First International Consensus Report on Adnexal Masses: Management Recommendations.

The First International Consensus Conference on Adnexal Masses was convened to thoroughly examine the state of the science and to formulate recommendations for clinical assessment and management. The panel included representatives of societies in the fields of gynecology, gynecologic oncology, radiology, and pathology and clinicians from Europe, Canada, and the United States. In the United States, there are approximately 9.1 surgeries per malignancy compared to the European International Ovarian Tumor Analysis center trials, with only 2.3 (oncology centers) and 5.9 (other centers) reported surgeries per malignancy, suggesting that there is room to improve our preoperative assessments. The American College of Obstetricians and Gynecologists Practice Bulletin on "Management of Adnexal Masses," reaffirmed in 2015 (Obstet Gynecol 2007; 110:201-214), still states, "With the exception of simple cysts on a transvaginal ultrasound finding, most pelvic masses in postmenopausal women will require surgical intervention." The panel concluded that patients would benefit not only from a more conservative approach to many benign adnexal masses but also from optimization of physician referral patterns to a gynecologic oncologist in cases of suspected ovarian malignancies. A number of next-step options were offered to aid in management of cases with sonographically indeterminate adnexal masses. This process would provide an opportunity to improve risk stratification for indeterminate masses via the provision of alternatives, including but not limited to evidence-based risk-assessment algorithms and referral to an "expert sonologist" or to a gynecologic oncologist. The panel believed that these efforts to improve clinical management and preoperative triage patterns would ultimately improve patient care.

Gestational Trophoblastic Disease: Opportunities for a National Registry Collaboration.

OBJECTIVE: In rare entities such as gestational trophoblastic disease (GTD), only multi-institutional registries can gather significant number of patients to build up valuable clinical databases. No Canada-wide GTD registry currently exists. We conducted a survey among members of the Canadian Society of Gynecologic Oncology (GOC) to investigate their interest in a pan-Canadian GTD registry. We also took the opportunity to explore their management of GTD. METHODS: An electronic survey was conducted. The target group was the entire GOC Canadian Membership. The survey consisted of 25 questions. RESULTS: The survey participation rate was 39% (67/171). Seventy-six percent of responders treat patients with molar pregnancy or gestational trophoblastic neoplasia (GTN), and the majority treat only 5 or less cases of molar pregnancy and 5 or less cases of GTN per year. In cases of low-risk GTN, 80% of responders use generally recommended single-agent chemotherapy regimens. In cases of high-risk GTN, 76% use generally recommended multiagent chemotherapy regimens. Most respondents do not submit either molar pregnancy or GTN patients to any formal registry, although the vast majority (92%) would do so if they had access to a registry, given that most believe that a registry can or probably can help patients with GTD. Responders indicated that the jurisdiction of such a registry should be national (59%), provincial (25%), and regional (11%). CONCLUSIONS: Despite some variation, responders were generally knowledgeable about contemporary management issues. Canadian Society of Gynecologic Oncology members acknowledge generally low exposure to GTD patients in Canada and support the creation of a national GTD registry to facilitate optimal patient care, education, and research.

Placental Molar Disease: What are the Benefits and Barriers to the Adoption of a Comprehensive Diagnostic Service?

The molecular cytogenetic analysis of specimens (genotyping) suspicious for hydatidiform mole (HM) significantly improves diagnostic accuracy over histopathology and immunohistochemical analysis alone, particularly in the classification of partial mole. However, the implementation of this advance in diagnostics has been slow. This study sought to identify the major benefit and potential barriers to the adoption of genotyping. A pilot Placental Molar Diagnostic (PMD) Service was established combining histopathology, p57 immunohistochemistry, and molecular genotyping analysis for both in-house and referred-in cases suspicious for HM or with a preliminary diagnosis of HM. A retrospective analysis of 117 cases received in the first 16 mo was conducted to identify the utility of the PMD Service and factors or barriers which precluded optimal results. A final diagnosis of HM was made in 73 cases (37 complete HMs and 36 partial HMs). The remaining 44 cases were hydropic abortuses. Three potential barriers were identified that could lead to less than optimal results from a PMD Service: prevalence of noninformative genotyping, lack of any available or appropriate paraffin blocks, and inappropriate deferral of genotyping. The major utility of this pilot PMD Service was to increase the specificity of a diagnosis of HM, and avoid unnecessary clinical follow-up in 37% of cases with an initial suspicion or diagnosis of HM. Measures can be undertaken to address potential barriers to the implementation of a comprehensive placental diagnostic platform. Underutilization of molecular genotyping in the diagnosis of HM likely leads to inappropriate management and "downstream" costs in a significant proportion of patients suspected of having HM.

