[Assessment of trainee urologists' knowledge in urogenital anatomy]. / Évaluation des connaissances en anatomie uro-génitale des urologues en formation.

The purpose of this study was to assess trainee urologists' [interns and assistant heads of university hospitals (CHU)] knowledge of the anatomy of the urogenital system. An examination consisting of 10 timed (16minutes) multiple-choice questions (MCQ) based on urogenital anatomy assessments for students in third year of the general medical science diploma program (DFGSM3) was sent to members of the French Association of Trainee Urologists (AFUF) in May 2018 in order to compare the average scores of these two populations. In addition, a questionnaire consisting of epidemiological data, their opinion on the quality of education in anatomy and the willingness to have more courses on this subject was included in the examination. The same scale based on a score out of 20 was applied to both populations. Of the 501 AFUF members solicited, 144 answered all the questions (28.7%). The mean score for urologists was lower than that of DFGSM3 students (10.56±1.82 vs. 11.4±2.37 respectively) (P=0.0013). Moreover, the desire for further education in anatomy was widespread among urologists (87%). According to our study, urologists have less knowledge of urogenital anatomy than third year medical students. Many means are being implemented or are available to rectify this failing, especially since the majority of trainee urologists consider that there are insufficient anatomy lessons in the curriculum and would like to receive further education in anatomy. LEVEL IF EVIDENCE: 3.

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.

[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.

Pentoxifylline inhibits tumor necrosis factor-alpha (TNF alpha)-induced T-lymphoma cell adhesion to endothelioma cells.

Pentoxifylline, a methylxanthine derivative, has been shown to inhibit T-cell-mediated cutaneous immune response by yet ill-understood mechanisms. Because cell adhesion to endothelial cells is a critical step in the initiation of such immune responses, we analyzed whether pentoxifylline would affect this process. To address this issue, adhesion of mouse T-lymphoma cells (TK-1) to mouse endothelioma cells (eEnd.2), either untreated or stimulated with tumor necrosis factor-alpha (TNF alpha), was studied. Pentoxifylline reduced the ability of endothelioma cells stimulated with different concentrations of TNF alpha, but not of untreated endothelioma cells, to bind T-lymphoma cells in dose-dependent (10(-5)-10(-3) M) fashion. Selective incubation of either endothelioma cells or T-lymphoma cells revealed that pentoxifylline acted exclusively on the endothelioma cells, even when added after TNF alpha stimulation. We questioned whether pentoxifylline suppressed T-lymphoma cell/endothelioma cell interactions by interfering with adhesion molecules expressed by either cell. However, as determined by flow cytometry, pentoxifylline did not alter TNF alpha-induced upregulation of intercellular adhesion molecule-1 or vascular cellular adhesion molecule-1 on endothelioma cells nor did it affect constitutive CD11a, CD18, or alpha 4-integrin expression on T-lymphoma cells, suggesting that rather than affecting quantitative expression of these adhesion molecules, pentoxifylline might modulate their avidity. We conclude that pentoxifylline in therapeutically achievable concentrations is a potent inhibitor of TNF alpha-induced T-lymphoma cell adhesion to endothelioma cells. This finding may account, at least in part, for the recently discovered anti-inflammatory action of pentoxifylline.

Possible role of coagulation factor XIII in the pathogenesis of venous leg ulcers.

BACKGROUND: Aim of this placebo-controlled clinical study was to examine the expression pattern of coagulation factor XIIIa in patients with chronic venous leg ulcers and the impact of a 10 day topical factor XIII treatment on ulcer healing, leg ulcer size and radius reduction. PATIENTS AND METHODS: 24 patients were stratified into two groups, each consisting of 12 patients, with leg ulcers > 1.000 mm2, or < 1.000 mm2. Four patients of each study group were assigned to the control group (n = 8). All leg ulcers were treated by topical application of non-adhering dressings and compression therapy. Patients of the treatment group (n = 16) were treated by additional topical treatment off factor XIII twice daily for ten days. Immunohistochemical staining of leg ulcer specimens before and after treatment (day 10) was performed in all patients. RESULTS: The immunohistochemical staining of factor XIIIa in all specimens before and after therapy showed no significant increase in the expression of factor XIIIa. Comparison of the leg ulcer size, radius and daily radius reduction in the treatment and control group showed no significant differences in values of patients with leg ulcers > 1.000 mm2. However, a decreased leg ulcer size and radius was found in patients of the treatment group with more acute leg ulcers < 1.000 mm2 in contrast to patients with larger leg ulcers (daily ulcer radius reduction from day 0-10; 0.31 mm versus 0.13 mm, p < 0.015). CONCLUSIONS: These results indicate that locally applied factor XIII promotes especially wound healing of more acute smaller venous leg ulcers. Since immunohistochemical staining of factor XIIIa showed no significant differences before and after therapy, we propose that factor XIII is inactivated rapidly after local application on venous leg ulcers.

[Selective photothermolysis of superficial varicose veins telangiectasias of the lower extremity]. / Selektive Photothermolyse von Besenreiservarizen und Teleangiektasien der unteren Extremität.

