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Introduction: Vulvar cancer is a rare cancer, it most often affects older women, with tumours of more advanced size and stage than in younger patients. The first-line treatment for vulvar cancer is surgery. Current European and American guidelines recommend negative histological margins. As tumor size is greater in older patients, the aim of this study was to assess the impact of patient age on surgical excision margins in squamous cell carcinomas of the vulva., Material and Method: This was a retrospective multicenter observational study. A descriptive analysis of the population was performed and a univariate analysis was performed according to patient age. Survival data were plotted using the Kaplan-Meier method and compared using a log rank test. Survival was analyzed using a Cox model to calculate the Hazard Ratio., Results: Among the 547 patients included, there were 206 patients <65 years and 341 ≥ 65 years, including 135 ≥ 80 years. Median postoperative histological lesion size and interquartile range was greater in patients ≥65 years (30 mm [18-45] versus 26 mm [14-34], p < 0.001). Patients ≥65 years of age more often benefited from radical total vulvectomy (n = 103 (28.8 %) versus n = 44 (20.4 %), p = 0.03). However, negative surgical excision margins were identical between the 2 groups (n = 180 (87.4 %) versus n = 286 (83.9 %), p = 0.21). Revision surgery was performed more frequently in patients <65 years. Recurrence-free survival was better in patients aged <65 years (HR = 0.60; CI95 % (0.45-0.82), p = 0.001)., Conclusion: Despite larger tumour size, age is not a factor influencing the achievement of negative excision margins in squamous cell carcinomas of the vulva, at the cost of more radical surgery., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: The aims of this study were to describe survival outcomes in patients with ovarian cancer aged ≥80 years and to explore predictors of poor prognosis., Methods: We collected clinical, demographic, histologic, surgical and follow-up data for patients with ovarian cancer aged ≥80 years from a multicenter French cohort (FRANCOGYN) who underwent surgery from 1999 to 2019. Primary endpoints were overall survival (OS) and disease-free survival (DFS). We performed a descriptive analysis of demographic and clinical data and a survival time analysis and comparison using the Kaplan Meier method and log-rank test., Results: Of 1671 patients treated for ovarian cancer during the study period, 83 were aged ≥80 years (median age at diagnosis, 83 years; range, 80-99). Median OS was 39.6 months (range, 23.64-60.24). Factors significantly associated with OS in the univariate analysis were adjusted Charlson comorbidity index (ACCI) (HR 2.32; 95 % CI, 1.00-5.42 for ACCI >4), FIGO stage (HR 4.07 for FIGO stage >IIA; 95 % CI, 1.43-11.54), debulking surgery (HR 0.40; 95 % CI, 0.20-0.78), residual disease after surgery (HR 3.00; 95 % CI, 1.31-6.87), and postoperative complications (HR 2.24; 95 % CI, 1.04-4.81). Significant independent predictors of worse OS in the multivariate analysis were ACCI >4 (HR 4.96; 95 % CI, 1.57-15.75), perioperative complications (HR 5.01; 95 % CI, 1.32-18.95), and residual tumor after surgical debulking (HR 3.78; 95 % CI, 1.23-11.61)., Conclusion: Age by itself should not refrain surgeons and oncologist from proposing surgical debulking and chemotherapy, as recommended by international guidelines for patients with ovarian cancer aged ≥80 years., Competing Interests: Declaration of competing interest All authors declare no conflict of interest with present work., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Objective: Vulvar cancer is a rare pathology affecting mainly elderly women. This study aims to evaluate the impact of age on tumor size in vulvar cancer., Material and Methods: This was a multicenter retrospective observational study carried out between January 1, 1998, and December 31, 2020, in patients operated on for vulvar cancer. Univariate analysis was performed according to patients' age ≥ or <65 years. Factors associated with tumor size found to be significant according to age were then included in a multiple linear regression model., Results: Of the 382 patients included, there were 133 patients aged <65 years and 249 ≥ 65 years. Radical total vulvectomy surgeries were more frequently performed in women ≥65 years (n = 72 (28.9 %) versus n = 20 (15 %); p = 0.004). The median histological tumor size and interquartile range was 20 mm [13-29] in the <65 years and 30 mm [15-42] in patients ≥65 years (p = 0.001). Multiple linear regression showed that age ≥65 years had a regression