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8 results on '"MESH: Intraoperative Period"'

1. Association of Autofluorescence-Based Detection of the Parathyroid Glands During Total Thyroidectomy With Postoperative Hypocalcemia Risk : Results of the PARAFLUO Multicenter Randomized Clinical Trial

Author

Nicolas Turrin, Fares Benmiloud, Laurent Chiche, Régis Gras, Nathalie Chereau, Gaelle Godiris-Petit, Séverine Noullet, Jean-Charles Gillot, Stanislas Rebaudet, Guillaume Penaranda, Jean Gaudart, Hôpital Européen [Fondation Ambroise Paré - Marseille], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Saint-Joseph [Marseille], ALPHABIO - Laboratoire de biologie médicale, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biostatistique et technologies de l'information et de la communication (BioSTIC) - [Hôpital de la Timone - APHM] (BiosTIC ), Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Dupuis, Christine, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Male, Organs at Risk, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Surgical Wound, 030230 surgery, law.invention, Intraoperative Period, 0302 clinical medicine, Postoperative Complications, Randomized controlled trial, law, MESH: Postoperative Complications, Single-Blind Method, Prospective Studies, Prospective cohort study, MESH: Middle Aged, MESH: Organs at Risk, Confounding, Optical Imaging, Middle Aged, MESH: Transplantation, Autologous, 3. Good health, [SDV] Life Sciences [q-bio], MESH: Parathyroid Glands, 030220 oncology & carcinogenesis, Thyroidectomy, Female, MESH: Hypocalcemia, medicine.medical_specialty, Randomization, Transplantation, Autologous, Fluorescence, MESH: Thyroidectomy, Parathyroid Glands, 03 medical and health sciences, medicine, Humans, MESH: Intraoperative Period, MESH: Optical Imaging, MESH: Humans, Hypocalcemia, business.industry, MESH: Surgical Wound, MESH: Fluorescence, Odds ratio, MESH: Single-Blind Method, MESH: Prospective Studies, MESH: Male, Surgery, Transplantation, business, MESH: Female
Abstract

International audience; Importance: Because inadvertent damage of parathyroid glands can lead to postoperative hypocalcemia, their identification and preservation, which can be challenging, are pivotal during total thyroidectomy.Objective: To determine if intraoperative imaging systems using near-infrared autofluorescence (NIRAF) light to identify parathyroid glands could improve parathyroid preservation and reduce postoperative hypocalcemia.Design, setting, and participants: This randomized clinical trial was conducted from September 2016 to October 2018, with a 6-month follow-up at 3 referral hospitals in France. Adult patients who met eligibility criteria and underwent total thyroidectomy were randomized. The exclusion criteria were preexisting parathyroid diseases.Interventions: Use of intraoperative NIRAF imaging system during total thyroidectomy.Main outcomes and measures: The primary outcome was the rate of postoperative hypocalcemia (a corrected calcium

Published
2020

2. Efficacy and safety of an insulin infusion protocol during and after cardiac surgery

Author

C. Studer, W. Sankou, Alfred Penfornis, Marc Puyraveau, Emmanuel Samain, A. Cordier, Joseph-Philippe Etievent, Sebastien Pili-Floury, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de Diabétologie - Endocrinologie [CHRU Besançon], Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( EA 3920) (PCVP / CARDIO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital Jean Minjoz, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Service de diabétologie - endocrinologie, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz, Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( PCVP / CARDIO ), and Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ) -Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon )

