Robotic-assisted surgery for endometrial cancer is safe in morbidly and extremely morbidly obese patients.

OBJECTIVE: Obesity has risen to affect >25% of the Canadian population. Perioperative challenges with increased morbidity are encountered. We evaluated the outcome of robotic-assisted surgery for endometrial cancer (EC) in obese patients. METHODS: We retrospectively reviewed all robotic surgeries performed for EC in women with BMI ≥40 kg/m2, from 2012 to 2020 in our center. Patients were divided into 2 groups (class III: 40-49 kg/m2, class IV: ≥50 kg/m2). Complications and outcome were compared. RESULTS: 185 patients were included: 139 class III and 46 class IV. The main histology was endometrioid adenocarcinoma (70,5% of class III and 58,1% of class IV (p = 0,138)). The mean blood loss, overall sentinel node detection and median length of stay were similar in both groups. Six class III (4,3%) and 3 class IV (6,5%) patients required conversion to laparotomy due to poor surgical field exposure (p = 0,692). The rate of intraoperative complications was similar between the 2 groups (1.4% in class III vs none in class IV, p = 1). There were 10 class III (7,2%) and 10 class IV (21,7%) post-operative complications (p = 0.011), but most were grade 2 (3,6% in class III vs 13% in class IV, p = 0.029)). Grade 3 and 4 postoperative complications were low (2.7%) and not statistically different between the 2 groups. Readmission rate was low in both groups (4 in each group, p = 1.07). Recurrence occurred in 5,8% of class III and 4,3% of class IV patients (p = 1). CONCLUSION: Robotic-assisted surgery for EC in class III and class IV obese patients is a safe and feasible procedure, with low complication rate, similar oncologic outcome, conversion rate, blood loss, readmission rate and length of hospital stay.

Low BRCA1 and BRCA2 Germline Mutation Rates in a French-Canadian Population with a Diagnosis of Epithelial Tubo-Ovarian Carcinoma.

OBJECTIVE: Universal genetic testing has become increasingly important in the management of epithelial tubo-ovarian and peritoneal carcinoma. Worldwide, reported incidences of deleterious BRCA mutations vary between 12% and 15%. We sought to evaluate the incidence in our population, given its specific genetic background (French-Canadian ancestry). METHOD: Mainstream genetic testing was implemented in our service in May 2017 and offered to all patients with epithelial tubo-ovarian or peritoneal carcinomas, except mucinous and borderline tumours. Data were prospectively collected in a database and retrospectively analyzed. RESULTS: We tested 222 patients in our centre, of whom 183 (82.4%) had high-grade serous carcinoma (HGSC). Overall, 139 patients had no identified mutation (62.6%). Deleterious BRCA1 and BRCA2 mutations were found in 12 patients (5.4%): 6 had BRCA1, and 6 BRCA2 mutations; 11 of these patients had HGSC. Other non-BRCA mutations (ATM, RAD51C, RAD51D, BRIP1, CDH1, MRE11, MSH6, MUTYH, PALB2, and PMS2) were observed in an additional 20 patients (9.0%), of whom 18 had HGSC. A total of 63 different variants of unknown significance (VUS) were found, of which 4 were in the BRCA1 and BRCA2 genes. Deleterious mutations were not identified in clear cell carcinomas, and only 1 was found in low-grade serous carcinoma. CONCLUSION: In our French-Canadian population, the incidence of deleterious germline BRCA mutations was surprisingly low at 5.4%-less than half that reported in the literature. This may affect patient response to poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi) therapy. Mainstream genetic testing was successfully implemented in our service and facilitated access to genetic testing in our patient population.

Predicting recurrence and recurrence-free survival in high-grade endometrial cancer using machine learning.

