Use of mesenchymal stem cells for cutaneous repair and skin substitute elaboration.

Human mesenchymal stem cells (MSCs) are a heterogeneous population of fibroblast-like cells, which are present in different locations, including bone marrow, adipose tissue, extra-foetal tissues, gingiva and dermis. MSCs, which present multipotency capacities, important expansive potential and immunotolerance properties, remain an attractive tool for tissue repair and regenerative medicine. Currently, several studies and clinical trials highlight the use of MSCs in cutaneous repair underlining that their effects are essentially due to the numerous factors that they release. MSCs are also used in skin substitute development. In this study, we will first discuss the different sources of MSCs actually available. We will then present results showing that bone marrow-derived MSCs prepared according to Good Manufacturing Practices and included in a dermal equivalent are able to promote appropriate epidermis growth and differentiation. These data demonstrate that bone marrow-derived MSCs represent a satisfactory alternative to dermal fibroblasts in order to develop skin substitute. In addition, MSCs could provide a useful alternative to sustain epidermis development and to promote wound healing.

[Low invasion in sentinel lymph node according to the European Working Group In Breast Screening Pathology (EWGBSP) recommendations and non sentinel invasion risk in breast cancer]. / Atteinte minime du ganglion sentinelle selon les recommandations de l'European Working Group in Breast Screening Pathology (EWGBSP) et risque d'atteinte non sentinelle dans le cancer du sein.

OBJECTIVE: Because of variability in histopathological interpretations in studies, it's difficult to elucidate the risk of non-sentinel lymph node involvement in case of sentinel node nanometastases (lesions not larger than 0.2 mm) and micrometastases (lesions not larger than 2 mm but larger than 0.2 mm) in breast cancer. In this study, we have evaluated this risk according to the European Working Group for Breast Screening Pathology (EWGBSP) recommendations. PATIENTS AND METHODS: Among patients who underwent sentinel lymph node dissection between February 2001 and April 2008 in our unit, we reviewed the files of patients who had sentinel lymph node involvement smaller than 2mm. A second interpretation of all sentinel lymph node sections was made according to the EWGBSP recommendations. Each patient had complete axillary dissection. RESULTS: Among 608 patients who had sentinel lymph node dissection for breast cancer, 72 (11.84%) had sentinel lymph node involvement smaller than 2 mm (27 pN0i+ and 45 pN1mi). The percentage of pN1mi patients who had non sentinel involvement is 8.89%. None of pN0i+ patients had non sentinel involvement. DISCUSSION AND CONCLUSION: After making a minimal sentinel lymph node involvement strict interpretation according to EWGBSP restrictive recommendations, nanometastases rate was smaller. Any non sentinel involvement was detected in case of sentinel lymph node nanometastases.

[Risk of axillary recurrence after sentinel lymph node biopsy before neoadjuvant chemotherapy in breast cancer]. / Récidive axillaire après prélèvement du ganglion sentinelle avant chimiothérapie néoadjuvante dans le cancer du sein.

OBJECTIVES: In case of large breast cancer, neoadjuvant chemotherapy (NAC) can be performed to reduce the size of the tumor and thus perform a conservative surgery. The place of the sentinel lymph node biopsy (SLNB) in case of NAC is still debated. The main aim of this study is to assess the risk of axillary recurrence after negative SLNB before NAC. METHODS: It is a retrospective, observational and uni-centric study. We included 18 to 80-year-old patients with unilateral breast cancer requiring a NAC and with a negative SLNB before NAC. Our primary endpoint was axillary recurrence. RESULTS: Between August 2006 and October 2016, 64 patients had a negative GS performing before a NAC and did not benefit from axillary dissection after NAC. The average duration of follow-up was 37 months. During our follow-up, we did not find any cases of axillary recurrence. CONCLUSION: This study supports the reliability of lymph node status assessment using the SLNB before CNA.

How to avoid the uncertainties of intraoperative examination of the sentinel lymph node in breast cancer?

Numerous researchers have confirmed the diagnostic relevance of the sentinel lymph node (SLN) examination in breast carcinoma. Many technical problems are analyzed which are correlated with the intraoperative examination of the SLN and its sensitivity and specificity. In order to avoid the incidence of false positive or false negative intraoperative diagnoses, the authors propose the examination of SLN under local anesthesia, awaiting its definitive analysis before carrying out tumorectomy and/or axillary lymphadenectomy.

