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1.
Angiogenesis ; 27(2): 211-227, 2024 May.
Article in English | MEDLINE | ID: mdl-38294582

ABSTRACT

Heterozygous activin receptor-like kinase 1 (ALK1) mutations are associated with two vascular diseases: hereditary hemorrhagic telangiectasia (HHT) and more rarely pulmonary arterial hypertension (PAH). Here, we aimed to understand the impact of ALK1 mutations on BMP9 and BMP10 transcriptomic responses in endothelial cells. Endothelial colony-forming cells (ECFCs) and microvascular endothelial cells (HMVECs) carrying loss of function ALK1 mutations were isolated from newborn HHT and adult PAH donors, respectively. RNA-sequencing was performed on each type of cells compared to controls following an 18 h stimulation with BMP9 or BMP10. In control ECFCs, BMP9 and BMP10 stimulations induced similar transcriptomic responses with around 800 differentially expressed genes (DEGs). ALK1-mutated ECFCs unexpectedly revealed highly similar transcriptomic profiles to controls, both at the baseline and upon stimulation, and normal activation of Smad1/5 that could not be explained by a compensation in cell-surface ALK1 level. Conversely, PAH HMVECs revealed strong transcriptional dysregulations compared to controls with > 1200 DEGs at the baseline. Consequently, because our study involved two variables, ALK1 genotype and BMP stimulation, we performed two-factor differential expression analysis and identified 44 BMP9-dysregulated genes in mutated HMVECs, but none in ECFCs. Yet, the impaired regulation of at least one hit, namely lunatic fringe (LFNG), was validated by RT-qPCR in three different ALK1-mutated endothelial models. In conclusion, ALK1 heterozygosity only modified the BMP9/BMP10 regulation of few genes, including LFNG involved in NOTCH signaling. Future studies will uncover whether dysregulations in such hits are enough to promote HHT/PAH pathogenesis, making them potential therapeutic targets, or if second hits are necessary.


Subject(s)
Pulmonary Arterial Hypertension , Telangiectasia, Hereditary Hemorrhagic , Adult , Infant, Newborn , Humans , Endothelial Cells/metabolism , Growth Differentiation Factor 2/genetics , Growth Differentiation Factor 2/metabolism , Pulmonary Arterial Hypertension/metabolism , Telangiectasia, Hereditary Hemorrhagic/genetics , Telangiectasia, Hereditary Hemorrhagic/metabolism , Bone Morphogenetic Proteins/genetics , Mutation/genetics , Gene Expression Profiling , Activin Receptors, Type II/genetics , Activin Receptors, Type II/metabolism
3.
Eur J Med Genet ; 65(1): 104370, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34737116

ABSTRACT

Hereditary haemorrhagic telangiectasia (HHT) is a complex, multisystemic vascular dysplasia affecting approximately 85,000 European Citizens. In 2016, eight founding centres operating within 6 countries, set up a working group dedicated to HHT within what became the European Reference Network on Rare Multisystemic Vascular Diseases. By launch, combined experience exceeded 10,000 HHT patients, and Chairs representing 7 separate specialties provided a median of 24 years' experience in HHT. Integrated were expert patients who focused discussions on the patient experience. Following a 2016-2017 survey to capture priorities, and underpinned by more than 40 monthly meetings, and new data acquisitions, VASCERN HHT generated position statements that distinguish expert HHT care from non-expert HHT practice. Leadership was by specialists in the relevant sub-discipline(s), and 100% consensus was required amongst all clinicians before statements were published or disseminated. One major set of outputs targeted all healthcare professionals and their HHT patients, and include the new Orphanet definition; Do's and Don'ts for common situations; Outcome Measures suitable for all consultations; COVID-19; and anticoagulation. The second output set span aspects of vascular pathophysiology where greater understanding will assist organ-specific specialist clinicians to provide more informed care to HHT patients. These cover cerebral vascular malformations and screening; mucocutaneous telangiectasia and differential diagnosis; anti-angiogenic therapies; circulatory interplays between anaemia and arteriovenous malformations; and microbiological strategies to counteract loss of normal pulmonary capillary function. Overall, the integrated outputs, and documented current practices, provide frameworks for approaches that augment the health and safety of HHT patients in diverse health-care settings.


