An SGO commentary: U.S. News and World Report gynecologic oncology procedural ratings-Do they reflect high-quality care?

▪ ▪ ▪.

Impact of pharmacogenomic profiles on post-surgical pain following laparotomy for gynecologic pathology.

OBJECTIVES: The aim of this prospective study was to compare perioperative opioid use in women by status of CYP2D6, a highly polymorphic pharmacogene relevant to opioid metabolism. METHODS: Patients undergoing laparotomy were prospectively recruited and provided a preoperative saliva swab for a pharmacogenomic (PGx) gene panel. Postoperative opioid usage and pain scores were evaluated via chart review and a phone survey. Pharmacogenes known to be relevant to opioid metabolism were genotyped, and opioid metabolizing activity predicted by CYP2D6 genotyping. Patient and procedural factors were compared using Fisher's exact and Kruskal-Wallis tests. RESULTS: The 96 enrolled patients were classified as ultra-rapid (N = 3, 3%), normal (58, 60%), intermediate (27, 28%), and poor (8, 8%) opioid metabolizers. There was no difference in surgical complexity across CYP2D6 categories (p = 0.61). Morphine Milligram Equivalents (MME) consumed during the first 24 h after peri-operative suite exit were significantly different between groups: ultrarapid metabolizers had the highest median MME (75, IQR 45-88) compared to the other three groups (normal metabolizers 23 [8-45], intermediate metabolizers 48 [20-63], poor metabolizers 31 [12-53], p = 0.03). Opioid requirements were clinically greater in ultrarapid metabolizers during the second 24 h and last 24 h but were statistically similar (p = 0.07). There was no difference in MME prescribed at discharge (p = 0.22) or patient satisfaction with pain control (p = 0.64) between groups. CONCLUSIONS: A positive association existed between increased CYP2D6 activity and in-hospital opioid requirements, especially in the first 24 h after surgery. This provides important information to further individualize opioid prescriptions for patients undergoing laparotomy for gynecologic pathology.

Mendelian randomization analyses suggest a role for cholesterol in the development of endometrial cancer.

Blood lipids have been associated with the development of a range of cancers, including breast, lung and colorectal cancer. For endometrial cancer, observational studies have reported inconsistent associations between blood lipids and cancer risk. To reduce biases from unmeasured confounding, we performed a bidirectional, two-sample Mendelian randomization analysis to investigate the relationship between levels of three blood lipids (low-density lipoprotein [LDL] and high-density lipoprotein [HDL] cholesterol, and triglycerides) and endometrial cancer risk. Genetic variants associated with each of these blood lipid levels (P < 5 × 10-8 ) were identified as instrumental variables, and assessed using genome-wide association study data from the Endometrial Cancer Association Consortium (12 906 cases and 108 979 controls) and the Global Lipids Genetic Consortium (n = 188 578). Mendelian randomization analyses found genetically raised LDL cholesterol levels to be associated with lower risks of endometrial cancer of all histologies combined, and of endometrioid and non-endometrioid subtypes. Conversely, higher genetically predicted HDL cholesterol levels were associated with increased risk of non-endometrioid endometrial cancer. After accounting for the potential confounding role of obesity (as measured by genetic variants associated with body mass index), the association between genetically predicted increased LDL cholesterol levels and lower endometrial cancer risk remained significant, especially for non-endometrioid endometrial cancer. There was no evidence to support a role for triglycerides in endometrial cancer development. Our study supports a role for LDL and HDL cholesterol in the development of non-endometrioid endometrial cancer. Further studies are required to understand the mechanisms underlying these findings.

Image-guided tumor ablation in gynecologic oncology: Review of interventional oncology techniques and case examples highlighting a collaborative, multidisciplinary program.