Subjects
Blood Glucose, Male, MESH: Hypoglycemia, MESH : Insulin, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, MESH : Aged, Aorta, Thoracic, 030204 cardiovascular system & hematology, law.invention, Intraoperative Period, 0302 clinical medicine, Endocrinology, MESH: Postoperative Period, law, Insulin, MESH : Female, Postoperative Period, 030212 general & internal medicine, Coronary Artery Bypass, Infusions, Intravenous, Prospective cohort study, MESH: Aged, MESH: Middle Aged, MESH: Cardiac Surgical Procedures, MESH : Vascular Surgical Procedures, MESH : Infusions, Intravenous, General Medicine, [ SDV.MHEP.CSC ] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Middle Aged, Intensive care unit, 3. Good health, Cardiac surgery, MESH : Intraoperative Period, Female, Safety, Vascular Surgical Procedures, medicine.medical_specialty, MESH : Male, MESH: Aorta, Thoracic, MESH : Drug Administration Schedule, MESH: Monitoring, Intraoperative, MESH: Insulin, MESH: Drug Administration Schedule, Hypoglycemia, MESH : Cardiac Surgical Procedures, Drug Administration Schedule, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, MESH: Hypoglycemic Agents, Monitoring, Intraoperative, Diabetes mellitus, Internal Medicine, medicine, Humans, Hypoglycemic Agents, MESH : Middle Aged, MESH : Safety, Cardiac Surgical Procedures, MESH: Infusions, Intravenous, MESH: Vascular Surgical Procedures, Pancreatic hormone, MESH : Aorta, Thoracic, Aged, MESH : Postoperative Period, MESH: Intraoperative Period, MESH: Humans, MESH : Hypoglycemia, business.industry, MESH: Coronary Artery Bypass, MESH : Humans, MESH: Safety, Perioperative, MESH : Blood Glucose, medicine.disease, MESH : Hypoglycemic Agents, MESH : Coronary Artery Bypass, MESH: Male, Surgery, Hyperglycemia, MESH : Hyperglycemia, MESH: Blood Glucose, MESH : Monitoring, Intraoperative, MESH: Hyperglycemia, business, MESH: Female
Abstract

International audience; AIM: Perioperative tight blood glucose (BG) control using insulin therapy after major surgery is a difficult, time-consuming task that also raises some concerns over the risk of severe hypoglycaemia. The aim of the present prospective study was to evaluate the efficacy and safety of an insulin therapy protocol in use at our institution. METHODS: A total of 230 consecutive patients (mean+/-SD age: 67+/-11 years; diabetic patients: n=62) undergoing cardiac surgery (coronary artery bypass grafting: n=137; 20% off-pump) or intrathoracic aortic (n=10) surgery were included. BG control was managed according to an insulin therapy protocol, described by Goldberg et al. (2004) [11], in use for 6 months in our intensive care unit. Insulin infusion rate and frequency of BG monitoring were both adjusted according to: (1) the current BG value; (2) the previous BG value; and (3) the current insulin infusion rate. Efficacy was assessed by the percentage of time spent at the target BG level (100-139 mg/dL) intraoperatively and during the first 2 postoperative days (POD). RESULTS: All patients received postoperative insulin therapy. Patients spent 57.3% and 69.7% of time within the BG target range on POD 1 and 2, respectively. The percentage of time was significantly higher in nondiabetics than in diabetics. Mean BG measurements per patient intraoperatively, on POD 1 and on POD 2 were 4+/-1, 10+/-2 and 7+/-2, respectively. No patient experienced any severe hypoglycaemic events (BG

Published
2010

3. Population Pharmacokinetics and Dosing Recommendations for Cisplatin during Intraperitoneal Peroperative Administration

Author

Xavier Pivot, Bruno Chauffert, Jean-Pierre Kantelip, Emmanuel Guardiola, Vincent Jullien, Bruno Heyd, Bernard Royer, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Pharmacologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Epilepsies de l'Enfant et Plasticité Cérébrale (U1129), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Service de chirurgie viscérale et digestive - Unité de transplantation hépatique, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( UR 3920) (PCVP / CARDIO), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( EA 3920) (PCVP / CARDIO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Cochin-Saint Vincent de Paul, Epilepsies de l'Enfant et Plasticité Cérébrale ( U1129 ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'oncologie Médicale, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( PCVP / CARDIO ), Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ) -Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) ( HOTE GREFFON ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( EA 3920) ( PCVP / CARDIO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université de Franche-Comté ( UFC ) -Université Bourgogne Franche-Comté [COMUE] ( UBFC ), and Saas, Philippe

