Information needs of Lynch syndrome and BRCA 1/2 mutation carriers considering risk-reducing gynecological surgery: a qualitative study of the decision-making process.

BACKGROUND: Risk-reducing gynecological surgery (RRGS) is a prophylactic procedure that may be offered to BRCA1, BRCA2, and Lynch syndrome (LS) mutation carriers to reduce the risk of developing gynecological cancer. This study was conducted to better understand patients' information needs and evaluate how patients weigh different sources of information in their decision-making process surrounding RRGS. METHODS: This study used a qualitative approach to understanding women's perspectives towards RRGS. Semi-structured interviews were conducted virtually with 8 women. Women offered RRGS between 35 and 70 years of age who are English-speaking and have an identifiable BRCA or LS mutation were included. Data from interviews was coded with constant comparative analysis to develop themes. RESULTS: Of the eight women, six had selected to undergo either prophylactic hysterectomy or oophorectomy: 5 decided yes to RRGS; 1 decided no; 2 were undecided. Thematic analysis found that the key factors affecting women's decisions around prophylactic surgery were cancer risk, surgical menopause, and psychological readiness. To make an informed decision, women relied most heavily on information provided by healthcare professionals (e.g. doctors, genetic counselors) and family members with prior cancer experience. However, some women reported that they did not feel adequately informed enough to make a decision and identified COVID-19 as a significant barrier affecting access to information. CONCLUSION: This qualitative study revealed the key sources of information influencing attitudes regarding RRGS and how women consulted different sources of information to reach a decision. Results underscore the need for greater attention to women's information needs in the context of psychological readiness, particularly amidst the pandemic. Research involving a larger sample size may help to better inform how support can be provided to individuals with BRCA and LS mutations considering RRGS.

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.

Palliative care utilization across health sectors for patients with gynecologic malignancies in Ontario, Canada from 2006 to 2018.

OBJECTIVE: Early palliative care (PC) is associated with improved patient quality of life, less aggressive end-of-life care, and prolonged survival. We evaluated patterns of PC delivery in gynecologic oncology. METHODS: We conducted a population-based, retrospective cohort study of gynecologic cancer decedents in Ontario from 2006 to 2018 using linked administrative health care data. RESULTS: The cohort included 16,237 decedents; 51.1% died of ovarian cancer, 30.3% uterine cancer, 12.1% cervical cancer, and 6.5% vulvar/vaginal cancers. Palliative care was most often delivered in the hospital inpatient setting in 81%, and 53% received specialist PC. PC was first received during hospital admission in 53%, and by outpatient physician care in only 23%. Palliative care was initiated a median 193 days prior to death, with the lowest two quintiles initiating care ≤70 days before death. The average user of PC resources (third quintile) received 68 days of PC. While cumulative use of community PC gradually increased over the final year of life, institutional palliative care use exponentially rose from 12 weeks until death. On multivariable analyses, predictors of initiating palliative care during a hospital admission included age ≥70 years at death, ≤3 month cancer survival, having cervical or uterine cancer, not having a primary care provider, or being in the lowest 3 income quintiles. CONCLUSION: Most palliative care is initiated and delivered during hospital admission, and is initiated late in a significant proportion. Strategies to increase access to anticipatory and integrated palliative care may improve the quality of the disease course and the end of life.

Canadian Guideline on the Management of a Positive Human Papillomavirus Test and Guidance for Specific Populations.

The purpose of this paper is to provide evidence-based guidance on the management of a positive human papilloma virus (HPV) test and to provide guidance around screening and HPV testing for specific patient populations. The guideline was developed by a working group in collaboration with the Gynecologic Oncology Society of Canada (GOC), Society of Colposcopists of Canada (SCC), and the Canadian Partnership Against Cancer. The literature informing these guidelines was obtained through a systematic review of relevant literature by a multi-step search process led by an information specialist. The literature was reviewed up to July 2021 with manual searches of relevant national guidelines and more recent publications. The quality of the evidence and strength of recommendations were developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. The intended users of this guideline include primary care providers, gynecologists, colposcopists, screening programs, and healthcare facilities. The implementation of the recommendations will ensure an optimum implementation of HPV testing with a focus on the management of positive results. Recommendations for appropriate care for underserved and marginalized groups are made.

