Vol. 114. December Printed in U.S.A.
THE ,JoURNAL OF UROLOGY
Copyright © 1975 by The Williams & Wilkins Co.
HISTOLOGIC APPEARANCE OF THE INTESTINAL URINARY CONDUIT J. W. GARNER, A. M. B. GOLDSTEIN
AND
M. D. COSGROVE
From the Department of Urology, Los Angeles County-University of Southern California Medical Center, Los Angeles, California
ABSTRACT
The histology of intestinal urinary conduits (8 ileal and 2 sigmoid) in place for 10 months to 10 years was studied in 10 patients between 20 and 65 years old. It is concluded that the ileum and the large intestine do not undergo adaptive meta plastic transformation. The only changes observed are related to a condition of chronic irritation to which the response is a chronic inflammatory reaction. Structures proving to be the most resistant were the cells of Paneth. The latter were not damaged in appearance and number as compared to normal, even when the conduit was in place for 10 years. Urine diversion with an isolated intestinal segment, such as the ilea! conduit described by Bricker' or the colon conduit described by Mogg,' has prolonged and saved the lives of many patients with varied urological afflictions. The untoward effects resulting from the intestinal urinary conduit, such as hyperchloremic acidosis and calculus formation, although generally not severe are caused by electrolyte imbalance developed during the passage of urine through the conduit. To visualize any adaptive changes that may occur in the intestine when it functions as a conduit of urine, several histologic studies have been reported. Because of the differences and discrepancies among these reports we thought that a further attempt to study the histology of the intestinal urinary conduit was justified. MATERIALS AND METHODS
We studied 10 patients between 20 and 65 years old with intestinal cutaneous urinary diversions that had been in existence for 3 months to 10 years (see table). Eight patients had ilea! conduits and 2 had sigmoid colon conduits. Two biopsy specimens were taken from each conduit at a depth of approximately 6 cm. from the external stoma with the cup biopsy forceps. No anesthetic was used. One of the specimens was fixed in 10 per cent formaldehyde for standard histologic staining and the other was placed in gluteraldehyde for electron microscopic studies of the cells of Paneth. A full clinical, radiological, biochemical and bacteriological diagnostic study was performed on each patient. Ilea! mucosa was studied in 3 patients undergoing intestinal operation and was used for control.
OBSERVATIONS
The mucosa of all conduits displayed chronic inflammatory changes varying from very mild to quite accentuated. Mild mucosa! edema was found in 9 cases. Shortening, flattening or absence of villi of the ileum was found in 4 of the 8 patients. The duration of the conduit did not seem to be a factor in this finding since these 4 patients had had their conduits for intervals ranging from 10 months to 10 years. In all 10 patients the goblet cells in the crypts appeared normal. No surface epithelial cells or surface goblet cells were in areas of flattened or absent villi (fig. 1). The striated border appeared well preserved but of patchy distribution in 6 of the 8 conduits. It is of interest that the 2 cases in which no striated borders were found, were in the patients whose conduits were in place for the greatest length of time. In all cases the cells of Paneth were well developed and numerous (figs. 2 and 3). They did not seem to be less numerous than in the normal ileum, even in conduits in place for 10 years (fig. 3, B). Electron microscopic studies have shown that Paneth's cells in the urinary conduit do not differ in any way from normal (fig. 4). The 2 sigmoid conduits were in place for 3 and 13 months, respectively. The surface epithelial cells and the lining epithelium of the crypts including the goblet cells were well preserved. No chronic inflammatory changes of the mucosa were noted. In 1 patient Paneth's cells were found although normally these cells are absent in the large intestine. Only 1 patient displayed electrolytic imbalance in the form of hyperchloremic acidosis. In this instance the ilea! mucosa was well preserved.
