Gender and Racial Diversity Among Obstetrics and Gynecology Departments and Gynecologic Oncology Divisions in Canada: Are We There Yet?

OBJECTIVES: Gender and racial diversity in academic Canadian departments of obstetrics and gynecology (OBGYN) have not been previously described. We examined gender representation in leadership in academic OBGYN departments and gynecologic oncology (GO) divisions, and determined factors predictive of leadership and promotion including racialized status. METHODS: This cross-sectional study of Canadian residency-affiliated academic OBGYN departments queried institutional websites in January 2021 to compile a list of academic faculty. Subjective gender was assessed using photographs and pronouns, and racialized status was determined using photographs. Logistic regression analyses determined predictive factors for leadership roles. Fassiotto et al. rank equity indices (REI) and Hofler et al. representation ratios were calculated. RESULTS: Within 16 Canadian institutions there were 354 (33.6%) men and 699 (66.4%) women, with 18.3% racialized faculty. Men were more likely to reach full professorship (P < 0.00001) and leadership positions of department chair, vice-chair or division head (P = 0.01). Representation ratios for women in OBGYN were <1 for all administrative leadership positions, and pairwise comparisons of the probability of promotion for women OBGYNs using REI reveal significant disparities between senior and junior administrative leadership and professorial ranks. Racialized physicians were less likely to have attained full professorship (P = 0.002). Ninety-seven academic GOs were identified: 68 (70.1%) were women, 17 (17.5%) racialized. Seven GO divisions (44%) had no racialized members. On multivariate analysis, only year of completion of fellowship was predictive of leadership. CONCLUSION: In academic Canadian OBGYN departments women are underrepresented in leadership and full professor positions. Racialized faculty are underrepresented in full professorship.

Intraoperative predictors of appendiceal abnormalities in patients with mucinous ovarian neoplasms.

OBJECTIVE: To evaluate intraoperative factors predicting appendiceal pathology during gynecologic oncology surgery for suspected mucinous ovarian neoplasms. METHODS: We conducted a retrospective study on 225 patients with mucinous ovarian neoplasms who underwent surgery for an adnexal mass with concurrent appendectomy between 2000 and 2018. Regression analyses were used to evaluate intraoperative factors, such as frozen section of the ovarian mass and surgeon's impression of the appendix in predicting appendiceal pathology. RESULTS: Most patients (77.8%) had a normal appendix on final pathology. Abnormal appendix cases (n = 26) included: metastasis from high-grade adenocarcinoma of the ovary (n = 1), neuroendocrine tumor of the appendix (n = 4), and low-grade appendiceal mucinous neoplasms (n = 26; 23 associated with a mucinous ovarian adenocarcinoma, 2 with a benign mucinous ovarian cystadenoma, and 1 with a borderline mucinous ovarian tumor). Combining normal intraoperative appearance of the appendix with benign or borderline frozen section yielded a negative predictive value of 85.1%, with 14.9% of patients being misclassified, and 6.0% having a neuroendocrine tumor or low-grade appendiceal neoplasm. CONCLUSION: Benign or borderline frozen section of an ovarian mucinous neoplasm and normal appearing appendix have limited predictive value for appendiceal pathology. Appendectomy with removal of the mesoappendix should be considered in all cases of mucinous ovarian neoplasm, regardless of intraoperative findings.

Evaluating equity of access and predictors of minimally invasive hysterectomy for endometrial and cervical cancer from 2000 to 2017 in Ontario, Canada: A population-based cohort study.

INTRODUCTION: We sought to assess the uptake of minimally invasive hysterectomy among patients with endometrial and cervical cancer in Ontario, Canada, and assess the equity of access to minimally invasive surgery (MIS) by evaluating associations with patient, disease, institutional, and provider factors. METHODS: This is a retrospective population-based cohort study of hysterectomy for endometrial and cervical cancer in Ontario (2000-2017). Surgical approach, clinicopathologic, sociodemographic, institutional, and provider factors were identified through administrative databases. Fisher's exact, χ2 , Wilcoxon rank sum, logistic regression, and Cox proportional hazards modeling were used to explore factors associated with MIS. RESULTS: A total of 27 652 patients were included. In total, 6199/24 264 (26%) endometrial and 842/3388 (25%) cervical cancer patients received MIS. The proportion of MIS to open surgeries increased from <0.1% in 2000 to over 55% in 2017 (odds ratio [OR] = 1.31, confidence interval [CI] = 1.28-1.34). Low-income quintile, rurality, low hospital volume, nonacademic hospital, nongynecologic oncology surgeon, and earlier year of surgeon graduation were associated with reduced odds of MIS (OR < 1). CONCLUSIONS: The uptake of MIS hysterectomy increased steadily over the time period. Receipt of MIS is dependent upon multiple social determinants, provider variables, and systems factors. These disparities raise concern for health equity in Ontario and have significant implications for health systems planning and resource allocation.