Subject(s)
Telangiectasia, Hereditary Hemorrhagic/therapy , Disease Management , Europe , Humans , Practice Guidelines as Topic , Rare Diseases , Telangiectasia, Hereditary Hemorrhagic/diagnosis
4.
Cancer Radiother ; 24(6-7): 726-729, 2020 Oct.
Article in French | MEDLINE | ID: mdl-32807684

ABSTRACT

Efficient communication between professionals is of upmost importance in improving treatment safety in a radiotherapy department, and is also necessary to enhance the quality of work life. Taking as example the organizations in industry, a self-managed team centred on patients with head and neck cancers treated with radiation has been implemented in 2018 in centre Jean-Bernard (Le Mans, France). After over a year's experience, a real benefice has been found and validates the plan to extend this model to other departments.


Subject(s)
Communication , Head and Neck Neoplasms/radiotherapy , Hospital Departments , Interprofessional Relations , Patient Care Team/organization & administration , Radiation Oncology , France , Humans
5.
Eur J Cancer ; 104: 108-116, 2018 11.
Article in English | MEDLINE | ID: mdl-30343254

ABSTRACT

AIM OF THE STUDY: The optimal therapeutic strategy in patients with rectal cancer and synchronous unresectable metastases remains unknown. We evaluated the efficacy of FOLFIRINOX induction therapy in this setting. PATIENTS AND METHODS: Chemotherapy-naïve patients received at least 8 cycles of FOLFIRINOX. The primary end-point was the 4-month disease control (4 m DC) rate. Tumour responses were centrally reviewed and assessed by computed tomography scan for metastases (Response Evaluation Criteria in Solid Tumours criteria) and magnetic resonance imaging for rectal tumorus. With a Simon 2-stage design and a targeted (H1) 4 m DC > 75%, 65 patients were enrolled from July 2012 to February 2015: male, 78%; median age, 61 years; performance status, 0-1, 98%; liver metastases, 92%; ≥2 metastatic sites, 63%. RESULTS: Fifty-six (85%) of the 65 patients received the 8 planned FOLFIRINOX cycles. The primary objective was achieved (4 m DC rate: 94%; 95% confidence interval [CI], 86.3-97.8). Primary tumour symptoms decreased from 72% at baseline to 10% at 4 months. Response rate was 86%, and a >70% primary tumour volume decrease was seen in 63% of patients. Forty-four patients (68%) had at least one grade 3 side-effect; no toxic deaths occurred. Median follow-up was 35.0 months (95% CI, 31.3-43.7). Median progression-free survival and overall survival were 10.9 m (95% CI, 8.8-12.9) and 33.4 m (95% CI, 22.6-38.2), respectively. CONCLUSION: Upfront FOLFIRINOX is feasible and allows good local and distant control. It therefore offers the opportunity to choose the best therapeutic strategy for each patient and to personalise treatment according to the local and distant efficacy results of this induction step. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01674309.


Subject(s)
Adenocarcinoma/secondary , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Rectal Neoplasms/drug therapy , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Combined Modality Therapy , Fatigue/chemically induced , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Follow-Up Studies , Gastrointestinal Diseases/chemically induced , Hematologic Diseases/chemically induced , Humans , Irinotecan/administration & dosage , Irinotecan/adverse effects , Kaplan-Meier Estimate , Leucovorin/administration & dosage , Leucovorin/adverse effects , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/drug therapy , Liver Neoplasms/secondary , Liver Neoplasms/surgery , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/drug therapy , Lung Neoplasms/secondary , Magnetic Resonance Imaging , Male , Middle Aged , Oxaliplatin/administration & dosage , Oxaliplatin/adverse effects , Paresthesia/chemically induced , Progression-Free Survival , Remission Induction , Tomography, X-Ray Computed , Treatment Outcome
6.
Ann Oncol ; 28(10): 2436-2442, 2017 Oct 01.
Article in English | MEDLINE | ID: mdl-28961836

ABSTRACT

BACKGROUND: Outcome of intermediate risk rectal cancer may be improved by the addition of oxaliplatin during 5-fluoruracil concomitant neoadjuvant chemoradiotherapy. The purpose of this study is to analyze the main clinical results of the ACCORD12 trial (NCT00227747) in rectal cancer after 5 years of follow-up. PATIENTS AND METHODS: Inclusion criteria were as follows: rectal adenocarcinoma accessible to digital examination staged T3-T4 Nx M0 (or T2 Nx distal anterior rectum). Two neoadjuvant chemoradiotherapy regimens were randomized: CAP45 (RT 45 Gy + capecitabine) and CAPOX50 (RT 50 Gy + capecitabine and oxaliplatin). Main end point was sterilization of the operative specimen. Acute and late toxicities were prospectively analyzed with dedicated questionnaires. RESULTS: Between November 2005 and July 2008, 598 patients were included in the trial. After a median follow-up of 60.2 months, there was no difference between treatment arms in multivariate analysis either for disease-free survival or overall survival (OS) [P = 0.9, hazard ratio (HR)=1.02; 95% confidence interval (CI), 0.76-1.36 and P = 0.3, HR = 0.87; 95% CI, 0.66-1.15, respectively]. There was also no difference of local control in univariate analysis (P = 0.7, HR = 0.92; 95% CI, 0.51-1.66). Late toxicities were acceptable with 1.6% G3 anal incontinence, and <1% G3 diarrhea, G3 rectal bleeding, G3 stenosis, G3-4 pain, G3 urinary incontinence, G3 urinary retention and G3 skeletal toxicity. There was a slight increase of erectile dysfunction over time with a 63% rate of erectile dysfunction at 5 years. There was no significant statistical difference for these toxicities between treatment arms. CONCLUSIONS: The CAPOX50 regimen did not improve local control, disease-free survival and overall survival in the ACCORD12 trial. Late toxicities did not differ between treatment arms.


