Multiorgan failure following intravesical bacillus Calmette-Guerin administration: a case report]

We describe a case of multiorgan failure after intravesical bacillus Carmette-Guern (BCG) immunotherapy for bladder cancer. A 58-year-old man with superficial transitional cell carcinoma of the bladder was initially treated by transurethral resection and intravenous chemotherapy, and then administered 11 sessions of BCG intravesically. He was administered BCG intravesically after cystoscopic examination. The next day he complained of nausea and malaise. He became hypotensive. The symptom progressed with multiorgan failure, disseminated intravascular coagulation and respiratory failure. The patient gradually improved with administration of antibiotics and corticosteroid, and hemodialysis, without antituberculous antibiotics. Intravesical instillation of BCG should not be carried out immediately after cystoscopic examination.     

Complications after intravesical instillation of bacillus Calmette-Guerin: rhabdomyolysis and metastatic infection

Two cases of adverse reaction to bacillus Calmette-Guerin (BCG) bladder instillations are reported. In both cases transient fevers and systemic symptoms developed following the instillations. After an additional instillation 1 patient had high fevers, severe myalgias and profound weakness followed by rhabdomyolysis and anuric renal failure, which required 3 weeks of hemodialysis before recovery. Extensive evaluation revealed no cause other than the BCG instillations. In the other patient a firm subcutaneous nodule gradually developed on the chest wall, which contained nonviable acid fast bacilli.     

A case of granulomatous hepatitis after intravesical bacillus Calmette-Guerin administration

A 61-year-old man received intravesical bacillus Calmette-Guerin (BCG) as treatment for superficial bladder carcinoma. High spiking relapsing fevers began 39 days after the initial treatment. A liver biopsy revealed noncaseating granuloma. Deoxyribonucleic acid hybridization of the bone marrow was positive for Mycobacterium tuberculosis complex. Pressure exerted to instill the BCG may have favored dissemination.     

Nephrogenic adenoma associated with intravesical bacillus Calmette-Guerin treatment: a report of 2 cases

Nephrogenic adenoma, a rare metaplastic change of urothelium, was observed in 2 patients after intravesical bacillus Calmette-Guerin instillation. The lesion has not been reported previously in relation to bacillus Calmette-Guerin immunotherapy. We discuss the pathogenesis of nephrogenic adenoma and suggest that the marked prolonged cystitis induced by bacillus Calmette-Guerin has an etiological role.     

Prospective randomized comparison of intravesical with percutaneous bacillus Calmette-Guerin versus intravesical bacillus Calmette-Guerin in superficial bladder cancer

Conflicting reports of the necessity for percutaneous bacillus Calmette-Guerin (BCG) administration with intravesical BCG prompted us to evaluate its benefit in a randomized prospective comparison of intravesical versus intravesical with percutaneous BCG therapy. Intravesical Tice BCG was given in a dose of 50 mg. with or without percutaneous BCG weekly for 6 weeks, at 8, 10 and 12 weeks, at 6 months and every 6 months thereafter. Tumor recurrence was documented in 13 of 30 patients (43%) receiving only intravesical BCG and in 15 of 36 patients (42%) receiving intravesical plus percutaneous BCG. The addition of percutaneous BCG to intravesical therapy did not increase treatment efficacy in this study.     

Persistent acid-fast bacilli following intravesical bacillus Calmette-Guerin

Intravesical bacillus Calmette-Guerin immunotherapy has great efficacy in the treatment of superficial transitional cell carcinoma of the bladder. We report a case of persistent acid-fast bacilli contained within granulomas of the bladder, prostate and epididymides 1 year after treatment with intravesical bacillus Calmette-Guerin. Although commonly encountered immediately after therapy, there are no reported cases of persistent acid-fast bacilli following intravesical administration of bacillus Calmette-Guerin.     

Squamous cell carcinoma of the urinary bladder after intravesical bacillus Calmette-Guerin therapy for carcinoma in situ: a case report

A 88-year-old woman presented with bladder tamponade caused by gross hematuria. She had received 2 courses of bacillus-Calmette-Guerin (BCG) intravesical instillation therapy 4 months previously because of the bladder tumor with carcinoma in situ (CIS). Imaging studies and cystoscopy showed a bladder tumor invading into perivesical fat. She underwent total cystectomy and bilateral ureterocutaneostomy on May 27, 2002. Histopathologically, the tumor consisted of squamous cell carcinoma and transitional cell carcinoma.     

