Genomic profiling in low grade serous ovarian cancer: Identification of novel markers for disease diagnosis and therapy.

OBJECTIVES: Low grade serous ovarian cancer (LGSOC) differs from high grade serous in terms of pathogenesis, molecular, genetic, and clinical features. Molecular studies have been hampered by small sample sizes, heterogenous histology, and lack of comprehensive testing. We sought to molecularly profile LGSOC in a homogenously tested, histologically confirmed cohort. METHODS: Using hot-spot and whole exome next generation sequencing (NGS), fusion gene analysis interrogating RNA, fragment analysis, in situ hybridization and/or immunohistochemistry, 179 specimens were evaluated by Caris Life Sciences (Phoenix, AZ). A second independent histologic review confirmed histology in 153 specimens. RESULTS: Most frequently mutated genes (5% or greater) were members of the mitogen-activated protein kinase (MAPK) pathway: KRAS (23.7%, n = 36), NRAS (11.2%, n = 19), NF1 (7.9%, n = 5), and BRAF (6.6%, n = 10). Class III mutations were seen in 3 of 10 BRAF mutations while 7 were Class I V600E. Overall, estrogen and progesterone receptor expression was 80.2% (n = 130) and 27.8% (n = 45), respectively. Of those that were hormone negative, nearly 50% contained KRAS or NF1 mutations. None were NRAS mutated. Markers of response to immunotherapy were low to absent. CONCLUSION: BRAF mutations were seen to be lower than those traditionally reported. With increased MAPK activation resulting in ligand independent activation of ERα, a role of combination therapy with hormonal and targeted therapy should be considered as 49.2% of hormone negative specimens were KRAS or NF1 mutated. Absence of immunotherapy biomarkers suggest limited benefit to immunotherapeutic agents.

A rare case of follicular dendritic sarcoma of the vagina.

Follicular dendritic sarcoma of the vagina is an exceptionally rare malignancy. Here, we present a reproductive-aged female with no pertinent past medical history who initially presented with a protruding vaginal mass. Pathology from initial excision was consistent with follicular dendritic sarcoma of the vagina. This was ultimately treated with wide radical resection of the mass leading to iatrogenic vaginal stenosis.

Same-day discharge after robotic surgery for endometrial cancer.

To assess the safety of same-day discharge (SDD) following robotic-assisted endometrial cancer staging and identify risk factors for postoperative admission in a diverse population. A review of patients who underwent robotic-assisted endometrial cancer staging from April 1, 2017 to April 1, 2019 was performed. Patients were evaluated for SDD if they met the following criteria: tolerating oral intake, voiding spontaneously, ambulating, negative orthostatic vitals, postoperative hemoglobin ≤ 2 g/dL from baseline, pain controlled on oral medications, and desire to be discharged. Risk factors for admission were identified. One hundred eighty-seven patients were identified. SDD criteria were met in 158, of which 132 (83.5%) were discharged same day. Median length of stay was 4.5 h. Reasons for admission despite meeting criteria were late surgery time (n = 15), abnormal vitals (n = 9), and personal concerns (n = 2), with risk factors being age ≥ 68 years (OR 2.72; 95% CI, 1.13-6.59), start time 1400 or later (OR = 11.25; 95% CI, 4.35-29.10), ASA ≥ 4 (OR 23.82; 95% CI, 2.54-223.15), history of CVA/MI (OR 5.61; 95% CI, 1.07-29.52), and operative time ≥ 120 min (OR = 3.83; 95% CI 1.36-10.77). Of the SDD cohort, 2 patients (1.3%) presented to the emergency room within 30 days (postoperative day 5 and 23). SDD following robotic-assisted endometrial cancer staging is safe and feasible. Age ≥ 68 years, surgery start time after 1400, ASA ≥ 4, history of CVA/MI, and operative time ≥ 120 min appear predictive of inpatient admission despite meeting SDD criteria.

Integrin-Linked Kinase Is a Novel Therapeutic Target in Ovarian Cancer.

OBJECTIVE: The objective of this study is to identify and validate novel therapeutic target(s) in ovarian cancer. BACKGROUND: Development of targeted therapeutics in ovarian cancer has been limited by molecular heterogeneity. Although gene expression datasets are available, most of them lack appropriate pair-matched controls to define the alterations that result in the transformation of normal ovarian cells to cancerous cells. METHODS: We used microarray to compare the gene expression of treatment-naïve ovarian cancer tissue samples to pair-matched normal adjacent ovarian tissue from 24 patients. Ingenuity Pathway Analysis (IPA) was used to identify target pathways for further analysis. Integrin-linked kinase (ILK) expression in SKOV3 and OV90 cells was determined using Western blot. ILK was knocked down using CRISPR/Cas9 constructs. Subcutaneous xenograft study to determine the effect of ILK knockdown on tumor growth was performed in NOD SCID gamma mice. RESULTS: Significant upregulation of the ILK pathway was identified in 22 of the 24 cancer specimens, identifying it as a potential player that could contribute to the transformation of normal ovarian cells to cancerous cells. Knockdown of ILK in SKOV3 cells resulted in decreased cell proliferation and tumor growth, and inhibition of downstream kinase, AKT (protein kinase B). These results were further validated using an ILK-1 chemical inhibitor, compound 22. CONCLUSION: Our initial findings validate ILK as a potential therapeutic target for molecular inhibition in ovarian cancer, which warrants further investigation.

