[Lipofilling in the management of breast cancer: An update based on a literature review and national and international guidelines]. / Le lipomodelage du sein dans un contexte cancérologique : mise au point à partir d'une revue de littérature actualisée et des référentiels nationaux et internationaux.

BACKGROUND: Lipomodelling (LM) is an increasingly used technique to reconstruct or correct an aesthetic defect linked to a loss of substance. In France, the Haute Autorité de santé (HAS) published recommendations in 2015 and 2020 concerning the conditions of use of LM on the treated and contralateral breast. These appear to be inconsistently followed. METHODS: Twelve members of the Senology Commission of the Collège national des gynécologues-obstétriciens français (French College of Gynecologists and Obstetricians) reviewed the carcinological safety of LM and the clinical and radiological follow-up of patients after breast cancer surgery, based on French and international recommendations and a review of the literature. The bibliographic search was conducted via Medline from 2015 to 2022, selecting articles in French and English and applying PRISMA guidelines. RESULTS: A total of 14 studies on the oncological safety of LM, 5 studies on follow-up and 7 guidelines were retained. The 14 studies (6 retrospective, 2 prospective and 6 meta-analyses) had heterogeneous inclusion criteria and variable follow-up, ranging from 38 to 120 months. Most have shown no increased risk of locoregional or distant recurrence after LM. A retrospective case-control study (464 LMs and 3100 controls) showed, in patients who had no recurrence at 80 months, a subsequent reduction in recurrence-free survival after LM in cases of luminal A cancer, highlighting the number of lost to follow-up (more than 2/3 of luminal A cancers). About follow-up after LM, the 5 series showed the high frequency after LM of clinical mass and radiological images (in » of cases), most often corresponding to cytosteatonecrosis. Most of the guidelines highlighted the uncertainties concerning oncological safety of LM, due to the lack of prospective data and long-term follow-up. DISCUSSION AND PERSPECTIVES: The members of the Senology Commission agree with the conclusions of the HAS working group, in particular by advising against LM "without cautionary periods", excessively, or in cases of high risk of relapse, and recommend clear, detailed information to patients before undergoing LM, and the need for postoperative follow-up. The creation of a national registry could address most questions regarding both the oncological safety of this procedure and the modalities of patient follow-up.

[Women with a very high risk of breast cancer: Contraceptives, hormonal replacement therapy use and personalized screening]. / Femmes à très haut risque de cancer du sein : contraception, traitement hormonal substitutif et dépistage personnalisé.

Women with a high family risk of breast cancer are those with an identified genetic predisposition or those who have a suggestive family history without an identified germinal mutation, particularly for BRCA1 and BRCA2. Among these women with a very high risk of breast cancer, the fear of a potentially increased risk of breast cancer linked to some hormonal contraceptives and to the use of hormone replacement therapy, in connection with the general population data collected in literature, has led to certain reluctance to prescribe them to these women. Moreover, confusion often sets due to poor knowledge of the literature. Furthermore, the monitoring procedures consist of breast screening and strategies of risk reduction, based on recent recommendations. In order to improve the gynaecological monitoring throughout their lives, we offer here a review based on an analysis of recent literature and of the recommendations concerning personalized screening, contraception and hormone replacement therapy among women with a very high risk of breast cancer free from this illness.

[Cancer during pregnancy: Proposal of a clinical care pathway based on a regional cohort]. / Cancer et grossesse : état des lieux en Occitanie et proposition d'un parcours de soin.

OBJECTIVES: Cancer during pregnancy affects 1 in 1000 pregnancies. This situation requires multidisciplinary team, however there is no care pathway dedicated to these patients. The main objective was to describe oncological, obstetrical, and neonatal care through a regional inventory. Our secondary objective was to define a regional "cancer and pregnancy" care pathway. MATERIAL AND METHOD: We carried out an observational, retrospective study from 2013 to 2019 including 48 women (all cancer types) from 2013 to 2019 in Occitania. Then, we defined an "optimal care pathway" and we assessed whether it was respected in the breast cancer subgroup of our cohort. RESULTS: Live births occurred in 79% of the women included. Maternal treatment was initiated during pregnancy for 67% of our population (44% chemotherapy). The most frequent pregnancy complication was preterm delivery (39%), mainly iatrogenic (86.6%). No patient in the group of breast cancer benefited from all of the ten criteria of the "optimal care pathway" that we proposed. CONCLUSIONS: A coordinated regional care pathway seems necessary to optimize communication between the healthcare providers (oncologists, gynecologists and multidisciplinary prenatal diagnosis centers, pharmacologists, pediatricians, psychologists, and general practitioners). This study identifies weaknesses in the management of women with cancer during pregnancy and suggests regional improvement opportunities.

