[Nipple projection augmentation in breast reconstruction by artificial derm injection]. / Augmentation de la projection du mamelon dans les reconstructions mammaires par injection de derme artificiel.

INTRODUCTION: The reconstruction of the Nipple-Areola Complex (NAC) is the last step and a key part in breast reconstruction. The technique to be used should be chosen as to avoid any complications on previous reconstruction steps. The use of local flaps for NAC reconstruction could be associated with implant exposure especially in the presence of a history of radiation therapy. The pure dermal flap could be indicated for the nipple reconstruction after breast reconstruction by implant after radiotherapy. The limit stay in the nipple hypoprojection. We suggest to assess the increase of the nipple projection, reconstructed by pure dermal flap, by injection of Integra® Flowable Wound Matrix (Integra LifeSciences®, Plainsboro, New jersey). PATIENTS AND METHOD: Nipple projection has been measured among patients enclosed from february to March 2016 reconstructed by pure dermal flap: before, after and also at a 6months term from the injection of Integra® Flowable Wound Matrix. Patient satisfaction and complications have been measured retrospectively. RESULTS: Ten patients with an average of 55years have been enclosed, with an average limit of time of 19months (7 to 33months) between the breast nipple reconstruction by dermal flap and the injection. A volume of 1 to 1.6cc has been injected. A significative increase projection of 2mm at a 6months term has been measured (1.5 to 2.5mm, P<0.01), without complication and a satisfaction rate of 4.5/5. CONCLUSION: The injection of an artificial derm-like Integra® Flowable Wound Matrix seems to be efficient to increase the nipple projection reconstructed by pure dermal flap after a breast reconstruction and moreover, without complications.

Penetration of daptomycin into bone and synovial fluid in joint replacement.

Daptomycin exhibits clinical activity in the treatment of infections with Gram-positive organisms, including infections due to methicillin-resistant Staphylococcus aureus. However, little is known about its penetration into bone and synovial fluid. The aim of our study was to assess the penetration of daptomycin into bone and synovial fluid after a single intravenous administration. This study was conducted in 16 patients who underwent knee or hip replacement and received a single intravenous dose of 8 mg of daptomycin per kg of body weight prior to surgery. Plasma daptomycin concentrations were measured 1 h after the end of daptomycin infusion and when bone fragments were removed. Daptomycin concentrations were also measured on bone fragments and synovial fluid collected at the same time during surgery. All samples were analyzed with a diode array-high-performance liquid chromatography (HPLC) method. After a single-dose intravenous infusion, bone daptomycin concentrations were above the MIC of daptomycin for Staphylococcus aureus in all subjects, and the median bone penetration percentage was 9.0% (interquartile range [IQR], 4.4 to 11.4). These results support the use of daptomycin in the treatment of Staphylococcus aureus bone and joint infections.

Esophageal cancer - French intergroup clinical practice guidelines for diagnosis, treatments and follow-up (TNCD, SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, ACHBT, SFP, RENAPE, SNFCP, AFEF, SFR).

INTRODUCTION: This document is a summary of the French intergroup guidelines regarding the management of esophageal cancer (EC) published in July 2022, available on the website of the French Society of Gastroenterology (SNFGE) (www.tncd.org). METHODS: This collaborative work was conducted under the auspices of several French medical and surgical societies involved in the management of EC. Recommendations were graded in three categories (A, B and C), according to the level of evidence found in the literature until April 2022. RESULTS: EC diagnosis and staging evaluation are mainly based on patient's general condition assessment, endoscopy plus biopsies, TAP CT-scan and 18F FDG-PET. Surgery alone is recommended for early-stage EC, while locally advanced disease (N+ and/or T3-4) is treated with perioperative chemotherapy (FLOT) or preoperative chemoradiation (CROSS regimen) followed by immunotherapy for adenocarcinoma. Preoperative chemoradiation (CROSS regimen) followed by immunotherapy or definitive chemoradiation with the possibility of organ preservation are the two options for squamous cell carcinoma. Salvage surgery is recommended for incomplete response or recurrence after definitive chemoradiation and should be performed in an expert center. Treatment for metastatic disease is based on systemic therapy including chemotherapy, immunotherapy or combined targeted therapy according to biomarkers testing such as HER2 status, MMR status and PD-L1 expression. CONCLUSION: These guidelines are intended to provide a personalised therapeutic strategy for daily clinical practice and are subject to ongoing optimization. Each individual case should be discussed by a multidisciplinary team.

