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Ureteral Complications after Intravesical Formalin Instillation
0022-5347 /79/1222-0160$02.00/0 THE JOURNAL OF UROLOGY
Vol. 122, August Printed in U.S.A.
Copyright© 1979 by The Williams & Wilkins Co.
URETERAL COMPLICATIONS AFTER INTRAVESICAL FORMALIN INSTILLATION MAGNUS FALL
AND
SILAS PETTERSSON
From the Department of Urology, Sahlgrenska sjukhuset, University of Goteborg, Goteborg, Sweden
ABSTRACT
Results of formalin therapy for hemorrhage owing to post-radiation cystitis have been studied with special reference to the frequency and severity of ureteral complications. Gross bleeding stopped in 25 of 27 patients within 48 hours. However, 5 patients became anuric immediately after the instillation and in another 7 patients a transient increase in the serum creatinine level was observed. Urinary diversion was necessary in 11 of the 27 patients. The complication rate in the present study is considerably higher than reported previously. Complications may be explained by vesicoureteral reflux of a too strong formalin-alcohol solution. To avoid future complications we suggest that 1) a high diuresis should be induced peroperatively, 2) a 1 to 2 per cent formalin solution without alcohol should be used and 3) the instillation pressure should not exceed 15 cm. water. Persistent gross hematuria remains a challenging problem in connection with radiation therapy for bladder carcinoma. Since the bleeding in these cases occurs from telangiectatic vessels scattered over the mucosa local fulguration seldom is successful. Bladder irrigation with silver nitrate or bilateral hypogastric artery ligations has been used with limited success. 1 Supravesical urinary diversion, with or without palliative simple cystectomy, is not always possible because of the poor general condition of the patient and the fixation of the bladder in the pelvis. In this situation local instillation of formalin into the bladder has been reported to be of value. 1- 6 After the instillation the patients often experienced suprapubic pain, dysuria, a reduction in bladder capacity and urgency of urination. 1 However, the frequency of serious complications has been low. 1• 7-II Our subsequent identification of 3 patients with anuria immediately after instillation of formalin into the bladder prompted us to review our results with this method. This review was done with special reference to the frequency and severity of ureteral complications. PATIENTS AND METHODS
Between 1966 and 1977, 27 patients (19 men and 8 women) were treated with intravesical formalin instillation for massive hemorrhage from the bladder owing to post-radiation cystitis. All of the patients had been subjected previously to external irradiation (6,500 to 7,000 rad) because of infiltrating bladder carcinoma. The mean age of the patients was 72 years, with a range of 52 to 85 years. The hemorrhage usually occurred from 1 to several years after irradiation. Evacuation of bladder clots with subsequent irrigation of the bladder and administration of antifibrinolytics was inadequate in the patients selected for formalin treatment. All blood clots and debris were evacuated carefully from the bladder with the patient under general or spinal anesthesia. Then, 100 ml. of a 3 per cent formalin in 65 per cent alcohol solution was instilled from a glass syringe. The resistance to injection was observed carefully to avoid instillation against pressure. The solution was left in the bladder for 10 minutes and was then allowed to drain. The bladder was irrigated subsequently with physiological saline. A catheter was left indwelling until the urine became clear. RESULTS
Formalin therapy was effective in most patients. Gross bleeding stopped within 48 hours in 25 of the 27 patients (93 per Accepted for publication October 27, 1978.
