Small bite fascial closure technique reduces incisional hernia rates in gynecologic oncology patients.

BACKGROUND: The potential for the technique of small bite fascial closure in mitigating incisional hernias in gynecologic oncology patients still needs to be investigated. OBJECTIVE: To evaluate the impact of closure of small fascial bites compared with prior standard closure on incisional hernia rates in gynecologic oncology patients. METHODS: This is a retrospective cohort study comparing patient outcomes before and after the intervention at a single institution at a comprehensive cancer center. Patients who underwent laparotomy with a vertical midline incision for a suspected or known gynecologic malignancy with a 1-year follow-up were included. The pre-intervention cohort (large bites) had 'mass' or modified running Smead-Jones closure. In contrast, the post-intervention cohort had fascial bites taken 5-8 mm laterally with no more than 5 mm travel (small bites) closure using a 2-0 polydioxanone suture.The primary outcome was the incisional hernias rate determined by imaging or clinical examination within the first year of follow-up. Patient factors and peri-operative variates of interest were investigated for their association with hernia formation through univariate and multivariate analyses. These included age, body mass index (BMI), smoking history, estimated blood loss, pre-operative albumin, American Society of Anesthesia (ASA) physical status classification, or treatment with chemotherapy post-operatively. RESULTS: Of the 255 patients included, the total hernia rate was 12.5% (32/255 patients). Patient characteristics were similar in both cohorts. Small bite closure led to a significant reduction in hernia rates from 17.2% (22/128 patients) to 7.9% (10/127 patients), p=0.025. According to logistic regression modeling, small bite closure (OR=0.40, 95% CI 0.17 to 0.94, p=0.036) was independently associated with lower odds of hernia formation. Other factors associated with increased hernia rates were chemotherapy (OR=3.22, 95% CI 1.22 to 8.51, p=0.019) and obesity (OR=23.4, 95% CI 3.09 to 177, p=0.002). In obese patients, small bite closures led to maximal hernia rate reduction compared with large bites. CONCLUSIONS: The small bite closure technique effectively reduces hernia rates in gynecologic oncology patients undergoing midline laparotomy.

Cross-sectional survey of surgical practices among gynecologic oncologists in the United States.

OBJECTIVE: We sought to document current surgical practices among gynecologic oncologists in the United States. METHODS: In March/April 2020, we conducted a cross-sectional survey among members of the Society of Gynecologic Oncology to identify gynecologic oncology practice trends in the United States. The survey collected demographic data and queried participants on types of surgical procedures performed and chemotherapy use. Univariant and multivariant analyses were used to evaluate the association between surgeon practice type, region of practice, working with gynecologic oncology fellows, time in practice, and dominant surgical modality of practice on performance of specific procedures. RESULTS: Among 1199 gynecologic oncology surgeons who were emailed the survey, 724 completed the survey (60.4% response rate). Of these respondents, 170 (23.5%) were within 6 years of fellowship graduation, 368 (50.8%) identified as female; and 479 (66.2%) worked in an academic setting. Surgeons who worked with gynecologic oncology fellows were more likely to perform bowel surgery, upper abdominal surgery, complex upper abdominal surgery, and prescribe chemotherapy. Surgeons who were ≥ 13 years out from fellowship graduation were more likely to perform bowel surgery and complex abdominal surgery and less likely to prescribe chemotherapy and perform sentinel lymph node dissections (P < 0.05). CONCLUSIONS: These findings highlight the variation in surgical procedures performed by gynecologic oncologists in the United States. These data support that there are practice variations that would benefit from further investigation.

Provider compliance with a tailored opioid prescribing calculator in gynecologic surgery.

