- Email: [email protected]
Ureterosigmoid anastomosis: risk of colorectal cancer and implications for colonoscopists
REVIEW ARTICLE
tomy, and follow-up requirements for patients who had undergone this operation. METHODS
Ureterosigmoid anastomosis: risk of colorectal cancer and implications for colonoscopists David P. Hurlstone, MB, ChB, MRCP (UK), Jason M. Wells, FRCS (Eng), Neeraj Bhala, MB, ChB, Mark E. McAlindon, PhD, FRCP (UK) Sheffield, United Kingdom
Ureterosigmoidostomy is a surgical method used for total diversion of the urinary stream into the sigmoid colon, with the anus supplying the means for urinary as well as fecal continence. It originally was intended for treatment of several conditions, including bladder exstrophy, bladder cancer, incontinent epispadias, and severe postirradiation cystitis.1 Although superseded by other methods of urinary diversion, such as the ileal conduit, ureterosigmoidostomy offers adequate urinary continence and minimal interference with lifestyle, and it is simple to perform.1 In addition, studies have found the ureterosigmoidostomy to remain continuously functional for extended periods of time.2-4 Complications arising from ureterosigmoidostomies or any of the urinary diversional variations (i.e., Mansoura or Mainz II procedures) are well described.5 Along with urologic sequelae (such as urinary reflux, ureterocolic obstruction with hydronephrosis, pyelonephritis, calculus formation, and chronic hypochloremic acidosis),5 it also is recognized that patients with ureterosigmoidostomies constitute a group at high risk for the development of colonic neoplasia at the site of the anastomosis.6-9 Malignant sequalae are rare; however, given the continued use of ureterosigmoidostomy and the fact that patients may have undergone the procedure years earlier as infants, it is important that colonoscopists be aware of the pathogenesis of neoplastic lesions, potential complications of ureterosigmoidos-
Current affiliations: The Gastroenterology and Liver Unit, Department of Urology, Royal Hallamshire Hospital, Sheffield, South Yorkshire, United Kingdom. Dr. David P. Hurlstone is a Smith and Nephew Endoscopy Research Fellow. Reprint requests: Dr. David P. Hurlstone, 17 Alexandra Gardens, Lyndhurst Rd., Nether Edge, Sheffield, S11 9DQ, United Kingdom. Copyright Ó 2004 by the American Society for Gastrointestinal Endoscopy 0016-5107/$30.00 PII: S0016-5107(03)02706-8 248
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The MEDLINE database was searched for the years 1920-2002 by using the following medical subject headings and search methodology: (1) ureterosigmoidostomy and neoplasia and urinary diversion, and (2) follow-up and gastrointestinal endoscopy. A total of 29 relevant publications were identified, with further articles sourced from the list of references citations in the MEDLINE database. In addition, material was obtained from published abstracts for the meetings of the European Association of Urology and the American Urological Association (1993-2003), leading to a total list of 283 publications. BACKGROUND Ureterosigmoidostomy presently is performed in less than 10% of infants with exstrophy of the bladder because of an increasing surgical trend toward primary bladder closure.6 However, a select group of patients continues to require ureterosigmoidostomy formation after bladder extirpation for malignancy. The association of carcinoma at the site of the ureterosigmoidostomy, therefore, continues to be a significant problem within this patient cohort for which ongoing colonoscopic surveillance is required.8,10 Ureterosigmoidostomy as a continent urinary diversion initially was described by Simon11 in 1852. It became increasingly popular after technical modifications described by Coffey12 in 1911. The incorporation of ureteric submucosal tunneling reduced the occurrence of mechanical-related complications of the operation, such as hydronephrosis, urinary reflux, and infection.12 However, after the initial report of neoplasia arising at the ureterosigmoid anastomosis by Hammer13 in 1929 and, subsequently, numerous other case series,8 ileal diversional procedures, such as the ileal conduit, gained in surgical popularity. But, as with ureterosigmoidostomies, ileal diversions are similarly complicated by metabolic acidosis, electrolyte imbalance, calculus formation, pyelonephritis, progressive renal impairment, and neoplasia.6 Recent advances in the management of associated electrolyte disturbance,5 and, in addition, the increasing use of the low-pressure Mainz pouch6 means that patients will continue to be referred for endoscopic surveillance. The most commonly performed urinary diversions are described in diagrammatic format by Figures 1 to 4. VOLUME 59, NO. 2, 2004
Ureterosigmoid anastomosis: risk of colorectal cancer and implications for colonoscopists
Figure 1. Schematic diagram of ileal conduit. Ureters are spatulated and sutured to create a plate that then is anastomosed to the proximal end of a 15-cm segment of distal ileum mobilized on a vascular mesenteric pedicle (Wallace anastomosis). The distal ileum is delivered through a right iliac fossa stoma to form a urostomy.
Pathogenesis of colorectal cancer complicating urinary diversion The development of tumors at the ureterosigmoid anastomosis is thought to depend on the interaction of urine and feces at the site of healing.14 Historically, neoplastic disease is postulated to follow the adenoma-carcinoma histopathogenic sequence.10 The carcinogen is considered to be a N-nitrous compound present in the ureterosigmoid effluent.6,7,10,15 But, this is controversial, because tumor induction without the formation of nitrosamines has been demonstrated in a rat model.16 Furthermore, neoplastic transformation has been described without exposure to the fecal stream.17 However, one study also demonstrated increased expression of enzymes required to metabolize nitrosamines into carcinogenetic agents in patients with adenocarcinoma after ureterosigmoidostomy.18 Production of potentially carcinogenic N-nitrosamines is thought to occur in conjunction with DNA damage caused by release of oxygen free radicals by neutrophils as a consequence of chronic inflammation.5 This hypothesis is supported by the study of Dull et al.,19 which found a significantly greater proportion of superoxide radicals in rats who developed tumors after ureterosigmoidostomy compared with those who did not. At the histopathologic level, alterations of mucus glycoproteins in the mucosa surrounding the ureterosigmoid anastomosis have been shown to increase as the postoperative interval VOLUME 59, NO. 2, 2004
D Hurlstone, J Wells, N Bhala, et al.