Detection of the sentinel lymph node under local anaesthesia in early-stage breast cancer: feasibility study in a series of 78 unselected patients.

AIMS: To evaluate the feasibility of excision of the sentinel lymph node under local anaesthesia in early-stage breast cancer. METHODS: Sentinel lymph node detection under local anaesthesia was carried out on all patients presenting with breast cancer at Stage T0, T1 or T2 < 3 cm and N0, M0. The lymph node was mapped using a radioisotope and patent blue dye and lymphoscintigraphy was routinely performed. No premedication was given, and local anaesthesia was carried out with xylocaine. The patients underwent tumorectomy one week later under general anaesthesia, with or without complete axillary dissection, depending on the results of the definitive histopathological examination of the sentinel lymph node. RESULTS: 78 patients underwent this procedure over a period of 20 months. The procedure was successful in 76 out of the 78 patients, with one failure in mapping and one failure in detection (detection rate = 97.4%). The mean time to detection was 21 min (range: 6-45). It was unnecessary to interrupt the procedure due to patient discomfort in any of the cases. One allergic reaction to patent blue dye was noted and required corticosteroid therapy without interruption of the procedure. The time to detection was correlated with the experience of the surgeon carrying of the procedure, the patient's body mass index and the number of labelled lymph nodes found at lymphoscintigraphy. CONCLUSION: We have shown that it is feasible to detect the sentinel lymph node under local anaesthesia in an unselected population. Using this procedure, patients can undergo surgery with the knowledge of their axillary lymph node status while at the same time avoiding the uncertainties of an intraoperative examination of the sentinel lymph node--a source of many false negatives, particularly in the event of micrometastases.

[Non-medicamentous prevention of thromboembolic disease]. / Prévention non médicamenteuse de la maladie thrombo-embolique.

Virchow's work has showed that thrombogenic situations may have a hematological, either congenital or acquired, parietal or hemodynamic nature. Primary and secondary non-medicamentous prevention of thromboembolism is aimed at screening the patients at risk, avoiding or reducing the alterations of the venous walls, and, most importantly, improving failing or altered venous hemodynamics. The authors review the various clinical and biological situations entailing an increased thrombogenic risk. They sum up the various methods of prevention of venous stasis: Nard's method, associating bandages and deambulation, as well as various techniques of contention, hemodilution, compression with inflatable boots, electric stimulation or assisted mobilization. These methods are used as ambulatory or bedside treatments and in the intra- and perioperative periods, as the case may be. The few studies relating to non-medicamentous methods of prevention of thromboembolism demonstrate their great effectiveness, which is equal to that of the modern heparin treatments. The prevention of thromboembolism is best carried out by associating the latest chemical therapies to non-medicamentous physical methods, which are still of current interest.

[Ultrasonic test of key zones and collateral pathways in cases of arteriopathies of the lower extremities]. / Examen ultrasonique des zones clés et des voies de suppléance en matière d'artériopathie des membres inférieurs (A.M.I.).

Justification is provided for the use of maximal methodology of the Doppler arterial examination of lower limbs by an improved approach to the collateral and distal networks and the detection of possibly dangerous lesions in key zones such as the femoral fork. Details are given of the method used for examination of iliac artery axes, the femoral artery intersection, the deep femoral and popliteal arteries and the popliteal supply network, as well as for rating of the distal tibial circulation.

[The effect of vascular risk factors in arteriopathy of the legs in women]. / Influence des facteurs de risque vasculaire dans l'artériopathie des membres inférieurs de la femme.

Here the analysis of the results of a multicentered prospective epidemiologic study that has counted only the new cases of chronic atherosclerosis obliterans of the lower extremities. Included have been 989 patients (659 men and 330 women). Critical analysis of data allows a comparative study between the sexes. Thus, specifics of arteriopathy among women can be drawn. It appears that they are only the consequences of the fact that men and women reflect a different level of tobacco use in the two populations.

[40 years of blood gases and critical care analytes measurements]. / 40 ans de gazométrie sanguine et autres analytes de l'urgence.

Drawing on his professional experience of fourty years, the author retraces the history of the technological development of blood gases and other critical care analytes measurements from the end of the fifties until today. He reviews the various techniques now available and comments on the phases of their development from test bench to hospital acceptance and market availability. Pulse oximetry is noted as being of particular interest.