160
cent). However, in 3 of the patients a repeat instillation was necessary to clear the urine. Slight hematuria persisted after treatment in 1 patient and in another patient the urine was not clear until 3 weeks after repeated instillation. Five patients (19 per cent) became anuric immediately after the instillation and in another 7 (26 per cent) a transient increase in the serum creatinine level by 0.3 to 1.7 gm. per cent (mean 1.06 gm. per cent) was observed. Septicemia developed postoperatively in 2 patients. Pseudomonas and Klebsiella, respectively, were grown from blood and urine. Another 7 patients had a temperature of 2:38C 1 to 3 days after the treatment. These patients all responded well to antibiotics. Increased temperature was observed only in the 12 patients in whom anuria or elevation of the serum creatinine level was observed. Convalescence was uneventful in 3 men with previous urinary diversion. The 5 patients with anuria were treated as emergency cases. In 3 of the 5 patients a cutaneous ureterostomy was done and in 2 the urine was diverted temporarily by an in situ ureterostomy and a percutaneous pyelostomy, respectively. Within 14 months (14 days to 14 months) after the formalin treatment a permanent urinary diversion was necessary in another 6 patients (22 per cent) owing to progressive upper urinary tract dilatation or signs of renal failure, or both. Of the 6 patients 5 had had a transient increase of serum creatinine immediately after the instillation. In addition, 2 of these 5 patients (7 per cent of the total material) had suffered extremely reduced bladder capacity. In 2 patients with cutaneous ureterostomy severe fibrosis of the entire remaining ureter developed within 4 to 6 months, respectively, and a tube pyelostomy was necessary. A representative case of anuria after formalin treatment is reported. CASE REPORT
A 77-year-old man had a moderately differentiated transitional cell carcinoma of the bladder diagnosed in November 1970. He had been treated with external irradiation (6,500 rad). An excretory urogram in March 1971 showed no excretion of contrast medium from the left kidney. The serum creatinine at this time was 1.8 mg. per cent. Because of the age of the patient no further diagnostic procedures were done. In August 1972 the patient presented with massive hematuria. Hemoglobin was 7.5 gm. per cent and 4 units of blood were administered. Cystoscopy revealed generalized bleeding from telangiectatic vessels. The formalin solution was instilled into the bladder and the urine cleared within 24 hours. After the instillation the patient had a
URETERAL COMPLICATIONS AFTER INTRAVESICAL FORMALIN INSTILLATION
Clot appears as cast of ureter at operation
transient increase of body temperature and serum creatinine increased slowly from 2.0 to 7.3 mg. per cent. The patient became anuric 5 days after the instillation. At operation a yellowish clot, 15 cm. long, was found within the right ureter. The clot appeared as a cast of the ureter (see figure). A cutaneous ureterostomy was done and the ureter was intubated with a polyethylene tube. Convalescence was uneventful and the patient was discharged from the hospital 7 days postoperatively. The ureter remains permanently intubated because of a distal ureteral stricture.
solution has been recommended. In our department a 3 per cent formalin solution was used but, nevertheless, a remarkably high frequency of complications was observed. A factor of importance may be the alcohol content of our solution. It is a well known fact that alcohol precipitates protein and this may accentuate the effect of formalin. However, alcohol irrigation of the bladder after formalin instillation has been used previously with no disadvantages. 7 The complications may be attributed to an effect of the solution on either the bladder wall or the ureters. Immediately after the instillation an intense edema of the bladder wall may occlude the ureteral orifices and fibrosis of the bladder wall subsequently may obstruct the intramural parts of the ureters. The finding of extensive fibrosis of the bladder wall in connection with ureteral obstruction in 2 of our patients supports this hypothesis. The incidence of vesicoureteral reflux in patients treated previously for bladder carcinoma probably is high. 14 There are obvious difficulties in excluding reflux preoperatively in the patients to be treated with formalin. Reflux of the solution into the ureters may cause edema and, subsequently, fibrosis at this level. The existence of a reflux mechanism is supported by the finding of a cast in the ureter of 1 of our patients and by the late development of extensive ureteral fibrosis in another 2 patients. The finding of vesicoureteral reflux before formalin instillation led Gottesman and Ehrlich to suggest the occlusion of the ureter by means of a Fogarty embolectomy catheter during the instillation. 