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Although an infrequent occurrence, the placenta can adhere abnormally to the gravid uterus leading to significantly high maternal morbidity and mortality during cesarean delivery. Contemporary national statistics related to a morbidly adherent placenta, referred to as placenta accreta spectrum, are needed.This study aimed to examine national trends, characteristics, and perioperative outcomes of women who underwent cesarean delivery for placenta accreta spectrum in the United States.This is a population-based retrospective, observational study querying the National Inpatient Sample. The study cohort included women who underwent cesarean delivery from October 2015 to December 2017 and had a diagnosis of placenta accreta spectrum. The main outcome measures were patient characteristics and surgical outcomes related to placenta accreta spectrum assessed by the generalized estimating equation on multivariable analysis. The temporal trend of placenta accreta spectrum was also assessed by linear segmented regression with log transformation.Of 2,727,477 cases who underwent cesarean delivery during the study period, 8030 (0.29%) had the diagnosis of placenta accreta spectrum. Placenta accreta was the most common diagnosis (n=6205, 0.23%), followed by percreta (n=1060, 0.04%) and increta (n=765, 0.03%). The number of placenta accreta spectrum cases increased by 2.1% every quarter year from 0.27% to 0.32% (P=.004). On multivariable analysis, (1) patient demographics (older age, tobacco use, recent diagnosis, higher comorbidity, and use of assisted reproductive technology), (2) pregnancy characteristics (placenta previa, previous cesarean delivery, breech presentation, and grand multiparity), and (3) hospital factors (urban teaching center and large bed capacity hospital) represented the independent characteristics related to placenta accreta spectrum (all, P.05). The median gestational age at cesarean delivery was 36 weeks for placenta accreta and 34 weeks for both placenta increta and percreta vs 39 weeks for non-placenta accreta spectrum cases (P.001). On multivariable analysis, cesarean delivery complicated by placenta accreta spectrum was associated with increased risk of any surgical morbidities (78.3% vs 10.6%), Centers for Disease Control and Prevention-defined severe maternal morbidity (60.3% vs 3.1%), hemorrhage (54.1% vs 3.9%), coagulopathy (5.3% vs 0.3%), shock (5.0% vs 0.1%), urinary tract injury (8.3% vs 0.2%), and death (0.25% vs 0.01%) compared with cesarean delivery without placenta accreta spectrum. When further analyzed by subtype, cesarean delivery for placenta increta and percreta was associated with higher likelihood of hysterectomy (0.4% for non-placenta accreta spectrum, 45.8% for accreta, 82.4% for increta, 78.3% for percreta; P.001) and urinary tract injury (0.2% for non-placenta accreta spectrum, 5.2% for accreta, 11.8% for increta, 24.5% for percreta; P.001). Moreover, women in the placenta increta and percreta groups had markedly increased risks of surgical mortality compared with those without placenta accreta spectrum (increta, odds ratio, 19.9; and percreta, odds ratio, 32.1).Patient characteristics and outcomes differ across the placenta accreta spectrum subtypes, and women with placenta increta and percreta have considerably high surgical morbidity and mortality risks. Notably, 1 in 313 women undergoing cesarean delivery had a diagnosis of placenta accreta spectrum by the end of 2017, and the incidence seems to be higher than reported in previous studies.

To examine characteristics and short-term perioperative outcomes related to minimally invasive pelvic exenteration for gynecologic malignancy.This comparative effectiveness study is a retrospective population-based analysis of the National Inpatient Sample from 10/2008-9/2015. Women with cervical, uterine, vaginal, and vulvar malignancies who underwent pelvic exenteration were evaluated based on the use of laparoscopic or robotic-assisted surgery. Patient demographics and intraoperative/postoperative complications related to a minimally invasive surgical approach were assessed.Among 1376 women who underwent pelvic exenteration, 49 (3.6%) had the procedure performed via a minimally invasive approach. The majority of minimally invasive cases were robotic-assisted (51.0%). Women in the minimally invasive group were more likely to be old, white, have cervical/uterine cancers, and receive urinary diversion, but less frequently received vaginal reconstruction or colostomy when compared to those in the open surgery group (P0.05). Overall perioperative complication rates were similar between the minimally invasive and open surgery groups (79.6% versus 77.7%, P = 0.862), but the minimally invasive group had a decreased risk of high-risk complications compared to the open surgery group (adjusted-odds ratio 0.19, 95% confidence interval 0.07-0.51). Specifically, a minimally invasive approach was associated with decreased incidence of sepsis and thromboembolism compared to an open approach (P0.05). The minimally invasive group had a shorter length of stay (median, 9 versus 14 days) and lower total charge (median, $127,875 versus $208,591) compared to the open surgery group (P0.05).Laparotomy remains the main surgical approach for pelvic exenteration for gynecologic malignancy and minimally invasive surgery was infrequently utilized during the study period in the United States. Before widely adopting this surgical approach, the utility and role of minimally invasive pelvic exenteration requires further investigation.

Objective To examine the perioperative and survival outcomes in women with disseminated peritoneal uterine leiomyosarcoma (uLMS) who underwent cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Methods A comprehensive systematic review of literature was conducted using multiple public search engines, PubMed, Scopus, and the Cochrane Library, in compliance with the PRISMA guidelines. Women with disseminated peritoneal uLMS treated with CRS-HIPEC were analyzed. Perioperative morbidity and mortality rate as well as oncologic outcomes related to CRS-HIPEC were assessed. Results Ten studies met the inclusion criteria from 2004 to 2020, including 8 case series (n=28) and 2 original articles (n=47). Of the 75 patients, 68 (90.7%) were women with uLMS whereas 7 women were non-uLMS. Of these, 64 (85.3%) had recurrent disease, and 39 (52.0%) received chemotherapy or radiotherapy prior to CRS-HIPEC. The perioperative mortality rate was 4.0% (intraoperative 1.3%, and postoperative 2.7%), and postoperative complications (grade ≥3) rate ranged 21.4-22.2%. With regard to HIPEC regimens (n=75), cisplatin was most frequently used (n=55, 73.3%) followed by melphalan (n=17, 22.7%) and others (n=3, 4.0%). Among the two observational studies, the median overall survival after CRS-HIPEC treatment was 29.5-37 months. In one limited comparative effectiveness study (n=13), albeit statistically non-significant CRS-HIPEC was associated with higher progression-free survival versus CRS alone (3-year rates, 71.4% versus 0%, P=0.10). When the HIPEC regimens were compared, melphalan use was associated with decreased uLMS-related mortality compared to a cisplatin-based regimen, but the association was not statistically significant (hazard ratio 0.35, 95% confidence interval 0.04-3.05, P=0.35). Conclusion Effectiveness of CRS-HIPEC for disseminated peritoneal uLMS is yet to be determined. As interpretation of the available data on survival is limited due to small sample sizes or the lack of an active comparator, further study is warranted to examine the safety and survival effect of CRS-HIPEC in disseminated peritoneal uLMS.

The aim of this study was to examine the survival effect of adjuvant therapy in stage II–III endometrial cancer based on peritoneal cytology results. The National Cancer Institute’s Surveillance, Epidemiology, and End Results Program was retrospectively queried to examine 7467 women with stage II–III endometrial cancer who underwent hysterectomy, and with available peritoneal cytology results, from 2010 to 2016. A Cox proportional hazard regression model was fitted to assess the association between adjuvant therapy and all-cause mortality stratified by peritoneal cytology results. Malignant peritoneal cytology was reported in 1662 (22.3%) women and was associated with non-endometrioid histology, higher tumor stage, and nodal metastasis (p

To examine the association between surgical margin status and recurrence pattern in invasive vulvar Paget's disease.This is a preplanned secondary analysis of a previously organized nationwide retrospective study in Japan (JGOG-1075S). Women with stage I-IV invasive vulvar Paget's disease who received surgical treatment from 2001-2010 were examined (n=139). Multivariable analysis was performed to assess local-recurrence, distant-recurrence, and all-cause mortality based on surgical margin status.The median age was 70 years. The majority had stage I disease (61.2%), and the median tumor size was 5.0cm. Nodal metastasis was observed in 15.1%. Simple vulvectomy (46.0%) was the most common surgery type followed by radical vulvectomy (28.1%). More than half received vulvar reconstructive surgery (59.0%). Positive surgical margin was observed in 35.3%, and close margin1cm was observed in 29.5%. Vulvectomy type was not associated with surgical margin status (P=0.424). The median follow-up was 5.8 years. Positive surgical margin was associated with increased local-recurrence (5-year cumulative rates for positive versus negative margin: 35.8% versus 15.0%, P=0.010) but not distant-recurrence (18.3% versus 16.0%, P=0.567). Positive surgical margin was also associated with increased all-cause mortality (5-year overall survival rates for positive versus negative margin: 72.6% versus 88.2%, P=0.032). In multivariable analysis, positive surgical margin remained an independent factor associated with increased risk of local-recurrence (hazard ratio 2.80, 95% confidence interval 1.18-6.63) and all-cause mortality (hazard ratio 2.87, 95% confidence interval 1.20-6.83).Positive surgical margin appears to be common in invasive vulvar Paget's disease that is associated with increased local-recurrence and all-cause mortality risks. Role of alternative surgical technique or adjuvant therapy merits further investigation to improve local disease control.

