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The Treatment Of Urinary And Genital Tuberculosis With Streptomycin
THE TREATMENT OF URINARY AND GENITAL TUBERCULOSIS WITH STREPTOMYCIN FREDERICK LLOYD,
M.D.,
GEORGE BAUMRUCKER,
OUVER STONINGTON,
M.D.
AND
M. D.
THE tuberculous process in the urinary tract begins in the kidney. The renal lesion, once demonstrable clinically, has a definite tendency to progress and only very rarely heals spontaneously. This is largely due to the early formation of tuberculous calycal and ureteral strictures which produce a stasis of tuberculous urine in the kidney. Conservative medical management which is so effective in certain forms of pulmonary tuberculosis has proved very disappointing in renal tuberculosis. In fact, bed rest is harmful because it enhances urinary stasis. A cure following nephrectomy for unilateral renal tuberculosis depends upon the subsequent spontaneous healing of lesions in the remaining stump of the ureter and bladder. In such cases lesions are almost always present in the genitalia and in other organs in the body even though they may not as yet be demonstrable clinically. These lesions also must heal spontaneously if a cure is to be accomplished. That this often happens is proved by the fact that nephrectomy in unilateral renal tuberculosis is followed by a cure in 50 to 55 per cent of the cases, whereas failure to remove the kidney almost invariably leads to death within five years. In 45 to 50 per cent of the cases, however, the condition progresses in spite of nephrectomy, and a fatal outcome occurs, often after a long period of intense misery. The earlier cases offer a better chance of a cure following nephrectomy. In fact, in the earliest forms in which the renal lesion consists mainly of a small caseous ulcer on the summit of a single renal papilla, the possibility of a cure following nephrectomy is better than 90 per cent. Failure to remove the kidney at this stage almost invariably leads to progression of the lesion and a loss of the best and sometimes the only opportunity to achieve a cure. It requires great courage on the part of the surgeon to remove a kidney with a normal function, with normal From the Department of Urology, Veterans Administration Hospital, Hines, Illinois and the Colleges of Medicine, Northwestern University, and the University of Illinois, Chicago. Published with permission of the Chief Medical Director, Department of Medicine and Surgery, Veterans Administration, who assumes no responsibility for the opinions expressed or the conclusions drawn by the authors.
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1640
F. LLOYD, G. BAUMRUCKER, O. STONINGTON
pelvic contours, and which, except for the presence of a minute lesion, is otherwise normal. Theoretically such a case would seem to be ideal for conservative management. The fact that the symptoms at this stage are often minimal or even undergo complete remission for a time leads to a false feeling of security; hence, conservative management is usually employed with disastrous end results. It is obvious from a consideration of the above mentioned facts that nephrectomy, although it has up to the present been the most effective weapon at our command, leaves much to be desired. Conservative medical management, which has been so disappointing in the past, will eventually prove to be the ideal method of treatment, and it awaits only the discovery of an antibiotic of sufficient potency completely to destroy the tubercle bacillus. The discovery of streptomycin raised the hope that this might be the long awaited agent. Although subsequent investigations revealed that this was not the case, the use of this new antibiotic has proved to be a definite step forward in the treatment of urinary tuberculosis and genital tuberculosis in the male. THE RESULTS OF STREPTOMYCIN THERAPY
In an attempt to evaluate its effectiveness, twenty-three patients with urinary and genital tuberculosis were treated with streptomycin, in daily doses of 1 gm. (in two divided doses of 0.5 gm. each) for a period of 120 days. Each patient received a complete urinary study before treatment and at intervals of one month during and after treatment. Sixteen patients have completed their full course of streptomycin and have been observed for periods of one to eight months following completion of the therapy. Among thirteen cases with renal involvement nine were bilateral and four were unilateral. Ten of these patients had genital lesions. In three additional cases the disease was limited to the genitalia. The results may be summarized as follows: The Kidney and Ureter.-In nine kidneys with positive pyelographic evidence of tuberculosis the bacteriological findings became negative in three. In five the pyelograms showed no change after treatment and in four definite progresssion was noted. In one of these the kidney underwent rapid hydronephrotic dilatation and became functionless during the period of treatment, due to ureteral atresia resulting from fibrous healing of tuberculous ureteral lesions. Six of the kidneys in this group were subsequently removed. In all a very definite healing effect was noted but this was so far short of complete obliteration of the disease as not to be of clinical significance. The most
