Familial adenomatous polyposis. Surgical treatment - Springer Link

Tech Coloproctol (2004) 8:S309–S314 DOI 10.1007/s10151-004-0183-0 F A M I L I A R A D E N O M AT O U S P O LY P O S I S

E. Contessini-Avesani • F. Botti • C. Negri • A. Carrara • B. Oreggia • F. Quadri • C. Bagni

Familial adenomatous polyposis. Surgical treatment: when and how

Abstract Familial adenomatous polyposis is an autosomal dominated inherited disease, caused by the mutation of the tumour suppressor gene adenomatous polyposis coli on chromosome 5. Despite being a rare disorder, accounting for some 1% of colorectal cancers, it represents an interesting model of hereditary disease, because of its intrinsic characteristics, conventionally defined by the presence of more than 100 colorectal polyps, as well as extra-colon manifestations, the attenuated form of the disease, genetic aspects, the inevitable progression to colorectal cancer and hence the correct therapy to treat or prevent the fatal evolution of the disease. Surgical treatment is based above all on two techniques: ileorectal anastomosis, which requires careful surveillance of rectal remnant, and ileal pouch-anal anastomosis, which totally eradicates the disease. The suitability of using these two techniques is discussed in view of new genetic and clinical findings, acquired from personal experience and from the literature. Key words FAP • Surgery • Options

E. Contessini-Avesani • F. Botti • C. Negri • A. Carrara • B. Oreggia F. Quadri • C. Bagni 2nd Division of General Surgery IRCCS Maggiore Hospital, Milan, Italy E. Contessini-Avesani () • F. Botti • A. Carrara • C. Bagni Department of Surgical Sciences Milan University, Milan, Italy Via F. Sforza 35, 20122 Milan, Italy E-mail: [email protected]

The many aspects of this disease mean that deciding when and how it is most suitable to treat these patients, who are mainly young, calls for careful assessment. Based on the disease’s symptoms, the most appropriate treatment to reduce the risk of cancer needs to be chosen, whilst maintaining a good quality of life. This is fundamental for individuals having to undergo radical surgery when they do not have disabling symptoms or have moderate clinical symptoms. Over the last 25 years, experience in surgical therapies first represented by total proctocolectomy (TP) with permanent ileostomy and by ileorectal anastomosis (IRA) have been perfected. As in the case of ulcerative colitis, with just two surgical options available, IRA was often selected because of a lack of other choices, with the ensuing need to remove the rectum (Miles operation). For a short time before restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) became common, Koch [1] developed a reservoir allowing for a continent ileostomy (i.e., without the use of a collecting bag), which improved patients’ quality of life, but also implied a certain morbidity rate. The development of restorative proctocolectomy (Parks and Nicholls [2]), which enables the disease to be entirely eradicated at a colorectal level, whilst maintaining the anal canal, with excellent functional results, appears to be the most suitable option for treating familial adenomatous polyposis (FAP). How to operate? The reply to this question seems quite clear today, if the criteria adopted in the 1980s–90s are followed. These criteria are based mainly on clinical findings attributable to the overall number of polyps in the rectum, the occurrence and site of dysplasia and cancer and the occurrence of intra-abdominal and mesenteric desmoid tumours. Nowadays, the most suitable surgical option for each case should be chosen not only considering clinical criteria – which are still important – but also more recently defined parameters, such as genetics or age, occasional occurrence in the progenitor patient or affected family members, the patient’s wishes concerning the type of operation, willingness to undergo follow-ups, the possibili-

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E. Contessini-Avesani et al.: Surgical treatment of FAP

