Papillary Carcinoma of the Renal Pelvis retrograde dissemination of tumor is a subject of Following Cystectomy and Bricker somewhat more speculative interest. It is obvious Procedure for Carcinoma of the Bladder that if one supports the implantation theory, vesi- coureteral reflux will cause ureteral or pelvic tu- JERRY B. MILLER, M.D., and mors to be implanted from bladder tumors. JOSEPH J. KAUFMAN, M.D., Los Angeles We are reporting herein two cases of papillary THAT UROTHELIAL TUMORS are multicentric is basic tumor of the renal pelvis which occurred after total urological knowledge. Whether they are multicen- cystectomy for transitional cell carcinoma of the tric at the outset or become so by implantation is bladder and ureteroileocutaneous urinary diversion. yet to be resolved; there is evidence to support both We believe that these cases are of special interest theories.3'7 As the antegrade dissemination of uro- because the Bricker procedure provides for optimum thelial tumors is well recognized, primary papillary drainage of urine with no reservoir to allow pressure tumors of the renal pelvis and must be treated and reflux. Furthermore, the tumors appeared to by total nephroureterectomy, including dissection arise in the pelvis rather than by direct extension of a cuff of bladder in order to minimize the inci- up the ureter from the area of anastomosis. These dence of papillary tumor at this site. However, the factors would seem to substantiate, at least in these cases, the theory of multicentricity rather than im- From the Department of Surgery (Uroloy), University of Cali- fornia Medical Center, Los Angeles 24 California, and the Wads- plantation by reflux. The latter might occur in cases worth General Hospital, Veterans Administration Center, Los An- geles 25. of ileal or colonic reservoirs where intraluminal Presented before the Section on Urology at the 91st Annual Ses- pressure and reflux favor the implantation of tumors sion of the California Medical Association, San Francisco, April 15 to 18, 1962. in a retrograde manner.

Figure L-(Case 1).-Left, normal intravenous pyelogram, March 20, 1959. Right, filling defect in pelvis of right , suggesting renal papillary tumor, May 15, 1961. VOL. 97. NO. 6 * DECEMBER 1962 355 and bimanual examinations immediately before ad- mission revealed multiple exophytic tumors with no fixation of the bladder. Therefore, total cystectomy and bilateral ureteroileal anastomosis with cutane- ous ileostomy was carried out on March 9, 1959. The preoperative intravenous urogram showed nor- mal upper urinary tract architecture bilaterally with no evidence of ureteropelvic filling defects. After the operation, electrolyte and creatinine de- terminations remained within normal limits. With the exception of one episode of pyelonephritis characterized by chills and fever and responding promptly to sulfonamide therapy, the patient re- mained well until in May of 1961 he noticed blood in the urine. There was no pain associated with the gross hematuria or with the passage of clots. Whereas intravenous urograms on March 20, 1959, were normal, a pyelogram on May 15, 1961, showed filling defects in the pelvis of the right kidney and suggested papillary pelvic tumor (Figure 1). Papa- nicolaou study of the urine showed class II atypical cells, not suggestive of malignant disease. On May 24 the patient had severe right flank pain and gross hematuria. At this time an intravenous urogram Figure 2.-( Case 1 )-Ileostogram showing reflux up showed no appearance of dye in the right kidney, the left ureter revealing a normal left collecting system, and an ileostogram showed prompt reflux on the but complete blockage on the right. left, outlining a normal ureter, pelvis and calyces, but showed no reflux up the right ureter (Figure 2). REPORTS OF CASES On May 26, because of complete right renal block- CASE 1. The patient, a 53-year-old man, had had ade associated with fever, the right kidney was ex- transurethral resection of a transitional cell carci- amined through a flank incision and radical ne- noma of the bladder (grade II) six months before phrectomy and ureterectomy were carried out. There admission to hospital in March 1959. Cystoscopic were lymph nodes in the renal hilar area and along

