Comparison of Enhanced Recovery After Surgery (ERAS) metrics by race among gynecologic oncology patients: Ensuring equitable outcomes.

OBJECTIVES: Race and ethnicity are not routinely audited in Enhanced Recovery After Surgery (ERAS) pathways. Given known racial disparities in outcomes in gynecologic oncology, the purpose of this study was to compare differences in ERAS implementation and outcomes by race. METHODS: A cohort study was performed among gynecologic oncology patients enrolled in an ERAS pathway at one academic institution from March 2017 to December 2021. Compliance with ERAS metrics, postoperative complications, 30-day survival, reoperations, intensive care unit (ICU) transfers, and readmissions within 30 days were compared by race. RESULTS: Of 1083 patients (17.0% non-white), non-white women were younger (54.2 years ±13.1 vs. 60.7 years ±13.6, p < 0.001) and proportionally fewer spoke English (75.0% vs. 97.8%, p < 0.001). Fewer non-white women received preadmission ERAS education (73.4% vs. 79.9%, p = 0.05). There were no differences in ERAS implementation by race, including similar rates of preoperative nutritional assessment, carbohydrate loading, antibiotic and thrombosis prophylaxis, and unplanned surgeries by race. There were no differences in complications, reoperations, ICU transfers, or readmissions by race on univariate and multivariate analysis. Four non-white (2.2%) and two white women (0.2%, p = 0.009) died within 30 days of surgery. CONCLUSIONS: Fewer non-white women received preadmission education, possibly due to language barriers. ERAS compliance, postoperative complications, readmissions, reoperations, and ICU transfers did not differ by race. There were two additional deaths within 30 days postoperatively among non-white women compared to white women - which is difficult to interpret given the rarity of perioperative mortality - but appeared unlikely to be related to differences in ERAS protocol implementation. ERAS programs should ensure educational materials are translated into various languages and audit metrics by race to ensure equitable outcomes.

Graduate and Continuing Medical Education of Placenta Accreta Spectrum.

Surgical training experience in obstetrics-gynecology (OB-GYN) residency and fellowship training, particularly in open abdominal surgeries has declined over the last 2 decades. This is due, in part, due to a universal trend toward non-invasive treatments for gynecologic conditions once treated surgically. Management of placenta accreta spectrum (PAS) often requires complex surgical skills, including, but not limited to highly complex hysterectomy. The decline in surgical case numbers has fallen as the incidence of PAS has risen, which we anticipate will lead to a gap in critical skills needed for graduating obstetrician-gynecologists to able to safely care for people with PAS.

The MEMORY Study: MulticentEr study of Minimally invasive surgery versus Open Radical hYsterectomy in the management of early-stage cervical cancer: Survival outcomes.

OBJECTIVE: The Laparoscopic Approach to Cervical Cancer (LACC) trial found that minimally invasive radical hysterectomy compared to open radical hysterectomy compromised oncologic outcomes and was associated with worse progression-free survival (PFS) and overall survival (OS) in early-stage cervical carcinoma. We sought to assess oncologic outcomes at multiple centers between minimally invasive (MIS) radical hysterectomy and OPEN radical hysterectomy. METHODS: This is a multi-institutional, retrospective cohort study of patients with 2009 FIGO stage IA1 (with lymphovascular space invasion) to IB1 cervical carcinoma from 1/2007-12/2016. Patients who underwent preoperative therapy were excluded. Squamous cell carcinoma, adenocarcinoma, and adenosquamous carcinomas were included. Appropriate statistical tests were used. RESULTS: We identified 1093 cases for analysis-715 MIS (558 robotic [78%]) and 378. OPEN procedures. The OPEN cohort had more patients with tumors >2 cm, residual disease in the hysterectomy specimen, and more likely to have had adjuvant therapy. Median follow-up for the MIS and OPEN cohorts were 38.5 months (range, 0.03-149.51) and 54.98 months (range, 0.03-145.20), respectively. Three-year PFS rates were 87.9% (95% CI: 84.9-90.4%) and 89% (95% CI: 84.9-92%), respectively (P = 0.6). On multivariate analysis, the adjusted HR for recurrence/death was 0.70 (95% CI: 0.47-1.03; P = 0.07). Three-year OS rates were 95.8% (95% CI: 93.6-97.2%) and 96.6% (95% CI: 93.8-98.2%), respectively (P = 0.8). On multivariate analysis, the adjusted HR for death was 0.81 (95% CI: 0.43-1.52; P = 0.5). CONCLUSION: This multi-institutional analysis showed that an MIS compared to OPEN radical hysterectomy for cervical cancer did not appear to compromise oncologic outcomes, with similar PFS and OS.