Subject(s)
Adenocarcinoma/drug therapy , Adenocarcinoma/radiotherapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Capecitabine/therapeutic use , Rectal Neoplasms/drug therapy , Rectal Neoplasms/radiotherapy , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Capecitabine/administration & dosage , Capecitabine/adverse effects , Chemoradiotherapy, Adjuvant/adverse effects , Disease-Free Survival , Female , Humans , Male , Middle Aged , Neoadjuvant Therapy/adverse effects , Organoplatinum Compounds/administration & dosage , Oxaliplatin , Rectal Neoplasms/pathology , Survival Rate
7.
Ann Oncol ; 28(7): 1612-1617, 2017 Jul 01.
Article in English | MEDLINE | ID: mdl-28472235

ABSTRACT

BACKGROUND: In 2008, a study of the characteristics of hospitalised patients led to the development of a prognostic tool that distinguished three populations with significantly different 2-month survival rates. The goal of our study aimed at validating prospectively this prognostic tool in outpatients treated for cancer in terminal stage, based on four factors: performance status (ECOG) (PS), number of metastatic sites, serum albumin and lactate dehydrogenase. PATIENTS AND METHODS: PRONOPALL is a multicentre study of current care. About 302 adult patients who met one or more of the following criteria: life expectancy under 6 months, performance status ≥ 2 and disease progression during the previous chemotherapy regimen were included across 16 institutions between October 2009 and October 2010. Afterwards, in order to validate the prognostic tool, the score was ciphered and correlated to patient survival. RESULTS: Totally 262 patients (87%) were evaluable (27 patients excluded and 13 unknown score). Median age was 66 years [37-88], and women accounted for 59%. ECOG PS 0-1 (46%), PS 2 (37%) and PS 3-4 (17%). The primary tumours were: breast (29%), colorectal (28%), lung (13%), pancreas (12%), ovary (11%) and other (8%). About 32% of patients presented one metastatic site, 35% had two and 31% had more than two. The median lactate dehydrogenase level was 398 IU/l [118-4314]; median serum albumin was 35 g/l [13-54]. According to the PRONOPALL prognostic tool, the 2-month survival rate was 92% and the median survival rate was 301 days [209-348] for the 130 patients in population C, 66% and 79 days [71-114] for the 111 patients in population B, and 24% and 35 days for [14-56] the 21 patients in population A. These three populations survival were statistically different (P <0.0001). CONCLUSION: PRONOPALL study confirms the three prognostic profiles defined by the combination of four factors. This PRONOPALL score is a useful decision-making tool in daily practice.


Subject(s)
Ambulatory Care , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Decision Support Techniques , Neoplasms/drug therapy , Palliative Care , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/blood , Disease Progression , Female , France , Humans , Kaplan-Meier Estimate , L-Lactate Dehydrogenase/blood , Male , Middle Aged , Neoplasm Metastasis , Neoplasms/blood , Neoplasms/mortality , Predictive Value of Tests , Proportional Hazards Models , Prospective Studies , Reproducibility of Results , Risk Factors , Serum Albumin, Human/analysis , Time Factors , Treatment Outcome
8.
Cancer Radiother ; 21(4): 286-290, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28522278

