Anne Van Arsdale

Metformin use and endometrial cancer survival

OBJECTIVE Impaired glucose tolerance and diabetes are risk factors for the development of uterine cancer. Although greater progression free survival among diabetic patients with ovarian and breast cancers using metformin has been reported, no studies have assessed the association of metformin use with survival in women with endometrial cancer (EC). METHODS We conducted a single-institution retrospective cohort study of all patients treated for uterine cancer from January 1999 through December 2009. Demographic, medical, social, and survival data were abstracted from medical records and the national death registry. Overall survival (OS) was estimated using Kaplan-Meier methods. Cox models were utilized for multivariate analysis. All statistical tests were two-sided. RESULTS Of 985 patients, 114 (12%) had diabetes and were treated with metformin, 136 (14%) were diabetic but did not use metformin, and 735 (74%) had not been diagnosed with diabetes. Greater OS was observed in diabetics with non-endometrioid EC who used metformin than in diabetic cases not using metformin and non-endometrioid EC cases without diabetes (log rank test (p=0.02)). This association remained significant (hazard ratio=0.54, 95% CI: 0.30-0.97, p<0.04) after adjusting for age, clinical stage, grade, chemotherapy treatment, radiation treatment and the presence of hyperlipidemia in multivariate analysis. No association between metformin use and OS in diabetics with endometrioid histology was observed. CONCLUSION Diabetic EC patients with non-endometrioid tumors who used metformin had lower risk of death than women with EC who did not use metformin. These data suggest that metformin might be useful as adjuvant therapy for non-endometrioid EC.

The role and timing of palliative medicine consultation for women with gynecologic malignancies: Association with end of life interventions and direct hospital costs

OBJECTIVE Aggressive care interventions at the end of life (ACE) are reported metrics of sub-optimal quality of end of life care that are modifiable by palliative medicine consultation. Our objective was to evaluate the association of inpatient palliative medicine consultation with ACE scores and direct inpatient hospital costs of patients with gynecologic malignancies. METHODS A retrospective review of medical records of the past 100 consecutive patients who died from their primary gynecologic malignancies at a single institution was performed. Timely palliative medicine consultation was defined as exposure to inpatient consultation ≥ 30 days before death. Metrics utilized to tabulate ACE scores were ICU admission, hospital admission, emergency room visit, death in an acute care setting, chemotherapy at the end of life, and hospice admission <3 days. Inpatient direct hospital costs were calculated for the last 30 days of life from accounting records. Data were analyzed using Fishers Exact, Mann-Whitney U, Kaplan-Meier, and Students T testing. RESULTS 49% of patients had a palliative medicine consultation and 18% had timely consultation. Median ACE score for patients with timely palliative medicine consultation was 0 (range 0-3) versus 2 (range 0-6) p=0.025 for patients with untimely/no consultation. Median inpatient direct costs for the last 30 days of life were lower for patients with timely consultation,

Obesity and age at diagnosis of endometrial cancer.

0 (range 0-28,019) versus untimely,

Endometrial thickness, Caucasian ethnicity, and age predict clinical pregnancy following fresh blastocyst embryo transfer: a retrospective cohort.

7729 (0-52,720), p=0.01. CONCLUSIONS Timely palliative medicine consultation was associated with lower ACE scores and direct hospital costs. Prospective evaluation is needed to validate the impact of palliative medicine consultation on quality of life and healthcare costs.

Outcomes after an excisional procedure for cervical intraepithelial neoplasia in HIV-infected women.

OBJECTIVE: Obesity is an established risk factor for development of endometrial cancer. We hypothesized that obesity might also be associated with an earlier age at endometrial cancer diagnosis, because mechanisms that drive the obesity–endometrial cancer association might also accelerate tumorigenesis. METHODS: A retrospective chart review was conducted of all cases of endometrial cancer diagnosed from 1999 to 2009 at a large medical center in New York City. The association of body mass index (BMI) with age at endometrial cancer diagnosis, comorbidities, stage, grade, and radiation treatment was examined using analysis of variance and linear regression. Overall survival by BMI category was assessed using Kaplan-Meier method and the log-rank test. RESULTS: A total of 985 cases of endometrial cancer were identified. The mean age at endometrial cancer diagnosis was 67.1 years (±11.9 standard deviation) in women with a normal BMI, whereas it was 56.3 years (±10.3 standard deviation) in women with a BMI greater than 50. Age at diagnosis of endometrioid-type cancer decreased linearly with increasing BMI (y=67.89–1.86x, R2=0.049, P<.001). This association persisted after multivariable adjustment (R2=0.181, P<.02). A linear association between BMI and age of nonendometrioid cancers was not found (P=.12). There were no differences in overall survival by BMI category. CONCLUSIONS: Obesity is associated with earlier age at diagnosis of endometrioid-type endometrial cancers. Similar associations were not, however, observed with nonendometrioid cancers, consistent with different pathways of tumorigenesis. LEVEL OF EVIDENCE: II

Skin Preparation for Prevention of Surgical Site Infection After Cesarean Delivery: A Randomized Controlled Trial.

