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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.

Purpose We aimed to investigate the safety, adequacy and oncological outcomes of laparoscopic surgery (LS) and robot-assisted laparoscopic (RALS) approach for the treatment of early-stage ovarian cancer. Methods We performed a multicentric, retrospective cohort study, enrolling patients affected by early-stage ovarian cancer who underwent laparoscopic management for early-stage ovarian cancer between 2006 and 2014. Surgical, pathologic and oncologic outcome data were analyzed to compare LS and RALS performances for early-stage ovarian cancer management. Results 39 patients underwent laparoscopic staging for presumed stage I ovarian cancer: 23 underwent LS and 16 underwent RALS. The mean operative time was 281 ± 81 min (LS 288 ± 88 min; RALS 270 ± 72 min; p  = 0.49). No conversion to laparotomy occurred, and one patient had intraoperative hemorrhage requiring blood transfusion. Four patients (10.2 %) experienced postoperative complications of grade 3 according to the Clavien-Dindo classification. The median hospital stay was 3 days (1–15); the differences were not statistically significant between two groups [LS = 4 (1–15); RALS = 3 (1–7); p  = 0.43]. During a mean follow-up period of 19.4 months, tumor recurrence occurred in 3 patients: 2 (8.7 %) in the LS group and 1 (6.25 %) in the RALS group. Overall survival and disease-free survival for the entire cohort were 97.4 and 92.3 %, respectively. Conclusions LS and RALS seem to be adequate and feasible for the treatment of early-stage ovarian cancer in terms of the surgical outcomes and oncological safety. Furthermore, in our experience, perioperative outcomes are comparable between LS and RALS making them an acceptable approach in selected patients.

Endometrioid ovarian cancers (EOvC) are usually managed as serous tumors. In this study, we conducted a comprehensive molecular investigation to uncover the distinct biological characteristics of EOvC. This retrospective multicenter study involved patients from three European centers. We collected clinical data and formalin‐fixed paraffin‐embedded (FFPE) samples for analysis at the DNA level using panel‐based next‐generation sequencing and array‐comparative genomic hybridization. Additionally, we examined mRNA expression using NanoString nCounter® and protein expression through tissue microarray. We compared EOvC with other ovarian subtypes and uterine endometrioid tumors. Furthermore, we assessed the impact of molecular alterations on patient outcomes, including progression‐free survival (PFS) and overall survival (OS). Preliminary analysis of clinical data from 668 patients, including 86 (12.9%) EOvC, revealed more favorable prognosis for EOvC compared with serous ovarian carcinoma (5‐year OS of 60% versus 45%; P = 0.001) driven by diagnosis at an earlier stage. Immunohistochemistry and copy number alteration (CNA) profiles of 43 cases with clinical data and FFPE samples available indicated that EOvC protein expression and CNA profiles were more similar to endometrioid endometrial tumors than to serous ovarian carcinomas. EOvC exhibited specific alterations, such as lower rates of PTEN loss, mutations in DNA repair genes, and P53 abnormalities. Survival analysis showed that patients with tumors harboring loss of PTEN expression had worse outcomes (median PFS 19.6 months vs. not reached; P = 0.034). Gene expression profile analysis confirmed that EOvC differed from serous tumors. However, comparison to other rare subtypes of ovarian cancer suggested that the EOvC transcriptomic profile was close to that of ovarian clear cell carcinoma. Downregulation of genes involved in the PI3K pathway and DNA methylation was observed in EOvC. In conclusion, EOvC represents a distinct biological entity and should be regarded as such in the development of specific clinical approaches. We used tissue microarray, mRNA and DNA analyses to compare endometrioid ovarian cancer (EOvC) with serous ovarian cancer and endometrioid endometrial cancer. We observed that EovC exhibit specific protein, mRNA, and DNA profiles. PTEN expression was prognostic with shorter progression‐free survival in patients with PTEN loss. Our observations highlight the need to develop research programs dedicated to rare subtypes of ovarian cancer.

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). 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. 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 < 0.001). The proportions of postoperative complications were similar between the two groups (19.4% versus 17.1%; p = 0.59). Logistic regression analysis revealed a statistically insignificant trend in the association of RAL with a reduced likelihood of an LPO > 3 days after adjusting for predictors of prolonged hospitalization (adjusted OR = 0.573 [0.236-1.388]; p = 0.217). 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.

