SURGICAL APPROACH TO THE FAMILIAL ADENOMATOUS POLYPOSIS ACCORDING TO THE GENETIC BASIS

ABSTRACT Introduction Familial adenomatous polyposis (FAP) is an autosomic dominant syndrome defined by the presence of more than a hundred colonic adenomatous polyps. It results from germline mutations in APC gene. In FAP, the risk of malignant transformation is 100%, thus the need for prophylactic surgery is beyond question. Debate exists about which surgical technique should be carried out. Although, proctocolectomy with ileal pouch-anal anastomosis has been practiced more often, because of its postoperative complications and the impact on quality of life, other less extensive resections have been accomplished in some particular cases. Nowadays, there is a preference for individualized treatment, based upon genotype-phenotype correlations. Methods We present two cases showing different surgical treatment based on the location of the mutation within APC gene. Results CASE 1: A 28-year-old female with a family history of FAP was evaluated at the High Risk CRC Unit of our institution. A diagnostic colonoscopy was carried out in which more than 100 polyps were found along the whole length of the large bowel, including more than 20 in the rectum. Biopsies from some of them were reported as adenomatous polyps without dysplasia in any of them. A genetic analysis was carried out on her. A mutation in the APC gene was detected (exon 7, c.268 Gu003eT). Due to these clinical and molecular findings, she underwent prophylactic surgery, in which a proctocolectomy with ileal pouch-anal anastomosis was carried out. CASE 2: A 45- year-old male, with a medical history of only hypertension, osteochondrosis and gastroesophageal reflux disease, without any familial predisposition to cancer. He was examined in our institution because of nonspecific abdominal symptoms. A colonoscopy was carried out, which showed many polyps along the large bowel. In the rectum, only one lesion was found with same characteristics. Biopsies from some of them were reported as adenomatous polyps with several dysplasias. A mutation in the APC gene was detected (exon 1. c70cu003eT). The patient underwent total colectomy with ileorectal anastomosis, exceeding the rectal polyp. Conclusion Nowadays, it is recognised that a correlation might exist between the site of mutations in APC gene and clinical phenotype of FAP. Whilst, some mutations have been associated with the severity of colonic polyposis (case 1), others lead to attenuated forms of the disease (case 2). In the same way, the extracolonic manifestations of FAP, as upper intestinal tumors and desmoids, have also been correlated with the site of APC mutation. Therefore, the debate continuous about which operation should be carried out. Up to now, proctocolectomy was considered when u003e1000 polyps develop, a large number in the rectum, when rectal adenomas u003e3 cm are found, or when advanced histology appears. However, we support the idea that these recommendations should be completed with the consideration of the site of the mutations in the gene APC. This work was funded by the Spanish Fondo de Investigaciones Sanitarias (grant number FIS-PI10/0683).