ty of effective pharmacological treatment and lastly the allround experience of the surgeon in relation to all possible options, which is a decisive factor in pathologies requiring specialist expertise, in order to choose the most appropriate operation and achieve the best functional results. Once the possible operative choices are known, it is important to make the right choice and decide when to operate on patients. Some recently discovered factors concern a particular form of FAP – attenuated familial adenomatous polyposis (AFAP) [3], which differs from classic FAP as fewer polyps develop (less than 100), the polyps and tumours are located more proximally in the colon and the rectum is less affected, and the average age of symptoms occurring and diagnosis is later than for FAP (polyps diagnosed at 44 years, cancer at 56 years). Despite having similar hereditary characteristics, extracolonic manifestations and genetic errors, the when and how of treating these two forms can clearly be different. General aspects affecting treatment procedures and times include extracolonic manifestations of the disease, such as simple dermoid cysts and osteomas or more complex desmoid tumours (Gardner’s syndrome). When present, these manifestations may significantly impact surgical and therapeutic strategies, especially when they involve the mesenteric or retroperitoneal structures and the abdominal wall muscles. While brain tumours (Turcot’s syndrome) are rare, gastric, duodenal and periampullary polyps are very common. Treating periampullary polyps is not always easy: the possible progression of ampullary or periampullary polyps must be monitored, as this carries a serious additional risk, requiring a Whipple’s operation. Apart from monitoring and eliminating polyps in the rectum or pouch, routine upper endoscopy of the stomach and duodenum is necessary to eliminate and prevent any manifestations. Retinal spots are also a good marker of the illness and can help in screening affected family members. Another aspect affecting technical choices (Table 1) is the time of diagnosis and whether the individual is the progenitor patient (without previous family members affected

by FAP), or has been diagnosed based on a family tree or genetic screening (affected family member). As documented in a Finnish study [4] evaluating the characteristics of patients affected by FAP, progenitor patients have a higher risk of the disease manifesting in the advanced stage, in terms of symptoms and cancer, than family members undergoing diagnostic screening at a younger age. In patients diagnosed on the basis of their symptoms, irrespective of whether or not they are primogenitors of the disease or if they have not undergone genetic testing, radical surgery such as IPAA is generally recommended. This option is selected as it prevents leaving the rectum in situ with a higher cancer risk. The patient must be informed about the greater complexity of IPAA and be able to evaluate the risks and benefits of the two options. The patient’s wishes are particularly important in the case of teenagers who are inclined to opt for the same procedure used on family relatives already treated and above all when results were good, or to reject the best solution if a family relative has had serious problems arising from the surgical treatment. As Fazio describes [5], the presence of numerous, large polyps and obviously cancer in teenagers calls for IPAA irrespective of the patient’s wishes. In other cases, the patient’s wishes and surgeon’s experience are fundamental in choosing treatment. In our experience, in 4 out of 6 teenagers, the choice was influenced by the patient’s decision irrespective of our indications, which coincided in all but one case, and in 5 out of 6 cases IPAA was performed. Even the criterion of choosing treatment based on the number and characteristics of polyps is still effective, as a limited number of small polyps, conventionally below 20, allows for easier, subsequent removal and is generally accompanied by a less severe phenotype. However, clinical criteria should increasingly be linked to information from genetic testing, which is steadily gaining a predictive role in identifying patients where the rectum may be left in situ with a low cancer risk, or individuals with a high risk, when IPAA is recommended anyway. Even from as early on as 1996, a study by a Dutch Group [6] clearly showed the genetic error on chromosome

Table 1 Criteria for choosing from the two most common surgical options IRA

How to choose

IPAA

Age (teenagers)

Both options

Suffering relatives IRA 20 Patient desire Follow-up availability Severe dysplasia or colon cancer Severe dysplasia or rectal cancer Desmoid tumours (wall) Severe mutation


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5 as a marker for making the right IRA choice whenever the genetic error was before codon 1250, and indicated that IPAA was suitable for individuals with a genetic error after codon 1250. In 2000, the Bulow study [7] further defined the correlation between clinical and genetic aspects for preferring one surgical technique over another. They claim IRA is advisable in young patients with few rectal polyps belonging to a family with a slight mutation or in cases of attenuated FAP with a genetic error in codon 0–200 or above 1500, provided continual follow-up with rectal surveillance is accepted. In the case of patients with high numbers of rectal polyps with severe polyposis or a severe family mutation, only IPAA is recommended. In order to compare claims made in the literature with our case history findings, we highlighted a particular item of data concerning the ratio between the severity of the mutation, the type of operation performed and need for a further operation (Fig. 1). When a slight mutation was present, IPAA was performed in 8 cases and IRA in 6 cases. None of the IRA operations performed so far, for a slight mutation, have required conversion to IPAA. Only endoscopic removal of rectal polyps has been necessary. In patients with severe mutation, we performed IPAA in 8 cases and IRA in 7 cases. Out of the 7 cases of IRA, 5 asked for conversion. In 3 of the 5 cases, a Miles’ operation was performed, as cancer was detected in polyps that were so close to anal canal that conversion to IPAA was not possible, while in 2 cases conversion was successfully performed to treat widespread polyps, which could not be managed by endoscopic removal. However, the histological tests of one of these two patients indicated a stage B1 carcinoma that had not been detected in the pre-operative stage. In 3 of these 5 cases, IRA had been performed at another hospital, and decisions were not dictated by clinical criteria in use at the time, but by the experience of the surgeon and the patient’s wish to avoid having a permanent ileostomy. In the two patients we operated on previously, performing IRA, one underwent a Miles’ operation as a carcinoma was