Rectal cancer radiotherapy.

We present the updated recommendations of the French society of oncological radiotherapy for rectal cancer radiotherapy. The standard treatment for locally advanced rectal cancer consists in chemoradiotherapy followed by radical surgery with total mesorectal resection and adjuvant chemotherapy according to nodal status. Although this strategy efficiently reduced local recurrences rates below 5% in expert centres, functional sequelae could not be avoided resulting in 20 to 30% morbidity rates. The early introduction of neoadjuvant chemotherapy has proven beneficial in recent trials, in terms of recurrence free and metastasis free survivals. Complete pathological responses were obtained in 15% of tumours treated by chemoradiation, even reaching up to 30% of tumours when neoadjuvant chemotherapy is associated to chemoradiotherapy. These good results question the relevance of systematic radical surgery in good responders. Personalized therapeutic strategies are now possible by improved imaging modalities with circumferential margin assessed by magnetic resonance imaging, by intensity modulated radiotherapy and by refining surgical techniques, and contribute to morbidity reduction. Keeping the same objectives, ongoing trials are now evaluating therapeutic de-escalation strategies, in particular rectal preservation for good responders after neoadjuvant treatment, or radiotherapy omission in selected cases (Greccar 12, Opera, Norad).

[Dose optimization in 3D pulsed dose rate brachytherapy for patients with locally advanced cervical cancer: A French multicenter phase II trial]. / Optimisation de la curiethérapie utérovaginale de débit pulsé des cancers du col utérin localement évolués : résultats finaux du PHRC Tridicol.

PURPOSE: We present the results of the PHRC Tridicol, a prospective French phase II study whose objective was to increase the dose delivered to the target volume during brachytherapy for locally advanced cervical cancers. MATERIAL AND METHODS: Eight centers included 48 patients, treated with concomitant radiochemotherapy, then uterovaginal brachytherapy. RESULTS: The median follow-up was 63 months. The dose of brachytherapy delivered in biological equivalent dose (EQD2) to 90% of the High Risk CTV (D90 CTV HR) was 80Gy in median dose. The 5-year local control rate (LC) was 84%, close to the hypothesis of 86.7%. The rate of severe complications (grade 3-4) was 23% at 5 years. The rectal dose was correlated with the risk of severe complications. CONCLUSION: HR CTV dose was below the target (85Gy) due to low use of parametrial interstitial needles, as the centers did not always have an adequate applicator, or were at the time at the beginning of their learning curve. The 5-year LC rate was improved compared to that of the comparable STIC PDR group (78%) but lower than the retroEMBRACE cohort of GEC ESTRO (89%). The complication rate was higher than in the comparable group of STIC PDR but close to that of retroEMBRACE. Training brachytherapy teams in interstitial implantation or referring patients to referral centers should help improve the therapeutic index of cervical cancer.

[Impact of reconstructive or minimal invasive surgery on the assessment of current definitions of postoperative clinical target volume for head and neck cancers]. / Impact de la chirurgie reconstructrice avec lambeaux et de la chirurgie mini-invasive sur la définition du volume cible anatomoclinique des cancers de la sphère ORL.

Advances in the reconstructive surgery and minimally invasive endonasal endoscopic surgery of head and neck is poorly evaluated in terms of their impact on radiotherapy planning and outcomes. These surgical advances have resulted in reduced morbidity with equivalent or better tumor control. In the absence of a recommendation on how to delineate target volumes in patients with flaps or to consider margins after endoscopic endonasal surgery, radiotherapy practices are inevitably heterogeneous. Efforts are needed to increase the therapeutic index of postoperative radiotherapy in these situations. We analysed the rare existing literature and outlined a preliminary basis for a recommendation. Strengthening of multidisciplinarity to accurately define target volumes in these complex and relatively new situations, and "delineation concertation meetings" between radiologists, surgeons and radiation oncologists could probably contribute to improved outcomes.

[Helminths and inflammatory bowel diseases]. / Helminthes et maladies inflammatoires chroniques intestinales.

