Faculty Bibliography

PURPOSE/OBJECTIVE:To evaluate the outcomes of intraperitoneal chemotherapy (IP) compared with those of intravenous chemotherapy (IV) in patients with advanced ovarian cancer after neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS) or primary debulking surgery (PDS). METHODS:Patients with advanced epithelial ovarian carcinoma treated with PDS or NACT and IDS from 2006 to 2015 were identified. Comparative statistics were used to evaluate covariates, and survival rates were calculated using the Kaplan-Meier method and compared with log-rank tests. RESULTS:Sixty-six patients received NACT followed by IDS with residual disease of ≤ 1 cm; 42 of these patients (63.6%) received IP therapy; and 24 patients (36.3%) had IV therapy only after IDS. The median progression-free survival (PFS) was 16.0 months in the IP group and 13.5 months in the IV group (p = 0.13). The estimated median overall survival (OS) was 64.0 months with IP and 50.0 months with IV (p = 0.44). During the same study period, 149 patients underwent optimal PDS after which 93 patients (62.4%) received IP and 56 patients (37.6%) were given IV chemotherapy. Patients after IP demonstrated improved survival outcomes when compared to patients after IV therapy. The median PFS was 28.0 months after IP and 16.5 months after IV (p = 0.0006), and the median OS was not reached for IP and 50.0 months after IV (p < 0.0001). CONCLUSIONS:Although IP chemotherapy after PDS is associated with improved survival, IP therapy after NACT and IDS, despite high rates of completion, may not have the same degree of survival advantage over IV therapy.

Adult-type granulosa cell tumors (GCTs), although rare, are the most commonly diagnosed neoplasms arising in the endocrine-active ovarian stroma. They are characterized by excessive production of estrogens, antimullerian hormone and inhibins. In 2009, a specific mutation in FOXL2 was identified to be pathognomonic of GCTs. How dysregulation of this transcription factor, resulting in upregulation of aromatase, leads to unchecked proliferation, and progression to a malignancy, remains unclear. The key pathological and clinical feature of GCTs that affects their usually favorable outcomes is a diagnosis of greater than Stage 1 disease at presentation. Chemotherapy is given as adjuvant upon an advanced stage diagnosis; however, its effect on survival upon recurrence is modest. On the other hand, aromatase inhibitors also lead to tumor regression and are suitable for long-term maintenance.

OBJECTIVES/OBJECTIVE:Black race has been associated with increased 30-day morbidity and mortality following surgery for endometrial cancer. Black women are also less likely to undergo laparoscopy when compared to white women. With the development of improved laparoscopic techniques and equipment, including the robotic platform, we sought to evaluate whether there has been a change in surgical approach for black women, and in turn, improvement in perioperative outcomes. METHODS:Using the American College of Surgeons' National Surgical Quality Improvement Project's database, patients who underwent hysterectomy for endometrial cancer from 2010 to 2015 were identified. Comparative analyses stratified by race and hysterectomy approach were performed to assess the relationship between race and perioperative outcomes. RESULTS:A total of 17,692 patients were identified: of these, 13,720 (77.5%) were white and 1553 (8.8%) were black. Black women were less likely to undergo laparoscopic hysterectomy compared to white women (49.3% vs 71.3%, p<0.0001). Rates of laparoscopy in both races increased over the 6-year period; however these consistently remained lower in black women each year. Black women had higher 30-day postoperative complication rates compared to white women (22.5% vs 13.6%, p<0.0001). When laparoscopic hysterectomies were isolated, there was no difference in postoperative complication rates between black and white women (9.2% vs 7.5%, p=0.1). CONCLUSIONS:Overall black women incur more postoperative complications compared to white women undergoing hysterectomy for endometrial cancer. However, laparoscopy may mitigate this disparity. Efforts should be made to maximize the utilization of minimally invasive surgery for the surgical management of endometrial cancer.

Could hydroxychloroquine and quinacrine antimalarial therapy for dermatomyositis later attributed to a paraneoplasic manifestation of an ovarian cancer enhance its subsequent response to chemotherapy? Five months after being diagnosed with dermatomyositis, while somewhat improved with hydroxychloroquine, quinacrine and methotrexate, this 63-year-old woman presented with an advanced intra-abdominal epithelial ovarian cancer documented (but not resected) at laparotomy. Neoadjuvant carboplatin/paclitaxel resulted in remarkable improvement of symptoms, tumour markers and imaging findings leading to thorough cytoreductive surgery at completion of five cycles. No tumour was found in the resected omentum, gynaecologic organs, as well as hepatic and nodal sampling thus documenting a complete pathologic response; a subcutaneous port and an intraperitoneal (IP) catheter were placed for two cycles of IP cisplatin consolidation. She remains free of disease 3 years after such treatment and her dermatomyositis is in remission in the absence of any treatment. We discuss a possible role of autophagy in promoting tumour cell survival and chemoresistance that is potentially reversed by antimalarial drugs. Thus, chemotherapy following their use may subsequently lead to dramatic potentiation of anticancer treatment.

