How a Canadian federal organization integrated synoptic reporting and quality improvement tools to drive a national learning health system in cancer surgery.

Accurate and complete surgical and pathology reports are the cornerstone of treatment decisions and cancer care excellence. Synoptic reporting is a process for reporting specific data elements in a specific format in surgical and pathology reports. Since 2007, The Canadian Partnership Against Cancer has led the implementation of synoptic reporting mechanisms across multiple cancer disease sites and jurisdictions across Canada. While the implementation of synoptic reporting has been successful, its use to drive improvements in the quality of cancer care delivery has been lacking. Here we describe the Partnership's 4-year, national multi-jurisdictional quality improvement initiative to catalyse the use synoptic data to drive cancer system improvements. Resources provided to the jurisdictions included operational funding, training in quality improvement methodology, national forums, expert coaches, and ad hoc monitoring and support. The program emphasized foundational concepts including data literacy, audit and feedback reports, communities of practice, and positive deviance methodology.

Performance Feedback May Not Improve Radical Prostatectomy Outcomes: The Surgical Report Card (SuRep) Study.

PURPOSE: Oncologic, urinary, and sexual outcomes are important to patients receiving prostate cancer surgery. The objective of this study was to determine if providing surgical report cards (SuReps) to surgeons resulted in improved patient outcomes. MATERIALS AND METHODS: A prospective before-and-after study was conducted at The Ottawa Hospital. A total of 422 consecutive patients undergoing radical prostatectomy were enrolled. The intervention was provision of report cards to surgeons. The control cohort was patients treated before report card feedback (pre-SuRep), and the intervention cohort was patients treated after report card feedback (post-SuRep). The primary outcomes were postoperative erectile function, urinary continence, and positive surgical margins. RESULTS: Baseline characteristics were similar between groups. Almost all patients (99%) were continent and the majority (59%) were potent prior to surgery. Complete 1-year followup was available for 400 patients (95%). Nerve sparing surgery increased from 70% pre-SuRep to 82% post-SuRep (p=0.01). There was a nonstatistically significant increase in the proportion of patients with a positive surgical margin post-SuRep (31% pre-SuRep vs 39% post-SuRep, p=0.08). There was no difference in postoperative erectile function (17% vs 18%, p=0.7) and a decrease in continence (75% vs 65%, p=0.02) at 1 year postoperatively. CONCLUSIONS: The SuRep platform allows accurate reporting of surgical outcomes that can be used for patient counseling. However, the provision of surgical report cards did not improve functional or oncologic outcomes. Longer durations of feedback, report card modifications, or targeted interventions are likely necessary to improve outcomes.

No differences in the body fat after violating core bioelectrical impedance measurement assumptions.

OBJECTIVE: It is unclear to what degree acutely violating bioelectrical impedance analysis (BIA) measurement assumptions will alter the predicted percent fat mass (%FM) and whether this differs by sex or body mass index (BMI). METHODS: %FM was assessed under control, dehydration, exercise, water, food intake and non-voided bladder conditions with three BIA devices (Tanita: BC-418, TBF-314, & Omron HBF-306CN) for men (n = 23, age: 24.0 ± 5.2 years old) and women (n = 17, age: 22.5 ± 3.4 years old) separately. RESULTS: For all BIA devices, there were no differences in the %FM values between the control and the other conditions in men or women (- 1.9 to 0.4%, p > 0.05). Across the three devices and five conditions, 97% of %FM tests returned values within 5% of control (2 tests), and 86% of tests were within 2% of control despite violating an assumption. The errors were greatest with dehydration and women were more likely to have a %FM difference greater than 2% than men with dehydration using the hand-to-foot device (Tanita TBF-314: 59% versus 9%). There were no differences in %FM between control and the conditions when examined by BMI (overweight/obesity: - 2.8 to 0.1% and normal weight: - 1.7 to 0.5%; BMI*trial, p = 0.99). CONCLUSION: %FM estimates were similar despite acutely violating the preliminary measurement BIA assumptions across a range of different BMIs. The minor variations in %FM are smaller than what would be expected with day-to-day variability or weight loss intervention but may be larger in women than men.

Real-World Effectiveness of Pharmaceutical Smoking Cessation Aids: Time-Varying Effects.