The current etiologic model of inflammatory bowel diseases proposes a genetically predisposed host responding to a variety of environmental triggers by exhibiting an abnormal immune response to normal luminal flora. Crohn's disease is common in highly industrialized western countries where helminths are rare and uncommon in less developed areas of the world where most people carry worms. From this observation grew the hygiene hypothesis, which states that our failure to be exposed to previously common infectious agents alters the immune repertoire established in childhood. Helminths diminish immune responsiveness in naturally colonised humans and reduce inflammation in experimental colitis. Crohn's disease involves over reactive T-helper (Th1) pathways, and helminths blunt Th1 responses, inducing production of Th2 cytokines. Helminths also induce regulatory T cells to maintain host mucosal homeostasis. Thus, there is an immunological basis to expect that exposure to helminths such as Trichuris suis will prove beneficial in Crohn's disease. Exposure to helminths may be effective in treating inflammatory bowel diseases and was well tolerated, according to the results of few studies. Its long-term safety remains unknown.

[Anal canal cancer: In the era of intensity-modulated radiotherapy, outstanding issues]. / Cancer du canal anal : à l'ère de la radiothérapie conformationnelle avec modulation d'intensité, questions en suspens.

Intensity-modulated radiotherapy makes possible to optimize the irradiation and spare normal tissues. The toxicity remains important with concomitant chemotherapy often associated. The improvement of MRI and PET-CT define more precisely the target volumes, which need a higher dose, but necessitates to respect the rules of contouring. The treatment is uniform whatever the stage but should be individualized based on clinical stage and tumor response. New paradigms concern biology, staging, volumes and doses, fractionation and combined treatments.

[Small cell lung cancer (CPC). Small cell bronchial carcinoma: therapeutic management]. / Les cancers à petites cellules (CPC). Prise en charge thérapeutique.

Small cell bronchial carcinoma holds a prominent position among malignant tumours on account of its high incidence and the problems of its treatment. The diagnostic approach is dictated by the concern not to overlook any metastatic sites. Small cell bronchial carcinoma is often metastatic at the time of diagnosis and should be considered an actual or potential systemic disease. Chemotherapy is therefore the basis of treatment. It should consist of at least a two drug regime combining cisplatin and etoposide. In extensive disease, that is when all the disease cannot be contained within one irradiation field, chemotherapy alone is recommended. In limited disease combined simultaneous radiotherapy and chemotherapy is recommended. Prophylactic cranial irradiation is indicated in patients in complete remission after chemotherapy. The therapeutic armamentarium has recently been enlarged by the development of new antineoplastic drugs and the development of non-toxic targeted agents including those influencing angiogenesis. The understanding of the specific mechanisms of drug resistance and the study of the tumour phenotypes and genotypes will allow, in the future, the development of treatments adapted for each patient.

[Radiotherapy of rectal carcinoma]. / Radiothérapie des cancers du rectum.

Indications, doses and techniques of conformal radiotherapy for rectal carcinoma are presented. The recommendations for delineation of the target volumes and organs at risk are detailed.

[Head and neck adaptive radiotherapy: A tool for the detection of patients requiring adaptive radiotherapy]. / Radiothérapie adaptative des cancers ORL : un outil permettant d'identifier les patients nécessitant une adaptation de leur traitement.

PURPOSE: The purpose of this work was to implement a simple dosimetric alert tool in a retrospective study for six patients suffering from head and neck cancer to detect when a patient might require an adaptive radiotherapy. MATERIALS AND METHODS: The dosimetric tool generates a 3D cartography of two dosimetric complementary information: a dose variation tolerance map and a dose differential map. The tolerance map is calculated on the initial scanner (CTinit) using the planned dose distribution. It shows for each voxel of each delineated volume the availability for local dose variations during the course of radiotherapy without exceeding the dose threshold. The differential dose map is generated on the tomographic image CBCT (CBCTtreatment). It shows dose variations between the planned and the actual delivered dose distribution for each voxel. By comparing both maps, when a voxel presents a value superior to the corresponding dose variation tolerance, an alert is generated and the anatomical areas concerned are visually indicated to the physician. RESULTS: The application of the dosimetric tool on six patients with head and neck cancers reveals the ability of the tool to detect cases requiring a new treatment plan. Two patients whose the tumour shrinkage produced an increase of the delivered dose to the spinal cord beyond 45 Gy have been detected. CONCLUSION: The development of the dosimetric tool allows the automatic detection, with no delineation needs, of patients suffering from head and neck cancers requiring an adaptive strategy.

