125 results on '"N. Bakrin"'
Search Results
102. Intraperitoneal Vascular Endothelial Growth Factor: A Prognostic Factor and the Potential for Intraperitoneal Bevacizumab Use in Peritoneal Surface Malignancies.
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Chia CS, Glehen O, Bakrin N, Decullier E, You B, Gilly FN, and Passot G
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- Adult, Aged, Angiogenesis Inhibitors therapeutic use, Female, Follow-Up Studies, Humans, Injections, Intraperitoneal, Male, Middle Aged, Neoplasm Staging, Neoplasms blood, Neoplasms pathology, Peritoneal Neoplasms blood, Peritoneal Neoplasms secondary, Prognosis, Survival Rate, Ascitic Fluid metabolism, Bevacizumab therapeutic use, Biomarkers, Tumor blood, Neoplasms drug therapy, Peritoneal Neoplasms drug therapy, Vascular Endothelial Growth Factor A blood
- Abstract
Introduction: Intraperitoneal (IP) vascular endothelial growth factor (VEGF) levels have been shown to vary in the peritoneal cavity of patients with peritoneal surface malignancies. Our purpose was to correlate levels of IP VEGF with overall and disease-free survival to identify whether IP VEGF can be used to prognosticate patients and the possible role of IP bevacizumab., Methods: From February to October 2012, 97 consecutive patients with peritoneal carcinomatosis were treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Intravenous (IV) VEGF levels were taken before surgery, whereas IP VEGF levels were taken at various time points during and after surgery., Results: Median follow-up was 19.48 months. On univariate analysis, a lower IP VEGF taken just after incision (T1) was associated with improved overall (P = 0.0004) and disease-free survival (P = 0.0006) at 2 years. A lower T1/IV VEGF ratio also was associated with improved overall (P = 0.004) and disease-free survival (P = 0.0051). On multivariate analysis, a lower T1 was associated with improved overall survival, whereas a lower T1/IV VEGF was associated with improved disease-free survival. On subset analysis, these two variables were associated with improved survival in colorectal cancers., Conclusions: A lower IP VEGF level prior to surgery is associated with improved survival. The use of preoperative intraperitoneal bevacizumab for patients with a heavy disease load should be considered, especially in colorectal cancers.
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- 2015
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103. Glisson capsulectomy for extensive superficial liver involvement in peritoneal carcinomatosis (with video).
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Dagbert F, Passot G, Glehen O, and Bakrin N
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- Humans, Cytoreduction Surgical Procedures methods, Hepatectomy methods, Liver Neoplasms surgery, Peritoneal Neoplasms surgery, Pseudomyxoma Peritonei surgery
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- 2015
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104. Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for First Relapse of Ovarian Cancer.
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Classe JM, Glehen O, Decullier E, Bereder JM, Msika S, Lorimier G, Abboud K, Meeus P, Ferron G, Quenet F, Marchal F, Gouy S, Pomel C, Pocard M, Guyon F, and Bakrin N
- Subjects
- Adult, Aged, Combined Modality Therapy, Disease-Free Survival, Female, Humans, Injections, Intraperitoneal, Middle Aged, Morbidity, Neoplasm Recurrence, Local pathology, Ovarian Neoplasms mortality, Recurrence, Young Adult, Cytoreduction Surgical Procedures, Hyperthermia, Induced, Ovarian Neoplasms drug therapy, Ovarian Neoplasms surgery
- Abstract
Background: To assess impact of surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients treated for a first relapse of ovarian cancer (FROC)., Patients and Methods: Patients with a FROC treated with second-line chemotherapy, surgery and HIPEC were retrospectively included from 13 Institutions. Studied parameters were interval free between the end of initial treatment and the first relapse, second-line chemotherapy, peritoneal cancer index and completeness of surgery, HIPEC, mortality and morbidity, pathological results and survival., Results: From 2001 to 2010, 314 patients were included. The main strategy was secondary chemotherapy followed by surgery and HIPEC (269/314-85.6%). Mortality and morbidity rates were respectively 1% and 30.9%. Median follow-up was 50 months, 5-year overall survival was 38.0%, with no difference between platinum-sensitive or -resistant patients and 5-year disease-free survival was 14%., Conclusion: HIPEC allows encouraging survival in the treatment of FROC, better in case of complete surgery, with acceptable mortality and morbidity rates., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)
- Published
- 2015
105. Hyperthermic intraperitoneal chemotherapy (HIPEC) in ovarian cancer.
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Bakrin N, Classe JM, Pomel C, Gouy S, Chene G, and Glehen O
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- Antineoplastic Combined Chemotherapy Protocols adverse effects, Carcinoma secondary, Carcinoma therapy, Female, Gastrointestinal Neoplasms therapy, Humans, Hyperthermia, Induced, Ovarian Neoplasms pathology, Ovarian Neoplasms surgery, Peritoneal Neoplasms secondary, Ovarian Neoplasms therapy, Peritoneal Neoplasms therapy
- Abstract
Ovarian cancer remains the fourth leading cause of cancer death in women in France. It is all too often diagnosed at an advanced stage with peritoneal carcinomatosis (PC), but remains confined to the peritoneal cavity throughout much of its natural history. Because of cellular selection pressure over time, most tumor recurrences eventually develop resistance to systemic platinum. Options for salvage therapy include alternative systemic chemotherapies and further cytoreductive surgery (CRS), but the prognosis remains poor. Over the past two decades, a new therapeutic approach to PC has been developed that combines CRS with hyperthermic intraperitoneal chemotherapy (HIPEC). This treatment strategy has already been shown to be effective in non-gynecologic carcinomatosis in numerous reports. There is a strong rationale for the use of HIPEC for PC of ovarian origin. On the one hand, three prospective randomized trials have demonstrated the superiority of intraperitoneal chemotherapy (without hyperthermia) in selected patients compared to systemic chemotherapy. Moreover, retrospective studies and case-control studies of HIPEC have reported encouraging survival data, especially when used to treat chemoresistant recurrence. However, HIPEC has specific morbidity and mortality; this calls for very careful selection of eligible patients by a multidisciplinary team in specialized centers. HIPEC needs to be evaluated by means of randomized trials for ovarian cancer at different developmental stages: as first line therapy, as consolidation, and for chemoresistant recurrence. Several European phase III studies are currently ongoing., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)
- Published
- 2014
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106. Response to: "hyperthermic intraperitoneal chemotherapy in epithelial ovarian cancer should be proposed in eight time points".
