- Email: [email protected]
Surgical Management of Familial Adenomatous Polyposis
Surgical Management of Familial Adenomatous Polyposis Joseph C. Carmichael, MD, and Steven Mills, MD Familial adenomatous polyposis is an autosomal-dominant disease caused by a germline mutation of the adenomatous polyposis coli (APC) gene. It is characterized by the progressive development of hundreds to thousands of polyps in the colorectum. There are also associated extracolonic manifestations. The average age of colorectal carcinoma in these patients is 39 years. Surgery is the only effective treatment available to prevent the development of colorectal carcinoma. In the era of ileoanal pouch surgery, there are several surgical options available to patients. We review the current literature’s support for the various surgical options available at this time and the respective postoperative follow-up. Semin Colon Rectal Surg 22:108-111 Published by Elsevier Inc.
F
amilial adenomatous polyposis (FAP) is an autosomaldominant disease caused by a germline mutation of the adenomatous polyposis coli (APC) gene.1 The clinical diagnosis of FAP is supported when patients present with ⬎100 colorectal polyps. Because every mucosal cell of the colon and rectum carries the mutation, every mucosal cell has the potential to develop carcinoma. Further, patients with FAP are also at risk for extracolonic manifestations of the disease, such as desmoid tumors and gastroduodenal carcinoma.2,3 In the colon, surgery is designed to reduce the potential risk of colorectal cancer development while providing the patient with the best functional outcome.
Extent of Colonic Surgery The debate over the extent of surgery for FAP has been ongoing for many decades. Before the early 1970s, patients had 2 surgical options: they could undergo a proctocolectomy with ileostomy or a total abdominal colectomy with ileorectal anastomosis (IRA). In the past almost 40 years, ileal pouch anal anastomosis (IPAA) has become the primary option for many patients, especially those requiring a proctectomy. At the Cleveland Clinic, before the availability of IPAA, 97% of patients underwent IRA.4 The rate of subsequent completion proctectomy in those patients was 50% with a median time to completion proctectomy of 17 years.4 Patients generally underwent completion proctectomy because Division of Colon and Rectal Surgery, Department of Surgery, University of California, Irvine, CA. Address reprint requests to: Steven Mills, MD, Division of Colon and Rectal Surgery, Department of Surgery, University of California, Irvine, 333 City Blvd W, Ste 850, Orange, CA 92868. E-mail: [email protected]
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of the development of rectal cancer or uncontrolled rectal polyps. Subsequently, in the ileal pouch era, the rate of IRA has decreased to 56%, and a completion proctectomy was performed at a rate of 2%.4 Given this low rate of necessary completion proctectomy, it would seem that IRA is still appropriate in patients during the pouch era; however, appropriate patient selection for IRA is critical. Looking at similar data from Europe, Bulow et al5 noted that 10% of IRA patients developed rectal cancer in the prepouch era, whereas only 2% developed rectal cancer in the pouch era, suggesting that IRA is still appropriate in selected patients. The risk of rectal cancer after IRA increases with time after surgery. At 10, 15, and 20 years after IRA, the cumulative risk of was 7.7%, 13.1%, and 23%, respectively.6 Close endoscopic surveillance of the rectum does not seem to prevent cancer, as 75% of patients with an IRA had undergone an endoscopic examination within 12 months of the diagnosis of rectal cancer. However, endoscopic examination did lead to an increase in detection of early stage cancer.7 As will be discussed later, the cumulative risk of rectal cancer after IPAA is very low. A recent review shows only 8 reported cases in the literature.8 The rectal cancer risk is significantly greater in patients (a) who had colon cancer at the time of the initial operation, (b) with more than 30 rectal polyps at the initial operation, (c) with APC mutations between codons 1250 and 1464, and (d) with more than 1000 colonic adenomas.6,9 Patients with these risk factors are not good candidates for rectal preservation and should be offered a proctocolectomy with either IPAA or an ileostomy. Given this information, several groups have outlined criteria for patients to have the option of IRA. In general, IRA has
