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

Co-engineering participatory water management processes: theory and insights from Australian and Bulgarian interventions

Broad-scale, multi-governance level, participatory water management processes intended to aid collective decision making and learning are rarely initiated, designed, implemented, and managed by one person. These processes mostly emerge from some form of collective planning and organization activities because of the stakes, time, and budgets involved in their implementation. Despite the potential importance of these collective processes for managing complex water-related social-ecological systems, little research focusing on the project teams that design and organize participatory water management processes has ever been undertaken. We have begun to fill this gap by introducing and outlining the concept of a co-engineering process and examining how it impacts the processes and outcomes of participatory water management. We used a hybrid form of intervention research in two broad-scale, multi-governance level, participatory water management processes in Australia and Bulgaria to build insights into these coengineering processes. We examined how divergent objectives and conflict in the project teams were negotiated, and the impacts of this co-engineering on the participatory water management processes. These investigations showed: (1) that language barriers may aid, rather than hinder, the process of stakeholder appropriation, collective learning and skills transferal related to the design and implementation of participatory water management processes; and (2) that diversity in co-engineering groups, if managed positively through collaborative work and integrative negotiations, can present opportunities and not just challenges for achieving a range of desired outcomes for participatory water management processes. A number of areas for future research on co-engineering participatory water management processes are also highlighted

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

Guelb el Ahmar (Bathonian, Anoual Syncline, eastern Morocco): First continental flora and fauna including mammals from the Middle Jurassic of Africa

We report the discovery in Mesozoic continental “red beds” of Anoual Syncline, Morocco, of the new Guelb el Ahmar (GEA) fossiliferous sites in the Bathonian Anoual Formation. They produced one of the richest continental biotic assemblages from the Jurassic of Gondwana, including plants, invertebrates and vertebrates. Both the sedimentological facies and the biotic assemblage indicate a lacustrine depositional environment. The flora is represented by tree trunks (three families), pollen (13 species, five major clades) and charophytes. It suggests local forests and humid (non-arid) conditions. The vertebrate fauna is dominated by microvertebrates recovered by screening–washing. It is rich and diverse, with at least 29 species of all major groups (osteichthyans, lissamphibians, chelonians, diapsids, mammals), except chondrichthyans. It includes the first mammals discovered in the Middle Jurassic of Arabo-Africa. The GEA sites yielded some of the earliest known representatives of osteoglossiform fishes, albanerpetontid and caudate amphibians, squamates (scincomorphans, anguimorphan), cladotherian mammals, and likely choristoderes. The choristoderes, if confirmed, are the first found in Gondwana, the albanerpetontid and caudatan amphibians are among the very few known in Gondwana, and the anguimorph lizard is the first known from the Mesozoic of Gondwana. Mammals (Amphitheriida, cf. Dryolestida) remain poorly known, but are the earliest cladotherians known in Gondwana. The GEA biotic assemblage is characterized by the presence of Pangean and Laurasian (especially European) taxa, and quasi absence of Gondwanan taxa. The paleobiogeographical analysis suggests either a major fossil bias in Gondwana during the Middle Jurassic, and an overall vicariant Pangean context for the GEA assemblage, or alternatively, noticeable Laurasian (European) affinities and North-South dispersals. The close resemblance between the Bathonian faunas of GEA and Britain is remarkable, even in a Pangean context. The similarity between the local Anoual Syncline Guelb el Ahmar and Ksar Metlili faunas raises questions on the ?Berriasian age of the latter