Mural nodules in mucinous ovarian tumors represent a morphologic spectrum of clonal neoplasms: a morphologic, immunohistochemical, and molecular analysis of 13 cases.

Mucinous ovarian tumors rarely harbor mural nodules, which have historically been classified as sarcoma-like, anaplastic carcinomatous, or sarcomatous on the basis of predominant morphologic features. The molecular relationship between mural nodules and associated mucinous ovarian tumors remains poorly characterized, as does the molecular pathogenesis of these mural nodules. Thus, we analyzed the morphological, immunohistochemical, and genetic features of 13 mucinous ovarian tumors and associated mural nodule(s). Three harbored sarcoma-like mural nodules and ten contained anaplastic carcinomatous nodules, including 1 tumor with spatially discrete anaplastic carcinomatous and sarcomatous nodules. Twelve of 13 cases showed genetic evidence of clonality between the mural nodule(s) and associated mucinous ovarian tumor, including all three tumors with sarcoma-like morphology. Mural nodules were genetically identical in the five cases in which there were multiple discrete mural nodules that were sequenced separately. MTAP and p53 immunohistochemistry confirmed the distribution of neoplastic cells in a subset of sarcoma-like and anaplastic carcinomatous nodules. No single recurrent genetic alteration was associated with mural nodule development. No recurrent genetic differences were identified between mural nodules with sarcoma-like, anaplastic carcinomatous, and sarcomatous morphology. Of 11 patients with clinical follow-up, three died of disease 3, 8, and 9 months after diagnosis, but no recurrent genetic events were associated with poor outcome. These molecular data suggest that sarcoma-like, anaplastic carcinomatous, and sarcomatous nodules represent a morphologic spectrum of clonal neoplasms arising in mucinous ovarian tumors rather than three discrete biological entities.

Risk of venous thromboembolism for ovarian cancer patients during first-line therapy after implementation of an Enhanced Recovery After Surgery (ERAS) protocol.

OBJECTIVE: To determine incidence and risk factors for VTE for patients with advanced epithelial ovarian cancer undergoing first-line therapy, including cytoreductive surgery, on an Enhanced Recovery After Surgery (ERAS) protocol. METHODS: Medical records were reviewed for patients with FIGO stage IIIA-IVB epithelial ovarian, fallopian tube, or primary peritoneal cancer undergoing primary or interval cytoreductive surgery from March 2017 through September 2019. All patients were enrolled on an ERAS protocol, including 28-day postoperative VTE prophylaxis. Demographic information, medical history, perioperative characteristics, and ERAS compliance were evaluated using univariate and multivariate models. RESULTS: Of 230 patients undergoing cytoreductive surgery via laparotomy, 155 received neoadjuvant chemotherapy and 75 received primary cytoreduction. 38 patients had a VTE during the study period. 13 events (5.7%) were identified at time of diagnosis, 6 (3.9%) during neoadjuvant chemotherapy, 5 (2.2%) within 30 days after surgery, 5 (2.2%) between 30 days and 6 months after surgery, and 9 (3.9%) after the 6-month window. The cumulative incidence of VTE was 6.1% (95% CI, 4.3-8.8%) within 6 months after diagnosis and 8.5% (6.2-11.4%) within 1 year after diagnosis. Estimated blood loss (adjusted HR 1.22 [95% CI, 1.09-1.36], p = 0.001) and history of VTE (7.06 [2.34-21.29], p = 0.001) were independently associated with VTE. CONCLUSION: With implementation of an ERAS protocol, only 1 in 46 patients experienced a VTE within 30 days after surgery. However, overall VTE occurred in 1 in 16 patients during first-line therapy. Strategies to further reduce VTE risk, especially during neoadjuvant chemotherapy and surveillance, should be investigated.

