Comparison of Outcomes in Bowel Resections by Gynecologic Oncologists Versus General Surgeons During Maximal Cytoreductive Surgery for Advanced Ovarian Cancer: Gynecologic Oncology Research Investigators Collaboration Study (GORILLA-3006).

BACKGROUND: This report describes the oncologic outcomes for patients with advanced ovarian cancer who had bowel surgery performed by gynecologic oncologists (GOs) and compares the outcomes with those for bowel surgery performed by general surgeons (GSs) during maximal cytoreductive surgery. METHODS: Patients from six academic institutions who had FIGO stage III or IV ovarian cancer and underwent any bowel surgeries during maximal cytoreductive surgery were eligible for the study. The patients were divided into two groups according to whether bowel surgery was performed by a GO or a GS. In both groups, the GOs were mainly involved in extra bowel debulking procedures. Perioperative and survival outcomes were compared between the two groups. RESULTS: The 761 patients in this study included 113 patients who underwent bowel surgery by a GO and 648 who had bowel surgery by a GS. No discernible differences were observed in age, American Society of Anesthesiology (ASA) score, FIGO stage, histologic type, timing of cytoreductive surgery (primary or interval debulking surgery), or complications between the two groups. The GO group exhibited a shorter operation time than the GS group. Kaplan-Meier analysis showed no survival differences between the two groups. In the Cox analysis, non-serous cell types and gross residual diseases were associated with adverse effects on overall survival. However, performance of bowel surgery by a GO did not have an impact on survival. CONCLUSION: Performance of bowel surgery by a GO during maximal cytoreductive surgery is both feasible and safe. These results should be reflected in the training system for GOs regarding bowel surgery, and further research is needed to confirm that GOs can play a more leading role in performing extra-uterine procedures.

Evaluation of prognostic potential of ß-catenin and L1CAM expression according to endometrial cancer risk group.

OBJECTIVE: We investigate the prognostic role of ß-catenin and L1 neuronal cell-adhesion molecule (L1CAM) according to risk groups in endometrial carcinomas (EC). METHODS: A total of 335 EC patients were classified according to the Proactive Molecular Risk Classifier for Endometrial Cancer. We evaluated the expression of ß-catenin and L1CAM using immunohistochemistry, and their association with clinicopathological characteristics and survival. RESULTS: The expressions of ß-catenin and L1CAM were observed in 10.4% of all patients, respectively, and showed mutually exclusive pattern. While ß-catenin expression was associated with endometrioid histology (p = 0.035) and low tumor grade (p = 0.045), L1CAM expression was associated with non-endometrioid histology (p < 0.001), high tumor grade (p < 0.001), lymphovascular space invasion (p = 0.006), and advanced International Federation of Gynecology and Obstetrics (FIGO) stage (p = 0.001). ß-catenin expression was most frequent in the no specific molecular (NSMP) group (26/35, 74.3%), followed by the DNA polymerase-ε-mutated (POLE-mut) (6/35, 17.1%), and mismatch repair-deficiency (dMMR) (3/35, 8.6%). L1CAM expression was most frequent in the p53-abnormal group (22/35, 62.9%), followed by the NSMP (6/35, 17.1%), dMMR (4/35, 11.4%), and POLE-mut (3/35, 8.6%). Although both markers did not show statistical significance in multivariate analysis for both progression-free survival (PFS) and overall survival in entire cohort, ß-catenin positivity was identified as the sole factor associated with worse PFS in the high-intermediate risk subgroup (p = 0.001). CONCLUSION: The expression of nuclear ß-catenin may serve as a potential biomarker for predicting recurrence and guiding therapeutic strategies in high-intermediate risk EC patients.

Minimally Invasive Sacrohysteropexy Versus Vaginal Hysterectomy With Uterosacral Ligament Suspension for Pelvic Organ Prolapse: A Prospective Randomized Non-Inferiority Trial.

STUDY OBJECTIVE: To investigate whether minimally invasive Sacrohysteropexy (SH) is non-inferior to vaginal hysterectomy (VH) with uterosacral ligament suspension (USLS) in women with symptomatic uterovaginal prolapse. DESIGN: Prospective, randomized, non-inferiority study. SETTING: Tertiary university-based hospital. PATIENTS: A total of 146 patients with uterovaginal prolapse between July 2016 and August 2019. INTERVENTIONS: Patients were randomly assigned in a 1:1 ratio to either laparoscopic or robotic SH surgery or VH with USLS surgery. MEASUREMENTS AND MAIN RESULTS: The primary outcome was prolapse recurrence at 1 year after surgery, defined as prolapse ≥ stage 2 evaluated using the pelvic organ prolapse quantification system, bothersome vaginal bulge symptoms, or retreatment for prolapse. The secondary outcomes included operation time, estimated blood loss, hospital stay, operation-related complications, pain intensity, quality of life, and activities of daily living. Of 146 women who underwent randomization, 73 in the SH group and 73 in the VH with USLS group were analyzed. SH was non-inferior for recurrence compared with VH with USLS (16.4% vs 15.8%, 95% confidence interval: -13.0% to 14.2%). Operating duration and transvaginal length were significantly longer in the SH group, while there were no significant differences in the estimated blood loss, length of hospital stay, or postoperative complication rates. Although perioperative pain intensity was greater from 1 week to 1 month in the SH group, the quality of life and activities of daily living did not differ between the groups throughout postoperative year 1. CONCLUSION: Laparoscopic or robotic SH was non-inferior to VH with USLS for the recurrence of pelvic organ prolapse at the 1-year follow-up.

