BCGosis: case report of intravesicular bacille Calmette-Guérin causing upper tract granulomas simulating a renal mass without evidence of ipsilateral vesicoureteral reflux

Very rarely, dissemination of intravesical bacille Calmette-Guérin for superficial bladder cancer treatment can lead to a complication in the upper urinary tract. Two mechanisms for dissemination have been proposed: vesicoureteral reflux and hematogenous spread. We report a case of "BCGosis" with the clinical appearance of multifocal renal masses in a patient without ipsilateral reflux. This case highlights the importance of obtaining a renal biopsy in all patients previously treated with bacille Calmette-Guérin presenting with a renal mass. Furthermore, the findings from the present case suggest that vesicoureteral reflux might not be the only mechanism responsible for dissemination of bacille Calmette-Guérin to the upper urinary tract.     

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.     

Intravesical bacille Calmette-Guérin-induced multiorgan failure after treatment for transitional cell carcinoma

Intravesical bacille Calmette-Guérin (BCG) has been safely used to treat stage Ta and T1 bladder carcinoma since 1976. This report presents the case of a 56-year-old man who presented with multiorgan failure after bacille Calmette-Guérin (BCG) treatment for stage T1 transitional cell carcinoma of the bladder. On admission the patient was jaundiced, had inflammatory infiltrates on chest radiography and required dialysis for renal failure. He had a persisting fever of unknown origin and elevated cholestatic liver function tests, which prompted a liver biopsy.This demonstrated hypersensitivity hepatic granuloma but no organism was identified. He responded well to steroid and antimycobacterial treatment. A small percentage of BCG-treated patients suffer hypersensitivity side-effects (pneumonitis, hepatitis or interstitial nephritis). This complication most commonly follows a traumatic installation. Mycobacteriumbovis is rarely cultured or identified using polymerase chain reaction techniques, and the diagnosis is based on histological findings of granuloma.     

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.     

Recent perspectives in topical therapy in superficial bladder cancer

With regard to side-effects in intravesical bacillus Calmette-Guérin instillation therapy and the limited efficacy of intravesical chemotherapy, there is still a need for improvement of these standard therapies. Recently, technical adjuvant means or the modification of cytostatic drugs have been undertaken to improve the efficacy of intravesical chemotherapy. Prognostic indicators of the response to bacillus Calmette-Guérin immunotherapy have been identified, but indicators of side-effects are needed in order to improve the benefit-to-risk ratio of bacillus Calmette-Guérin instillation therapy. Many innovative treatment options, however, still require a definition of their clinical value.     

Immunotesting--a conditio sine qua non for therapeutic BCG instillation in bladder neck carcinoma?

The intravesical instillation of BCG (Bacillus Calmette-Guérin) in cases of relapsed superficial bladder cancer is an acknowledged kind of prophylaxis. It is uncertainly up to now whether a verification of the immune systems competence is necessary. The recommendations in this problem are very different. In conclusion to the recent literature we think that a verification of the immune system before BCG installation in the urinary bladder has not a prognostic value. Additionally, the legal obligingness of this immunotest is doubtful.     

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.     

Modified induction course: a solution to side-effects?

Side-effects are commonly manifested during intravesical Bacillus Calmette-Guérin (BCG) immunotherapy of superficial bladder cancer. This often causes delays or interruptions of the instillations and consequently reduces the efficacy of treatment. Treatment strategies aimed at reducing the side-effects of BCG immunotherapy while maintaining efficacy are currently being considered in the search for an optimal treatment regimen. The following two approaches to BCG immunotherapy were investigated at the Department of Urology of Padova University by specific Phase II and III trials designed to evaluate the possibility of reducing BCG-related side-effects without compromising therapeutic efficacy: (1) by reducing the dose of BCG per instillation 'low-dose' regimen, (2) by delaying the interval of the instillations 'slow-rate' regimen.     

Peritonitis carcinomatosa in a patient with recurrent "superficial" bladder cancer treated with cystectomy and nephroureterectomy

We report on a 45-year-old woman treated with cystectomy after failure of bacille Calmette-Guérin therapy for superficial transitional cell carcinoma. After 9 months, left-sided nephroureterectomy was performed for recurrence in the left ureter. The pathologic examination revealed carcinoma in situ and no tumor-positive lymph nodes (pTisN0Mx). At 2.5 years later, she complained of abdominal distension and pain. She underwent bilateral removal of the ovaries, infracolic omentectomy, and liver biopsy because of suspicious lesions on the liver. Pathologic examination revealed extensive peritoneal spread of transitional cell carcinoma. The seeding potential of high-grade urothelial cancer is well known; however, we found no clear explanation for the peritoneal spread of tumor cells in this patient that occurred years after the surgical procedures.     