coefficient of 7.15 95 % CI [2.32; 11.99] (p = 0.004), constituting a risk factor for larger histological tumour size. Patients aged ≥65 years old had a higher early complication rate (n = 150 (62 %) versus n = 56 (42.7 %), p = 0.001). They also had a greater risk of recurrence (HR = 1.89 (95%CI (1.24-2.89)), p = 0.003) with a worse overall survival (HR = 5.64 (95%CI (1.70-18.68)), p = 0.005)., Conclusion: Age is a risk factor for larger tumor size, leading to more radical surgery and a greater risk of complications in already fragile patients, with a greater risk of recurrence and an impact on overall survival., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Purpose: The present knowledge about lymphatic drainage of the ovary is based on carcinological studies, but it has only rarely been studied under physiological conditions. However, it is one of the preferential routes of dissemination in ovarian cancer, and understanding it is therefore vital for optimal carcinological management.Our purpose was to evaluate the feasibility of an innovative technique to study the lymphatic drainage territories of the ovary using a recirculation module on the cadaveric model., Methods: We injected patent blue into the cortex of twenty "revascularised" cadaver ovaries with the Simlife recirculation model. We observed the migration of the dye live and described the drainage territories of each ovary., Results: We observed a staining of the lymphatic vessels and migration of the dye in all the subjects, systematically ipsilateral to the injected ovary. We identified a staining of the lumbo-aortic territory in 65% of cases, with a preferential lateral-caval involvement (60%) for the right ovary and lateral-aortic territory (40%) for the left ovary. A common iliac involvement was observed in only 10% of cases. In 57% of cases, the staining of the lumbo-aortic territory was associated with a staining of the suspensory ligament. The pelvic territory was involved in 50% of cases, with an external iliac staining in 25% of cases and internal in 20%., Conclusion: Our study provides for a better understanding of lymphatic drainage of the ovary using a new detection method, and allows the possibility of improving the teaching for operators with a realistic model. Continuation of this work could lead to considering more targeted and thus less morbid lymph node sampling for lymph node staging in early-stage ovarian cancer., (© 2024. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

No data are currently available on the functional role of small conductance Ca 2+ -activated K + channels (SKCa) in ovarian cancer. Here, we characterized the role of SK2 (KCa2.2) in ovarian cancer cell migration and chemosensitivity. Using the selective non-cell-permeant SK2 inhibitor Lei-Dab7, we identified functional SK2 channels at the plasma membrane, regulating store-operated Ca 2+ entry (SOCE) in both cell lines tested (COV504 and OVCAR3). Silencing KCNN2 with short interfering RNA (siRNA), or blocking SK2 activity with Lei-Dab7, decreased cell migration. The more robust effect of KCNN2 knockdown compared to Lei-Dab7 treatment suggested the involvement of functional intracellular SK2 channels in both cell lines. In cells treated with lysophosphatidic acid (LPA), an ovarian cancer biomarker of progression, SK2 channels are a key player of LPA pro-migratory activity but their role in SOCE is abolished. Concerning chemotherapy, SK2 inhibition increased chemoresistance to Taxol® and low KCNN2 mRNA expression was associated with the worst prognosis for progression-free survival in patients with serous ovarian cancer. The dual roles of SK2 mean that SK2 activators could be used as an adjuvant chemotherapy to potentiate treatment efficacy and SK2 inhibitors could be administrated as monotherapy to limit cancer cell dissemination., (© 2024 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Abstract: Tumor-associated macrophages are targets of interest in triple-negative breast cancer (TNBC). The translocator protein 18 kDa (TSPO) is a sensitive marker for macrophages and holds potential relevance in TNBC stratification. This pilot prospective study (EITHICS, NCT04320030) aimed to assess the potential of TSPO PET/CT imaging using 18 F-DPA-714 in primary TNBC, compared with immunohistochemistry, autoradiography, and TSPO polymorphism., Patients and Methods: Thirteen TNBC patients were included. They underwent TSPO genotyping (HAB, MAB, LAB), 18 F-FDG PET/CT, and breast MRI. Semiquantitative PET parameters were computed. VOIs were defined on the tumor lesion, healthy breast tissue, and pectoral muscle to obtain SUV, tumor-to-background ratio (TBR), and time-activity curves (TACs). Additionally, immunohistochemistry, 3 H-DPA-714, and 3 H-PK-11195 autoradiography were conducted., Results: The majority of TNBC tumors (11/13, 84%) had a preponderance of M2-polarized macrophages with a median proportion of 82% (range, 44%-94%). 