PREVENTION OF THE RECURRENCE OF URINARY CALCULI* ALEXANDER RANDALL, M.D. PHILADELPHIA I WISH to present a preIiminary report of some work which I have been doing in an effort to avoid that unpIeasant surgica1 sequence where, after the remova of a renaI caIcuIus, a recurrence of stone rapidIy foIIows. I beIieve we are now ready to agree that in the kidney, as in the bIadder, caIcuIus disease is no Ionger a disease at aI1, but a symptom. No matter how diffrcuIt a surgi- ca1 probIem may grow out of the presence of renaI Iithiasis, fundamentaIIy, its per- manent rehef is not to be sought in the simpIe remova of the stone but demands at the same time an appreciation and cor- rection of the condition which aIIowed of its formation. So Iet us Iook at the factors on which can be pIaced some reIiance as being causative : Third: The roIe pIayed by infection must be separated into its component parts. If it can be proved absent, stasis and chemica1 changes remain to us. If it be present, it may be expected to vary its inff uence in accordance with the individua1 behavior of the specific organism’s habits. Testing these fundamenta1 ideas against our experience with cIinica1 cases has Ied me to fee1 that in one variety of stone we are apparentIy approaching some under- standing of its causative factors. This is the so-caIIed earthy, or tripIe phosphate stone. First: Urinary stasis takes its pIace in renaI stone formation in equa1 force and importance as is granted to it in bIadder stone. FauIty drainage and urinary stagna- tion is the essentia1 preparation of the heId, possibIy present in an unappreciated Iarge proportion of persons, and onIy awaiting the turn of events for the second Iink to be forged in the deveIopment of the chain of circumstances on which hangs the uItimate deveIopment of a caIcuIus growth. Second: The probIem of the chemica1 character of caIcuIus formation becomes increasingIy intricate as one deIves into it. No one hypothesis can be stretched to fit a11 cases. We are practicaIIy forced to acknowIedge that the chemica1 change that aIIows a pure uric acid caIcuIus to form, must differ from that whence an oxyIate stone crystaIIized. As the chemica1 resuIts vary, so must the chemica1 cause. Ever since Marcet and SheeIe did their earIy chemica1 anaIysis of urinary caIcuIi, we have recognized their observation that once the formation of deposits of tripIe phosphate takes pIace, it is very rareIy superseded by other saIts. Again, this variety is known to be the cause of both the Iarge and the rapidly growing caIcuIi. To these characteristics I beIieve can be added the observation that once a tripIe phosphate stone is removed, subsequent stone formation wiI1 be of a simiIar chemi- ca1 character. I beIieve these characteristics to depend upon the behavior of certain infecting organisms, and on this basis have evoIved a step in preventive therapy, thoroughIy tested in alIied conditions in the Iower urinary tract, checked by Iabora- tory methods for effxciency and safety, and aimed to contro1 and to prevent the infec- tion responsibIe for this variety of stone. It is recognized that bacteria often have a very Iimited range of chemica1 reaction in which they normaIIy thrive. Change their cuItura1 habitat in this one factor, and bacteriostatic, or bacteriocida1, action is obtained. * From the Department of UroIogy, HospitaI of the University of PennsyIvania. Read before the Section on Genito-urinary Surgery, N. Y. Academy of Medicine, ApriI 20, 1932. 482
Transcript
PREVENTION OF THE RECURRENCE OF
URINARY CALCULI* ALEXANDER RANDALL, M.D.
PHILADELPHIA
I WISH to present a preIiminary report of some work which I have been doing in an effort to avoid that unpIeasant
surgica1 sequence where, after the remova of a renaI caIcuIus, a recurrence of stone rapidIy foIIows.
I beIieve we are now ready to agree that in the kidney, as in the bIadder, caIcuIus disease is no Ionger a disease at aI1, but a symptom. No matter how diffrcuIt a surgi- ca1 probIem may grow out of the presence of renaI Iithiasis, fundamentaIIy, its per- manent rehef is not to be sought in the simpIe remova of the stone but demands at the same time an appreciation and cor- rection of the condition which aIIowed of its formation. So Iet us Iook at the factors on which can be pIaced some reIiance as being causative :
Third: The roIe pIayed by infection must be separated into its component parts. If it can be proved absent, stasis and chemica1 changes remain to us. If it be present, it may be expected to vary its inff uence in accordance with the individua1 behavior of the specific organism’s habits.
Testing these fundamenta1 ideas against our experience with cIinica1 cases has Ied me to fee1 that in one variety of stone we are apparentIy approaching some under- standing of its causative factors. This is the so-caIIed earthy, or tripIe phosphate stone.
First: Urinary stasis takes its pIace in renaI stone formation in equa1 force and importance as is granted to it in bIadder stone. FauIty drainage and urinary stagna- tion is the essentia1 preparation of the heId, possibIy present in an unappreciated Iarge proportion of persons, and onIy awaiting the turn of events for the second Iink to be forged in the deveIopment of the chain of circumstances on which hangs the uItimate deveIopment of a caIcuIus growth.
Second: The probIem of the chemica1 character of caIcuIus formation becomes increasingIy intricate as one deIves into it. No one hypothesis can be stretched to fit a11 cases. We are practicaIIy forced to acknowIedge that the chemica1 change that aIIows a pure uric acid caIcuIus to form, must differ from that whence an oxyIate stone crystaIIized. As the chemica1 resuIts vary, so must the chemica1 cause.
Ever since Marcet and SheeIe did their earIy chemica1 anaIysis of urinary caIcuIi, we have recognized their observation that once the formation of deposits of tripIe phosphate takes pIace, it is very rareIy superseded by other saIts. Again, this variety is known to be the cause of both the Iarge and the rapidly growing caIcuIi. To these characteristics I beIieve can be added the observation that once a tripIe phosphate stone is removed, subsequent stone formation wiI1 be of a simiIar chemi- ca1 character. I beIieve these characteristics to depend upon the behavior of certain infecting organisms, and on this basis have evoIved a step in preventive therapy, thoroughIy tested in alIied conditions in the Iower urinary tract, checked by Iabora- tory methods for effxciency and safety, and aimed to contro1 and to prevent the infec- tion responsibIe for this variety of stone.
