Alain Duhamel

Centre Hospitalier Régional Universitaire de Lille, Lille, Nord-Pas-de-Calais, France

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Publications (311)1189.43 Total impact

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    ABSTRACT: Our aim was to analyse the potential role of chemokines receptors CXCR2 and CXCR4 signalling pathways in liver metastatic colorectal cancer (CRC) relapse. CXCR2, CXCR4 and their chemokine ligands were evaluated in liver metastases of colorectal cancer in order to study their correlation with overall and disease-free survivals of patients having received or not a neoadjuvant chemotherapy regimen.qRT-PCR, and CXCR2 immunohistochemical staining were performed using CRC liver metastasis samples. Expression levels of CXCR2, CXCR4 and their ligands were statistically analysed according to the administration of neoadjuvant chemotherapy and patients’ outcome.CXCR2 and CXCL7 overexpression are correlated to shorter overall and disease-free survival By multivariate analysis, CXCR2 and CXCL7 expressions are independent factors of overall and disease-free survivals. Neoadjuvant chemotherapy increases significantly the expression of CXCR2: treated group 1.89(0.02-50.92) versus 0.55(0.07-3.22), p=0.016. CXCL7 is overexpressed close to significance, 0.40 (0.00- 7.85) vs. 0.15 (0.01-7.88), p=0.12.We show the involvement of CXCL7/CXCR2 signalling pathways as predictive factor of poor outcome in metastatic CRC. 5FU-based chemotherapy regimens increase the expression of these genes in liver metastasis, providing one explanation for aggressiveness of relapsed drug-resistant tumours. Selective blockage of CXCR2/CXCL7 signalling pathways could provide new potential therapeutic opportunities.This article is protected by copyright. All rights reserved.
    Cancer Science 01/2015; · 3.53 Impact Factor
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    ABSTRACT: Pseudomonas aeruginosa is an opportunistic Gram-negative bacterium that causes pneumonia in immunocompromised humans and severe pulmonary damage in patients with cystic fibrosis. Imbalanced fatty acid incorporation in membranes, including increased arachidonic acid and decreased DHA concentrations, is known to play a critical role in chronic inflammation associated with bacterial infection. Other lipids, such as EPA and alkylglycerols, are also known to play a role in inflammation, particularly by stimulating the immune system, decreasing inflammation and inhibiting bacterial growth. In this context, the goal of the present study was to assess the effect of dietary DHA/EPA, in a 2:1 ratio, and alkylglycerols, as natural compounds extracted from oils of rays and chimeras, respectively, on the inflammatory reaction induced by P. aeruginosa pulmonary infection in mice. To this end, mice were fed with a control diet or isolipidic, isoenergetic diets prepared with oils enriched in DHA/EPA (2:1) or alkylglycerols for 5 weeks before the induction of acute P. aeruginosa lung infection by endotracheal instillation. In our model, DHA/EPA (2:1) significantly improved the survival of mice after infection, which was associated with the acceleration of bacterial clearance and the resolution of inflammation leading to the improvement of pulmonary injuries. By contrast, alkylglycerols did not affect the outcomes of P. aeruginosa infection. Our findings suggest that supplementation with ray oil enriched in DHA/EPA (2:1) can be considered as a preventive treatment for patients at risk for P. aeruginosa infection.
    The British journal of nutrition. 01/2015;
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    ABSTRACT: Background Standardised measurement of remnant liver volume (RLV), where total liver volume (TLV) is calculated from patients’ body surface area (RLV-sTLV), has been advocated. Extrapolating the model of living donor liver transplantation, we showed in a pilot study that the simplified RLV/body weight ratio (RLVBWR) was accurate in assessing the functional limit of hepatectomy. The aim of the study was to compare in a prospective series of extended right hepatectomy the predictive value of the RLVBWR and the RLV-sTLV at a cut-off of 0.5% (RLVBWR0.5%) and 20% (RLV-sTLV20%), respectively. Methods We studied the impact of RLVBWR0.5% and of RLV-sTLV20% on three months morbidity and mortality in 74 non-cirrhotic patients operated on for malignant tumours. Of these, 47 patients who were not included in the initial pilot study were enrolled in a prospective validation cohort to reappraise the predictive value of each method. Results RLVBWR and RLV-sTLV were highly correlated (Pearson correlation coefficient, 0.966). Three months overall and severe morbidity (grade 3b–5) and mortality were significantly increased in groups RLVBWR ≤ 0.5% and RLV-sTLVs ≤ 20% compared to groups >0.5% and >20%, respectively. The sensitivity and specificity in predicting death from liver failure were 100 and 84.1% for RLVBWR0.5% and 60 and 94.2% for RLV-sTLV20%, respectively. Similar results were observed in the validation cohort for the RLVBWR0.5% (lack of statistical power for RLV-sTLV as only 2 patients showed a RLV-sTLV ≤ 20%). Conclusions The RLVBWR0.5% is a method of assessing the remnant liver that is simple and as reliable as the standardised RLV-sTLV20%.