A double-blinded, randomized trial comparing surgeon-administered transversus abdominis plane block with placebo after midline laparotomy in gynecologic oncology surgery.

BACKGROUND: Surgeon-administered transversus abdominis plane block is a contemporary approach to providing postoperative analgesia, and this approach is performed by transperitoneally administering local anesthetic in the plane between the internal oblique and transversus abdominis muscles to target the sensory nerves of the anterolateral abdominal wall. Although this technique is used in many centers, it has not been studied prospectively in patients undergoing a midline laparotomy. OBJECTIVE: This study aimed to evaluate whether surgeon-administered transversus abdominis plane block reduces postoperative opioid requirements and improves clinical outcomes. STUDY DESIGN: In this double-blind, randomized, placebo-controlled trial, patients with a suspected or proven gynecologic malignancy undergoing surgery through a midline laparotomy at 1 Canadian tertiary academic center were randomized to either the bupivacaine group (surgeon-administered transversus abdominis plane blocks with 40 mL of 0.25% bupivacaine) or the placebo group (surgeon-administered transversus abdominis plane blocks with 40 mL of normal saline solution) before fascial closure. The primary outcome was the total dose of opioids (in morphine milligram equivalents) received in the first 24 hours after surgery. The secondary outcomes included opioid doses between 24 and 48 hours, pain scores, postoperative nausea and vomiting, incidence of clinical ileus, time to flatus, and hospital length of stay. The exclusion criteria included contraindications to study medication, history of chronic opioid use, significant adhesions on the anterior abdominal wall preventing access to the injection site, concurrent nonabdominal surgical procedure, and the planned use of neuraxial anesthesia or analgesia. To detect a 20% decrease in opioid requirements with a 2-sided type 1 error of 5% and power of 80%, a sample size of 36 patients per group was calculated. RESULTS: From October 2020 to November 2021, 38 patients were randomized to the bupivacaine arm, and 41 patients were randomized to the placebo arm. The mean age was 60 years, and the mean body mass index was 29.3. A supraumbilical incision was used in 30 of 79 cases (38.0%), and bowel resection was performed in 10 of 79 cases (12.7%). Patient and surgical characteristics were evenly distributed. The patients in the bupivacaine group required 98.0±59.2 morphine milligram equivalents in the first 24 hours after surgery, whereas the patients in the placebo group required 100.8±44.0 morphine milligram equivalents (P=.85). The mean pain score at 4 hours after surgery was 3.1±2.4 (0-10 scale) in the intervention group vs 3.1±2.0 in the placebo group (P=.93). Clinically significant nausea or vomiting was reported in 1 of 38 patients (2.6%) in the intervention group vs 1 of 41 patients (2.4%) in the placebo group (P=.95). Time to first flatus, rates of clinical ileus, and length of stay were similar between groups. Subgroup analysis of patients with a body mass index of <25 and patients who received an infraumbilical incision showed similarly comparable outcomes. CONCLUSION: Surgeon-administered transversus abdominis plane block with bupivacaine was not found to be superior to the placebo intervention in reducing postoperative opioid requirements or improving other postoperative outcomes for patients undergoing a midline laparotomy. These results differed from previous reports evaluating the ultrasound-guided transversus abdominis plane block approach. Surgeon-administered transversus abdominis plane block should not be considered standard of care in postoperative multimodal analgesia.

Trends in quality indicators of end-of-life care for women with gynecologic malignancies in Ontario, Canada.