Accepted for publication May 30, 1975. Supported by a grant from the University of Southern California School of Medicine. 854
DISCUSSION
Joseph and Thomas reviewed the literature up to
855
HISTOLOGIC APPEARANCE OF INTESTINAL URINARY CONDUIT
Review of cases Pt. -Sex Age
Duration of Conduit (mos.)
50-F 45-F 40-F 20-F 51-F 65-F 35-F
13 19 23 36
46-M 55-M 62-F
46 69 120
3 6 10
Type of Conduit
Serum Chem.
Sigmoid Normal Ilea! Normal Ilea! Normal Sigmoid Creat. T Ilea! Normal Ilea! Normal Ilea! C}-f,CO,/ creat. T Ilea! Normal Ilea! Normal Ilea! Normal
PreConduit Irradiation -
-
-
+ -
+ +
Histology Goblet Cells
Paneth Cells
Normal Normal Normal Normal Normal Normal Normal
None Numerous Numerous Some Numerous Present Numerous
Normal Normal Normal
Numerous Numerous Numerous
Eosinophils -
+ ++ -
Plasma Edema Striated Cells Border
+ + ++ -
++ + +
++ + +
++ ++ ++
++ ++ ++
+ + + + + + +
Villi
-·
Normal Blunted
+ ++ -
+ + +
Normal Normal Normal
+
+
-
-
+
-
Blunted None Blunted
I
i
FIG. 2. High magnification of bottom of crypts of Lieberkiihn of ilea! conduit 10 months in duration. Note presence of well developed cells of Paneth (arrows).
FIG. 1. A, low power microscopic section of ilea! loop 10 months in duration. Note flattening and absence of villi and chronic inflammation. B, another area from same biopsy.
1956 and described histologic changes in the ilea! mucosa in ileocystoplasties. 3 They noted flattening of the villi, which they attributed to stretching of the intestinal segment. Shoemaker and associates drew similar conclusions from experimental work on animals. 4 Rattner and associates found that in most patients studied for 3 years the normal ilea! mucosa pattern was retained and there was no diminution in the production of mucus.' They also concluded that there was no anatomic reason to suspect a change in the absorptive capacity of the
mucosa because of exposure to urine. On the other hand, Kucera and Malinsky noted marked atrophy of the mucosa of the ilea! conduit, which was biopsied up to 7 years after construction. 6 Goldstein and associates described progressive shortening, blunting and broadening of the villi and deeper crypts in ilea! conduits from 7 days to 5 l/2 years. 7 These authors found no changes in the relative numbers of goblet or Paneth's cells. Under the electron microscope the microvilli were found to be shorter and fewer in number soon after the construction of the conduit. Dechner and associates concluded that in most patients with urinary ilea! conduits, mucosa! atrophy was complete by 2 years but noted that the surface epithelial cells, although atypical, had a normal distribution of cell types and an intact striated border. 8 These authors also concluded that progressive villus atrophy occurs in patches and that crypts become progressively shorter and fewer in number. Gracey and associates noted that nearly all conduits showed severe changes in 12 months but 2 patients had no mucosa! flattening after 42 and 54 months.• They noted that 4 patients with hyperchloremic acidosis had advanced mucosa! flattening within 4 months of the original operation and concluded that gross morphologic changes within the ilea! conduit do
856
GARNER, GOLDSTEIN AND COSGROVE
FIG. 4. Electron microscopic view of cell of Paneth in ilea! loop 23 months in duration.
FIG. 3. A, high magnification of section through bottom of glands of Lieberktihn of ilea! loop 69 months in duration. Note presence of well developed cells of Paneth (arrows). B, similar section of ilea! loop 120 months in duration. Note presence of cells of Paneth (arrows).