The management of superficial bladder cancer

From review of the currently available trial evidence, several clinical recommendations for bladder tumor management become apparent. Transurethral resection should be done, but this procedure is prone to both overestimating and underestimating staging. Restaging transurethral resection for patients with T1 tumors should, therefore, be performed. Data support the immediate postoperative instillation of a chemotherapeutic agent for patients with solitary, low-grade papillary tumors, whereas patients with multiple lesions might benefit from a more intensive adjuvant regimen. Although the use of intravesical immunotherapy for reducing tumor progression or as maintenance therapy is controversial, bacillus Calmette-Guérin has demonstrated significant benefit for tumor prophylaxis when no obvious residual disease is present. Early radical cystectomy can be beneficial and should be performed in patients with refractory T1 tumors or carcinoma in situ before progression to muscle invasion. In this Review I present an overview of the management of nonmuscle invasive bladder cancer. The most common intravesical chemotherapeutic agents are described as well as the impact of chemotherapy on the recurrence and progression of tumors. The effect of intravesical immunotherapy in bladder cancer is explored as well as the role of early cystectomy.     

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.     

Management of hepatic granulomatous tuberculosis complicating intravesical BCG for superficial bladder cancer

Intravesical bacille Calmette-Guérin (BCG) therapy is the most effective treatment for high-risk superficial bladder cancer. Severe systemic complications are rare, but may occur in approximately 1% of cases. We report a severe complication of intravesical BCG: a disseminated Mycobacterium bovis infection with biopsy-proven granulomatous hepatitis in a patient with bladder cancer. We also elaborate on the different management alternatives.     

Surgical treatment of an infant with Bacille Calmette-Guérin osteomyelitis extending across the growth plate

Bacille Calmette-Guérin osteomyelitis in infants is a known complication of Bacille Calmette-Guérin vaccination. Treatment consists of antituberculosis chemotherapy after biopsy/curettage; however, in cases of Bacille Calmette-Guérin osteomyelitis extending to the growth plate and epiphysis, the extent and time of surgical treatment such as curettage/biopsy is unknown because of bone growth disturbances. This article presents a case of an infant with this type of Bacille Calmette-Guérin osteomyelitis at the proximal tibia. A metaanalytic review was performed for possible risk factors of its recurrence. In our patient, primary curettage of partial lesion, excluding the part extending to the growth plate and epiphysis, failed, and recurettage of the extended lesion involving the growth plate and epiphysis was required for its eradication, resulting in bone growth disturbance. In the metaanalysis, 7 literatures reporting 14 cases of Bacille Calmette-Guérin osteomyelitis extending to the growth plate and epiphysis were included. Although statistical analysis showed no significant risk factors associated with the recurrence, these cases showed high recurrence rate in approximately 55.6%, requiring reoperation. Generally, the smaller damage to the growth plate can minimize bone growth disturbance. Taken together, it is suggested that Bacille Calmette-Guérin osteomyelitis extending to the growth plate and epiphysis is associated with high recurrence rate, and early curettage of the entire lesion should be performed to eradicate it and avoid resulting complications.     

Miliary tuberculosis in a patient treated with BCG intravesical instillation

Intravesical instillation of bacillus Calmette-Guérin is the elective treatment for transitional cell and in situ bladder carcinoma. Severe complications occur very seldom but must be known and promptly recognized. We present a case of miliary tuberculosis reactivation secondary to the mentioned treatment.     

Wirkmechanismen der intravesikalen BCG-Immuntherapie des oberflächlichen Harnblasenkarzinoms

Immunotherapy for treatment of solid cancer mostly is an experimental treatment. In contrast, intravesical immunotherapy of superficial bladder cancer with bacille Calmette-Guérin (BCG) is clinically well established and accepted worldwide because of better results compared to topical chemotherapy. BCG is currently regarded as the most successful immunotherapy of cancer. Unfortunately the mechanism of action has not yet been fully clarified. This article gives an overview on the complex research on the mechanisms of actionhighly successful therapy.     

