13 results on '"Goéré, Diane"'
Search Results
2. Primary Colorectal Tumor Displays Differential Genomic Expression Profiles Associated with Hepatic and Peritoneal Metastases.
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Gelli, Maximiliano, Desterke, Christophe, Bani, Mohamed Amine, Boige, Valérie, Ferté, Charles, Dartigues, Peggy, Job, Bastien, Perkins, Geraldine, Laurent-Puig, Pierre, Goéré, Diane, Mathieu, Jacques R. R., Cartry, Jerome, Ducreux, Michel, and Jaulin, Fanny
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PREDICTIVE tests ,LIVER ,IMMUNOHISTOCHEMISTRY ,METASTASIS ,RNA ,COLORECTAL cancer ,PERITONEUM ,GENOMICS ,GENE expression profiling ,MESSENGER RNA ,GENES ,DESCRIPTIVE statistics ,RESEARCH funding - Abstract
Simple Summary: Metastatic spread is the main prognostic factor in patients with colorectal cancer (CRC). We investigated the preferential metastatic spread of CRC toward two prevalent and clinically relevant metastatic sites, liver and peritoneum. By comparing the differential gene expression profile of primary tumors with isolated liver or peritoneal metastases, we identified a 61-gene signature associated with a specific metastatic route. Primary CRC tumors expressing the peritoneal signature were characterized by epithelial mesenchymal transition and apical epithelial junction activation but also an implication of stem cell signaling pathway. We identified specific clinico-pathological correlations and prognostic impacts of liver and peritoneal signatures in a TCGA dataset. As a future perspective, biomarkers identified in the primary tumor may contribute to improved risk stratification for individualized patient follow-up and to identify new therapeutic targets for a precision-based approach. Background: Despite improvements in characterization of CRC heterogeneity, appropriate risk stratification tools are still lacking in clinical practice. This study aimed to elucidate the primary tumor transcriptomic signatures associated with distinct metastatic routes. Methods: Primary tumor specimens obtained from CRC patients with either isolated LM (CRC-Liver) or PM (CRC-Peritoneum) were analyzed by transcriptomic mRNA sequencing, gene set enrichment analyses (GSEA) and immunohistochemistry. We further assessed the clinico-pathological associations and prognostic value of our signature in the COAD-TCGA independent cohort. Results: We identified a significantly different distribution of Consensus Molecular Subtypes between CRC-Liver and CRC-peritoneum groups. A transcriptomic signature based on 61 genes discriminated between liver and peritoneal metastatic routes. GSEA showed a higher expression of immune response and epithelial invasion pathways in CRC-Peritoneum samples and activation of proliferation and metabolic pathways in CRC-Liver samples. The biological relevance of RNA-Seq results was validated by the immunohistochemical expression of three significantly differentially expressed genes (ACE2, CLDN18 and DUSP4) in our signature. In silico analysis of the COAD-TCGA showed that the CRC-Peritoneum signature was associated with negative prognostic factors and poor overall and disease-free survivals. Conclusions: CRC primary tumors spreading to the liver and peritoneum display significantly different transcriptomic profiles. The implementation of this signature in clinical practice could contribute to identify new therapeutic targets for stage IV CRC and to define individualized follow-up programs in stage II-III CRC. [ABSTRACT FROM AUTHOR]
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- 2023
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3. Postoperative hepatic arterial chemotherapy in high-risk patients as adjuvant treatment after resection of colorectal liver metastases - a randomized phase II/III trial – PACHA-01 (NCT02494973)
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Goéré, Diane, Pignon, Jean-Pierre, Gelli, Maximiliano, Elias, Dominique, Benhaim, Léonor, Deschamps, Frédéric, Caramella, Caroline, Boige, Valérie, Ducreux, Michel, de Baere, Thierry, and Malka, David
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- 2018
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4. Cytoreductive Surgery plus HIPEC for Peritoneal Metastases from Colorectal Cancer
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Bhatt, Aditi and Goéré, Diane
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- 2016
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5. Major Hepatectomy for Colorectal Liver Metastases in Patients Aged Over 80: A Propensity Score Matching Analysis