OBJECTIVE: A large body of research has validated several quality indicators of end-of-life (EOL) cancer care, but few have examined these in gynecologic cancer at a population-level. We examined patterns of EOL care quality in patients with gynecologic cancers across 13 years in Ontario, Canada. METHODS: We conducted a population-based, retrospective cohort study of gynecologic cancer decedents in Ontario from 2006 to 2018 using linked administrative health care databases. Proportions of quality indices were calculated, including: emergency department (ED) use, hospital or intensive care unit (ICU) admission, chemotherapy ≤14 days of death, cancer-related surgery, tube or intravenous feeds, palliative home visits, and hospital death. We used multivariable logistic regression to examine factors associated with receipt of aggressive and supportive care. RESULTS: There were 16,237 included decedents over the study period; hospital death rates decreased from 47% to 37%, supportive care use rose from 65% to 74%, and aggressive care remained stable (16%). Within 30 days of death, 50% were hospitalized, 5% admitted to ICU, and 67% accessed palliative homecare. Within 14 days of death, 31% visited the ED and 4% received chemotherapy. Patients with vulvovaginal cancers received the lowest rates of aggressive and supportive care. Using multivariable analyses, factors associated with increased aggressive EOL care use included younger age, shorter disease duration, lower income quintiles, and rural residence. CONCLUSIONS: Over time, less women dying with gynecologic cancers in Ontario experienced death in hospital, and more accessed supportive care. However, the majority were still hospitalized and a significant proportion received aggressive care in the final 30 days of life.

The five-factor modified frailty index predicts adverse postoperative and chemotherapy outcomes in gynecologic oncology.

INTRODUCTION: Frailty is increasingly recognized as a predictor of postoperative morbidity and oncologic outcomes. Evidence of the predictive value of frailty assessment in gynecologic oncology remains sparse. OBJECTIVES: To evaluate the National Surgical Quality Improvement Program (NSQIP) comorbidity-based modified Frailty Index-5 (mFI-5) as predictor of severe postoperative complications, non-completion of chemotherapy and other patient-centered outcomes in gynecologic oncology patients >70 years-old undergoing surgery. METHODS: Prospectively-collected NSQIP data and retrospective chart review of patients undergoing elective laparotomies for gynecologic malignances at a tertiary academic center in Ontario, Canada, between 01/2016-09/2020 were reviewed. Primary outcome was rate of 30-day Clavien-Dindo (Clavien) grade III-V complications. Secondary outcomes included Clavien II-V complications, postoperative length of stay (LOS), non-home discharge and non-completion of chemotherapy. Logistic regression analyses and receiver-operator curves were performed. RESULTS: Two-hundred and fifty-nine patients were included; 103 were planned to receive adjuvant chemotherapy. Fifty-three patients (20.5%) had an mFI ≥ 2 and were categorized as frail. On multivariable analyses, frailty independently predicted grade III-V complications (OR 24.49, 95%CI 9.72-70.67, p < 0.0001), grade II-V complications (OR 4.64, 95%CI 2.31-9.94, p < 0.0001), non-home discharge (OR 7.37, 95%CI 2.81-20.46, p < 0.0001), LOS ≥ 7d (OR 3.6, 95% CI 1.54-8.6, p = 0.003) and non-completion of chemotherapy (OR 8.42, 95%CI 2.46-32.79, p = 0.001). Adjusted C-statistics demonstrated strong predictive value of the mFI-5 for grade III-V (0.92, 95%CI 0.86-0.97) and grade II-V (0.74, 95%CI 0.68-0.8) complications as well as non-home discharge (0.86, 95%CI 0.78-0.95) and chemotherapy non-completion (0.87, 95%CI 0.8-0.95). CONCLUSION: Frailty as assessed with the mFI-5 predicted adverse postoperative and chemotherapy outcomes in gynecologic oncology patients aged ≥70 undergoing a laparotomy. The mFI-5 is a concise tool that can be used for routine frailty screening and risk stratification.

Gender imbalance in gynecologic oncology authorship and impact of COVID-19 pandemic.

OBJECTIVE: Despite increased participation of women in academic medicine in recent decades, gender disparities persist. The gender gap in authorship and editorial boards in gynecologic oncology, and impact of the COVID-19 pandemic, have not been recently evaluated. We examined gender representation and the impact of COVID-19 on authorship and editorial boards of two major peer-reviewed gynecologic oncology journals. METHODS: We conducted a bibliometric analysis of original articles published in Gynecologic Oncology and the International Journal of Gynecological Cancer, comparing the most contemporary 5-year period (2016-2020) to single years in the two prior decades (1996, 2006). To assess the early impact of COVID-19, we compared publications from May 2020-April 2021 to 2019. Editorial boards were analyzed for gender composition. First names, pronouns, and institutional photographs were used to determine gender. RESULTS: There were 3022 original articles published between 2016 and 2020, 763 in 2006, and 203 in 1996. Gender was identified for 91.3% of first authors (3641 articles) and 95.6% of senior authors (3813 articles). Men comprised the majority of the editorial boards in 2021 at 57% and 61% for Gynecologic Oncology and the International Journal of Gynecological Cancer, respectively. Men were overrepresented as senior authors across all study periods: 93% in 1996, 77% in 2006, and 58% in 2016-2020. Over time, representation of women as first and senior authors increased (7% in 1996, 42% in 2016-2020, p<0.00001). There was no immediate impact of the early pandemic on gender distribution of authorship. CONCLUSIONS: Despite greater representation of women over time as authors in gynecologic oncology journals, there remains gender disparity in senior authorship and editorial board representation. This presents an opportunity for the academic publishing community to advocate for deliberate strategies to achieve gender parity. Although no impact of the early COVID-19 pandemic was found, this requires ongoing surveillance.

