Matrix-comparative genomic hybridization from multicenter formalin-fixed paraffin-embedded colorectal cancer tissue blocks

<p>Abstract</p> <p>Background</p> <p>The identification of genomic signatures of colorectal cancer for risk stratification requires the study of large series of cancer patients with an extensive clinical follow-up. Multicentric clinical studies represent an ideal source of well documented archived material for this type of analyses.</p> <p>Methods</p> <p>To verify if this material is technically suitable to perform matrix-CGH, we performed a pilot study using macrodissected 29 formalin-fixed, paraffin-embedded tissue samples collected within the framework of the EORTC-GI/PETACC-2 trial for colorectal cancer. The scientific aim was to identify prognostic genomic signatures differentiating locally restricted (UICC stages II-III) from systemically advanced (UICC stage IV) colorectal tumours.</p> <p>Results</p> <p>The majority of archived tissue samples collected in the different centers was suitable to perform matrix-CGH. 5/7 advanced tumours displayed 13q-gain and 18q-loss. In locally restricted tumours, only 6/12 tumours showed a gain on 13q and 7/12 tumours showed a loss on 18q. Interphase-FISH and high-resolution array-mapping of the gain on 13q confirmed the validity of the array-data and narrowed the chromosomal interval containing potential oncogenes.</p> <p>Conclusion</p> <p>Archival, paraffin-embedded tissue samples collected in multicentric clinical trials are suitable for matrix-CGH analyses and allow the identification of prognostic signatures and aberrations harbouring potential new oncogenes.</p

Le foie bioartificiel interne

Le foie bioartificiel interne (FBAI), encore expérimental, peut représenter une alternative intéressante à la transplantation hépatique. Il a pour but de réaliser un foie auxiliaire transitoire, le temps d’obtenir la régénération du foie natif. Son principe repose sur la transplantation d’hépatocytes isolés immunoprotégés par macroencapsulation, à l’intérieur de l’organisme du receveur. Ces hépatocytes peuvent être allogéniques ou provenir d’animaux, et, dans ce cas, être préparés à la demande, sans recourir à des méthodes de conservation. Le péritoine est probablement le meilleur site d’accueil du FBAI. Dans le futur, le FBAI pourrait être proposé comme traitement de maladies métaboliques par déficit enzymatique ou de certaines insuffisances hépatiques aiguës ou chroniques avec encéphalopathie. Il pourrait être également un traitement transitoire en attente d’un greffon hépatique

Systemic cytotoxic and biological therapies of colorectal liver metastases: expert consensus statement

Systemic therapy for colorectal cancer liver metastases (CRLM) has undergone significant development in the past 15 years. Therapy regimens consisting of combinations of cytotoxic chemotherapeutic agents have demonstrated greater efficacy and contributed to a significant survival improvement. As the majority of patients who undergo resection for liver-only CRLM are at risk of disease recurrence and cancer-related death, combining resection with systemic therapy appears sensible. However, trial-based evidence is sparse to support this concept. Peri-operative FOLFOX has demonstrated a progression-free survival benefit in a single Phase III trial; the safety of chemotherapy and subsequent operations was acceptable and only a few patients showed initial progression. Chemotherapy-associated liver injury (CALI), including sinusoidal obstruction syndrome and steatohepatitis, has been observed after cytotoxic therapy, and should have implications for chemotherapy plans prior to hepatectomy. In general, pre-operative chemotherapy should not extend beyond 3 months. For patients with unresectable liver-only CRLM, a response to chemotherapy could establish resectability and should be considered an initial treatment goal. In patients with unresectable CRLM, oxaliplatin- or irinotecan-containing combinations represent the standard options, although single-agent choices may be appropriate for individual patients. The addition of bevacizumab carries the potential for a greater response and possibly for reduced CALI risks. In tumours without K-ras mutations, anti-epidermal growth factor receptor (EGFR) agents are also reasonable choices for a greater response and improved survival outcomes. It is crucial that all systemic CRLM treatment decisions include proper definitions of treatment goals and endpoints, and are derived based on appropriate multidisciplinary considerations for other potentially applicable local or regional modalities

Adjuvant therapy of poor prognosis colon cancer with levamisole: Results of an EORTC double‐blind randomized clinical trial

From 1978 to 1985, 297 patients were entered in a double‐blind randomized trial comparing levamisole to placebo as adjuvant therapy of Dukes' C carcinoma of the colon. Therapy consisted of from two to five tablets of 50 mg levamisole (or placebo) twice a week, depending on bodyweight for 1 year. Levamisole was generally well tolerated, with only four reversible cases of agranulocytosis reported among 129 patients. The trial failed to show a benefit of levamisole on disease‐free survival (P = 0·53) or on survival (P = 0·35). There was no difference between the two treatment groups in terms of number of disease relapses, sites of relapse, or time to relapse. The proportion of patients still alive at 5 years was 51 per cent (standard error, 5·5 per cent) in the levamisole group versus 39 per cent (standard error, 5·4 per cent) in the placebo group. Copyright © 1989 British Journal of Surgery Society Ltd.SCOPUS: ar.jFLWNAinfo:eu-repo/semantics/publishe