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Tuberculosis of Urinary Tract
THE JOURNAL OF UROLOGY
Vol. 66, No. 5, November 1951 Printed in U.S.A.
TUBERCULOSIS OF URINARY TRACT D. VAN CAPPELLEN University of Amsterdam, Holland
The treatment of tuberculosis of the urinary tract has become a most fascinating one, and especially for me, who had to deal with this problem for nearly 40 years. How well I remember the first years, when we were less well equipped (no pyelograms, imperfect instruments). How proud was one to have established the fact that a patient had unilateral tuberculosis: nephrectomy could save him. Only a few years ago, many a hot discussion was heard among surgeons and urologists, but in the end nephrectomy was recognized as a good remedy. But little thought was given to the fact, nowadays generally recognized, that tuberculosis of the kidney was part of a generalization of the disease in the human body. Notwithstanding that, we booked remarkable results: once the kidney was removed, sometimes the cystitis subsided more or less, even to complete recovery. It was no wonder that we tried to make a diagnosis as early as possible, because we were in fear of the complicating cystitis tuberculosa. The sooner we operated therefor, the more was the chance that the bladder could be kept free of tuberculosis. That era I should like to name the Wildbolz era after that eminent Swiss urologist, who advocated this early nephrectomy, this "Fruhoperation" and who had many followers. Sometimes the operation took place in so early a period of the infection, that only after a long search one could find the small tuberculous lesion in the kidney. But after some years we came to the conclusion that so many patients, even after a most successful operation, were not restored to health. Even Wildbolz in his monograph mentioned the fact that in a rather astonishing percentage there remained a certain morbidity after nephrectomy. More recently Oppenheimer and N arins made a study of 106 patients after nephrectomy for unilateral tuberculosis: 15 developed genital or osseous tuberculosis, 17 had res;:::ual tuberculous cystitis, 17 had (later on?) tuberculosis of the remaining kidney. I cannot follow these authors in their conclusion that they will wait for a long followed series of cases with streptomycin before they will change their opinion, that cases of unilateral tuberculosis should be subjected to operation in every case. Nesbit and Bohne stated, that although a fair chance of recovery existed in 1380 patients to be cured by nephrectomy, only 50 per cent were alive after 5 years and that even if in the supposed healthy kidney bacilli were found. Semb came to the same conclusion: 50-60 per cent cure only even in very selected cases of unilateral tuberculosis. The persistence of tuberculosis of the bladder, genital-pulmonary and bone tuberculosis had their share in the appreciable morbidity after operation. My own experience and that of so many others are more or less the same. Read at annual meeting, American Urological Association, Washington, D. C., May 30, 1950. 619
620
r
r
D. VAN CAPPELLEN
Therefore the fact remains that nephrectomy for unilateral tuberculosis of the kidney does not restore the patients to a healthy life, but there is a large percentage who are more or less suffering from various forms of tuberculosis. In later years, Dos Santos of Lisbon and Bernard Fey of Paris opposed early nephrectomy. They were and are of the opinion that we should not operate as soon as possible after a diagnosis of unilateral tuberculosis. The idea is this: If the tuberculous kidney is still well functioning, they wait after careful examination of the case. If in months or years to come, the function becomes poor, then nephrectomy can be performed. The other kidney has been accustomed to do the work of the diseased kidney, and one is more sure of its condition. Examinations should be done at regular intervals. This point of view has at least the advantage that we do not operate in an acute phase of the tuberculosis, so that complications are to be feared much less. We could call this the era of delayed nephrectomy. De Beaufond is of the opinion that the prognosis is not influenced by the fact when the operation is performed. His statistics of more than 550 cases show it. He gives support to Fey's nephre~tomie retardee. De Beaufond had only 50 per cent of complete healing. Some of the bad results may be caused by the fact that we have to do with a generalization of the tuberculosis. We all know Medlar's beautiful work, in which he established the fact that far more cases are bilateral than we know, and that even advanced cases, with tuberculous cavities in the kidneys had sometime no clinical symptoms. We could easily fill a few pages with communications like these I mentioned above, but for our problem this is not necessary. It is clear that nephrectomy alone is not sufficient. And now we come to the