S.A. Sullivan

Obesity and perioperative pulmonary complications in robotic gynecologic surgery

OBJECTIVE Robotic gynecological surgery is feasible in obese patients, but there remain concerns about the safety of this approach because the positioning required for pelvic surgery can exacerbate obesity-related changes in respiratory physiology. The objective of our study was to evaluate pulmonary and all-cause complication rates in obese women undergoing robotic gynecological surgery and to assess variables that may be associated with complications. STUDY DESIGN A retrospective chart review was performed on obese patients (body mass index of ≥30 kg/m(2)) who underwent robotic gynecological surgery at 2 academic institutions between 2006 and 2012. The primary outcome was pulmonary complications and the secondary outcome was all-cause complications. Univariate and multivariate logistic regression analyses were used to determine the associations between patient baseline variables, operative variables, ventilator parameters, and complications. RESULTS Of 1032 patients, 146 patients (14%) had any complication, whereas only 33 patients (3%) had a pulmonary complication. Median body mass index was 37 kg/m(2). Only age was significantly associated with a higher risk of pulmonary complications (P = .01). Older age, higher estimated blood loss, and longer case length were associated with a higher rate of all-cause complications (P = .0001, P < .0001, and P = .004, respectively). No other covariates were strongly associated with complications. CONCLUSION The vast majority of obese patients can successfully tolerate robotic gynecological surgery and have overall low complications rates and even lower rates of pulmonary complications. The degree of obesity was not predictive of successful robotic surgery and subsequent complications.

Short-term mesh exposure after robotic sacrocolpopexy with and without concomitant hysterectomy.

Objectives The primary objective of this study was to compare the short-term rate of mesh exposure after a robotic sacrocolpopexy (RSCP) compared with those after RSCP with a concomitant hysterectomy. Secondary objectives included a comparison of mesh exposure from total hysterectomies (TH) versus supracervical hysterectomies (SCH) and determination of risk factors for mesh exposure. Methods This was a retrospective cohort study of women who underwent RSCP between January 2009 and December 2011 at one academic center. The primary outcome was mesh exposure at 6 weeks postoperation. Subjects were divided into two groups: those with concomitant hysterectomy and those with RSCP alone. The hysterectomy group was subdivided into TH versus SCH. Mesh exposures and mesh revision procedures were identified using International Classification of Diseases-9 and CPT codes, respectively, and confirmed by chart review. Results There were 230 eligible women who underwent RSCP during the study period and were followed up at a 6-week postoperative visit; 118 (51.7%) had RSCP only and 112 (48.7%) had a concomitant hysterectomy. Of those who underwent hysterectomy, 79 patients (70.5%) had TH and 33 (29.5%) had SCH. There were nine (3.9%) mesh exposures attributed to RSCP. The difference between the RSCP + hysterectomy group and the RSCP-only group was 2.7% versus 5.1% (P = 0.50). The 2.7% of mesh exposures in the hysterectomy group were associated with TH and none with SCH, but this difference was not significant (P = 0.55). Conclusions Although mesh exposure with RSCP is low, serious morbidity can be associated with mesh use and appropriate preoperative counseling is critical.

Dual inhibition of glycolysis and glutaminolysis as a therapeutic strategy in the treatment of ovarian cancer

Cancer cell metabolism is required to support the biosynthetic demands of cell growth and cell division, and to maintain reduction oxidaton (redox) homeostasis. This study was designed to test the effects of glucose and glutamine on ovarian cancer cell growth and explore the inter-relationship between glycolysis and glutaminolysis. The SKOV3, IGROV-1 and Hey ovarian cancer cell lines were assayed for glucose, pyruvate and glutamine dependence by analyzing cytotoxicity, cell cycle progression, apoptosis and ATP production. As determined by MTT assay, glucose stimulated cell growth while the combination of glucose, glutamine and pyruvate resulted in the greatest stimulation of cell proliferation. Furthermore, 2-deoxy-glucose (2-DG) and 3-bromopyruvate (3-BP) induced apoptosis, caused G1 phase cell cycle arrest and reduced glycolytic activity. Moreover, 2-DG in combination with a low dose of aminooxyacetate (AOA) synergistically increased the sensitivity to 2-DG in the inhibition of cell growth in the ovarian cancer cell lines. These studies suggest that dual inhibition of glycolysis and glutaminolysis may be a promising therapeutic strategy for the treatment of ovarian cancer.Cancer cell metabolism is required to support the biosynthetic demands of cell growth and cell division, and to maintain reduction oxidaton (redox) homeostasis. This study was designed to test the effects of glucose and glutamine on ovarian cancer cell growth and explore the inter-relationship between glycolysis and glutaminolysis. The SKOV3, IGROV-1 and Hey ovarian cancer cell lines were assayed for glucose, pyruvate and glutamine dependence by analyzing cytotoxicity, cell cycle progression, apoptosis and ATP production. As determined by MTT assay, glucose stimulated cell growth while the combination of glucose, glutamine and pyruvate resulted in the greatest stimulation of cell proliferation. Furthermore, 2-deoxy-glucose (2-DG) and 3-bromopyruvate (3-BP) induced apoptosis, caused G1 phase cell cycle arrest and reduced glycolytic activity. Moreover, 2-DG in combination with a low dose of aminooxyacetate (AOA) synergistically increased the sensitivity to 2-DG in the inhibition of cell growth in the ovarian cancer cell lines. These studies suggest that dual inhibition of glycolysis and glutaminolysis may be a promising therapeutic strategy for the treatment of ovarian cancer.

