[Breast conserving surgery in locoregional treatment of breast carcinoma after Hodgkin lymphoma]. / Traitement conservateur dans la prise en charge locorégionale du cancer du sein après lymphome de Hodgkin.

PURPOSE: To report characteristics and outcome of breast cancer after irradiation for Hodgkin lymphoma with special focus on breast conservation surgery. PATIENTS AND METHODS: Medical records of 72 women who developed either ductal carcinoma in situ or stage I-III invasive carcinoma of the breast after Hodgkin lymphoma between 1978 and 2009 were retrospectively reviewed. RESULTS: Median age at Hodgkin lymphoma diagnosis was 23 years old. Median total dose received by the mediastinum was 40 Gy, mostly by a mantle field technique. Breast cancer occurred after a median time interval of 21 years. Ductal invasive carcinoma and ductal carcinoma in situ represented respectively 71% and 19% of the cases. Locoregional treatment for breast cancer consisted of mastectomy with or without radiotherapy in 39 patients and of lumpectomy with or without adjuvant radiotherapy in 32 patients. The isocentric lateral decubitus radiation technique was used in 17 patients after breast conserving surgery (57%). With a median follow-up of 7 years, 5-year overall survival rate and locoregional control rate were respectively 74.5% and 82% for invasive carcinoma and 100% and 92% for in situ carcinoma. Thirteen patients died of progressive breast cancer and contralateral breast cancer was diagnosed in ten patients (14%). CONCLUSIONS: Breast conserving treatment can be an option for breast cancers that occur after Hodgkin lymphoma despite prior thoracic irradiation. It should consist of lumpectomy and adjuvant breast radiotherapy with use of adequate techniques, such as the lateral decubitus isocentric position.

Long-term results of mechanical and biological heart valves in dialysis and non-dialysis patients.

INTRODUCTION: We wanted to answer the question whether biological heart valves are inferior compared to mechanical heart valves in end-stage renal disease (ESRD) patients. METHODS: Between 01/1996 und 12/2006, 44 of 3293 patients undergoing aortic valve replacement (AVR) in a single institution suffered from dialysis-dependent ESRD and underwent a follow-up investigation after 1.9 years (median). Twelve (28.9 %) of these patients received a biological, 32 (71.1 %) of these patients a mechanical aortic valve prosthesis. To evaluate a possible influence of the valve type (biological/mechanical) on survival, uni- and multivariate logistic regression was used. RESULTS: ESRD patients after AVR had a relatively poor short-term (30-day mortality: 22.7 %) and long-term survival (median survival time: 24.7 months; 95 % CI: 0.2-47.7 months), irrespective of the type of heart valve prosthesis (hazard ratio for mortality depending on heart valve type in dialysis patients: 1.31, P = 0.400). Dialysis-dependent patients were not reoperated due to valve-related reasons. CONCLUSIONS: The long-term survival of dialysis-dependent patients after AVR is low (5-year survival: 29.5 %) irrespective of the type of heart valve prosthesis. Therefore, the use of biological AVR is not contraindicated in this group of patients.

[Malignant gliomas]. / Gliomes cérébraux.

Glial tumors represent 2000 to 3000 new cases per year in France and 75% of them are of high grade. Recent understanding of the molecular biology of these tumors revealed the importance of 1p19q codeletion and mgMT promotor methylation. Radiotherapy also recently evolved with the progress in medical imaging which allows a better definition of the target volumes. Even modest, therapeutic progress is based on chemoradiotherapy with temozolomide and on the development of non-coplanar conformational radiotherapy. Knowledge and precise evaluation of potential late effects of our treatments is necessary due to actual improvement of survival with chemoradiotherapy in glioblastoma.

[Normal tissue tolerance to external beam radiation therapy: brain and hypophysis]. / Dose de tolérance à l'irradiation des tissus sains: encéphale et hypophyse.

Anticancer treatments-induced central nervous system neurotoxicity has become a major problem in recent years. Real advances in therapeutic results for cancer treatments have improved patients' survival. Nowadays, central nervous system radiation therapy is widely prescribed, both for palliative and curative treatments in the management of malignant or benign tumors. Recent data on tolerance of normal central nervous system to radiation therapy are reviewed here, early and delayed radiation-induced effects are described and dose recommendations are suggested for clinical practice.

[Management of malignant phyllodes tumors of the breast: the experience of the Institut Curie]. / Prise en charge des tumeurs phyllodes malignes du sein: l'expérience de l'institut Curie.