15 However, we believe that this technique can be used rarely in the acute situations concerned. On the other hand, according to Ekman and associates, the induction of a high diuresis may inhibit vesicoureteral reflux. 16 Consequently, this method should reduce the risk of reflux of formalin peroperatively. In this context the importance of the technique of instillation also should be stressed. Although our ambition has been to maintain a low instillation pressure the solution per se no doubt elicits a violent bladder contraction, with a risk of subsequent ureteral reflux if the bladder contents cannot escape easily from the bladder. On the basis of our results, and in agreement with Fair, 8 we suggest the following procedure for safe use of intravesical formalin: 1) induction of high diuresis peroperatively, 2) use of a 1 to 2 per cent formalin solution without alcohol and 3) passive irrigation by gravity via a balloon catheter, at a maximum instillation pressure of 15 cm. water. REFERENCES
DISCUSSION
Hematuria stopped in 22 of the 27 patients after a single instillation and in another 3 patients after repeating the procedure. These results are in good agreement with those reported in the literature. 1- 5 However, the frequency of anuria (5 patients, 19 per cent), increased serum creatinine level (7 patients, 26 per cent) and subsequent urinary diversion (11 patients, 41 per cent) is considerably higher than reported previously. 1• 7• 8 Formalin precipitates protein by reducing and uniting with the protein amino groups. It was suggested by Brown for use in severe hematuria because of its ability to seal bleeding vessels. 2 Brown used a 10 per cent formalin solution when he observed the rapidity of fixation of cystectomy specimens by the solution and the lack of penetration beyond the superficial layers. 2 However, the results of recent experimental studies have been diverging in this respect. In investigations on the effect of different concentrations of formalin Pust and associates observed a complete necrosis of the epithelium, including parts of the submucosa, 12 while Rankin reported disintegration of the entire bladder wall after injection of a 10 per cent formalin solution. 13 In both investigations, however, only epithelial damage was found at low concentrations of the solution. The importance of the concentration with respect to the frequency of complications in the clinical application of formalin has been stressed further. 7• 8 To provide a safe approach a 1 to 4 per cent
161
1. Shrom, S. H., Donaldson, M. H., Duckett, J. W., Jr. and Wein, A.
2. 3. 4. 5. 6. 7. 8. 9. 10.
J.: Formalin treatment for intractable hemorrhagic cystitis. A review of the literature with 16 additional cases. Cancer, 38: 1785, 1976. Brown, R. B.: A method of management of inoperable carcinoma of the bladder. Med. J. Aust., 1: 23, 1969. Firlit, C. F.: Intractable hemorrhagic cystitis secondary to extensive carcinomatosis: management with formalin solution. J. Urol., 110: 57, 1973. Shah, B. C. and Albert, D. J.: lntravesical instillation of formalin for the management of intractable hematuria. J. Urol., 110: 519, 1973. Kumar, S., Rosen, P. and Grabstald, H.: Intravesical formalin for the control of intractable bladder hemorrhage secondary to cystitis or cancer. J. Urol., 114: 540, 1975. Servadio, C. and Nissenkorn, I.: Massive hematuria successfully treated by bladder irrigations with formalin solution. Cancer, 37: 900, 1976. Spiro, L. H., Hecht, H., Horowitz, A. and Orkin, L.: Formalin treatment for massive bladder hemorrhage. Urology, 2: 669, 1973. Fair, W. R.: Formalin in the treatment of massive bladder hemorrhage. Techniques, results, and complications. Urology, 3: 573, 1974. Scott, M. P., Jr., Marshall, S. and Lyon, R. P.: Bladder rupture following formalin therapy for hemorrhage secondary to cyclophosphamide therapy. Urology, 3: 364, 1974. Chugh, K. S., Singhal, P. C. and Banerjee, S. S.: Acute tubular
FALL AND PETTERSSON
162
11. 12. 13. 14. 15. 16.