Figure 2. Schematic diagram of ureterosigmoidostomy: mobilized ureters are re-implanted into distal sigmoid colon through the tenea coli. The use of an antireflux technique affords some protection against renal complications.
progresses.20 Localized glycoprotein accumulation at the ureterosigmoid anastomosis subsequently is associated with an increased inflammatory response.20 Chronic inflammation, it is thought, then drives the adenoma-carcinoma sequence. Other investigators have suggested that hydrolytic enzymes present in the urinary stream promote activation of conjugated carcinogens within the fecal stream.21 The interface of the urinary and fecal streams attains maximal concentration at the ureterosigmoidostomy,9 and this, therefore, is considered to account for the propensity for neoplastic transformation at this anatomical site. Most likely, however, a complex interaction of all the above postulated mechanisms occurs and may, in part, explain the development of colonic adenocarcinoma at sites completely excluded from the urinary stream.6 Colonoscopic surveillance The relative risk of developing colonic cancer for patients who have undergone ureterosigmoidostomy is difficult to evaluate because of the lack of a uniform population without other risk factors. Strachan and Woodhouse10 followed 103 patients for more than 20 years, including an ‘‘at-risk’’ group of 42 patients who had urinary and fecal streams mixed at some time, and a ‘‘low-risk’’ group of patients who had undergone successful exstrophy reconstruction or early urinary diversion into an ileal conduit.10 Malignancy did not occur in the latter GASTROINTESTINAL ENDOSCOPY
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Ureterosigmoid anastomosis: risk of colorectal cancer and implications for colonoscopists
Figure 3. Schematic diagram of Mansoura rectal bladder. The main limitation of the basic ureterosigmoidostomy is high rectal pressure, resulting in incontinence and recurrent pyelonephritis. Modified techniques were developed to address this problem. The Mansoura system uses a detubularized segment of ileum to augment the rectum, providing increased volume and decreased pressure. Kock nipples, formed by intussuscepting the bowel, prevent reflux to the kidneys and proximal colon.
group, whereas 24% (10 patients) of the ‘‘at-risk’’ group developed cancer, indicating a relative risk of cancer 1726 times greater than that of the ‘‘normal’’ population.10 The interval between ureterosigmoidostomy and malignant transformation has ranged from 1 to 50 years.6 However, the observed mean latent period for the development of adenoma in one study was 19.8 years, whereas that for overt carcinoma was 25.8 years, suggesting that this sequence requires a mean of 6 years.7 It has been postulated that the latency period also depends upon the original indication for ureterosigmoidostomy.6 In one series, when ureterosigmoidostomy was performed for primary neoplastic disease, neoplastic lesions appeared within 2 years (mean 7 years), compared with a mean of 22 years when the operation was performed for benign disease (range 10-40 years).22 Current guidelines for colonoscopic surveillance Recently published guidelines suggest that patients who have a ureterosigmoidostomy, or any of the modern variations of this operation, should undergo endoscopic examination up to and beyond the proximal ureteric anastomosis beginning during 250
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Figure 4. Schematic diagram of Mainz 2. In this simpler version of the modified ureterosigmoidostomy, the bowel is opened longitudinally and closed transversely, creating a pouch into which the ureters are reimplanted, again by using an antireflux technique.
the 10th postoperative year and annually thereafter.23 The increased risk of neoplasia also persists even if rediversion surgery (e.g., conversion to an ileal conduit) is performed.23 Furthermore, unless the ureteric anastomoses are removed, surveillance should continue in a similar manner for patients with a functional ureterosigmoidostomy.6,10,23 This recommendation was made on the basis of the first reported case of colonic malignancy presenting at 10 years after formation of ureterosigmoidostomy for bladder extrophy.24 Because neoplastic polyp formation precedes overt malignancy,25 regular and careful surveillance throughout life may lead to adenoma detection before the development of invasive malignancy. Shorter latent periods also have been described, particularly for benign lesions.26 This has led to a recommendation of annual colonoscopy beginning at 5 years after formation of a ureterosigmoid anastomosis.27 Given the lack of a uniform population, it is difficult to estimate the implications of such surveillance for health care costs. It would, therefore, seem prudent to commence colonoscopic screening of the ureterosigmoid anastomosis at between 5 and 10 years, except for patients in whom the primary indication for urinary diversion was urologic malignancy, in which case, it should commence at 5 years after surgery.23 VOLUME 59, NO. 2, 2004
Ureterosigmoid anastomosis: risk of colorectal cancer and implications for colonoscopists
D Hurlstone, J Wells, N Bhala, et al.
Adjunctive surveillance investigations In addition to colonoscopy, annual cytologic examination of urine has been advocated.6 Other investigations, such as serum electrolytes and transabdominal US under the supervision of a urologist, are also recommended.22 Furthermore, an association of neoplasia with the newer forms of urinary diversion, albeit at a lower frequency compared with ureterosigmoidostomy, has been noted in some case series. Thus, for these patients, Kotanagi et al.28 have advocated a surveillance strategy similar to that proposed for patients with a ureterosigmoidostomy. COLONOSCOPIC APPEARANCE OF THE URETEROSIGMOID ANASTOMOSIS Although the ureterosigmoid anastomosis typically appears as a pedunculated, small (4-5 mm diameter), cherry-like structure, colonoscopic identification of the ureteric implants can be challenging. Endoscopically, the implantation site also can assume a flat or sessile morphology.29 It is essential to identify correctly the anastomotic site endoscopically, because any attempt to obtain a biopsy specimen or resect the ‘‘polypoid’’ anastomosis may result in perforation or stricturing of the anastomosis.29 Furthermore, small flat lesions arising at the anastomotic margin may extend preferentially into the ureterosigmoid anastomotic lumen, making endoscopic detection difficult.6 Endoscopic localization can be enhanced by precolonoscopic intravenous infusion of saline solution to enhance visualization of urine flowing from the anastomosis or ‘‘labeling’’ of the urine by intravenous administration of indigo carmine dye.30 Because of associated risks of urinary leakage and secondary ureteric strictures, procurement of biopsy specimens and electrosurgical snare excision at the anastomotic margin, paradoxically the site most at risk of neoplastic transformation, are best avoided.7 Local surgical resection of a lesion suspected to be an adenoma or adenocarcinoma is advised, along with a wide surgical excision margin to include the regional lymphatic drainage.6 In addition, it is recommended that such patients have an alternative method of urinary diversion.6 HIGH-MAGNIFICATION CHROMOENDOSCOPY It may be possible to optimize surveillance of the ureterosigmoid anastomosis with the application of high-magnification chromoscopic colonoscopy (HMCC). Use of a magnifying colonoscope (CF240Z; Olympus Optical Co., Ltd., Tokyo, Japan) permits detailed examination of the colonic mucosa at VOLUME 59, NO. 2, 2004
Figure 5. Conventional endoscopic view of ureterosigmoidostomy showing ureteric implantation sites (white arrows).
