Late occurrence of bilateral tuberculous-like epididymo-orchitis after intravesical bacille Calmette-Guérin therapy for superficial bladder carcinoma

We report a case of bilateral tuberculous-like epididymo-orchitis occurring 3 years after intravesical bacille Calmette-Guérin instillation therapy in an 83-year-old patient with proven superficial bladder carcinoma. The patient had no previous history of tuberculosis. Because of persistent inflammation and painful swelling of the epididymides and testes, the patient underwent bilateral orchiectomy. This case demonstrates the late adverse effects that can occur after intravesical BCG therapy, which in our patient ended in surgical removal of both gonads.     

Tuberculous epididymitis following intravesical Bacillus Calmette-Guérin therapy

Bacillus Calmette-Guérin (BCG) immunotherapy is increasingly being accepted for management of some bladder transitional cell neoplastic lesions. Mild adverse reactions occur frequently. However, an unusual complication of tuberculous epididymitis is reported. A 64-year old man presented with bilateral epididymal mass. Four months earlier he had seven treatments with intravesical BCG instillation (Tokyo 172 strain) for a grade 2 transitional cell carcinoma in situ. Bilateral epididymectomy was performed. Microscopic examination of the epididymis revealed chronic inflammation and necrosis with granulomas and Langhans' giant cells. After the operation, there were no further complications.     

Isolated renal tuberculosis following intravesical Bacillus Calmette-Guérin therapy for bladder cancer

We present a case of isolated renal tuberculosis following bacillus Calmette-Guérin (BCG) therapy for bladder cancer. In the presurgical radiographic examination, we suspected an atypical renal cell carcinoma. According to the diagnosis of renal cell carcinoma, we performed a radical nephrectomy. The histological findings were tuberculosis-specific inflammatory changes and the patient received an antituberculous multiple drug therapy for a year. It is concluded that we should pay attention to the possibility of a renal tuberculosis granuloma in any patient who presented with subacute formed renal masses following BCG treatment before deciding on the strategy of the treatment of the renal masses, especially in patients who had received such a treatment which induced an immunocompromised state.     

Infected total hip arthroplasty after intravesical bacillus Calmette-Guérin therapy

An infected total hip arthroplasty remains one of the most challenging problems faced by orthopedic surgeons. We present the case of a 76-year-old man with an unusual infected total hip arthroplasty. Four years before presenting to our service, the patient was treated for vesical transitional cell carcinoma with intravesical administration of bacille Calmette-Guérin. The patient presented with groin pain, radiographic loosening of the hip implant, and elevated erythrocyte sedimentation rate and C-reactive protein. He underwent irrigation and debridement of the hip with removal of components. Cultures isolated bacille Calmette-Guérin necessitating treatment with antituberculosis chemotherapy. Bone cultures obtained under computed tomography guidance were negative, and reimplantation surgery was performed with a successful outcome. Pathway of infection spread, diagnosis, and treatment of this rare infection are discussed with review of the literature.     

Superficial transitional cell carcinoma: bacillus Calmette-Guérin (BCG) and other intravesical agents

Adjuvant immuno- and/or chemotherapy intravesically has become a standard at least for patients with intermediate or high risk for recurrence. Whereas in the past cystectomy was a first-line therapy for patients with carcinoma in situ or high-grade T1 bladder tumor, radical surgery is today reserved for non-BCG responders or early recurrent disease.     

Cytological changes induced by intravesical bacillus Calmette-Guérin therapy for superficial bladder cancer

To evaluate cytological changes of urothelial cells with intravesical instillation therapy of the bacillus Calmette-Guérin (BCG), cytological specimens of voided urine from patients with superficial bladder cancer (pTa and pT1) treated with intravesical BCG therapy were examined. The following three groups of patients who had no evidence of recurrence more than 2 years after the treatment were studied: groups 1 and 2, patients who were treated with BCG (n = 22) and epirubicin, a derivative of doxorubicin (n = 22), respectively, for prophylaxis of intravesical recurrence after transurethral resection (TUR); and group 3, patients receiving no intravesical therapy after TUR (n = 12). Sixteen cytological characteristics were studied before and after the treatment in each group. In group 1 patients translucent nuclei and prominent nucleoli, vacuolization of cytoplasm, and eosinophilic cytoplasmic inclusions were frequently observed in urothelial cells as well as an increase in granulocytes, especially within 3 months after BCG instillation therapy. In group 2 patients an increased nuclear/cytoplasmic ratio, hyperchromatic nuclei and prominent nucleoli of urothelial cells were transiently found within 1-2 months after intravesical epirubicin therapy. In group 3, translucent nuclei and prominent nucleoli of urothelial cells were found within 1-2 months after TUR. In conclusion, cytological changes induced by BCG therapy are nonspecific and reactive in nature, different from those due to chemotherapeutic agents and distinguishable from malignant changes of urothelial cells.     