[Surgery or not on an atypical breast lesion? Taking anxiety into account in shared decision support from a prospective cohort of 300 patients]. / Opérer ou non une lésion atypique du sein ? Prise en compte de l'anxiété dans l'aide à la décision partagée à partir d'une cohorte prospective de 300 patientes.

INTRODUCTION: Organized and individual breast screening have been accompanied by an increase in the detection of "atypical breast lesions (ABL)". Recently, the NOMAT multicenter study proposed a predictive model of the risk of developing breast cancer after detection of an ABL in order to avoid surgical removal of "low-risk" lesions. It also aimed to provide information on psychological experience, in particularly anxiety, to assist in the shared medical decision process. METHODS: Three hundred women undergoing surgery for ABL were included between 2015 and 2018 at 18 French centers. Women completed questionnaires before and after surgery assessing their level of anxiety (STAI-State, STAI-Trait), their level of tolerance to uncertainty, their perceived risk of developing a breast cancer, and their satisfaction with the management care. RESULTS: One hundred nighty nine patients completed the STAI-Status before and after surgery. Overall, a decrease in anxiety level (35.4 vs 42.7, P<0.001) was observed. Anxious temperament and greater intolerance to uncertainty were significantly associated swith decreased anxiety (33%), whereas younger age was associated with increased anxiety (8%). CONCLUSION: Surgery for ABL seems to be associated with only a few cases with an increase in anxiety and seems to increase the perception of the risk of developing breast cancer. Taking into account the psychological dimension remains in all cases essential in the process of shared therapeutic decision.

[Techniques and complications of non-genetic risk reducing mastectomies: Guidelines of the National College of French Gynecologists and Obstetricians (CNGOF)]. / Modalités et morbidité des mastectomies de réduction de risque en dehors du risque avéré de prédisposition héréditaire : recommandations du Collège national des gynécologues et obstétriciens français (CNGOF).

OBJECTIVE: Based on an updated review of the international literature covering the different surgical techniques and complications of risk reducing mastectomies (RRM) in non-genetic context, the Commission of Senology (CS) of the College National des Gynécologues Obstétriciens Français (CNGOF) aimed to establish recommendations on the techniques to be chosen and their implementation. DESIGN: The CNGOF CS, composed of 24 experts, developed these recommendations. A policy of declaration and monitoring of links of interest was applied throughout the process of making the recommendations. Similarly, the development of these recommendations did not benefit from any funding from a company marketing a health product. The CS adhered to and followed the AGREE II (Advancing guideline development, reporting and evaluation in healthcare) criteria and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method to assess the quality of the evidence on which the recommendations were based. The potential drawbacks of making recommendations in the presence of poor quality or insufficient evidence were highlighted. METHODS: The CS considered 6 questions in 4 thematic areas, focusing on oncologic safety, risk of complications, aesthetic satisfaction and psychological impact, and preoperative modalities. RESULTS: The application of the GRADE method resulted in 7 recommendations, 6 with a high level of evidence (GRADE 1±) and 1 with a low level of evidence (GRADE 2±). CONCLUSION: There was significant agreement among the CS members on recommendations for preferred surgical techniques and practical implementation.

[Damage repair in breast cancer has to evolve]. / Évaluation du dommage corporel en sénologie : une nécessaire évolution.

Breast damage is likely to result in compensation according to the principle of full compensation. However, breast damage, little covered in the scales usually used, requires a specific methodology. The quantification of functional prejudice must be done with regard to the age of the victim and must take into account the possible repercussions on mobility (shoulder and/or spine) as well as the psychological repercussions. Whether or not the nipple and areola are preserved should be described. Temporary aesthetic damage (before breast reconstruction) must be assessed on the basis of objective elements, its duration and quantification on a scale of 0 to 7. Permanent aesthetic damage takes into account scars, deformities, amputations and quality of the prosthesis. A new scale for evaluating permanent aesthetic damage is proposed. Sexual prejudice must take into account an impairment of the pleasure related to sexuality and its erotic function, in line with the concept of sexual health. However, even after reconstruction, the areas of quality of sexual life and sexual satisfaction often remain affected. An exploration using standardized questions from validated questionnaires such as BREAST-Q can be useful. The sequelae linked to the damage on a breast can also lead the woman to limit certain pleasure activities, in particular because of psychological discomfort or even be the cause of a loss of opportunity to carry out a family's life plan.

Is there a role for locoregional treatment of the primary tumor in de novo metastatic breast cancer in the era of tailored therapies?: Evidences, unresolved questions and a practical algorithm.