IRA - genetic factors - IPAA retrospective aspects in our series of FAP patients 8 IPAA 0 6 IRA 10 IPAA

Mild mutation 14

Severe mutation 16

8 7

1 Miles 4

3

2 7 IRA

2 IRA

Fig. 1 Surgical options and genetic implications. Known mutation, n=30; unknown mutation, n=4; total patients treated, n=34

detected on a polyp close to the dentate line, which had not been noted during surveillance and endoscopic removal. IRA had been chosen for this patient due to the presence of a mesenteric desmoid, while in the other patient genetic testing was not carried out in the pre-operative stage, so the decision was dictated by a number of polyps bordering the rectum (around 20) and by the concurrent presence of jaundice, caused by an endopapillary duodenal adenomatous polyp. In this last case, despite the degenerated rectal polyp, conversion to IPAA was possible. To sum up, only 2 of the 7 patients with severe mutation undergoing an IRA are still treated for the routine removal of rectal polyps and at present have not requested conversion. From an assessment of the literature and on the basis of our experience, it is clear that today the decision to leave the rectum must be prompted by the presence of sporadic rectal polyps and a slight genetic mutation, the absence of severe dysplasia or colon of the cancer and more rarely by the presence of intra-abdominal or mesenteric desmoids which advise against IPAA. As stated by several authors, it is difficult to perform endoscopic surveillance when there are many, adjoining polyps: this increases the risk of progression on malignant transformation, even in patients who undergo regular follow-ups [8]. Thus, the risk of cancer of the rectum can easily be correlated to the above factors, as noted by Bertario’s study [9] on patients in the Italian FAP registry, and particularly when cancer of the colon is present when IRA is performed in conjunction with a genetic error between codon 1250 and codon 1464. As mentioned, even desmoid tumours are problematic for treating FAP. Intra-abdominal desmoid tumours may significantly affect the choice of surgical treatment, or if they develop during the post-operative stage they are extremely difficult to treat and results are often unsatisfactory. Abdominal wall desmoid tumours are less aggressive and easier to treat, so they can be entirely removed [10]. In our experience, parietal desmoid tumours appear in 3 out of 4 cases after surgery, at the site of surgical scarring. Having considered the procedures for choosing between IRA and IPAA, we shall now assess the objectives that can be achieved with these techniques. The only striking difference is the radical nature of the techniques, as the rectal stump remains with IRA. With both techniques, a preservation of anal sphincter function is maintained, which is particularly important for young patients, with the number of bowel movements after both IRA and IPAA acceptable in terms of urgency and particularly good after IPAA. Obviously, continence is normal in patients who have undergone IRA. In individuals who have had IPAA, a low percentage of daytime soiling, and a higher night-time percentage is reported [11]. In our experience, the results of IPAA are entirely satisfactory in terms of the number of bowel movements (3–4 in 24 h) and continence (no day-time soiling, 20% night-time soil-