BackgroundIn-vitro fertilization (IVF) with blastocyst as opposed to cleavage stage embryos has been advocated to improve success rates. Limited information exists on which to predict which patients undergoing blastocyst embryo transfer (BET) will achieve pregnancy. This studys objective was to evaluate the predictive value of patient and cycle characteristics for clinical pregnancy following fresh BET.MethodsThis was a retrospective cohort study from 2003–2007 at an academic assisted reproductive program. 114 women with infertility underwent fresh IVF with embryo transfer. We studied patients undergoing transfer of embryos at the blastocyst stage of development. Our main outcome of interest was clinical pregnancy. Clinical pregnancy and its associations with patient characteristics (age, body mass index, FSH, ethnicity) and cycle parameters (thickness of endometrial stripe, number eggs, available cleaving embryos, number blastocysts available, transferred, and cryopreserved, and embryo quality) were examined using Students T test and Mann-Whitney-U tests as appropriate. Multivariable logistic regression models were created to determine independent predictors of CP following BET. Receiver Operating Characteristic analyses were used to determine the optimal thickness of endometrial stripe for predicting clinical pregnancy.ResultsPatients achieving clinical pregnancy demonstrated a thicker endometrial stripe and were younger preceding embryo transfer. On multivariable logistic regression analyses, Caucasian ethnicity (OR 2.641, 95% CI 1.054–6.617), thickness of endometrial stripe, (OR 1.185, 95% CI 1.006–1.396) and age (OR 0.879, 95% CI 0.789–0.980) predicted clinical pregnancy. By receiver operating characteristic analysis, endometrial stripe ≥ 9.4 mm demonstrated a sensitivity of 83% for predicting clinical pregnancy following BET.ConclusionIn a cohort of patients undergoing fresh BET, thicker endometrial stripe, Caucasian ethnicity, and younger age are positive predictors of clinical pregnancy after fresh BET. These findings may be useful in clinical management of infertile patients undergoing fresh BET cycles.

Prevalence and factors associated with cognitive deficit in women with gynecologic malignancies

OBJECTIVE To determine predictors of treatment failure and recurrence after surgical excisional procedures for CIN in HIV-infected women. METHODS A retrospective cohort study was conducted in which 136 eligible HIV-infected women treated for CIN between 1999 and 2005 were included. Data were abstracted from charts and computer databases. Treatment failures were defined as the presence of CIN 1+ at initial follow-up. Recurrences were defined as the presence of CIN 1+ subsequent to initial normal follow-up. RESULTS Treatment failure at initial follow-up was common, occurring in 51% of CIN 1 and 55% of CIN 2+. Most lesions detected at treatment failure were high grade (>70%), regardless of the grade of initial lesion. Significant risk factors for treatment failure were loop electrosurgical excision procedure (LEEP) compared to cold knife conization (RR=1.76; 95% CI: 1.15-2.64), and low CD4+ count (p=0.04). Among those with an initial normal clinical evaluation, 55% eventually recurred. As with treatment failure, most lesions detected at recurrence were high grade. Risk factors for recurrence included use of LEEP (hazard ratio [HR]=3.38; 95% CI: 1.55-7.39), higher HIV RNA level, and the presence of positive margins at treatment (HR=6.12; 95% CI: 1.90-19.73). CONCLUSIONS Most CIN treatment of HIV-infected women studied either failed or resulted in recurrence. Of particular concern, many of these subsequent lesions were high grade. Conization, however, was associated with significantly less failure/recurrence than LEEP. Clinicians treating CIN in HIV-infected women should avoid raising expectations of cure and instead focus on the achievable goal of cancer prevention until there are better therapies for this patient population.

