[Prognostic factors of acute radiodermatitis in breast cancer after adjuvant radiotherapy treated with RT3D or IMRT]. / Étude des facteurs pronostiques de radiodermite aiguë dans le cancer du sein traité par irradiation conformationnelle adjuvante avec ou sans modulation d'intensité.

PURPOSE: Real life study of prognostic factors of acute radiodermatitis in a monocentric cohort of 200 patients with breast cancer treated with RT3D or IMRT for adjuvant radiotherapy. PATIENTS AND METHODS: This study comprises 200 patients with breast cancer treated with adjuvant radiotherapy, included consecutively. For each patient, their clinical and tumoral characteristics and the irradiation schedule was retrospectively collected. The severity of acute radiodermatitis was also collected, during the treatment and 6weeks after the end of irradiation. The objective was to identify risk factors for acute radiodermatitis grade≥2. RESULTS: The univariate analysis found that a more important BMI (p<0.001), a more important volume of PTV (p<0.001) a normofractionated schedule (p=0.002) were statistically associated to a greater risk of occurrence of grade≥2 acute radiodermatitis. The multivariate analysis found BMI>30 (OR=9.31, p=0.04), light phototype (OR=0.04, p=0.02) and histology other than invasive breast carcinomas (OR=0.07, p=0.04) to be statistically associated to the occurrence of grade≥2 acute radiodermatitis. CONCLUSION: In this monocentric retrospective study, with a prospective collection of the severity of acute radiodermatitis, no grade 3 radiodermatitis has been observed and the frequency of occurrence of grade 2 radiodermatitis was lower than previously published. In contrast to previously published results, IMRT was not associated to a lower risk of grade≥2 acute radiodermatitis. Multivariate analysis found BMI, phototype, and histology to be risk factors of grade≥2 acute radiodermatitis.

Metastatic mediastinal mature teratoma with malignant transformation in a young man with an adenocarcinoma in a Klinefelter's syndrome: Case report and review of the literature.

Malignant transformation of mediastinal mature teratoma is extremely rare and worsens the prognosis of the disease. Transformation can appear synchronously to or several years after the initial diagnosis. Clinical and radiological signs can orientate the clinician but the definitive diagnosis is obtained thanks to histology. An 11 year-old boy presented with a mediastinal mature teratoma and bone and pulmonary metastases. He received six cycles of chemotherapy combining etoposide, ifosfamide, cisplatin, followed by resection of a 16×14×9cm mediastinal mass. Karyotype analysis revealed the presence of an additional sex chromosome X (47 XXY) pathognomonic of Klinefelter's syndrome. Ten years later, sciatalgia revealed malignant transformation of a pre-existing sacral bone metastasis into gastrointestinal adenocarcinoma. The patient received four cycles of chemotherapy combining oxaliplatin, 5-fluorouracil and cetuximab. This treatment was followed by a complete resection of the sacral metastasis and completed with adjuvant irradiation of 54Gy in 30 daily fractions. Twelve months after the diagnosis of relapse, the patient remained alive without disease. To our knowledge, this is the first case of adenocarcinoma developed in bone metastases of a mediastinal mature teratoma in a boy with a Klinefelter's syndrome. We propose a review of the literature and an analysis of 20 others published cases of mediastinal teratoma with malignant transformation into adenocarcinoma.

[Radiotherapy of bone metastases in France: A descriptive monocentric retrospective study]. / Radiothérapie des métastases osseuses en France : étude descriptive rétrospective monocentrique.

