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Regeneration of Transitional Epithelium of the Human Bladder after Total Surgical Excision for Recurrent, Multiple Bladder Cancer: Apparent Tumor Inhibition
Vol. 93, May Printed in U.S.A.
THE JOURNAL OF UROLOGY
Copyright © 1965 by The Williams & Wilkins Co.
REGENERATION OF TRANSITIONAL EPITHELIUM OF THE HUMAN BLADDER AFTER TOTAL SURGICAL EXCISION FOR RECURRENT, MULTIPLE BLADDER CANCER: APPARENT TUMOR INHIBITION ROGER BAKER, WILLIAM C. MAXTED
AND
NED DIPASQUALE
From the Department of Surgery (Urology), Georgetown University, Washington, D. C.
The purposes of this paper are: 1) to prove that excision of the entire mucosa of the bladder in a human subject is followed by regeneration of normal epithelium; 2) to describe a technique for epithelial excision; 3) to demonstrate the technique in a patient with frequent and multiple recurrences of bladder cancer. So far the regenerated epithelium has not formed any tumors. The precise manner of epithelial regeneration is not clear. Our laboratory observations indicate differentiation of a totipotent mesenchymal cell to a transitional epithelial cell which then undergoes proliferation to ultimately re-epithelialize the entire lining of the bladder. Based upon animal experiments, other investigators believe that there is proliferation of cells from remaining viable epithelial cells which migrate over the denuded area and ultimately lead to complete re-epithelialization. The question of migration versus differentiation has not been resolved. In fact, it has not been established that the mucous membrane of the bladder in the human is capable of regeneration after it has been totally de-epithelialized. Previous studies in our laboratory showed that regeneration of the total bladder wall is possible in both dog and human subjects.1- 2 This regeneration applies not only to smooth muscle but also the epithelial lining. It is reasonable to assume, on the basis of mucosal regeneration associated with total bladder regeneration, that selective excision of just bladder mucosa in a patient will probably result in epithelial regeneration. There is a high incidence of bladder involvement associated with transitional cell lesions of
the renal pelvis. The bladder lesions (benign or malignant) tend to recur. The current concept is that these patients have a urothelial predisposition to tumor formation either genetically controlled or acquired. The data that support this concept are not conclusive. For example, patients who have cancer of the renal pelvis of one kidney should have cancer in the contralateral kidney in a statistically high per cent of cases. However, tumor formation in the opposite renal calyces, pelvis or ureter is rare, suggesting that the facts do not support the theory. Thomas and Regneir found only 4.2 per cent of patients with cancer of the renal pelvis having involvement of the contralateral pelvis. 3 Even this very small rate is probably unrealistically higher than the absolute incidence. For example, in a review of more than 170 cases of carcinoma of the renal pelvis, Riches did not find a single patient with involvement of the contralateral kidney. 4 If the involvement were truly as great as the 4.2 per cent reported by Thomas and Regnier, it would appear reasonable that Riches should have encountered at least one such patient in his study. Colston, who reported a case of bilateral renal papillomas in 1955, could find only five proven cases of bilateral involvement in the literature. 5 The absolute incidence of contralateral involvement of the renal pelvis with tumor is not known, but certainly only rarely observed. Excluding isolated exceptional results, the long-term management of patients with frequently recurring, multiple, proven bladder cancers has not been characterized by uniformly successful results; the majority of these patients eventually require cystectomy. Prior to infiltra-
Accepted for publication September 23, 1964. This study is supported in part by United States Public Health Grant Number GM 07431-03 and by Baker Research Foundation. 1 Baker, R.: Influence of clinical and laboratory investigation in establishing current therapy of bladder cancer. Bull. New York Acad. Med., 30:
3 Thomas, G. J. and Regnier, E. A.: Tumors of the kidney, pelvis and ureters. J. Urol., 11: 205-
919, 1954.
2 Baker, R.. , Tehan, T. and Kelly, T.: Regeneration of urinary bladder after subtotal resection for carcinoma. Amer. Surg., 25: 348-352, 1959.