Malignant Melanoma of Vulva and Vagina: A Histomorphological Review and Mutation Analysis--A Single-Center Study.

OBJECTIVES: The aim of this work was to determine molecular characteristics and specifically, the frequency of BRAF, C-KIT, and NRAS mutations in vulvar and vaginal melanomas. METHODS: A retrospective review of all cases of vulvar and vaginal melanoma between 2002 and 2013 was performed. We reviewed the clinical and histological characteristics of all cases and performed genotyping studies on cases that had tissue available for the study, using next-generation sequencing. RESULTS: We identified 33 vulvar and 11 vaginal melanomas in women with mean ages 58 and 61 years, respectively. Next-generation sequencing analysis on 20 cases (15 vulvar and 5 vaginal) identified a BRAF mutation in 7.6%, C-KIT mutation in 27.6%, NRAS mutation in 27.6%, and TP53 mutation in 7.6% of the vulvar cases. We detected only a single TP53 mutation in the vaginal cases. We did not identify any statistically significant relationship between the mutation status and patients' outcome, depth of invasion, ulceration, stage at presentation, or lymph node metastasis. CONCLUSIONS: BRAF mutations are infrequent, whereas C-KIT and NRAS mutations are seen with higher frequency in vulvar melanomas than melanomas of other sites. These mutations can be considered as potential therapeutic targets in patients harboring them. Further studies are necessary to increase our understanding of mutational events occurring in melanoma of the lower female genital tract and their relationship with clinical parameters/outcome.

The impacts of neoadjuvant chemotherapy and of debulking surgery on survival from advanced ovarian cancer.

OBJECTIVES: Women with advanced ovarian cancer are treated with chemotherapy either before (neoadjuvant) or after surgery (primary debulking). The goal is to leave no residual disease post-surgery; for women treated with primary debulking surgery this has been associated with an improvement in survival. It has not been shown that the survival advantage conferred by having no residual disease post-surgery is present for women who receive neoadjuvant chemotherapy. METHODS: We reviewed the records of 326 women with stage IIIc or IV serous ovarian cancer. We determined if they received neoadjuvant chemotherapy or primary debulking surgery and we measured the extent of residual disease post-surgery. We estimated seven-year survival rates for women after various treatments. RESULTS: Women who had neoadjuvant chemotherapy were more likely to have no residual disease than women who had primary debulking surgery (50.1% versus 41.5%; p=0.03) but they experienced inferior seven-year survival (8.6% versus 41%; p<0.0001). Among women who had primary debulking surgery, those with no residual disease had much better seven-year survival than women who had any residual disease (73.6% versus 21.0%; p<0.0001). Women who had no residual disease after debulking surgery and who received intraperitoneal chemotherapy had a seven-year survival of 90%. CONCLUSIONS: Neoadjuvant chemotherapy should be reserved for ovarian cancer patients who are not candidates for primary debulking surgery. Among women with no residual disease after primary debulking surgery, intraperitoneal chemotherapy extends survival.

Surgical management of a suspicious adnexal mass: a systematic review.