OBJECTIVES: In June 2011, the SGO recommended that physical exam and symptoms be the primary surveillance methods in patients with endometrial cancer. We sought to evaluate adherence to these guidelines by comparing the use of CT scans, paps and serum CA125 ordered for endometrial cancer surveillance before and after publication of these guidelines. METHODS: A retrospective review was performed for all patients undergoing surveillance for endometrial cancer at a single institution between June 2009 and June 2013. We assessed the number of patients without symptoms or abnormal physical exam findings who underwent surveillance CT scans, paps and/or CA125 during the 2years pre- and 2years post-SGO guidelines. RESULTS: 92 patients (n=48 pre-6/2011, n=44 post-6/2011) were identified. Mean patient age was 58years. No significant difference in age, ethnicity, body mass index, or disease grade or stage was noted. There was a significant decline in surveillance CT scans (n=13, 27% vs. n=4, 9%, p=0.03), CA125 (n=14, 29% vs. 5, 11%, p=0.035) and paps (n=34, 71% vs. n=8 vs. 18%, p<0.001). There was no significant difference in disease status at the last follow-up. Institutional cost of surveillance also declined ($14,102.46 2years pre-guidelines, $3,054.99 2years post-guidelines). CONCLUSIONS: In a single urban academic public hospital, after only 2years, clinical adherence to the 2011 SGO endometrial cancer surveillance guidelines resulted in a significant decline in the use of CT scans, CA125 and paps. This reduction does not appear to affect patient outcomes and led to an appreciable decrease in surveillance costs.

OBJECTIVE: To evaluate the results of multigene panel testing among Ashkenazi Jewish compared with non-Ashkenazi Jewish patients. METHODS: We reviewed the medical records for all patients who underwent multigene panel testing and targeted BRCA1/2 testing at a single institution between 6/2013-1/2015. Clinical actionability for identified pathogenic mutations was characterized based on the National Comprehensive Cancer Network (NCCN) guidelines and consensus statements and expert opinion for genes not addressed by these guidelines. RESULTS: Four hundred and fifty-four patients underwent multigene panel screening, including 138 Ashkenazi Jewish patients. The median patient age was fifty-two years. Three hundred and fifty-four patients (78%) had a personal history of cancer. Two hundred and fifty-one patients had breast cancer, 49, ovarian cancer, 26, uterine cancer and 20, colorectal cancer. We identified 62 mutations in 56 patients and 291 variants of uncertain significance in 196 patients. Among the 56 patients with mutations, 51 (91%) had actionable mutations. Twenty mutations were identified by multigene panels among Ashkenazi Jewish patients, 18 of which were in genes other than BRCA1/2. A review of targeted BRCA1/2 testing performed over the same study period included 103 patients and identified six mutations in BRCA1/2, all of which occurred in Ashkenazi Jewish patients. Among all Ashkenazi Jewish patients undergoing genetic testing, 25/183 (14%) had a mutation, 24/25 of which were actionable (96%) and 17/25 patients (68%) had mutations in non BRCA1/2 genes. CONCLUSIONS: With the rapid acceptance of multigene panels there is a pressing need to understand how this testing will affect patient management. While traditionally many Ashkenazi Jewish patients have undergone targeted BRCA1/2 testing, our data suggest consideration of multigene panels in this population as the majority of the results are clinically actionable and often in genes other than BRCA1/2.

Objective: Approximately 30% of ovarian cancer is attributable to germline mutations, and genetic assessment is recommended for all women with ovarian cancer. However, only 15-30% are currently being offered genetic evaluation. We sought to determine whether a patient-centered, facilitated genetics referral pathway, whereby all newly diagnosed ovarian cancer patients are contacted by a genetics navigator to schedule genetic assessment as part of routine care, could increase rates of genetic counseling and uptake of testing. Method: Patients with epithelial ovarian cancer were referred for genetic assessment by their gynecologic oncologist within 6 weeks of diagnosis and consented for participation in our institutional review board-approved facilitated genetics pathway. Enrolled patients were contacted by a genetics navigator to schedule a genetic counselor appointment within 6 weeks. Patients who did not schedule or missed sessions were recontacted by the navigator. The genetic counselors offered pre-and post-test counseling and multigene panel testing. Primary outcome was feasibility of this pathway as defined by presentation for genetic assessment or declining genetic evaluation. Results: From October 2015 to July 2016, 50 patients were enrolled. Thirty-six patients (72%) underwent genetic assessment and, of these patients, 34 (94%) had genetic testing. Three patients (6%) are currently scheduled for appointments. Eleven patients (22%) did not undergo genetic assessment for the following reasons: not interested (4), not feeling well (2), missed appointment (2), nervous about testing (1), unable to see genetics counselors within 6 weeks (1), and death (1). Median time from diagnosis to genetics appointment was 13 days (range 0-53). Among the 32 patients for whom results are available, 7 (22%) had pathogenic mutations (BRCA1, 4; BRCA2, 3). Conclusion: The genetic testing pathway we present, characterized by facilitated referral to genetic counselors at time of ovarian cancer diagnosis, is both effective and efficient, resulting in genetic assessment of 72% of patients with newly diagnosed ovarian cancer, testing in 94% of these patients, and discovery of pathogenic mutations in 22% of those tested. Because germline mutations have both prognostic and therapeutic implications, the time of diagnosis may present an idealwindow to offer genetic testing