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.

Inguinofemoral sentinel lymph node biopsy by scar injection in vulvar cancer: an assessment of feasibility and long-term outcomes.

BACKGROUND: Performing inguinofemoral sentinel lymph node biopsy for vulvar cancer following a previous vulvar excision, often referred to as 'scar injection', is debated. OBJECTIVE: To assess the feasibility of sentinel lymph node biopsy following scar injection and the long-term outcomes in patients undergoing this procedure. METHODS: We conducted a retrospective observational cohort study of patients with vulvar cancer. We assessed detection rates and outcomes in patients who underwent sentinel lymph node biopsy by scar injection and compared them with patients who had injection around a visible tumor and with patients who had an inguinofemoral lymphadenectomy following previous vulvar excision. Sentinel node detection rates are described per patient and per groin and are compared using Χ2 analysis. Cox regression analysis was used to assess the association of recurrence and survival with surgical technique and recognized pathological variables. RESULTS: Data were analyzed for 173 groins in 97 patients. At least one sentinel lymph node was detected in 162 (94%) groins examined, and detection rate did not differ whether the groin was assessed following tumor injection (n=122, 94%) or scar injection (n=40, 93%; p=0.85). Patients in the scar-injection group had less frequent lymph node metastases (p<0.02), smaller tumors (p<0.001), and more superficial invasion (p<0.02). Median follow-up was 34.7 months (range 0-108). Scar injection was not independently associated with recurrence or death on multivariable analysis, and depth of invasion was the only independent predictor of disease recurrence (hazards ratio (HR)=1.14, p=0.03). Recurrence and survival were also comparable for patients who had a sentinel lymph node biopsy or inguinofemoral lymphadenectomy following previous vulvar excision (log rank p=0.30; p=0.67). CONCLUSIONS: Sentinel lymph node biopsy by scar injection is feasible and demonstrates similar long-term outcomes in patients having scar or tumor injections, and in patients following previous tumor excision undergoing sentinel lymph node biopsy or lymphadenectomy.

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.

Brief family history questionnaire to screen for Lynch syndrome in women with newly diagnosed non-serous, non-mucinous ovarian cancers.

OBJECTIVES: While ovarian cancer is the third most common Lynch syndrome-associated cancer in women, there is no established screening strategy to identify Lynch syndrome in this population. The objective of this study was to assess whether the 4-item brief Family History Questionnaire can be used as a screening tool to identify women with ovarian cancer at risk of Lynch syndrome. METHODS: In this prospective cohort study, participants with newly diagnosed non-serous, non-mucinous ovarian cancer completed the brief Family History Questionnaire, extended Family History Questionnaire, and had tumors assessed with immunohistochemistry for mismatch repair proteins, MLH1 methylation, and microsatellite instability testing. All underwent universal germline testing for Lynch syndrome. Performance characteristics were compared between the brief Family History Questionnaire, extended Family History Questionnaire, immunohistochemistry±MLH1 methylation, and microsatellite instability testing. RESULTS: Of 215 participants, 169 (79%) were evaluable with both the brief Family History Questionnaire and germline mutation status; 12 of these 169 were confirmed to have Lynch syndrome (7%). 10 of 12 patients (83%) with Lynch syndrome were correctly identified by the brief Family History Questionnaire, compared with 6 of 11 (55%) by the extended Family History Questionnaire, 11 of 13 (85%) by immunohistochemistry±MLH1 methylation, and 9 of 11 (82%) by microsatellite instability testing. The sensitivity, specificity, positive predictive values, and negative predictive values of the brief Family History Questionnaire were 83%, 65%, 15%, and 98%, respectively. A combined approach with immunohistochemistry and the brief Family History Questionnaire correctly identified all 12 patients with Lynch syndrome. The brief Family History Questionnaire was more sensitive than the extended Family History Questionnaire and took <10 min for each patient to complete. CONCLUSIONS: The brief Family History Questionnaire alone or combined with immunohistochemistry may serve as an adequate screening strategy, especially in centers without access to universal tumor testing.