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Glehen O and Bakrin N
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- Female, Humans, Antineoplastic Agents administration & dosage, Carcinoma drug therapy, Carcinoma surgery, Chemotherapy, Cancer, Regional Perfusion, Ovarian Neoplasms pathology, Peritoneal Neoplasms drug therapy, Peritoneal Neoplasms surgery
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- 2014
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107. Postoperative outcomes of laparoscopic vs open cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy for treatment of peritoneal surface malignancies.
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Passot G, Bakrin N, Isaac S, Decullier E, Gilly FN, Glehen O, and Cotte E
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- Adult, Aged, Case-Control Studies, Chemotherapy, Adjuvant, Feasibility Studies, Female, France, Humans, Male, Middle Aged, Patient Safety, Peritoneal Cavity, Peritoneal Neoplasms drug therapy, Peritoneal Neoplasms surgery, Postoperative Complications etiology, Postoperative Period, Pseudomyxoma Peritonei drug therapy, Pseudomyxoma Peritonei surgery, Retrospective Studies, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Chemotherapy, Cancer, Regional Perfusion methods, Hyperthermia, Induced, Laparoscopy adverse effects, Laparotomy, Length of Stay statistics & numerical data, Peritoneal Neoplasms therapy, Postoperative Complications prevention & control, Pseudomyxoma Peritonei therapy
- Abstract
Background: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are considered the only curative treatment for many peritoneal surface malignancies. The purpose of this study was to evaluate feasibility and safety of CRS combined with HIPEC by laparoscopy for patients with limited peritoneal disease and to compare postoperative outcomes with those for an open procedure., Methods: Between January 2011 and November 2012, all patients with low-grade pseudomyxoma peritonei (PMP) or multicystic mesothelioma (MM) and limited peritoneal disease (Peritoneal Cancer Index [PCI] less than 10) underwent CRS and HIPEC by a laparoscopic approach. The study cohort was matched with a historical cohort of patients with the same characteristics (completeness of cytoreduction, HIPEC agent, PCI ± 11 and age ± 20 years) treated with CRS and HIPEC by laparotomy., Results: Eight patients (five low-grade PMP and three MM) treated by a laparoscopic approach were compared to eight patients treated by laparotomy. All patients underwent complete cytoreductive surgery with HIPEC, and no conversion to laparotomy was needed. The median surgical length was 210 min (150-300) vs 240 (210-360), with a median hospital stay of 12 days (9-18) vs 19 (13-33). One patient had a postoperative complication (intraperitoneal haematoma treated by radiological drainage) vs four in the laparotomy group., Conclusion: Laparoscopic CRS combined with HIPEC is feasible and safe for curative treatment of strictly selected patients with peritoneal surface malignancy and might reduce postoperative complications and length of hospital stay., (Copyright © 2013 Elsevier Ltd. All rights reserved.)
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- 2014
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108. Quality of life after cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy: a prospective study of 216 patients.
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Passot G, Bakrin N, Roux AS, Vaudoyer D, Gilly FN, Glehen O, and Cotte E
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- Aged, Camptothecin administration & dosage, Camptothecin analogs & derivatives, Carcinoma secondary, Cisplatin administration & dosage, Cohort Studies, Colorectal Neoplasms pathology, Combined Modality Therapy, Female, Humans, Irinotecan, Male, Mesothelioma therapy, Middle Aged, Mitomycin administration & dosage, Organoplatinum Compounds administration & dosage, Ovarian Neoplasms pathology, Oxaliplatin, Peritoneal Neoplasms secondary, Prospective Studies, Stomach Neoplasms pathology, Stomach Neoplasms therapy, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma therapy, Colorectal Neoplasms therapy, Hyperthermia, Induced, Neoplasms, Multiple Primary therapy, Ovarian Neoplasms therapy, Peritoneal Neoplasms therapy, Peritoneum surgery, Pseudomyxoma Peritonei therapy, Quality of Life
- Abstract
Introduction: Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) have demonstrated promising results in the treatment of peritoneal carcinomatosis (PC). The purpose of this study was to assess the impact of this combined procedure on quality of life (QoL)., Materials and Methods: A prospective single centre study of 216 consecutive patients treated with CRS and HIPEC was conducted using the Gastro-Intestinal Quality of Life Index questionnaire (GIQLI), completed preoperatively and at 1, 3, 6 and 12 months., Results: Questionnaire compliance was 81%, 90%, 89%, 89% and 74% at baseline, 1, 3, 6 and 12 months respectively. QoL was significantly decreased up to 6 months and returned to baseline at 12 months. In multivariate analysis, factors decreasing QoL were origin of PC at 3 months, presence of stoma at 6 months and length of surgery over 270 min and disease recurrence at 12 months., Conclusions: Despite morbidity associated with CRS and HIPEC, QoL returned to baseline at one year after surgery. This treatment strategy should be considered for the treatment of peritoneal carcinomatosis., (Copyright © 2013 Elsevier Ltd. All rights reserved.)