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de Blasi, Vito, Memeo, Riccardo, Adam, René, Goéré, Diane, Cherqui, Daniel, Régimbeau, Jean-Marc, Rivoire, Michel, Perotto, Laura Ornella, Navarro, Francis, Sa Cunha, Antonio, Pessaux, Patrick, On~behalf~of~the~french~colorectal~liver~metastases~working~group, ~association~française~de~chirurgie, L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, CHU Strasbourg, Institut de Recherche Contre les Cancers de l'Appareil Digestif-European Institute of Telesurgery (IRCAD/EITS), Hôpital Paul Brousse, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse, Institut Gustave Roussy (IGR), CHU Amiens-Picardie, CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hôpital Paul Brousse-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), and Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
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Male ,Adult ,medicine.medical_specialty ,Colorectal cancer ,medicine.medical_treatment ,[SDV]Life Sciences [q-bio] ,030230 surgery ,Gastroenterology ,Metastasis ,03 medical and health sciences ,Liver metastases ,0302 clinical medicine ,Elderly ,Internal medicine ,80 and over ,Medicine ,Humans ,Hepatectomy ,In patient ,Propensity Score ,Selection Bias ,Aged ,Aged, 80 and over ,business.industry ,Liver Neoplasms ,Perioperative ,Middle Aged ,medicine.disease ,3. Good health ,030220 oncology & carcinogenesis ,Propensity score matching ,Cohort ,Surgery ,Female ,Morbidity ,business ,Colorectal Neoplasms ,Major hepatectomy - Abstract
Background: The aim of this study was to evaluate the results of major hepatectomies for metastasis in elderly colorectal cancer patients, for whom limited data exist in the literature. Methods: From January 2006 to January 2013, 3,034 patients underwent hepatectomy for colorectal liver metastasis in 32 French surgical centers. Repeat hepatectomies were excluded from the study. Based on a 1: 4 propensity score matching model, 42 patients aged ≥80 (OG) were matched with 168 patients Results: The unmatched cohort consisted of 744 patients (OG: n = 42; YG: n = 702). After PS matching, there was no difference in terms of general morbidity, rates of Dindo-Clavien score ≥III (OG: 16% vs. YG: 21%, p = 0.663), surgical morbidity (OG: 16% vs. YG: 21%, p = 0.663), reoperation (OG:10% vs. YG: 5%, p = 0.263), 90-day mortality (OG: 0% vs. YG:2%, p = 1), and total median hospital stay (OG: 12 vs. YG: 12, p = 0.972). Both groups experienced similar 3- and 5-year overall survival (82 and 82% OG vs.78 and 67% YG) and disease-free survival (40 and 35% OG vs. 45 and 35% YG at 3 and 5 years). Conclusions: No difference in perioperative and postoperative outcomes and disease-free and overall survival was found. Major hepatectomy in selected octogenarian patients is safe and feasible.
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- 2018
6. Ninety percent of the adverse outcomes occur in 10% of patients: can we identify the populations at high risk of developing peritoneal metastases after curative surgery for colorectal cancer?
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Honoré, Charles, Gelli, Maximiliano, Francoual, Julie, Benhaim, Léonor, Elias, Dominique, and Goéré, Diane
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COLON cancer treatment ,PERITONEAL cancer ,OVARIAN cancer ,MUCINOUS adenocarcinoma ,CURATIVE medicine ,CANCER treatment - Abstract
Background:Peritoneal metastases (PM) occur in 3.4–6.3% after curative surgery for non-metastatic colorectal cancer. Systematic “2nd look” surgery helps overcoming the diagnostic problem but can be only proposed to selected patients. The aim of this study was to update the knowledge on risk factors of developing PM after curative surgery for colorectal cancer. Methods:A systematic review of the literature published between 2011 and 2016 was made, searching for all clinical studies reporting the incidence of recurrent PM after curative surgery for colorectal cancer and factors associated with the primary tumour that were likely to influence this recurrence rate. Results:Seven new clinical studies were considered informative for risk factors and added to the 16 reviewed in 2013. Even if the level of evidence was low, data suggested rates of recurrent PM at 1 year between 54% and 71% after completely resected synchronous PM, between 62% and 71% after resection of isolated synchronous ovarian metastases, of 27% after surgery for a perforated primary tumour, of 16% after surgery for a pT4 tumour, and between 11% and 36% after surgery for a mucinous histological subtype. No new risk factor was identified. Conclusions:Evidence regarding the incidence of recurrent PM after curative surgery for colorectal cancer is poor. Situations at higher risk of recurrent PM are synchronous PM, synchronous isolated ovarian metastases, perforated primary tumour with serosa invasion and mucinous histological subtype. [ABSTRACT FROM AUTHOR]
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- 2017
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7. Prognostic Similarities and Differences in Optimally Resected Liver Metastases and Peritoneal Metastases From Colorectal Cancers.