not prevent an occurrence of severe electrolytic disturbances. Watson and associates not only observed that the enzymes normally present in the surface epithelium, namely alkaline phosphatase, acid phosphatase and leucine amino peptidase, all persisted but also noted no changes in the surface epithelial cells, goblet cells or striated border. 10 Paneth's cells appeared distended with the characteristic granules. Kucera and Malinsky, as well as Guerrero-Alcazar and associates believe that the mucosa! changes noted in the ilea! conduits are adaptive ones which may protect from absorption of urine. 6 • 11 However, Rattner and associates believe that absorption does occur as proved by the hyperchloremic acidosis although less commonly than with ureterocolic anastomosis.• Watson and Cockett have observed in the junctional area between ileum and bladder that the simple columnar epithelium of the tips of the villi was replaced by transitional epithelium. 12 A similar observation was made by Joseph and Thomas but they concluded on serial sections that such transitional epithelium was in reality continuous at some point with the rest of transitional epithelium. 3 However, a possible seeding mechanism of the transitional
epithelium over the denuded tips of villi should be considered. 13 In no study on humans including the present one have such observations been made. It is possible that in none of these studies have biopsies been taken in the immediate proximity of the junction between the ureters and intestine. In the present study flattening of the villi was foun,d in 1 case after only 10 months while normal villi were found in ileal conduits in place 36 months. The striated border, which is related to the absorptive ability of intestinal surface epithelium, appears to be a resistant feature and was absent in only the oldest of ileal conduits 69 months and 12 years, respectively. Goblet cells were found even in these 2 cases in the crypts. Paneth's cells showed no changes in number and morphology compared to normal ileum even in the oldest conduits. Paneth's cells are considered to secrete different peptidases for splitting disaccharides into monosaccharides, lipase and small amounts of intestinal amylase for splitting carbohydrates into disaccharides. 14 Thus, the structures considered most related to the enzymatic function of the small intestinal mucosa proved to be the most stable and least influenced by the change in function of the ilea! conduits. Pathological changes seem to have no influence on the cells of Paneth. They are numerous in the small intestine in cases of gastritis. 15 Numerous cells of Paneth have been found on the intestinal side of the stoma in gastroenteroanastomoses. 1 • The cells of Paneth can be found in the glandular polyps of the small but also of the large intestine. 17• 18 Numerous cells of Paneth were even noted in a case of large intestinal metaplasia of the bladder. 19 In this study the only case of hyperchloremic acidosis occurred in the patient with normal appearing villi, while the other cases with normal electrolyte levels had normal and abnormal appearing mucosa. Therefore, one must conclude that the condition of the mucosa does not appear to influence the amount of absorption of urine that takes place.
HISTOLOGIC APPEARANCE OF INTESTINAL URINARY CONDUIT REFERENCES
1. Bricker, E. M.: Symposium on clinical surgery; bladder substitution after pelvic evisceration. Surg. Clin. N. Amer., 30: 1511, 1950. 2. Mogg, R. A.: Urinary diversion using the colonic conduit. Brit. ,J. Ural., 39: 687, 1967. 3. Joseph, J. and Thomas, G. A.: The behavior of autografts of ileum transplanted into the urinary bladder of rabbits. J. Anat., 92: 551, 1958. 4. Shoemaker, W. C., Tedeschi, C. G. and Grotzinger, P. ,J.: Morphologic changes of intestinal grafts used m bladder reconstruction. Arch. Surg., 72: 525, 1956. 5. Rattner, VI. H., Moran, J. J. and Murphy, ,J. ,J.: The histologic appearance of small bowel segments used as conduits. J. Urol., 82: 236, 1959. 5. Ku Cera) rJ. and "'"'"''""" eJ.: The mucous merDbrane of the intestinal loop-introduced into the urinary passages-as observed by light and electron microscopy. In: XIII Congres de la Societe Internationale d'Urologie. London: E. & S. Livingstone Ltd., vol. 2, p. 218, 1965. 7. Goldstein, M. J., Melamed, M. R., Grabstald, H. and Sherlock, P.: Progressive villous atrophy of the ileum used as a urinary conduit. Gastroenterology, 52: 859, 1967. 8. Dechner, E. E., Goldstein, M. J., Melamed, M. R. and Sherlock, P.: A histological and kinetic study of an ilea] conduit. Gastroenterology, 64: 920, 1973. 9. Gracey, M., R., Bishop, R. F., Smith, E. D. and Anderson, C. · Mucosa! morphology and bacte-
10.