PURPOSE: Bone metastases cause pain and affect patients' quality of life. Radiation therapy is one of the reference analgesic treatments. The objective of this study was to compare the current practices of a French radiotherapy department for the treatment of uncomplicated bone metastases with data from the literature in order to improve and optimize the management of patients. MATERIAL AND METHODS: A retrospective monocentric study of patients who underwent palliative irradiation of uncomplicated bone metastases was performed. RESULTS: Ninety-one patients had 116 treatments of uncomplicated bone metastases between January 2014 and December 2015, including 44 men (48%) and 47 women (52%) with an average age of 63years (25-88years). Primary tumours most commonly found were breast cancer (35%), lung cancer (16%) and prostate cancer (12%). The regimens used were in 29% of cases 30Gy in ten fractions (group 30Gy), in 21% of cases 20Gy in five fractions (group 20Gy), in 22% of cases 8Gy in one fraction (group 8Gy) and in 28% of cases 23.31Gy in three fractions of stereotactic body irradiation (stereotactic group). The general condition of the patient (P<0.001), pain score and analgesic (P<0.001), oligometastatic profile (P=0.003) and practitioner experience (P<0.001) were factors influencing the choice of the regimen irradiation. Age (P=0.46), sex (P=0.14), anticancer treatments (P=0.56), concomitant hospitalization (P=0.14) and the distance between the radiotherapy centre and home (P=0.87) did not influence the decision significantly. A total of three cases of spinal compression and one case of post-therapeutic fracture were observed, occurring between one and 128days and 577days after irradiation, respectively. Eight percent of all irradiated metastases were reirradiated with a delay ranging between 13 and 434days after the first irradiation. The re-irradiation rate was significantly higher after 8Gy (P=0.02). The rate of death was significantly lower in the stereotactic arm (P<0.001) and overall survival was significantly greater in the stereotactic arm (P<0.001). CONCLUSION: This study showed that patients' analysed was comparable to the population of different studies. Predictive factors for the choice of the treatment regimen were identified. Non-fractionnated therapy was underutilised while stereotactic treatment was increasingly prescribed, showing an evolution in the management of patients.

Clinical and diagnosis characteristics of breast cancers in women with a history of radiotherapy in the first 30years of life: A French multicentre cohort study.

PURPOSE: Irradiation (>3Gy) to the breast or axillae before 30years of age increases the risk of secondary breast cancer (SBC). The purpose of this article is to describe the clinical characteristics of SBC and the way of diagnosis in young women (before the age of national screening) in France who had received previous radiotherapy for a childhood or a young adulthood cancer. PATIENTS AND METHODS: This retrospective, multicentre study reviewed the medical records of women with SBC before the age of the national screening who had received irradiation (≥3Gy) on part or all of the breast before 30years of age, for any type of tumour except BC. RESULTS: A total of 121 SBC were detected in 104 women with previous radiotherapy. Twenty percent of SBC were detected during regular breast screening and 16% of the women had a regular radiological follow-up. CONCLUSION: Our results points out that the main proportion of childhood cancer survivors did not benefit from the recommended breast cancer screening. This result is comparable to other previously published studies in other countries. A national screening programme is necessary and should take into account the patient's age, family history, personal medical history and previous radiotherapy to reduce the number of SBC diagnosed at an advanced stage.

[French organization of paediatric radiation treatment: Results of a survey conducted by the radiotherapy Committee of the French Society of Paediatric Cancers (SFCE)]. / Organisation française de la radiothérapie pédiatrique : résultats d'une enquête du comité radiothérapie de la Société française des cancers de l'enfant (SFCE).

PURPOSE: Radiotherapy is a rare indication in paediatric oncology, with 800 to 900 children in treatment per year in France. Child cancers represent approximately 1% of cancers in France and half occur before the age of 5 years. Paediatric radiation requires appropriate tools, local, time and specific training. In France, in 2015, 18 centres are accredited by the French National Cancer Institute (INCa) for this activity. MATERIAL AND METHODS: Survey conducted in February 2015 on the care of children (0 to 18 years) in radiotherapy departments in France. The survey was sent to the radiation oncologists involved in the 18 centres. The questions concerned the qualitative and quantitative aspect, medical and organizational aspects, and the involvement of assistant practitioners in the management of this activity. RESULTS: Seventeen centres responded. In 2014, 889 children under 18 were treated in radiotherapy departments. These departments are working together with one to four paediatric oncology departments. Regarding access to general anaesthesia: three centres perform one to seven treatment(s) under anaesthesia per year, three centres eight to ten treatments under anaesthesia per year, three centres ten to 24 treatments under anaesthesia per year and nine centres out of 17 use hypnosis techniques. In terms of human resources, in 2015, 29 radiation therapists have a paediatric radiotherapy activity. Involvement of assistant practitioners is growing and specific training are desired. Regarding treatment preparation and delivery, 13 centres have specific paediatric contentions, 14 of 16 centres employ radiation intensity modulated if dosimetry is more satisfying with 11 regularly to the craniospinal irradiation. Radiotherapy on moving areas with respiratory gating or hypofractionation is under developed. CONCLUSION: Paediatric radiation therapy is a specific activity requiring a dedicated management, both in human, organizational, medical and scientific aspects.

