FAP History Through a Patients Story

Gian Gaetano Delaini, Gianluca Colucci, Filippo Nifosi

This is the story of Rosa Gallo, a young and bright student of medicine, who died of Gardner's syndrome at 21 years of age; this story allows us to more easily explain the history of the disease, the various aspects of which (aetiology, clinical history, diagnostic and therapeutical approach) are extensively covered in several chapters of this book.

Rosa Gallo was born on 6 August 1982, second born of the Gallo family, 4 years younger than the first born, Carmine. She was a happy child and soon stood out among her friends of the same age, for her lively wit. Fondly loved by mom and dad, the two children grew up happy and carefree. In 1990, Rosa's paternal aunt, who moved from Altavilla Salentina to Milan, underwent coloscopy due to lower gastroin testinal (GI) bleeding. The result of the examination would upset the life of the whole Gallo family: the diagnosis was familial adenomatous polyposis coli (FAP). All first degree relatives underwent coloscopy, and Rosa's father, Rosario, was found to be bearer of this disease. Now the high presence of rectal cancer in the Gallo family could be explained (Fig. 1).

FAP coli is a well-described autosomal syndrome characterised by diffused polyposis of the colon. The first description of intestinal polyposis dates back to 1721 with Menzelio [1]. In 1882, Cripps [2] described the inhered predisposition (brother and sister, both affected by FAP) while Smith [3] found the progress of the disease from an adenoma to a cancer that was then histologically described, in 1890 by Handford [4]. This disease is the most diffused heritable cause

Genetic Tree
Fig. 1. Gallo family genetic tree

of colorectal cancer (CRC), second only to the Lynch syndrome. FAP stems from mutation of the APC gene localised on 5q21. The APC gene plays several important roles in cells, influencing cell adhesion, cytoskeleton and cell cycle [5, 6.] Since the first description in 1986 [7], much progress has been accomplished in determining the mutations causing this disease, thanks to the cloning technique, and over 1,000 mutations have been found [8], which have been inserted into an international reference database (http://perso.curie.fr/tsoussi). Now it seems certain that there is a correlation between genotype and phenotypic manifestation of the disease, as mutation in different areas of the APC leads to different manifestations of the disease [9]

Clinically, FAP is characterised by the presence of a high number (>100) of adenomatous polyps of the colon and rectum [10]. These polyps are characterised by a neoplastic degeneration, and these patients with them, if they do not undergo prophylactic colectomy, will develop colon cancer and will be doomed because of this neoplasty. Sometimes the disease has a slower course and a lower number of polyps, probably because of a milder form of the disease called attenuated adenomatous polyposis coli AAPC [11]. Usually in AAPC, polyps are right-sided and the rectum is spared. The disease develops over time. Bulow [12], in a now historic review, determined that the onset of polyps usually begins at 16 years of age (range: 5-38), at 29 years of age (range 12-73) the first symptoms begin (generally lower GI bleeding) and at 36 years of age (range: 17-63) rec-tal/colonic cancer appears.

Besides in the colon-rectum, the disease is characterised by the high incidence (from 28% to 68%) [13-15] of polyps in the stomach and duodenum. With the diffusion of the prophylactic colectomy, this associated pathology grew increasingly important, as extension of the average duration of life in these patients brought to light the risk of neoplastic degeneration. It also evidenced the need to perform a suitable follow-up with gastroscopy [16] and stratification of patients using Spigelman's classification [17] to determine which patients may be treated with endoscopic polypectomy only and which must undergo surgery, usually consisting of a pancreatico-duodenectomy.

Rosa's father and aunt were operated in London by Prof. Nicholls and underwent total colectomy with ileorectal anastomosis because preoperative examinations revealed the absence of polyps at rectum level.

The surgical therapy chosen to treat FAP was restorative proctocolectomy with ileal pouch anal anastomosis [18-20] due to the high risk of neoplas-tic degeneration in the residual rectal stump even though ileal rectal anastomosis might be a surgical option acceptable by patients with rectal sparing and a good compliance to follow-up [21, 22].

The years went by peacefully. Rosario's and his sister's follow-ups showed an absence of residual disease. The risk of this disease hung over Rosario's children, too. At 18 years of age, Carmine underwent the first colonoscopy and the diagnosis, for him, too, was FAP. He was then hospitalised at the Verona Surgery Clinic and underwent restorative procto-colectomy with ileal pouch anal anastomosis (RP-IPAA). The postoperative course went without complications, and after about 45 days, the loop ileosto-my was closed.

Rosa, who by the time was a happy-go-lucky teenager, attended high school with very good results. She was always happy; she supported her family with her happiness and maturity during the

Fig. 2a, b. Preoperative computed tomography (CT) scan. D, desmoid tumour
Crohn Disease Scan

hard times, well aware of the risk that she could suffer from the disease, too. In May 1998, when she was 17 years old, Rosa began to complain about a pain localised in the left side, which grew increasingly annoying. Her parents decided to subject the girl to a series of examinations. Rosa underwent colonoscopy, which revealed many polyps in the colon and rectum. Moreover, she underwent a computed tomography (CT) scan (Fig. 2) and magnetic resonance imaging (MRI) (Fig. 3), which revealed a voluminous mass filling the left hemiabdomen and infiltrating the spleen, pancreas, kidney and left ureter. The diagnostic procedure included, moreover, an ophthalmology exam, which revealed congenital hypertrophy of the retinal pigment epithelium. The cranial radiography did not reveal supernumerary teeth or osteomas. The diagnosis was then clear: Gardner's syndrome.

FAP may be associated with the presence of many extraintestinal manifestations characterising various syndromes, such as Gardner's syndrome [23] and Turcot's syndrome [24]. Table 1 summarises the main features of these syndromes.

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