Granulomatous nephritis as a complication of intrarenal bacille Calmette-Guérin therapy

A case of granulomatous nephritis after intrarenal bacille Calmette-Guérin (BCG) therapy is reported. High fever greater than 38.5 degrees C lasted for 1 month, without response to conservative therapy. Standard nephroureterectomy was subsequently carried out. Histopathologic findings from the surgical specimen were compatible with BCG-induced granulomatous nephritis. The use of a syringe pump for retrograde instillation of BCG was thought to be the major cause of this severe complication.     

Results of adjuvant intravesical Bacillus Calmette-Guérin therapy for grade 3 superficial bladder cancer

To examine the incidence of recurrence, progression and survival in patients with grade 3 superficial bladder cancer after transurethral resection (TUR) and adjuvant intravesical instillation of Bacillus Calmette-Guérin (BCG), we retrospectively studied 39 patients with grade 3 superficial bladder cancer. Nineteen patients with high-grade superficial bladder cancer (pTa, pT1) and 5 patients with grade 3 carcinoma in situ (CIS) received intravesical instillation of BCG after transurethral resection of the bladder tumor (BCG group and CIS-BCG group). The Tokyo 172 strain BCG was given for 8 weeks, as a rule, in a dose of 80 mg in 40 ml of saline instilled into the bladder. As a control, 15 patients with grade 3 superficial bladder cancer who did not receive BCG therapy after TUR were compared (non-BCG group). Of the BCG group (n=19), 4 patients (21.1%) had recurrent tumor and 3 had invasive progression after BCG therapy and died as a result of tumor progression, while in the non-BCG group (n=15), 8 cases (53.3%) developed recurrence, only one case had progression and died of cancer. In the CIS-BCG group (n=5), 3 patients (60.0%) had recurrent tumor and 2 had invasive progression. Univariate analysis (Logrank test) demonstrated that tumor size and adjuvant instillation of BCG were associated with tumor recurrence except for carcinoma in situ, but tumor progression and survival did not differ significantly. Our results suggest that BCG therapy prevents grade 3 superficial bladder cancer (pT1, pTa) recurrence.     

Long-term follow-up of T1 high-grade bladder cancer after intravesical bacille Calmette-Guérin treatment

Study Type – Therapy (cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? High‐grade non muscle invasive bladder cancer is a very aggressive disease, potentially lethal if not managed adequately, because of the ability of these tumours to invade surrounding tissues and become metastatic. Treatment with intravesical BCG has been shown to delay progression to muscle invasive or/and metastatic disease, preserve the bladder, and decrease the risk of death from bladder cancer. However, most studies have analyzed patients with short follow‐up, and long‐term data about the real efficacy of BCG to prevent tumour recurrence, progression and impact mortality are lacking. This study has analyzed a large series of patients with high‐grade non muscle invasive bladder cancer treated with intravesical BCG in two University Institutions (Toronto and Rotterdam), with a central pathology review by a very experienced uro‐pathologist. It provides further insight into the long‐term risks of progression of patients harbouring high‐grade T1 bladder cancer treated with BCG, demonstrating that about 30% of patients are at risk of progression and that late progressions even more than 3 years after the initial resection and BCG treatment are rare but not exceptional.

OBJECTIVE

To report the long‐term results of bacille Calmette‐Guérin (BCG) intravesical therapy in relation to disease progression and recurrence in primary T1 high‐grade (HG) bladder cancer (BC) confirmed by central pathological review.

PATIENTS AND METHODS

In all, 136 patients from two university centres (Rotterdam, n= 49; Toronto, n= 87) were diagnosed with primary T1HG BC. One experienced uro‐pathologist reviewed all slides, ensuring all cases were indeed HG and that muscle was present in all specimens. Patients were treated with BCG induction (six instillations) after transurethral resection (TUR) of the tumour and followed with cystoscopy and urinary cytology. Predictors for recurrence, progression and survival were assessed with multivariable Cox regression models.

RESULTS

Mean (range) follow‐up was 6.5 (0.3–21.6) years. There were no significant differences for recurrence (P= 0.52), progression (P= 0.35) and disease‐specific survival (DSS) (P= 0.69) between the two centres. Among the cohort, 47 patients (35%) recurred and 42 (30.9%) progressed with a median time to progression of 2.1 years; 16 (38%) of these progressions occurred ≥3 years after the initial BCG course; 22 (16%) patients who progressed died from BC. Overall, 96 (71%) patients had no evidence of disease at the last follow‐up. Carcinoma in situ was the only independent predictor for recurrence in multivariate analysis (P= 0.011). No independent predictors were found for progression.

