Kinome expression profiling and prognosis of basal breast cancers

<p>Abstract</p> <p>Background</p> <p>Basal breast cancers (BCs) represent ~15% of BCs. Although overall poor, prognosis is heterogeneous. Identification of good- <it>versus </it>poor-prognosis patients is difficult or impossible using the standard histoclinical features and the recently defined prognostic gene expression signatures (GES). Kinases are often activated or overexpressed in cancers, and constitute targets for successful therapies. We sought to define a prognostic model of basal BCs based on kinome expression profiling.</p> <p>Methods</p> <p>DNA microarray-based gene expression and histoclinical data of 2515 early BCs from thirteen datasets were collected. We searched for a kinome-based GES associated with disease-free survival (DFS) in basal BCs of the learning set using a metagene-based approach. The signature was then tested in basal tumors of the independent validation set.</p> <p>Results</p> <p>A total of 591 samples were basal. We identified a 28-kinase metagene associated with DFS in the learning set (N = 73). This metagene was associated with immune response and particularly cytotoxic T-cell response. On multivariate analysis, a metagene-based predictor outperformed the classical prognostic factors, both in the learning and the validation (N = 518) sets, independently of the lymphocyte infiltrate. In the validation set, patients whose tumors overexpressed the metagene had a 78% 5-year DFS <it>versus </it>54% for other patients (p = 1.62E-4, log-rank test).</p> <p>Conclusions</p> <p>Based on kinome expression, we identified a predictor that separated basal BCs into two subgroups of different prognosis. Tumors associated with higher activation of cytotoxic tumor-infiltrative lymphocytes harbored a better prognosis. Such classification should help tailor the treatment and develop new therapies based on immune response manipulation.</p

Endometrial Tumor Microenvironment Alters Human NK Cell Recruitment, and Resident NK Cell Phenotype and Function

Endometrial Cancer is the most common cancer in the female genital tract in developed countries, and with its increasing incidence due to risk factors such as aging and obesity tends to become a public health issue. However, its immune environment has been less characterized than in other tumors such as breast cancers. NK cells are cytotoxic innate lymphoid cells that are considered as a major anti-tumoral effector cell type which function is drastically altered in tumors which participates to tumor progression. Here we characterize tumor NK cells both phenotypically and functionally in the tumor microenvironment of endometrial cancer. For that, we gathered endometrial tumors, tumor adjacent healthy tissue, blood from matching patients and healthy donor blood to perform comparative analysis of NK cells. First we found that NK cells were impoverished in the tumor infiltrate. We then compared the phenotype of NK cells in the tumor and found that tumor resident CD103+ NK cells exhibited more co-inhibitory molecules such as Tigit, and TIM-3 compared to recruited CD103− NK cells and that the expression of these molecules increased with the severity of the disease. We showed that both chemokines (CXCL12, IP-10, and CCL27) and cytokines profiles (IL-1β and IL-6) were altered in the tumor microenvironment and might reduce NK cell function and recruitment to the tumor site. This led to hypothesize that the tumor microenvironment reduces resident NK cells cytotoxicity which we confirmed by measuring cytotoxic effector production and degranulation. Taken together, our results show that the tumor microenvironment reshapes NK cell phenotype and function to promote tumor progression

Recommendations for a standardised educational program in robot assisted gynaecological surgery: consensus from the Society of European Robotic Gynaecological Surgery (SERGS)

Background: the Society of European Robotic Gynaecological Surgery (SERGS) aims at developing a European consensus on core components of a curriculum for training and assessment in robot assisted gynaecological surgery. Methods: a Delphi process was initiated among a panel of 12 experts in robot assisted surgery invited through the SERGS. An online questionnaire survey was based on a literature search for standards in education in gynaecological robot assisted surgery. The survey was performed in three consecutive rounds to reach optimal consensus. The results of this survey were discussed by the panel and led to consensus recommendations on 39 issues, adhering to general principles of medical education. Results: on review there appeared to be no accredited training programs in Europe, and few in the USA. Recommendations for requirements of training centres, educational tools and assessment of proficiency varied widely. Stepwise and structured training together with validated assessment based on competencies rather than on volume emerged as prerequisites for adequate and safe learning. An appropriate educational environment and tools for training were defined. Although certification should be competence based, the panel recommended additional volume based criteria for both accreditation of training centres and certification of individual surgeons. Conclusions: consensus was reached on minimum criteria for training in robot assisted gynaecological surgery. To transfer results into clinical practice, experts recommended a curriculum and guidelines that have now been endorsed by SERGS to be used to establish training programmes for robot assisted surgery