It is recognized that bacteria often have a very Iimited range of chemica1 reaction in which they normaIIy thrive. Change their cuItura1 habitat in this one factor, and bacteriostatic, or bacteriocida1, action is obtained.
* From the Department of UroIogy, HospitaI of the University of PennsyIvania. Read before the Section on Genito-urinary Surgery, N. Y. Academy of Medicine, ApriI 20, 1932.
482
NEW SERIES VOL. XVIII, No. 3 RandaII-Urinary CaIcuIi American Jourd of Surgery 483
There is a recognized group of organisms carried out the foIIowing steps in our which reguIarIy produce, and then flourish cIinica1 materia1 in an effort to obtain a in an aIkaIine urine, and in this media prevention of the infection by changing
FIG.
of ii’ r0’
30mi ,arative curves of four weak acids, giving point of simiIar osmotic pressc
and on right the pH vaIue or acidity, whiIe betow is percentage strength or aIkaIi
find a suitabIe habitat wherein they rapidIy change urea into ammonia, with a resuIting precipitation of the aIkaIine inorganic saIts of caIcium, magnesium and ammonia, of which the characteristic phosphatic caIcuIi are formed.
In order to controI this chemica1 change in the urine favorabIe for bacteria1 growth and phosphatic precipitation, we have
to
ldil
serum,
lg capac
point
:ity.
the chemistry of the urine, and in so doing creating a habitat in which bacteria responsibIe for the same wiI1 not grow.
Our first step was in the treatment of suprapubic fistuIae foIIowing cystostomy with subsequent drainage. The picture is famiIiar to you a11 of the postoperative prostatic patient, whose wound breaks down, creating a surgica1 menace, that is
484 American Journal of Surgery RandaILUrinary CaIcuIi
a marked detriment to normaI heaIing and cIosure. These wounds appear to be essen- tiaIIy reIated to an aIkaIinization of the urine, and at their worst present an ugIy, sloughing gangrenous sore on whose waIIs and even on the abdomina1 skin there is IikeIy to be deposited encrustations of phosphates. Some time ago we experienced the ease with which such encrustations could be removed, in fact dissoIved, by the topica appIication of a 3 or IO per cent phosphoric acid soIution. The response in heaIing foIIowing such IocaI treatment is marked; a heaIthy wound rapidIy foIIows the separation of the ugIy sIough, with the compIete disappearance of phosphatic en- crustations. Even in the absence of such breaking-down of the wound, an ammonia- ca1 odor appearing in the dressings, to the initiated, is a warning that troubIe is in store. Since adopting this step; the hand- ling of such bIadder cases by the topica apphcation of this weak acid soIution has made this compIication gratifyingIy infrequent.
The second step in our cIinica1 handIing of these cases was in certain patients where, though the bIadder wound was saved from the threatened breaking down, nevertheIess, the constant threat of such a possibihty was evident in the persistent poo1 of aIkaIine urine draining from the bIadder. No amount of acidifying drugs by mouth appears to be sufficient in these cases to change the reaction of such an aIkaIine urine to a norma acidity, whiIe topica appIications to the f%tuIa orifice fai1 of sufficient penetration to reach the bIadder urine. It was in such a case, some time ago, that I first attempted a direct irrigation of the bIadder cavity with a soIution of I per cent phosphoric acid. To our surprise it became evident that the bIadder not onIy toIerated this soIution without discomfort, but even a stronger soIution couId be used without marked irritation being experienced by the patient. One or two such irrigations caused a prompt return of norma bIadder urinary acidity, and this once obtained it was
easiIy heId by the administration of the acidifying drugs by mouth.
This improvement in the handIing of these cases has since become a routine in a11 our suprapubic cystostomies, and I fee1 it is a definite step in advance in controIIing the possibiIity of postoperative infection with the type of organism which is recog- nized to have the foregoing characteristics of both aIkaIinizing the urine and causing a precipitation of the earthy phosphates.
This finding in the Iower urinary tract naturaIIy Ied to our third step in attempt- ing to accomplish the same end in cases of recurrent caIcuIi in the upper urinary tract. As stated before, these stone repeaters practicaIIy aIways form phosphatic stones, and with this in view, I wish to report to you our experiences to date in I I cases in which we have irrigated the renaI peIvis postoperativeIy with phosphoric acid soIu- tion. It is my hope that by so doing we can cause a steriIization of the infection with the organisms which have the afore-de- scribed characteristics if they be present, or be a prophyIactic against their impIan- tation. Such, I feeI, to be a justifiabIe step towards the prevention of recurrent phos- phatic caIcuIus in the upper urinary tract.
In acidifying the urinary passages by irrigation, three quaIities are desired in the acid chosen: (I) It shouId not have to be used in a concentration which wouId have an osmotic pressure greatIy above that of serum for so it wouId tend to irritate the mucosa by its dehydrating effect. (2) It shouId have as high an aIkaIi binding capacity as possibIe to minimize the neutraIization by aIkaIi or buffers in the cavity. (3) It shouId have as high an acidity as the tissues wiI1 toIerate.
Phosphoric acid in concentration of I
gm. per I00 c.c. is approximateIy 0. I00 moIar, has a pH about 1.5 to 1.6 and pos- sesses 46 per cent of the osmotic pressure of the serum. This acidity, pH 1.6, is somewhat Iess than that of norma stomach contents after a test mea1 which, with a free HCI of 40, have a pH of about 1.4. A soIution of hydrochIoric acid having the
NEW SERIES VOL. XVIII, No. 3 RandaII-Urinary CaIcuIi American Journal of Surgery 485
same pH of 1.6 has a concentration of onIy o.oIg moIar and hence has onIy $g the aIkaIi binding power of phosphoric acid at this same pH.
Lactic acid at a concentration of 2.7 gm. per IOO C.C. has an osmotic pressure equa1 to serum but a pH of onIy 2.2, about one- sixth as acid as phosphoric acid of the same concentration; indeed even at IO per cent concentration the pH of Tactic acid is 0nIy 1.9.