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Elias, Dominique, Faron, Matthieu, Iuga, Bogdan Stan, Honor'e, Charles, Dumont, Fr'ed'eric, Bourgain, Jean-Louis, Dartigues, Peggy, Ducreux, Michel, and Goéré, Diane
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- 2015
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8. Therapeutic efficiency of everolimus and lapatinib in xenograft model of human colorectal carcinoma with KRAS mutation.
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Chu, Céline, Noël‐Hudson, Marie‐Sophie, Boige, Valérie, Goéré, Diane, Marion, Sylvie, Polrot, Mélanie, Bigot, Ludovic, Gonin, Patrick, Farinotti, Robert, and Bonhomme‐Faivre, Laurence
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XENOGRAFTS ,IMMUNOGLOBULINS ,TRANSPLANTATION of organs, tissues, etc. ,CANCER patients ,CANCER treatment - Abstract
KRAS mutation is a negative predictive prognostic factor during metastatic colorectal cancer treatment with antiepidermal growth factor receptor antibodies. For affected patients, new therapeutics must be explored. Our objective was to study efficacy of two drugs with different mechanisms of action, everolimus (mTOR inhibitor) and lapatinib (tyrosine kinase inhibitor), in a mouse xenograft model. We chose a model obtained after engraftment of a tumor originating from a human tumor collection. The patient was affected by a metastasis colorectal carcinoma resistant to cetuximab with KRAS mutation. From a previous study in mice, we know that everolimus is a P-glycoprotein (P-gp) substrate and that a lapatinib pretreatment increases significantly (2.6-fold) everolimus AUC by inhibiting its intestinal P-gp efflux. We hence tested the effect of these drugs alone or combined. Mice bearing the xenografts were divided in four groups: control, lapatinib, everolimus, and L/E group (L/E: 2 days of lapatinib 200 mg/kg and then 3 days of everolimus 1 mg/kg). Tumor volumes and treatment toxicities were evaluated. Sixteen days after treatment initiation, the group L/E was the first one in which tumor volume average was significantly lower than the one of control group (193 ± 90 vs. 395 ± 171 mm
3 ; P = 0.0025). After 4 weeks of treatment, inhibition of tumor growth in lapatinib, everolimus, and L/E groups reached, respectively, 49, 53, and 57%. Each drug showed significant antitumor activity. Only moderate hematologic toxicity signs were observed. These results lead to new perspectives for new oral drugs in metastatic KRAS-mutated colorectal cancer resistant to standard chemotherapy. [ABSTRACT FROM AUTHOR]- Published
- 2013
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9. Incidence and prognosis of synchronous colorectal carcinomatosis.
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Goéré, Diane, Allard, Marc-Antoine, Honoré, Charles, Dumont, Frédéric, and Elias, Dominique
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- 2013
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10. Complete Radiological Response of Colorectal Liver Metastases after Chemotherapy: What Can We Expect?
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Gaujoux, Sébastien, Goéré, Diane, Dumont, Frédéric, Souadka, Amine, Dromain, Clarisse, Ducreux, Michel, and Elias, Dominique
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DRUG therapy , *METASTASIS , *RADIOLOGY , *TOMOGRAPHY , *MAGNETIC resonance imaging , *COLON cancer , *CANCER patients - Abstract
Missing metastases, also called vanishing or disappearing liver metastases, concern about 5% of patients with colorectal liver metastasis undergoing chemotherapy, and this phenomenon is likely to become more frequent in the near future, with the widespread use of highly efficient chemotherapy. As their definition is highly dependent on the quality of initial imaging, a DLM on preoperative computed tomography scan should be systematically confirmed by a second imaging modality, ideally magnetic resonance imaging. It is important to note that a complete clinical response does not mean a complete pathologic response. Currently, there are no absolute criteria of a complete pathologic response. However, treatment with neoadjuvant and adjuvant hepatic arterial infusion in patients <60 years old with an initially low carcinoembryonic antigen level that normalizes under chemotherapy and who have no detectable lesion on both computed tomography and magnetic resonance imaging is probably more likely to yield a complete pathologic response. Whatever their treatment, patients with DLM run a high risk of recurrence that could be decreased with the use of HAI. Despite a high recurrence rate, the overall 5-year survival rate of patients with DLM ranges from 40 to 80%. Having a DLM should no longer be a contraindication to hepatic surgery since long-term survival is expected in these highly chemosensitive patients. The use of adjuvant HAI in addition to efficient systemic chemotherapy could reduce the risk of hepatic relapse. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]
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- 2011
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11. Hepatic arterial oxaliplatin plus intravenous 5-fluorouracil and cetuximab for first-line treatment of colorectal liver metastases: A multicenter phase II trial.