necrosis following intravesical instillation of formalin. Urol. Int., 32: 454, 1977. Lourie, J. A., Drysdale, H. C. and Wynne, E. J.C.: Death following intravesical formalin instillation. Brit. J. Urol., 49: 476, 1977. Pust, R., Butz, M., Rost, A., Ogbuihi, S. and Riedel, B.: Denudation of the urinary bladder mucosa in the cat by formaldehyde. Urol. Res., 4: 55, 1976. Rankin, K. N.: lntravesical formalin. Invest. Urol., 12: 150, 1974. Schmidt, J. D., Jacobo, E. C. and Weinstein, S. H.: Vesicoureteral reflux in recurrent carcinoma of the bladder - implications for treatment and prognosis. J. Urol., 116: 734, 1976. Gottesman, J. and Ehrlich, R. M.: Preventing vesicoureteral reflux during intravesical formalin instillation. Urology, 3: 494, 1974. Ekman, H., Jacobsson, B., Kock, N. G. and Sundin, T.: High diuresis, a factor in preventing vesicoureteral reflux. J. Urol., 95: 511, 1966. EDITORIAL COMMENT
It is not clear why the authors used formalin in alcohol solution, since this is a departure from previous publications in which formalin was used in water or saline solution. Nonetheless, the precautions that were outlined in 1974 bear repeating (reference 8 in the article). In particular, the need for sterile urine and a pre-instillation cystogram to eliminate the possibility of ureterovesical reflux. In the presence of reflux our experience has been quite satisfactory by simply placing the patient in the reverse Trendelenburg position and ensuring that the
amount of pressure used for the instillation does not exceed 15 cm. Lastly, it must be certain that formalin, a 37 per cent solution of formaldehyde, and not formaldehyde per se is used. W.R.F. REPLY BY AUTHORS The precautions for the prevention of vesicoureteral reflux of formalin suggested by Doctor Fair are valuable. We agree with him that the technique of instillation is of crucial importance. Our choice of a formalin solution containing alcohol was, in fact, based on results obtained with unintentional treatment. In July 1966, that is before publication of Brown's paper,2 we had to perform bladder evacuation in a patient with massive hemorrhage caused by postradiation cystitis. The patient was brought to the endoscopy theater late in the afternoon. The glass cistern for irrigation fluids had been emptied of sterile water and filled with a solution for sterilization overnight. However, this was not observed until too late and the bladder irrigation was done with this solution (30 gm. 37 per cent formaldehyde, 650 gm. 96 per cent alcohol and distilled water to 1,000 gm.). As soon as the mistake was observed the bladder was washed out repeatedly with saline. However, the procedure was effective. Since no complications were observed postoperatively we began to use 3 per cent formalin and 65 per cent alcohol instillations as treatment in massive bladder hemorrhage and were later encouraged by Brown's report.
Vol. 122, August Printed in U.S.A.
Copyright© 1979 by The Williams & Wilkins Co.
URETERAL COMPLICATIONS AFTER INTRAVESICAL FORMALIN INSTILLATION MAGNUS FALL
AND
SILAS PETTERSSON
From the Department of Urology, Sahlgrenska sjukhuset, University of Goteborg, Goteborg, Sweden
ABSTRACT
Results of formalin therapy for hemorrhage owing to post-radiation cystitis have been studied with special reference to the frequency and severity of ureteral complications. Gross bleeding stopped in 25 of 27 patients within 48 hours. However, 5 patients became anuric immediately after the instillation and in another 7 patients a transient increase in the serum creatinine level was observed. Urinary diversion was necessary in 11 of the 27 patients. The complication rate in the present study is considerably higher than reported previously. Complications may be explained by vesicoureteral reflux of a too strong formalin-alcohol solution. To avoid future complications we suggest that 1) a high diuresis should be induced peroperatively, 2) a 1 to 2 per cent formalin solution without alcohol should be used and 3) the instillation pressure should not exceed 15 cm. water. Persistent gross hematuria remains a challenging problem in connection with radiation therapy for bladder carcinoma. Since the bleeding in these cases occurs from telangiectatic vessels scattered over the mucosa local fulguration seldom is successful. Bladder irrigation with silver nitrate or bilateral hypogastric artery ligations has been used with limited success. 1 Supravesical urinary diversion, with or without palliative simple cystectomy, is not always possible because of the poor general condition of the patient and the fixation of the bladder in the pelvis. In this situation local instillation of formalin into the bladder has been reported to be of value. 1- 6 After the instillation the patients often experienced suprapubic pain, dysuria, a reduction in bladder capacity and urgency of urination. 1 However, the frequency of serious complications has been low. 1• 7-II Our subsequent identification of 3 patients with anuria immediately after instillation of formalin into the bladder prompted us to review our results with this method. This review was done with special reference to the frequency and severity of ureteral complications. PATIENTS AND METHODS