A differential diagnosis between uterine leiomyoma and leiomyosarcoma using transcriptome analysis.

BACKGROUND: The objective of this study was to estimate the accuracy of transcriptome-based classifier in differential diagnosis of uterine leiomyoma and leiomyosarcoma. We manually selected 114 normal uterine tissue and 31 leiomyosarcoma samples from publicly available transcriptome data in UCSC Xena as training/validation sets. We developed pre-processing procedure and gene selection method to sensitively find genes of larger variance in leiomyosarcoma than normal uterine tissues. Through our method, 17 genes were selected to build transcriptome-based classifier. The prediction accuracies of deep feedforward neural network (DNN), support vector machine (SVM), random forest (RF), and gradient boosting (GB) models were examined. We interpret the biological functionality of selected genes via network-based analysis using GeneMANIA. To validate the performance of trained model, we additionally collected 35 clinical samples of leiomyosarcoma and leiomyoma as a test set (18 + 17 as 1st and 2nd test sets). RESULTS: We discovered genes expressed in a highly variable way in leiomyosarcoma while these genes are expressed in a conserved way in normal uterine samples. These genes were mainly associated with DNA replication. As gene selection and model training were made in leiomyosarcoma and uterine normal tissue, proving discriminant of ability between leiomyosarcoma and leiomyoma is necessary. Thus, further validation of trained model was conducted in newly collected clinical samples of leiomyosarcoma and leiomyoma. The DNN classifier performed sensitivity 0.88, 0.77 (8/9, 7/9) while the specificity 1.0 (8/8, 8/8) in two test data set supporting that the selected genes in conjunction with DNN classifier are well discriminating the difference between leiomyosarcoma and leiomyoma in clinical sample. CONCLUSION: The transcriptome-based classifier accurately distinguished uterine leiomyosarcoma from leiomyoma. Our method can be helpful in clinical practice through the biopsy of sample in advance of surgery. Identification of leiomyosarcoma let the doctor avoid of laparoscopic surgery, thus it minimizes un-wanted tumor spread.

Conization before radical hysterectomy in patients with early-stage cervical cancer: A Korean multicenter study (COBRA-R).

OBJECTIVE: To investigate the impact of conization on survival outcomes and to identify a specific population that might benefit from conization before radical hysterectomy (RH) in patients with early-stage cervical cancer. METHODS: From six institutions in Korea, we identified node-negative, margin-negative, parametria-negative, 2009 FIGO stage IB1 cervical cancer patients who underwent primary type C RH between 2006 and 2021. The patients were divided into multiple groups based on tumor size, surgical approach, and histology. We performed a series of independent 1:1 propensity score matching and compared the survival outcomes between the conization and non-conization groups. RESULTS: In total, 1254 patients were included: conization (n = 355) and non-conization (n = 899). Among the matched patients with a tumor size of >2 cm, the conization group showed a significantly better 3-year disease-free survival (DFS) rate compared with the non-conization group when RH was conducted via minimally invasive surgery (MIS), in those with squamous cell carcinoma (96.3% vs. 87.4%, P = 0.007) and non-squamous cell carcinoma (97.0% vs. 74.8%, P = 0.021). However, no difference in DFS was observed between the two groups among the matched patients with a tumor size of ≤2 cm, regardless of surgical approach or histological type. In patients who underwent MIS RH, DFS significantly worsened as the residual tumor size increased (P < 0.001). CONCLUSION: Cervical conization was associated with a lower recurrence rate in patients with early-stage cervical cancer with a tumor size of >2 cm who underwent primary MIS RH. Cervical conization may be performed prior to MIS RH to minimize the uterine residual tumor.

Is minimally invasive radical surgery safe for patients with cervical cancer ≤2 cm in size? (MISAFE): Gynecologic Oncology Research Investigators coLLborAtion study (GORILLA-1003).

