Timing of surgery in FAP
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1 Timing of surgery in FAP Sue Clark Consultant Colorectal Surgeon, The Polyposis Registry, St Mark s Hospital, London, UK.
2
3 Does this person need an operation? General population Surveillance and IRA No surgery Age groups
4 Which operation? When?
5
6
7 Heptad repeats (dimerisation) 3x 15-amino acid repeats (b -catenin binding) S(T)PXX repeats (DNA binding) SAMP repeats (axin binding) LXXLX(L/I/M/V) motif (nuclear export) Basic domain (microtubule binding, tubulin polymerisation) EB1 binding Armadillo repeats (asef binding) 7x 20-amino acid repeats (b-catenin binding & regulation, GSK3-b phosphorylation) Nuclear localisation signal VTSV motif (hdlg & PLP-BL binding sites) AAPC Classical FAP AAPC CHRPE 1250 severe FAP Desmoids
8 child of FAP patient bowel symptoms or anaemia? Y P55 urgent genetic testing / colonoscopy N wait until 12-14y family mutation known? Y predictive genetic testing N annual flexible sigmoidoscopy from 20y add colonoscopy every 5y
9 child of FAP patient bowel symptoms or anaemia? Y urgent genetic testing / colonoscopy N wait until 12-14y family mutation known? predictive genetic testing negative Y N positive annual flexible sigmoidoscopy from 20y add colonoscopy every 5y adenomas 1-2 yearly colonoscopy discharge prophylactic surgery at y depending on polyp burden after IRA 6-12 monthly flexible sigmoidoscopy and clinical examination after RPC annual flexible pouchoscopy and clinical examination OGD at age 25y - timing of repeat dependent on Spigelman stage
10 Choice of operation for FAP IRA RPC?
11 IRA Low complication rates - relatively straightforward salvage Ileostomy rarely needed Better function No risk to sexual function / fertility RPC Higher complication rates - salvage much more problematic Most have temporary ileostomy - 5% pouch failure and permanent stoma Poorer function Small risk of erectile / ejaculatory dysfunction Reduced female fertility Risk of rectal cancer rises in 40 s and 50 s - regular surveillance crucial - most can be converted to a pouch Small but definite risk of cuff and pouch body polyps and cancer - very difficult to manage
12 Survival with a healthy rectum following IRA
13 Br J Surg 2010; 97: MCR mutation
14
15 Indications for RPC rather than IRA APC mutation codon Dense polyposis > 500 in colon > 20 in rectum
16
17
18 Ileoanal pouch adenomas 10.1 yrs 83% PPI 8.1 yrs Median polypfree survival: 7.2 yrs 41% ATZ 18% Body Log rank test, p < (years after pouch surgery)
19 Desmoid disease Risk factors FH Mutation 3 to codon 1400 Stimulated by trauma Most present in 1-3 years following colectomy Less desmoid if surgery delayed o Durno et al. Clin Gastroenterol Hepatol 2007; 5:
20 Timing of bowel surgery for FAP Immediately if cancer present / likely -20% new mutations -Failure of cascade testing/surveillance Urgently if real possibility of invasive disease -Carpeting adenomas -High grade dysplasia (other than isolated and completely excised) -Large adenomas o<5mm 4% o5-10mm 14% o>10mm 39%
21 Planned prophylactic
22 Planned prophylactic -Very rare to develop cancer before age 20 -Aim to minimise educational / social disruption -Surgery aged 16-18y if possible o younger if symptoms or concerning polyps o delay if at high risk of desmoid
23
24
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