Center Hospitalier Robert Debre
Center Hospitalier Robert Debre
Bachmeyer C.,Assistance Publique Hopitaux de Paris |
Reguiai Z.,Center Hospitalier Robert Debre |
Peuvrel L.,Nantes University Hospital Center |
Bachet J.-B.,University Pierre and Marie Curie |
And 5 more authors.
Bulletin du Cancer | Year: 2013
The epidermal growth factor receptors (EGFR)-inhibitors are frequently responsible for cutaneous adverse drug reactions that may alter the patients' quality of life and hamper the continuation of treatment. We present here the experience of a group of French multidisciplinary experts-the PROCUR group (PRise en charge de la tOxicité CUtanée des anti-EGFR)-created in order to establish a therapeutic algorithm. It was built in three steps under the responsibility of a steering committee: (1) a systematic literature review was performed by a group of three dermatologists and one oncologist; (2) regional meetings evaluated practical aspect of the treatments in France; (3) a final meeting confrontating the practices in France and the evidence-based medicine including the steering committee, the bibliographic group, and oncologists, radiotherapists, dermatologists and hepato-gastroenterologists involved in regional scientific committees, resulted in a therapeutic algorithm, resulting in the collegial writing of this algorithm. This multidisciplinary study should facilitate the standardised, optimised management of skin toxicity associated with EGFR-inhibitors.
Brue T.,Aix - Marseille University |
Quentien M.-H.,Aix - Marseille University |
Khetchoumian K.,Institute Of Recherches Cliniques Of Montreal |
Bensa M.,Ospedale Bufalini |
And 12 more authors.
BMC Medical Genetics | Year: 2014
Background: DAVID syndrome is a rare condition combining anterior pituitary hormone deficiency with common variable immunodeficiency. mutations have recently been identified in patients with ACTH and variable immunodeficiency. A similar mutation was previously found in in the immunodeficient mouse strain, but the effect of the mutation on endocrine function was not evaluated. Methods: We ascertained six unrelated DAVID syndrome families. We performed whole exome and traditional Sanger sequencing to search for causal genes. mice were examined for endocrine developmental anomalies. Results: Mutations in the gene were identified in three of our families through whole exome sequencing, and in a fourth by direct Sanger sequencing. origin of the mutations could be demonstrated in three of the families. All mutations lie near the C-terminus of the protein-coding region, near signals required for processing of NFKB2 protein by the alternative pathway. Two of the probands had anatomical pituitary anomalies, and one had growth and thyroid hormone as well as ACTH deficiency; these findings have not been previously reported. Two children of one of the probands carried the mutation and have to date exhibited only an immune phenotype. No mutations were found near the C-terminus of in the remaining two probands; whole exome sequencing has been performed for one of these. mice, carrying a similar C-terminal mutation, showed normal pituitary anatomy and expression of proopiomelanocortin (POMC). Conclusions: We confirm previous indings that mutations near the C-terminus of cause combined endocrine and immunodeficiencies. status of the mutations was confirmed in all cases for which both parents were available. The mutations are consistent with a dominant gain-of-function effect, generating an unprocessed super-repressor protein. We expand the potential phenotype of such NFKB2 mutations to include additional pituitary hormone deficiencies as well as anatomical pituitary anomalies. The lack of an observable endocrine phenotype in mice suggests that the endocrine component of DAVID syndrome is either not due to a direct role of NFKB pathways on pituitary development, or else that human and mouse pituitary development differ in its requirements for NFKB pathway function. © 2014 Brue et al.; licensee BioMed Central.
Gourgou-Bourgade S.,Center Val dAurelle |
Bascoul-Mollevi C.,Center Val dAurelle |
Desseigne F.,Center Leon Berard |
Ychou M.,Center Val dAurelle |
And 8 more authors.
