Histological Changes in Ileal Conduits

0022-534 7/84/1326-1108$02.00/0 Vol. 132, December

THE JOURNAL OF UROLOGY

Copyright© 1984 by The Williams & Wilkins Co.

Printed in U.S.A.

HISTOLOGICAL CHANGES IN ILEAL CONDUITS A. M. DEANE, C. R. J. WOODHOUSE AND M. CONSTANCE PARKINSON From the Academic Unit, Department of Histopathology, The Institute of Urology and St. Peter's Hospitals, London, England

ABSTRACT

The histological appearances of 20 excised ileal conduits are described, 9 of which had been present for more than 10 years. Partial and subtotal villous atrophy associated with a chronic inflammatory infiltrate was seen in all cases. The more severe changes were seen adjacent to the stoma and ureteral orifices, and in the older conduits_ The muscularis mucosa was thickened and splintered, and the submucosa showed edema and lymphatic dilatation. These appearances could not be related to the presence of infection or obstruction. The cause of the morphological abnormalities is likely to be multifactorial but the changes are not premalignant. The 2 carcinomas seen were recurrences from primaries elsewhere in the urinary tract_ The consequences of using parts of the intestinal tract for urinary diversion are well documented but not appreciated widely. The incidence of carcinoma in ureterosigmoidostomies has been calculated as 80 to 100 times the cumulative incidence in the general population. 1 Therefore, morphological examination of intestine exposed to urine has concentrated on premalignant or malignant epithelial changes. Despite this awareness cases of malignant or benign neoplasms in ileal2· 3 and colonic conduits are rare. 4 However, findings in a series of biopsies from colonic conduits were said to indicate a malignant potential and followup of these diversions was advocated. 5 This retrospective review was done to assess the morphological abnormalities in resected ileal conduits, with emphasis on premalignant features, and also to document and correlate morphological changes with the clinical findings. PATIENTS AND METHODS

At any given time the population of our hospitals includes >200 patients with ileal conduits attending for regular review. Many patients had undergone diversion in childhood for benign and malignant conditions, and continue the followup in the adult clinics. All ileal conduits resected between 1974 and 1983 were included in this study. A total of 20 partially or totally excised specimens was available for review. The clinical and bacteriological details are shown in table 1. Of the patients 16 had undergone diversion for benign conditions and 4 for bladder carcinoma. Use of the loop varied from 8 months to 25 years but 9 were used for > 10 years. Six loops were excised when not obstructed (4 for undiversion and 2 for ureteral obstruction), while 12 loops were removed for stomal problems (8 of which were obstructed) and 2 were excised for recurrent carcinoma. An average of 4 blocks had been obtained from each case and all sections were reviewed by 1 ofus (M. C. P.). RESULTS

Stoma. All 12 patients in whom the stoma was removed had acute superficial ulceration. In 1 case in which the stoma had sloughed acute necrosis involved the mucosal and muscle layers. A granulomatous reaction was present in the submucosa adjacent to the skin in 2 patients, the cause of which was unclear since no associated infective or systemic etiology was demonstrated. Mucosa. Transitional epithelium extended from the ureter to cover the ileal mucosa for 5 to 10 mm. in 5 conduits (fig. 1). Foci of pseudo-pyloric metaplasia were seen in 3 loops and Accepted for publication August 2, 1984.