Estrogen receptor-positive adenocarcinoma of the cervix presenting during pregnancy: Two case reports and review of the literature.

The incidence of adenocarcinoma of the cervix in pregnancy is exceptionally rare, and thus there is no consensus on its management. Here, we report two cases of adenocarcinoma of the cervix diagnosed in the context of pregnancy. In our first case, a patient referred to colposcopy for atypical glandular cells of undetermined significance was subsequently diagnosed with well differentiated endocervical adenocarcinoma on cone biopsy. Just prior to the cone biopsy, she was incidentally found to have a first trimester pregnancy loss. The patient subsequently underwent a radical hysterectomy and bilateral sentinel lymph node dissection. Final pathology revealed a stage 1B1 (FIGO 2009) well differentiated adenocarcinoma of the cervix. Interestingly, the tumour was positive for estrogen receptor, which is unusual for cervical adenocarcinoma. In our second case, a patient presented with a pedunculated, exophytic cervical neoplasm at 31 weeks GA with self-limiting antepartum hemorrhage. The primary lesion measured 52 mm in diameter on MRI and was amputated at the base during the patient's elective repeat cesarean section. Final pathology revealed a stage IB2 (FIGO 2009) mucinous adenocarcinoma of the cervix. The patient subsequently underwent a radical hysterectomy and bilateral pelvic lymph node dissection 17 weeks after initial presentation. The depth of invasion was 2.2 mm, restricted to the inner third of the cervical wall, and there was no lymphovascular space invasion in the surgical specimen. Surgical margins, parametria, and lymph nodes were all negative for adenocarcinoma. This tumour was also found to be estrogen receptor/progesterone receptor (ER/PR) positive, again unusual for cervical adenocarcinoma. P16 was strongly positive and HPV DNA studies were also positive for human papilloma virus 18. The patient received adjuvant external beam radiotherapy to the pelvis and currently remains in remission.

Maximizing cancer prevention through genetic navigation for Lynch syndrome detection in women with newly diagnosed endometrial and nonserous/nonmucinous epithelial ovarian cancer.

BACKGROUND: Despite recommendations for reflex immunohistochemistry (IHC) for mismatch repair (MMR) proteins to identify Lynch syndrome (LS), the uptake of genetic assessment by those who meet referral criteria is low. The authors implemented a comprehensive genetic navigation program to increase the uptake of genetic testing for LS in patients with endometrial cancer (EC) or nonserous/nonmucinous ovarian cancer (OC). METHODS: Participants with newly diagnosed EC or OC were prospectively recruited from 3 cancer centers in Ontario, Canada. Family history questionnaires were used to assess LS-specific family history. Reflex IHC for MMR proteins was performed with the inclusion of clinical directives in pathology reports. A trained genetic navigator initiated a genetic referral on behalf of the treating physician and facilitated genetic referrals to the closest genetics center. RESULTS: A total of 841 participants (642 with EC, 172 with OC, and 27 with synchronous EC/OC) consented to the study; 194 (23%) were MMR-deficient by IHC. Overall, 170 women (20%) were eligible for a genetic assessment for LS: 35 on the basis of their family history alone, 24 on the basis of their family history and IHC, 82 on the basis of IHC alone, and 29 on the basis of clinical discretion. After adjustments for participants who died (n = 6), 149 of 164 patients (91%) completed a genetic assessment, and 111 were offered and completed genetic testing. Thirty-four women (4.0% of the total cohort and 30.6% of those with genetic testing) were diagnosed with LS: 5 with mutL homolog 1 (MLH1), 9 with mutS homolog 2 (MSH2), 15 with mutS homolog 6 (MSH6), and 5 with PMS2. CONCLUSIONS: The introduction of a navigated genetic program resulted in a high rate of genetic assessment (>90%) in patients with gynecologic cancer at risk for LS.