As interventional oncology services within radiology mature, image-guided ablation techniques are increasingly applied to recurrent gynecologic malignancies. Ablation may be performed using thermal techniques like cryoablation, microwave ablation, or radiofrequency ablation, as well as non-thermal ones, such as focused ultrasound or irreversible electroporation. Feasibility and approach depend on tumor type, size, number, anatomic location, proximity of critical structures, and goals of therapy. Current indications include local control of limited metastatic disease or palliation of painful bone metastases refractory or unsuitable to conventional therapies. Technical aspects of these procedures, including methods to protect nearby critical structures are presented through illustrative examples. Cases amenable to image-guided ablation include, but are not limited to, hepatic or pulmonary metastases, musculoskeletal metastases, retroperitoneal nodal metastases, pelvic side wall disease, abdominal wall disease, and vaginal or vulvar tumors. Protective maneuvers, such as hydro-displacement of bowel, neuromonitoring, and retrograde pyeloperfusion through ureteral stents, permit safe ablation despite close proximity to vulnerable nerves or organs. Image-guided ablation offers an alternative modality to achieve local tumor control without the risks associated with surgery or systemic treatment in appropriately selected patients. A multidisciplinary approach to use of image-guided ablation includes collaboration between gynecologic oncology, interventional radiology, anesthesia, urology and radiation oncology teams allowing for appropriate patient-centered case selection. Long-term follow up and additional studies are needed to determine the oncologic benefits of such techniques.

PP2A and E3 ubiquitin ligase deficiencies: Seminal biological drivers in endometrial cancer.

OBJECTIVE: PI3K-AKT pathway mutations initiate a kinase cascade that characterizes endometrial cancer (EC). As kinases seldom cause oncogenic transformation without dysregulation of antagonistic phosphatases, pivotal interactions governing this pathway were explored and correlated with clinical outcomes. METHODS: After exclusion of patients with POLE mutations from The Cancer Genome Atlas EC cohort with endometrioid or serous EC, the study population was 209 patients with DNA sequencing, quantitative gene-specific RNA expression, copy number variation (CNV), and surveillance data available. Extracted data were annotated and integrated. RESULTS: A PIK3CA, PTEN, or PIK3R1 mutant (-mu) was present in 83% of patients; 57% harbored more than 1 mutation without adversely impacting progression-free survival (PFS) (P = .10). PIK3CA CNV of at least 1.1 (CNV high [-H]) was detected in 26% and linked to TP53-mu and CIP2A expression (P < .001) but was not associated with PFS (P = .24). PIK3CA expression was significantly different between those with CIP2A-H and CIP2A low (-L) expression (the endogenous inhibitor of protein phosphatase 2A [PP2A]), when stratified by PIK3CA mutational status or by PIK3CA CNV-H and CNV-L (all P < .01). CIP2A-H or PPP2R1A-mu mitigates PP2A kinase dephosphorylation, and FBXW7-mu nullifies E3 ubiquitin ligase (E3UL) oncoprotein degradation. CIP2A-H and PPP2R1A-mu (PP2A impairment) and FBXW7-mu (E3UL impairment) were associated with compromised PFS (P < .001) and were prognostically discriminatory for PIK3CA-mu and PIK3CA CNV-H tumors (P < .001). Among documented recurrences, 84% were associated with impaired PP2A (75%) and/or E3UL (20%). CONCLUSION: PP2A and E3UL deficiencies are seminal biological drivers in EC independent of PIK3CA-mu, PTEN-mu, and PIK3R1-mu and PIK3CA CNV.

Uterine carcinosarcomas: From pathology to practice.

OBJECTIVE: Uterine carcinosarcoma (UCS) is a rare but aggressive cancer. In early-stage disease data guiding treatment is sparse. The purpose of this review is to summarize the findings from the 2019 NRG oncology group summer symposium meeting as well as a review of the current literature, with a particular focus on molecular targets, ongoing clinical trials, and treatment of early and advanced/recurrent disease. METHODS: A combination of expert presentations and an extensive literature search was undertaken to summarize the literature in this review. MEDLINE was queried for peer-reviewed publications on UCS. This search was not limited by year or study design, but was limited to English language publications. ClinicalTrials.gov was queried for ongoing trials in UCS. RESULTS: UCS is a rare cancer that is biphasic, with the carcinomatous component driving its aggressive nature. Level 3 evidence regarding early stage disease is lacking, but retrospective data suggests adjuvant therapy is warranted. The recent results of GOG 261 have contributed valuable information towards treatment strategy, including use of paclitaxel and carboplatin for UCS. Clinical trials are ongoing to investigate new targeted agents in UCS. CONCLUSION: Ongoing endometrial cancer clinical trials now include UCS patients. In combination with advances in molecular profiling, this will provide patients with UCS improved therapeutic options. Until that time, surgical resection and traditional cytotoxic chemotherapy remains standard of care.

