The adenoma-carcinoma adenomasequence revisited: has the era of genetic tailoring finally arrived?

Ahnen DJ. Am J Gastroenterol. 2011 Feb;106(2):190-8. Epub 2011 Jan 25.

Histology of serrated polyps of the colon. A hyperplastic polyp (a) with serrated crypt borders in the upper two third of the crypt. A sessile serrated adenoma (b) with serrated architecture extending to the base of the crypt with dilated crypt lumen and flask- and L-shaped crypt lumens at the crypt bases. A sessile serrated adenoma with cytological dysplasia (c) with features of a sessile serrated adenoma on the right and a focus of classic dysplasia on the left.

Acta Gastroenterol Latinoam. 2011 Mar;41(1):10-6. [Colorectal cancer screening at Clínica Alemana, Santiago de Chile]. Silva Mde L, Santander R, Gobelet J, Valdivieso E, Ramírez MA, Sáenz R, Alarcón G, Elías S, Olivares L. INTRODUCTION: Colorectal cancer (CRC) incidence is rapidly increasing. It has been demonstrated that it can be prevented and cured when the diagnosis is made in early stages. OBJECTIVE: For this reason it is necessary to apply a screening program in asymptomatic patients. METHOD: Since 2003, we conducted a CRC screening plan called "Mes del Colon" at Clínica Alemana Santiago. A press and local diffusion campaign was designed. Open to the community CRC talks were scheduled. An ad hoc database was designed. An informed consent was available. Patients older than 50 years and high risk patients were included. Total colonoscopy and a medical interview after the procedure were included in the plan with favorable economic conditions. RESULTS: Since 2003, 1158 patients were included The 1.8% of them were excluded because of incomplete data or because they did not meet the inclusion criteria. The 54% of patients were women. Mean age was 58.4 years old and mean body mass index 25.5 kg/m2. Polipoid lesions were seen in 45% of the patients. Six (1%) of them were adenocarcinomas, 291 (57%) adenomas (98% tubular adenomas), 189 (37%) hyperplastic polyps and 25 (5%) miscellaneous lesions. In this series, the necessary number to investigate for 1 adenoma was 3.9. CONCLUSIONS: CRC prevention campaigns are needed due to the continuous increase of the incidence in our country. The detection of precursor or early lesions that are longstanding before becoming advanced cancer allows its treatment avoiding progression.

Colorectal cancer (CRC) remains a common and often lethal disease. The classic adenoma-carcinoma sequence was defined on histologic grounds but over the last 25 years, the molecular basis of this process has been progressively clarified. There are at least three distinct molecular pathways to CRC: the chromosomal instability (CIN) pathway is thought to be largely driven by mutational events in oncogenes and tumor suppressor genes, the microsatellite instability pathway is responsible for Lynch syndrome CRCs and is driven by mutations in one of the DNA mismatch repair genes, and the epigenetic pathway is thought to be driven in large part by hypermethylation-induced silencing of tumor suppressor-like genes. The molecular understanding of this sequence has had a profound impact on our understanding of the process(s) of colonic carcinogenesis and this understanding has begun to change the clinical care of patients with colonic polyps and cancer including changes in therapy of established CRCs (antiepidermal growth factor receptor antibody therapy is no longer offered to patients with mutant KRAS CRCs), identification of high-risk groups (diagnosis of Lynch syndrome by molecular analysis of CRCs) and the management of precursor lesions (identification of the serrated polyp pathway to CRC). Ahnen DJ. Am J Gastroenterol. 2011 Feb;106(2):190-8. Epub 2011 Jan 25.

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