The core of the clinical and diagnostic problem is the nature of APC gene itself. The APC gene is a germline mutation, which means there is a wide possibility that the mutation will find expression not only in intestinal but also in extra-intestinal sites including the thyroid, pancreas and duodenum, adrenal glands and liver. Such variability in clinical manifestation of the same genetic disorder represents real problems for physicians in terms of the right initial diagnosis, therapeutic options, follow-up and need for accurate clinical surveillance of the relatives.
The classical intestinal syndrome has a specific and more or less severe pattern including intestinal bleeding, abdominal pain, diarrhoea, mucous discharge. A patient reporting these symptoms usually refers to the family doctor and then will be sent to a gastrointestinal unit for a visit or colonoscopy. What a surprise for the endoscopist and for the patient as well in discovering hundreds of polyps along the colon.
The presence of a hypercatabolic balance with weight loss, anaemia and intestinal obstruction makes the development of a neoplasia suspicious and approximately 25% of patients present colorectal cancer at first diagnosis . Moreover, the risk of developing a CRC is directly related to the number of polyps . The first point at this time is to be aware of the peculiar genetic pathology and of the wide display of clinical features and to create a task force involving all the needed specialists-the pathologist, the gastroenterologist, the surgeon, the radiologist and the geneticist-in the management of the patient.
While waiting for molecular genetic tests, which need months to be completed, the patient should undergo a full diagnostic program to detect or exclude other clinical relevant diseases, due to the wide clinical expression of the genetic alteration. Genetic testing is the sole and most efficient procedure for discovering gene carriers in a suspected FAP patient and in the relatives. Once a distinct mutation is recognised in a subject, the linkage analysis on chromosome 5 has an accuracy of 70-90% .
Screening colonoscopy in patients known as carriers of an APC mutation should start at the age of 10-12 years and in the risk population of 15 years of age, with colonoscopic follow up every year between 15-26 years of age, every second year from 26-35 years of age and then every 3 years . In spite of the lack of a clear, validated diagnostic protocol, all patients should undergo an upper tract endoscopy with forward- and side-viewing instruments.
Duodenal polyps are found in the majority of polyposis patients and may lead to carcinoma development. An endoscopic and histological classification for the evaluation of the severity of duodenal adenomatosis was published in 1998 and has become the gold standard in several subsequent studies .
As in the colon, duodenal and ampullary polyps have to be resected, either endoscopically or surgically, and then regular scheduled follow-ups have to start, based on the histology of the removed polyps. Carcinoma of the duodenum, ampulla of Vater or pancreas have been strongly associated with Gardner's syndrome and a research at St. Mark's Hospital documented a 12% incidence of periampullary cancer in a series of patients 5 years after colonoscopy . That means that every patient should undergo frequent upper gastrointestinal endoscopies yearly, a full clinical examination and many other examinations because of the risk of developing diseases in extra-colonic sites.
Mesenteric fibrosis and desmoid tumours are often severe complications of FAP with a reported incidence of 3.5-5.7% between 1 and 3 years after colectomy . Desmoid tumours usually arise in the abdominal cavity, in the retroperitoneum or in the abdominal incision; extensive small bowel and urinary resections are often needed to resolve complications usually secondary to intestinal or vascular occlusion [18, 19]. Epidermal cysts are common benign findings, but seldom appear before puberty, so an early diagnosis could represent a warning for the physician to proceed with further evaluations for gastrointestinal polyps .
Sites for osteomas are typically found in the mandibula and skull and may be the only extra-colonic manifestation of the disease [21, 22]. Annual examinations should screen the thyroid and liver because of the risk of neoplasia. Lastly, the presence of ocular alteration as asymptomatic pigmented fundic lesions are reported in more than 90% of FAP and Gardner's patients. The congenital hypertrophy of the retinal pigmented epithelium, when present in the relatives, is almost 100% predictive of FAP (Table 1) [6, 7].
So the familial adenomatous polyposis is much more than a disease of the bowel and a very close cooperation between different physicians is necessary to ensure that our patients receive the best chances for an early and correct diagnosis, the best possible management and an optimal follow-up.
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