Attenuated adenomatous polyposis of the large bowel: Present and future

Attenuated adenomatous polyposis(AAP) is a poorly understood syndrome, that can be defined as the presence of 10-99 synchronous adenomas in the large bowel, and it is considered a phenotypic variant of familial adenomatous polyposis(FAP). This definition has the advantage of simplicity, but it may include sporadic multiple adenomas of the large bowel at an extreme, or FAP cases on the other side. AAP shows a milder phenotype than FAP, with an older age of onset of adenomas and cancer, and less frequent extracolonic manifestations. AAP may be diagnosed as a single case in a family or, less frequently, it may be present in other family members, and it shows distinct pattern of inheritance. In less than 50% of cases, it may be caused by adenomatous polyposis coli(APC) or MUTYH mutations, referred to as APC-associated polyposis, inherited as an autosomal dominant trait, or MUTYH-associated polyposis, which shows an autosomal recessive mechanism of inheritance, respectively. Surveillance should rely on colonoscopy at regular intervals, with removal of adenomas and careful histological examination. When removal of polyps is not possible or advanced lesions are observed, the surgical approach is mandatory, being subtotal colectomy with ileo-rectal anastomosis the treatment of choice. Studies on this syndrome are lacking, and controversies are still present on many issues, thus, other clinical and genetic studies are requested.

Inflammatory pathways in the early steps of colorectal cancer development

Colorectal cancer is a major cause of cancer-related death in many countries.Colorectal carcinogenesis is a stepwise process which,from normal mucosa leads to malignancy.Many factors have been shown to influence this process,however,at present,several points remain obscure.In recent years some hypotheses have been considered on the mechanisms involved in cancer development,expecially in its early stages.Tissue injury resulting from infectious,mechanical,or chemical agents may elicit a chronic immune response resulting in cellular proliferation and regeneration.Chronic inflammation of the large bowel(as in inflammatory bowel diseases),has been associated with the subsequent development of colorectal cancer.In this review we examine the inflammatory pathways involved in the early steps of carcinogenesis,with particular emphasis on colorectal.Firstly,we describe cells and proteins recently suggested as central in the mechanism leading to tumor development.Macrophages and neutrophils are among the cells mostly involved in these processes and proteins,as cyclooxygenases and resolvins,are crucial in these inflammatory pathways.Indeed,the activation of these pathways establishes an oxidative and anaerobic microenvironment with DNA damage to epithelial cells,and shifting from an aerobic to an anaerobic metabolism.Many cellular mechanisms,such as proliferation,apoptosis,and autophagy are altered causing failure to control normal mucosa repair and renewal.