Outcomes and patient perspectives following implementation of tiered opioid prescription guidelines in gynecologic surgery.

OBJECTIVES: To report the impact of implementing standardized guidelines for opioid prescriptions after gynecologic surgery and describe patient perspectives before and after implementation for those undergoing laparotomy for ovarian cancer. METHODS: Patients undergoing gynecologic surgery between October 2017 and May 2018 were prescribed opioids at discharge using tiered guidelines; prescriptions were compared to consecutive historical controls (March 2017-October 2017). A subset of ovarian cancer laparotomy patients were surveyed regarding postoperative opioid consumption and patient experience. RESULTS: A total of 620 women in the tiered guideline cohort were compared with 599 historical controls. Following implementation, 95.8% of prescriptions met guidelines. Median milligram morphine equivalents (MME) prescribed decreased from 150 to 75 (p ≤ 0.001) with no change in opioid refills (7.7 vs 6.9%, p = 0.62). In surveyed ovarian cancer patients, 100% of tiered guideline patients and 92% of historical controls felt satisfied with pain control (p = 0.24), despite a 50% reduction in prescribed MME and 14.6% receiving no opioids at discharge (p = 0.002). The median (IQR) MME consumed after discharge was 15 (0, 75) in tiered guideline patients vs. 24 (0, 135) in historical controls, and 38.2% and 42.4% consumed no opioids, respectively. Mean time between surgery and opioid use cessation was <1 week in both groups; patients' perceptions of opioid prescription appropriateness did not change (p = 0.49). More than 75% of patients kept their remaining opioids rather than dispose of them. CONCLUSIONS: Reducing prescribed opioids after gynecologic surgery using tiered guidelines did not increase opioid refills or worsen patients' perceptions of postoperative pain. Even after laparotomy, very little opioids were required over a short duration after dismissal. Infrequent disposal of leftover opioids highlights the need to avoid over-prescribing.

Using evidence to direct quality improvement efforts: Defining the highest impact complications after complex cytoreductive surgery for ovarian cancer.

OBJECTIVE: We sought to identify postoperative complications with the greatest impact on patient-centric outcomes to serve as high yield QI targets in ovarian cancer (OC) surgery. METHODS: Women undergoing complex CRS (defined as cytoreductive surgery with colon resection) for OC between January 1, 2012 and 12/31/2016 were identified from the National Surgical Quality Improvement Program (NSQIP) database. We determined the population attributable fraction (PAF) to quantify the contribution of each major complication towards adverse outcomes. PAF represents the burden of adverse outcomes that could be eliminated if the corresponding complication was prevented. Organ space surgical site infection (SSI) was used as a surrogate for anastomotic leak (AL). RESULTS: A total of 1434 women met inclusion criteria. Any adverse clinical outcome (composite of death, reoperation, or end organ dysfunction) occurred in 9.1% of women, and AL was the largest contributor to adverse clinical outcomes [PAF = 33.4% (95%CI: 22.3%-45.6%)]. The rates of increased resource utilization were as follows; prolonged hospitalization in 23.7%, non-home discharge in 10.7% and unplanned readmission in 14.8% of women. AL was the largest contributor to prolonged hospitalizations [PAF = 75.7% (95%CI: 51.4%-90.0%)] and readmissions [PAF = 17.1% (95%CI: 11.5%-22.6%)]; while transfusion was the largest contributor to non-home discharge [PAF = 22.8% (95%CI: 0.7%-42.4%)]. By comparison, the impact of other complications, including those targeted by the Surgical Care Improvement Project (SCIP), such as incisional SSI, venous thromboembolism, myocardial infarction, and urinary infection, was small. CONCLUSIONS: Anastomotic leak is the largest contributor to adverse clinical outcomes and increased resource utilization after complex cytoreductive surgery. Quality improvement efforts to reduce AL and its impact should be of highest priority in OC surgery.

