Notably, the Wnt antagonist DKK1 was the most strikingly upregulated gene in response to STAT3 attenuation in ovarian cancer cells. STAT3 signaling maintained stemness and interconnected Wnt/β-catenin signaling via the miR-92a/DKK1–regulatory pathways. Targeting STAT3 in combination with paclitaxel synergistically reduced peritoneal seeding and prolonged survival in a murine model of intraperitoneal ovarian cancer. Overall, our findings define a STAT3–miR-92a–DKK1 pathway in the generation of cancer stem–like cells in ovarian tumors, with potential therapeutic applications in blocking their progression. Cancer Res; 77(8); 1955–67. ©2017 AACR.

Supplemental Digital Content is available in the text, Rationale: Rare uterine choriocarcinoma can be differentiated gestational from nongestational choriocarcinoma by using short tandem repeats (STRs). Patient concerns: A 56-year-old Taiwanese woman underwent staging surgery because of suspicion of high-grade endometrial cancer. The pathology-confirmed uterine tumor with syncytiotrophoblasts and decidual change of the endometrium was harvested. Diagnosis: Uterine nongestational choriocarcinoma. Interventions: The tumor specimen, the patient's blood, and her husband's blood were drawn for STRs analysis using polymerase chain reaction amplification kit. The genotype of the tumor cells was solely maternal and made the diagnosis of uterine nongestational choriocarcinoma. Outcome: Adjuvant chemotherapy with etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine regimen achieved good response in the patient. The patient is now recurrence-free for 12 months. Lessons: STRs aid precise classification of rare choriocarcinoma. We encourage using the method to analyze suspicious choriocarcinoma.