Prophylactic Ureteral Stent Placement and Urinary Injury During Hysterectomy for Placenta Accreta Spectrum.

OBJECTIVE: To evaluate the association between prophylactic ureteral stent placement at the time of hysterectomy for placenta accreta spectrum and genitourinary injury. METHODS: We conducted a retrospective cohort study of patients with placenta accreta spectrum who underwent hysterectomy at two referral centers from 2001 to 2021. The exposure was prophylactic ureteral stent placement. The primary outcome, genitourinary injury, was a composite of bladder injury, ureteral injury, or vesicovaginal fistula. Secondary outcomes included components of the primary outcome. We evaluated differences between groups using χ 2 and t test. To evaluate differences in the primary outcome, we reported odds ratios (ORs) and adjusted odds ratios (aORs) using multivariable logistic regression analyses to control for potential confounding variables. We used a Cochran-Armitage χ 2 trend test to evaluate difference in stent use and injury over time. RESULTS: In total, 236 patients were included. Prophylactic ureteral stents were used in 156 surgeries (66%). Overall, genitourinary injury occurred less frequently in the stent group compared with the no stent group (28% vs 51%, OR 0.37, 95% CI 0.21-0.65). This association persisted after controlling for urgency of delivery, three or more prior cesarean deliveries, and whether a gynecologic oncologist was present (aOR 0.27, 95% CI 0.14-0.52). Unintentional bladder injury occurred less frequently in the stent group compared with the no stent group (13% vs 25%, P =.018), as did ureteral injury (2% vs 9%, P =.019). CONCLUSION: Prophylactic ureteral stent placement was associated with a decreased risk of genitourinary injury during hysterectomy for placenta accreta spectrum.

Refusal of surgery and survival outcomes in endometrial cancer.

OBJECTIVES: The goal of this study was to determine the impact refusal of surgery has on overall survival in patients with endometrial cancer. METHODS: From January 2004 to December 2015, the National Cancer Database was queried for patients with pathologically proven endometrial cancer who were recommended surgery and refused. Inverse probability of treatment weighting was used to account for differences in baseline characteristics between patients who underwent surgery and those who refused. Kaplan-Meier analyses and doubly robust estimation with multivariate Cox proportional hazards modeling were used to analyze overall survival. RESULTS: Of the 300 675 patients identified, 534 patients (0.2%) were recommended surgical treatment but refused: 18% (95/534) were age ≤40 years. The 5-year overall survival for all patients who refused surgery was significantly decreased compared with patients who underwent surgery (29.2% vs 71.9%, P<0.01). This was demonstrated at ages 41-64 years (65.5% vs 91.0%, P<0.01) and ≥65 years (23.4% vs 75.3%, P<0.01). The 5-year overall survival did not meet statistical significance at age ≤40 years (90.1% vs 87.8% P<0.19). However, there were few patients in this cohort. On multivariate analysis, factors associated with refusal of surgery included: Medicaid insurance, Black race, Hispanic Race, Charlson Comorbidity Index scores of 2 or greater, stage II or III, and if patient received external beam radiation therapy alone. Factors associated with undergoing surgery included: age greater than 41, stage IB, and if the patient received brachytherapy. CONCLUSIONS: Refusal of surgery for endometrial cancer is uncommon and leads to decreased overall survival.

Risk of secondary malignancies in ovarian cancer survivors: 52,680 patients analyzed with over 40 years of follow-up.

OBJECTIVE: Survivors of ovarian cancer are at risk of developing a secondary malignancy (SM). We sought to evaluate the risk of developing SM, stratified by treatment modality. METHODS: Standardized incidence ratios (SIR, observed-to-expected [O/E] ratio) were assessed in 52,680 patients diagnosed with ovarian cancer between 1975 and 2016 in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. RESULTS: Of the 52,680 patients, 3366 patients (6.4%) developed SM, which was more than the endemic rate (O/E 1.13; p < .05). Patients who received any radiation (RT) had an increased risk of overall SM compared to those who didn't (O/E 1.42 vs 1.11; p < .05), and specifically, in the bladder (O/E 2.81). Patients who received any chemotherapy (CT) had an increased risk of leukemia (O/E 3.06), and a similar risk of overall SM compared to those not treated with CT (O/E 1.11 vs 1.14; p < .05). The excess risk of developing a solid tumor SM was greatest at latencies of 10-20 years. Patients younger than 50 had the highest risk of developing SM. Non-White patients had a higher risk of SM compared to White patients. CONCLUSIONS: This is the largest study to examine the risk of SM in patients with ovarian cancer and has the longest follow-up. Risk of SM was increased after ovarian cancer and varied with treatment modality, race, latency, and age. These results may help inform SM screening protocols for women diagnosed with ovarian cancer.