Stepping into survivorship pilot study: Harnessing mobile health and principles of behavioral economics to increase physical activity in ovarian cancer survivors.

OBJECTIVE: Physical activity improves physical function, quality of life, and mental health, yet fewer than 80% of ovarian cancer survivors meet activity guidelines. This pilot intervention study aimed to increase physical activity in ovarian cancer survivors by leveraging principles of behavioral economics, gamification, and social support. METHODS: This 24-week study (12-week intervention; 12-week follow-up) enrolled women with ovarian cancer after completion of first-line treatment with a self-selected "teammate." Participants used Fitbits to measure daily steps, select an increased step goal, and enroll in a collaborative game, including points and levels for achieving step goals. Primary outcomes were feasibility (defined a priori as ≥60% approach-to-consent ratio and ≥ 70% adherence to Fitbit), acceptability (≤20% of participants reporting burden or regret for participation) and preliminary efficacy (≥70% reporting increased motivation); exploratory outcomes included change in steps. RESULTS: We recruited 24 participants (mean age = 63 years, range = 37-79 years) with a 94% approach-to-consent ratio. All participants completed the intervention with 94% tracker adherence. At 24-week follow-up, 1/24 (≤5%) of participants reported burden; 0/24 (0%) reported regret for study participation; and 22/24 (>90%) agreed/strongly agreed that "the study motivated me to increase activity levels." Participants' mean daily steps were 6210.7 (±3328.1) at baseline and increased to 7643 (± 3610.9) steps (p < 0.001) during the 12-week intervention. CONCLUSIONS: This pilot study demonstrated feasibility, acceptability, and preliminary efficacy, justifying a larger randomized clinical trial to test efficacy at increasing activity levels. Future studies should examine strategies for maintaining increased activity levels in survivors over time.

Perioperative glycemic measures among non-fasting gynecologic oncology patients receiving carbohydrate loading in an enhanced recovery after surgery (ERAS) protocol.

INTRODUCTION: Preoperative carbohydrate loading is an effective method to control postoperative insulin resistance. However, data are limited concerning the effects of carbohydrate loading on preoperative hyperglycemia and possible impacts on complication rates. METHODS: A prospective cohort study was performed of patients enrolled in an enhanced recovery after surgery pathway at a single institution. All patients underwent laparotomy for known or suspected gynecologic malignancies. Patients who had been diagnosed with diabetes preoperatively and those prescribed total parenteral nutrition by their providers were excluded. Data regarding preoperative carbohydrate loading with a commercial maltodextrin beverage, preoperative glucose testing, postoperative day 1 glucose, insulin administration, and complications (all complications, infectious complications, and hyperglycemia-related complications) were collected. The primary endpoint of the study was the incidence of postoperative infectious complications, defined as superficial or deep wound infection, organ/space infection, urinary tract infection, pneumonia, sepsis, or septic shock. RESULTS: Of 415 patients, 76.9% had a preoperative glucose recorded. The mean age was 60.5±12.4 years (range 18-93). Of those with recorded glucose values, 30 patients (9.4%) had glucose ≥180 mg/dL, none of whom were actually given insulin preoperatively. Median preoperative glucose value was significantly increased after carbohydrate loading (122.0 mg/dL with carbohydrate loading vs 101.0 mg/dL without, U=3143, p=0.001); however, there was no relationship between carbohydrate loading and complications. There was a significantly increased risk of hyperglycemia-related complications with postoperative day 1 morning glucose values ≥140 mg/dL (OR 1.85, 95% CI 1.07 to 3.23; p=0.03). Otherwise, preoperative and postoperative hyperglycemia with glucose thresholds of ≥140 mg/dL or ≥180 mg/dL were not associated with increased risk of other types of complications. DISCUSSION: Carbohydrate loading is associated with increased preoperative glucose values; however, this is not likely to be clinically significant as it does not have an impact on complication rates. Preoperative hyperglycemia is not a risk factor for postoperative complications in a carbohydrate-loaded population when known diabetic patients are excluded. PRECIS: While glucose increased with carbohydrate loading in non-diabetic patients, this was not associated with complications.