Role of conventionnal laparoscopy and robotic-assisted laparoscopy in the management of cervix and endometrial carcinoma

Depuis 25 ans, la voie d’abord coelioscopique a pris une place importante dans laprise en charge des cancers pelviens, en particulier gynécologique. Cette voie miniinvasive est utilisée pour des procédures diagnostiques, de stadifications outhérapeutiques.Les évolutions technologiques et instrumentales ont permis d’étendre sesapplications à des indications réservées à la laparotomie.Si à la vue des données de la littérature la coelioscopie est devenue la voie d’abord àrecommander dans la prise en charge des cancers du col utérin et de l’endomètre,elle doit faire face à l’arrivée de l’assistance robotisée.Le robot chirurgical Da Vinci se développe depuis 10 ans et ses applications se sontmultipliées. La chirurgie gynécologique et oncologique constitue un éventaild’indications intéressantes pour cette technologie, surtout en cancérologie. De plusen dehors des avantages évidents qu’offre le robot Da Vinci pour le chirurgien, ilsemble que certains paramètres per opératoires soient améliorés, la qualité desprélèvements et la morbidité en particulier.A travers une revue de la littérature et l’exposé des travaux menés, nous démontronsl’applicabilité et l’intérêt potentiel de cette nouvelle approche coelioscopique dans laprise en charge des cancers gynécologiques.Cependant, l’impact médico économique de cette technique ainsi que le gain enterme de morbidité pour nos patientes, par rapport à la voie coelioscopiqueconventionnelle, doivent être précisés par les essais que nous avons initiés et quisont actuellement en cours.Since 25 years, laparoscopic approach has gained an increasing role in cancertreatment, especially of colorectal - and gynecological cancers. The laparoscopicapproach is used for staging and exploratory purposes, as well as for therapeuticpurposes.Recent developments in surgical instruments and techniques allowed to extend theindication of laparoscopy to cases that were formerly reserved for open surgery.As the laparoscopic approach has become the Gold Standard, especially for uteruscancer (cervix and endometrial), the domain of robot-assisted surgery deserves ourattention.The robotic surgical system named « DaVinci » has undergone further developmentsand the indications for this system have been multiplied. The use in gynecologyseems to be an ideal indication for this surgical technique, especially for cancertreatment. Moreover, it might be postulated that the DaVinci surgical system canmodify several peri operative factors, which might result in less morbidity and earlierrecovery from surgery.Though a literature review and our publications we demonstrate the feasibility of thistechnique and its potential place in gynecologic cancers management.However, before this innovative but expensive technique is generally used andaccessible, it is necessary to thoroughly evaluate its surgical quality, its relatedcancer outcome, its economic impact and its related patients’ quality of life

Role of robot-assisted laparoscopy in adjuvant surgery for locally advanced cervical cancer

International audienceThe aim of this study was to compare the feasibility and efficacy of robot-assisted laparoscopy with traditional laparotomy and conventional laparoscopy in a series of patients with locally advanced cervical cancer managed in our two institutions

Liquid Biopsies for Ovarian Carcinoma: How Blood Tests May Improve the Clinical Management of a Deadly Disease

International audienc

Choosing the most appropriate minimally invasive approach to treat gynecologic cancers in the context of an enhanced recovery program: Insights from a comprehensive cancer center