OBJECTIVE: To systematically review the existing literature in order to determine the optimal recommended protocols for the surgical management of adnexal masses suspicious for apparent early stage malignancy. METHODS: A review of all systematic reviews and guidelines published between 1999 and 2009 was conducted as a first step. After the identification of two systematic reviews on the topic, searches of MEDLINE for studies published since 2004 were also conducted to update and supplement the evidentiary base. RESULTS: The updated literature search identified 31 studies that met the inclusion criteria. A bivariate random effects analysis of 15 frozen section diagnosis studies yielded an overall sensitivity of 89.2% (95% CI, 86.3 to 91.5%) and specificity of 97.9% (95% CI, 96.6 to 98.7%). The surgical evidence suggests that systematic lymphadenectomy and proper surgical staging improve survival. Conservative fertility-preserving surgical approaches are an acceptable option in women with low malignant potential tumours. The accuracy and the adequacy of surgical staging by laparotomy or laparoscopic approaches appear to be comparable, with neither approach conferring a survival advantage. Intraoperative tumour rupture was indeed reported to occur more frequently in patients undergoing laparoscopy versus laparotomy in two retrospective cohort studies. CONCLUSIONS: The best available evidence was collected and included in this rigorous systematic review. The abundant evidentiary base provided the context and direction for the surgical management of adnexal masses suspicious for apparent early stage malignancy.

Preoperative identification of a suspicious adnexal mass: a systematic review and meta-analysis.

OBJECTIVE: To systematically review the existing literature in order to determine the optimal strategy for preoperative identification of the adnexal mass suspicious for ovarian cancer. METHODS: A review of all systematic reviews and guidelines published between 1999 and 2009 was conducted as a first step. After the identification of a 2004 AHRQ systematic review on the topic, searches of MEDLINE for studies published since 2004 was also conducted to update and supplement the evidentiary base. A bivariate, random-effects meta-regression model was used to produce summary estimates of sensitivity and specificity and to plot summary ROC curves with 95% confidence regions. RESULTS: Four meta-analyses and 53 primary studies were included in this review. The diagnostic performance of each technology was compared and contrasted based on the summary data on sensitivity and specificity obtained from the meta-analysis. Results suggest that 3D ultrasonography has both a higher sensitivity and specificity when compared to 2D ultrasound. Established morphological scoring systems also performed with respectable sensitivity and specificity, each with equivalent diagnostic competence. Explicit scoring systems did not perform as well as other diagnostic testing methods. Assessment of an adnexal mass by colour Doppler technology was neither as sensitive nor as specific as simple ultrasonography. Of the three imaging modalities considered, MRI appeared to perform the best, although results were not statistically different from CT. PET did not perform as well as either MRI or CT. The measurement of the CA-125 tumour marker appears to be less reliable than do other available assessment methods. CONCLUSION: The best available evidence was collected and included in this rigorous systematic review and meta-analysis. The abundant evidentiary base provided the context and direction for the diagnosis of early-staged ovarian cancer.

Teaching cervical cancer surgery in low- or middle-resource countries.

BACKGROUND: With the widespread implementation of screening programs internationally, there will be an increase in early stage cervical cancer cases. In response to this, the Ministry of Health in each country will need to plan strategies to provide care such as radical surgery or radiation for this potentially curable group of women. METHODS: The Gynaecologic Oncologists of Canada created a teaching module to intensively train a small number of locally identified gynecologists to perform radical hysterectomy and pelvic lymphadenectomy. The process was based on adult learning principles; it involved a Canadian gynecologic oncologist working in the low- or middle-resource country with the gynecologists and problem-solving local issues in health care delivery. RESULTS: The teaching process included a pretest and a posttest on the basis of the objectives of the module. There were 7 modules including preoperative evaluation of the patient, cone biopsy, radical hysterectomy, pelvic lymphadenectomy, ureteric injury, vascular injury, and follow-up after surgery. Each module was divided into background information, techniques, and complications. There were video clips imbedded in the modules. After the educational modules had been reviewed, the learners were walked through the surgical procedures repeatedly including a detailed assessment of performance after each case. Participants had the opportunity to provide feedback on the training program. The module was reviewed in Mongolia and implemented in Kenya. CONCLUSIONS: In low- and middle-resource countries where there is an urgent need to provide a curative surgical option for the management of early cervical cancer, a focused high-intensity curriculum delivered by a trained surgeon can translate into immediate change in clinical and surgical practice.