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Malka, David, Verret, Benjamin, Faron, Matthieu, Guimbaud, Rosine, Caramella, Caroline, Edeline, Julien, Galais, Marie-Pierre, Bengrine-Lefevre, Leïla, Smith, Denis, Dupont-Bierre, Eric, De Baere, Thierry, Goéré, Diane, Dartigues, Peggy, Lacroix, Ludovic, Boige, Valérie, Gelli, Maximiliano, Pignon, Jean-Pierre, and Ducreux, Michel
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HEPATIC artery , *DRUG efficacy , *RESEARCH , *FOLINIC acid , *DISEASE progression , *INTRAVENOUS therapy , *LIVER tumors , *DRUG tolerance , *CONFIDENCE intervals , *CLINICAL trials , *ONCOGENES , *MONOCLONAL antibodies , *METASTASIS , *ANTINEOPLASTIC agents , *FLUOROURACIL , *COLORECTAL cancer , *CANCER patients , *DESCRIPTIVE statistics , *OXALIPLATIN , *PROGRESSION-free survival , *INTRA-arterial infusions , *DRUG toxicity , *ABLATION techniques , *LONGITUDINAL method , *OVERALL survival , *EVALUATION - Abstract
The efficacy and tolerability of hepatic arterial infusion (HAI) oxaliplatin plus systemic 5-fluorouracil and cetuximab as frontline treatment in patients with colorectal liver metastases (CRLM) are unknown. In this multicenter, single-arm phase II study, patients with CRLM not amenable to curative-intent resection or requiring complex/major liver resection, and no prior chemotherapy for metastatic disease, received HAI oxaliplatin and intravenous 5-fluorouracil, leucovorin and cetuximab, every two weeks until disease progression, limiting toxicity or at least 3 months after complete response or curative-intent resection/ablation. The primary endpoint was overall response rate (ORR). 35 patients, mostly with bilateral (89%), multiple CRLM (>4, 86%; >10, 46%) were enrolled in eight centers. The ORR was 88% (95% CI, 71%−96%) among evaluable patients (n = 32), and 95% (95% CI 70–100%) among the 22 wild-type RAS/BRAF evaluable patients. After a median follow-up of 8.8 years (95% CI, 8.7-not reached), median progression-free survival was 17.9 months (95% CI, 15–23) and median overall survival (OS) was 46.3 months (95% CI, 40.0-not reached). 23 of the 35 patients (66%), including 22 (79%) of the 25 patients with wild-type RAS tumor, underwent curative-intent surgical resection and/or ablation of CRLM. HAI catheter remained patent in 86% of patients, allowing for a median of eight oxaliplatin infusions (range, 1–19). Treatment toxicity was manageable, without toxic death. HAI oxaliplatin plus systemic 5-fluorouracil and cetuximab appears highly effective in the frontline treatment of patients with unresectable CRLM and should be investigated further. • First Phase 2 study of hepatic arterial oxaliplatin plus systemic LV5FU2-cetuximab. • Patients with colorectal liver metastases, unresectable or requiring major surgery. • ORR was 88% (95% in wild-type RAS/BRAF patients). • 66% of the patients had sufficient response to undergo secondary resection. • Median PFS and OS were 17.9 and 46.3 months. [ABSTRACT FROM AUTHOR]
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- 2023
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12. Peritoneal and extraperitoneal relapse after previous curative treatment of peritoneal metastases from colorectal cancer: What survival can we expect?