Endometrial cancer (EC) can easily be cured when diagnosed at an early stage. However, advanced and metastatic EC is a common disease, affecting more than 15,000 patients per year in the United Sates. Only limited treatment options were available until recently, with a taxane–platinum combination as the gold standard in first-line setting and no efficient second-line chemotherapy or hormone therapy. EC can be split into four molecular subtypes, including hypermutated cases with POLE mutations and 25–30% harboring a microsatellite instability (MSI) phenotype with mismatch repair deficiency (dMMR). These tumors display a high load of frameshift mutations, leading to increased expression of neoantigens that can be targeted by the immune system, including (but not limited) to T-cell response. Recent data have demonstrated this impact of programmed death 1 and programmed death ligand 1 (PD-1/PD-L1) inhibitors on chemo-resistant metastatic EC. The uncontrolled KEYNOTE-158 and GARNET trials have shown high response rates with pembrolizumab and dostarlimab in chemoresistant MSI-high tumors. Most responders experiment long responses that last more than one year. Similar, encouraging results were obtained for MMR proficient (MMRp) cases treated with a combination of pembrolizumab and the angiogenesis inhibitor lenvatinib. Approvals have, thus, been obtained or are underway for EC with immune checkpoint inhibitors (ICI) used as monotherapy, and in combination with antiangiogenic agents. Combinations with other targeted therapies are under evaluation and randomized studies are ongoing to explore the impact of ICI-chemotherapy triplets in first-line setting. We summarize in this review the current knowledge of the immune environment of EC, both for MMRd and MMRp tumors. We also detail the main clinical data regarding PD-1/PD-L1 inhibitors and discuss the next steps of development for immunotherapy, including various ICI-based combinations planned to limit resistance to immunotherapy.

ObjectivesEnhanced recovery after surgery programs (ERAS) have been proven to decrease the length of hospital stay without increasing readmission rates or complications. However, the patient and operative characteristics that improve the chance of a successful early hospital discharge are not well established. The aim of this study was to design a nomogram which could be used before surgery, using the characteristics of patients, to establish who could benefit from early discharge (POD ≤ 2 days).MethodsThis observational study has been prospectively conducted. All the included patients were referred for surgical treatment of gynecologic cancer. We defined two sub-groups of patients on surgical procedure characteristics: isolated procedures (hysterectomy or lymphadenectomy) and combined procedures (at least the association of two procedures).Results230 patients were enrolled during the study protocol. 83.9% of patients were treated with a minimally invasive surgery (MIS). 159 patients (69.1%) were discharged on or before POD 2. On multivariate analysis, the surgical approach (open surgery vs. laparoscopy, OR  0.02 (95% CI [0–0.07]), p < 0.001) and the type of surgery (combined procedure versus isolated procedure, OR  0.41 (95% CI [0.18–0.91]), p = 0.028) were found to be significant predictors of increased hospital stay. A nomogram has been built for the purpose of predicting eligible patients for early post-operative discharge based on the multivariate analysis results (AUC = 0.86, 95% CI [0.81–0.92]).ConclusionThe use of MIS for isolated procedures in oncologic indications constitutes an independent factor of early discharge in a setting of ERAS. These promising preliminary results still require to be validated on a prospective cohort.

Ovarian cancers (OvC) are frequent, with more than 22,000 new cases each year for 14,000 deaths in the United States. Except for patients with BRCA1 or BRCA2 mutations, diagnostic methods, prognostic tools, and therapeutic strategies have not much improved in the last two decades. High throughput tumor molecular analyses have identified important alterations involved in ovarian carcinoma growth and spreading. However, these data have not modified the clinical management of most of patients. Moreover, tumor sample collection requires invasive procedures not adapted to objectives, such as the screening, prediction, or assessment of treatment efficacy, monitoring of residual disease, and early diagnosis of relapse. In recent years, circulating tumor biomarkers (also known as “liquid biopsies”) such as circulating tumor cells, circulating nucleotides (DNA or miRNA), or extracellular vesicles, have been massively explored through various indications, platforms, and goals, but their use has not yet been validated in routine practice. This review describes the methods of analysis and results related to liquid biopsies for ovarian epithelial cancer. The different settings that a patient can go through during her journey with OvC are explored: screening and early diagnosis, prognosis, prediction of response to systemic therapies for advanced stages, and monitoring of residual subclinical disease.

