Colorectal disease

Of the many adenomatous polyps which develop in the colon and rectum of patients with FAP, "...one or more of the adenomata form... a malignant adenocarcinoma" [2]. Cancer preventative surgery was instituted in the 1940's. Subsequently screening of patients with a family history of FAP was commenced to ensure that prophylactic treatment, including surgery, was being offered [3]. The timing of prophylactic surgery depends on various factors, such as age. Although there are reports of carcinoma of the rectum developing in children aged less than 10 years [4], elective surgery is usually deferred until after puberty. Quality of life issues for an adolescent are very different from that of an adult, often influenced by schooling, and this is factored into the planning of surgery. Most patients should have been offered a colectomy by the start of their third decade of life, as 15% of FAP patients will present with colorectal cancer before the age of 25 [5]; surveillance usually starts from the age of 10 [6].

The nature of the prophylactic surgery performed depends on the clinical findings pre-operatively, the patients' wishes and the surgeons' preference (Table 1, Fig. 1) [7].

Figure 1
figure 1

Decision tree for colorectal surgical options in FAP.

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Table 1 Indications and advantages of colectomy options in patients with FAP
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Procedure

Total colectomy and ileorectal anastomosis (IRA)

This procedure is unsuitable in patients with marked rectal polyposis and/or rectal carcinoma, or when adequate follow-up and surveillance of the rectal stump cannot be guaranteed [8–10]. The procedure entails mobilisation of the whole colon to the point at which the taeniae coli fuse, considered the upper border of the rectum. Dissection to this level maintains the reservoir function of the rectum and ensures that the anastomosis can be reached with ease by the rigid sigmoidoscope for surveillance purposes. A simple ileorectal anastomosis is fashioned either hand-sewn or stapled. To eliminate blind loops, inaccessible to rigid sigmoidoscopy, formation of an end-to-end anastomosis is recommended [11, 12].

Proctocolectomy

This is either total or restorative. The former involves a permanent ileostomy and will not be discussed in detail. The latter, first described in 1978 [13], avoids a permanent stoma by constructing a new reservoir which is re-anastomosed to the anal canal. This panproctocolectomy with ileal pouch-anal anastomosis (IPAA) requires the whole colon and rectum to be mobilised and the large bowel removed by dividing the intestine at the ileocaecal and anorectal junctions. The reservoir is fashioned from the terminal ileum and this in turn is anastomosed to the anal canal.

Indications

The phenotype of the individual FAP patient and any symptoms experienced at presentation are the most important factors determining which surgical procedure is carried out [6, 8, 9, 12].

Operative morbidity and mortality

Total colectomy and IRA are considered a relatively safe procedure with a low operative mortality [9]. There is a fairly steep learning curve with IPAA but the operative mortality can be as good as IRA [14]. IPAA is more likely to be a two-stage procedure with a temporary defunctioning ileostomy requiring subsequent closure often being formed, but such stomas are not always necessary [8, 15].

Functional outcome

Whilst increased bowel frequency [8, 16] and urgency [16] are common following IRA, patients experience nocturnal defecation [8, 17], greater use of anti-diarrhoeal medication [18], and problems with faecal soiling, incontinence and flatus/faeces discrimination [17, 19] are more commonly following IPAA procedures. Studies comparing IRA and IPAA procedures have shown similar overall quality of life outcomes [20].

The preservation of the pelvic sympathetic plexus is considered a relative indication for IRA in young men [21].

Post-operative surveillance

Ileorectal anastomosis

Having an IRA implies lifelong surveillance with a minimum of rigid sigmoidoscopy every 6 months [6], although sigmoidoscopy every 4 months has been suggested [5]. Standard polyp surveillance should be carried out with all remaining polyps removed [22]. A combination of snare polypectomy or diathermy is appropriate. The risk of rectal cancer increases with chronological age rather than time from surgery [5, 11, 12] with an approximately 25% risk of rectal cancer by the age of 70 years [11]. The cumulative risk for rectal excision following IRA may be as high as 60% for those aged 70 years [11].

Bjork et al found many of the rectal cancers had developed very close to the anal verge, a notoriously difficult area to assess with the rigid sigmoidoscope [11]. In a like manner, patients in whom an IRA has been constructed higher than 12 cm from the anal verge are more likely to develop rectal cancer as the rectum cannot be adequately assessed in rigid sigmoidoscopy [11, 12]. Older age at the time of IRA and multiple/dense pre-operative polyps are additional risk factors for the development of rectal cancer; however, these factors would preclude a patient from receiving an IRA today. Church et al investigated this, finding that in the past all patients were offered a sphincter sparing procedure (IRA) before IPAA became widely available. They found that all patients with very severe polyposis had an IRA in the pre-pouch era and only 39% with severe polyposis had chosen this in the pouch era [23]. They hypothesised and showed, albeit with a shorter period of follow-up, that patients who have an IRA in the pouch-era have a lower risk of post IRA rectal cancer than those operated during the pre-pouch era. Attributing this to patient selection (that is, those with less severe phenotypes now receive an IRA) they cautioned that the choice of surgery now should not be influenced by data that were generated before the current range of surgical options became available.

