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Some Recent Advances in Urologic Surgery
Some Recent Advances in Urologic Surgery ROGER BAKER, M.D., PH.D. *
THERE are fewer new instruments and operative technics introduced in urology today than in former years. The phenomenal progress curve of urologic diagnostic instruments and operative procedures has apparently approached a plateau. The most important recent advances in urologic surgery have been made not in the field of technical improvements but in those areas where attention has been concentrated on the research aspects of abnormal physiology. By its very nature progress in this direction is painfully slow but highly significant and durable. Some of these advances will be presented. A review of this type must be limited necessarily to a discussion of the latest forms of treatment or to trends in urology. Complete descriptions may be located in the specific urologic literature indicated. ANTIBIOTIC DRUGS
Urologists in particular have profited greatly by the research leading to discovery of the newer antimicrobial agents. It is often necessary to use indwelling catheters for long periods of time to divert the urinary stream or to splint anastomoses. These catheters are foreign bodies and promote infection. In addition many urologic wounds--are constantly bathed in urine which perforce also fosters infection. Use of the newer drugs effectively control most of these urologic infections and contribute immeasurably to improve operative results. Prior to prescribing antibiotic drugs it is advisable to obtain if possible a voided specimen of urine from males, utilizing the two-glass test, and a catheterized specimen from females. Gross examination and Gram stain are performed and the specimen sent to the laboratory for culture and sensitivity studies. Careful inquiry is made regarding any previous drug reaction. As Herrold has indicated, there is a substantial per cent From the Department of Surgery (Division of Urology), the University of Chicago, Chicago.
* Assistant Professor of Urology, University of Chicago School of Medicine; Attending Surgeon, Albert Merritt Billings Hospital of the University of Chicago. 311
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of the population already sensitized to the sulfonamides, penicillin or streptomycin so they can no longer be administered safely. Rarely, Gram stain will reveal all organisms to be gram-positive and if this be the case penicillin is administered. More frequently, the Gram stain will reveal mixed coccal and gram-negative bacilli. Penicillin and aureomycin are recommended for these patients. They are also administered to most postoperative patients until sensitivity tests are completed indicating use of a more specific drug. Penicillin continues to occupy a real place in treatment of infections due to gram-positive organisms. Though oral administration has been improved and is recommended by many there appears to be little need for its use in our clinic. There are several repository penicillin preparations containing compounds which delay absorption to the extent that blood levels of at least 0.15 unit per cubic centimeter may be obtained at the end of the two days. We believe this to be adequate for all but the most severe infections when more frequent injections are to be preferred. Gantrisin appears to be of greater value than the other sulfonamide drugs. It is effective apparently for the same range of bacteria inhibited by other sulfonamide compounds. In addition, gantrisin will also cure a high incidence of infections due to Pseudomonas aeruginosa and Escherichia coli which are not effectively treated by these compounds. Carroll and his associates have obtained no evidence of the development of increased resistance on the part of the organisms to gantrisin, which is in contrast with other sulfonamide drugs. In addition, the likelihood of crystalluria and the deposition of crystals within the renal collecting system is greatly reduced. Schnitzer and co-workers have evaluated this drug experimentally and find excellent solubility over a wide pH range. It is nearly impossible to form crystals at the physiologic range of pH 6.0 to 8.0. The maintenance of a large fluid intake and alkalinization of the urine usually necessary during therapy with other sulfonamide drugs is eliminated by use of gantrisin. This work has been confirmed clinically by Lazarus and Schwarz. Aureomycin and chloramphenicol (chloromycetin) have proved their therapeutic effectiveness against gram-positive cocci and gram-negative bacilli. Aureomycin is more effective than chloromycetin, terramycin or penicillin in combating streptococcal and staphylococcal infections. Instances of serious toxicity have been rare. The incidence of nausea, vomiting and diarrhea accompanying aureomycin administration has become very low as the drug has become further purified by removal of . foreign proteins. It has been suggested that tincture of belladonna be given prior to oral administration of aureomycin. Aureomycin combined with streptomycin (1 gm. daily) has been found more effective against Pseudomonas aeruginosa than chloromycetin. Chloromycetin combined with gantrisin (2 gm. daily) has been effective in treatment of some
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infections due to B. proteus. Herrold and Boand administer the same dosage for both aureomycin and chloromycetin: 3 gm. the first day, 2 gm. daily for the five succeeding days and then 1 gm. daily for four days. Others believe 2 gm. a day is adequate for severe infections, decreasing the dose to 1 gm. daily when the infection responds to therapy. Terramycin will cure some gram-negative urinary tract infections which have been refractive to other therapy. Knight finds it of little use in combating urinary tract infection in which the organism involved is either B. proteus or Pseudomonas aeruginosa. Interestingly enough, however, Linsell and Fletcher find nearly three-quarters of the strains of Pseudomonas were sensitive to terramycin. A few patients will develop nausea, vomiting and diarrhea. Nesbit believes an initial loading dose of 2 gm. should be followed by 1 gm. dosages at six hour intervals. Dihydrostreptomycin has a practically nonexistent incidence of neurotoxicity. Many sulfonamide-resistant gram-negative bacilli may be eradicated by use of this drug. Miller believes this to be the most effective known agent in treatment of infections due to B. proteus. Best results of treatment of tuberculosis of the urinary tract is obtained apparently with a combination of dihydrostreptomycin (1 gm. daily) and para-aminosalicylic acid (5 to 10 gm. daily) for periods of about twelve weeks. Deep infected wounds containing sloughing, nonviable tissue are best treated by local use of streptokinase-streptodornase. Administration of these fibrinolytic enzymes results in a clean granulating wound which greatly accelerates healing. Bacitracin will produce rapid healing of most superficial infections. RENAL TUMORS
It is still impossible to distinguish infallibly between renal cyst and renal tumor except by surgical exploration. Prather mentions several criteria to consider in the differential diagnosis but concludes his review by stating that "until a blood or biological test for malignancy is available, surgical exploration is indicated whenever a space displacing lesion is suspected in the kidney." If a renal cyst instead of tumor be found at the time of the exploration it should be opened, as a certain small percentage have cancer at the base. Hypernephroma
Advances in treatment of hypernephroma have been confined to surgical approach of nephrectomy. Certain basic tenets apply irrespective of the technic used. Early ligation of the renal pedicle before the kidney is manipulated will tend to decrease the traumatic dissemination of tumor particles. Besides venous metastases these lesions spread also by direct extension through the capsule of the tumor into the perirenal fat. In a study by Beare and McDonald of 488 cases of surgically removed hypernephroma, 343 were found to have malignant involvement