Acetic acid is stiI1 weaker and when at a concentration of I .8 gm. per IOO c.c., which has an osmotic pressure equa1 to serum, its pH is onIy 2.6; even at IO per cent con- centration its pH is onIy 2.2. It has about one-thirteenth the acidity of a phosphoric acid soIution of the same concentration.
It folIows that both acetic and Iactic acids are too weak to be suitabIe for an irrigating soIution. On the other hand, a soIution of hydrochIoric acid wiII have this pH at so Iow a concentration that it has onIy one-fifth the aIkaIi-binding capacity of the corresponding phosphoric acid.
Of these four acids onIy phosphoric acid fuIfiIIs the requirements for an irrigating soIution with pH of about 1.6.
Experiments on dogs’ kidneys have been performed and repeated by injecting the peIvis through the ureter from a Iaparot- omy incision with a I, 3 and 5 per cent phosphoric acid soIution. One kidney was removed immediateIy, and the second one removed at the end of forty-eight hours. We have not been abIe to demonstrate, on microscopic study of these experimenta dogs’ kidneys, any evidence of damage to the peIvic epitheIia1 Iining or the renaI papiIIae; nor is there any evidence in these sections of any caustic action from the use of the drug in the afore-named strengths.
CASE REPORTS
CASE I. S. N., maIe, white, aged thirty- eight years. In September, 1925, the patient was suddenIy taken with an attack of Ieft uretera coIic. A diagnosis of Ieft uretera stone was made, and a Ieft ureteroIithotomy was performed.
Three months Iater, December, 1925, he experienced a duI1 pain in the right Ioin which was subsequentIy diagnosed as stone in the right kidney. He was again operated upon and seven smaI1 stones removed. Subsequent to this he spontaneousIy passed two smaI1 stones.
For the next four years he had miId attacks of right renaI pain, Iasting from two to six hours. During this interva1 he was twice admitted to other hospitaIs for study, but on each occasion he refused operation, and apparentIy a11 that was done was a catheter drainage of the kidney, with the subsidence of chiI1 and fever which had accompanied each attack.
His first admission to the University HospitaI was on July 17, 1930. Study showed a ureteral caIcuIus in the lower third of the right ureter. After severa attempts to aid the stone’s passage, a right ureteroIithotomy was per- formed on July 25, 1930, under spinal anes- thesia. ConvaIescence was uneventfu1 and he Ieft the hospita1 on August I 2,Igso. A foIIow-up cystoscopic examination, on September 8, 1930, showed no obstruction to the right ureter, though the peIvic urine was Ioaded with pus ceIIs, and a Iavage with I per cent mercurochrome soIution was performed. The patient was re-admitted in November, 1930, remaining in t.he hospita1 four days for study. Diagnosis : Right pyelitis, with an x-ray shadow suspicious of right renaI caIcuIus.
He was again admitted to the hospital in January, 193 I, for seven days, compIaining of constant right-sided pain radiating down the Iine of the right ureter. At this time a puruIent right peIvic urine was obtained. An x-ray pIate suggestive of a shadow in the right kidney region was obtained, whiIe Iow in the ureter appeared an oval shadow similar to that seen in the pIates at the time of his right ureteroIithotomy. There was no obstruction to catheter passage, nor in the previous, or this admission had there been any fever. His next admission was three months Iater, in March, 1931, when a more compIete study was aIIowed and a recurrence of his caIcuIus in the Iower right ureter substantiated. Two operations were attempted at this time and both faiIed: the first, from an inabiIity to satisfactorily expose the lower third of the ureter extraperitoneaIIy; and the second, when this was successfuIIy done, the stone was
486 American Journal of Surgery RandaII-Urinary CaIcuIi DECEMBER, ,932
found to have migrated away from the fieId FoIIowing his discharge, the patient has of attack. reported reguIarIy at intervaIs of two weeks
After further attempts at dilating the Iower for right peIvic Iavage and uretera diIatation.
TABULATION OF CASES
1 _
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__ ._ __ ._ _. __ ._ ._ -
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NO. ! I Name Operations Chemistry PeIvic Lavage Drain
Removed Final Studies Uretera Lavage
Every z weeks
4 mos. Iater R. peIvic urine pH 6.1
7 mos. later R. pelvic urine PH 7.4
L. pelvic urine pH 5.9
Every 2 6 mos. later R. pelvic urine weeks pH 6.0
Ca. & mg. phos. Ca. carbon.
I. S. N. I. L. Ureterolithot. a. R. NephroIithot.
(Voided caIcuIi) 3. R. Ureterolithot.
4. R. UreteroIithot.
Daily 1% sot. 8th p.o. day phosphoric acid
once 3 % sol.
2. G. E. I. R. Pyelolithot.
-- 3. J. W. L. I. R. Ureterolithot.
2. L. Pyelolithot. 3. L. Pyelolithot. 4. R. Ureterolithot. 5. R. Ureterolithot.
R. Pyelolithot. R. Nephrolithot.
Uric acid Ca. carbon.
Ca. & msg. phos
Q.z.d.I% sol. 11th p.o. day
Q.z.d.I% soI. zrst p.o. day 5 mos. later R. pelvic urine PH 5.8
Has coral calculus in L. pelvis
Every 3 weeks
once 2 % sol. Ca. oxylate
Ca. carbon
I. L. Pyelolithot. Ca. carbon. Na. “rate
DaiIy I % sol. 17th p.o. day 2 mos. Iater L. pelvic urine PH 5.3
I. R. PyeIolithot. Ca. carbon. Na. urate Uric acid
Daily I % sol. 1 5th p.0. day 2 mos. Iater R. peIvic urine pH 6.0
NOIll?
NOIE Ca., oxylate
Ca. carbon.
Fragment in pelvis post- operatively. Attempted to dissolve it to no wait. Removed with forceps on z3rd p.o. day
II. H. B. Congenital solitary kid- ney
I. R. PyeIo!ithot. R. Nephrolithot.
Every other z3rd p.o. day hour for one hour.
I % SOI.