- Published
- 2014
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109. Intraperitoneal vascular endothelial growth factor burden in peritoneal surface malignancies treated with curative intent: the first step before intraperitoneal anti-vascular endothelial growth factor treatment?
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Passot G, Bakrin N, Garnier L, Roux A, Vaudoyer D, Wallet F, Gilly FN, Glehen O, and Cotte E
- Subjects
- Ascites metabolism, Bevacizumab, Combined Modality Therapy, Female, Gastrointestinal Neoplasms drug therapy, Gastrointestinal Neoplasms metabolism, Gastrointestinal Neoplasms pathology, Gastrointestinal Neoplasms surgery, Humans, Injections, Intraperitoneal, Injections, Intravenous, Male, Middle Aged, Ovarian Neoplasms drug therapy, Ovarian Neoplasms metabolism, Ovarian Neoplasms pathology, Ovarian Neoplasms surgery, Peritoneal Neoplasms secondary, Peritoneal Neoplasms surgery, Prognosis, Pseudomyxoma Peritonei drug therapy, Pseudomyxoma Peritonei metabolism, Pseudomyxoma Peritonei pathology, Pseudomyxoma Peritonei surgery, Remission Induction, Vascular Endothelial Growth Factor A analysis, Vascular Endothelial Growth Factor A immunology, Antibodies, Monoclonal, Humanized administration & dosage, Peritoneal Neoplasms drug therapy, Peritoneal Neoplasms metabolism, Vascular Endothelial Growth Factor A metabolism
- Abstract
Introduction: Vascular endothelial growth factor (VEGF) is one of the most important angiogenic factors in solid tumours and plays an important role in ascites development in peritoneal surface malignancies (PSM). The main goal of this study was to determine the evolution and factors influencing intraperitoneal (IP) VEGF burden during cytoreductive surgery (CRS) with curative intent., Patients and Methods: Ninety-seven consecutive patients with PSM were treated with CRS at a single centre with curative intent. Patient data were collected prospectively between February 2012 and October 2012. An enzyme-linked immunosorbent assay technique was used to assess VEGF levels in intravenous (IV) systemic blood samples before incision and after abdominal closure, and in IP samples during abdominal cavity exploration, after completion of CRS, after hyperthermic IP chemotherapy, and at 1 and 24h after abdominal closure., Results: The IP VEGF burden increased significantly after CRS, and then decreased progressively (p<0.005). In multivariate analysis, neoadjuvant IV bevacizumab significantly decreased the preoperative IP VEGF burden, tumour load according to Peritoneal Cancer Index value increased significantly the preoperative IP VEGF burden and a low preoperative IP VEGF burden was associated with significantly increased postoperative complications. Neoadjuvant IV bevacizumab is the only factor that influences the preoperative IV VEGF concentration., Conclusion: For patients with PSM who were treated with curative intent, the IP VEGF burden increased after CRS, and was reduced prior to surgery by the administration of neoadjuvant IV bevacizumab., (Copyright © 2013 Elsevier Ltd. All rights reserved.)
- Published
- 2014
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110. Early preinvasive lesions in ovarian cancer.
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Chene G, Lamblin G, Le Bail-Carval K, Chabert P, Bakrin N, and Mellier G
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- Female, Humans, Neoplasm Grading, Ovarian Neoplasms pathology, Prognosis, Biomarkers, Tumor genetics, Early Detection of Cancer, Ovarian Neoplasms etiology, Ovarian Neoplasms genetics
- Abstract
Faced with the catastrophic prognosis for ovarian cancer due to the fact that it is most often diagnosed late at the peritoneal carcinomatosis stage, screening and early detection could probably reduce the mortality rate. A better understanding of the molecular characteristics of the different ovarian cancer subtypes and their specific molecular signatures is indispensable prior to development of new screening strategies. We discuss here the early natural history of ovarian cancer and its origins.
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- 2014
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111. Peritoneal carcinomatosis treated with cytoreductive surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for advanced ovarian carcinoma: a French multicentre retrospective cohort study of 566 patients.
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Bakrin N, Bereder JM, Decullier E, Classe JM, Msika S, Lorimier G, Abboud K, Meeus P, Ferron G, Quenet F, Marchal F, Gouy S, Morice P, Pomel C, Pocard M, Guyon F, Porcheron J, and Glehen O
- Subjects
- Adult, Aged, Antineoplastic Agents therapeutic use, Carcinoma secondary, Digestive System Fistula etiology, Disease-Free Survival, Female, France, Humans, Hyperthermia, Induced, Kaplan-Meier Estimate, Leukopenia chemically induced, Middle Aged, Peritoneal Neoplasms secondary, Postoperative Hemorrhage etiology, Proportional Hazards Models, Renal Insufficiency etiology, Retrospective Studies, Survival Rate, Antineoplastic Agents administration & dosage, Carcinoma drug therapy, Carcinoma surgery, Chemotherapy, Cancer, Regional Perfusion adverse effects, Ovarian Neoplasms pathology, Peritoneal Neoplasms drug therapy, Peritoneal Neoplasms surgery
- Abstract
Background: Despite a high response rate to front-line therapy, prognosis of epithelial ovarian carcinoma (EOC) remains poor. Approaches that combine Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) have been developed recently. The purpose of this study was to assess early and long-term survival in patients treated with this strategy., Patients and Methods: A retrospective cohort multicentric study from French centres was performed. All consecutive patients with advanced and recurrent EOC treated with CRS and HIPEC were included., Results: The study included 566 patients from 13 centres who underwent 607 procedures between 1991 and 2010. There were 92 patients with advanced EOC (first-line treatment), and 474 patients with recurrent EOC. A complete cytoreductive surgery was performed in 74.9% of patients. Mortality and grades 3 to 4 morbidity rates were 0.8% and 31.3%, respectively. The median overall survivals were 35.4 months and 45.7 months for advanced and recurrent EOC, respectively. There was no significant difference in overall survival between patients with chemosensitive and with chemoresistant recurrence. Peritoneal Cancer Index (PCI) that evaluated disease extent was the strongest independent prognostic factor for overall and disease-free survival in all groups., Conclusion: For advanced and recurrent EOC, curative therapeutic approach combining optimal CRS and HIPEC should be considered as it may achieve long-term survival in patients with a severe prognosis disease, even in patients with chemoresistant disease. PCI should be used for patient's selection., (Copyright © 2013 Elsevier Ltd. All rights reserved.)