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of the capsule. Perinephric fat and Gerota's capsule should be removed en bloc therefore with the hypernephroma. In addition, all regional lymph nodes and fat should be stripped from about the pedicle, along the aorta and the vena cava. Surgical Approaches. The specific surgical approach to the hypernephroma is individual and must depend on the size of the tumor and the configuration of the patient's bony thorax. To be committed to one type incision for all renal tumors is unwise. Small renal tumors, particularly those of the upper pole, may be excised easily in the average patient by use of the routine posterior lumbar retroperitoneal or abdominal transperitoneal approach. Large renal tumors situated high under the rib cage may be exposed completely by the thoraco-abdominal route popularized by Chute. The technic of this nephrectomy is as follows: With the patient placed on his side the incision is made from the lateral border of the rectus at the level of the umbilicus, running laterally and upwards and posteriorly over the eleventh rib to the spine. The rib is resected in the usual manner. The pleural cavity is opened through the periosteal bed. Chute believes the phrenic nerve should be crushed with a hemostat at the point where it leaves the surface of the pericardium to enter the diaphragm. This stops diaphragmatic excursions. We have not found this necessary except in an occasional case where the motion interfered with the progress of the operation. The diaphragm is then incised in line with the skin incision. This incision is then carried forward through the decussation of the diaphragm with the transversus abdominis muscle and then continued through the oblique muscles opening the peritoneal cavity. The spleen is packed off and the renal artery and vein are dissected out and clamped. Nephrectomy is performed removing all perinephric fat and kidney en bloc. The diaphragm is approximated with interrupted silk sutures. After complete expansion of the lung the pleura is closed without drainage. Chute believes this surgical route should be employed for all kidney tumors as most nephrectomies for cancer will require more extensive surgery than simple nephrectomy, due to local extension, and this route provides best exposure. He claims that the incision is indispensable in cases where extreme kyphosis or scoliosis contraindicates use of the usual type of lumbar approach. O'Conor has reported use of transthoracic nephrectomy for Wilms' tumor in a 2 year old girl. We believe this procedure to be ideal for nephrectomy for most large hypernephromas, particularly those situated high under the rib cage. The principal objection has been the great length of time necessary to perform exposure and closure of the wound. Recently we have attempted with gratifying results the technic recommended by N agamatsu. In essence this consists of an incision just along the superior border of the twelth rib, extending posteriorly and upward just medial to the angle of the ribs to the inter-
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space between the tenth and ninth ribs. Segments of these ribs are removed and the entire osteoplastic flap is elevated. An important point is the resection of rib segments of such length as to prevent overriding of the cut ends after closure has been made. I t would appear reasonable to use the N agamatsu incision for cases where it is doubtful whether adequate careful nephrectomy could be performed by the usual posterior lumbar incision. Those kidneys situated high under the rib cage are best treated in our hands by Chute's thoracoabdominal approach. This incision is particularly applicable when node dissection is necessary as with adenectomy for testis tumor. In regard to prognosis it would appear likely that tumors of the kidney that are so large that thoraco-abdominal technic is necessary will 'perforce have a poor prognosis. Wilms' Tumors
Treatment of Wilms' tumor is a subject of much controversy. The cells of this adenomyosarcoma are far more sensitive to radiation therapy than hypernephroma. Dean has treated this tumor by deep x-ray therapy without nephrectomy but does not recommend it as a routine policy as it may take many months to completely devitalize the tumor and during this time metastases can take place. Ladd and White and others have obtained best results by simple nephrectomy without radiation. Gross in Boston and also Hazzard, Melicow and Seidel favor nephrectomy and postoperative radiation as they believe the waiting period for the administration of preoperative radiation may permit metastases to occur in the interim. Rusche contends that four to six weeks of radiation prior to surgery shrinks and avascularizes the tumor, thus avoiding the freeing of malignant cells into the circulation as well as facilitating extirpation of the tumor mass at the time of surgery. Recently Rusche has reported an excellent review and a presentation of 40 cases of Wilms' tumor. Mortality in his series was approximately 70 per cent to date. The average mortality previously reported by various authors is approximately 90 per cent. Rusche also states that, though it has been considered reasonable to consider this disease cured if the patient survives two years without evidence of metastasis or recurrence, 3 of his 40 patients died of recurrence of the tumor after two years. The indication of cure should probably be five years as with most other cancers. Rusche did not use the same form of therapy on all patients. No standard treatment has been used in a large series of these cases. Reported cures are too few in number to evaluate significantly a regimen of treatment for Wilms' tumor. Consequently no justification for dogmatism concerning therapy is possible. Certain conclusions are obvious, nonetheless. As either deep x-ray or nephrectomy will cure a small percentage of patients with this lesion, a combination of both will yield
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more cures than either modality used alone. The situation is not unlike that of seminoma of the testis. Whether radiation should precede or follow nephrectomy is still a matter of opinion. Our philosophy on this problem is as follows: For a regimen of therapy it must be assumed that in the natural course of these cancers at one period no metastasis has occurred. It is this period toward which treatment is directed. It is made more difficult by the fact that malignant metastatic cells must proliferate greatly before becoming clinically detectable by roentgenograms. No laboratory or clinical diagnostic test is available to predict the precise hour metastasis occurs. A four week course of preoperative radiation will not occlude the renal vascular pedicle to prevent metastases as effectively as a clamp on the renal vessels. In addition the primary aim of nephrectomy is early ligation of the renal pedicle and removal of the malignant kidney. Radiation to reduce the size of the tumor mass for the convenience of the operator must be of secondary importance. It is our policy therefore to perform nephrectomy as soon as possible. Palpation of the mass is restricted to that necessary to establish the diagnosis. The size and deflection of the tumor determine the operative approach. If the tumor is situated high under the ribs a thoraco-abdominal incision is indicated. We have found the T-shaped transperitoneal abdominal approach satisfactory, however, for extirpation of most Wilms' tumors. One arm of the incision extends from just below the tip of the sternum to the pubic symphysis. The posterolateral incision joins the vertical incision superior to the umbilicus. Following surgery a full course of radiation is administered, the first treatment being given after leaving the operating room. This has been recommended by Gross and appears to be a reasonable suggestion. No untoward wound reaction has been observed provided dressings are secured with cellophane tape instead of routine adhesive tape. URINARY CALCULI
Beard and Goodyear have done much toward correcting urologic perspective relative to hyperparathyroidism and urolithiasis. The classical conc~pt of multiple, bilateral, renal calculi as characteristic of the disease is no longer tenable. One hundred and fifty cases of renal calculi were studied and 12 cases (8 per cent) had proven hyperparatyphoid adenomas. Only 3 of these cases had bilateral calculi. The disease is therefore neither rare nor necessarily bilateral. Bone changes of osteitis fibrosis cystica are present in less than one-third of cases. The diagnosis is established mainly by minor elevations of serum calcium concentrations. Any value above 10.5 mg. per 100 cc. is to be considered to be suggestive of hyperparathyrodism. Serum phosphorus levels below 3 mg. per 100 cc., when associated with an elevated calcium, are diagnostic. The urinary output of 130 to 200 mg. of calcium in twenty-four hours is
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suggestive of the disease if the patient is ambulatory and the calcium intake has been controlled for two days prior to collecting the specimen (Fig. 136). Use of Solvents
Gehres and Raymond as well as Abeshouse and Weinberg have introduced a new chemical compound for the dissolution of urinary calculi. This is versene, an aqueous solution of the tetra-sodium salt of ethylenediamine tetra-acetic acid.