BACKGROUND: There are a limited number of studies that have examined the real-world effectiveness of smoking cessation aids and relapse longitudinally in population-representative samples. This study examines the association between use of nicotine gum, patch, bupropion, and varenicline and time to relapse as well as any changes in the association with increased length of abstinence. METHODS: Data of 1821 current adult smokers (18+) making their first serious quit attempt were compiled from 4504 individuals enrolled in the Ontario Tobacco Survey, a representative telephone survey of Ontario adults, which followed smokers every 6 months for up to 3 years. Use of cessation aids at the time of initial report of a quit attempt was analyzed. A flexible parametric survival model was developed to model length of abstinence, controlling for potential confounders. RESULTS: The best fit model found knots at 3, 13, 43, and 212 days abstinent, suggesting different rates of relapse in the periods marked by those days. Use of the patch and varenicline was associated with lower rates of relapse, but no positive effect was found for bupropion or nicotine gum. The effectiveness of the patch reversed in effect after the first month of abstinence. CONCLUSIONS: This study is one of few reports of long-term quitting in a population-representative sample and demonstrates that the effectiveness of some pharmacological cessation aids (the patch and varenicline can be seen in a population sample). Previous failures in real-world studies of the effectiveness of smoking cessation aids may reflect differences in the products individuals use and differences in the timing of self-reported cessation. IMPLICATIONS: While a large number of randomized controlled trials have shown the efficacy of many pharmaceutical smoking cessation aids, evidence of their effectiveness in observational studies in the real world is ambiguous. This study uses a longitudinal cohort of a representative sample of smokers to show that the effectiveness of pharmaceutical cessation aids can be demonstrated in real-world use situations, but effectiveness varies by product type and has time-varying effects.

A comparison of disease recurrence between robotic versus laparotomy approach in patients with intermediate-risk endometrial cancer.

OBJECTIVE: Advances in minimally invasive surgery, particularly with robotic surgery, have resulted in improved peri-operative outcomes in patients with endometrial cancer. In addition, randomized trials have shown that addition of adjuvant radiotherapy following surgery improves loco-regional disease control among stage I intermediate-risk endometrial cancer patients. We aimed to investigate the efficacy and safety of combined treatment of robotic surgery and adjuvant radiotherapy in this patient population. METHODS: A single-center retrospective study was conducted on stage I endometrioid-type endometrial cancer patients with intermediate-risk features (<50% myometrial involvement and grade 2-3 histopathology, or >50% myometrial involvement and grade 1-2 histopathology) treated with hysterectomy and adjuvant radiotherapy between January 2010 and December 2015. Data on surgery and radiotherapy were collected and correlated with clinical and surgical outcomes using log-rank. Oncologic outcomes were then compared between robotic surgery and laparotomy. RESULTS: A total of 179 intermediate-risk endometrial cancer patients were identified, of whom 135 (75.4%) received adjuvant radiotherapy and were included in the final analysis. Median age at diagnosis was 63 years (range 40-89) and median follow-up was 4.7 years (range 1.1-8.8). Seventy-seven patients (57%) underwent robotic surgery and 58 patients (43%) underwent laparotomy. Surgical staging with lymph node dissection was performed on 79.3% of the patients. The majority of patients (79.3%) received vaginal brachytherapy as part of adjuvant radiotherapy, while 20.7% received external-beam radiotherapy. Among the entire cohort, eight (5.9%) patients recurred and all eight recurrences occurred in the robotic surgery group; no recurrence was found in the laparotomy group. This translated into 5 year disease-free survival of 100% in the laparotomy group, compared with 91.8% in the robotic surgery group (p=0.005). No difference in overall survival was found between the two groups (p=0.51). CONCLUSION: Oncologic outcomes for stage I intermediate-risk endometrial cancer treated with hysterectomy and adjuvant radiotherapy at our institution are comparable to the previously published literature. The higher recurrence rate observed with robotic surgery at our institution has not been observed previously and requires further investigation.

Exploring international differences in ovarian cancer treatment: a comparison of clinical practice guidelines and patterns of care.