Therapeutic advances in hormone-dependent cancers: focus on prostate, breast and ovarian cancers.

Hormonal cancers affect over 400,000 men and women and contribute collectively to over 100,000 deaths in the United States alone. Thanks to advances in the understanding of these cancers at the molecular level and to the discovery of several disease-modifying therapeutics, the last decade has seen a plateauing or even a decreasing trend in the number of deaths from these cancers. These advanced therapeutics not only effectively slow the growth of hormonal cancers, but also provide an insight on how these cancers become refractory and evolve as an altogether distinct subset. This review summarizes the current therapeutic trends in hormonal cancers, with focus on prostate, breast and ovarian cancers. The review discusses the clinical drugs being used now, promising molecules that are going through various stages of development and makes some predictions on how the therapeutic landscape will shift in the next decade.

Celecoxib versus ketorolac following robotic hysterectomy for the management of postoperative pain: An open-label randomized control trial.

OBJECTIVE: Compare postoperative pain scores following hysterectomy in patients receiving perioperative celecoxib versus postoperative ketorolac as part of a multimodal pain regimen. METHODS: Patients undergoing hysterectomy were randomized to receive scheduled intravenous ketorolac in the immediate postoperative period or oral celecoxib prior to surgery and continued for a total seven days. All patients received a common multimodal pain protocol consisting of scheduled acetaminophen, gabapentin, and opioids as needed. Inpatient pain scores and postoperative opioid use were analyzed. A questionnaire regarding outpatient opioid use and return to normal activities of daily living (ADLs) was returned two weeks postoperatively. RESULTS: 192 patients were assessed for eligibility and 170 patients were randomized. Enrollment of patients undergoing open hysterectomy was closed prematurely for poor accruement (n = 32). 138 patients undergoing robotic hysterectomy were included were analyzed. There were no differences for inpatient pain scores (2.7 ±â€¯1.9 v. 2.4 ±â€¯1.6, p = 0.21). Average length of stay was similar between the two arms (11.6 ±â€¯8.1 h v. 11.9 ±â€¯7.6 h, p = 0.41). Patients in the celecoxib arm used less prescription opioids (6.0 ±â€¯3.6 v. 8.1 ±â€¯4.0, p = 0.001) and stopped using oral opioids earlier (3.8 ±â€¯2.6 days v. 5.7 ±â€¯2.8 days, p < 0.001). No differences were seen in inpatient opioid or anti-emetic usage, perioperative complications, or days to return to ADLs. CONCLUSIONS: There was no difference in inpatient pain scores between patients who received celecoxib or ketorolac as part of multimodal pain control following robotic hysterectomy. Patients who received scheduled celecoxib for seven days after surgery used less prescription narcotics.

Hypomagnesemia Is Prevalent in Patients Undergoing Gynecologic Surgery by a Gynecologic Oncologist.

OBJECTIVE: The aim of this study was to assess the incidence of and risk factors for hypomagnesemia in patients undergoing gynecologic surgery by a gynecologic oncologist. METHODS: A retrospective chart review was performed on all patients undergoing surgery for gynecologic pathology from July 2011 to July 2015 by a single surgeon. Demographic data, surgical indication, surgery performed, preoperative laboratory values, postoperative laboratory values, and medical history were examined. Hypomagnesemia was defined as less than 1.8 mg/dL. Hypermagnesemia was defined as greater than 2.5 mg/dL. RESULTS: Six hundred sixty-nine patients were identified for analysis. One hundred ninety-seven patients had hypomagnesemia (29.4%). Four hundred sixty-six patients had normal magnesium levels (69.5%), and 6 patients had hypermagnesemia (1%). Among patients with benign disease, 24.9% had preoperative hypomagnesemia compared with 32.7% of patients with a gynecologic malignancy. African American race (P = 0.041), diabetes mellitus (P < 0.001), and malignancy (P = 0.029) were all associated with preoperative hypomagnesemia. Diabetes and major surgery were associated with postoperative hypomagnesemia (P = 0.012 and P = 0.048, respectively). Hypomagnesemia was associated with increased preoperative and postoperative pain (P = 0.049 and P < 0.001, respectively) as well as postoperative hypokalemia (P = 0.001). Age, body mass index, hypertension, cancer type, hematocrit, surgical indication, and length of hospital stay were not associated with hypomagnesemia. CONCLUSIONS: Perioperative hypomagnesemia is prevalent in patients undergoing gynecologic surgery by a gynecologic oncology, especially in patients who have a gynecologic malignancy. We recommend routine preoperative and postoperative evaluation of serum magnesium in all patients undergoing gynecologic surgery by a gynecologic oncologist.

Video-assisted genetic counseling in patients with ovarian, fallopian and peritoneal carcinoma.