238, 1924. 4 Riches, E.W., Griffiths, I. H. and Thackray, A. C.: New growths of kidney and ureter. Brit. J. Urol., 23: 297-356, 1951. 5 Colston, J. A. C. and Arcadi, J. A.: Bilateral renal papillomas: Transpelvic electroresection with preservation of the kidney. Contralateral nephrectomy; four-year survival. J. Urol., 73:
460--467, 1955. 593
594
BAKER, MAXTED AND DIPASQUALE
tion, bladder cancer is an epithelial disease. Total cystectomy may not be indicated if excision of just the mucous membrane of the bladder can result in: 1) subsequent regeneration of normal bladder mucous membrane; and 2) the newly formed bladder epithelium does not have the same malignant potential as the original epithelium. PROCEDURE
The bladder is approached suprapubically and opened widely. Physiologic saline is injected with pressure into the lamina propria thus elevating the mucosa which is then immediately dissected from the underlying muscle wall. The process is repeated until the entire mucosa is excised but for a narrow disk, about 2 mm. wide, around each ureteral orifice. The area of the bladder outlet and the urethral mucous membrane which can be reached are similarly treated. If there is any question relative to adequacy of depth of the mucosal excision, the excision is made deeper into the superficial muscle to insure total mucosal resection. The bladder incision is closed in 2 layers with 2-0 chromic catgut after a onequarter inch empty Penrose drain has been inserted in the bladder and the other end brought through the wound and sutured to the skin. An indwelling urethral catheter with a 5 cc bag is used for 3 to 4 weeks. The bladder drain is utilized until bleeding from the bladder is insignificant. The prevesical space is drained as usual. CASE REPORT AND RESULTS
W. F., Georgetown University Hospital No. 100775, a 48-year-old male engineer, was first seen in November 1959 because of intermittent gross, total, painless hematuria a year in duration. Nephro-ureterectomy was performed for a huge transitional cell cancer of the renal pelvis. The patient underwent cystoscopy 8 times during the next 28 months. On each occasion multiple transitional cell carcinomas, grade 2, were resected transurethrally from the bladder and urethra. There was no invasion of the muscularis. Due to the frequency of recurrences, the number of lesions found at each cystoscopy and the fact that each tumor was malignant, on November 26, 1962 the lining of the bladder was excised as previously described. The mucosa of the urethra was chemically cauterized with 50 per
cent phenol for 30 seconds after which the urethra was irrigated with alcohol followed by saline. During convalescence, the blood urea nitrogen (BUN) and serum electrolytes remained within normal range. There were two episodes of chills associated with temperature elevation due to urinary tract infection. Blood cultures were sterile but urine cultures were not. There was prompt and complete response to specific antibiotic therapy. Urine cultures were obtained every fourth day postoperatively; each was positive. The bladder drain was removed 12 days postoperatively and the drain in the prevesical space was removed 5 days later. The Foley catheter was removed 27 days postoperatively after which there was urinary frequency of approximately every 30 minutes. Slight stress incontinence, slight dysuria and terminal urinary dribbling improved rapidly. The patient was discharged 30 days following operation with full urinary control and voiding maximum volumes of 100 cc about every 1 to 2 hours, with no discomfort. Five and one-half months postoperatively the patient was admitted for evaluation. He was working full-time and had no urinary complaints. He voided about every 2 hours during the day and 3 to 4 times at night. The voiding volumes varied from 150 to 200 cc. He had no discomfort when the bladder was full, no urgency, no lack of urinary control and no discomfort on voiding. The maximum bladder capacity was 225 cc. There was no urethral stricture. The mucosal lining of the prostatic urethra appeared grossly normal. The remainder of the urethra was likewise unremarkable except for a single papillary lesion in the urethra at the penile-scrotal junction which was resected. The histological diagnosis was transi-
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25
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\.
JulJ60 oot,60
Moy6L
S•Pl,610tc.61Mor,62. June62.