OBJECTIVE: To evaluate the impact a tailored opioid prescription calculator has on meeting individual patient opioid needs while avoiding opioid over prescriptions. METHODS: Our group previously developed and published an opioid prescribing calculator incorporating patient risk factors (history of depression, anxiety, chronic opioid use, substance abuse disorder, and/or chronic pain) and type of surgery (laparotomy or laparoscopy). This calculator was implemented on 1/1/2021 and its impact on opioid prescriptions was evaluated until 12/31/21. The primary outcome of the present study is to determine prescriber compliance with the calculator (defined as not overprescribing from the number of pills indicated by the calculator). The secondary outcome is to determine the excess prescription rate (defined as proportion of patients reporting more than 3 pills remaining at 30 days post-surgery). Refill rates and pain related patient phone calls were collected. Descriptive statistics were used to summarize the cohort. RESULTS: Of the 355 patients included, 54.7% (N = 194) underwent laparoscopy and 45.4% (N = 161) underwent laparotomy. One hundred and forty-two patients (40%) had at least one risk factor for opioid usage. The median number of opioid pills prescribed following laparoscopy was 3 (range 0-15) and 6 (0-20) after laparotomy. The prescriber compliance was 88.2% and the excess prescription rate was 25.1% (N = 89 patients). CONCLUSIONS: Our tailored opioid calculator has a high prescriber compliance. Implementation of this calculator led to a standardization of tailored opioid prescribing, while limiting the number of over prescriptions. A free web version of the calculator can be easily accessed at www.opioidcalculator.org.

Implementation of routine venous thromboembolism prophylaxis during neoadjuvant chemotherapy for patients with ovarian cancer.

OBJECTIVE: To compare the venous thromboembolism (VTE) rate in patients with ovarian cancer undergoing neoadjuvant chemotherapy before and after implementing routine thromboprophylaxis. METHODS: This is a quasi-experimental pre-post study evaluating the VTE rate in patients with ovarian cancer who received neoadjuvant chemotherapy following a quality improvement initiative of routine thromboprophylaxis within a single healthcare system that started in January 2017. Patients were excluded if VTE was diagnosed before initiating chemotherapy. Patient factors and perioperative variables of interest were investigated for their association with VTE through univariate and multivariate models. RESULTS: Of the 136 patients in the pre-implementation group, 3.7% (n = 5) received thromboprophylaxis. Of the 154 patients in the post-implementation group, 65.6% (n = 101) received thromboprophylaxis. Provider compliance varied from 51% in 2019 to 79.3% in 2021. The overall rate of VTE, from the start of chemotherapy to the end of treatment, was 21.3% (n = 29) pre- and 8.4% (n = 13) in the post-implementation group (p < 0.01). There was no difference in major bleeding events between groups (0% vs. 0.68%, p = 0.63). On univariate analysis, thromboprophylaxis (OR 0.19; 95% CI 0.07-0.52) and post-implementation period (OR 0.34; 95% CI 0.17-0.69) were associated with a decreased risk of any VTE during primary treatment. On multivariate analysis, only thromboprophylaxis remained significantly associated with reduced VTE rates (aOR 0.19; 95% CI 0.07-0.53). CONCLUSION: Routine thromboprophylaxis during neoadjuvant chemotherapy is associated with reduced risk of VTE throughout primary treatment and is not associated with increased bleeding events.

Ten-year conditional probability of survival for patients with ovarian cancer: A new metric tailored to Long-term survivors.

