Identifying novel ovarian tumor biomarkers through mining of the transcriptome of circulating immune cells: A proof-of-concept study.

OBJECTIVE: Treatment of high-grade serous ovarian cancer (HGSOC) will benefit from early detection of cancer. Here, we provide proof-of-concept data supporting the hypothesis that circulating immune cells, because of their early recognition of tumors and the tumor microenvironment, can be considered for biomarker discovery. METHODS: Longitudinal blood samples from C57BL/6 mice bearing syngeneic ovarian tumors and peripheral blood mononuclear cells (PBMC) from healthy postmenopausal women and newly diagnosed for HGSOC patients were subjected to RNASeq. The results from human immune cells were validated using Affymetrix microarrays. Differentially expressed transcripts in immune cells from tumor-bearing mice and HGSOC patients were compared to matching controls. RESULTS: A total of 1282 transcripts (798 and 484, up- and downregulated, respectively) were differentially expressed in the tumor-bearing mice as compared with controls. Top 100 genes showing longitudinal changes in gene expression 2, 4, 7, and 18 days after tumor implantation were identified. Analysis of the PBMC from healthy post-menopausal women and HGSOC patients identified 4382 differentially expressed genes and 519 of these were validated through Affymetrix microarray analysis. A total of 384 genes, including IL-1R2, CH3L1, Infitm1, FP42, CXC42, Hdc, Spib, and Sema6b, were differentially expressed in the human and mouse datasets. CONCLUSION: The PBMC transcriptome shows longitudinal changes in response to the progressing tumor. Several potential biomarker transcripts were identified in HGSOC patients and mouse models. Monitoring their expression in individual PBMC subsets can serve as additional discriminator for the diagnosis of HGSOC.

The Safety and Feasibility of Gynecologic Cancer Surgery Combined With Surgery for Pelvic Floor Dysfunction.

OBJECTIVES: Women with gynecologic cancer may also present with pelvic floor dysfunction that can have a significant effect on quality of life. Combined surgical intervention for both malignancy and pelvic floor dysfunction may improve quality of life with minimal additional risk. We sought to determine the safety, feasibility, and frequency of combined gynecologic cancer surgery and surgery for pelvic floor dysfunction. METHODS: This is a retrospective cohort study that utilized the National Surgical Quality Improvement Program database provided through the American College of Surgeons. The National Surgical Quality Improvement Program database was queried for patients with a final diagnosis of gynecologic malignancy from 2011 to 2015. Common Procedural Terminology codes for gynecologic oncology procedures and pelvic floor dysfunction surgery were used to identify the study population. Baseline demographics and postoperative complications were abstracted from the database for these patients and compared for patients with combined surgeries versus gynecologic cancer surgeries alone. RESULTS: One hundred twenty-nine women underwent combined procedures compared with 25,838 women undergoing gynecologic cancer surgery alone. Patients who underwent combined procedures were older, had lower body mass index, had higher preoperative albumin and hematocrit, and lower morbidity estimates (P < 0.05). Mean operative time was longer (226.4 vs 174.4 minutes, P < 0.01). There were no statistically significant differences in race, ethnicity, or medical comorbidities. There were no statistically significant differences in postoperative complications or readmissions between the 2 groups (P > 0.1). CONCLUSIONS: Combined gynecologic cancer and pelvic floor dysfunction procedures are feasible and can safely be performed without differences in postoperative complications in appropriately selected patients.

A Systematic Assessment of Google Search Queries and Readability of Online Gynecologic Oncology Patient Education Materials.