Journal of Clinical Oncology | Year: 2013
Purpose: To compare the quality of life (QoL) of patients receiving oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) or gemcitabine as first-line chemotherapy and to assess whether pretreatment QoL predicts survival in patients with metastatic pancreatic cancer. Patients and Methods: Three hundred forty-two patients with performance status 0 or 1 were randomly assigned to receive FOLFIRINOX (oxaliplatin, 85 mg/m2; irinotecan, 180 mg/m2; leucovorin, 400 mg/m2; and fluorouracil, 400 mg/m2 bolus followed by 2,400 mg/m2 46-hour continuous infusion, once every 2 weeks) or gemcitabine 1,000 mg/m 2 weekly for 7 of 8 weeks and then weekly for 3 of 4 weeks. QoL was assessed using European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire C30 every 2 weeks. Results: Improvement in global health status (GHS; P < .001) was observed in the FOLFIRINOX arm and improvement in emotional functioning (P < .001) was observed in both arms, along with a decrease in pain, insomnia, anorexia, and constipation in both arms. A significant increase in diarrhea was observed in the FOLFIRINOX arm during the first 2 months of chemotherapy. Time until definitive deterioration ≥ 20 points was significantly longer for FOLFIRINOX compared with gemcitabine for GHS, physical, role, cognitive, and social functioning, and six symptom domains (fatigue, nausea/vomiting, pain, dyspnea, anorexia, and constipation). Physical functioning, constipation, and dyspnea were independent significant prognostic factors for survival with treatment arm, age older than 65 years, and low serum albumin. Conclusion: FOLFIRINOX significantly reduces QoL impairment compared with gemcitabine in patients with metastatic pancreatic cancer. Furthermore, baseline QoL scores improved estimation of survival probability when added to baseline clinical and demographic variables. © 2012 by American Society of Clinical Oncology.
Dubernard X.,CLCC Institute Jean Godinot |
Dubernard X.,Center Hospitalier Robert Debre |
Dabakuyo S.,CLCC Institute Jean Godinot |
Ouedraogo S.,CLCC Institute Jean Godinot |
And 9 more authors.
Head and Neck | Year: 2016
Background The benefit of neck dissection is the subject of debate in differentiated thyroid cancer (DTC). We analyze the risk-benefit of neck dissection for low-risk DTC without detectable lymph nodes. Methods We conducted a retrospective study from 1983 to 2003; which included 295 patients without detectable lymph nodes who were treated by thyroidectomy with (C+) or without (C-) neck dissection. All patients had iodine131 therapy. We compared the frequency of remission, disease progression, and permanent complications between groups. Results Two hundred twelve patients comprised the C+ group, and 83 patients the C- group. Respectively for C+ versus C-, remission rates were 92% versus 89.2% (p =.40), and progressive disease observed was 3.3% versus 7.2% (p =.10). Permanent hypoparathyroidism occurred in 15.1% in C+ versus 3.6% in C- (p =.006). Conclusion The risk-benefit analysis of neck dissection in patients with low-risk DTC shows no benefit in terms of complete remission or occurrence of progression. However, risk of complications seems to be higher in patients with neck dissection. © 2016 Wiley Periodicals, Inc.
Bouligand J.,Assistance Publique Ho pitaux de Paris |
Bouligand J.,French Institute of Health and Medical Research |
Bouligand J.,University Paris - Sud |
Delemer B.,Center Hospitalier Robert Debre |
And 19 more authors.
PLoS ONE | Year: 2010
Primary glucocorticoid resistance (OMIM 138040) is a rare hereditary disease that causes a generalized partial insensitivity to glucocorticoid action, due to genetic alterations of the glucocorticoid receptor (GR). Investigation of adrenal incidentalomas led to the discovery of a family (eight affected individuals spanning three generations), prone to cortisol resistance, bilateral adrenal hyperplasia, arterial hypertension and hypokalemia. This phenotype exacerbated over time, cosegregates with the first heterozygous nonsense mutation p.R469[R,X] reported to date for the GR, replacing an arginine (CGA) by a stop (TGA) at amino-acid 469 in the second zinc finger of the DNA-binding domain of the receptor. In vitro, this mutation leads to a truncated 50-kDa GR lacking hormone and DNA binding capacity, devoid of hormone-dependent nuclear translocation and transactivation properties. In the proband's fibroblasts, we provided evidence for the lack of expression of the defective allele in vivo. The absence of detectable mutated GR mRNA was accompanied by a 50% reduction in wild type GR transcript and protein. This reduced GR expression leads to a significantly below-normal induction of glucocorticoid-induced target genes, FKBP5 in fibroblasts. We demonstrated that the molecular mechanisms of glucocorticoid signaling dysfunction involved GR haploinsufficiency due to the selective degradation of the mutated GR transcript through a nonsense-mediated mRNA Decay that was experimentally validated on emetine-treated propositus' fibroblasts. GR haploinsufficiency leads to hypertension due to illicit occupation of renal mineralocorticoid receptor by elevated cortisol rather than to increased mineralocorticoid production reported in primary glucocorticoid resistance. Indeed, apparent mineralocorticoid excess was demonstrated by a decrease in urinary tetrahydrocortisone-tetrahydrocortisol ratio in affected patients, revealing reduced glucocorticoid degradation by renal activity of the 11b-hydroxysteroid dehydrogenase type 2, a GR regulated gene. We propose thus that GR haploinsufficiency compromises glucocorticoid sensitivity and may represent a novel genetic cause of subclinical hypercortisolism, incidentally revealed bilateral adrenal hyperplasia and mineralocorticoid-independent hypertension. © 2010 Bouligand et al.