OBJECTIVE: To identify clinicopathological factors associated with disease recurrence for patients with 2018 FIGO stage IA with lymphovascular invasion to IB1 cervical cancer treated with minimally invasive surgery (MIS). METHODS: A total of 722 patients with cervical cancer between January 2010 and February 2021 were identified. Clinicopathological factors related to disease recurrence were analyzed. Disease-free survival (DFS) and overall survival (OS) rates were estimated using the Kaplan-Meier method. To determine prognostic factors for DFS, a Cox proportional hazard regression model was used. RESULTS: Of 722 patients, 49 (6.8%) experienced disease recurrence (37 pelvis, 1 para-aortic lymph node, and 11 peritoneum). Five-year DFS and OS rates were 90.7% and 98.1%, respectively. In multivariate analysis, risk factors associated with disease recurrence were residual disease in the remaining cervix (OR, 3.122; 95% CI, 1.152-8.461; p = 0.025), intracorporeal colpotomy (OR, 3.252; 95% CI, 1.507-7.017; p = 0.003), and positive resection margin (OR, 3.078; 95% CI, 1.031-9.193; p = 0.044). The non-conization group had a higher percentage of stage IB1 (77.4% vs. 64.6%; p = 0.004) and larger tumor (10 mm vs. 7 mm; p < 0.001) than the conization group. Intracorporeal colpotomy and residual disease in the remaining cervix were independent variables associated with disease recurrence in patients undergoing MIS following conization. CONCLUSION: During MIS, patients with cervical cancer ≤2 cm in size can be vulnerable to peritoneal recurrences. Patients diagnosed with invasive cancer through conization often have low-risk pathological features, which may affect their survival outcomes.

Survival outcomes of laparoscopic versus open radical hysterectomy in early cervical cancer with incidentally identified high-risk factors.

OBJECTIVE: Previously, we suggested that patients with cervical cancer (CC) with tumors ≤2 cm on preoperative magnetic resonance imaging (MRI) are safe candidates for laparoscopic radical hysterectomy (LRH). Here, we aim to investigate whether LRH deteriorates the prognosis of patients with incidentally identified high-risk factors; lymph node metastasis (LNM) or parametrial invasion (PMI). METHODS: We identified patients with 2009 FIGO stage IB1 CC who underwent Type C LRH or open radical hysterectomy (ORH) at three tertiary hospitals between 2000 and 2019. Those with a tumor ≤2 cm on preoperative MRI who were not suspicious of LNM or PMI preoperatively were included, while those who were indicated to receive adjuvant treatment but did not actually receive it were excluded. Survival outcomes were compared between the LRH and ORH groups in the overall population, then narrowed down to those with LNM, and then to those with PMI. RESULTS: In total, 498 patients were included: 299 in the LRH group and 199 in the ORH group. The LRH and ORH groups showed similar 3-year progression-free survival (PFS) (94.0% vs. 93.6%; P = 0.615) and 5-year overall survival (OS) rates (97.2% vs. 96.8%; P = 0.439). On pathologic examination, 49 (9.8%) and 16 (3.2%) patients had LNM and PMI, respectively, and 10 (2.0%) had both. In the LNM subgroup, 5-year PFS rate was not significantly different between the LRH and ORH groups (73.2% vs. 91.7%; P = 0.169). In the PMI subgroup, no difference in PFS was observed between the two groups (P = 0.893). CONCLUSIONS: LRH might not deteriorate recurrence and mortality rates in CC patients with tumors ≤2 cm when adjuvant treatment is appropriately administered, even if pathologic LNM and PMI are incidentally identified.

Fertility-sparing hormonal treatment in patients with stage I endometrial cancer of grade 2 without myometrial invasion and grade 1-2 with superficial myometrial invasion: Gynecologic Oncology Research Investigators coLLaborAtion study (GORILLA-2001).

OBJECTIVES: To evaluate oncologic and pregnancy outcomes of fertility-sparing treatment (FST) using progestin in patients with stage I grade 2 endometrioid endometrial cancer (EC) without myometrial invasion (MI) or grade 1-2 with superficial MI. METHODS: Multicenter data of patients with stage I grade 2 EC without MI or grade 1-2 EC with superficial MI, who received FST between 2005 and 2021, were analyzed. Cox regression analysis identified independent factors for progressive disease (PD) during the FST. RESULTS: Altogether, 54 patients received FST [medroxyprogesterone acetate (500-1000 mg) in 44, megestrol acetate (40-800 mg) in 10] with concurrent levonorgestrel-releasing intrauterine devices use in 31. With median time to achieve a complete response (CR) of 10 (3-24) months, 39 patients (72.2%) achieved CR. Of the 15 patients who attempted to conceive after achieving CR, 7 (46.7%) became pregnant (2 abortions, 5 live births). During a median FST duration of 6 (3-12) months, nine patients (16.6%) were diagnosed with PD. Fifteen (38.5%) experienced recurrence with a median recurrence-free survival of 23 (3-101) months. In the multivariable analysis, tumor size before FST ≥2 cm (HR 5.456, 95% CI 1.34 to 22.14; p = 0.018) was significantly associated with a high PD rate during FST. CONCLUSION: The overall response rate to FST was promising, however, the PD rate was significant during the first 12 months of FST. Therefore, performing thorough endometrial biopsy and imaging studies is essential to strictly evaluate the extent of the disease every 3 months from FST initiation.

