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Journal of Clinical Oncology, Vol 26, No 10 (April 1), 2008: pp. 1755-1757 © 2008 American Society of Clinical Oncology. DOI: 10.1200/JCO.2007.14.6126
Colon Cancer 15 Years After UreterosigmoidostomyDepartment of Internal Medicine, St Louis University School of Medicine, St Louis, MO
Division of Hematology Oncology, Department of Internal Medicine, St Louis University School of Medicine, St Louis, MO A 29-year-old white man presented to our hospital with a 4-week history of left lower abdominal pain, constipation, and rectal bleeding. The patient was born with bladder exstrophy and subsequently had an ureterosigmoidostomy as an infant. At the age of 14, the ureterosigmoidostomy was converted to an Indiana pouch because chronic urinary incontinence. On examination, his vital signs were within normal range. The patient had generalized pallor. The abdomen was tender and mildly distended, and bowel sounds were hypoactive. There was also a catheterizable stoma in the left upper quadrant which is the insertion site to access the neobladder. A stool specimen from the rectal exam demonstrated evidence of fecal occult blood. A complete blood count showed evidence of iron deficiency anemia with hemoglobin of 11 g/dL. A review of his computed tomography scan showed fluid and inflammation around the large bowel anastomosis and retroperitoneal and pelvic lymphadenopathy. The patient underwent a flexible sigmoidoscopy, which showed a tight, obstructing rectal stricture at 16 cm from the anal verge with circumferential inflammation and edema. The colonoscope was unable to pass through the stricture. Multiple local biopsies were taken and two polyps were removed from the distal rectum. Histological examination revealed a poorly differentiated adenocarcinoma with signet ring cell morphology (Fig 1) in the rectosigmoid colon, and two hyperplastic polyps of the distal rectum. A whole-body positron emission tomography scan showed intense fluorodeoxyglucose uptake in the rectosigmoid junction (Fig 2) involving the retroperitoneal and pelvic lymph nodes (Fig 2) consistent with malignancy. The patient then underwent another sigmoidoscopy for bowel decompression. Two metal stents were placed across the stricture which resulted in a good flow of stool. The patient was then treated with the first cycle of neoadjuvant chemotherapy: oxaliplatin + leucovorin + fluorouracil1 and bevacizumab.
Ureterosigmoidostomy (US) as a means of urinary diversion was first introduced by Smith in 1878. One of the uncommon late complications of this procedure is the potential of developing urocolonic tumors (from benign polyps to most commonly adenocarcinoma) at the anastomotic site. It was first reported by Hammer2 in 1929, and to date, roughly a dozen of new cases per decade are being reported in the literature. In patients with US, the incidence of colonic carcinoma is between 2% and 15%.2-4 The risk of developing colonic carcinoma is 100 to 550 times greater than the general population3,5 and 7,000 times greater than people  25 years.4 The incidence of developing polyps involving or near the anastomotic site is also markedly increased at 41%.5 The average latent period for tumors to develop after US is 26 years with a range of 3 to 53 years.2,6 The latency period is generally longer for carcinoma than for benign polyps. The peak incidence of urocolonic tumor is usually in the third or fourth decades of life, but the development could occur as early as age 7 years.6 Although this rare long-term complication of malignant transformation has been well recognized, the pathogenesis remains to be controversial. It appears the three key elements that are involved in US all have implications in the process of malignant transformation: (1) the urinary stream, (2) the fecal stream, and (3) the intestinal mucosa at the site of the anastomosis. The most accepted theory is that the fecal flora generates the production of nitrosamine, which is a carcinogen found in the urinary source.7 This theory was challenged when tumor induction was successful despite any evidence of nitrosamine formation.8 It has also been suggested that the interaction of both urine and feces are necessary for carcinogenesis to occur, as perhaps the hydrolytic enzymes in the urine activate the conjugated carcinogens in the stool, and the anastomotic site of the two streams are the most active as they have the greatest concentration.8 