Late bacille Calmette-Guérin infection with a large focal urinary bladder ulceration as a complication of bladder cancer treatment

Study Type – Therapy (case series)
Level of Evidence 4 What's known on the subject? and What does the study add? Intravesical BCG treatment has been used worldwide for many decades but there are only a few published reports on persisting BCG infection of the urinary bladder. This is the first report on large tuberculosis‐like ulcers of the urinary bladder after intravesical BCG treatment. The finding results in a recommendation to take urine cultures for mycobacteriae in patients with unclear inflammatory lesions in the bladder after instillation of BCG.

OBJECTIVE

• ? To report a late bacille Calmette–Guérin (BCG) complication previously not described in the literature.

PATIENTS AND METHODS

• ? We reviewed our database with 858 patients treated with BCG from 1986 to 2008 and identified 13 male patients (1.8% of all male patients) who had a large tuberculous‐like bladder ulcer.

RESULTS

• ? All patients had high‐grade tumours and seven had tumours invading lamina propria before BCG treatment. A solitary ulceration or inflammatory lesion, 10–50 mm in diameter, was seen at routine follow‐up cystoscopy 2–34 months (median 8 months) after the first instillation. Significantly more patients had been treated with BCG‐RIVM than with BCG‐Tice (10/320 vs. three of 454, P < 0.01). BCG was cultured from urine 3–34 months (median 14 months) after the last instillation.
• ? So far, eight patients have been successfully treated with rifampicin and isoniazid. Nine patients are still tumour‐free 15–66 months (median 44 months) after the last transurethral resection before BCG treatment.
• ? Another three patients had one to two non‐invasive recurrences. One patient had an invasive recurrence and underwent cystectomy. The present study is limited by biases associated with its retrospective design.

CONCLUSIONS

• ? This is the first report on persisting BCG infections with large inflammatory lesions in the bladder. Treatment is effective and the oncological outcome is good.
• ? Mycobacterial cultures of the urine should be performed in BCG‐patients with unclear inflammatory lesions in the bladder since a delayed diagnosis of a persistent BCG infection could result in a permanently reduced bladder capacity.
• ? Large studies are warranted to study differences in efficacy and side‐effects between different BCG strains.

     

Mycobacterium bovis infection of total hip arthroplasty after intravesicular bacille Calmette-Guérin therapy

Bacille Calmette-Guérin (BCG) is a live, attenuated strain of Mycobacterium bovis. Intravesicular BCG therapy is the most effective treatment for superficial bladder cancer. The most common complication of this treatment is cystitis; there is a wide range of other complications. The English-language literature includes reports of 3 total hip arthroplasty infections and 1 total knee arthroplasty infection with M bovis after BCG therapy. These secondary infections may present either acutely during the therapy, months, or even years later. In this article, we report the case of a patient who presented with a painful right hip 6 years after successful total hip arthroplasty and 3 years after treatment for bladder cancer. Left total hip arthroplasty was performed 2 years after right hip arthroplasty. Surgeons examining a painful joint arthroplasty should be particularly suspicious of infection if the patient has a history of BCG therapy.     

Treatment of high-risk superficial bladder cancer with maintenance bacille Calmette-Guérin therapy: preliminary results

OBJECTIVE: To evaluate, in a prospective study, the effects and results of maintenance therapy with bacille Calmette-Guérin (BCG) in treating patients with high-risk superficial bladder cancer. PATIENTS AND METHODS: In all, 155 patients were enrolled in a randomized study of transurethral resection alone (53) or combined with intravesical BCG (102) as a treatment for superficial bladder cancer. BCG was administered for six consecutive weeks followed by three weekly instillations in months 3, 6, 12, 18, 24, 30 and 36 after resection. Recurrence, progression, prognostic factors and side-effects were assessed and analysed. RESULTS: After a median (range) follow-up of 23 (6-42) months, 83 of the 102 patients treated with BCG (81%) were disease-free, compared with 24 of the 53 treated with resection alone (45%). There was also a significant difference in tumour progression and time to progression between the trial arms. The disease progressed in eight patients (8%) treated with BCG and in 12 (23%) of those treated by resection alone. Independent risk factors for progression were DNA ploidy status and stage. Only the completion of treatment was predictive of outcome (risk of recurrence) for patients treated with BCG. CONCLUSION: Maintenance BCG therapy was better than resection alone in reducing the incidence of recurrence and progression in patients with high-risk superficial bladder cancer.     

Second-line intravesical therapy versus cystectomy for bacille Calmette-Guérin (BCG) failures

PURPOSE OF REVIEW: To give an update on the new modalities in treating patients with superficial bladder cancer who have failed bacille Calmette-Guérin. RECENT FINDINGS: The addition of interferon to bacille Calmette-Guérin has proven to be an effective combination therapy for bacille Calmette-Guérin failures. Electromotive intravesical mitomycin C as well as local microwave hyperthermia have been shown to improve drug delivery and increase response rates. Intravesical gemcitabine has shown some promising results in phase I studies and is being investigated in phase II trials. Photodynamic therapy is proposed as a second-line therapy for bacille Calmette-Guérin failures. SUMMARY: New treatment modalities are being introduced and existing ones improved to treat bacille Calmette-Guérin-refractory superficial bladder cancer. These agents need to be studied in large randomized trials. Until these agents prove to decrease recurrence rates and delay progression of high-risk superficial bladder cancer, cystectomy remains the standard of care for the patient who is a good surgical candidate and willing to undergo such major surgery.     

Induction of controlled prostatic tissue necrosis by bacille Calmette-Guérin derivatives

Summary Intraprostatic administration of live bacille Calmette-Guérin (BCG) in humans has been found to produce tumor necrosis; unfortunately, the number of severity of complications have made its clinical use prohibitive. Previous studies have shown that soluble and microparticulate components present in the supernatants obtained after centrifugation of a reconstituted BCG preparation exhibit similar immunogenicity to the one shown by live bacteria. The supernatants, however, are not associated with disseminated infection of the progressive regional tissue destruction observed with the use of viable vaccine.Experiments were conducted to determine the effect of intraprostatic injection of BCG and its supernatants. Adult dogs, after positive conversion to protein purified derivative (PPD), were randomly assigned to three groups. Under direct vision and with digital rectal control, intraprostatic injections of various agents were given as follows: group I, normal saline; group II, live BCG; group III, 200 g of BCG supernatants. Two months later the animals were sacrificed, and the prostates removed in toto and submitted for a thorough histological examination. Extensive but variable tissue necrosis was noted in groups II and III. No histological alterations were present in group I. The histological picture of the animals receiving BCG supernatants conclusively demonstrated circumscribed necrosis of the gland. Side effects and complications were present in animals receiving live BCG but conspicuously absent in the ones receiving supernatants. The observed effectiveness and safety of BCG supernatants for intraprostatic administration in an experimental system may lead to a simple, safe, and efficacious therapeutic modality for localized carcinoma of the prostate in humans.Supported by the Cancer Research Institute of New York     

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.     

Xanthogranulomatous orchitis in a patient with a history of instrumentation and bacillus Calmette-Guérin therapy

Xanthogranulomatous orchitis (XGO) is a rare histological finding that is generally diagnosed at orchiectomy. To date, fewer than 10 reports of XGO exist in the literature. The exact pathogenesis of XGO is unknown and patients may present with a rapid onset of symptoms or a longer, more indolent course. We report a patient who presented with symptoms of epididymoorchitis, leukocytosis, and fever after an instillation of bacillus Calmette-Guérin therapy for bladder cancer.     

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.     

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.     

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.