Improvements in systemic therapies have changed the face of de novo metastatic breast cancer (dnMBC), with a 5-year survival rate exceeding 25 %. Increasing evidence suggests that a subset of patients could benefit from a locoregional treatment (LRT) with prolonged survival, although the diversity of publications on the subject make it difficult to draw any conclusions. In this review, we summarize the available data on retrospective, prospective and current ongoing clinical trials. Since factors such as tumor biology, pattern of metastatic dissemination and the timing of the treatment are closely linked to the therapeutic strategy, we focus on papers which include these aspects. We discuss recent studies indicating that exclusive radiotherapy provides results comparable with those obtained by surgery. We will then discuss the biological rationale for LRT. Finally, we propose a decision-tree to select the optimal candidates for LRT in dnMBC patients.

Identification of a group with high risk of postoperative complications after deep bowel endometriosis surgery: a retrospective study on 164 patients.

PURPOSE: Identify a group with a high risk of postoperative complications after deep bowel endometriosis surgery. METHODS: We conducted a retrospective study on patients treated from 2012 to 2018 in two departments of gynecological surgery at the Toulouse University Hospital, France. The postoperative complications were evaluated in relation to the surgical management, associated with or without non-digestive surgical procedures, initial disease and patient's characteristics. RESULTS: 164 patients were included. A postoperative complication occurred in 37.8% (n = 62) of the cases and required a secondary surgery in 18.3% (n = 30) of the cases. In the univariate analysis, the risk of postoperative complications increased significantly in the presence of segmental resection, disease progression, and associated urinary tract procedure or vaginal incision. In the multivariate analysis, the risk of overall postoperative complications was associated with the surgical management (p = 0.013 and 0.017) and particularly in the presence of segmental resection [Odds Ratio (OR): 20.87; CI 95% (1.96-221.79)]. The risk of rectovaginal fistula increased in the presence of segmental resection [OR: 22.71; CI 95% (2.74-188.01)] as well as in vaginal incision [OR: 19.67; CI 95% (2.43-159.18); p = 0.005]. CONCLUSION: The risk of overall postoperative complications and rectovaginal fistula in particular increases significantly in the presence of vaginal incision, segmental resection and urinary tract procedures after deep bowel endometriosis surgery.

[Regional state-of-the-art of the access to oncofertility consultation for young women with breast cancer]. / État des lieux régional de l'accès à une consultation d'oncofertilité chez les femmes jeunes ayant un cancer du sein.

OBJECTIVES: According to the 2004 Bioethics Act, oncofertility counselling must be systematically offered to all women of childbearing age before they are exposed to potentially gonadotoxic treatment. The main objective of this study was to evaluate the proportion of women under 40 years of age treated with chemotherapy for breast cancer in Midi-Pyrénées who have received an oncofertility consultation. A secondary objective was to assess practitioners' knowledge on the subject. METHODS: A cross-reference was made between the databases of the oncology network in Midi-Pyrénées and the two approved centres for the preservation of fertility in the region. A computerized practitioner questionnaire was sent to all surgeons and oncologists who could manage these patients. RESULTS: From 2012 and 2017, 667 women aged≤40 years received (neo)adjuvant chemotherapy treatment: only 156 (23.4%) had access to an oncofertility consultation and 58 (8.7%) received preservation. This rate (23.4%) varied according to the age of the patients, ranging from 56.9% for those aged 25-29 to 13.4% for those aged 35-39 and the managing institution. Of the 85 practitioners surveyed, 45 (55%) responded to the questionnaire, and of these 20 (44%) knew that ovarian stimulation treatment could be used even in hormone-dependent breast cancer situations and 13 (29%) of practitioners believed that the time required to preserve fertility was more than 1 month. CONCLUSION: Our study revealed a significant disparity in access to oncofertility consultation. It is essential to set up information and awareness-raising actions on the subject.

Multidisciplinary team meeting and EUSOMA quality indicators in breast cancer care: A French regional multicenter study.