Uterine carcinosarcoma (UCS) is a biphasic aggressive high-grade endometrial cancer in which the sarcoma element has de-differentiated from the carcinoma element. UCS is considered a rare tumor, but its incidence has gradually increased in recent years (annual percent change from 2000 to 2016 1.7%, 95% confidence interval 1.2–2.2) as has the proportion of UCS among endometrial cancer, exceeding 5% in recent years. UCS typically affects the elderly, but in recent decades patients became younger. Notably, a stage-shift has occurred in recent years with increasing nodal metastasis and decreasing distant metastasis. The concept of sarcoma dominance may be new in UCS, and a sarcomatous element >50% of the uterine tumor is associated with decreased survival. Multimodal treatment is the mainstay of UCS. Lymphadenectomy, chemotherapy, and brachytherapy have increased in the past few decades, but survival outcomes remain dismal: the median survival is less than two years, and the 5-year overall survival rate has not changed in decades (31.9% in 1975 to 33.8% in 2012). Carboplatin/paclitaxel adjuvant chemotherapy improves progression-free survival compared with ifosfamide/paclitaxel, particularly in stages III-IV disease (GOG-261 trial). Twenty-six clinical trials previously examined therapeutic effectiveness in recurrent/metastatic UCS. The median response rate and progression-free survival were 37.5% and 5.9 months, respectively, after first-line therapy, but after later therapies, the outcomes were far worse (5.5% and 1.8 months, respectively). One significant discovery was that epithelial-mesenchymal transition (EMT) plays a pivotal role in the pathogenesis of sarcomatous dedifferentiation in UCS and that heterologous sarcoma is associated with a higher EMT signature compared with homologous sarcoma. Furthermore, next-generation sequencing has revealed that UCS tumors are serous-like and that common somatic mutations include those in TP53, PIK3CA, FBXW7, PTEN, and ARID1A. This contemporary review highlights recent clinical and molecular updates in UCS. A possible therapeutic target of EMT in UCS is also discussed.

Given the improved survival prediction of a tumor size-based 3-tier grouping system for stage IB cervical cancer under the new staging guidelines, this study examined the survival utility of a tumor size-based 3-tier system for stage T2a cervical cancer.This is a population-based retrospective observational study utilizing the Surveillance, Epidemiology, and End Result Program from 1988 to 2016. Women with stage T2a/N0-1-x/M0-x cervical cancer were grouped by tumor size in a 3-tier system: stage T2a (≤2 cm), T2a (2.1-4.0 cm), and T2a (4 cm). Survival outcome was examined by non-proportional hazard analysis with restricted mean survival time (RMST) at 5 years.Among 2449 cases, the most common group was T2a (4 cm) (n = 1,392, 56.8%), followed by T2a (2.1-4 cm) (n = 783, 32.0%) and T2a (≤2 cm) (n = 274, 11.2%). The median follow-up was 5.2 years. The proposed 3-tier system clearly discriminated survival outcome between the groups: average overall survival time during 5 years of follow-up, 51.0, 47.2, and 43.8 months for T2a (≤2 cm), T2a (2.1-4 cm), and T2a (4 cm) group, respectively (P 0.001). Adjusted between-group difference of average overall survival time in the 3-tier system (8.8 months, 95% confidence interval [CI] 6.2-11.3, P 0.001) was larger compared to the between-group difference in the historical 2-tier system (5.9 months, 95%CI 4.2-7.6, P 0.001). Women in the T2a (≤2 cm) group were more likely to have longer average overall survival time during 5 years of follow-up compared to those in the T2a (2.1-4 cm) group (3.6 months, 95%CI 1.1-6.1, P = 0.004).Our study suggests that a tumor size-based 3-tier grouping system may be useful for improved prediction of survival in stage IIA cervical cancer.

Objectives: Current cancer staging uses a 2-tier schema for stage I uterine leiomyosarcoma based on tumor size (≤5cm versus >5cm). Given the majority of stage I uterine leiomyosarcomas are >5cm in tumor size, this study examined the utility of a 3-tier schema (≤5cm, 5.1-10cm, and >10cm) in determining survival in stage I uterine leiomyosarcoma. Methods: This retrospective study queried the Surveillance, Epidemiology, and End Result 36 Program from 1988-2016. Surgically-treated stage I uterine leiomyosarcomas with known tumor size were examined (N=2,217). Trends, characteristics, and survival were assessed based on tumor size. Results: The most common tumor size was 5.1-10cm (45.7%) followed by >10cm (35.0%) and ≤5cm (19.4%). Tumor size-shift occurred during the study period and the number of tumor size >10cm increased from 12.9% to 44.5% whereas the number of other tumor size groups decreased (P 10cm versus ≤5cm reached nearly two-fold (hazard ratio 1.96, 95% confidence interval 1.78-2.16). Women with tumor size >10cm were nearly twice more likely to receive adjuvant chemotherapy versus those with Conclusions: In the past decades, tumors of stage I uterine leiomyosarcoma have become larger. A tumor size-based 3-tier staging system may be useful to differentiate survival in stage I uterine leiomyosarcoma. Tumor size appears to be a deciding factor for adjuvant chemotherapy use but it did not improve survival. Download : Download high-res image (108KB) Download : Download full-size image

INTRODUCTION The US population has witnessed an epidemic expansion of obesity in the past several decades; nearly 50% of the population is projected to be obese by 2030 and 25% morbidly obese. This study examined trends, characteristics and outcomes of morbidly obese women who underwent benign hysterectomy. MATERIAL AND METHODS This is a population-based retrospective observational study querying the National Inpatient Sample from January 2012 to September 2015. The study population included 509 395 women who underwent hysterectomy for benign gynecological disease: 430 865 (84.6%) non-obese women, 50 435 (9.9%) women with class I-II obesity and 28 095 (5.5%) women with class III obesity. Main outcome measures were (i) cohort-level trends of obesity and perioperative complications assessed by piecewise linear regression with log transformation and (ii) patient-level perioperative complication risk by body habitus assessed with a generalized estimating equation after using a multiple-group generalized boosted model. RESULTS The rate of class III obesity increased by 40.4%, higher than the rate of class I-II obesity (22.2%) (both, P

Objective Angular and interstitial pregnancies have been reported with live births and are often complicated by adherent placentas. Most cases had been treated with hysterectomy or corneal resection. Case report We successfully treated four patients with conservative management (including one reported previously). Case 1 had a vaginal delivery, but the placenta remained attached. We maintained the patient under observation and delivered the placenta on postpartum day 9. Case 2 underwent a C-section. Uterine artery embolization controlled the hemorrhage without placenta removal. The placenta had disappeared by postpartum day 136. Case 3 underwent a C-section. The right uterine angle, where the placenta was attached, was bulging. We manually removed the placenta. Conclusion We propose a new entity in angular or interstitial pregnancies called “angular placenta attachment” that could be diagnosed during C-sections or after vaginal delivery without placental separation. Expectant management may be considered for adherent placentas in these cases.

Granulosa cell tumors of the ovary (GCT) are the most common type of sex cord stromal tumors. Although most of patients are diagnosed at early stage and has favorable 5-year overall survival rate, 16-23% of GCT ultimately develop recurrent disease. Recurrences are characterized by disseminated peritoneal metastasis. The treatment options include systemic chemotherapy, secondary CRS or palliative localized radiation therapy have not yet standardized due to the rarity of disease. Aggressive CRS followed up by hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to provide benefit in other peritoneal disease but limited data available for recurrent GCT. We have a case of recurrent Adult-type GCT (AGCT) who was treated with CRS followed by HIPEC with mitomycin C and doxorubicin. The patient has no evidence of recurrence for approximately 11 years. An electronic search of the PubMed database with the following search terms: GCT, HIPEC showed that there were total 21 patients with recurrent GCT treated in seven different studies and 13 of 21 (61.9%) patients had no evidence of disease during follow-up ranging from 6 to 100 months. Three patients (14.2%) died of the disease. Six studies used cisplatin for HIPEC. At least 76.2% (16 of 21, data not available for five patients) had complete cytoreduction with total 16 cases of perioperative complications but no perioperative mortality was observed. Although further investigation is needed, we propose that CRS and HIPEC can be an effective therapeutic option for recurrent GCT at experienced institutions.

