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Carcinoma of the Bladder in a Renal Transplant Patient
THE JOURNAL OF UROLOGY
Vol. 109, March
Copyright © 1973 by The Williams & Wilkins Co.
Printed in U.S.A.
CARCINOMA OF THE BLADDER IN A RENAL TRANSPLANT PATIENT ALBERT W. BIGGS
From the Department of Urology, University of Tennessee College of Medicine, Memphis, Tennessee
A number of primary malignancies have been reported in renal transplant recipients on immunosuppressive therapy. A recent publication records 52 primary malignancies (28 epithelial and 24 mesenchyrpal tumors) developing in approximately 5,000 allograph recipients. 1 Twenty-two of the 24 mesenchymal tumors were malignant lymphomas. Transitional cell carcinoma of the bladder has not been described in a transplant patient. A case of bladder carcinoma in an allograph recipient is reported herein. CASE REPORT
T. W., a 50-year-old white man, was found to have hypertension and albuminuria in 1963. A clinical diagnosis of chronic glomerulonephritis was made and the patient was followed on conservative management. As renal failure progressed, he was placed on henrodialysis. In June 1969 he underwent bilateral nephrectomy, which was complicated by a staphylococcal wound infection. In October the patient received a transplant, using his sister's kidney. Rejection developed immediately following the transplant and the kidney had to be removed. In November 1969 hepatitis developed. In May 1970 a second renal transplant was successfully performed. The patient had total gross painless hematuria in July 1971, which cleared spontaneously after 3 or 4 days. Since that time he had had 4 episodes of gross painless hematuria. An excretory urogram (IVP) in November 1971 was normal. He was cystoscoped and found to have a number of papillary lesions scattered over the bladder wall. He was admitted to the hospital for therapy. Physical examination was essentially negative, except for shortening of the left leg (due to aseptic necrosis of the head of the femur). Urinalysis was within normal range except for microscopic examination, which showed 20 white and 3 red cells per high power field. The blood urea nitrogen was 19 mg. per cent, serum creatinine 1.2 mg. per cent, serum protein 5.8 mg. per cent and albumin 3.6 mg. per cent. Otherwise, all chemistry studies were within normal limits. An IVP revealed slight calicectasis but no definite obstruction was noted. The ureter emptied readily. The patient was taking 20 mg. prednisone every Accepted for publication July 21, 1972. Read at annual meeting of Southeastern Section, American Urological Association, New Orleans, Louisiana, March 26-30, 1972. 1 Schreck, S. A. and Penn, I.: De-novo brain tumors in renal transplant recipients. Lancet, 1: 983, 1971.
other day and 150 mg. azathioprine daily. On December 1, 1971 the patient was given general anesthesia and cystoscoped; 12 papillary lesions were noted in the bladder (see figure). None was around the ureteral orifice. These tumors were resected and the bases were fulgurated. The pathology report revealed these to be well differentiated, non-invasive grade 2 transitional cell carcinoma. The patient was kept on catheter drainage for 5 days. After removal of the catheter 2 urine cultures were negative for bacteria. The patient was discharged from the hospital on immunosuppressive therapy: 150 mg. azathioprine daily and 20 mg. prednisone every other day. He was also given ascorbic acid and pyridoxin in an attempt to prevent activation of carcinogens in the urine. DISCUSSION
The major problem complicating operations in renal transplant recipients is infection. An operation must be undertaken with continued immunosuppression or rejection will take place. In general, patients with malignancies who undergo transplantation seem to do well, from the standpoint of infection and development of metastatic disease. 2 Therefore, a conservative endoscopic operation was decided upon for this patient. He tolerated the procedure well and infection did not develop. It is too early to determine if this procedure will be successful in controlling the cancer. The over-all incidence (52/5,000) of development of primary malignancy in allograph recipients is much greater than that expected in a comparable population group (8.2/100,000). Since most of these patients were on immunosuppression with azathioprine and steroids, some authors believe that there is a direct relationship between immunosuppression with these agents and the reported increase in malignancies. 2 , 3 There is probably more to this than just the use of azathioprine and prednisone. An increased incidence of malignancy has not been observed in patients with a variety of autoimmune diseases, treated with azathioprine alone or combined with steroids. Organ transplantation provides constant antigenic stimulation of the lymphoid system of the recipient and could possibly supply the sub2 Belzer, F. 0., Schweizer, R. T., Kountz, S. L. and deLorimier, A. A.: Malignancy and immunosuppression: renal homotransplantation in patients with primary renal neoplasms. Transplantation, 13: 164, 1972. 'McKhann, C. F.: Primary malignancy in patients undergoing immunosuppression for renal transplantation. Transplantation, 8: 209, 1969.
418
BIGGS
Endoscopic photographs of representative bladder lesion
strate from which neoplasms might develop. 4 This in association with immunosuppression, especially azathioprine, may explain the high percentage of primary malignancies in transplanted patients. Whatever the mechanism of carcinogenesis and/or breakdown of a tumor surveillance system, the inescapable fact is that transplant recipients on immunosuppressive therapy are 'Leibowitz, S. and Schwartz, R. S.: Malignancy as a complication of immunosuppressive therapy. In: Advances in Internal Medicine. Edited by G. H. Stollerman. Chicago: Year Book Medical Publishers, Inc., vol. 17, 1971.
having a greater incidence of cancer than comparable population groups. SUMMARY
A case of transitional cell carcinoma of the bladder in a transplant patient is presented. Considering the growing amount of evidence that these patients have a higher incidence of malignancy, we should be on the alert for its development. Dr. Harold P. McDonald, Jr. provided the endoscopic photographs.