STREPTOMYCIN IN URINARY AND GENITAL TUBERCULOSIS
1641
pronounced healing effect was seen on the mucous membranes of the calyces, pelvis and ureter. The most striking results were seen in the ten patients with tuberculous kidneys showing normal pyelograms. One of these could not be catheterized for follow-up study, but in the remaining nine the bacteriologic findings became negative, and there was an appreciable reduction of the leukocyte count of the urine specimen obtained by ureteral catheter. The possibility of a cure, although very strong in this group of cases, can only be evaluated by a five to ten year follow-up study. The Urinary Bladder.-Eleven patients showed involvement of the bladder. In seven definite specific lesions were identified (tubercles, ulcers, granuloma). In the remaining four the lesions were more inflammatory in appearance. In five cases the bladder returned to normal after treatment, four were improved, one remained the same, and one was worse. The symptomatic improvement was most pronounced in these cases. Six patients had had severe symptoms with reduced bladder capacity. After treatment the capacity was increased in four, remained the same in one, and decreased in one. Definite improvement was usually noted after four to six weeks of treatment. The lesions in the bladder have a tendency to recur after the cessation of streptomycin therapy if the offending kidney has not previously been removed. Genital Tuberculosis.-Twelve patients had genital involvement. The results in this group were not very encouraging. Significant improvement in lesions of the prostate, seminal vesicles, and epididymides, as demonstrated by rectal and scrotal palpation, did not occur after streptomycin therapy. In two patients there was a slight to moderate decrease in the size of the epididymis. Seven epididymides were removed and upon pathological study showed extensive caseous disintegration. In one of these definite progression with involvement of the testis occurred during therapy. Lesions in the prostate and seminal vesicles also progressed. Five months after epididymo-orchiectomy the rectal findings had returned to normal. Scrotal abscesses were present in three patients. These progressed or showed no change under streptomycin therapy alone; however, after incision during therapy they promptly healed without fistula formation. In one case bilateral scrotal fistulas and partial extrusion of the left testis were present following bilateral epididymectomy. Prompt healing followed the administration of streptomycin.
1642
F. LLOYD, G. BAUMRUCKER, O. STONINGTON
SUMMARY AND CONCLUSIONS
It is obvious from these results that streptomycin is of very limited value when employed by itself in the treatment of urinary tuberculosis and genital tuberculosis in the male. The symptomatic improvement which so often accompanies its use in involvement of the urinary tract is due to the temporary healing of bladder lesions and is apt to be very misleading to the unwary. Renal tuberculosis with positive pyelographic findings does not respond well to streptomycin; in fact, the destruction of the kidney may occasionally be accelerated by its use. In very early renal lesions with a low leukocyte count in the urine obtained by ureteral catheter and with normal pyelographic findings the response to streptomycin seems to be excellent. However, only a prolonged follow-up study (five to ten years) will make it possible to tell if such cases actually heal or only become quiescent, to flare up again later. Streptomycin has little effect upon lesions in the male genitalia but it does cause prompt healing of scrotal fistulas. When used in conjunction with surgery it will undoubtedly prove of tremendous value. The partial healing effect which is not adequate by itself will probably enhance the results of operative treatment. The percentage of cures following nephrectomy for unilateral renal tuberculosis should be increased appreciably. Only further studies with long periods of observation will give the final answer to this problem. The healing of tuberculous lesions in the bladder, which respond slowly after nephrectomy, is accelerated by streptomycin therapy. When the bladder responds poorly because the ureteral stump fails to heal following nephrectomy, the use of streptomycin should render secondary ureterectomy a far safer procedure. Loin fistulas and postoperative tuberculous wound disruption, which have been such an annoying problem in the past, heal promptly on streptomycin therapy. <
M.D.,
GEORGE BAUMRUCKER,
OUVER STONINGTON,
M.D.