OBJECTIVE. To examine the survival of women with stage I non-endometrioid endometrial cancer with malignant peritoneal cytology. METHODS. A retrospective observational cohort study was conducted to examine the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program from 2010 to 2016. Women with stage I serous, clear cell, carcinosarcoma, undifferentiated, and mixed endometrial cancer with known peritoneal cytology results at hysterectomy were examined (N = 4506). Propensity score inverse probability of treatment weighting was used to balance the measured covariates, and survival outcomes were assessed according to peritoneal cytology results. RESULTS. Malignant peritoneal cytology was reported in 401 (8.9%) women. In multivariable analysis, older age, serous histology, and large tumors were associated with an increased likelihood of malignant peritoneal cytology (all, P < 0.05). In a propensity score weighted model, malignant peritoneal cytology was associated with a nearly two-fold increase in all-cause mortality risk compared to negative peritoneal cytology (5-year rates, 63.4% versus 80.2%, hazard ratio 2.18, 95% confidence interval 1.78–2.66). In sensitivity analyses, malignant peritoneal cytology was associated with decreased overall survival in old and young age groups, serous, clear cell, carcinosarcoma, and mixed histology groups, stage T1a disease, and staged and unstaged cases, but not for stage T1b disease. Difference in 5-year overall survival rates between the malignant and negative peritoneal cytology groups was particularly large among those with clear cell histology (24.0%), stage T1a disease (19.4%), aged >78 years(18.2%), and serous tumors (17.6%). CONCLUSION. Malignant peritoneal cytology can be prevalent in stage I non-endometrioid endometrial cancer. Our study suggests that malignant peritoneal cytology is a prognostic factor for decreased survival in stage I non-endometrioid endometrial cancer.

OBJECTIVE. To examine trends and associated characteristics and outcomes of minimally invasive surgery (MIS) for women with early-stage ovarian cancer. METHODS. The National Inpatient Sample was queried to examine early-stage ovarian cancer treated with MIS from 2001 to 2011. Annualized hospital surgical volume was defined in the unweighted model as the average number of procedures performed per year in which at least one case was performed. Trends, characteristics, and outcomes related to MIS use were assessed in the weighted model. RESULTS. Among 73,707 oophorectomy cases, there were 4822 (6.5%) MIS cases. Utilization of MIS increased from 3.9% to 13.5% from 2001 to 2011 (3.5-fold increase, P < 0.001), and the number of MIS-offering centers also increased from 10.6% to 36.2% (3.4-fold increase, P < 0.001). MIS was associated with a decreased complication rate (20.3% versus 35.4%) and shorter hospital stay (median, 2 versus 4 days) compared to laparotomy (both, P < 0.001). Of the 472 hospitals at which MIS was performed, the majority were minimum-volume with one MIS oophorectomy per year (340 [72.0%], n = 1929 [40.0%]), followed by mid-volume (85 [18.0%], n = 1272 [26.4%]) and topdecile-volume (47 [10.0%] hospitals, n = 1621 [33.6%]). The topdecile-volume group had the highest rate of lymphadenectomy compared to other groups (62.2% versus 39.2–55.1%, P < 0.05). On multivariable analysis, a one increment increase in annualized hospital surgical volume was associated with an 11% decrease in multiple complications (adjusted-odds ratio 0.89, 95% confidence interval 0.82–0.97, P = 0.006). CONCLUSION. Utilization of MIS for early-stage ovarian cancer has significantly increased in the United States in 2000s. In 2011, one in eight surgeries performed for early ovarian cancer were performed via MIS. MIS procedures performed at hospitals with a higher surgical volume may be associated with improved short-term perioperative outcomes.

BACKGROUND: To examine the association between malignant peritoneal cytology and survival in women with early-stage endometrioid endometrial cancer. METHODS: This is a retrospective cohort study using the Surveillance, Epidemiology, and End Results Program from 2010 to 2016. Women with stage I endometrioid endometrial cancer who had peritoneal cytology testing at hysterectomy were examined (N = 24,800). Characteristics and survival related to malignant peritoneal cytology were assessed. The propensity score inverse probability of treatment weighting was used to balance the measured covariates. FINDINGS: Malignant peritoneal cytology was reported in 1081 (4.4%) women. In multivariable analysis, stage IB disease and moderately/poorly differentiated tumours were associated with an increased likelihood of malignant peritoneal cytology (both P < 0.05). In a weighted model, malignant peritoneal cytology was associated with decreased cause-specific survival (5-year rates, 92.1% versus 96.8%, hazard ratio [HR] 1.98, 95% confidence interval [CI] 1.56–2.52) and overall survival (89.4% versus 93.1%, HR 1.41, 95% CI 1.16–1.72). In sensitivity analyses, malignant peritoneal cytology was associated with decreased overall survival in the high–intermediate-risk group (5-year rates, 77.8% versus 83.6%, HR 1.57, 95% CI 1.20–2.06) and decreased cause-specific survival in the low-risk group (95.4% versus 98.0%, HR 1.64, 95% CI 1.01–2.68). In the high–intermediate-risk group with malignant peritoneal cytology, postoperative chemotherapy was associated with improved overall survival compared to whole pelvic radiotherapy (5-year rates, 82.7% versus 64.6%, HR 0.36, 95% CI 0.14–0.96). This association was not observed in negative cytology cases (81.5% versus 79.7%, HR 0.78, 95% CI 0.53–1.14). INTERPRETATION: Malignant peritoneal cytology may be associated with decreased survival in stage I endometrioid endometrial cancer.

OBJECTIVE. To determine changes in the characteristics of low-grade serous ovarian cancer (LGSOC) and serous borderline ovarian tumor (serous-BOT) in a time-specific manner. METHODS. We conducted a population-based retrospective study examining the Surveillance, Epidemiology, and End Results Program from 1988 to 2000. Trends, demographics, and outcomes of 775 women with well-differentiated serous ovarian cancer, used as a surrogate for LGSOC, were compared to 3937 women with serous-BOT. RESULTS. In the multivariable analysis, women with LGSOC were more likely to be older, have stage II-IV disease, and have undergone hysterectomy at surgery, but less likely to be a Western U.S. resident compared to those with serous-BOT (all, adjusted-P < 0.05). During the study period, the number of LGSOCs decreased by 25.9%, particularly stage I disease (37.6% relative decrease) compared to stage II-IV disease (21.1% relative decrease) (all, P < 0.05). With a median follow-up of 16.9 years, there was a decreasing trend in the 15-year overall survival rates among LGSOC (28.7% relative decrease, P = 0.056) but not in serous-BOT (2.5% relative increase, P = 0.416) as a whole cohort. The magnitude of hazard risk from all-cause death for women with LGSOC compared to those with serous-BOT increased by 68.9% from 1988 to 2000 (P < 0.001). LGSOC remained an independent prognostic factor for decreased overall survival compared to serous-BOT (adjusted-P < 0.05). CONCLUSION. Our study suggests that the decreasing number and survival of LGSOC over time may be due to a diagnosis-shift from LGSOC to serous-BOT. Given the distinct characteristics and outcomes of LGSOC compared to serous-BOT, our study endorses the importance of making the correct diagnosis upfront. Whether this diagnostic-shift supports a hypothesis that serous-BOT is a precursor lesion of LGSOC merits further investigation.

OBJECTIVE. To examine the association between hospital surgical volume and perioperative outcomes for fertility-sparing trachelectomy performed for cervical cancer. METHODS. This is a population-based retrospective observational study utilizing the Nationwide Inpatient Sample from 2001 to 2011. Women aged ≤45 years with cervical cancer who underwent trachelectomy were included. Annualized hospital surgical volume was defined as the average number of trachelectomies a hospital performed per year in which at least one case was performed. Perioperative outcomes were assessed based on hospital surgical volume in a weighted model, specifically comparing the top-decile centers to the lower volume centers. RESULTS. There were a total of 815 trachelectomies performed at 89 centers, and 76.4% of the trachelectomy-performing centers had a minimum surgical volume of one trachelectomy per year. The top-decile group had a higher rate of lymphadenectomy performance compared to the lower volume group (96.4% versus 82.4%, odds ratio [OR] 5.65, 95% confidence interval [CI] 2.81–11.4, P < 0.001). There was a significant inverse linear association between annualized surgical volume and the number of perioperative complications (P = 0.020). The top-decile group also had a lower rate of perioperative complications (9.7% versus 21.0%, P < 0.001) and prolonged hospital stay ≥7 days (2.0% versus 6.5%, P = 0.006) compared to the lower volume group. In a multivariable analysis, the top-decile group had a 65% relative decrease in perioperative complication risk compared to the lower volume group (adjusted-OR 0.35, 95%CI 0.20–0.59, P < 0.001). CONCLUSION. Fertility-sparing trachelectomy for young women with cervical cancer is a rare surgical procedure

OBJECTIVE: To describe how population-based statistics for rare epithelial ovarian cancers are evolving. METHODS: This is a retrospective observational study examining the Surveillance, Epidemiology, and End Results Program from 1988 to 2016. Overall survival (OS) of clear cell (OCCC), mucinous (MOC), and low-grade serous (LGSOC) ovarian cancers were compared to high-grade serous ovarian cancer (HGSOC) by fitting a propensity score matching. RESULTS: Among 113,365 ovarian malignancies, 5780 OCCCs (5.1%), 7561 MOCs (6.7%), and 2021 LGSOCs (1.8%) were compared to 38,199 HGSOCs. OCCCs and MOCs were more likely to be diagnosed with stage I disease compared to HGSOC (57.0–59.5% versus 8.6%, P < 0.001). For early-stage disease, OCCC (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.82–1.01) and MOC (HR 0.94, 95% CI 0.85–1.04) had similar OS to HGSOC whereas LGSOC had superior OS (HR 0.93, 95% CI 0.89–0.97) versus HGSOC. Conversely, for advanced-stage disease, OCCC (HR 1.42, 95% CI 1.32–1.53) and MOC (HR 1.11, 95% CI 1.09–1.13) had poorer OS whereas LGSOC (HR 0.86, 95% CI 0.84–0.89) had superior OS compared to HGSOC. OCCC (HR range, 1.92–2.45) and MOC (HR range, 1.73–2.22) had particularly poorer OS in the first three years following diagnosis compared to HGSOC. Population-level statistics for advanced-stage disease showed that 5-year OS rates have increased in HGSOC (16.9% to 36.8%, P < 0.001) and LGSOC (50.8% to 66.4%, P = 0.010); but remain unchanged for OCCC (21.0% to 28.2%, P = 0.174) and MOC (21.4% to 16.5%, P = 0.102). CONCLUSION: OCCC, MOC, and LGSOC comprise 2–7% of ovarian malignancies, have distinct characteristics and survival compared to HGSOC. While these rare tumors have a favorable to comparable prognosis in early-stage disease, disproportionally poor survival in advanced-stage OCCC and MOC highlights the need for further research into novel treatment strategies.