11.
12.
13.
14.
15. 16. 17. 18.
19.
857
rial flora of ilea! conduits. Invest. Urol., 8: 596, 1971. Watson, A. J., Watson, J. W. and Walker, F. C.: The behavior of pedicle autografts of ileum transplanted into the colon in the rat. Amer. ,J. Path., 46: 553, 1965. Guerrero-Alcazar, M., Gonzalez-Angulo, A. and Ortiz-Quesada, F.: Histochemical and ultrastructural changes observed in the mucosa of the ilea! conduit. J. Urol., HJ4: 406, 1970. Watson, D. W. and Cockett, A. T. K.: Intestinal mucosa of dogs with ileocystoplasties. Urology, 2: 385, 1973. Goldstein, A. M. B., Harp, G. E., ,Jones, W. G. and Morrow, J. W.: Epithelial seeding. Possible mechanism in regeneration of urothelium. Urology, 3: 101. 1974. Guyton, A. C.: Textbook of Medical Physiology, 3rd ed. Philadelphia: W. B. Saunders Co., p. 747, 1966. Ko-Kubo, K.: Cited by Patzelt. 18 Hamper!, H.: Cited by Patzelt. 18 Feyrter, F.: Cited by Patzelt. 18 Patzelt, V.: Der Darm. In: Hand bu ch der Mikroskopischen Anatomie des Menschen. Edited by W. von Mollendorff. Berlin: Verlag-Von Julius Springer, vol. v/3, 1936. Davis, E. L., Goldstein, A. M. B. and Morrow J W · Unusual bladder mucosa[ metap!asia in a 'ca~e chronic prostatitis and cystitis. ,J. Urol., Hl: 767, 1974.
~f
THE ,JoURNAL OF UROLOGY
Copyright © 1975 by The Williams & Wilkins Co.
HISTOLOGIC APPEARANCE OF THE INTESTINAL URINARY CONDUIT J. W. GARNER, A. M. B. GOLDSTEIN
AND
M. D. COSGROVE
From the Department of Urology, Los Angeles County-University of Southern California Medical Center, Los Angeles, California
ABSTRACT
The histology of intestinal urinary conduits (8 ileal and 2 sigmoid) in place for 10 months to 10 years was studied in 10 patients between 20 and 65 years old. It is concluded that the ileum and the large intestine do not undergo adaptive meta plastic transformation. The only changes observed are related to a condition of chronic irritation to which the response is a chronic inflammatory reaction. Structures proving to be the most resistant were the cells of Paneth. The latter were not damaged in appearance and number as compared to normal, even when the conduit was in place for 10 years. Urine diversion with an isolated intestinal segment, such as the ilea! conduit described by Bricker' or the colon conduit described by Mogg,' has prolonged and saved the lives of many patients with varied urological afflictions. The untoward effects resulting from the intestinal urinary conduit, such as hyperchloremic acidosis and calculus formation, although generally not severe are caused by electrolyte imbalance developed during the passage of urine through the conduit. To visualize any adaptive changes that may occur in the intestine when it functions as a conduit of urine, several histologic studies have been reported. Because of the differences and discrepancies among these reports we thought that a further attempt to study the histology of the intestinal urinary conduit was justified. MATERIALS AND METHODS
We studied 10 patients between 20 and 65 years old with intestinal cutaneous urinary diversions that had been in existence for 3 months to 10 years (see table). Eight patients had ilea! conduits and 2 had sigmoid colon conduits. Two biopsy specimens were taken from each conduit at a depth of approximately 6 cm. from the external stoma with the cup biopsy forceps. No anesthetic was used. One of the specimens was fixed in 10 per cent formaldehyde for standard histologic staining and the other was placed in gluteraldehyde for electron microscopic studies of the cells of Paneth. A full clinical, radiological, biochemical and bacteriological diagnostic study was performed on each patient. Ilea! mucosa was studied in 3 patients undergoing intestinal operation and was used for control.