Surgical management of FAP been recommended for patients with few (⬍20) rectal adenomas, mild colonic phenotype (⬍1000 colon polyps), no colorectal cancer, family history of mild phenotype, attenuated FAP, patients without codon 1309 mutations, and no severe rectal dysplasia.4,5 Lifelong surveillance endoscopy every 6 to 12 months is necessary.10
The Role of Genotype in Surgery Traditionally, the decision to proceed with IRA versus IPAA in patients with FAP has been determined on the basis of phenotypic factors. As noted previously, patients with an attenuated pattern of FAP (⬍100 polyps, aFAP) and few rectal polyps are good candidates to proceed with a rectal sparing IRA procedure. However, the phenotypic expression of FAP does leave room for error, and some authors have sought to determine whether genetic markers may be useful in predicting the clinical course of patients with FAP.11 Wu et al12 have noted that mutations at APC gene codons 1309 and 1328 lead to a very poor prognosis for retaining the rectum. These authors recommend IPAA for patients with these mutations. Genotypes corresponding to phenotypes of aFAP, intermediate FAP, and severe FAP have been established. aFAP is associated with mutations at the 5= and 3= ends of the APC gene and the alternatively spliced site of exon 9. Severe FAP is the result of mutations between codons 1250 and 1464, and intermediate FAP corresponds to mutations in the remainder of the FAP gene.13 Results of retrospective genotype analysis reveal that 20 years after IRA, the risk of secondary proctectomy was 10%, 39%, and 61% in patients with attenuated, intermediate, and severe FAP genotypes, respectively.13 Although these results are interesting, they currently do not replace the use of FAP phenotype in surgical decision-making.
Technical Aspects of the Surgery IPAA: Mucosectomy versus Double Stapled Anastomosis One of the critical debates in FAP pouch surgery is centered on the decision to perform a mucosectomy with handsewn pouch-anal anastomosis versus a stapled anastomosis. Proponents of a mucosectomy claim a reduced risk of postpouch neoplasia in the anal transition zone (ATZ). Proponents of stapled anastomosis argue that functional outcomes are improved with stapled anastomosis, that the risk of cancer in the ATZ is very small, and that even mucosectomy patients can develop carcinoma in the area. The incidence of ATZ polyps after handsewn anastomosis is 10%-19%, whereas after stapled anastomosis, it is 28%38%.14-16 Severe colonic disease was a statistically significant risk factor for the development of ATZ polyps.15 A literature review in 2005 revealed 8 reported cases of adenocarcinoma developed at the anastomosis after IPAA for FAP.8 The diagnosis was made a median of 8 years after
109 pouch reconstruction (range, 3-20 years). One-half of these cancers followed stapled anastomosis and one-half followed mucosectomy. Clearly, cancer may occur regardless of the selected type of procedure. Mucosectomy is likely not protective of cancer because islands of rectal mucosa remain in the anal canal after the procedure.17,18 Mucosectomy has been recommended for patients with cancer of the rectum or carpeting of the ATZ with polyps.19 In function, the evidence supports a stapled anastomosis. A meta-analysis of handsewn versus stapled anastomosis for both ulcerative colitis (UC) and FAP showed that functional outcomes were superior for stapled IPAA in continence to liquid stool, nighttime seepage, and nocturnal pad usage. This correlates with anorectal physiology studies showing a significant reduction in the resting and squeeze pressure in the hand-sewn group. No difference in sexual function was reported, with an overall incidence of postoperative impotence of 8%.20 Comparison of hand-sewn versus stapled in IPAA specifically for FAP shows more compelling results. Patients with stapled anastomosis had better functional outcomes in every category, including incontinence, daytime and nighttime seepage, and pad usage.15
Laparoscopic versus Open Surgery Laparoscopic-assisted IPAA is gaining in popularity. Casematched evaluation of the procedures shows that it compares favorably with open surgery. Equivalence is noted in both postoperative complications and functional outcomes, such as continence, stool frequency and medication usage.21 In addition, the feasibility of single incision laparoscopic proctocolectomy with IPAA has now been demonstrated anecdotally.22 With positioning the ileostomy at the single incision site, this offers patients a virtually scarless surgery. However, the complexity of the procedure could limit its wider use and data will be needed to determine whether the effort is justified.