Figure 3.-(Case 1)-Left, photomicrograph (X250) showing papillary transitional cell carcinoma of the uri- nary bladder. Right, (X250) showing papillary transitional cell carcinoma of the renal pelvis. The slides are shown side by side to demonstrate the same type of tumor cell present in bladder and renal pelvis. 356 CALIFORNIA MEDICINE the vena cava which were grossly involved by tu- mor. The ureter was removed flush with the ileum. The postoperative course was uneventful and the patient was discharged on the eighth postoperative day. The pathologist reported transitional cell carci- noma of the inferior calyx of the right kidney with extension to the ureter (Figure 3). Metastatic tran- sitional cell carcinoma was found in one of four hilar lymph nodes. The kidney showed chronic and acute pyelonephritis and the ureter chronic and acute ureteritis with ureteritis cystica. The patient thereafter was examined regularly in the outpatient department. The gross renal function and electrolytes always were within normal limits, as was an intravenous urogram shortly before the time of this report. Although the patient has sur- vived one year since right nephrectomy, the prog- nosis is obviously poor. CASE 2. A 70-year-old white man was admitted to the Veterans Administration Hospital in Los An- geles on April 25, 1957, because of obstructive uri- nary symptoms. He was found to have moderate prostatic enlargement and a fungating lesion on the floor of the bladder. Blood creatinine was within normal limits and no abnormalities were seen in roentgen examination of the chest and bones. An intravenous urogram disclosed a duplex collecting Figure 4.- (Case 2) -Normal intravenous pyelogram system on the right with ureteral duplication down taken in December of 1957. Note right-side duplication to the bladder. On the left, there was a single col- radiologically complete. lecting system (Figure 4). Neither side showed fill- ing defects in the hollow portion. The bladder tumor was removed by transurethral resection and the pathologist reported grade II tran- sitional cell carcinoma with no evidence of muscle invasion. Two weeks later, transurethral resection of the prostate was done. In July 1957, transurethral resection of a recur- rent bladder tumor was done. The diagnosis was transitional cell carcinoma grade II of the urinary bladder. Another recurrence in November 1957 was treated by transurethral resection. In 1958, cystos- copy showed an extensive bladder tumor about the left ureteral orifice. On this occasion, biopsies showed transitional cell carcinoma, grade II to III. No mass was felt on bimanual examination. Because of the progressive frequency and size of the recur. rences, cystectomy and ureteroileal anastomosis with ilealcutaneous conduit were done. Figure 5.-(Case 2)-Photomicrograph (X250) of pap- The surgeon failed to bring one of the on illary transitional cell carcinoma from the urinary bladder. the right (the duplication) into the anastomosis and the patient developed retroperitoneal urinary intravenous urograms showed good appearance of extravasation with pelvic and retroperitoneal ab- the upper tracts until December of 1959, at which scesses. Another operation was carried out to join time there was a suggestion of a filling defect in the the second right ureter to the ileal conduit. After a left renal pelvis. stormy postoperative course, during which time the On April 27, 1961, an intravenous urogram (Fig- body weight dropped from 124 pounds to 69, the ure 6) showed an unquestionable filling defect in patient gradually began to regain strength, and was the left renal pelvis and upper ureter, and a clinical gaining weight when he was discharged. The pathol- diagnosis of papillary tumor of the left renal pelvis ogist reported papillary transitional cell carcinoma was made. Left radical nephrectomy was performed of the urinary bladder (Figure 5). Six lymph nodes to remove the left ureter at its juncture with the were negative for tumor. Occasional postoperative ileal conduit. There was gross tumor extension to VOL. 97, NO. 6 * DECEMBER 1962 357 Figure 6.-(Case 2)-Intravenous pyelogram on April 27, 1961, showing an unquestionable filling defect in the left renal pelvis and left ureter. A diagnosis of papillary Figure 7.-(Case 2)-Photomicrograph (X250) of in- tumor of the left renal pelvis was made following this filtrating transitional cell carcinoma of the renal pelvis. film. This tumor also extended down the ureter. the hilar and . After the op- eration the patient gained weight to the preoperative level of approximately 110 pounds. Tissue examina- tion of the kidney showed infiltrating transitional cell carcinoma, grade IV, extending from the renal pelvis down the ureter (Figure 7). Two lymph nodes showed diffuse tumor metastasis (Figure 8). It was decided to give no irradiation therapy postopera- tively. At last report, eight months following left nephrectomy, the patient's weight was being main- tained at 105 to 110 pounds and he had no com- plaints. However, the outlook was considered dismal.