PURPOSE: To examine trends, characteristics and outcomes of women who develop both ovarian and breast cancers. METHODS: This is a retrospective study examining the Surveillance, Epidemiology, and End Results Program from 1973 to 2013. Among ovarian cancer (n = 133,149) and breast cancer (n = 1,143,219) cohorts, women with both diagnoses were identified and temporal trends, tumor characteristics and survival were examined. RESULTS: There were 6446 women with both malignancies, representing 4.8% of the ovarian cancer cohort and 0.6% of the breast cancer cohort. Women with ovarian cancer who had secondary breast cancer were younger than those without secondary breast cancer early in the study period (52.3 versus 59.2 in 1973) but older in more recent years (68.5 versus 62.1 in 2013, P < 0.001). The number of breast cancer survivors who developed postcedent ovarian cancer decreased from 1.5 to 0.2% from 1979 to 2008 (relative risk reduction 90.0%, P < 0.05). Similarly, the number of ovarian cancer survivors who developed postcedent breast cancer decreased from 7.2 to 2.0% from 1973 to 2008 (relative risk reduction 72.4%, P < 0.05). Tumor characteristics were more likely to be favorable in women with ovarian cancer who developed postcedent breast cancer but unfavorable in those who had antecedent breast cancer (all, P < 0.05). Women with ovarian cancer who had secondary breast cancer had superior cause-specific survival compared to those who did not develop breast cancer regardless of breast cancer timing (P < 0.05). CONCLUSION: Our study demonstrated that the demographics of women who develop breast cancer and ovarian cancer have changed over time and diagnosis of secondary breast cancer after ovarian cancer has decreased.

OBJECTIVE To analyse populational trends and perioperative complications following conservative surgery versus oophorectomy in women

Background Uterine artery embolization (UAE) is used to treat severe postpartum hemorrhage (PPH). According to a few studies, UAE for PPH was associated with preterm birth, fetal growth restriction (FGR), and placenta accreta spectrum (PAS) in subsequent pregnancies. These previous studies, however, lacked controls, and to the best of our knowledge, no systematic literature reviews have been conducted thus far. We report the results of our retrospective case-control study of pregnancies after UAE at a single center and include a literature review to evaluate the risk of PAS in pregnancies after UAE. Methods We retrospectively reviewed data from deliveries at our hospital between January 2012 and October 2017. We divided the delivery data into cases with previous UAEs performed for PPH (the post-UAE group) and those without UAEs (the non-UAE group, which included women without previous PPH). We defined PAS as cases in which hysterectomy was performed and pathological examination confirmed the diagnosis. Results are presented as odds ratios (ORs) with 95% confidence intervals (95% CIs). Results We used data from 3155 patients in this study, of whom 16 patients had undergone UAE (post-UAE group) and 3139 had not (non-UAE group). We found no differences between the groups in terms of frequency of preterm births (12.5% versus 14.2%, respectively; OR, 0.863; 95% CI, 0.218 to 3.414; P = 0.84) or FGR (6.2% versus 10.0%, respectively; OR, 0.602; 95% CI, 0.104 to 3.584; P = 0.61). However, cases of PAS were significantly more common in the post-UAE group (37.5%) than in the non-UAE group (1.2%; OR, 50.303; 95% CI, 17.38 to 145.592; P < 0.01). Conclusion Our results suggest that previous UAE is a significant risk factor for PAS.

Background Retained products of conception (RPOC) with hemorrhage need intervention when RPOC persist and remain symptomatic. The safety and efficacy of uterine artery embolization (UAE) for RPOC using gelatin sponge (GS) alone, and fertility after UAE for RPOC remain unknown. The purpose of this study is to retrospectively investigate the efficacy of UAE for RPOC with bleeding and future pregnancy outcomes. Methods Between 2007 and 2016, 14 patients (mean age, 33 years old) diagnosed as RPOC with bleeding received UAE using GS at our institution. Pregnancy outcomes were vaginal delivery (n = 7), miscarriage (n = 4), and termination (n = 3). Four patients received dilation and curettage/evacuation (D&C/E) for treatment of RPOC before bleeding occurred. The mean time interval from the end of pregnancy to bleeding was 28 days. Technical success, clinical success, complications, angiographic features and fertility after UAE were retrospectively assessed. Results Technical success was achieved in 13 patients (93%) and clinical success was achieved in all 14 patients. No major complications occurred. The angiographic features of RPOC were tortuous feeders with flow into a focal blush of contrast (n = 14). Additional findings were pseudoaneurysm (n = 6), early venous return (n = 4), and extravasation (n = 2). Pseudoaneurysm was observed significantly more often in patients who received D&C/E before UAE compared to those who received conservative treatment alone (P = 0.015). The mean follow-up period was 29 months. Six patients achieved six pregnancies an average of 29 months after UAE. Conclusion UAE using GS may be an effective and safe treatment for RPOC with hemorrhage that can preserve fertility.

In Japan, the governmental recommendation for HPV vaccination was suspended in June 2013 because of media reports of so-called adverse vaccine events. The HPV vaccination rate in Japan prior to this suspension was almost 70%, but fell afterward to almost zero. To explore ways to bolster HPV vaccination, between 2014 and 2019 we conducted three serial surveys of the opinions of obstetricians and gynecologists about HPV vaccination. This study aimed to discuss the changing attitudes found in this 5-year follow-up survey. In August 2014, January 2017, and June 2019, we posted questionnaires to about 570 obstetricians and gynecologists practicing in Osaka, Japan. All three surveys used the same structured and closed-ended questionnaire, including questions about their personal opinions regarding HPV vaccination. We compared our new results to those of the previous two surveys. The response rate for the latest survey was 51.1% (293/573), which was equivalent to the previous two surveys. Among the responders, 83.3% (244/293) now thought that the Japanese government should restart its HPV vaccine recommendation, and 84.6% (248/293) were already recommending HPV vaccines for teenagers in their daily care. Eleven of 30 doctors (36.7%) had their own teenage daughters vaccinated against HPV after the suspension of recommendation. The rate has maintained an increasing trend from the previous two surveys. This study indicated that the attitude of obstetricians and gynecologists in Japan toward HPV vaccination has changed positively over 5 years. The results should serve as an encouragement to resume the governmental recommendation of HPV vaccines.

BACKGROUND AND OBJECTIVES: To examine the association between hospital surgical volume and perioperative mortality of pelvic exenteration performed for gynecologic malignancies. METHODS: A population-based retrospective study utilizing the Nationwide Inpatient Sample was conducted to examine pelvic exenteration for gynecologic malignancies from 2001 to 2011. Annualized hospital surgical volume was defined as the average number of procedures a hospital performed per year in which at least one case was performed, and this was correlated to perioperative mortality. RESULTS: A total 1912 exenterations performed at 181 centers were included. Nearly two thirds of exenteration-performing centers had a minimum surgical volume of one case per year (121 centers, 66.9%). Perioperative mortality rate was 1.8%. In multivariable analysis surgical volume remained an independent factor for perioperative mortality (adjusted-odds ratio 0.21; 95% confidence interval, 0.09–0.49; P < .001). Perioperative mortality rates were 3.7% for the centers with minimum surgical volume (1 exenteration a year), 1.4% for the centers performing more than one but two or less exenterations a year, and 0% for the top decile centers (>2 exenterations a year), respectively (P < .001). CONCLUSION: Pelvic exenteration for gynecologic malignancy is a rare surgical procedure with most hospitals performing few cases annually. A higher surgical volume of pelvic exenteration was associated with lower perioperative mortality.