a b Fig. 136. a, Normal parathyroid. b, Parathyroid adenoma of the pink cell type removed from a patient with calculous pyonephrosis.
Divalent metal ions, e.g. calcium, form a complex with versene salts. In vitro studies reveal a 10 per cent solution of versene to have the most effective solvent action. Uric acid and urate stones were not affected by the compound. Calcium carbonate calculi were dissolved more readily than other calculi, i.e. 52 per cent dissolved in six hours with a 10 per cent solution of versene. Using the same dilution 45 to 50 per cent dissolution was obtained with mixed alkaline earth phosphatic calculi but only 31.1 per cent of calcium oxalate stones were dissolved in six hours. Cystine calculi exhibited a 15 per cent dissolution in the same period of time. Experiments oh the toxic action of versene reveal that no irritation of the renal pelvis occurs following irrigation with a 3 per cent solution. Gehres believes that a 1.5 per cent solution of versene with a pH of 7.5 to be superior to concentrations previously used.
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318 HYDROCEPHALUS
Without treatment the vast majority of patients with congenital hydrocephalus die in infancy. Until recently therapy for this condition has been unsuccessful. As a result of -the 'work of Donald Matson, progress in the management of communicating hydrocephalus has made great strides. The treatment consists of the following: An intravenous pyelogram is taken to determine whether both kidneys are normal. A nephrectomy is then performed with high division of the ureter in order to leave a flare of pelvis on the end of the ureter. Laminectomy is next carried out and a section of polyethylene tubing is introduced downward into the subarachnoid space and sutured to the dura. This tubing must be of the largest caliber which will fit into the ureter without undue force. By blunt dissection a passageway is made between the paravertebral muscles and the vertebrae just above L 2, into the renal fossa. The tube is passed through and then well down into the ureter. The free end of the ureter is sutured to the fascia and muscles around the point of emergence of the tube into the renal bed. The diet must be supplemented daily with salt. All published results of this procedure are excellent, provided the salt deficit is replaced. Twelve patients so treated have been reported by Dees. Ten of these are alive and well, one for almost three years. Our experience with this procedure has been limited. Within forty-eight hours of operation the increased intracranial pressure has been reduced and the bulging of cranial defects is replaced by marked depressions. It is believed that more complete preoperative urologic evaluation is indicated than commonly practiced. The success of the procedure depends on competence of the ureterovesical valve of the ureter used in the anastomosis. Cystography should be performed preoperatively to determine whether ureteral reflux is present which might permit bladder urine and spinal fluid to flow retrograde into the subarachnoid space. Endoscopy should be performed also to determine if contracture of the bladder neck or urethral valves or other anomalies are present which may result at a later time in ureterovesical valvular incompetence due to increased intravesical pressure. EXSTROPHY OF THE BLADDER
The standard treatment of exstrophy of the bladder is cystectomy and bilateral uretero-intestinal implantation and repair of the defect in the abdominal wall. The results have not been completely encouraging. These patients frequently develop recurrent bouts of pyelonephritis. Occasionally death will occur as a result of uremia from chronic hydronephrosis and pyelonephritis. One of the most realistic, and therefore most contributory, studies of exstrophy is reported by Harvard and Thompson of Mayo Clinic.
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One hundred and forty-four cases treated by uretero-intestinal anastomosis are discussed. Forty-eight of the 69 patients followed developed pyelonephritis. Eighty-eight per cent of patients had obstructive phenomenon as determined by excretory urograms. Fifty-six per cent of hospital deaths were due to pyelonephritis, ureteritis or uremia. Sixty-six per cent of deaths after the patients left the hospital were due to uremia, pyelonephritis with hydronephrosis or stones, or both. Twenty-nine
a
b
Fig. 137. a, Dog 446. Vesicorectal anastomosis. Eight months postoperative. Normal voiding: 400-500 cc. Cystorectogram using 200 cc. sodium iodide demonstrating incompetency of ureterovesical valve and ureteral reflux. b, Dog 693. Vesicorectal anastomosis. Nineteen months postoperative. Normal voiding: 250-300 cc. Cystorectogram using 100 cc. sodium iodide demonstrating incompetency of ureterovesical valve and ureteral reflux.
per cent (41 patients of 144 comprising the series) died of upper urinary tract disease directly attributable to the uretero-intestinal anastomosis. Vest, using a modification of Maydl's technic, has demonstrated recently a surgical approach intended to avoid some of the renal complications following uretero-intestinal implantation in this condition. The fecal stream is diverted by a transverse colostomy. The trigone of the bladder is split lengthwise and anastomosed to the rectum or rectosigmoid. The anterior portion of the bladder is then closed and the bladder replaced in the abdomen. Ureteral urine passes through a normal ureterovesical valve and empties into the clean rectum. Theoreticallv
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ureterorenal reflux of urine could not occur using this technic. Closure of the colostomy may be performed at a later time. Vest has been reluctant to close the colostomy as his patients are progressing so nicely. For several years we have studied experimentally in dogs the physi-
Fig. 138. Dog 296. Vesicorectal anastomosis. Sixteen months postoperative Photomicrograph (X275) of ureterovesical juncture. Bladder inferiorly. Epithelial proliferation, periureteral fibrosis and incompetency of valve demonstrated.