Multicenter study comparing oncologic outcomes after lymph node assessment via a sentinel lymph node algorithm versus comprehensive pelvic and paraaortic lymphadenectomy in patients with serous and clear cell endometrial carcinoma.

OBJECTIVES: To compare survival after nodal assessment using a sentinel lymph node (SLN) algorithm versus comprehensive pelvic and paraaortic lymphadenectomy (LND) in serous or clear cell endometrial carcinoma, and to compare survival in node-negative cases. METHODS: Three-year recurrence-free survival (RFS) and overall survival were compared between one institution that used comprehensive LND to the renal veins and a second institution that used an SLN algorithm with ultra-staging with inverse-probability of treatment weighting (IPTW) derived from propensity scores to adjust for covariate imbalance between cohorts. RESULTS: 214 patients were identified (118 SLN cohort, 96 LND cohort). Adjuvant therapy differed between the cohorts; 84% and 40% in the SLN and LND cohorts, respectively, received chemotherapy ± radiation therapy. The IPTW-adjusted 3-year RFS rates were 69% and 80%, respectively. The IPTW-adjusted 3-year OS rates were 88% and 77%, respectively. The IPTW-adjusted hazard ratio (HR) for the association of surgical approach (SLN vs LND) with progression and death was 1.46 (95% CI: 0.70-3.04) and 0.44 (95% CI: 0.19-1.02), respectively. In the 168 node-negative cases, the IPTW-adjusted 3-year RFS rates were 73% and 91%, respectively. The IPTW-adjusted 3-year OS rates were 88% and 86%, respectively. In this subgroup, IPTW-adjusted HR for the association of surgical approach (SLN vs LND) with progression and death was 3.12 (95% CI: 1.02-9.57) and 0.69 (95% CI: 0.24-1.95), respectively. CONCLUSION: OS was not compromised with the SLN algorithm. SLN may be associated with a decreased RFS but similar OS in node-negative cases despite the majority receiving chemotherapy. This may be due to differences in surveillance.

When to Operate, Hesitate and Reintegrate: Society of Gynecologic Oncology Surgical Considerations during the COVID-19 Pandemic.

The COVID-19 pandemic has challenged our ability to provide timely surgical care for our patients. In response, the U.S. Surgeon General, the American College of Srugeons, and other surgical professional societies recommended postponing elective surgical procedures and proceeding cautiously with cancer procedures that may require significant hospital resources and expose vulnerable patients to the virus. These challenges have particularly distressing for women with a gynecologic cancer diagnosis and their providers. Currently, circumstances vary greatly by region and by hospital, depending on COVID-19 prevalence, case mix, hospital type, and available resources. Therefore, COVID-19-related modifications to surgical practice guidelines must be individualized. Special consideration is necessary to evaluate the appropriateness of procedural interventions, recognizing the significant resources and personnel they require. Additionally, the pandemic may occur in waves, with patient demand for surgery ebbing and flowing accordingly. Hospitals, cancer centers and providers must prepare themselves to meet this demand. The purpose of this white paper is to highlight all phases of gynecologic cancer surgical care during the COVID-19 pandemic and to illustrate when it is best to operate, to hestitate, and reintegrate surgery. Triage and prioritization of surgical cases, preoperative COVID-19 testing, peri-operative safety principles, and preparations for the post-COVID-19 peak and surgical reintegration are reviewed.

Patient-reported outcomes after surgery for endometrial carcinoma: Prevalence of lower-extremity lymphedema after sentinel lymph node mapping versus lymphadenectomy.