OBJECTIVE: To develop machine-learning models to predict recurrence and time-to-recurrence in high-grade endometrial cancer (HGEC) following surgery and tailored adjuvant treatment. METHODS: Data were retrospectively collected across eight Canadian centers including 1237 patients. Four models were trained to predict recurrence: random forests, boosted trees, and two neural networks. Receiver operating characteristic curves were used to select the best model based on the highest area under the curve (AUC). For time to recurrence, we compared random forests and Least Absolute Shrinkage and Selection Operator (LASSO) model to Cox proportional hazards. RESULTS: The random forest was the best model to predict recurrence in HGEC; the AUCs were 85.2%, 74.1%, and 71.8% in the training, validation, and test sets, respectively. The top five predictors were: stage, uterus height, specimen weight, adjuvant chemotherapy, and preoperative histology. Performance increased to 77% and 80% when stratified by Stage III and IV, respectively. For time to recurrence, there was no difference between the LASSO and Cox proportional hazards models (c-index 71%). The random forest had a c-index of 60.5%. CONCLUSIONS: A bootstrap random forest model may be a more accurate technique to predict recurrence in HGEC using multiple clinicopathologic factors. For time to recurrence, machine-learning methods performed similarly to the Cox proportional hazards model.

Endometrial carcinoma molecular subtype correlates with the presence of lymph node metastases.

BACKGROUND: The role of lymph node assessment/dissection (LND) in endometrial cancer (EC) has been debated for decades, with significant practice variation between centers. Molecular classification of EC provides prognostic information and can be accurately performed on preoperative endometrial biopsies. We assessed the association between molecular subtype and lymph node metastases (LNM) in order to determine if this tool could be used to stratify surgical decision making. METHODS: All EC patients undergoing primary staging surgery with planned complete pelvic +/- para-aortic LND from a single institution in the 2015 calendar year were identified, with clinicopathological and outcome data assessed in the context of retrospectively assigned molecular classification. RESULTS: 172 patients were included. Molecular classification of the total cohort showed 21 POLEmut (12.2%), 47 MMRd (27.3%), 74 NSMP (43.1%), and 30 p53abn (17.4%) ECs. Complete pelvic +/- para-aortic LND was performed in 171 of 172 patients, and LNM were found in 31/171 (18.1%). This included macrometastases (19/31), micrometastases (5/31), and isolated tumour cells (ITCs) (7/31). LNM were pelvic only in 83.9%, and pelvic plus para-aortic in 16.1%. There were no isolated para-aortic LNM. Molecular subtype was significantly associated with LNM (p = 0.004). There was a strong association between the presence of LNM and p53abn EC (nodal involvement in 44.8% of cases), with LNM detected in 14.2% of POLEmut, 14.9% of MMRd, and 10.8% of NSMP EC. On multivariate analysis, molecular subtype and preoperative CA 125 > 25 were significantly associated with LNM (p = 0.021 and p = 0.022 respectively) but preoperative grade and histotype were not (p = 0.24). CONCLUSION: EC molecular subtype is significantly associated with the presence of LNM. As molecular classification can be obtained on preoperative diagnostic specimens, this information can be used to guide surgical treatment planning and may reduce the cost and morbidity of unnecessary lymph node staging in EC care.

Five-Year Experience in the Surgical Treatment of Endometrial Cancer: Comparing Laparotomy with Robotic and Minimally Invasive Hysterectomy.

OBJECTIVES: To compare surgical and oncological outcomes in the treatment of endometrial cancer between laparotomy and minimally invasive surgery. The secondary objective was to determine which MIS approach was the most beneficial. METHODS: This was a single-centre retrospective review of all endometrial cancer surgeries performed between November 1, 2012 and October 31, 2017 in a gynaecologic oncology unit of a university hospital. Descriptive statistics were used to compare histopathologic results and oncological outcomes, and Kaplan-Meier estimates were used to compare survival. RESULTS: A total of 735 cases were reviewed. The majority of patients (77%) underwent either laparotomy (35%) or robotic-assisted hysterectomy (42%); the remaining patients underwent total laparoscopic hysterectomy (12%) or a laparoscopic-assisted vaginal hysterectomy (8.7%). There was a statistically significant overall survival benefit (P = 0.02), a shorter hospital stay (P < 0.0001), and fewer early surgical complications (<30 d; P = 0.0002), as well as a survival benefit in elderly patients (>70 y) in the robotic-assisted hysterectomy group (P = 0.043) than the laparotomy group. Operating time was shorter in the laparotomy group (P < 0.0001). Recurrence rates in stage 1 low-risk disease were similar between groups. CONCLUSION: Minimally invasive surgical approaches, particularly robotic surgery, do not compromise oncologic outcomes, especially for early-stage low-risk disease. In addition, these approaches are associated with fewer early surgical complications and shorter hospital stay, with significantly more same-day discharges. Overall survival and survival in a subgroup of elderly patients were significantly better in the robotic-assisted hysterectomy group.