Figure 6. Non-magnified chromoscopic view (0.5% indigo carmine) of ureterosigmoidostomy showing numerous flat (IIa) lesions (arrow) around the anastomotic margin. Magnification showed a Kudo type I/II pit pattern indicating benign hyperplasia/metaplasia alone.
magnifications of up to 3100.31 By using HMCC, discrete crypt or pit patterns that correlate closely with those observable by stereomicroscopy can be distinguished.31,32 Kudo et al.31 proposed a pit pattern classification, currently the most widely accepted, that includes 5 discrete types (types I, II, IIIL/IIIS, IV, V). The correlation of observed pit patterns with normal mucosa or hyperplastic lesions (I/II), adenoma (IIIL,IV,IIIS), and invasive neoplasia (V) forms the basis for the HMCC ‘‘optical biopsy’’ technique.33,34 Our group has applied HMCC for detailed examination of ureterosigmoid anastomotic sites. At HMCC, a clear change from the Kudo type I pit pattern of ‘‘normal’’ colonic mucosal crypts can be seen adjacent to the larger, oval transitional cell epithelium of the ureteric implant (Figs. 5 to 8). GASTROINTESTINAL ENDOSCOPY
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Ureterosigmoid anastomosis: risk of colorectal cancer and implications for colonoscopists
Figure 7. Magnified endoscopic view (orig. mag. 3100) of anastomotic margin of ureterosigmoidostomy showing clear circular Kudo type I crypt pattern indicating normal colonic mucosa.
Figure 8. Magnified chromoendoscopic view (orig. mag. 3100) of transitional epithelium within ureteric hood, showing elongated oval structure of transitional cell epithelium (arrow).
High-magnification chromoscopic colonoscopy also allows identification of emerging regional histopathologic abnormalities as adenomatous transformation and malignancy (Figs. 9 and 10).35 Use of this technique to examine the pan-anastomotic and perianastomotic regions may lead to identification of neoplastic lesions at earlier stages. High-magnification chromoscopic colonoscopy is a highly sensitive imaging modality that makes it possible to anticipate a histopathologic diagnosis in vivo. Because procurement of biopsy specimens from an ureterosigmoid anastomosis carries significant risk,6 HMCC is invaluable for neoplasia surveillance in patients 252
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Figure 9. Conventional endoscopic view of flat adenoma (IIa) with central nodule at anastomotic margin of ureterosigmoidostomy that is extending preferentially into ureterosigmoid anastomotic lumen. Local endoscopic excision of such a lesion can be complicated by perforation, secondary stenosis, and incomplete resection.
Figure 10. Conventional endoscopic view of flat (IIa) invasive adenocarcinoma arising at ureterosigmoid anastomosis 25 years after ureterosigmoidostomy in a patient who presented with obstructive nephropathy.
who have undergone ureterosigmoidostomy. The identification of focal crypt architecture in centrally depressed areas at the anastomosis is of particular importance.36 Here, the identification of a Kudo type IIIs/V pit pattern may signify neoplastic progression and prompt referral for either local resection and/or formation of an alternative urinary diversion.37,38 A prospective study of the overall accuracy of HMCC for detection of neoplasia in this high-risk cohort of patients is currently underway at our center. VOLUME 59, NO. 2, 2004
Ureterosigmoid anastomosis: risk of colorectal cancer and implications for colonoscopists
CONCLUSIONS Neoplastic disease can occur at the anastomosis of the ureter and colon in patients with ureterosigmoidostomies or surgical variations of this operation, such as the Mainz II or Mansoura procedures.24 Both colonic adenoma and adenocarcinoma occur.22-24 Controversy persists regarding pathogenesis and, indeed, whether neoplastic disease arises from the colonic mucosa, ureteric epithelium, or the anastomosis itself. Uretero-ileal neoplasia is, however, much less commonly associated with the ileal conduit where there is no fecal stream contamination.7 Current guidelines suggest that all patients with a ureterosigmoidostomy undergo flexible sigmoidoscopy at 10 years after surgery and at 1-year intervals thereafter.23 For patients with a ureterosigmoidostomy who subsequently have undergone an alternative urinary diversional procedure, flexible sigmoidoscopic surveillance should continue on an annual basis, unless the ureterosigmoid anastomosis has been resected.23 High-magnification chromoscopic colonoscopy may improve endoscopic visualization of the anastomotic site and may be used to predict the emergence of localized neoplastic disease. Further studies are underway to validate this hypothesis. REFERENCES 1. Stein R, Fisch M, Stockle M, Hohenfeller R. Urinary diversion in bladder exstrophy and incontinent epispadias: 25 years of experience. J Urol 1995;154:1177-81. 2. Koo HP, Avolio L, Duckett JWJ. Long-term results of ureterosigmoidostomy in children with bladder exstrophy. J Urol 1996;156:2037-40. 3. Kamidono S, Oda Y, Hamami G, Hikosoka K, Kataoka N, Ishigami J. Urinary diversion: anastamosis of the ureters into a sigmoid pouch and end-to-side sigmoidorectomstomy. J Urol 1985;133:391-4. 