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Urethral hyperthermia An alternative to urethrectomy
URETHRAL
HYPERTHERMIA*
An Alternative to Urethrectomy
THOMAS P. COOPER,
M.D.
JAMES A. TREMANN,
M.D.
From the Department of Urology, Seattle Veterans Administration Hospital, and University of Washington School of Medicine, Seattle, Washington
ABSTRACT - Nine male dogs were subjected to cystoprostatectomy, ileal loop diversion, and urethral hyperthermia. Five of the 9 dogs survived six weeks. Three of the 5 surviving dogs had complete destruction of the urethral epithelium, and the other 2 dogs had 95 per cent and 50 per cent destruction with the proximal urethral e.nd incompletely destroyed. Complete urethral destruction may have been obtained with resection of the proximal urethra postirrigation. The irrigation added no extra time to the surgical procedure and was accompanied by few complications. Complications may have been averted with a dorsal slit and meatotomy.
Primary or secondary deposits of transitional cell carcinoma in the distal male urethra at the time of cystectomy for carcinoma of the bladder is not unusual. More commonly, transitional cell carcinoma of the anterior urethra is discovered in the first several years following cystectomy. Table I illustrates the recurrence rate reported in various series. Series published by Ashworth,’ Cordonnier and Spjut,’ and Wallace3 demonstrated a recurrence rate between 4 and 12 per cent. Stams, Gursel, and Veenema,4 noting high percentages of recurrence, have elected to do urethrectomy on all patients undergoing cystectomy. One of their first 9 patients treated in this fashion had an anterior urethral carcinoma which would have been left in situ with either simple or radical cystoprostatectomy. Gowing demonstrated an 18 per cent incidence of carcinoma in situ of the urethra of male patients who died of carcinoma of the bladder. When there is urethral recurrence, death occurs rapidly in the majority of the patients. 2*4 Several authors have described surgical techniques for complete urethrectomy and indicate that it can be accomplished expeditiously with *Supported by the Veterans Administration Medical Research Information System 8536.
308
little blood 10ss.~,’However, most urologists find a complete urethrectomy time-consuming and usually attendant with significant blood loss. In addition, extending an already lengthy cystectomy or cystectomy and diversion have made most urologists elect periodic follow-up urethroscopy instead of urethrectomy at the time of cystectomy. An alternative method of destruction of transitional cell epithelium has been investigated by several groups. Pond, Shurin, and Schirmer* demonstrated patchy destruction of the transitional epithelium of female dog bladders heated to 45.1” C. with sterile water for thirty minutes. Linke et al. g diverted female dogs with cutaneous ureterostomies and noted complete destruction of bladder mucosa and muscularis in bladders
TABLE
I.
Urethral recurrences in animals with bladder carcinoma No. of Year
Cases
Ashworth’ 1952 Cordonnier and Spjut’ 1962 Wallace3 1968
1,307
Author
UROLOGY
174 ?
/ SEPTEMBER1975
Urethral Recurrences 54
Percentage 4
7
4
?
12
/ VOLUMEVI,
NUMBER3
irrigated for eight minutes to tissue temperatures between 59” and 69” C. The procedure was well tolerated and without major complications. Netto, Elbadawi, and Linke” noted complete absence of recognizable bladder muscular and epithelial elements in male dog bladders irrigated with water heated to 85” C. for fifteen minutes. No harmful systemic side effects ensued, and there was no damage to other pelvic organs. It was our contention that if the urothelium of the bladder could be destroyed with hyperthermia, so could that of the urethra. Urethral hyperthermia performed at the time of the cystectomy might substitute for urethrectomy and prove to be easier and have fewer complications. It would also offer an attractive alternative to follow-up urethroscopy.
FIGURES.