An in-home rehabilitation program for the treatment of urinary incontinence symptoms in endometrial cancer survivors: a single-case experimental design study.

INTRODUCTION AND HYPOTHESIS: There is a high prevalence of urinary incontinence among endometrial cancer survivors. They are also known to present with pelvic floor muscle alterations. Evidence on the effects of conservative interventions for the management of UI is scarce. This study aims at verifying the effects of an in-home rehabilitation program, including the use of a mobile technology, to reduce UI severity in endometrial cancer survivors. METHODS: This study used a single-case experimental design with replications. Primary outcome for UI severity was the pad test, and secondary outcomes were the ICIQ-UI SF questionnaire and 3-day bladder diary. Pelvic floor muscle function was assessed using 2D-transperineal ultrasound and intravaginal dynamometry. Adherence was documented using mobile technology and an exercise log. Visual and non-parametric analyses of longitudinal data were conducted. RESULTS: Results show a reduction in UI severity for 87.5% of participants, with a significant relative treatment effect of moderate size (RTE: 0.30). Significant small relative treatment effects were found for the quick contraction and endurance dynamometric tests. CONCLUSION: This study provides new evidence that endometrial cancer survivors can improve the severity of their UI following an in-home rehabilitation program, including the use of a mobile technology. This mode of delivery has the potential to address a gap in access to pelvic floor physiotherapy services for survivors of EC living in rural and remote communities.

High-grade endometrial carcinoma limited to the endometrium or a polyp: is adjuvant treatment necessary?

OBJECTIVE: High-grade endometrial carcinoma limited to the endometrium or a polyp is a rare clinical entity. Currently there is no consensus on standard treatment. Thus, the goal of this study was to evaluate the clinical outcomes of patients with type II endometrial carcinoma without myometrial infiltration or limited to a polyp. METHODS: We retrospectively identified type II endometrial carcinoma (FIGO endometrioid grade 3, serous, clear cell, mixed and carcinosarcoma) with spread limited to the endometrium or a polyp from April 2013 to November 2017. Medical records were reviewed for the following information: age at diagnosis, patient characteristics, type of surgery, histology, stage according to FIGO 2009 classification, adjuvant treatments, and site of recurrence. Descriptive statistics and the Kaplan-Meier estimate were used for analysis. RESULTS: A total of 25 patients with a type II stage IA adenocarcinoma were included. All were surgically staged with total hysterectomy, salpingo-oophorectomy, and lymph nodes assessment. The median age at diagnosis was 69 years. All patients had either disease limited to the endometrium (60%) or a polyp (40%). Only four patients had lymphovascular space invasion (16%). The median follow-up was 44 (range 2-67) months. Six patients (24%) received vault brachytherapy only and all others received no adjuvant treatment after surgery (n=19, 76%). Three patients (12%) experienced recurrences at 15, 21, and 55 months after surgery. Following systemic treatment all are alive and disease-free. The 3-year progression-free survival and overall survival were 91% and 100%, respectively. CONCLUSION: Expectant management with surveillance alone following surgery appears to be safe for patients with high-grade endometrial carcinoma limited to a polyp or the endometrium without myometrial invasion.

