Rectal cancer with synchronous unresectable metastases: arguments for therapeutic choice

Environ 4 000 patients sont pris en charge chaque année en France pour un cancer du rectum avec des métastases synchrones jugées non résécables en réunion de concertation pluridisciplinaire (RCP). Il n’existe pas de consensus sur la stratégie thérapeutique à proposer et parmi les trois options possibles, les critères de choix restent relativement imprécis. – La chirurgie première est certes le meilleur traitement pour contrôler les symptômes rectaux mais elle n’a pas démontré qu’elle augmentait la survie et la résécabilité secondaire des métastases par rapport aux autres options et comporte un risque de résection incomplète, de complications pouvant retarder ou empêcher la chimiothérapie, de progression accélérée de la maladie métastatique et de mortalité comprise entre 1 et 5 %. – La radio-chimiothérapie première suivie d’une chirurgie permet le contrôle des symptômes rectaux mais retarde la chimiothérapie pour les métastases qui dominent le pronostic ; elle expose aux mêmes risques de complications que la chirurgie première. – La chimiothérapie première nous paraît intéressante en absence de complications locales sévères (occlusion, hémorragie) ; elle est potentiellement efficace sur les métastases à distance qui conditionnent le pronostic et sur la tumeur primitive qui répond souvent de manière similaire ; elle ne fige pas la stratégie et offre la possibilité de l’adapter à chaque évaluation selon la réponse, la tolérance et les possibilités de résection (tumeur primitive et métastases). Dans tous les cas, il est fondamental de discuter ces dossiers au cas par cas en RCP pour adapter la stratégie thérapeutique aux caractéristiques du patient, de la tumeur primitive et de l’extension métastatique, ainsi qu’à la réponse obtenue aux traitements proposés successivement.Rectal cancers with synchronous unresectable metastases are diagnosed in about 4 000 patients. There is yet no consensus on the therapeutic strategy for these cases which must be discussed during multidisciplinary meeting. Three options are available and arguments of choice remain relatively weak. – First-line resection of the primary rectal tumour is indeed the best treatment to control rectal symptoms but it does not seem to improve survival and secondary resectability of metastases when compared to other options; moreover incomplete resection or complications may delay chemotherapy, accelerate the metastastic process and mortality rate ranges from 1 to 5%. – First-line radio-chemotherapy followed by surgery allows for controlling rectal symptoms but delays chemotherapy for metastases dominating the prognosis; it exposes the patients to the same morbidity and mortality as first-line surgery. – First-line chemotherapy is the third valid option in the absence of major rectal symptoms (occlusion, haemorrhage); chemotherapy is potentially efficient on distant metastases bearing a high prognosis impact and on the primary rectal tumour, which often has a similar response. First-line chemotherapy allows for adapting the therapeutic strategy after each evaluation according to the tumour response, side effects and possibility of resection (primary rectal tumour and metastases). In all cases, medical records of such patients should be discussed during a multidisciplinary meeting to adapt the therapeutic strategy to the patient’s characteristics, primary rectal tumor, metastases staging and evolution

Chemotherapy of advanced small-bowel adenocarcinoma: a multicenter AGEO study

Les adénocarcinomes de l’intestin grêle (AIG) sont des tumeurs rares et de mauvais pronostic à un stade avancé. Les données publiées concernant l’efficacité de la chimiothérapie palliative sont peu nombreuses. Le but de notre étude était d’évaluer l’efficacité et la tolérance de différents protocoles « modernes » de chimiothérapie et de comparer l’efficacité des chimiothérapies à base de sels de platine dans le traitement de première ligne des AIG avancés. Cette étude rétrospective multicentrique a inclus 93 patients (sexe masculin : 53 % ; âge médian : 56 ans ; site primitif duodénal : 53 %) avec un AIG avancé (métastatique : 86 %) traités par LV5FU2 (n = 10), FOLFOX (n = 48), FOLFIRI (n = 19) ou LV5FU2- cisplatine (n = 16). Le taux de toxicité grade 3-4 était significativement plus fréquent dans le groupe de patients traités par LV5FU2-cisplatine (75 %) comparativement aux autres groupes de patients (p = 0,001). Les médianes de survie sans progression (SSP) étaient de 7,7 ; 6,9 ; 6,0 et 4,8 mois (p = 0,16) et les médianes de survie globale (SG) étaient de 13,5 ; 17,8 ; 10,6 et 9,3 mois (p = 0,25) pour les quatre groupes de patients traités par LV5FU2, FOLFOX, FOLFIRI et LV5FU2-cisplatine, respectivement. En analyse multivariée, l’indice de performance OMS à 2 (p < 0,0001) ainsi que des taux élevés d’ACE (p = 0,02) et de CA 19-9 (p = 0,03) avant traitement étaient les seuls facteurs indépendants significativement associés à un mauvais pronostic. Dans le sous-groupe de patients traités par sels de platine, ceux qui ont reçu une chimiothérapie par FOLFOX avaient de meilleures SSP et SG que les patients traités par LV5FU2-cisplatine. En analyse multivariée, le traitement par FOLFOX était un facteur significatif et indépendant de survie prolongée en termes de SSP (p < 0,0001) et SG (p = 0,02). Ainsi, cette étude, la plus grande rapportée à ce jour, suggère d’une part que l’indice de performance OMS et les taux d’ACE et CA 19-9 avant traitement sont des facteurs pronostiques indépendants de survie et, d’autre part que la chimiothérapie par FOLFOX est le traitement de choix en première ligne des AIG avancés