AND
M. D.
THE tuberculous process in the urinary tract begins in the kidney. The renal lesion, once demonstrable clinically, has a definite tendency to progress and only very rarely heals spontaneously. This is largely due to the early formation of tuberculous calycal and ureteral strictures which produce a stasis of tuberculous urine in the kidney. Conservative medical management which is so effective in certain forms of pulmonary tuberculosis has proved very disappointing in renal tuberculosis. In fact, bed rest is harmful because it enhances urinary stasis. A cure following nephrectomy for unilateral renal tuberculosis depends upon the subsequent spontaneous healing of lesions in the remaining stump of the ureter and bladder. In such cases lesions are almost always present in the genitalia and in other organs in the body even though they may not as yet be demonstrable clinically. These lesions also must heal spontaneously if a cure is to be accomplished. That this often happens is proved by the fact that nephrectomy in unilateral renal tuberculosis is followed by a cure in 50 to 55 per cent of the cases, whereas failure to remove the kidney almost invariably leads to death within five years. In 45 to 50 per cent of the cases, however, the condition progresses in spite of nephrectomy, and a fatal outcome occurs, often after a long period of intense misery. The earlier cases offer a better chance of a cure following nephrectomy. In fact, in the earliest forms in which the renal lesion consists mainly of a small caseous ulcer on the summit of a single renal papilla, the possibility of a cure following nephrectomy is better than 90 per cent. Failure to remove the kidney at this stage almost invariably leads to progression of the lesion and a loss of the best and sometimes the only opportunity to achieve a cure. It requires great courage on the part of the surgeon to remove a kidney with a normal function, with normal From the Department of Urology, Veterans Administration Hospital, Hines, Illinois and the Colleges of Medicine, Northwestern University, and the University of Illinois, Chicago. Published with permission of the Chief Medical Director, Department of Medicine and Surgery, Veterans Administration, who assumes no responsibility for the opinions expressed or the conclusions drawn by the authors.
1639
1640
F. LLOYD, G. BAUMRUCKER, O. STONINGTON
pelvic contours, and which, except for the presence of a minute lesion, is otherwise normal. Theoretically such a case would seem to be ideal for conservative management. The fact that the symptoms at this stage are often minimal or even undergo complete remission for a time leads to a false feeling of security; hence, conservative management is usually employed with disastrous end results. It is obvious from a consideration of the above mentioned facts that nephrectomy, although it has up to the present been the most effective weapon at our command, leaves much to be desired. Conservative medical management, which has been so disappointing in the past, will eventually prove to be the ideal method of treatment, and it awaits only the discovery of an antibiotic of sufficient potency completely to destroy the tubercle bacillus. The discovery of streptomycin raised the hope that this might be the long awaited agent. Although subsequent investigations revealed that this was not the case, the use of this new antibiotic has proved to be a definite step forward in the treatment of urinary tuberculosis and genital tuberculosis in the male. THE RESULTS OF STREPTOMYCIN THERAPY
In an attempt to evaluate its effectiveness, twenty-three patients with urinary and genital tuberculosis were treated with streptomycin, in daily doses of 1 gm. (in two divided doses of 0.5 gm. each) for a period of 120 days. Each patient received a complete urinary study before treatment and at intervals of one month during and after treatment. Sixteen patients have completed their full course of streptomycin and have been observed for periods of one to eight months following completion of the therapy. Among thirteen cases with renal involvement nine were bilateral and four were unilateral. Ten of these patients had genital lesions. In three additional cases the disease was limited to the genitalia. The results may be summarized as follows: The Kidney and Ureter.-In nine kidneys with positive pyelographic evidence of tuberculosis the bacteriological findings became negative in three. In five the pyelograms showed no change after treatment and in four definite progresssion was noted. In one of these the kidney underwent rapid hydronephrotic dilatation and became functionless during the period of treatment, due to ureteral atresia resulting from fibrous healing of tuberculous ureteral lesions. Six of the kidneys in this group were subsequently removed. In all a very definite healing effect was noted but this was so far short of complete obliteration of the disease as not to be of clinical significance. The most
