[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Currently there is no reliable technique for predicting clinical or pathologic complete tumor response after radiochemotherapy (RCT) in patients with rectal cancer. We applied reverse phase protein microarray (RPMA) technology to find a signal pathway that may predict the response to preoperative treatment. PATIENTS AND METHODS: Fifteen rectal cancer samples were collected during preoperative RCT. Seven patients had a good response to preoperative therapy (Mandard grade I-II) and 8 patients had a poor response (Mandard grade III-V). Using laser capture microdissection (LCM) and RPMA analysis, we measured the phosphorylation level of nearly 80 end points and analyzed the signaling pathways. RESULTS: We identified 4 signaling proteins whose phosphorylation levels were significantly different (P < .05) between the good vs. poor responders; CHK2 and β-catenin were more highly phosphorylated in poor responders, whereas PDK1 and glycogen synthase kinase (GSK)-3α/β had lower phosphorylation levels in poor responders. Interestingly GSK-3α/β, β-catenin, and PDK1 are all present in the phosphatidylinositol-3-kinase (PI3K)-AKT signaling pathway. CONCLUSIONS: Based on our results, we hypothesize that the activating state of the PI3K-AKT pathway can stratify patients who could benefit most from neoadjuvant treatment. Moreover, identification of theranostic targets has the potential to pinpoint new therapeutic strategies for the nonresponsive population.
Clinical Colorectal Cancer 06/2012; · 1.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although surgery is the gold standard treatment of hepatic metastasis from colorectal cancer (CRC), many patients ultimately die of their disease. We tested the hypothesis that the detection of circulating tumor cells (CTC) might identify patients at high risk of dying of disease recurrence after apparently radical liver surgery.
We considered 50 patients undergoing radical surgery for liver-confined hepatic metastasis from CRC. The expression of a panel of cancer-related genes, as assessed by quantitative real-time PCR, was used to detect CTC in the peripheral blood of these patients immediately before surgery. Survival analysis was performed by the Cox regression model.
Univariate analysis of the expression levels of CD133 (a marker of colon cancer stem cells) and survivin (an antiapoptotic factor) resulted in statistically significant association with patient survival [hazard ratio (HR) 2.7, 95% confidence interval (CI) 1.9-3.7, P < 0.0001; and hazard ratio 2.1, 95% CI 1.4-3.2, P < 0.0001, respectively]. Remarkably, multivariate analysis found that only the transcriptional amount of CD133 resulted in statistical significance (HR 2.6, 95% CI 1.9-3.6, P < 0.0001), indicating that this biomarker can independently predict the survival of these patients.
CD133-positive CTC may represent a suitable prognostic marker to stratify the risk of patients who undergo liver resection for CRC metastasis, which opens the avenue to identifying and potentially monitoring the patients who are most likely to benefit from adjuvant treatments.
Annals of Surgical Oncology 11/2011; 19(2):402-8. · 4.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Liver metastases are the leading cause of death in patients with colorectal carcinoma: approximately 25% present with metastases at diagnosis of the primary tumor and 30-50% will eventually develop metastases. Surgical therapy for metastases is the only curative treatment that will ensure five-year survival in 30-60% of patients; however, in 30-50% of these patients liver disease will recur. To improve these rates, various different studies have investigated the efficacy of postsurgical adjuvant therapy. The majority of randomized studies evaluated the efficacy of intra-arterial infusion associated or not with postsurgical systemic adjuvant treatment: this approach demonstrated benefit in terms of control of recurrent of liver disease but not in terms of overall survival. A reduction in the recurrence of liver disease was found in the two randomized studies published to date on the efficacy of systemic adjuvant therapy, and an improvement in survival in one trial. Given these data and the results obtained with the use of last generation chemotherapeutic agents (oxaliplatin and irinotecan) in the treatment of unresectable liver metastases from colorectal carcinoma, it can be conjectured that ongoing randomized clinical trials may confirm a significant advantage of adjuvant chemotherapy in the control of recurrence of liver disease and overall survival.
[Show abstract][Hide abstract] ABSTRACT: The hypothesis was tested that systemic chemotherapy might contribute to improving overall survival (OS) of patients with unresectable colorectal liver metastases treated with hepatic arterial infusion (HAI).
We considered 153 consecutive patients retrospectively divided into group A (n=72) treated with HAI alone (floxuridine [FUDR] + leucovorin [LV]), and group B (n=81) treated with HAI combined with systemic chemotherapy (5-fluorouracil [5FU] + LV).
No significant difference in OS was observed between the two groups. Median OS was better in patients with <50% of liver involvement (21.3 vs. 13.2 months; p<0.0001) and in responders vs. non-responders (24.4 vs. 13.4 months; p<0.0001). The combination of low tumor load with good tumor response to HAI was the only variable retained on multivariate survival analysis, associated with a better clinical outcome (median OS: 34.2 months).
Our study does not support the use of FUDR-based HAI combined or not with 5FU-based systemic chemotherapy as the first-line therapeutic approach to unresectable colorectal cancer liver metastases. The identification of responsive patients would improve the therapeutic index of this HAI regimen.
Anticancer research 10/2009; 29(10):4139-44. · 1.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Le tronc coelio-mésentérique (TCM) est une variante anatomique très rare qui se caractérise par une origine commune du tronc coeliaque et de l'artère mésentérique supérieure à partir de l'aorte. Le TCM représente moins de 1% des variations anatomiques des artères splanchniques. L'anévrysme du TCM est une anomalie vasculaire encore plus rare et, à notre connaissance, seulement huit cas ont été rapportés dans la littérature. Nous décrivons l'observation d'un patient asymptomatique chez qui a été découvert de façon fortuite un anévrysme du TCM. Le diagnostic a été évoqué sur une radiographie du rachis dorso-lombaire et confirmé par un scanner et une artériographie. Malgré l'absence de symptôme, nous avons décidé un traitement chirurgical par anévrysmorraphie, en raison du risque potentiel de rupture.