A pneumococcal pneumonia and influenza vaccination quality improvement program for women receiving chemotherapy for gynecologic cancers at a major tertiary cancer Centre.

OBJECTIVE: International guidelines recommend pneumococcal pneumonia and influenza vaccination for all patients with solid organ malignancies prior to initiating chemotherapy. Baseline vaccination rates (March 2019) for pneumococcal pneumonia and influenza at our tertiary cancer centre were 8% and 40%, respectively. The aim of this study was to increase the number of gynecologic chemotherapy patients receiving pneumococcal and influenza vaccinations to 80% by March 2020. METHODS: We performed an interrupted time series study using structured quality improvement methodology. Three interventions were introduced to address vaccination barriers: an in-house vaccination program, a staff education campaign, and a patient care bundle (pre-printed prescription, information brochure, vaccine record booklet). Process and outcome data were collected by patient survey and pharmacy audit and analyzed on statistical process control charts. RESULTS: We identified 195 eligible patients. Pneumococcal and influenza vaccination rates rose significantly from 5% to a monthly mean of 61% and from 36% to a monthly mean of 67%, respectively. The 80% target was reached for both vaccines during one or more months of study. The in-house vaccination and staff education programs were major contributors to the improvement, whereas the information brochure and record booklet were minor contributors. CONCLUSIONS: Three interventions to promote pneumococcal and influenza vaccination among chemotherapy patients resulted in significantly improved vaccination rates. Lessons learned about promoting vaccine uptake may be generalizable to different populations and vaccine types. In response to the global COVID-19 pandemic, initiatives to expand the program to all chemotherapy patients at our centre are underway.

Thirty-day outcomes after gynecologic oncology surgery: A single-center experience of enhanced recovery after surgery pathways.

INTRODUCTION: The purpose of the study is to evaluate the impact of an enhanced recovery after surgery (ERAS) program implemented in a Gynecologic Oncology population undergoing a laparotomy at a Canadian tertiary care center. MATERIAL AND METHODS: Prospectively collected data, using the American College of Surgeons' National Surgical Quality Improvement Program dataset (ACS NSQIP), was used to compare 30-day postoperative outcomes of gynecologic oncology patients undergoing a laparotomy before and after the 2018 implementation of an ERAS program in a Canadian regional cancer center. Patient demographics, surgical variables and postoperative outcomes of 187 patients undergoing surgery in 2019 were compared with those of 441 patients undergoing surgery between January 2016 and December 2017. Student's t, Mann-Whitney U and Chi-square tests, as well as multivariate linear and logistic regressions were used to evaluate baseline characteristics and 30-day postoperative complications. RESULTS: Length of stay was significantly shortened in the study population after introducing the ERAS protocol, from a mean of 4.7 (SD = 3.8) days to a mean of 3.8 (SD = 3.2) days (P = .0001). The overall complication rate decreased from 24.3% to 16% (P = .02). Significant decreases in the rates of postoperative infections (adjusted odds ratio [OR] 0.56, 95% confidence interval [CI] 0.31-0.99) and cardiovascular complications (adjusted OR 0.27, 95% CI 0.09-0.79) were noted, without a significant increase in readmission rate (adjusted OR 0.50, 95% CI 0.21-1.07). CONCLUSIONS: Introducing an ERAS program for gynecologic oncology patients undergoing laparotomy was effective in shortening length of stay and the overall complication rate without a significant increase in readmission. Advocacy for broader implementation of ERAS among gynecologic oncology services and ongoing discussion on challenges and opportunities in the implementation process are warranted to improve patient outcomes and experiences.

Current Quality of Gynecologic Cancer Care in North America.

Evaluating the quality of care received by gynecologic cancer patients in the real world is essential for excellent outcomes. The recent population-based literature looking at quality of care was reviewed for all gynecologic malignancies. Outcomes are generally highest when care is provided by high-volume providers in high-volume cancer centers. Provision of care according to clinical practice guidelines has also been demonstrated to improve outcomes in many situations. Disparities exist for marginalized groups in terms of the care they receive and subsequent outcomes. Health systems need to improve care for these populations.