Between 1966 and 1977, 27 patients (19 men and 8 women) were treated with intravesical formalin instillation for massive hemorrhage from the bladder owing to post-radiation cystitis. All of the patients had been subjected previously to external irradiation (6,500 to 7,000 rad) because of infiltrating bladder carcinoma. The mean age of the patients was 72 years, with a range of 52 to 85 years. The hemorrhage usually occurred from 1 to several years after irradiation. Evacuation of bladder clots with subsequent irrigation of the bladder and administration of antifibrinolytics was inadequate in the patients selected for formalin treatment. All blood clots and debris were evacuated carefully from the bladder with the patient under general or spinal anesthesia. Then, 100 ml. of a 3 per cent formalin in 65 per cent alcohol solution was instilled from a glass syringe. The resistance to injection was observed carefully to avoid instillation against pressure. The solution was left in the bladder for 10 minutes and was then allowed to drain. The bladder was irrigated subsequently with physiological saline. A catheter was left indwelling until the urine became clear. RESULTS
Formalin therapy was effective in most patients. Gross bleeding stopped within 48 hours in 25 of the 27 patients (93 per Accepted for publication October 27, 1978.
160
cent). However, in 3 of the patients a repeat instillation was necessary to clear the urine. Slight hematuria persisted after treatment in 1 patient and in another patient the urine was not clear until 3 weeks after repeated instillation. Five patients (19 per cent) became anuric immediately after the instillation and in another 7 (26 per cent) a transient increase in the serum creatinine level by 0.3 to 1.7 gm. per cent (mean 1.06 gm. per cent) was observed. Septicemia developed postoperatively in 2 patients. Pseudomonas and Klebsiella, respectively, were grown from blood and urine. Another 7 patients had a temperature of 2:38C 1 to 3 days after the treatment. These patients all responded well to antibiotics. Increased temperature was observed only in the 12 patients in whom anuria or elevation of the serum creatinine level was observed. Convalescence was uneventful in 3 men with previous urinary diversion. The 5 patients with anuria were treated as emergency cases. In 3 of the 5 patients a cutaneous ureterostomy was done and in 2 the urine was diverted temporarily by an in situ ureterostomy and a percutaneous pyelostomy, respectively. Within 14 months (14 days to 14 months) after the formalin treatment a permanent urinary diversion was necessary in another 6 patients (22 per cent) owing to progressive upper urinary tract dilatation or signs of renal failure, or both. Of the 6 patients 5 had had a transient increase of serum creatinine immediately after the instillation. In addition, 2 of these 5 patients (7 per cent of the total material) had suffered extremely reduced bladder capacity. In 2 patients with cutaneous ureterostomy severe fibrosis of the entire remaining ureter developed within 4 to 6 months, respectively, and a tube pyelostomy was necessary. A representative case of anuria after formalin treatment is reported. CASE REPORT
A 77-year-old man had a moderately differentiated transitional cell carcinoma of the bladder diagnosed in November 1970. He had been treated with external irradiation (6,500 rad). An excretory urogram in March 1971 showed no excretion of contrast medium from the left kidney. The serum creatinine at this time was 1.8 mg. per cent. Because of the age of the patient no further diagnostic procedures were done. In August 1972 the patient presented with massive hematuria. Hemoglobin was 7.5 gm. per cent and 4 units of blood were administered. Cystoscopy revealed generalized bleeding from telangiectatic vessels. The formalin solution was instilled into the bladder and the urine cleared within 24 hours. After the instillation the patient had a
URETERAL COMPLICATIONS AFTER INTRAVESICAL FORMALIN INSTILLATION
Clot appears as cast of ureter at operation
transient increase of body temperature and serum creatinine increased slowly from 2.0 to 7.3 mg. per cent. The patient became anuric 5 days after the instillation. At operation a yellowish clot, 15 cm. long, was found within the right ureter. The clot appeared as a cast of the ureter (see figure). A cutaneous ureterostomy was done and the ureter was intubated with a polyethylene tube. Convalescence was uneventful and the patient was discharged from the hospital 7 days postoperatively. The ureter remains permanently intubated because of a distal ureteral stricture.