Retrospective detection of isolated tumor cells by immunohistochemistry in sentinel lymph node biopsy performed for endometrial carcinoma: is there clinical significance?

INTRODUCTION: Several studies have reported optimizing ultrastaging protocols using immunohistochemistry for sentinel lymph node (SLN) biopsy in endometrial carcinoma; however, the clinical significance of isolated tumor cells (ITCs) detected by ultrastaging is unknown. This study aimed to: (1) determine the frequency of retrospective ITC detection in patients with endometrial carcinoma and reported negative SLNs determined by hematoxylin and eosin (H&E) examination only; and (2) determine the clinicopathological features and outcomes of patients with endometrial carcinoma and previously undetected ITCs. METHODS: 474 SLNs from 155 patients with endometrial carcinoma and reported negative SLNs were subjected to an immunohistochemistry protocol which included staining slides with cytokeratin at 1, 10, 20, and 50 µm levels, to examine for ITCs. Clinicopathological data of patients with ITCs detected by this method were analyzed to determine patient outcomes. RESULTS: Using immunohistochemistry, ITCs were detected in 5.7% (27/474) of SLNs and 13.5% (21/155) of patients with previously reported negative SLNs. In this patient cohort, 95.2% (20/21) had endometrioid histology, with the remaining case being carcinosarcoma. 38.1% (8/21) received adjuvant therapy (either brachytherapy alone (4/8) or chemotherapy and radiation (4/8)) based on other parameters, while 61.9% (13/21) had no adjuvant therapy. Of the patients who did not receive adjuvant therapy, all had endometrioid histology and 84.6% (11/13) were International Federation of Gynecology and Obstetrics (FIGO) stage IA. No patients (0/13) recurred after a median follow-up of 31.5 (range 2-84.4) months. DISCUSSION: In this study, 38.1% of patients with previously undetected ITCs had adjuvant treatment based on other high risk factors; as such, reporting ITCs would not have altered patient management for those who received adjuvant chemotherapy. To date, no patients with previously undetected ITCs without adjuvant treatment had a recurrence, suggesting that ITC detection may not be clinically relevant.

Assessment of a Chemotherapy Response Score (CRS) System for Tubo-Ovarian High-Grade Serous Carcinoma (HGSC).

A chemotherapy response score (CRS) system was recently described to assess the histopathologic response and prognosis of patients with tubo-ovarian high-grade serous carcinoma (HGSC) receiving neoadjuvant chemotherapy. The current study was performed as an independent assessment of this CRS system. We retrospectively identified advanced stage HGSC patients who received neoadjuvant chemotherapy and underwent interval debulking. If available, a hemotoxylin and eosin slide from the omentum and the adnexa was selected for the study. Slides were independently scored by 13 pathologists using the 3-tiered CRS system. Reviewers then received web-based training and rescored the slides. Overall survival and progression-free survival were estimated using the Kaplan-Meier method and compared using the log-rank test. A total of 68 patients with omental (n=65) and/or adnexal (n=59) slides were included in the study. Interobserver reproducibility was moderate for omentum (κ, 0.48) and poor for adnexa (κ, 0.40), which improved for omentum (κ, 0.62) but not for adnexa (κ, 0.38) after online training. For omental slides, a consensus CRS of 1/2 was associated with a shorter median progression-free survival (10.9 mo; 95% confidence interval, 9-14) than a CRS of 3 (18.9 mo; 95% CI, 18-24; P=0.020). In summary, a 3-tiered CRS system of hemotoxylin and eosin-stained omental deposits can yield prognostic information for HGSC patients receiving neoadjuvant chemotherapy, and web-based training improved reproducibility but did not alter determination of clinical outcomes. The CRS system may allow oncologists to identify potential nonresponders and triage HGSC patients for heightened observation and/or clinical trials.

Evidence for lineage continuity between early serous proliferations (ESPs) in the Fallopian tube and disseminated high-grade serous carcinomas.