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- 2013
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112. Intraperitoneal cytokine level in patients with peritoneal surface malignancies. A study of the RENAPE (French Network for Rare Peritoneal Malignancies).
- Author
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Vlaeminck-Guillem V, Bienvenu J, Isaac S, Grangier B, Golfier F, Passot G, Bakrin N, Rodriguez-Lafrasse C, Gilly FN, and Glehen O
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- Adolescent, Adult, Aged, Aged, 80 and over, Ascitic Fluid metabolism, Biomarkers, Tumor blood, Carcinoma pathology, Case-Control Studies, Cytokines blood, Female, Humans, Intercellular Adhesion Molecule-1 blood, Interleukin-10 blood, Interleukin-10 metabolism, Interleukin-6 blood, Interleukin-6 metabolism, Interleukin-8 blood, Interleukin-8 metabolism, Male, Mesothelioma pathology, Middle Aged, Peritoneal Neoplasms pathology, Pseudomyxoma Peritonei pathology, Statistics, Nonparametric, Tumor Necrosis Factor-alpha blood, Tumor Necrosis Factor-alpha metabolism, Young Adult, Biomarkers, Tumor metabolism, Carcinoma metabolism, Cytokines metabolism, Intercellular Adhesion Molecule-1 metabolism, Mesothelioma metabolism, Peritoneal Neoplasms metabolism, Pseudomyxoma Peritonei metabolism
- Abstract
Background: Prognosis of peritoneal surface malignancies is influenced by the adequacy of surgical and chemotherapeutic treatment and by tumor spread at the time of diagnosis. By promoting morphological changes in the mesothelium, inflammatory cytokines reflect tumor biology and could be evaluated as biomarkers. Our objective was to evaluate intraperitoneal levels of IL-6, IL-8, IL-10, TNF-alpha, and sICAM in patients with pseudomyxoma peritonei and peritoneal mesothelioma., Methods: Serum and peritoneal fluid samples were prospectively collected in patients managed for peritoneal surface malignancies including pseudomyxoma peritonei (PMP), mesotheliomas, and other rare primitive peritoneal cancers (cancer group) and patients who underwent intraperitoneal laparoscopic surgical procedures for benign diseases (noncancer group). Samples were analyzed for IL-6, IL-8, IL-10, TNF-alpha, and sICAM concentrations. Correlations were assessed with tumor spread related clinical scores., Results: In both patient groups, intraperitoneal cytokine levels were higher than serum levels. Cancer patients had significantly higher intraperitoneal cytokine levels than noncancer patients. Peritoneal levels tended to increase in cancer patients with free tumor cells in peritoneal fluid. They were significantly higher in patients with tumor implants ≥2 cm and/or patients with peritoneal carcinomatosis index (PCI) >19. Furthermore, patients with malignant pseudomyxoma peritonei (grades II and III) had higher levels than patients with nonmalignant disease (grade I)., Conclusions: Assessment of intraperitoneal IL-6, IL-8, IL-10, TNF-alpha, and sICAM levels can be performed in patients with peritoneal surface malignancies. They can be considered as both diagnostic and prognostic biomarkers that could be used as useful adjuncts for therapeutic decision making.
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- 2013
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113. Primary peritoneal serous carcinoma treated by cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy. A multi-institutional study of 36 patients.
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Bakrin N, Gilly FN, Baratti D, Bereder JM, Quenet F, Lorimier G, Mohamed F, Elias D, and Glehen O
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- Adult, Aged, Analysis of Variance, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Carcinoma pathology, Chemotherapy, Adjuvant, Cohort Studies, Combined Modality Therapy, Disease-Free Survival, Female, France, Humans, Hypothermia, Induced methods, Kaplan-Meier Estimate, Male, Middle Aged, Neoplasm Staging, Peritoneal Neoplasms pathology, Prognosis, Retrospective Studies, Risk Assessment, Survival Analysis, Treatment Outcome, Carcinoma mortality, Carcinoma therapy, Chemotherapy, Cancer, Regional Perfusion methods, Peritoneal Neoplasms mortality, Peritoneal Neoplasms therapy
- Abstract
Aim: Primary peritoneal serous carcinoma (PPSC) is a rare condition, histologically identical to ovarian serous carcinoma and often diagnosed at late stage. There is not any standardized treatment for PPSC. A retrospective multicentric study was performed in French speaking centers to evaluate cytoreduction surgery and Hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of peritoneal carcinomatosis from different origins. The manuscript's aim was to study the particular population with PPSC., Methods: Between September 1997 and July 2007, 36 patients with PPSC from 9 institutions underwent 39 procedures., Results: Mortality and morbidity rates were 5.6% and 20.6% respectively. The overall survival at 1, 3 and 5 years are respectively 93.6, 71.5 and 57.4%. The median overall survival was not reached. By univariate analysis, the only factor that had prognostic value was PCI (p = 0.03)., Conclusions: The therapeutic approach combining cytoreductive surgery with HIPEC may achieve long-term survival in patients with PPSC., (Copyright © 2013 Elsevier Ltd. All rights reserved.)