CONCLUSIONS

Conservative treatment with BCG is a valid option in primary T1HG BC. Nevertheless, the aggressive nature of T1HG BC is evident in the fact that 30% progressed, with a high proportion of these progression events occurring ≥3 years after BCG. Caution should be exercised when relying on the long‐term effects of BCG, and close follow‐up of these patients should not be neglected.     

A case with hepatitis and interstitial pneumonitis caused by intravesical bacillus Calmette-Guérin (BCG) instillation

A 49-year man, with past history of right total nephroureterectomy due to urothelial carcinoma of the right renal pelvis in September 2006 and left partial ureterectomy due to contralateral ureteral recurrence in October 2007, underwent TUR-BT due to superficial high-grade recurrent bladder cancer. After TUR-Bt, he was treated with intravesical Bacillus Calmette-Guérin (BCG) instillation at weekly intervals. Just after 5th instillation, he suffered a continuous high fever up to 38 degrees C and complained of general fatigue. Chest CT showed diffuse micronodular shadows in both lungs, and serum liver enzyme was markedly elevated. All cultures from his sputum and urine were negative for mycobacterium tuberculosis. TB-PCR test and quantiferon were also negative. These findings together with no improvement of the symptoms with anti-tuberculous treatment finally made us to judge that this was due to a hypersensitivity reaction to BCG. Soon after pulse steroid therapy, body temperature was normalized and the abnormal findings of the lung and liver disappeared.     

Prognostic factors in patients with carcinoma in situ treated with intravesical bacille Calmette-Guérin

OBJECTIVE: To report prognostic factors and follow-up data for an unselected group of patients with carcinoma in situ (CIS) of the urinary bladder treated with bacille Calmette-Guérin (BCG). MATERIAL AND METHODS: The clinical records of patients with CIS treated with BCG were reviewed. All 173 patients treated between 1986 and 1997 in four hospitals in two Swedish cities were included. The median follow-up period was 72 months (range 6-154 months). The impact of 18 variables on the times to recurrence and progression was studied using multivariate Cox proportional hazard regression and Kaplan-Meier analyses. RESULTS: No pre-treatment variables, including type of CIS and T1G3 tumour, had prognostic value in terms of time to progression. The result of the first cystoscopy had a very strong prognostic importance: 44% of patients with a positive first cystoscopy progressed in stage, 59% were BCG failures and 35% died from urothelial cancer. The corresponding values for patients with a negative first cystoscopy were 11%, 18% and 8%. Fourteen patients (8%) were diagnosed with an upper urinary tract tumour but no variable had prognostic significance. The diagnoses of the upper urinary tract tumours were evenly distributed during follow-up. CONCLUSIONS: We were not able to predict which patients would respond favourably to BCG. Cystectomy should be strongly considered even after a positive first cystoscopy. The accumulated incidence of patients with bladder CIS and a subsequent upper urinary tract tumour is rather high but it is questionable whether the prognosis will improve if routine follow-up urographies are performed.     

Long-term results of intravesical bacillus Calmette-Guérin therapy for stage T1 superficial bladder cancer

OBJECTIVES: To examine in a prospective study the incidence of recurrence and progression in patients with Stage T1 bladder carcinoma after complete transurethral resection of the bladder tumor and adjuvant immunotherapy with bacillus Calmette-Guérin (BCG). METHODS: Between July 1987 and April 1999, 126 patients presenting to our clinic with a superficial urothelial carcinoma of the bladder (Stage pT1, grade 1-3) received adjuvant intravesical immunotherapy with BCG after complete transurethral resection of the bladder tumor. In the case of recurrence of superficial tumor (pTa, pT1, or carcinoma in situ), patients received a second cycle of BCG. For muscle-invasive tumor progression (pT2, pT3, or pT4), radical cystectomy was recommended. Six of the patients (5%) presented with Stage pT1,G1 tumor, 74 (59%) with Stage pT1,G2 tumor, and 46 patients (36%) with Stage pT1,G3 tumor. Median follow-up was 53 months (range 3 to 144). RESULTS: One hundred eight patients (86%) remained tumor-free with a retained bladder during the follow-up after one or two 6-week cycles of BCG. Twenty-four patients (19%) had a recurrence of superficial tumor, 13 (10%) had muscle-invasive progression after the first BCG cycle, and an additional 4 (3%) had progression after the second BCG cycle. Six patients (5%) underwent radical cystectomy, and 9 patients (7%) died as a result of tumor progression. The tumor-free survival rate of all patients was 89% (112 of 126). CONCLUSIONS: Adjuvant immunotherapy with BCG after complete transurethral resection of the bladder tumor represents a highly effective primary treatment for Stage T1 carcinoma of the bladder. Even in Stage pT1,G3 tumor, immediate radical cystectomy does not appear necessary.