ABSTRACT

PURPOSE: The main objective of this study was to evaluate the 5-year efficacy of exclusive laryngeal radiotherapy without node prophylactic irradiation for localized cancers of the vocal cords. PATIENTS AND METHODS: We retrospectively reviewed charts from 258 patients with T1-T2N0 glottic carcinoma irradiated from April 1987 to March 2015 in four France western centers, including pretreated patients. Toxicity was analyzed according to CTCAE v4.0 classification. RESULTS: The median follow-up was 50 months. The median age was 67 years with 87% men and 85.5% had T1 tumor. Five years overall survival was 77.5% (95% confidence interval [95% CI]: 71.4-83.5), 5 years local control was 86.8% (95% CI: 82.3-91.3), specific survival rate was 95% (95% CI: 92.2-97.9) and final laryngectomy-free survival was 87.5% (95% CI: 82.2-92.9). Most toxicities were grade 1 and 2. Grade 3 acute toxicity was 15.5% for the radiation laryngitis, 3.5% for radiodermatitis and 7.7% for dysphonia. Grade 3 chronic toxicity was 3.5% for dysphonia and there were two cases of tracheal stenosis treated by tracheotomy. CONCLUSION: Radiotherapy provides good results in local control of stage I and II vocal cords cancers as well as the toxicity level.


Subject(s)
Laryngeal Neoplasms/radiotherapy , Vocal Cords , Aged , Aged, 80 and over , Female , France , Humans , Laryngeal Neoplasms/mortality , Laryngeal Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Radiotherapy/adverse effects , Retrospective Studies , Survival Rate
9.
J Gynecol Obstet Biol Reprod (Paris) ; 45(8): 924-928, 2016 Oct.
Article in French | MEDLINE | ID: mdl-26874667

ABSTRACT

OBJECTIVES: Determine the frequency at which palpation of two fontanelles is possible, in order to describe a new clinical diagnosis approach: "the two fontanelles sign". MATERIALS AND METHODS: Descriptive study established in the obstetric and gynecology department at Lyon-Sud university hospital between March and November 2013. We followed-up one thousand successive singleton deliveries in cephalic presentation after 30 weeks of gestation. Before starting expulsive efforts, the number of fontanelles perceived (1, 2 or any) was documented. If the number of fontanelles were not noted, the patient was excluded. RESULTS: Nine hundred and seventy-eight patients were included. In 39.3% of cases (n=384), 2 fontanelles were found, in 57.5% (n=563) only one and in 3.2% (n=31), none. CONCLUSION: Both fontanelles palpation is frequently possible and enables quality control of fetal head presentation variety without ultrasound assessment. In order to prove the reliability of clinical examination, study comparing presentation ultrasonography and digital examination finding 2 fontanelles is needed.


Subject(s)
Cranial Fontanelles , Labor Presentation , Obstetrics/methods , Palpation/methods , Quality Control , Adult , Female , Follow-Up Studies , Humans , Pregnancy
10.
J Gynecol Obstet Biol Reprod (Paris) ; 45(4): 343-52, 2016 Apr.
Article in French | MEDLINE | ID: mdl-26096348

ABSTRACT

OBJECTIVES: The aim of this study is to describe knowledge on forceps delivery in the area of Lyon. MATERIAL AND METHODS: It is a multicentric observational study carried between January 1, 2013 and June 9, 2013. A questionnaire was sent to obstetricians and residents of the area of Lyon. It related prerequisites for operative vaginal delivery, the method used to apply forceps, practices and preferences of operators. RESULTS: Seventy-five responses were obtained (47 obstetricians, 28 residents). About prerequisites: 6.4% of the obstetricians and 14.3% of the residents never do urinary catheterization. Instrumental delivery is never performed when the fetal head is not engaged. Mid-pelvic operative vaginal delivery is performed by 51.1% of obstetricians. Trans-abdominal ultrasound assessment is conducted in cases of clinical doubts about the fetal head position. For occipital anterior and left anterior positions, the left blade is first applied. A flexion of the fetal head is applied for anterior positions but not in posterior positions. Most of operators do not perform instrumental rotation. Vacuum extractor is the privileged instrument for obstetricians and forceps is often used in second line. CONCLUSION: This study shows that most of the recommendations for forceps delivery are followed. In front of the lake of statistical power of this study, it might be interesting to improve a largest study with a comparison between obstetricians and residents' practices.


Subject(s)
Clinical Competence/statistics & numerical data , Extraction, Obstetrical/statistics & numerical data , Obstetrical Forceps/statistics & numerical data , Obstetrics/statistics & numerical data , Physicians/statistics & numerical data , Practice Patterns, Physicians'/statistics & numerical data , Adult , Female , France , Humans , Pregnancy
11.
J Gynecol Obstet Biol Reprod (Paris) ; 45(3): 307-14, 2016 Mar.
Article in French | MEDLINE | ID: mdl-25977141

