Faculty Bibliography

OBJECTIVES:The aim of this study was to investigate the impact of body mass index (BMI) on completion, complications, and clinical outcomes of intraperitoneal (IP) chemotherapy in patients with advanced-stage ovarian cancer. METHODS:Patients with optimally cytoreduced International Federation of Gynecology and Obstetrics stage IIIC ovarian cancer treated with IP chemotherapy were retrospectively identified using an institutional review board-approved database. Clinical data were abstracted from the longitudinal medical record. Survival estimates were calculated using the Kaplan-Meier method. RESULTS:Ninety-two patients (35.5%) completed at least one cycle of IP chemotherapy. For these patients, there was no difference in histology, surgical complexity, or degree of cytoreduction based on BMI. Sixty-five percent of normal weight, 70% of overweight, and 59.1% of obese women completed 6 cycles (P = 0.697). There was also no significant difference in IP chemotherapy complications (P = 0.303). Body mass index had no impact on disease-free survival (P = 0.44) or overall survival, with a median overall survival of 68.5 months for normal weight, 65.9 months for overweight, and 61.7 months for obese women (P = 0.25). However, on multivariate analysis, obesity had an odds ratio of 2.92 (P = 0.02) for mortality. There was a trend toward treatment with intravenous chemotherapy (84.2%) over IP (15.8%) in patients with class II obesity (P = 0.06). DISCUSSION:There was no difference in completion of IP chemotherapy or complications with respect to BMI; however, there was a trend away from treatment with IP therapy in extreme obesity. These data suggest that IP chemotherapy is feasible in obese patients without incurring increased morbidity.

IMPORTANCE/OBJECTIVE:Patients with squamous cell carcinoma (SCC) of the cervix or vulva have limited therapeutic options, and the potential for immunotherapy for this population has not been evaluated. Recent trials suggest that tumors with a genetic basis for PD-1 (programmed cell death protein 1) ligand expression are highly sensitive to therapeutic antibodies targeting PD-1. OBJECTIVE:To determine the genetic status of CD274 (encoding PD-L1 [programmed cell death 1 ligand 1]) and PDCD1LG2 (encoding PD-L2 [programmed cell death 1 ligand 2]) in SCCs of the cervix and vulva and to correlate the findings with PD-L1 protein expression. DESIGN, SETTING, AND PARTICIPANTS/METHODS:We performed fluorescence in situ hybridization (FISH) using probes targeting CD274, PDCD1LG2, and the centromeric portion of chromosome 9, and immunohistochemistry (IHC) using an antibody recognizing PD-L1 on formalin-fixed, paraffin-embedded (FFPE) biopsy specimens from 48 cervical SCCs and 23 vulvar SCCs. MAIN OUTCOMES AND MEASURES/METHODS:Tumors were categorized according to the genetic abnormality in CD274 and PDCD1LG2 (coamplification > cogain > polysomy > disomy) as detected by FISH, and evaluated on a semiquantitative scale (modified H score, the product of the percentage of tumor cells with positive staining and the maximum intensity of positive staining) for PD-L1 protein expression as detected by IHC. RESULTS:Overall, 71 samples of FFPE tissue from cases of cervical SCCs (n = 48) and vulvar SCCs (n = 23) were retrieved from the archives of Brigham and Women's Hospital and included in this study. We observed cogain or coamplification of CD274 and PDCD1LG2 in 32 of 48 cervical SCCs (67%) and 10 of 23 vulvar SCCs (43%). Median PD-L1 protein expression was highest among tumors with CD274 and PDCD1LG2 coamplification and lowest among tumors with disomy. CONCLUSIONS AND RELEVANCE/CONCLUSIONS:Recurrent copy number gain of the genes encoding the PD-1 ligands provides a genetic basis for PD-L1 expression in a subset of cervical and vulvar SCCs and identifies a class of patients that are rational candidates for therapies targeting PD-1.