4. Bissada NK, Morcos BB, Morgan WM, Hanash KA. Ureterosigmoidostomy. Is it a viable procedure in the age of continent urinary diversion and bladder substitution? J Urol 1995;153:1429-31. 5. Fichtner J. Follow-up after urinary diversion. Urol Int 1999;63:40-5. 6. Azimuddin K, Khubchandani IT, Stasik JJ, Rosen L, Riether RD. Neoplasia after ureterosigmoidostomy. Dis Colon Rectum 1999;42:1632-8. 7. Stewart M, Macrae FA, Williams CB. Neoplasia and ureterosigmoidostomy: a colonoscopic review. Br J Surg 1982;69:414-6. 8. Husmann DA, Spence HM. Current status of tumor of the bowel following ureterosigmoidostomy: a review. J Urol 1990; 144:607-10. 9. Gill RW. Urocolonic tumors. J Urol 1988;139:1330. 10. Strachan JR, Woodhouse CRJ. Malignancy following ureterosigmoidostomy in patients with exstrophy. Br J Surg 1991; 78:1216-8. 11. Simon J. Operation for directing the orifices of ureters into the rectum; temporary success, subsequent failure; autopsy. Lancet 1852;II:568-70. VOLUME 59, NO. 2, 2004
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12. Coffey RC. Physiologic implantation of the severed ureter or common bile-duct into the intestine. JAMA 1911;56:397403. 13. Hammer E. Cancer du colon sigmoide dix ans pres implantation des ureters d’une vessu extrophi [French]. J Urol (Paris) 1929;28:260-3. 14. Gittes RF. Carcinogenesis in ureterosigmoidostomy. Urol Clin North Am 1986;13:201-5. 15. Crissey MM, Steele GD, Grittes RF. Rat model for carcingenesis in ureterosigmoidostomy. Science 1980;207: 1079-80. 16. Kalble T, Tricker AR, Berger M, Amelung F, Waldherr R, Hothom L, et al. Tumor induction in a rat model for ureterosigmoidostomy without evidence of nitrosamine formation. J Urol 1981;146:862-8. 17. Shokeir AA, Shamaa M, el-Mekresh MM, el-Baz M, Ghoneim MA. Late malignancy in bowel segments exposed to urine without fecal stream. Urology 1995;46:657-61. 18. Brauers A, Baron J, Jung P, Winkeltau G, Fuzesi L, Merk H, et al. Expression of cytochrome P-450 2E1 messenger ribonucleic acid in adenocarcinoma at ureterosigmoidostomy site after bladder exstrophy. J Urol 1988;159:979-80. 19. Dull BJ, Gittes RF, Goldman P. Nitrate production and phagocyte activation: differences among Sprague-Dawley, Wistar-Furth and Lewis rats. Carcinogenesis 1988;43: 625-7. 20. Shimamoto C, Hirata I, Takao Y, Takiuchi H, Morikawa H, Nakagawa Y, et al. Alteration of colonic mucin after ureterosigmoidostomy. Dis Colon Rectum 2000;43:526-31. 21. Urdaneta LF, Duffell D, Creevy CD, Aust JB. Late development of a primary carcinoma of the colon following ureterosigmoidostomy: report of three cases and literature review. Ann Surg 1966;164:503-13. 22. Badalament RA, Cirulli C, Zerick W, Lucas JG, Drago JR. Colon carcinoma associated with ureterosigmoidostomy. J Surg Oncol 1990;45:207-11. 23. Woodhouse CRJ. Guidelines for monitoring of patients with ureterosigmoidstomy. Gut 2002;51:v15-6. 24. Spence HM, Hoffman WW, Fosmire GP. Tumour of the colon as a late complication of ureterosigmoidostomy for exstrophy of the bladder. Br J Urol 1979;51:466-70. 25. Morson BC. Evolution of cancer of the colon and rectum. Cancer 1974;34(Suppl):845-9. 26. Starling JR, Uehling DT, Gilchrist KW. Value of colonoscopy after ureterosigmoidostomy. Surgery 1984;96:784-90. 27. Bissada NK, Morcos RR, Morgan WM, Hanash KA. Ureterosigmoidostomy. Is it a viable procedure in the age of continent urinary diversion and bladder substitution? J Urol 1995;153:1429-31. 28. Kotanagi H, Ito M, Koyama K, Sato K, Kato T. Colon cancer in rectal bladder. J Gastroenterol 2001;36:718-22. 29. Takasaki N, Kaneda K, Demura A, Ono S, Numata M, Matsuse K, et al. Surveillance colonoscopy after ureterosigmoidostomy [In Japanese with an English abstract]. Hinyokika Kiyo 1983;29:1401-9. 30. Huang C, Lichtenstein DR, Farraye FA. Ureterosigmoidostomy. Gastrointest Endosc 2002;56:272. 31. Kudo S, Rubio CA, Teixeira CR, Kashida H, Kogure E. Pit pattern in colorectal neoplasia: endoscopic magnifying view. Endoscopy 2001;33:367-73. 32. Kato S, Fujii T, Koba I, Sano Y, Fu KI, Parra-Blanco A, et al. Assessment of colorectal lesions using magnifying colonoscopy and mucosal dye spraying: can significant lesions be distinguished? Endoscopy 2001;33:306-10. GASTROINTESTINAL ENDOSCOPY
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33. Tung SY, Wu CS, Su MY. Magnifying colonoscopy in differentiating neoplastic from nonneoplastic colorectal lesions. Am J Gastroenterol 2001;96:2628-32. 34. Togashi K, Konishi F, Ishizuka T, Sato T, Senba S, Kanazawa K. Efficacy of magnifying endoscopy in the differential diagnosis of neoplastic and non-neoplastic polyps of the large bowel. Dis Colon Rectum 1999;42:1602-8. 35. Hurlstone DP, Fujii T, Lobo AJ. Early detection of colorectal cancer using high-magnification chromoscopic colonoscopy. Br J Surg 2002;89:272-82.
36. Kudo S, Tamure S, Nakajima T, Hirota S, Asano M, Ito O, Kusaka H. Depressed type of colorectal cancer. Endoscopy 1995;27:54-7. 37. Kudo S, Kashida H, Nakajima T, Tamura S, Nakajo K. Endoscopic diagnosis and treatment of early colorectal cancer. World J Surg 1997;21:694-701. 38. Kudo S, Kashida H, Tamura T, Kogure E, Imai Y, Yamano H, et al. Colonoscopic diagnosis and management of nonpolypoid early colorectal cancer. World J Surg 2000;24: 1081-90.