18 F-DPA-714 PET/CT clearly identified TNBC tumors with an excellent TBR. Three distinct patterns of 18 F-DPA-714 TACs were identified, categorized as "above muscular," "equal to muscular," and "below muscular" with reference to the muscular background. For the "above muscular" group (2 HAB and 2 MAB), "equal muscular" group (3 HAB, 3 MAB, and 1 LAB), and "below muscular" group (1 LAB and 1 MAB), tumor TACs showed a 18 F-DPA-714 accumulation slope of 1.35, 0.62, and 0.22, respectively, and a median SUV mean of 4.02 (2.09-5.31), 1.66 (0.93-3.07), and 0.61 (0.43-1.02)., Conclusions: This study successfully demonstrated TNBC tumor targeting by 18 F-DPA-714 with an excellent TBR, allowing to stratify 3 patterns of uptake potentially influenced by the TSPO polymorphism status. Further studies in larger populations should be performed to evaluate the prognostic value of this new biomarker., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: In women, ovarian cancer is the eighth most frequent cancer in incidence and mortality. It is often diagnosed at advanced stages; relapses are frequent, with a poor prognosis. When platinum resistant, subsequent lines of chemotherapy are of limited effect and often poorly tolerated, leading to quality of life deterioration. Various studies suggest a hormonal role in ovarian carcinogenesis, with a rationale for endocrine therapy in these cancers., Patients and Methods: This multicenter, retrospective study assessed the use of endocrine treatment for high-grade ovarian epithelial carcinomas treated between 2010 and 2020., Results: Eighty-one patients with ovarian cancers were included. The median duration of platinum sensitivity was 29 months. We observed a 35% disease control rate with endocrine therapy, and 10% reported symptom improvement. For 19 patients (23.5%), the disease was stabilized for more than 6 months. Median overall survival from diagnosis was 62.6 months. Regarding endocrine therapy predictive factors of response, in a multivariate analysis, 3 factors were statistically significant in favoring progression-free survival: platinum sensitivity (P = .021), an R0 surgical resection (P = .020), and the indication for hormone therapy being maintenance therapy (P = .002)., Conclusion: This study shows real-life data on endocrine therapy in ovarian cancer. As it is a low-cost treatment with many advantages such as its oral administration and its safety, it may be an option to consider. A perspective lies in the search for cofactors to aim as future therapeutic targets to improve the effectiveness of hormone treatment by means of combination therapy., (© The Author(s) 2024. Published by Oxford University Press.)

Epithelial ovarian cancer is mostly discovered at the stage of peritoneal carcinosis. Complete cytoreductive surgery improves overall survival. The Fagotti score is a predictive score of resectability based on peritoneal laparoscopic exploratory. Our aim was to study the inter-observer concordance in an external validation of the Fagotti score. An observational, prospective, multicenter study was conducted using the Francogyn research network. The primary outcome was inter-observer concordance of the Fagotti score. 15 patients in which an ovarian mass was discovered were included. For each patient, the first exploratory laparoscopy before any treatment/chemotherapy was recorded. This bank of 15 videos was subject to blind review accompanied by a Fagotti score rating by 11 gynecological surgeons specializing in oncology. A total of 165 blind reviews were performed. Inter-observer concordance was very good for the Fagotti score with an intraclass correlation coefficient (ICC) of 0.83 [95% CI 0.71; 0.93]. Inter-observer concordance for the adjusted Fagotti score, which accounts for unexplorable areas with extensive carcinomatosis, resulted in an ICC of 0.64 [95% CI 0.46; 0.82]. According to the reviewers, the three least explorable parameters were mesentery involvement, stomach infiltration and liver damage. The ICC of the explorable Fagotti score, i.e. score with deletion of the parameters most often unexplored by laparoscopy, was 0.86 [0.75-0.94]. This study confirms the reproducibility of the Fagotti score during first assessment laparoscopies in cases of advanced ovarian cancer. The explorable Fagotti score has an equivalent or better inter-observer concordance than the Fagotti score., (© 2024. The Author(s).)