OBJECTIVES: We assessed a conditional probability of survival (CPS) model to determine the probability of living 10 years after ovarian cancer diagnosis after having already survived 5 years. METHODS: We identified patients newly diagnosed with high-grade epithelial ovarian cancer from 1/1/2001-12/31/2009 and treated at our institution. Patients with <3 years follow-up were excluded. CPS was defined as the probability of surviving additional years (y) based on the condition a patient had already survived a given time (x): S(x + y)/S(x). Confidence intervals were estimated using a variation of Greenwood's formula. RESULTS: Of 916 patients meeting inclusion criteria, 473 (52%) were diagnosed from 2001 to 2005 and 443 (48%) from 2006 to 2009. Median age at diagnosis was 60 years (range, 25-95). The conventional 10-year OS rate for all patients was 29% (95% CI: 26%-32%)-75% (95% CI: 68%-82%) for stage I/II disease, 22% (95% CI: 19%-26%) for stage III, and 6.9% (95% CI: 3.9%-12%) for stage IV. For patients <65 years, the 10-year CPS for 5-year survivors was 65% (95% CI: 59%-70%); for those ≥65 years, it was 48% (95% CI: 38%-57%). For patients <65 years, the 10-year CPS for 5-year survivors by stage was: stage I/II, 89% (95% CI: 81%-94%); stage III, 58% (95% CI: 50%-66%); and stage IV, 26% (95% CI: 12%-42%). For patients ≥65 years, rates by stage were 78% (95% CI: 53%-91%), 42% (95% CI: 30%-53%), and 29% (95% CI: 7%-56%), respectively. CONCLUSIONS: For long-term survivors with high-grade epithelial ovarian cancer, CPS provides better prediction of survival than conventional methods.

A modern-day experience with Brunschwig's operation: Outcomes associated with pelvic exenteration.

OBJECTIVE: To evaluate postoperative and oncologic outcomes associated with pelvic exenteration for non-ovarian gynecologic malignancies. METHODS: This was a retrospective review of patients who underwent pelvic exenteration for non-ovarian gynecologic malignancies at our institution from 1/1/2010-12/31/2019. Palliative exenteration cases were excluded from survival analysis. Postoperative complications were early (≤30 days) or late (31-180 days). Complications were graded using a validated institutional scale. Major complications were considered grade ≥ 3. Categorical variables were compared using the chi-square test, and the Kaplan-Meier method was used for survival analysis. RESULTS: Of 100 patients identified, 89 underwent pelvic exenteration for recurrent disease, 5 for palliation, 5 for primary disease, and 1 for persistent disease. Thirty percent had cervical, 27% vulvar, 24% uterine, and 19% vaginal cancer. Sixty-two percent underwent total, 30% anterior, and 8% posterior exenteration. No deaths occurred intraoperatively or within 30 days of surgery. Six patients died after 30 days. Ninety-seven experienced a perioperative complication-49 early, 1 late, and 47 both. Fifty experienced a major complication-22 (44%) early, 19 (38%) late, and 9 (18%) both. No variables were statistically associated with complication development. The 3-year progression-free survival rate was 61.0%; the 3-year overall survival rate was 61.6%. Of 58 surviving patients, 16 (28%) and 4 (7%) were alive after 5 and 10 years, respectively. CONCLUSION: The overall complication rate for pelvic exenteration remains high. No variables demonstrated association with complication development as the rate was nearly 100%. The low rate of perioperative mortality is likely due to improved perioperative care.

Gastric-type adenocarcinoma of the cervix: Clinical outcomes and genomic drivers.

OBJECTIVES: Gastric-type endocervical adenocarcinoma (GEA) is a rare form of cervical cancer not associated with human papilloma virus (HPV) infection. We summarize our experience with GEA at a large cancer center. METHODS: Clinical and demographic information on all patients diagnosed with GEA between June 1, 2002 and July 1, 2019 was obtained retrospectively from clinical charts. Kaplan-Meier survival analysis was performed to describe progression-free survival (PFS) and overall survival (OS). Tumors from a subset of patients underwent next generation sequencing (NGS) analysis. RESULTS: A total of 70 women with GEA were identified, including 43 who received initial treatment at our institution: of these 4 (9%) underwent surgery alone, 15 (35%) underwent surgery followed by adjuvant therapy, 10 (23%) were treated with definitive concurrent chemoradiation (CCRT), 7 (16%) with chemotherapy alone, and 3 (7%) with neoadjuvant CCRT and hysterectomy with or without chemotherapy. One-third (n = 14) of patients experienced disease progression, of whom 86% (n = 12) had prior CCRT. The median PFS and OS for patients with stage I GEA were 107 months (95% CI 14.8-199.2 months) and 111 months (95% CI 17-205.1 months) respectively, compared to 17 months (95% CI 5.6-28.4 months) and 33 months (95% CI 28.2-37.8 months) for patients with stages II-IV, respectively. On NGS, 4 patients (14%) had ERBB2 alterations, including 2 patients who received trastuzumab. CONCLUSIONS: GEA is an aggressive form of cervical cancer with poor PFS and OS when diagnosed at stage II or later. Further investigation is needed to identify the optimal management approach for this rare subtype.