-
No•.62
TOTAL MUCOSAL EXCISION
May63
Sopt.63
Jon.64
,..,64
FIG. 1. Graph demonstrates frequency rate and
number of bladder cancers formed. Transurethral resection used each time. Since epithelial excision and regeneration there has been no tumor recurrence.
REGENEHA'J'ION OF TRANS1'l'IONAL BLADDER EPITHELIUl\I
tional cell carcinonia, grade 1. The mucosa of the bladder \yap paler than nornial but no mucosa! lesions 1yere present. Urine culture was sterile. l\Iultiple biop,,ies were obtained of bladder and urethra.
[i9:5
Endoscopy 11 months postoperatively revealed no recurrence of urethral or bladder lesions, The bladder mucosa was normal in appearance. l\lultiple biopsies were obtained from the bladder wall and also the pro.static urethra. Urine cultures were
FrG. 2. A, representative section of tot al mucous membrane surgically excised. Dcmonst,ration of adequa,te rnucos0,l excision, including many areas of superfieial museularis. Absence of actlrnl is due to multiple packing of bladder during phenoli½aticm of urethra just prior to its excisicrn_ , biops)· of regenerating human bladder mucous membrane 5 months 0,fter surgical excision of origiua.l mucmm. Transitional epithelium cell depth of on]>, 1 to 5. Edema. with cellular infiltrate in lamina prr,pria.
596
BAKER, lVlAXTED AND DIPASQUALE
Fm. 3. Biopsy of prostatic urethra 5 months after excision of original mucous membrane. Demonstration of regeneration to normal prostatic urethral epithelium.
sterile. The patient had a normal diurnal voiding pattern but nocturia twice. He had no discomfort when the bladder was full or during voiding. Subsequent endoscopies failed to show recurrence of cancer (fig. 1). A biopsy obtained at the time of surgical excision of the original mucosa demonstrated that adequate resection of the mucosa was accomplished, including many areas of superficial muscularis (fig. 2, A). The absence of actual epithelium was due to traumatic denuding caused by repeated packing of the bladder with vasalinized gauze to protect it from burns from phenol which was used for urethral mucosal destruction prior to excision of bladder mucous membrane. Multiple biopsies of the bladder wall obtained 5 months postoperatively (fig. 2, B) revealed regeneration of the epithelial lining of the bladder but it was not entirely normal. The cell layers varied from 1 cell to 4 and 5 cells in thickness. The lamina propria was edematous with mononuclear and polymorphonuclear cellular infiltrate. Biopsy of the prostatic urethra 5 months postoperatively (fig. 3) also demonstrated regeneration of normal epithelium. A biopsy 11 months postoperatively (fig. 4) revealed regeneration of a nearly normal transitional epithelial lining in the bladder.
Fm. 4. Biopsy of completely regenerated human bladder mucous membrane 11 months after excision of original mucosa. Regenerated epithelium almost indistinguishable from normal transitional epithelium of bladder.
REGENERATION OF TRANSITIONAL BLADDER EPITHELIUM DISCUSSION
The submucosa of the regenerated bladder epithelium showed some thickening, edema and inflammatory infiltrate but no extensive fibrosis. The muscularis was not characterized by any fibrosis or cellular infiltrate. This observation deserves specific attention as it has generally been assumed that loss of a major area of the epithelial lining of the bladder, and certainly its total loss, would result in contracture of the bladder with gross reduction in capacity. Some authors who have studied regeneration of the dog bladder have been of the opinion that bladder contracture might result from intramural fibrosis due to epithelial loss. Others have wondered whether continuous. catheter drainage of such a bladder, by preventmg the natural dilatation that occurs during the storage phase of micturition, might also contribute to bladder fibrosis and contracture. Postoperative biopsies and the course of the patient do not support these assumptions. Clinically, there was no evidence of bladder fibrosis. After removal of the urethral catheter there was a progressive increase in bladder capacity. Five months postoperatively the patient voided 200 to 225 cc urine. Other theoretical complications of denuding the bladder mucosa and observations noted in the laboratory animal either did not occur in the patient under discussion or caused no trouble. Sanders and associates noted mild, temporary elevation of the BUN and serum sodium in doo-s in which the bladder had been completely d:nuded of mucosa. 6 These values had returned to normal levels 14 days after operation. At no time in the postoperative course of our patient was the BUN elevated or the serum electrolytes of abnormal concentration. 6 Sanders, A. R., Sch~in, C. J. and Orkin, L.A.: Total mucosal denndat10n of the canine bladder· ~xperimental observations and clinical implica~ t10ns-final report. J. Urol., 79: 63-77, 1958.