Optimum selection criteria for secondary cytoreductive surgery in patients with recurrent epithelial ovarian cancer: A multicenter study from the Gynecologic Oncology Research Investigators coLLaborAtion group (GORILLA-3001).

BACKGROUND: To identify those most likely to benefit from secondary cytoreductive surgery (SCS), we evaluated the survival outcomes and factors predictive of prognosis in patients with recurrent ovarian cancer. METHODS: We retrospectively reviewed the medical records of patients with recurrent ovarian cancer treated at five high-volume Korean hospitals between 2010 and 2021. Recurrence characteristics, treatment methods, and potential predictors of survival were compared between the chemotherapy and surgery groups. RESULTS: Among all 670 patients, 88.1% had initial stage III/IV disease, and 215 (32.1%) underwent SCS. Among patients who underwent SCS, only those who achieved complete resection exhibited improved survival. Even in patients with residual disease < 1 cm after SCS, we observed no significant survival benefit (p = 0.942). In the multivariate Cox analysis, residual disease at primary surgery, progression-free interval, recurrence sites (≤3 regions or limited carcinomatosis), ascites, and SCS were significant predictors of survival. Meanwhile, the only factor predictive of complete resection after SCS was recurrence sites (p < 0.001). CONCLUSIONS: The benefits of SCS appear to be exclusive to cases of complete resection. We propose limited regional platinum-sensitive recurrence (≤3 regions or limited carcinomatosis) without ascites as the optimum selection criteria for SCS.

External validation of the de novo stress urinary incontinence prediction model after pelvic organ prolapse surgery in Korean women: a retrospective cohort study.

BACKGROUND: De novo stress urinary incontinence (SUI) may develop following pelvic organ prolapse surgery. Performing prophylactic continence surgery may reduce the risk of de novo SUI and subsequent continence surgery; however, it may increase the risk of complications. Therefore, many surgeons try to identify women at high risk for de novo SUI and perform continence surgery selectively. Recently, a model for predicting the risk of de novo SUI after prolapse surgery was developed using data from the Outcomes following vaginal Prolapse repair and midUrethral Sling (OPUS) trial; its prediction accuracy was significantly better than that of the stress test alone. However, few studies have verified its prediction accuracy in discrete populations. The aim of this study was to externally validate the prediction model for de novo SUI after prolapse surgery in Korean women. METHODS: This retrospective cohort study included 320 stress-continent women who underwent prolapse surgery for pelvic organ prolapse quantification stage 2-4 anterior or apical prolapse and who completed a 1-year follow-up. Predicted probabilities by the de novo SUI online risk calculator were compared with observed outcomes and quantitated using the model's area under the curve and calibration plot. Subgroup analyses were also performed by the type of prolapse surgery. RESULTS: The de novo SUI prediction model showed moderate discrimination in our study cohort; area under the curve (95% confidence interval) = 0.73 (0.67-0.78) in the whole cohort, 0.69 (0.61-0.78) in women who underwent native tissue repair or colpocleisis, and 0.74 (0.65-0.82) in those who underwent sacrocolpopexy. Calibration curves demonstrated that the model accurately predicted the observed outcomes of de novo SUI in women who underwent native tissue repair or colpocleisis but underestimated outcomes in those who underwent sacrocolpopexy. The predicted probability cutoff points corresponding to an actual risk of 50% were 40% in women who underwent native tissue repair or colpocleisis and 30% in those who underwent sacrocolpopexy. CONCLUSIONS: The de novo SUI prediction model is acceptable for use in Korean women and may aid in shared decision-making regarding prophylactic continence procedure at the time of prolapse surgery.

HOXB9 Overexpression Confers Chemoresistance to Ovarian Cancer Cells by Inducing ERCC-1, MRP-2, and XIAP.