[French experience in paediatric total body irradiation: A study from the radiotherapy committee of the Société française des cancers de l'enfant (SFCE)]. / Expérience française de l'irradiation corporelle totale en pédiatrie : étude du comité de radiothérapie de la Société française des cancers de l'enfant (SFCE).

A survey was conducted in 2015 in France on the care of children in radiotherapy services. We present the results for total body irradiation in children, a specific technique of radiation treatment, which needs dedicated controls for this particular population. Of the 17 centres interviewed, 16 responded, and 13 practiced total body irradiation. Patients are positioned in lateral decubitus in 11 centres and supine/prone in two centres. Doses used for total body irradiation in myeloablative bone marrow transplantation are the same in all centres (12Gy); treatments are always fractionated. Lung shielding is positioned to limit the dose at an average of 8Gy with extremes ranging from 6 to 10Gy. The shape of the shieldings varies depending on departments' protocol, with a smaller size in case of mediastinal mass. Four centres have experience of total body irradiation under general anaesthesia, despite twice-daily fractions. In total, practice is relatively homogeneous throughout France and is inspired by the knowledge obtained in adults.

[Pediatric medulloblastoma: Retrospective series of 52 patients]. / Médulloblastomes de l'enfant: étude rétrospective portant sur 52 patients.

PURPOSE: Retrospective analysis of the results of 52 children irradiated for a medulloblastoma. PATIENTS AND METHODS: Between 1974 and 2012, 52 children with an average age of 6 years and a half (11 months-17 years and a half) were treated with surgery then with radiotherapy at the Comprehensive Cancer Centre of Strasbourg (France). For 44 children, the treatment consisted of a chemotherapy. RESULTS: After a mean follow-up of 106.6 months (7-446 months), 13 relapses and 24 deaths were observed. Overall survival at 5 years and 10 years were 62% and 57%, respectively. Disease-free survival at 5 years and 10 years were 80% and 63%, respectively. Univariate analysis found the following adverse prognostic factors: the existence of a postoperative residue, the positivity of the cerebrospinal fluid, the metastatic status and medulloblastoma of high-risk. Positivity of the cerebrospinal fluid remains a negative factor in multivariate analysis. CONCLUSION: These results confirm the survival rate obtained by a conventional approach (surgery then irradiation). Insufficiency of results and rarity of medulloblastoma require the establishment of international protocols.

[Adult medulloblastoma: Retrospective series of 21 patients]. / Médulloblastomes de l'adulte: étude rétrospective portant sur 21 patients.

PURPOSE: Retrospective analysis of the results of 21 adults treated for medulloblastoma. PATIENTS AND METHODS: Between 1978 and 2011, 21 adults with an average age of 31 years (18.3-50) were treated with surgery then with radiotherapy (n=20) at the Comprehensive Cancer Center of Strasbourg. For some (n=12), treatment consisted of chemotherapy. RESULTS: After a mean follow-up of 122 months (19-423), six relapses and seven deaths were observed. Overall survival at 5 years and 10 years was 89.4 ± 7.1% for both. Disease-free survival at 5 years and 10 years was 79.6 ± 9.2% and 85.7 ± 7.6% and 60.6 ± 17.7%, respectively. CONCLUSION: The rarity of medulloblastoma, especially in adults and these results confirm the necessity of international protocols.

[Evolution of the management of pediatric and adult medulloblastoma]. / Évolution de la prise en charge des médulloblastomes de l'enfant et de l'adulte.