INTRODUCTION: We evaluate breast cancer (BC) pathway at a regional level including public, private and university institutions. We assessed the quality of multidisciplinary team meetings (MTM) and compliance with a panel of European high-quality indicators (EUSOMA QIs). METHODS: We conducted a retrospective multicenter (n = 20) study in the largest health care region in France. Between January and April 2015, we included all patients discussed at an MTM after a diagnosis of BC (n = 619). We analyzed quality of MTM by assessing the quorum, the reliability of data transcription and the exhaustivity of pre-therapeutic MTM. We then analyzed the compliance with a selected panel of 16 EUSOMA QIs. RESULTS: During MTM discussion, data were more than 95% consistent with medical records for 9/11 items. Pre-operative tumor histology (90.6%) and post-operative resection margins (84.3%) were the least concordant between medical records and MTM. Minimum standards as defined by EUSOMA were reached for 11/16 QIs, but not reached for pathology reports in non-invasive BC (78.2%), proportion of exclusive sentinel lymph node biopsies in patients with clinically negative axilla (85.2%), performing adjuvant chemotherapy (76.6%), and proportion of patients discussed in pre-therapeutic and post-operative MTM (63.5%). CONCLUSIONS: In this multicentric study evaluating the quality of BC care with a representative sample of institutions, compliance with EUSOMA indicators was satisfactory for all type of institutions. However, too few patients were discussed in pre-therapeutic MTM (especially in non-university hospitals 43.7% [39.4-48.1]) versus 88.7% for others [82.2-95.1]) and data transcription was likely responsible for up to 15% of discordance.

Dietary n-3 long chain PUFA supplementation promotes a pro-resolving oxylipin profile in the brain.

The brain is highly enriched in long chain polyunsaturated fatty acids (LC-PUFAs) that display immunomodulatory properties in the brain. At the periphery, the modulation of inflammation by LC-PUFAs occurs through lipid mediators called oxylipins which have anti-inflammatory and pro-resolving activities when derived from n-3 LC-PUFAs and pro-inflammatory activities when derived from n-6 LC-PUFAs. However, whether a diet rich in LC-PUFAs modulates oxylipins and neuroinflammation in the brain has been poorly investigated. In this study, the effect of a dietary n-3 LC-PUFA supplementation on oxylipin profile and neuroinflammation in the brain was analyzed. Mice were given diets deficient or supplemented in n-3 LC-PUFAs for a 2-month period starting at post-natal day 21, followed by a peripheral administration of lipopolysaccharide (LPS) at adulthood. We first showed that dietary n-3 LC-PUFA supplementation induced n-3 LC-PUFA enrichment in the hippocampus and subsequently an increase in n-3 PUFA-derived oxylipins and a decrease in n-6 PUFA-derived oxylipins. In response to LPS, n-3 LC-PUFA deficient mice presented a pro-inflammatory oxylipin profile whereas n-3 LC-PUFA supplemented mice displayed an anti-inflammatory oxylipin profile in the hippocampus. Accordingly, the expression of cyclooxygenase-2 and 5-lipoxygenase, the enzymes implicated in pro- and anti-inflammatory oxylipin synthesis, was induced by LPS in both diets. In addition, LPS-induced pro-inflammatory cytokine increase was reduced by dietary n-3 LC-PUFA supplementation. These results indicate that brain n-3 LC-PUFAs increase by dietary means and promote the synthesis of anti-inflammatory derived bioactive oxylipins. As neuroinflammation plays a key role in all brain injuries and many neurodegenerative disorders, the present data suggest that dietary habits may be an important regulator of brain cytokine production in these contexts.

Anatomical description of the umbilical arteries and impact of their ligation on pelvic and perineal vascular supply after cystectomy in women.

OBJECTIVE: In radical cystectomy, the surgeon generally ligates the umbilical artery at its origin. This artery may give rise to several arteries that supply the sexual organs. Our aim was to evaluate pelvic and perineal devascularisation in women after total cystectomy. PATIENTS AND METHODS: We carried out a prospective anatomical and radiological study. We performed bilateral pelvic dissections of fresh adult female cadavers to identify the dividing branches of the umbilical artery. In parallel, we examined and compared the pre- and postoperative imaging investigations [magnetic resonance imaging (MRI) angiography] in patients undergoing cystectomy for benign disease to quantify the loss of pelvic vascularisation on the postoperative images by identifying the occluded arteries. RESULTS: The anatomical study together with the radiological study visualised 35 umbilical arteries (n = 70) with their branching patterns and collateral arteries. The uterine artery originated from the umbilical artery in more than 75% of cases (n = 54) of the internal pudendal artery in 34% (n = 24) and the vaginal artery in 43% (n = 30). The postoperative MRI angiograms showed pelvic devascularisation in four patients. Devascularisation was dependent on the level of surgical ligation. In the four patients with loss of pelvic vascular supply, the umbilical artery had been ligated at its origin. CONCLUSION: The umbilical artery gives rise to various branches that supply the pelvis and perineum. If the surgeon ligates the umbilical artery at its origin during total cystectomy, there is a significant risk of pelvic and perineal devascularisation.

Cell-assisted lipotransfer: Current concepts.