The purpose of this study was to identify the role of HOXB9 and associated molecular mechanism in acquiring chemoresistance to ovarian cancer cells. After establishing HOXB9-overexpressing cells (HOXB9-OE/SKOV3), cisplatin resistance-induced cells (Cis-R/SKOV3), and an ovarian cancer xenograft mouse model, the effects of HOXB9 were evaluated in vitro and in vivo. Expression levels of ERCC-1, MRP-2, XIAP, and Bax/Bcl-2 were assessed as putative mechanisms mediating chemoresistance. Cisplatin-induced apoptosis was significantly decreased in HOXB9-OE/SKOV3 compared to SKOV3. Cisplatin treatment of SKOV3 strongly induced ERCC-1, MRP-2, and XIAP, and apoptosis was strongly induced through the inhibition of Bcl-2 and activation of Bax. ERCC-1, MRP-2, XIAP, and Bcl-2 were also strongly induced in HOXB9 OE/SKOV3. In contrast to SKOV3, cisplatin treatment alone of HOXB9 OE/SKOV3 did not affect the expression of Bcl-2 and Bax, and consequently, there was no increase in apoptosis. HOXB9 knockdown suppressed the expression of ERCC-1 and XIAP, but did not affect MRP-2 and Bcl-2/Bax expression in HOXB9 OE/SKOV3 and Cis-R/SKOV3, and caused a small increase in apoptosis. Treatment of SKOV3 with both cisplatin and siRNA_HOXB9 led to complete suppression of ERCC-1, MRP-2, and XIAP, and significantly increased apoptosis through inhibition of Bcl-2 expression and activation of Bax. The results observed in Cis-R/SKOV3 were similar to that in HOXB9 OE/SKOV3. Our data suggest that HOXB9 overexpression may cause chemoresistance in ovarian cancer cells by differential induction of ERCC-1, MRP-2, and XIAP depending on the strength of HOXB9 expression through inhibition of the mitochondrial pathway of apoptosis, including Bax/Bcl-2.

Clinical implications of neoadjuvant chemotherapy in advanced endometrial cancer: a multi-center retrospective cohort study.

BACKGROUND: The mainstay of endometrial cancer treatment is surgical resection of tumors and postoperative adjuvant treatment is recommended if necessary. However, there is no consensus on the management of unresectable metastatic endometrial cancer. This study aimed to assess the feasibility and effectiveness of neoadjuvant chemotherapy followed by interval debulking surgery (NAC-IDS) in unresectable, metastatic endometrial cancer. METHODS: From the endometrial cancer cohorts of four institutions in Korea, we identified patients with International Federation of Gynecology and Obstetrics stages IIIC-IVB endometrial cancer who received NAC-IDS between January 2008 and December 2020. Through a medical record review, we collected patients' clinicopathological data. Progression-free survival (PFS), overall survival (OS), and the factors affecting survival outcomes were analyzed. RESULTS: Overall, 32 patients were included with endometrioid (n = 18), serous (n = 5), carcinosarcoma (n = 6), and other histological types (n = 3). Among them, 28 (87.5%) patients had stage IVB disease. The most common neoadjuvant chemotherapy (NAC) regimen was paclitaxel-carboplatin (n = 25, 78.1%), which was administered for a median of six cycles. While 26 (81.3%) patients showed an objective response, two (6.3%) progressed despite NAC. At the time of interval debulking surgery (IDS), 23 (71.9%) patients achieved complete cytoreduction. During 31.0 months of the median follow-up, there were 23 recurrences and 11 deaths, corresponding to a median PFS of 19.7 months and a 3-year OS rate of 69.7%. In multivariate analyses, non-endometrioid histology and residual tumor after IDS were identified as independent poor prognostic factors for PFS (adjusted hazard ratio [HR], 7.322; P < 0.001 and 5.934; P = 0.001, respectively). Multivariate analysis for OS could not be conducted because of the small number of events, although non-endometrioid histology was the only factor associated with worse OS in univariate analysis (adjusted HR, 4.523; P = 0.032). CONCLUSIONS: NAC-IDS may be a treatment option for unresectable metastatic endometrial cancer. Tumor histology and the possibility of complete cytoreduction are the primary considerations for NAC-IDS.

A phase IA dose-escalation study of PHI-101, a new checkpoint kinase 2 inhibitor, for platinum-resistant recurrent ovarian cancer.

BACKGROUND: PHI-101 is an orally available, selective checkpoint kinase 2 (Chk2) inhibitor. PHI-101 has shown anti-tumour activity in ovarian cancer cell lines and impaired DNA repair pathways in preclinical experiments. Furthermore, the in vivo study suggests the synergistic effect of PHI-101 through combination with PARP inhibitors for ovarian cancer treatment. The primary objective of this study is to evaluate the safety and tolerability of PHI-101 in platinum-resistant recurrent ovarian cancer. METHODS: Chk2 inhibitor for Recurrent EpitheliAl periToneal, fallopIan, or oVarian cancEr (CREATIVE) trial is a prospective, multi-centre, phase IA dose-escalation study. Six cohorts of dose levels are planned, and six to 36 patients are expected to be enrolled in this trial. Major inclusion criteria include ≥ 19 years with histologically confirmed epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal cancer. Also, patients who showed disease progression during platinum-based chemotherapy or disease progression within 24 weeks from completion of platinum-based chemotherapy will be included, and prior chemotherapy lines of more than five will be excluded. The primary endpoint of this study is to determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of PHI-101. DISCUSSION: PHI-101 is the first orally available Chk2 inhibitor, expected to show effectiveness in treating recurrent ovarian cancer. Through this CREATIVE trial, DLT and MTD of this new targeted therapy can be confirmed to find the recommended dose for the phase II clinical trial. This study may contribute to developing a new combination regimen for the treatment of ovarian cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04678102 .