A Collaborative Model to Implement Flexible, Accessible and Efficient Oncogenetic Services for Hereditary Breast and Ovarian Cancer: The C-MOnGene Study.

Medical genetic services are facing an unprecedented demand for counseling and testing for hereditary breast and ovarian cancer (HBOC) in a context of limited resources. To help resolve this issue, a collaborative oncogenetic model was recently developed and implemented at the CHU de Québec-Université Laval; Quebec; Canada. Here, we present the protocol of the C-MOnGene (Collaborative Model in OncoGenetics) study, funded to examine the context in which the model was implemented and document the lessons that can be learned to optimize the delivery of oncogenetic services. Within three years of implementation, the model allowed researchers to double the annual number of patients seen in genetic counseling. The average number of days between genetic counseling and disclosure of test results significantly decreased. Group counseling sessions improved participants' understanding of breast cancer risk and increased knowledge of breast cancer and genetics and a large majority of them reported to be overwhelmingly satisfied with the process. These quality and performance indicators suggest this oncogenetic model offers a flexible, patient-centered and efficient genetic counseling and testing for HBOC. By identifying the critical facilitating factors and barriers, our study will provide an evidence base for organizations interested in transitioning to an oncogenetic model integrated into oncology care; including teams that are not specialized but are trained in genetics.

Factors associated with an increased risk of recurrence in patients diagnosed with high-grade endometrial cancer undergoing minimally invasive surgery: A study of the society of gynecologic oncology of Canada (GOC) community of practice (CoP).

BACKGROUND: Minimally invasive surgery (MIS) is a standard surgical approach for comprehensive surgical staging in women with endometrial cancer. As rates and complexity of MIS are steadily increasing, it is important to identify potential risk factors which may be associated with this approach. This study evaluates the impact of local factors on the risk of disease recurrence. METHODS: A retrospective cohort study was conducted of patients diagnosed with high grade endometrial cancer (HGEC) who underwent MIS between 2012 and 2016 at eight Canadian centers. Data was collected from medical records. The 75th percentile was calculated for estimated uterine volume and weight. All recurrences were categorized into two groups; intra-abdominal vs. extra-abdominal. To search for significant covariates associated with recurrence-free survival a Cox proportional hazard model was performed. RESULTS: A total of 758 patients were included in the study. Intra-uterine manipulator was used in 497 (35.8%) of patients. Vaginal lacerations were documented in 9.1%. Median follow-up was 30.5 months (interquartile range 20-47). There were 157 who had disease recurrence (20.71%), including 92 (12.14%) intra-abdominal and 60 (7.92%) extra-abdominal only recurrences. In univariate analysis myometrial invasion, LVI, stage, uterine volume and weight > 75th percentile and chemotherapy were associated with increased risk of intra-abdominal recurrence. In multivariable analysis only stage, and specimen weight > 75th percentile (OR 2.207, CI 1.123-4.337) remained significant. Uterine volume, and weight were not associated with increased risk of extra-abdominal recurrences. CONCLUSION: For patients diagnosed with HGEC undergoing MIS, extracting a large uterus is associated with a significantly increased risk for intra-abdominal recurrence.

Development of a 3D functional assay and identification of biomarkers, predictive for response of high-grade serous ovarian cancer (HGSOC) patients to poly-ADP ribose polymerase inhibitors (PARPis): targeted therapy.