OBJECTIVE: To compare the prevalence of patient-reported lower-extremity lymphedema (LEL) with sentinel lymph node (SLN) mapping versus comprehensive lymph node dissection (LND) for the surgical management of newly diagnosed endometrial carcinoma. METHODS: Patients who underwent primary surgery for endometrial cancer from 01/2006-12/2012 were mailed a survey that included a validated 13-item LEL screening questionnaire in 08/2016. Patients diagnosed with LEL prior to surgery and those who answered ≤6 survey items were excluded. RESULTS: Of 1275 potential participants, 623 (49%) responded to the survey and 599 were evaluable (180 SLN, 352 LND, 67 hysterectomy alone). Median BMI was similar among cohorts (P = 0.99). External-beam radiation therapy (EBRT) was used in 10/180 (5.5%) SLN and 35/352 (10%) LND patients (P = 0.1). Self-reported LEL prevalence was 27% (49/180) and 41% (144/352), respectively (OR, 1.85; 95% CI, 1.25-2.74; P = 0.002). LEL prevalence was 51% (23/45) in patients who received EBRT and 35% (170/487) in those who did not (OR, 1.95; 95% CI, 1.06-3.6; P = 0.03). High BMI was associated with increased prevalence of LEL (OR, 1.04; 95% CI, 1.02-1.06; P = 0.001). After controlling for EBRT and BMI, LND retained independent association with an increased prevalence of LEL over SLN (OR, 1.8; 95% CI, 1.22-2.69; P = 0.003). Patients with self-reported LEL had significantly worse QOL compared to those without self-reported LEL. CONCLUSIONS: This is the first study to assess patient-reported LEL after SLN mapping for endometrial cancer. SLN mapping was independently associated with a significantly lower prevalence of patient-reported LEL. High BMI and adjuvant EBRT were associated with an increased prevalence of patient-reported LEL.

Adjuvant therapy for early stage, endometrial cancer with lymphovascular space invasion: Is there a role for chemotherapy?

OBJECTIVES: Lymphovascular space invasion (LVSI) is an independent risk factor for recurrence and poor survival in early-stage endometrioid endometrial cancer (EEC), but optimal adjuvant treatment is unknown. We aimed to compare the survival of women with early-stage EEC with LVSI treated postoperatively with observation (OBS), radiation (RAD, external beam and/or vaginal brachytherapy), or chemotherapy (CHEMO)+/-RAD. METHODS: This was a multi-institutional, retrospective cohort study of women with stage I or II EEC with LVSI who underwent hysterectomy+/-lymphadenectomy from 2005 to 2015 and received OBS, RAD, or CHEMO+/-RAD postoperatively. Progression-free survival and overall survival were evaluated using Kaplan-Meier estimates and Cox proportional hazards models. RESULTS: In total, 478 women were included; median age was 64 years, median follow-up was 50.3 months. After surgery, 143 (30%) underwent OBS, 232 (48.5%) received RAD, and 103(21.5%) received CHEMO+/-RAD (95% of whom received RAD). Demographics were similar among groups, but those undergoing OBS had lower stage and grade. A total of 101 (21%) women recurred. Progression-free survival (PFS) was improved in both CHEMO+/-RAD (HR = 0.18, 95% CI: 0.09-0.39) and RAD (HR = 0.31, 95% CI: 0.18-0.54) groups compared to OBS, though neither adjuvant therapy was superior to the other. However, in grade 3 tumors, the CHEMO+/-RAD group had superior PFS compared to both RAD (HR 0.25; 95% CI: 0.12-0.52) and OBS cohorts (HR = 0.10, 95% CI: 0.03-0.32). Overall survival did not differ by treatment. CONCLUSIONS: In early-stage EEC with LVSI, adjuvant therapy improved PFS compared to observation alone. In those with grade 3 EEC, adjuvant chemotherapy with or without radiation improved PFS compared to observation or radiation alone.

Use of bowel preparation does not reduce postoperative infectious morbidity following minimally invasive or open hysterectomies.