One-Stage versus Two-Stage IPAA Choice between 1-stage and 2-stage IPAA (with vs without diverting ileostomy) seems to be operator dependent. A review of 119 procedures for FAP at the Cleveland Clinic revealed that the type of anastomosis (hand-sewn vs stapled) was a determining factor of whether a diverting ileostomy was chosen. Although all hand-sewn IPAA patients were diverted (n ⫽ 42), only 48% of stapled IPAA patients (37 of 77) were diverted. There were no significant differences in rates of postoperative leak, anastomotic stricture or fistula noted.15
Functional Outcomes of IRA versus IPAA When counseling FAP patients in regard to surgery (IPAA vs IRA), the information about functional outcomes is useful. FAP accounts for only 8.9%-11% of all cases of IPAA.14,23 Although the results of IPAA generally are excellent for both situations, a recent meta-analysis confirmed that the functional outcomes are significantly better for FAP than for UC.24 Patients undergoing IPAA for FAP have significantly lower
J.C. Carmichael and S. Mills
110 bowel frequency (on average, 1 bowel movement less per day) and rarely experience pouchitis (5.5% vs 30.1% for UC).24 Radiating a newly created ileal pouch invariably has a detrimental effect on the pouch function and should therefore be avoided. Preoperative staging of a rectal cancer in FAP may be very difficult, not to say often impossible, particularly if multiple polyps are present in the rectum. To ensure that even in FAP patients a correct oncological multimodality treatment is offered, one should always consider neoadjuvant chemoradiation before performing the pouch surgery. A recent retrospective analysis of ileal pouch construction for FAP at St Mark’s Hospital reviewed the impact of the pouch design on outcomes, such as stool frequency and continence. W-, J-, and S-pouch designs were found to have a statistically significant difference in median 24-hour stool frequency (4.3 vs 5 vs 3, respectively, P ⫽ 0.018). The authors claim that S-pouches fared better in stool frequency, but they were associated with a significantly increased need for abdominal salvage surgery, typically related to outlet obstruction and constipation secondary to a long efferent limb. Overall 10-year pouch survival rates did not show a significant difference.14 On an editorial note, one should keep in mind that one of the reasons for the great success of IPAA lies in the standardizable simplicity of creating a double-stapled J-pouch. The use of the aforementioned W- and S-pouch configuration should be limited to exceptional circumstances. In general, IRA has better functional outcomes than IPAA, but quality of life is not significantly different.25,26 patients with IRA have significant functional advantages over patients with IPAA in bowel frequency (2-6.1 vs 3.8-8 bowel movements per 24 h), fecal incontinence, need for night-time defecation, and use of pads. However, patients with IRA report more overall fecal urgency compared with patients with IPAA.27
Pregnancy Issues Although 23% of women choose not to become pregnant because of their diagnosis of FAP,28 any discussion with female patients about the surgery should include a discussion regarding fertility and pregnancy. Fecundity, defined as being capable of becoming pregnant and giving birth, is only little affected by an IRA. However, fecundity decreased to 54% after a proctocolectomy with IPAA for FAP. Interestingly, for reasons not well understood, fecundity decreased to 17% after IPAA for UC.28 considering this information, it may be appropriate for a woman contemplating pregnancy to first undergo an IRA with the intention to convert to IPAA at a later date.
Extracolonic Manifestations Desmoid tumors are benign myofibroblastic tumors occurring in approximately 12% of patients with FAP.29 Desmoid disease is the second leading cause of death in FAP patients, accounting for 10.5% of all deaths.3 Risk factors for desmoids
include female sex, positive family history of desmoids, and previous abdominal surgery.29 A meta-analysis showed no significant difference between the incidences of intraabdominal desmoids following IRA versus IPAA.27 Although desmoids may shorten the small bowel mesentery and render a pelvic pouch very difficult to reach, their presence as such does not represent a specific contraindication to form a pouch. Surgery for intraabdominal desmoid tumors should be reserved for small, well-defined tumors with a clear margin.30 Additional studies into the incidence of desmoid tumors after laparoscopic surgery are needed. In many series, duodenal cancer is the third-leading cause of death after colorectal cancer and desmoid disease. It has been shown to cause death in 0%-5% of FAP patients.2,3 There are not sufficient data to recommend for or against combining a duodenal resection or pancreaticoduodenectomy with the colectomy; however, one must turn to common sense and good clinical judgment to decide whether to stage the resections or to combine them. Both surgeries are major undertakings with huge physiological stresses, and consideration for combining them at one setting should not be taken lightly. That said, there is no specific evidence that for safety issues would preclude combining the 2 operations for carefully selected in this generally young and healthy patient population.