I I
ureter in the hope that this stone wouId pass spontaneousIy, the fina operation was per- formed in October, 1931, and the stone removed from the upper third of the ureter after fixing it by an indweIIing catheter. A tube was pIaced in the ureter up to the peIvis and the wound cIosed about it. The peIvis was daiIy irrigated with I per cent phosphoric acid and on one occasion a 3 per cent soIution was used. There was no evidence of any IocaI disturbance or pain, and when the tube was removed on the eighth postoperative day, primary cIosure of the wound rapidIy foIIowed.
During his stay in the hospita1, and subsequent to his discharge, he has been put on the reguIar administration of a dram of cod liver oil twice daiIy, and urged to continue a diet containing Iarge quantities of miIk and eggs. On January 8, 1932, his right peIvic urine was cIear of pus, but stiI1 weakIy aIkaIine; whiIe on February 23, 1932, it was steriIe to cuIture, and of a pH 6.5. On ApriI 30, 1932, the right peIvic urine was stiI1 aIkaIine to Iitmus and had a pH of 7.4, whiIe the Ieft peIvic urine was acid to Iitmus and had a pH of 5.7. This case is stiI1 under observation.
NEW SERIES VOL.. XVIII, No. 3 RandaII-Urinary CaIcuIi American Journal of Surgery 487
His recent caIcuIus was composed of caI- cium and magnesium phosphate and caIcium carbonate.
CASE II. G. E., maIe, white, aged thirty-six years, admitted to the University Hospital, November 6, 1931. Diagnosis: CaIcuIus in the right renal peIvis. This caIcuIus occurred in an intrarena1 peIvis and at operation diffIcuIty was experienced in getting sufficient exposure for the tota remova of the stone, so that during traction the caIcuIus broke and numer- ous fragments were obtained after carefu1 search. A tube was inserted in the peIvis and the wound cIosed about the drainage. The peIvis was irrigated daiIy with a I per cent mercurochrome soIution, aIternating with a I per cent phosphoric acid soIution. The tube was removed on the eIeventh postoperative day. The patient was discharged on November 26, 1931.
Since the date of his discharge the patient has reported at two-week intervaIs for renaI peIvic Iavage with phosphoric acid and has been pIaced upon a diet rich in vitamin A,
and cod Iiver oi1 in doses of I dram twice daily. On February 6, 1932, the catheterized specimen was cIear, and of a pH 5.8. On May I, 1932, the right peIvic urine was acid to Iitmus and had a pH of 6.0.
The caIcuIus was composed of uric acid and caIcium carbonate. A postoperative x-ray was negative for any evidence of fragments.
CASE III. J. Vc’. L., white, aged forty-two years. The patient was first seen in June, 1919, at which time chronic prostatitis was present, and for which treatment was given at intervaIs for the subsequent four years. In 1923 dysuria with frequency deveIoped and for the first time the patient reported the passage of four urinary caIcuIi from the right kidney. In previous years, and at this study, his urine was found to be aIkaIine, with a definite infection in the right kidney pelvis. During the succeeding years, unti1 September, 1928, numerous studies were made in an effort to determine the presence of tubercuIosis; as we11 as an intermittent series of treatments for a persistent chronic prostati- tis. During this time the bIadder continued to get more and more intoIerant, with a persistent aIkaIine urine and areas of marked uIceration. X-rays and pyeIograms as earIy as February, 1923, had shown minute shadows in the Iower caIyx of each kidney. These were considered
to be caIcuIi, but as they measured but 6 X 4 mm. in size on the x-ray fiIm, no operative interference was advised. Functiona studies repeatedIy showed the Ieft kidney to have haIf the function of the right, and both dimin- ished beIow normaI. Three cuIture studies of the prostatic secretion remained steriIe; whiIe repeated studies for the tubercIe baciIIus (eIeven in aI1) brought forth but one report of organisms suspected of being the tubercIe baciIIus. In September, 1928 an acute right uretera bIockage required an immediate ure- teroIithotomy in the upper third of the right ureter; recovery from which was prompt.
The finding of the one positive cuIture for the tubercIe baciIIus, pIus his persistent and aggravated cystitis, caused the advice for him to go into the southwest, and whiIe in New Mexico, during the summer of 1929, two operations were performed a month apart for an acute uretera caIcuIus bIockage on the Ieft side.
On his return, in the faI1 of 1929, x-ray exami- nation reveaIed pocketed caIcuIi in the Iower caIyx of the right kidney, and two smaI1 but suspicious shadows in the region of the Ieft kidney peIvis. On June 4, 1930, a second acute caIcuIus bIockage of the right ureter neces- sitated a second ureteroIithotomy to be per- formed on the right side in the upper third of the ureter. In November, 1930, a uroseIectan study demonstrated the growth of the smaI1 shadows in both the right and Ieft kidney peIves, but their size was no greater than couId be expected to be passed in case disIodgement occurred. In fact, on numerous occasions, smaI1 caIcuIi varying in size up to 5 mm. in diameter were spontaneously voided, and during this time the bIadder capacity rareIy exceeded 4 ounces. On November 28, 1930, a sizabIe soft stone was passed from the Ieft ureter after a coIic of a few hours’ duration. During the ten months’ interva1 between November, 1930, and September, 1931, enormous growth of stone took pIace and a uroseIectan study of September, 1931, showed typica cora1 caIcuIi in both the right and Ieft renaI peIves.
On November, 2, 1931, a faI1 from horseback was sustained and five days later severe colic with compIete right uretera bIockage occurred, again associated with aIarming cIinica1 symp- toms of an infectious character. A catheter was successfuIIy passed by the stone and peIvic drainage obtained, and on November 16, 193 I,
488 American Journal of Surgery RandaII-Urinary CaIcuIi
a third ureteroIithotomy was performed foI- Iowed by a pyeIotomy, with remova of the Iarge peIvic stone; then a nephrotomy into the Iower calyx was done with the complete evacuation of the nest of caIcuIi which had been observed there over a period of four years. (X-ray studies prior to this operation compared with the studies made two months before showed convincing evidence that the trauma sustained at the time of his faII had fractured the cora1 stone in his right kidney, a portion of which had caused the right uretera bIockage.)