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ing). Usually sexual function is not impaired in patients who have undergone IRA, nor in individuals who have had IPAA, unless there is a risk of damage to the pelvic nerves due to the radical nature of the operation. A proper technique which takes into consideration anatomical planes, even performing a total mesorectal excision, involves a very small risk of impairing sexual function. With both techniques, the quality of life is very satisfactory, enabling patients to return to work or study, without a stoma that can have a negative effect on their social life. Contrary to previously held opinions, the patient must be willing to undergo follow up, in the case of IRAs, where endoscopic rectal surveillance is mandatory, and in both techniques for gastroduodenal surveillance to remove polyps and particularly at a duodenal and papillary level. More recently, the need for endoscopic pouch surveillance has come to light, as adenomatous polyps have been known to form at the ileal mucosa. In strictly surgical terms, IRA has the advantage of requiring one operation, with a moderate complication rate and good functional results. Since it has been possible to perform video laparoscopic colectomies, the right choice for IRA, based on the above criteria involves a low risk of the patient developing rectal cancer and at the same time damage to the abdominal wall is reduced, with excellent aesthetic results, in relation as well to the patients’ young age. For reasons mentioned previously, a subsequent proctectomy with conversion to ileoanal anastomosis or total proctectomy and permanent ileostomy, may be necessary. IPAA is technically more complex. In addition to the colectomy, the time needed to carry out the proctectomy, the ileal reservoir, the mucosectomy, manual ileo-anal anastomosis and the temporary ileostomy needs to be considered. This operation can also be performed by partially or fully assisted video laparoscopic procedure. In our 8 years of experience, we developed a technique valid for both IRA and IPAA after an initial learning curve. The operation begins with a small, 7 cm Pfannestiel incision, through which the caecum is mobilised and the ileum at the ileocaecal valve is sectioned by GIA (Auto Suture Multifire 60 mm). If IRA is to be performed, the rectum is prepared at the point where it joins the sigmoid and at the same time it is separated by GIA. A handport is positioned in the incision and after inserting three other 12-mm ports, a radiofrequency system (Ligasure®) is used to mobilise the colon and seal the colonic vessels, and the entire colon is removed. If IPAA is to be performed, the rectum is not separated from the sigmoid, but is removed using video laparoscopic technique if indicated, or through the Pfannestiel incision, to reach the perineal plane. Before carrying out a proctectomy, it is standard practice to check whether the last section of the ileum can easily reach the anus without being taut. The rectum is therefore sectioned at the levator plane and removed. Details on the reservoir’s shape and how it is created are no longer discussed


to a great extent, as the literature shows that the most capacious reservoirs, such as W or S reservoirs, achieve better results in the first few post-operative months, and after 12 months their performance is similar to J reservoirs. In our experience, we have always preferred threeloop (S) reservoirs, for both FAP and ulcerative colitis. As the perineum can be reached more distally compared to the “J” loop, this technique seems particularly suitable for patients where it is even more important to maintain a natural way than in patients affected by ulcerative colitis. Moreover, as the mucosectomy has to be carried out from the dentate line, the “S” reservoirs seem to be the most suitable, in our experience. An aspect that is still being discussed, however, concerns the suitability of performing a mucosectomy and thus a hand-sewn, end-to-end ileo-anal anastomosis (for the S reservoir) removing the residual rectal mucosa (1.5–3 cm long) from the dentate line including the transitional epithelium between the anal and rectal mucosa. If a mucosectomy is not performed and stapling (often double stapling) is carried out, the entire transitional zone – as a minimum – is left: further centimetres of rectal mucosa may easily be left, in relation to the thickness of the pelvic floor, the patient’s sex and surgeon’s skills. The benefits of stapling include faster operating times, slightly better functional results and the possibility of avoiding a protective ileostomy. However, a 28% risk of adenomas forming in the transition zone and in the residual rectal mucosa exists, as demonstrated by Remzi et al. [12]. In our opinion, the risk of cancer developing is relevant as it is not always easy to monitor and treat polyps close to the dentate line and malignant transformation can also occur during endoscopic follow up [8]. Even Ooi et al. [13], in a recent work, points out the need to carefully monitor the transitional zone left in situ for cancer risks, and reconsiders the suitability of mucosectomy in patients with widespread polyps on the rectal mucosa. In our experience, we have always carried out mucosectomy from the dentate line and in the second case of FAP, operated in 1985, this decision was prompted by the discovery of a stage A Dukes carcinoma in the removed mucosa section. Moreover, mucosectomy in patients with FAP is far easier than in individuals affected by ulcerative colitis, as inflammation is not present, so the risk of ileo-anal anastomosis stenosis is practically nil. Functional results are excellent, both in terms of the number of bowel movements (3.8 on average in our 19 patients with FAP), and continence, and as observed and described by nearly all authors, pouchitis is practically absent in patients with FAP. In our cases (Fig. 2) the operation is always performed with a hand-sewn suture for ileo-anal anastomosis and the reservoir, which are protected by a temporary ileostomy. Even though the suitability of performing an ileostomy is controversial, as some patients complain about its significant impact, we think it can help avoid pelvic sepsis or anasto-