Subjects
MESH: Combined Modality Therapy, MESH : Aged, MESH : Dose-Response Relationship, Drug, MESH : Models, Biological, MESH: Risk Assessment, 030226 pharmacology & pharmacy, MESH: Dose-Response Relationship, Drug, Intraoperative Period, MESH : Metabolic Clearance Rate, 0302 clinical medicine, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Medicine, MESH : Female, Pharmacology (medical), MESH : Risk Assessment, Ovarian Neoplasms, MESH: Aged, Volume of distribution, education.field_of_study, MESH: Middle Aged, Middle Aged, MESH : Adult, MESH : Nonlinear Dynamics, Combined Modality Therapy, 3. Good health, MESH : Antineoplastic Agents, MESH: Nonlinear Dynamics, MESH: Ovarian Neoplasms, Area Under Curve, 030220 oncology & carcinogenesis, Toxicity, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH : Intraoperative Period, Risk assessment, Monte Carlo Method, Injections, Intraperitoneal, MESH: Injections, Intraperitoneal, Adult, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Metabolic Clearance Rate, MESH : Drug Administration Schedule, Population, Urology, Antineoplastic Agents, MESH: Monte Carlo Method, MESH: Drug Administration Schedule, Models, Biological, Risk Assessment, Drug Administration Schedule, MESH : Cisplatin, 03 medical and health sciences, Pharmacokinetics, Humans, MESH : Middle Aged, Dosing, education, Aged, MESH: Intraoperative Period, MESH: Metabolic Clearance Rate, Pharmacology, MESH : Injections, Intraperitoneal, MESH: Humans, Dose-Response Relationship, Drug, MESH : Ovarian Neoplasms, business.industry, MESH : Humans, MESH: Models, Biological, MESH: Adult, Nomogram, NONMEM, MESH : Monte Carlo Method, Nonlinear Dynamics, MESH: Cisplatin, MESH: Antineoplastic Agents, MESH: Area Under Curve, MESH : Area Under Curve, Cisplatin, MESH : Combined Modality Therapy, business, MESH: Female
Abstract

International audience; BACKGROUND: Ovarian cancer is the leading cause of gynaecological cancer-related death in Western countries. Intraperitoneal (IP) peroperative chemotherapy is an interesting therapeutic option. However, very few data are available regarding pharmacokinetics and especially population pharmacokinetics. PATIENTS AND METHODS: Thirty-one patients with advanced epithelial cancer classified as International Federation of Gynecology and Obstetrics stage IIIC were included in the study. Blood and IP samples were taken over a 24-hour period during and after IP treatment. Both total and ultrafiltered (Uf) platinum (Pt) concentrations were analysed using a population approach with nonlinear mixed-effects modelling (NONMEM) software. Improvement of the model with covariates was performed as well as assessment of the model using bootstrap and posterior visual predictive methods. RESULTS: Both IP fluid and serum pharmacokinetics were satisfactorily described with a three-compartment model for both Uf Pt and total Pt concentrations. The covariates were bodyweight for the IP volume of distribution in the Uf Pt model, and both IP and serum protein concentrations for the clearance from the central compartment in the total Pt model. A nomogram, based on the results of the Monte Carlo simulations, displays a dose recommendation regarding both the risk of renal toxicity and the potent efficacy of the treatment. A limited sampling strategy (LSS) allowing the estimation of potential risk of renal toxicity is also described. CONCLUSION: The pharmacokinetics of cisplatin during peroperative IP chemotherapy could be successfully fitted with the present model, which allowed a dosing strategy accompanied by an LSS to facilitate the follow-up of patients.