Outcomes of Adjuvant Therapy for Stage IA Serous Endometrial Cancer.

PURPOSE: Serous adenocarcinoma is a rare, aggressive histologic subtype of endometrial cancer with a high rate of recurrence and a poor prognosis. The optimal adjuvant treatment for early-stage patients is unclear. Our objective was to evaluate the outcomes of stage IA serous endometrial cancers only treated at a single institution and determine whether our current approach of chemotherapy plus vaginal brachytherapy (VBT) is sufficient. METHODS: A retrospective chart review of our institution's pathology database, including all cases of stage IA serous endometrial carcinoma from 2000-2014 was completed. Kaplan-Meier estimates were calculated for Overall and Recurrence-Free Survival (OS and RFS); hazard ratios were calculated using Cox proportional hazards modeling for independent prognostic factors. RESULTS: There were 63 patients with stage IA serous endometrial cancer of whom 79.4% were surgically staged. Percent RFS was 76.5% at five years while OS was 84.7% for the whole cohort. One of the 23 patients receiving VBT and chemotherapy recurred at the vagina versus four of 32 patients who were observed. Two patients in the observation group recurred in the pelvis while there were no first pelvic recurrences in the VBT and chemotherapy group (non- significant). Overall survival was 95% in the brachytherapy and chemotherapy group versus 79.6% in the observation group (non-significant). Post-operative management included observation (n=33), combination VBT and chemotherapy (n=21), or chemotherapy with or without external beam radiation therapy (EBRT) (n=9). DISCUSSION: We report one of the largest cohorts of serous endometrial cancer stage IA patients. Our results emphasize the inferior RFS and OS of stage IA serous versus endometrioid endometrial cancer patients. While some centers continue to use EBRT for these patients, our results demonstrate low pelvic recurrence rates with radiotherapy limited to VBT, as well as the high systemic risk regardless of treatment. We advocate for combination chemotherapy and brachytherapy given the poor outcomes in these patients.

Recommendations for Follow-up Care for Gynecologic Cancer Survivors.

Gynecologic cancer survivors are expected to increase in number over the coming years. This is attributable in part to an increased incidence of gynecologic malignancies as the population ages. Earlier detection and improved treatments will lead to improved survival. Women who have completed their cancer treatment and are disease-free enter a phase of follow-up care. This care can be provided by gynecologic oncologists, general gynecologists, or primary care practitioners, depending on local practices and geographic area. The key components of follow-up include complete history and physical examination. There should be judicious use of appropriate testing to detect disease recurrence, assessment, and management of therapy-related symptoms and provision of psychosocial support. Well-woman care and ongoing screening for other malignancies remain an important component of care that should not be overlooked. This review provides recommendations regarding follow-up care for women with gynecologic malignancies. There is very little high-quality evidence available to guide such care.

Incorporating ulipristal acetate in the care of symptomatic uterine fibroids: a Canadian cost-utility analysis of pharmacotherapy management.

OBJECTIVE: To present a Canadian economic evaluation on the cost-utility of ulipristal acetate (5 mg orally daily) compared to leuprolide acetate (3.75 mg intramuscular monthly) in the treatment of moderate-to-severe symptoms of uterine fibroids in women eligible for surgery. METHODS: A probabilistic decision tree was constructed to model the pre-operative pharmacological management of uterine fibroids under the primary perspective of the Ontario public payer. The model parameterized data from clinical trials, observational studies, and public costing databases. The outcome measure was the incremental cost-utility ratio. Uncertainty in the model was explored through sensitivity and scenario analyses. RESULTS: Ulipristal was associated with faster control of excessive menstrual bleeding, fewer symptoms of hot flashes and lower health care resource consumption. The ulipristal strategy dominated leuprolide as it provided patients with more quality-adjusted life years (0.177 versus 0.165) at a lower cost ($1,273 versus $1,366). Across a range of sensitivity analyses, the results remained robust except to the dose of the comparator drug. If leuprolide was administered at 11.25 mg, once every 3 months, the expected cost for the leuprolide strategy would decline and the associated incremental cost-utility ratio for ulipristal would be $168/quality-adjusted life year. CONCLUSION: Ulipristal offers a unique opportunity to effectively and rapidly control menstrual bleeding in patients with uterine fibroids; thereby improving their quality of life while minimizing the probability of moderate-to-severe hot flashes that are common with leuprolide. The current economic analysis suggests that ulipristal remains the dominant strategy across extensive sensitivity analyses.