The distal Fallopian tube is a site of origin for many 'ovarian' high-grade serous carcinomas (HGSCs) with intraepithelial carcinomas (STICs) that share identical TP53 mutations with metastatic tumors. TP53 mutation-positive early serous proliferations (ESPs) comprise a spectrum including p53 signatures and serous tubal intraepithelial lesions (STILs) and are not considered malignant; however, ESPs are often the only abnormality found in Fallopian tubes of women with metastatic HGSC. The purpose of this study was to determine if a relationship exists between isolated ESPs and concurrent metastatic HGSCs in the absence of STIC. Fallopian tubes from 32 HGSCs without a co-existing STIC/HGSC in the endosalpinx were exhaustively sectioned. The presence of either STIC/HGSC or ESP in the endosalpinx was documented and DNA from tissues containing ESPs, concurrent HGSC, and control epithelia were interrogated for TP53 mutations by targeted amplicon-based sequencing with average coverage reads >4000 across DNA replicate samples. Serial sectioning revealed a previously unrecognized STIC/HGSC in 3 of 32 (9.3%) and ESPs in 13 (40.6%). Twelve contained TP53 mutations. Nine (75%) shared identical TP53 mutations with concurrent HGSCs, four at high (≥ 5%) and five at low (< 5%) allele frequency. All control epithelia were TP53 mutation-negative. This study, for the first time, indicates lineage identity between ESPs in the distal tube and some metastatic HGSCs via a shared site-specific TP53 mutation. It supports a novel serous carcinogenic sequence in which an ESP could eventually culminate in a metastatic serous cancer via 'precursor escape' and would explain the apparent sudden onset of cancers without co-existing STICs. This paradigm for serous cancer development underscores the likelihood that multiple precursor types in the Fallopian tube contribute to serous cancer development with implications for the evolution, pathologic classification, and prevention of this lethal malignancy. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

The impact of health insurance status on the stage of cervical cancer diagnosis at a tertiary care center in Massachusetts.

OBJECTIVE: To evaluate the impact of insurance status on the stage of cervical cancer diagnosed and treated at a tertiary care center in Massachusetts and review the preceding screening history. METHODS: An IRB approved retrospective cohort study was conducted of patients with a diagnosis of cervical cancer treated at Brigham and Women's Hospital (BWH) between January 2011 and June 2016. Clinical and demographic data was extracted from the longitudinal medical record. Statistical analysis was performed using SAS. RESULTS: 117 cases of cervical cancer met the inclusion criteria during the study period. Most patients (76%) were diagnosed with stage I disease. On univariate analysis, compared to patients with private insurance, patients with public insurance or no documented insurance presented at older ages, were more likely to be non-white races, and present with advanced stage disease. In an adjusted model, the risk of being diagnosed with advanced stage disease persisted among women with public or no documented insurance, adjusted odds ratio (aOR) 4.13 (1.37-12.45). There was no difference in screening history among women with private vs. public insurance, p = 0.30. CONCLUSIONS: Despite access to insurance, patients with public issued insurance had an increased risk of presenting with advanced stage cervical cancer in this cohort. These data suggest that additional barriers to screening and prevention may exist and are important for future investigation.

Evaluation of AJCC and an Alternative Tumor Classification System for Primary Vulvar Squamous Cell Carcinoma.

Background: Currently, no studies have attempted to validate the AJCC tumor (T) class for vulvar cancer or examine its performance via clinical data. The goal of this study was to identify risk factors associated with poor outcomes in vulvar squamous cell carcinoma (vSCC) and compare prognostic discrimination of these outcomes between the AJCC T-classification system and the newly developed Brigham and Women's Vulvar Tumor Classification system (BWVTC). Methods: A 15-year, 2-center retrospective cohort study of primary vSCCs (N=226) was undertaken. Risk factors for poor outcomes, including local recurrence (LR), nodal and distant metastasis (NM and DM, respectively), disease-specific death (DSD), and overall death (OD) were determined using competing risks models. Poor outcomes were analyzed by T stage with regard to each classification system's distinctiveness, homogeneity, and monotonicity. Results: AJCC T stages were indistinct, with overlapping 95% confidence intervals for 10-year cumulative incidences of poor outcomes. Most poor outcomes occurred in low AJCC T stages: T1a/T1b contained 77% of LR, 79% of NM, 66% of DM/DSD, and 78% of OD, indicating poor homogeneity and monotonicity. Five risk factors were independent predictors of poor outcomes: history of lichen sclerosus, tumor diameter ≥2.0 cm, tumor depth ≥3.0 mm, poor differentiation, and mucosal involvement, and these were used to develop the BWVTC (BWVTC BWT1 = 0 risk factors; BWT2 = 1 risk factor; BWT3 = 2 risk factors; and BWT4 = ≥3 risk factors). The BWVTC displayed superior homogeneity and monotonicity, with most poor outcomes occurring in high T stages: T3/T4 contained 87% of LR, 92% of NM, 91% of DM/DSD, and 78% of OD (P<.001), although not all T stages were statistically distinct in this small cohort. Conclusions: The BWVTC offers improved prognostic discrimination over the AJCC T-classification system. Validation in population-based cohorts and in vulvar cancers other than SCC is needed.