BACKGROUND: Poly(ADP-ribose) polymerase inhibitors (PARPis) specifically target homologous recombination deficiency (HRD) cells and display good therapeutic effect in women with advanced-stage BRCA1/2-mutated breast and epithelial ovarian cancer (EOC). However, about 50% of high grade serous ovarian cancers (HGSOC) present with HRD due to epigenetic BRCA1 inactivation, as well as genetic/epigenetic inactivation(s) of other HR genes, a feature known as "BRCAness". Therefore, there is a potential for extending the use of PARPis to these patients if HR status can be identified. METHODS: We have developed a 3D (spheroid) functional assay to assess the sensitivity of two PARPis (niraparib and olaparib) in ascites-derived primary cell cultures (AsPCs) from HGSOC patients. A method for AsPCs preparation was established based on a matrix (agarose), allowing for easy isolation and successive propagation of monolayer and 3D AsPCs. Based on this method, we performed cytotoxicity assays on 42 AsPCs grown both as monolayers and spheroids. RESULTS: The response to PARPis treatment in monolayer AsPCs, was significantly higher, compared to 3D AsPCs, as 88% and 52% of the monolayer AsPCs displayed sensitivity to niraparib and olaparib respectively, while 66% of the 3D AsPCs were sensitive to niraparib and 38% to olaparib, the latter being more consistent with previous estimates of HRD (40%-60%) in EOC. Moreover, niraparib displayed a significantly stronger cytotoxic effect in both in 3D and monolayer AsPCs, which was confirmed by consecutive analyses of the HR pathway activity (γH2AX foci formation) in PARPis-sensitive and resistant AsPCs. Global gene expression comparison of 6 PARPi-resistant and 6 PARPi-sensitive 3D AsPCs was indicative for the predominant downregulation of numerous genes and networks with previously demonstrated roles in EOC chemoresistance, suggesting that the PARPis-sensitive AsPCs could display enhanced sensitivity to other chemotherapeutic drugs, commonly applied in cancer management. Microarray data validation identified 24 potential gene biomarkers associated with PARPis sensitivity. The differential expression of 7 selected biomarkers was consecutively confirmed by immunohistochemistry in matched EOC tumor samples. CONCLUSION: The application of this assay and the potential biomarkers with possible predictive significance to PARPis therapy of EOC patients now need testing in the setting of a clinical trial.

Evaluating the diagnostic performance of preoperative endometrial biopsies in patients diagnosed with high grade endometrial cancer: A study of the Society of Gynecologic Oncology (GOC) Community of Practice (CoP).

BACKGROUND: High grade cancers account for a disproportionate number of recurrences in patients with endometrial cancer. Accurately identifying these cases on endometrial biopsies allows for better surgical planning. This study evaluates the diagnostic accuracy of general pathologists (GP) compared to gynecological pathologists (GYNP) in interpreting preoperative biopsies. METHODS: A retrospective cohort study was conducted of patients diagnosed with high grade endometrial cancer (HGEC) between 2012 and 2016 at eight Canadian cancer centres. Data was collected from medical records. Pre-operative biopsies were categorized into groups; biopsies read by GP, GYNP and GP reviewed by GYNP. Rates of HGEC on pre-operative biopsy were calculated. Fisher exact test was used to compare differences between the groups. Univariate logistic regression analysis was conducted for HGEC prediction. RESULTS: Of 1237 patients diagnosed with HGEC, 245 (19.8%) did not have a preoperative diagnosis of high-grade disease. Discordancy was identified in 91/287 (31.71%) of biopsies reported by GP, and in 114/910 (12.53%) of biopsies reported by a GYNP (p < 0.0001). Compared to GP, GYNP were 3.24 (CI 2.36-4.45) times more likely to identify high grade disease on preoperative biopsy. Patients whose biopsy was reported by a GYNP were more likely to have a comprehensive staging procedure (OR 1.77 CI 1.33-2.38) and less likely to receive adjuvant therapy (OR 0.71 CI 0.52-0.96). CONCLUSION: GYNP are more likely to identify HGEC on pre-operative biopsies. Due to high rates of overall discordancy, it is possible that surgical staging procedures should not be based solely on preoperative biopsy. Further strategies to improve pre-operative biopsies' accuracy are needed.

Simple vaginal trachelectomy in women with early-stage low-risk cervical cancer who wish to preserve fertility: the new standard of care?