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VOLUME 59, NO. 2, 2004
tomy, and follow-up requirements for patients who had undergone this operation. METHODS
Ureterosigmoid anastomosis: risk of colorectal cancer and implications for colonoscopists David P. Hurlstone, MB, ChB, MRCP (UK), Jason M. Wells, FRCS (Eng), Neeraj Bhala, MB, ChB, Mark E. McAlindon, PhD, FRCP (UK) Sheffield, United Kingdom
Ureterosigmoidostomy is a surgical method used for total diversion of the urinary stream into the sigmoid colon, with the anus supplying the means for urinary as well as fecal continence. It originally was intended for treatment of several conditions, including bladder exstrophy, bladder cancer, incontinent epispadias, and severe postirradiation cystitis.1 Although superseded by other methods of urinary diversion, such as the ileal conduit, ureterosigmoidostomy offers adequate urinary continence and minimal interference with lifestyle, and it is simple to perform.1 In addition, studies have found the ureterosigmoidostomy to remain continuously functional for extended periods of time.2-4 Complications arising from ureterosigmoidostomies or any of the urinary diversional variations (i.e., Mansoura or Mainz II procedures) are well described.5 Along with urologic sequelae (such as urinary reflux, ureterocolic obstruction with hydronephrosis, pyelonephritis, calculus formation, and chronic hypochloremic acidosis),5 it also is recognized that patients with ureterosigmoidostomies constitute a group at high risk for the development of colonic neoplasia at the site of the anastomosis.6-9 Malignant sequalae are rare; however, given the continued use of ureterosigmoidostomy and the fact that patients may have undergone the procedure years earlier as infants, it is important that colonoscopists be aware of the pathogenesis of neoplastic lesions, potential complications of ureterosigmoidos-
Current affiliations: The Gastroenterology and Liver Unit, Department of Urology, Royal Hallamshire Hospital, Sheffield, South Yorkshire, United Kingdom. Dr. David P. Hurlstone is a Smith and Nephew Endoscopy Research Fellow. Reprint requests: Dr. David P. Hurlstone, 17 Alexandra Gardens, Lyndhurst Rd., Nether Edge, Sheffield, S11 9DQ, United Kingdom. Copyright Ó 2004 by the American Society for Gastrointestinal Endoscopy 0016-5107/$30.00 PII: S0016-5107(03)02706-8 248
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The MEDLINE database was searched for the years 1920-2002 by using the following medical subject headings and search methodology: (1) ureterosigmoidostomy and neoplasia and urinary diversion, and (2) follow-up and gastrointestinal endoscopy. A total of 29 relevant publications were identified, with further articles sourced from the list of references citations in the MEDLINE database. In addition, material was obtained from published abstracts for the meetings of the European Association of Urology and the American Urological Association (1993-2003), leading to a total list of 283 publications. BACKGROUND Ureterosigmoidostomy presently is performed in less than 10% of infants with exstrophy of the bladder because of an increasing surgical trend toward primary bladder closure.6 However, a select group of patients continues to require ureterosigmoidostomy formation after bladder extirpation for malignancy. The association of carcinoma at the site of the ureterosigmoidostomy, therefore, continues to be a significant problem within this patient cohort for which ongoing colonoscopic surveillance is required.8,10 Ureterosigmoidostomy as a continent urinary diversion initially was described by Simon11 in 1852. It became increasingly popular after technical modifications described by Coffey12 in 1911. The incorporation of ureteric submucosal tunneling reduced the occurrence of mechanical-related complications of the operation, such as hydronephrosis, urinary reflux, and infection.12 However, after the initial report of neoplasia arising at the ureterosigmoid anastomosis by Hammer13 in 1929 and, subsequently, numerous other case series,8 ileal diversional procedures, such as the ileal conduit, gained in surgical popularity. But, as with ureterosigmoidostomies, ileal diversions are similarly complicated by metabolic acidosis, electrolyte imbalance, calculus formation, pyelonephritis, progressive renal impairment, and neoplasia.6 Recent advances in the management of associated electrolyte disturbance,5 and, in addition, the increasing use of the low-pressure Mainz pouch6 means that patients will continue to be referred for endoscopic surveillance. The most commonly performed urinary diversions are described in diagrammatic format by Figures 1 to 4. VOLUME 59, NO. 2, 2004
Ureterosigmoid anastomosis: risk of colorectal cancer and implications for colonoscopists
Figure 1. Schematic diagram of ileal conduit. Ureters are spatulated and sutured to create a plate that then is anastomosed to the proximal end of a 15-cm segment of distal ileum mobilized on a vascular mesenteric pedicle (Wallace anastomosis). The distal ileum is delivered through a right iliac fossa stoma to form a urostomy.
Pathogenesis of colorectal cancer complicating urinary diversion The development of tumors at the ureterosigmoid anastomosis is thought to depend on the interaction of urine and feces at the site of healing.14 Historically, neoplastic disease is postulated to follow the adenoma-carcinoma histopathogenic sequence.10 The carcinogen is considered to be a N-nitrous compound present in the ureterosigmoid effluent.6,7,10,15 But, this is controversial, because tumor induction without the formation of nitrosamines has been demonstrated in a rat model.16 Furthermore, neoplastic transformation has been described without exposure to the fecal stream.17 However, one study also demonstrated increased expression of enzymes required to metabolize nitrosamines into carcinogenetic agents in patients with adenocarcinoma after ureterosigmoidostomy.18 Production of potentially carcinogenic N-nitrosamines is thought to occur in conjunction with DNA damage caused by release of oxygen free radicals by neutrophils as a consequence of chronic inflammation.5 This hypothesis is supported by the study of Dull et al.,19 which found a significantly greater proportion of superoxide radicals in rats who developed tumors after ureterosigmoidostomy compared with those who did not. At the histopathologic level, alterations of mucus glycoproteins in the mucosa surrounding the ureterosigmoid anastomosis have been shown to increase as the postoperative interval VOLUME 59, NO. 2, 2004
D Hurlstone, J Wells, N Bhala, et al.
