Elodie Chantalat

The AF-1-deficient estrogen receptor ERα46 isoform is frequently expressed in human breast tumors.

BackgroundTo date, all studies conducted on breast cancer diagnosis have focused on the expression of the full-length 66-kDa estrogen receptor alpha (ERα66). However, much less attention has been paid to a shorter 46-kDa isoform (ERα46), devoid of the N-terminal region containing the transactivation function AF-1. Here, we investigated the expression levels of ERα46 in breast tumors in relation to tumor grade and size, and examined the mechanism of its generation and its specificities of coregulatory binding and its functional activities.MethodsUsing approaches combining immunohistochemistry, Western blotting, and proteomics, antibodies allowing ERα46 detection were identified and the expression levels of ERα46 were quantified in 116 ERα-positive human breast tumors. ERα46 expression upon cellular stress was studied, and coregulator bindings, transcriptional, and proliferative response were determined to both ERα isoforms.ResultsERα46 was expressed in over 70% of breast tumors at variable levels which sometimes were more abundant than ERα66, especially in differentiated, lower-grade, and smaller-sized tumors. We also found that ERα46 can be generated via internal ribosome entry site-mediated translation in the context of endoplasmic reticulum stress. The binding affinities of both unliganded and fully-activated receptors towards co-regulator peptides revealed that the respective potencies of ERα46 and ERα66 differ significantly, contributing to the differential transcriptional activity of target genes to 17β estradiol (E2). Finally, increasing amounts of ERα46 decrease the proliferation rate of MCF7 tumor cells in response to E2.ConclusionsWe found that, besides the full-length ERα66, the overlooked ERα46 isoform is also expressed in a majority of breast tumors. This finding highlights the importance of the choice of antibodies used for the diagnosis of breast cancer, which are able or not to detect the ERα46 isoform. In addition, since the function of both ERα isoforms differs, this work underlines the need to develop new technologies in order to discriminate ERα66 and ERα46 expression in breast cancer diagnosis which could have potential clinical relevance.

Cervical cancer with paraaortic involvement: do patients truly benefit from tailored chemoradiation therapy? A retrospective study on 8 French centers

We retrospectively studied the therapeutic significance of extended-field radiotherapy combined with concurrent platinum-based chemotherapy for the management of cervical carcinoma with paraaortic spread. Treatment response and survival outcomes were evaluated. One hundred and fifteen women were retrospectively studied. Radiological staging was conducted in 101 (87.8%) patients and paraaortic lymphadenectomy in 78 (67.8%). Patterns of treatment comprised chemoradiation therapy (100%), intracavitary brachytherapy (81.7%), completion surgery (60%) and neoadjuvant chemotherapy (4.3%). Four-year overall and disease-free survivals were 32.7% and 28.8%, respectively. Progression and relapse mostly involved the locoregional area and distant organs, rather than the paraaortic area. Advanced FIGO stage at baseline was the most significant prognostic factor (HR=3.02, p=0.01). Despite systematic extended-field chemoradiation therapy, paraaortic involvement in cervical cancer is associated with poor survival outcomes. The patterns of progression and recurrence suggest the existence of occult metastatic disease at presentation. Additional systemic treatment might thus be beneficial.

Historical perspective on the “discovery” of the anterolateral ligament of the knee

There is a lively debate about the existence, origins and discoverer of the anterolateral ligament of the knee. The complex anatomy of the lateral aspect of the knee has made it difficult to differentiate between various structures such as the iliotibial band, capsulo-osseous layer, Kaplan’s fibres and the anterolateral capsule. The “discovery” of a new anterolateral structure in 2013 was the culmination of many historical studies. In 1879, Paul Ferdinand Segond described a tibial plateau fracture in which he noted a pearly band reinforcing the joint capsule. Other anatomists had their suspicions about this ligament; it was described by Vallois in 1914 in his thesis and extensively studied by Jost in 1921. References to it can be found in comparative anatomy studies. This historical review serves as a reminder that understanding and treating knee sprains is not something new.Level of evidenceV.

Intractable epistaxis: which arteries are responsible? An angiographic study

PurposeEpistaxis constitutes a significant proportion of the Otolaryngologist’s emergency workload. Optimal management differs in relation to the anatomic origin of the bleeding. The outcome of our study was to determine which artery(ies) could be considered as the cause of severe bleeding in the context of severe epistaxis.MethodsFifty-five procedures of embolization preceded by angiography were reviewed. Medical records of interventionally treated patients were analysed for demographics, medical history, risk factors and clinical data. Angiographic findings were also assessed for active contrast extravasation (blush), vascular abnormality and embolised artery.ResultsPrevious angiography showed an active contrast extravasation in only 20 procedures. The most common bleeding source was the sphenopalatine artery (SPA) followed by anterior ethmoïdal artery (AEA) and facial artery. Majority of multiple or bilateral extravasations occured in patients with systemic factors.ConclusionsA better understanding of the potential bleeding source might help and limit the risk of treatment failures. Our study confirms that the SPA is the most common cause of severe bleeding. We also emphasise the role of the AEA not only in traumatic context. Others arteries are rarely involved except in patients with comorbidities or frequent recurrences.