Bevacizumab plus FOLFIRI or FOLFOX in chemotherapy-refractory patients with metastatic colorectal cancer: a retrospective study

<p>Abstract</p> <p>Background</p> <p>The anti-VEGF antibody bevacizumab associated with an irinotecan or oxaliplatin-based chemotherapy was proved to be superior to the chemotherapy alone in first or second line treatment of metastatic colorectal cancer (mCRC). However, it was reported to have no efficacy in 3^rdor later-line, alone or with 5FU. The aim of this study was to evaluate the activity of bevacizumab combined with FOLFIRI or FOLFOX in mCRC who have failed prior chemotherapy with fluoropyrimidine plus irinotecan and/or oxaliplatin.</p> <p>Methods</p> <p>Thirty one consecutive patients treated between May 2005 and October 2006 were included in this retrospective study. All of them have progressed under a chemotherapy with fluoropyrimidine plus irinotecan and/or oxaliplatin and received bevacizumab (5 mg/kg) in combination with FOLFIRI or simplified FOLFOX4 every 14 days.</p> <p>Results</p> <p>Ten patients (32.2%) had an objective response (1 CR, 9 PR) and 12 (38.8%) were stabilized. The response and disease control rates were 45.4% and 100% when bevacizumab was administered in 2^ndor 3^rdline and 25% and 55% in 4^thor later line respectively (p = 0.024 and p = 0.008). Among the patients who had previously received the same chemotherapy than that associated with bevacizumab (n = 28) the overall response rate was 35.7% and 39.3% were stabilized. Median progression free survival (PFS) and overall survival (OS) were of 9.7 and 18.4 months respectively. Except a patient who presented a hypertension associated reversible posterior leukoencephalopathy syndrome, tolerance of bevacizumab was acceptable. A rectal bleeding occurred in one patient, an epistaxis in five. Grade 1/2 hypertension occurred in five patients.</p> <p>Conclusion</p> <p>This study suggests that bevacizumab combined with FOLFOX or FOLFIRI may have the possibility to be active in chemorefractory and selected mCRC patients who did not receive it previously.</p

Transcriptomic Analysis of Human Retinal Detachment Reveals Both Inflammatory Response and Photoreceptor Death

Background Retinal detachment often leads to a severe and permanent loss of vision and its therapeutic management remains to this day exclusively surgical. We have used surgical specimens to perform a differential analysis of the transcriptome of human retinal tissues following detachment in order to identify new potential pharmacological targets that could be used in combination with surgery to further improve final outcome. Methodology/Principal Findings Statistical analysis reveals major involvement of the immune response in the disease. Interestingly, using a novel approach relying on coordinated expression, the interindividual variation was monitored to unravel a second crucial aspect of the pathological process: the death of photoreceptor cells. Within the genes identified, the expression of the major histocompatibility complex I gene HLA-C enables diagnosis of the disease, while PKD2L1 and SLCO4A1 -which are both down-regulated- act synergistically to provide an estimate of the duration of the retinal detachment process. Our analysis thus reveals the two complementary cellular and molecular aspects linked to retinal detachment: an immune response and the degeneration of photoreceptor cells. We also reveal that the human specimens have a higher clinical value as compared to artificial models that point to IL6 and oxidative stress, not implicated in the surgical specimens studied here. Conclusions/Significance This systematic analysis confirmed the occurrence of both neurodegeneration and inflammation during retinal detachment, and further identifies precisely the modification of expression of the different genes implicated in these two phenomena. Our data henceforth give a new insight into the disease process and provide a rationale for therapeutic strategies aimed at limiting inflammation and photoreceptor damage associated with retinal detachment and, in turn, improving visual prognosis after retinal surgery

Multi-trait genome-wide association study identifies new loci associated with optic disc parameters

A new avenue of mining published genome-wide association studies includes the joint analysis of related traits. The power of this approach depends on the genetic correlation of traits, which reflects the number of pleiotropic loci, i.e. genetic loci influencing multiple traits. Here, we applied new meta-analyses of optic nerve head (ONH) related traits implicated in primary open-angle glaucoma (POAG); intraocular pressure and central corneal thickness using Haplotype reference consortium imputations. We performed a multi-trait analysis of ONH parameters cup area, disc area and vertical cup-disc ratio. We uncover new variants; rs11158547 in PPP1R36-PLEKHG3 and rs1028727 near SERPINE3 at genome-wide significance that replicate in independent Asian cohorts imputed to 1000 Genomes. At this point, validation of these variants in POAG cohorts is hampered by the high degree of heterogeneity. Our results show that multi-trait analysis is a valid approach to identify novel pleiotropic variants for ONH

« Les projets d’ouvrages collectifs... c’est ce que je conteste le plus... »

Jean Mitry participe à l'entreprise d'Aristarco mais il n'y croit pas. Dans un entretien avec Marcel Oms il s'explique sur sa conception d'historien du cinéma individuel. Par ailleurs il rompt quelques lances méthodologiques avec Jacques Deslandes qui avait contesté sa démarche historiographique dans le cas d'une filmographie de Griffith.Jean Mitry takes part in Aristarco's project but he does not believe in it. In an interview with Marcel Oms, he explains his idea of the individual film historian. Besides this, he comments upon his methodological differences with Jacques Deslandes, who had criticised his historical methodology in the case of a filmography of D.W. Griffith

De l'origine des Ciné Clubs

Mitry Jean. De l'origine des Ciné Clubs. In: 1895, revue d'histoire du cinéma, n°3, 1987. pp. 7-14