Postoperative Pouch Surveillance As mentioned previously, there is a significant incidence of polyp formation at the pouch-anal anastomosis. In addition, polyps and carcinomas can form within the pouch itself. Given this information, most groups recommend annual endoscopic surveillance.14,16 Some authors support even more frequent surveillance if no mucosectomy was performed31 or if there is a history of recurring polyps.19 Cyclooxygenase inhibitors may also be used in patients with recurring polyps in the ATZ or pouch.19 Although cyclooxygenase inhibitors have been shown to decrease the occurrence of colorectal polyps, they have not demonstrated a benefit in preventing the occurrence of rectal cancer.32
Conclusions Selecting the appropriate surgery for a patient with FAP is a complicated process that must take into account phenotypic and perhaps genotypic characteristics of the disease. The patient must be well informed regarding the functional outcomes of the various surgical procedures that are offered, including the risks of infertility. Patients must understand that postoperative surveillance is a lifelong endeavor regardless of the type of surgery chosen. “It is becoming clear that taking on FAP patients means taking them on for life.” —Robin Phillips, MSc, FRCS, Harrow, UK33
Surgical management of FAP
References 1. Groden J, Thliveris A, Samowitz W, et al: Identification and characterization of the familial adenomatous polyposis coli gene. Cell 66:589 – 560, 1991 2. Belchetz LA, Berk T, Bapat BV, et al: Changing causes of mortality in patients with familial adenomatous polyposis. Dis Colon Rectum 39: 384-387, 1996 3. Campos FG, Perez RO, Imperiale AR, et al: Evaluating causes of death in familial adenomatous polyposis. J Gastrointest Surg 14:1943-1949, 2010 4. da Luz-Moreira A, Church JM, Burke CA: The evolution of prophylactic colorectal surgery for familial adenomatous polyposis. Dis Colon Rectum 52:1481-1486, 2009 5. Bulow S, Bulow C, Vasen H, et al: Colectomy and ileorectal anastomosis is still an option for selected patients with familial adenomatous polyposis. Dis Colon Rectum 51:1318-1323, 2008 6. Bertario L, Russo A, Radice P, et al: Genotype and phenotype factors as determinants for rectal stump cancer in patients with familial adenomatous polyposis. Hereditary Colorectal Tumors Registry. Ann Surg 231:538-543, 2000 7. Vasen HFA, van Duijvendijk P, Buskens E, et al: Decision analysis in the surgical treatment of patients with familial adenomatous polyposis: A Dutch-Scandinavian collaborative study including 659 patients. Gut 49:231-235, 2001 8. Church J: Ileoanal pouch neoplasia in familial adenomatous polyposis: An underestimated threat. Dis Colon Rectum 48:1708-1713, 2005 9. Debinski HS, Love S, Spigelman AD, et al: Colorectal polyp counts and cancer risk in familial adenomatous polyposis. Gastroenterology 110: 1028-1030, 1996 10. Bulow C, Vasen H, Jarvinen H, et al: Ileorectal anastomosis is appropriate for a subset of patients with familial adenomatous polyposis. Gastroenterology 119:1454-1460, 2000 11. Nieuwenhuis MH, Bulow S, Bjork J, et al: Genotype predicting phenotype in familial adenomatous polyposis: A practical application to the choice of surgery. Dis Colon Rectum 52:1259-1263, 2009 12. Wu J, Philip P, McGannon EA, et al: APC genotype, polyp number, and surgical options in familial adenomatous polyposis. Ann Surg 227:5762, 1998 13. Nieuwenhuis MG, Vasen HF: Correlations between mutation site in APC and phenotype of familial adenomatous polyposis (FAP): A review of the literature. Crit Rev Oncol/Hematol 61:153-161, 2007 14. von Roon AC, Tekkis PP, Clark SK, et al: The impact of technical factors on outcome of restorative proctocolectomy for familial adenomatous polyposis. Dis Colon Rectum 50:952-961, 2007 15. Remzi FH, Church JM, Bast J, et al: Mucosectomy vs. stapled ileal pouch-anal anastomosis in patients with familial adenomatous polyposis: Functional outcome and neoplasia control. Dis Colon Rectum 44:1590-1596, 2001 16. van Duijvendijk P, Vasen HFA, Bertario L, et al: Cumulative risk of developing polyps or malignancy at the ileal pouch-anal anastomosis in patients with familial adenomatous polyposis. J Gastrointest Surg 3:325-330, 1999