Drainage was instituted at this operation to both the pyeIotomy and the nephrotomy incisions. This drainage was sustained for a period of three weeks and the peIvis was irrigated daiIy, aIternating between potassium permanganate followed by mercurochrome, and a I per cent phosphoric acid. It is of especia1 note that the phosphoric acid caused no renaI discomfort, but reguIarIy produced a sense of burning, not unbearabIe, in the bIadder. The drainage tubes were removed at the end of three weeks and the fistuIa cIosed four days Iater. X-ray on December 18, 1931, the date of discharge from the hos- pitaI, proved the right kidney negative for calcuIi.
Since his hospita1 discharge, the patient has reported at ten day intervaIs for cystoscopic right ureteral catheterization and Iavnge. It is of importance to record that the first time in the period of eight or more years, the bIadder has become toIerant of cystoscopy without sacra1 or spina anesthesia. Its capacity has increased from 4 ounces to 14 ounces. The vesica1 Iesions have retrogressed to a point where onIy an area possibIy 1.3 X 2 cm. in size in the fundus of the bIadder where the mucous membrane is stiI1 redundant, sodden and red. On January 12, 193 I, urine coIIected from the right renaI peIvis was briIIiantIy cIear and weakIy acid; whiIe the bIadder urine was stir1 aIkaIine. Catheterization on January 28, 1932, showed the right kidney peIvic urine to have a pH of 5.8; whiIe cuIture showed, on March 28, 1932, from the right side-an organism cIoseIy reIated to encapsuIatus pneu- monia and B. atrosepticus, and a pH 6.2; and from the Ieft side (stiI1 stone bearing) a simiIar infection, and a pH 7.6.
The Iast stone removed from the right kidney was composed of caIcium and magnesium
phosphate, caIcium oxyIate, and caIcium carbonate.
CASE IV. C. S., male, aged twenty-nine years, admitted to the hospita1 February 26, 1932, compIaining of attacks of pain in the Ieft Ioin and Ieft abdomen. These symptoms have been present at intervaIs over the past six years. X-ray showed a caIcuIus in the upper third of the Ieft ureter opposite the Iower poIe of the kidney. On March 2, 1932, an indweIIing catheter was pIaced to the renaI peIvis, foIIow- ing which a Ieft ureteroIithotomy was per- formed under a spina anesthesia. The stone was found just below the ureteropeIvic junction and the uretera waI1 markedIy thickened. Incision of the ureter faiIed to find the stone, and incision enlarged to peIvis through which the stone was found in the Iower caIyx and removed in toto. A No. 16 F. catheter was passed down the ureter and the ureter cIosed about it bringing it out through the posterior peIvic waI1. A Iarger tube drain was pIaced in the peIvis through the same peIvic opening. Through the drainage tube the peIvis was irrigated daiIy with a I per cent soIMion of phosphoric acid. The tube was removed on the seventeenth postoperative day.
Two months later, on ApriI 30, 1932, urine coIIected from the Ieft renaI pelvis was strongIy acid to Iitmus, and gave a pH reading of 5.3.
On anaIysis the stone was found to consist of caIcium carbonate and sodium urate.
CASE v. S. D., femaIe, aged fifty-seven years, was transferred from the MedicaI Service and found to have huge biIatera1 stag-horn caIcuIi in both renaI pelvis. She suffered particuIarIy from pain in the right Ioin and seemed quite weak and Iethargic. An indigocarmine test appeared from the right ureter in fourteen minutes, and from the Ieft ureter in ten minutes, but with only fair concentration of the dye. PhenoIsuIphonephthaIein test gave 20 per cent for the first hour; IO per cent for the second hour. BIood urea nitrogen 24 mg. per 100 C.C.
Operation was performed on February 24, 1932, and a large stone successfuIIy removed from the right kidney pelvis, by a pyeIoIithot- omy, and a Iarge drainage tube was pIaced through a nephrotomy incision. She received a daiIy irrigation of the renal peIvis with I per cent soIution of phosphoric acid during twenty postoperative days, at the end of which time the tube was removed.
NEW SERIES VOL. XVIII, No. 3 RandaII-Urinary CaIcuIi American Journal of Surgery 489
One week after this operation her bIood urea nitrogen was 27 mg. per IOO C.C. On March 13,
the blood urea nitrogen was 19 mg. per 100
C.C. On March 22, the blood urea nitrogen was 26 mg. per IOO C.C.
Her convaIescence was uninterrupted, though she went home, on March 24, against our advice and before compIete heaIing was accom- pIished. Subsequent observations have not been obtainable.
AnaIvsis of the stone showed it to consist of caIcium carbonate and tripIe phosphates.
CASE VI. F. T., maIe, aged forty-four years, entered the hospita1 December 3, 1931, com- pIaining of Ieft Ioin pain. Sixteen years ago the patient suffered a simiIar attack which was relieved by a hypodermic, and there is no record of a stone being passed. Four months prior to admission he was seized with a severe Ieft abdomina1 pain which was again reIieved by a hypodermic of morphia, and a third attack of simiIar colic occurred five days before admission, continuing to date of same. X-ray study reveaIed a stone in the Iower third of the Ieft ureter, measuring 8 X 6 mm. The catheter obstructed at 8 cm. from the uretera orifice. His urograms showed no evidence of peIvic back pressure. Nineteen days were consumed in various attempts at cystoscopic reduction and remova1. This being unsuccessfu1, a ureteroIithotomy was performed on Decem- ber 23, 193 I, and a soIitary stone removed. A catheter drainage was pIaced to the peIvis through which, on one occasion onIy, a I per cent solution of phosphoric acid was instiIled. This drain was removed on the fourth day, and on four occasions, postoperativeIy, the renaI peIvis was irrigated at two-weekly intervaIs by cystoscopic uretera catheterization.
The stone was not anaIyzed, but has the appearance of a caIcium 0xyIate caIcuIus.
CASE VII. M. G., femaIe, aged fifty-one years. This patient was admitted to the service of Dr. F. E. Keene on December 13, 1931.