PURPOSE: Given the scarcity of malignant phyllode tumours of the breast and the absence of consensus regarding their management justify the need for institutional retrospective evaluations of clinical practices. PATIENTS AND METHODS: Retrospective study with central pathology review of the 25 consecutive patients treated at the Institut Curie (Paris, France) between 1969 and 2006 for non metastatic malignant phyllodes tumors of the breast. The median follow-up was 65 months (7-257 months). RESULTS: Median age at diagnosis was 52 years (20-64 years). Breast surgery was conservative in five patients (20%). Surgical margins were wide (> 10mm), narrow, involved or unknown in respectively 17 (68%), three (12%), three (12%) and two (8%) patients. Median tumour size was 65 mm (12-250 mm). Adjuvant radiotherapy was delivered in seven (28%) patients (two patients, post-tumorectomy; five patients, post-mastectomy) and 13 patients (52%) received anthracycline-based adjuvant chemotherapy. Five-year overall survival rate was 91% (95% CI, 80-100%). Five patients (20%) developed distant metastases (one after chemotherapy) and three (12%) locoregional relapse (one after tumorectomy and unknown margin without radiotherapy, two after mastectomy and involved margins with radiotherapy). CONCLUSION: Wide breast surgery (that can be conservative in selected patients) is the mainstay of the treatment of non metastatic malignant phyllodes tumors of the breast. To better determine the respective roles of adjuvant systemic treatment and radiotherapy, further clinical studies and the search for new prognostic and predictive factors remain necessary.

[Targeting of the AKT-mTOR pathway in head and neck and lung cancer]. / Traitements ciblant la voie AKT-mTOR en pathologies tumorales ORL et thoraciques.

AKT-mTOR pathway is considered as a key actor of the regulation of cell metabolism, interacting in network with multiple pathways implied in immune regulation and carcinogenesis. mTOR inhibitors were initially proposed as immunomodalting agents and are now developed as targeted therapy for non-hematologic solid tumours or lymphomas. This review proposes to synthesize knowledge on the AKT-mTOR pathway and the currently available data for head and neck or pulmonary tumours in order to present the value of these agents in this setting. Rational and preclinic results will then allow us to discuss potential future development of mTOR inhibitors.

Effect of alternative crosslinking methods on the low strain rate viscoelastic properties of bovine pericardial bioprosthetic material.

Early failures of bovine pericardial heart valves have been due to leaflet perforation/tearing and calcification. Since glutaraldehyde fixation has been shown to produce marked changes in leaflet mechanics and has been linked to the development of calcification, alternative crosslinking techniques have been suggested as means to overcome these obstacles. We have examined the low strain rate viscoelastic behavior of bovine pericardium: (1) fresh; (2) chemically treated with glutaraldehyde, cyanimide, or polyglycidyl ether; or (3) physically treated by freeze-drying or heat-drying. Shrinkage temperature tests were conducted to assess intrahelical crosslinking. Polyglycidyl ether and glutaraldehyde both produced substantial crosslinking, with the shrinkage temperature rising above 80 degrees C. Mechanical changes were nearly equivalent, both showing decreased stress relaxation and increased extensibility consistent with intrahelical crosslinking and shrinkage during fixation. Cyanimide, known to crosslink pure collagen materials, showed no evidence of crosslinking intact tissue. Heat-drying, also effective in pure collagen preparations, produced an increase in UTS and tissue modulus, but otherwise left the tissue unchanged. Freeze-drying had no mechanical effect, and therefore provides an attractive means for the storage of connective tissues for later mechanical testing.

The bovine pericardial xenograft: I. Effect of fixation in aldehydes without constraint on the tensile viscoelastic properties of bovine pericardium.

Tensile testing of tissue strips has been used to examine the effect of simple fixation in glutaraldehyde and formaldehyde on the viscoelastic properties of bovine pericardium. To assess tissue anisotropy, tissue strips were cut at 0 degree, 30 degrees, 60 degrees, and 90 degrees relative to the base-to-apex direction. Fresh anterior pericardium was modestly anisotropic, being least extensible in the base-to-apex direction; however, fixation removed this anisotropy. Fixation also produced a marked change in the response of the material to initial cyclic loading during preconditioning. Overall extensibility of the fixed material was significantly greater than that for the fresh tissue, consistent with a 10.7% shrinkage in aldehydes calculated from strain at fracture data. Reductions in stress relaxation and creep after fixation were noted as well, consistent with intrafibrillar crosslinking. Cyclic hysteresis and ultimate tensile strength were unaffected. Since the observed changes in the stress-strain response were largely attributable to shrinkage, control of shrinkage by physical means would allow for engineering modification of bovine pericardial mechanics for controlled anisotropy.