FAP surgical options: personal experience - Total proctocolectomy: 4, of those 3 conversions from IRA due to cancer presence (1 Kock’s pouch) - Ileal pouch anal anastomosis (IPAA): 19 of those 2 conversion from IRA - Ileorectal anastomosis (IRA): 13 Patients: n=34 Operations: 40 - Segmentary resection: 1 Dead of colon cancer: 2 Dead of pancreatic cancer: 1

- Desmoid tumors 7 (7/34) - 9 cancers in 8 patients (2A-5B2-1C-1D Dukes A.C.) - 1 duodenectomy to remove an intrampullary adenoma - 1 palliative derivation for periampullary-pancreatic cancer - 1 total gastrectomy for gastric cancer - 45% FAP patients with duodenal and gastric polyps Mean follow-up time: 9.8 years Lost to follow-up: 1 Fig. 2 Operations for familial adenomatous polyposis

motic complications, which would then affect functional results [14]. In our experience, and in the experience of many authors, complications arising from IPAA in patients affected by FAP exceed those relating to IRA and in any case are fewer than complications observed in the same operation for ulcerative colitis. These factors, combined with the possibility of eradicating colorectal disease and easier mandatory endoscopy follow-up times for IRA, led us to select this approach as our first choice [15]. In practice, if the risk of colorectal cancer is eliminated by performing radical surgery (mucosectomy from the dentate line), endoscopic surveillance must be carried out at both a gastric and duodenal level for all FAP patients, irrespective of the operating technique used. Mandatory rectal endoscopic surveillance for IRA must be extended to patients with a pouch. Whereas we initially focused on trying to understand why these pouches did not show signs of inflammation observed in patients with ulcerative colitis, the presence of microadenomas and adenomas, especially in more dated pouches, was gradually noted. In 13 of the pouches, with a mean follow-up time of 9 years, evaluated in 2000, we observed evident polyps in 2 patients (1 and 10 polyps respectively), with mild and moderate dysplasia, while microadenomas were noted in a further 2, and in the remaining patients biopsies showed lymphoid hyperplasia or slight signs of inflammation. Another aspect, which has no statistical significance, however, as the figures are limited, is linked to the fact that 3 of the 13 patients examined had colon cancer at the time of the operation (1 Tis-2 T1, N0, M0) and all three had polyps in the ileal pouch years after the operation [16]. Although cases of polyp malignant transformation in ileal pouches are still rare, this factor calls for surveillance – with local treatment if necessary or systemic treatment with drugs [17].

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Conclusions When and how to operate are two factors which have become more evident compared to the recent past. Choosing a suitable operation to treat FAP is less of a random task than before, and is related to a lesser extent to the surgeon’s preferences. As the morbidity and functional results of IPAA, which is a more complex operation, are quite similar to the results of IRA, accurate choices must be made which are increasingly guided by genetic-based predictions. IPAA today appears to be the radical solution for preventing the risk of colorectal cancer, particularly in patients who have been diagnosed on the basis of their symptoms or who are progenitor patients, or individuals with a genetic error indicating a severe disease. Genetic testing indicating a mild mutation or clinical diagnosis of attenuated FAP means that IRA can be chosen with safer criteria and is not only linked to the clinical factor of the number of rectal polyps or a patient’s choice of one operation over another. Interest in performing IRA has also grown as the operation can now be performed by video laparoscopy, with minimum impact on the abdominal wall and only one surgical operation, which is particularly important for these young patients. The possibility of using drugs that can prevent rectal polyps re-forming provides further care prospects, even though endoscopic surveillance and removal of metachronous polyps are still mandatory. In individuals with unfavourable development and an increase in rectal polyps, conversion to IPAA is possible and results are similar to IPAA performed as a first operation. Lastly, the problem of polyps growing in pouches, as highlighted recently in the literature, should be carefully evaluated. This could lead us back to the question of how to operate on these unlucky patients, who have to undergo endoscopic gastroduodenal surveillance – despite having radical, permanent surgery – but also must undergo pouch surveillance to guard against the future development of polyps and cancer.