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- 2013
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114. Subcutaneous trastuzumab: development of a new formulation for treatment of HER2-positive early breast cancer.
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Hamizi S, Freyer G, Bakrin N, Henin E, Mohtaram A, Le Saux O, and Falandry C
- Abstract
Trastuzumab is a monoclonal antibody directed against the human epidermal growth factor receptor 2 (HER2). HER2 is amplified or overexpressed in about 15% of breast cancers and is associated with aggressive disease. Clinical benefits of trastuzumab have been established in the treatment of both early and metastatic HER2-positive breast cancer. Patients with HER2-positive early breast cancer have to be treated with trastuzumab for one year in combination with and sequentially after chemotherapy. This requires that trastuzumab is intravenously infused over 30-90 minutes every 3 weeks for one year which is time-consuming for both the patient and the health care provider. Consequently, a subcutaneous formulation of trastuzumab using a recombinant human hyaluronidase has been developed. Recombinant human hyaluronidase transiently increases absorption and dispersion in the subcutaneous space of large therapeutic proteins, such as monoclonal antibodies, allowing subcutaneous administration of trastuzumab in about 5 minutes. Thus, subcutaneous trastuzumab could represent a new treatment option that could have benefit to both the patient and the health care system. This review focuses on the development of the subcutaneous trastuzumab formulation and analyzes clinical trials assessing the pharmacokinetics, efficacy, and safety of this new formulation.
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- 2013
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115. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for persistent and recurrent advanced ovarian carcinoma: a multicenter, prospective study of 246 patients.
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Bakrin N, Cotte E, Golfier F, Gilly FN, Freyer G, Helm W, Glehen O, and Bereder JM
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- Adult, Aged, Carcinoma, Ovarian Epithelial, Chemotherapy, Adjuvant, Combined Modality Therapy, Female, Follow-Up Studies, Humans, Middle Aged, Neoplasm Recurrence, Local mortality, Neoplasm Recurrence, Local pathology, Neoplasms, Glandular and Epithelial mortality, Neoplasms, Glandular and Epithelial pathology, Ovarian Neoplasms mortality, Ovarian Neoplasms pathology, Peritoneal Neoplasms mortality, Peritoneal Neoplasms secondary, Prognosis, Prospective Studies, Retrospective Studies, Survival Rate, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Hyperthermia, Induced, Neoplasm Recurrence, Local therapy, Neoplasms, Glandular and Epithelial therapy, Ovarian Neoplasms therapy, Peritoneal Neoplasms therapy
- Abstract
Background: Epithelial ovarian carcinoma is the main cause of death from gynaecological cancers in the western world. The initial response rate to the frontline therapy is high. However, the prognosis of persistent and recurrent disease remains poor. During the two past decades, a new therapeutic approach to peritoneal carcinomatosis has been developed, combining maximal cytoreductive effort with hyperthermic intraperitoneal chemotherapy (HIPEC)., Methods: A retrospective, multicentric study of 246 patients with recurrent or persistent ovarian cancer, treated by cytoreductive surgery and HIPEC in two French centers between 1991 and 2008, was performed., Results: An optimal cytoreductive surgery was possible in 92.2 % of patients. Mortality and morbidity rates were 0.37 % and 11.6 %, respectively. The overall median survival was 48.9 months. There was no significant difference in overall survival in patients with persistent or recurrent disease. In multivariate analysis, performance status was a significant prognostic factor in patients with extensive peritoneal carcinomatosis (peritoneal cancer index >10)., Conclusions: Salvage therapy combining optimal cytoreductive surgery and HIPEC is feasible and may achieve long-term survival in highly selected patients with recurrent ovarian carcinoma, including those with platinum resistant disease, with acceptable morbidity.
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- 2012
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116. Intraperitoneal bevacizumab combined with cytoreductive surgery: a pre-clinical study of tolerance and pharmacokinetics in an animal model.
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Passot G, Dupré A, Rivoire M, Mohamed F, Bakrin N, and Glehen O
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- Animals, Bevacizumab, Chemotherapy, Cancer, Regional Perfusion, Female, Injections, Intraperitoneal, Rabbits, Random Allocation, Antibodies, Monoclonal, Humanized adverse effects, Antibodies, Monoclonal, Humanized pharmacokinetics, Antineoplastic Agents adverse effects, Antineoplastic Agents pharmacokinetics, Peritoneal Neoplasms drug therapy, Peritoneal Neoplasms surgery
- Abstract
Introduction: Cytoreductive Surgery (CRS) combined with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is currently the only potentially curative treatment for peritoneal carcinomatosis (PC). Systemic administration of bevacizumab improves survival in patients with metastatic colorectal or ovarian cancer. Intraperitoneal administration of bevacizumab has been shown to be safe and effective in treating malignant ascites. The combination of CRS with intraperitoneal (IP) bevacizumab could maximize local control and survival from PC, but the associated morbidity from this is unknown. The aim of this study was to evaluate the safety of the combination of CRS with IP bevacizumab and to determine the pharmacokinetics of the drug in a rabbit model., Methods: Twenty healthy rabbits underwent a standardized procedure of debulking surgery, including peritonectomy and gastrointestinal anastomosis and were randomized to receive IP bevacizumab (25 mg/kg) or placebo. Another group of three rabbits underwent an instillation of IP bevacizumab (25 mg/kg) without surgery., Results: One rabbit that received IP bevacizumab died with no complication associated with the use of bevacizumab at autopsy. There was no significant difference between IP bevacizumab and placebo in weight loss, length of surgery or morbidity. The plasma concentration of bevacizumab increased to a peak at 24 h post IP administration. Bevacizumab was not detected in the plasma of animals without surgery., Conclusion: This study suggests that IP bevacizumab does not increase morbidity and mortality of debulking surgery in an animal model. When surgery is performed, the pharmacokinetics of IP bevacizumab are modified in plasma.
