BRCA-mutated ovarian cancer commonly develops resistance to poly (ADP-ribose) polymerase (PARP) inhibitors. Here, we investigated the DNA repair protein RAD52 as a potential target to overcome resistance. In analysis of The Cancer Genome Atlas datasets and immunohistochemistry of tissue microarrays, elevated RAD52 expression correlated with poor overall survival in patients with high-grade serous ovarian cancers. We tested two PARP inhibitor-resistant Brca2-deficient mouse ovarian cancer models, ID8-OR and HGS2-OR. HGS2-OR cells had higher RAD52 expression than parental lines. Rad52 knockout or knockdown restored PARP inhibitor sensitivity in both models. In syngeneic mice, ID8-OR cells in which Rad52 was knocked out yielded lower tumor burden and longer overall survival than control cells. Rad52 depletion impaired single-strand annealing and homologous recombination and led to accumulation of DNA double-strand breaks after PARP inhibitor treatment. RNA sequencing demonstrated that PARP inhibitor treatment induced Polq expression in Brca2- and Rad52-deficient cells, suggesting a switch to microhomology-mediated end joining. Finally, the RAD52 inhibitor D-I03 synergized with a PARP inhibitor to reduce cell viability and tumor burden and prolong survival. Collectively, our findings establish RAD52 as a promising therapeutic target to overcome PARP inhibitor resistance in BRCA2-mutated ovarian cancer and offer mechanistic insights to inform future clinical strategies.

Table S1 - Antibody Details Table S2 - Primer Sequences Table S3 - AP1 shRNA Screen Details Table S4 - Patient Characteristics from Tissue Microarray Table S5 - Transcription factor overlap Figure S1 - Dose response, AP1 activity and AP1 subunit expression. Figure S2 - ATF6 Immunohistochemistry, KM Curve, and AP1 transcriptional targets Figure S3 - P38 Inhibitor Dose Response Figure S4 - DNA Damage in OVCA420 cell line and qPCR expression of BRCA1 and PARP1 Figure S5 - Controls for animal study

Background:Ovarian cancer treatment includes cytoreductive surgery, platinum-based chemotherapy, and often poly (ADP-ribose) polymerase (PARP) inhibitors. Homologous recombination (HR)-deficiency is a well-established predictor of therapy sensitivity. However, over 50% of HR-proficient tumors also exhibit sensitivity to standard-of-care treatments. Currently, there are no biomarkers to identify which HR-proficient tumors will be sensitive to standard-of-care therapy. Replication stress may serve as a key determinant of response. Methods:We evaluated phospho-RPA2-T21 (pRPA2) foci via immunofluorescence as a potential biomarker of replication stress in formalin-fixed, paraffin-embedded tumor samples collected at diagnosis from patients treated with platinum chemotherapy (discovery cohort: n = 31, validation cohort: n = 244) or PARP inhibitors (n = 87). Recurrent tumors (n = 37) were also analyzed. pRPA2 scores were calculated using automated imaging analysis. Samples were defined as pRPA2-High if > 16% of cells had ≥ 2 pRPA2 foci. Results:In the discovery cohort, HR-proficient, pRPA2-High tumors demonstrated significantly higher rates of pathologic complete response to platinum chemotherapy than HR-proficient, pRPA2-Low tumors. In the validation cohort, patients with HR-proficient, pRPA2-High tumors had significantly longer survival after platinum treatment than those with HR-proficient, pRPA2-Low tumors. Additionally, the pRPA2 assay effectively predicted survival outcomes in patients treated with PARP inhibitors and in recurrent tumor samples. Conclusion:Our study underscores the importance of considering replication stress markers alongside HR status in therapeutic planning. Our work suggest that this assay could be used throughout a patient's treatment course to expand the number of patients receiving effective therapy while reducing unnecessary toxicity.