Sentinel Lymph Node Technique in Endometrial Cancer

Importance Endometrial cancer (EMCA) is the most common gynecologic malignancy, with an estimated 54,000 new cases and 10,000 deaths in the United States in 2015. Lymph node metastasis is the most significant prognostic factor in EMCA. Sentinel lymph node (SLN) mapping has become a well-accepted procedure in surgical oncology and may strike a balance between the risks and benefits of lymphadenectomy. Objective The aim of this study was to review the current literature regarding the history, techniques, and clinical application of SLN mapping in EMCA. Evidence Acquisition Evidence was obtained through systematic literature review through PubMed and ClinicalTrials.gov. Conclusions Sentinel lymph node biopsy for EMCA is an accepted approach to the staging of this cancer; however, a consensus approach to the SLN biopsy technique and pathologic assessment is needed. Surgeons newly adopting the technique should proceed with caution and care to monitor outcomes.

Sentinel Lymph Node Biopsy in Endometrial Cancer: a New Standard of Care?

Opinion statementLymph node status is one of the most important factors in determining prognosis and the need for adjuvant treatment in endometrial cancer (EMCA). Unfortunately, full lymphadenectomy bears significant surgical and postoperative risks. The majority of patients with clinical stage I disease will not have metastatic disease; thus, a full lymphadenectomy only increases morbidity in this population of patients. The use of the sentinel lymph node (SLN) biopsy has emerged as an alternative to complete lymphadenectomy in EMCA. By removing the highest yield lymph nodes, the SLN biopsy has the same diagnostic ability as lymphadenectomy while minimizing morbidity. The sensitivity of sentinel lymph node identification with robotic fluorescence imaging for detecting metastatic endometrial and cervical cancer (FIRES) trial published this year is the largest prospective, multi-institution trial investigating the accuracy of the SLN biopsy for endometrial and cervical cancer. Results of this trial found an excellent sensitivity (97.2%) and false negative rate (3%) with the technique. The conclusions from the FIRES trial and those of a recent meta-analysis are that SLN biopsy has an acceptable diagnostic accuracy in detecting lymphatic metastases, and can replace lymphadenectomy for this diagnostic purpose. There remains controversy surrounding the SLN biopsy in high-risk disease and the use of adjuvant therapy in the setting of low volume disease detected with ultrastaging. Current data suggests that the technique is accurate in high-risk disease and that the increased detection of metastasis helps guide adjuvant therapy such that oncologic outcomes are likely not affected by forgoing a full lymphadenectomy. Further prospective study is needed to investigate the impact of low volume metastatic disease on oncologic outcomes and the need for adjuvant therapy in these patients.

Impact of Trainee Involvement in Cervical Excision Procedures: Does Trainee Involvement Impact Quality?

Objective Cervical excision procedures are essential to the care of cervical dysplasia and malignancy. We sought to determine whether learner involvement in cervical excision procedures affects the quality of excision specimen. Materials and Methods A retrospective cohort study of cervical cancer patients diagnosed from July 1, 2000, to July 1, 2015, was performed. We included patients who had (1) a cervical excision procedure, either loop electrosurgical excision procedure or cold knife cone, and (2) pathologic information available. Primary outcome was the margin status of the specimen; secondary outcome was the size of the excision specimen including both width and depth. The exposure of interest was trainee participation, defined as resident physicians under the supervision of either a gynecologist or gynecologic oncologist. Descriptive statistics and general linear models were used for analysis. Results Ninety-four patients were identified. Overall, 58% (n = 54) of procedures were performed with trainee involvement. There was no difference in age, body mass index, or specimen width between trainee-performed and nontrainee-performed excisions. There was no significant difference in the status of margins with or without a trainee [44/57 (77%) and 29/37 (78%), respectively, p = .89]. There was a statistically significant difference in median specimen depth between trainee-performed and nontrainee-performed cases (15.4 mm vs 12 mm, p < .02). When adjusting for age, body mass index, excision type, indication, presence of trainee, and type of supervising physician, only the indication and type of excision were associated with greater depth of excision, (p < .01). Conclusions Trainee involvement in cervical excision procedures does not alter the quality of excision specimen.