INTRODUCTION: The International Cancer Benchmarking Partnership demonstrated international differences in ovarian cancer survival, particularly for women aged 65-74 with advanced disease. These findings suggest differences in treatment could be contributing to survival disparities. OBJECTIVE: To compare clinical practice guidelines and patterns of care across seven high-income countries. METHODS: A comparison of guidelines was performed and validated by a clinical working group. To explore clinical practice, a patterns of care survey was developed. A questionnaire regarding management and potential health system-related barriers to providing treatment was emailed to gynecological specialists. Guideline and survey results were crudely compared with 3-year survival by 'distant' stage using Spearman's rho. RESULTS: Twenty-seven guidelines were compared, and 119 clinicians completed the survey. Guideline-related measures varied between countries but did not correlate with survival internationally. Guidelines were consistent for surgical recommendations of either primary debulking surgery or neoadjuvant chemotherapy followed by interval debulking surgery with the aim of complete cytoreduction. Reported patterns of surgical care varied internationally, including for rates of primary versus interval debulking, extensive/'ultra-radical' surgery, and perceived barriers to optimal cytoreduction. Comparison showed that willingness to undertake extensive surgery correlated with survival across countries (rs=0.94, p=0.017). For systemic/radiation therapies, guideline differences were more pronounced, particularly for bevacizumab and PARP (poly (ADP-ribose) polymerase) inhibitors. Reported health system-related barriers also varied internationally and included a lack of adequate hospital staffing and treatment monitoring via local and national audits. DISCUSSION: Findings suggest international variations in ovarian cancer treatment. Characteristics relating to countries with higher stage-specific survival included higher reported rates of primary surgery; willingness to undertake extensive/ultra-radical procedures; greater access to high-cost drugs; and auditing.

Marketing IQOS in a dark market.

INTRODUCTION: Phillip Morris International (PMI) is pushing hard to promote IQOS heat-not-burn cigarettes in Ontario, Canada. Canada regulates IQOS as a tobacco product so that the robust tobacco marketing ban creates challenges to its promotion. METHODS: We collected data on IQOS promotion in 49 retail outlets, and through interviews with clerks and observations outside an IQOS store. RESULTS: The dominant marketing channel is the visible availability of IQOS in a large number of tobacco retail outlets-1029 across Ontario. Several stores display the price of 'heated tobacco' on one of three price signs which are permitted despite Ontario's total display ban. IQOS boutique stores are the locus of aggressive promotion including exchanging a pack of cigarettes or lighter for an IQOS device, launch parties, 'meet and greet' lunches and after-hour events. Outside the store, promotion includes a prominent IQOS sign, a sandwich board sign reading 'Building a Smoke-Free Future' and sales representatives regularly smoking IQOS. Membership services: Upon acquiring an IQOS device one can register to access the IQOS website store5 and receive customer support services, a map of retail locations and a product catalogue. Members receive regular email invitations to complete surveys with opportunities to win prizes. CONCLUSIONS: These promotion activities have undoubtedly made substantial numbers of Ontarians aware of IQOS. Yet, the government has not provided guidance as to absolute and relative potential harms. Our observations of tactics to promote a new tobacco product in a dark market may inform government regulatory policy and non-governmental organisation efforts wherever heat-not-burn products are introduced.

Evolution of genetic assessment for BRCA-associated gynaecologic malignancies: a Canadian multisociety roadmap.

The landscape of genetic testing in ovarian cancer patients has changed dramatically in recent years. The therapeutic benefits of poly ADP-ribose polymerase (PARP) inhibitors in treatment of BRCA1/2-related ovarian cancers has resulted in an increased demand and urgency for genetic testing results, while technological developments have led to widespread use of multi-gene cancer panels and development of tumour testing protocols. Traditional genetic counselling models are no longer sustainable and must evolve to match the rapid evolution of genetic testing technologies and developments in personalized medicine. Recently, representatives from oncology, clinical genetics, molecular genetics, pathology, and patient advocacy came together to create a national multi-disciplinary Canadian consortium. By aligning stakeholder interests, the BRCA Testing to Treatment (BRCA TtoT) Community of Practice aims to develop a national strategy for tumour and germline BRCA1/2 testing and genetic counselling in women with ovarian cancer. This article serves to provide an overview of the recent evolution of genetic assessment for BRCA1/2-associated gynecologic malignancies and outline a Canadian roadmap to facilitate change, improve genetic testing rates, and ultimately improve outcomes for hereditary ovarian cancer patients and their families.

Business school teams up with clinical innovators: An opportunity for health system transformation.