She entered the ward with a permanent right nephrostomy sinus. Her previous history recounts an appendectomy, a Ieft nephrectomy for stone, an oophorectomy, a right nephro- Iithotomy, and Iater an operation for bIadder uIcer and a permanent drainage for a recurrent caIcuIus pyonephrosis of the remaining right kidney, which was performed JuIy 6, 1930. She was in a critica condition from renaI insuffIciency, and her sinus tract was coated
with phosphatic concretions. X-ray showed numerous irreguIar shadows extendmg down the sinus and invoIving the remains of a Iarge pyonephrotic kidney. Her urinary drainage was strongIy aIkaIine with a typica ammoniaca odor. After x-ray studies and various IocaI measures had been tried, irrigations of the sinus tract with I per cent phosphoric acid solution was started on February 28, 1932. These were continued daiIy for five days with- out apparent discomfort, and with marked improvement in the wound’s condition. The patient died suddenIy of cardiac failure on the night of March 3, 1932.
AnaIysis of the caIcuIus showed it to be of typica tripIe phosphates. This shouId have been a test condition in which to have obtained an ideal therapeutic resuIt, and it is regrettabIe that sudden death defeated the outcome.
CASE VIII. H. H., maIe, aged forty-three years, admitted to the hospita1 March 2, 1932. History recounts a previous left pyeIoIithotomy for two renaI caIcuIi. The patient had suffered soreness and pain in the Ieft side for the past three years. X-ray examination reveaIed two stone shadows in the Ieft pelvis; whiIe uro- grams showed one to be in the Ieft renaI peIvis, and the other in the Iower major caIyx.
Operation performed on March g, 1932, demonstrated a stricture at the ureteropeIvic junction, through which the incision was carried and two Iarge stones were removed through this pyelotomy opening. A nephrotomy was per- formed through the Iower major caIyx and tube drainage brought into the peIvis. PyeIotomy incision was closed about a No. 12 rubber catheter inserted down the ureter and brought out through the nephrotomy wound with pIastic reconstruction of the ureteropeIvic junction. Daily irrigations with a I per cent soIution of phosphoric acid were carried on through the drainage tube for seventeen days; the pH of the peIvic urine remaining at 6.0. The tube was removed on the seventeenth day.
ConvaIescence was uncompIicated. CuIture of the urine showed baciIIus coIi communis.
AnaIysis of the stone reveaIed it to be of caIcium carbonate and sodium urate.
CASE IX. J. A., maIe, aged twenty-eight years, admitted to the hospita1 ApriI 4, 1932, compIaining of pain in the right side of the abdomen. There had been no previous opera- tions. Study reveaIed a Iarge caIcuIus in the
490 American Journal of Surgery RandaII-Urinary CaIcuIi
right renaI peIvis, which was moderateIy hydronephrotic.
An operation was performed on ApriI 6, 1932, at which time a Iarge stone was removed by a right pyeIoIithotomy, with a tube drainage to the renaI peIvis. Irrigations of a I per cent soIution of phosphoric acid were carried on through this tube every other day for three appIications. The tube was removed on the sixth postoperative day.
ConvaIescence was uncompIicated. AnaIysis of the stone showed it to be of
caIcium carbonate. CASE x. S. F., maIe, aged forty-three
years, admitted to the hospita1 March g, 1932, compIaining of pain in the right renaI region of six months’ duration. Study reveaIed a stone of eIongated shape fiIIing a smaI1 intrarena1 peIvis and pIugging the uretero- peIvic 0utIet.
Operation was performed on March 16, 1932, and the stone removed through a smaI1 pyeIotomy incision. The onIy obstruction demonstrated was the adhesion of the ureter to the Iower poIe of the kidney, with moderate distortion of its course. A smaI1 rubber catheter was pIaced as a drain, through which a daiIy irrigation of I per cent phosphoric acid soIution was carried on for the foIIowing five post- operative days.
ConvaIescence was rapid and uneventfu1. On May 5, 1932 his right peIvic urine was found to be cIear with a pH of 6.0.
AnaIysis of the stone proved it to be of caIcium carbonate, sodium urate and uric acid.
CASE XI. H. B., maIe, aged twenty-eight years, admitted to the hospita1 ApriI I, 1932, compIaining of right Ioin pain. This patient had been carefuIIy studied before admission and a11 evidence pointed to the fact that he had a congenita1 absence of the Ieft kidney, with a large stag-horn caIcuIus in the peIvis and Iower caIyx of the soIitary right kidney.
Operation was performed on April 12, 1932, and after a Iarge pyeIotomy incision was obtained, the calcuIus unfortunateIy broke on attempted removaL The portion remaining was impacted in the Iower caIyx. A nephrotomy was then performed over this point and the fragment was successfuIIy removed. Recon- struction of the stone suggested that a third fragment was absent, though thorough search at operation and copious Iavage of the peIvis faiIed to detect it. A large tube drain was
pIaced through the nephrotomy wound to the peIvis and bIeeding controIIed by a mattress suture on either side of it. No repair of the pyeIotomy incision was attempted.
Five days after operation, x-ray study re- veaIed a fragment 7 mm. in diameter apparentIy Iying in the peIvis 3 cm. from the end of the drainage tube. Before obtaining an anaIysis of the stone an attempt was made to dissoive this fragment by intermittent irrigations of I per cent soIution of phosphoric acid. This was accompIished by passing a uretera catheter through the lumen of the drainage tube into the renaI peIvis. This catheter was connected through a Murphy drip with a transfusion burette, and for the subsequent fourteen days irrigation with I per cent soIution of phosphoric acid was run through this at intervaIs of an hour on and an hour off. No discomfort was experienced except occasionaIIy when the patient voided smaI1 quantities of urine there was a feeIing of slight burning in the bIadder and urethra. At the end of two weeks x-ray study faiIed to revea1 any change in the stone’s size, and a second smaI1 shadow was observed in the upper caIyx. When comparing this pIate with the one taken five days after operation (the Iatter having been taken in bed without preparation, and was not as cIear as couId be desired) showed that this second shadow was probabIy Iikewise present in the earIier pIate too.