Published
2009

4. Validation of a hybrid Doppler ultrasound vessel-based registration algorithm for neurosurgery

Author

D. Rolando Del Maestro, Sean Jy-Shyang Chen, Laurence Mercier, Charles X. B. Yan, Pierrick Coupé, D. Louis Collins, Ingerid Reinertsen, McConnell Brain Imaging Centre (MNI), Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada]-McGill University = Université McGill [Montréal, Canada], Stiftelsen for INdustriell og TEknisk Forskning Digital [Trondheim] (SINTEF Digital), Laboratoire Bordelais de Recherche en Informatique (LaBRI), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB), and McGill University = Université McGill [Montréal, Canada]

Subjects
Male, MESH: Magnetic Resonance Angiography, 02 engineering and technology, Neurosurgical Procedures, 030218 nuclear medicine & medical imaging, Intraoperative Period, 0302 clinical medicine, [INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, 0202 electrical engineering, electronic engineering, information engineering, Computer vision, MESH: Aged, MESH: Middle Aged, medicine.diagnostic_test, Phantoms, Imaging, Brain, General Medicine, Middle Aged, Computer Graphics and Computer-Aided Design, Computer Science Applications, [INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV], Preoperative Period, cardiovascular system, MESH: Neuronavigation, 020201 artificial intelligence & image processing, Female, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Computer Vision and Pattern Recognition, Algorithm, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Algorithms, Adult, Biomedical Engineering, Health Informatics, MESH: Algorithms, MESH: Preoperative Period, Article, 03 medical and health sciences, MESH: Brain, medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, Radiology, Nuclear Medicine and imaging, Neuronavigation, Aged, MESH: Intraoperative Period, MESH: Humans, business.industry, Brain shift, Mr angiography, Magnetic resonance imaging, Ultrasonography, Doppler, MESH: Adult, MESH: Neurosurgical Procedures, MESH: Male, MESH: Phantoms, Imaging, MESH: Ultrasonography, Doppler, Surgery, Artificial intelligence, Doppler ultrasound, business, MESH: Female, Magnetic Resonance Angiography
Abstract

International audience; PURPOSE: We describe and validate a novel hybrid nonlinear vessel registration algorithm for intra-operative updating of preoperative magnetic resonance (MR) images using Doppler ultrasound (US) images acquired on the dura for the correction of brain-shift and registration inaccuracies. We also introduce an US vessel appearance simulator that generates vessel images similar in appearance to that acquired with US from MR angiography data. METHODS: Our registration uses the minimum amount of preprocessing to extract vessels from the raw volumetric images. This prevents the removal of important registration information and minimizes the introduction of artifacts that may affect robustness, while reducing the amount of extraneous information in the image to be processed, thus improving the convergence speed of the algorithm. We then completed 3 rounds of validation for our vessel registration method for robustness and accuracy using (i) a large number of synthetic trials generated with our US vessel simulator, (ii) US images acquired from a real physical phantom made from polyvinyl alcohol cryogel, and (iii) real clinical data gathered intra-operatively from 3 patients. RESULTS: Resulting target registration errors (TRE) of less than 2.5 mm are achieved in more than 90 % of the synthetic trials when the initial TREs are less than 20 mm. TREs of less than 2 mm were achieved when the technique was applied to the physical phantom, and TREs of less than 3 mm were achieved on clinical data. CONCLUSIONS: These test trials show that the proposed algorithm is not only accurate but also highly robust to noise and missing vessel segments when working with US images acquired in a wide range of real-world conditions.

Published
2012

5. Intraperitoneal clearance as a potential biomarker of cisplatin after intraperitoneal perioperative chemotherapy: a population pharmacokinetic study