Securing
irrigat&
Material
FIGURE
UROLOGY
1. Diagram
of surgical
/ SEPTEMBER1975
into urethra.
and Methods
Cystoprostatectomy with transection and suture ligation of the urethra was accomplished on 9 male dogs (Fig. 1). A 12 F red rubber catheter was inserted into the urethral meatus, and the urethra was tied off around the catheter (Fig. 2). During abdominal closure repeated hand irrigations of the urethra were performed under gentle pressure. The irrigant used was sterile water heated on a hot plate in an open beaker. Each individual irrigation measured 8 to 10 cc., remained in the urethra for fifteen seconds to allow heat transfer, and was then aspirated. This was done repeatedly for thirty minutes. The characteristics of the irrigation are shown in Table II. Following irrigation the catheter was removed and the fossa navicularis fulgurated to destroy any epithelium that may have been protected from the irrigant by compression against the catheter. The animals were given routine postoperative care and were sacrificed at six weeks. It is generally recognized that epithelial surfaces will regenerate within six weeks of thermal injury if they are going to do so. Autopsies with gross inspection of all organs were performed on the animals. The urethras were removed en bloc and fixed in 20 per cent acetate buffered formalin. Serial gross sections of each urethra were made and stained with hematoxylin, eosin, and paraaminohippuric acid.
procedure.
/ VOLUMEVI,
catheter
NUMBER3
309
Dog 776. (A) Urethra demonstrating normal penile wall on right and obliteration of urethral lumen FIGURE 3. with scar tissue on left (hematoxylin and eosin reduced from x 6.8). (B) Urethra showing scar tissue and chronic injlammatory cells (hematoxylin and eosin reduced from x 24).
TABLE
>
TABLE
I
III.
Urethral
3 weeks 2 days 6 weeks1 week 6 weeks 6 weeks 6 weeks 1 week 7 weeks
complications
579 338 903 319
70 45 56 <67 90 80 70 80 78
time, irrigation
L
450 700 700 700 600 700 650 550 400
of irrigation
None None None None Sloughed distal one third of penis secondary to phimosis Meatal stenosis and urethral cutaneous fistula phimosis Meatal stenosis and urethral cutaneous fistula phimosis None None Results
The survival of the 9 animals is shown in Table II: 5 of 9 dogs survived six weeks; 2 (408 and 409) died of pneumonia within the first week; 1 (42) died of intussusception at one week; the fourth animal (213) died of unknown causes at three weeks. Three of the 5 animals which survived six weeks had complete destruction of all epithelial elements of the urethra, and a sample histologic picture of dog 776 is shown in Figure 3. The other
310
method,
of Amount of Amount Returned Irrigant (cc.) (cc.)
Complications
Dog 213 408 328 42 776
Survival
Temperature Irrigant (“C.)
Survival Dog Time 213 408 329 I+ 42 776 579 338 903 319
II.
320 600 590 500 300 500 500 220 200
and result
Amount of Per Cent Urothelial Absorbed Destruction 29
Total
14
Total
::
Total 95 per cent
50 29 23 60 50
Total 95 per cent 50 per cent Total Total
2 dogs (579 and 338) had over 95 per cent destruction of their urethral-epithelial surface. Two of the 3 dogs which had epithelium remaining in their urethras, had it only at the proximal end. This may have been due to our technique of suture ligation of the membranous urethra and then irrigation of only that portion of the urethra distal to the suture as shown in Figure 1. Had we resected that portion of the urethra proximal to the suture following the irrigation, we probably would have achieved complete epithelial destruction in 8 of 9 animals instead of 6 and 9. One dog (338) had only 50 per cent destruction of the urethral epithelium. This cannot be explained by the temperature of the irrigant, volumes, or per cent absorbed. Table III lists the complications of the urethral irrigations. All dogs demonstrated at least transient swelling of the penis as demonstrated in dog 903 at the completion of his irrigation (Fig. 4). Retrospectively this was believed to be caused by the tight foreskin which may have contributed to venous or lymphatic obstruction (Fig. 4). The most serious complication occurred in dog 776 who sloughed the distal one third of his penis, again caused by his tight foreskin. At
UROLOGY