third era, which I should like to name after your world-famed countryman, the Waksman era. In this name I include the antibiotics and the drugs now in use and which give sometimes results, so astonishingly good, that our patients have got a new and more favorable outlook on life. I can only give you personal experience with 3 of them: streptomycin, PAS and moogrol. Although I used vitamin D 2 and calcium in a few cases with no remarkable results, Stobbaerts' demonstration of a case, in which a small cavity was filled with a stone and the patient free of bacilli, made a very favorable impression. Before I will speak about streptomycin and PAS, a few words about the use of chaulmoogra oil and its derivative esters, later on called moogrol. This oil should be able to dissolve the protective cell wall of the bacilli and make them more vulnerable for our new antibiotics and drugs. Slotkin in his publication gives a not convincing reproduction of the electronic micrograph magnification of Mycobacterium tuberculosis; but his successes in many cases treated with moogrol-streptomycin are most remarkable. And still more interesting is the publication of Duvergey: in a case of bilateral tuberculosis of the kidney. The bacilli disappeared definitely after treatment with chaulmoogra oil alone. I made it my practice to use moogrol in combination with streptomycin, (as Slotkin did). And now I proceed with streptomycin and the results obtained with that
TUBERCl~LOSIS OF URINARY TRACT
621
antibiotic. Among the publications I will first mention those of Lattimer. His results were most encouraging: 235 patients were treated. The best results were
FIG. 1. X, drawn-up pyelum. Little is to be seen of tuberculous structure
FIG. 2. Regressive epitheloid tubercle, just under mucous lining (cut in part of pyelum)
obtained when streptomycin 2 gr. was given daily in 6 equal doses during 120 days. Most patients got vestibular symptoms, which in nearly all cases disappeared after the eure was ended. Streptomycin acts best in small unilateral
622
D. VAN CAPPELLEN
tuberculous alterations and when both kidneys produced bacilli without evident destruction in the pyelograms. In 80 per cent no bacilli could be found 12 months after the treatment. Reed M. Nesbit reported 29 cases. His best results were obtained with streptomycin 2 gr. daily. If after 60 days there is no improvement, then operation. He keeps his patients in a sanatorium. Most of his patients got vestibular trouble. Another potent drug against the bacilli which was discovered a few years ago is para amino salicylic acid (PAS). Now it is known that streptomycin given for a longer period makes the bacilli resistant against this antibiotic. Compared with streptomycin, PAS has the advantage that bacilli become resistant to PAS only after a longer period of treatment; streptomycin-resistant bacilli are
Fw. 3. A, cortex of kidney (in neighborhood of pyelum). Pseudothyroid structure as seen in chronic pyelonephritis. B, single fibrous tubercle in cortex near pyclum.
susceptible to PAS; it enhances the action of streptomycin. It delays the emergence of streptomycin-resistant bacilli. For these reasons streptomycin should always be combined with PAS. If we are obliged to operate upon a patient in a later period we must be very careful in administering streptomycin for longer than 6 weeks, for the patient will need the streptomycin after operation to avoid complications and the bacilli then must not have become resistent. The influence of PAS alone in a few patients, treated with it, was very promising. My treatment nowadays is as follows: Urine should be made alkaline with sodium bicarbonate, then 1 gm. streptomycin, 12-16 gm. PAS or 20 gm. sodium PAS, 1 cc moogrol daily. I am well aware that I cannot give in detail my results. If I eliminate cases with complicating genital tuberculosis, I am very well
TUBERCULOSIS OF URIKARY TRACT
623
satisfied with the results, although time since treatment is perhaps too short to speak of definite healing. In 7 cases with combined tuberculosis of bladder and single kidney (without cavities) after shorter or longer treatment, patients were free of symptoms; culture and guinea pigs became negative. Of another case, I shall give a short summary: A girl aged 23 had tuberculosis of the knee and the twelfth rib. She was in S,Yitzerland for a cure. In Hl48 a urological examination disc:losed that the urine was positive for tuberculosis. Destruction was in the upper pole of the right kidney. rrine from the left kidney was positi,-e. The patient was sent to me for a right nephrectomy after a cure with streptomycin and large doses of PAS. In August examma-
FIG. 4. A, wall of cavity covered b:v granulations. No necrosis, no tuberculous structurnThis is part of tuberculous cavit:v, which we consider as healed. B, only in circumscript part of cavity we find wall covered with active tuberculous gnmulations and necrosis (fibroblasts in palisade stand).