Extramammary Paget Disease of the Vulva: A Case Series Examining Treatment, Recurrence, and Malignant Transformation.

OBJECTIVES: Extramammary Paget disease (EMPD) of the vulva is a rare lesion with a high recurrence rate ranging from 12% to 61%. The rate of underlying adenocarcinoma varies, but in the largest series was reported at 4%. Given the rarity of the disease there is a paucity of data to optimize treatment. This study aims to describe the management and recurrence patterns in a tertiary care setting and to offer suggestions for management in a modern-day setting. METHODS: Patients with pathologically confirmed EMPD treated from 2000 to 2015 were retrospectively identified using an IRB approved database. Clinical data were abstracted from the electronic medical record. Pathology underwent central review. RESULTS: Forty-four patients met criteria and underwent central pathology review. Forty-two patients were treated with surgical excision. Alternative treatment modalities included Mohs surgery in 3 patients and medical therapy in 20 patients. The median number of surgical procedures was 1 and the number of procedures ranged from 1 to 16. Twenty-five patients (56.8%) had recurrent disease with a median of 2 (1-6) recurrences per patient. The median disease-free interval was 28.7 months with a median follow up of 45.8 months (1.2-178.9 months). Three patients (7%) had invasive cancer and 7 patients (16%) were diagnosed with a separate malignancy at or following diagnosis of EMPD. Despite radical resection, the majority of patients had positive margins and there was no significant difference in disease recurrence between simple and radical resection (P = 0.69). CONCLUSIONS: Patients with EMPD in this series have a high rate of recurrence. Many undergo multi-modal therapy often with multiple providers. However, patients experience relatively long disease-free intervals with a low rate of associated malignancy. We propose an algorithm for management that focuses on symptom control and minimizing morbidity of treatment intervention once invasive disease has been excluded.

Sentinel lymph node mapping reduces practice pattern variations in surgical staging for endometrial adenocarcinoma: A before and after study.

OBJECTIVE: To examine the effects of universal sentinel lymph node mapping on the use of nodal staging in endometrial adenocarcinoma. METHODS: Two approaches to laparoscopic staging for endometrial adenocarcinoma were compared using a before and after study design. The before cohort underwent selective lymphadenectomy from January 1, 2014-October 1, 2015 while the after cohort underwent universal sentinel lymph node (SLN) mapping from October 2, 2015-September 29, 2016. RESULTS: The before cohort comprised 215 patients and the after cohort 166 patients. In women undergoing SLN mapping, a sentinel node was identified at least unilaterally in 146/153 cases (95.4%), and bilaterally in 114/153 (74.5%) of cases. Pelvic nodes were removed in 35.8% of the before cohort versus 92.2% of the after cohort (p<0.0001) with more nodal evaluation among both low risk (9.6% vs. 91%, p<0.0001) and high risk cases (66% vs. 94%, p<0.0001). While the proportion of low risk cases diagnosed with nodal involvement did not significantly change (0.9% to 3.1%, p=0.32), there was a trend toward more diagnoses of nodal involvement in high risk cases (5% to 13.2%, p=0.06). Mean number of pelvic lymph nodes removed (15 vs. 4, p<0.0001), mean operative time (181min vs. 137min, p<0.0001), estimated blood loss (80ml vs. 56ml, p=0.004), and rate of post-operative complications (13% vs. 5.2%, p=0.04) all decreased after the adoption of SLN dissection. CONCLUSIONS: Universal sentinel lymph node dissection for laparoscopic endometrial cancer staging reduces heterogeneity in surgeon staging practice, increases nodal detection, and lowers post-operative complications.