/ SEPTEMBER 1975 / VOLUME VI, NUMBER 3
the time of autopsy there was no gross evidence of damage to any pelvic organs or the testicles of any of the dogs. Comment We have demonstrated that the epithelium of the canine urethra can be effectively destroyed by using hyperthermic irrigations. The only animals which can reliably support this statement are those 5 dogs (329, 776, 574, 338, and 319) which survived six weeks. The other 4 animals may have regenerated their urethral epithelium as they did not survive six weeks. This is the time period within which an epithelial surface will regenerate if it is going to do so. Reviewing only the 5 animals which survived six weeks, 3 animals (329, 776, and 319) achieved the desired result 100 per cent destruction of the urethral epithelium. One (579) had 95 per cent destruction and one (338) had only 50 per cent destruction. Animal 579 may have had complete success, had we resected the proximal portion of his urethra following irrigation; but we are at a loss to explain the 50 per cent destruction with dog 338. The temperature of the irrigant appeared to have little result on the final outcome. Others have shown that pigskin, human skin, and rat tumors are necrosed at tissue temperatures of approximately 48” C. for thirty minutes - the time we used during our irrigations.’ We did not measure tissue temperatures in order to keep the procedure as simple and practical as possible. We were surprised to find complete destruction in dog 408 because we used an irrigant of only 45” C. However, his urothelium may have regenerated because he died before six weeks. It was also surprising to see complete destruction of the urethra in dog 329 since the irrigant was only 56” C. while dog 338 showed only 50 per cent destruction with the irrigant at 70” C. This suggests there is a biologic variation regarding heat sensitivity of the canine urethral epithelium. This phenomenon of individual variability is supported by Hall, Schade, and Swinney’sll clinical experience with hyperthermic irrigations of human bladder tumors. In addition, destruction did not appear to be related to the amount of irrigant absorbed. In those animals living six weeks, irrigation absorption varied from 16 to 60 per cent. This range occurred in dogs 329 and 903, both of which had complete epithelial destruction. The complications were minor in 2 instances while the third was of major significance. All of
UROLOGY /
FIGURE 4.
Dog 903 showing
pent irntncv/iatelc~ following irrigation demonstrating s1i“ ‘!ing if~l(I ertrernely tight fmeskin (
SEF’TEMBER 1975 / VOLUME VI, NUMBER 3
these could have been prevented u ith meatotomies and a dorsal slit. The procedure appears reliable. and we are currently planning its application in humans. Meatotomies, circumcisions, and thorough fulguration or resection of the distal urethral stump should be emphasized in applying this technique in humans. Department Seattle,
of Urology RL-10 Washington 98195 (DR. COOPER)
References 1. ASHWORTH, A.: Papillomatosis of the urethra, Br. J. Urol. 28: 3 (1956). 2. CORDONNIER,J., and SPJUT, H. J.: Urethral occurrence of bladder carcinoma following cystectomy, J. Urol. 87: 398 (1962). 3. WALLACE, D.: Cancer of the bladder, Am. J. Roentgenol. 102: 581 (1968). 4. STAMS, U. K., GURSEL, E. O., and VEENEMA, R. J.: Prophylactic urethrectomy in male patients with bladder cancer, J. Urol. 111: 177(1974). 5. GOWING, N. F. C.: Urethral carcinoma associated with cancer of the bladder, Br. J. Urol. 32: 428 (1960). 6. JOHNSON,D. E., and GUINN, G. A. : Surgical management of urethral recurrence occurring after cystectomy, J. Urol. 103: 314 (1970). 7. WHITMORE, W. F., JR., and MOUNT, B. M.: A technique of urethrectomy in the male, Surg. Gynecol. Obstet. 131: 303 (1970). 8. POND, H. S., SHURIN,P. A., and SCHIRMER,H. K. A.: The effect of moderate hyperthermia on canine bladder, Invest. Urol. 7: 460 (1970). 9. LINKE, C., et al. : Effect of marked hyperthermia upon the canine bladder, J. Ural. 107: 599 (1972). 10. NETTO, I. C. V., ELBADAWI, A., and LINKE, C. A.: Marked hyperthermia effect on male canine urinary bladder, Urology 1: 347 (1973). 11. HALL, R. R., SCHADE, R. 0. K., and SWINNEY, J.: Effects of hyperthermia on bladder cancer, Br. Med. J. 2: 593 (1974).