Effectiveness of the risk of malignancy index and the risk of ovarian malignancy algorithm in a cohort of women with ovarian cancer: does histotype and stage matter?

OBJECTIVE: To examine the performance of the Risk of Malignancy Index (RMI) and Risk of Ovarian Malignancy Algorithm (ROMA) by histologic subtype and stage of disease in a cohort of women with ovarian cancer. METHODS: All patients with confirmed ovarian cancer at the Princess Margaret Hospital between February 2011 and January 2013 were eligible for study inclusion. Preoperative cancer antigen 125, human epididymis protein 4, and ultrasound findings were reviewed, and the sensitivity and false-negative rates of the RMI and ROMA were determined by stage of disease and tumor histology. RESULTS: A total of 131 patients with ovarian cancer were identified. High-grade serous (HGS) histology was most frequently associated with stage III/IV disease (n = 46 [72% of stage III/IV]) vs stage I (n = 5 [11% of stage I]; P < 0.0001). Clear cell (CC) and endometrioid (EC) histology presented most commonly with stage I disease (n = 9 [20%] and n = 13 [29% of stage I cases], respectively). Median cancer antigen 125 and human epididymis protein 4 values were significantly higher for HGS than for EC or CC histology. Risk of Malignancy Index II demonstrated the highest sensitivity of the 3 RMI algorithms. All RMIs and ROMA were significantly more sensitive in predicting malignancy in patients with HGS than EC or CC histology. Risk of Malignancy Index II (n = 38) and ROMA (n = 35) exhibited sensitivities of 68% and 54% and false-negative rates of 32% and 46%, respectively, for patients with stage I disease vs sensitivities of 94% and 93% and false-negative rates of 6% and 7% for patients with stage III/IV disease. CONCLUSION: Both RMI and ROMA performed well for the detection of advanced ovarian cancer and HGS histology. These triaging algorithms do not perform well in patients with stage I disease where EC and CC histologies predominate. Clinicians should be cautious using RMI or ROMA scoring tools to triage isolated adnexal masses because many patients with stage I malignancies would be missed.

Sentinel lymph node biopsy in vulvar cancer: Systematic review, meta-analysis and guideline recommendations.

OBJECTIVES: Traditionally, treatment for early stage vulvar cancer has included removal of the primary tumor and inguinofemoral lymph node dissection (IFLD). Sentinel lymph node biopsy (SLNB) has been proposed as an alternative to IFLD for early stage vulvar cancer patients. The aim of this project was to systematically review and assess the potential for harms and benefits with the SLNB procedure in order to make recommendations regarding the adoption of the procedure, selection of patients and appropriate technique and procedures. METHODS: A working group with expertise in gynecologic oncology and health research methodology was formed to lead the systematic review and process of guideline development. MEDLINE, Embase and The Cochrane Database of Systematic Reviews were searched for relevant articles published up to September 2014. Outcomes of interest included detection, false negative, complication and recurrence rates and indicators related to pathology. Meta-analyses were conducted where appropriate. RESULTS: The evidence-base of a previously published health technology assessment was adopted. An additional search to update the HTA's evidence base located three systematic reviews, and eleven individual studies that met the inclusion criteria. According to a meta-analysis, per groin detection rate for SLNB using radiocolloid tracer and blue dye was 87% [82-92]. The false negative rate with SLNB was 6.4% [4.4-8.8], and the recurrence rates with SLNB and IFLD were 2.8% [1.5-4.4] and 1.4% [0.5-2.6], respectively. An internal and external review process elicited concerns about the necessity of performing this procedure in an appropriate organizational context. CONCLUSION: SLNB is recommended for women with unifocal tumors<4 cm and clinically non-suspicious nodes in the groin, provided that specific infrastructure and human resource needs are met. Some recommendations for appropriate techniques and procedures are also provided.

Outcomes for patients with the same disease treated inside and outside of randomized trials: a systematic review and meta-analysis.