Multicentre study on factors affecting the gynaecologic oncology career choice of canadian residents in obstetrics and gynaecology.

INTRODUCTION: The provision of optimal care for women with gynaecologic cancer may be threatened due to the changing demographics of patients and the projected increasing shortage of gynaecologic oncologists in Canada. We evaluated the career plans of Canadian residents in obstetrics and gynaecology to determine the proportion of residents currently considering a career in gynaecologic oncology (GO) and to explore factors that may affect their career decisions. METHODS: Following institutional ethics approval, all residents at 13 participating Canadian obstetrics and gynaecology residency training programs were contacted by email to complete a 20-item confidential questionnaire examining career plans. Quantitative data were analyzed using SAS v9.1. Qualitative data were coded by theme and grouped into various domains. RESULTS: Of 293 residents, 105 (36%) participated. More than half of these were considering at least one obstetrics and gynaecology subspecialty, but 53% indicated that their most appealing career path was general obstetrics and gynaecology. Although 50% of residents had ever considered a career in GO, only 17% were considering a GO career at the time of the survey. When rated as positive influences, medical school exposure, resident exposure, role models within GO, colleagues, other health care professionals, "my individual life circumstances," "my personal attributes," the clinical, research, and educational components of GO, the GO patient population, and relation with gynaecologic oncologists and other specialists were significant predictors of current GO interest. Themes that emerged from qualitative analysis revealed that the clinical, professional, and research domains were predominant influences among residents currently considering a career in GO. CONCLUSIONS: GO is an infrequent career choice for Canadian residents in obstetrics and gynaecology, and a number of factors significantly affect GO career decisions. Modifying factors such as educational experiences, work environment, and current practice models may lead to improved recruitment to the subspecialty, which is crucial for meeting the future needs of women with gynaecologic malignancies in Canada.

Evaluation of an intraperitoneal chemotherapy program implemented at the Princess Margaret Hospital for patients with epithelial ovarian carcinoma.

OBJECTIVE: A prospective evaluation of an ambulatory intraperitoneal (IP) /intravenous (IV) chemotherapy regimen for women with epithelial ovarian carcinoma (EOC). METHODS: Cisplatin 100 mg/m(2) (option for 75 mg/m(2)) IP combined with paclitaxel 175 mg/m(2) IV (3 h infusion) administered every 21 days was adopted by our institution as a single day, outpatient regimen for women with stage III EOC who had undergone optimal cytoreductive (

Epithelial ovarian cancer surgical staging by Ontario gynaecologic surgeons: is there a gap between current practice and the Canadian clinical practice guidelines?

OBJECTIVES: By determining, through self-report, Ontario gynaecologic surgeons' practices regarding surgical staging for epithelial ovarian cancer, this study aimed to quantify the gap between current practice and the ideal practice of surgical staging for ovarian cancer, as defined by the corresponding Canadian clinical practice guidelines. METHODS: All 711 active Ontario gynaecologic surgeons identified from the website of the College of Physicians and Surgeons of Ontario were confidentially surveyed by mail, using a structured questionnaire to explore individuals' surgical management of an adnexal mass suspicious for epithelial ovarian cancer, using a clinical case simulation. Specifically, gynaecologic surgeons' adherence to the CPGs was determined by self-report, and various physician characteristics were explored for potential associations with adherence to the CPGs in the clinical case simulation using the Fisher exact test. RESULTS: The survey response rate was 69.8%. Only 44.3% of Ontario gynaecologic surgeons adhered to the CPGs in their responses to the clinical case simulation. Gynaecologic oncologists were more likely than non-oncologists to self-report surgical staging according to the CPGs during the clinical case simulation (P = 0.0004). Adherence was also significantly associated with practice at a university centre (P = 0.013) and practice at a centre with a gynaecologic oncologist (P = 0.001) but was not associated with surgical volume. CONCLUSION: This study has confirmed that a significant gap exists between current practice and the ideal practice of surgical staging for epithelial ovarian cancer in Ontario, as defined by the corresponding Canadian CPGs. Further investigation will explore potential barriers to optimal practice to facilitate the development of a knowledge translation strategy to improve surgical staging for ovarian cancer in Ontario.

