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The Treatment of Papillomatosis with Podophyllin
THE JOURNAL OF UROLOGY
Vol. 64, No. 6, December 1950 Printed in U.S.A.
THE TREATMENT OF PAPILLOMATOSIS WITH PODOPHYLLIN D.A.DUCKWORTH From St. Michael's Hospital, Toronto, Ontario, Canada
The successful use of a suspension of podophyllin in mineral oil in the treatment of genital warts was reported by Kaplan in 1942. Following this report, many cases of penile, vulvar and peri-anal warts have been successfully treated with this drug. The application of this drug to meatal and urethral papillomas revealed an apparent resistance of normal transitional epithelium to its caustic action; this suggested the possibility of its use in treating papillomas of the bladder. In 1948 Semple reported its use in the treatment of 4 cases of papillomas of the bladder. A suspension of the drug in mineral oil was introduced into the bladder through the window of the cystoscope which was placed directly over the tumor. One, two, four and five applications at 4 to 7 day intervals were used. In all 4 cases the growth was sufficiently reduced in size to allow per urethram fulguration. CASE REPORT
A man aged 64 years had had recurring hematuria for the past year with the last attack being very severe. The urine was grossly bloody and contained many clots. There was no associated pain but nocturia 3 to 4 times. The patient felt weak and dizzy. He was admitted to the medical service where an indwelling catheter was placed in the bladder and transfusions of whole blood were given. The patient experienced chills and fever which were considered to be a manifestation of transfusion reaction. The fever was remittent in type with a peak of 105 F. Despite the possible reaction to transfusion, 3,500 cc of whole blood were given over a period of 4 days. In spite of transfusions, the general condition remained poor and gross hematuria persisted. Hemoglobin estimation was 39 per cent. The blood pressure remained approximately 110/70. Pulse rate was 92. A cystoscope was easily introduced to the bladder and a large amount of blood clot evacuated. The bladder was filled with a papillomatous growth, no normal landmarks being visible. The growth appeared to originate in the region of the right ureteral orifice but one could not be sure. There was a generalized oozing of blood but no very active bleeding. The patient had a chill ,vhile on the table. An indwelling catheter was placed in the bladder and the patient returned to bed. He was placed on penicillin, 2,500 units every 3 hours. Following cystoscopy, the urine was pink in color only, but the temperature remained remittent in type for a period of 5 days with an elevation to 107 F. Tumor washings from the bladder at cystoscopy were diagnosed as benign papilloma. The temperature then returned to normal and ten days following the cystoscopy, podophyllin instillations were begun. Four instillations of podophyllin in liquid paraffin were given at approximately 7 day intervals in strengths increasing from 1 to 12 per cent. The hemoglobin at the end of this treatment was 45 per cent. Four days after the last instillation cystoscopy was carried out. The blad740
TREATMENT OF PAPILLOMATOS,IS WITH PODOPHYLLIN
741
der mucosa appeared normal except for a papilloma (about the size of a small cherry) above the right ureteral orifice. This growth was resected with its base and the area lightly fulgurated. The pathological diagnosis of this specimen was benign papilloma. Progress was rapid from this stage onward and the patient was discharged two weeks later with a hemoglobin of 70 per cent. Appointments for follow up were not kept and an observation cystoscopy was not again performed until 5 months later. At this time three very small buds were found above the right ureteral orifice and were fulgurated per urethram. The hemoglobin was 76 per cent and the patient stated that he had had no haematuria since discharge from the hospital 5 months previously. The patient again did not keep follow up appointments and was not seen for a period of 1 year, when an attack of acute sinusitis returned him to hospital. Cystoscopy showed a normal bladder and urethra. TECHNIQUE
The suspension of podophyllin in mineral oil was introduced through a urethral catheter, using three ounces of a 1 per cent suspension. The patient was turned on his right side for 15 minutes, then on the left for 15 minutes. No anesthetic was used. One week later 3 ounces of 4 per cent podophyllin in oil was instilled through the catheter and left in for 40 minutes with the patient lying on alternate sides for 20 minutes. At weekly intervals 1 8 per cent and 12 per cent suspensions were instilled into the bladder, the latter being held in the bladder for 3 hours. During these instillations, the catheter drainage was dark in color and contained bits of tissue. At no time was there any evidence of bleeding. The patient did not complain of pain, nor require sedation during treatment. Four days after this last treatment cystoscopy was carried out and the remaining small tumor resected and the area lightly fulgurated. DISCUSSION
The active principle of commercial podophyllin powder has not been determined. The powder is a mixture of the resins produced from the American and Indian podophyllin rhizome by alcohol extraction and water precipitation. No immediate or remote ill-effects followed the application of this drug in this or the previously reported 4 cases. This case has been observed for a period of I½ years. Cystoscopy or urethroscopy has disclosed no reaction of the normal bladder or urethral mucosa. The result obtained in this case and those of Semple are encouraging enough to warrant a further trial of this drug or of drugs having a similar action (such as colchicine, auramine and urethane). The author has not seen a suitable case for this treatment since the above and this report is published in the hope that the treatment may be used at other clinics ,vith similar success. SUMMARY AND CONCLUSIONS
A fifth case of papilloma of the urinary bladder treated with podophyllin in liquid paraffin is added to the 4 already published by Semple The extent and
742
D. A. DUCKWORTH
size of the tumor would have required cystotomy and open fulguration but after the application of podophyllin it was sufficiently reduced in size that it could be successfully treated per urethram. The number of cases in which this method has been carried out is too small to allow any definite conclusions to be drawn but the results appear to warrant further trial of this drug and those allied to it in action. REFERENCES 120: 251, 1944.
CuLP, 0. S. AND KAPLAN, I. W.: Ann. Surg., SEMPLE, J.E.: Brit. Med. J., 1: 1235, 1948.