111 17. von Herbay A, Stern J, Herfarth C: Pouch-anal cancer after restorative proctocolectomy for familial adenomatous polyposis. Am J Surg Pathol 20:995-999, 1996 18. O’Connell PR, Pemberton JH, Weiland LH, et al: Does rectal mucosa regenerate after ileoanal anastomosis? Dis Colon Rectum 30:1-5, 1987 19. Ooi BS, Remzi FH, Gramlich T, et al: Anal transitional zone cancer after restorative proctocolectomy and ileoanal anastomosis in familial adenomatous polyposis: report of two cases. Dis Colon Rectum 46:14181423, 2003 20. Lovegrove RE, Constantinides VA, Heriot AG, et al: A comparison of hand-sewn versus stapled ileal pouch anal anastomosis (IPAA) following proctocolectomy: a meta-analysis of 4183 patients. Ann Surg 244: 18-26, 2006 21. Larson DW, Dozois EJ, Piotrowicz K, et al: Laparoscopic-assisted vs. open ileal pouch-anal anastomosis: functional outcome in a casematched series. Dis Colon Rectum 48:1845-1850, 2005 22. Geisler DP, Condon ET, Remzi FH: Single incision laparoscopic total proctocolectomy with ileopouch anal anastomosis. Colorectal Dis 12: 941-943, 2010 23. Hueting WE, Bushens E, van der Tweel I, et al: Results and complications after ileal pouch anal anastomosis: A meta-analysis of 43 observational studies comprising 9,317 patients. Dig Surg 22:69-79, 2005 24. Lovegrove RE, Tilney HS, Heriot AG, et al: A comparison of adverse events and functional outcomes after restorative proctocolectomy for familial adenomatous polyposis and ulcerative colitis. Dis Colon Rectum 49:1293-1306, 2006 25. van Duijvendijk P, Slors JFM, Taat CW, et al: Quality of life after total colectomy with ileorectal anastomosis or proctocolectomy and ileal pouch-anal anastomosis for familial adenomatous polyposis. Br J Surg 87:590-596, 2000 26. Soravia C, Klein L, Berk T, et al: Comparison of ileal pouch-anal anastomosis and ileorectal anastomosis in patients with familial adenomatous polyposis. Dis Colon Rectum 42:1028-1034, 1999 27. Aziz O, Athanasiou T, Fazio VW, et al: Meta-analysis of observational studies of ileorectal versus ileal pouch-anal anastomosis for familial adenomatous polyposis. Br J Surg 93:407-417, 2006 28. Olsen KO, Juul S, Bulow S, et al: Female fecundity before and after operation for familial adenomatous polyposis. Br J Surg 90:227-231, 2003 29. Sinha A, Tekkis PP, Gibbons DC, et al: Risk factors predicting desmoid occurrence in patients with familial adenomatous polyposis: A metaanalysis. Colorectal Dis, 2010 30. Church J, Simmang C: Practice parameters for the treatment of patients with dominantly inherited colorectal cancer (familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer). Dis Colon Rectum 46:1001-1012, 2003 31. Vrouenraets BC, Duijvendijk P, Bemelman WA, et al: Adenocarcinoma in the anal canal after ileal pouch-anal anastomosis for familial adenomatous polyposis using a double-stapled technique: Report of two cases. Dis Colon Rectum 47:530-534, 2004 32. Steinbach LT, Lynch P, Phillips RKS, et al: The effect of celecoxib, a cyclo-oxygenase inhibitor, in familial adenomatous polyposis. N Engl J Med 342:1946-1952, 2000 33. Phillips R: Invited Commentary. Re: Anal transitional Zone Cancer after Restorative proctocolectomy and ileoanal anastomosis in Familial adenomatous polyposis (editorial). Dis Colon Rectum 46:1423, 2003
F
amilial adenomatous polyposis (FAP) is an autosomaldominant disease caused by a germline mutation of the adenomatous polyposis coli (APC) gene.1 The clinical diagnosis of FAP is supported when patients present with ⬎100 colorectal polyps. Because every mucosal cell of the colon and rectum carries the mutation, every mucosal cell has the potential to develop carcinoma. Further, patients with FAP are also at risk for extracolonic manifestations of the disease, such as desmoid tumors and gastroduodenal carcinoma.2,3 In the colon, surgery is designed to reduce the potential risk of colorectal cancer development while providing the patient with the best functional outcome.