Maternal luteoma of pregnancy presenting with virilization of the female infant.

BACKGROUND: Virilization in female newborns typically results from congenital adrenal hyperplasia, requiring immediate diagnosis and treatment. We report a rare cause of virilization, maternal pregnancy luteoma, responsible for virilization of both a newborn and the mother. Luteomas are usually asymptomatic tumour-like ovarian lesions of pregnancy that secrete androgens in only 25% of cases. Many female infants born to masculinized mothers will also be virilized. CASE: A term infant born with ambiguous genitalia was transferred to a referral centre for investigation, diagnosis, and treatment. Assessment identified Prader II-III genitalia, an elevated serum testosterone level, a normal serum 17-hydroxyprogesterone level, and a normal female karyotype (46,XX). The mother had had virilization from the second trimester and was found to have an elevated serum testosterone level. Pelvic ultrasound assessment in the mother showed a complex right ovarian mass. Laparotomy was performed, and the mass was excised. Histopathology examination confirmed a luteoma. CONCLUSION: High maternal serum testosterone levels due to a luteoma can result in virilization in the female newborn. This report emphasizes the need to consider possible underlying maternal pathology in evaluating a virilized female infant.

Identifying educationally influential specialists: issues arising from the use of "classic" criteria.

INTRODUCTION: Educationally influential physicians (EIPs) are identified by their colleagues as people who (1) encourage learning and enjoy sharing their knowledge, (2) are clinical experts and always seem up to date, and (3) treat others as equals. We aimed to identify surgical and pathologist EIPs for colorectal cancer (CRC) in Ontario as part of a blended knowledge transfer program. METHODS: A population-based cohort of surgeons (n = 794) and pathologists (n = 449) were sent surveys modeled on the Hiss method for identifying EIPs. Four formal mailings (including incentives) and telephone calls and faxes were completed. This labor-intensive process identified "general" EIPs and surgery or pathology EIPs for CRC. The characteristics of EIPs in these groups were studied. RESULTS: The response rate was 41% for surgeons and 42% for pathologists. One hundred eighteen general EIPs were identified and substantially more surgical EIPs for CRC (n = 63) than pathology EIPs for CRC (n = 6) were recognized. Forty-two of 81 medical centers in Ontario identified an EIP We also identified a cohort of "domain experts, " physicians whose opinion was valued for CRC but who did not meet the Hiss EIP criteria. This cohort of "domain experts" was larger than the cohort of ElPs for CRC for both surgeons (63 vs. 154) and pathologists (6 vs. 154). DISCUSSION: In this population study, we identified EIPs for CRC using the Hiss method, although significantly more surgical than pathology EIPs for CRC were recognized. The educational influence of domain experts who do not fulfill the Hiss characteristics compared with EIPs for CRC remains to be determined.

Follow-up after primary therapy for endometrial cancer: a systematic review.