ology of this anastomosis of the bladder to a defunctionalized rectum. The immediate results are excellent. Unfortunately after twelve to twenty-four months the ureterovesical valve becomes incompetent and regurgitation of urine occurs from the rectum back up the ureters to the kidneys (Fig. 137). As a result of this valvular incompetency 60 per cent of the dogs studied died from renal disease. The remaining animals were sacrificed at twenty to twenty-four months and all had chronic
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bilateral pyelonephritis. Several dogs had renal calculi and pyonephrosis. Data to be published soon indicate that the defecation reflex is initiated at such a high level of pressure that there is a persistently elevated intrarectal pressure which results in eventual breakdown of the ureterovesical valve (Fig. 138). A comparable phenomenon is observed frequently in humans with longstanding increased intravesical pressure secondary to bladder neck obstruction (Fig. 139). Infection would undoubtedly hasten the process. It is hoped that the results of treatment of exstrophy of the bladder
•
Fig. 139. Cystogram of a patient with benign prostatic hypertrophy demonstrating incompetency of the ureterovesical valves and ureterorenal reflux.
in humans by the procedure recommended by Vest will be superior to those observed in dogs. In any case the principles employed are more sound than any used before to correct this unfortunate anomaly. Following surgery for correction of exstrophy the repair of the defect in the anterior abdominal wall remains a problem. Strong advises the use of tantalum mesh to close the defect. Hepburn has been impressed with the thickness of the bladder muscle and feels this structure should be utilized in the closure. He suggests trimming the bladder to correct size, curetting off the mucous membrane and resuturing it. The rectus muscle sheaths are left intact, the skin is undermined, brought over on top of the bladder and then sutured. Hepburn believes the resulting closure to form a satisfactory, solid, abdominal wall. Emphasis might be more strongly directed toward complete removal of all bladder
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epithelium prior to closure. Huggins has observed that subcutaneously implanted bladder epithelium undergoes calcification. REFERENCES Abeshouse, B. S. and Weinberg, T.: Experimental Study of Solvent Action of Versene on Urinary Calculi. J. Urol. 65: 316-332 (Feb.) 1951. Baker, R. and Miller, G. H.: Physiology of the Uretero-Intestinal Anastomosis. I. Ureteral Reflux. J. Urol. To be published. Baker, R., Huffer, J. and Miller, G. H.: Physiology of the Uretero-Intestinal Anastomosis. II. Ureteral Action Potentials. To be published. Baker, Roger: Physiology of the Uretero-Intestinal Anastomosis. III. Prevention of Stricture Formation by Use of Cortisone. To be published. Beard, D. E. and Goodyear, W. E.: Hyperparathyroidism and Urolithiasis. J. Urol. 64-: 638-643 (Nov.) 1950. Beare, J,. B. and McDonald, J. R.: Involvement of the Renal Capsule in Surgically Removed Hypernephroma: A Gross and Histopathologic Study. J. Urol: 61: 857-862 (May) 1949. Carroll, G., Allen, H. N. and Flynn, H.: Gantrisin in the Treatment of Urinary Infections. J.A.M.A., 142: 85-86 (Jan. 14), 1950. Chute, R. and Soutter, L.: Thoraco-Abdominal Nephrectomy for Large Kidney . Tumors. J. Urol. 61: 688-697 (April) 1949. Chute, Richard: The Thoraco-Abdominal Incision in Urological Surgery. J. Urol. 65: 784-795 (May) 1951. Dean, A. L.: Wilms' Tumors. New York State J. Med. 4-5: 1213-1217, 1945. Dees, J. E.: Ureterosubarachnoid Anastomosis for Cummunicating Hydrocephalus. J. Urol. 65: 994-998 (June) 1951. Gehres, R. F. and Raymond, S.: A New Chemical Approach to the Dissolution of Urinary Calculi. J. Urol. 65: 474-484 (March) 1951. Harvard, B. M. and Thompson, G. J.: Congenital Exstrophy of the Urinary Bladder: .Late Results of Treatment by the Coffey-Mayo Method of Uretero-Intestinal Anastomosis. J. Urol. 65: 223-235 (Feb.) 1951. Hazzard, C. T., Melicono, M. M. and Seidel, R. F.: Wilms' Tumor. New York State J. Med. 4-9: 649-657,1949. Hepburn, T. N.: Repair of Exstrophy of the Bladder. J. Urol. 65: 389-391 (March) 1951. Herrold, R. D. and Boand, A. V.: Indications for Aureomycin and Chloromycetin in Urinary Infections. J. Urol. 64-: 618-621 (Oct.) 1950. Herrold, R. D.: The Present Status of Antibiotic and Other Agents for the Treatment of Urinary Infections. S. CLIN. NORTH AMERICA. 30: 61-71 (Feb.) 1950. Knight, Vernon: Clinical Evaluation of Aureomycin, Chloramphenicol and Terramycin. New York State J. Med. 50: 2173-2180 (Sept. 15) 1950. Ladd, W. E. and White, R. R.: Embryoma of the Kidney (Wilms' Tumor). J.A.M.A. 117: 1858-1863, 1941. Lazarus, J. A. and Schwarz, L. H.: A Clinical Study of a New Sulfonamide (NU445) in the Treatment of Urinary Tract Infections. J. Urol. 61: 649-658 (March) 1949. Linsell, W. D. and Fletcher, A. P.: Laboratory and Clinical Experience with Terramycin Hydrochloride. Brit. M. J. No. 4690, 1190-1195 (Nov. 25) 1950. Miller, C.:p.: Personal communication. Nagamatsu, George: Dorso-Lumbar Approach to the Kidney and Adrenal with Osteoplasis Flap. J. Urol. 63: 569-578 (April) 1950. Nesbit, R. M., Adcock, J., Baum, W. C. and Owens, C. R.: Clinical Experience with Terramycin in Treatment of Refractory Urinary Tract Infections. J. Urol. 65: 336-343 (Feb.) 1951. O'Conor, V. J. and Head, J. R.: Transthoracic Nephrectomy (Left) for Wilms' Tumor. J. Urol. 65: 193-197 (Feb.) 1951.
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Prather, George: Differential Diagnosis Between Renal Tumor and Renal Cyst. J. Urol. 64: 193-200 (August) 1950. Rusche, Carl: Treatment of Wilms' Tumor. J. Urol. 65: 950--964 (June) 1951. Schnitzer, R. J., Foster, R. H. K., Ercoli, N., Soo-Hoo, G., Mangieri, C. N. and Roe, M. D.: Pharmocological and Chemotherapeutic Properties of 3,4dimethyl-5-sulfanilamidoisoxazole. J. Pharmacol. & Exper. Therap. 88: 47-57, 1946. Strong, George: Repair of Large Abdominal Defects Following Cystectomy for Congenital Vesical Exstrophy: A New Technique. J. Urol. 64: 743-746 (Dec.) 1950. Vest, S. A. and Boyce, W. H.: Paper read at annual meeting of American Urological Association, Chicago, Ill., May, 1951.