ABSTRACT

AIM: To show the effectiveness of ultrasound-guided puncture in the treatment of lactational breast abscess and identify its risk factors. MATERIALS AND METHODS: Retrospective descriptive study at the CHU of Lyon-Sud from December 2007 to December 2013, including patients with lactational breast abscess confirmed on ultrasound and treated with antibiotics and analgesics. Realisation of ultrasound-guided needle under local anesthesia by the radiologist and washing the cavity with physiological serum. RESULTS: Forty patients had lactational abscesses at an average of 10 weeks post-partum. Thirty-four patients were treated by needle aspiration, of which 2 had first surgical drainage. The average size of the abscess was 41.2mm. The success rate of needle aspiration was 91.2%. No cases of recurrence were observed, however, there were 5 fistulisations. In all, 91.2% were treated on an outpatient basis. In 87.8% of cases, breastfeeding was continued on the healthy side and in 48.5% of cases on the affected side. The major risk factor for abscess was mastitis in 91.1% of cases. CONCLUSION: Ultrasound guidance of needle aspiration should be gold standard for the treatment of lactational breast abscesses to continue breastfeeding including the affected side.


Subject(s)
Abscess/etiology , Abscess/surgery , Breast Diseases/etiology , Breast Diseases/surgery , Breast Feeding/adverse effects , Drainage/statistics & numerical data , Abscess/microbiology , Abscess/pathology , Adult , Biopsy, Needle , Breast/microbiology , Breast/pathology , Breast Diseases/microbiology , Breast Diseases/pathology , Female , Humans , Lactation/physiology , Mastitis/etiology , Mastitis/microbiology , Mastitis/pathology , Mastitis/surgery , Puerperal Disorders/etiology , Puerperal Disorders/pathology , Puerperal Disorders/surgery , Retrospective Studies , Treatment Outcome , Ultrasonography, Interventional/statistics & numerical data
12.
Cancer Radiother ; 19(6-7): 616-20, 2015 Oct.
Article in French | MEDLINE | ID: mdl-26278991

ABSTRACT

In August 2013, the French nuclear safety agency (ASN) requested the permanent group of experts in radiation protection in medicine (GPMED) to propose recommendations on the implementation of new technology and techniques in radiation oncology. These recommendations were finalized in February 2015 by the GPMED. In April 2015, the ASN sent a letter to the French ministry of health (DGS/DGOS), and its national health agencies (ANSM, INCa, HAS). In these letters, ASN proposed that, from the 12 recommendations made by the GPMED, an action plan should be established, whose control could be assigned to the French national cancer institute (INCa), as a pilot of the national committee for radiotherapy and that this proposal has to be considered at the next meeting of the national committee of radiotherapy.


Subject(s)
Neoplasms/radiotherapy , Patient Safety/standards , Radiation Oncology/standards , Humans , Radiotherapy/standards
13.
Diabetes Metab ; 41(5): 393-400, 2015 Nov.
Article in English | MEDLINE | ID: mdl-25890778

ABSTRACT

AIM: This study aimed to determine whether third-trimester adipokines during gestational diabetes (GDM) are associated with higher metabolic risk. METHODS: A total of 221 women with GDM (according to IADPSG criteria) were enrolled between 2011/11 and 2013/6 into a prospective observational study (IMAGE), and categorized as having elevated fasting blood glucose (FBG) or impaired fasting glucose (IFG, n = 36) if levels were ≥ 92 mg/dL during a 75-g oral glucose tolerance test (OGTT), impaired glucose tolerance (IGT, n = 116) if FBG was < 92 mg/dL but with elevated 1-h or 2-h OGTT values, or impaired fasting and stimulated blood glucose (IFSG, n = 69) if both FBG was ≥ 92 mg/dL and 1-h or 2-h OGTT values were elevated. RESULTS: Pre-gestational body mass index (BMI) was higher in women with IFG or IFSG compared with IGT (P < 0.001), as were leptin levels in women with IFG vs IGT [34.7 (10.5-119.7) vs 26.6 (3.56-79.4) ng/L; P = 0.008]. HOMA2-IR scores were higher in women with IFG or IFSG vs IGT (1.87 ± 1.2 or 1.72 ± 0.9 vs 1.18 ± 0.8, respectively; P < 0.001). Also, those with IFSG vs those with IGT had significantly lower HOMA2-B scores (111.4 ± 41.3 vs 127.1 ± 61.6, respectively; P < 0.05) and adiponectin levels [5.00 (1.11-11.3) vs 6.19 (2.11-17.7) µg/mL; P < 0.001], and higher levels of IL-6 [1.14 (0.33-20.0) vs 0.90 (0.31-19.0); P = 0.012] and TNF-α [0.99 (0.50-10.5) vs 0.84 (0.45-11.5) pg/mL; P = 0.003]. After adjusting for age, parity, and pre-gestational and gestational BMI, the difference in adiponectin levels remained significant. CONCLUSION: Diagnosing GDM by IADSPG criteria results in a wide range of heterogeneity. Our study has indicated that adipokine levels in addition to FBG may help to select women at high metabolic risk for appropriate monitoring and post-delivery interventions (ClinicalTrials.gov number NCP02133729).