Gastrointestinal/genitourinary perforation and fistula formation with or without bevacizumab in patients with previously irradiated recurrent cervical cancer: a Korean multicenter retrospective study of the Gynecologic Oncology Research Investigators Collaboration (GORILLA) group (GORILLA-1001).

BACKGROUND: This study aims to evaluate the incidence of and identify risk factors for gastrointestinal (GI) and genitourinary (GU) fistula or perforation formation with or without bevacizumab in patients with recurrent cervical cancer who underwent pelvic radiation therapy (RT). METHODS: Medical records of patients with recurrent cervical cancer who previously underwent pelvic RT between 2007 and 2020 were retrospectively reviewed. Clinicopathological factors were compared between groups that are stratified according to: 1) fistula/perforation (+) versus (-); and 2) bevacizumab plus conventional chemotherapy (BC) versus chemotherapy alone (C). Univariate and multivariate regression analyses were performed to identify risk factors for fistula/perforation. Overall survival (OS) was compared between the different groups. RESULTS: Of 219 participants, fistula/perforation of any grade occurred in 36 patients (16.4%); 27 fistulas and 9 perforations. Bevacizumab was more frequently used in Bevacizumab was more frequently used ( +) group than fistula/perforation (-) group (p = 0.015). Multivariate analysis showed that bevacizumab administration was the only independent risk factor for fistula or perforation (HR, 3.27; 95% CI, 1.18-9.10; P = 0.023). F/P was observed more frequently in women receiving BC (n = 144) than those receiving C (n = 75) (20.8% vs. 8.0%; P = 0.019). During median follow-up of 33.7 months (1.2-185.6 months), no significant OS difference was observed between fistula/perforation ( +) vs. (-) (hazards ratio [HR], 1.78; median 84.2 months [95% CI, 59.3-109.0] vs. 129.5 months [95% CI, 114.1-144.9]; P = 0.065) or BC vs. C (HR, 1.03; median 119.8 months [95% CI, 97.3-142.3] vs. 115.7 months [95% CI, 96.0-135.4]; P = 0.928). CONCLUSIONS: This study suggests that incorporation of bevacizumab in chemotherapy regimens for treating recurrent cervical cancer in patients who underwent pelvic RT incurs considerable risk for GI/GU fistula or perforation. There were no other independent risk factors for developing GI/GU fistula or perforation in this study population.

Open versus minimally invasive radical hysterectomy for early cervical cancer: A two-center retrospective cohort study with pathologic review of usual-type adenocarcinoma and adenosquamous carcinoma.

OBJECTIVE: To compare survival outcomes of minimally invasive surgery (MIS) and open surgery for radical hysterectomy (RH) in early cervical cancer patients with histologic subtypes of usual-type adenocarcinoma and adenosquamous carcinoma. METHODS: From two centers' cervical cancer cohorts, patients with 2009 FIGO stage IB1-IB2 who underwent RH between 2007 and 2020 were retrospectively identified. Patients with usual-type adenocarcinoma and adenosquamous carcinoma were included in the analysis after pathologic review according to the updated World Health Organization Classification of Tumors. Clinicopathologic characteristics and survival outcomes were compared in terms of open surgery or MIS. RESULTS: This study included 161 patients. No significant differences were noted in overall survival (OS; P = 0.241) and disease-free survival (DFS; P = 0.156) between patients with usual-type adenocarcinoma (n = 136) and those with adenosquamous carcinoma (n = 25). MIS RH group (n = 99) had a significantly smaller tumor size (P < 0.001), lesser pathologic parametrial invasion (P = 0.001), and lesser lymph node metastasis (P < 0.001) than open RH group (n = 62). MIS and open RH groups showed similar OS (P = 0.201) and 3-year DFS rate (87.9% vs. 75.1%; P = 0.184). In multivariate analysis, worse DFS was not associated with MIS (P = 0.589) but was associated with pathologic parametrial invasion (adjusted HR, 3.41; 95% CI, 1.25-9.29; P = 0.016). Consistent results were observed among patients with usual-type adenocarcinoma; MIS was not associated with worse DFS. CONCLUSIONS: Comparable survival outcomes were found for MIS and open RH in early-stage cervical usual-type adenocarcinoma and adenosquamous carcinoma. Although MIS RH was not a poor prognostic factor, pathologic parametrial invasion was significantly associated with worse DFS in cervical usual-type adenocarcinoma and adenosquamous carcinoma.