The bovine pericardial xenograft: II. Effect of tethering or pressurization during fixation on the tensile viscoelastic properties of bovine pericardium.

Our previous article suggested that control of the extensibility of aldehyde-fixed pericardium could be achieved by controlling shrinkage during fixation. Therefore, to prevent shrinkage, we have used sandpaper-lined plexiglass plates to clamp circular samples of bovine pericardium during fixation in glutaraldehyde, tethering them at their original dimensions. As well, we have applied transmural pressures of 50 or 100 mm Hg during fixation using a hydraulic column of glutaraldehyde solution. Strips cut at 0 degree, 30 degrees, 60 degrees, and 90 degrees to the base-to-apex cardiac direction have been examined for cyclic stress-strain response, stress relaxation, plastic deformation, and fracture behavior. Under physiological stresses, tethered and pressure-fixed materials were both nearly isotropic. Tethering during fixation produced a material with extensibility nearly identical to that of fresh tissue. Plastic deformation during cyclic loading was reduced below that seen in simple fixation while stress relaxation was unchanged. Pressure-fixation produced reduced extensibility similar to that produced in porcine aortic valve leaflets. Plastic deformation and stress relaxation were both markedly reduced. Pressure-fixation reduced the strain at fracture, but fracture behavior was otherwise unaffected. Tethering and pressure-fixation offer attractive means to control the mechanical behavior of bovine xenograft materials.

The bovine pericardial xenograft: III. Effect of uniaxial and sequential biaxial stress during fixation on the tensile viscoelastic properties of bovine pericardium.

Our previous two articles have shown that glutaraldehyde-fixed bovine pericardium is nearly isotropic, whether fixed without constraints, with tethering, or with pressure. In this study, we have used uniaxial stress during fixation to produce bovine pericardial material with marked tensile anisotropy. Rectangular and cruciate pericardial samples have been mechanically examined after one of four treatments: (i) fixation under 88-kPa uniaxial stress, (ii) fixation under 176-kPa uniaxial stress, (iii) 3 h of 176-kPa uniaxial stress in saline followed by 24-h fixation under the same stress, (iv) fixation under 176-kPa uniaxial stress followed by a second fixation under 176-kPa stress in a direction normal to the first. Strips of material were cut at 0 degree, 30 degrees, 60 degrees, and 90 degrees to direction of the initial stress, and tested for response to cyclic loading, stress relaxation, plastic deformation, and fracture properties. Fixation under uniaxial stress produced anistropy similar to that seen in porcine aortic valve leaflets; however, the overall extensibility of the material depended on the applied stress and the aspect ratio of the stressed sample. While loading in saline produced no change, the sequential biaxial stressing produced a reduction in anisotropy, suggesting exposure of additional crosslinking sites. Uniaxial stress during fixation may be a useful method for construction of anisotropic heart valve leaflets.

Guar gum consumption in adolescent and adult rats: short- and long-term metabolic effects.

Metabolic responses to short- and long-term guar gum consumption were studied in adolescent and adult rats. For the long-term study, male adolescent rats were divided into four groups (n = 60/group) and fed guar gum, cellulose, or bran diet for 67 weeks. Metabolic studies (food--water intake, feces--urine output, body weight, carbohydrate tolerance) were performed eight times during the 67 weeks. The guar gum group consumed less diet throughout the entire study and gained less weight over the first 20 weeks compared with the cellulose and bran groups. A second bran-fed group was food restricted over the first 20 weeks to match the reduced weight gain of the guar gum group and then fed ad libitum. Reduced plasma glucose excursions were measured for only the guar gum group after both fibre-free glucose and sucrose challenges at weeks 6, 12, and 18; from 24 to 64 weeks all four groups had similar glucose tolerance responses. Twenty-four hour urinary glucose excretion was similar during all eight metabolic studies up to 64 weeks for guar gum and cellulose groups. In the short-term study, male adolescent (200 g; n = 10/group) and adult (630 g; n = 15/group) rats were divided into five and four groups, respectively, and fed guar gum, guar by-product (GBP), cellulose, or bran diet for 6 weeks. A metabolic study was performed during the 6th week. Adolescent rats fed guar gum or GBP diets gained less weight than the cellulose group; only the guar gum group displayed improved carbohydrate tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)