colonic metaplasia in 1. In 2 loops there were foci of epithelial atypia, including stratification and nuclear enlargement, but marked pleomorphism, an excess of mitotic figures or bizarre forms were not seen. These findings are interpreted as regen erative rather than carcinoma in situ (fig. 2). Partial and/or subtotal villous atrophy was seen to a varying extent in all specimens, while areas of normal ileal mucosa were present in only 4 (patients 14, 15, 18 and 19) (fig. 3). In partial villous atrophy the over-all thickness of the mucosa is unchanged but the villi are shortened markedly and the basal layer (containing the crypts of Lieberkiihn) is thickened. In the more severe subtotal atrophy the villi almost disappear, which makes the basal layer thicker and results in an appearance resembling colonic mucosa. The scale and distribution of mucosal change are summarized in figure 4. Subtotal atrophy was present throughout the sections of ileum excised from 5 patients and alternated with partial villous atrophy in 2. In 12 patients the mucosal changes could be related to the stoma or ureteral orifices. Subtotal atrophy was seen adjacent to the stoma in all instances when the cutaneous junction had been resected and was confined to this area in 5 patients, the mucosa away from this site showing partial atrophy. In 5 of 6 patients in whom the ureteroileal anastomosis had been sectioned subtotal atrophy was present adjacent to the transitional epithelium merging with partial atrophy away from this junction. In only 1 patient were the mucosal changes more severe away from than adjacent to the ureteral orifices. Although new conduits could show severe changes, mucosal atrophy generally worsened with increasing use (table 2). All conduits showed an increase in chronic inflammatory cells in the mucosa but there were normal areas in 4. The number of eosinophils was increased strikingly in 4 instances. The inflammatory infiltrate extended into the submucosa and muscle in patients 2 and 14. Two recurrent carcinomas were seen: a transitional cell carcinoma in the terminal ureter and adjacent conduit in a patient who had had a cystectomy for transitional cell carcinoma 15 years earlier (patient 11), while 1 patient who had been born with exstrophy and had undergone ureterosigmoidostomy suffered an adenocarcinoma at the point of anastomosis. The adenocarcinoma was resected and the urine was diverted into an ileal conduit. The carcinoma recurred in the conduit 5 years later. Muscularis mucosa and submucosa. In all patients the muscularis mucosa was thickened and splintered. The submucosa always showed marked edema and lymphatic channel dilatation (fig. 3).

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HISTOLOGICAL CHANGES IN ILEAL CONDUITS TABLE

Pt.-Sex No.

Indication for

1-F 2-F 3-F 4-M 5-M 6-M 7-M 8-M 9-M 10-M 11-M 12-M 13-M 14-F 15-F 16-M 17-M 18-M 19-F 20-F

Neuropathic Neuropathic Neuropathic Neuropathic Neuropathic Neuropathic Neuropathic Bladder Ca Bladder Ca Bladder Ca Bladder Ca Exstrophy Exstrophy Urge incontinence Urge incontinence Tuberculosis Epispadias Bilat. megaureters Stress incontinence Interstitial cystitis

Diversion

1. Clinical and bacteriological details of patients Yrs. With Loop

Reason for Removal of Loop

Infected Urine (loop specimen)

Infection at Time of Excision

25 22 14 11 9 8 1.5 12 8 4 2 18 13 5 0.75 18 15 9 5 1.5

Stomal obstruction Stomal obstruction Undiversion (was obstructed) Stomal obstruction Undiversion Stomal retraction Stomal prolapse Ureteral obstruction Stomal obstruction Recurrent Ca Recurrent Ca Stomal retraction/obstruction Stomal retraction/obstruction Stomal retraction Ureteral obstruction Undiversion Stomal obstruction Undiversion Stomal retraction Stomal obstruction

Chronic Occasional

Yes No No No Yes Yes No No No Yes No No Yes Yes No Yes Yes No Yes Yes

Chronic Chronic Occasional Chronic Occasional Occasional Chronic Occasional Chronic Occasional Occasional Chronic Chronic

FIG. 2. Atrophic atypical ilea! conduit mucosa in which superficial epithelium is stratified, and nuclear hyperchromatism and pleomorphism are present. H & E, reduced from Xl40.

FIG. 1. Transitional epithelium covering glands in atrophic small intestinal mucosa adjacent to ureteroileal anastomosis. H & E, reduced from Xl40.

Muscle and serosa. The muscle and serosa were normal. A granulomatous reaction around suture material was seen adjacent to the ureteroileal anastomosis in 1 patient. DISCUSSION

The changes that we have found in ileal conduits were confined to the mucosa, submucosa and muscularis mucosa, and consisted of villous atrophy with chronic inflammation of the mucosa, fragmentation and thickening of the muscularis mucosa, and edema of the submucosa. Similar changes have been reported in biopsies from human conduits 6- 9 and in canine ileal patch cystoplasties. 10 However, contrary to the earlier reports, in our series a variation in appearances in different parts of the conduit and with time was seen. The older the conduit the more severe were the changes found. The changes