THERE are fewer new instruments and operative technics introduced in urology today than in former years. The phenomenal progress curve of urologic diagnostic instruments and operative procedures has apparently approached a plateau. The most important recent advances in urologic surgery have been made not in the field of technical improvements but in those areas where attention has been concentrated on the research aspects of abnormal physiology. By its very nature progress in this direction is painfully slow but highly significant and durable. Some of these advances will be presented. A review of this type must be limited necessarily to a discussion of the latest forms of treatment or to trends in urology. Complete descriptions may be located in the specific urologic literature indicated. ANTIBIOTIC DRUGS
Urologists in particular have profited greatly by the research leading to discovery of the newer antimicrobial agents. It is often necessary to use indwelling catheters for long periods of time to divert the urinary stream or to splint anastomoses. These catheters are foreign bodies and promote infection. In addition many urologic wounds--are constantly bathed in urine which perforce also fosters infection. Use of the newer drugs effectively control most of these urologic infections and contribute immeasurably to improve operative results. Prior to prescribing antibiotic drugs it is advisable to obtain if possible a voided specimen of urine from males, utilizing the two-glass test, and a catheterized specimen from females. Gross examination and Gram stain are performed and the specimen sent to the laboratory for culture and sensitivity studies. Careful inquiry is made regarding any previous drug reaction. As Herrold has indicated, there is a substantial per cent From the Department of Surgery (Division of Urology), the University of Chicago, Chicago.
* Assistant Professor of Urology, University of Chicago School of Medicine; Attending Surgeon, Albert Merritt Billings Hospital of the University of Chicago. 311
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of the population already sensitized to the sulfonamides, penicillin or streptomycin so they can no longer be administered safely. Rarely, Gram stain will reveal all organisms to be gram-positive and if this be the case penicillin is administered. More frequently, the Gram stain will reveal mixed coccal and gram-negative bacilli. Penicillin and aureomycin are recommended for these patients. They are also administered to most postoperative patients until sensitivity tests are completed indicating use of a more specific drug. Penicillin continues to occupy a real place in treatment of infections due to gram-positive organisms. Though oral administration has been improved and is recommended by many there appears to be little need for its use in our clinic. There are several repository penicillin preparations containing compounds which delay absorption to the extent that blood levels of at least 0.15 unit per cubic centimeter may be obtained at the end of the two days. We believe this to be adequate for all but the most severe infections when more frequent injections are to be preferred. Gantrisin appears to be of greater value than the other sulfonamide drugs. It is effective apparently for the same range of bacteria inhibited by other sulfonamide compounds. In addition, gantrisin will also cure a high incidence of infections due to Pseudomonas aeruginosa and Escherichia coli which are not effectively treated by these compounds. Carroll and his associates have obtained no evidence of the development of increased resistance on the part of the organisms to gantrisin, which is in contrast with other sulfonamide drugs. In addition, the likelihood of crystalluria and the deposition of crystals within the renal collecting system is greatly reduced. Schnitzer and co-workers have evaluated this drug experimentally and find excellent solubility over a wide pH range. It is nearly impossible to form crystals at the physiologic range of pH 6.0 to 8.0. The maintenance of a large fluid intake and alkalinization of the urine usually necessary during therapy with other sulfonamide drugs is eliminated by use of gantrisin. This work has been confirmed clinically by Lazarus and Schwarz. Aureomycin and chloramphenicol (chloromycetin) have proved their therapeutic effectiveness against gram-positive cocci and gram-negative bacilli. Aureomycin is more effective than chloromycetin, terramycin or penicillin in combating streptococcal and staphylococcal infections. Instances of serious toxicity have been rare. The incidence of nausea, vomiting and diarrhea accompanying aureomycin administration has become very low as the drug has become further purified by removal of . foreign proteins. It has been suggested that tincture of belladonna be given prior to oral administration of aureomycin. Aureomycin combined with streptomycin (1 gm. daily) has been found more effective against Pseudomonas aeruginosa than chloromycetin. Chloromycetin combined with gantrisin (2 gm. daily) has been effective in treatment of some
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infections due to B. proteus. Herrold and Boand administer the same dosage for both aureomycin and chloromycetin: 3 gm. the first day, 2 gm. daily for the five succeeding days and then 1 gm. daily for four days. Others believe 2 gm. a day is adequate for severe infections, decreasing the dose to 1 gm. daily when the infection responds to therapy. Terramycin will cure some gram-negative urinary tract infections which have been refractive to other therapy. Knight finds it of little use in combating urinary tract infection in which the organism involved is either B. proteus or Pseudomonas aeruginosa. Interestingly enough, however, Linsell and Fletcher find nearly three-quarters of the strains of Pseudomonas were sensitive to terramycin. A few patients will develop nausea, vomiting and diarrhea. Nesbit believes an initial loading dose of 2 gm. should be followed by 1 gm. dosages at six hour intervals. Dihydrostreptomycin has a practically nonexistent incidence of neurotoxicity. Many sulfonamide-resistant gram-negative bacilli may be eradicated by use of this drug. Miller believes this to be the most effective known agent in treatment of infections due to B. proteus. Best results of treatment of tuberculosis of the urinary tract is obtained apparently with a combination of dihydrostreptomycin (1 gm. daily) and para-aminosalicylic acid (5 to 10 gm. daily) for periods of about twelve weeks. Deep infected wounds containing sloughing, nonviable tissue are best treated by local use of streptokinase-streptodornase. Administration of these fibrinolytic enzymes results in a clean granulating wound which greatly accelerates healing. Bacitracin will produce rapid healing of most superficial infections. RENAL TUMORS
It is still impossible to distinguish infallibly between renal cyst and renal tumor except by surgical exploration. Prather mentions several criteria to consider in the differential diagnosis but concludes his review by stating that "until a blood or biological test for malignancy is available, surgical exploration is indicated whenever a space displacing lesion is suspected in the kidney." If a renal cyst instead of tumor be found at the time of the exploration it should be opened, as a certain small percentage have cancer at the base. Hypernephroma
Advances in treatment of hypernephroma have been confined to surgical approach of nephrectomy. Certain basic tenets apply irrespective of the technic used. Early ligation of the renal pedicle before the kidney is manipulated will tend to decrease the traumatic dissemination of tumor particles. Besides venous metastases these lesions spread also by direct extension through the capsule of the tumor into the perirenal fat. In a study by Beare and McDonald of 488 cases of surgically removed hypernephroma, 343 were found to have malignant involvement