311
HYPERTHERMIA*
An Alternative to Urethrectomy
THOMAS P. COOPER,
M.D.
JAMES A. TREMANN,
M.D.
From the Department of Urology, Seattle Veterans Administration Hospital, and University of Washington School of Medicine, Seattle, Washington
ABSTRACT - Nine male dogs were subjected to cystoprostatectomy, ileal loop diversion, and urethral hyperthermia. Five of the 9 dogs survived six weeks. Three of the 5 surviving dogs had complete destruction of the urethral epithelium, and the other 2 dogs had 95 per cent and 50 per cent destruction with the proximal urethral e.nd incompletely destroyed. Complete urethral destruction may have been obtained with resection of the proximal urethra postirrigation. The irrigation added no extra time to the surgical procedure and was accompanied by few complications. Complications may have been averted with a dorsal slit and meatotomy.
Primary or secondary deposits of transitional cell carcinoma in the distal male urethra at the time of cystectomy for carcinoma of the bladder is not unusual. More commonly, transitional cell carcinoma of the anterior urethra is discovered in the first several years following cystectomy. Table I illustrates the recurrence rate reported in various series. Series published by Ashworth,’ Cordonnier and Spjut,’ and Wallace3 demonstrated a recurrence rate between 4 and 12 per cent. Stams, Gursel, and Veenema,4 noting high percentages of recurrence, have elected to do urethrectomy on all patients undergoing cystectomy. One of their first 9 patients treated in this fashion had an anterior urethral carcinoma which would have been left in situ with either simple or radical cystoprostatectomy. Gowing demonstrated an 18 per cent incidence of carcinoma in situ of the urethra of male patients who died of carcinoma of the bladder. When there is urethral recurrence, death occurs rapidly in the majority of the patients. 2*4 Several authors have described surgical techniques for complete urethrectomy and indicate that it can be accomplished expeditiously with *Supported by the Veterans Administration Medical Research Information System 8536.
308
little blood 10ss.~,’However, most urologists find a complete urethrectomy time-consuming and usually attendant with significant blood loss. In addition, extending an already lengthy cystectomy or cystectomy and diversion have made most urologists elect periodic follow-up urethroscopy instead of urethrectomy at the time of cystectomy. An alternative method of destruction of transitional cell epithelium has been investigated by several groups. Pond, Shurin, and Schirmer* demonstrated patchy destruction of the transitional epithelium of female dog bladders heated to 45.1” C. with sterile water for thirty minutes. Linke et al. g diverted female dogs with cutaneous ureterostomies and noted complete destruction of bladder mucosa and muscularis in bladders
TABLE
I.
Urethral recurrences in animals with bladder carcinoma No. of Year
Cases
Ashworth’ 1952 Cordonnier and Spjut’ 1962 Wallace3 1968
1,307
Author
UROLOGY
174 ?
/ SEPTEMBER1975
Urethral Recurrences 54
Percentage 4
7
4
?
12
/ VOLUMEVI,
NUMBER3
irrigated for eight minutes to tissue temperatures between 59” and 69” C. The procedure was well tolerated and without major complications. Netto, Elbadawi, and Linke” noted complete absence of recognizable bladder muscular and epithelial elements in male dog bladders irrigated with water heated to 85” C. for fifteen minutes. No harmful systemic side effects ensued, and there was no damage to other pelvic organs. It was our contention that if the urothelium of the bladder could be destroyed with hyperthermia, so could that of the urethra. Urethral hyperthermia performed at the time of the cystectomy might substitute for urethrectomy and prove to be easier and have fewer complications. It would also offer an attractive alternative to follow-up urethroscopy.
FIGURES.