Ileal pouch-anal anastomosis

With increasing reports of adenomas [24, 25] and even carcinomas [26] in pouches, regular surveillance of these is advocated, with most groups suggesting annual rigid sigmoidoscopy [6] (Fig. 2).

Figure 2
figure 2

Decision tree for surveillance following colonic surgery in FAP.

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Controversies in IPAA

As FAP is primarily a mucosal disease it seems logical to remove all the colorectal mucosa to prevent polyps and ultimately cancer developing at a later date. Mucosectomy was an essential part of Parks and Nicholls' original description [13]. To avoid this time-consuming component of restorative proctocolectomy double stapled anastomoses are used [19, 27–29]. Stapled anastomoses leave a greater cuff of mucosa than that left following mucosectomy and hand-sewn anastomosis [30], with pouch/anal polyps seen more commonly following stapled than with hand-sewn IPAA [30].

Patients subjected to a hand-sewn anastomosis are more likely to experience a poorer functional outcome [14, 29], with increased bowel action and faecal incontinence more common [29]. This may be a consequence of the anal stretch required to facilitate the anastomosis, or the removal of the anal transitional zone during the mucosectomy [26]. The anal transitional zone, a highly innervated area 1 cm above the dentate line, is believed to be responsible for the discrimination of faeces and flatus [26, 31]. Pouch-anal strictures do occur, with reported rates as high as 42% [27, 29]. They are more commonly found following stapled anastomoses [27]. Strictures following stapled anastomoses tend to be less troublesome and more amenable to simple dilatation than those which occur in hand-sewn anastomosis; which are inclined to be more severe, requiring operative dilatation [27].

Pouchitis, often seen in IPAA procedures carried out for inflammatory bowel disease [32], is very unusual in FAP patients [17, 29].

Duodenal polyposis

Extra-colonic polyps have been described in the stomach and duodenum of FAP patients for over 100 years [1], but their true incidence and significance were only fully documented in the late 1980's [33, 34]. It is now recognised that up to 90% of FAP patients will develop duodenal polyposis by the age of 70 [35], and once colectomy has been carried out duodenal cancer is one of the main causes of death in FAP patients [36, 37]. As part of their prospective study of duodenal polyposis in FAP patients, Spigelman et al defined a now widely used classification score for severity of duodenal polyposis [33] (Table 2a).

Table 2a Spigelman Staging [33] of Duodenal Polyposis
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Surveillance

The first surveillance upper gastrointestinal endoscopy should be carried out by the age of 25-30 [36, 38, 39]. This should then be followed up by a further endoscopy 12 months later [36], and a Spigelman stage derived. Random biopsies of apparently normal mucosa should also be taken initially, with Bulow et al finding 12% of adenomas in their series to be invisible [35]. The region of the ampulla is of considerable importance and this is best viewed and biopsied with a side or oblique-viewing endoscope [33]. A suitable surveillance program based on the Spigelman stage is then employed [40] (Table 2b). Disease progression does occur and Spigelman stage IV patients have a crude risk of developing duodenal cancer of 36% [40], compared with 2% for those with stage II or III disease.

Table 2b Suggested surveillance/treatment for Duodenal Polyposis based on Spigelman Staging [38]
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Endoscopic treatments

Various endoscopic treatments have been used to control duodenal adenomas locally. These include polyp ablation by electro-diathermy, Nd-YAG laser, ionised argon diathermy, photodynamic therapy, snare polypectomy and mucosal resection [38, 39]. These procedures have a risk of complications including bleeding, perforation, and pancreatitis as well as late-onset duodenal stenosis [39]. Recurrence is also likely [36, 41], making the decision to persevere with further endoscopic treatments or proceed to surgery a difficult one.

Surgery

If duodenal carcinoma has developed a pancreaticoduodenectomy (Whipple's or modified Whipple's procedure) should be carried out [39]. For patients with benign adenomatous change but Spigelman stage IV less radical surgery can be performed. Recent advances in surgical technique have resulted in pancreas or pylorus sparing duodenectomy being carried out [41–43]. Such procedures involve resection of the whole of the duodenum with its associated malignant potential, preserving the function of the pylorus and/or the pancreas. This is of considerable importance to patients who have already had a colectomy, as daily bowel movements can be doubled, particularly in patients with an IPAA [41].