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of the capsule. Perinephric fat and Gerota's capsule should be removed en bloc therefore with the hypernephroma. In addition, all regional lymph nodes and fat should be stripped from about the pedicle, along the aorta and the vena cava. Surgical Approaches. The specific surgical approach to the hypernephroma is individual and must depend on the size of the tumor and the configuration of the patient's bony thorax. To be committed to one type incision for all renal tumors is unwise. Small renal tumors, particularly those of the upper pole, may be excised easily in the average patient by use of the routine posterior lumbar retroperitoneal or abdominal transperitoneal approach. Large renal tumors situated high under the rib cage may be exposed completely by the thoraco-abdominal route popularized by Chute. The technic of this nephrectomy is as follows: With the patient placed on his side the incision is made from the lateral border of the rectus at the level of the umbilicus, running laterally and upwards and posteriorly over the eleventh rib to the spine. The rib is resected in the usual manner. The pleural cavity is opened through the periosteal bed. Chute believes the phrenic nerve should be crushed with a hemostat at the point where it leaves the surface of the pericardium to enter the diaphragm. This stops diaphragmatic excursions. We have not found this necessary except in an occasional case where the motion interfered with the progress of the operation. The diaphragm is then incised in line with the skin incision. This incision is then carried forward through the decussation of the diaphragm with the transversus abdominis muscle and then continued through the oblique muscles opening the peritoneal cavity. The spleen is packed off and the renal artery and vein are dissected out and clamped. Nephrectomy is performed removing all perinephric fat and kidney en bloc. The diaphragm is approximated with interrupted silk sutures. After complete expansion of the lung the pleura is closed without drainage. Chute believes this surgical route should be employed for all kidney tumors as most nephrectomies for cancer will require more extensive surgery than simple nephrectomy, due to local extension, and this route provides best exposure. He claims that the incision is indispensable in cases where extreme kyphosis or scoliosis contraindicates use of the usual type of lumbar approach. O'Conor has reported use of transthoracic nephrectomy for Wilms' tumor in a 2 year old girl. We believe this procedure to be ideal for nephrectomy for most large hypernephromas, particularly those situated high under the rib cage. The principal objection has been the great length of time necessary to perform exposure and closure of the wound. Recently we have attempted with gratifying results the technic recommended by N agamatsu. In essence this consists of an incision just along the superior border of the twelth rib, extending posteriorly and upward just medial to the angle of the ribs to the inter-
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space between the tenth and ninth ribs. Segments of these ribs are removed and the entire osteoplastic flap is elevated. An important point is the resection of rib segments of such length as to prevent overriding of the cut ends after closure has been made. I t would appear reasonable to use the N agamatsu incision for cases where it is doubtful whether adequate careful nephrectomy could be performed by the usual posterior lumbar incision. Those kidneys situated high under the rib cage are best treated in our hands by Chute's thoracoabdominal approach. This incision is particularly applicable when node dissection is necessary as with adenectomy for testis tumor. In regard to prognosis it would appear likely that tumors of the kidney that are so large that thoraco-abdominal technic is necessary will 'perforce have a poor prognosis. Wilms' Tumors
Treatment of Wilms' tumor is a subject of much controversy. The cells of this adenomyosarcoma are far more sensitive to radiation therapy than hypernephroma. Dean has treated this tumor by deep x-ray therapy without nephrectomy but does not recommend it as a routine policy as it may take many months to completely devitalize the tumor and during this time metastases can take place. Ladd and White and others have obtained best results by simple nephrectomy without radiation. Gross in Boston and also Hazzard, Melicow and Seidel favor nephrectomy and postoperative radiation as they believe the waiting period for the administration of preoperative radiation may permit metastases to occur in the interim. Rusche contends that four to six weeks of radiation prior to surgery shrinks and avascularizes the tumor, thus avoiding the freeing of malignant cells into the circulation as well as facilitating extirpation of the tumor mass at the time of surgery. Recently Rusche has reported an excellent review and a presentation of 40 cases of Wilms' tumor. Mortality in his series was approximately 70 per cent to date. The average mortality previously reported by various authors is approximately 90 per cent. Rusche also states that, though it has been considered reasonable to consider this disease cured if the patient survives two years without evidence of metastasis or recurrence, 3 of his 40 patients died of recurrence of the tumor after two years. The indication of cure should probably be five years as with most other cancers. Rusche did not use the same form of therapy on all patients. No standard treatment has been used in a large series of these cases. Reported cures are too few in number to evaluate significantly a regimen of treatment for Wilms' tumor. Consequently no justification for dogmatism concerning therapy is possible. Certain conclusions are obvious, nonetheless. As either deep x-ray or nephrectomy will cure a small percentage of patients with this lesion, a combination of both will yield
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more cures than either modality used alone. The situation is not unlike that of seminoma of the testis. Whether radiation should precede or follow nephrectomy is still a matter of opinion. Our philosophy on this problem is as follows: For a regimen of therapy it must be assumed that in the natural course of these cancers at one period no metastasis has occurred. It is this period toward which treatment is directed. It is made more difficult by the fact that malignant metastatic cells must proliferate greatly before becoming clinically detectable by roentgenograms. No laboratory or clinical diagnostic test is available to predict the precise hour metastasis occurs. A four week course of preoperative radiation will not occlude the renal vascular pedicle to prevent metastases as effectively as a clamp on the renal vessels. In addition the primary aim of nephrectomy is early ligation of the renal pedicle and removal of the malignant kidney. Radiation to reduce the size of the tumor mass for the convenience of the operator must be of secondary importance. It is our policy therefore to perform nephrectomy as soon as possible. Palpation of the mass is restricted to that necessary to establish the diagnosis. The size and deflection of the tumor determine the operative approach. If the tumor is situated high under the ribs a thoraco-abdominal incision is indicated. We have found the T-shaped transperitoneal abdominal approach satisfactory, however, for extirpation of most Wilms' tumors. One arm of the incision extends from just below the tip of the sternum to the pubic symphysis. The posterolateral incision joins the vertical incision superior to the umbilicus. Following surgery a full course of radiation is administered, the first treatment being given after leaving the operating room. This has been recommended by Gross and appears to be a reasonable suggestion. No untoward wound reaction has been observed provided dressings are secured with cellophane tape instead of routine adhesive tape. URINARY CALCULI
Beard and Goodyear have done much toward correcting urologic perspective relative to hyperparathyroidism and urolithiasis. The classical conc~pt of multiple, bilateral, renal calculi as characteristic of the disease is no longer tenable. One hundred and fifty cases of renal calculi were studied and 12 cases (8 per cent) had proven hyperparatyphoid adenomas. Only 3 of these cases had bilateral calculi. The disease is therefore neither rare nor necessarily bilateral. Bone changes of osteitis fibrosis cystica are present in less than one-third of cases. The diagnosis is established mainly by minor elevations of serum calcium concentrations. Any value above 10.5 mg. per 100 cc. is to be considered to be suggestive of hyperparathyrodism. Serum phosphorus levels below 3 mg. per 100 cc., when associated with an elevated calcium, are diagnostic. The urinary output of 130 to 200 mg. of calcium in twenty-four hours is
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suggestive of the disease if the patient is ambulatory and the calcium intake has been controlled for two days prior to collecting the specimen (Fig. 136). Use of Solvents
Gehres and Raymond as well as Abeshouse and Weinberg have introduced a new chemical compound for the dissolution of urinary calculi. This is versene, an aqueous solution of the tetra-sodium salt of ethylenediamine tetra-acetic acid.