The utility of physical examination in ovarian cancer recurrence detection: a retrospective analysis informing virtual surveillance care.

OBJECTIVES: Given the recent rapid increase in telemedicine in the setting of the COVID-19 pandemic, we sought to investigate the utility of symptom review, CA125, and physical examination in the detection of ovarian cancer recurrence to determine the role of virtual surveillance care in the COVID-19 era. METHODS: This retrospective cohort study included patients diagnosed with ovarian cancer between 2013 and 2020 who achieved remission after primary treatment and then had recurrence while in a routine surveillance program. Modalities that detected recurrence including symptoms, CA125, physical examination, or 'other,' which was denoted if imaging was obtained for reasons other than suspected recurrence and recurrence was incidentally identified, were recorded. Descriptive statistics were performed to summarize the cohort. RESULTS: One hundred and nine patients met inclusion criteria. At time of recurrence, elevated CA125 was present in 97 (89.0%) patients, symptoms in 41 (37.6%), and abnormal physical exam findings in 27 (24.8%). Recurrence was incidentally found with imaging obtained for reasons other than suspicion of recurrence in six (5.5%) patients. Recurrence was suspected based on multiple modalities in 46 (42.2%) patients. Elevated CA125, symptoms, or both were present in 102 (93.6%) patients. Of patients with abnormal physical exam findings, 26 (96.3%) also had elevated CA125 or symptoms present. Recurrence was suspected based on physical exam findings alone in one (0.9%) patient. CONCLUSIONS: Over 90% of ovarian cancer recurrences were detected by rising CA125, symptoms, or both. Only one patient had recurrence detected by physical examination alone. Given that review of symptoms and CA125 can be conducted virtually, virtual visits may offer a reasonable alternative to in-person visits for ovarian cancer surveillance for patients who have pre-treatment elevated CA125.

Optimization of postoperative opioid prescriptions in gynecologic oncology: Striking a balance between opioid reduction and pain control.

OBJECTIVE: To implement a quality-improvement initiative to assess the impact various patient and procedural factors have on postoperative opioid use. To develop a tailored opioid prescribing algorithm for gynecologic oncology patients. METHODS: A retrospective cohort study was performed of patients who underwent a laparoscopy or laparotomy procedure for a suspected or known gynecologic malignancy between 3/2019-9/2020. Patients were assessed preoperatively for the presence of suspected risk factors for opioid misuse (depression, anxiety, chronic pain, current opioid use, or substance abuse). Patients completed a 30-day postoperative questionnaire assessing for total opioid pill use and refills requests. Multivariate models were developed to estimate the independent effect of sociodemographic characteristics, risk factors for opioid misuse and procedural factors on patient reported postoperative opioid use. RESULTS: A total of 390 patients were analyzed. Thirty-nine percent (N = 151/390) of patients reported not using opioids after discharge and 5% (N = 20/390) received an opioid refill. For both minimally invasive procedures and laparotomy procedures, body mass index, comorbidities, intraoperative or postoperative complications and final diagnosis of malignancy were not associated with the amount of opioid consumption. However, younger age and history of risk factors for opioid misuse significantly impacted postoperative opioid use. In multivariate analysis, age (p = 0.038) and risk factors (p < 0.001) remained significant after controlling for other factors. CONCLUSIONS: Two out of every five patients did not use opioids after surgery. Younger patients and those with risk factors for opioid misuse need a tailored approach to prescribing opioids to balance the need for adequate pain control with the risk of misuse.