    World Journal of Surgery 01/2015; · 2.35 Impact Factor
  • Christophe Mariette, Caroline Gronnier, Alain Duhamel, Jean-Yves Mabrut, Jean-Pierre Bail, Nicolas Carrere, Jérémie H Lefevre, Bernard Meunier, Denis Collet, Guillaume Piessen
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    ABSTRACT: Self-expanding metallic stents (SEMSs) have been used as a bridge to surgery, relieving dysphagia and maintaining nutrition, in patients with operable but obstructive esophageal cancer (EC). However, the impact of SEMSs on oncologic outcomes is unknown. The aim of this study was to evaluate the impact of SEMS insertion before EC surgery on oncologic outcomes. From 2000 to 2010, two thousand nine hundred and forty-four patients who underwent an operation for EC with a curative intent were included in a multicenter European cohort. Through propensity score analysis, patients who underwent SEMS insertion (SEMS group, n = 38) were matched 1:4 to control patients who did not undergo SEMS insertion (control group, n = 152). The SEMS and control groups were comparable according to age, sex, tumor location, clinical stage, American Society of Anesthesiologists score, dysphagia, malnutrition, neoadjuvant treatment administration, histology, and surgical procedure. Self-expanding metallic stent insertion was complicated by tumoral perforation in 2 patients. The in-hospital postoperative mortality and morbidity rates for the SEMS vs control groups were 13.2% vs 8.6% (p = 0.370) and 63.2% vs 59.2% (p = 0.658), respectively. The R0 resection rate (71.0% vs 85.5%; p = 0.041), median time to recurrence (6.5 vs 9.0 months; p = 0.040), and 3-year overall survival (25% vs 44%; p = 0.023) were significantly reduced in the SEMS group, and the 3-year locoregional recurrence rate was increased (62% vs 34%; p = 0.049). The results remained significant after excluding SEMS-related esophageal perforations. After adjusting for confounding factors, SEMS insertion was a predictor of poor prognosis (hazard ratio = 1.6; p = 0.038). Self-expanding metallic stent insertion, as a bridge to surgery, has a negative impact on oncologic outcomes in EC. Clinicaltrials.gov ID: NCT 01927016. Copyright © 2015 American College of Surgeons. Published by Elsevier Inc. All rights reserved.
    Journal of the American College of Surgeons 12/2014; · 4.45 Impact Factor
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    ABSTRACT: Background and purposeSelective agonists of sigma-1 (σ1) protein are generally reported to protect against neuronal damage and modulate oligodendrocyte differentiation. Human and rodent lymphocytes possess saturable, high-affinity binding sites for σ ligands and potential immunomodulatory properties have been described for σ1 compounds. Experimental auto-immune encephalomyelitis (EAE) has unequivocal value as a model of the inflammatory aspects of multiple sclerosis (MS). Here, we have assessed the role of σ1 agonist containing the tetrahydroisoquinoleine-hydantoin structure in EAE.Experimental approachEAE was induced in SJL/J female mice by active immunization with myelin proteolipid protein (PLP)139-151 peptide. The σ1 agonist was injected i.p. at immunization time (D0). Disease severity was assessed clinically and by histopathological evaluation of the central nervous system (CNS). Phenotyping of B-cell subsets and Tregs were performed by flow cytometry in spleen and cervical lymph nodes.Key resultsProphylactic treatment of EAE mice with σ1 agonist prevented mononuclear cell accumulation and demyelination in brain and spinal cord and increased T2 B cells and Tregs, resulting in an overall reduction in the clinical progression of EAE.Conclusions and implicationsσ1 agonist containing the tetrahydroisoquinoleine-hydantoin structure dampened the magnitude of inflammation in EAE. This was associated with the increase in the proportion of B-cell subsets and Tregs with potential immunoregulatory functions. Targeting σ1 might thus provide new therapeutic opportunities for MS.