The Internet is a major source of health information for gynecologic cancer patients. In this study, we systematically explore common Google search terms related to gynecologic cancer and calculate readability of top resulting websites. We used Google AdWords Keyword Planner to generate a list of commonly searched keywords related to gynecologic oncology, which were sorted into five groups (cervical cancer, ovarian cancer, uterine cancer, vulvar cancer, vaginal cancer) using five patient education websites from sgo.org . Each keyword was Google searched to create a list of top websites. The Python programming language (version 3.5.1) was used to describe frequencies of keywords, top-level domains (TLDs), domains, and readability of top websites using four validated formulae. Of the estimated 1,846,950 monthly searches resulting in 62,227 websites, the most common was cancer.org . The most common TLD was *.com. Most websites were above the eighth-grade reading level recommended by the American Medical Association (AMA) and the National Institute of Health (NIH). The SMOG Index was the most reliable formula. The mean grade level readability for all sites using SMOG was 9.4 ± 2.3, with 23.9% of sites falling at or below the eighth-grade reading level. The first ten results for each Google keyword were easiest to read with results beyond the first page of Google being consistently more difficult. Keywords related to gynecologic malignancies are Google-searched frequently. Most websites are difficult to read without a high school education. This knowledge may help gynecologic oncology providers adequately meet the needs of their patients.

Neoadjuvant chemotherapy is associated with a high rate of perioperative blood transfusion at the time of interval cytoreductive surgery.

BACKGROUND: The oncologic safety of allogeneic blood transfusion in ovarian cancer patients is unknow. We sought to determine the prevalence and oncologic safety of perioperative allogeneic blood transfusion during interval cytoreduction surgery among women receiving neoadjuvant chemotherapy for ovarian cancer. METHODS: We utilized retrospective chart review to identify a cohort of patients undergoing interval cytoreduction at a large academic tertiary referral center. We compared outcomes in patients who were exposed to perioperative blood transfusion compared with patients who were not exposed. Our primary endpoint was progression free survival; our secondary endpoint was overall survival. Baseline clinical characteristics were collected for patients in each group. RESULTS: Sixty-six women were included in the final cohort of women undergoing interval cytoreductive surgery after NACT. A total of 51 women (77%) were exposed to allogeneic perioperative pRBC transfusion. Fifteen women (23%) were not exposed to transfusion. The baseline characteristics were generally well matched. Women who were not exposed to a perioperative blood transfusion were more likely to have a normalized CA125 prior to undergoing cytoreductive surgery. Preoperative hemoglobin concentration was lower in the transfusion group (10.5 g/dLvs 11.5 g/dL, p < 0.009). Perioperative transfusion was not associated with a significant difference in progression free survival (PFS = 7.6 months for transfused, 9.4 months for not transfused; log-rank test p = 0.4617). Similarly, there was no observed difference between groups for overall survival (OS = 23.6 months for transfused, 22.5 months for not transfused; log-rank test p = 0.1723). CONCLUSIONS: Women undergoing neoadjuvant chemotherapy for ovarian cancer are at high risk of exposure to blood transfusion at the time of interval cytoreductive surgery. Future studies will continue to evaluate the safety and impact of transfusion on ovarian cancer survival in this at risk population.

Trends and Complications of Vulvar Reconstruction After Vulvectomy: A Study of a Nationwide Cohort.

OBJECTIVES: The objective of this study was to determine complications associated with primary closure compared with reconstruction after vulvar excision and predisposing factors to these complications. METHODS: Patients undergoing vulvar excision with or without reconstruction from 2011 to 2015 were abstracted from the National Surgical Quality Improvement Program database. Common Procedural Terminology codes were used to characterize surgical procedures as vulvar excision alone or vulvar excision with reconstruction. Patient characteristics and 30-day outcomes were used to compare the 2 procedures. Descriptive and univariate statistics were performed. Adjusted odds ratios and confidence intervals were calculated using a logistic regression model to control for potential confounders. Two-sided α with P < 0.05 was designated as significant. RESULTS: A total of 2698 patients were identified; 78 (2.9%) underwent reconstruction. There were no differences in age, race, body mass index, diabetes, hypertension, tobacco use, heart failure, renal failure, or functional status between the 2 groups. American Society of Anesthesiologists class 3 and 4 patients and those with disseminated cancer were more likely to undergo reconstruction (both P < 0.001). On univariate analysis, reconstruction was associated with increased risk of readmission, surgical site infection, pulmonary complications, urinary tract infection, transfusion, deep venous thrombosis, sepsis, septic shock, unplanned reoperation, longer hospital stay, need for skilled nursing or subacute rehab on discharge, and death within 30 days. On logistic regression analysis, disseminated cancer, American Society of Anesthesiologists classes 3 and 4 and reconstruction remained significant risk factors for readmission and any postoperative complication. CONCLUSIONS: Patients undergoing vulvar excision with reconstruction are at increased risk for readmission and postoperative complications compared with those undergoing excision alone. Careful patient selection and efforts to optimize surgical readiness are needed to improve outcomes. Long-term data could help determine if these 30-day outcomes are a reliable measure of surgical quality in vulvar surgery.