Advanced ovarian cancer and cytoreductive surgery: Independent validation of a risk-calculator for perioperative adverse events.

OBJECTIVE: To independently validate a published risk-calculator for adverse perioperative outcomes in patients with epithelial ovarian cancer undergoing debulking surgery at a high-volume surgical center. METHODS: Using our institution's curated prospective ovarian cancer database, we identified patients with epithelial ovarian cancer who underwent a debulking procedure from 7/2015 to 5/2019, to be used as the validation cohort. Variables used in the published nomogram were collected. These included American Society of Anesthesiology classification, preoperative albumin, history of bleeding disorder, presence of ascites on preoperative imaging, designation of elective or emergent surgery, age of the patient, and a procedure score. Patients were included if they had information available for all the variables used in the nomogram, and 30-day follow-up within our institution. The primary outcome was Clavien-Dindo Class IV with specific conditions (postoperative sepsis, septic shock, cardiac arrest, myocardial infarction, pulmonary embolism, ventilation >48 h, or unplanned intubation) and 30-day mortality. The combination of these endpoints is called the combined complication rate. RESULTS: A total of 700 patients who underwent debulking surgery for epithelial ovarian cancer during the timeframe met inclusion criteria. The combined complication rate was 11.7%; 9.9% of patients were readmitted; 2.7% required reoperation. Sepsis was the most common primary endpoint complication (4.4%), followed by septic shock (1.4%). There was no 30-day mortality in our cohort. The nomogram performed well, with a c index of 0.715 (95% CI 0.66-0.768), which was comparable to the published nomogram. CONCLUSIONS: We independently validated a complication nomogram at a high-volume surgical center. This nomogram performs well at predicting a lower likelihood of serious postoperative complications. An enhanced nomogram would help identify patients at higher risk for serious complications.

Pelvic exenteration for recurrent or persistent gynecologic malignancies: Clinical and histopathologic factors predicting recurrence and survival in a modern cohort.

OBJECTIVES: To explore pre-operative factors and their impact on overall survival (OS) in a modern cohort of patients who underwent pelvic exenteration (PE) for gynecologic malignancies. METHODS: A retrospective review was performed for all patients who underwent a PE from 1/1/2010 through 12/31/2018 at our institution. Inclusion criteria were exenteration due to recurrent or progressive carcinoma of the uterus, cervix, vagina or vulva, with histologically confirmed complete surgical resection of the malignancy. Exclusion criteria included PE for palliation of symptoms without recurrence, and for ovarian or rare histologic malignancies. Univariable and multivariable analysis were performed to identify factors predicting prolonged survival. RESULTS: Overall, 71 patients met the inclusion criteria. Median age at time of exenteration was 62 years (range, 28-86 years). Vulvar cancer was the most common primary diagnosis (32%); 30% had cervical cancer; 23%, uterine cancer; 15%, vaginal cancer. Median OS was 55.1 months (95% confidence interval (CI): 36-not estimable) with a median follow-up time of 40.8 months (95% CI: 1-116.1). On univariable analysis, age > 62 years (hazard ratio (HR) 2.71, 95% CI 1.27-5.79), American Society of Anesthesia (ASA) 3-4 (HR: 3.41 (95% CI 1.03-11.29), and vulvar cancer (HR 4.19 (95% CI 1.17-14.96) predicted worse OS. Tumor size and prior progression-free interval (PFI) did not meet statistical significance in OS analyses. On multivariable analysis, there were no significant factors associated with worse OS. CONCLUSIONS: PE performed with curative intent may be considered a treatment option in well-counseled, carefully selected patients, irrespective of tumor size and PFI before exenteration.