Figure 2. Schematic diagram of ureterosigmoidostomy: mobilized ureters are re-implanted into distal sigmoid colon through the tenea coli. The use of an antireflux technique affords some protection against renal complications.
progresses.20 Localized glycoprotein accumulation at the ureterosigmoid anastomosis subsequently is associated with an increased inflammatory response.20 Chronic inflammation, it is thought, then drives the adenoma-carcinoma sequence. Other investigators have suggested that hydrolytic enzymes present in the urinary stream promote activation of conjugated carcinogens within the fecal stream.21 The interface of the urinary and fecal streams attains maximal concentration at the ureterosigmoidostomy,9 and this, therefore, is considered to account for the propensity for neoplastic transformation at this anatomical site. Most likely, however, a complex interaction of all the above postulated mechanisms occurs and may, in part, explain the development of colonic adenocarcinoma at sites completely excluded from the urinary stream.6 Colonoscopic surveillance The relative risk of developing colonic cancer for patients who have undergone ureterosigmoidostomy is difficult to evaluate because of the lack of a uniform population without other risk factors. Strachan and Woodhouse10 followed 103 patients for more than 20 years, including an ‘‘at-risk’’ group of 42 patients who had urinary and fecal streams mixed at some time, and a ‘‘low-risk’’ group of patients who had undergone successful exstrophy reconstruction or early urinary diversion into an ileal conduit.10 Malignancy did not occur in the latter GASTROINTESTINAL ENDOSCOPY
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Ureterosigmoid anastomosis: risk of colorectal cancer and implications for colonoscopists
Figure 3. Schematic diagram of Mansoura rectal bladder. The main limitation of the basic ureterosigmoidostomy is high rectal pressure, resulting in incontinence and recurrent pyelonephritis. Modified techniques were developed to address this problem. The Mansoura system uses a detubularized segment of ileum to augment the rectum, providing increased volume and decreased pressure. Kock nipples, formed by intussuscepting the bowel, prevent reflux to the kidneys and proximal colon.
group, whereas 24% (10 patients) of the ‘‘at-risk’’ group developed cancer, indicating a relative risk of cancer 1726 times greater than that of the ‘‘normal’’ population.10 The interval between ureterosigmoidostomy and malignant transformation has ranged from 1 to 50 years.6 However, the observed mean latent period for the development of adenoma in one study was 19.8 years, whereas that for overt carcinoma was 25.8 years, suggesting that this sequence requires a mean of 6 years.7 It has been postulated that the latency period also depends upon the original indication for ureterosigmoidostomy.6 In one series, when ureterosigmoidostomy was performed for primary neoplastic disease, neoplastic lesions appeared within 2 years (mean 7 years), compared with a mean of 22 years when the operation was performed for benign disease (range 10-40 years).22 Current guidelines for colonoscopic surveillance Recently published guidelines suggest that patients who have a ureterosigmoidostomy, or any of the modern variations of this operation, should undergo endoscopic examination up to and beyond the proximal ureteric anastomosis beginning during 250
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Figure 4. Schematic diagram of Mainz 2. In this simpler version of the modified ureterosigmoidostomy, the bowel is opened longitudinally and closed transversely, creating a pouch into which the ureters are reimplanted, again by using an antireflux technique.
the 10th postoperative year and annually thereafter.23 The increased risk of neoplasia also persists even if rediversion surgery (e.g., conversion to an ileal conduit) is performed.23 Furthermore, unless the ureteric anastomoses are removed, surveillance should continue in a similar manner for patients with a functional ureterosigmoidostomy.6,10,23 This recommendation was made on the basis of the first reported case of colonic malignancy presenting at 10 years after formation of ureterosigmoidostomy for bladder extrophy.24 Because neoplastic polyp formation precedes overt malignancy,25 regular and careful surveillance throughout life may lead to adenoma detection before the development of invasive malignancy. Shorter latent periods also have been described, particularly for benign lesions.26 This has led to a recommendation of annual colonoscopy beginning at 5 years after formation of a ureterosigmoid anastomosis.27 Given the lack of a uniform population, it is difficult to estimate the implications of such surveillance for health care costs. It would, therefore, seem prudent to commence colonoscopic screening of the ureterosigmoid anastomosis at between 5 and 10 years, except for patients in whom the primary indication for urinary diversion was urologic malignancy, in which case, it should commence at 5 years after surgery.23 VOLUME 59, NO. 2, 2004
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Adjunctive surveillance investigations In addition to colonoscopy, annual cytologic examination of urine has been advocated.6 Other investigations, such as serum electrolytes and transabdominal US under the supervision of a urologist, are also recommended.22 Furthermore, an association of neoplasia with the newer forms of urinary diversion, albeit at a lower frequency compared with ureterosigmoidostomy, has been noted in some case series. Thus, for these patients, Kotanagi et al.28 have advocated a surveillance strategy similar to that proposed for patients with a ureterosigmoidostomy. COLONOSCOPIC APPEARANCE OF THE URETEROSIGMOID ANASTOMOSIS Although the ureterosigmoid anastomosis typically appears as a pedunculated, small (4-5 mm diameter), cherry-like structure, colonoscopic identification of the ureteric implants can be challenging. Endoscopically, the implantation site also can assume a flat or sessile morphology.29 It is essential to identify correctly the anastomotic site endoscopically, because any attempt to obtain a biopsy specimen or resect the ‘‘polypoid’’ anastomosis may result in perforation or stricturing of the anastomosis.29 Furthermore, small flat lesions arising at the anastomotic margin may extend preferentially into the ureterosigmoid anastomotic lumen, making endoscopic detection difficult.6 Endoscopic localization can be enhanced by precolonoscopic intravenous infusion of saline solution to enhance visualization of urine flowing from the anastomosis or ‘‘labeling’’ of the urine by intravenous administration of indigo carmine dye.30 Because of associated risks of urinary leakage and secondary ureteric strictures, procurement of biopsy specimens and electrosurgical snare excision at the anastomotic margin, paradoxically the site most at risk of neoplastic transformation, are best avoided.7 Local surgical resection of a lesion suspected to be an adenoma or adenocarcinoma is advised, along with a wide surgical excision margin to include the regional lymphatic drainage.6 In addition, it is recommended that such patients have an alternative method of urinary diversion.6 HIGH-MAGNIFICATION CHROMOENDOSCOPY It may be possible to optimize surveillance of the ureterosigmoid anastomosis with the application of high-magnification chromoscopic colonoscopy (HMCC). Use of a magnifying colonoscope (CF240Z; Olympus Optical Co., Ltd., Tokyo, Japan) permits detailed examination of the colonic mucosa at VOLUME 59, NO. 2, 2004
Figure 5. Conventional endoscopic view of ureterosigmoidostomy showing ureteric implantation sites (white arrows).
