Phenotype & Clinical Management
In a paper published in 2002 on 36 FAP families, the Registry reported that the strategy of pre-symptomatic diagnosis by screening and appropriate surgery reduced the incidence of CRC in FAP patients [
11]. In our most recent update on 51 FAP families, we confirmed the previous observation.
This update included 151 documented FAP subjects (86 men and 65 women) from 51 families including three families with the attenuated phenotype. Forty-five of these subjects died before Registry recruitment.
The diagnosis of polyposis was made by screening in 58 individuals (30 men and 28 women), whereas the remaining 93 were diagnosed due to bowel symptoms. The median age at FAP diagnosis was significantly younger for those due to screening than those due to symptoms (28.0 ± 14.0 years vs. 36.0 ± 13.2 years, p = 0.000). Upon diagnosis, 66 (71%) of those with bowel symptoms had already developed CRC, whereas only 4 (6.9%) of those diagnosed by screening had synchronous CRC (p = 0.000). Two subjects diagnosed by screening more than 10 years ago refused prophylactic surgery. Both later presented with bowel symptoms due to CRC and succumbed to malignancy. Even with treatment, 56 individuals diagnosed by bowel symptoms ultimately died from CRC except one. This gives a CRC mortality rate at 59.1% for this group of patients. For those diagnosed by screening, three (5.2%) have died from CRC to date, including the two who refused prophylactic colectomy. Therefore, the overall mortality rate was significantly lower for FAP subjects diagnosed by screening than those diagnosed by symptoms (5.2% vs. 60.2%, p = 0.000). Moreover, the median age at FAP diagnosis was significantly younger for those without synchronous CRC than those with synchronous CRC (29.0 ± 12.6 years vs. 40.0 ± 12.7 years, p = 0.000).
For the type of prophylactic colectomy, restorative proctocolectomy (IPAA) is the most commonly performed procedure for the classical profuse type of polyposis, whereas total abdominal colectomy with ileorectal anastomosis (IRA) is the procedure of choice for attenuated polyposis.
Apart from CRC, our FAP subjects are prone to develop other serious extra-colonic lesions. This can be illustrated by the clinical data of 106 FAP subjects (57 men, 49 women) recruited by the Registry up to June 2005.
Papillary thyroid cancer is the only extra-colonic malignancy identified in our subjects to date. Six female FAP subjects have developed papillary thyroid cancers: two before and four after the diagnosis of FAP. All except one of the thyroid cancers developed before 30 years of age. All six women survived after treatment.
Desmoid tumours occurred in 17 individuals (7 men and 10 women) at a median age of 36.0 years (S.D. 9.2; range 21-49) with significant morbidity. Regarding the location of desmoids, three occurred extra-abdominally, three were on the abdominal wall, seven were entirely intra-abdominal and four had both abdominal wall and intra-abdominal components (combined).
Two of the intra-abdominal desmoids occurred without previous abdominal surgery; one of the desmoids precluded colectomy and another precluded restorative proctocolectomy. For the remaining abdominal desmoids (on the wall or intra-abdominal), they occurred at a median interval of 2.5 years (S.D. 4.7, range 1-18) after colectomy.
Regarding treatment of desmoid tumours, we offered surgical resection for extra-abdominal and abdominal wall desmoids. Two out of three extra-abdominal desmoids recurred after resection, whereas all abdominal wall desmoids did not recur. For intra-abdominal and combined types of desmoids, we usually adopted conservative treatment which included expectant treatment and various medical therapies unless complication occurred. Excision of the abdominal wall component was performed in one patient with combined desmoids without recurrence. Debulking surgery of intra-abdominal desmoids had been performed in three patients resulting in enterocutaneous fistula in one and recurrence in another two.
Six patients developed various complications due to their intra-abdominal desmoids. These complications and their corresponding treatment include: obstructive uropathy in four requiring ureteric stenting; uretero-enteric fistula in three requiring ureteric stenting and long-term prophylactic antibiotics against urinary tract infection; enterocutaneous fistula in three treated conservatively; bowel ischaemia in one requiring massive small bowel resection resulting in short gut syndrome; intestinal obstruction in one treated by intestinal bypass; and inferior vena caval (IVC) obstruction in one requiring IVC stenting. One of these patients ultimately died of sepsis due to a combination of short gut syndrome and obstructive uropathy.
The protocol of endoscopic surveillance for FAP patients after prophylactic colectomy is detailed in Table
3. Surveillance endoscopy revealed adenomatous polyposis in the remaining gastrointestinal tract in a number of them. Pouch adenomatous polyposis occurred in five patients at a median interval of 9 years (S.D. 3.7; range 7-15) after IPAA. Two of these patients were treated with sulindac (Merck Sharp & Dohme, Herts, UK) which had resulted in histological resolution of pouch polyposis in one [
12].
Table 3
Endoscopic surveillance protocol for patients with familial adenomatous polyposis after prophylactic colectomy
1. Flexible sigmoidoscopy every 6 months after total abdominal colectomy and ileorectal anastomosis. |
2. Pouchoscopy every 2 years after restorative proctocolectomy. |
3. Upper endoscopy and duodenoscopy every 2 years for all patients. |
Gastric and duodenal adenomata were detected in three and eight patients, respectively. Microadenomatous changes in the duodenal papilla were detected in 23 subjects at a median age of 35.0 years (S.D. 7.7; S.D. 21-47). The natural history of duodenal microadenoma and its malignant potential is unknown. In one patient, serial upper endoscopies documented progression of duodenal microadenoma to adenoma over five years.