Objectives Tissue banking procedures have evolved to keep pace with precision medicine, technology, emerging understanding of racial disparities, and regulatory requirements. However, there is little published guidance regarding strategies to create and maintain a successful biorepository. Our objective is to describe the infrastructure and protocols used by our Gynecologic Oncology Tissue Bank. Methods Our Tissue Bank was founded in 1992. In August 2022, internal funding was used to modernize the Tissue Bank. We hired three full-time employees, implemented universal screening of patients treated by gynecologic oncology faculty, updated consenting protocols, and standardized communication with providers. Tumor tissue, blood derivatives, ascites, and pleural fluid were collected from eligible, consenting patients and processed. Patient-derived cell lines and organoids were generated. For quality control purposes, one formalin-fixed, paraffin-embedded (FFPE) sample per tissue site was analyzed by a board-certified pathologist. All samples were labeled and tracked in an OpenSpecimen collection protocol and clinically annotated in a secure database. Results From August 2022 to October 2023, 227 patients (83% white, 15% Black, 1% Asian) were enrolled and 4249 specimens were collected. Adherent cell lines were generated from 15 patients with ovarian cancer and cell suspensions for organoid generation were collected from 46 patients with ovarian cancer. A recharge center was established to self-sustain the Tissue Bank. Samples have been shared with academic and commercial collaborators. Conclusions Our Tissue Bank has enrolled a large number of diverse patients, collected numerous specimen types, and collaborated widely. The procedures described here provide guidance for other institutions establishing similar resources.

Endogenous human retroviruses (ERVs) are remnants of exogenous retroviruses that have integrated into the human genome. Using publicly available RNA-seq data from 63 cervical cancer patients, we investigated the expression of ERVs in cervical cancers. Four aspects of cervical cancer were investigated: patient ancestral background, tumor HPV type, tumor stage and patient survival. Between the racial subgroups, 74 ERVs were significantly differentially expressed, with Black Americans having 30 upregulated and 44 downregulated (including MER21C, HERV9-int, and HERVH-int) ERVs when compared to White Americans. We found that 3313 ERVs were differentially expressed between HPV subgroups, including MER41A, HERVH-int and HERVK9. There were 28 downregulated (including MLT1D and HERVH-int) and 61 upregulated (including MER41A) ERVs in locally advanced-stage compared to early-stage samples. Tissue microarrays of cervical cancer patients were used to investigate the protein expression of ERVs with protein coding potential (i.e., HERVK and ERV3). Significant differences in protein expression of ERV3 (p = 0.000905) were observed between early-stage and locally advanced-stage tumors. No significant differential expression at the protein level was found for HERVK7 (p = 0.243). We also investigated a prognostic model, supplementing a baseline prediction model using FIGO stage, age and HPV positivity with ERVs data. The expression levels of all ERVs in the HERVd were input into a Lasso-Cox proportional hazards model, developing a predictive 67-ERV panel. When ERVs expression levels were supplemented with the clinical data, a significant increase in prognostic power (p = 9.433 × 10−15) relative to that obtained with the clinical parameters alone (p = 0.06027) was observed. In summary, ERV RNA expression in cervical cancer tumors is significantly different among racial cohorts, HPV subgroups and disease stages. The combination of the expression of certain ERVs in cervical cancers with clinical factors significantly improved prognostication compared to clinical factors alone; therefore, ERVs may serve as future prognostic biomarkers and therapeutic targets. Novelty and Impact: When endogenous retroviral (ERV) expression signatures were combined with currently employed clinical prognosticators of relapse of cervical cancer, the combination outperformed prediction models based on clinical prognosticators alone. ERV expression signatures in tumor biopsies may therefore be useful to help identify patients at greater risk of recurrence. The novel ERV expression signatures or adjacent genes possibly impacted by ERV expression described here may also be targets for the development of future therapeutic interventions.