Healthcare represents one of the largest sectors in the economy with the health spending on average accounting for about 9% of GDP in OECD countries. Canada was projected in 2018 to spend about 11% of its GDP on healthcare with an expected health expenditure growth of 4.2%. Addressing this issue asks for a redesign of health delivery system and associated cultural shift allowing for incorporation of industry and business best practices. To make this redesign happen, system transformation requires seeking out new institutional mechanisms, partnerships, and forums where industry leaders in business and healthcare can develop a top-down approach with a shared vision, shared best practices, and support coming from a bottom-up approach through pilots and scaling-up initiatives. In this article, we describe one successful partnership initiative-Telfer Health Transformation Exchange at the Telfer School of Management at the University of Ottawa.

Approaches for triaging women who test positive for human papillomavirus in cervical cancer screening.

Substantial evidence exists to support the introduction of molecular testing for human papillomavirus (HPV) as the primary technology in cervical cancer screening. While HPV testing is much more sensitive than cytology for detection of high-grade precancerous lesions, it is less specific. To improve efficiency, it is therefore recommended that a specific test (like cytology) be used in triaging HPV positive women to colposcopy. A number of studies have been conducted that support the use of cytology alone or in conjunction with HPV genotyping for triage. The decision to incorporate genotyping also depends on the commercial HPV test that is selected since not all tests provide results for certain individual high-risk types. Regardless of whether policy officials decide to adopt a triage approach that incorporates genotyping, the use of liquid based cytology (LBC) may also improve screening performance by reducing diagnostic delays. With LBC, the same cell suspension from a single collection may be used for HPV testing and a smear can be immediately prepared if HPV status is positive. This was a critical lesson from a community based demonstration project in Montreal (VASCAR study), where conventional cytology exists and specimen co-collection was not permitted for ethical reasons, requiring HPV positive women to return for an additional screening visit prior to colposcopy.

Introduction of molecular HPV testing as the primary technology in cervical cancer screening: Acting on evidence to change the current paradigm.

Since being introduced in the 1940s, cervical cytology - despite its limitations - has had unequivocal success in reducing cervical cancer burden in many countries. However, we now know that infection with human papillomavirus (HPV) is a necessary cause of cervical cancer and there is overwhelming evidence from large-scale clinical trials, feasibility studies and real-world experience that supports the introduction of molecular testing for HPV as the primary technology in cervical cancer screening (i.e., "HPV primary screening"). While questions remain about the most appropriate age groups for screening, screening interval and triage approach, these should not be considered barriers to implementation. Many countries are in various stages of adopting HPV primary screening, whereas others have not taken any major steps towards introduction of this approach. As a group of clinical experts and researchers in cervical cancer prevention from across Canada, we have jointly authored this comprehensive examination of the evidence to implement HPV primary screening. Our intention is to create a common understanding among policy makers, agencies, clinicians, researchers and other stakeholders about the evidence concerning HPV primary screening to catalyze the adoption of this improved approach to cervical cancer prevention. With the first cohort of vaccinated girls now turning 21, the age when routine screening typically begins, there is increased urgency to introduce HPV primary screening, whose performance may be less adversely affected compared with cervical cytology as a consequence of reduced lesion prevalence post-vaccination.

Complement C5a potentiates uric acid crystal-induced IL-1ß production.

Anaphylatoxin C5a released upon complement activation is associated with both acute and chronic inflammations such as gout. The pathogenesis of gout was identified as uric acid crystal deposition in the joints that activates inflammasome, leading to IL-1ß release. However, little is known about the interaction between complement activation and monosodium urate/uric acid (MSU) crystal-induced inflammasome activation or IL-1ß production. Here, we report that MSU crystal-induced proinflammatory cytokines/chemokines in human whole blood is predominantly regulated by C5a through its interaction with C5a receptor. C5a induces pro-IL-1ß and IL-1ß production in human primary monocytes, and potentiates MSU or cholesterol crystals in IL-1ß production. This potentiation is caspase-1 dependent and requires intracellular Ca(2+) mobilization, K(+) efflux, and cathepsin B activity. Our results provide insight into the role of C5a as an endogenous priming signal that is required for the initiation of uric acid crystal-induced IL-1ß production. C5a could potentially be a therapeutic target together with IL-1ß antagonists for the treatment of complement-dependent and inflammasome-associated diseases.

Strategies targeting the IL-4/IL-13 axes in disease.