INTRODUCTION: Ovarian cancer is the leading cause of gynecologic cancer death, owing to high rates of incurable, recurrent disease after initial treatment. Serine threonine kinases (STKs) have been proposed as potential therapeutic targets in ovarian cancer because of their role in the initiation and progression of cancers. Experience in non-ovarian cancers suggests that STK inhibitors are active against tumors with specific molecular alterations. AREAS COVERED: This review discusses STK inhibitors in active development in phase II/III clinical trials for ovarian cancer. PubMed and ClinicalTrials.gov were systematically searched to identify STK inhibitor trials for ovarian cancer; active development was confirmed via Pharmaprojects. Available data regarding the efficacy and safety of these compounds are explored. EXPERT OPINION: STK inhibitors currently in development have modest activity as single agents and are unlikely to achieve approval as monotherapy for unselected ovarian cancer patients. Combination trials of STK inhibitors with chemotherapy and/or targeted therapies have suggested an acceptable efficacy/toxicity ratio for certain combinations but confirmatory studies are needed. Carefully designed trials, especially those including somatic molecular analysis, may help identify the subsets of patients most likely to benefit from these therapeutic strategies and determine the role of STK inhibitors in the evolving landscape of precision oncology.

Cervical cancer screening rate is extremely low and the governmental recommendation of HPV vaccine has been suspended for 5 years in Japan. Here, we utilized data from the Osaka Cancer Registry, collected between 1976 and 2012, to evaluate cervical cancer trends in Japan. Age-adjusted incidence, relative survival, and conditional survival rates were calculated using multiple imputation methods and period analyses in 25,826 cervical cancer cases. Association of survival rates and clinical factors, including patients' age, clinical stage, and treatment procedures, were also analyzed. A trend for significantly decreasing age-adjusted incidence of cervical cancer (per 100,000) began in 1976 but reversed after 2000, increasing significantly to date (annual percent change = 3.8, 95% confidence interval, 2.7–4.8; age-adjusted rate: 28.0 in 1976, 9.1 in 2000, 14.1 in 2012). The 10-year relative survival rate improved significantly after 2002, especially in cases of “localized” and “adjacent organs” disease; this was likely due to the introduction of concurrent chemotherapy and radiation. The conditional 5-year relative survival rate improved significantly yearly until the fourth survival year. In the surgery-based group, we observed no age-dependent differences in outcomes. Unexpectedly, however, prognosis for younger age groups was poorer in the radiation-based treatment group. These results indicate that although relative survival rates have recently increased, treatment for more advanced cases with distant metastasis requires further improvement. In addition, this study is the first to suggest that age might be an important predictor of radiotherapy resistance in cervical cancer. Significance: A large-cohort analysis of cervical cancer cases reveals that age-adjusted incidence in Japan has increased since 2000 and that age may negatively correlate with resistance to radiotherapy.

In this study, we aimed to investigate whether there was a significant prognostic difference between single and multiple cervical dilations when inducing second-trimester abortion.We conducted a retrospective review of 238 pregnant women who underwent termination of pregnancy at 12-21 weeks of gestation at Osaka University Hospital in Osaka, Japan, between January 2010 and May 2018. Termination of pregnancy was performed by vaginal administration of 1 mg gemeprost every 3 h for up to five doses per day after uterine cervical dilation using lamicel.The women were categorized into two groups: 191 women had a delivery time of24 h, whereas 47 had delivery times24 h. Contrasting the groups, there were significant differences with regard to numbers of primiparas (88 [46.1%] and 32 [68.1%], respectively) and lamicel exchanges ± SD (1.9 ± 0.67 for24 h and 2.4 ± 0.87 for24 h, respectively). Additionally, we compared the prognosis of primiparas that received just a single lamicel with that of primiparas that had ≥2 exchanged, but no significant differences were noted in the number of patients with a delivery time of24 h and the number of used gemeprost.Primipara is a risk factor for delayed delivery time of induced abortion. However, increasing the number of exchanged lamicel did not significantly reduce the delivery time; therefore, it should be performed as minimally as possible.

BACKGROUND AND OBJECTIVES Suspicious peritoneal cytology refers to the result of peritoneal cytology testing that is insufficient in either quality or quantity for a definitive diagnosis of malignancy. This study examined characteristics and survival outcomes related to suspicious peritoneal cytology in endometrial cancer. METHODS A population-based retrospective study by querying the National Cancer Institute's Surveillance, Epidemiology, and End Results Program was conducted. A total of 41,229 women with Stage I-III endometrial cancer who had peritoneal cytologic sampling at hysterectomy from 2010 to 2016 were examined. A Cox proportional hazard regression model and a competing risk analysis with Fine-Gray model were fitted to assess survival outcome related to suspicious peritoneal cytology. RESULTS Suspicious peritoneal cytology was seen in 702 (1.7%) cases. In multivariable models, suspicious peritoneal cytology was associated with increased risk of endometrial cancer mortality (subdistribution-hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.29-2.20, p

Background: Targeting DNA repair and immune checkpoint pathways has been the focus of multiple clinical trials. In this study, we explore the association between DNA repair proteins, immune response markers, and clinical outcome in women with EOC. Methods: Immunohistochemical analysis of TMA with 181 EOC samples was used to determine expression levels for DNA repair proteins (PARP, PTEN, p53, H2Ax, FANCD2, and ATM) and immune-markers (CD4, CD8, CD68, PD-L2, PD-L1, and FOXP3). Biomarker expression was correlated to clinical data. Prognostic discriminatory ability was assessed per the combination of biomarkers. Results: Tumor immunity biomarkers correlated with HRD biomarkers. High PD-L2 was significantly associated with high expression of CD8 (r = 0.18), CD68 (r = 0.17), and FOXp3 (r = 0.16) (all, p &lt, 0.05). In a multivariate analysis, PD-L2 (hazard ratio (HR) 1.89), PARP (HR 1.75), and PTEN (HR 1.96) expressions were independently associated with decreased progression-free survival (PFS), whereas PD-L1 (HR 0.49) and CD4 (HR 0.67) were associated with improved PFS (all, p &lt, 0.05). In 15 biomarker combinations, six combinations exhibited a discriminatory ability of &gt, 20% for the 4.5-year PFS rate, with four based on PD-L2 (PARP, PTEN, CD4, and PD-L1, 20.5–30.0%). Conclusions: Increased PD-L2 expression is a prognostic marker of decreased survival in EOC. Interaction between tumor DNA repair and microenvironment determines tumor progression and survival.

Objective To examine the influence of the first level I evidence (Laparoscopic Approach to Cervical Cancer [LACC] trial) on minimally invasive hysterectomy use and perioperative complications for cervical cancer surgery. Methods This was population-based retrospective observational study, querying National Inpatient Sample. Women with cervical cancer who underwent hysterectomy and lymphadenectomy from 10/2015–12/2018 were examined. A quasi-experimental analysis with interrupted-time series was performed to assess the influence of the LACC trial report on minimally invasive hysterectomy use and perioperative complication rates. Results 5120 women in the pre-LACC period and 1645 women in the post-LACC period were compared. Following the LACC trial report on 3/2018, the minimally invasive hysterectomy use dropped by 19.7 percent points in one month (55.2% in 3/2018 to 35.5% in 4/2018), followed by a continued decline of 8.0% (95% confidence interval 0.1–15.3) monthly. By 12/2018, minimally invasive hysterectomy was used in 17.9% of cases, which was 38.8 percent points lower than the expected rate per the pre-LACC period projection. In multivariable analysis, women in the post-LACC period were 63% less likely to undergo minimally invasive hysterectomy (adjusted-odds ratio 0.37, 95% confidence interval 0.33–0.42) but 23% more likely to have a perioperative complication (38.6% versus 29.1%, adjusted-odds ratio 1.23, 95% confidence interval 1.08–1.40) compared to those in the pre-LACC period. Women in the post-LACC group were more likely to have a longer hospital stay compared to those in the pre-LACC group (median, 3 versus 2 days, P Conclusion Following the LACC trial results, U.S. surgeons rapidly shifted from minimally invasive to open hysterectomy for cervical cancer. Decreasing utilization of minimally invasive surgery was associated with an increase in perioperative complications and longer hospital admissions.

Increasing evidence suggests a relationship between in vitro fertilization-embryo transfer (IVF-ET) and placenta accreta spectrum (PAS). Some studies have reported a lower rate of antenatal diagnosis of PAS after IVF-ET compared to PAS with spontaneous conception. This study aimed to review the diagnostic accuracy of PAS after IVF-ET and to explore the relationship between IVF-ET pregnancy and PAS. According to the PRISMA guidelines, a comprehensive systematic review of the literature was conducted through August 31, 2020 to determine the effects of IVF-ET on PAS. In addition, a meta-analysis was conducted to explore the relationship between IVF-ET pregnancy and PAS. Twelve original studies (2011–2020) met the inclusion criteria. Among these, 190,139 IVF-ET pregnancies and 248,534 spontaneous conceptions met the inclusion criteria. In the comparator analysis between PAS after IVF-ET and PAS with spontaneous conception (n = 2), the antenatal diagnosis of PAS after IVF-ET was significantly lower than that of PAS with spontaneous conception (22.2% versus 94.7%, P versus 46.9%, P P P P