OBJECTIVE: There is a trend toward less radical surgery in women with small-volume disease who wish to preserve fertility. The objective of our study was to evaluate the oncologic and obstetrical outcome of simple vaginal trachelectomy and lymph node assessment in patients with low-risk early-stage cervical cancer (<2 cm). METHODS: From May 2007 to January 2020, 50 patients underwent a simple vaginal trachelectomy/conization with laparoscopic sentinel lymph node mapping±complete pelvic node dissection. Patients underwent loop electrocautery excision (LEEP), cone/cervical biopsies, or simple trachelectomy. A preoperative pelvic MRI with gadolinium contrast was systematically performed in all cases. The size of the lesion was established by review of the LEEP, cone or trachelectomy specimen, MRI, and clinical examination. Data was collected prospectively in a computerized database. Descriptive statistics and the Kaplan-Meier estimate were used for analysis. RESULTS: The median age was 29 years (range: 21-44) and 35 (70%) patients were nulliparous. As per FIGO 2009 classification, 11 patients had stage IA1 with lymphovascular space invasion (LVSI), 13 patients had stage IA2, and 26 patients had stage IB1. Twenty-six patients had squamous histology, 20 patients adenocarcinoma, and four patients other histologies. On final pathology, lymph nodes were negative in 46 patients (92%), three patients had isolated tumor cells, and one patient had micrometastasis. Thirty patients (60%) had either no residual disease in the trachelectomy specimen (22) or residual dysplasia only (eight). With a median follow-up of 76 months (range: 1-140), only one local recurrence occurred which was treated initially with chemoradiation. She recurred again locally and underwent a pelvic exenteration: the patient progressed again and died of disease. The 5-year progression-free survival and overall survival was 97.9% and 97.6%, respectively. There were 40 pregnancies: five (12.5%) ended in the first trimester, one (2.5%) in the second trimester, and three (7.5%) were late preterm: all the others (30 or 75%) delivered >36 weeks and one pregnancy is ongoing. CONCLUSION: Simple trachelectomy/conization and lymph node assessment is an oncologically safe fertility-preserving surgery in well-selected patients with low-risk early-stage cervical cancer (<2 cm). Obstetrical outcomes are comparable to the general population.

Effectiveness of an Enhanced Recovery After Surgery Program in Gynaecology Oncologic Surgery: A Single-Centre Prospective Cohort Study.

OBJECTIVE: This study sought to evaluate whether the partial implementation of an Early Recovery After Surgery (ERAS) program lowers length of hospital stay (LOS) without compromising postoperative outcome. METHODS: A single-centre prospective cohort study was conducted in a tertiary gynaecologic oncology department, by comparing standard perioperative care with a partially implemented ERAS protocol. Data on postoperative evolution were gathered for patients who underwent laparotomy for suspected or confirmed endometrial, adnexal, or cervical neoplasia between July 1, 2015 and June 30, 2017 at the Hôtel-Dieu de Québec. RESULTS: A total of 390 cases were identified; 140 patients followed the ERAS protocol, and 250 patients received standard perioperative care. The median LOS in hours was significantly reduced for patients in the ERAS group (65.5 hours [interquartile range 59.8, 71.0] vs. 69.0 hours [interquartile range 64.3, 81.0], P < 0.001). There was no difference in complication rates, neither grade 1 (3% vs. 7%, P = 0.155) nor grades 2 to 4 (7% vs. 5%, P = 0.577), or in readmission rates (0.7% vs. 1.2%, P > 0.99). CONCLUSION: Even a partially implemented ERAS program can significantly affect LOS without compromising patient care.

No. 291-Epidemiology and Investigations forSuspected Endometrial Cancer.