However, it was shown that malignancy can be developed in the bowel segments only exposed to the urinary stream without fecal interaction.9 Another study suggested is that the anastomotic site undergoes reactive hyperplasia caused by the mechanical trauma or suture material, and the subsequent adenoma or benign juvenile polyp developed may represent a precancerous lesion in this peculiar patient population.3 Another etiology suggested is that the chronic irritation of the suture line, where the ureters are implanted to the colonic mucosa, causes a local inflammatory response, which leads to the increased quantities of reactive oxygen radicals produced by phagocytes which in turn causes DNA damage.2,6 The reason is that the ureteric stumps are sometimes left attached in the colon in the conversion procedure, allowing the fecal stream to continue to irritate the site.6,7,11 This could potentially explain carcinogenesis in those who were exposed to the urinary-fecal mixture in the colon for a very brief period (6 months or less) before the conversion procedure.6 This present case is a classic clinical presentation of carcinoma after US in an otherwise young healthy male with a relative long life expectancy. Unfortunately, the lack of proper follow-up leads to the poor prognosis of this patient as he presented with an advanced stage of the disease with metastasis to regional lymph nodes. Patients who have undergone an ureterosigmoidostomy and present with symptoms of abdominal pain, hematuria, rectal bleeding, constipation, and any symptoms related to urinary or bowel obstruction should warrant a thorough work-up including a colonoscopy to rule out this iatrogenic neoplasm.4 The phenomenon of neoplasia associated with US has been well established for over half of a century, yet a considerable number from this subset of patients have presented with advanced stage carcinomas in recent decades. Although this procedure is done in less than 10% of infants with exstrophy today,2 it is still one of several other viable options of urinary diversion for other means. Hence, whenever encountering this subgroup of patients, the physician should ensure that the patient is being appropriately followed. If a patient is deemed to be noncompliant, prophylactic surgery should be offered.2 Otherwise, patients should undergo life-long surveillance colonoscopy and screening for occult blood.5 In addition, if recurrent polyps, dysplasia, or neoplasia is identified, conversion to an alternative diversion should be strongly considered5 along with resection of the previous anastomotic site in the sigmoid colon attached by the ureteric stump.11 AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest.
REFERENCES
1. De Gramont A, Figer M, Seymour M, et al: Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol 18:2938-2947, 2000 2. Azimuddin K, Khubchandani IT, Stasik JJ, et al: Neoplasia after ureterosigmoidostomy. Dis Colon Rectum 42:1632-1638, 1999[CrossRef][Medline] 3. Cipolla R, Garcia RL: Colonic polyps and adenocarcinoma complicating ureterosigmoidostomy: Report of a case. Am J Gastroenterol 79:453-457, 1984[Medline] 4. Eraklis AJ, Folkman MJ: Adenocarcinoma at the site of ureterosigmoidostomies for exstrophy of the bladder. J Pediatr Surg 13:730-734, 1978[CrossRef][Medline] 5. Starling JR, Uehling DT, Gilchrist KW: Value of colonoscopy after ureterosigmoidostomy. Surgery 96:784-790, 1984[Medline] 6. Husmann DA, Spence HM: Current status of tumor of the bowel following ureterosigmoidostomy: A Review. J Urol 144:607-609, 1990[Medline] 7. Cohen MS, Hilz ME, Davis CP, et al: Urinary carcinogen [nitrosamine] production in a rat animal model for ureterosigmoidostomy. J Urol 138:449-452, 1987[Medline] 8. Kälble T, Tricker AR, Berger M, et al: Tumor induction in a rat model for ureterosigmoidostomy without evidence of nitrosamine formation. J Urol 146:862-866, 1991[Medline] 9. Crissey MM, Steele GD, Gittes RF: Rat model for carcinogenesis in ureterosigmoidostomy. Science 207:1079-1080, 1980 10. Shokeir AA, Shamaa M, El-Mekresh MM, et al: Late malignancy in bowel segments exposed to urine without fecal stream. Urology 46:657-661, 1995[CrossRef][Medline] 11. Leadbetter GW Jr., Zickerman P, Pierce E: Ureterosigmoidostomy and carcinoma of the colon. J Urol 121:732-735, 1979[Medline]
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Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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