were most severe around the ureteral orifices and close to the stoma. These points are missed when conduits are studied by biopsy alone. Most biopsy series have failed to demonstrate progressive mucosal damage, perhaps owing to the range that can be seen in a single loop, although 1 series found a positive relationship between pathological findings and conduit age, and stated that villous atrophy began at 1 week and was complete at 1 year. 7 Another series showed, as we did, progressive changes with time but a varying rate from patient to patient. 8 Foci of metaplasia resembling pyloric or colonic mucosa were seen in 5 conduits, which could explain excessive mucous production by some conduits. It is not possible to determine the cause of these changes. Morphological changes in ileal conduits have been considered to follow radiotherapy, chronic ischemia, lymphatic obstruction or bacterial infection, or to be the direct result of contact with urine. Only 1 of our patients had received radiotherapy but the conduit did not differ from that of the others. Chronic ischemia may cause mucosal atrophy but other features of this condition (ulceration and submucosal granulation tissue with hemosiderin-laden macrophages) were not apparent. Acquired lymphatic obstruction may be associated with villous distortion but in this disorder, unlike our findings, dilated lymphatics are evident in the lamina propria and an inflammatory infiltrate is not a feature.

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DEANE, WOODHOUSE AND PARKINSON

B

FIG. 3. A, partial villous atrophy in ilea! conduit mucosa. B, ilea! conduit mucosa in which subtotal atrophy is present but occasional short deformed villi are seen in center of photomicrograph. H & E, reduced from X60.

/

Centraltortion. \ Partial/Subtotal villous atrophy.

Stoma.

Uretero-ileal anastomosis. Transitional epithelium

extends 5-10mm onto the ilea I mucosa in 5 cases.

Acute superficial ulceration.

Peri-stomal and peri-ureteric

Subtotal villous atrophy.

FIG. 4. Diagram of scale and distribution of mucosa! changes within ilea! conduits

TABLE 2.

Re/,ationship between mucosal appearances and conduit "age" in 20 patients

Villous atrophy but some normal architecture retained Mixed partial and subtotal villous atrophy Widespread subtotal villous atrophy

No. Pts.

Mean Yrs. of Conduit

4

4.9

11

10.6

5

13

The changes seen in infection vary according to the organism. Those described in Escherichia coli infestation (the most common isolate in this series) include mucosal erosions and congestion associated with a mixed inflammatory infiltrate in the lamina propria and submucosa. In the ileal conduits erosions were confined to the area adjacent to the stoma; congestion was not a feature and the inflammatory infiltrate was predominantly chronic in nature_ The clinical condition of the conduits in our series did not have a relationship with the histological findings. Thus, it seems unlikely that infection or obstruction is the cause of the morphological changes that were seen. It is most likely that several factors were involved. Although no single cause has been identified, these changes should be regarded as the consequence of use of ileum as an isolated urinary conduit. The marked villous atrophy helps to explain the lack of absorptive capacity, at least for glucose, that we have found in long established conduits. 11 The risk of carcinoma following ureterosigmoidostomy is established. 1 The cause appears to lie in the confluence of urine

and feces. 12• 13 More relevant, therefore, to the discussion of neoplasia in ileal conduits is the evidence for tumor development in colonic conduits. Only a single case of primary carcinoma in a colonic conduit has been described. 4 In a recent study of colonic conduits the investigators claimed to indicate a risk of malignancy. 5 This claim was based on the demonstration of a persistent and progressive chronic mucosal inflammation that induced a comparison with ulcerative colitis and Crohn's disease, conditions associated with carcinoma. Despite this conclusion dysplastic change could not be demonstrated in any of the biopsies nor was it stated that any of the patients suffered overt carcinoma during a followup of>15 years. Thus, the risk of carcinoma in colonic conduits would appear to be a theoretical possibility but not a proved fact. Ileal conduits have been used for urinary diversion for >30 years. There are only 2 reported cases of associated primary tumors: an adenomatous polyp and a carcinoma. 2 • 3 There were no primary neoplasms in our series. The only 2 tumors noted represented recurrent disease from a primary bladder carcinoma and a carcinoma at the ureterosigmoid anastomosis. In addition, there was no evidence of dysplasia or premalignant epithelial change. Since these conduits had been used for > 10 years in 9 patients our results do not indicate a malignant potential in ileal conduit mucosa. When patients have undergone diversion for a benign condition the risk of neoplasia appears to be small. Our study supports the view that endoscopic followup of symptomless patients is not indicated. Patients who underwent diversion for a malignant condition may suffer recurrence in the conduit, especially at the ureteroileal junction. Endoscopy of the conduit would be prudent.

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