Figure 6. Non-magnified chromoscopic view (0.5% indigo carmine) of ureterosigmoidostomy showing numerous flat (IIa) lesions (arrow) around the anastomotic margin. Magnification showed a Kudo type I/II pit pattern indicating benign hyperplasia/metaplasia alone.
magnifications of up to 3100.31 By using HMCC, discrete crypt or pit patterns that correlate closely with those observable by stereomicroscopy can be distinguished.31,32 Kudo et al.31 proposed a pit pattern classification, currently the most widely accepted, that includes 5 discrete types (types I, II, IIIL/IIIS, IV, V). The correlation of observed pit patterns with normal mucosa or hyperplastic lesions (I/II), adenoma (IIIL,IV,IIIS), and invasive neoplasia (V) forms the basis for the HMCC ‘‘optical biopsy’’ technique.33,34 Our group has applied HMCC for detailed examination of ureterosigmoid anastomotic sites. At HMCC, a clear change from the Kudo type I pit pattern of ‘‘normal’’ colonic mucosal crypts can be seen adjacent to the larger, oval transitional cell epithelium of the ureteric implant (Figs. 5 to 8). GASTROINTESTINAL ENDOSCOPY
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Figure 7. Magnified endoscopic view (orig. mag. 3100) of anastomotic margin of ureterosigmoidostomy showing clear circular Kudo type I crypt pattern indicating normal colonic mucosa.
Figure 8. Magnified chromoendoscopic view (orig. mag. 3100) of transitional epithelium within ureteric hood, showing elongated oval structure of transitional cell epithelium (arrow).
High-magnification chromoscopic colonoscopy also allows identification of emerging regional histopathologic abnormalities as adenomatous transformation and malignancy (Figs. 9 and 10).35 Use of this technique to examine the pan-anastomotic and perianastomotic regions may lead to identification of neoplastic lesions at earlier stages. High-magnification chromoscopic colonoscopy is a highly sensitive imaging modality that makes it possible to anticipate a histopathologic diagnosis in vivo. Because procurement of biopsy specimens from an ureterosigmoid anastomosis carries significant risk,6 HMCC is invaluable for neoplasia surveillance in patients 252
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Figure 9. Conventional endoscopic view of flat adenoma (IIa) with central nodule at anastomotic margin of ureterosigmoidostomy that is extending preferentially into ureterosigmoid anastomotic lumen. Local endoscopic excision of such a lesion can be complicated by perforation, secondary stenosis, and incomplete resection.
Figure 10. Conventional endoscopic view of flat (IIa) invasive adenocarcinoma arising at ureterosigmoid anastomosis 25 years after ureterosigmoidostomy in a patient who presented with obstructive nephropathy.
who have undergone ureterosigmoidostomy. The identification of focal crypt architecture in centrally depressed areas at the anastomosis is of particular importance.36 Here, the identification of a Kudo type IIIs/V pit pattern may signify neoplastic progression and prompt referral for either local resection and/or formation of an alternative urinary diversion.37,38 A prospective study of the overall accuracy of HMCC for detection of neoplasia in this high-risk cohort of patients is currently underway at our center. VOLUME 59, NO. 2, 2004
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CONCLUSIONS Neoplastic disease can occur at the anastomosis of the ureter and colon in patients with ureterosigmoidostomies or surgical variations of this operation, such as the Mainz II or Mansoura procedures.24 Both colonic adenoma and adenocarcinoma occur.22-24 Controversy persists regarding pathogenesis and, indeed, whether neoplastic disease arises from the colonic mucosa, ureteric epithelium, or the anastomosis itself. Uretero-ileal neoplasia is, however, much less commonly associated with the ileal conduit where there is no fecal stream contamination.7 Current guidelines suggest that all patients with a ureterosigmoidostomy undergo flexible sigmoidoscopy at 10 years after surgery and at 1-year intervals thereafter.23 For patients with a ureterosigmoidostomy who subsequently have undergone an alternative urinary diversional procedure, flexible sigmoidoscopic surveillance should continue on an annual basis, unless the ureterosigmoid anastomosis has been resected.23 High-magnification chromoscopic colonoscopy may improve endoscopic visualization of the anastomotic site and may be used to predict the emergence of localized neoplastic disease. Further studies are underway to validate this hypothesis. REFERENCES 1. Stein R, Fisch M, Stockle M, Hohenfeller R. Urinary diversion in bladder exstrophy and incontinent epispadias: 25 years of experience. J Urol 1995;154:1177-81. 2. Koo HP, Avolio L, Duckett JWJ. Long-term results of ureterosigmoidostomy in children with bladder exstrophy. J Urol 1996;156:2037-40. 3. Kamidono S, Oda Y, Hamami G, Hikosoka K, Kataoka N, Ishigami J. Urinary diversion: anastamosis of the ureters into a sigmoid pouch and end-to-side sigmoidorectomstomy. J Urol 1985;133:391-4. 4. Bissada NK, Morcos BB, Morgan WM, Hanash KA. Ureterosigmoidostomy. Is it a viable procedure in the age of continent urinary diversion and bladder substitution? J Urol 1995;153:1429-31. 