tion me disclosed that urine from the left kidney and bladder was positive. But to my surprise, the right kidney no longer was tuberculous, as established by culture and p1inca pig inoculation. After a cure of 1 month with streptomycin, PAS and rnoogrol, the urine was negative. Another case I should like to present ended with a nephrectomy, but a careful examination of this kidney shows clearly the healing power of streptomycinmoogrol. The patient was a man aged 42. He had tuberculosis of the right knee. Albumin, pus and bacilli in a density seldom seen appeared in the urine. Frography showed a small cavity in the right upper pole near the pyelum. The left kidney was normal. Streptomycin 1 gr. and moogrol 1 cc daily were given for 2 months, after which the urine became clear, with only a trace of albumin, a
624
D. VAN CAPPELLEN
few pus cells, and with great difficulty one or two bacilli were found. I was inclined to continue treatment, but the patient and his family desired operation, which I performed with reluctance. Professor Deelman of the -Cniversity of Amsterdam has examined this very precious piece with great care. He found a tuberculous process with every tendency to healing. I add some illustrations (figs. 1, 2, 3, and 4) to show you the details. It was a revelation for me to see a kidney which had produced purulent urine, with enormous quantities of bacilli, and where a cavity was on its way, to be cleansed. Which in the end will be the best treatment remains to be seen. But in addition to the remedies, of utmost importance to bring all these patients to a cure is that they must be treated in a sanatorium. REFERENCES DEBEAUFOND: 7th Congress of International Society of Urology, 1947. DuvERGEY, H.: J. d'urol., 55: 348, 1949. FEY, B.: J. d'urol., 49: 383, 1941. LATTIMER, J. K., AMBERSON, J.B. AND BRAHAM, S.: J. Urol., 62: 875, 1949. MEDLAR, E. M., SPAIN, D. M. AND HOLLIDAY, R. W.: J. Urol., 61: 1078, 1949. NESBIT, R. M. AND BoHxE, A. W.: J.A.M.A., 138: 927, 1948. OPPEi'iHEIMER, G.D. AND NARINS, L.: J. Urol., 62: 804, 1949. SE!vIB, C.: Acta chir. Scandinav., 98: 457, 1949. SLOTKIN, G. E.: J. Urol., 58: 464, 1947.
Vol. 66, No. 5, November 1951 Printed in U.S.A.
TUBERCULOSIS OF URINARY TRACT D. VAN CAPPELLEN University of Amsterdam, Holland
The treatment of tuberculosis of the urinary tract has become a most fascinating one, and especially for me, who had to deal with this problem for nearly 40 years. How well I remember the first years, when we were less well equipped (no pyelograms, imperfect instruments). How proud was one to have established the fact that a patient had unilateral tuberculosis: nephrectomy could save him. Only a few years ago, many a hot discussion was heard among surgeons and urologists, but in the end nephrectomy was recognized as a good remedy. But little thought was given to the fact, nowadays generally recognized, that tuberculosis of the kidney was part of a generalization of the disease in the human body. Notwithstanding that, we booked remarkable results: once the kidney was removed, sometimes the cystitis subsided more or less, even to complete recovery. It was no wonder that we tried to make a diagnosis as early as possible, because we were in fear of the complicating cystitis tuberculosa. The sooner we operated therefor, the more was the chance that the bladder could be kept free of tuberculosis. That era I should like to name the Wildbolz era after that eminent Swiss urologist, who advocated this early nephrectomy, this "Fruhoperation" and who had many followers. Sometimes the operation took place in so early a period of the infection, that only after a long search one could find the small tuberculous lesion in the kidney. But after some years we came to the conclusion that so many patients, even after a most successful operation, were not restored to health. Even Wildbolz in his monograph mentioned the fact that in a rather astonishing percentage there remained a certain morbidity after nephrectomy. More recently Oppenheimer and N arins made a study of 106 patients after nephrectomy for unilateral tuberculosis: 15 developed genital or osseous tuberculosis, 17 had res;:::ual tuberculous cystitis, 17 had (later on?) tuberculosis of the remaining kidney. I cannot follow these authors in their conclusion that they will wait for a long followed series of cases with streptomycin before they will change their opinion, that cases of unilateral tuberculosis should be subjected to operation in every case. Nesbit and Bohne stated, that although a fair chance of recovery existed in 1380 patients to be cured by nephrectomy, only 50 per cent were alive after 5 years and that even if in the supposed healthy kidney bacilli were found. Semb came to the same conclusion: 50-60 per cent cure only even in very selected cases of unilateral tuberculosis. The persistence of tuberculosis of the bladder, genital-pulmonary and bone tuberculosis had their share in the appreciable morbidity after operation. My own experience and that of so many others are more or less the same. Read at annual meeting, American Urological Association, Washington, D. C., May 30, 1950. 619