The collection of a peritoneal cytologic sample at the time of surgery for endometrial cancer has traditionally been an important part of surgical staging. In 2009, the International Federation of Gynecology and Obstetrics revised the cancer staging schema for endometrial cancer and removed peritoneal cytology from the staging criteria. The current National Comprehensive Cancer Network guidelines and the International Federation of Gynecology and Obstetrics organization, however, recommend evaluation of peritoneal cytology at the time of hysterectomy. This study examined population-based trends, characteristics, and outcomes of peritoneal cytologic sampling for endometrial cancer surgery following the 2009 staging revision in the United States.This is a retrospective observational study querying the Surveillance, Epidemiology, and End Results Program to examine women with stage I-III endometrial cancer who underwent hysterectomy from 2010 to 2017. Trends, characteristics, and survival associated with peritoneal cytologic evaluation at the time of hysterectomy were assessed in multivariable analysis and with propensity score weighting.Among 62,809 women who underwent hysterectomy, 43,873 (69.9%) had peritoneal cytologic evaluation at surgery and 18,936 (30.1%) did not. Utilization of peritoneal cytologic evaluation decreased from 75.5% to 64.9% during the study period (P 0.001). In multivariable analysis, more recent year of surgery was independently associated with a decreased likelihood of performance of peritoneal cytology (adjusted-odds ratio of peritoneal cytology evaluation in 2017 versus 2010 0.56, 95% confidence interval [CI] 0.52-0.60). Peritoneal cytologic evaluation at the time of hysterectomy was associated with improved all-cause mortality (hazard ratio in the whole cohort 0.94, 95%CI 0.89-0.99; and hazard ratio in endometrioid histology 0.90, 95%CI 0.84-0.97).Performance of peritoneal cytologic sampling has gradually decreased following the 2009 staging revision in the United States. Our study suggests that peritoneal cytology evaluation at hysterectomy may be associated with improved survival in certain tumor groups.

Background A diagnostic sign on magnetic resonance imaging, suggestive of posterior extrauterine adhesion (PEUA), was identified in patients with placenta previa. However, the clinical features or surgical outcomes of patients with placenta previa and PEUA are unclear. Our study aimed to investigate the clinical characteristics of placenta previa with PEUA and determine whether an altered management strategy improved surgical outcomes. Methods This single institution retrospective study examined patients with placenta previa who underwent cesarean delivery between 2014 and 2019. In June 2017, we recognized that PEUA was associated with increased intraoperative bleeding; thus, we altered the management of patients with placenta previa and PEUA. To assess the relationship between changes in practice and surgical outcomes, a quasi-experimental method was used to examine the difference-in-difference before (pre group) and after (post group) the changes. Surgical management was modified as follows: (i) minimization of uterine exteriorization and adhesion detachment during cesarean delivery and (ii) use of Nelaton catheters for guiding cervical passage during Bakri balloon insertion. To account for patient characteristics, propensity score matching and multivariate regression analyses were performed. Results The study cohort (n = 141) comprised of 24 patients with placenta previa and PEUA (PEUA group) and 117 non-PEUA patients (control group). The PEUA patients were further categorized into the pre (n = 12) and post groups (n = 12) based on the changes in surgical management. Total placenta previa and posterior placentas were more likely in the PEUA group than in the control group (66.7% versus 42.7% [P = 0.04] and 95.8% versus 63.2% [P n = 72), intraoperative blood loss was significantly higher in the PEUA group (n = 24) than in the control group (n = 48) (1515 mL versus 870 mL, P t = 2.46, P = 0.02). Intraoperative blood loss in the post group was successfully reduced, as opposed to in the pre group (1180 mL versus 1827 mL, P = 0.04). Conclusions PEUA was associated with total placenta previa, posterior placenta, and increased intraoperative bleeding in patients with placenta previa. Our altered management could reduce the intraoperative blood loss.

Simple Summary Epithelial ovarian cancer is one of the most lethal cancers in women and is typically diagnosed at an advanced-stage. Historically, primary tumor reductive surgery was attempted followed by postoperative chemotherapy in most patients diagnosed with advanced ovarian cancer. However, neoadjuvant chemotherapy followed by interval tumor reductive surgery is an alternative approach for patients with advanced-stage ovarian cancer where primary tumor reductive surgery is not feasible. Here, we review proposed models that can assist in selecting patients who would benefit most from neoadjuvant chemotherapy followed by surgery. Abstract Epithelial ovarian cancer remains a leading cause of death amongst all gynecologic cancers despite advances in surgical and medical therapy. Historically, patients with ovarian cancer underwent primary tumor reductive surgery followed by postoperative chemotherapy; however, neoadjuvant chemotherapy followed by interval tumor reductive surgery has gradually become an alternative approach for patients with advanced-stage ovarian cancer for whom primary tumor reductive surgery is not feasible. Decision-making about the use of these approaches has not been uniform. Hence, it is essential to identify patients who can benefit most from neoadjuvant chemotherapy followed by interval tumor reductive surgery. Several prospective and retrospective studies have proposed potential models to guide upfront decision-making for patients with advanced ovarian cancer. In this review, we summarize important decision-making models that can improve patient selection for personalized treatment. Models based on clinical factors (clinical parameters, radiology studies and laparoscopy scoring) and molecular markers (circulating and tumor-based) are useful, but laparoscopic staging is among the most informative diagnostic methods for upfront decision-making in patients medically fit for surgery. Further research is needed to explore more reliable models to determine personalized treatment for advanced epithelial ovarian cancer.

This study was designed to examine the association between malignant peritoneal cytology and survival of women with uterine sarcoma. This retrospective, observational study queried the National Cancer Institute’s Surveillance, Epidemiology, and End Result Program. Uterine sarcoma cases diagnosed from 2010 to 2016 with known peritoneal cytology results were examined. Propensity score inverse probability of treatment weighting was fitted to balance the measured covariates. Overall survival (OS) was compared between malignant and negative cytology cases. A total of 1481 uterine sarcomas were examined. Malignant peritoneal cytology was seen in 146 (9.9%) cases. Women who had T3 disease and distant metastases had the highest incidence of malignant peritoneal cytology (43.1%). In multivariable analysis, higher T stage, nodal involvement, distant metastasis, poorer tumor differentiation, and rhabdomyosarcoma/endometrial stromal sarcoma were significantly associated with an increased risk of malignant peritoneal cytology (all, P

The term 'intra-operative tumor spillage' refers to the unexpected or unplanned exposure of tumor cells into the sterile surgical field during cases with otherwise no tumor cells outside the affected organ site. As a result, tumor spillage could theoretically lead to tumor seeding and metastasis.

In 2020, endometrial cancer continues to be the most common gynecologic malignancy in the United States. The majority of endometrial cancer is low grade, and nearly 1 of every 8 low-grade endometrial cancer diagnoses occurs in women younger than 50 years with early-stage disease. The incidence of early-stage, low-grade endometrial cancer is increasing particularly among women in their 30s. Women with early-stage, low-grade endometrial cancer generally have a favorable prognosis, and hysterectomy-based surgical treatment alone can often be curative. In young women with endometrial cancer, consideration of ovarian conservation is especially relevant to avoid both the short-term and long-term sequelae of surgical menopause including menopausal symptoms, cardiovascular disease, metabolic disease, and osteoporosis. Although disadvantages of ovarian conservation include failure to remove ovarian micrometastasis (0.4%-0.8%), gross ovarian metastatic disease (4.2%), or synchronous ovarian cancer (3%-5%) at the time of surgery and the risk of future potential metachronous ovarian cancer (1.2%), ovarian conservation is not negatively associated with endometrial cancer-related or all-cause mortality in young women with early-stage, low-grade endometrial cancer. Despite this, utilization of ovarian conservation for young women with early-stage, low-grade endometrial cancer remains modest with only a gradual increase in uptake in the United States. We propose a framework and strategic approach to identify young women with early-stage, low-grade endometrial cancer who may be candidates for ovarian conservation. This evidence-based schema consists of a 2-step assessment at both the preoperative and intraoperative stages that can be universally integrated into practice.

The current coronavirus pandemic caused a significant decrease in cancer-related encounters resulting in a delay in treatment of cancer patients. The objective of this study was to examine the survival effect of delay in starting concurrent chemo-radiotherapy (CCRT) in women with locally-advanced cervical cancer.This is a retrospective observational study querying the National Cancer Database from 2004 to 2016. Women with stage IB2-IVA squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix who received definitive CCRT with known wait-time for CCRT initiation after cancer diagnosis were eligible (N=13,617). Cox proportional hazard regression model with restricted cubic spline transformation was fitted to assess the association between CCRT wait-time and all-cause mortality in multivariable analysis.The median wait-time to start CCRT was 6 (IQR 4-8) weeks. In a multivariable analysis, older age, non-Hispanic black and Hispanic ethnicity, recent year of diagnosis, Medicaid and uninsured status, medical comorbidities, and absence of nodal metastasis were associated with longer CCRT wait-time (P.05). Women with aggressive tumor factors (poorer differentiation, large tumor size, nodal metastasis, and higher cancer stage) were more likely to have a short CCRT wait-time (P.05). After controlling for the measured covariates, CCRT wait-time of 6.1-9.8 weeks was not associated with increased risk of all-cause mortality compared to a wait-time of 6 weeks. Similar association was observed when the cohort was stratified by histology, cancer stage, tumor size, or brachytherapy use.An implication of this study for the current coronavirus pandemic is that in the absence of aggressive tumor factors, a short period of wait-time to start definitive CCRT may not be associated with increased risk of mortality in women with locally-advanced cervical cancer.