597
Fear has been expressed with respect to the likelihood of bacteremia resulting from infection of an extensively denuded bladder surface in the presence of an indwelling urethral catheter. In spite of constant infection of the bladder, there were only two episodes suggestive of bacteremia. However, blood cultures were sterile. On each occasion there was prompt clinical response to antibiotic therapy. SUMMARY
Transitional epithelium in the human bladder can regenerate to normal epithelium after total surgical removal. A method for the excision is presented. Urethral irrigation with phenol to inhibit or destroy urethral mucous membrane is reported. Subsequent biopsies demonstrated that the urethral mucous membrane as well as the bladder regenerated to normal epithelium. Postoperatively, bacteremia and electrolyte abnormalities were absent, the bladder capacity was nearly normal and there was full control of urethral sphincters. The procedure described was used in a patient with transitional cell carcinoma of the left kidney who underwent nephro-ureterectomy. He subsequently had multiple, frequent recurrences of proven bladder cancer. During the 28 months preceding epithelial excision, cystoscopy was performed approximately every 4 months. On each occasion, multiple bladder cancers were excised transurethrally. In the 18 months since denudation of the lining of the bladder and regeneration of a new mucous membrane, there have been no cancer recurrences within the bladder and only one recurrence in the phenolized urethra. Regardless of these facts, followup evaluation of the patient is of too short duration to formulate anything other than a favorable impression relative to cancer elimination or inhibition of the regenerated epithelium compared to the original epithelium.
THE JOURNAL OF UROLOGY
Copyright © 1965 by The Williams & Wilkins Co.
REGENERATION OF TRANSITIONAL EPITHELIUM OF THE HUMAN BLADDER AFTER TOTAL SURGICAL EXCISION FOR RECURRENT, MULTIPLE BLADDER CANCER: APPARENT TUMOR INHIBITION ROGER BAKER, WILLIAM C. MAXTED
AND
NED DIPASQUALE
From the Department of Surgery (Urology), Georgetown University, Washington, D. C.
The purposes of this paper are: 1) to prove that excision of the entire mucosa of the bladder in a human subject is followed by regeneration of normal epithelium; 2) to describe a technique for epithelial excision; 3) to demonstrate the technique in a patient with frequent and multiple recurrences of bladder cancer. So far the regenerated epithelium has not formed any tumors. The precise manner of epithelial regeneration is not clear. Our laboratory observations indicate differentiation of a totipotent mesenchymal cell to a transitional epithelial cell which then undergoes proliferation to ultimately re-epithelialize the entire lining of the bladder. Based upon animal experiments, other investigators believe that there is proliferation of cells from remaining viable epithelial cells which migrate over the denuded area and ultimately lead to complete re-epithelialization. The question of migration versus differentiation has not been resolved. In fact, it has not been established that the mucous membrane of the bladder in the human is capable of regeneration after it has been totally de-epithelialized. Previous studies in our laboratory showed that regeneration of the total bladder wall is possible in both dog and human subjects.1- 2 This regeneration applies not only to smooth muscle but also the epithelial lining. It is reasonable to assume, on the basis of mucosal regeneration associated with total bladder regeneration, that selective excision of just bladder mucosa in a patient will probably result in epithelial regeneration. There is a high incidence of bladder involvement associated with transitional cell lesions of