Abstract High-grade serous ovarian cancer (HGSOC) is the deadliest ovarian cancer histotype due in-part to the lack of therapeutic options for chemotherapy-resistant disease. PARP inhibitors (PARPi) represent a targeted treatment. However, PARPi resistance is becoming a significant clinical challenge. There is an urgent need to overcome resistance mechanisms to extend disease-free intervals. We established isogeneic PARPi-sensitive and -resistant HGSOC cell lines. In three PARPi-resistant models, there is a significant increase in AP-1 transcriptional activity and DNA repair capacity. Using RNA-sequencing and an shRNA screen, we identified activating transcription factor 6 (ATF6) as a mediator of AP-1 activity, DNA damage response, and PARPi resistance. In publicly available datasets, ATF6 expression is elevated in HGSOC and portends a poorer recurrence-free survival. In a cohort of primary HGSOC tumors, higher ATF6 expression significantly correlated to PARPi resistance. In PARPi-resistant cell lines and a PDX model, inhibition of a known ATF6 regulator, p38, attenuated AP-1 activity and RAD51 foci formation, enhanced DNA damage, significantly inhibited tumor burden, and reduced accumulation of nuclear ATF6. Implications: This study highlights that a novel p38-ATF6-mediated AP-1 signaling axis contributes to PARPi resistance and provides a clinical rationale for combining PARPi and AP-1 signaling inhibitors.

Low-risk gestational trophoblastic neoplasia (GTN) is generally treated with single agent chemotherapy, including methotrexate (MTX) or dactinomycin. We present a case of a patient with low-risk GTN who underwent single agent MTX therapy, developed Pneumocystis jirovecii pneumonia (PJP), recovered, and ultimately completed consolidation treatment for GTN on single agent MTX. While MTX administration is associated with an increased risk of PJP, this association is best described in rheumatology literature. This is the first case of PJP complicating MTX therapy within the gynecologic oncology literature.

Supplementary Data from Targeting DUSP Activity as a Treatment for High-Grade Serous Ovarian Carcinoma

Small cell carcinoma of the ovary hypercalcemic type (SCCOHT) is a rare and aggressive disease. While classically linked to mutations in SMARCA4, we describe a case in a patient with both SMARCA4 and BRCA2 germline mutations. We describe her disease presentation, histopathology and treatment with adjuvant systemic chemotherapy, interval hyperthermic intraperitoneal chemotherapy, high dose chemotherapy with stem cell rescue, and maintenance with a poly-ADP-ribose polymerase inhibitor (PARPi). Additionally, we share spatial transcriptomics completed on original tumor.

Abstract Identifying novel, durable treatments for high-grade serous ovarian cancer (HGSOC) is paramount to extend both progression-free survival (PFS) and overall survival (OS) in patients afflicted with this disease. Dual-specificity phosphatase 1 (DUSP1) was identified as one of seven genes that may significantly affect prognosis in patients with HGSOC; however, the role of DUSP inhibition (DUSPi) in the treatment of HGSOC remains largely unknown. In this study, we show that DUSP1 is highly expressed in HGSOC and confers worse PFS and OS. Further, we corroborate data that show DUSP1 expression is directly associated with therapy resistance. Using a tissue microarray of 137 different serous ovarian carcinomas, we demonstrate the high expression of DUSP1 in primary and recurrent serous ovarian cancer. In both acquired and de novo therapy HGSOC-resistant models, DUSPi both inhibited cellular proliferation and promoted cell death. RPPA analysis of HGSOC cells revealed DUSPi led to the differential regulation of several pathways, including AMPK and mTORC. Further, in a patient-derived xenograft HGSOC model, DUSPi significantly inhibited tumor progression.

Biases in application review may limit access of applicants who are underrepresented in medicine (URM) to graduate medical training opportunities. We aimed to evaluate the association between blinding interviewers to written applications and final ranking of all applicants and URM applicants for Gynecologic Oncology fellowship. During 2020 virtual Gynecologic Oncology fellowship interviews, we blinded one group of interviewers to written applications, including self-reported URM status. Interviewers visually interacted with the applicants but did not review their application. Interviewers submitted independent rank lists. We compared pooled rankings of blinded and non-blinded interviewers for all applicants and for URM applicants using appropriate bivariate statistics. We received 94 applications for two positions through the National Resident Matching Program, of which 18 (19%) self-identified as URM. We invited 40 applicants to interview and interviewed 30 applicants over six sessions. Ten interviewees (33%) self-identified as URM. Of 12 or 13 faculty interviewers during each interview session, 3 or 4 were blinded to the written application. There was no statistically significant difference in rank order when comparing blinded to non-blinded interviewers overall. However, blinded interviewers ranked URM applicants higher than non-blinded interviewers (p = 0.04). Blinding of written application metrics may allow for higher ranking of URM individuals.

