Publications (3)28.58 Total impact
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Article: Biology and diagnosis of aberrant crypt foci.
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ABSTRACT: Aberrant crypt foci (ACFs) are clusters of colonic crypts that can be identified after staining and that have a different behaviour than the surrounding crypts. They have been hypothesized to be the potential precursors of colonic neoplastic lesions. Since they are detectable in vivo with endoscopic stains, they have been proposed as early biomarkers for colonic carcinogenesis. Our aim was to examine the literature regarding the role of ACFs in the pathogenesis of colorectal cancer (CRC). An intensive PubMed search was performed with the following terms: aberrant crypt foci, colorectal cancer, biomarker, carcinogenesis. Aberrant crypt foci have a variable prevalence and little is known about their natural history. They can be classified as hyperplastic or dysplastic. There is evidence that supports their role as preneoplastic lesions and features detectable by chromoendoscopy have been related to CRC risk. Moreover, ACFs have been shown to harbour genetic and epigenetic alterations common in adenomas and CRC. However, contradictory results have been obtained and difficulties in endoscopic detection and characterization have been described in large-scale studies. Despite the inconsistencies in ACF detection and characterization, several genetic and epigenetic changes common in both ACFs and CRC have been verified throughout the studies. This evidence is increasingly strong and it grows along with progress in the knowledge of carcinogenesis molecular pathways. Clinical application of ACFs as an intermediate endpoint for colorectal carcinogenesis is under development and a deeper knowledge of cancer mechanisms is needed before it can be applied or discarded.Colorectal Disease 12/2011; 14(4):e157-64. · 2.93 Impact Factor -
Article: Validation microsatellite path score in a population-based cohort of patients with colorectal cancer.
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ABSTRACT: Bethesda guidelines are used to recognize patients at risk for Lynch syndrome. However, obtaining personal and familial tumor data can sometimes be difficult. The Microsatellite Path Score (MsPath), a pathological score, based on age, tumor location, and pathologic features, has been developed to effectively predict colorectal cancer with DNA mismatch repair (MMR) deficiencies. However, the MsPath model's performance in an unselected, population-based colorectal cancer (CRC) population is unknown. We analyzed all patients with CRC regardless of age, personal or family history, and tumor characteristics from the EPICOLON study, an independent, prospective, multicenter, population-based cohort (N = 1,222). All patients underwent tumor microsatellite instability (MSI) analysis and immunostaining for MLH1/MSH2, and those with MMR underwent tumor BRAF mutation analysis and MLH1/MSH2 germline testing. All the pathologic features were centralized and evaluated blinded to the MMR status. MsPath score for prediction of having MSI high, with the recommended MsPath cutoff score ≥1.0, had a sensitivity, specificity, and positive predictive value (PPV) of 92.8% (95% CI, 86.9 to 98.3), 64.1% (95% CI, 61.1 to 66.8), and 15.8% (95% CI, 12.2 to 18.6), respectively. MsPath score had a sensitivity, specificity, and PPV of 81.8% (95% CI, 59.0 to 99.8), 60.6% (95% CI, 57.8 to 63.4), and 1.9% (95% CI, 0.7 to 3.1), respectively, for the identification of MLH1/MSH2 gene carriers. Application of the MsPath score, resulted in two (18%) of 11 mutation carriers being missed, both pathogenic germline MSH2 mutations. In the general nonselected population, the MsPath score accurately predicted the probability of bearing a MSI high CRC, but it was insufficiently accurate to use for the selection of patients warranting MLH1/MSH2 mutation testing in the setting of Lynch syndrome.Journal of Clinical Oncology 07/2011; 29(25):3374-80. · 18.37 Impact Factor -
Article: Endoscopic ultrasonography in patients with large gastric folds at endoscopy and biopsies negative for malignancy: predictors of malignant disease and clinical impact.
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ABSTRACT: The aims of the study were to assess in patients with large gastric folds at endoscopy and endoscopic biopsies that tested negative for malignancy: (i) the predictive variables of malignancy in endoscopic ultrasonography (EUS), (ii) the impact of EUS. Patients with this condition evaluated with radial EUS (following the standard study protocol of our Unit in these patients) during a 5-yr period were included. Nine variables were evaluated as possible predictors of malignancy (chi2, t-test, and logistic regression procedure) using pathology results, or a minimum of 2 yr of follow-up as gold standard. Likelihood ratios (LR), pre-EUS, and post-EUS probabilities for the diagnosis of malignancy were used to assess the clinical impact of the technique. Sixty-one patients were included (40 benign and 21 malignant). Predictive factors of malignancy were as follows: thickened gastric wall, thickened deep layers, impaired gastric distension, loss of the wall structure, and presence of ascites or lymph nodes, whereas the enlargement of superficial layers was a predictor of a benign condition. The enlargement of deep layers, as assessed by EUS was the only independent predictive factor for malignancy. When using this parameter, the pre-EUS probability of malignancy in our series (34%) increased up to 95% when EUS suggested malignancy (positive LR = 45), whereas it decreased to 4.7% when EUS precluded this diagnosis (negative LR = 0.102). (i) The enlargement of deep layers is the only independent predictive factor for malignancy in patients with large gastric folds at endoscopy and biopsies testing negative for malignancy and (ii) EUS has a high clinical impact in these patients.The American Journal of Gastroenterology 02/2006; 101(1):64-9. · 7.28 Impact Factor
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2011
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Hospital Clínic de Barcelona
Barcelona, Catalonia, Spain
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