Extent of Colonic Surgery The debate over the extent of surgery for FAP has been ongoing for many decades. Before the early 1970s, patients had 2 surgical options: they could undergo a proctocolectomy with ileostomy or a total abdominal colectomy with ileorectal anastomosis (IRA). In the past almost 40 years, ileal pouch anal anastomosis (IPAA) has become the primary option for many patients, especially those requiring a proctectomy. At the Cleveland Clinic, before the availability of IPAA, 97% of patients underwent IRA.4 The rate of subsequent completion proctectomy in those patients was 50% with a median time to completion proctectomy of 17 years.4 Patients generally underwent completion proctectomy because Division of Colon and Rectal Surgery, Department of Surgery, University of California, Irvine, CA. Address reprint requests to: Steven Mills, MD, Division of Colon and Rectal Surgery, Department of Surgery, University of California, Irvine, 333 City Blvd W, Ste 850, Orange, CA 92868. E-mail: [email protected]
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of the development of rectal cancer or uncontrolled rectal polyps. Subsequently, in the ileal pouch era, the rate of IRA has decreased to 56%, and a completion proctectomy was performed at a rate of 2%.4 Given this low rate of necessary completion proctectomy, it would seem that IRA is still appropriate in patients during the pouch era; however, appropriate patient selection for IRA is critical. Looking at similar data from Europe, Bulow et al5 noted that 10% of IRA patients developed rectal cancer in the prepouch era, whereas only 2% developed rectal cancer in the pouch era, suggesting that IRA is still appropriate in selected patients. The risk of rectal cancer after IRA increases with time after surgery. At 10, 15, and 20 years after IRA, the cumulative risk of was 7.7%, 13.1%, and 23%, respectively.6 Close endoscopic surveillance of the rectum does not seem to prevent cancer, as 75% of patients with an IRA had undergone an endoscopic examination within 12 months of the diagnosis of rectal cancer. However, endoscopic examination did lead to an increase in detection of early stage cancer.7 As will be discussed later, the cumulative risk of rectal cancer after IPAA is very low. A recent review shows only 8 reported cases in the literature.8 The rectal cancer risk is significantly greater in patients (a) who had colon cancer at the time of the initial operation, (b) with more than 30 rectal polyps at the initial operation, (c) with APC mutations between codons 1250 and 1464, and (d) with more than 1000 colonic adenomas.6,9 Patients with these risk factors are not good candidates for rectal preservation and should be offered a proctocolectomy with either IPAA or an ileostomy. Given this information, several groups have outlined criteria for patients to have the option of IRA. In general, IRA has
Surgical management of FAP been recommended for patients with few (⬍20) rectal adenomas, mild colonic phenotype (⬍1000 colon polyps), no colorectal cancer, family history of mild phenotype, attenuated FAP, patients without codon 1309 mutations, and no severe rectal dysplasia.4,5 Lifelong surveillance endoscopy every 6 to 12 months is necessary.10
The Role of Genotype in Surgery Traditionally, the decision to proceed with IRA versus IPAA in patients with FAP has been determined on the basis of phenotypic factors. As noted previously, patients with an attenuated pattern of FAP (⬍100 polyps, aFAP) and few rectal polyps are good candidates to proceed with a rectal sparing IRA procedure. However, the phenotypic expression of FAP does leave room for error, and some authors have sought to determine whether genetic markers may be useful in predicting the clinical course of patients with FAP.11 Wu et al12 have noted that mutations at APC gene codons 1309 and 1328 lead to a very poor prognosis for retaining the rectum. These authors recommend IPAA for patients with these mutations. Genotypes corresponding to phenotypes of aFAP, intermediate FAP, and severe FAP have been established. aFAP is associated with mutations at the 5= and 3= ends of the APC gene and the alternatively spliced site of exon 9. Severe FAP is the result of mutations between codons 1250 and 1464, and intermediate FAP corresponds to mutations in the remainder of the FAP gene.13 Results of retrospective genotype analysis reveal that 20 years after IRA, the risk of secondary proctectomy was 10%, 39%, and 61% in patients with attenuated, intermediate, and severe FAP genotypes, respectively.13 Although these results are interesting, they currently do not replace the use of FAP phenotype in surgical decision-making.
