Side-to-end reanastomosis after low-anterior resection (STELAR): Outcomes, feasibility, and description of procedure performed by a gynecologic oncology service.

BACKGROUND AND OBJECTIVES: Low anterior rectosigmoid resection for a gynecologic disease is usually performed in concert with other procedures and can result in significant morbidity should anastomotic complication occur. This study examined surgical outcomes of side-to-end reanastomosis after low anterior resection (STELAR) performed by gynecologic oncology service. METHODS: This is a case series examining consecutive patients who underwent STELAR for gynecologic indications by a single gynecologic oncology group from 2009 to 2018. Prospectively collected institutional surgical database was searched for STELAR, and standard descriptive statistics were used to describe intraoperative and postoperative complications specific to reanastomosis. RESULTS: A total of 69 women underwent STELAR, with median age and body mass index of 54 years and 24 kg/m2 , respectively. 63.8% of patients had ovarian cancer and 84.4% had stage III-IV disease. The median estimated blood loss was 875 ml. Four (5.8%) women underwent protective loop colostomy at the time of STELAR. Postoperatively, there was 1 (1.4%) case of abscess formation within 30 days and 1 (1.4%) case of anastomotic leak 5 weeks after STELAR that required reoperation and diversion. No cases of fistula were clinically identified. CONCLUSION: Side-to-end reanastomosis may be a safe and feasible procedure to accomplish low rectosigmoid anastomosis in women with gynecologic disease.

Inhibition of poly(ADP-ribose) polymerase induces synthetic lethality in BRIP1 deficient ovarian epithelial cells.

OBJECTIVE: Pathogenic variations in the homologous recombination (HR) gene, BRCA1 interacting protein C-terminal helicase 1 (BRIP1) increase the risk for ovarian cancer. PARP inhibitors (PARPi) exert a synthetic lethal effect in BRCA-mutated ovarian cancers. Effective HR requires cooperation between BRCA1 and BRIP1; therefore, BRIP1-incompetancy may predict vulnerability to synthetic lethality. Here we investigated the response of ovarian epithelial cells with defective BRIP1 function to PARPi, and compared these cells to those lacking BRCA1 activity. METHODS: We engineered Chinese Hamster ovarian (CHO) epithelial cells to express deficient BRIP1 or BRCA1, and exposed them to olaparib with or without carboplatin or cisplatin. We assessed cellular proliferation and survival; we calculated inhibitory concentrations and combination and reduction drug indices. RESULTS: BRIP1 and BRCA1 inactivation impedes HR activity, decreases cellular proliferation and compromises DNA damage recovery. Platinum agent exposure impairs cellular survival. Olaparib exposure alone decreases cell viability in BRCA1-deficient cells, although has no effect on BRIP1-deficient cells. Combining carboplatin or cisplatin with olaparib synergistically attenuates cellular survival, consistent with synthetic lethality. CONCLUSIONS: BRIP1-deficient ovarian epithelial cells exhibit defective HR, resulting in synthetic lethality when exposed to a platinum agent/PARPi combination. PARPi alone had no effect; this lack of effect may result from distinguishing molecular properties of BRIP1and/or consequences of genomic background. Our study identifies altered BRIP1 as a target for precision medicine-based therapies for ovarian cancers. This investigation supports consideration of the use of a platinum agent/PARPi combination in ovarian cancers depending upon genetic profile and genomic background.

The rapid adoption of opportunistic salpingectomy at the time of hysterectomy for benign gynecologic disease in the United States.