BACKGROUND: Literature on the use of bowel preparation in gynecologic surgery is scarce and limited to minimally invasive gynecologic surgery. The decision on the use of bowel preparation before benign or malignant hysterectomies is mostly driven by extrapolating data from the colorectal literature. OBJECTIVE: Bowel preparation is a controversial element within enhanced recovery protocols, and literature investigating its efficacy in gynecologic surgery is scarce. Our aim was to determine if mechanical bowel preparation alone, oral antibiotics alone, or a combination are associated with decreased rates of surgical site infections or anastomotic leaks compared to no bowel preparation following benign or malignant hysterectomy. STUDY DESIGN: We identified women who underwent hysterectomy between January 2006 and July 2017 using OptumLabs, a large US commercial health plan database. Inverse propensity score weighting was used separately for benign and malignant groups to balance baseline characteristics. Primary outcomes of 30-day surgical site infection, anastomotic leaks, and major morbidity were assessed using multivariate logistic regression that adjusted for race, census region, household income, diabetes, and other unbalanced variables following propensity score weighting. RESULTS: A total of 224,687 hysterectomies (benign, 186,148; malignant, 38,539) were identified. Median age was 45 years for the benign and 54 years for the malignant cohort. Surgical approach was as follows: benign: laparoscopic/robotic, 27.2%; laparotomy, 32.6%; vaginal, 40.2%; malignant: laparoscopic/robotic, 28.8%; laparotomy, 47.7%; vaginal, 23.5%. Bowel resection was performed in 0.4% of the benign and 2.8% of the malignant cohort. Type of bowel preparation was as follows: benign: none, 93.8%; mechanical bowel preparation only, 4.6%; oral antibiotics only, 1.1%; mechanical bowel preparation with oral antibiotics, 0.5%; malignant: none, 87.2%; mechanical bowel preparation only, 9.6%; oral antibiotics only, 1.8%; mechanical bowel preparation with oral antibiotics, 1.4%. Use of bowel preparation did not decrease rates of surgical site infections, anastomotic leaks, or major morbidity following benign or malignant hysterectomy. Among malignant abdominal hysterectomies, there was no difference in the rates of infectious morbidity between mechanical bowel preparation alone, oral antibiotics alone, or mechanical bowel preparation with oral antibiotics, compared to no preparation. CONCLUSION: Bowel preparation does not protect against surgical site infections or major morbidity following benign or malignant hysterectomy, regardless of surgical approach, and may be safely omitted.

Guidelines for vulvar and vaginal surgery: Enhanced Recovery After Surgery Society recommendations.

This is the first collaborative Enhanced Recovery After Surgery Society guideline for optimal perioperative care for vulvar and vaginal surgeries. An Embase and PubMed database search of publications was performed. Studies on each topic within the Enhanced Recovery After Surgery vulvar and vaginal outline were selected, with emphasis on meta-analyses, randomized controlled trials, and prospective cohort studies. All studies were reviewed and graded according to the Grading of Recommendations, Assessment, Development and Evaluation system. All recommendations on the Enhanced Recovery After Surgery topics are based on the best available evidence. The level of evidence for each item is presented.

Adjuvant treatment improves overall survival in women with high-intermediate risk early-stage endometrial cancer with lymphovascular space invasion.