Effect mechanism of intravesical BCG immunotherapy of superficial bladder cancer

Immunotherapy for treatment of solid cancer mostly is an experimental treatment. In contrast, intravesical immunotherapy of superficial bladder cancer with bacille Calmette-Guérin (BCG) is clinically well established and accepted worldwide because of better results compared to topical chemotherapy. BCG is currently regarded as the most successful immunotherapy of cancer. Unfortunately the mechanism of action has not yet been fully clarified. This article gives an overview on the complex research on the mechanisms of actionhighly successful therapy.     

Urinary cytokines reflecting the immunological response in the urinary bladder to biological response modifiers: their practical use

BACKGROUND: Intravesical bacillus Calmette-Guérin (BCG) immunotherapy is currently the most effective treatment for superficial transitional cell carcinoma (TCC) of the urinary bladder. In recent years, the substantial number of patients not responding to BCG or experiencing considerable toxicities has stimulated studies addressing either the development of improved BCG treatment schedules or the exploration of the therapeutic value of a series of (novel) biological response modifiers, like interferons (IFNs), interleukin (IL) 2 and keyhole limpet hemocyanin. Although the actual mechanism by which BCG exerts its antitumor effect still needs detailed unraveling, current available knowledge suggests the induction of a T helper 1 (Th1) or Th1-like cytokine profile, represented by IL-2, IL-12 and IFN-gamma, as essential in the development of a cell-mediated antitumor activity. CONCLUSIONS: In this review, it is argued that incorporation of urinary cytokine determinations, like IL-2 and possibly IL-12 and IFN-gamma, may represent a valuable approach in the optimization and individualization of the BCG therapy and an early, initial evaluation of the potential efficacy of novel immunomodulating agents in the treatment of superficial TCC.     

Failure of intravesical interferon-alfa-2b for the treatment of patients with superficial bladder cancer previously failing intravesical BCG Therapy

Twelve patients with superficial bladder cancer who had failed one or two 6-week courses of intravesical bacillus Calmette-Guérin (BCG) therapy were treated with recombinant interferon-alfa-2b (rIFN-alfa-2b). Patients received 12 weekly instillations of rIFN-alfa-2b (100 MU) in 50 cc of normal saline. Those with an initial tumor-free response at the 3-month follow-up received maintenance rIFN-alfa-2b instillations (100 MU) monthly for an additional 9 months. Prior to rIFN-alfa-2b treatment, 6 patients had carcinoma in situ (CIS) with concurrent papillary tumor (pTa or pT I), and 6 had grades I or 2 pTa tumors. Patients were monitored every 3 months with urinary cytologies, cystoscopies, and biopsies when indicated. Median follow-up was 18 months (range 12 to 26 months). At the 3-month follow-up tumor recurrence was noted in 8 (66%) of 12 patients. An additional 3 (25%) patients had tumor recurrence at the 6-month follow-up period, and 3 (25%) patients also developed upper tract tumors during follow-up. Only 1 (8%) patient has maintained a continuous tumor-free response for 24 months. We are unable to demonstrate that rIFN-alfa-2b is likely to induce a tumor-free response in superficial bladder tumor patients who have failed intravesical BCG therapy, including those with CIS.     

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.     

The effect of isoniazid on BCG-induced toxicity in patients with superficial bladder cancer

The use of bacillus Calmette-Guérin in the treatment of transitional cell cancer of the bladder has caused concern because of its associated adverse effects. We conducted a randomized prospective, double-blind, multicentre study to determine whether isoniazid prophylaxis could reduce BCG-induced toxicity without compromising its immunotherapeutic effects. Patients (n = 160) with histologically documented urothelial cancer (pTa-T1, pTis, G1-3) were treated with 6 weekly instillations of BCG Connaught strain, 81 mg, administered concomitantly with a 3-day course of isoniazid (300 mg o.d.) or placebo. Side-effects were recorded with each treatment and at follow-up. Of the patients treated with isoniazid, 19% remained free from side-effects, compared with 16% of the placebo group. Local side-effects confined to the bladder were significantly lower among those receiving isoniazid (35% vs. 48%, p < 0.01). Local side-effects together with systemic adverse effects such as fever, nausea or skin rash were experienced by 30% of patients in each arm. There were no differences in tumour recurrence between the two patient groups. Concomitant isoniazid reduces the local, but not the systemic side-effects of topically applied BCG without compromising the antitumour effect on superficial, transitional cell cancer of the bladder during a follow-up period that now exceeds 2 years.