620
r
r
D. VAN CAPPELLEN
Therefore the fact remains that nephrectomy for unilateral tuberculosis of the kidney does not restore the patients to a healthy life, but there is a large percentage who are more or less suffering from various forms of tuberculosis. In later years, Dos Santos of Lisbon and Bernard Fey of Paris opposed early nephrectomy. They were and are of the opinion that we should not operate as soon as possible after a diagnosis of unilateral tuberculosis. The idea is this: If the tuberculous kidney is still well functioning, they wait after careful examination of the case. If in months or years to come, the function becomes poor, then nephrectomy can be performed. The other kidney has been accustomed to do the work of the diseased kidney, and one is more sure of its condition. Examinations should be done at regular intervals. This point of view has at least the advantage that we do not operate in an acute phase of the tuberculosis, so that complications are to be feared much less. We could call this the era of delayed nephrectomy. De Beaufond is of the opinion that the prognosis is not influenced by the fact when the operation is performed. His statistics of more than 550 cases show it. He gives support to Fey's nephre~tomie retardee. De Beaufond had only 50 per cent of complete healing. Some of the bad results may be caused by the fact that we have to do with a generalization of the tuberculosis. We all know Medlar's beautiful work, in which he established the fact that far more cases are bilateral than we know, and that even advanced cases, with tuberculous cavities in the kidneys had sometime no clinical symptoms. We could easily fill a few pages with communications like these I mentioned above, but for our problem this is not necessary. It is clear that nephrectomy alone is not sufficient. And now we come to the third era, which I should like to name after your world-famed countryman, the Waksman era. In this name I include the antibiotics and the drugs now in use and which give sometimes results, so astonishingly good, that our patients have got a new and more favorable outlook on life. I can only give you personal experience with 3 of them: streptomycin, PAS and moogrol. Although I used vitamin D 2 and calcium in a few cases with no remarkable results, Stobbaerts' demonstration of a case, in which a small cavity was filled with a stone and the patient free of bacilli, made a very favorable impression. Before I will speak about streptomycin and PAS, a few words about the use of chaulmoogra oil and its derivative esters, later on called moogrol. This oil should be able to dissolve the protective cell wall of the bacilli and make them more vulnerable for our new antibiotics and drugs. Slotkin in his publication gives a not convincing reproduction of the electronic micrograph magnification of Mycobacterium tuberculosis; but his successes in many cases treated with moogrol-streptomycin are most remarkable. And still more interesting is the publication of Duvergey: in a case of bilateral tuberculosis of the kidney. The bacilli disappeared definitely after treatment with chaulmoogra oil alone. I made it my practice to use moogrol in combination with streptomycin, (as Slotkin did). And now I proceed with streptomycin and the results obtained with that
TUBERCl~LOSIS OF URINARY TRACT
621
antibiotic. Among the publications I will first mention those of Lattimer. His results were most encouraging: 235 patients were treated. The best results were
FIG. 1. X, drawn-up pyelum. Little is to be seen of tuberculous structure
FIG. 2. Regressive epitheloid tubercle, just under mucous lining (cut in part of pyelum)
obtained when streptomycin 2 gr. was given daily in 6 equal doses during 120 days. Most patients got vestibular symptoms, which in nearly all cases disappeared after the eure was ended. Streptomycin acts best in small unilateral
622
D. VAN CAPPELLEN
tuberculous alterations and when both kidneys produced bacilli without evident destruction in the pyelograms. In 80 per cent no bacilli could be found 12 months after the treatment. Reed M. Nesbit reported 29 cases. His best results were obtained with streptomycin 2 gr. daily. If after 60 days there is no improvement, then operation. He keeps his patients in a sanatorium. Most of his patients got vestibular trouble. Another potent drug against the bacilli which was discovered a few years ago is para amino salicylic acid (PAS). Now it is known that streptomycin given for a longer period makes the bacilli resistant against this antibiotic. Compared with streptomycin, PAS has the advantage that bacilli become resistant to PAS only after a longer period of treatment; streptomycin-resistant bacilli are
Fw. 3. A, cortex of kidney (in neighborhood of pyelum). Pseudothyroid structure as seen in chronic pyelonephritis. B, single fibrous tubercle in cortex near pyclum.
