膀胱癌之膀胱內卡介苗灌注免疫治療導致結核性副睪睪丸炎之個案報告

邱亮維、張兆祥

中國醫藥大學附設醫院 泌尿部

Tuberculous Epididymo-Orchitis caused by Intravesical Bacillus Calmette-Guérin Immunotherapy for Bladder Cancer: A Case Report

Liang-Wei Chiu, Chao-Hsiang Chang

Department of Urology, China Medical University Hospital, Taichung, Taiwan

Introduction: Intravesical BCG immunotherapy is a treatment option for non-muscle invasive bladder cancer (NMIBC), especially intermediate and high-risk groups based on American Urological Association (AUA) risk stratification. Only about 5% of patients do not tolerate the intravesical BCG with significant adverse effect. The complications caused by intravesical BCG vary from self-limited irritative voiding symptoms to systemic sepsis. Incidence of tuberculous epididymo-orchitis following intravesical BCG is about 0.4%. We report a case of tuberculous orchitis 1 year after the last intravesical BCG immunotherapy.

Case report: In 2012, a 78-year-old man with hypertension and enlarged prostate with lower urinary tract symptoms (LUTS) under medical control presented with painless gross hematuria for 10 days. A bladder tumor was identified by cystourethroscopy exam. He was then diagnosed of non-invasive papillary urothelial carcinoma, high grade, without muscle layer invasion after undergoing transurethral resection of bladder tumor (TURBT) in July 2012. Since then, he had regular follow-ups with cystoscopy. Due to recurrent bladder cancer, he received additional TURBT operations in 2019, followed by a course of intravesical BCG immunotherapy (six instillations weekly). A further three weeks maintenance course of intravesical BCG was given after about three months from surgery. He underwent TURBT again in 2020 because of a positive finding of the cystoscopy exam. The histology reveals infiltrating urothelial carcinoma of bladder, high grade, with lamina-propria invasion. A six-weeks course of intravesical BCG was then given after 2 weeks from surgery. The last dose of intravesical BCG was given in October 2020. According to recurrent bladder cancer, we suggested radical cystectomy, but the patient refused. We prescribed him intravenous form Pembrolizumab from August 2020 to August 2021.  

One year later after the last BCG therapy, he complained of right scrotal pain for about 1 week. Right orchitis was suspected according to the clinical symptoms and scrotum echogram finding. Empiric antibiotic administration with Ciprofloxacin 500mg/tab 1tab Q12H was given for 10 weeks. But the symptom of right scrotal pain persisted after complete antibiotic treatment. Rechecked ultrasonography of the scrotum reveals a heterogeneous, hypoechoic and solid mass surrounded with increased flow in the right testis. The image was ambiguous. Blood tests for testicular malignancy, including alpha-fetoprotein (AFP) and beta- human chorionic gonadotropin (β-HCG), were all within normal limits. Lactate dehydrogenase (LDH) level was elevated mildly. Malignancy can not be ruled out totally. After discussion with patient, he underwent the right orchiectomy. The post-operation specimen showed a 3.0 x 2.5 x 2.0 cm necrotic tumor with pus content in testis, invading through tunica albuginea to tunica vaginalis grossly. The histology revealed necrotizing granulomatous inflammation involving testis, epididymis, and spermatic cord, with giant cell formation. The acid-fast stain (AFS) of pus was positive and Mycobacteria tuberculosis (MTB) complex was found from pus culture. AFS of tumor tissue was positive. MTB quantitative polymerase chain reaction (PCR) from pus was also positive. The diagnosis of post-BCG tubercular orchitis was confirmed. He was then referred to the infectious diseases outpatient department. He subsequently received treatment of Rifampicin, Isoniazid, Ethambutol, and Pyrazinamide.

Discussion: Although the incidence of BCG-related epididymo-orchitis is rare, about 0.4% of complications associated with intravesical BCG, it has been reported to manifest as long as 17 years after the last intravesical BCG instillation. With history of intravesical BCG immunotherapy, tuberculous epididymo-orchitis should be suspected if the empiric antibiotics typically used to treat common epididymo-orchitis fails. In clinical practices, it might be difficult to differentiate tuberculous epididymo-orchitis from other bacterial pathogen infection. The clinical presentation of all epididymo-orchitis includes dysuria, scrotum swelling and scrotal pain. Ultrasound (US) might provide some clues. US features of BCG-related epididymo-orchitis include heterogeneous, hypoechoic, and solid mass with the decreased flow, but surrounded with hyperemia. Sometimes, it might mimic malignancy. If the mass extends beyond the tunica albuginea, malignancy should be suspected. However, because of the lack of diagnostic methods with high sensitivity and specificity, tuberculous epididymo-orchitis is often misdiagnosed with bacterial infection or tumor.  

Conclusions: Intravesical BCG immunotherapy is a useful treatment for NMIBC after TURBT, and most patients could tolerate the adverse effect. However, it still has the risk of tuberculous epididymo-orchitis even ten more years after intravesical BCG instillation. The BCG related epididymo-orchitis should be suspected after empiric antibiotic treatment fails. Sometimes it is difficult to differentiate from malignancy based on clinical presentation and image findings. The orchiectomy could be performed as a diagnostic and therapeutic procedure.