IL-4 and IL-13 are pleiotropic Th2 cytokines produced by a wide variety of different cell types and responsible for a broad range of biology and functions. Physiologically, Th2 cytokines are known to mediate host defense against parasites but they can also trigger disease if their activities are dysregulated. In this review we discuss the rationale for targeting the IL-4/IL-13 axes in asthma, atopic dermatitis, allergic rhinitis, COPD, cancer, inflammatory bowel disease, autoimmune disease and fibrotic disease as well as evaluating the associated clinical data derived from blocking IL-4, IL-13 or IL-4 and IL-13 together.

An organizational guideline for gynecologic oncology services.

OBJECTIVES: Documented variations in practice compelled the need to establish a network that would facilitate the flow of patients through the care continuum of a provincial health care system in accordance with best practices. Therefore, a guideline was developed to provide recommendations for the optimal organization of gynecologic oncology services in this higher resource location to improve access to multidisciplinary care and appropriate treatment. METHODS: A systematic review was conducted of Web sites of international guideline developers, relevant cancer agencies, and Medline and EMBASE from 1996 to 2011 using search terms related to gynecologic malignancies, combined with organization of services, patterns of care, and various facility and physician characteristics. The results of the review were combined with expert consensus and stakeholder consultation to develop a gynecologic oncology services organizational guideline. RESULTS: The evidence review yielded a lower quality evidence base; therefore, recommendations were determined through consensus, including guidance for physician and hospital specialization, and other domains including human and physical resources. Definitive surgical treatment of most invasive cancers by subspecialist gynecologic oncologists is recommended. In addition, it is recommended that these subspecialists provide care within designated gynecologic oncology centers. The recommendations also outline which services, such as radiation therapy, may be provided in other affiliated centers. Multidisciplinary team management is also endorsed. CONCLUSIONS: These recommendations are intended to allow a collaborative community of practice, supported by formal interorganizational processes, to evolve to facilitate adherence to guidelines and best practices at a system-wide level.

Experiencing Health Advocacy During Cervical Cancer Awareness Week: A National Initiative for Obstetrics and Gynaecology Residents.

OBJECTIVE: The Royal College of Physicians and Surgeons of Canada requires that residents demonstrate competence in health advocacy (HA). We sought to develop and implement a national educational module for obstetrics and gynaecology residents to address the role of HA. This pilot program was centred on cervical cancer prevention, which lends itself to applying the principles of advocacy. METHODS: An educational module was developed and disseminated to all obstetrics and gynaecology residency programs in Canada. The module describes options for HA involving cervical dysplasia screening, such as an outreach clinic or a forum for public/student education, which were to be implemented during Cervical Cancer Awareness Week. The measures of success were the number of programs implementing the curriculum, number of residents who participated, diversity of projects implemented, individuals (patients or learners) reached by the program, and the overall experience of the trainees. RESULTS: Three programs implemented the curriculum in 2011, one in 2012, and seven in 2013. After three years, the module has involved seven of 16 medical schools, over 100 residents, and thousands of women either directly or indirectly. Additionally, attributes of HA experienced by the residents were identified: teamwork, leadership, increased systems knowledge, increased social capital within the community, creativity, innovation, and adaptability. CONCLUSION: We have demonstrated that an educational module can be implemented nationally, helping our residents fulfill their HA requirements. Other specialties could use this module in building HA into their own programs.

Objectif : Le Collège royal des médecins et chirurgiens du Canada exige que les résidents fassent preuve de compétence dans le rôle de promoteur de la santé (PS ou promotion de la santé). Nous avons cherché à élaborer et à mettre en œuvre, à l'intention des résidents en obstétrique-gynécologie, un module pédagogique national traitant de ce rôle de PS. Ce programme pilote était centré sur la prévention du cancer du col utérin, soit un sujet se prêtant bien à l'application des principes de la promotion de la santé. Méthodes : Un module pédagogique a été élaboré et transmis à tous les programmes de résidence en obstétrique-gynécologie au Canada. Ce module décrit les options de PS mettant en jeu le dépistage de la dysplasie cervicale (telles qu'une clinique visant l'élargissement de la population desservie ou un forum d'éducation visant le public / la population étudiante) qui devaient être mises en œuvre au cours de la Semaine de sensibilisation au cancer du col de l'utérus. La réussite a été mesurée en fonction du nombre de programmes mettant en œuvre le curriculum, du nombre de résidents y ayant participé, de la diversité des projets mis en œuvre, de la nature des personnes (patientes ou apprenants) atteintes par le programme et de l'expérience globale des stagiaires. Résultats : Trois programmes ont mis en œuvre le curriculum en 2011, un programme l'a fait en 2012 et sept l'ont fait en 2013. Après trois ans, le module s'est attiré la participation directe ou indirecte de sept des 16 facultés de médecine, de plus de 100 résidents et de milliers de femmes. De plus, les attributs de la PS vécus par les résidents ont été identifiés : travail d'équipe, leadership, connaissances accrues au sujet des systèmes, capital social accru au sein de la communauté, créativité, innovation et adaptabilité. Conclusion : Nous avons démontré qu'un module pédagogique, visant à aider nos résidents à répondre à leurs exigences en matière de PS, peut être mis en œuvre à l'échelle nationale. D'autres spécialités pourraient utiliser ce module pour incorporer la PS dans leurs programmes respectifs.