International audienceOBJECTIVE:The aim of the study was to compare the characteristics of procedures for gynecologic cancers conducted with conventional laparoscopy (CL) or robotically assisted laparoscopy (RAL) in the context of an enhanced recovery program (ERP).METHODS:This is a secondary analysis of prospectively collected data from a cohort study conducted between 2016 (when the ERP was first implemented at the Institut Paoli-Calmettes, a comprehensive cancer center in France) and 2018. We included patients who had undergone minimally invasive surgery for gynecological cancers and followed our ERP. The endpoints were the analysis of postoperative complications, the length of postoperative hospitalization (LPO), and the proportion of combined procedures depending on the approach (RAL or CL). Combined procedures were defined by the association of at least two of the following operative items: hysterectomy, pelvic lymphadenectomy, and para-aortic lymphadenectomy.RESULTS:A total of 362 women underwent either CL (n = 187) or RAL (n = 175) for gynecologic cancers and followed our ERP. The proportion of combined procedures performed by RAL was significantly higher (85/175 [48.6%]) than that performed by CL (23/187 [12.3%]; p 3 days after adjusting for predictors of prolonged hospitalization (adjusted OR = 0.573 [0.236-1.388]; p = 0.217).CONCLUSION:Experts from our cancer center preferentially choose RAL to perform gynecologic oncological procedures that present elements of complexity. More studies are needed to determine whether this strategy is efficient in managing complex procedures in the framework of an ERP

Enhanced recovery after surgery program in older patients undergoing gynaecologic oncological surgery is feasible and safe

Background. Enhanced Recovery After Surgery Programs (ERP) include multimodal approaches of perioperative patient's clinical pathways designed to achieve early recovery after surgery and a decreased length of hospital stay (LOS). By allowing patients to return rapidly to their everyday surroundings, older patients are those who could take the greatest benefit from ERP. This is the first study to date to assess feasibility and safety of ERP on older patients undergoing gynaecologic oncological surgery. Methods. Data were prospectively collected between December 2015 and September 2017 at the Institut Paoli-Calmettes, a French comprehensive cancer centre. All the patients included in the study were referred for hysterectomy and/or pelvic or para-aortic lymphadenectomy for gynaecological cancer. The primary objective was to achieve similar LOS in patients >= 70 years old compared to younger patients without increasing the propor- tion of complications and readmission rates. A binary (LOS = 2 days) logistic regression was built, including age, Charlson score, BMI, ASA score, oncological indication, surgical procedures and surgical approaches. G8 score was estimated for all the >= 70years old patients. Results. Of a total of 329 patients, 75 were >= 70 years old and 254 were = 70 years old population, G8 score was not predictive of LOS, morbidities or readmissions. Conclusion. Although it is already widely accepted that ERP improves early recovery, our study shows that ERP for patients over 70 years of age undergoing gynaecologic oncological surgery is as safe and feasible as on younger patients. (C) 2018 Elsevier Inc. All rights reserved

Robotic Nipple-Sparing Mastectomy and Immediate Breast Reconstruction With Robotic Latissimus Dorsi Flap Harvest: Technique and Results

International audienceIntroduction. Only few cases of robotic latissimus dorsi flap reconstruction (RLDFR) have been reported in indication of reconstruction for breast cancer (BC). We report our experience of combined robotic nipple-sparing mastectomy (R-NSM) and RLDFR, and analyze technique, indications, and reproducibility. Methods. All patients with R-NSM and RLDFR from November 2016 to August 2, 2018, were analyzed, and technics have been described. Complication rate with Clavien-Dindo grading and postoperative hospitalization length (days) are reported. Results. Thirty-five R-NSM with RLDFR were performed in 22 cases for primitive BC and 13 for local recurrence. In 12 patients, another surgical procedure was performed during the same time (axillary lymph node dissection or contralateral breast surgery). R-NSM was realized through a short axillar incision, with inside-only installation for 12 patients (34.3%): 18 nonautologous and 17 autologous RLDFR associated with implant in 9 patients. In logistic regression, mastectomy weight >330 g was significantly associated with the use of implant (odds ratio [OR] = 17, P = .015), and significant factor of the time of anesthesia >= 380 minutes was 2 installations (OR = 10.4, P = .049). The median duration of hospitalization stay was 4 days. Complications rates were 51.4% (18/35; 9 grade-1, 2 grade-2, and 7 grade-3). In logistic regression, associated other surgical procedure was predictive of grade-3 complications (OR = 6.87, P = .053). Conclusion. We confirmed the reproducibility and safety of R-NSM and RLDFR with a decreased complication rate. NSM was performed in 42.8% of our patients after previous radiotherapy. We observed an increase of grade-3 complications when R-NSM and RLDFR was combined to another surgical procedure