5. Fichtner J. Follow-up after urinary diversion. Urol Int 1999;63:40-5. 6. Azimuddin K, Khubchandani IT, Stasik JJ, Rosen L, Riether RD. Neoplasia after ureterosigmoidostomy. Dis Colon Rectum 1999;42:1632-8. 7. Stewart M, Macrae FA, Williams CB. Neoplasia and ureterosigmoidostomy: a colonoscopic review. Br J Surg 1982;69:414-6. 8. Husmann DA, Spence HM. Current status of tumor of the bowel following ureterosigmoidostomy: a review. J Urol 1990; 144:607-10. 9. Gill RW. Urocolonic tumors. J Urol 1988;139:1330. 10. Strachan JR, Woodhouse CRJ. Malignancy following ureterosigmoidostomy in patients with exstrophy. Br J Surg 1991; 78:1216-8. 11. Simon J. Operation for directing the orifices of ureters into the rectum; temporary success, subsequent failure; autopsy. Lancet 1852;II:568-70. VOLUME 59, NO. 2, 2004
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12. Coffey RC. Physiologic implantation of the severed ureter or common bile-duct into the intestine. JAMA 1911;56:397403. 13. Hammer E. Cancer du colon sigmoide dix ans pres implantation des ureters d’une vessu extrophi [French]. J Urol (Paris) 1929;28:260-3. 14. Gittes RF. Carcinogenesis in ureterosigmoidostomy. Urol Clin North Am 1986;13:201-5. 15. Crissey MM, Steele GD, Grittes RF. Rat model for carcingenesis in ureterosigmoidostomy. Science 1980;207: 1079-80. 16. Kalble T, Tricker AR, Berger M, Amelung F, Waldherr R, Hothom L, et al. Tumor induction in a rat model for ureterosigmoidostomy without evidence of nitrosamine formation. J Urol 1981;146:862-8. 17. Shokeir AA, Shamaa M, el-Mekresh MM, el-Baz M, Ghoneim MA. Late malignancy in bowel segments exposed to urine without fecal stream. Urology 1995;46:657-61. 18. Brauers A, Baron J, Jung P, Winkeltau G, Fuzesi L, Merk H, et al. Expression of cytochrome P-450 2E1 messenger ribonucleic acid in adenocarcinoma at ureterosigmoidostomy site after bladder exstrophy. J Urol 1988;159:979-80. 19. Dull BJ, Gittes RF, Goldman P. Nitrate production and phagocyte activation: differences among Sprague-Dawley, Wistar-Furth and Lewis rats. Carcinogenesis 1988;43: 625-7. 20. Shimamoto C, Hirata I, Takao Y, Takiuchi H, Morikawa H, Nakagawa Y, et al. Alteration of colonic mucin after ureterosigmoidostomy. Dis Colon Rectum 2000;43:526-31. 21. Urdaneta LF, Duffell D, Creevy CD, Aust JB. Late development of a primary carcinoma of the colon following ureterosigmoidostomy: report of three cases and literature review. Ann Surg 1966;164:503-13. 22. Badalament RA, Cirulli C, Zerick W, Lucas JG, Drago JR. Colon carcinoma associated with ureterosigmoidostomy. J Surg Oncol 1990;45:207-11. 23. Woodhouse CRJ. Guidelines for monitoring of patients with ureterosigmoidstomy. Gut 2002;51:v15-6. 24. Spence HM, Hoffman WW, Fosmire GP. Tumour of the colon as a late complication of ureterosigmoidostomy for exstrophy of the bladder. Br J Urol 1979;51:466-70. 25. Morson BC. Evolution of cancer of the colon and rectum. Cancer 1974;34(Suppl):845-9. 26. Starling JR, Uehling DT, Gilchrist KW. Value of colonoscopy after ureterosigmoidostomy. Surgery 1984;96:784-90. 27. Bissada NK, Morcos RR, Morgan WM, Hanash KA. Ureterosigmoidostomy. Is it a viable procedure in the age of continent urinary diversion and bladder substitution? J Urol 1995;153:1429-31. 28. Kotanagi H, Ito M, Koyama K, Sato K, Kato T. Colon cancer in rectal bladder. J Gastroenterol 2001;36:718-22. 29. Takasaki N, Kaneda K, Demura A, Ono S, Numata M, Matsuse K, et al. Surveillance colonoscopy after ureterosigmoidostomy [In Japanese with an English abstract]. Hinyokika Kiyo 1983;29:1401-9. 30. Huang C, Lichtenstein DR, Farraye FA. Ureterosigmoidostomy. Gastrointest Endosc 2002;56:272. 31. Kudo S, Rubio CA, Teixeira CR, Kashida H, Kogure E. Pit pattern in colorectal neoplasia: endoscopic magnifying view. Endoscopy 2001;33:367-73. 32. Kato S, Fujii T, Koba I, Sano Y, Fu KI, Parra-Blanco A, et al. Assessment of colorectal lesions using magnifying colonoscopy and mucosal dye spraying: can significant lesions be distinguished? Endoscopy 2001;33:306-10. GASTROINTESTINAL ENDOSCOPY
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33. Tung SY, Wu CS, Su MY. Magnifying colonoscopy in differentiating neoplastic from nonneoplastic colorectal lesions. Am J Gastroenterol 2001;96:2628-32. 34. Togashi K, Konishi F, Ishizuka T, Sato T, Senba S, Kanazawa K. Efficacy of magnifying endoscopy in the differential diagnosis of neoplastic and non-neoplastic polyps of the large bowel. Dis Colon Rectum 1999;42:1602-8. 35. Hurlstone DP, Fujii T, Lobo AJ. Early detection of colorectal cancer using high-magnification chromoscopic colonoscopy. Br J Surg 2002;89:272-82.
36. Kudo S, Tamure S, Nakajima T, Hirota S, Asano M, Ito O, Kusaka H. Depressed type of colorectal cancer. Endoscopy 1995;27:54-7. 37. Kudo S, Kashida H, Nakajima T, Tamura S, Nakajo K. Endoscopic diagnosis and treatment of early colorectal cancer. World J Surg 1997;21:694-701. 38. Kudo S, Kashida H, Tamura T, Kogure E, Imai Y, Yamano H, et al. Colonoscopic diagnosis and management of nonpolypoid early colorectal cancer. World J Surg 2000;24: 1081-90.
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