Preoperative obstructive sleep apnea screening in gynecologic oncology patients.

BACKGROUND: Women with a gynecologic cancer tend to be older, obese, and postmenopausal, characteristics that are associated with an increased risk for obstructive sleep apnea. However, there is limited investigation regarding the condition's prevalence in this population or its impact on postoperative outcomes. In other surgical populations, patients with obstructive sleep apnea have been observed to be at increased risk for adverse postoperative events. OBJECTIVE: We sought to estimate the prevalence of obstructive sleep apnea among gynecologic oncology patients undergoing elective surgery and to investigate for a relationship between obstructive sleep apnea and postoperative outcomes. STUDY DESIGN: Patients referred to an academic gynecologic oncology practice were approached for enrollment in this prospective, observational study. Patients were considered eligible for study enrollment if they were scheduled for a nonemergent inpatient surgery and could provide informed consent. Enrolled patients were evaluated for a preexisting diagnosis of obstructive sleep apnea. Those without a prior diagnosis were screened using the validated, 4-item STOP questionnaire (ie, Snore loudly, daytime Tiredness, Observed apnea, elevated blood Pressure). All patients who screened positive for obstructive sleep apnea were referred for polysomnography. The primary outcome was the prevalence of women with obstructive sleep apnea or those who screened at high risk for the condition. Secondary outcomes examined the correlation between body mass index (kg/m2) with obstructive sleep apnea and assessed for a relationship between obstructive sleep apnea and postoperative outcomes. RESULTS: Over a 22-month accrual period, 383 eligible patients were consecutively approached to participate in the study. A cohort of 260 patients were enrolled. A total of 33/260 patients (13%) were identified as having a previous diagnosis of obstructive sleep apnea. An additional 66/260 (25%) screened at risk for the condition using the STOP questionnaire. Of the patients who screened positive, 8/66 (12%) completed polysomnography, all of whom (8/8 [100%]) were found to have obstructive sleep apnea. The prevalence of previously diagnosed obstructive sleep apnea or screening at risk for the condition increased as body mass index increased (P < .001). Women with untreated obstructive sleep apnea and those who screened at risk for the condition were found to have an increased risk for postoperative hypoxemia (odds ratio, 3.5; 95% confidence interval, 1.8-4.7; P = .011) and delayed return of bowel function (odds ratio, 2.1; 95% confidence interval, 1.3-4.5; P = .009). CONCLUSION: The prevalence of obstructive sleep apnea or screening at risk for the condition is high among women presenting for surgery with a gynecologic oncologist. Providers should consider evaluating a patient's risk for obstructive sleep apnea in the preoperative setting, especially when risk factors for the condition are present.

The role of radiation therapy in the treatment of Stage II endometrial cancer: A large database study.