OBSERVATIONS
The mucosa of all conduits displayed chronic inflammatory changes varying from very mild to quite accentuated. Mild mucosa! edema was found in 9 cases. Shortening, flattening or absence of villi of the ileum was found in 4 of the 8 patients. The duration of the conduit did not seem to be a factor in this finding since these 4 patients had had their conduits for intervals ranging from 10 months to 10 years. In all 10 patients the goblet cells in the crypts appeared normal. No surface epithelial cells or surface goblet cells were in areas of flattened or absent villi (fig. 1). The striated border appeared well preserved but of patchy distribution in 6 of the 8 conduits. It is of interest that the 2 cases in which no striated borders were found, were in the patients whose conduits were in place for the greatest length of time. In all cases the cells of Paneth were well developed and numerous (figs. 2 and 3). They did not seem to be less numerous than in the normal ileum, even in conduits in place for 10 years (fig. 3, B). Electron microscopic studies have shown that Paneth's cells in the urinary conduit do not differ in any way from normal (fig. 4). The 2 sigmoid conduits were in place for 3 and 13 months, respectively. The surface epithelial cells and the lining epithelium of the crypts including the goblet cells were well preserved. No chronic inflammatory changes of the mucosa were noted. In 1 patient Paneth's cells were found although normally these cells are absent in the large intestine. Only 1 patient displayed electrolytic imbalance in the form of hyperchloremic acidosis. In this instance the ilea! mucosa was well preserved.
Accepted for publication May 30, 1975. Supported by a grant from the University of Southern California School of Medicine. 854
DISCUSSION
Joseph and Thomas reviewed the literature up to
855
HISTOLOGIC APPEARANCE OF INTESTINAL URINARY CONDUIT
Review of cases Pt. -Sex Age
Duration of Conduit (mos.)
50-F 45-F 40-F 20-F 51-F 65-F 35-F
13 19 23 36
46-M 55-M 62-F
46 69 120
3 6 10
Type of Conduit
Serum Chem.
Sigmoid Normal Ilea! Normal Ilea! Normal Sigmoid Creat. T Ilea! Normal Ilea! Normal Ilea! C}-f,CO,/ creat. T Ilea! Normal Ilea! Normal Ilea! Normal
PreConduit Irradiation -
-
-
+ -
+ +
Histology Goblet Cells
Paneth Cells
Normal Normal Normal Normal Normal Normal Normal
None Numerous Numerous Some Numerous Present Numerous
Normal Normal Normal
Numerous Numerous Numerous
Eosinophils -
+ ++ -
Plasma Edema Striated Cells Border
+ + ++ -
++ + +
++ + +
++ ++ ++
++ ++ ++
+ + + + + + +
Villi
-·
Normal Blunted
+ ++ -
+ + +
Normal Normal Normal
+
+
-
-
+
-
Blunted None Blunted
I
i
FIG. 2. High magnification of bottom of crypts of Lieberkiihn of ilea! conduit 10 months in duration. Note presence of well developed cells of Paneth (arrows).
FIG. 1. A, low power microscopic section of ilea! loop 10 months in duration. Note flattening and absence of villi and chronic inflammation. B, another area from same biopsy.
