Risk factors predicting intra-abdominal desmoids in familial adenomatous polyposis: a single centre experience.

BACKGROUND: Desmoids are myofibroblastic proliferations occurring in 15% of patients with familial adenomatous polyposis (FAP), 70% being intra-abdominal desmoids (IAD). Since the morbidity and mortality due to desmoids is almost entirely attributable to IAD, we aimed to identify specifically risk factors predicting IAD development in FAP. METHODS: We undertook a retrospective review of our institutional database. Multivariate analysis was performed, and hazard ratios (HR) calculated for variables including female gender, 3' APC mutation, surgical intervention for FAP (colectomy with ileo-rectal anastomosis or restorative proctocolectomy), age at surgery and family history (FH) of desmoids. RESULTS: Of the 558 patients analysed, 49 (9%) developed IAD; 22 (4%) diagnosed intra-operatively and 27 (5%) developing over a median post-operative period of 34 (7-120) months. 75% of IAD had developed before age 40. A 3' APC mutation (HR 5.2, 95% CI 2.1-13.3, P = 0.001), positive FH (HR 2.5, 95% CI 1.4-4.6, P = 0.003) and female gender (HR 1.9, 95% CI 1.0-3.5, P = 0.04) were found to be predictive of IAD development. No significant difference in IAD risk was detected between the type of surgical intervention (P = 0.37) or age at surgery (P = 0.29). CONCLUSIONS: Our analysis confirms 3' APC mutation to be the most significant risk factor for IAD development. The independent association between positive FH and IAD risk suggests the existence of modifier genes, independent of the APC genotype-phenotype correlation. Few of these risk factors can be meaningfully modified. Delaying prophylactic surgery may be appropriate in female patients with a 3' APC mutation and attenuated polyposis.

Comparison of outcomes of ileal pouch-anal anastomosis for familial adenomatous polyposis with and without previous ileorectal anastomosis.

BACKGROUND: It is reported that previous colectomy and ileorectal anastomosis (IRA) has no effect on postoperative complications and functional outcomes of secondary proctectomy and ileal pouch-anal anastomosis (IPAA) in patients with familial adenomatous polyposis (FAP). This retrospective study re-examined the question in a single centre. METHODS: Some 185 patients were grouped by either IPAA as the initial prophylactic surgical procedure (primary IPAA) or IPAA preceded by IRA (secondary IPAA). Data on functional outcomes were available for 104, 83 and 56 patients at years 1, 5 and 10 respectively. RESULTS: The 78 patients who had secondary IPAA were older at the time of operation than the 107 who underwent primary IPAA (35.7 versus 29.2 years; P < 0.001). Six (8 per cent) of the secondary IPAA procedures could not be completed. Otherwise, apart from more wound infections in the secondary IPAA group (9 versus 0.9 per cent in the primary IPAA group; P = 0.012), there were no significant differences in rates of complications, functional outcomes, desmoid disease or pouch failure. CONCLUSION: Conversion from IRA to IPAA may not be possible in patients with FAP. Where conversion is successful, pouch outcomes are similar but wound infections are more frequent.

Evidence for genetic predisposition to desmoid tumours in familial adenomatous polyposis independent of the germline APC mutation.

BACKGROUND: Many patients with familial adenomatous polyposis (FAP) die from desmoid tumours which can arise spontaneously but often appear to be surgically induced by prophylactic colectomy. FAP results from germline adenomatous polyposis coli (APC) gene mutations and desmoids arise following biallelic APC mutation, with one change usually occurring distal to the second beta-catenin binding/degradation repeat of the gene (3' to codon 1399). We have suggested that because families with germline mutations in this region already have the requisite change, they are more likely to develop desmoids. However, there are families with 5' germline mutations where desmoids are common. PATIENTS AND METHODS: We examined desmoid risk dependent on germline APC mutation, sex, history of abdominal surgery, and family history in FAP patients from the St Mark's Hospital Polyposis Registry. RESULTS: Overall desmoid prevalence was 15%. Desmoids tended to cluster in susceptible individuals, irrespective of the germline APC mutation. Independent predictors of increased desmoid risk were: germline mutation distal to codon 1399; any family history of disease; and a strong family history of desmoids. A family history of multiple desmoids (>1) increased an individual's own risk of multiplicity. Females had twice the odds of developing desmoids compared with males. There was no significant interaction between any of the three explanatory variables. CONCLUSIONS: Our results indicate the influence of unknown genetic factors independent of APC in susceptibility to desmoid tumours in FAP. The data have implications in terms of clinical management of FAP patients and assessing the balance between chemoprevention and prophylactic colectomy.

Desmoid tumours complicating familial adenomatous polyposis.