BACKGROUND: Adjuvant therapy in early-stage endometrial cancer has not shown a clear overall survival benefit, and hence, patient selection remains crucial. OBJECTIVE: To determine whether women with high-intermediate risk, early-stage endometrial cancer with lymphovascular space invasion particularly benefit from adjuvant treatment in improving oncologic outcomes. METHODS: A multi-center retrospective study was conducted in women with stage IA, IB, and II endometrial cancer with lymphovascular space invasion who met criteria for high-intermediate risk by Gynecologic Oncology Group (GOG) 99. Patients were stratified by the type of adjuvant treatment received. Clinical and pathologic features were abstracted. Progression-free and overall survival were evaluated using multivariable analysis. RESULTS: 405 patients were included with the median age of 67 years (range 27-92, IQR 59-73). 75.0% of the patients had full staging with lymphadenectomy, and 8.6% had sentinel lymph node biopsy (total 83.6%). After surgery, 24.9% of the patients underwent observation and 75.1% received adjuvant therapy, which included external beam radiation therapy (15.1%), vaginal brachytherapy (45.4%), and combined brachytherapy + chemotherapy (19.1%). Overall, adjuvant treatment resulted in improved oncologic outcomes for both 5-year progression-free survival (77.2% vs 69.6%, HR 0.55, p=0.01) and overall survival (81.5% vs 60.2%, HR 0.42, p<0.001). After adjusting for stage, grade 2/3, and age, improved progression-free survival and overall survival were observed for the following adjuvant subgroups compared with observation: external beam radiation (overall survival HR 0.47, p=0.047, progression-free survival not significant), vaginal brachytherapy (overall survival HR 0.35, p<0.001; progression-free survival HR 0.42, p=0.003), and brachytherapy + chemotherapy (overall survival HR 0.30 p=0.002; progression-free survival HR 0.35, p=0.006). Compared with vaginal brachytherapy alone, external beam radiation or the addition of chemotherapy did not further improve progression-free survival (p=0.80, p=0.65, respectively) or overall survival (p=0.47, p=0.74, respectively). CONCLUSION: Adjuvant therapy improves both progression-free survival and overall survival in women with early-stage endometrial cancer meeting high-intermediate risk criteria with lymphovascular space invasion. External beam radiation or adding chemotherapy did not confer additional survival advantage compared with vaginal brachytherapy alone.

A phase II, multicenter, open-label trial of OTL38 injection for the intra-operative imaging of folate receptor-alpha positive ovarian cancer.

PURPOSE: OTL38 is a folate-indole-cyanine green-like conjugate to folate receptor alpha (FRa). The objectives of this prospective trial were to assess the safety and efficacy (sensitivity and positive predictive value (PPV)) of OTL38 for intraoperative imaging during epithelial ovarian cancer surgery. METHODS: Patients with suspected ovarian cancer planned for cytoreductive surgery were eligible to receive OTL38. Near-infrared (NIR) imaging was used to visualize target lesions that were evaluated by two blinded pathologists. A modified intent to treat (mITT) population of lesions from all patients who received OTL38-NIR imaging, underwent surgery, and had at least one FRa + target lesion was used to determine sensitivity and PPV. Two generalized linear models, with and without random effects, were employed to estimate sensitivity and PPV. RESULTS: Forty-four patients were evaluated for safety, and 225 lesions from 29 patients (the mITT population) were evaluated for efficacy. When assuming no correlation of interlesional results within a patient, sensitivity was estimated at 85.93% (95% lower boundary CI = 81.19) and PPV at 88.14% (95% lower boundary CI = 83.59). When controlling for actual correlation of detection among multiple lesions within a single patient (a random effect), sensitivity was estimated at 97.97% (95% lower boundary CI = 87.75) and PPV at 94.93% (95% lower boundary CI = 86.13). A total of 48.3% [14/29, (95% CI 0.29-0.67)] of patients had at least one additional lesion detected by OTL38 alone. Eight patients had mild drug-related adverse events including infusion reaction, nausea, vomiting, and abdominal pain. CONCLUSIONS: OTL38-NIR was safe and efficacious in this phase II study regardless of folate expression levels and merits phase III evaluation.

A pilot study of non-routine events in gynecological surgery: Type, impact, and effect.