PURPOSE: The optimum adjuvant treatment for Stage II endometrial cancer patients is unknown. External beam radiation therapy (EBRT) is often considered the standard of care; however, retrospective series suggest that brachytherapy (BT) alone may be sufficient for selected patients. As randomized data are lacking, we used a large database to explore this question. METHODS AND MATERIALS: The National Cancer Data Base was queried for patients with pathologic International Federation of Gynecology and Obstetrics Stage II disease. Demographic, clinic-pathologic, and treatment details were compared between patients. Multivariable analysis was used to determine factors associated with receiving radiation therapy (RT). To account for imbalances between groups, a matched-pair analysis was completed. RESULTS: Eight thousand one hundred forty patients were included. RT was associated with overall survival (OS), with EBRT (hazard ratio [HR] 0.64), BT (HR 0.47), and combination (HR 0.54) showing increased OS on univariate analysis. Facility, urban location, diagnosis year, hysterectomy type, and chemotherapy did not reach significance. On multivariate analysis, RT was associated with OS, with EBRT (HR 0.69), BT (HR 0.60), and combination (HR 0.54) showing benefit. Using propensity-score matching, RT continued to show improved OS regardless of type: BT (82% vs. 73% 5-year OS) and EBRT (77% vs. 71%). BT as compared to EBRT had equivalent survival (81% vs. 79%, not statistically significant). CONCLUSION: This study of over 8,000 patients demonstrates that adjuvant RT confers a survival benefit in Stage II endometrial cancer and supports the continued use of RT in these patients. BT alone may be reasonable in carefully selected patients.

Obstructive Sleep Apnea and the Impact on Surgical Outcomes in Gynecology.

IMPORTANCE: Obstructive sleep apnea syndrome (OSAS) is a common medical condition in the United States and affects gynecologic surgical outcomes. OBJECTIVE: The aim of this review was to improve perioperative diagnosis and management of OSAS in patients presenting for gynecologic surgery and ultimately improve perioperative outcomes. The role of preoperative evaluation and screening is also addressed. EVIDENCE ACQUISITION: Medical databases were queried for publications pertaining to OSAS complications, risk factors, screening, and perioperative management. Pertinent articles were reviewed by the study authors. RESULTS: Obstructive sleep apnea syndrome is underdiagnosed in the preoperative surgical population. Obesity and other risk factors for OSAS are prevalent in patients with gynecologic issues but are not fully assessed with screening prior to surgery. Effective treatment modalities, such as continuous positive airway pressure, and perioperative management strategies are available to improve patient outcomes. CONCLUSIONS AND RELEVANCE: Increased diagnosis and treatment for OSAS in the perioperative period can improve perioperative outcomes, surgical outcomes, and long-term patient outcomes. Strategies to increase effective management in patients presenting for gynecologic surgery are needed.

Primary, non-germinal center, double-expressor diffuse large B cell lymphoma confined to a uterine leiomyoma: A case report.

•Primary lymphoma of the female genital tract accounts for 1% of extranodal lymphomas.•Approximately 13% are diffuse large B cell lymphoma of the uterus, most often involving the endometrial stroma or cervix.•The first double-expressor diffuse large B cell lymphoma confined to a uterine leiomyoma is described.

The Adoption of Single-port Laparoscopy for Full Staging of Endometrial Cancer: Surgical and Oncology Outcomes and Evaluation of the Learning Curve.