BACKGROUND: Desmoid tumours are one of the most important and intriguing extracolonic manifestations of familial adenomatous polyposis (FAP). They have been studied only in small numbers of patients. METHODS: Patients with FAP who also had desmoid tumour were identified from a polyposis registry database and their hospital notes were reviewed. RESULTS: There were 166 desmoids in 88 patients (median age 32 (interquartile range 22-38) years; 51 (58 per cent) female); 83 tumours (50 per cent) were within the abdomen and 80 (48 per cent) were in the abdominal wall. All but 16 individuals (18 per cent) had already undergone abdominal surgery, which was significantly more recent in women (P = 0.01, Mann-Whitney U test). Intra-abdominal desmoids caused small bowel and ureteric obstruction and resulted in ten deaths; survival was significantly poorer than in patients with abdominal wall desmoid alone (chi2 = 3. 93, 1 d.f., P = 0.047, log rank test), and eight of 22 patients who underwent resection of intra-abdominal desmoid died in the perioperative period. CONCLUSION: Abdominal wall desmoids caused no deaths or significant morbidity; although recurrence was common after excision, the treatment was safe. Intra-abdominal desmoids can cause serious complications and treatment is often unsuccessful; in particular, surgery for desmoids at this site is hazardous.

A survey of phenotypic features in juvenile polyposis.

Solitary juvenile polyps are quite frequent in children, but juvenile polyposis (JP) is a rare autosomal dominant trait characterised by the occurrence of numerous polyps in the gastrointestinal tract. Extracolonic phenotypic abnormalities are well documented in patients with familial adenomatous polyposis and Peutz-Jeghers syndrome and can allow a clinical diagnosis to be made before the bowel pathology becomes available. Though described, characteristic extracolonic abnormalities have not been clearly defined in juvenile polyposis. We sought to determine whether there are consistent extracolonic phenotypic abnormalities in JP patients and how frequently this would allow diagnosis of one of the genetic syndromes known to be associated with juvenile polyposis. Twenty-two JP patients underwent clinical examination and data from one patient were obtained from case notes. Those consenting to further investigations had x rays of the skull, chest, and hands and an echocardiogram if clinically indicated. Significant extracolonic phenotypic abnormalities were present in 18 patients (14 male and four female), and included dermatological (13), skeletal (16), neurological (5), cardiopulmonary (4), gastrointestinal (3), genitourinary (4), and ocular (1) features. In five patients the diagnosis of a genetic syndrome was possible: two had Bannayan-Riley-Ruvalcaba syndrome, two had Gorlin syndrome, and one had hereditary haemorrhagic telangiectasia (HHT, also known as Osler-Rendu-Weber syndrome). Other patients had some features of these conditions and of Cowden and Simpson-Golabi-Behmel syndromes, but these were not sufficient to allow a definitive diagnosis.

Juvenile polyposis.

Juvenile polyposis is an uncommon condition characterized by the development of multiple juvenile polyps, predominantly in the colon but also in the rest of the gastrointestinal tract. The condition usually presents in childhood; only 15 per cent of patients present as adults. The rarer and often fatal form, namely, juvenile polyposis of infancy, is typified by diarrhoea, protein-losing enteropathy, bleeding and rectal prolapse. The more common form of juvenile polyposis (affecting the colon, stomach and small bowel) occurs in the first or second decade with rectal bleeding and anaemia. A family history of the condition is found in 20-50 per cent of patients with apparently an autosomal dominant trait. The gene for juvenile polyposis has not yet been identified. Epithelial dysplasia is common and the cumulative risk of colorectal cancer is > 50 per cent. Various extracolonic abnormalities may also occur. Most patients are treated surgically for colonic polyps, although endoscopic polypectomy is also an option. The rest of the gastrointestinal tract should be screened as should asymptomatic first-degree relatives.

Comparison of morbidity and function after colectomy with ileorectal anastomosis or restorative proctocolectomy for familial adenomatous polyposis.

Restorative proctocolectomy with an ileal reservoir (RPC) should prevent colorectal cancer in patients with familial adenomatous polyposis. Until this is confirmed its role compared with total colectomy and ileorectal anastomosis (IRA) will depend on the relative morbidity and postoperative bowel function after the two procedures. This was analysed in 99 patients (37 RPC, 62 IRA) operated on between 1977 and 1989. Morbidity was greater after RPC with subsequent ileostomy closure (median hospital stay, 24 versus 11 days; complications, 60 versus 21 per cent; reoperation, 29 versus 3 per cent; return to normal activity; 31 versus 14 weeks). There was little difference in bowel function; after IRA median frequency was 3/24 h and urgency (unable to wait 15 min) occurred in 50 per cent, compared with 4.5/24h and 17 per cent after RPC. Night evacuation occurred in 10 and 43 per cent respectively. IRA was performed in younger patients (median 19 versus 31 years) who had fewer bowel motions before operation (2 versus 5/24 h). The greater morbidity of RPC suggests that it should be restricted to patients at higher risk of developing later rectal cancer, including those unavailable for follow-up and those with large or confluent rectal polyps or with curable colon cancer at the initial colectomy.