Author

Virginie Nerich, Sebastien Pili-Floury, Marielle Combe, Antoine Thiery-Vuillemin, Sylvain Onteniente, Damien Montange, Emmanuel Guardiola, Vincent Jullien, Bruno Chauffert, Patrice Muret, Xavier Pivot, Bernard Royer, Bruno Heyd, Delphine Delroeux, Jean-Pierre Kantelip, Sarah Piedoux, Elsa Kalbacher, Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Laboratoire de Pharmacologie Clinique et Toxicologie [CHRU Besancon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Service d'Oncologie Médicale [CHRU Besançon], Service de pharmacologie, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Saint-Vincent de Paul-Université Paris Descartes - Paris 5 (UPD5), Epilepsies de l'Enfant et Plasticité Cérébrale (U1129), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'oncologie chirurgicale, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service d'anesthésie et soins intensifs [CHRU Besançon], Pôle pharmaceutique [CHRU Besançon], Service d'oncologie, CHU Amiens-Picardie, Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Centre d'Investigation Clinique de Besançon ( CICB ), Etablissement Français du Sang Bourgogne Franche-Comté-Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Franche-Comté ( UFC ), Université de Franche-Comté ( UFC ), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Laboratoire de Pharmacologie Clinique et Toxicologie [Besancon], Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz-Université de Franche-Comté ( UFC ), Service d'oncologie Médicale, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz, CHU Cochin [AP-HP]-Hôpital Saint-Vincent de Paul-Université Paris Descartes - Paris 5 ( UPD5 ), Epilepsies de l'Enfant et Plasticité Cérébrale ( U1129 ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Service d'anesthésie et soins intensifs, Hôpital Jean Minjoz, Service de pharmacie, Saas, Philippe, and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Cancer Research, MESH : Aged, cisplatin, MESH : Models, Biological, Pharmacology, intraperitoneal perioperative chemotherapy, 030226 pharmacology & pharmacy, Intraoperative Period, MESH : Metabolic Clearance Rate, 0302 clinical medicine, population pharmacokinetics, Clinical Studies, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Female, Ovarian Neoplasms, Volume of distribution, MESH: Aged, education.field_of_study, MESH: Middle Aged, MESH: Peritoneum, MESH : Chemotherapy, Adjuvant, Middle Aged, MESH : Adult, 3. Good health, MESH : Antineoplastic Agents, MESH: Ovarian Neoplasms, Epinephrine, Oncology, Chemotherapy, Adjuvant, MESH: Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Toxicity, biomarker, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH : Intraoperative Period, Peritoneum, Injections, Intraperitoneal, MESH: Injections, Intraperitoneal, medicine.drug, Adult, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Metabolic Clearance Rate, MESH: Epinephrine, MESH : Drug Administration Schedule, Population, Urology, Antineoplastic Agents, MESH: Drug Administration Schedule, Models, Biological, Drug Administration Schedule, MESH : Cisplatin, 03 medical and health sciences, Pharmacokinetics, medicine, Humans, MESH : Middle Aged, education, MESH : Peritoneum, Aged, Cisplatin, MESH: Intraoperative Period, MESH: Metabolic Clearance Rate, MESH : Injections, Intraperitoneal, MESH: Humans, MESH : Ovarian Neoplasms, business.industry, MESH : Humans, MESH: Models, Biological, MESH: Biological Markers, MESH: Adult, medicine.disease, NONMEM, MESH : Biological Markers, MESH: Cisplatin, MESH : Epinephrine, MESH: Antineoplastic Agents, Ovarian cancer, business, MESH: Female, Biomarkers
Abstract

International audience; BACKGROUND: Intraperitoneal (IP) perioperative chemotherapy with cisplatin is an interesting option in ovarian cancer treatment. A combination of cisplatin with IP epinephrine (already shown to improve IP and decrease systemic platinum (Pt) exposure) was evaluated using a population pharmacokinetic analysis. METHODS: Data from 55 patients treated with cisplatin-based IP perioperative chemotherapy with (n=26) or without (n=29) epinephrine were analysed using NONMEM. RESULTS: Epinephrine halves clearance between peritoneum and serum (IPCL) and increases the Pt central volume of distribution, IP exposure and penetration in tissue. IPCL has a better predictive value than any other parameter with respect to renal toxicity. CONCLUSION: This confirms that IPCL could be useful in assessing renal toxicity. As IPCL is also linked to tissue penetration and IP exposure, it may be proposed as biomarker. In addition to a Bayesian estimation, we propose a single-sample calculation-way to assess it. Prospective studies are needed to validate IPCL as a biomarker in this context.