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.

Understanding the clinical implication of mismatch repair deficiency in endometrioid endometrial cancer through a prospective study.

OBJECTIVES: Findings on impact of mismatch repair deficiency (MMRd) on patient outcomes in endometrial cancer (EC) have been inconsistent to date. The objective of this study was to compare the oncologic outcomes and recurrence patterns between MMRd and MMR-intact (MMRi) endometrioid EC (EEC). METHODS: Between 2015 and 2018, we prospectively recruited 492 EEC cases from three cancer centers in Ontario, Canada. Tumors were reflexively assessed for MMR protein expression by immunohistochemistry (IHC). Clinicopathological, survival and recurrence patterns were compared between MMRd and MMRi cases. RESULTS: Of 492 EEC, 348 were MMRi (71%) and 144 were MMRd (29%) with median follow-up of 16.8 months (0-69.6). MMRd tumors tended to be grade 2 or 3 (56% vs. 29%, p < 0.001), with propensity for lymphovascular space invasion (28% vs. 18%, p = 0.024), lymph node involvement (7% vs. 5%, p < 0.001) and received more adjuvant treatment (46% vs. 33%, p = 0.027). This group also had significantly lower 3-year recurrence-free survival (78% vs. 90%, p = 0.014) although there was no difference in OS (p = 0.603). MMRd cases were more likely to recur in retroperitoneal lymph nodes (p = 0.045). Upon subgroup analysis, MLH1 methylated tumors had the worst prognostic features and survival outcomes. CONCLUSIONS: MLH1 methylated EECs exhibit more aggressive features compared to other MMRd and MMRi EECs. This may indicate an inherent difference in tumor biology, suggesting the importance of individualized management based on EC molecular phenotype.

Directive clinique no 408 : Prise en charge des maladies gestationnelles trophoblastiques.