OBJECTIVE: To review the evidence relating to the epidemiology of endometrial cancer and its diagnostic workups. OPTIONS: Women with possible endometrial cancer can undergo an endometrial evaluation by office biopsy, hysteroscopy, or dilatation and curettage. To assist in treatment planning, pelvic ultrasound, CT scan, or MRI may be considered. OUTCOMES: The identification of optimal diagnostic tests to evaluate patients with possible endometrial cancer. EVIDENCE: Published literature was retrieved through searches of PubMed, CINAHL, and The Cochrane Library, using appropriate controlled vocabulary (e.g., endometrial neoplasms) and key words (e.g., endometrium cancer, endometrial carcinoma). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no date or language restrictions. Searches were updated on a regular basis and incorporated in the guideline to December 31, 2011. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, national and international medical specialty societies, and recent conference abstracts. VALUES: The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1). BENEFITS, HARMS, AND COSTS: This document is intended to guide the development of a standardized cost-effective investigation of patients with suspected endometrial cancer. VALIDATION: The guideline was reviewed for accuracy by experts in pathology, radiation oncology, and medical oncology. Guideline content was also compared with relevant documents from the American Congress of Obstetricians and Gynecologists.

Correction to: HtrA1 expression and the prognosis of high-grade serous ovarian carcinoma: a cohort study using digital analysis.

It has been highlighted that the original article [1] contained a typesetting mistake in the family name of Dominique Trudel.

HtrA1 expression and the prognosis of high-grade serous ovarian carcinoma: a cohort study using digital analysis.

BACKGROUND: The expression of high temperature requirement factor A1 (Htra1) has been reported to be decreased in ovarian carcinoma, but its prognostic effect remains undetermined. METHODS: We evaluated the impact of HtrA1 downregulation in tumoral tissues on cancer progression and death in women with serous ovarian carcinoma. HtrA1 staining was performed on tissue microarrays (TMA) comprised of tumor samples from a cohort of 106 women who were diagnosed with primary high-grade serous ovarian carcinoma and receiving standard treatment at the Québec University Hospital between 1993 and 2006. HtrA1 expression was assessed visually (percentage of positive nuclei) and by digital image analysis (percentage of positive area). Cox regression multivariate models included standard prognostic factors and were used to estimate adjusted hazard ratios (aHR) for progression or death in the cohort. RESULTS: By visual analysis, a low percentage of HtrA1-positive nuclei (< 10% vs ≥10%) tend to be associated with a lower risk of progression (aHR = 0.71; 95% Confidence interval (CI) = 0.46-1.09; P = 0.11) and mortality (aHR = 0.65; 95% CI = 0.41-1.04; P = 0.07). Low nuclear HtrA1 expression assessed by digital image analysis (< median % vs ≥ median %) showed a significant association with lower risk of progression (aHR = 0.62; 95% CI = 0.40-0.95; p = 0.03) and death (aHR = 0.60; 95% CI = 0.38-0.95; p = 0.03). CONCLUSION: Altogether, our results demonstrate that nuclear downregulation of HtrA1 is associated with a better prognosis in women with high grade serous ovarian carcinoma.

Tips and tricks to improve sentinel lymph node mapping with Indocyanin green in endometrial cancer.

OBJECTIVE: To determine the validity of sentinel lymph node (SLN) biopsy with ICG in endometrial cancer and to evaluate the factors associated with poor mapping or false negative. METHODS: We reviewed all patients who underwent primary surgery for endometrial carcinoma with SLN mapping using ICG followed by pelvic lymphadenectomy from February 2014 to December 2015. SLNs were ultrastaged on final pathology. Patients' demographics, surgical approach and histopathological factors were prospectively collected. Detection rate, sensitivity and negative predictive value (NPV) were calculated and univariate analysis was performed to evaluate factors associated with failed bilateral detection of SLNs. RESULTS: A total of 119 patients were included. The overall and bilateral detection rates were 93% and 74%. Sensitivity and NPV were 100% in patients with bilateral detection; 95% and 99% respectively in cases with at least unilateral detection. Advanced FIGO stage (III or IV) was the only factor related to failed bilateral detection (p = 0.01). In 14 hemi-pelvis, the specimen labelled as SLN did not contain nodal tissue on final pathology (only lymphatic channels), which represented 37% of the "failed detection" cases. One false negative occurred in a patient with an ipsilateral clinically suspicious enlarged lymph node. CONCLUSION: ICG is an excellent tracer for SLN mapping in endometrial cancer. Advanced FIGO stage correlated with failed bilateral detection (p = 0.01). Suspicious lymph nodes should be removed regardless of the mapping. Care should be taken to ensure that SLN specimen actually contains nodal tissue and not only swollen lymphatic channels, as this represents a significant cause of failed SLN mapping.