Vol. 64, No. 6, December 1950 Printed in U.S.A.
THE TREATMENT OF PAPILLOMATOSIS WITH PODOPHYLLIN D.A.DUCKWORTH From St. Michael's Hospital, Toronto, Ontario, Canada
The successful use of a suspension of podophyllin in mineral oil in the treatment of genital warts was reported by Kaplan in 1942. Following this report, many cases of penile, vulvar and peri-anal warts have been successfully treated with this drug. The application of this drug to meatal and urethral papillomas revealed an apparent resistance of normal transitional epithelium to its caustic action; this suggested the possibility of its use in treating papillomas of the bladder. In 1948 Semple reported its use in the treatment of 4 cases of papillomas of the bladder. A suspension of the drug in mineral oil was introduced into the bladder through the window of the cystoscope which was placed directly over the tumor. One, two, four and five applications at 4 to 7 day intervals were used. In all 4 cases the growth was sufficiently reduced in size to allow per urethram fulguration. CASE REPORT
A man aged 64 years had had recurring hematuria for the past year with the last attack being very severe. The urine was grossly bloody and contained many clots. There was no associated pain but nocturia 3 to 4 times. The patient felt weak and dizzy. He was admitted to the medical service where an indwelling catheter was placed in the bladder and transfusions of whole blood were given. The patient experienced chills and fever which were considered to be a manifestation of transfusion reaction. The fever was remittent in type with a peak of 105 F. Despite the possible reaction to transfusion, 3,500 cc of whole blood were given over a period of 4 days. In spite of transfusions, the general condition remained poor and gross hematuria persisted. Hemoglobin estimation was 39 per cent. The blood pressure remained approximately 110/70. Pulse rate was 92. A cystoscope was easily introduced to the bladder and a large amount of blood clot evacuated. The bladder was filled with a papillomatous growth, no normal landmarks being visible. The growth appeared to originate in the region of the right ureteral orifice but one could not be sure. There was a generalized oozing of blood but no very active bleeding. The patient had a chill ,vhile on the table. An indwelling catheter was placed in the bladder and the patient returned to bed. He was placed on penicillin, 2,500 units every 3 hours. Following cystoscopy, the urine was pink in color only, but the temperature remained remittent in type for a period of 5 days with an elevation to 107 F. Tumor washings from the bladder at cystoscopy were diagnosed as benign papilloma. The temperature then returned to normal and ten days following the cystoscopy, podophyllin instillations were begun. Four instillations of podophyllin in liquid paraffin were given at approximately 7 day intervals in strengths increasing from 1 to 12 per cent. The hemoglobin at the end of this treatment was 45 per cent. Four days after the last instillation cystoscopy was carried out. The blad740
TREATMENT OF PAPILLOMATOS,IS WITH PODOPHYLLIN
741
der mucosa appeared normal except for a papilloma (about the size of a small cherry) above the right ureteral orifice. This growth was resected with its base and the area lightly fulgurated. The pathological diagnosis of this specimen was benign papilloma. Progress was rapid from this stage onward and the patient was discharged two weeks later with a hemoglobin of 70 per cent. Appointments for follow up were not kept and an observation cystoscopy was not again performed until 5 months later. At this time three very small buds were found above the right ureteral orifice and were fulgurated per urethram. The hemoglobin was 76 per cent and the patient stated that he had had no haematuria since discharge from the hospital 5 months previously. The patient again did not keep follow up appointments and was not seen for a period of 1 year, when an attack of acute sinusitis returned him to hospital. Cystoscopy showed a normal bladder and urethra. TECHNIQUE
The suspension of podophyllin in mineral oil was introduced through a urethral catheter, using three ounces of a 1 per cent suspension. The patient was turned on his right side for 15 minutes, then on the left for 15 minutes. No anesthetic was used. One week later 3 ounces of 4 per cent podophyllin in oil was instilled through the catheter and left in for 40 minutes with the patient lying on alternate sides for 20 minutes. At weekly intervals 1 8 per cent and 12 per cent suspensions were instilled into the bladder, the latter being held in the bladder for 3 hours. During these instillations, the catheter drainage was dark in color and contained bits of tissue. At no time was there any evidence of bleeding. The patient did not complain of pain, nor require sedation during treatment. Four days after this last treatment cystoscopy was carried out and the remaining small tumor resected and the area lightly fulgurated. DISCUSSION
The active principle of commercial podophyllin powder has not been determined. The powder is a mixture of the resins produced from the American and Indian podophyllin rhizome by alcohol extraction and water precipitation. No immediate or remote ill-effects followed the application of this drug in this or the previously reported 4 cases. This case has been observed for a period of I½ years. Cystoscopy or urethroscopy has disclosed no reaction of the normal bladder or urethral mucosa. The result obtained in this case and those of Semple are encouraging enough to warrant a further trial of this drug or of drugs having a similar action (such as colchicine, auramine and urethane). The author has not seen a suitable case for this treatment since the above and this report is published in the hope that the treatment may be used at other clinics ,vith similar success. SUMMARY AND CONCLUSIONS
A fifth case of papilloma of the urinary bladder treated with podophyllin in liquid paraffin is added to the 4 already published by Semple The extent and
742
D. A. DUCKWORTH
size of the tumor would have required cystotomy and open fulguration but after the application of podophyllin it was sufficiently reduced in size that it could be successfully treated per urethram. The number of cases in which this method has been carried out is too small to allow any definite conclusions to be drawn but the results appear to warrant further trial of this drug and those allied to it in action. REFERENCES 120: 251, 1944.
CuLP, 0. S. AND KAPLAN, I. W.: Ann. Surg., SEMPLE, J.E.: Brit. Med. J., 1: 1235, 1948.