Refusal of surgery and survival outcomes in endometrial cancer.

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

Electronic patient-reported symptom monitoring in patients recovering from ambulatory minimally invasive gynecologic surgery: A prospective pilot study.

OBJECTIVE: To evaluate the feasibility of an electronic symptom-tracking platform for patients recovering from ambulatory surgery. METHOD: We assessed user response to an electronic system designed to self-report symptoms. Endpoints included compliance, postoperative symptoms, patient satisfaction. An 8-item symptom inventory (pain, nausea, vomiting, shortness of breath, fever, swelling, discharge, redness) was developed and made available on postoperative days (POD) 2-6. Responses exceeding defined thresholds of severity triggered alerts to healthcare providers. Symptoms, alerts, actions taken, urgent care center (UCC) visits, hospital admissions were tracked until POD 30. Patient satisfaction was evaluated on POD 7. A patient was defined as "responder" if at least 5/8 items on at least 3 PODs were completed. The assessment method was deemed successful if 64/100 patients responded. RESULTS: 97/102 patients were evaluable; 65 met "responder" criteria (67% responder rate; 95% CI 57-76%). 321 surveys were completed (median 4/patient), 248 (77%) in ≤2 min. Involving caregivers and allowing additional symptom-reporting improved the responder rate to 72% (95% CI 58-84%). Most commonly-reported moderate, severe, very severe symptoms were pain, nausea, swelling; 71% reported moderate to very severe pain on POD 2. Phone calls and adjustment of medications adequately addressed most symptoms. Two patients (2%) presented at UCC before, 6 (6%) after, POD 6; 1 (1%) was admitted. Most agreed or strongly agreed that electronic symptom-tracking was helpful, easy to use, and would recommend it to others. CONCLUSION: Electronic symptom-tracking is feasible for patients undergoing ambulatory gynecologic cancer surgery. Symptom burden is high in the early postoperative period. Addressing patient-reported symptoms in a timely, automated manner may prevent severe downstream adverse events, reduce UCC visits and admission rates, and improve outcomes.

A multimodality triage algorithm to improve cytoreductive outcomes in patients undergoing primary debulking surgery for advanced ovarian cancer: A Memorial Sloan Kettering Cancer Center team ovary initiative.

OBJECTIVE: To describe outcomes using a multimodal algorithm to triage patients with advanced epithelial ovarian cancer (EOC) to primary debulking surgery (PDS) versus neoadjuvant chemotherapy (NACT). METHODS: All patients with EOC treated at our institution from 04/2015-08/2018 were identified. We included patients without contraindication to PDS who underwent prospective calculation of a Resectability (R)-score. A low risk score for suboptimal cytoreduction was defined as ≤6, and a high risk score ≥7. Patients were triaged to laparotomy/PDS, laparoscopic evaluation of resectability (LSC), or NACT depending on R-score. RESULTS: Among 299 participants, 226 (76%) had a low risk score and 73 (24%) a high risk score. For patients with a low risk score, management included laparotomy/PDS, 181 (80%); LSC, 43 (19%) (with subsequent triage: PDS, 31; NACT, 12); and NACT, 2 (1%). For patients with a high risk score, management included laparotomy/PDS, 9 (12%); LSC, 51 (70%) (with subsequent triage: PDS, 28; NACT, 23); and NACT, 13 (18%). Overall, 83% underwent PDS, with a 75% CGR rate and 94% optimal cytoreduction rate. Use of the algorithm resulted in a 31% LSC rate and a 6% rate of suboptimal PDS. CONCLUSIONS: The multimodal algorithm led to excellent surgical results; 94% of patients achieved an optimal resection, with a very low rate of suboptimal cytoreduction.

Update on the role of surgery in the management of advanced epithelial ovarian cancer.