susceptible to PAS; it enhances the action of streptomycin. It delays the emergence of streptomycin-resistant bacilli. For these reasons streptomycin should always be combined with PAS. If we are obliged to operate upon a patient in a later period we must be very careful in administering streptomycin for longer than 6 weeks, for the patient will need the streptomycin after operation to avoid complications and the bacilli then must not have become resistent. The influence of PAS alone in a few patients, treated with it, was very promising. My treatment nowadays is as follows: Urine should be made alkaline with sodium bicarbonate, then 1 gm. streptomycin, 12-16 gm. PAS or 20 gm. sodium PAS, 1 cc moogrol daily. I am well aware that I cannot give in detail my results. If I eliminate cases with complicating genital tuberculosis, I am very well
TUBERCULOSIS OF URIKARY TRACT
623
satisfied with the results, although time since treatment is perhaps too short to speak of definite healing. In 7 cases with combined tuberculosis of bladder and single kidney (without cavities) after shorter or longer treatment, patients were free of symptoms; culture and guinea pigs became negative. Of another case, I shall give a short summary: A girl aged 23 had tuberculosis of the knee and the twelfth rib. She was in S,Yitzerland for a cure. In Hl48 a urological examination disc:losed that the urine was positive for tuberculosis. Destruction was in the upper pole of the right kidney. rrine from the left kidney was positi,-e. The patient was sent to me for a right nephrectomy after a cure with streptomycin and large doses of PAS. In August examma-
FIG. 4. A, wall of cavity covered b:v granulations. No necrosis, no tuberculous structurnThis is part of tuberculous cavit:v, which we consider as healed. B, only in circumscript part of cavity we find wall covered with active tuberculous gnmulations and necrosis (fibroblasts in palisade stand).
tion me disclosed that urine from the left kidney and bladder was positive. But to my surprise, the right kidney no longer was tuberculous, as established by culture and p1inca pig inoculation. After a cure of 1 month with streptomycin, PAS and rnoogrol, the urine was negative. Another case I should like to present ended with a nephrectomy, but a careful examination of this kidney shows clearly the healing power of streptomycinmoogrol. The patient was a man aged 42. He had tuberculosis of the right knee. Albumin, pus and bacilli in a density seldom seen appeared in the urine. Frography showed a small cavity in the right upper pole near the pyelum. The left kidney was normal. Streptomycin 1 gr. and moogrol 1 cc daily were given for 2 months, after which the urine became clear, with only a trace of albumin, a
624
D. VAN CAPPELLEN
few pus cells, and with great difficulty one or two bacilli were found. I was inclined to continue treatment, but the patient and his family desired operation, which I performed with reluctance. Professor Deelman of the -Cniversity of Amsterdam has examined this very precious piece with great care. He found a tuberculous process with every tendency to healing. I add some illustrations (figs. 1, 2, 3, and 4) to show you the details. It was a revelation for me to see a kidney which had produced purulent urine, with enormous quantities of bacilli, and where a cavity was on its way, to be cleansed. Which in the end will be the best treatment remains to be seen. But in addition to the remedies, of utmost importance to bring all these patients to a cure is that they must be treated in a sanatorium. REFERENCES DEBEAUFOND: 7th Congress of International Society of Urology, 1947. DuvERGEY, H.: J. d'urol., 55: 348, 1949. FEY, B.: J. d'urol., 49: 383, 1941. LATTIMER, J. K., AMBERSON, J.B. AND BRAHAM, S.: J. Urol., 62: 875, 1949. MEDLAR, E. M., SPAIN, D. M. AND HOLLIDAY, R. W.: J. Urol., 61: 1078, 1949. NESBIT, R. M. AND BoHxE, A. W.: J.A.M.A., 138: 927, 1948. OPPEi'iHEIMER, G.D. AND NARINS, L.: J. Urol., 62: 804, 1949. SE!vIB, C.: Acta chir. Scandinav., 98: 457, 1949. SLOTKIN, G. E.: J. Urol., 58: 464, 1947.