Testosterone Prevents Cutaneous Ischemia and Necrosis in Males Through Complementary Estrogenic and Androgenic Actions

Objective— Chronic nonhealing wounds are a substantial medical concern and are associated with morbidity and mortality; thus, new treatment strategies are required. The first step toward personalized/precision medicine in this field is probably in taking sex differences into account. Impaired wound healing is augmented by ischemia, and we previously demonstrated that 17&bgr;-estradiol exerts a major preventive effect against ischemia-induced skin flap necrosis in female mice. However, the equivalent effects of testosterone in male mice have not yet been reported. We then investigated the role of steroid hormones in male mice using a skin flap ischemia model. Approach and Results— Castrated male mice developed skin necrosis after ischemia, whereas intact or castrated males treated with testosterone were equally protected. Testosterone can (1) activate the estrogen receptor after its aromatization into 17&bgr;-estradiol or (2) be reduced into dihydrotestosterone, a nonaromatizable androgen that activates the androgen receptor. We found that dihydrotestosterone protected castrated wild-type mice by promoting skin revascularization, probably through a direct action on resistance arteries, as evidenced using a complementary model of flow-mediated outward remodeling. 17&bgr;-estradiol treatment of castrated male mice also strongly protected them from ischemic necrosis through the activation of estrogen receptor-&agr; by increasing skin revascularization and skin survival. Remarkably, 17&bgr;-estradiol improved skin survival with a greater efficiency than dihydrotestosterone. Conclusions— Testosterone provides males with a strong protection against cutaneous necrosis and acts through both its estrogenic and androgenic derivatives, which have complementary effects on skin survival and revascularization.

Vulvar necrosis after surgical treatment of femoral neck fracture: a case report and investigation of the mechanism of injury

We report the case of a young patient, presenting with total bilateral vulvar necrosis after reduction of a femoral neck fracture. This report describes the management of this complication, its mechanism of injury and the associated means of prevention. We present an investigation of the vulvar vasculature in order to understand the mechanism of injury. The study of the vulvar vasculature rejects the anatomical hypothesis of selective damage to the internal and external arteries. Instead, it suggests intraoperative impingement of the terminal blood vessels caused by compression against the perineal post prompting discussion on the use of moulded countertraction posts during orthopaedic surgery.

Prospective study feasibility: Screening of antenatal total abnormal pulmonary venous return

Total abnormal pulmonary venous return is a heart defect often missed prenatally, yet at birth, it is a surgical emergency. Antenatal detection could be improved by sonographic visualization of the anastomosis of 2 pulmonary veins in a sinus into the left atrium. The objective of this study is to evaluate the feasibility of this screening method.

Distal femoral torsion: Differences between caucasians and asians. A multicentre computed tomography study of 515 distal femurs

BACKGROUND The posterior condylar angle (PCA) is formed by the posterior condylar line (PCL) and the clinical (or anatomic) transepicondylar line (TEL). The primary objective of this study was to compare the distribution of PCA values in Caucasians and Asians free of knee osteoarthritis. The secondary objectives were to assess PCA variability according to age, gender, and side. HYPOTHESIS PCA values differ between Caucasians and Asians. METHODS The study included the computed tomography scans of 515 healthy femurs, 259 from Asians in China and 256 from Caucasians in France. PCA values were determined based on four landmarks, namely, the two femoral epicondyles and the most prominent point of each condyle at the posterior aspect of the knee. The Mann-Whitney test was chosen to compare PCA values according to ethnic group, gender, and side and Spearmans correlation coefficient to assess correlations with age. Inter-observer and intra-observer variability of PCA measurements was assessed. RESULTS Mean PCA was 6.0°±2.5° (range, 0°-14°) overall, 6.4° (range, 0.31°-14.1°) in the Asians, and 5.5° (range, 0°-13.1°) in the Caucasians (p<0.0001). Chinese femurs are significantly more internally rotated. No differences in PCA values were found according to age (p=0.4307), gender (p=0.7113), or side (p=0.4304). Inter-observer and intra-observer variability was limited for each of the landmarks, indicating that PCA measurement was reliable. CONCLUSION PCA varies not only across individuals as reported previously, but also across ethnic groups. This finding further supports routine PCA measurement on imaging studies before total knee arthroplasty. LEVEL OF EVIDENCE III, comparative retrospective study.

Discovery of a neuroendocrine tumor of the caecum by mammary metastasis using 18F‐DOPA‐PET

Neuroendocrine tumors (NET) develop from the diffuse endocrine system. These are rare tumors that can affect diverse organs. We present here the case of a 42‐year‐old female patient in whom a NET of the breast was discovered that was likely not of mammary origin. The main challenge was finding the primary tumor using immunohistochemistry and specific medical imaging modalities for NET. The primary tumor was localized at the last ileal loop upstream of the Bauhin valve thanks to the use of 18F‐DOPA‐PET. Ileocaecal resection by laparoscopy was performed. A WHO grade 2 NET of the ileum measuring 2.2 cm × 1.5 cm was found that infiltrated the submucosa with six metastatic lymph nodes of the eight removed (6N+/8).

Variability in facial-muscle innervation: A comparative study based on electrostimulation and anatomical dissection: Variability in facial-muscle innervation

Facial‐nerve palsy is the most common complication during facial surgery. However, there are few detailed reports on the distribution of the terminal branches of the facial nerve to the mimetic muscles. This also applies to the communicating branches. The aim of our study was to assess the variability of communicant and terminal branches of the facial nerve in humans. This prospective study involved anatomical dissections and intraoperative electric stimulation of facial nerves. We first performed 30 dissections to define the branching patterns of the extracranial facial nerve, with particular focus on the penetrating points into the mimetic muscles. We then studied and compared these preliminary data with 14 operative facial stimulations conducted during parotidectomies. Each trunk and branch received systematic electrostimulation. The electrostimulation and facial‐and‐neck movements were analyzed by two independent reviewers. The peripheral branching and intercommunication of the facial branches were highly variable. Combining electrostimulation and dissections, the frontalis muscle, the depressor labii inferioris and the platysma showed little nerve recuperation whereas the sphincter muscles (orbicularis ori and oculi) were anatomically protected. Facial‐muscle innervation differed among individuals. We found complex variations in the facial branching mode. Our study highlights the branches and corresponding areas that could be considered anatomically risky. Clin. Anat. 32:169–175, 2019.