Securing
irrigat&
Material
FIGURE
UROLOGY
1. Diagram
of surgical
/ SEPTEMBER1975
into urethra.
and Methods
Cystoprostatectomy with transection and suture ligation of the urethra was accomplished on 9 male dogs (Fig. 1). A 12 F red rubber catheter was inserted into the urethral meatus, and the urethra was tied off around the catheter (Fig. 2). During abdominal closure repeated hand irrigations of the urethra were performed under gentle pressure. The irrigant used was sterile water heated on a hot plate in an open beaker. Each individual irrigation measured 8 to 10 cc., remained in the urethra for fifteen seconds to allow heat transfer, and was then aspirated. This was done repeatedly for thirty minutes. The characteristics of the irrigation are shown in Table II. Following irrigation the catheter was removed and the fossa navicularis fulgurated to destroy any epithelium that may have been protected from the irrigant by compression against the catheter. The animals were given routine postoperative care and were sacrificed at six weeks. It is generally recognized that epithelial surfaces will regenerate within six weeks of thermal injury if they are going to do so. Autopsies with gross inspection of all organs were performed on the animals. The urethras were removed en bloc and fixed in 20 per cent acetate buffered formalin. Serial gross sections of each urethra were made and stained with hematoxylin, eosin, and paraaminohippuric acid.
procedure.
/ VOLUMEVI,
catheter
NUMBER3
309
Dog 776. (A) Urethra demonstrating normal penile wall on right and obliteration of urethral lumen FIGURE 3. with scar tissue on left (hematoxylin and eosin reduced from x 6.8). (B) Urethra showing scar tissue and chronic injlammatory cells (hematoxylin and eosin reduced from x 24).
TABLE
>
TABLE
I
III.
Urethral
3 weeks 2 days 6 weeks1 week 6 weeks 6 weeks 6 weeks 1 week 7 weeks
complications
579 338 903 319
70 45 56 <67 90 80 70 80 78
time, irrigation
L
450 700 700 700 600 700 650 550 400
of irrigation
None None None None Sloughed distal one third of penis secondary to phimosis Meatal stenosis and urethral cutaneous fistula phimosis Meatal stenosis and urethral cutaneous fistula phimosis None None Results
The survival of the 9 animals is shown in Table II: 5 of 9 dogs survived six weeks; 2 (408 and 409) died of pneumonia within the first week; 1 (42) died of intussusception at one week; the fourth animal (213) died of unknown causes at three weeks. Three of the 5 animals which survived six weeks had complete destruction of all epithelial elements of the urethra, and a sample histologic picture of dog 776 is shown in Figure 3. The other
310
method,
of Amount of Amount Returned Irrigant (cc.) (cc.)
Complications
Dog 213 408 328 42 776
Survival
Temperature Irrigant (“C.)
Survival Dog Time 213 408 329 I+ 42 776 579 338 903 319
II.
320 600 590 500 300 500 500 220 200
and result
Amount of Per Cent Urothelial Absorbed Destruction 29
Total
14
Total
::
Total 95 per cent
50 29 23 60 50
Total 95 per cent 50 per cent Total Total
2 dogs (579 and 338) had over 95 per cent destruction of their urethral-epithelial surface. Two of the 3 dogs which had epithelium remaining in their urethras, had it only at the proximal end. This may have been due to our technique of suture ligation of the membranous urethra and then irrigation of only that portion of the urethra distal to the suture as shown in Figure 1. Had we resected that portion of the urethra proximal to the suture following the irrigation, we probably would have achieved complete epithelial destruction in 8 of 9 animals instead of 6 and 9. One dog (338) had only 50 per cent destruction of the urethral epithelium. This cannot be explained by the temperature of the irrigant, volumes, or per cent absorbed. Table III lists the complications of the urethral irrigations. All dogs demonstrated at least transient swelling of the penis as demonstrated in dog 903 at the completion of his irrigation (Fig. 4). Retrospectively this was believed to be caused by the tight foreskin which may have contributed to venous or lymphatic obstruction (Fig. 4). The most serious complication occurred in dog 776 who sloughed the distal one third of his penis, again caused by his tight foreskin. At
UROLOGY