solution has been recommended. In our department a 3 per cent formalin solution was used but, nevertheless, a remarkably high frequency of complications was observed. A factor of importance may be the alcohol content of our solution. It is a well known fact that alcohol precipitates protein and this may accentuate the effect of formalin. However, alcohol irrigation of the bladder after formalin instillation has been used previously with no disadvantages. 7 The complications may be attributed to an effect of the solution on either the bladder wall or the ureters. Immediately after the instillation an intense edema of the bladder wall may occlude the ureteral orifices and fibrosis of the bladder wall subsequently may obstruct the intramural parts of the ureters. The finding of extensive fibrosis of the bladder wall in connection with ureteral obstruction in 2 of our patients supports this hypothesis. The incidence of vesicoureteral reflux in patients treated previously for bladder carcinoma probably is high. 14 There are obvious difficulties in excluding reflux preoperatively in the patients to be treated with formalin. Reflux of the solution into the ureters may cause edema and, subsequently, fibrosis at this level. The existence of a reflux mechanism is supported by the finding of a cast in the ureter of 1 of our patients and by the late development of extensive ureteral fibrosis in another 2 patients. The finding of vesicoureteral reflux before formalin instillation led Gottesman and Ehrlich to suggest the occlusion of the ureter by means of a Fogarty embolectomy catheter during the instillation. 15 However, we believe that this technique can be used rarely in the acute situations concerned. On the other hand, according to Ekman and associates, the induction of a high diuresis may inhibit vesicoureteral reflux. 16 Consequently, this method should reduce the risk of reflux of formalin peroperatively. In this context the importance of the technique of instillation also should be stressed. Although our ambition has been to maintain a low instillation pressure the solution per se no doubt elicits a violent bladder contraction, with a risk of subsequent ureteral reflux if the bladder contents cannot escape easily from the bladder. On the basis of our results, and in agreement with Fair, 8 we suggest the following procedure for safe use of intravesical formalin: 1) induction of high diuresis peroperatively, 2) use of a 1 to 2 per cent formalin solution without alcohol and 3) passive irrigation by gravity via a balloon catheter, at a maximum instillation pressure of 15 cm. water. REFERENCES
DISCUSSION
Hematuria stopped in 22 of the 27 patients after a single instillation and in another 3 patients after repeating the procedure. These results are in good agreement with those reported in the literature. 1- 5 However, the frequency of anuria (5 patients, 19 per cent), increased serum creatinine level (7 patients, 26 per cent) and subsequent urinary diversion (11 patients, 41 per cent) is considerably higher than reported previously. 1• 7• 8 Formalin precipitates protein by reducing and uniting with the protein amino groups. It was suggested by Brown for use in severe hematuria because of its ability to seal bleeding vessels. 2 Brown used a 10 per cent formalin solution when he observed the rapidity of fixation of cystectomy specimens by the solution and the lack of penetration beyond the superficial layers. 2 However, the results of recent experimental studies have been diverging in this respect. In investigations on the effect of different concentrations of formalin Pust and associates observed a complete necrosis of the epithelium, including parts of the submucosa, 12 while Rankin reported disintegration of the entire bladder wall after injection of a 10 per cent formalin solution. 13 In both investigations, however, only epithelial damage was found at low concentrations of the solution. The importance of the concentration with respect to the frequency of complications in the clinical application of formalin has been stressed further. 7• 8 To provide a safe approach a 1 to 4 per cent
161
1. Shrom, S. H., Donaldson, M. H., Duckett, J. W., Jr. and Wein, A.
2. 3. 4. 5. 6. 7. 8. 9. 10.