the renal pelvis. The bladder lesions (benign or malignant) tend to recur. The current concept is that these patients have a urothelial predisposition to tumor formation either genetically controlled or acquired. The data that support this concept are not conclusive. For example, patients who have cancer of the renal pelvis of one kidney should have cancer in the contralateral kidney in a statistically high per cent of cases. However, tumor formation in the opposite renal calyces, pelvis or ureter is rare, suggesting that the facts do not support the theory. Thomas and Regneir found only 4.2 per cent of patients with cancer of the renal pelvis having involvement of the contralateral pelvis. 3 Even this very small rate is probably unrealistically higher than the absolute incidence. For example, in a review of more than 170 cases of carcinoma of the renal pelvis, Riches did not find a single patient with involvement of the contralateral kidney. 4 If the involvement were truly as great as the 4.2 per cent reported by Thomas and Regnier, it would appear reasonable that Riches should have encountered at least one such patient in his study. Colston, who reported a case of bilateral renal papillomas in 1955, could find only five proven cases of bilateral involvement in the literature. 5 The absolute incidence of contralateral involvement of the renal pelvis with tumor is not known, but certainly only rarely observed. Excluding isolated exceptional results, the long-term management of patients with frequently recurring, multiple, proven bladder cancers has not been characterized by uniformly successful results; the majority of these patients eventually require cystectomy. Prior to infiltra-
Accepted for publication September 23, 1964. This study is supported in part by United States Public Health Grant Number GM 07431-03 and by Baker Research Foundation. 1 Baker, R.: Influence of clinical and laboratory investigation in establishing current therapy of bladder cancer. Bull. New York Acad. Med., 30:
3 Thomas, G. J. and Regnier, E. A.: Tumors of the kidney, pelvis and ureters. J. Urol., 11: 205-
919, 1954.
2 Baker, R.. , Tehan, T. and Kelly, T.: Regeneration of urinary bladder after subtotal resection for carcinoma. Amer. Surg., 25: 348-352, 1959.
238, 1924. 4 Riches, E.W., Griffiths, I. H. and Thackray, A. C.: New growths of kidney and ureter. Brit. J. Urol., 23: 297-356, 1951. 5 Colston, J. A. C. and Arcadi, J. A.: Bilateral renal papillomas: Transpelvic electroresection with preservation of the kidney. Contralateral nephrectomy; four-year survival. J. Urol., 73:
460--467, 1955. 593
594
BAKER, MAXTED AND DIPASQUALE
tion, bladder cancer is an epithelial disease. Total cystectomy may not be indicated if excision of just the mucous membrane of the bladder can result in: 1) subsequent regeneration of normal bladder mucous membrane; and 2) the newly formed bladder epithelium does not have the same malignant potential as the original epithelium. PROCEDURE
The bladder is approached suprapubically and opened widely. Physiologic saline is injected with pressure into the lamina propria thus elevating the mucosa which is then immediately dissected from the underlying muscle wall. The process is repeated until the entire mucosa is excised but for a narrow disk, about 2 mm. wide, around each ureteral orifice. The area of the bladder outlet and the urethral mucous membrane which can be reached are similarly treated. If there is any question relative to adequacy of depth of the mucosal excision, the excision is made deeper into the superficial muscle to insure total mucosal resection. The bladder incision is closed in 2 layers with 2-0 chromic catgut after a onequarter inch empty Penrose drain has been inserted in the bladder and the other end brought through the wound and sutured to the skin. An indwelling urethral catheter with a 5 cc bag is used for 3 to 4 weeks. The bladder drain is utilized until bleeding from the bladder is insignificant. The prevesical space is drained as usual. CASE REPORT AND RESULTS