References 1. Koch NG (1969) Intra-abdominal ‘reservoir’ in patients with permanent ileostomy. Arch Surg 99:223–231 2. Parks AG, Nicholls RJ (1978) Proctocolectomy without ileostomy for ulcerative colitis. BMJ 2:85–88 3. Hernegger GS, Moore HG, Guillem JG (2002) Attenuated familial adenomatous polyposis. An evolving and poorly understood entity. Dis Colon Rectum 45:2 4. Heiskanen I, Luostarinen T, Jarvinen HJ (2000) Impact of screening examinations on survival in familial adenomatous polyposis. Scand J Gastroenterol 35:1284–1287 5. Ziv Y, Church JM, Oakley JR, Mc Gannon E, Fazio VW (1995) Surgery for the teenager with familial adenomatous polyposis: ileo-rectal anastomosis or restorative proctocolectomy? Int J Colorectal Dis 10:6–9

S314 6. Vasen HF, Van der Luijt RB, Slors JF et al (1996) Molecular genetic tests as a guide to surgical management of familial adenomatous polyposis. Lancet 348:433–435 7. Bulow C, Vasen H, Jarvinen H, Bjork J, Bisgaard ML, Bulow S (2000) Ileorectal anastomosis is appropriate for a subset of patients with familial adenomatous polyposis. Gastroenterology 119:1454–1460 8. Vasen HF, van Duijvendijk P, Buskens E et al (2001) Decision analysis in the surgical treatment of patients with familial adenomatous polyposis: a Dutch–Scandinavian collaborative study including 659 patients. Gut (England) 49:231–235 9. Bertario L, Russo A, Radice P, Varesco L, Eboli M, Spinelli P, Reyna A, Sala P. On behalf of the Hereditary Colorectal Tumors Registry (2000) Genotype and phenotype factors as determinants for rectal stump cancer in patients with familial adenomatous polyposis. Ann Surg 231:538–543 10. Clark SK, Neale KF, Landgrebe JC, Phillips RK (1999) Desmoid tumours complicating familial adenomatous polyposis. Br J Surg 86:1185–1189 11. Björk J, Åkerbrant H, Iselius L, Svenberg T, Resland TÖ, Påhlman L, Hultcrantz R (2001) Outcome of primary and secondary ileal pouch-anal anastomosis and ileorectal anastomosis in patients with familial adenomatous polyposis. Dis Colon Rectum 44:984–992

E. Contessini-Avesani et al.: Surgical treatment of FAP 12. Remzi FH, Church JM, Bast J et al (2001) Mucosectomy vs. stapled ileal pouch-anal anastomosis in patients with familial adenomatous polyposis. Functional outcome and neoplasia control. Dis Colon Rectum 44:1590–1596 13. Ooi BS, Remzi FH, Gramlich T, Church JM, Preen M, Fazio VW (2003) Anal transitional zone cancer after restorative proctocolectomy and ileoanal anastomosis in familial adenomatous polyposis: report of two cases. Dis Colon Rectum 46:1418–1423 14. Williamson MER, Lewis WG, Sagar PM, Holdsworth PJ, Johnston D (1997) One-stage restorative proctocolectomy without temporary ileostomy for ulcerative colitis: a note of caution. Dis Colon Rectum 40:1019–1022 15. Kartheuser AH, Parc R, Penna CP, Tiret E, Frileux P, Hannoun L (1996) Ileal pouch-anal anastomosis as the first choice operation in patients with familial adenomatous polyposis: a tenyear experience. Surgery 119:615–623 16. Contessini-Avesani E, Grossano L, Botti F, Carrara A, Cioffi U, De Simone M (2001) Adenomas in the ileal pouch after restorative proctocolectomy in patients with familial adenomatous polyposis (FAP). Gut 49[Suppl III]:5 17. Thompson-Fawcett MW, Marcus VA, Redston M, Cohen Z, McLeo RS (2001) Adenomatous polyps develop commonly in the ileal pouch of patients with familial adenomatous polyposis. Dis Colon Rectum 44:347–353