BACKGROUND:Episiotomy dehiscence can result in a large vulvovaginal defect not amenable to delayed primary closure. CASE/METHODS:A 26-year-old woman who underwent a forceps-assisted vaginal delivery with mediolateral episiotomy presented on postpartum day 5 with complete wound breakdown. Surgical exploration of the wound revealed a defect extending from the perineum into the vagina and deep into the ischiorectal fossa with poor tissue quality not amenable to a timely delayed primary closure. A vacuum-assisted closure device was used in lieu of traditional wound preparation and resulted in wound closure after 11 days of vacuum-assisted wound therapy. CONCLUSION/CONCLUSIONS:A vacuum-assisted closure device may be appropriate in cases of complex episiotomy breakdown and may expedite wound healing in the outpatient setting.

OBJECTIVES/OBJECTIVE: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.

OBJECTIVE:The aim of this study is to explore the previously unexamined role of the Gynecologic Oncologist as an intraoperative consultant during general gynecologic surgery. METHODS:Demographic and clinical data were collected on 98 major gynecologic surgeries that included both a general Gynecologist and a Gynecologic Oncologist between October 2010 and August 2014. Data were analyzed using XLSTAT-Prov2014.2.02. RESULTS:Of 794 major gynecologic surgeries, 98 (12.3%) cases that involved an intraoperative consultation were identified. There were 36 (37%) planned consults and 62 (63%) unplanned consults. Significantly more planned consults were during laparoscopy (100% v 58%; p<0.01) and significantly more unplanned consults were during laparotomy (42% v 0%; p<0.01). The majority of planned consults were for surgical training (86%) and the most common reasons for unplanned consults were adhesions (40%), bowel injury (19%), inability to identify ureter (19%), and cancer (11%). The most common interventions performed during unplanned consults were identification of anatomy (55%), lysis of adhesions (42%), and retroperitoneal dissection (27%). Average surgeon years in practice were significantly lower for unplanned consults (9 v 15; p<0.01). A total of 25 major adverse events occurred in 15 cases with the majority occurring in cases with unplanned consults (23% v 3%; p<0.01). After controlling for laparotomy, unplanned consultation was not significantly associated with major events (OR=6.67, 95%CI 0.69-64.39; p=0.10). CONCLUSIONS:Gynecologic Oncologists play a pivotal role in the support of generalist colleagues during pelvic surgery. In this series, Gynecologic Oncologists were consulted frequently for complex major benign surgeries. It is important to incorporate the skills required of an intraoperative consultant into Gynecologic Oncology fellowship training.

BACKGROUND:Although prior studies have suggested an inverse association between liver transplant centre volume and postoperative patient mortality, more recent analyses have failed to confirm this association. To date, all studies of the relationship between centre volume and outcomes in liver transplantation have been cross-sectional in design. OBJECTIVE:The objective of our study was to examine temporal trends in the volume-outcomes relationship for liver transplantation. METHODS:We used information obtained from the Scientific Registry of Transplant Recipients (SRTR) programme-specific data reports to examine the outcomes of adult liver transplant recipients stratified by annual centre volume. This relationship between centre volume and patient outcomes was assessed over three consecutive time periods from 2000 through 2007. RESULTS:The overall 25% increase in adult liver transplant volume in the USA from 2000 to 2007 appeared to be distributed fairly equally among existing transplant centres. In the earliest time period of our analysis, high-volume centres achieved superior risk-adjusted 1-year patient outcomes compared with low-volume centres. By the third and most recent time period of the analysis, this discrepancy between the outcomes of high- and low-volume centres was no longer statistically apparent. CONCLUSIONS:The relationship between centre volume and patient outcomes for liver transplantation in the USA has become less pronounced over time, suggesting that the use of procedure volume as a marker of liver transplant centre quality cannot be justified. The performance-based review process currently utilized in the USA may have contributed to this diminishing influence of centre volume on liver transplant recipient outcomes. This type of review process should be considered as a potential alternative to the volume-based referral initiatives that have been developed for other non-transplant, complex surgical procedures.