BACKGROUND: Mounting evidence for the role of distal fallopian tubes in the pathogenesis of epithelial ovarian cancer has led to opportunistic salpingectomy being increasingly performed at the time of benign gynecologic surgery. Opportunistic salpingectomy has now been recommended as best practice in the United States to reduce future risk of ovarian cancer even in low-risk women. Preliminary analyses have suggested that performance of opportunistic salpingectomy is increasing. OBJECTIVE: To examine trends in opportunistic salpingectomy in women undergoing benign hysterectomy and to determine how the publication of the tubal hypothesis in 2010 may have contributed to these trends. STUDY DESIGN: This is a population-based, retrospective, observational study examining the National Inpatient Sample between January 2001 and September 2015. Women younger than 50 years who underwent inpatient hysterectomy for benign gynecologic disease were grouped as hysterectomy alone vs hysterectomy with opportunistic salpingectomy. All women had ovarian conservation, and those with adnexal pathology were excluded. Linear segmented regression with log transformation was used to assess temporal trends. An interrupted time-series analysis was then used to assess the impact of the 2010 publication of the tubal hypothesis on opportunistic salpingectomy trends. A regression-tree model was constructed to examine patterns in the use of opportunistic salpingectomy. A binary logistic regression model was then fitted to identify independent characteristics associated with opportunistic salpingectomy. Sensitivity analysis was performed in women aged 50-65 years to further assess surgical trends in a wider age group. RESULTS: There were 98,061 (9.0%) women who underwent hysterectomy with opportunistic salpingectomy and 997,237 (91.0%) women who underwent hysterectomy alone without opportunistic salpingectomy. The rate at which opportunistic salpingectomy was being performed gradually increased from 2.4% to 5.7% between 2001 and 2010 (2.4-fold increase; P<.001), predicting a 7.0% rate of opportunistic salpingectomy in 2015. However, in 2010, the rate of opportunistic salpingectomy began to increase substantially and reached 58.4% by 2015 (10.2-fold increase; P<.001). In multivariable analysis, the largest change in the performance of opportunistic salpingectomy occurred after 2010 (adjusted odds ratio, 5.42; 95% confidence interval, 5.34-5.51; P<.001). In a regression-tree model, women who had a hysterectomy at urban teaching hospitals in the Midwest after 2013 had the highest chance of undergoing opportunistic salpingectomy during benign hysterectomy (76.4%). In the sensitivity analysis of women aged 50-65 years, a similar exponential increase in opportunistic salpingectomy was observed from 5.8% in 2010 to 55.8% in 2015 (9.8-fold increase; P<.001). CONCLUSION: Our study suggests that clinicians in the United States rapidly adopted opportunistic salpingectomy at the time of benign hysterectomy following the publication of data implicating the distal fallopian tubes in ovarian cancer pathogenesis in 2010. By 2015, nearly 60% of women had undergone opportunistic salpingectomy at benign hysterectomy.

Identification of a novel diagnostic gene expression signature to discriminate uterine leiomyoma from leiomyosarcoma.

Leiomyosarcomas are rare, aggressive tumors, which exhibit a poor prognosis regardless of stage. Pre-operative diagnosis can be difficult as leiomyosarcoma can mimic features of the more common, benign uterine leiomyoma. The goal of this study was to identify specific molecular markers to discriminate between uterine leiomyosarcomas and leiomyomas to facilitate timely, accurate diagnosis and treatment. Gene expression profiles of three leiomyosarcomas, leiomyomas, and normal myometrial tissue samples were analyzed using the Affymetrix Human Gene 1.0 ST Array. GC-robust multiarray average calculation and ANOVA statistical testing were used to identify differentially expressed genes. Sixty genes, with functional roles in tumor progression or suppression, exhibited divergent expression profiles in leiomyosarcomas and leiomyomas, compared to normal myometrium. Differential RNA and protein levels of seven genes, with the most discriminatory expression patterns, were confirmed by RTPCR and immunohistochemistry in an additional 10 leiomyosarcoma and 20 leiomyoma independent samples. CHI3L1, MELK, PRC1, TOP2A, and TPX2 were overexpressed in leiomyosarcomas, while HPGD and TES were overexpressed in leiomyomas. Distinguishing leiomyosarcomas from leiomyomas represents a diagnostic challenge, particularly in the context of minimally invasive surgery. The unique gene expression signatures identified in this study may accurately differentiate between these tumor types at the earliest stage and provides potential prognostic factors and novel therapeutic targets for the treatment of leiomyosarcoma.

Performance and outcome of pelvic exenteration for gynecologic malignancies: A population-based study.

