This systematic review has highlighted some very important differences in outcome between restorative proctocolectomy and IRA for the patient with FAP. The results on functional outcome suggest a favourable outcome towards the IRA procedure with regards to stool frequency over a 24-h period, need for defecation at night, incontinence (both over a 24-h period and at night) and pad usage. These finding are perhaps expected in a patient with a retained, functioning rectum. Interestingly, IPAA was not significantly different to IRA in stool frequency at night, day incontinence, and need for anti-diarrhoeal medication, all of which are outcomes that may make it acceptable for many young patients. Another inter

Fig. 5. Meta-analysis of bowel frequency

esting finding was that faecal urgency (the ability to defer defecation for at least 15 min) was significantly better in the IPAA group. This finding is important, as urgency can be a very detrimental outcome, particularly with regards to patient embarrassment, social behaviour, and ultimately patient satisfaction with the IRA procedure. A patient may therefore prefer the IPAA and increased frequency of stools, or even pad usage, for this outcome. Whether hand-sewn or stapled IPAA offers the best functional option for the patient undergoing surgery for FAP remains to be seen.

There was no significant difference between IPAA and IRA in the quality of life outcomes of dietary restriction and male and female sexual dysfunction. This is an important finding, particularly with regards to sexual dysfunction, as the patient facing FAP surgery is often young and likely to want to conceive at a later point in their lives. Normal sexual function is also an important outcome with regards to patient satisfaction with the procedure. One outcome that was significantly different between IPAA and IRA groups, was social restriction as a result of the procedure, which significantly favoured the IRA group. These results should, however, be treated with caution as there were only two studies reporting this outcome, containing at total of 58 patients in the IPAA and 85 patients in the IRA groups respectively.

As previously mentioned, restorative proctocolectomy with IPAA is perceived to be a more complicated procedure than IRA because of the increased pelvic dissection and potential for damage to the internal anal sphincter. The result of this meta-analy-sis showed that the incidence of all post-operative complications was significantly higher with IPAA (10%), as compared to IRA (6.8%). This was also reflected in an increased rate of 30-day re-operation with IPAA (23.4%) vs. IRA (11.6%). With regards to the individual post-operative outcomes, there was no significant difference between IPAA and IRA for bowel obstruction, haemorrhage, intra-abdominal sepsis, anastomotic separation and wound infection. The findings of this paper support this, although the magnitude of this overall increase (3.2%) is probably smaller than expected. The use of temporary defunc-tioning ileostomy adds another procedure to the primary IPAA where it is used, and although our study did not mention the morbidity associated with its reversal, there was little on this documented in the papers included in our meta-analysis.

With regards to long-term adverse events, IRA was associated with significantly less perianal irritation than IPAA (57.4 vs. 62.7%) as well as anastomotic stricture formation (2 vs. 8.1%). There was, however, no significant difference between the groups for the incidence of intra-abdominal desmoids, and no evidence that this is higher for primary IPAA as compared to IRA (5.4% with IPAA vs. 8.7% with IRA).

Although the choice of whether to perform IRA or IPAA as the primary operation for young patients with FAP relies on several factors as illustrated by our paper, the risk of cancer recurrence plays a significant part in this decision. Cancer recurrence was 5.5% following IRA as compared to 0% following IPAA, which is not surprising as the retained rectum (following IRA) has a higher chance of undergoing polyposis than the stapled IPAA with 1-2 cm of retained rectal mucosa, and the hand-sewn IPAA

Fig. 6. Meta-analysis of functional outcomes

with mucosectomy. The decision to undertake IRA as the primary operation for FAP is therefore justified on the basis of post-operative morbidity and functional outcome (except for faecal urgency, which is greater than in IPAA), but at the expense of cancer recurrence. Whether regression of rectal polyps with drugs such as sundilac, a non-steroidal anti-inflammatory agent used to reduce rectal polyp size and number in FAP patients following IRA [49], remains to be seen. Whilst a selective COX-2 inhibitor has also recently been shown to reduce the number of colorectal polyps in patients with FAP [50], concerns over the long-term risks of this class of drug have made its role uncertain.

Molecular genetic testing may be useful in guiding the surgical management of patients with FAP, with authors suggesting that patients with APC mutations following codon 1250 are at higher risk of developing rectal cancer and should therefore undergo IPAA rather than IRA [51]. Other mutations that have been implicated include codons 1309 and 1328, again suggesting the need for IPAA in these patients [9]. It is important to consider, however, that these patients are also at higher risk of developing pouch adenomas, and will therefore require close follow-up of their pouch following IPAA. In the FAP patient where molecular genetic testing has not detected mutations predisposing to a higher risk of cancer, severity of polyposis must also be taken into account. For example IPAA may be the best primary surgical intervention for patients with over 20 rectal polyps and greater than 2 000 colonic polyps, whereas those with less than five rectal polyps and fewer than 1 000 colonic polyps would qualify for IRA and surveillance of the rectal stump as they may represent an attenuated FAP group. Careful patient selection is required in the intermediate group (those with more than five but less than twenty rectal polyps) before deciding on their primary surgical interventional strategy.

This chapter highlights the merits and weaknesses of both IPAA and IRA as the primary treatment of FAP, both of which require close follow-up after surgery. Although it highlights several factors that should be considered, it also highlights the need for further investigation of which patients benefit most from which operation depending on their risk factors. The age of the patient, their sex, lifestyle and preferences, occupation, and compliance to follow-up are all very important in deciding the operative outcome most appropriate for them.

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