Objective A global pandemic caused by a novel coronavirus (Covid-19) has created unique challenges to providing timely care for cancer patients. In early-stage cervical cancer, postponing hysterectomy for 6–8 weeks is suggested as a possible option in the Covid-19 burdened hospitals. Yet, literature examining the impact of surgery wait-time on survival in early-stage cervical cancer remains scarce. This study examined the association between surgery wait-time of 8 weeks and oncologic outcome in women with early-stage cervical cancer. Methods This is a single institution retrospective observational study at a tertiary referral medical center examining women who underwent primary hysterectomy or trachelectomy for clinical stage IA-IIA invasive cervical cancer between 2000 and 2017 (N = 217). Wait-time from the diagnosis of invasive cervical cancer via biopsy to definitive surgery was categorized as: short wait-time (, Highlights • Examined effect of long wait-time (≥8 weeks) for surgical treatment on survival of women with early-stage cervical cancer. • Long surgery wait-time was not associated with short-term disease recurrence of women with early-stage cervical cancer. • Systematic review suggests that surgery wait-time for up to 8 weeks may have limited/modest effect on disease recurrence.

A battery of analyses of the LACC trial has now added additional information that minimally invasive radical hysterectomy for early cervical cancer is not associated with improved quality of life after surgery compared with open radical hysterectomy.[1–3][1] Taken together with the prior principal

To examine trends and outcomes related to neoadjuvant chemotherapy (NACT) use for advanced ovarian cancer based on patient and tumor factors.This retrospective cohort study queried the National Cancer Institute's Surveillance, Epidemiology, and End Results Program to examine women with stage III-IV high-grade serous ovarian carcinoma from 2010 to 2016. Propensity score inverse probability of treatment weighting was used to assess the age-, cancer stage-, and tumor extent-specific survival estimates related to NACT use.Utilization of NACT has significantly increased in older women (≥65 years; 48.4% relative increase), followed by stage IV disease (35.2% relative increase), and stage III disease (25.0% relative increase) (all, P-trend 0.05). Women who received NACT had overall survival (OS) similar to those who had primary cytoreductive surgery (PCS) in older women (hazard ratio [HR] 1.07, 95% confidence interval [CI] 0.95-1.20, P = 0.284), stage IV disease (HR 0.96, 95%CI 0.84-1.10, P = 0.564), and more disease extent cases (T3/N1/M1, HR 1.06, 95%CI 0.84-1.32, P = 0.640). Moreover, NACT use was associated with decreased other cause mortality risk compared to PCS in the older women (sub-distribution HR 0.61, 95%CI 0.40-0.94, P = 0.025) and stage IV disease (sub-distribution HR 0.49, 95%CI 0.27-0.90, P = 0.021). In contrast, women who received NACT had decreased OS compared to those who had PCS in the younger group (HR 1.22, 95%CI 1.07-1.38, P = 0.004), stage III disease (HR 1.26, 95%CI 1.13-1.41, P 0.001), and lesser disease extent cases (T3/N0/M0, HR 1.38, 95%CI 1.20-1.58, P 0.001).Our study suggests that survival effect of NACT for advanced ovarian cancer may differ based on patient and tumor factors. In older women, stage IV disease, and greater disease extent, NACT was associated with similar OS compared to PCS.

The risk of uterine rupture in subsequent pregnancy is 1%‐12% in patients with prior classical uterine incision. Management of mild/moderate abdominal pain without an obvious abnormal finding before 36 weeks is challenging owing to fetal immaturity.

Background Uterine leiomyosarcoma is a rare and aggressive gynecologic malignancy originating in the myometrium of the uterine corpus that tends to recur even after complete surgical excision. Current therapeutic agents have only modest effects on uterine leiomyosarcoma. Although antibodies and antibody-drug conjugates have been recognized as useful targeted therapies for other cancers, no study has yet evaluated the effects of this approach on uterine leiomyosarcoma. Objective This study aimed to examine the activity of tumoral CD70 in uterine leiomyosarcoma and assess the antitumor activity of CD70–antibody-drug conjugate treatment in uterine leiomyosarcoma. Study Design Target membrane proteins were screened by profiling and comparing membrane protein expression in 3 uterine leiomyosarcoma cell lines (SK-UT-1, SK-LMS-1, and SKN) and normal uterine myometrium cells using the isobaric tags for relative and absolute quantitation labeling method. Western blotting, fluorescence-activated cell sorting analyses, and immunohistochemistry were used to examine CD70 expression in the membrane proteins in uterine leiomyosarcoma cell lines and clinical samples. We developed an antibody-drug conjugate with a monoclonal antibody of the target membrane protein linked to monomethyl auristatin F and investigated its antitumor effects against uterine leiomyosarcoma (in vitro, in vivo, and in patient-derived xenograft models). Results CD70 was identified as a specific antigen highly expressed in uterine leiomyosarcoma cell lines. Of the 3 uterine leiomyosarcoma cell lines, CD70 expression was confirmed in SK-LMS-1 cells by western blotting and fluorescence-activated cell sorting analysis. CD70 overexpression was observed in 19 of 21 (90.5%) tumor specimens from women with uterine leiomyosarcoma. To generate CD70–antibody-drug conjugate, anti-CD70 monoclonal antibody was conjugated with a novel derivative of monomethyl auristatin F. CD70–antibody-drug conjugate showed significant antitumor effects on SK-LMS-1 cells (half maximal inhibitory concentration, 0.120 nM) and no antitumor effects on CD70-negative uterine leiomyosarcoma cells. CD70–antibody-drug conjugate significantly inhibited tumor growth in the SK-LMS-1 xenograft mouse model (tumor volume, 129.8 vs 285.5 mm3; relative reduction, 54.5%; P Conclusion Uterine leiomyosarcoma tumors highly express CD70 and targeted therapy with CD70–antibody-drug conjugate may have a potential therapeutic implication in the treatment of uterine leiomyosarcoma.

To review and discuss the present evidence of surgery- and radiation-based treatment strategies for stage IIB cervical cancer. Recently, two randomized controlled trials compared the efficacy of neoadjuvant chemotherapy followed by radical hysterectomy (NACT + RH) with that of concurrent chemoradiotherapy (CCRT) for stage IB3–IIB cervical cancer. When these studies were combined (N = 1259), NACT + RH was associated with a shorter disease-free survival [hazard ratio (HR) 1.36, 95% confidence interval (CI) 1.13–1.64], but with a similar overall survival (HR 1.11, 95% CI 0.90–1.36) when compared with the findings for CCRT. Stage-specific analysis for stage IIB cervical cancer demonstrated that disease-free survival was significantly worse with NACT + RH than with CCRT (HR 1.90, 95% CI 1.25–2.89); however, no significant difference was observed for stage IB3–IIA cervical cancer. Based on the results of recent level I evidence, the standard treatment for stage IIB cervical cancer remains CCRT.

Aim Epithelial ovarian cancer (EOC) can be a devastating diagnosis in women of reproductive age who desire future fertility. However, in early-stage disease, fertility-sparing surgery (FSS) can be considered in appropriately selected patients. Methods This is a narrative descriptive review of the recent literature on FSS for EOC from oncologic, reproductive and endocrinologic perspectives. Results The recurrence rate following FSS performed for stage I EOC in published retrospective studies collectively is 13% but ranges from 5 to 29%, while mortality ranges from 0 to 18%. Five-year disease-free survival following FSS is over 90% but decreases with higher stage and grade. Recurrences following FSS are more likely to be localized with a more favorable prognosis compared to recurrences following radical surgery. Adjuvant chemotherapy is recommended in women with high-risk disease, and strategies to minimize gonadotoxicity during chemotherapy such as gonadotropin-releasing hormone (GnRH) agonists may be considered. Oocyte, embryo and/or ovarian cryopreservation can also be offered to patients desiring future biologic children. Reproductive outcomes following FSS, including pregnancy and miscarriage rates, resemble those of the general population, with a chance of successful pregnancy of nearly 80%. Conclusion In retrospective data, FSS appears to be oncologically safe in stage IA and IC grade 1-2 non-clear cell EOC. In patients with grade 3 tumors or clear cell histology, treatment can be individualized, weighing a slightly higher risk of recurrence with fertility goals. A multidisciplinary approach with oncology and reproductive endocrinology may be of utility to help these patients achieve their fertility goals.

Histopathologic analysis through biopsy has been one of the most useful methods for the assessment of malignant neoplasms. However, some aspects of the analysis such as invasiveness, evaluation range, and turnaround time from biopsy to report could be improved. Here, we report a novel method for visualizing human cervical tissue three-dimensionally, without biopsy, fixation, or staining, and with sufficient quality for histologic diagnosis. Near-infrared excitation and nonlinear optics were employed to visualize unstained human epithelial tissues of the cervix uteri by constructing images with third-harmonic generation (THG) and second-harmonic generation (SHG). THG images enabled evaluation of nuclear morphology in a quantitative manner with six parameters after image analysis using deep learning. It was also possible to quantitatively assess intraepithelial fibrotic changes based on SHG images and another deep learning analysis. Using each analytical procedure alone, normal and cancerous tissue were classified quantitatively with an AUC ≥0.92. Moreover, a combinatory analysis of THG and SHG images with a machine learning algorithm allowed accurate classification of three-dimensional image files of normal tissue, intraepithelial neoplasia, and invasive carcinoma with a weighted kappa coefficient of 0.86. Our method enables real-time noninvasive diagnosis of cervical lesions, thus constituting a potential tool to dramatically change early detection. Significance: This study proposes a novel method for diagnosing cancer using nonlinear optics, which enables visualization of histologic features of living tissues without the need for any biopsy or staining dye.