Background A strong correlation between breast cancer (BC) molecular subtypes and axillary status has been shown. It would be useful to predict the probability of lymph node (LN) positivity. Objective : To develop the performance of multivariable models to predict LN metastases, including nomograms derived from logistic regression with clinical, pathologic variables provided by tumor surgical results or only by biopsy. Methods A retrospective cohort was randomly divided into two separate patient sets: a training set and a validation set. In the training set, we used multivariable logistic regression techniques to build different predictive nomograms for the risk of developing LN metastases. The discrimination ability and calibration accuracy of the resulting nomograms were evaluated on the training and validation set. Results Consecutive sample of 12,572 early BC patients with sentinel node biopsies and no neoadjuvant therapy. In our predictive macro metastases LN model, the areas under curve (AUC) values were 0.780 and 0.717 respectively for pathologic and pre-operative model, with a good calibration, and results with validation data set were similar: AUC respectively of 0.796 and 0.725. Among the list of candidate’s regression variables, on the training set we identified age, tumor size, LVI, and molecular subtype as statistically significant factors for predicting the risk of LN metastases. Conclusions Several nomograms were reported to predict risk of SLN involvement and NSN involvement. We propose a new calculation model to assess this risk of positive LN with similar performance which could be useful to choose management strategies, to avoid axillary LN staging or to propose ALND for patients with high level probability of major axillary LN involvement but also to propose immediate breast reconstruction when post mastectomy radiotherapy is not required for patients without LN macro metastasis.

Reoperation after breast-conserving surgery (BCS) could be proposed for positive or close margins. Reoperation type, re-excision or mastectomy, depends on several factors in relation to patient's and tumor's characteristics. We have analyzed our breast cancer (BC) database in order to determine second and third attempts for BCS and mastectomy rates, as well as associated factors for type of surgery. All patients with BCS between 1995 and 2017 were included. Patient's characteristics, pathologic results, and treatments were analyzed. Reoperation rate, type of reoperation, second reoperation, and associated factors of reoperation, mastectomy, and third intervention were determined. Three periods were determined: P1-P3. We analyzed 10,761 patients: 1,161 with ductal carcinoma in situ (DCIS) and 9,600 with invasive BC. The reoperation rate was 41.4% for DCIS and 28.0% for invasive BC. Using multivariate analysis, we identified tumor size >20 mm as being a risk factor for reoperation, whereas age >50 years, P2-3, and some localization decreased reoperation rates. For invasive BC, age >40 years, triple-negative tumors, neoadjuvant chemotherapy, and noncentral tumors decreased reoperation rates and lobular tumor, multifocal tumors, lymphovascular invasion, DCIS component, and Her2-positive tumors increased reoperation rates. For patients requiring reoperation, re-excision was performed in 48.1% (1,523/3,168) and mastectomy was required after first re-excision in 13.46% (205/1,523). For DCIS, mastectomy rates were higher for grade 2 and tumor ≥20 mm. For invasive BC, mastectomy rates were higher for lobular, multifocal, ≥20 mm, Her2-positive tumors and diffuse positive margins and lower for age >50 years and during the last period. Even if interval time between surgery and adjuvant treatments was higher for patients with reoperation, survival rates were not different between patients with and without reoperation. A decrease in reoperation and mastectomy rates had been reported with several associated factors. A third intervention with mastectomy was required in 13.5% of patients. This information should be done in case of reoperation.

Background Robotic latissimus dorsi-flap reconstruction (RLDFR) after skin-sparing mastectomy (SSM) for breast cancer (BC) has been performed through a single nipple incision. We report results of SSM with RLDFR, mainly with analysis of feasibility, morbidity, indications, and technique standardization. Methods We determined characteristics of patients, previous treatment of BC, and type of reconstruction. Surgical technique, duration of surgery, and complication rate were reported according to three successive periods: P1–3. Results Forty RLDFR, with breast implant for 16 patients, with previous breast radiotherapy in 30% had been performed. In logistic regression, factors significantly associated with duration of surgery ≥ 300 min were P2 (OR 0.024, p  = 0.004) and P3 (OR 0.012, p  = 0.004) versus P1. The median mastectomy weight was 330 g and 460 g for BMI < and ≥ 23.5 ( p  = 0.025). Length of hospitalization was 4 days. Total complication rate was 20% (8/40): seven breast complications (four re-operations) and one RLDF complication with re-operation. Periods were significantly predictive of complications ( p  = 0.045). Conclusion SSM with RLDFR is feasible, safe, and reproducible. We reported a decrease of duration of surgery, length of post-operative hospitalization, and complication rate.