BACKGROUND: It is unclear whether participation in a randomized controlled trial (RCT), irrespective of assigned treatment, is harmful or beneficial to participants. We compared outcomes for patients with the same diagnoses who did ("insiders") and did not ("outsiders") enter RCTs, without regard to the specific therapies received for their respective diagnoses. METHODS: By searching the MEDLINE (1966-2010), Embase (1980-2010), CENTRAL (1960-2010) and PsycINFO (1880-2010) databases, we identified 147 studies that reported the health outcomes of "insiders" and a group of parallel or consecutive "outsiders" within the same time period. We prepared a narrative review and, as appropriate, meta-analyses of patients' outcomes. RESULTS: We found no clinically or statistically significant differences in outcomes between "insiders" and "outsiders" in the 23 studies in which the experimental intervention was ineffective (standard mean difference in continuous outcomes -0.03, 95% confidence interval [CI] -0.1 to 0.04) or in the 7 studies in which the experimental intervention was effective and was received by both "insiders" and "outsiders" (mean difference 0.04, 95% CI -0.04 to 0.13). However, in 9 studies in which an effective intervention was received only by "insiders," the "outsiders" experienced significantly worse health outcomes (mean difference -0.36, 95% CI -0.61 to -0.12). INTERPRETATION: We found no evidence to support clinically important overall harm or benefit arising from participation in RCTs. This conclusion refutes earlier claims that trial participants are at increased risk of harm.

Non-radical surgery for small early-stage cervical cancer. Is it time?

OBJECTIVES: Non-radical surgery has been proposed in women with early-stage cervical cancer to reduce morbidity. Our objective was to evaluate the outcomes of women with early-stage cervical cancer treated with non-radical surgery. METHODS: Between March 1991 and July 2013, 51 women with early-stage cervical cancer underwent simple hysterectomy or cone biopsy. All patients had assessment of pelvic lymph nodes. Patient demographics, stage, perioperative complications, pathology findings and disease-free interval were collected prospectively. RESULTS: Twenty-six women had squamous cell carcinoma (SCC), 22 adenocarcinoma (AC) and 3 adenosquamous (AS) carcinoma. Thirty women were FIGO stage 1A1, 8 women IA2, and 13 women 1B1. Twenty-two (43%) and 29 (57%) women underwent simple hysterectomy and cone biopsy respectively. Median measurable tumor size was 10mm (range 2-11), and median depth of invasion was 2.0mm (range 0.1-12 mm). Lymphovascular space invasion (LVSI) was present in 18 women (35%). Surgical margins were negative in all women. Two women received adjuvant chemoradiation (one had deep stromal invasion with LVSI, and one had two micrometastases to pelvic nodes). Forty-nine women (96%) had their Foley catheter removed on the day of surgery or post-operative day 1. No intraoperative or postoperative complications occurred and the median blood loss was 100ml. Median follow-up was 21 months (range 1-112). None of the 51 women developed a recurrence during follow-up (95% CI: 0-6%). CONCLUSION: Non-radical surgery in appropriately selected early-stage cervical cancer patients results in a low complication rate and excellent oncologic outcomes. This approach seems to be a reasonable option in well-selected patients.

The fallopian tube as the origin of high grade serous ovarian cancer: review of a paradigm shift.

Research published over the past 10 years has suggested that most "ovarian cancer," and specifically the high-grade serous carcinoma (HGSC) subtype of ovarian cancer, actually originates in the fallopian tube. In this review, we examine the evidence supporting the tubal origin hypothesis for HGSC, and discuss the clinical implications of our improved understanding of the pathogenesis of ovarian cancer. We searched Medline R and Medline in-process and non-indexed citations from inception to December 15, 2012, to identify all English or French language articles discussing the origins of HGSC. Articles and findings were summarized descriptively. A step-wise transformation from normal epithelium to a lesion with the ability to invade and metastasize has been demonstrated within the fallopian tube. Intraepithelial or early invasive carcinoma of the fallopian tube is frequently identified in BRCA mutation carriers who undergo prophylactic risk-reducing salpingo-oophorectomy. In both BRCA mutation carriers and women from the general population, pre-invasive changes within the fimbriated end of the fallopian tube appear in association with early HGSC. Molecular and genetic studies, as well as in vitro and animal models, have also supported a tubal origin for HGSC. Whether the removal of fallopian tubes (salpingectomy) at the time of pelvic surgery for other reasons will lead to reductions in mortality from ovarian cancer is currently unknown, but it is an important area for future clinical research.