[Evaluation of portable point of care instrument: the i-Stat . Report of 7,000 analyses]. / Evaluation d'un analyseur de sant portable: l'i-STAT. Bilan de 7000 analyses.

To validate the use of the i-STAT portable point-of-care instrument, performance checks have been conducted to verify its accuracy for PCO2/PO2 (tonometry) and precision for pH/PCO2/PO2 (control solutions). Results obtained with the i-STAT (pH/PCO2/PO2/Hct) were also compared to those provided by the Bayer Rapidlab 865 routinely used in our laboratory. All these measurements have been conducted under the same conditions using three types of i-STAT cartridges (G3, EG6, EG7) with two of different life duration to each cartridge with a view to observing their potential variability between types and any effect that ageing may have on analytical performances. Differences observed in this respect are not clear enough to draw firm conclusions. On the other hand, we consider the level of PCO2 and particularly PO2 performances not sufficient to warranty their use in the absence of a very strict quality control coupled with a highly developed clinical sense. No real use can be made of values noted for hematocrit (1998 survey).

[Performance limiting causes in single use unit systems for the measurement of PO2 and PCO2 in blood]. / Facteurs de limitation des performances des appareils a cassettes a usage unique pour la mesure de la PO2 et de la PCO2 du sang total.

Having had the opportunity of testing two of the three commercially available single use unit systems (i-STAT and OPTI-1), we have listed a series of performance limiting factors which they share, even though, their detectors being based on different methodologies, they have specific causes of dysfunction. PO2 detectors face the worse problems for different reasons. Temperature control is critical: the cassette or at last the detectors, the internal solution and the specimen have to be heated to 37 C, thermostabilisation to one tenth of degree centigrade is a must. Gas equilibration between liquid phases, the outside ambiance and the plastic material can raise problems: a decrease of the external barometric pressure alters the result, an absence of oxygen buffer capacity can induce modifications of the PO2 in the solutions. The transition of the detectors from a dry to a wet stage can provoke changes of the final result in case of accidental pre-humidication of the cassette. The presence of a single internal solution generates problems linked to a single point calibrage procedure which is a source of variability. The general quality of the cassette can only be evaluated by numerous internal electronic checks: increasing the severity of the controls improves quality but increases the number of rejected cassettes. External quality control through classical procedures are not applicable and finally the quality of the cassettes depends primarily on rigorous manufacturing conditions.

[How to avoid the uncertainties of intraoperative examination of the sentinel lymph node in breast cancer?]. / Comment éviter les aléas de l'examen extemporané du ganglion sentinelle dans le cancer du sein?

The sentinel lymph node procedure is now admitted by many teams for axillary evaluation in the early stage of breast cancer. The classical technique consists in an intraoperative examination of the sentinel lymph node under general anaesthesia during tumorectomy, deciding whether or not complete axillary lymphadenectomy must be done. Intraoperative examination seems to us to have a poor predictive value. In the case of a false positive, the surgeon would perform lymphadenectomy unnecessarily, while a false negative would mean that the patient would have to be re-operated for lymphadenectomy once the definitive results have become available. For all these reasons, we propose the detection of the sentinel lymph node under local anaesthesia and to await its definitive analysis before carrying out tumorectomy on the patient and axillary lymphadenectomy if necessary under general anesthesia. Hence, we consider that the best way to avoid the uncertainties of an intraoperative examination of the sentinel lymph node is not to carry out intraoperative examinations.

[Treatment of uterine fibromas]. / Le traitement des fibromes utérins.

Uterine myomas are frequent tumors, but only some of them need to be treated: only when they are symptomatic. After describing the role of oestrogen and growth factors on the development, and the value of clinical examination and imaging techniques (ultrasonography, outpatient hysteroscopy without anesthesia), the authors study the various treatments. Medical treatments essentially consist of progesterone and preoperative GnRH agonists or in peri-menopause (add-back therapy). When if medical treatment fails, surgery consists of: myomectomy and hysterectomy (by abdominal, laparoscopic or vaginal routes), myolysis and hysteroscopic resection. Three cases are isolated: infertility, pregnancy and menopause associated with uterine myomata.

[Functional venous explorations]. / Explorations fonctionnelles veineuses.