STUDY OBJECTIVE: To study the safety, feasibility, learning curve, and surgical outcome for single-port laparoscopic full staging of endometrial cancer. DESIGN: A retrospective study (Canadian Task Force classification II-3). SETTING: A university academic hospital. PATIENTS: Women with endometrial cancer undergoing single-port laparoscopic full surgical staging. INTERVENTIONS: This was a single-center, retrospective consecutive study of patients undergoing single-port laparoscopic full staging of endometrial cancer from March 2012 to December 2015. MEASUREMENTS AND MAIN RESULTS: One hundred ten consecutive cases were included in the study. The mean age was 63 years (standard deviation = 14), and the mean body mass index was 34 kg/m2 (standard deviation = 7). Medical comorbidity was noted in 62% (68/110) of patients, and 55% (61/110) of patients had previous abdominal surgery. Preoperative histology included grade 1 (63%), grade 2 (23%), grade 3 (4%), papillary serous (6%), clear cell (3%), and mixed (1%). Postoperatively, 73% of patients were stage I, 2% were stage II, 21% were stage III, and 4% were stage IV. The conversion rate to multiple ports or to laparotomy was 6.3%. The average total surgical time was 186 minutes. Comparing the last 30 cases of our cohort with the first 20, there was a significant improvement in the reduction of the total operative time (191 vs 152 minutes, p = .036), estimated blood loss (389 vs 121 mL, p = .002), conversion rate (20 % vs 0%, p = .02), and rate of surgical complication (10% vs. 0%, p = .03). The readmission rate was 11% (12/110) with 75% of those patients being readmitted for surgical indications and 25% for medical indications. The rate of ventral hernia was 1.8% (2/110) with an average follow-up of 298 days (31-1085 days). CONCLUSION: Single-port laparoscopic staging of endometrial cancer is a safe and feasible technique to introduce into a gynecologic oncology practice that is compatible with other minimally invasive modalities with similar complication rates, discharge timing, and operative times. Drastic improvement in surgical time can be seen after approximately the first 20 cases.

Endometriosis inflammation mimicking pseudomyxoma peritonei: A case report.

•Endometriosis may mimic other pathologic processes•Fertility preservation can be considered in young women with atypical endometriosis•Referral to experienced surgeons for maligancy is warranted in atypical endometriosis.

Predictors of 30-day readmission and impact of same-day discharge in laparoscopic hysterectomy.

OBJECTIVE: The objective of the study was to identify the predischarge predictors of 30-day readmission and the impact of same-day discharge after laparoscopic hysterectomy. STUDY DESIGN: Patients undergoing only laparoscopic hysterectomy with or without bilateral salpingo-oophorectomy participated in the study. RESULTS: The 30-day readmission rate was 3.1% (277 of 8890). Factors predictive of higher rates of readmission were diabetes (4.4% vs 3.0%; P = .03), chronic obstructive pulmonary disease (8.5% vs 3.1%; P = .02), disseminated cancer (20% vs 3.1%; P < .001), chronic steroid use (7.1% vs 3.1%; P = .03), daily alcohol use of more than 2 drinks (12.5% vs 2.5%; P = .04), and bleeding disorder (10.8% vs 3%; P = .001). Operative factors included surgical time of 2 hours or greater (3.5% vs 2.7%; P = .014). After surgery, patients had a higher rate of readmission when they experienced any 1 or more complications prior to discharge, (6.9% vs 3.1%; P = .01) as well as any complication after discharge (3.6% vs 1.6%; P = .01). Infections (35.7%) and surgical complications (24.2%) were the most common reasons of readmissions. Of these patients, 20.9% were discharged the same day (n = 1855) and had a similar rate of readmission (2.6% vs 3.2%; P = n.s.). Laparoscopic hysterectomy readmission score (LHRS) can be calculated by assigning 1 point to diabetes, chronic obstructive pulmonary disease, disseminated cancer, chronic steroid use, bleeding disorder, length of surgery of 2 hours or longer, and 2 points to any postoperative complication prior to discharge. Readmission rates for the LHRS score were score 1 (2.4%), score 2 (3.3%), score 3 (5.8%), or score 4 (9.5%). CONCLUSION: The overall readmission rate after laparoscopic hysterectomy is low. Patients discharged the same day have similar rates of readmission. Higher LHRS is indicative of higher rates of readmission and may identify a population not suitable for same-day discharge and in need of higher vigilance to prevent readmissions.

Awareness of symptoms and risk factors of ovarian cancer in a population of women and healthcare providers.