/ SEPTEMBER 1975 / VOLUME VI, NUMBER 3
the time of autopsy there was no gross evidence of damage to any pelvic organs or the testicles of any of the dogs. Comment We have demonstrated that the epithelium of the canine urethra can be effectively destroyed by using hyperthermic irrigations. The only animals which can reliably support this statement are those 5 dogs (329, 776, 574, 338, and 319) which survived six weeks. The other 4 animals may have regenerated their urethral epithelium as they did not survive six weeks. This is the time period within which an epithelial surface will regenerate if it is going to do so. Reviewing only the 5 animals which survived six weeks, 3 animals (329, 776, and 319) achieved the desired result 100 per cent destruction of the urethral epithelium. One (579) had 95 per cent destruction and one (338) had only 50 per cent destruction. Animal 579 may have had complete success, had we resected the proximal portion of his urethra following irrigation; but we are at a loss to explain the 50 per cent destruction with dog 338. The temperature of the irrigant appeared to have little result on the final outcome. Others have shown that pigskin, human skin, and rat tumors are necrosed at tissue temperatures of approximately 48” C. for thirty minutes - the time we used during our irrigations.’ We did not measure tissue temperatures in order to keep the procedure as simple and practical as possible. We were surprised to find complete destruction in dog 408 because we used an irrigant of only 45” C. However, his urothelium may have regenerated because he died before six weeks. It was also surprising to see complete destruction of the urethra in dog 329 since the irrigant was only 56” C. while dog 338 showed only 50 per cent destruction with the irrigant at 70” C. This suggests there is a biologic variation regarding heat sensitivity of the canine urethral epithelium. This phenomenon of individual variability is supported by Hall, Schade, and Swinney’sll clinical experience with hyperthermic irrigations of human bladder tumors. In addition, destruction did not appear to be related to the amount of irrigant absorbed. In those animals living six weeks, irrigation absorption varied from 16 to 60 per cent. This range occurred in dogs 329 and 903, both of which had complete epithelial destruction. The complications were minor in 2 instances while the third was of major significance. All of
UROLOGY /
FIGURE 4.
Dog 903 showing
pent irntncv/iatelc~ following irrigation demonstrating s1i“ ‘!ing if~l(I ertrernely tight fmeskin (
SEF’TEMBER 1975 / VOLUME VI, NUMBER 3
these could have been prevented u ith meatotomies and a dorsal slit. The procedure appears reliable. and we are currently planning its application in humans. Meatotomies, circumcisions, and thorough fulguration or resection of the distal urethral stump should be emphasized in applying this technique in humans. Department Seattle,
of Urology RL-10 Washington 98195 (DR. COOPER)
References 1. ASHWORTH, A.: Papillomatosis of the urethra, Br. J. Urol. 28: 3 (1956). 2. CORDONNIER,J., and SPJUT, H. J.: Urethral occurrence of bladder carcinoma following cystectomy, J. Urol. 87: 398 (1962). 3. WALLACE, D.: Cancer of the bladder, Am. J. Roentgenol. 102: 581 (1968). 4. STAMS, U. K., GURSEL, E. O., and VEENEMA, R. J.: Prophylactic urethrectomy in male patients with bladder cancer, J. Urol. 111: 177(1974). 5. GOWING, N. F. C.: Urethral carcinoma associated with cancer of the bladder, Br. J. Urol. 32: 428 (1960). 6. JOHNSON,D. E., and GUINN, G. A. : Surgical management of urethral recurrence occurring after cystectomy, J. Urol. 103: 314 (1970). 7. WHITMORE, W. F., JR., and MOUNT, B. M.: A technique of urethrectomy in the male, Surg. Gynecol. Obstet. 131: 303 (1970). 8. POND, H. S., SHURIN,P. A., and SCHIRMER,H. K. A.: The effect of moderate hyperthermia on canine bladder, Invest. Urol. 7: 460 (1970). 9. LINKE, C., et al. : Effect of marked hyperthermia upon the canine bladder, J. Ural. 107: 599 (1972). 10. NETTO, I. C. V., ELBADAWI, A., and LINKE, C. A.: Marked hyperthermia effect on male canine urinary bladder, Urology 1: 347 (1973). 11. HALL, R. R., SCHADE, R. 0. K., and SWINNEY, J.: Effects of hyperthermia on bladder cancer, Br. Med. J. 2: 593 (1974).
311