Serum Human Epididymis Protein 4 as a Prognostic Marker in Cervical Cancer.

OBJECTIVES: The objective is to evaluate the prognostic value of serum human epididymis protein 4 (HE4) as a tumor marker in patients with cervical cancer. METHODS: Sixty-seven patients with cervical cancer treated at Seoul National University Bundang Hospital from September 2014 to May 2018 were retrospectively reviewed. Serum HE4 levels were measured by immunoassay before starting primary treatment. A mean serum HE4 level of 72.6 pmol/L was used to divide the patients into low and high HE4 groups. Patient characteristics, clinicopathological variables, and survival outcomes were compared between the two groups. RESULTS: The low and high HE4 groups included 55 (82.1%) and 12 (17.9%) patients at diagnosis, respectively. Higher HE4 levels were significantly associated with older age at diagnosis (age <50: .0% vs age ≥50: 100.0%; P = .002), menopause (premenopause: 8.3% vs postmenopause: 91.7%; P = .009), higher FIGO stage (stage I-II: 33.3% vs III-IV: 66.7%; P = .017), large tumor size (<4.0 cm: 41.7% vs ≥4.0 cm: 58.3%; P = .029), positive lymph node metastasis (negative: 41.7% vs positive: 58.3%; P = .049), and involvement of the parametrium (negative: 25.0% vs positive: 75.0%; P = .002). Higher HE4 level was a predictive factor for worse overall survival but not for progression-free survival. Elevated HE4 levels were not independent factors for the prediction of either overall survival or progression-free survival. Subgroup analysis by histological type revealed similar results for patients with squamous cell carcinoma. CONCLUSIONS: High levels of HE4 expression correlated with poor overall survival, indicating that elevated HE4 levels are associated with a poor prognosis for patients with cervical cancer.

Development and validation of a prediction model for bothersome stress urinary incontinence after prolapse surgery: A retrospective cohort study.

OBJECTIVE: To develop and validate a prediction model for bothersome stress urinary incontinence after prolapse surgery and to compare it with an existing clinical prediction model (CUPIDO model). DESIGN: Retrospective cohort study. SETTING: Two tertiary hospitals in South Korea. POPULATION: A total of 1142 patients who underwent prolapse surgery with or without a concomitant midurethral sling. METHODS: To construct a prediction model, we performed logistic regression using both exhaustive and stepwise variable selection, validating the model both internally and externally. MAIN OUTCOME MEASURES: Bothersome stress urinary incontinence defined as the presence of bothersome symptoms of stress urinary incontinence and/or subsequent continence procedure one year after surgery. RESULTS: Postoperative bothersome stress urinary incontinence occurred in 10% of patients. A model containing six predictors (age, diabetes mellitus, subjective urinary incontinence, prolapse reduction stress test result, type of prolapse surgery, and a concomitant midurethral sling) showed excellent performance for predicting bothersome stress urinary incontinence (area under the curve 0.74, 95% confidence interval 0.62-0.86) and outperformed the CUPIDO model (area under the curve 0.63, 95% confidence interval 0.49-0.76; DeLong's test P = 0.014). CONCLUSIONS: This prediction model might be a useful tool to guide patient decision making regarding a concomitant continence procedure at the time of prolapse surgery. The predictive value of this model needs to be validated further in cohorts with different characteristics. TWEETABLE ABSTRACT: The proposed prediction model for bothersome stress urinary incontinence after prolapse surgery outperforms an existing model.

Efficacy and safety of skin-adhesive low-level light therapy for overactive bladder: a Phase III study.

INTRODUCTION AND HYPOTHESIS: Overactive bladder (OAB) is a common condition that remains challenging to treat. We hypothesized that skin-adhesive low-level light therapy (LLLT) would be an effective treatment for OAB caused by bladder muscle contraction. Accordingly, we aimed to evaluate the efficacy and safety of an LLLT device for the treatment of OAB. METHODS: This prospective, randomized, double-blind, placebo-controlled, multicenter trial included patients with a clinical diagnosis of OAB who were treated at either of two university hospitals. Patients were instructed to apply an LLLT device (Color DNA-WSF) or a sham device at home three times daily for 12 weeks. The primary outcome was the change in the mean daily number of urge urinary incontinence (UUI) episodes between baseline and 12 weeks. The secondary outcomes were the mean changes in incontinence, voiding, and nocturia episodes from baseline and the likelihood of achieving a > 50% reduction in UUI and incontinence episodes after 12 weeks. All patients completed the Overactive Bladder Symptom Score (OABSS), Urogenital Distress Inventory-6 (UDI-6), and Impact Urinary Incontinence-7 (IIQ-7) questionnaires. Safety parameters included treatment-emergent adverse events. RESULTS: Compared with those in the sham group, the numbers of UUI and urinary incontinence episodes in the LLLT group were significantly decreased at week 12 (UUI, (-1.0 ± 1.7 vs. -0.4 ± 2.5, P = 0.003; urinary incontinence, -1.1 ± 1.9 vs. -0.5 ± 2.9, P=0.002). Furthermore, the OABSS, UDI-6, and IIQ-7 scores at week 12 tended to be better in the LLLT group than in the sham group. The incidence of device-related treatment-emergent adverse events was similar between groups. CONCLUSIONS: LLLT may be clinically useful and safe for the treatment of OAB.