OBJECTIVE. Minimally invasive radical hysterectomy (MIS-RH) for early-stage cervical cancer is a relatively new surgical procedure with increased utilization in the mid-/late-2000s. This study examined the association between hospital surgical volume for MIS-RH and perioperative outcomes for early-stage cervical cancer in the period of early adoption. METHODS. This population-based retrospective study queried the National Inpatient Sample from 2007 to 2011. Cervical cancer cases treated with MIS-RH were examined (n = 2202 from 163 hospitals). Annualized hospital surgical volume was defined as the average number of procedures performed per year in which at least one case was performed. Characteristics and outcomes related to MIS-RH use were assessed. The comparator cohort included RH by laparotomy (Open-RH; n = 11,187 from 405 hospitals). RESULTS. Among MIS-RH-offering centers, 42.3% had average 1 case/year and surgical volume of >4 cases/year represented the top decile. When stratified by MIS-RH types, on average 31.3 centers performed robotic-assisted approach per year versus 11.5 centers for the traditional approach. Small bed capacity centers were most likely to perform robotic-assisted RH (adjusted-odds ratio 4.07, P < 0.001). In the traditional MIS-RH group, higher hospital surgical volume was associated with lower surgical morbidity (P = 0.025) whereas in the robotic-assisted approach higher hospital surgical volume was associated with higher surgical morbidity (P < 0.001). In the Open-RH cohort, higher hospital surgical volume was significantly associated with decreased surgical morbidity and mortality (both, P < 0.001). CONCLUSION. In the mid-/late-2000s, MIS-RH surgical volume was modest in the United States. Small bed capacity centers adopted robotic-assisted MIS-RH more frequently, and there was a statistically significant association of increased perioperative complications among higher volume centers. In contrast, higher surgical volume was associated with improved perioperative outcomes with the traditional MIS-RH and open-RH approaches.

BACKGROUND: Though hysterectomy remains the standard treatment for complex atypical hyperplasia, patients who desire fertility or who are poor surgical candidates may opt for progestin therapy. However, the effectiveness of the levonorgestrel-releasing intrauterine device compared to systemic therapy in the treatment of complex atypical hyperplasia has not been well studied. OBJECTIVE: We sought to examine differences in treatment response between local progestin therapy with the levonorgestrel-releasing intrauterine device and systemic progestin therapy in women with complex atypical hyperplasia. METHODS: This single-institution retrospective study examined women with complex atypical hyperplasia who received progestin therapy between 2003 and 2018. Treatment response was assessed by histopathology on subsequent biopsies. Time-dependent analyses of complete response and progression to cancer were performed comparing the levonorgestrel-releasing intrauterine device and systemic therapy. A propensity score inverse probability of treatment weighting model was used to create a weighted cohort that differed based on treatment type but was similar with respect to other characteristics. An interaction-term analysis was performed to examine the impact of body habitus on treatment response, and an interrupted time-series analysis was employed to assess if changes in treatment patterns correlated with outcomes over time. RESULTS: A total of 245 women with complex atypical hyperplasia received progestin therapy (levonorgestrel-releasing intrauterine device n = 69 and systemic therapy n = 176). The mean age and body mass index were 36.9 years and 40.0 kg/m(2), respectively. In the patient-level analysis, women who received the levonorgestrel-releasing intrauterine device had higher rates of complete response (78.7% vs 46.7%; adjusted hazard ratio, 3.32; 95% confidence interval, 2.39–4.62) and a lower likelihood of progression to cancer (4.5% vs 15.7%; adjusted hazard ratio, 0.28; 95% confidence interval, 0.11–0.73) compared to those who received systemic therapy. In particular, women with class III obesity derived a higher relative benefit from levonorgestrel-releasing intrauterine device therapy in achieving complete response compared to systemic therapy: class III obesity, adjusted hazard ratio 4.72, 95% confidence interval 2.83–7.89; class I–II obesity, adjusted hazard ratio 1.83, 95% confidence interval 1.09–3.09; and nonobese, adjusted hazard ratio 1.26, 95% confidence interval 0.40–3.95. In the cohort-level analysis, the obesity rate increased during the study period (77.8% to 88.2%, 13.4% relative increase, P =.033) and levonorgestrel-releasing intrauterine device use significantly increased after 2007 (6.3% to 82.7%, 13.2-fold increase, P < .001), both concomitant with a higher proportion of women achieving complete response (32.9% to 81.4%, 2.5-fold increase, P = .005). CONCLUSION: Our study suggests that local therapy with the levonorgestrel-releasing intrauterine device may be more effective than systemic therapy for women with complex atypical hyperplasia who opt for nonsurgical treatment, particularly in morbidly obese women. Shifts in treatment paradigm during the study period toward increased levonorgestrel-releasing intrauterine device use also led to improved complete response rates despite increasing rates of obesity.

Objective Bakri intrauterine balloon (BIUB) placement is an effective treatment for postpartum hemorrhage (PPH). This study aims to evaluate the risk of infection during BIUB placement. Study Design Data for all deliveries (n = 2,144) at our institution between January 2014 and March 2018 were retrospectively reviewed. Patients diagnosed with PPH (n = 758) were included in our analysis, further divided into BIUB (n = 80) and non-BIUB groups (n = 678), and subdivided into vaginal delivery (VD), elective cesarean delivery (CD), and emergency CD groups. Postpartum endometritis rate was compared in each group. A single dose of prophylactic antibiotics was administered for BIUB placement in the VD group. In the CD groups, antibiotics were administered preoperatively once, and no additional antibiotics for BIUB placement were administered. To obtain an antibiotics administration protocol to be applied during BIUB placement, we electronically searched the PubMed and Scopus databases. Results No significant differences were observed in endometritis rates between BIUB and non-BIUB groups of all groups. In the literature review, of 27 suitable publications identified, multiple doses of antibiotics were administered in 17 (62.9%) studies and none investigated the efficacy of a protocol for antibiotic. Conclusion Our protocol might be effective and sufficient in preventing postpartum BIUB placement-related endometritis.

AIM The use of less radical surgery for early stage cervical cancer has often been discussed. To better determine eligible candidates for less radical surgery, we investigated the risk factors for parametrial involvement (PI). METHODS The study included 193 patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB cervical cancer who were treated with radical hysterectomy and pelvic lymphadenectomy between 2008 and 2014. The patients were divided into two groups according to whether or not the parametrium was involved pathologically. The two groups were compared with regards to clinical and histopathological variables. RESULTS Univariate analysis showed that International Federation of Gynecology and Obstetrics stage, clinical tumor size, depth of stromal invasion, lymphovascular space invasion and pelvic lymph node metastasis were significantly associated with PI (P < 0.05 each). Multivariate analysis showed pelvic lymph node metastasis was an independent risk factor for PI (odds ratio, 10.70; [95% confidence interval, 3.02-48.08]; P = 0.0006). All patients with clinical tumor size less than or equal to 2 cm and negative for pelvic lymph node metastasis had no PI. CONCLUSION Cervical cancer with the tumor less than or equal to 2 cm and negative for pelvic lymph node metastasis seldom has PI. These patients are good candidates for less radical surgery.

ObjectiveThe phenotypic and pathological features of small cell cervical carcinoma (SMCC) and small small cell lung cancer (SCLC) are very similar; thus, the chemotherapy regimens used for the rare SMCC have been routinely based on regimens used for common SCLC. We set out to explore the protein expression profile similarities between these 2 cancers to prove that linking their therapeutic regimens is justified, with a secondary aim of finding tumor-specific proteins to use as additional biomarkers for more accurate diagnosis of SMCC, and potentially to use as therapeutic targets.MethodsProtein expression analysis was performed for 3 cases of SMCC and 1 example each of SCLC, mucinous adenocarcinoma of the cervix (MACC), lung mucinous adenocarcinoma (MACL), and squamous cell carcinoma of the cervix (SCC). We used cancer tissue–originated spheroids (CTOS) and isobaric tags for relative and absolute quantitation (iTRAQ)–based comprehensive and quantitative protein expression profile analysis. Expression in corresponding clinical samples was verified by immunohistochemistry.ResultsRather than organ of origin–specific patterns, the SMCC and SCLC samples revealed remarkably similar protein expression profiles—in agreement with their matching tumor pathology phenotypes. Sixteen proteins were expressed at least 2-fold higher in both small cell carcinomas (SMCC and SCLC) than in MACC or SCC. Immunohistochemical analysis confirmed higher expression of creatine kinase B-type in SMCC, compared with MACC and SCC.ConclusionsWe demonstrate a significant overlapping similarity of protein expression profiles of lung and cervical small cell carcinomas despite the significant differences in their organs of origin.