Trabado S.,University Paris - Sud |
Trabado S.,Laboratoire Of Genetique Moleculaire |
Trabado S.,French Institute of Health and Medical Research |
Maione L.,University Paris - Sud |
And 15 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2014
Context: Insulin-like factor 3 (INSL3) is a testicular hormone secreted during fetal life, the neonatal period, and after puberty. Objective: To measure INSL3 levels in a large series of men with congenital hypogonadotropic hypogonadism (CHH)/ Kallmann syndrome (KS), in order to assess its diagnostic value and to investigate its regulation. Patients: We studied 281 CHH/KS patients (91 untreated, 96 receiving T, and 94 receiving combined gonadotropin therapy [human chorionic gonadotropin, hCG, and FSH]) and 72 age-matched healthy men. Methods: Serum INSL3 was immunoassayed with a validated RIA. Results: Mean (-SD) INSL3 levels (pg/mL) were 659 - 279 in controls and lower (60 - 43; P < .001) in untreated CHH/KS patients, with no overlap between the two groups,whenthe threshold of 250 pg/mL was used. Basal INSL3 levels were lower in both untreated CHH/KS men with cryptorchidism than in those with intrascrotal testes and in patients with testicular volumes below 4 mL. Significant positive correlations between INSL3 and both serum total T and LH levels were observed in untreated CHH/KS. Mean INSL3 levels remained low in T-treated CHH/KS patients and were significantly higher in men receiving combined hCG-FSH therapy (P < .001), but the increase was lower cryptorchid patients. FSH-hCG combination therapy or hCG monotherapy, contrary to T and FSH monotherapies, significantly increased INSL3 levels in CHH/KS. Conclusions: INSL3 is as sensitive a marker as T for the evaluation of altered Leydig cell function in CHH/KS patients. INSL3 levels correlate with LH levels in CHH/KS men showing, together with the rise in INSL3 levels during hCG therapy, that INSL3 secretion seems not constitutively secreted during adulthood but is dependence on pituitary LH. Copyright © 2014 by the Endocrine Society.
PubMed | CLCC Institute Jean Godinot, Polyclinique de Courlancy and Center Hospitalier Robert Debre
Type: Journal Article | Journal: Head & neck | Year: 2016
The benefit of neck dissection is the subject of debate in differentiated thyroid cancer (DTC). We analyze the risk-benefit of neck dissection for low-risk DTC without detectable lymph nodes.We conducted a retrospective study from 1983 to 2003; which included 295 patients without detectable lymph nodes who were treated by thyroidectomy with (C+) or without (C-) neck dissection. All patients had iodine131 therapy. We compared the frequency of remission, disease progression, and permanent complications between groups.Two hundred twelve patients comprised the C+ group, and 83 patients the C- group. Respectively for C+ versus C-, remission rates were 92% versus 89.2% (p = .40), and progressive disease observed was 3.3% versus 7.2% (p = .10). Permanent hypoparathyroidism occurred in 15.1% in C+ versus 3.6% in C- (p = .006).The risk-benefit analysis of neck dissection in patients with low-risk DTC shows no benefit in terms of complete remission or occurrence of progression. However, risk of complications seems to be higher in patients with neck dissection. 2016 Wiley Periodicals, Inc. Head Neck 38: 1091-1096, 2016.