Medulloblastoma are cerebellar tumours belonging to the group of primitive neuroectodermal tumours (PNET) and are the most common malignant brain tumours of childhood. These tumours are rare and heterogeneous, requiring some multicentric prospective studies and multidisciplinary care. The classical therapeutic approaches are based on clinical, radiological and surgical data. They involve surgery, radiation therapy and chemotherapy. Some histological features were added to characterize risk. More recently, molecular knowledge has allowed to devise risk-adapted strategies and helped to define groups with good outcome and reduce long-term sequelae, improve the prognostic of high-risk medulloblastoma and develop new therapeutic tools.

[Hydrogen sulfide: A promising therapy in neuroprotection following cardiac arrest?]. / Le sulfure d'hydrogène : une thérapeutique d'avenir dans la neuroprotection post-arrêt cardiorespiratoire ?

Each year, in France, the number of cardiac arrests is evaluated between 30,000 to 50,000. When a patient survives, he undergoes a post-resuscitation syndrome which can aggravate the injuries and for which nowadays, no medication is available. In some kinds of cardiac arrest, a hypothermia protocol can be applied with a need for monitoring because of the appearance of side effects. In this context, hydrogen sulfide, which is a gasotransmitter with numerous physiological and pharmacological properties, may be interesting. Indeed, its use could protect against oxidative, inflammatory and apoptotic troubles induced by the post-resuscitation syndrome. The implied biochemical mechanisms are adenosine triphosphate potassium channels activation and cytochrome c oxidase inhibition. This molecule can also induce a suspended animation state characterized by a metabolism decrease, which could give a delay for physicians to start a therapeutic monitoring. Thus, in spite of a modest and sometimes contradictory literature, this compound could become the first neuroprotective molecule in cardiac arrest.

[Radio-induced breast morphoea: an unrecognized complication]. / Morphée du sein radio-induite : une complication méconnue.

Morphoea is a localized scleroderma. Since the 1990s, it is described as a complication after irradiation for breast cancer. This complication is unrecognized and underdiagnosed. Irradiation seems to be a factor inducing an autoimmune process. Clinicians should be aware in case of an erythema in a treated area, appearing on average one year after the end of the irradiation. Histology alone can prove the diagnosis and rule out differential diagnoses: principally mastitis (carcinomatous, infectious), chronic radiodermatitis or radiation recall. Treatment of this rare complication is not consensual; it is most often topical steroids. The evolution is marked by a gradual decrease from the initial inflammation. Sclerosis persists, more or less substantially.

[General anesthesia in pediatric radiotherapy]. / Anesthésie générale en radiothérapie pédiatrique.

BACKGROUND: The majority of children under 3 years require anesthesia for radiotherapy. METHODS: This work reports the experience of Paul-Strauss Center over a 4-year period on 15 children and covering 386 general anesthesia. RESULTS AND CONCLUSION: The rate of anesthesia-related complications was low (0.5%) subject to the experience of the anesthesiologists and follow-up recommendations.

[Acquired alpha-thalassemia as early sign for myelodysplastic syndrome (refractory anaemia) with secondary haemochromatosis]. / Alpha-thalassémie acquise révélatrice d'un syndrome myélodysplasique de type anémie réfractaire avec hémochromatose secondaire.

We report the case of a 59 year old man presenting a regenerative microcytic hypochromic anaemia. The investigations revealed the presence of haemoglobin H, suggesting abnormalities in the alpha-globin chains synthesis. Alpha-thalassemia was thus suspected. The patient had no personal or familial history. The association with aniso-poïkilocytosis and a marked iron overload (ferritinemia > 1,500 microg/L) suggested a myelodysplastic syndrome, which was confirmed with a bone marrow aspiration. The pattern was consistent with the Acquired alpha-Thalassemia-Myelodysplastic Syndrome (ATMDS). About a hundred cases are listed worldwidely and collected in an international registry. The causes of ATMDS are ignored, but recent reports indicate that the ATRX gene may be implicated in the pathogenesis. ATRX is a chromatin-associated protein, involved in the transcription of several genes. The alpha globin genes could be one of the targets of the ATRX protein.

[Interindividual variability in the laboratory response to the aspirin-clopidogrel combination: are patients with stent occlusion "resistant" to treatment?]. / Existe-t-il une "résistance" biologique au traitement antiplaquettaire associant aspirine et clopidogrel chez les patients ayant présenté une occlusion de stent?