OBJECTIF: Cette directive passe en revue l'évaluation clinique et la prise en charge des maladies gestationnelles trophoblastiques, notamment les traitements chirurgicaux et médicamenteux des tumeurs bénignes, prémalignes et malignes. L'objectif de la présente directive clinique est d'aider les fournisseurs de soins de santé à rapidement diagnostiquer les maladies gestationnelles trophoblastiques, à normaliser les traitements et le suivi et à assurer des soins spécialisés précoces aux patientes dont l'atteinte est maligne ou métastatique. PROFESSIONNELS CONCERNéS: Gynécologues généralistes, obstétriciens, médecins de famille, sages-femmes, urgentologues, anesthésistes, radiologistes, anatomopathologistes, infirmières autorisées, infirmières praticiennes, résidents, gynécologues-oncologues, oncologues médicaux, radio-oncologues, chirurgiens, omnipraticiens en oncologie, infirmières en oncologie, pharmaciens, auxiliaires médicaux et autres professionnels de la santé qui traitent des patientes atteintes d'une maladie gestationnelle trophoblastique. La présente directive vise également à fournir des renseignements aux parties intéressées qui prodiguent des soins de suivi à ces patientes après le traitement. POPULATION CIBLE: Femmes en âge de procréer atteintes d'une maladie gestationnelle trophoblastique. OPTIONS: Les femmes ayant reçu un diagnostic de maladie gestationnelle trophoblastique doivent être orientées vers un gynécologue afin qu'il réalise une évaluation initiale, envisage une intervention chirurgicale primaire (évacuation ou hystérectomie) et effectue un suivi. Il y a lieu d'orienter les femmes ayant reçu un diagnostic de tumeur trophoblastique gestationnelle vers un gynécologue-oncologue afin qu'il effectue la stadification tumorale, établisse le score de risque et envisage l'intervention chirurgicale primaire ou un traitement systémique (mono- ou polychimiothérapie) et la nécessité d'éventuels traitements supplémentaires. Il est recommandé de discuter de chaque cas de néoplasie gestationnelle trophoblastique lors d'une réunion multidisciplinaire de cas oncologiques et de l'inscrire dans une base de données centralisée (régionale et/ou nationale). DONNéES PROBANTES: Des recherches ont été effectuées au moyen des bases de données Embase et MEDLINE, du Cochrane Central Register of Controlled Trials et de la Cochrane Database of Systematic Reviews afin de trouver les études publiées depuis 2002 utilisant un ou plusieurs des mots clés suivants : trophoblastic neoplasms, choriocarcinoma, trophoblastic tumor, placental site, gestational trophoblastic disease, hydatidiform mole, drug therapy, surgical therapy, radiotherapy, cure, complications, recurrence, survival, prognosis, pregnancy outcome, disease outcome, treatment outcome et remission. La recherche initiale a été effectuée en avril 2017; une mise à jour a été faite en mai 2019. Les données probantes pertinentes ont été sélectionnées aux fins d'inclusion selon l'ordre suivant : méta-analyses, revues systématiques, directives cliniques, essais cliniques randomisés, études de cohortes prospectives, études observationnelles, revues non systématiques, études de séries de cas et rapports. D'autres articles pertinents ont été trouvés en recoupant les revues répertoriées. Le nombre total d'études relevées était de 673, dont 79 études sont citées dans la présente revue. MéTHODES DE VALIDATION: Le contenu et les recommandations ont été rédigés et acceptés par les auteurs. La direction et le conseil d'administration de la Société de gynéco-oncologie du Canada ont passé en revue le contenu de la version préliminaire et ont soumis des commentaires à prendre en considération. Le conseil d'administration de la Société des obstétriciens et gynécologues du Canada a approuvé la version définitive aux fins de publication. La qualité des données probantes a été évaluée au moyen des critères de l'approche GRADE (Grading of Recommendations Assessment, Development and Evaluation). Consulter les tableaux dans l'annexe en ligne pour connaître les critères de notation et d'interprétation des recommandations. BéNéFICES, RISQUES, COûTS: Les présentes recommandations aideront les médecins à diagnostiquer rapidement les maladies gestationnelles trophoblastiques et à orienter de façon urgente les patientes ayant reçu un diagnostic de maladie gestationnelle trophoblastique en gynécologie oncologique pour une prise en charge spécialisée. Le traitement des néoplasies gestationnelles trophoblastiques en centre spécialisé combiné à l'utilisation de bases de données centralisées permet de recueillir et de comparer des données sur les résultats thérapeutiques des patientes atteintes de ces tumeurs rares et d'optimiser les soins aux patientes. DÉCLARATIONS SOMMAIRES (CLASSEMENT GRADE ENTRE PARENTHèSES): RECOMMANDATIONS (CLASSEMENT GRADE ENTRE PARENTHèSES).

Guideline No. 408: Management of Gestational Trophoblastic Diseases.