Objectives Endogenous human retroviruses (ERVs) are remnants of exogenous retroviruses that have been integrated into the human genome. Some ERVs may become activated allowing epigenetic alterations through DNA methylation or histone modification, which can further translate into altered gene regulation or transcription. This is a novel area of exploration in cervical cancer. Methods We applied ERV mapping tools to RNA-seq data from 63 cervical cancers to investigate expression of ~550,000 ERV elements from the Human Endogenous Retrovirus database (HERVd) to investigate ERV expression among various cohorts. We also investigated a prognostic model, supplementing a baseline prediction model using FIGO stage, age and HPV-positivity with ERVs. Results 98 ERVs were differentially expressed (padj < 0.1), with Black American patients having 40 upregulated and 58 downregulated (including MER21C, HERVH-int) ERVs when compared to white American patients. Of the 138 ERVs differentially expressed between early-stage and locally advanced-stage groups, 38 were upregulated, including ERV3, and 100 were downregulated. 26,916 ERVs were differentially expressed between HPV positive and negative cohorts. There were significant differences in ERV3 protein expression (p = 0.000905). While clinical parameters are predictive of progression free survival at p = 0.06027, our supplemented model combining a 67-ERV panel and the clinical data, discriminated the two risk groups at p = 9.433 x 1015. Conclusions ERV RNA expression differences in cervical cancers is significantly different among racial cohorts, HPV-subgroups and disease stages. The correlation of ERV expression alongside clinical factors significantly improves prognostication when compared to clinical factors alone and may serve as future therapeutic targets.