1956 and described histologic changes in the ilea! mucosa in ileocystoplasties. 3 They noted flattening of the villi, which they attributed to stretching of the intestinal segment. Shoemaker and associates drew similar conclusions from experimental work on animals. 4 Rattner and associates found that in most patients studied for 3 years the normal ilea! mucosa pattern was retained and there was no diminution in the production of mucus.' They also concluded that there was no anatomic reason to suspect a change in the absorptive capacity of the
mucosa because of exposure to urine. On the other hand, Kucera and Malinsky noted marked atrophy of the mucosa of the ilea! conduit, which was biopsied up to 7 years after construction. 6 Goldstein and associates described progressive shortening, blunting and broadening of the villi and deeper crypts in ilea! conduits from 7 days to 5 l/2 years. 7 These authors found no changes in the relative numbers of goblet or Paneth's cells. Under the electron microscope the microvilli were found to be shorter and fewer in number soon after the construction of the conduit. Dechner and associates concluded that in most patients with urinary ilea! conduits, mucosa! atrophy was complete by 2 years but noted that the surface epithelial cells, although atypical, had a normal distribution of cell types and an intact striated border. 8 These authors also concluded that progressive villus atrophy occurs in patches and that crypts become progressively shorter and fewer in number. Gracey and associates noted that nearly all conduits showed severe changes in 12 months but 2 patients had no mucosa! flattening after 42 and 54 months.• They noted that 4 patients with hyperchloremic acidosis had advanced mucosa! flattening within 4 months of the original operation and concluded that gross morphologic changes within the ilea! conduit do
856
GARNER, GOLDSTEIN AND COSGROVE
FIG. 4. Electron microscopic view of cell of Paneth in ilea! loop 23 months in duration.
FIG. 3. A, high magnification of section through bottom of glands of Lieberktihn of ilea! loop 69 months in duration. Note presence of well developed cells of Paneth (arrows). B, similar section of ilea! loop 120 months in duration. Note presence of cells of Paneth (arrows).
not prevent an occurrence of severe electrolytic disturbances. Watson and associates not only observed that the enzymes normally present in the surface epithelium, namely alkaline phosphatase, acid phosphatase and leucine amino peptidase, all persisted but also noted no changes in the surface epithelial cells, goblet cells or striated border. 10 Paneth's cells appeared distended with the characteristic granules. Kucera and Malinsky, as well as Guerrero-Alcazar and associates believe that the mucosa! changes noted in the ilea! conduits are adaptive ones which may protect from absorption of urine. 6 • 11 However, Rattner and associates believe that absorption does occur as proved by the hyperchloremic acidosis although less commonly than with ureterocolic anastomosis.• Watson and Cockett have observed in the junctional area between ileum and bladder that the simple columnar epithelium of the tips of the villi was replaced by transitional epithelium. 12 A similar observation was made by Joseph and Thomas but they concluded on serial sections that such transitional epithelium was in reality continuous at some point with the rest of transitional epithelium. 3 However, a possible seeding mechanism of the transitional
epithelium over the denuded tips of villi should be considered. 13 In no study on humans including the present one have such observations been made. It is possible that in none of these studies have biopsies been taken in the immediate proximity of the junction between the ureters and intestine. In the present study flattening of the villi was foun,d in 1 case after only 10 months while normal villi were found in ileal conduits in place 36 months. The striated border, which is related to the absorptive ability of intestinal surface epithelium, appears to be a resistant feature and was absent in only the oldest of ileal conduits 69 months and 12 years, respectively. Goblet cells were found even in these 2 cases in the crypts. Paneth's cells showed no changes in number and morphology compared to normal ileum even in the oldest conduits. Paneth's cells are considered to secrete different peptidases for splitting disaccharides into monosaccharides, lipase and small amounts of intestinal amylase for splitting carbohydrates into disaccharides. 14 Thus, the structures considered most related to the enzymatic function of the small intestinal mucosa proved to be the most stable and least influenced by the change in function of the ilea! conduits. Pathological changes seem to have no influence on the cells of Paneth. They are numerous in the small intestine in cases of gastritis. 15 Numerous cells of Paneth have been found on the intestinal side of the stoma in gastroenteroanastomoses. 1 • The cells of Paneth can be found in the glandular polyps of the small but also of the large intestine. 17• 18 Numerous cells of Paneth were even noted in a case of large intestinal metaplasia of the bladder. 19 In this study the only case of hyperchloremic acidosis occurred in the patient with normal appearing villi, while the other cases with normal electrolyte levels had normal and abnormal appearing mucosa. Therefore, one must conclude that the condition of the mucosa does not appear to influence the amount of absorption of urine that takes place.