Universal Screening for Mismatch-Repair Deficiency in Endometrial Cancers to Identify Patients With Lynch Syndrome and Lynch-like Syndrome.

Although consensus has yet to be reached on universal mismatch-repair (MMR) protein immunohistochemical (IHC) screening for Lynch syndrome (LS) in endometrial cancer (EC), an increasing number of institutions have adopted universal screening protocols similar to those used for colorectal carcinoma. Here we describe our institution's experience with a prospective universal screening protocol in which all ECs resected over a period of 19 months (n=242) were screened for MLH1, PMS2, MSH2, and MSH6 deficiencies using IHC, followed by MLH1 promoter methylation testing when appropriate. When consent was obtained, tumor samples underwent next-generation sequencing. A total of 11 unmethylated MMR-deficient cases (4.5% of cohort) were identified through IHC screening. Germline testing was performed in 10 cases and confirmed LS in 4 patients (1.7% of cohort). Of our 4 confirmed LS cases, 1 did not meet traditional LS screening criteria (eg, age below 50 y, Revised Bethesda criteria). In addition, universal screening identified 6 germline-negative MMR-deficient nonmethylated cases, 4 of which occurred in women older than 50. Although our next-generation sequencing data suggest somatic mutations in 4 of these cases, it is possible that these cases may represent cases of "Lynch-like syndrome." We conclude that a subset of LS cases could be missed using traditional screening guidelines. The value of screening for Lynch-like syndrome has yet to be determined. Although the cost-effectiveness of universal screening in EC has yet to be elucidated, we conclude that universal IHC screening is currently a reasonable, and arguably superior, approach to screening for LS.

Same-Day Discharge After Laparoscopic Hysterectomy for Endometrial Cancer.

PURPOSE: The aim of this study was to investigate the relationship between same-day discharge (SDD) and postoperative complications within 30 days of laparoscopic hysterectomy for endometrial cancer and endometrial intraepithelial neoplasia (EIN). METHODS: This single-institution retrospective cohort included all patients who underwent conventional and robotic-assisted laparoscopic hysterectomy for endometrial cancer or EIN in a large teaching hospital between 2011 and 2013. Temporal trends in frequency of SDD and rates of postoperative complications were investigated to assess whether adoption of routine SDD was associated with increased postoperative complications. Associations between SDD and postoperative complications were also investigated in univariate and multivariate models. RESULTS: Overall, 696 patients underwent laparoscopic hysterectomy. Of these, 37.1 % had pelvic lymphadenectomy, 3.0 % had para-aortic lymphadenectomy, and 9.3 % underwent omentectomy. The rate of SDD increased from 3.9 to 69.6 % during the study period (p < 0.001), and the frequency of postoperative readmission, unscheduled surgery, infection, and composite complications within 30 days of hysterectomy did not differ during the study period. The composite complication rate did not differ significantly between patients who underwent surgery before and after the adoption of routine SDD (rate ratio 0.7, 95 % CI 0.4-1.2, p = 0.24). After controlling for demographic, intraoperative, and comorbid factors, patients who underwent SDD were not at increased risk for postoperative complications. CONCLUSIONS: Adoption of routine SDD after laparoscopic surgery for endometrial cancer and EIN did not result in increased complication rates within our institution. A larger prospective study is required to definitively establish the safety of this approach.

Does plastic surgical consultation improve the outcome of patients undergoing radical vulvectomy for squamous cell carcinoma of the vulva?