Refusal of Radiation Results in Inferior Survival in Endometrial Cancer.

OBJECTIVE: We sought to understand factors associated with refusal of adjuvant radiotherapy in endometrial cancer and its impact on outcomes. METHODS: Data from the National Cancer Database for patients who underwent surgery for nonmetastatic endometrial cancer between 2004 and 2015 were pooled. The Pearson χ test and multivariate logistic regression analyses were used to assess demographic, clinical, and treatment factors. Inverse probability of treatment weighting was used to account for differences in baseline characteristics. Kaplan-Meier analyses and doubly-robust estimation with multivariate Cox proportional hazards modeling were used to analyze overall survival (OS). RESULTS: We identified 4739 of 80,803 patients (5.9%) who refused radiotherapy. Factors associated with refusal were: no insurance (relative risk [RR]=1.66, P<0.01), Medicare (RR=1.42, P<0.01), living >50 miles from treatment (RR=1.34, P<0.01), Charlson-Deyo Comorbidity Scores of 1 (RR=1.16, P<0.01) or ≥2 RR=1.38, P<0.01), age above 60 years (RR=1.28, P<0.01), International Federation of Gynecology and Obstetrics (FIGO) stages IIIA (RR=1.63, P<0.01) and IIIC (RR=1.65, P<0.01) disease, papillary (RR=1.69, P<0.01) and clear cell histology (RR=1.64, P<0.01). Factors associated with radiation therapy receipt included: Hispanic race (RR=0.61, P<0.01), income >$63,000 (RR=0.89, P=0.044), undergoing chemotherapy (RR=0.17, P<0.01), FIGO stages IB (RR=0.81, P<0.01) and II (RR=0.70, P<0.01) disease, and lymphadenectomy (RR=0.79, P<0.01). After weighting, 5-year OS was significantly lower with refusal (74.3% vs. 79.7%, P<0.01). This survival decrement was maintained across FIGO stages. CONCLUSIONS: We identified characteristics associated with radiation refusal, including socioeconomic barriers, advanced disease stage, and histology. Refusal of radiotherapy conferred decreased OS across FIGO stages.

The variable impact of positive lymph nodes in cervical cancer: Implications of the new FIGO staging system.

OBJECTIVE: The 2018 International Federation of Gynecology and Obstetrics (FIGO) staging system for cervical cancer changed from a clinical system to a clinical/pathologic/radiologic system with stages IIIC1 and IIIC2 indicating positive pelvic and para-aortic lymph nodes, respectively. We evaluated the National Cancer Database (NCDB) for the impact on survival of lymph node metastases (LNM). METHODS: The NCDB from 2004 to 2015 was queried for patients with cervical cancer, yielding 115,819 patients. Patients with FIGO IVB (22,569), non-adeno/squamous cell histologies (5,909), unknown nodal status (60,695), or unknown survival time (9,473) were excluded. Survival was compared using Cox proportional hazard model based on nodal status. Univariate (UVA) and multivariate analyses (MVA) were done for the overall cohort, followed by UVA by individual stage. RESULTS: In 17,173 eligible patients, LNM negatively affected survival (UVA IIIC1 Hazard Ratio [HR] 2.0, p < 0.001, IIIC2 HR 3.9, p < 0.001, MVA IIIC1 HR 1.36, p < 0.001, IIIC2 HR 2.14, p < 0.001). In T1B, the effect of IIIC2 was most pronounced (HR 5.38, p < 0.001 versus HR 1.5 p = 0.001 for IIIC1 disease). In T3, the effect of LNM was markedly less: (HR 1.7, p < 0.001 for IIIC2 versus HR 1.2 p = 0.02 for IIIC1). Within T1B, there was no difference in survival for IIIC1 for the smaller T stages (IB1-2). CONCLUSION: In this study, LNM negatively affects prognosis in cervical cancer. The impact on survival varies by T stage with the greatest effect seen in stage T1B with IIIC2 disease.

LVSI positive and NX in early endometrial cancer: Surgical restaging (and no further treatment if N0), or adjuvant ERT?

Early endometrial cancer has an overall survival of greater than 80% (1). One of the poor prognostic factors that may be associated with the 20% who do not survive 5 years is the presence of lymphovascular space invasion (LVSI). LVSI is associated with increased nodal metastasis and decreased progression free survival (PFS) and overall survival (OS). (2-8). Therefore, unstaged, LVSI positive early endometrial cancer requires additional management with either completion of staging with lymphadenectomy or adjuvant radiation. We focus on reviewing the management of natural history and management of early endometrial cancer followed by the prognostic impact of LVSI, management options and recommendations.

Ovarian remnant syndrome in an aromatase inhibitor-treated patient with BRCA2 mutation following bilateral oophorectomy.