BACKGROUND: Awareness of ovarian cancer among women and healthcare providers is understudied. An early awareness of ovarian cancer may lead to early detection and treatment of ovarian cancer. OBJECTIVES: The purpose of this study was to determine the level of that awareness among a sample of women and providers. METHODS: Written surveys were developed by the authors based on available literature and were administered to women (n = 857) and healthcare providers (n = 188) attending or volunteering at a community health fair. Chi-square tests for independence and z tests were used for analysis. FINDINGS: Healthcare providers were significantly more likely to identify the symptoms and risk factors for ovarian cancer. Forty percent of women reported being at least slightly familiar with the symptoms of ovarian cancer. Women who were familiar with symptoms were significantly more likely to identify symptoms and risk factors correctly and to report symptoms immediately to a provider. Identification of symptoms among healthcare providers ranged from 59%-93%. Identification of ovarian cancer symptoms and risk factors is poor among women, and knowledge deficits are present in providers. Increasing familiarity and awareness could lead to improvements in early diagnosis.

Uterine rupture disguised by urinary retention following a second trimester induced abortion: a case report.

BACKGROUND: Uterine rupture classically presents with severe abdominal pain, loss of fetal station, vaginal bleeding, and shock. CASE PRESENTATION: We present a case of uterine rupture presenting as significant urinary retention that occurred following a second trimester abortion induced with mifepristone and misoprostol. Uterine rupture was discovered unexpectedly on diagnostic laparoscopy. The uterine rupture was contained by dense adhesions between the omentum and bladder with the previous uterine cesarean hysterotomy scar. CONCLUSION: This case highlights the difficulties in diagnosis of abnormal placentation and an unusual presentation of uterine rupture. This case was managed successfully laparoscopically.

Robotic surgery for early stage cervical cancer: Evolution and current trends.

The management of early stage cervical cancer often includes surgery in the form of radical hysterectomy, radical trachelectomy, or radical parametrectomy. Surgical techniques have evolved to include minimal invasive approaches, and more recently, to include robotic assisted techniques. This review highlights the evolution of surgical management of early cervical cancer and specifically explores robotic assisted radical hysterectomy, radical trachelectomy, radical parametrectomy, and the role of neoadjuvant chemotherapy.

Association between gelatin-thrombin matrix use and abscesses in women undergoing pelvic surgery.

OBJECTIVE: To assess the association between the use of gelatin-thrombin matrix and the development of pelvic abscess during hysterectomy as well as factors associated with surgeons' use of this product. METHODS: Data for patients undergoing hysterectomy for obstetric-gynecologic pathology were abstracted from databases at a tertiary hospital between 2009 and 2012. Open and minimally invasive hysterectomies were included and vaginal hysterectomies were excluded. Blood loss, surgery type, comorbidities, abscess formation, and use of gelatin-thrombin matrix were examined. Abscess was defined as a walled-off fluid collection (documented with computed tomography scan) with fever (greater than 38°C) or leukocytosis (greater than 11,000/microliter). Standard statistical models were used. RESULTS: Of the 413 patients identified, 213 (51%) underwent surgery for malignancy. Gelatin-thrombin matrix was used in 166 patients (40%). The overall rate of abscess was low (3%). In bivariate analyses, blood loss greater than 500 mL (odds ratio [OR] 3.9, 95% confidence interval [CI] 1.1-12.9, P=.021], ascites (OR 6.5, 95% CI 1.6-26.1, P=.023), drain placement (OR 4.5, 95% CI 1.3-15.1, P=.009), and gelatin-thrombin matrix use (OR 7.0, 95% CI 1.5-32.9, P=.009) were significantly associated with abscess formation. Multivariate logistic regression revealed that only gelatin-thrombin matrix use predicted the development of pelvic abscess (OR 7.0, 95% CI 1.5-32.9, P=.013). CONCLUSION: We found that gelatin-thrombin matrix use was associated with an increased risk of pelvic abscess. Although these products are important in the setting of bleeding, these data suggest that the liberal use of sealants is not without risk. LEVEL OF EVIDENCE: III.