a b Fig. 136. a, Normal parathyroid. b, Parathyroid adenoma of the pink cell type removed from a patient with calculous pyonephrosis.
Divalent metal ions, e.g. calcium, form a complex with versene salts. In vitro studies reveal a 10 per cent solution of versene to have the most effective solvent action. Uric acid and urate stones were not affected by the compound. Calcium carbonate calculi were dissolved more readily than other calculi, i.e. 52 per cent dissolved in six hours with a 10 per cent solution of versene. Using the same dilution 45 to 50 per cent dissolution was obtained with mixed alkaline earth phosphatic calculi but only 31.1 per cent of calcium oxalate stones were dissolved in six hours. Cystine calculi exhibited a 15 per cent dissolution in the same period of time. Experiments oh the toxic action of versene reveal that no irritation of the renal pelvis occurs following irrigation with a 3 per cent solution. Gehres believes that a 1.5 per cent solution of versene with a pH of 7.5 to be superior to concentrations previously used.
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Without treatment the vast majority of patients with congenital hydrocephalus die in infancy. Until recently therapy for this condition has been unsuccessful. As a result of -the 'work of Donald Matson, progress in the management of communicating hydrocephalus has made great strides. The treatment consists of the following: An intravenous pyelogram is taken to determine whether both kidneys are normal. A nephrectomy is then performed with high division of the ureter in order to leave a flare of pelvis on the end of the ureter. Laminectomy is next carried out and a section of polyethylene tubing is introduced downward into the subarachnoid space and sutured to the dura. This tubing must be of the largest caliber which will fit into the ureter without undue force. By blunt dissection a passageway is made between the paravertebral muscles and the vertebrae just above L 2, into the renal fossa. The tube is passed through and then well down into the ureter. The free end of the ureter is sutured to the fascia and muscles around the point of emergence of the tube into the renal bed. The diet must be supplemented daily with salt. All published results of this procedure are excellent, provided the salt deficit is replaced. Twelve patients so treated have been reported by Dees. Ten of these are alive and well, one for almost three years. Our experience with this procedure has been limited. Within forty-eight hours of operation the increased intracranial pressure has been reduced and the bulging of cranial defects is replaced by marked depressions. It is believed that more complete preoperative urologic evaluation is indicated than commonly practiced. The success of the procedure depends on competence of the ureterovesical valve of the ureter used in the anastomosis. Cystography should be performed preoperatively to determine whether ureteral reflux is present which might permit bladder urine and spinal fluid to flow retrograde into the subarachnoid space. Endoscopy should be performed also to determine if contracture of the bladder neck or urethral valves or other anomalies are present which may result at a later time in ureterovesical valvular incompetence due to increased intravesical pressure. EXSTROPHY OF THE BLADDER
The standard treatment of exstrophy of the bladder is cystectomy and bilateral uretero-intestinal implantation and repair of the defect in the abdominal wall. The results have not been completely encouraging. These patients frequently develop recurrent bouts of pyelonephritis. Occasionally death will occur as a result of uremia from chronic hydronephrosis and pyelonephritis. One of the most realistic, and therefore most contributory, studies of exstrophy is reported by Harvard and Thompson of Mayo Clinic.
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One hundred and forty-four cases treated by uretero-intestinal anastomosis are discussed. Forty-eight of the 69 patients followed developed pyelonephritis. Eighty-eight per cent of patients had obstructive phenomenon as determined by excretory urograms. Fifty-six per cent of hospital deaths were due to pyelonephritis, ureteritis or uremia. Sixty-six per cent of deaths after the patients left the hospital were due to uremia, pyelonephritis with hydronephrosis or stones, or both. Twenty-nine
a
b
Fig. 137. a, Dog 446. Vesicorectal anastomosis. Eight months postoperative. Normal voiding: 400-500 cc. Cystorectogram using 200 cc. sodium iodide demonstrating incompetency of ureterovesical valve and ureteral reflux. b, Dog 693. Vesicorectal anastomosis. Nineteen months postoperative. Normal voiding: 250-300 cc. Cystorectogram using 100 cc. sodium iodide demonstrating incompetency of ureterovesical valve and ureteral reflux.
per cent (41 patients of 144 comprising the series) died of upper urinary tract disease directly attributable to the uretero-intestinal anastomosis. Vest, using a modification of Maydl's technic, has demonstrated recently a surgical approach intended to avoid some of the renal complications following uretero-intestinal implantation in this condition. The fecal stream is diverted by a transverse colostomy. The trigone of the bladder is split lengthwise and anastomosed to the rectum or rectosigmoid. The anterior portion of the bladder is then closed and the bladder replaced in the abdomen. Ureteral urine passes through a normal ureterovesical valve and empties into the clean rectum. Theoreticallv
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ureterorenal reflux of urine could not occur using this technic. Closure of the colostomy may be performed at a later time. Vest has been reluctant to close the colostomy as his patients are progressing so nicely. For several years we have studied experimentally in dogs the physi-
Fig. 138. Dog 296. Vesicorectal anastomosis. Sixteen months postoperative Photomicrograph (X275) of ureterovesical juncture. Bladder inferiorly. Epithelial proliferation, periureteral fibrosis and incompetency of valve demonstrated.