OBJECTIVE: This guideline reviews the clinical evaluation and management of gestational trophoblastic diseases, including surgical and medical management of benign, premalignant, and malignant entities. The objective of this guideline is to assist health care providers in promptly diagnosing gestational trophoblastic diseases, to standardize treatment and follow-up, and to ensure early specialized care of patients with malignant or metastatic disease. INTENDED USERS: General gynaecologists, obstetricians, family physicians, midwives, emergency department physicians, anaesthesiologists, radiologists, pathologists, registered nurses, nurse practitioners, residents, gynaecologic oncologists, medical oncologists, radiation oncologists, surgeons, general practitioners in oncology, oncology nurses, pharmacists, physician assistants, and other health care providers who treat patients with gestational trophoblastic diseases. This guideline is also intended to provide information for interested parties who provide follow-up care for these patients following treatment. TARGET POPULATION: Women of reproductive age with gestational trophoblastic diseases. OPTIONS: Women diagnosed with a gestational trophoblastic disease should be referred to a gynaecologist for initial evaluation and consideration for primary surgery (uterine evacuation or hysterectomy) and follow-up. Women diagnosed with gestational trophoblastic neoplasia should be referred to a gynaecologic oncologist for staging, risk scoring, and consideration for primary surgery or systemic therapy (single- or multi-agent chemotherapy) with the potential need for additional therapies. All cases of gestational trophoblastic neoplasia should be discussed at a multidisciplinary cancer case conference and registered in a centralized (regional and/or national) database. EVIDENCE: Relevant studies from 2002 onwards were searched in Embase, MEDLINE, the Cochrane Central Register of Controlled Trials, and Cochrane Systematic Reviews using the following terms, either alone or in combination: trophoblastic neoplasms, choriocarcinoma, trophoblastic tumor, placental site, gestational trophoblastic disease, hydatidiform mole, drug therapy, surgical therapy, radiotherapy, cure, complications, recurrence, survival, prognosis, pregnancy outcome, disease outcome, treatment outcome, and remission. The initial search was performed in April 2017 and updated in May 2019. Relevant evidence was selected for inclusion in the following order: meta-analyses, systematic reviews, guidelines, randomized controlled trials, prospective cohort studies, observational studies, non-systematic reviews, case series, and reports. Additional significant articles were identified through cross-referencing the identified reviews. The total number of studies identified was 673, with 79 studies cited in this review. VALIDATION METHODS: The content and recommendations were drafted and agreed upon by the authors. The Executive and Board of Directors of the Society of Gynecologic Oncology of Canada reviewed the content and submitted comments for consideration, and the Board of Directors for the Society of Obstetricians and Gynaecologists of Canada approved the final draft for publication. The quality of evidence was rated using the criteria described in the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology framework. See the online appendix tables for key to grading and interpretation of recommendations. BENEFITS: These guidelines will assist physicians in promptly diagnosing gestational trophoblastic diseases and urgently referring patients diagnosed with gestational trophoblastic neoplasia to gynaecologic oncology for specialized management. Treating gestational trophoblastic neoplasia in specialized centres with the use of centralized databases allows for capturing and comparing data on treatment outcomes of patients with these rare tumours and for optimizing patient care. SUMMARY STATEMENTS (GRADE RATINGS IN PARENTHESES): RECOMMENDATIONS (GRADE RATINGS IN PARENTHESES).

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.

Bullous vesicant-type reaction to docetaxel along the venous tract: A case report.

Docetaxel is an anti-neoplastic agent commonly used to treat major solid tumors. Common toxicities of docetaxel include neutropenia, alopecia, nausea and vomiting. While docetaxel is typically considered an irritant, we present the case report of a 54-year-old female with high-grade undifferentiated uterine sarcoma who experienced a standard infusion reaction during a docetaxel infusion, followed by an atypical, delayed vesicant-type reaction, without a clear extravasation history.

Tumor site discordance in mismatch repair deficiency in synchronous endometrial and ovarian cancers.

OBJECTIVES: For synchronous endometrial and ovarian cancers, most centers rely on mismatch repair testing of the endometrial cancer to identify Lynch syndrome, and neglect the ovarian tumor site completely. We examined the mismatch repair immunohistochemistry and microsatellite instability results from the endometrium and ovary to assess discordance between the tumor sites and between tests. METHODS: 30 women with newly diagnosed synchronous endometrial and ovarian cancer were prospectively recruited from three cancer centers in Ontario, Canada. Both tumor sites were assessed for mismatch repair deficiency by immunohistochemistry and microsatellite instability test; discordance in results between tumor sites and discordance between test results at each site was examined. Cases with discordant results had tumors sequenced with a targeted panel in order to reconcile the findings. All women underwent mismatch repair gene germline testing. RESULTS: Of 30 patients, 11 (37%) were mismatch repair deficient or microsatellite instable at either tumor site, with 5 (17%) testing positive for Lynch syndrome. Mismatch repair immunohistochemistry expression was discordant between endometrial and ovarian tumor sites in 2 of 27 patients (7%) while microsatellite instability results were discordant in 2 of 25 patients (8%). Relying on immunohistochemistry or microsatellite instability alone on the endometrial tumor would have missed one and three cases of Lynch syndrome, respectively. One patient with Lynch syndrome with a PMS2 pathogenic variant was not detected by either immunohistochemistry or microsatellite instability testing. The rate of discordance between immunohistochemistry and microsatellite instability test was 3.8% in the ovary and 12% in the endometrium. CONCLUSIONS: There was discordance in immunohistochemistry and microsatellite instability results between tumor sites and between tests within each site. Endometrial tumor testing with mismatch repair immunohistochemistry performed well, but missed one case of Lynch syndrome. Given the high incidence of Lynch syndrome (17%), consideration may be given to germline testing in all patients with synchronous endometrial and ovarian cancers.