Leg venectasia is a common problem. Although there are a variety of therapeutic modalities, none of them gives satisfactory results. The effects of sclerotherapy in the treatment of telangiectasia with a small diameter are poor. Electrocoagulation and argon laser treatment often result in scarring. We studied the effectiveness of the flashlamp pumped pulsed dye laser at a wavelength of 585 nm in the treatment of leg venectasia. After repeated treatments using this laser system, only 30% of the vessels that looked blue on clinical examination could be removed; we obtained better lightening of smaller red, telangiectatic vessels with a diameter up to 0.4 mm. However, hyperpigmentation frequently developed after treatment. In post-treatment biopsies, occlusion of the vessels was found. Based on these results, we recommend a combined therapy for leg venectasia. Larger diameter vessels should be treated with sclerotherapy, while finer telangiectasia can be treated with the flashlamp pumped pulsed dye laser.

Expression of the adhesion molecules ICAM-1, VCAM-1, and E-selectin and their ligands VLA-4 and LFA-1 in chronic venous leg ulcers.

BACKGROUND: Leukocyte binding to endothelial cells (ECs) is thought to contribute to the pathogenesis of leg ulcers caused by chronic venous insufficiency. In other systems, such binding is mediated by the interaction of adhesion molecules such as intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule- (VCAM-1) and E-selectin (on ECs), and leukocyte function-associated antigen-1(LFA-1) and very late activated antigen-4 (VLA-4) (on Leukocytes). OBJECTIVE: Our purpose was to determine whether an increased expression of these adhesion molecules contributes to the pathogenesis of chronic venous insufficiency. METHODS: Twenty-seven biopsy specimens of inflamed dermatoliposclerotic skin adjacent to venous leg ulcers were stained immunohistochemically with monoclonal antibodies against ICAM-1, VCAM-1, LFA-1, VLA-4, and E-selectin. Staining intensity was compared with that of normal skin. RESULTS: Specimens of leg ulcers caused by chronic venous insufficiency showed increased expression of ICAM-1 and VCAM-1 but not of E-selectin on The expression of LFA-1 and VLA-4 on perivascular leukocytes was increased dramatically in comparison to healthy skin. CONCLUSION: Upregulation of ICAM-1 and VCAM-1 on ECs may contribute to the increased adherence and extravasation of LFA-1 and VLA-4-positive leukocytes in chronic venous insufficiency.

Expression of the adhesion molecules ICAM-1, VCAM-1, LFA-1 and VLA-4 in the skin is modulated in progressing stages of chronic venous insufficiency.

In inflammation and wound healing, dynamic changes in cell adhesion and migration are fundamental properties of the cells involved. Disturbed interaction of leukocytes with microvascular endothelial cells has been proposed to be a central pathogenic factor in chronic venous insufficiency. This disease may therefore serve to elucidate dysregulated modulation of adhesion molecule expression in conditions of chronic inflammation and impaired wound healing. In this study, we determined how the expression of ICAM-1/VCAM-1 on endothelial cells and their ligands LFA-1/VLA-4 on leukocytes is modulated in skin of progressing stages of chronic venous insufficiency. Immunohistochemical staining of skin biopsies revealed an increase in the expression of ICAM-1 and VCAM-1 on endothelial cells in an early stage of venous disease such as stasis dermatitis. Such protein expression correlated with an increase of corresponding mRNA in skin biopsies. Expression of these CAMs on endothelial cells was accompanied by the occurrence of a marked perivascular infiltration of leukocytes, which expressed increased levels of LFA-1 and VLA-4. In progressing stages of chronic venous insufficiency, characterized by hyperpigmentation and lipodermatosclerosis, which precede skin ulceration, all these CAMs remained upregulated on endothelial cells and infiltrating leukocytes. Our findings indicate that following an initial peak expression during stasis dermatitis, vascular ICAM-1 and VCAM-1 expression is not downmodulated to baseline levels, but remains upregulated. This possibly promotes tissue damage by a perpetuated, upregulated influx of activated leukocytes, finally leading to skin ulceration.

Prostaglandin E1 inhibits TNF alpha-induced T-cell adhesion to endothelial cells by selective down-modulation of ICAM-1 expression on endothelial cells.

Prostaglandins have been shown to be involved in the suppression of contact hypersensitivity (CHS) by so-far ill understood mechanisms. T-cell migration across the lining of cytokine-activated endothelial cells (EC) is thought to be a central step in the initiation of CHS. The aim of our investigation was therefore to examine whether prostaglandin E1 (PGE1) influences cytokine-induced TK-1 mouse T-cell lymphoma adhesion to eEnd.2 mouse endothelioma cells. Here, we report that PGE1 (10(-12)-10(-8) M) dose-dependently reduced TNF alpha-induced T-cell binding, while TNF alpha-unstimulated adhesion was not affected. To test whether PGE1 acted primarily on T-cells or on EC, they were separately pretreated with PGE1 prior to the adhesion assay. Selective PGE1 pretreatment of eEnd.2, but not of TK-1 dose-dependently inhibited TNF alpha, stimulated T-cell adhesion. Since binding of TK-1 to TNF alpha-treated eEnd.2 is mediated by the interaction of ICAM-1 and VCAM-1 (on EC) with their receptors LFA-1 and VLA-4 (on T-cells), we further investigated whether PGE1 would modulate the expression of these molecules. FACS-analysis revealed PGE1 to inhibit TNF alpha-induced upregulation of ICAM-1, but not of VCAM-1 on EC. Furthermore, constitutive LFA-1 and VLA-4 expression on T-cells was not affected by PGE1. We conclude that PGE1 supresses T-cell adhesion to EC by selectively inhibiting TNF alpha-induced upregulation of ICAM-1 on EC. This may be one mechanism by which prostaglandins suppress immune responses requiring T-cell EC interactions such as contact hypersensitivity in skin.