ology of this anastomosis of the bladder to a defunctionalized rectum. The immediate results are excellent. Unfortunately after twelve to twenty-four months the ureterovesical valve becomes incompetent and regurgitation of urine occurs from the rectum back up the ureters to the kidneys (Fig. 137). As a result of this valvular incompetency 60 per cent of the dogs studied died from renal disease. The remaining animals were sacrificed at twenty to twenty-four months and all had chronic
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bilateral pyelonephritis. Several dogs had renal calculi and pyonephrosis. Data to be published soon indicate that the defecation reflex is initiated at such a high level of pressure that there is a persistently elevated intrarectal pressure which results in eventual breakdown of the ureterovesical valve (Fig. 138). A comparable phenomenon is observed frequently in humans with longstanding increased intravesical pressure secondary to bladder neck obstruction (Fig. 139). Infection would undoubtedly hasten the process. It is hoped that the results of treatment of exstrophy of the bladder
•
Fig. 139. Cystogram of a patient with benign prostatic hypertrophy demonstrating incompetency of the ureterovesical valves and ureterorenal reflux.
in humans by the procedure recommended by Vest will be superior to those observed in dogs. In any case the principles employed are more sound than any used before to correct this unfortunate anomaly. Following surgery for correction of exstrophy the repair of the defect in the anterior abdominal wall remains a problem. Strong advises the use of tantalum mesh to close the defect. Hepburn has been impressed with the thickness of the bladder muscle and feels this structure should be utilized in the closure. He suggests trimming the bladder to correct size, curetting off the mucous membrane and resuturing it. The rectus muscle sheaths are left intact, the skin is undermined, brought over on top of the bladder and then sutured. Hepburn believes the resulting closure to form a satisfactory, solid, abdominal wall. Emphasis might be more strongly directed toward complete removal of all bladder
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epithelium prior to closure. Huggins has observed that subcutaneously implanted bladder epithelium undergoes calcification. REFERENCES Abeshouse, B. S. and Weinberg, T.: Experimental Study of Solvent Action of Versene on Urinary Calculi. J. Urol. 65: 316-332 (Feb.) 1951. Baker, R. and Miller, G. H.: Physiology of the Uretero-Intestinal Anastomosis. I. Ureteral Reflux. J. Urol. To be published. Baker, R., Huffer, J. and Miller, G. H.: Physiology of the Uretero-Intestinal Anastomosis. II. Ureteral Action Potentials. To be published. Baker, Roger: Physiology of the Uretero-Intestinal Anastomosis. III. Prevention of Stricture Formation by Use of Cortisone. To be published. Beard, D. E. and Goodyear, W. E.: Hyperparathyroidism and Urolithiasis. J. Urol. 64-: 638-643 (Nov.) 1950. Beare, J,. B. and McDonald, J. R.: Involvement of the Renal Capsule in Surgically Removed Hypernephroma: A Gross and Histopathologic Study. J. Urol: 61: 857-862 (May) 1949. Carroll, G., Allen, H. N. and Flynn, H.: Gantrisin in the Treatment of Urinary Infections. J.A.M.A., 142: 85-86 (Jan. 14), 1950. Chute, R. and Soutter, L.: Thoraco-Abdominal Nephrectomy for Large Kidney . Tumors. J. Urol. 61: 688-697 (April) 1949. Chute, Richard: The Thoraco-Abdominal Incision in Urological Surgery. J. Urol. 65: 784-795 (May) 1951. Dean, A. L.: Wilms' Tumors. New York State J. Med. 4-5: 1213-1217, 1945. Dees, J. E.: Ureterosubarachnoid Anastomosis for Cummunicating Hydrocephalus. J. Urol. 65: 994-998 (June) 1951. Gehres, R. F. and Raymond, S.: A New Chemical Approach to the Dissolution of Urinary Calculi. J. Urol. 65: 474-484 (March) 1951. Harvard, B. M. and Thompson, G. J.: Congenital Exstrophy of the Urinary Bladder: .Late Results of Treatment by the Coffey-Mayo Method of Uretero-Intestinal Anastomosis. J. Urol. 65: 223-235 (Feb.) 1951. Hazzard, C. T., Melicono, M. M. and Seidel, R. F.: Wilms' Tumor. New York State J. Med. 4-9: 649-657,1949. Hepburn, T. N.: Repair of Exstrophy of the Bladder. J. Urol. 65: 389-391 (March) 1951. Herrold, R. D. and Boand, A. V.: Indications for Aureomycin and Chloromycetin in Urinary Infections. J. Urol. 64-: 618-621 (Oct.) 1950. Herrold, R. D.: The Present Status of Antibiotic and Other Agents for the Treatment of Urinary Infections. S. CLIN. NORTH AMERICA. 30: 61-71 (Feb.) 1950. Knight, Vernon: Clinical Evaluation of Aureomycin, Chloramphenicol and Terramycin. New York State J. Med. 50: 2173-2180 (Sept. 15) 1950. Ladd, W. E. and White, R. R.: Embryoma of the Kidney (Wilms' Tumor). J.A.M.A. 117: 1858-1863, 1941. Lazarus, J. A. and Schwarz, L. H.: A Clinical Study of a New Sulfonamide (NU445) in the Treatment of Urinary Tract Infections. J. Urol. 61: 649-658 (March) 1949. Linsell, W. D. and Fletcher, A. P.: Laboratory and Clinical Experience with Terramycin Hydrochloride. Brit. M. J. No. 4690, 1190-1195 (Nov. 25) 1950. Miller, C.:p.: Personal communication. Nagamatsu, George: Dorso-Lumbar Approach to the Kidney and Adrenal with Osteoplasis Flap. J. Urol. 63: 569-578 (April) 1950. Nesbit, R. M., Adcock, J., Baum, W. C. and Owens, C. R.: Clinical Experience with Terramycin in Treatment of Refractory Urinary Tract Infections. J. Urol. 65: 336-343 (Feb.) 1951. O'Conor, V. J. and Head, J. R.: Transthoracic Nephrectomy (Left) for Wilms' Tumor. J. Urol. 65: 193-197 (Feb.) 1951.
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Prather, George: Differential Diagnosis Between Renal Tumor and Renal Cyst. J. Urol. 64: 193-200 (August) 1950. Rusche, Carl: Treatment of Wilms' Tumor. J. Urol. 65: 950--964 (June) 1951. Schnitzer, R. J., Foster, R. H. K., Ercoli, N., Soo-Hoo, G., Mangieri, C. N. and Roe, M. D.: Pharmocological and Chemotherapeutic Properties of 3,4dimethyl-5-sulfanilamidoisoxazole. J. Pharmacol. & Exper. Therap. 88: 47-57, 1946. Strong, George: Repair of Large Abdominal Defects Following Cystectomy for Congenital Vesical Exstrophy: A New Technique. J. Urol. 64: 743-746 (Dec.) 1950. Vest, S. A. and Boyce, W. H.: Paper read at annual meeting of American Urological Association, Chicago, Ill., May, 1951.