Published
2012

6. Improvement in intraperitoneal intraoperative cisplatin exposure based on pharmacokinetic analysis in patients with ovarian cancer

Author

Jean-Pierre Kantelip, Xavier Pivot, Bruno Chauffert, Emmanuel Guardiola, Delphine Delroeux, Marielle Combe, Bernard Royer, Guillaume Hoizey, Bruno Heyd, Damien Montange, Laboratoire de Pharmacologie Clinique et Toxicologie [Besancon], Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz-Université de Franche-Comté ( UFC ), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Service de chirurgie viscérale et digestive - Unité de transplantation hépatique, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz, Service d'oncologie Médicale, Département d'Anesthésie, Université de Reims Champagne-Ardenne ( URCA ), Mort cellulaire et cancer, Université de Bourgogne ( UB ) -IFR100 - Structure fédérative de recherche Santé-STIC-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Saas, Philippe, Laboratoire de Pharmacologie Clinique et Toxicologie [CHRU Besancon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service d'Oncologie Médicale [CHRU Besançon], Université de Reims Champagne-Ardenne (URCA), and Université de Bourgogne (UB)-IFR100 - Structure fédérative de recherche Santé-STIC-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Cancer Research, medicine.medical_treatment, FIGO Stage IIIC, MESH : Aged, Toxicology, MESH : Antineoplastic Agents, Phytogenic, Carboplatin, Intraoperative Period, 0302 clinical medicine, MESH: Carboplatin, Medicine, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Pharmacology (medical), Infusions, Parenteral, MESH : Neoplasm Staging, MESH : Female, 030212 general & internal medicine, Ovarian Neoplasms, MESH: Aged, MESH: Middle Aged, Area under the curve, MESH : Protein Binding, MESH: Neoplasm Staging, Middle Aged, MESH : Adult, Debulking, 3. Good health, MESH: Ovarian Neoplasms, MESH : Antineoplastic Agents, MESH : Infusions, Parenteral, Oncology, 030220 oncology & carcinogenesis, Area Under Curve, MESH : Paclitaxel, MESH : Carboplatin, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH : Intraoperative Period, medicine.drug, Protein Binding, Adult, medicine.medical_specialty, Paclitaxel, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Antineoplastic Agents, Phytogenic, Urology, Antineoplastic Agents, MESH : Cisplatin, 03 medical and health sciences, Pharmacokinetics, Humans, MESH: Protein Binding, MESH : Middle Aged, MESH: Paclitaxel, Aged, Neoplasm Staging, Pharmacology, Cisplatin, MESH: Intraoperative Period, Chemotherapy, MESH: Humans, business.industry, MESH : Ovarian Neoplasms, MESH : Humans, Cancer, MESH: Adult, medicine.disease, Antineoplastic Agents, Phytogenic, Surgery, MESH: Infusions, Parenteral, MESH: Cisplatin, MESH: Antineoplastic Agents, MESH: Area Under Curve, MESH : Area Under Curve, business, Ovarian cancer, MESH: Female
Abstract

International audience; Ovarian cancer is the leading cause of gynecological cancer-related death in Western countries. The present treatment standards for ovarian cancer are based on the association of debulking surgery with platinum-based chemotherapy. Another strategy that could be further investigated is intraperitoneal chemotherapy (IP). We previously described that the 2-h administration of intraoperative IP cisplatin did not reach satisfactory concentrations. In the present study, we present the results of a pharmacokinetic analysis performed after two consecutive 1-h IP 30 mg/l cisplatin administrations. Twenty-seven patients with advanced epithelial cancer classified FIGO stage IIIC were included in the study. Blood and IP samples were taken over a 24-h period, during and after IP treatment. Both total and ultrafiltered (Uf) platinum (Pt) concentration levels were analyzed. Biological and clinical toxicities were also recorded. With this strategy, IP Pt concentrations stayed above the target concentration (10 mg/l) for a satisfactory length of time. The serum Pt concentrations were higher than those observed with the "one-bath" protocol and they induced the occurrence of recoverable renal toxicities (3 grade 1, 7 grade 2 and 4 grade 3). The best predictive parameter for renal failure was the total Pt 24-h Area Under the Curve (AUC) with a threshold value of 25 mg h/l RR = 0.31 (95% CI 0.13 - 0.49, P < 0.01). Administration of an increased amount of cisplatin is feasible and a satisfactory level of IP Pt concentrations is obtained. However, this improvement is associated with an increase in serum Pt levels and resulting renal toxicities. An attractive solution would be to decrease Pt transfer from peritoneum to bloodstream. A phase 1 study using intraoperative IP epinephrine in order to decrease this transfer is presently being carried out.