OBJECTIVE: To examine changes in performance and outcomes of pelvic exenteration for gynecologic malignancies. METHODS: This is a population-based retrospective study examining the Nationwide Inpatient Sample between 2001 and 2015. Women with cervical, uterine, vaginal, and vulvar malignancies who underwent pelvic exenteration were examined. Comorbidity, perioperative complications, total charges, length of stay, and mortality were assessed. RESULTS: There were 2647 cases included. Cervical cancer was the most common malignancy (45.1%), followed by vaginal cancer (27.6%). 26.9% of women had a Charlson Comorbidity Index ≥3, which significantly increased from 23.3% in 2001-2005 to 33.3% in 2011-2015 (42.9% relative increase, P < 0.001). Obese women undergoing exenteration increased significantly from 4.5% in 2001-2005 to 19.4% in 2011-2015 (3.3-fold relative increase, P < 0.001). The perioperative complication rate was 68.1%, including 38.7% with multiple complications. The mortality rate was 1.9%. The number of women with multiple perioperative complications increased from 29.4% in 2001-2005 to 52.8% in 2011-2015 (78.6% relative increase, P < 0.001). More recent year of surgery, obesity, higher comorbidity, higher household income, surgery at large bedsize hospital, urinary diversion, vaginal reconstruction, and vulvar cancer were associated with an increased risk of multiple complications on multivariable analysis (all, P < 0.05). Median length of stay was 14 (IQR 9-21) days, and the number of women hospitalized ≥28 days significantly increased from 12.6% in 2001-2005 to 19.1% in 2011-2015 (51.6% relative increase, P < 0.001). The median corrected total charges increased from $121,854 to $185,100 between 2001 and 2015 (net difference +$63,246, 51.9% relative increase, P < 0.001). CONCLUSION: Women undergoing pelvic exenteration for gynecologic malignancies became more obese and comorbid during the study period. Pelvic exenteration for women with gynecologic malignancies is associated with high morbidity and mortality as well as substantial treatment-related costs.

Intrauterine Manipulator Use During Minimally Invasive Hysterectomy and Risk of Lymphovascular Space Invasion in Endometrial Cancer.

OBJECTIVE: This study aimed to examine an association between intrauterine manipulator (IUM) use and frequency of lymphovascular space invasion (LVSI) in women with endometrial cancer undergoing minimally invasive hysterectomy. METHODS: A retrospective case-control study was conducted among stage I-IV endometrial cancer patients who underwent hysterectomy between 2008 and 2015. Medical records were reviewed for patient demographics, surgical details, and tumor characteristics. Women who underwent total laparoscopic hysterectomy (TLH) with IUM use were compared with women who underwent total abdominal hysterectomy (TAH). Review of archived medical record for data collection and propensity score matching were performed to adjust for background differences between TLH-IUM and TAH groups. A systematic literature review with pooled analysis was performed to examine frequency of LVSI. RESULTS: There were 687 women who underwent hysterectomy for endometrial cancer. Of those, 419 women underwent TLH with IUM use and 194 women underwent TAH. The most common type of IUM was VCare (89.5%). There was no statistically significant difference in the frequency of LVSI between the 2 groups: 15.1% for TLH-IUM vs 19.9% for TAH (P = 0.14). After propensity score matching, frequencies of LVSI were similar between the 2 groups: 21.2% for TLH-IUM vs 19.6% for TAH (P = 0.78). Systematic literature review identified 1371 cases of TLH-IUM and 1246 cases of TAH performed for endometrial cancer, and frequencies of LVSI were similar between the 2 groups (15.0% vs 13.6%, P = 0.31). CONCLUSION: Our study suggests that IUM use during TLH for endometrial cancer is not associated with increased frequency of LVSI.

Significance of lymph node metastasis on survival of women with uterine adenosarcoma.

OBJECTIVE: Uterine adenosarcoma (UAS) is a rare gynecologic malignancy and the significance of lymph node metastasis on survival has not been well studied. METHODS: A retrospective study was performed utilizing the Surveillance, Epidemiology, End Results Program to examine UAS (n=994), endometrial stromal sarcoma (ESS, n=2910), and uterine leiomyosarcoma (LMS, n=5506) diagnosed between 1973 and 2013. The impact of lymph node metastasis on cause-specific survival (CSS) was cross-compared by multivariable analysis. Systematic literature review was conducted to examine the impact of nodal metastasis on progression-free survival (PFS) in UAS. RESULTS: UAS had the lowest incidence of lymph node metastasis among the sarcoma subtypes examined (UAS 2.9%, LMS 3.4%, and ESS 6.6%, P<0.001). Lymph node metastasis was independently associated with decreased CSS in all three tumor types (all, P<0.01); however, magnitudes of statistical significance of lymph node metastasis for CSS were similar across the three tumor types: adjusted-hazard ratio (aHR) for UAS 2.34, ESS 2.43, and LMS 2.10. Systematic literature review identified 230 unique cases of surgically treated UAS. On multivariable analysis, lymph node metastasis (aHR 4.72) had the greatest degree of significance for PFS compared to other tumor factors including sarcomatous overgrowth (aHR 2.88), heterologous elements (aHR 2.08), and deep myometrial invasion (aHR 1.51). Large tumor, deep myometrial invasion, and sarcomatous overgrowth were associated with increased risk of lymph node metastasis (all, P<0.05). CONCLUSION: While uterine adenosarcoma had a low incidence of lymph node metastasis, the impact of lymph node metastasis on survival was comparable to ESS or LMS.