Ovarian remnant syndrome (ORS), in which a portion of the ovary is retained following bilateral salpingo-oophorectomy (BSO), is uncommon but can negatively impact patient management. Evaluation should be performed in a patient who has clinical signs or symptoms suggestive of ORS, especially in a premenopausal woman with breast cancer who is treated with an aromatase inhibitor following bilateral salpingo-oophorectomy (BSO), or a woman with a pathogenic variant in BRCA1 or BRCA2 who undergoes BSO for ovarian cancer risk reduction.

Estrogen Signaling in Endometrial Cancer: a Key Oncogenic Pathway with Several Open Questions.

Endometrial cancer is the most common gynecological cancer in the developed world, and it is one of the few cancer types that is becoming more prevalent and leading to more deaths in the USA each year. The majority of endometrial tumors are considered to be hormonally driven, where estrogen signaling through estrogen receptor α (ER) acts as an oncogenic signal. The major risk factors and some treatment options for endometrial cancer patients emphasize a key role for estrogen signaling in the disease. Despite the strong connections between estrogen signaling and endometrial cancer, important molecular aspects of ER function remain poorly understood; however, progress is being made in our understanding of estrogen signaling in endometrial cancer. Here, we discuss the evidence for the importance of estrogen signaling in endometrial cancer, details of the endometrial cancer-specific actions of ER, and open questions surrounding estrogen signaling in endometrial cancer.

Too many women are dying from cervix cancer: Problems and solutions.

One woman dies from cervix cancer every 2 min, adding up to over 270,000 deaths globally per year. This cancer affects a young population, and hence, the loss of life is staggering. There are many aspects of prevention, screening, and care that are suboptimal. A great deal is known about HPV induced carcinogenesis, yet clinical outcomes have been stagnant over decades. There has been no improvement in cervix cancer survival in the US since the mid-1970s [1]. With increased knowledge of the disease and greater worldwide resources including prevention, screening, and improved therapeutics, there is significant promise for fewer women to die from this virally induced cancer. We focus here on the major problems in prevention, screening, and delivery of care for cervix cancer and provide concrete solutions. With appropriate focus, a major improvement in survival from cervix cancer could be achieved in a short time span.

Referring survivors of endometrial cancer and complex atypical hyperplasia to bariatric specialists: a prospective cohort study.

OBJECTIVE: The purpose of this study was to describe the acceptability of bariatric referrals when offered by gynecologic oncologists to women with a history of complex atypical hyperplasia or early-stage endometrial cancer and to detail compliance with referrals and weight loss attempts that are initiated 3 months after the referral. STUDY DESIGN: Obese women with complex atypical hyperplasia or early-stage endometrial cancer were approached for inclusion in this prospective cohort study. Those women who were not in the care of a bariatric specialist were offered a medical referral with or without a surgical referral. A survey was administered at inclusion and after 3 months. RESULTS: Of 121 women who were approached, 106 women were consented. Women reported that it was acceptable for their gynecologic oncologist to discuss weight loss (91.09%) and that a 10% loss of body weight would be beneficial (86.14%). Six women were already in the care of a bariatric specialist. Of the remaining 100 women, 43 accepted a referral: 35 of 100 medical and 8 of 66 surgical referrals that were offered. At 3 months, 17 women complied with a referral (16 medical and 1 surgical), and 59 women had initiated any weight loss attempt. On multivariate analysis, a higher initial weight (P = .0403), Charlson Comorbidity Index ≥5 (P = .0278), and shorter time from surgery to bariatric referral (P = .0338) predicted acceptance of a referral. CONCLUSION: Weight-loss counseling is well received by these women. After being offered bariatric referral, only 17% comply, but most women (59%) subsequently initiate a weight loss attempt. Referrals should be offered early in the course of cancer care to maximize acceptance.

The Impact of Percent Reduction in CA-125 Levels on Prediction of the Extent of Interval Cytoreduction and Outcome in Patients With Advanced-Stage Cancer of Müllerian Origin Treated With Neoadjuvant Chemotherapy.