HISTOLOGIC APPEARANCE OF INTESTINAL URINARY CONDUIT REFERENCES
1. Bricker, E. M.: Symposium on clinical surgery; bladder substitution after pelvic evisceration. Surg. Clin. N. Amer., 30: 1511, 1950. 2. Mogg, R. A.: Urinary diversion using the colonic conduit. Brit. ,J. Ural., 39: 687, 1967. 3. Joseph, J. and Thomas, G. A.: The behavior of autografts of ileum transplanted into the urinary bladder of rabbits. J. Anat., 92: 551, 1958. 4. Shoemaker, W. C., Tedeschi, C. G. and Grotzinger, P. ,J.: Morphologic changes of intestinal grafts used m bladder reconstruction. Arch. Surg., 72: 525, 1956. 5. Rattner, VI. H., Moran, J. J. and Murphy, ,J. ,J.: The histologic appearance of small bowel segments used as conduits. J. Urol., 82: 236, 1959. 5. Ku Cera) rJ. and "'"'"''""" eJ.: The mucous merDbrane of the intestinal loop-introduced into the urinary passages-as observed by light and electron microscopy. In: XIII Congres de la Societe Internationale d'Urologie. London: E. & S. Livingstone Ltd., vol. 2, p. 218, 1965. 7. Goldstein, M. J., Melamed, M. R., Grabstald, H. and Sherlock, P.: Progressive villous atrophy of the ileum used as a urinary conduit. Gastroenterology, 52: 859, 1967. 8. Dechner, E. E., Goldstein, M. J., Melamed, M. R. and Sherlock, P.: A histological and kinetic study of an ilea] conduit. Gastroenterology, 64: 920, 1973. 9. Gracey, M., R., Bishop, R. F., Smith, E. D. and Anderson, C. · Mucosa! morphology and bacte-
10.
11.
12.
13.
14.
15. 16. 17. 18.
19.
857
rial flora of ilea! conduits. Invest. Urol., 8: 596, 1971. Watson, A. J., Watson, J. W. and Walker, F. C.: The behavior of pedicle autografts of ileum transplanted into the colon in the rat. Amer. ,J. Path., 46: 553, 1965. Guerrero-Alcazar, M., Gonzalez-Angulo, A. and Ortiz-Quesada, F.: Histochemical and ultrastructural changes observed in the mucosa of the ilea! conduit. J. Urol., HJ4: 406, 1970. Watson, D. W. and Cockett, A. T. K.: Intestinal mucosa of dogs with ileocystoplasties. Urology, 2: 385, 1973. Goldstein, A. M. B., Harp, G. E., ,Jones, W. G. and Morrow, J. W.: Epithelial seeding. Possible mechanism in regeneration of urothelium. Urology, 3: 101. 1974. Guyton, A. C.: Textbook of Medical Physiology, 3rd ed. Philadelphia: W. B. Saunders Co., p. 747, 1966. Ko-Kubo, K.: Cited by Patzelt. 18 Hamper!, H.: Cited by Patzelt. 18 Feyrter, F.: Cited by Patzelt. 18 Patzelt, V.: Der Darm. In: Hand bu ch der Mikroskopischen Anatomie des Menschen. Edited by W. von Mollendorff. Berlin: Verlag-Von Julius Springer, vol. v/3, 1936. Davis, E. L., Goldstein, A. M. B. and Morrow J W · Unusual bladder mucosa[ metap!asia in a 'ca~e chronic prostatitis and cystitis. ,J. Urol., Hl: 767, 1974.
~f