OBJECTIVE: To determine the optimum follow-up of women who are clinically disease-free following potentially curative treatment for endometrial cancer. METHODS: A systematic search of MEDLINE, EMBASE and the Cochrane Library databases (1980 to October 2005) was conducted. Data were pooled across trials to determine overall estimates of recurrence patterns. RESULTS: Sixteen non-comparative retrospective studies were identified. The overall risk of recurrence was 13% for all patients and 3% or less for patients at low risk. Approximately 70% of all recurrences were symptomatic, and 68% to 100% of recurrences occurred within approximately the first 3 years of follow-up. No reliable differences in survival were detected between patients with symptomatic or asymptomatic recurrences nor were differences in patient outcomes reported by type of follow-up strategy employed. Detection of asymptomatic recurrences ranged from 5% to 33% of patients with physical examination, 0% to 4% with vaginal vault cytology, 0% to 14% with chest X-ray, 4% to 13% with abdominal ultrasound, 5% to 21% with abdominal/pelvic CT scan, and 15% in selected patients with CA 125. CONCLUSIONS: There is limited evidence to inform whether intensive follow-up schedules with multiple routine diagnostic interventions result in survival benefits any more or less than non-intensive follow-up schedules without multiple routine diagnostic interventions. Routine testing seems to be of limited benefit for patients at low risk of disease. Most recurrences tend to occur in high risk patients within 3 years, and most recurrences involve symptoms. The most appropriate follow-up strategy is likely one based upon the risk of recurrence and the natural history of the disease. Counseling on the potential symptoms of recurrence is extremely important because the majority of patients with recurrences were symptomatic. A proposed routine follow-up schedule is offered.

Who should operate on patients with ovarian cancer? An evidence-based review.

OBJECTIVE: To evaluate the relationship between surgical specialty and survival in patients receiving initial surgical management for ovarian epithelial cancer. STUDY METHODS: An analytic framework was constructed to address the principle question 'does the type of surgeon operating on patients with newly diagnosed ovarian epithelial cancer influence survival?' A literature search addressing the components of this analytic framework was carried out using the Cochrane Library, Medline, EMBASE, and HealthSTAR databases. Relevant articles were selected and graded using U.S. Preventive Services Task Force and Canadian Task Force guidelines. Results were summarized by quality as well as level of evidence. RESULTS: Eighteen studies were reviewed. The quality of evidence was good in 3, fair in 8, and poor in 7 of the studies. The most common study flaws encountered were 'failure to account for confounders' and 'incompleteness of data'. In studies focusing on advanced disease, there was good quality evidence to support a 6- to 9-month median survival benefit for patients operated on by gynecologic oncologists rather than general gynecologists and/or general surgeons (P values 0.009 to 0.01). Studies focusing on early stage disease found gynecologic oncologists more likely to carry out optimal staging (P values 0.001 to 0.01). Increased survival could be explained by improved identification of true stage I patients. CONCLUSION: Patients receiving initial surgical management for ovarian epithelial cancer should be operated on by gynecologic oncologists.

Slide review in gynecologic oncology ensures completeness of reporting and diagnostic accuracy.

OBJECTIVE: We reviewed patient records in our tertiary care teaching hospital to assess the value of the mandatory slide review policy in gynecologic oncology with emphasis on completeness of reports. METHODS: Cases reviewed between October 2001 to September 2002 were studied. Clinical information was gathered from discussions at the weekly tumor board and from chart review. The standardized reporting guidelines in benchmark surgical pathology textbooks were used to assess the completeness of original pathology reports of excisional specimens. Diagnostic discrepancies were classified as major if the resultant change led to alteration of management or minor if it did not. RESULTS: Three hundred fifty-one cases were reviewed; 173 biopsies and 178 excisional specimens. Only 140 (78.7%) of the original pathology reports of the latter group conformed to standardized reporting guidelines. Of the 38 incomplete reports, 18 were missing critical information necessary for planning of further therapy, representing 10.1% of reports of all excisional specimens. We agreed with the original diagnosis in 252 cases (71.8%). Minor discrepancies were noted in 70 (19.9%) and major discrepancies in 29 cases (8.3%). No major discrepancy resulted from reviewing any of the vulvar specimens or cases that were already reviewed by gynecologic pathologists of other academic institutes. CONCLUSION: Mandatory slide review in gynecologic oncology is an important component in the management of gynecologic cancer patients because it completes reporting on missing parameters required for planning subsequent therapy in 10.1% of cases and recognizes discrepancies altering management in 8.3% of patients.