Technical Aspects of the Surgery IPAA: Mucosectomy versus Double Stapled Anastomosis One of the critical debates in FAP pouch surgery is centered on the decision to perform a mucosectomy with handsewn pouch-anal anastomosis versus a stapled anastomosis. Proponents of a mucosectomy claim a reduced risk of postpouch neoplasia in the anal transition zone (ATZ). Proponents of stapled anastomosis argue that functional outcomes are improved with stapled anastomosis, that the risk of cancer in the ATZ is very small, and that even mucosectomy patients can develop carcinoma in the area. The incidence of ATZ polyps after handsewn anastomosis is 10%-19%, whereas after stapled anastomosis, it is 28%38%.14-16 Severe colonic disease was a statistically significant risk factor for the development of ATZ polyps.15 A literature review in 2005 revealed 8 reported cases of adenocarcinoma developed at the anastomosis after IPAA for FAP.8 The diagnosis was made a median of 8 years after
109 pouch reconstruction (range, 3-20 years). One-half of these cancers followed stapled anastomosis and one-half followed mucosectomy. Clearly, cancer may occur regardless of the selected type of procedure. Mucosectomy is likely not protective of cancer because islands of rectal mucosa remain in the anal canal after the procedure.17,18 Mucosectomy has been recommended for patients with cancer of the rectum or carpeting of the ATZ with polyps.19 In function, the evidence supports a stapled anastomosis. A meta-analysis of handsewn versus stapled anastomosis for both ulcerative colitis (UC) and FAP showed that functional outcomes were superior for stapled IPAA in continence to liquid stool, nighttime seepage, and nocturnal pad usage. This correlates with anorectal physiology studies showing a significant reduction in the resting and squeeze pressure in the hand-sewn group. No difference in sexual function was reported, with an overall incidence of postoperative impotence of 8%.20 Comparison of hand-sewn versus stapled in IPAA specifically for FAP shows more compelling results. Patients with stapled anastomosis had better functional outcomes in every category, including incontinence, daytime and nighttime seepage, and pad usage.15
Laparoscopic versus Open Surgery Laparoscopic-assisted IPAA is gaining in popularity. Casematched evaluation of the procedures shows that it compares favorably with open surgery. Equivalence is noted in both postoperative complications and functional outcomes, such as continence, stool frequency and medication usage.21 In addition, the feasibility of single incision laparoscopic proctocolectomy with IPAA has now been demonstrated anecdotally.22 With positioning the ileostomy at the single incision site, this offers patients a virtually scarless surgery. However, the complexity of the procedure could limit its wider use and data will be needed to determine whether the effort is justified.
One-Stage versus Two-Stage IPAA Choice between 1-stage and 2-stage IPAA (with vs without diverting ileostomy) seems to be operator dependent. A review of 119 procedures for FAP at the Cleveland Clinic revealed that the type of anastomosis (hand-sewn vs stapled) was a determining factor of whether a diverting ileostomy was chosen. Although all hand-sewn IPAA patients were diverted (n ⫽ 42), only 48% of stapled IPAA patients (37 of 77) were diverted. There were no significant differences in rates of postoperative leak, anastomotic stricture or fistula noted.15
Functional Outcomes of IRA versus IPAA When counseling FAP patients in regard to surgery (IPAA vs IRA), the information about functional outcomes is useful. FAP accounts for only 8.9%-11% of all cases of IPAA.14,23 Although the results of IPAA generally are excellent for both situations, a recent meta-analysis confirmed that the functional outcomes are significantly better for FAP than for UC.24 Patients undergoing IPAA for FAP have significantly lower
J.C. Carmichael and S. Mills
110 bowel frequency (on average, 1 bowel movement less per day) and rarely experience pouchitis (5.5% vs 30.1% for UC).24 Radiating a newly created ileal pouch invariably has a detrimental effect on the pouch function and should therefore be avoided. Preoperative staging of a rectal cancer in FAP may be very difficult, not to say often impossible, particularly if multiple polyps are present in the rectum. To ensure that even in FAP patients a correct oncological multimodality treatment is offered, one should always consider neoadjuvant chemoradiation before performing the pouch surgery. A recent retrospective analysis of ileal pouch construction for FAP at St Mark’s Hospital reviewed the impact of the pouch design on outcomes, such as stool frequency and continence. W-, J-, and S-pouch designs were found to have a statistically significant difference