Skin test reactions to a phenol-soluble antigen of Brucella abortus among veterinary students, Lyon, France, 1984.

In December 1984, 424 students at the National Veterinary College, Lyon, France, were skin-tested with a phenol-soluble antigen of Brucella abortus B19. Of all students, 2.6% had a positive intradermal reaction indicating previous contact with Brucella. Prevalence of positive reactions was significantly lower among students from the three first school years (less than 2%) compared with students in their last school year (5.9%). These results are discussed and compared to the prevalence of brucellosis among cattle. Specificity (94%) of the intradermal testing resembles that of serological testing but its sensitivity (75%) seems to be better.

Virus isolation, polymerase chain reaction and in vitro antibody production for the diagnosis of pediatric human immunodeficiency virus infection.

Viral culture (VC), polymerase chain reaction (PCR) and in vitro antibody production (IVAP) by peripheral blood mononuclear cells were compared for the early diagnosis of HIV-1 infection in 46 infants born to HIV-1 seropositive mothers. The ten children considered infected on the basis of clinical signs and persistence of anti-HIV-1 antibodies had at least one positive viral culture and seven were always positive in both PCR and IVAP tests. PCR and IVAP tests were occasionally negative in three infected children. Among 30 healthy children who became seronegative and were always negative for viral culture, 22 (73.3%) were also repeatedly negative in PCR and IVAP. We report 6 cases of children classified as P2A at the term of this study but who had lost anti-HIV-1 antibodies. They presented at least one positive viral culture and occasional positive PCR and/or IVAP results. The results indicate that the combination of viral culture, PCR and IVAP tests improves the early diagnosis of pediatric HIV infection.

Variations of cytokine levels and production in CAPD patients.

Macrophages, predominant cells in dialysates of patients on CAPD without peritonitis, produce a wide variety of substances including cytokines. The aim of this study was to examine the cytokine production in five uninfected patients. This work investigated the presence in dialysates of interleukin-1beta, interleukin-6, interleukin-8, tumor necrosis factor alpha and the ability of peritoneal macrophages to produce these cytokines. These results were compared with values obtained from control group in non-uremic conditions (peritoneal lavage with isotonic saline or dialysis fluid). All cytokines were detectable in dialysates. Interindividual variations in cytokine concentration in dialysates were wider than variations of production of cytokines ex vivo by stimulated and unstimulated cells. In control group, dialysis fluid inhibited the cytokine production and with isotonic saline, cells produced less cytokines than dialysis patients' cells. The highest levels of interleukin-1 and tumor necrosis factor in dialysates and the highest capacity to respond to LPS were observed in patients having the shortest duration of dialysis. The variability observed did not seem to be due to cells themselves but to their environment.

[Concomitant use of radiotherapy and gemcitabine: preclinical findings and clinical practice]. / Association concomitante de la radiothérapie et de la gemcitabine: données précliniques et études cliniques.

Gemcitabine is pyrimidine analog which has demonstrated antitumoral activity in a variety of solid tumors. Laboratory studies demonstrating that gemcitabine is a potent radiosensitizer led to a variety of trials combining radiation and gemcitabine. In the clinic, phase I-II studies are still trying to determine the optimal dose and schedule which could be use in daily clinical practice. This review summarizes the mechanisms of interaction between radiotherapy and gemcitabine and presents several therapeutic schemes for each tumor location.

[Living conditions of prostitutes: consequences for the prevention of HIV infection]. / Conditions de vie de personnes prostituées: conséquences sur la prévention de l'infection à VIH.