DISCUSSION The prognosis of papillary tumors of the renal pelvis and ureter has been spectacularly improved by application of complete nephroureterectomy. This was emphasized by O'Connor.8 Kaminsky also stressed that the tendency of pelvic ureteral tumors to spread by reimplantation dictates nephroureterec. tomy.5 He also posed a question as to whether spread is direct or by lymphatic channel. Probably in our cases, lymphatic spread would be the most likely, for two reasons. First, the lymphatic pathway is from the bladder to the area of the renal pelvis. Second, in both cases the lymph nodes were in- Figure 8.-( Case 2)-Photomicrograph (X250) of volved with tumor. showing tumorous involvement. Same type of tumor in lymph node as in renal pelvis. Exactly same Garcia and Bradfield2 reported a case of bilateral type of tumor present in Figures 5, 7, and 8. 358 CALIFORNIA MEDICINE simultaneous primary carcinoma of the ureter. They 5. Kaminsky, A. F.: Associated kidney and bladder tu- cited Felber,' who reported an asynchronous bilat- mors, J. Urol., 61:997, 1949. 6. Lewis, L.: In Discussion of: Kerr, W. S., Jr., and eral benign papilloma of the ureter with subsequent Colby, F. H.: Carcinoma of the bladder: A correlation of of the ureteral stump, bladder and vagina. pathology with treatment and prognosis, (in discussion), They also mentioned Ratliff,9 who reported a case J. Urol., 65:841, 1951. of primary bilateral carcinoma of the ureter. Evi- 7. Melicow, M. M.: Tumors of the urinary bladder: A dence that carcinogenic agents in the urine produce clinicopathological analysis of over 2,500 specimens and urothelial papillary tumors is, of course, now rather biopsies, J. Urol., 74:498, 1955. substantial.4 8. O'Connor, V. J.: The treatment and prognosis of papil- lary tumors of the renal pelvis and ureter, J. Urol., 61:488, Riches and Page'0 reported a case in which a car- 1949. cinoma developed in the sigmoid colon following 9. Ratliff, R. K., Baum, W. C., and Butler, W. J.: Bi- cystectomy and ureterosigmoidostomy for carcinoma lateral primary cancer of the ureter: A case report, Cancer, of the bladder. They thought that this was the first 2:815, 1949. case of this type to be reported. 10. Riches, E. W., and Page, B. H.: Transitional cell car- cinoma of the colon following cystectomy and uretero-sig- Hueper and coworkers4 were able to produce moidostomy for carcinoma of the bladder, Brit. J. Urol., bladder tumors in dogs by feeding them B-naphthyl- 28:288, 1956. amine, but could not produce these tumors in the colon when the urine had been diverted into an iso- lated sigmoid loop. They suggested that the secre- tion from the mucous glands prevented contact of Acute Radiation Nephritis the carcinogenic agent with the epithelium or in JOHN N. BALDWIN, M.D., San Francisco. and some way counteracted or destroyed its effective- JACK W. C. M.D.. New York ness.4 HAGSTROM, Lewis,6 in a discussion of a paper by Kerr and WITH THE MULTITUDE of beneficial uses made pos- Colby, cited the case of a patient with total cystec- sible in the present era of high-energy x-ray tech- tomy who had had no evidence of a lesion of either niques, the recognition of side effects and hazards ureter before operation but died of a new growth assumes new importance. In this regard, the syn- of a grade II tumor in the ureter, 4 inches above drome of radiation nephritis has not received wide- the site of a ureterosigmoidostomy, three and a half spread attention. years after operation. Lewis expressed belief that As far back as 1927, American investigators5 since we cannot eradicate the cause of the cancer demonstrated the production of renal insufficiency or eliminate the source tissue, treatment must be in dogs following deep irradiation, and described adequate to remove the local lesion and, when indi- the interstitial fibrosis, tubular atrophy and glo- cated, the lymphatic drainage tracts. In his opinion merular hyalinization which characterize radiation lymph node dissection should be part of the pro- nephritis. They stated, contrary to widespread opin- cedure of total cystectomy. ion then prevalent, that the kidney was quite sus- ceptible to the effects of x-ray. SUMMARY Shortly afterward, Domagk4 reported the first fatal case of radiation nephritis, in a nine-year-old Two cases of carcinoma of the renal pelvis after girl who had received x-irradiation to the cystectomy for carcinoma of the bladder, the first for mesenteric lymphadenitis. He described the pre- in the literature, are reported. The delayed appear- senting symptoms of anemia, albuminuria and a ance of these tumors suggested lymphatic spread progressive downhill course terminating in renal rather than direct extension. De novo origin of these failure six months following the therapy. Recently, tumors cannot be excluded although this theory Redd10 added one more case of nephritis to the re- (multicentric origin) seems less likely to us than ported series, bringing the total to 64. The patient that of lymphatic spread. he described had carcinoma of the and, fol- Department of Surgery/Urology, UCLA Medical Center, Los An- lowing the administration of a 4,200 r mid-plane geles 24 (Miller). dose over a period of 47 days, developed hyperten- REFERENCES sion, anemia, albuminuria, azotemia and cardio- renal failure. 1. Felber, E.: Asynchronous bilateral benign papilloma of Despite this documentation, cases continue to ap- the ureter with subsequent cancer of the ureteral stump, bladder, and vagina, J.M.A. Georgia, 42:198, 1953. pear, and for this reason the case below is presented. 2. Garcia, V., and Bradfield, E. O.: Simultaneous bilateral transitional cell carcinoma of the ureter: A case report, REPORT OF A CASE J. Urol., 79:925, 1958. 3. Hinman, F., Jr.: The recurrence of bladder tumors, A 63-year-old white man entered The New York J. Urol., 83:294, 1960. Hospital for the first time in August, 1959, with 4. Hueper, W. C., Wiley, F. H., and Wolfe, H. D.: Ex- From the Department of Surgery, University of California Medical perimental production of bladder tumors in dogs by admin- Center, San Francisco (Baldwin), and the Department of Pathology, istration of beta-naphthylamine, J. Industrial Hygiene, The New York Hospital-Cornell Medical Center (Hagstrom). 20:48, 1938. Submitted April 13, 1962.

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