W. F., Georgetown University Hospital No. 100775, a 48-year-old male engineer, was first seen in November 1959 because of intermittent gross, total, painless hematuria a year in duration. Nephro-ureterectomy was performed for a huge transitional cell cancer of the renal pelvis. The patient underwent cystoscopy 8 times during the next 28 months. On each occasion multiple transitional cell carcinomas, grade 2, were resected transurethrally from the bladder and urethra. There was no invasion of the muscularis. Due to the frequency of recurrences, the number of lesions found at each cystoscopy and the fact that each tumor was malignant, on November 26, 1962 the lining of the bladder was excised as previously described. The mucosa of the urethra was chemically cauterized with 50 per
cent phenol for 30 seconds after which the urethra was irrigated with alcohol followed by saline. During convalescence, the blood urea nitrogen (BUN) and serum electrolytes remained within normal range. There were two episodes of chills associated with temperature elevation due to urinary tract infection. Blood cultures were sterile but urine cultures were not. There was prompt and complete response to specific antibiotic therapy. Urine cultures were obtained every fourth day postoperatively; each was positive. The bladder drain was removed 12 days postoperatively and the drain in the prevesical space was removed 5 days later. The Foley catheter was removed 27 days postoperatively after which there was urinary frequency of approximately every 30 minutes. Slight stress incontinence, slight dysuria and terminal urinary dribbling improved rapidly. The patient was discharged 30 days following operation with full urinary control and voiding maximum volumes of 100 cc about every 1 to 2 hours, with no discomfort. Five and one-half months postoperatively the patient was admitted for evaluation. He was working full-time and had no urinary complaints. He voided about every 2 hours during the day and 3 to 4 times at night. The voiding volumes varied from 150 to 200 cc. He had no discomfort when the bladder was full, no urgency, no lack of urinary control and no discomfort on voiding. The maximum bladder capacity was 225 cc. There was no urethral stricture. The mucosal lining of the prostatic urethra appeared grossly normal. The remainder of the urethra was likewise unremarkable except for a single papillary lesion in the urethra at the penile-scrotal junction which was resected. The histological diagnosis was transi-
.
25
\. I
./
\.
JulJ60 oot,60
Moy6L
S•Pl,610tc.61Mor,62. June62.
-
No•.62
TOTAL MUCOSAL EXCISION
May63
Sopt.63
Jon.64
,..,64
FIG. 1. Graph demonstrates frequency rate and
number of bladder cancers formed. Transurethral resection used each time. Since epithelial excision and regeneration there has been no tumor recurrence.
REGENEHA'J'ION OF TRANS1'l'IONAL BLADDER EPITHELIUl\I
tional cell carcinonia, grade 1. The mucosa of the bladder \yap paler than nornial but no mucosa! lesions 1yere present. Urine culture was sterile. l\Iultiple biop,,ies were obtained of bladder and urethra.
[i9:5
Endoscopy 11 months postoperatively revealed no recurrence of urethral or bladder lesions, The bladder mucosa was normal in appearance. l\lultiple biopsies were obtained from the bladder wall and also the pro.static urethra. Urine cultures were
FrG. 2. A, representative section of tot al mucous membrane surgically excised. Dcmonst,ration of adequa,te rnucos0,l excision, including many areas of superfieial museularis. Absence of actlrnl is due to multiple packing of bladder during phenoli½aticm of urethra just prior to its excisicrn_ , biops)· of regenerating human bladder mucous membrane 5 months 0,fter surgical excision of origiua.l mucmm. Transitional epithelium cell depth of on]>, 1 to 5. Edema. with cellular infiltrate in lamina prr,pria.
596
BAKER, lVlAXTED AND DIPASQUALE
Fm. 3. Biopsy of prostatic urethra 5 months after excision of original mucous membrane. Demonstration of regeneration to normal prostatic urethral epithelium.