    British Journal of Pharmacology 12/2014; · 5.07 Impact Factor
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    ABSTRACT: Apathy is a frequent and disabling behavioral disorder in patients with Parkinson's disease (PD). Its prevalence in treatment-naive patients with early-stage PD has not been extensively investigated. Moreover, whether apathy is related to other non-motor symptoms in early-stage PD is unknown. Our objective was to determine the prevalence and features of apathy and associated factors in a group of treatment-naive patients with early-stage PD. Ninety-five treatment-naive patients with early-stage PD participated in the study. Apathy, depression, motor symptoms, and overall cognitive efficiency were assessed. The presence of the main non-motor symptoms was checked during a detailed clinical interview. Group comparisons were carried out to investigate the association with apathy. Eighteen patients (18.95%) were diagnosed as apathetic, and five of the latter had concomitant depression. Apathetic patients had significantly more severe motor symptoms (P < 0.001) and a lower cognitive status (P = 0.032) than non-apathetic patients. When considering non-motor symptoms, apathy was significantly associated only with fatigue (P = 0.007) and anhedonia (P = 0.010), both of which were more prevalent in apathetic patients than in non-apathetic patients. In treatment-naive patients with early-stage PD, apathy was significantly associated with more severe motor symptoms and a lower cognitive status. After adjustment for these factors, apathy appeared to be a relatively isolated, independent symptom because the only other associated non-motor symptoms were fatigue and anhedonia. © 2014 International Parkinson and Movement Disorder Society
    Movement Disorders 11/2014; · 5.63 Impact Factor
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    ABSTRACT: To assess the impact of neoadjuvant chemoradiotherapy (NCRT) on anastomotic leakage (AL) and other postoperative outcomes after esophageal cancer (EC) resection.
    Annals of Surgery 11/2014; 260(5):764-771. · 7.19 Impact Factor
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    ABSTRACT: Background Uncontrolled use of tanning beds is a major public health problem. The role of UV in skin carcinogenesis has in fact been clearly demonstrated. Aims The main purpose of the study was to assess the motivations and beliefs of the population concerning the use of indoor tanning. The secondary objectives were to compare the knowledge of users and non-users and to screen for addiction criteria among users. Patients and methods This was a transversal descriptive study conducted between April and June 2013 in Lille town center. The motivations of the participants were determined using a multiple-choice questionnaire. A Likert scale was used to assess beliefs and an m-CAGE questionnaire was used to screen for addiction. Results Of the 200 respondents, 30% (n = 60) had used tanning beds in a non-medical setting. The median age of first use was 23 years (15–59). 11.7% of respondents had started before the authorised age of 18 years. “To prepare the skin for exposure to the sun” was the main reason given (68.3%) for use of tanning beds. The population was aware that use of such apparatus favours onset of skin cancer and ageing of the skin. Users were more convinced than non-users that UV cabins “prepare the skin for exposure to the sun” (75% vs. 49.6%, P = 0.0009) and that they “favour skin cancer” (56.9% against 36.2%, P = 0.0444). Addictive behaviour was detected in 3.3% (2/60) of users. Conclusion Users are aware of the carcinogenic risk of UV cabins but expose themselves to such risk, as they believe it prepares their skin for sun exposure.
    Annales de Dermatologie et de Vénéréologie 10/2014; · 0.67 Impact Factor
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    ABSTRACT: Objective: The question of whether breastfeeding has a protective effect against the development of overweight or obesity later in life remains controversial, especially during adolescence. The objective was to assess the relationship between breastfeeding and adolescents' body composition. Methods: The HELENA study is a cross-sectional study involving 3,528 adolescents from 10 European cities. The outcome measures were body weight and height, subscapular skinfolds as well as waist circumferences. Breastfeeding, smoking status, and parental socioeconomic status were assessed by self-administered questionnaires. Dietary intake was recorded using two 24-hour recall surveys. Two adjustment approaches were used: i) covariance analysis adjusted for confounding factors (propensity score adjustment) and ii) multivariate quantile regression. Results: After adjustment, no significant associations were observed between breastfeeding and body composition parameters (BMI Z-score; sum of skinfolds; waist-to-height ratio). An adjusted quantile regression analysis showed a non-significant trend for a protective effect of breastfeeding toward the highest percentiles of adiposity in boys but not in girls. This is of particular interest with respect to the superiority of the waist-to-height ratio over waist circumference and BMI for detecting cardiometabolic risk factors. Conclusion: This first European study, including a large set of factors influencing adolescents' body composition, showed a non-significant trend toward a protective effect of breastfeeding on highest percentiles of adolescent's abdominal adiposity. © 2014 S. Karger GmbH, Freiburg.
    Obesity Facts 10/2014; 7(5):289-301. · 1.58 Impact Factor
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    ABSTRACT: Can cluster analysis can be used to identify a homogeneous subpopulation of women with polycystic ovarian morphology (PCOM) within a very large population of control women in a non-subjective way?