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Gelli, Maximiliano, Huguenin, Janina F.L., de Baere, Thierry, Benhaim, Léonor, Mariani, Antoine, Boige, Valerie, Malka, David, Sourouille, Isabelle, Ducreux, Michel, Elias, Dominique, and Goéré, Diane
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COLON tumors , *CANCER relapse , *PERITONEUM tumors , *COMBINED modality therapy , *LONGITUDINAL method , *METASTASIS , *MULTIVARIATE analysis , *REGRESSION analysis , *OPERATIVE surgery , *SURVIVAL , *TREATMENT effectiveness , *PROPORTIONAL hazards models , *KAPLAN-Meier estimator , *ODDS ratio , *DIAGNOSIS , *PROGNOSIS , *TUMOR treatment ,RECTUM tumors - Abstract
Introduction Over the last 20 years, complete cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) dramatically increased the survival of patients with colorectal peritoneal metastases (CRPM). However, despite better knowledge of the disease, around 70% of patients relapse after CRS with HIPEC. This study was designed to analyse the pattern of recurrence and the outcomes of different treatment modalities. Methods Patients relapsing after CRS plus HIPEC for CRPM were selected from a prospective database. The impact of iterative curative-intent treatments was analysed using Kaplan–Meier estimates and multivariate Cox regression models. Results Between April 1993 and December 2014, 190 of 274 (69%) patients previously treated by CRS plus HIPEC developed relapse, as an isolated peritoneal recurrence (31%), isolated distant recurrence (35%), or multisite recurrence (34%). The curative-intent treatment rate was 48% for isolated peritoneal recurrences, 49% for isolated distant recurrences and 22% for multisite recurrences (p = 0.002). From the diagnosis of relapse, 3- and 5-year overall survival were 77% and 46% after curative-intent treatment and 14% and 4.7% after non-curative treatment, with median survival of 59.7 and 18.3 months (log-rank p < 0.0001), respectively. Regression analysis identified the initial extent of CRPM (hazard ratio [HR]: 2.25; p < 0.0001), iterative curative-intent treatment (HR: 0.22; p < 0.0001) and disease-free interval (HR: 1.77; p = 0.01) as independent predictors of prolonged survival. Conclusions Iterative curative-intent treatment can be performed in up to 40% of patients with relapse after CRS and HIPEC for CRPM, and is associated with prolonged survival in selected patients. [ABSTRACT FROM AUTHOR]
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- 2018
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13. Apport de l'imagerie en fluorescence au vert d'indocyanine dans le staging et le traitement du cancer colorectal
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Liberale, Gabriel, Donckier De Donceel, Vincent, Bergmann, Pierre, Flamen, Patrick, Remmelink, Myriam, Van Laethem, Jean-Luc, Ceelen, Wim, and Goéré, Diane
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ICG ,Staging ,Vert d'indocyanine ,Carcinose péritonéale ,Colorectal cancer ,Fluorescence imaging ,Optical imaging ,Cancérologie ,Cancer colorectal ,Ganglion sentinelle ,Imagerie en fluorescence ,Imagerie médicale, radiologie, tomographie ,Sentinel lymph node ,Peritoneal carcinomatosis ,lymph node metastases - Abstract
Résumé:IntroductionLa chirurgie reste le seul traitement à visée curative pour les patients porteurs d’un cancer colorectal (CCR) primitif ou métastatique. L’établissement précis de l’extension de la maladie, au niveau de la tumeur primitive, des ganglions loco-régionaux et des métastases à distance représente un élément essentiel pour la prise en charge thérapeutique. Les ganglions locorégionaux et la technique du ganglion sentinellePour les patients présentant un CCR non métastatique, l’analyse pathologique des ganglions (pN) conditionne la décision d’administrer ou non une chimiothérapie adjuvante. Les patients présentant un envahissement ganglionnaire (pN+) recevront un traitement adjuvant, celui-ci n’étant le plus souvent pas indiqué chez les patients sans envahissement ganglionnaire (pN0). Près de 20 à 30% des patients classés pN0 vont cependant développer des récidives tumorales. Parmi ces patients, il est probable qu’une partie ait été sous-classée au moment du diagnostic. La technique du ganglion sentinelle (GS) permet d’identifier les ganglions les plus susceptibles d’être envahis et de réaliser des analyses anatomopathologiques plus approfondies sur un nombre plus limité d’échantillon. Cette technique est recommandée dans le cancer du sein et dans le mélanome, mais son rôle reste discuté dans le CCR. Le premier