OBJECTIVES: To analyze margin status and prognostic factors for complications in patients undergoing vulvectomy for invasive squamous cell cancer (iSCC) with and without plastic-assisted closure. METHODS: Demographic and clinical data were collected on 94 patients with iSCC who underwent vulvectomy between 2004 and 2013. All pathology slides were re-reviewed by two gynecologic pathologists. Data were analyzed using XLSTAT-Pro v2014.2.02. RESULTS: Of 88 eligible patients, 15 (17%) had plastic-assisted vulvar closure and 73 (83%) did not. There were significantly more patients in the plastics group with recurrent disease (53% v 10%) and history radiation therapy prior to surgery (40% versus 5%). Plastic-assisted closure was associated with larger tumors (3.73 cm versus 2.03 cm, p<0.01) and a higher frequency of adequate margins (53% versus 29%, p=0.06). For tumors≥3.0 cm, plastic-assisted closure was significantly associated with adequate margins (44% versus 6%, p=0.03). Prior radiation use was associated with plastic-assisted closure, larger tumors, older age, and recurrent disease. Complications occurred in 36 patients (41%) and significantly more occurred in those with plastic-assisted closure (67% versus 36%, p=0.04). On multivariate analysis including age, tumor size, recurrent disease, plastic-assisted closure, and history of radiation, only history of radiation therapy was a significant predictor of complications (OR=17, 95%CI 2.05-141.35; p=0.01). CONCLUSIONS: Plastic-assisted vulvectomy closure was more often utilized in cases involving past radiation therapy and larger tumors. Plastic-assisted closure significantly increased the frequency of adequate margins in tumors≥3 cm and did not impact complications.

Concepts in creating an evidence-based anesthetic protocol for robot-assisted laparoscopic pelvic surgery.

BACKGROUND: Robotic-assisted surgery has increased in popularity in recent years. Benefits have been observed for both the patient and hospital system as the technology shifts surgery from the open to the laparoscopic arena. Some of the advantages of robotic-assisted surgery include increased patient satisfaction along with shorter hospital stays, decreased risk of infection, and improved postsurgical cosmetic outcomes. METHODS: We developed an evidence-based protocol for the anesthetic management of the preoperative, intraoperative, and postoperative phases of patient care based on the review of primary literature and consensus from surgeons and anesthesiologists at our institution. RESULTS: Robotic-assisted surgery creates a unique set of anesthetic considerations to ensure patient safety. Anesthetic considerations include the physiological changes associated with steep Trendelenburg patient positioning, pneumoperitoneum, fluid management, management of pressure points, and spatial restrictions imposed by the robot relative to the conventional anesthetic area. CONCLUSION: A perioperative protocol can help ensure optimal clinical care, patient safety, and better patient and provider satisfaction with the utilization of robotic surgery.

A prospective feasibility study of radiation and concurrent bevacizumab for recurrent endometrial cancer.

OBJECTIVES: To determine the toxicity and survival rates in a trial of concurrent bevacizumab and external beam radiation (EB) for patients with recurrent endometrial or ovarian cancer. METHODS: Nineteen women with recurrent endometrial (n = 15) or ovarian (n = 4) cancer with gross disease involving the vaginal cuff, and/or pelvic nodes and/or para-aortic nodes, cancer were enrolled between 2008 and 2010. All patients received bevacizumab during radiation. Toxicity was assessed at baseline, weekly during treatment and every 3 months for at least 1 year after treatment. RESULTS: All patients completed EB on schedule. For the 15 patients with recurrent endometrial cancer, the 1- and 3-year progression-free survival (PFS was) 80%/67% and overall survival (OS) was 93%/80%. Patients that had a vaginal cuff recurrence alone had a 1- and 3-year PFS of 75%/63% and OS of 100%/75%. Two patients with pelvic node involvement did not recur throughout the entire follow-up period. The 5 patients with para-aortic node involvement had a 1- and 3-year PFS of 80%/60% and OS of 80%/80%. Of the 4 ovarian cancer patients 3 relapsed with 1- and 3-year PFS of 80%/40% and OS of 100%/60%. Toxicities included thrombosis and 1 embolic event in the setting of metastatic disease. No gastrointestinal perforations were noted. CONCLUSIONS: Delivering bevacizumab with concurrent radiation provides excellent local tumor control and survival for women with recurrent endometrioid endometrial cancer, particularly those with unresectable nodes. Caution must be used in those at highest risk of developing metastatic disease given the increased risk of thromboembolic events. This regimen may be considered for recurrent gynecologic malignancies in future trials.