SK3 channels are potassium channels found to promote tumor aggressiveness. We have previously demonstrated that SK3 is regulated by synthetic ether lipids, but the role of endogenous ether lipids is unknown. Here, we have studied the role of endogenous alkyl- and alkenyl-ether lipids on SK3 channels and on the biology of cancer cells. Experiments revealed that the suppression of alkylglycerone phosphate synthase or plasmanylethanolamine desaturase 1, which are key enzymes for alkyl- and alkenyl-ether-lipid synthesis, respectively, decreased SK3 expression by increasing micro RNA (miR)-499 and miR-208 expression, leading to a decrease in SK3-dependent calcium entry, cell migration, and matrix metalloproteinase 9-dependent cell adhesion and invasion. We identified several ether lipids that promoted SK3 expression and found a differential role of alkyl- and alkenyl-ether lipids on SK3 activity. The expressions of alkylglycerone phosphate synthase, SK3, and miR were associated in clinical samples emphasizing the clinical consistency of our observations. To our knowledge, this is the first report showing that ether lipids differentially control tumor aggressiveness by regulating an ion channel. This insight provides new possibilities for therapeutic interventions, offering clinicians an opportunity to manipulate ion channel dysfunction by adjusting the composition of ether lipids., Competing Interests: Conflict of interest The authors declare that they have no conflict of interests with the contents of article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: In this study, we conducted a comprehensive evaluation of metastatic profiles and survival outcomes in patients with infiltrating ductal carcinoma (IDC) and infiltrating lobular carcinoma (ILC) treated at our university hospital center., Methods: We collected and analyzed data from all patients diagnosed with invasive breast cancer at our center between January 1, 2007, and 31 December 2014. We specifically compared three subgroups: patients with IDC, patients with ILC and patients with mixed carcinoma, which is a combination of IDC and ILC., Results: Among the 1963 patients treated for invasive breast cancer in our center during the study period, 1435 had IDC, 466 had ILC, and 59 had mixed carcinoma. The incidence of patients with at least one positive axillary lymph node differed significantly: 40 % for IDC, 36 % for ILC, and 45 % for mixed carcinoma (p = 0.001). However, there was no significant difference in the mean number of positive nodes (p = 0.1633). The occurrence of distant metastases was lower in patients with ILC (p = 0.04), particularly in the case of brain metastases (p = 0.01), although there was no difference in bone or visceral metastatic sites. Patients with ILC exhibited a longer mean time to metastasis from the initial diagnosis of invasive breast carcinoma. Overall survival (p = 0.0525) and survival without locoregional recurrence (p = 0.026) were significantly different. Specifically, the 5-year overall survival rates for IDC, ILC, and mixed carcinoma were approximately 95 %. Distance metastatic-free survival at 5 years was 85 % for IDC, 91 % for ILC, and 87 % for mixed carcinoma (p = 0.00506)., Conclusion: Our findings indicate variations in the distribution of distant metastatic sites among patients with IDC, ILC, and mixed carcinoma, as well as differences in survival outcomes. This study sheds light on the unique characteristics and clinical implications associated with these two distinct subtypes of invasive breast cancer., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier Masson SAS.)

Objectives: Describing the constitution of the FRANCOGYN group (a national French research group in Oncological and Gynecological Surgery) and present its current and future development., Methods: Literature review using PUBMed database with the keyword "FRANCOGYN"., Objectives: Describing the constitution of the FRANCOGYN group (a national French research group in Oncological and Gynecological Surgery) and present its current and future development., Results: The FRANCOGYN group was formed in December 2015, bringing together over the years more than 17 gynecological and oncological surgical department in France. The group carries out clinical research on gynecological pelvic cancers by constituting retrospective cohorts. Its legitimacy allows it to lead or co-lead the drafting of recommendations for clinical practice in the field of gynecological cancers. It now offers prospective randomized research funded by national grants., Conclusion: The FRANCOGYN network allows us to propose a national reflection on the surgical management of pelvic cancers in women, resulting in numerous international reference publications., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)