J.: Formalin treatment for intractable hemorrhagic cystitis. A review of the literature with 16 additional cases. Cancer, 38: 1785, 1976. Brown, R. B.: A method of management of inoperable carcinoma of the bladder. Med. J. Aust., 1: 23, 1969. Firlit, C. F.: Intractable hemorrhagic cystitis secondary to extensive carcinomatosis: management with formalin solution. J. Urol., 110: 57, 1973. Shah, B. C. and Albert, D. J.: lntravesical instillation of formalin for the management of intractable hematuria. J. Urol., 110: 519, 1973. Kumar, S., Rosen, P. and Grabstald, H.: Intravesical formalin for the control of intractable bladder hemorrhage secondary to cystitis or cancer. J. Urol., 114: 540, 1975. Servadio, C. and Nissenkorn, I.: Massive hematuria successfully treated by bladder irrigations with formalin solution. Cancer, 37: 900, 1976. Spiro, L. H., Hecht, H., Horowitz, A. and Orkin, L.: Formalin treatment for massive bladder hemorrhage. Urology, 2: 669, 1973. Fair, W. R.: Formalin in the treatment of massive bladder hemorrhage. Techniques, results, and complications. Urology, 3: 573, 1974. Scott, M. P., Jr., Marshall, S. and Lyon, R. P.: Bladder rupture following formalin therapy for hemorrhage secondary to cyclophosphamide therapy. Urology, 3: 364, 1974. Chugh, K. S., Singhal, P. C. and Banerjee, S. S.: Acute tubular
FALL AND PETTERSSON
162
11. 12. 13. 14. 15. 16.
necrosis following intravesical instillation of formalin. Urol. Int., 32: 454, 1977. Lourie, J. A., Drysdale, H. C. and Wynne, E. J.C.: Death following intravesical formalin instillation. Brit. J. Urol., 49: 476, 1977. Pust, R., Butz, M., Rost, A., Ogbuihi, S. and Riedel, B.: Denudation of the urinary bladder mucosa in the cat by formaldehyde. Urol. Res., 4: 55, 1976. Rankin, K. N.: lntravesical formalin. Invest. Urol., 12: 150, 1974. Schmidt, J. D., Jacobo, E. C. and Weinstein, S. H.: Vesicoureteral reflux in recurrent carcinoma of the bladder - implications for treatment and prognosis. J. Urol., 116: 734, 1976. Gottesman, J. and Ehrlich, R. M.: Preventing vesicoureteral reflux during intravesical formalin instillation. Urology, 3: 494, 1974. Ekman, H., Jacobsson, B., Kock, N. G. and Sundin, T.: High diuresis, a factor in preventing vesicoureteral reflux. J. Urol., 95: 511, 1966. EDITORIAL COMMENT
It is not clear why the authors used formalin in alcohol solution, since this is a departure from previous publications in which formalin was used in water or saline solution. Nonetheless, the precautions that were outlined in 1974 bear repeating (reference 8 in the article). In particular, the need for sterile urine and a pre-instillation cystogram to eliminate the possibility of ureterovesical reflux. In the presence of reflux our experience has been quite satisfactory by simply placing the patient in the reverse Trendelenburg position and ensuring that the
amount of pressure used for the instillation does not exceed 15 cm. Lastly, it must be certain that formalin, a 37 per cent solution of formaldehyde, and not formaldehyde per se is used. W.R.F. REPLY BY AUTHORS The precautions for the prevention of vesicoureteral reflux of formalin suggested by Doctor Fair are valuable. We agree with him that the technique of instillation is of crucial importance. Our choice of a formalin solution containing alcohol was, in fact, based on results obtained with unintentional treatment. In July 1966, that is before publication of Brown's paper,2 we had to perform bladder evacuation in a patient with massive hemorrhage caused by postradiation cystitis. The patient was brought to the endoscopy theater late in the afternoon. The glass cistern for irrigation fluids had been emptied of sterile water and filled with a solution for sterilization overnight. However, this was not observed until too late and the bladder irrigation was done with this solution (30 gm. 37 per cent formaldehyde, 650 gm. 96 per cent alcohol and distilled water to 1,000 gm.). As soon as the mistake was observed the bladder was washed out repeatedly with saline. However, the procedure was effective. Since no complications were observed postoperatively we began to use 3 per cent formalin and 65 per cent alcohol instillations as treatment in massive bladder hemorrhage and were later encouraged by Brown's report.