Performance characteristics of screening strategies to identify Lynch syndrome in women with ovarian cancer.

BACKGROUND: For women with ovarian cancer (OC), the optimal screening strategy to identify Lynch syndrome (LS) has not been determined. In the current study, the authors compared the performance characteristics of various strategies combining mismatch repair (MMR) immunohistochemistry (IHC), microsatellite instability testing (MSI), and family history for the detection of LS. METHODS: Women with nonserous and/or nonmucinous ovarian cancer were recruited prospectively from 3 cancer centers in Ontario, Canada. All underwent germline testing for LS and completed a family history assessment. Tumors were assessed using MMR IHC and MSI. The sensitivity, specificity, and positive and negative predictive values of screening strategies were compared with the gold standard of a germline result. RESULTS: Of 215 women, germline data were available for 189 (88%); 13 women (7%) had pathogenic germline variants with 7 women with mutS homolog 6 (MSH6); 3 women with mutL homolog 1 (MLH1); 2 women with PMS1 homolog 2, mismatch repair system component (PMS2); and 1 woman with mutS homolog 2 (MSH2). A total of 28 women had MMR-deficient tumors (13%); of these, 11 had pathogenic variants (39%). Sequential IHC (with MLH1 promoter methylation analysis on MLH1-deficient tumors) followed by MSI for nonmethylated and/or MMR-intact patients was the most sensitive (92.3%; 95% confidence interval, 64%-99.8%) and specific (97.7%; 95% confidence interval, 94.2%-99.4%) approach, missing 1 case of LS. IHC with MLH1 promoter methylation analysis missed 2 patients of LS. Family history was found to have the lowest sensitivity at 55%. CONCLUSIONS: Sequential IHC (with MLH1 promoter methylation analysis) followed by MSI was found to be most sensitive. However, IHC with MLH1 promoter methylation analysis also performed well and is likely more cost-effective and efficient in the clinical setting. The pretest probability of LS is high in patients with MMR deficiency and warrants universal screening for LS.

Guideline No. 403: Initial Investigation and Management of Adnexal Masses.