OBJECTIVES: To compare the proportion of patients with ovarian, fallopian or peritoneal carcinoma who receive genetic testing after observing a genetic counseling video versus after traditional referral for genetic counseling and testing at physician discretion. METHODS: A retrospective chart review was performed of all patients seen at the West Cancer Center for evaluation of ovarian, fallopian or peritoneal carcinoma from 7/2014 to 8/2015. Patients seen between 7/2014 and 12/2014 were offered standard genetic counseling. We adopted a new standard of care from 3/2015 to 8/2015 involving the use of a genetic counseling video on a digital tablet. The video was shown to patients with ovarian, fallopian or peritoneal cancer, who were then given the option to undergo genetic testing at the end of the viewing. We compared the number and proportion of patients who received genetic testing in both groups. RESULTS: The initial group of 267 patients received referral and te\sting at the physician's discretion between 8/2014 and 12/2014. 77/267 (29%) of these patients underwent genetic testing. 295 patients viewed the condensed genetic counseling video with the option to receive testing the same day between 3/2015 and 8/2015. 162/295 (55%) of these patients received testing. The transition from a referral method to the video counseling method resulted in a significant increase of patients tested (p<0.001). CONCLUSION: Using a genetic counseling video and providing an immediate option for testing significantly increased the proportion of patients with ovarian, fallopian or peritoneal carcinoma who received genetic testing.

Position-related injury is uncommon in robotic gynecologic surgery.

OBJECTIVE: To assess the rate and risk factors for position-related injury in robotic gynecologic surgery. METHODS: A prospective database from 12/2006 to 1/2014 of all planned robotic gynecologic procedures was retrospectively reviewed for patients who experienced neurologic injury, musculoskeletal injury, or vascular compromise related to patient positioning in the operating room. Analysis was performed to determine risk-factors and incidence for position-related injury. RESULTS: Of the 831 patients who underwent robotic surgery during the study time period, only 7 (0.8%) experienced positioning-related injury. The injuries included minor head contusions (n=3), two lower extremity neuropathies (n=2), brachial plexus injury (n=1) and one large subcutaneous ecchymosis on the left flank and thigh (n=1). There were no long term sequelae from the positioning-related injuries. The only statistically significant risk factor for positioning-related injury was prior abdominal surgery (P=0.05). There were no significant associations between position-related injuries and operative time (P=0.232), body mass index (P=0.847), age (P=0.152), smoking history (P=0.161), or medical comorbidities (P=0.229-0.999). CONCLUSIONS: The incidence of position-related injury among women undergoing robotic surgery was extremely low (0.8%). Due to the low incidence we were unable to identify modifiable risk factors for position-related injury following robotic surgery. A standardized, team-oriented approach may significantly decrease position-related injuries following robotic gynecologic surgery.

Multimodal pain control is associated with reduced hospital stay following open abdominal hysterectomy.

OBJECTIVE: To study the association of a multimodal pain protocol (MMPC) and reduced hospital stay after open abdominal hysterectomy. STUDY DESIGN: The study design was a comparison of a prospective cohort with a retrospective historical control. We enrolled endometrial cancer patients undergoing open abdominal hysterectomy with lymphadenectomy by the same surgeon. Control patients from 2008 to 2010 who received morphine PCA alone were compared with a similar demographic group of patients from 2011 to 2013 who received MMPC. MMPC consisted of gabapentin (900mg PO) and acetaminophen (1g IV) administered 45-60min preoperatively. The surgical site was injected with bupivacaine with 0.5% epinephrine prior to incision. The postoperative pain control regimen consisted of gabapentin (300mg PO every 6h), acetaminophen (1g IV every 8h for 24h postoperatively), ketorolac (15mg IV every 6h for 48h postoperatively), morphine PCA (2mg IV every 10min, no basal rate) and oxycodone/acetaminophen (10/325mg PO every 6h as needed). RESULTS: Length of hospital stay (LOH) of the study cohort (N=105 with MMPC) was compared with the historical with postoperative morphine alone (N=113 without MMPC). There were no differences in demographic, uterine cancer stage, or comorbidities between the two arms. The LOH was 1.6 days for patients receiving MMPC and 3.3 days for patients who received morphine alone (P<0.001). CONCLUSION: Multimodal pain control is associated with significantly reduced hospital stay after open abdominal hysterectomy.

Endometrioid adenocarcinoma in an extrauterine adenomyoma.

BACKGROUND: Focal involvement by endometrioid adenocarcinoma in an extrauterine adenomyoma in a patient with stage 1 endometrioid adenocarcinoma presented a unique problem in staging and management of extrauterine endometrial cancer. CASE: A 49-year-old white woman, gravida 0, referred for endometrioid adenocarcinoma was found to have an extrauterine adenomyoma involved with endometrioid adenocarcinoma in the inguinal canal after surgical staging. The endometrioid adenocarcinoma involving the extrauterine adenomyoma was low-grade and noninvasive, representing an embryological anomaly transformed into endometrioid adenocarcinoma by unopposed estrogen. Stage 1A, grade 2 endometrioid adenocarcinoma was diagnosed and observed. CONCLUSION: Stage 1 endometrioid adenocarcinoma with concurrent, noninvasive, focal involvement in an extrauterine adenomyoma represents a secondary site and does not alter disease stage.