in median 24-hour stool frequency (4.3 vs 5 vs 3, respectively, P ⫽ 0.018). The authors claim that S-pouches fared better in stool frequency, but they were associated with a significantly increased need for abdominal salvage surgery, typically related to outlet obstruction and constipation secondary to a long efferent limb. Overall 10-year pouch survival rates did not show a significant difference.14 On an editorial note, one should keep in mind that one of the reasons for the great success of IPAA lies in the standardizable simplicity of creating a double-stapled J-pouch. The use of the aforementioned W- and S-pouch configuration should be limited to exceptional circumstances. In general, IRA has better functional outcomes than IPAA, but quality of life is not significantly different.25,26 patients with IRA have significant functional advantages over patients with IPAA in bowel frequency (2-6.1 vs 3.8-8 bowel movements per 24 h), fecal incontinence, need for night-time defecation, and use of pads. However, patients with IRA report more overall fecal urgency compared with patients with IPAA.27
Pregnancy Issues Although 23% of women choose not to become pregnant because of their diagnosis of FAP,28 any discussion with female patients about the surgery should include a discussion regarding fertility and pregnancy. Fecundity, defined as being capable of becoming pregnant and giving birth, is only little affected by an IRA. However, fecundity decreased to 54% after a proctocolectomy with IPAA for FAP. Interestingly, for reasons not well understood, fecundity decreased to 17% after IPAA for UC.28 considering this information, it may be appropriate for a woman contemplating pregnancy to first undergo an IRA with the intention to convert to IPAA at a later date.
Extracolonic Manifestations Desmoid tumors are benign myofibroblastic tumors occurring in approximately 12% of patients with FAP.29 Desmoid disease is the second leading cause of death in FAP patients, accounting for 10.5% of all deaths.3 Risk factors for desmoids
include female sex, positive family history of desmoids, and previous abdominal surgery.29 A meta-analysis showed no significant difference between the incidences of intraabdominal desmoids following IRA versus IPAA.27 Although desmoids may shorten the small bowel mesentery and render a pelvic pouch very difficult to reach, their presence as such does not represent a specific contraindication to form a pouch. Surgery for intraabdominal desmoid tumors should be reserved for small, well-defined tumors with a clear margin.30 Additional studies into the incidence of desmoid tumors after laparoscopic surgery are needed. In many series, duodenal cancer is the third-leading cause of death after colorectal cancer and desmoid disease. It has been shown to cause death in 0%-5% of FAP patients.2,3 There are not sufficient data to recommend for or against combining a duodenal resection or pancreaticoduodenectomy with the colectomy; however, one must turn to common sense and good clinical judgment to decide whether to stage the resections or to combine them. Both surgeries are major undertakings with huge physiological stresses, and consideration for combining them at one setting should not be taken lightly. That said, there is no specific evidence that for safety issues would preclude combining the 2 operations for carefully selected in this generally young and healthy patient population.
Postoperative Pouch Surveillance As mentioned previously, there is a significant incidence of polyp formation at the pouch-anal anastomosis. In addition, polyps and carcinomas can form within the pouch itself. Given this information, most groups recommend annual endoscopic surveillance.14,16 Some authors support even more frequent surveillance if no mucosectomy was performed31 or if there is a history of recurring polyps.19 Cyclooxygenase inhibitors may also be used in patients with recurring polyps in the ATZ or pouch.19 Although cyclooxygenase inhibitors have been shown to decrease the occurrence of colorectal polyps, they have not demonstrated a benefit in preventing the occurrence of rectal cancer.32
Conclusions Selecting the appropriate surgery for a patient with FAP is a complicated process that must take into account phenotypic and perhaps genotypic characteristics of the disease. The patient must be well informed regarding the functional outcomes of the various surgical procedures that are offered, including the risks of infertility. Patients must understand that postoperative surveillance is a lifelong endeavor regardless of the type of surgery chosen. “It is becoming clear that taking on FAP patients means taking them on for life.” —Robin Phillips, MSc, FRCS, Harrow, UK33
Surgical management of FAP
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