STREPTOMYCIN IN URINARY AND GENITAL TUBERCULOSIS
1641
pronounced healing effect was seen on the mucous membranes of the calyces, pelvis and ureter. The most striking results were seen in the ten patients with tuberculous kidneys showing normal pyelograms. One of these could not be catheterized for follow-up study, but in the remaining nine the bacteriologic findings became negative, and there was an appreciable reduction of the leukocyte count of the urine specimen obtained by ureteral catheter. The possibility of a cure, although very strong in this group of cases, can only be evaluated by a five to ten year follow-up study. The Urinary Bladder.-Eleven patients showed involvement of the bladder. In seven definite specific lesions were identified (tubercles, ulcers, granuloma). In the remaining four the lesions were more inflammatory in appearance. In five cases the bladder returned to normal after treatment, four were improved, one remained the same, and one was worse. The symptomatic improvement was most pronounced in these cases. Six patients had had severe symptoms with reduced bladder capacity. After treatment the capacity was increased in four, remained the same in one, and decreased in one. Definite improvement was usually noted after four to six weeks of treatment. The lesions in the bladder have a tendency to recur after the cessation of streptomycin therapy if the offending kidney has not previously been removed. Genital Tuberculosis.-Twelve patients had genital involvement. The results in this group were not very encouraging. Significant improvement in lesions of the prostate, seminal vesicles, and epididymides, as demonstrated by rectal and scrotal palpation, did not occur after streptomycin therapy. In two patients there was a slight to moderate decrease in the size of the epididymis. Seven epididymides were removed and upon pathological study showed extensive caseous disintegration. In one of these definite progression with involvement of the testis occurred during therapy. Lesions in the prostate and seminal vesicles also progressed. Five months after epididymo-orchiectomy the rectal findings had returned to normal. Scrotal abscesses were present in three patients. These progressed or showed no change under streptomycin therapy alone; however, after incision during therapy they promptly healed without fistula formation. In one case bilateral scrotal fistulas and partial extrusion of the left testis were present following bilateral epididymectomy. Prompt healing followed the administration of streptomycin.
1642
F. LLOYD, G. BAUMRUCKER, O. STONINGTON
SUMMARY AND CONCLUSIONS
It is obvious from these results that streptomycin is of very limited value when employed by itself in the treatment of urinary tuberculosis and genital tuberculosis in the male. The symptomatic improvement which so often accompanies its use in involvement of the urinary tract is due to the temporary healing of bladder lesions and is apt to be very misleading to the unwary. Renal tuberculosis with positive pyelographic findings does not respond well to streptomycin; in fact, the destruction of the kidney may occasionally be accelerated by its use. In very early renal lesions with a low leukocyte count in the urine obtained by ureteral catheter and with normal pyelographic findings the response to streptomycin seems to be excellent. However, only a prolonged follow-up study (five to ten years) will make it possible to tell if such cases actually heal or only become quiescent, to flare up again later. Streptomycin has little effect upon lesions in the male genitalia but it does cause prompt healing of scrotal fistulas. When used in conjunction with surgery it will undoubtedly prove of tremendous value. The partial healing effect which is not adequate by itself will probably enhance the results of operative treatment. The percentage of cures following nephrectomy for unilateral renal tuberculosis should be increased appreciably. Only further studies with long periods of observation will give the final answer to this problem. The healing of tuberculous lesions in the bladder, which respond slowly after nephrectomy, is accelerated by streptomycin therapy. When the bladder responds poorly because the ureteral stump fails to heal following nephrectomy, the use of streptomycin should render secondary ureterectomy a far safer procedure. Loin fistulas and postoperative tuberculous wound disruption, which have been such an annoying problem in the past, heal promptly on streptomycin therapy. <