Objectives: Dual Specificity Phosphatase (DUSP) proteins regulate signaling cascades involved in tumor progression, but there are limited studies of DUSPs in epithelial ovarian carcinoma, especially in high-grade serous ovarian carcinoma (HGSOC). The study objective was to elucidate DUSP1’s contribution to HGSOC progression and examine a DUSP1/6 inhibitor (DUSPi) in therapy-resistant HGSOC. Methods: Bioinformatic analyses were conducted using The Cancer Genome Atlas (TCGA) Ovarian Serous Cystadenocarcinoma Firehose Database and PanCancer Atlas. qPCR was completed to determine the mRNA expression of DUSP1. Fifty percent inhibitory concentration of DUSPi was determined using colony formation assays. Reverse-phase protein array (RPPA) examined the effect of DUSPi on cellular signaling. The antitumoral effect of DUSPi was examined using a patient-derived xenograft (PDX) model. Quantitative data were expressed as mean +/- standard error of the mean. RPPA relative protein levels were determined for each and designated as log2 intensities and subsequently median-centered. Analysis of variance with Tukey correction was used for multiple comparisons. The level of significance was set at 0.05. Results: Of 24 DUSP proteins examined in HGSOC, DUSP1 mRNA was significantly upregulated (p<0.001, one-way ANOVA). Progression-free survival (PFS) and overall survival (OS) were significantly higher in patients with low DUSP1 expression (PFS: 15.41 vs 22.22 months, Log-rank test, p=0.0010, HR: 1.65, 95% CI: 1.213-2.259; OS: 41.52 vs 52.40 months, Log-rank test, p=0.0183, HR: 1.462, 95% CI: 1.064-2.00). Elevated DUSP1 protein expression was noted in our tissue microarray of 137 serous ovarian carcinoma primary and recurrent tumors. Olaparib-resistant HGSOC cells had significantly increased DUSP1 expression compared to olaparib-sensitive HGSOC cells (unpaired t-test, p<0.0001). The RPPA analysis revealed 34 proteins with significantly (p<0.05) altered expression after treatment with DUSPi. DUSPi led to the significant downregulation of WEE1 and ATR. Phosphor-AMPK (AMPK-a2_pS345), part of the mTORC pathway that can serve both tumor-suppressive and oncogenic roles, was elevated and dual phosphorylated ERK (MAPK_pT202_Y204). RPPA findings were confirmed in TCGA data and by immunoblotting. A therapy-resistant PDX model was used to examine DUSPi in vivo activity. DUSPi led to a decrease in total flux (photons/sec), indicating tumor regression, in the mice treated with DUSPi compared to control. At the end of the study, there was no evidence of ascites or tumor burden in mice treated with DUSPi. Conclusions: DUSP1 expression is associated with poor progression-free and overall survival. After treatment with a novel DUSP1/6 inhibitor (DUSPi), cell viability was significantly reduced. We defined the differential activation of signaling following DUSPi via RPPA. DUSP inhibition significantly resulted in altering the expression of multiple pathway proteins, including increasing AMPK phosphorylation. Finally, we identified a robust in vivo antitumor response with DUSPi in PDX models. Objectives: Dual Specificity Phosphatase (DUSP) proteins regulate signaling cascades involved in tumor progression, but there are limited studies of DUSPs in epithelial ovarian carcinoma, especially in high-grade serous ovarian carcinoma (HGSOC). The study objective was to elucidate DUSP1’s contribution to HGSOC progression and examine a DUSP1/6 inhibitor (DUSPi) in therapy-resistant HGSOC. Methods: Bioinformatic analyses were conducted using The Cancer Genome Atlas (TCGA) Ovarian Serous Cystadenocarcinoma Firehose Database and PanCancer Atlas. qPCR was completed to determine the mRNA expression of DUSP1. Fifty percent inhibitory concentration of DUSPi was determined using colony formation assays. Reverse-phase protein array (RPPA) examined the effect of DUSPi on cellular signaling. The antitumoral effect of DUSPi was examined using a patient-derived xenograft (PDX) model. Quantitative data were expressed as mean +/- standard error of the mean. RPPA relative protein levels were determined for each and designated as log2 intensities and subsequently median-centered. Analysis of variance with Tukey correction was used for multiple comparisons. The level of significance was set at 0.05. Results: Of 24 DUSP proteins examined in HGSOC, DUSP1 mRNA was significantly upregulated (p<0.001, one-way ANOVA). Progression-free survival (PFS) and overall survival (OS) were significantly higher in patients with low DUSP1 expression (PFS: 15.41 vs 22.22 months, Log-rank test, p=0.0010, HR: 1.65, 95% CI: 1.213-2.259; OS: 41.52 vs 52.40 months, Log-rank test, p=0.0183, HR: 1.462, 95% CI: 1.064-2.00). Elevated DUSP1 protein expression was noted in our tissue microarray of 137 serous ovarian carcinoma primary and recurrent tumors. Olaparib-resistant HGSOC cells had significantly increased DUSP1 expression compared to olaparib-sensitive HGSOC cells (unpaired t-test, p<0.0001). The RPPA analysis revealed 34 proteins with significantly (p<0.05) altered expression after treatment with DUSPi. DUSPi led to the significant downregulation of WEE1 and ATR. Phosphor-AMPK (AMPK-a2_pS345), part of the mTORC pathway that can serve both tumor-suppressive and oncogenic roles, was elevated and dual phosphorylated ERK (MAPK_pT202_Y204). RPPA findings were confirmed in TCGA data and by immunoblotting. A therapy-resistant PDX model was used to examine DUSPi in vivo activity. DUSPi led to a decrease in total flux (photons/sec), indicating tumor regression, in the mice treated with DUSPi compared to control. At the end of the study, there was no evidence of ascites or tumor burden in mice treated with DUSPi. Conclusions: DUSP1 expression is associated with poor progression-free and overall survival. After treatment with a novel DUSP1/6 inhibitor (DUSPi), cell viability was significantly reduced. We defined the differential activation of signaling following DUSPi via RPPA. DUSP inhibition significantly resulted in altering the expression of multiple pathway proteins, including increasing AMPK phosphorylation. Finally, we identified a robust in vivo antitumor response with DUSPi in PDX models.