Subject(s)
Adiponectin/blood , Diabetes Mellitus, Type 2/etiology , Diabetes, Gestational/physiopathology , Insulin Resistance , Leptin/blood , Overweight/physiopathology , Pregnancy Complications/physiopathology , Biomarkers/blood , Body Mass Index , Cohort Studies , Diabetes Mellitus, Type 2/epidemiology , Diabetes, Gestational/diagnosis , Diabetes, Gestational/etiology , Diabetes, Gestational/metabolism , Female , France/epidemiology , Humans , Postpartum Period , Pregnancy , Pregnancy Trimester, Third , Prenatal Diagnosis , Prospective Studies , Risk Factors , Severity of Illness Index
14.
Ann Oncol ; 26(6): 1208-1215, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25739671

ABSTRACT

BACKGROUD: The R98 trial explores the addition of irinotecan to a 5-fluorouracil (5-FU) plus leucovorin (5-FU/LV) adjuvant regimen in optimally resected stages II-III rectal cancers. We report the updated long-term results. Disease-free survival (DFS) was the primary end point. PATIENST AND METHODS: Between March 1999 and December 2005, 357 patients were randomized: 178 in 5-FU/LV and 179 in LV5-FU2 + irinotecan arm. The trial was stratified by control arm: Mayo Clinic regimen or LV5-FU2 regimen. RESULTS: Three hundred and fifty-seven randomized patients were evaluable for efficacy. With a follow-up of 156 months, the DFS was in favour of experimental arm but did not reach statistical significance [hazard ratio (HR) = 0.80, P = 0.154]. The same was observed for overall survival (OS) (HR = 0.87, P = 0.433). The 5-year DFS was 58% in the control arm and 63% in the experimental arm. The 5-year OS was 74% in the control arm and 75% in the experimental arm. Patients allocated to the experimental arm had more grade 3-4 neutropenia when compared with the LV5-FU2 arm (33% versus 6%, P = 0.03), but not when compared with the Mayo Clinic arm (33% versus 36%, P = 0.84). Grade 3-4 diarrhoea tended to be higher in the experimental arm, but analyses stratified by control arm or by radiotherapy failed to show significant differences across strata (test for interaction P = 0.44). CONCLUSION: Even though a benefit of irinotecan in subgroups of patients cannot be excluded, due to early termination and lack of power, the study does not support the addition of irinotecan to 5-FU/LV in routine in patients with resected stage II-III rectal cancer.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Camptothecin/analogs & derivatives , Rectal Neoplasms/drug therapy , Rectal Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Camptothecin/adverse effects , Camptothecin/therapeutic use , Chemotherapy, Adjuvant , Disease Progression , Disease-Free Survival , Early Termination of Clinical Trials , Female , Fluorouracil/therapeutic use , France , Humans , Irinotecan , Leucovorin/therapeutic use , Male , Middle Aged , Neoplasm Staging , Rectal Neoplasms/mortality , Rectal Neoplasms/pathology , Risk Factors , Survival Analysis , Time Factors , Treatment Outcome
15.
Oncologie (Paris) ; 16(5): 267-276, 2014.
Article in English | MEDLINE | ID: mdl-26190928

ABSTRACT

BACKGROUND: In 2006, bevacizumab, a targeted therapy agent was combined with FOLFIRI for the firstline treatment of patients with unresectable metastatic colorectal cancer. METHODS/RESULTS: A study on a homogenous series of 111 patients from the Brittany and Pays de la Loire areas who received bevacizumab-FOLFIRI as first-line treatment in 2006 showed the following results: 51 responses, 29 stabilisations, 21 progressions and 10 cases of toxicity prior to assessment. Median overall survival (OS) was 25.1 months and median progression-free survival was 10.2 months. Surgery secondary to treatment tripled median OS which reached 59.2 months in resected patients versus 18.8 months in unresected patients. Comparison of patients aged more or less than 70 years showed no differences in terms of benefits or risks. CONCLUSION: Bevacizumab-FOLFIRI could be administered as part of a routine care protocol to elderly patients previously evaluated by a geriatric assessment and validated by a multidisciplinary staff.