volet de cette thèse concerne les résultats d’études cliniques que nous avons menées pour évaluer le rôle de la technique du GS au bleu patenté (BP) et de l’imagerie en fluorescence (IF) au vert d’indocyanine ou indocyanine green (ICG) dans le staging ganglionnaire des patients présentant un CCR. Les principaux objectifs de ces travaux étaient d’évaluer la faisabilité de ces techniques et leur apport dans le staging des patients présentant un CCR.Notre première étude sur la technique du GS au BP, représentant la plus grande cohorte monocentrique européenne, a permis de démontrer la faisabilité de la technique. En outre, cette approche a modifié le geste chirurgical dans 12% des cas (technique in vivo) et a permis de reclasser 10% des patients initialement classés pN0 en pN+ par la réalisation de coupes sériées spécifiquement réalisées sur les ganglions démontrés comme GS. Dans une seconde étude sur la technique du GS comparant l’IF-ICG à la technique au BP, nous avons montré que ces 2 techniques étaient complémentaires, permettant d’augmenter la sensibilité globale pour la détection des métastases ganglionnaires. De plus, l’IF-ICG apparaît comme plus sensible chez les patients présentant une surcharge pondérale. En termes de sensibilité, la recherche du GS par IF est supérieure à la technique BP, ces résultats restant cependant limités, notamment en raison d’un taux élevé de faux négatifs (FN) pour les tumeurs localement avancées (pT3-4). Les métastases ganglionnaires et la carcinose péritonéaleDans le CCR, les patients métastatiques, présentant une carcinose péritonéale (CP) et/ou un envahissement ganglionnaire, ont un pronostic sombre. La chirurgie d’exérèse de la CP associée à une chimiothérapie hyperthermique intrapéritonéale (CHIP) et la réalisation de curages ganglionnaires chez les patients porteurs d’une maladie oligométastatique permettent toutefois d’obtenir des survies prolongées et parfois des guérisons, avec des résultats similaires à ceux observés chez les patients opérés pour métastases hépatiques isolées. Pour la CP, l’étendue de la maladie et la radicalité de la résection sont les principaux facteurs pronostiques de survie. La sensibilité des examens d’imagerie conventionnelle et métabolique reste cependant faible pour déterminer l’extension de la maladie péritonéale. L’évaluation de l’étendue de la CP et son exérèse sont donc essentiellement fondées sur la palpation et l’exploration visuelle réalisée durant l’intervention chirurgicale, représentant un facteur limitant pour la radicalité de la chirurgie. De façon similaire, chez les patients présentant une maladie métastatique ganglionnaire limitée, la détection peropératoire est souvent difficile, nécessitant la réalisation de curages étendus de principe, afin de s’assurer de l’exérèse des ganglions pathologiques.L’utilisation de l’IF après injection iv intra-opératoire d’ICG a été rapportée comme une technique permettant la détection de tissu tumoral tant visible que non visible (infraclinique), pouvant potentiellement aider le chirurgien et guider les gestes de résection. Aucune étude n’avait particulièrement analysé le rôle de l’IF-ICG dans la détection de CP et de métastases ganglionnaires de CCR. Le second volet de cette thèse concerne l’évaluation de l’apport de l’IF après injection iv d’ICG pour la détection de la CP et des métastases ganglionnaires dans le CCR. L’objectif primaire était de vérifier si les métastases péritonéales (MP) et ganglionnaires visibles par le chirurgien étaient effectivement détectées par l’IF-ICG peropératoire. En parallèle, nous avons évalué si l’IF-ICG permettait de détecter une maladie infraclinique, non détectée par le chirurgien dans les conditions habituelles. La première étude de cette seconde partie a permis de montrer que les MP étaient visualisées comme hyperfluorescentes à l’IF-ICG pour autant qu’elles ne soient pas d’origine mucineuse. De plus, l’IF-ICG a permis de détecter des MP non visualisées en lumière visible, permettant d’adapter le geste chirurgical et d’augmenter la radicalité de la résection dans près de 38% des cas. Dans une seconde étude, nous avons rapporté que la technique d’IF utilisée in vivo et ex vivo après injection iv d’ICG permettait d’identifier des ganglions métastatiques, détectés ou non par les imageries conventionnelles et métaboliques préopératoires. Les résultats de cette étude constituant une preuve de concept ont été ensuite confirmés dans une étude rétrospective réalisée sur l’analyse ex vivo des ganglions de patients ayant reçu une injection iv d’ICG. Dans