Vol. 109, March
Copyright © 1973 by The Williams & Wilkins Co.
Printed in U.S.A.
CARCINOMA OF THE BLADDER IN A RENAL TRANSPLANT PATIENT ALBERT W. BIGGS
From the Department of Urology, University of Tennessee College of Medicine, Memphis, Tennessee
A number of primary malignancies have been reported in renal transplant recipients on immunosuppressive therapy. A recent publication records 52 primary malignancies (28 epithelial and 24 mesenchyrpal tumors) developing in approximately 5,000 allograph recipients. 1 Twenty-two of the 24 mesenchymal tumors were malignant lymphomas. Transitional cell carcinoma of the bladder has not been described in a transplant patient. A case of bladder carcinoma in an allograph recipient is reported herein. CASE REPORT
T. W., a 50-year-old white man, was found to have hypertension and albuminuria in 1963. A clinical diagnosis of chronic glomerulonephritis was made and the patient was followed on conservative management. As renal failure progressed, he was placed on henrodialysis. In June 1969 he underwent bilateral nephrectomy, which was complicated by a staphylococcal wound infection. In October the patient received a transplant, using his sister's kidney. Rejection developed immediately following the transplant and the kidney had to be removed. In November 1969 hepatitis developed. In May 1970 a second renal transplant was successfully performed. The patient had total gross painless hematuria in July 1971, which cleared spontaneously after 3 or 4 days. Since that time he had had 4 episodes of gross painless hematuria. An excretory urogram (IVP) in November 1971 was normal. He was cystoscoped and found to have a number of papillary lesions scattered over the bladder wall. He was admitted to the hospital for therapy. Physical examination was essentially negative, except for shortening of the left leg (due to aseptic necrosis of the head of the femur). Urinalysis was within normal range except for microscopic examination, which showed 20 white and 3 red cells per high power field. The blood urea nitrogen was 19 mg. per cent, serum creatinine 1.2 mg. per cent, serum protein 5.8 mg. per cent and albumin 3.6 mg. per cent. Otherwise, all chemistry studies were within normal limits. An IVP revealed slight calicectasis but no definite obstruction was noted. The ureter emptied readily. The patient was taking 20 mg. prednisone every Accepted for publication July 21, 1972. Read at annual meeting of Southeastern Section, American Urological Association, New Orleans, Louisiana, March 26-30, 1972. 1 Schreck, S. A. and Penn, I.: De-novo brain tumors in renal transplant recipients. Lancet, 1: 983, 1971.
other day and 150 mg. azathioprine daily. On December 1, 1971 the patient was given general anesthesia and cystoscoped; 12 papillary lesions were noted in the bladder (see figure). None was around the ureteral orifice. These tumors were resected and the bases were fulgurated. The pathology report revealed these to be well differentiated, non-invasive grade 2 transitional cell carcinoma. The patient was kept on catheter drainage for 5 days. After removal of the catheter 2 urine cultures were negative for bacteria. The patient was discharged from the hospital on immunosuppressive therapy: 150 mg. azathioprine daily and 20 mg. prednisone every other day. He was also given ascorbic acid and pyridoxin in an attempt to prevent activation of carcinogens in the urine. DISCUSSION
The major problem complicating operations in renal transplant recipients is infection. An operation must be undertaken with continued immunosuppression or rejection will take place. In general, patients with malignancies who undergo transplantation seem to do well, from the standpoint of infection and development of metastatic disease. 2 Therefore, a conservative endoscopic operation was decided upon for this patient. He tolerated the procedure well and infection did not develop. It is too early to determine if this procedure will be successful in controlling the cancer. The over-all incidence (52/5,000) of development of primary malignancy in allograph recipients is much greater than that expected in a comparable population group (8.2/100,000). Since most of these patients were on immunosuppression with azathioprine and steroids, some authors believe that there is a direct relationship between immunosuppression with these agents and the reported increase in malignancies. 2 , 3 There is probably more to this than just the use of azathioprine and prednisone. An increased incidence of malignancy has not been observed in patients with a variety of autoimmune diseases, treated with azathioprine alone or combined with steroids. Organ transplantation provides constant antigenic stimulation of the lymphoid system of the recipient and could possibly supply the sub2 Belzer, F. 0., Schweizer, R. T., Kountz, S. L. and deLorimier, A. A.: Malignancy and immunosuppression: renal homotransplantation in patients with primary renal neoplasms. Transplantation, 13: 164, 1972. 'McKhann, C. F.: Primary malignancy in patients undergoing immunosuppression for renal transplantation. Transplantation, 8: 209, 1969.
418
BIGGS
Endoscopic photographs of representative bladder lesion
strate from which neoplasms might develop. 4 This in association with immunosuppression, especially azathioprine, may explain the high percentage of primary malignancies in transplanted patients. Whatever the mechanism of carcinogenesis and/or breakdown of a tumor surveillance system, the inescapable fact is that transplant recipients on immunosuppressive therapy are 'Leibowitz, S. and Schwartz, R. S.: Malignancy as a complication of immunosuppressive therapy. In: Advances in Internal Medicine. Edited by G. H. Stollerman. Chicago: Year Book Medical Publishers, Inc., vol. 17, 1971.
having a greater incidence of cancer than comparable population groups. SUMMARY
A case of transitional cell carcinoma of the bladder in a transplant patient is presented. Considering the growing amount of evidence that these patients have a higher incidence of malignancy, we should be on the alert for its development. Dr. Harold P. McDonald, Jr. provided the endoscopic photographs.