OBJECTIVE: To investigate the role of CA-125 percent reduction after neoadjuvant chemotherapy in predicting the extent of the interval debulking surgery (IDS) and outcomes in patients with advanced-stage müllerian carcinoma. METHODS: Patients who received neoadjuvant chemotherapy for advanced-stage müllerian carcinoma from 2000 to 2013 were identified. Percent reduction in CA-125 was categorized into 2 groups: ≥ 90% (CA ≥ 90%) and <90% (CA < 90%) reduction from prechemotherapy to preoperative CA-125. RESULTS: Of the 115 patients identified, 73% had CA ≥ 90% and 27% had CA < 90%. Optimal and complete IDS were achieved in 87% and 38%, respectively. Compared with the CA < 90% group, the CA ≥ 90% group was more likely to have complete IDS (P = 0.035), less likely to have a bowel resection (P < 0.001), and more likely to have no viable tumor/microscopic disease with treatment effect (P < 0.001). No difference in overall survival (OS; P = 0.81) and progression-free survival (PFS; P = 0.60) was noted between the groups. In multivariable analysis, CA ≥ 90% was not a predictor of PFS (hazard ratio [HR], 1.08; 95% confidence interval [CI], 0.65-1.79; P = 0.77) or OS (HR, 1.45; 95% CI, 0.73-2.9; P = 0.29). Patients with preoperative CA-125 < 20 had significantly longer OS (P = 0.05) and PFS (P = 0.005) than did those with preoperative CA-125 ≥ 20. In multivariable analysis, preoperative CA-125 < 20 was a predictor of PFS (HR, 0.37; 95% CI, 0.20-0.66; P < 0.001) but not OS (HR, 0.64; 95% CI, 0.34-1.21; P = 0.17). CONCLUSIONS: A reduction in CA-125 of at least 90% is associated with complete IDS, favorable pathologic response, and fewer bowel resections. A preoperative CA-125 < 20 suggests improved outcome. These findings are helpful for treatment planning and patient counseling.

Impact of age on 30-day mortality and morbidity in patients undergoing surgery for endometrial cancer.

OBJECTIVES: To investigate the impact of age on postoperative mortality and morbidity for women undergoing surgery for endometrial cancer. METHODS: Patients with endometrial cancer who had a hysterectomy were identified in the 2005-2011 National Surgical Quality Improvement Program database. Patient characteristics and outcomes were compared between age groups. Multivariable logistic regression models were used. RESULTS: 4000 patients met inclusion criteria. Octogenarians (n=328) were less likely to undergo laparoscopic surgery (p<0.001) but there was no difference in surgical complexity among age groups (p=0.54). In multivariate analysis, ages 60-69 (OR 0.9, 95% CI 0.3-2.8, p=0.82), 70-79 (OR 1.4, 95% CI 0.4-4.3, p=0.60) and ≥80 years (OR 2.4, 95% CI 0.7-8.1, p=0.17) were not associated with increased mortality compared to age<60 years. Significant predictors of mortality were respiratory or renal disease, dependent functional status, and hypoalbuminemia. Octogenarians were more likely to have non-surgical complications (8% vs. 3-5%, p=0.001) but there was no difference in surgical complications (p=0.89). In multivariate analysis, ages 60-69 (OR 1.2, 95% CI 1.0-1.6, p=0.09), 70-79 (OR 1.3, 95% CI 1.0-1.8, p=0.05) and ≥80 years (OR 1.3, 95% CI 0.9-2.5, p=0.14) were not associated with increased complications compared to age<60 years. Significant predictors of complications were higher ASA class, anemia, and thrombocytosis. CONCLUSIONS: Older patients should not be denied surgery for endometrial cancer based on age alone as they do not have higher rates of 30-day morbidity or mortality after adjusting for other factors. An increased effort should be made to perform minimally invasive surgery in octogenarians.

Same-day cervical preparation with misoprostol prior to second trimester D&E: a case series.

BACKGROUND: Traditionally, overnight cervical preparation with osmotic dilators has been used for second trimester dilation and evacuation (D&E) procedures. Misoprostol offers an alternative treatment that could shorten cervical preparation time. STUDY DESIGN: This study reports on a case series of patients who received only buccal or vaginal misoprostol for cervical preparation on the same day as the D&E procedure. Data were collected from charts of women undergoing second trimester D&E at an outpatient women's health clinic. Eligible cases included procedures performed between January 2001 and December 2010 at 17 0/7 to 23 0/7 weeks of gestation. RESULTS: Chart review identified 1177 cases of D&E during the study period. After deletion of 96 multiple-day cases using laminaria, 1081 misoprostol-only cases remained for analysis. Two of the cases were not able to be completed in the same day (0.2%). Ninety-eight percent of cases were 17-20 weeks of gestation. The average time from either vaginal or buccal placement of the first misoprostol dose to procedure completion was 4.9 h (SD±1.7 h). The average procedure length was 13.0 min (SD±10.2 min). Complications were reported in 21 of 1079 same-day procedures (2%) and included resuction (n=4), hemorrhage (n=5), cervical laceration (n=4), endometritis (n=5), pulmonary embolus (n=1), disseminated intravascular coagulation (n=1) and perforation (n=1). CONCLUSION: Same-day cervical preparation with misoprostol for second trimester D&E is both safe and effective. With the continuing shortage of D&E providers, the resulting increase in travel distance to obtain the procedure, mandatory waiting periods and the capability of having the procedure completed in a single day may increase patient access, reduce cost and improve patient satisfaction.