The methods for exploring venous function globally are presented first. These methods include venous pressure and plethysmography for which the methods using a garrot are separated from those using air volumetry which give reliable physiological and reproducible results. The Nachev method, the thermometry, the thermography and isotope clearances are also reviewed since they have been important in the development of exploration of venous function. The methods giving morphological or segmentary data are then presented in historical order: phlebography (completed by tomodensitography and nuclear magnetic resonance), then ultrasonography with Doppler, echography and duplex and colour techniques. Finally promising methods for the future including oxygen partial pressures, laser-Doppler, capillaroscopy and venous endoscopy are discussed. For each method, there is a description of the technique, a presentation of the measured parameters and their reliability, the signification of the measurement and its clinical use. Finally, each method is discussed in the context of concrete clinical situations with a schema for management of diagnosis.

[Chronic venous insufficiency: prevention and drugless therapy]. / Insuffisance veineuse chronique: prévention et thérapeutiques non médicamenteuses.

The superficial and deep venous network of patients with chronic venous insufficiency is constantly undergoing change requiring careful follow-up and adapted therapy. Prevention, whether physical or medical, is recommended at all stages of the disease. The veins must be protected from factors which worsen venous abnormalities and drugs improving venous return should be prescribed. It is essential to avoid further aggravation of chronic venous insufficiency. The treatment has two objectives. First, and most important, to diminish or alleviate global or local venous hyperpressure which can be attained by surgery or sclerotherapy of venous leaking, via the crosses or perforating veins, into the superficial network. Venous hyperpressure can also be reduced by re-establishing normal venous haemodynamics with conservative techniques included elastic support or surgical techniques including CHI-VA. Finally, the second objective is to diminish or alleviate inaesthetic varicose veins and telangiectases.

[Medical treatment of chronic venous insufficiency]. / Traitement médical de l'insuffisance veineuse chronique.

Several aspects comprise the medical treatment of chronic venous insufficiency: adoption of daily routines favouring mechanisms for return of venous blood; wearing of elastic stocking to reduce superficial venous hypertension, the basis of medical treatment; use of venotonic agents as adjuvant therapy; association of crenotherapy; and finally the possibility of sclerotherapy when such treatment can correct the dysfunction of the superficial venous network. Various therapeutic strategies should be considered to manage not only the functional and/or clinical signs of chronic venous insufficiency, but also the complications which may occur (varicose thrombosis and haemorrhage, or deep venous thrombosis). Lastly, prevention is based not only on respect of daily hygienic measures but above all on early treatment that is adapted to any deep venous thrombosis.

[Support and compression of the legs]. / Contention et compression des membres inférieurs.

Physical methods are essential in the treatment of venolymphatic insufficiency. The available materials have two modes of action, support and compression; they may be used alone or in association. Clinical experience and a few scientific works formed the basis for establishing protocols adapted to each situation. Like any major treatment, these should be under the full responsibility of physicians. Prescriptions should be precise and, in particular, evaluated for each patient by the physician himself.

Lanreotide Autogel 90 mg and lymphorrhea prevention after axillary node dissection in breast cancer: a phase III double blind, randomized, placebo-controlled trial.

AIM: The aim of this study was to assess the efficacy of Lanreotide Autogel 90 mg PR to prevent lymphorrhea after axillary dissection in breast cancer. METHODS: A Phase III double-blind, randomized, placebo-controlled trial was performed between April 1st, 2008, and December 31st, 2010. The primary endpoint was the lymphorrhea volume (ml) in the axillary drain during the first four postoperative days. The secondary end points were the number of days until axillary drain removal, hospital stay duration (days), lymphorrhea volume (ml) up to days 15, 30 and 180, number of cases with seroma aspiration and number of seroma aspirations, evaluation of wound, arm pain and mobility on days 15, 30 and 180. RESULTS: A total of 148 patients were recruited for the study. Altogether 145 patients were randomized and analysed on an intention-to-treat basis. On the day before surgery 73 patients received the placebo and 72 patients received lanreotide. At four postoperative days, there was a tendency towards a reduction of the lymphorrhea volume in the lanreotide group (median 292 ml, range 1-965 ml) as compared to the placebo group (median 337 ml, range 0-1230 ml), although it was not statistically significant (p = 0.18). There was no significant difference for the secondary end points. In the group with axillary dissection performed alone (n = 24), the lymphorrhea volume was shown to be significantly reduced in the lanreotide group, (p = 0.035) as compared to the placebo group. CONCLUSION: Our study did not identify any overall significant reduction of lymphorrhea on lanreotide.