Kynurenine 3-monooxygenase mediates inhibition of Th17 differentiation via catabolism of endogenous aryl hydrocarbon receptor ligands.

The aryl hydrocarbon receptor (AhR) is a key transcriptional regulator of Th17-cell differentiation. Although endogenous ligands have yet to be identified, evidence suggests that tryptophan metabolites can act as agonists for the AhR. Tryptophan metabolites are abundant in circulation, so we hypothesized that cell intrinsic factors might exist to regulate the exposure of Th17 cells to AhR-dependent activities. Here, we find that Th17 cells preferentially express kynurenine 3-monooxygenase (KMO), which is an enzyme involved in catabolism of the tryptophan metabolite kynurenine. KMO inhibition, either with a specific inhibitor or via siRNA-mediated silencing, markedly increased IL-17 production in vitro, whereas IFN-γ production by Th1 cells was unaffected. Inhibition of KMO significantly exacerbated disease in a Th17-driven model of autoimmune gastritis, suggesting that expression of KMO by Th17 cells serves to limit their continuous exposure to physiological levels of endogenous AhR ligands in vivo.

Incidental endometrial carcinoma diagnosed at first trimester pregnancy loss: a case report.

BACKGROUND: All cases reported to date of endometrioid endometrial adenocarcinoma (EEA) associated with pregnancy have been treated surgically or medically. We describe a case of EEA in pregnancy that was managed expectantly, allowing for observation of the natural course of the disease. CASE: A 36-year-old woman, gravida 2 para 1, presented at eight weeks of pregnancy with heavy vaginal bleeding. Ultrasound assessment confirmed a missed abortion, and the patient underwent dilatation and curettage. Tissue pathology primarily suggested grade 1 EEA. The patient chose expectant management. Eight months later, she returned with vaginal bleeding. Hysterectomy was performed and the hysterectomy specimen showed FIGO grade 1 stage 1A EEA. CONCLUSION: Treating EEA associated with pregnancy is challenging. Our experience in the case described here suggests that expectant management should not be undertaken due to a high risk of recurrence.

Contexte : Tous les cas signalés à ce jour d'adénocarcinome endométrial endométrioïde (AEE) associé à la grossesse ont fait l'objet d'une prise en charge chirurgicale ou médicale. Nous décrivons un cas d'AEE pendant la grossesse ayant fait l'objet d'une prise en charge non interventionniste, ce qui a permis l'observation de l'évolution naturelle de la maladie. Cas : Une femme de 36 ans, gravida 2 para 1, nous a consultés à huit semaines de grossesse en raison de saignements vaginaux abondants. L'évaluation échographique a confirmé la présence d'une rétention fœtale et la patiente a subi une dilatation-curetage. L'analyse pathologique des tissus a d'abord indiqué qu'il s'agissait probablement d'un AEE de grade 1. La patiente a alors choisi une prise en charge non interventionniste. Huit mois plus tard, elle nous a consultés à nouveau en raison de ses saignements vaginaux. Une hystérectomie a été menée et le spécimen d'hystérectomie indiquait la présence d'un AEE de stade 1A grade 1 FIGO. Conclusion : La prise en charge de l'AEE associé à la grossesse est complexe. Notre expérience dans le cas décrit aux présentes semble indiquer qu'une prise en charge non interventionniste ne devrait pas être mise en œuvre, en raison d'un risque élevé de récurrence.

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.