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- 2012
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117. Iterative procedures combining cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for peritoneal recurrence: postoperative and long-term results.
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Golse N, Bakrin N, Passot G, Mohamed F, Vaudoyer D, Gilly FN, Glehen O, and Cotte E
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- Adult, Aged, Chemotherapy, Adjuvant, Cholangiocarcinoma secondary, Cholangiocarcinoma therapy, Colorectal Neoplasms pathology, Disease-Free Survival, Feasibility Studies, Female, Humans, Leiomyosarcoma secondary, Leiomyosarcoma therapy, Male, Mesothelioma secondary, Mesothelioma therapy, Middle Aged, Neoplasm Recurrence, Local drug therapy, Neoplasm Recurrence, Local surgery, Ovarian Neoplasms pathology, Peritoneal Neoplasms drug therapy, Peritoneal Neoplasms surgery, Pseudomyxoma Peritonei therapy, Reoperation, Risk Assessment, Risk Factors, Stomach Neoplasms pathology, Time Factors, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Chemotherapy, Cancer, Regional Perfusion methods, Hyperthermia, Induced, Neoplasm Recurrence, Local therapy, Patient Selection, Peritoneal Neoplasms secondary, Peritoneal Neoplasms therapy
- Abstract
Objective: Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is the best treatment of several peritoneal surface malignancies. Isolated peritoneal recurrence may be treated by iterative procedures. The aim of this study was to evaluate immediate postoperative and long-term results after iterative CRS-HIPEC., Methods: From 1990 to 2010, 30 patients with isolated peritoneal recurrence underwent iterative procedures combining CRS-HIPEC., Results: Origins of peritoneal carcinomatosis were ovarian, colorectal, pseudomyxoma peritonei, peritoneal mesothelioma, gastric cancer, cholangiocarcinoma, leiomyosarcoma, and primary peritoneal serous carcinoma. Median recurrence-free survival (RFS) was 16.2 months from the first procedure. After the second procedure, one (3.3%) postoperative death occurred. Severe morbidity following the second procedure was 40% versus 30% after the first procedure (P = 0.37). At most recent follow up, 11 patients were disease-free, 10 were alive with recurrence, and 9 were dead with recurrence. Five-year overall survival after initial CRS with HIPEC was 65%, and overall median survival from diagnosis was 140 months., Conclusion: Iterative procedures combining CRS-HIPEC are feasible and allow long-term survival but may result in significant morbidity and mortality. Patients must be carefully selected, based on the following criteria: Origin of carcinomatosis, magnitude of first procedure, length of RFS, physiological age, co-morbidity, and possibility of complete cytoreduction., (Copyright © 2012 Wiley Periodicals, Inc.)
- Published
- 2012
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118. [HIPEC and ovarian carcinoma: base judgment on evidence].
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Bakrin N, Glehen O, and Golfier F
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- Female, Humans, Infusions, Parenteral, Randomized Controlled Trials as Topic, Treatment Outcome, Antineoplastic Agents administration & dosage, Carcinoma drug therapy, Carcinoma surgery, Hyperthermia, Induced, Organoplatinum Compounds administration & dosage, Ovarian Neoplasms drug therapy, Ovarian Neoplasms surgery
- Published
- 2012
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119. Closed abdomen hyperthermic intraperitoneal chemotherapy with irinotecan and mitomycin C: a phase I study.
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Cotte E, Passot G, Tod M, Bakrin N, Gilly FN, Steghens A, Mohamed F, and Glehen O
- Subjects
- Adolescent, Adult, Aged, Camptothecin administration & dosage, Camptothecin analogs & derivatives, Colorectal Neoplasms pathology, Combined Modality Therapy, Female, Follow-Up Studies, Humans, Irinotecan, Male, Maximum Tolerated Dose, Middle Aged, Mitomycin administration & dosage, Neoplasm Staging, Peritoneal Neoplasms secondary, Stomach Neoplasms pathology, Survival Rate, Treatment Outcome, Young Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Colorectal Neoplasms drug therapy, Hyperthermia, Induced, Peritoneal Neoplasms drug therapy, Stomach Neoplasms drug therapy
- Abstract
Purpose: Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is now a recognized treatment for peritoneal carcinomatosis (PC). The objective of this phase I study is to determine the maximum tolerated dose of irinotecan (CPT-11) when used with mitomycin C (MMC) for closed abdomen HIPEC., Methods: Patients with PC fulfilling the inclusion criteria were studied. All underwent cytoreductive surgery and closed abdomen HIPEC with 0.7 mg/kg MMC and an escalating dose of irinotecan. Grade 4 (National Cancer Institute grading system) surgical and hematological complications were used to identify dose-limiting toxicity (DLT)., Results: 12 patients were studied. At the first dose level of irinotecan (100 mg/m(2)), one patient developed a grade 4 hematological toxicity. Three other patients were included at the same level with no toxicity. Three patients were then included at the second dose level (150 mg/m(2) irinotecan), of whom one developed a grade 4 surgical complication. Three further patients were thus included at the second dose level. Of these three, two patients developed DLT [grade 4 neutropenia in one, grade 4 neutropenia and thrombocytopenia with an intra-abdominal lymphatic fistula requiring reoperation (grade 4 surgical complication) in the other]. Dose escalation was stopped at this level. The maximum tolerated dose of irinotecan was determined to be 100 mg/m(2)., Conclusion: Closed HIPEC combining MMC and irinotecan is safe and feasible. For HIPEC, the maximum tolerated dose of irinotecan is 100 mg/m(2) when used with 0.7 mg/kg MMC.