Les recherches publiées au cours des 10 dernières années ont laissé entendre que la plupart des « cancers de l'ovaire ¼ (et plus particulièrement le sous-type « carcinome séreux de haut grade histologique ¼ [CSHG] du cancer de l'ovaire) trouvent en fait leur origine dans la trompe de Fallope. Dans le cadre de cette analyse, nous examinons les données soutenant l'hypothèse de l'origine tubaire du CSHG et nous discutons des implications cliniques de notre compréhension améliorée de la pathogenèse du cancer de l'ovaire. Nous avons mené des recherches dans Medline R et dans les citations en traitement et non répertoriées de Medline en vue d'en tirer tous les articles publiés en anglais ou en français discutant des origines du CSHG, et ce, du début de notre étude jusqu'au 15 décembre 2012. Les articles et les constatations ont été résumés de façon descriptive. Une transformation progressive de l'épithélium normal en lésion ayant la capacité d'envahir les tissus voisins et de produire des métastases a été démontrée au sein de la trompe de Fallope. La présence d'un carcinome intraépithélial ou invasif précoce de la trompe de Fallope est fréquemment identifiée chez les porteuses de la mutation BRCA qui subissent une salpingo-ovariectomie prophylactique d'atténuation du risque. Tant chez les porteuses de la mutation BRCA que chez les femmes de la population générale, des modifications préinvasives affectant la frange ovarienne se manifestent en association avec l'apparition d'un CSHG précoce. Des études moléculaires et génétiques (ainsi que des études in vitro et menées sur des modèles animaux) ont également soutenu l'hypothèse de l'origine tubaire du CSHG. Bien que nous ne disposions toujours pas d'une réponse à la question de savoir si le retrait des trompes de Fallope (salpingectomie) au moment d'une chirurgie pelvienne effectuée pour d'autres raisons mène à une baisse du taux de mortalité attribuable au cancer de l'ovaire, elle demeure néanmoins un domaine d'intérêt important pour les futures recherches cliniques.

Systemic therapy in squamous cell carcinoma of the vulva: current status and future directions.

OBJECTIVE: The advances achieved in the surgical management of vulvar squamous cell carcinoma (SCC) have not been mirrored in systemic therapy options. The objective of this paper is to summarize current evidence regarding systemic therapy in vulvar cancer, review the latest research on the biology of this disease, and identify future strategies to improve patient management. METHODS: MEDLINE and EMBASE were searched for all relevant English-language articles from inception to December 10, 2012. Existing evidence regarding systemic therapy in vulvar SCC was synthesized descriptively, with an emphasis on prospective studies when available. Single-patient case-reports were excluded. RESULTS: We identified 12 studies of neoadjuvant chemoradiation, 8 studies of neoadjuvant chemotherapy alone, 18 studies of chemoradiation as primary therapy, 4 studies of chemotherapy in the adjuvant setting, and 8 studies of chemotherapy for recurrent or metastatic disease. Review of the biology of vulvar cancer was performed, and promising targets for the future were identified based on the two biologic pathways of disease development. New therapeutic strategies such as immune-therapy and targeted agents hold promise for the future. CONCLUSIONS: Advances in systemic therapy for vulvar SCC are urgently needed, especially in the setting of recurrent and metastatic disease. A focus on the investigation of new targeted agents is encouraged and consideration of quality of life and sexual health issues is essential. International cooperation and adaptive trial designs are required to improve outcomes for this group of traditionally under-served women.

Risks and benefits of screening asymptomatic women for ovarian cancer: a systematic review and meta-analysis.

OBJECTIVE: We performed a systematic review and meta-analysis to quantify risks and benefits of screening asymptomatic women for ovarian cancer. METHODS: We searched MEDLINE, EMBASE, CINAHL, and Cochrane CENTRAL, without language restrictions, from January 1, 1979 to February 5, 2012. Eligible studies randomly assigned asymptomatic women to screening or usual care. Two reviewers independently screened studies for eligibility, extracted data using a standardized, piloted extraction form, and assessed bias and strength of inference for each outcome using the GRADE framework. Chance-corrected agreement was calculated at each step, and disagreements were resolved through consensus. RESULTS: Ten randomized trials proved eligible. Screening did not reduce all-cause mortality (relative risk (RR)=1.0, 95% confidence interval (CI) 0.96-1.06), ovarian cancer specific mortality (RR=1.08, 95% CI 0.84-1.38), or risk of diagnosis at an advanced stage (RR of diagnosis at FIGO stages III-IV=0.86, 95% CI 0.68-1.11). Transvaginal ultrasound resulted in a mean of 38 surgeries per ovarian cancer detected (95% CI 15.7-178.1) while screening with CA-125 led to 4 surgeries per ovarian cancer detected (95% CI 2.7-4.5). Surgery was associated with severe complications in 6% of women (95% CI 1%-11%). Quality of life was not affected by screening; however, women with false-positive results had increased cancer-specific distress compared to those with normal results (odds ratio (OR)=2.22, 95% CI 1.23-3.99). CONCLUSIONS: Screening asymptomatic women for ovarian cancer does not reduce mortality or diagnosis at an advanced stage and is associated with unnecessary surgery.