Objective: With the growing use of robotic surgery, there is an increased occurrence of port-site hernias requiring operative intervention. Currently there is limited literature, and prior studies have failed to find surgical or patient-related risk factors. We sought to identify patient and surgical risk factors, evaluate clinical presentation, and report management of this postoperative complication at a high-volume multispecialty robotic surgical center. Method: All robotic surgeries performed at a single institution from September 1, 2010, to September 1, 2015, were included. Univariate analysis was used to compare patient demographics and medical conditions for those who did and did not develop port-site hernias. Results: A total of 4,858 robotic surgeries were completed during the study period. A total of 37 (0.7%) port-site hernias requiring operative intervention were identified following urologic (23/1,888, 1.2%), gynecologic (13/2,661, 0.5%), and general surgery (1/309, 0.3%) procedures. Hernias occurred at the umbilical (n = 23) and 8-mm lateral port sites (n = 14). Only umbilical ports were closed under direct visualization. Median time from surgery to hernia diagnosis was 201 days (range 2-975). Presentation included bulge symptoms (n = 29) and nausea/vomiting (n = 6). The herniated contents included bowel/omentum (n =19), fat (n =14), or empty sac (n = 4). All cases were managed surgically, 21 with laparoscopy and 16 with laparotomy, with presentation within 30 days necessitating urgent surgery (n = 6). A total of 7/37 patients had complications from reoperation (bowel resection, n = 3; abscess formation, n=2; blood transfusion, n = 1). There was no difference between patients who did and did not develop a port-site hernia with regards to age, gender, BMI, smoking status, hypertension, diabetes, rheumatologic disease, HIV, prior hernia, or cancer diagnosis. (See Table 1.) Conclusion: Port-site hernias necessitating operative intervention following robotic surgery are rare, occurring in 0.7% of patients in our cohort. We found no patient or surgical variable to be predictive of this complication. Hernias occurred at both the umbilical and lateral ports. Despite needing a second surgery, all patients recovered and did not suffer significant long-term morbidity

Objective: Minimally invasive surgery is the preferred surgical method to treat women with endometrial cancer, with advantages including faster recovery, fewer postoperative complications (POC), and shorter hospital stays. Prior studies have shown same-day discharge (SDD) after laparoscopic hysterectomy (LH) to be safe, but the majority of patients are routinely admitted overnight. The objective of this study is to evaluate the rates and timing of 30-day POC in patients undergoing LH for endometrial cancer, and the association between POC and hospital admission status. Method: Patients who underwent hysterectomy for endometrial cancer from 2010 to 2014 were identified from the American College of Surgeons National Surgical Quality Improvement Program database by ICD-9 and CPT codes. Comparative analyses were performed and stratified by POC to evaluate for hospital lengths of stay. Results: We identified 13,745 patients who underwent hysterectomy for endometrial cancer: 4,457 had open hysterectomies (OH), 9,020 had LH, and 268 had vaginal hysterectomies (VH). POC rates were significantly lower in the LH and VH groups compared to OH: 16.9% of OH had POC compared to 5.3% of LH and 7.5 % of VH (P b 0.0001). There were 9,020 patients who underwent LH, and of these, 8,291 were admitted and 729 underwent SDD. Out of the 9,020 LH patients, 633 patients had at least 1 POC (7.0%), and of these, 221 (34.9%) had more than 1 POC. There were a total of 978 POC captured, as listed in Table 1. A median of 10 days elapsed from the surgery date to the development of any POC (range 0-30 days). Only 45 patients had a POC on either postoperative day 0 or 1 (0.5% of all patients after LH, 7.1% of patients with POC). Of the 633 patients who had a POC, 593 patients (93.7%) were admitted after surgery and 40 patients (6.3%) underwent SDD. SDD patients were younger, had lower BMI, and fewer medical comorbidity conditions than admitted patients, but there was no significant difference in POC rates between the admitted and SDD patients (P = 0.1). Conclusion: The most common POC was hospital readmission followed by urinary tract and surgical site infection. The majority of POC occur after postoperative day 1, and there is no association between SDD and POC rates. Patients may be safely discharged home the same day after LH without an increased risk of POC