Cosmesis and feasibility of transvaginal natural orifice Specimen extraction (NOSE) for large organ specimen: a prospective pilot study.

BACKGROUND: This study aimed to evaluate cosmetic outcomes and feasibility of transvaginal natural orifice specimen extraction (NOSE) in patients who underwent laparoscopic or robotic surgery for the treatment of benign or malignant diseases of the kidney, liver, stomach, adrenal gland, and bladder. METHODS: This prospective study was conducted at a tertiary hospital between March 2015 and May 2020. The main outcome was cosmetic outcomes of scars assessed using the Patient and Observer Scar Assessment Scale (POSAS) 1 and 8 weeks after surgery. The secondary outcomes were postoperative pain, operating time, and complications. Sexual function was assessed using the Female Sexual Function Index (FSFI) questionnaire 6 months after surgery in 17 patients who were sexually active at the time of surgery. RESULTS: A total of 38 transvaginal NOSE procedures were performed for the extraction of 33 kidneys, 2 livers, 1 stomach, 1 adrenal gland, and 1 bladder. Observers rated pigmentation and relief scores as most deviant from normal skin (2.9 ± 1.7, 3.0 ± 2.1 at postoperative 1 week; 3.6 ± 1.9, 3.5 ± 2.2 at postoperative 8 weeks, respectively), but the overall scores of each item were low. The patients' overall satisfaction with postoperative scars was high, and the mean scores for pain and itching were low, with significant improvement from the first week to the eighth week (P = 0.014 and P = 0.006, respectively). Patients also reported low scores on vaginal assessment items, indicating better symptoms, and bleeding improved significantly between the two time points (P = 0.001). Postoperative pain was reduced from moderate during the first 24 h after surgery to mild after 24 h. The mean operative time of the transvaginal NOSE procedure was 28.3 ± 13.3 min. No postoperative complications were associated with the procedure. The mean FSFI total score was 21.2 ± 8.7 (cutoff score for dysfunction is 21), with higher scores indicating better sexual functioning. CONCLUSION: Transvaginal NOSE seems to be a feasible procedure with promising cosmetic benefits, for patients who undergo minimally invasive surgery for large organs including the kidney, liver, stomach, adrenal gland, and bladder. A prospective randomized clinical trial is needed to provide solid evidence to support transvaginal NOSE. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov (NCT05113134).

Risk factors for and prognosis of carboplatin-related hypersensitivity in patients with epithelial ovarian cancer.

PURPOSE: We aimed to identify the predictive risk factors for carboplatin-related hypersensitive reactions (HRs) and investigate their impact on survival outcomes in patients with epithelial ovarian cancer (EOC). METHODS: This retrospective study included 222 patients with EOC who received carboplatin infusion between July 2016 and November 2019. We compared the clinicopathologic characteristics and survival outcomes between carboplatin-related hypersensitivity and non-hypersensitivity groups. Hypersensitivity data were classified using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, categorizing grades from 1 to 5 as mild/moderate/severe/life-threatening/death. Multiple logistic regression analysis was used to analyze risk factors of HRs. The Cox proportional hazard regression model was used to determine the factors of being significantly associated with overall survival. RESULTS: Of the 222 patients, eight exhibited HRs (incidence rate, 3.6%). All HRs were of grade 3 or 4 (life-threatening). In all cases, a desensitization protocol was followed. Advanced stage (III or IV) (P = 0.022), previous history of carboplatin use (P < 0.001), and recurrent ovarian cancer (P = 0.001) were significantly associated with HR to carboplatin. Multivariate logistic analysis showed that a previous history of carboplatin was the only independent risk factor for carboplatin-related hypersensitivity (OR, 20.19; 95% CI 1.22 - 3034.10; P = 0.034). However, HR to carboplatin did not influence the overall survival (P = 0.526). CONCLUSION: In EOC patients, prior use of carboplatin was an independent risk factor for carboplatin-related HRs; HRs to carboplatin did not influence the overall survival. Clinicians should not underestimate the possibility risk of carboplatin HSRs when re-administrating carboplatin in EOC patients.