ce travail, nous avons montré que les ganglions envahis étaient plus fluorescents que les ganglions non envahis. Toutefois, cette preuve de concept doit encore être confirmée et évaluée plus largement dans une étude prospective. Ces 2 travaux montrent donc le bénéfice potentiel de l’utilisation de l’IF après injection iv d’ICG à 2 niveaux, pour guider la chirurgie en améliorant la détection peropératoire des sites métastatiques infracliniques et pour guider l’analyse histologique, en identifiant des ganglions fluorescents sur la pièce de résection, permettant une étude anatomopathologique plus ciblée et plus approfondie. Conclusions et perspectivesNos travaux sur la recherche du GS dans le CCR par la technique au BP et à l’IF-ICG ont montré que ces techniques étaient faisables mais que leurs sensibilités restaient limitées, en particulier chez les patients porteurs de tumeurs localement avancées. Dans la CP d’origine colorectale, nous avons montré que l’IF-ICG permettait d’améliorer la stadification de la CP des patients opérés de métastases péritonéales non mucineuses, de révéler des lésions non visibles dans les conditions standards et d’améliorer la radicalité de la chirurgie. Pour la détection de ganglions métastatiques, nous avons montré que l’IF-ICG permettait, in vivo, de détecter des ganglions infracliniques durant l’intervention et ex vivo, de guider l’analyse anatomopathologique de la pièce de résection. Enfin, nous pensons que ces observations pourraient nous permettre d’élaborer un nouveau concept de GS systémique par opposition au GS classique correspondant aux ganglions de drainage anatomique de la tumeur. Nous proposons que les capacités particulières de rétention de l’ICG dans les tissus cancéreux après injection par voie systémique pourraient permettre d’identifier des sites ganglionnaires métastatiques en dehors des sites de drainage révélés par les injections de marqueurs au sein ou en périphérie de la tumeur elle-même. Pour vérifier cette hypothèse, nous avons élaboré un nouveau protocole d’une étude clinique prospective dans laquelle la détection du GS systémique après injection iv d’ICG sera comparée aux résultats obtenus suite à l’injection péritumorale de BP. Les ganglions révélés par ces 2 techniques seront recherchés ex vivo sur la pièce de résection et analysés en anatomopathologie. Outre la démonstration de métastases ganglionnaires extra-anatomiques, nous pensons que cette approche systémique pourrait permettre de réduire le taux de FN observé suite à une injection péritumorale, notamment pour les tumeurs localement avancées, celles-ci pouvant perturber le drainage lymphatique selon les voies anatomiques. Summary:This thesis reports several clinical research works on the role of indocyanine green (ICG) fluorescence imaging (FI) for the detection of colorectal tumoral tissue. We first evaluate and compare the role of ICG-FI in the detection of sentinel lymph node (SLN) in colorectal cancer (CRC) in view to upstage patients. We have reported that both techniques (blue dye and ICG-FI) are similar in term of sensitivity with a high rate of false negative results. Therefore, we think that new approaches for SLN detection should be developped in CRC. Secondarily, we evaluate the role of ICG-FI after IV ICG injection for the detection of peritoneal carcinomatosis (PC) from CRC origin. We have reported that ICG-FI is able to detect non-mucinous PM with a sensitivity of 86%. Moreover, ICG-FI was able to guide surgery modifying the surgical procedure in 38% of patients. Thirdly, we investigate the role of ICG-FI for the detection lymph node (LN) metastases. We have reported that ICG-FI performed after IV ICG injection is able to detect LN metastases both in vivo and ex vivo. These findings have been confirmed in a retrospective study. Fiinally, we propose a new protocol to evaluate a new approach for SLN detection. In comparison with the standard technique using peritumoral injection, we propose a new approach using systemic (intravenous) ICG injection. We have called this approach the 'systemic' SLN detetion. This approach will be compared with the standard one using peritumoral blue dye injection. Sensitivity, specificity of both technique will be compared. In conclusion, the results of these preliminary clinical studies using ICG-FI for tumoral staging and treatment are encouraging and further larger studies should be performed., Doctorat en Sciences médicales (Médecine), info:eu-repo/semantics/nonPublished
- Published
- 2017
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