Published
2008

7. Contrasting acute and slow-growing lesions: a new door to brain plasticity

Author

Michel Desmurget, Hugues Duffau, François Bonnetblanc, Cerveau et vision, Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-IFR19-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Imagerie Fonctionnelle (LIF), Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-IFR49-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de neurochirurgie, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and Saidi, Vanessa

Subjects
MESH: Cheval, Poison control, MESH: Magnetic Resonance Imaging, MESH: Glioma, Intraoperative Period, 0302 clinical medicine, Cerebrovascular Accident, MESH: Cerebrovascular Accident, Medicine, MESH: Animals, MESH: Neuronal Plasticity, Stroke, Neuronal Plasticity, Brain Neoplasms, 05 social sciences, Brain, Glioma, MESH: Recovery of Function, Magnetic Resonance Imaging, medicine.anatomical_structure, Acute Disease, MESH: Brain Neoplasms, MESH: Acute Disease, [SDV.IB]Life Sciences [q-bio]/Bioengineering, medicine.symptom, Slow Growing, Central nervous system, Context (language use), 050105 experimental psychology, Lesion, 03 medical and health sciences, Animal data, MESH: Brain, Neuroplasticity, Animals, Humans, 0501 psychology and cognitive sciences, [SDV.IB] Life Sciences [q-bio]/Bioengineering, MESH: Intraoperative Period, MESH: Humans, business.industry, Animal, Recovery of Function, medicine.disease, Disease Models, Animal, MESH: Nerve Net, Brain Injuries, Disease Models, MESH: Brain Injuries, Neurology (clinical), Nerve Net, MESH: Disease Models, Animal, business, Neuroscience, 030217 neurology & neurosurgery, Cheval
Abstract

The concept of plasticity describes the mechanisms that rearrange cerebral organization following a brain injury. During the last century, plasticity has been mainly investigated in humans with acute strokes. It was then shown: (i) that the brain is organized into highly specialized functional areas, often designated 'eloquent' areas and (ii) that a lesion within the eloquent area gives rise to major irrevocable deficits. However, in sharp contrast with these observations, it was recently found that patients with low-grade gliomas were able to undergo massive cerebral resections without detectable functional consequence. In this paper, we tackle this puzzling observation and address the idea that brain plasticity cannot be fully understood and fruitfully studied without considering the temporal pattern of the injury inflicted to the brain. To achieve this goal, we first review experimental evidence showing that functional recovery is considerably better in the context of slow-growing injuries than after acute lesions. Both human and animal data are considered. In a second step, we emphasize that slow and acute lesions involve very different patterns of reorganization. In agreement with this idea, we show that the recruitment of remote brain areas in the ipsi- and contralesional hemispheres is much more efficient in slow growing than acute lesions. Finally in a last section, we briefly discuss the main implications of these results.