    Human Reproduction 09/2014; · 4.59 Impact Factor
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    ABSTRACT: To assess the relevance of the International Study Group of Liver Surgery (ISGLS) definition of posthepatectomy liver failure compared with 2 well-established criteria, 50-50 and PeakBili >7, as early predictors of posthepatectomy outcome.
    Annals of Surgery 09/2014; · 7.19 Impact Factor
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    ABSTRACT: In an attempt to reduce the incidence of chronic GVHD (cGVHD) after reduced-intensity conditioning (RIC), we used BM instead of PBSC and added melphalan 100 mg/m(2) to the classical association of fludarabine, 30 mg/m(2)/day for 3 days and TBI, 200 cGy (FLUIM regimen). Between 2000 and 2012, 51 patients received BM with the FLUIM regimen (group A), and 124 received BM (n=22) or PBSC (n=102) with another RIC regimen (group B). Donors were siblings (n=123) or HLA-matched 10/10 unrelated (n=52). Full donor-type chimerism at day 100 was more often recorded in group A (86%) than in group B (62%); P<0.001. There was no difference between the two groups in terms of OS and EFS, acute GVHD, relapse and non-relapse mortality incidence. cGVHD occurred more often in group B (41%) than in group A (23%); P=0.021. In multivariate analysis, the two risk factors associated with the development of cGVHD were conditioning in group B (hazard ratio (HR)=2.871, 95% confidence interval (CI) (1.372-6.006); P=0.005) and CD34(+) count (HR=1.009, 95% CI (1.006-1.011); P<0.001). In conclusion, the FLUIM regimen followed by BM leads to more frequent full-donor chimerism and a reduced incidence of cGVHD without compromising relapse and survival.Bone Marrow Transplantation advance online publication, 15 September 2014; doi:10.1038/bmt.2014.193.
    Bone Marrow Transplantation 09/2014; · 3.47 Impact Factor
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    ABSTRACT: Auditory-verbal hallucinations (AVHs) are associated with an impaired connectivity of large-scale networks. To examine the relationship between white-matter integrity and AVHs, we conducted a meta-analysis of diffusion-tensor-imaging studies that compared patients with schizophrenia and AVHs with matched healthy controls (HCs). Five studies were retained gathering 256 DTI data points, divided into AVHs (n = 106) and HCs (n = 150). The meta-analysis demonstrated a reduced fractional anisotropy in the left Arcuate Fasciculus (AF) of hallucinators (hg = − 0.42; CI[− 0.69,− 0.16]; p < 10− 3). The current meta-analysis confirmed disruptions of white matter integrity in the left AF bundle of schizophrenia patients with AVHs.
    Schizophrenia Research 08/2014; · 4.43 Impact Factor
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    ABSTRACT: Background The aim of the authors was to reassess the impact of a positive surgical margin (R1) after a liver resection for colorectal liver metastases (CLMs) on survival in the era of modern chemotherapy, through their own experience and a literature review.Methods Inclusion criteria were: R1 or R0 resection with no local treatment modalities, extra-hepatic metastases or other cancer.ResultsAmong 337 patients operated between 2000 and 2010, 273 patients were eligible (214 R0/59 R1). The mean follow-up was 43 ± 29 months. Compared with a R0 resection, a R1 resection offered a lower 5-year overall (39.1% versus 54.2%, P = 0.010), disease-free (15.2% versus 31.1%, P = 0.021) and progression-free (i.e. time to the first non-curable recurrence; 33.1% versus 47.3%, P = 0.033) survival rates. Metastases in the R1 group were more numerous, larger and more frequently synchronous. Independent factors of poor survival were: number, size and short-time interval of CLM occurrence, N status, rectal primary, absence of adjuvant chemotherapy, but not a R1 resection. With the more-systematic administration of chemotherapy since 2005, the intergroup difference in progression-free survival disappeared (P = 0.264).ConclusionA R1 resection had no prognostic value per se but reflected a more severe disease. The recent change in the prognostic value of a R1 resection may be linked to the beneficial effect of chemotherapy.
    HPB 08/2014; · 2.05 Impact Factor
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    ABSTRACT: Benefits of recombinant human growth hormone (rhGH) alone or combined with glutamine in patients with intestinal failure because of short-bowel syndrome remain controversial.