- Published
- 2011
- Full Text
- View/download PDF
120. Childbearing after hyperthermic intraperitoneal chemotherapy: results from an international survey.
- Author
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Ortega-Deballon P, Glehen O, Levine E, Piso P, Sugarbaker PH, Hayes-Jordan A, Facy A, Bakrin N, and Rat P
- Subjects
- Adolescent, Adult, Cisplatin administration & dosage, Combined Modality Therapy, Female, Follow-Up Studies, Humans, International Agencies, Mitomycin administration & dosage, Peritoneal Neoplasms drug therapy, Peritoneal Neoplasms surgery, Pregnancy, Pregnancy Complications, Neoplastic drug therapy, Pregnancy Complications, Neoplastic pathology, Pregnancy Complications, Neoplastic surgery, Surveys and Questionnaires, Survival Rate, Treatment Outcome, Young Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Chemotherapy, Cancer, Regional Perfusion, Hyperthermia, Induced, Peritoneal Neoplasms therapy
- Abstract
Background: Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) can improve survival in selected patients with primary or secondary peritoneal malignancies. With the opportunity for long-term survival, questions about the impact of those procedures in fertility in women of childbearing age can be raised., Materials and Methods: An international survey was performed among all teams participating in the International Peritoneal Surface Malignancy Group in order to collect data about pregnancies and their outcome in women having undergone previous CRS with adjuvant HIPEC., Results: There were 7 pregnancies reported after CRS and HIPEC in women treated for peritoneal malignancies. All these women conceived spontaneously, most of them within 2 years after the procedure. They delivered most often by vaginal way after an uneventful pregnancy. Their newborns were healthy, except 1 case of congenital diaphragmatic hernia requiring emergent surgery. There were 2 additional uneventful pregnancies reported after the diagnosis of pseudomyxoma peritonei and before CRS and HIPEC, with the support of the medical team. Another woman having undergone oocytes retrieval and embryo cryopreservation prior to the surgery was mother of twins after the procedure via a surrogate mother., Conclusion: Childbearing after cytoreductive surgery and heated intraperitoneal chemotherapy is possible in women conserving their genital organs after the procedure. The question of fertility should be considered and discussed in women in reproductive age prior to cytoreductive surgery and heated intraperitoneal chemotherapy. Different options could be offered in this setting. Multidisciplinary decision making involving surgical oncologists and fertility specialists is important.
- Published
- 2011
- Full Text
- View/download PDF
121. Peritoneal carcinomatosis from appendiceal cancer: early adequate therapeutic management for long-term survival.
- Author
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Glehen O, Bakrin N, and Passot G
- Subjects
- Appendiceal Neoplasms pathology, Appendiceal Neoplasms surgery, Humans, Peritoneal Neoplasms secondary, Peritoneal Neoplasms surgery, Survival Rate, Treatment Outcome, Appendiceal Neoplasms mortality, Appendiceal Neoplasms therapy, Peritoneal Neoplasms mortality, Peritoneal Neoplasms therapy
- Published
- 2011
- Full Text
- View/download PDF
122. Population pharmacokinetics and pharmacodynamics of cisplatinum during hyperthermic intraperitoneal chemotherapy using a closed abdominal procedure.
- Author
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Cotte E, Colomban O, Guitton J, Tranchand B, Bakrin N, Gilly FN, Glehen O, and Tod M
- Subjects
- Antineoplastic Agents administration & dosage, Antineoplastic Agents pharmacology, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols pharmacokinetics, Antineoplastic Combined Chemotherapy Protocols pharmacology, Area Under Curve, Cisplatin administration & dosage, Cisplatin pharmacology, Combined Modality Therapy, Female, Humans, Hyperthermia, Induced methods, Male, Middle Aged, Mitomycin administration & dosage, Nonlinear Dynamics, Peritoneal Neoplasms pathology, Peritoneal Neoplasms surgery, Tissue Distribution, Antineoplastic Agents pharmacokinetics, Cisplatin pharmacokinetics, Models, Biological, Peritoneal Neoplasms drug therapy
- Abstract
The aim of this work was to study the pharmacokinetics of cisplatinum during closed abdominal hyperthermic intraperitoneal chemotherapy (HIPEC) using a population pharmacokinetics approach. Forty patients were treated between January 2003 and December 2004. Peritoneal and blood concentrations of cisplatinum were used to develop a pharmacokinetic model of the peritoneal and plasma compartments using NONMEM software. Different covariables were analyzed to identify those that explain part of the interindividual variability of the pharmacokinetic parameters. Relationships between the area under the concentration-time curve (AUC) and hematological and renal toxicity and efficiency were explored. The pharmacokinetics of cisplatinum were modeled with a 3-compartment model. Estimations of the plasma and peritoneal pharmacokinetic parameters were obtained. No clinical or biological covariates correlated with these parameters. No direct relationship between the AUC of the peritoneal or plasma and toxicity or efficiency was demonstrated. The pharmacokinetics during HIPEC could be modeled with a 3-compartment model using a population pharmacokinetics approach. This work is the basis of further studies. Notably, studies including new patients will analyze the impact of abdominal cavity volume and the variation of the abdominal pressure during HIPEC on the pharmacokinetics of cisplatinum.