OBJECTIVES: To aid primary care physicians, emergency medicine physicians, and gynaecologists in the initial investigation of adnexal masses, defined as lumps that appear near the uterus or in or around ovaries, fallopian tubes, or surrounding connective tissue, and to outline recommendations for identifying women who would benefit from a referral to a gynaecologic oncologist for further management. INTENDED USERS: Gynaecologists, obstetricians, family physicians, general surgeons, emergency medicine specialists, radiologists, sonographers, nurses, medical learners, residents, and fellows. TARGET POPULATION: Adult women 18 years of age and older presenting for the evaluation of an adnexal mass. OPTIONS: Women with adnexal masses should be assessed for personal risk factors, history, and physical findings. Initial evaluation should also include imaging and laboratory testing to triage women for management of their care either by a gynaecologic oncologist or as per SOGC guideline no. 404 on the initial investigation and management of benign ovarian masses. EVIDENCE: A search of PubMed, Cochrane Wiley, and the Cochrane systematic reviews was conducted in January 2018 for English-language materials involving human subjects published since 2000 using three sets of terms: (i) ovarian cancer, ovarian carcinoma, adnexal disease, ovarian neoplasm, adnexal mass, fallopian tube disease, fallopian tube neoplasm, ovarian cyst, and ovarian tumour; (ii) the above terms in combination with predict neoplasm staging, follow-up, and staging; and (iii) the above two sets of terms in combination with ultrasound, tumour marker, CA 125, CEA, CA19-9, HE4, multivariable-index-assay, risk-of-ovarian-malignancy-algorithm, risk-of-malignancy-index, diagnostic imaging, CT, MRI, and PET. Relevant evidence was selected for inclusion in descending order of quality of evidence as follows: meta-analyses, systematic reviews, guidelines, randomized controlled trials, prospective cohort studies, observational studies, non-systematic reviews, case series, and reports. Additional articles were identified through cross-referencing the identified reviews. The total number of studies identified was 2350, with 59 being included in this review. VALIDATION METHODS: The content and recommendations were drafted and agreed upon by the authors. The Executive and Board of the Society of Gynecologic Oncology of Canada reviewed the content and submitted comments for consideration. The Board of Directors of the Society of Obstetricians and Gynaecologists of Canada approved the final draft for publication. The quality of evidence was rated using the criteria described in the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology framework (Table A1 of Online Appendix A). See Table A2 of Online Appendix A for the interpretation of strong and weak recommendations. The summary of findings is available upon request. BENEFITS, HARMS, COSTS: Adnexal masses are common, and guidelines on how to triage them and manage the care of patients presenting with adnexal masses will continue to guide the practice of primary care providers and gynaecologists. Ovarian cancer outcomes are improved when initial surgery is performed by a gynaecologic oncologist, likely as a result of complete surgical staging and optimal cytoreduction. Given these superior outcomes, guidelines to assist in the triage of adnexal masses and the referral and management of the care of patients with an adnexal mass are critical. SUMMARY STATEMENTS (GRADE RATINGS IN PARENTHESES): RECOMMENDATIONS (GRADE RATINGS IN PARENTHESES).

Interobserver Agreement for Mismatch Repair Protein Immunohistochemistry in Endometrial and Nonserous, Nonmucinous Ovarian Carcinomas.

Immunohistochemistry (IHC) for mismatch repair (MMR) proteins is an established test to identify Lynch syndrome (LS) in patients with colorectal cancer and is being increasingly used to identify LS in women with endometrial and/or nonserous ovarian cancer (OC). We assessed interobserver agreement in the interpretation of MMR-IHC on endometrial and ovarian carcinomas. The study consisted of 73 consecutive endometrial cancers (n=48) and nonserous, nonmucinous epithelial OCs (n=25). Six pathologists from 2 cancer centers, one with and the other without, previous experience in interpreting MMR-IHC, evaluated MLH1, MSH2, MSH6, and PMS2 stains. Before the study, an experienced pathologist led a review of 9 teaching cases. A decision tool was developed as a guide in MMR-IHC interpretation. Staining was interpreted as intact, deficient, or equivocal for each protein. Interobserver agreement for the patient MMR status was categorized as "almost perfect" with κ=0.919 (95% CI, 0.863-0.976). All observers were in agreement in 66 (92%) tumors. Four of the less experienced pathologists had at least 1 discrepant interpretation. There were 6 discordant cases: 3 MMR-deficient cases and 2 MMR-intact cases by majority opinion were called equivocal by at least 1 observer, and 1 MMR-deficient case by majority opinion was interpreted as MMR intact by 1 pathologist. Only the latter case (1/73 patients, 1.4%) had an unequivocal disagreement that could affect patient management. Issues associated with discordant interpretation included heterogeneous staining, intratumoral lymphocytes, regional reduced internal control tissue staining, and scattered absent/weak staining adjacent to tumor cells with strong nuclear staining.