Published
2007

8. Does the left inferior longitudinal fasciculus play a role in language? A brain stimulation study

Author

Hugues Duffau, Emmanuel Mandonnet, Peggy Gatignol, Aurélien Nouet, Laurent Capelle, Laboratoire d'Imagerie Fonctionnelle ( LIF ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -IFR14-IFR49-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Neurochirurgie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Laboratoire de la Cognition et du Comportement, Université Paris Descartes - Paris 5 ( UPD5 ) -Centre National de la Recherche Scientifique ( CNRS ), Département de neurochirurgie, Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Saidi, Vanessa, Laboratoire d'Imagerie Fonctionnelle (LIF), Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-IFR49-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Male, MESH : Postoperative Per, MESH : Brain Mapping, MESH : Electric Stimulation, MESH: Language Disorders, MESH : Anomia, MESH: Magnetic Resonance Imaging, MESH: Glioma, Intraoperative Period, 0302 clinical medicine, MESH : Neural Pathways, Neural Pathways, Arcuate fasciculus, Semantic memory, MESH : Female, Postoperative Period, [ SDV.IB ] Life Sciences [q-bio]/Bioengineering, MESH: Brain Mapping, Language, Temporal cortex, Cerebral Cortex, Brain Mapping, MESH: Middle Aged, Brain Neoplasms, 05 social sciences, MESH: Electric Stimulation, Glioma, Middle Aged, MESH : Adult, Magnetic Resonance Imaging, MESH : Language Disorders, Temporal Lobe, Semantics, medicine.anatomical_structure, MESH: Anomia, MESH: Language, MESH: Brain Neoplasms, MESH : Cerebral Cortex, Female, [SDV.IB]Life Sciences [q-bio]/Bioengineering, MESH : Intraoperative Period, Psychology, Adult, MESH : Male, Uncinate fasciculus, Anomia, Occipitofrontal fasciculus, 050105 experimental psychology, Temporal lobe, 03 medical and health sciences, MESH : Language, MESH : Magnetic Resonance Imaging, medicine, Humans, 0501 psychology and cognitive sciences, MESH : Middle Aged, Inferior longitudinal fasciculus, MESH : Brain Neoplasms, [SDV.IB] Life Sciences [q-bio]/Bioengineering, MESH: Intraoperative Period, Language Disorders, MESH: Humans, MESH: Neural Pathways, MESH : Humans, MESH: Adult, Electric Stimulation, MESH: Male, MESH: Cerebral Cortex, MESH: Postoperative Per, MESH: Nerve Net, MESH : Glioma, Brain stimulation, MESH : Nerve Net, Neurology (clinical), Nerve Net, Neuroscience, MESH: Female, 030217 neurology & neurosurgery
Abstract

Although advances in diffusion tensor imaging have enabled us to better study the anatomy of the inferior longitudinal fasciculus (ILF), its function remains poorly understood. Recently, it was suggested that the subcortical network subserving the language semantics could be constituted, in parallel with the inferior occipitofrontal fasciculus, by the left ILF, joining the posterior occipitotemporal regions to the temporal pole, then relayed by the uncinate fasciculus connecting the anterior temporal pole to the frontobasal areas. Nevertheless, this hypothesis was solely based on neurofunctional imaging, allowing a cortical mapping but with no anatomofunctional information regarding the white matter. Here, we report a series of 12 patients operated on under local anaesthesia for a cerebral low-grade glioma located within the left temporal lobe. Before and during resection, we used the method of intraoperative direct electrostimulation, enabling us to perform accurate and reliable anatomofunctional correlations both at cortical and subcortical levels. In order to map the ILF. Using postoperative MRI, we correlated these functional findings with the anatomical locations of the sites where language disturbances were elicited by stimulations, both at cortical and subcortical levels. Our goal was to study the potential existence of parallel and distributed language networks crossing the left dominant temporal lobe, subserved by distinct subcortical pathways--namely the inferior occipitofrontal fasciculus and the ILF. Intraoperative stimulation of the anterior and middle temporal cortex elicited anomia in four patients. At the subcortical level, semantic paraphasia were induced in seven patients during stimulation of the inferior occipitofrontal fasciculus, and phonological paraphasia was generated in seven patients by stimulating the arcuate fasciculus. Interestingly, subcortical stimulation never elicited any language disturbances when performed at the level of the ILF. In addition, following a transient postoperative language deficit, all patients recovered, despite the resection of at least one part of the ILF, as confirmed by control MRI. On the basis of these results, we suggest that the "semantic ventral stream" could be constituted by at least two parallel pathways within the left dominant temporal lobe: (i) a direct pathway, the inferior occipitofrontal fasciculus, that connects the posterior temporal areas and the orbitofrontal region, crucial for language semantic processing, since it elicits semantic paraphasia when stimulated; (ii) and also possibly an indirect pathway subserved by the ILF, not indispensable for language, since it can be compensated both during stimulation and after resection.

Published
2007

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