En 2006, bevacizumab-FOLFIRI représente la thérapie ciblée administrable dès la première ligne chez les patients porteurs d'un cancer colorectal métastatique non opérable. Une série homogène de 111 patients colligés en région Bretagne et Pays de la Loire ayant reçu du bevacizumab- FOLFIRI en première ligne en 2006 révèle les résultats suivants: 51 réponses, 29 stabilités, 21 progressions et 10 toxicités avant évaluation. La médiane de survie globale (OS) est de 25,1 mois et la médiane de survie sans progression (PFS) de 10,2 mois. Dans le cas d'une chirurgie secondaire, l'OS médian triple de 18,8 mois chez les patients non réséqués versus 59,2 mois ceux réséqués. En comparant les sujets âgés de plus et de moins de 70 ans, aucune différence n'a été mise en évidence en termes de bénéfice ou de risque. Bevacizumab-FOLFIRI pourrait être administré en pratique courante chez les personnes âgées sous couvert d'une évaluation gériatrique et d'une approche multidisciplinaire.

16.
Diabetes Metab ; 39(2): 132-8, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23182459

ABSTRACT

OBJECTIVE: The International Association of Diabetes and Pregnancy Study Group (IADPSG) guidelines for gestational diabetes mellitus (GDM) diagnosis determines that fasting, 1-h and 2-h glucose values may contribute independently to adverse outcomes. However, given the different physiological bases of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), differences in pregnancy outcomes are to be expected. This study aimed to determine whether classification of GDM women according to glucose homoeostasis results in heterogeneity in maternal and/or fetal outcomes. MATERIAL AND METHODS: Of the 75 pregnant women included after a 75-g 2-h OGTT performed between weeks 24-32 of gestation as per WHO criteria, 55 were classified as GDM (16 with IFG and 39 with IGT) according to IADSPG criteria. Their anthropometric and metabolic characteristics were compared with those of non-GDM women with IFG or IGT. Maternal and neonatal outcomes were prospectively recorded for each group. RESULTS: GDM women with IFG, including isolated IFG and combined IFG+IGT, were significantly heavier, had higher leptin values and were more frequently multiparous than GDM women with isolated IGT. HOMA-IR was significantly higher when fasting glucose was impaired. There were no significant differences in maternal outcomes according to metabolic status. In addition, large for gestational age (LGA) neonates were significantly seen more often in the IFG group. Fasting glucose was significantly associated with LGA independently of BMI and 2-h OGTT glucose. The>5.1mmol/L cut-off value for fasting glucose was highly predictive of delivery of LGA infants. CONCLUSION: IFG in GDM women was associated with increases in BMI, fat mass and hepatic insulin resistance. Delivery of LGA neonates was more frequent when fasting glycaemia was increased during the third trimester of pregnancy, and was independent of BMI and 2-h OGTT glucose values.


Subject(s)
Blood Glucose/metabolism , Diabetes, Gestational/diagnosis , Fetal Macrosomia/diagnosis , Adult , Apgar Score , Birth Weight , Body Mass Index , Diabetes, Gestational/blood , Diabetes, Gestational/epidemiology , Fasting/blood , Female , Fetal Macrosomia/epidemiology , France , Glucose Intolerance/blood , Glucose Tolerance Test , Guidelines as Topic , Homeostasis , Humans , Hypoglycemia , Infant , Infant, Newborn , Insulin Resistance , Jaundice , Male , Parity , Pregnancy , Pregnancy Outcome , Prospective Studies , Risk Factors , World Health Organization
17.
Gynecol Obstet Fertil ; 40(11): 711-4, 2012 Nov.
Article in French | MEDLINE | ID: mdl-23099023

ABSTRACT

Spontaneous hemoperitoneum is not frequent. We report here a rare cause of spontaneous hemoperitoneum during the second trimester of pregnancy. A ruptured uterine artery aneurysm was revealed in a patient who came for important abdominal pain. A CT scan showed a large hemoperitoneum and an additional arterial image. The patient underwent rapidly an embolization, which allowed a complete closure of the aneurysm. The patient gave birth to a healthy child. The diagnosis of hemoperitoneum must be discussed without delay. Once imagery realised, a good management of the patient must be done depending on the origin of the hemoperitoneum.