OBJECTIVE: Quantifying non-routine events (NREs) assists with identify underlying sociotechnical factors that could lead to adverse events. NREs are considered any event that is unusual or atypical during surgical procedures. This study aimed to use prospective observations to characterize the occurrence of non-routine events in gynecological surgeries. METHODS: Observational data were collected prospectively within one surgical gynecology department over a five month period. Researchers captured NREs in real time using a validated tablet PC-based tool according to the NRE type, impact, whom was affected, and duration. Researchers also noted what surgical approach (i.e. open, laparoscopic, robotic) was used. RESULTS: Across 45 surgical cases, 554 non-routine events (M = 12.31 NREs per case, SD = 9.81) were identified. The majority of non-routine events were external interruptions (40.3%), teamwork (26.7%), or equipment (21.3%). The circulating nurse was most frequently affected by NREs (43.2%) followed by the entire surgical team (13.7%). There was no statistically significant difference in non-routine events based on surgical approach. CONCLUSION: Non-routine events are prevalent in the gynecological surgical setting. Identifying the sociotechnical factors that influence non-routine events are important in determining interventions that will combat the associated risks. Interventions focusing on teamwork, managing external interruptions, and coordinating equipment may have the greatest impact to reduce or eliminate NREs in gynecological surgeries.

Improving the rate of surgical normothermia in gynecologic surgery.

OBJECTIVE: To increase the rate of normothermia (core temperature ≥ 36 °C) in patients undergoing gynecologic surgery. METHODS: The rate of surgical normothermia was evaluated in a single institution. A two-phase quality improvement project was undertaken; Phase 1 included the use of intra-operative room temperature regulation and intra-operative patient warming and Phase 2 included pre-operative patient warming. Clinical characteristics, median temperatures, and rate of normothermia were abstracted for patients in each phase. Cohorts were compared using chi-square and t-tests. RESULTS: The project was performed in two phases, each with a historic and intervention cohort. There were 503 patients in the historical cohort and 636 patients in the intervention cohort in phase 1; there were 291 patients in the historical cohort and 259 patients in the intervention cohort for Phase 2. Patient characteristics and anesthetic type and duration did not differ between cohorts. After intra-operative temperature regulation and patient warming in Phase 1, significantly more patients achieved normothermia (79% versus 68%, P < 0.0001). However operating room staff were more likely to rate the temperature as very hot in 40% of cases post-intervention, compared to only 2% historically. In Phase 2, after the intervention of pre-warming patients, there was no difference in achieving normothermia, 78% versus 83%, P = 0.09. Staff had no statistical difference in personal comfort with the temperature, however did feel efforts were very effective more frequently, 7.7% historic versus 32.7% post-intervention, P < 0.0001. CONCLUSIONS: Quality improvement methodology can be applied to pre- and intra-operative decision making to improve rates of surgical patient normothermia.

Beyond prophylaxis: Extended risk of venous thromboembolism following primary debulking surgery for ovarian cancer.

OBJECTIVE: To determine the incidence and risk factors for venous thromboembolism (VTE) within six months after primary debulking surgery (PDS) for epithelial ovarian cancer (EOC). METHODS: In a historical cohort, we estimated the cumulative incidence of clinically diagnosed VTE within 6 months among consecutive women who underwent PDS for EOC at a single institution from 1/1/2003 to 12/31/2011. We evaluated perioperative variables as potential risk factors of VTE within 6 months during the postoperative period using univariate and multivariable Cox proportional hazards models. RESULTS: Among 860 women without an immediate history (past 30 days) of a VTE, the cumulative incidence of VTE was 7.5% (95% CI, 5.7-9.3) by 30 days and 13.8% (95% CI, 11.4-16.2) by 6 months following surgery. Macroscopic residual disease (adjusted HR 1.99 [95% CI 1.35-2.94] vs microscopic), increasing estimated blood loss (1.25 [1.05-1.49] per doubling), longer hospital length of stay (3.00 [1.57-5.75]), and experiencing a cardiac event within 30 postoperative days (2.72 [1.55-4.80]) were independently associated with subsequent VTE within 6 months. In-hospital VTE prophylaxis included heterogeneous approaches; dual prophylaxis did not impact 30-day or 6-month VTE rates. CONCLUSIONS: VTE occurred in 1 in 7 women with EOC within 6 months of PDS-a substantial risk of VTE that extends into the adjuvant chemotherapy period. Novel prophylactic measures should be explored in these women at high risk for VTE.