FaiIing of dissoIution of the stone, an aIIigator forceps was passed through the drainage tube and the Iarger and Iower stone successfuIIy removed with the tube at one time. Since we feIt somewhat uncertain of the smaIIer shadow in the upper caIyx, the wound was aIIowed to hea and the patient voided a smaI1 stone with- out coIic four days after the removal of the other stone. AnaIysis of these stones proved them to be of caIcium carbonate and caIcium 0xyIate.
SUMMARY
I. Phosphoric acid I per cent has a pH acidity of approximateIy 1.6. Its bacterio- cida1 vaIue is based thereon.
2. Phosphoric acid I per cent is practi- caIIy isotonic and is sIightIy Iess acid than the gastric acidity after a test meal.
3. In experimenta dogs, renaI peIves injected with I, 3 and 5 per cent phosphoric
NEW SERIES VOL. XVIII, No. 3 RandaII-Urinary CaIcuIi American Journal of Surgery 491
acid fai1 to show any destruction of peIvic Iining epitheIium, or damage to the renaI papiIIae.
4. Eleven patients in whom renaI peIvic Iavage with I and 2 per cent phosphoric acid soIution has been used, either through a postoperative drainage tube, through a uretera catheter, or both, have not experi- enced discomfort or excessive renaI pain. The bIadder is Iess toIerant than the ureter Qr kidney peIvis, and the urethra is the least toIerant of aI1.
5. The renaI peIvic urine in recorded cases has been re-studied and with one exception has been found to retain a norma acidity foIIowing this postoperative Iavage.
6. This step in prophyIactic treatment in cases of recurrent renaI caIcuIi has a rationaIe in both co-reIated conditions in the Iower urinary tract and in bacterioIogi- ca1 findings.
CONCLUSIONS
I. By bIadder Iavage with phosphoric acid postoperativeIy, aIkaIinization and phosphatic encrustations can be prevented.
2. The treatment of staphyIococcic cys- titis, encrusting cystitis, IeucopIakia and aIIied conditions by this means is indicated.
3. The prevention of recurrent renaI caIcuIi of the phosphatic variety is being attempted with every indication of success.
4. The possibIe dissoIution of smaI1 phosphatic caIcuIi, or fragments Ieft at operation, may be expected by the recog- nized action of such strengths of phosphoric acid in vitro, and the toIerance of such topica appIications in vivo.
5. As a postoperative prophyIactic meas- ure against infection with the aIkaIi producing organisms, it is herein proven safe and efficacious in kidney surgery and shouId therefore aid in the prevention of recurrent renaI caIcuIi of the phosphatic variety.
DISCUSSION
DR. OSWALD S. LOWSLEY: Nothing can possibIy be more embarrassing than to have to
operate on patients repeatedIy for the same condition. It is happening to a11 of us. The prevention of urinary calculi is one of the most important things that we can consider. It has been our practice for some time to change the reaction of the urine in such patients by feeding them acid or aIkaIine, depending on the type of caIcuIus found at operation. It is true that in a Iarge stone, when one saws through it, such as a bIadder stone, there may be severa kinds of materia1, both alkaIine and acid, in the substance of the stone, therefore one cannot in every case be sure that the recurrence of stone wiI1 be eliminated by changing the reaction of the urine, but we are quite con- vinced that in most cases a change in the reaction of the urine will prevent recurrence of stone, because they seem to have a certain specificity. I have mentioned many times a spectacmar case in which we had to operate every six months for a period of time. About eight years has gone by now, and this Iady, who had had seven operations, five of them by us, has not had a recurrence in eight years, due mereIy to changing the reaction of her urine. The patient does this herseIf by taking acid, in her case, and testing her urine with Iitmus paper. She has Iearned how to keep her urine acid without going into acidosis, into which we promptIy put her when we instituted this treatment.
Dr. RandaII has mentioned a most important thing in connection with this, and that is, you must have good drainage. There is no question about it. I remember severa years ago Dr. McCarthy mentioned in the discussion of a paper here that his patients were reIieved of caIcium deposits on wounds by giving phos- phoric acid, and so we have been giving it, and it seems to work as we11 as IocaI irrigation.
I think it is proper in this connection to remember that one must ehminate a11 possibIe sources of foca1 infection. The brihiant work done at the Mayo CIinic in isoIating bacteria from the tooth and actuaIIy producing stone in the dog’s kidneys by injecting these bacteria must make us be alive to the fact that there may be specificity of bacteria, and therefore it is part of our routine always to eIiminate every possibIe source of infection, in the mouth, tonsils, teeth, sinuses, and so on.
DR. J. A. KILLIAN: For a number of years we have been interested in the probIem of urinary caIcuIi from the standpoint of the reIationship
492 American Journal of Surgery RandaII-Urinary CaIcuIi
of their formation to metabohc reactions in the body, and up to date we have no informa- tion of positive value, either concerning their etioIogy, or methods of preventing their recur- rence. However, our work has brought to Iight a few suggestions which we consider of some practica1 vaIue. With regard to the change in the reaction of the urine, I think it is important to bear in mind that not onIy bacteria have the abiIity to transform urea or amides into ammonia; norma kidney tissue aIso has that property, and according to the work of BIiss, it is probabIy most potent of a11 the tissues in the body in its reaction of de-amidization. Moreover, this abiIity to de-amidize on the part of the kidney tissue may vary with renaI function, either in one direction or the other. At the present time we cannot say whether a diminution of renaI function, so far as nitrogen excretion is concerned, is associated with a corresponding impairment of de-amidization. The increase in aIkaIinity in the urine, due to the ammonia formation, may not be entireIy the property of bacteria; it may be due to disturbance in renaI function. It is true that vitamin A deficiency changes the character of the epitheIium so that it is possibIe for crystaIs to become fixed or adherent to the epitheIia1 Iining, and the use of cod Iiver oiI to suppIy the necessary vitamin A is wise, not onIy on account of its suppIying Iarge quantities of vitamin A, but aIso because it suppIies vitamin D, whose principal function is concerned with the fixation of calcium and phosphorus in the body, and of course, preventing the Ioss of caIcium or phosphorus from the body in the excreta. In our advice to uroIogists to be handed on to patients, what we attempt to do is to avoid changes in the reaction of the urine (we are speaking now entireIy of phosphate caIcuIi), changes in the urine in the direction of increased aIkaIinity, and aIso to avoid an excess of caIcium, magnesium and phosphate which may be excreted in the urine. I think by carefu1 restriction of the diet we can do more to reguIate the reaction of the urine than we can by the administration of acids by mouth, with the possibIe exception of phos- phoric acid.