Subject(s)
Aneurysm/complications , Hemoperitoneum/etiology , Pregnancy Complications, Cardiovascular/therapy , Uterine Artery , Abdominal Pain , Adult , Aneurysm/diagnostic imaging , Aneurysm/therapy , Cesarean Section , Embolization, Therapeutic , Female , Gestational Age , Hemoperitoneum/diagnostic imaging , Humans , Pregnancy , Pregnancy Outcome , Tomography, X-Ray Computed
18.
Gynecol Obstet Fertil ; 40(10): 566-71, 2012 Oct.
Article in French | MEDLINE | ID: mdl-22959082

ABSTRACT

OBJECTIVES: At birth, evaluation of neonatal well-being is crucial. It is though important to perform umbilical cord blood gas analysis, and then to analyze the samples. We wanted to establish the feasibility and reliability of systematic umbilical cord blood sampling in a French labour ward. PATIENTS AND METHODS: Study of systematic umbilical cord blood gas analysis was realized retrospectively from 1000 consecutive deliveries. We first established the feasibility of the samples. Feasibility was defined by the ratio of complete cord acid-base data on the number of deliveries from alive newborns. Afterwards, we established the reliability on the remaining cord samples. Reliability was the ratio of samples that fulfilled quality criteria defined by Westgate et al. and revised by Kro et al., on the number of complete samples from alive newborns. At last, we looked for factors that would influence these results. RESULTS: The systematic umbilical cord blood sample feasibility reached 91.6%, and the reliability reached 80.7%. About the delivery mode, 38.6% of emergency caesarians (IC 95% [30.8-46.3]; P<0.0001) led to non-valid samples, when only 11.3% of programmed caesarians (IC 95% [4.3-18.2]; P<0.0001) led to non-valid samples. Umbilical cord blood analysis were significantly less validated during emergency caesarians. DISCUSSION AND CONCLUSION: Realization of systematic cord blood gas analysis was followed by 8.4% of incomplete samples, and by 19.3% that were uninterpretable. Training sessions should be organized to improve the feasibility and reliability, especially during emergency caesarians.


Subject(s)
Blood Gas Analysis , Fetal Blood/chemistry , Acid-Base Equilibrium , Cesarean Section , Delivery, Obstetric/methods , Feasibility Studies , Female , France , Humans , Hydrogen-Ion Concentration , Infant, Newborn , Labor, Obstetric , Pregnancy , Reproducibility of Results , Retrospective Studies
19.
Ann Fr Anesth Reanim ; 31(7-8): 652-65, 2012.
Article in French | MEDLINE | ID: mdl-22796177
20.
Gynecol Obstet Fertil ; 39(7-8): 412-7, 2011.
Article in French | MEDLINE | ID: mdl-21742533

ABSTRACT

OBJECTIVE: The main objective of this study was to calculate the percentage of preterm births before 28 weeks gestational age (weeks GA) outside level-3 maternity wards and determine how many could have been prevented. METHODS: This was an observational, multicenter, retrospective cohort study, which included all the deliveries that occurred between 24 and 27 weeks GA + 6 days in the Greater Lyon perinatal network (France) occurring between first of March 2008 and first of March 2009. In utero transfers (IUTs) and newborn transfers (NBTs) which were carried out outside the network, medical abortions, and foetal deaths in utero were excluded. The duration between patient's arrival in the level 1 and 2 maternity and birth was compared at the 97(th) percentile of the mother's transfer time in level-3 maternity. Births that occurred outside of level-3 maternity wards were considered avoidable each time the first duration was more than the second. RESULTS: During the study period, 113 infants were born alive between 24 and 27 weeks GA+6 days in the network. They were all included in the study. Ninety were born in a level-3 maternity ward and 23 were born in level-1 and 2 maternity wards (20%). There were 35 requests for IUT and 28 were carried out (80%). In 65% of non-level 3 births, no IUT was requested. In 17% of cases, an IUT request could have prevented births in level 1/2 maternity wards. If twin pregnancies had been transferred to a level-3 maternity ward, 26% of non-level 3 births would have been avoided. If all high-risk pregnancies had been transferred to a level-3 maternity ward, 40% of non-level 3 births would have been avoided. DISCUSSION AND CONCLUSION: Any time a pregnant woman is hospitalized in a type 1/2 maternity ward before 28 weeks GA, doctors should consider an in utero transfer to a level-3 maternity ward. It may be possible to lower the birth-rate of non-level 3 births by a targeted increase in in utero transfers and by transferring high-risk pregnancies to a level-3 maternity ward.


Subject(s)
Infant, Premature , Intensive Care Units, Neonatal/statistics & numerical data , Pregnancy Complications/prevention & control , Premature Birth/prevention & control , Female , France/epidemiology , Hospitals, Maternity , Hospitals, University , Humans , Infant, Newborn , Patient Transfer/statistics & numerical data , Pregnancy , Pregnancy Outcome , Pregnancy Trimester, Second , Pregnancy, High-Risk , Pregnancy, Triplet/statistics & numerical data , Pregnancy, Twin/statistics & numerical data , Premature Birth/mortality , Retrospective Studies
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