The utility of sentinel lymph node mapping in the management of endometrial atypical hyperplasia.

OBJECTIVES: To determine the risk of endometrial cancer (EC) and lymph node involvement in patients with a preoperative diagnosis of "AH-only" versus "AH - cannot rule out carcinoma" and to study the value of SLN mapping. METHODS: We reviewed all patients with a preoperative diagnosis of atypical hyperplasia, who underwent primary surgery with SLN mapping followed by pelvic lymphadenectomy. Sensitivity and negative predictive value (NPV) of SLN and rates of endometrial cancer were calculated. RESULTS: Overall, 64/120 (53.3%) patients were found to have EC on final pathology: 58 stage IA, 3 IB, and 3 IIIC1. In patients with preoperative diagnosis of "AH", 44.3% (31/70) had EC on final pathology compared to 66% (33/50) in patients with "AH - cannot rule out cancer" (p=0.02). Overall, 3.3% of the patients (4/120) had lymph node involvement. In patients with EC with a pre-operative diagnosis of "AH", none had lymph node metastasis (0/31), compared to 12.1% (4/33) in patients with "AH - cannot rule out cancer" (p=0.06). Elevated preoperative CA125 levels (>25U/mL) were statistically associated with the risk of lymph node metastasis on final pathology (p=0.024). Unilateral and bilateral SLN detection occurred in 93.7% and 78.1% respectively. In patients with EC and bilateral SLN mapping, sensitivity and NPV were respectively 66.6% and 97.9%. There was one false negative (ITCs in non-SLN). CONCLUSION: Our data indicate that the risk of lymph node involvement in patients with a preoperative diagnosis of "AH-only" is null. Lymph node assessment could be omitted in those patients. Conversely this risk is significant in patients with "AH - cannot rule out cancer". SLN mapping could be a valuable staging procedure in these patients.

Hic-5 regulates epithelial to mesenchymal transition in ovarian cancer cells in a TGFß1-independent manner.

The molecular basis of epithelial ovarian cancer (EOC) dissemination is still poorly understood. We have previously identified the hydrogen peroxide-inducible clone-5 (Hic-5) gene as hypomethylated in high-grade (HG) serous EOC tumors, compared to normal ovarian tissues. Hic-5 is a focal adhesion scaffold protein and has been primarily studied for its role as a key mediator of TGF-ß-induced epithelial-to-mesenchymal transition (EMT) in epithelial cells of both normal and malignant origin; however, its role in EOC has been never investigated. Here we demonstrate that Hic-5 is overexpressed in advanced EOC, and that Hic-5 is upregulated upon TGFß1 treatment in the EOC cell line with epithelial morphology (A2780s), associated with EMT induction. However, ectopic expression of Hic-5 in A2780s cells induces EMT independently of TGFß1, accompanied with enhancement of cellular proliferation rate and migratory/invasive capacity and increased resistance to chemotherapeutic drugs. Moreover, Hic-5 knockdown in the EOC cells with mesenchymal morphology (SKOV3) was accompanied by induction of mesenchymal-to-epithelial transition (MET), followed by a reduction of their proliferative, migratory/invasive capacity, and increased drugs sensitivity in vitro, as well as enhanced tumor cell colonization and metastatic growth in vivo. The modulation of Hic-5 expression in EOC cells resulted in altered regulation of numerous EMT-related canonical pathways and was indicative for a possible role of Hic-5 in controlling EMT through a RhoA/ROCK mediated mechanism. To our knowledge, this is the first report examining the role of Hic-5 in EOC, and its role in maintaining the mesenchymal phenotype of EOC cells independently of exogenous TGFß1 treatment.