Interindividual variability of biological response to antiplatelet agents is an opened question, which constitute the purpose of recent publications. Indeed, a wide interindividual variability in the laboratory response to antiplatelet agents such as aspirin and/or clopidogrel has been shown. However, only few clinical data are available to demonstrate the relationship between a poor laboratory response to antiplatelet treatment and the occurrence of stent thrombosis. The aim of this study is to compare photometric platelet aggregation profiles of two groups of patients who had undergone percutaneous coronary intervention with stent implantation (one group with at least one subacute thrombotic event following stent implantation and one historical control group free of thrombotic events) to determine whether there is a parameter which could be useful in identifying patients with a risk of having a thrombotic event related to poor response to antiplatelet treatment. We found some differences between the two groups regarding the maximal light transmission after stimulation with arachidonic acid (1,39 mM) or collagen at low concentration (Horm, 2 microg/mL) but not after stimulation with ADP irrespective of the concentration studied (10, 5 and 2,5 microM). However, platelet inhibition response to ADP could be assessed with another parameter, the disaggregation percentage, which was significantly lower in patients with than without thrombosis, and may be used as marker to distinguish patients with a higher risk of thrombosis.

Biological response of human aortic endothelial cells exposed to acellular hemoglobin solutions developed as potential blood substitutes.

The cardiovascular effects of hemoglobin-based oxygen carriers (HBOCs) are mainly related to their nitric oxide (NO) scavenging properties but other effects such as the impact of these hemoglobins on the endothelial cell (EC) biology are not well understood. We hypothesized that HBOCs could modify EC functions by altering gene expression, in particular the endothelial NO synthase (NOS3) and/or by activating EC. Cultured human aortic endothelial cells (HAEC) were incubated for 3 hours with purified cell-free Hb, Dex-BTC-Hb or alpha alpha-Hb (16 g/L). Expression of NOS3 mRNA and protein were assessed by semi-quantitative RT-PCR and Western blot respectively immediately after and 24 hours after incubation. The expression and localization of the adhesion molecule ICAM-1 were detected by fluorescence microscopy. None of the solutions tested modified NOS3 mRNA and protein expression despite adequate controls that up- or down-regulate NOS3 expression. The expression and the localization of ICAM-1 on the cell membrane were modified after 3 hours of incubation with all the hemoglobin solutions tested in a manner similar to tumor necrosis factor-alpha. In conclusion, HAEC incubation with clinically relevant concentrations of HBOCs induced changes in the pattern of ICAM-1 expression consistent with cell activation/cell signaling mechanisms. However, HBOCs did not alter NOS3 gene expression.

The virucidal effect of platelet concentrates: preliminary study and first conclusions.

Despite the increased safety of blood components, achieved through improved donor selection and testing, transfusion recipients remain at risk of transfusion-associated diseases. Transfusion of cellular blood components has been implicated in transmission of viral, bacterial and protozoan diseases. Investigators have studied a myriad of processes for pathogen depletion and/or inactivation. No successful treatments, apart the leukodepletion, have already been identified for red cells and platelets. And more, several evidences indicate that platelets play a key role in host defence against infection. High levels of pathogens were added to single-donor platelet concentrates (PC) containing 3 to 5 10(11) platelets in 300 ml. The infectivity of each pathogen was measured with established biologic assays. The following levels of pathogen inactivation were achieved : >10(2.63) plaque-forming units (PFU) per ml of adenovirus 5 (ADV5), >10(5.6) PFU per ml of Poliovirus 1 (P1) and >10(4.1) PFU per ml of vaccinia virus (VaV). In conclusion, the PC show a potential virucidal effect. This inactivation process has been found with bacteria and still remains unknown for viruses.

Effect of follicular size on meiotic and developmental competence of porcine oocytes.