Objectives: To describe the genomic alterations present in three matched bio-specimens (tumor, ascites, plasma) of patients with serous ovarian cancer. Methods: Eighteen patients were diagnosed with primary serous ovarian cancer between 9/2015 and 6/2019 and agreed to participate in the study. Tumor, ascites and plasma were obtained from the University of Colorado Gynecologic Tumor and Fluid Bank (GTFB) and additional data were collected from the electronic medical record. All eighteen patients had tumor and plasma samples that were sent for molecular tumor profiling (MTP), and thirteen of the eighteen patients additionally had ascites collected and sent for MTP. All samples were sent for 50-gene panel somatic testing and BRCA somatic testing. Germline BRCA testing was also performed and compared to germline testing previously completed and recorded in the patient electronic medical record. Results: Median age at diagnosis was 61 (range: 48-80). Ninety-four percent of bio-specimens were collected at time of primary diagnosis. Eighty-nine percent of tumors were high grade, and the majority of patients were at least stage IIIC (n=11, 61%). Forty-four percent received neo-adjuvant chemotherapy (NACT), while 56% did not. Eight patients recurred during the study period, and there were no deaths reported in the patient electronic medical record as of the time of final data analysis. BRCA somatic mutations were not more likely to be identified in plasma as compared to ascites or tumor (p=0.17). Co-occurring mutations between plasma and ascites were less common in comparison to co-occurring mutations between tumor and plasma or tumor and ascites, though not significantly (p=0.68). Somatic mutations in KDR and TP53 were most likely to be conserved across all three bio-specimens. Mutant allele frequencies (MAF) in individual mutations varied across biospecimens, though tended to be highest in tumor, followed by ascites. Conclusions: In order to understand the molecular signature of a cancer, MTP of various bio-specimens at a single point in time may aid in delineating a more comprehensive understanding of the critical mutational events. Use of such testing could further stratify patient prognoses and broaden the possibility of patient enrollment in basket and umbrella clinical trials. To describe the genomic alterations present in three matched bio-specimens (tumor, ascites, plasma) of patients with serous ovarian cancer. Eighteen patients were diagnosed with primary serous ovarian cancer between 9/2015 and 6/2019 and agreed to participate in the study. Tumor, ascites and plasma were obtained from the University of Colorado Gynecologic Tumor and Fluid Bank (GTFB) and additional data were collected from the electronic medical record. All eighteen patients had tumor and plasma samples that were sent for molecular tumor profiling (MTP), and thirteen of the eighteen patients additionally had ascites collected and sent for MTP. All samples were sent for 50-gene panel somatic testing and BRCA somatic testing. Germline BRCA testing was also performed and compared to germline testing previously completed and recorded in the patient electronic medical record. Median age at diagnosis was 61 (range: 48-80). Ninety-four percent of bio-specimens were collected at time of primary diagnosis. Eighty-nine percent of tumors were high grade, and the majority of patients were at least stage IIIC (n=11, 61%). Forty-four percent received neo-adjuvant chemotherapy (NACT), while 56% did not. Eight patients recurred during the study period, and there were no deaths reported in the patient electronic medical record as of the time of final data analysis. BRCA somatic mutations were not more likely to be identified in plasma as compared to ascites or tumor (p=0.17). Co-occurring mutations between plasma and ascites were less common in comparison to co-occurring mutations between tumor and plasma or tumor and ascites, though not significantly (p=0.68). Somatic mutations in KDR and TP53 were most likely to be conserved across all three bio-specimens. Mutant allele frequencies (MAF) in individual mutations varied across biospecimens, though tended to be highest in tumor, followed by ascites. In order to understand the molecular signature of a cancer, MTP of various bio-specimens at a single point in time may aid in delineating a more comprehensive understanding of the critical mutational events. Use of such testing could further stratify patient prognoses and broaden the possibility of patient enrollment in basket and umbrella clinical trials.

The clinical use of molecular tumor profiling (MTP) is expanding and there is an increasing use of MTP data to manage patient care. At the University of Colorado, 18 patients were diagnosed with primary serous ovarian cancer between 9/2015 and 6/2019 and consented for banking and analysis of tumor, ascites and plasma. All 18 patients had tumor and plasma samples that were sent for MTP, and 13 of 18 patients additionally had ascites collected and sent for MTP. 50-gene panel testing and BRCA testing were performed on primary tumor. BRCA genetic variants were more likely to be identified in plasma as compared to ascites or tumor, though not statistically significant ( P = 0.17). Co-occurring genetic variants between plasma and ascites were less common in comparison to co-occurring variants between tumor and plasma or tumor and ascites, though not statistically significant ( P = 0.68). Variants in KDR (VEGFR2) and TP53 were most likely to be conserved across all 3 biocompartments. Mutant allele frequencies (MAF) of individual genetic variants varied across biocompartments, though tended to be highest in the tumor, followed by ascites.