sterile. The patient had a normal diurnal voiding pattern but nocturia twice. He had no discomfort when the bladder was full or during voiding. Subsequent endoscopies failed to show recurrence of cancer (fig. 1). A biopsy obtained at the time of surgical excision of the original mucosa demonstrated that adequate resection of the mucosa was accomplished, including many areas of superficial muscularis (fig. 2, A). The absence of actual epithelium was due to traumatic denuding caused by repeated packing of the bladder with vasalinized gauze to protect it from burns from phenol which was used for urethral mucosal destruction prior to excision of bladder mucous membrane. Multiple biopsies of the bladder wall obtained 5 months postoperatively (fig. 2, B) revealed regeneration of the epithelial lining of the bladder but it was not entirely normal. The cell layers varied from 1 cell to 4 and 5 cells in thickness. The lamina propria was edematous with mononuclear and polymorphonuclear cellular infiltrate. Biopsy of the prostatic urethra 5 months postoperatively (fig. 3) also demonstrated regeneration of normal epithelium. A biopsy 11 months postoperatively (fig. 4) revealed regeneration of a nearly normal transitional epithelial lining in the bladder.
Fm. 4. Biopsy of completely regenerated human bladder mucous membrane 11 months after excision of original mucosa. Regenerated epithelium almost indistinguishable from normal transitional epithelium of bladder.
REGENERATION OF TRANSITIONAL BLADDER EPITHELIUM DISCUSSION
The submucosa of the regenerated bladder epithelium showed some thickening, edema and inflammatory infiltrate but no extensive fibrosis. The muscularis was not characterized by any fibrosis or cellular infiltrate. This observation deserves specific attention as it has generally been assumed that loss of a major area of the epithelial lining of the bladder, and certainly its total loss, would result in contracture of the bladder with gross reduction in capacity. Some authors who have studied regeneration of the dog bladder have been of the opinion that bladder contracture might result from intramural fibrosis due to epithelial loss. Others have wondered whether continuous. catheter drainage of such a bladder, by preventmg the natural dilatation that occurs during the storage phase of micturition, might also contribute to bladder fibrosis and contracture. Postoperative biopsies and the course of the patient do not support these assumptions. Clinically, there was no evidence of bladder fibrosis. After removal of the urethral catheter there was a progressive increase in bladder capacity. Five months postoperatively the patient voided 200 to 225 cc urine. Other theoretical complications of denuding the bladder mucosa and observations noted in the laboratory animal either did not occur in the patient under discussion or caused no trouble. Sanders and associates noted mild, temporary elevation of the BUN and serum sodium in doo-s in which the bladder had been completely d:nuded of mucosa. 6 These values had returned to normal levels 14 days after operation. At no time in the postoperative course of our patient was the BUN elevated or the serum electrolytes of abnormal concentration. 6 Sanders, A. R., Sch~in, C. J. and Orkin, L.A.: Total mucosal denndat10n of the canine bladder· ~xperimental observations and clinical implica~ t10ns-final report. J. Urol., 79: 63-77, 1958.
597
Fear has been expressed with respect to the likelihood of bacteremia resulting from infection of an extensively denuded bladder surface in the presence of an indwelling urethral catheter. In spite of constant infection of the bladder, there were only two episodes suggestive of bacteremia. However, blood cultures were sterile. On each occasion there was prompt clinical response to antibiotic therapy. SUMMARY
Transitional epithelium in the human bladder can regenerate to normal epithelium after total surgical removal. A method for the excision is presented. Urethral irrigation with phenol to inhibit or destroy urethral mucous membrane is reported. Subsequent biopsies demonstrated that the urethral mucous membrane as well as the bladder regenerated to normal epithelium. Postoperatively, bacteremia and electrolyte abnormalities were absent, the bladder capacity was nearly normal and there was full control of urethral sphincters. The procedure described was used in a patient with transitional cell carcinoma of the left kidney who underwent nephro-ureterectomy. He subsequently had multiple, frequent recurrences of proven bladder cancer. During the 28 months preceding epithelial excision, cystoscopy was performed approximately every 4 months. On each occasion, multiple bladder cancers were excised transurethrally. In the 18 months since denudation of the lining of the bladder and regeneration of a new mucous membrane, there have been no cancer recurrences within the bladder and only one recurrence in the phenolized urethra. Regardless of these facts, followup evaluation of the patient is of too short duration to formulate anything other than a favorable impression relative to cancer elimination or inhibition of the regenerated epithelium compared to the original epithelium.