Comparison of Subcuticular Suture Type for Skin Closure after Cesarean Delivery: A Randomized Controlled Trial

OBJECTIVE: To compare chlorhexidine with alcohol, povidone–iodine with alcohol, and both applied sequentially to estimate their relative effectiveness in prevention of surgical site infections after cesarean delivery. METHODS: Women undergoing nonemergent cesarean birth at greater than 37 0/7 weeks of gestation were randomly allocated to one of three antiseptic skin preparations: povidone–iodine with alcohol, chlorhexidine with alcohol, or the sequential combination of both solutions. The primary outcome was surgical site infection reported within the first 30 days postpartum. Based on a surgical site infection rate of 12%, an anticipated 50% reduction for the combination group relative to either single skin preparation group, with a power of 0.90 and an &agr; of 0.05, 430 women per group were needed to detect a difference. RESULTS: From January 2013 to July 2014, 1,404 women were randomly assigned to one of three groups: povidone–iodine with alcohol (n=463), chlorhexidine with alcohol (n=474), or both (n=467). The groups were similar with respect to demographics, medical disorders, indication for cesarean delivery, operative time, and blood loss. The overall rate of surgical site infection—4.3%—was lower than anticipated. The skin preparation groups had similar surgical site infection rates: povidone–iodine 4.6%, chlorhexidine with alcohol 4.5%, and sequential 3.9% (P=.85). CONCLUSION: The skin preparation techniques resulted in similar rates of surgical site infections. Our study provides no support for any particular method of skin preparation before cesarean delivery. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01870583. LEVEL OF EVIDENCE: I

The gynecologic oncology fellowship interview process: Challenges and potential areas for improvement

OBJECTIVE Cognitive impairment has implications in counseling, treatment, and survivorship for women with gynecologic malignancies. The purpose of our study was to evaluate the prevalence and risk factors associated with cognition in women with gynecologic malignancies. METHODS After Institutional Review Board approval, 165 women at an urban ambulatory gynecologic oncology facility were queried using a Montreal Cognitive Assessment (MoCA), Wong-Baker pain scale, neuropathy scale, Patient Health Questionnaire 9 (PHQ-9) Depression Scale, and Generalized Anxiety Disorder Scale (GAD 7). Univariate and multivariate analyses were utilized to evaluate the association of cognitive deficit with age, education, race/ethnicity, disease site, stage, treatment, pain, neuropathy, anxiety, and depression. RESULTS The mean MoCA score for the entire cohort was 24.1 (range 13-30.) 24% of patients had MoCA scores less than 22. Low scores (<22) were associated with older age, non-white race/ethnicity, lower education level, uterine and vulvar cancers, and pain ≥5 (p<0.05). There was a trend toward lower cognition scores for women treated with both chemotherapy and radiation (p=0.10). While clinically significant pain was associated with low cognition, there was no association with use of opioid pain medication and low cognition scores. CONCLUSIONS There was a high prevalence of cognitive deficit in women with gynecologic malignancies. The association of low cognition with report of clinically significant pain, but not with use of opioid pain medications, should be further explored. Research is needed to evaluate the impact of cognitive deficits on treatment adherence and outcomes for women with gynecologic malignancies.

Expression of βV-tubulin in secretory cells of the fallopian tube epithelium marks cellular atypia

OBJECTIVE To compare the rate of wound complications among women who underwent cesarean delivery through a Pfannenstiel skin incision followed by subcuticular closure with either poliglecaprone 25 suture or polyglactin 910 suture. METHODS Patients undergoing nonemergent cesarean delivery at or beyond 37 weeks of gestation were randomized to undergo subcuticular skin closure with either poliglecaprone 25 or polyglactin 910. The primary outcome was a wound composite outcome of one or more of the following: surgical site infection, wound separation, hematoma, or seroma within the first 30 days postpartum. To detect a reduction in the primary outcome rate from 12% to 4%, with a power of 0.90 and a two-tailed α of 0.05, 237 women per study group were required. Analysis was performed according to the intent-to-treat principle. RESULTS From May 28, 2015, to August 5, 2016, 275 women were randomized to poliglecaprone 25 and 275 to polyglactin 910, of whom 520 (95%) were included in the final analysis: 263 in the poliglecaprone 25 group [of whom 231 (88%) actually underwent poliglecaprone 25 closure) and 257 in the polyglactin 910 group [of whom 209 (81%) actually underwent polyglactin 910 closure]. The groups were similar in demographic characteristics, medical comorbidities, and perioperative characteristics. Poliglecaprone 25 was associated with a significantly decreased rate of overall wound complications when compared with polyglactin 910, 8.8% compared with 14.4% (relative risk 0.61, 95% CI 0.37-0.99; P=.04). CONCLUSION Closure of the skin after cesarean delivery with poliglecaprone 25 suture decreases the rate of wound complications compared with polyglactin 910 suture. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, NCT02459093.