Chemoprevention

Trials of the non-steroidal anti-inflammatory drugs (NSAIDs) Sulindac and Celecoxib (COX-2 inhibitor) have shown regression of duodenal polyps [44] and their use is probably best reserved for patients with stage III or IV (initially) polyposis [38].

Future developments

Jejunal and ileal polyps occur in FAP patients [42]. The advent of capsule endoscopy will allow for a more precise estimation of their prevalence and natural history. Similar advances in CT imaging herald hope for less invasive surveillance of the duodenum [45].

Desmoid disease

Desmoid tumours account for 0.03% of all tumours in the non-FAP population, but occur in up to 32% of those with FAP [46]. They result from proliferation of myofibroblasts [47], arising within the abdomen or the abdominal wall in FAP patients. They are more common in women, particularly in the non-FAP population, leading to the suggestion that female hormones may play some role in their development [48, 49]. There is a tendency for desmoids to run in certain FAP families and previous trauma or surgery is thought to initiate their development. The St. Mark's group have described early desmoid tumour type lesions (desmoid precursor lesion) in people who have no history of surgery or trauma [50] but their significance has yet to be fully assessed.

Desmoid tumours are classified as benign as they do not spread to distant sites; however they are potentially lethal when they occur within the abdominal cavity by surrounding other structures such as small or large bowel, ureters and the mesentery [51].

Surgery

Desmoid tumours of the abdominal wall and the extremities

It is recommended that surgery should include excision of the mass with some surrounding tissue. This can be done with relatively few complications but the recurrence rate varies from 10% to 68% [46].

Desmoid tumours within the abdomen

Surgery is often technically demanding and may even be impossible. The complication rate is high with a post-operative mortality rate of anywhere between 10% and 60%, and a recurrence rate of up to 78% [46]. It is recommended that desmoid tumours should only be surgically removed when bowel obstruction has occurred or when the blood supply to the bowel has been compromised. As operative removal is complex this should be done by experienced surgeons [7, 52].

A recent report found the presence of incidental desmoid tumours at laparotomy for colectomy that required modifications or precluded the intended procedure from being carried out in 26% of 266 patients [47].

With a risk of recurrence following surgical removal, various other treatment modalities have been trialled.

Other treatment modalities

Commonly used NSAIDs like Sulindac have been shown to cause some reduction in the size or to halt further enlargement of desmoid tumours [53, 54]. Anti-oestrogen drugs such as Tamoxifen have been studied, in conjunction with NSAIDs, providing similar results to the use of NSAIDs alone [54–56]. Cytotoxic chemotherapy has been found to be similarly effective as the NSAIDs and anti-oestrogens but with more marked side effects. The use of chemotherapy is currently reserved for large inoperable desmoid tumours that have not responded to other drug treatments [57–60]. Radiotherapy is not recommended in FAP, as most tumours are within the abdomen and unacceptable post-treatment complications affecting the small bowel may occur [7, 46]. Warfarin, Prednisolone and Interferon have been used, but without evidence from clinical trials [46, 61].

Summary of treatment options

For desmoid tumours of the abdominal wall and extremities wide surgical excision is recommended. If recurrent, further surgery may be attempted and radiotherapy may be used for tumours of the extremities [51].

Intra-abdominal desmoid tumours should be assessed every 6-12 months with CT scan and medical management with NSAIDs (Sulindac) with Tamoxifen may be beneficial. Renal tract obstruction may require ureteric stent insertion [53]. If progression occurs the dose of Sulindac can be increased and Tamoxifen replaced with Toremifene [46]. This should be maintained for several years before dose reduction is considered. If further progression of the desmoid tumour occurs or they become more symptomatic surgery may be attempted either to remove the desmoid tumours if a small discrete mass and no vital structures are involved; or palliative surgery to relieve the symptoms. When surgery is not possible or there has been subsequent recurrence then cytotoxic chemotherapy may be considered [46].

Prognosis

About 4-6% of desmoid tumours resolve spontaneously [46, 52]. Desmoid tumours cause significant morbidity and in cases of unresectable mesenteric desmoid tumours the mortality rate has been reported to be as high as 30%. The overall survival rate after 10 years is 63% [46].

Surveillance and cancer registries

The importance of familial cancer registries cannot be underestimated. The familial cancer registry undertakes the time-consuming task of documenting the full family pedigree, followed by the requisite genetic counselling [62]. They may also coordinate genetic testing as appropriate, family member contact and provide assistance to ensure that surveillance is being performed. It is noteworthy that "all published data from cancer prevention programmes that have reduced cancer incidence in family members... have used family [cancer] registries" [63].

Conclusion

Surgical management of FAP has improved over the years with a greater emphasis on preventative/prophylactic surgery. Deciding which prophylactic large bowel procedure is difficult. With such prophylactic procedures almost eliminating the risk of colorectal cancer, patients with FAP now face new challenges from duodenal polyposis and desmoid disease.