Surgical cytoreduction and platinum/taxane-based chemotherapy are the cornerstones of the management of advanced ovarian cancer; however, the optimal timing and order of these interventions remain a topic of debate. Interpreting the available data, specifically regarding the role of neoadjuvant chemotherapy in the primary setting and surgical cytoreduction in the recurrent setting, requires careful evaluation of surgical quality and patient selection. One tenet that has persisted throughout the historical and modern literature is the prognostic effect of the volume of residual disease after cytoreductive surgery. The goal of debulking surgery has appropriately evolved to that of the complete gross resection of all visible disease, and the repertoire of the gynecologic cancer surgeon has grown to include radical pelvic, upper abdominal, and thoracic procedures. Novel surgical techniques are under investigation, such as minimally invasive cytoreductive procedures and the intraoperative utilization of heated intraperitoneal chemotherapy. Of equal importance is a recent refocusing of attention on patient preferences and the patient's experience during treatment and recovery. In this review article, we examine the literature supporting the role of surgery in the management of advanced ovarian cancer.

Hyperglycosylated hCG and Placenta Accreta Spectrum.

OBJECTIVE: We aimed to evaluate the relationship between hyperglycosylated human chorionic gonadotropin (hCG-H) and placenta accreta spectrum (PAS) in the second and third trimesters of pregnancy. STUDY DESIGN: This was a case-control study of PAS and controls. hCG-H was measured in the second and third trimesters of pregnancy in women with pathologically confirmed cases of PAS and in gestational age-matched controls without PAS. We compared serum hCG-H levels in cases and controls, calculated summary statistics for diagnostic accuracy, and used receiver operating characteristic (ROC) curves to define an optimal cut-point for diagnosis of PAS using hCG-H. RESULTS: Thirty case samples and 30 control samples were evaluated for hCG-H. Mean hCG-H was lower in the case compared with control group (7.8 ± 5.9 µg/L vs. 11.8 ± 8.8 µg/L, p = 0.03). At an optimal cut-point for hCG-H of ≤7.6 µg/L, the sensitivity, specificity, positive likelihood ratios, negative likelihood ratios, and area under the ROC curve were 66.7%, 69.7%, 2.20%, 0.48%, and 0.68%, respectively. CONCLUSION: Hyperglycosylated hCG levels in the second and third trimesters of pregnancy were lower in patients with PAS than in controls, but hCG-H showed only modest capability as a diagnostic test for PAS.

Extension of overall survival beyond objective responses in patients with metastatic renal cell carcinoma treated with high-dose interleukin-2.

PURPOSE: In metastatic renal cell carcinoma (mRCC), survival benefit associated with objective response rates of 16-20 % with high-dose interleukin-2 (HDIL-2) is well established and discussed. Based on recently emerged data on efficacy of cancer immunotherapy, we hypothesized that the survival benefit with HDIL-2 extends beyond those achieving objective responses, i.e., to those who achieve stable disease as the best response to treatment. MATERIALS AND METHODS: All sequential treatment naïve mRCC patients treated with HDIL-2 at the University of Utah (1988-2013) and University of Michigan (1997-2013) were included. Best responses on treatment were associated with survival outcomes using log-rank and COX regression with a landmark analysis at 2 months. RESULTS: 391 patients (75 % male; median age 55 years) were included and belonged to the following prognostic risk categories: 20 % good, 64 % intermediate, and 15 % poor. Best responses on treatment were complete response (9 %), partial response (10 %), stable disease (32 %), progressive disease (42 %), and not evaluable for response (7 %). No significant differences in progression-free survival (HR 0.74, 95 % CI 0.48-1.1, p = 0.14) or overall survival (HR 0.66, 95 % CI 0.39-1.09, p = 0.11) were observed between patients achieving partial response versus stable disease. Significant differences in progression-free survival (HR 0.13, 95 % CI 0.09-0.22, p < 0.0001) and overall survival (HR 0.33, 95 % CI 0.23-0.48, p < 0.0001) were observed between patients achieving stable disease compared to those with progressive disease and who were not evaluable. CONCLUSIONS: Survival benefit with HDIL-2 is achieved in ~50 % patients and extends beyond those achieving objective responses.