Since 1990, several community-based interventions have been set up for populations of prostitutes in France with the principal objective of preventing HIV infection in prostitutes and their sexual partners. Field workers have suggested that extremely precarious living conditions are a major obstacle for the diffusion of prevention messages. A multidisciplinary working group thus set up a study in order to determine which living conditions could affect the adoption of behaviour at low risk for HIV infection. In May 1995, six of the seven teams conducting prevention actions among prostitutes in France used a short standardised questionnaire to collect information including type of housing, health insurance cover, physical aggressions, drug use. It was planned to collect data from all persons attending the drop-in centres. A total of 355 questionnaires were completed (sampling was exhaustive for 3 of the 6 teams). The population comprised women, men and transvestites. The median age was 28 years. Only 39% (135/348) of the subjects had access to health insurance. Approximately 50% (160/324) of the persons lived in precarious accommodation (hotel or no fixed address) and 33% (119/355) had been victims of physical aggressions during the 5 months preceding the study. Transvestites and young people had the most precarious living conditions. Despite the limits of this study due to the difficulty in carrying out a survey in this very marginalised population, the unique information collected may enable community health action strategies to be suitably adapted. In particular, it is important to improve partnership between field workers and existing social and health services, to improve access to better accommodation, health care and physical security while disseminating prevention messages and distributing condoms.

[Kinetics of erythropoietin blood levels from D-1 to D-29 in kidney transplantation]. / Cinétique de l'érythropoïétinémie de J-1 à J29 en transplantation rénale.

This study of serum erythropoietin levels and reticulocytes counts in the first month after kidney transplantation shows that the erythropoietin peak is efficient only when serum creatinine level at the time of the peak is under 200 mumol/l.

[Use of flow cytometry in the study of a non-specific immunodeficiency in children. A case]. / Utilisation de la cytométrie en flux dans l'étude des déficits de l'immunité non spécifique de l'enfant. Une observation.

Using flow cytometry, we explored a case of nonspecific immunodeficiency in a seven month old girl with repeated infections. This method showed evidence of granulocyte phagocytosis and oxidative metabolism abnormalities suggesting the diagnosis of a variant form of chronic granulomatous disease (CGD). Findings also showed that flow cytometry can be useful to study phagocytic cells during the neonatal period as it allows rapid multiparametric analysis with a very small amount of blood.

[Radiochemotherapy for esophageal cancer: which nodes should be irradiated?]. / Chimioradiothérapie des cancers de l'œsophage : quelles aires ganglionnaires faut-il irradier ?

Esophageal cancer has a high likelihood of distant lymphatic spread even at an early stage. Radiotherapy plays a major role in the management of localized or locally-advanced esophageal cancer with a regional or distant lymph node involvement. Radiotherapy can sterilize micrometastatic nodes and cancer cells in transit in the peri-esophageal fat that are not removed by surgery. After preoperative chemoradiotherapy followed by monobloc esophagectomy including lymph node dissection above and below the diaphragm, the locoregional failure rate was around 3% in the Chemoradiotherapy for Esophageal Cancer followed by Surgery Study Group (CROSS) trial. This is significantly lower than that observed with surgery alone or following exclusive chemoradiotherapy delivering 50 Gy over 5 weeks. Patterns of failure usually combine local and nodal failure. These results suggest that: (1) radiotherapy plays a major role in the management of micrometastatic nodes that are not removed by surgery; (2) the total dose of radiotherapy without surgery may be too low to control macroscopic disease. Better knowledge of regional failure sites and the enhancement of clinical practices through homogenized nodal radiotherapy could lead to a decrease in regional relapses, but at the expense of irradiated volumes greater than the macroscopic tumor volume. Intensity-modulated radiotherapy or volumetric modulated arctherapy makes it possible to increase mediastinal irradiated volumes while effectively protecting healthy tissues.

[Reirradiations of head and neck cancers: state of the concept and ways of development]. / Ré-irradiations des cancers de la tête et du cou : état du concept et voies de développement.

The treatment of local recurrence or second primary developed in irradiated area in the field of head and neck carcinoma, should be planned and organized through multidisciplinary discussions. The outcome of such a clinical situations benefits from second line and advanced technology treatments. Only a few patients are amenable to salvage surgery, hence radiation therapy, combined or not with chemotherapy, takes a major role in these indications. This overview of the literature describes recent development in this field, aiming to improve local control while the sparing of organ at risk remains an important goal. Radiation therapy is currently implementing major new technologies set to improve external beam irradiation with new concepts on dose, fractionation, intensity modulated radiation therapy and stereotactic approach - as well as in brachytherapy. Apart from dedicated studies, the great heterogeneity of the treated patients should be underlined and taken into consideration. However, current data confirm the feasibility of reirradiation with acceptable local control and toxicity.