Autologous fat transfer, or lipofilling, is a common technique used for soft tissue reconstruction. It has been used for many years, but the technique is associated with a significant graft resorption rate (20% to 80%). To improve the fat graft survival rate, several methods have been tested, and one has appeared more promising: cell-assisted lipotransfer (CAL). In the CAL method, fat is enriched with adipose-derived stromal cells (ASC), contained in the stromal vascular fraction (SVF) obtained after enzymatic digestion of fat or after cell culture to improve the fat survival rate. In this concise review, we present the clinical indications, and the technical principles of CAL, as well as a presentation of ASC. To conclude, we present the main results (efficacy, complications and safety) obtained from different studies of this technique.

Resolvin D1 and E1 promote resolution of inflammation in microglial cells in vitro.

Sustained inflammation in the brain together with microglia activation can lead to neuronal damage. Hence limiting brain inflammation and activation of microglia is a real therapeutic strategy for inflammatory disease. Resolvin D1 (RvD1) and resolvin E1 (RvE1) derived from n-3 long chain polyunsaturated fatty acids are promising therapeutic compounds since they actively turn off the systemic inflammatory response. We thus evaluated the anti-inflammatory activities of RvD1 and RvE1 in microglia cells in vitro. BV2 cells were pre-incubated with RvD1 or RvE1 before lipopolysaccharide (LPS) treatment. RvD1 and RvE1 both decreased LPS-induced proinflammatory cytokines (TNF-α, IL-6 and IL-1ß) gene expression, suggesting their proresolutive activity in microglia. However, the mechanisms involved are distinct as RvE1 regulates NFκB signaling pathway and RvD1 regulates miRNAs expression. Overall, our findings support that pro-resolving lipids are involved in the resolution of brain inflammation and can be considered as promising therapeutic agents for brain inflammation.

Impact of various emulsifiers on ALA bioavailability and chylomicron synthesis through changes in gastrointestinal lipolysis.

Formulating healthy food rich in omega 3 fatty acids requires prior knowledge of the parameters influencing their bioavailability and their metabolic fate. In this context, we studied the effects of various emulsifiers widely used in the food industry, on the gastrointestinal lipolysis of flaxseed oil emulsions in an in vitro model and on the intestinal absorption and lymphatic secretion of alpha-linolenic acid (ALA) in rats. In vitro data showed that the emulsification of flaxseed oil with soya lecithin improved the gastric lipolysis of the oil (+30%), while the presence of Tween 80 or of sodium caseinate decreased it (-80% and -40%, respectively). The in vivo data demonstrated that the intestinal absorption and the lymphatic secretion of ALA were improved with soya lecithin (Cmax = 24 mg mL(-1)) and reduced in the presence of sodium caseinate (Cmax = 7 mg mL(-1)) compared to unemulsified flaxseed oil (Cmax = 16 mg mL(-1)); Tween 80 had no effect. In addition, the synthesized chylomicrons were notably larger and more numerous with soya lecithin whereas they were smaller in the presence of sodium caseinate (p < 0.05). This study shows that the intestinal bioavailability of ALA was increased by the emulsification of flaxseed oil with soya lecithin via an improved lipolysis, favouring the intestinal absorption of ALA and the secretion of many large chylomicrons in lymph.

[Lipofilling in breast reconstruction: is there any population with higher risk of local recurrence? Literature systematic review]. / Transfert de tissu adipeux en reconstruction mammaire: y a-t-il des populations à risque? Revue systématique de la littérature.

Safety of the autologous fat grafting (AFG) in the breast parenchyma remains a debated topic, particularly in reconstruction following breast cancer. This procedure still raises many questions, especially considering recent in vitro studies warning about the fact that lipofilling could promote tumor recurrence through increased neoangiogenesis, or facilitate metastasis. Through a systematic literature review on oncological risk and radiological follow-up, conducted from January 2010 to August 2014, we tried to identify populations at risk of recurrence after AFG. The study selection process was adapted from the Prisma statement. Out of the seven analysed patients cohorts, i.e. approximately 1500 AFG procedures, results on the risk of local recurrence appear reassuring after an average follow-up of 42 months. These results should be cautiously interpreted because of the heterogeneity of the studies. However, recurrences have been analysed based on the characteristics of the original tumor and many of them warn about population that seem more at risk of recurrence. Studies on radiological modifications after AFG emphasize the need for the radiologists to know the importance of radiological images induced by this procedure, however, AFG does not seem to interfere with radiological screening of local recurrence. In order to deliver clear information to patients receiving breast reconstruction by lipofilling, prospective studies focused on populations that seem to be most at risk of recurrence are required.