Cost effectiveness of neoadjuvant chemotherapy followed by interval cytoreductive surgery versus primary cytoreductive surgery for patients with advanced stage ovarian cancer during the initial treatment phase

OBJECTIVE Advanced stage epithelial ovarian cancer (AEOC) can be treated with either neoadjuvant chemotherapy (NACT) or primary cytoreductive surgery (PCS). Although randomized controlled trials show that NACT is non-inferior in overall survival compared to PCS, there may be improvement in short-term morbidity. We sought to investigate the cost-effectiveness of NACT relative to PCS for AEOC from the US Medicare perspective. METHODS A cost-effectiveness analysis using a Markov model with a 7-month time horizon comparing (1) 3cycles of NACT with carboplatin and paclitaxel (CT), followed by interval cytoreductive surgery, then 3 additional cycles of CT, or (2) PCS followed by 6cycles of CT. Input parameters included probability of chemotherapy complications, surgical complications, treatment completion, treatment costs, and utilities. Model outcomes included costs, life-years gained, quality-adjusted life-years (QALYs) gained, and incremental cost-effectiveness ratios (ICER), in terms of cost per life-year gained and cost per QALY gained. We accounted for differences in surgical complexity by incorporating the cost of additional procedures and the probability of undergoing those procedures. Probabilistic sensitivity analysis (PSA) was performed via Monte Carlo simulations. RESULTS NACT resulted in a savings of

Abstract 3229: Drug repurposing of topiramate in obesity-driven endometrial cancer

7034 per patient with a 0.035 QALY increase compared to PCS; therefore, NACT dominated PCS in the base case analysis. With PSA, NACT was the dominant strategy more than 99% of the time. CONCLUSIONS In the short-term, NACT is a cost-effective alternative compared to PCS in women with AEOC. These results may translate to longer term cost-effectiveness; however, data from randomized control trials continues to mature.

Sebaceous carcinoma of the vulva: A case report and review of the literature

Introduction: Topiramate (TPM) is a B-D-fructopyranose sulfamate that acts by inhibiting carbonic anhydrases (CAs) and has been implicated as a novel inhibitor of angiogenesis. TPM is commonly used for the treatment of epilepsy and migraine headaches; however, when combined with phentermine, TPM can induce weight loss. Due to its weight loss and anti-angiogenic properties, we assessed TPM’s potential as an anti-tumorigenic agent in endometrial cancer (EC), a highly obesity-driven disease. Methods: Cell proliferation was assessed by MTT assay after exposure to TPM for 72 hours in the HEC-1A, KLE, Ishikawa and ECC-1 EC cell lines. Two representative cell lines, ECC-1 and Ishikawa, were used to analyze apoptosis, cell cycle progression, cell adhesion and invasion. Apoptosis was analyzed by Annexin V-FITC assay. Inhibition of adhesion and invasion by TPM were assessed by ELISA and transwell assay, respectively. Cell cycle progression was evaluated by Cellometer. Western immunoblotting was performed to assess downstream targets of the MAPK and mTOR pathways. The LKB1fl/flp53fl/fl EC mouse model was utilized to assess the in vivo effects of TPM. AdCre was injected at six weeks of age to induce invasive EC. Eight wks following AdCre injection, mice (N=10 per group) were treated with placebo or TPM (200 mg/kg/day, oral) for four weeks. The expression of phosphorylated-S6 and Ki-67 was assessed by IHC. Results: TPM inhibited cell proliferation in a dose dependent manner in all four EC cell lines (IC50 range=1500-3000 mM). Treatment with TPM resulted in G1 arrest and induction of apoptosis (p Conclusion: TPM inhibited cell proliferation and tumor growth in EC cell lines and an EC mouse model. Therefore, TPM may be worthy of drug repurposing as an anti-tumorigenic agent in EC, with the potential added benefit of weight loss in this obesity-linked disease. Citation Format: Arthur-Quan Tran, Stephanie A. Sullivan, Chunxiao Zhou, David Kaufman, Victoria Bae-Jump. Drug repurposing of topiramate in obesity-driven endometrial cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3229. doi:10.1158/1538-7445.AM2017-3229

Association between timing of cervical excision procedure to minimally invasive hysterectomy and surgical complications

Highlights • Sebaceous carcinoma (SC) is rare with only nine cases reported in the literature.• Extraocular SC likely has similar prognosis to ocular SC.• Reporting of vulvar SC should include detailed pathologic information so that risk factor associations can be made.