Durable response to BRAF inhibitor monotherapy in recurrent metastatic low grade serous ovarian cancer.

Low grade serous ovarian cancers (LGSOC) in an advanced setting have limited systemic treatment options. In this paper we report a case of metastatic LGSOC harboring a BRAF mutation, treated with dabrafenib. We discuss the clinical, pathologic and molecular characteristics as well as surgical considerations and ongoing investigations in LGSOC.

Margin status in vulvovaginal melanoma: Management and oncologic outcomes of 50 cases.

Objectives: To determine the influence of margin status, including preinvasive disease at the margin, on local recurrence and overall survival (OS) in patients with vulvovaginal melanoma. Methods: All patients with Stage 0-III vulvovaginal melanoma treated with primary surgical management between 1/2010-12/2019 were included. Margin status was categorized as negative, preinvasive disease (atypical junctional melanocytic hyperplasia and melanoma in situ), and invasive melanoma. Kaplan-Meier analyses were performed for local progression free survival (PFS) and OS. The impact of clinical and pathologic factors on local PFS and OS were assessed with Cox-regression analyses. Results: Fifty patients with a median follow-up of 48 months (range 3-119) were included. The median age was 63 years (range 20-83). Twenty percent (N = 10) had Stage 0 disease, 18% (N = 9) had Stage I, 46% (N = 23) had Stage II, and 16% (N = 8) had Stage III. Forty-four percent (N = 22) of patients had negative surgical margins, 46% (N = 23) had preinvasive disease at the margins, and 10% (N = 5) had invasive melanoma at the margins. The 5-year local PFS was 63% (95% CI: 42-78%) and OS was 60% (95% CI: 42-74%). Age, Breslow depth, stage, margin status, and re-resection did not significantly impact local PFS. In patients with preinvasive disease at the margin, all who recurred locally had Stage I-II disease. Conclusion: Preinvasive disease at the surgical margins may play an important role in local recurrence in patients with Stage I-II vulvovaginal melanoma. Patients with early (Stage 0) and advanced (Stage III) disease rarely recur locally and may not benefit from re-resection.

Successful treatment of low-grade endometrial cancer in premenopausal women with an aromatase inhibitor after failure with oral or intrauterine progesterone.

INTRODUCTION: Young women with endometrial intraepithelial hyperplasia or low-grade endometrial carcinoma are potential candidates for conservative fertility sparing therapy utilizing progesterone rather than hysterectomy. High-dose progesterone treatment is associated with 55-80% initial response but high relapse rates. Using aromatase inhibitors in conjunction with high-dose progesterone has largely been unstudied. CASE DESCRIPTIONS: Three obese premenopausal women with endometrial cancer failed to respond to oral or intrauterine progesterone as first line therapy. Due to their desire to continue to pursue fertility sparing treatment options, an aromatase inhibitor was added to their treatment regimen. This resulted in resolution of their malignancy in each case. DISCUSSION: In obese premenopausal women, the mechanism of malignant transformation in endometrial carcinoma is considered to be an association with relatively high levels of serum estrogen from peripheral conversion of androgens to estrone in adipose tissue with a deficiency in progesterone exposure due to chronic anovulation. Using aromatase inhibitors seems reasonable as an adjunct to progesterone given the high likelihood that this population has a significant proportion of their estrogen production coming from peripheral conversion in adipose tissue. This case series is unique in that each woman initially failed to respond to progesterone but had resolution when an aromatase inhibitor was added to their treatment regimen. This would suggest that obese women with low grade malignancy or hyperplasia who have no radiographic evidence of deep myometrial invasion, ovarian or retroperitoneal metastases and who wish to retain their fertility may be treated with intrauterine progesterone and an aromatase inhibitor.