Tomoyuki Kaneko md, Department of Urology, Japanese Red Cross Medical Center, Hiro-o 4-1-22, Shibuya-ku, Tokyo 150-8935, Japan. Email: firstname.lastname@example.org
Abstract A 76-year-old man received intravesical bacillus Calmette-Guérin (BCG) instillations for recurrent superficial bladder cancer. He had undergone right nephroureterectomy for right renal pelvic cancer 9 months previously. He presented with anuria and left hydronephrosis after the fourth instillation, with serum creatinine increasing up to 15.7 mg/dL. Percutaneous nephrostomy was indwelled, and antegrade pyelography showed left vesicoureteral obstruction. There was no sign of recurrent bladder cancer or ureteral cancer. He started spontaneous voiding on day 4 and the nephrostomy was removed on day 8. Most of the side-effects of intravesical BCG therapy are minor, and major adverse reactions are rare. Life-threatening ureteral obstruction would be a rare complication of BCG immunotherapy. Although BCG intravesical instillation after nephroureterectomy is a common practice, special care should be taken of renal function in patients with unilateral kidney during BCG therapy.
Topical bacillus Calmette-Guérin (BCG) immunotherapy is a highly effective treatment for superficial bladder cancer and has been widely used since the 1970s. Although this therapy is often associated with side-effects including cystitis, hematuria or low-grade fever, serious complications are rare.1,2 We report a case of transient anuria due to vesicoureteral obstruction requiring nephrostomy after intravesical BCG instillations.
A 76-year-old man was referred for the evaluation of gross hematuria. Excretory urography and computed tomography of the abdomen showed right renal pelvic tumor. Subsequently right nephroureterectomy was performed and histological examination revealed transitional cell carcinoma, grade 2 T3, of the renal pelvis. Five and nine months postoperatively, he underwent transurethral resection of the bladder tumor (TUR-Bt) for recurrent superficial bladder tumors, which were pathologically transitional cell carcinoma, grade 2 Ta. Both times the recurrent tumors did not involve the left ureteral orifice. Weekly instillation of intravesical BCG (Tokyo 172 strain, 80 mg in 40 mL saline) was started 2 weeks after the second TUR-Bt. Tuberculin skin test and urine cytology before the BCG therapy were negative. No major adverse reactions were seen until the fourth instillation. At 7 days after the fourth instillation, he presented with anuria lasting for 3 days. Ultrasonography showed left mild hydronephrosis, and laboratory data revealed serum creatinine increasing up to 15.7 mg/dL (normal 0.5–1.2 mg/dL). Percutaneous nephrostomy was indwelled and antegrade pyelography showed complete obstruction of the left vesicoureteral junction. On postoperative day 4 after indwelling nephrostomy, he started spontaneous voiding with gradual increase in volume day by day. Antegrade pyelography on day 6 showed no obstruction at the left vesicoureteral junction (Fig. 1). The nephrostomy tube was removed on day 8. Radiological examinations including computed tomography, cystoscopy and urine cytology revealed no evidence of recurrent bladder cancer or ureteral cancer 10 months after nephrostomy removal.
A number of local and systemic complications of intravesical BCG therapy have been reported since Morales et al. presented the results of BCG immunotherapy for bladder cancer in 1976.3 Cystitis, hematuria and low grade fever are common side-effects of BCG therapy, which usually subside within 48 h and do not require specific treatment.4 Reviewing 2602 patients treated with various strains of intravesical BCG instillations, Lamm et al. reported that minor side-effects were common, such as cystitis (about 90%), hematuria (about 30%) and low-grade fever (about 30%), while major adverse reactions occurred in less than 5%.1,2 The most frequently reported major adverse reaction was high fever more than 39.5°C (2.9%) and the second was granulomatous prostatitis (0.9%).1,2 Ureteral obstruction was reported in eight patients (0.3%); however, details were not available in the article.1,2 Ureteral obstruction has not been found in a report from Japan reviewing 3431 patients treated with the Tokyo 172 strain.5 Therefore, life-threatening ureteral obstruction would be a rare complication of intravesical BCG therapy. In the present case it is deduced that severe inflammation of the bladder mucosa caused by BCG therapy led to transient left vesicoureteral obstruction.
Lamm et al. stated that ureteral obstruction after BCG instillation was temporary and self-limited in general, which held true in our case except that it could be fatal without medical treatment. They also reported that carcinoma in situ and vesicoureteral reflux may predispose ureteral obstruction1,2 neither of which was the case with ours.
Bacillus Calmette-Guérin intravesical instillation after nephroureterectomy is a common practice for recurrent bladder cancer. Although ureteral obstruction after BCG therapy is rare and generally transient, a special care should be taken on renal function in patients with unilateral kidney during BCG intravesical instillation therapy.