To compare delivery timing between patients with clinical signs or symptoms of preterm labor evaluated in our triage and antepartum units. A retrospective cohort study of singleton gestations seen for preterm labor concerns between 22w0d and 33w6d who delivered at our institution from 7/1/15 – 6/30/16. Triage visits and antepartum admissions were examined for: 1) symptomatic patients with clinical findings (transvaginal cervical length < 2.5 cm or cervical dilation > 2 cm), 2) asymptomatic patients with clinical findings, and 3) symptomatic patients without clinical findings. Primary outcomes were preterm delivery (< 37w0d) and time from presentation to delivery, assessed using Fisher's exact test. 491 hospital encounters for 371 patients met inclusion criteria. Patients were symptomatic without clinical findings in 65% of encounters, symptomatic with clinical findings in 24%, and asymptomatic with clinical findings in 11%. Of these, 70% were triaged and 30% were admitted. Symptomatic patients with clinical findings were more likely to deliver preterm (54%) than those who were asymptomatic with clinical findings (36%) or symptomatic without clinical findings (17%, p < 0.0001). Admitted patients were more likely to deliver preterm than those triaged home. For example, among symptomatic patients with clinical findings, 62% of admissions delivered preterm versus 14% of triage discharges (p < 0.0001). More specifically, 21% of admissions delivered within 48 hours (0% triage), 30% within 1 week (0% triage), and 43% within 1 month (8% triage). A combination of symptoms and clinical findings suggestive of preterm labor were most predictive of preterm delivery. Our institution was relatively accurate in determining which patients were likely to deliver preterm, as evidenced by how frequently antepartum admissions delivered within 1 month of evaluation relative to triage discharges. However, additional insight is needed into which patients with preterm labor symptoms and clinical findings most benefit from intervention, as over 46% still delivered at term.

Abstract The objective of this study was to examine the rate of and indications for readmission in patients with advanced staged ovarian cancer undergoing rectosigmoid resection and primary anastomosis, an important quality metric. A retrospective review was conducted of patients with primary ovarian cancer who underwent rectosigmoid resection as part of cytoreductive surgery between July 2003 and July 2014. Univariate analysis identified rates and predictors of readmission. Fifty patients were eligible for analysis. The unanticipated 30-day readmission rate was 18% (n = 9). Of those readmitted less than 30 days from date of discharge, 3 were readmitted more than once, making 14 total readmissions. A total of 21 indications for readmission were reported, with the most common being: infection (23.8%, n = 5); thromboembolic events (19%, n = 4); and severe malnutrition (14.3%, n = 3). The median time to readmission was 14 days (range, 2–26). There were no deaths within 30 days of surgery in this cohort. IMPACT STATEMENT What is already known about the subject? Unanticipated 30-day readmission rates are reported to be between 12 and 20% among patients undergoing cytoreductive surgery for the management of ovarian cancer. The relative contribution of rectosigmoid resection at the time of cytoreductive surgery to readmission is not well studied. What do the results of this study add? In the examined cohort, the unanticipated 30-day readmission rate following rectosigmoid resection with primary reanastomosis at the time of cytoreductive surgery is 18%, similar to the readmission rate for patients undergoing cytoreductive surgery, in general. While the sample size is limited, the perioperative complications in this cohort appear similar to those of patients undergoing cytoreductive surgery. What are the implications of these findings for clinical practice and/or further research? Efforts to reduce unanticipated 30-day readmission following cytoreductive surgery is warranted. Future studies may benefit from multi-centre approaches and prospective data collection, while simultaneously assessing the impact of enhanced recovery programs. Ultimately, identification of risk factors, and programmatic initiatives to drive down readmission will be important across surgical platforms, and the opportunity exists in patients with advanced stage ovarian cancer.