    American Journal of Clinical Nutrition 07/2014; 100(3). · 6.50 Impact Factor
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    ABSTRACT: Objective: Patients with temporal lobe epilepsy (TLE) have impaired theory of mind (ToM). However, ToM involves a variety of processes, such as understanding a person's intentions ("cognitive" ToM) and emotional states ("affective" ToM). The objectives of the present study were to characterize ToM disorders in TLE patients, identify patients at risk of ToM disorders, and study the relationships between psychobehavioral and quality of life factors and ToM disorders. Method: Fifty TLE patients and 50 controls performed ToM tasks assessing their understanding of verbal clumsiness (faux pas), sarcastic remarks, and mentalistic actions. Demographic, cognitive, and psychobehavioral data, and (for TLE patients) clinical and quality of life factors, were recorded. Results: Compared with controls, TLE patients showed impairments in all ToM tasks: 84% misunderstood faux pas, and around 50% misunderstood sarcasm. A long duration of epilepsy and young age at onset were risk factors for ToM impairments. In TLE patients, ToM impairments were associated with impaired empathy and anhedonia. Their affective states were less positively and more negatively valenced than in controls. Low positive affectivity was predictive of greater cognitive and affective ToM impairments for the faux pas task, and high negative affectivity was predictive of greater cognitive ToM abilities for the sarcasm task. The lack of social support was correlated with impaired ToM but was not a predictive factor. Conclusions: Both cognitive and affective ToM processes are impaired in TLE patients. Impaired ToM has an impact on empathy abilities and is related to affective disturbances in TLE patients. (PsycINFO Database Record (c) 2014 APA, all rights reserved).
    Neuropsychology 07/2014; · 3.58 Impact Factor
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    ABSTRACT: Multiple organ dysfunction, not respiratory failure, is the major cause of death in children with acute lung injury or acute respiratory distress syndrome. This study was undertaken to estimate the predictive value of death of the nonrespiratory Pediatric Logistic Organ Dysfunction-2 in children with acute respiratory failure.
    Pediatric Critical Care Medicine 06/2014; 15(7). · 2.33 Impact Factor
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    ABSTRACT: Before introducing 70-kVp settings in the low-kilovoltage strategies for pediatric examinations, it was mandatory to demonstrate, at similar dose levels, an equivalence of image quality at 70 kVp and 80 kVp.
    Pediatric Radiology 06/2014; · 1.65 Impact Factor
  • Annals of the Rheumatic Diseases 06/2014; 73(Suppl 2):1008-1009. · 9.27 Impact Factor
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    ABSTRACT: Background Because of growing body of interest on the association between fibrosing idiopathic interstitial pneumonias (f-IIP) and ischemic heart disease, we initiated this prospective study to evaluate the prevalence of asymptomatic coronary artery disease (CAD) in patients with f-IIP. Methods 42 patients with f-IIP underwent noninvasive screening for CAD that included (a) a chest CT examination enabling calculation of the coronary artery calcium (CAC) score, then depiction of coronary artery stenosis; and (b) stress myocardial perfusion scintigraphy (MPS). Patients with significant coronary abnormalities, defined by a CAC score >400 or coronary artery stenosis >50% at CT and/or perfusion defect > 5% at MPS, were referred to the cardiologist. Coronary angiography was indicated in presence of a perfusion defect > 10% at MPS or significant left main or proximal left anterior descending stenosis whatever MPS findings. Results Combining CT and MPS, significant abnormalities were detected in 32/42 patients (76%). The cardiologist: (a) did not consider further investigation in 21 patients (CT abnormalities but no ischemia at MPS: 12/21; false-positive findings at MPS: 3/21; poor respiratory condition: 6/21); (b) proceeded to coronary angiography in 11 patients which confirmed significant stenoses in 5 patients (5/42; 12%). In the worst-case-scenario (i.e., inclusion of 6 patients with significant coronary artery abnormalities who were not investigated due to poor respiratory condition), the prevalence of CAD reached 26% (11/42). Conclusion In the studied population of patients with f-IIP, asymptomatic CAD ranged between 12% and 26%.
    European Journal of Radiology 06/2014; · 2.16 Impact Factor

Publication Stats

4k Citations
1,189.43 Total Impact Points

Institutions

  • 1999–2014
    • Centre Hospitalier Régional Universitaire de Lille
      • Division of Neurology
      Lille, Nord-Pas-de-Calais, France
  • 1997–2014
    • University of Lille Nord de France
      Lille, Nord-Pas-de-Calais, France
  • 2013
    • Clinique de l'Yvette
      Longjumeau, Île-de-France, France
  • 2001–2013
    • Université du Droit et de la Santé Lille 2
      • Faculty of Medicine
      Lille, Nord-Pas-de-Calais, France
  • 2001–2011
    • CHRU de Strasbourg
      Strasburg, Alsace, France
    • Lille Catholic University
      Lille, Nord-Pas-de-Calais, France