In several species, the developmental competence of the oocyte is acquired progressively during late follicular growth, after the acquisition of the competence to resume and complete meiosis. In the pig, full meiotic competence of the oocyte is reached in ovarian follicles with a diameter of 3 mm or more. However, there is no information about developmental competence acquisition. We analyzed the ability of oocytes from three foll icular size classes to resume and complete meiosis, to be fertilized, and to develop in vitro to the blastocyst stage. A total of 941 follicles were dissected from slaughterhouse gilt ovaries and classified as small (<3 mm, n = 330), medium (3-5 mm, n = 373), or large (>5 mm, n = 238). The cumulus-oocyte complexes recovered from these follicles were submitted to in vitro maturation for 44 h in TCM199 supplemented with 10 ng/ml EGF, 400 ng/ml pFSH and 570 microM cysteamine; in vitro fertilized for 18 h in mTBM with 10(5) frozen-thawed percoll-selected sperms/ml; and developed for 7 days in mSOF. Samples of oocytes or presumptive zygotes were fixed and stained at the end of maturation and fertilization. Groups of oocytes were cultured for 3 h in the presence of 35S-methionine before or after maturation for SDS-PAGE analysis of protein neosynthesis. More oocytes originating from medium and large follicles were competent for maturation than oocytes from small follicles (77 and 86% of metaphase II, respectively, versus 44%, P < 0.05). More oocytes from medium and large follicles werepenetratedby spermatozoa during in vitro fertilization, resulting in significantly more oocytes presenting two or more pronuclei at the end of fertilization (73 and 77% for medium and large follicles, respectively, versus 53% for small follicles, P < 0.05). More oocytes from medium and large follicles developed to the blastocyst stage (14 and 23%, respectively) than those from small follicles (3%, P < 0.05), even if the development rates were corrected by the maturation or fertilization rates. It is concluded that a high proportion of oocytes harvested from follicles of less than 3 mm in the pig are not fully competent for meiosis and are cytoplasmically deficient for development.

Protein C-loaded monomethoxypoly (ethylene oxide)-poly(lactic acid) nanoparticles.

This paper deals with the preparation and characterization of monomethoxypoly(ethylene oxide)-poly(lactic acid) (MPEO-PLA) nanoparticles containing protein C, a plasma inhibitor which regulates the mechanism of blood coagulation. Protein C was entrapped in MPEO-PLA nanoparticles using the double emulsion method. The influence of MPEO-PLA copolymers on the different parameters was evaluated: characteristics of protein C-loaded nanoparticles, in vitro release of the protein, evolution of the particle size with incubation time and MPEO release. The nanoparticle size does not depend on copolymer characteristics (MPEO and/or PLA block molecular weight). On the other hand, the efficiency of protein C entrapment is affected by the copolymer characteristics. The burst effect during the protein C release is increased with the hydrophilic character of the copolymer. Moreover, protein C adsorption on the particle surface during its release may be related to MPEO release. Only 25% of the released protein C is active, which clearly illustrates that it is altered during its encapsulation. The optimization of the experimental parameters which disturbed entrapped protein C activity, i.e. sonication time and organic solvent was investigated and has led to a preservation of protein C activity. Then, to optimize its entrapment efficiency, a blend PLA/MPEO-PLA (25/75) was used to prepare nanoparticles. This blend limited burst effect of protein C and its adsorption. However, protein C is only partially released which implicates further investigation for a potential therapeutic use.

[Diagnosis and treatment of bladder tumors by photodynamic therapy]. / Diagnostic et traitement des tumeurs de vessie par thérapie photodynamique.

Experimental results and clinical trials showed that bladder tumours Tis and pT1a can be diagnosed by photodynamic diagnosis and treated by photodynamic therapy. These photochemical methods are based on a selective photosensitizer uptake in the tumour tissue. After subsequent irradiation, these tissues emit a fluorescence (diagnosis) or can be destroyed by chemically induced oxidative compounds (treatment). Hematoporphyrin derivative and its oligomeric part have been the light-sensitizing drugs the most commonly studied. Interest has now shifted to 5-aminolevulinic acid, or its hexylester form, inducing protoporphyrin IX which shows better tumour localising properties and could avoid side effects. While photodynamic treatment is still an experimental modality, photodynamic diagnosis could achieve a more accurate detection of occult dysplasia compared to white light cystoscopy.