- Published
- 2011
- Full Text
- View/download PDF
123. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for the treatment of recurrent endometrial carcinoma confined to the peritoneal cavity.
- Author
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Bakrin N, Cotte E, Sayag-Beaujard A, Raudrant D, Isaac S, Mohamed F, Gilly FN, and Glehen O
- Subjects
- Adenocarcinoma secondary, Aged, Cisplatin administration & dosage, Combined Modality Therapy, Endometrial Neoplasms pathology, Female, Gynecologic Surgical Procedures, Humans, Hyperthermia, Induced, Infusions, Parenteral, Middle Aged, Mitomycin administration & dosage, Peritoneal Neoplasms secondary, Adenocarcinoma therapy, Antineoplastic Agents administration & dosage, Endometrial Neoplasms therapy, Neoplasm Recurrence, Local therapy, Peritoneal Neoplasms therapy
- Abstract
Our objective was to determine if cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a feasible therapeutic option for treatment of peritoneal recurrence of endometrial carcinoma. Between August 2002 and May 2007, 5 patients with recurrent endometrial carcinoma confined to the peritoneal cavity who underwent CRS with HIPEC. Cisplatin (1 mg/kg) and mitomycin C (0.7 mg/kg) were perfused at an inflow temperature of 46 to 48-C for 90 minutes under systemic hypothermia (32 °C). Of the 5 patients treated, histopathological type and International Federation of Gynecology and Obstetrics stage were as follows: IB endometrioid (n = 1), IIIA endometrioid (n = 1), IIIC endometrioid (n = 2), and IC endometrioid + pseudosarcomatoid component (n = 1). The mean interval from initial surgery to CRS with HIPEC was 47.5 months (10-120 months). In all patients, CRS was complete. One patient with pseudosarcomatoid component developed recurrent disease 10 months after surgery and died 2 months later. One patient experienced early recurrence with a malignant pleural effusion and died. Three patients are alive and disease free at 7, 23, and 39 months from surgery with good performance status. Regarding the toxicity of the procedure, highly selected patients with recurrent endometrial carcinoma confined to the peritoneal cavity may benefit from improved survival after CRS with HIPEC.
- Published
- 2010
- Full Text
- View/download PDF
124. Appraisal of peritoneal cavity's capacity in order to assess the pharmacology of liquid chemotherapy solution in hyperthermic intraperitoneal chemotherapy.
- Author
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Duez A, Cotte E, Glehen O, Cotton F, and Bakrin N
- Subjects
- Abdominal Neoplasms drug therapy, Adult, Aged, Aged, 80 and over, Antineoplastic Agents administration & dosage, Body Mass Index, Body Size, Carcinoma drug therapy, Female, Hot Temperature, Humans, Infusions, Parenteral, Male, Middle Aged, Peritoneal Cavity diagnostic imaging, Tomography, Spiral Computed, Young Adult, Antineoplastic Agents pharmacokinetics, Peritoneal Cavity anatomy & histology
- Abstract
Background: Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is an aggressive strategy to treat patients presenting peritoneal carcinomatosis from various origins. The aim of this study was to evaluate the correlation between the peritoneal cavity's capacity and the weight, the size and the body mass index (BMI) of patients to see if it would be relevant to adapt the pharmacology of HIPEC based on these factors., Materials and Methods: This study included 100 patients who had chest-abdominal-pelvic Computerised Tomography (CAP-CT) for various reasons. They were chosen randomly (53 males; 47 females; age range 19-96; mean 58 years). Weight and height of each of them were recorded with their identity on a model sheet given to nurses accustomed to work in clinical trials, before the CAP-CT. The BMI was then calculated from these two values. All the subjects were scanned with CT (Philips Brilliance 40, Cleveland, USA) and the volume of the peritoneal cavity, the liver and the spleen of each was measured with Centricity PACS LS software or Volume Viewer 2 (AW Suite 2.0 6.5.1 u) software., Results: The rates of correlation between the weight, the size, the BMI and the volume of the peritoneal cavity in which the volumes of the liver and the spleen were removed are 0.674, 0.317 and 0.576, respectively; and those of the weight, the size, the BMI and the volume of the peritoneal cavity without taking into account the volume occupied by the liver and spleen are 0.749, 0.348 and 0.644, respectively., Conclusion: The peritoneal cavity's capacity is mainly correlated with weight and the interest to assess the volume of liver and spleen remains questionable in terms of results.
- Published
- 2009
- Full Text
- View/download PDF
125. [Severe gestational hypertriglyceridemia: related complications and management].
- Author
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Huissoud C, Robert JM, Bakrin N, Rudigoz RC, and Levrat A
- Subjects
- Acute Kidney Injury etiology, Acute Kidney Injury therapy, Adult, Female, Fetal Death etiology, Fetal Distress etiology, Humans, Pancreatitis complications, Pancreatitis prevention & control, Pregnancy, Pregnancy Outcome, Pregnancy Trimester, Second, Pregnancy Trimester, Third, Hypertriglyceridemia complications, Hypertriglyceridemia therapy, Pancreatitis etiology, Pregnancy Complications therapy
- Abstract
We present two cases of severe hypertriglyceridemia (HTG>10g/l) in pregnancy. The first reports the case of a primigravida with mild HTG before conception. Triglycerides (TG) increased thereafter (20.9g/l) during pregnancy causing pancreatitis and in utero fetal death at 24 weeks' gestation (WG). The second deals with the de novo occurrence of a severe HTG (19g/l) diagnosed incidentally at 34 WG and complicated by acute renal failure. Severe HTG in pregnancy threatens maternal and fetal prognosis. We have summarized the curative and preventive management of gravidic HTG.
- Published
- 2008
- Full Text
- View/download PDF
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