The first thing we do is to avoid the giving of bulky meals, because this is foIIowed by an aIkaIine tide in the urine. This is greatest foIIowing the morning mea1, Iess folIowing the noon or afternoon mea1, and it varies directIy
with the quantity of HCI secreted by the stomach, and the quantity of HCI secreted by the stomach varies again directIy with the bulk of the meat. About 1919 BIathewick pubIished a series of observations on the infIuence of fruits and vegetabIes on the reaction of the urine, and that Iist is vaIuabIe in the selection of fruits and vegetabIes which wiI1 increase the aIkaIinity of the urine. In choosing foods as a source of calcium and phosphorus, we bear in mind the fact that a11 observers who have studied the question of the utiIization of caIcium and phosphorus by the body, as for instance, Sherman, MendeI, ShohI, etc., have brought out the fact that when caIcium and phosphorus are utiIized by the body most satisfactoriIy under the influence of vitamin D, they are utilized or stored in about the same proportion in which they occur in miIk; usuaIIy two parts of caIcium to one part of phosphorus. In reguIating our caIcium and phosphorus in the diet, we attempt to observe that ratio.
Another important thing is this: it has been recentIy shown that probabIy the phosphate which occurs in the urine is not a11 fiItered from the bIood. It may be formed by the action of kidney tissue on hydroIyzabIe phosphates in the bIood. We therefore avoid giving a Iarge quantity of carbohydrate with any one meal because with a Iarge suppIy of carbohydrate we have an increase in the hydroIyzabIe phosphates in the bIood which furnishes avaiI- abIe materia1 for an increase of phosphate in the urine.
DR. JOSEPH F. MCCARTHY: Dr. KiIIian and I have conjointIy made it our ruIe to have the most precise quantitative and quaIitative estimations made of every stone removed; Dr. KiIIian then attempts to regulate the patient’s metaboIism as nearIy as possibIe from the biochemica1 standpoint. For quite a number of years we have been using aciduIated ffuids in the bIadder cases mentioned by Dr. RandaII with considerable success. I feel we are much indebted to Dr. RandaII for carrying out that idea to its IogicaI concIusion, the renaI pelvis. PersonaIIy, I think there are three factors: (I) the factor of obstruction, the primary factor; (2) the biochemical and (3) the factor of infection.
DR. VICTOR Cox PEDERSEN: The eIement of infection has been spoken of throughout the evening as to teeth and tonsiIs, but not materiaIIy as to the intestines. I think we do
NEW SERIES VOL. XVIII, No. 3 RandaIILUrinary CaIcuIi American Journal of Surgery 493
not do our duty by any of these cases unIess prevention is going to do anything of great we investigate what is going on in the intestinal benefit. It has been tried so many times and in canaI. Over and over again we find a very so many different ways. But that it is a factor active disorder, usuahy in the form of the in stone formation cannot be denied. I have failure of baIance of the bacteria that beIong been trying to read into stones the picture there, the B. coli group making up from 65 which most of us have of the necessity of finding to 95 per cent, associated with some of the an obstruction, and two weeks ago, in removing ordinary pus-producing organisms. Here we a kidney stone and being unabIe to demonstrate have a case in point. A man sixty-three years the reason for its being there, I had the oppor- oId, with no teeth, tons& out, suddenIy de- tunity of apoIogizing for my theory before the veIops hematuria. The phenoIsuIphonephthaIein cIass. I expounded on the idea of the dietary test is normaI; the urine is norma except for question as an answer in this patient. The bIood and numerous B. coli, staphyIococci and chap was under spina anesthesia, and I was enterococci. The intestina1 tract shows very taIking not to him, but to the cIass, of the active fermentation of carbohydrate with IikeIihood of dietary reasons being in his case butyric acid fermentation associated with it, the cause of stone formation, and the patient and some putrefaction. AI1 that is necessary spoke up and said: “You certainIy hit it on the in that man is obstruction somewhere in his head.” He ran a restaurant, and ate at the urine-secretory apparatus to produce pus there, most irreguIar hours and irreguIar food, and he either as a genera1 infection of the mucous said : “Moreover, my sister has had a stone membrane or a singIe focus of pus in the kidney, removed from her kidney, and my father died or muItipIe foci, or the precipitation of saIts of a kidney stone.” His was not a phosphatic in the formation of stone. By paying attention type of stone, but that there are factors, such to his diet and using urinary antiseptics we as diet, which enter into the problem, must have so far brought that man far aIong in the not be denied. Iine of convaIescence. If we can evoIve for him This study has three reasons for its presenta- the right kind of diet, that man shouId never tion: First, it begins to show that the renaI again have any troubIe from his urinary system, peIvis has been a noli me tangere for too Iong a but it was a hotbed of infection. I beIieve we time, and I beIieve we wiI1 Iearn to do more in are erring when we do not go into the intestine the way of IocaI handling of pelvic troubIes in for one of the sources of troubIe in a11 cases of the future. Secondly, I fee1 that the use of kidney trouble. phosphoric acid in the way outIined is a safe
DR. RANDALL (Closing) : The subject of stone step in preventive treatment, and a pro- is certainIy a bafhing one, and no theory is phyIactic against secondary phosphatic stone going to soIve the question in its entirety; formation. Thirdly, it may be curative in those the causes are too diversified. My remarks have been Iimited to phosphatic stone. I do
cases where aIkaIine forming organisms aIready
not think that dietary regime as a treatment or dominate the heId and are causing recurrent precipitation of phosphate concretions.