The fate of bacillus Calmette-Guerin after intravesical instillation

PURPOSE: Long-term activation of immunocompetent cells of the bladder wall as well as case reports of systemic infections some months or years after intravesical bacillus Calmette-Guerin (BCG) therapy imply that mycobacteria may persist in the body. Therefore. we investigated the fate of BCG in patients after uncomplicated intravesical instillation therapy. MATERIAL AND METHODS: A total of 49 patients were included in the study, from whom various numbers of specimens were used for mycobacterial culture and molecular biological detection techniques. In 23 patients who received a total of 128 instillations urine, sputum, venous blood and bladder biopsies were screened for BCG by acid-fast staining and culture at different times before and after instillation. From 16 of the 23 patients and from an additional 26 a total of 180 bladder biopsies obtained at intervals 3 to 30 months after instillation were screened for mycobacterial 16S ribosomal DNA by a nested polymerase chain reaction protocol. RESULTS: No viable BCG was found in venous blood or in 127 of 128 sputum specimens before and 2 hours after instillation. Two of 56 bladder biopsies were culture positive. In urine BCG was detected in 96.4% of the specimens after 2 hours and in 67.9% after 24 hours after instillation. The number of positive specimens decreased and it was 27.1% on day 7 immediately before the next instillation. In 14 of 44 bladder biopsies (31.8%) mycobacterial ribosomal DNA was found within 1 week after the sixth instillation. A positive polymerase chain reaction was evident up to 24 months in between 4.2% and 37.5% of the investigated biopsies. After 30 months no ribosomal DNA was evident in the 6 samples available for testing. CONCLUSIONS: Nontraumatic intravesical instillation of BCG is not accompanied by systemic mycobacterial spread. Local persistence during the instillation course is evident since viable BCG is commonly found in the urine. Long lasting and persistent BCG DNA in the bladder wall may account for long-term immuno-activation. However, the remaining BCG may be a possible source of late systemic infections.     

Fatal disseminated mycobacterial infection following intravesical bacillus Calmette-Guerin

We describe a fatal case of disseminated mycobacteriosis after intravesical bacillus Calmette-Guerin immunotherapy. We summarize the prior safety record of this therapeutic modality, discuss local and systemic pathophysiological mechanisms by which dissemination might have occurred, and review the reported clinical experience with antituberculous chemotherapy for significant bacillus Calmette-Guerin infection. Finally, we offer suggestions for prophylaxis of certain patients with a history of exposure to intravesical bacillus Calmette-Guerin.     

Superficial bladder cancer treated by intravesical bacillus Calmette-Guerin or adriamycin: Multicenter study interim report

One hundred sixteen patients with superficial bladder cancers (Stages Ta, T1, and TIS) were evaluated and treated with either intravesical bacillus Calmette-Guerin [Tice strain] (BCG) or doxorubicin hydrochloride (Adriamycin [ADR]), in a multicenter study. One hundred nine of these patients currently have follow-up. Of these, 54 were completely resected and 55 incompletely resected. For complete resections, based on recurrence rates per 100 patient months, both BCG (0.22) and ADR (0.91) worked well, although BCG had a slightly lower recurrence rate. However, for incomplete resections, BCG (0.20) had a markedly lower recurrence rate than ADR (2.52). Eighteen patients failed initial treatment, with either BCG or ADR. All have been placed on long-term therapy schedules. Of the 12 failures who currently have follow-up, 11 (92%) have either partially or completely responded with additional intravesical therapy. No patients in this study have yet required cystectomies.     

Hypersensitivity systemic reaction following intravesical bacillus Calmette-Guerin: successful treatment with steroids.

Intravesical bacillus Calmette-Guerin (BCG) is an effective treatment for superficial bladder carcinoma. Serious complications, including disseminated BCG infection, are infrequent. We report a case of granulomatous hepatitis with pneumonitis following intravesical administration of BCG. Cultures for mycobacteria were negative in sputum, bronchoalveolar lavage, liver and blood specimens. All symptoms disappeared within days after steroid therapy. Hypersensitivity reaction should be considered in patients with systemic symptoms after immunotherapy with BCG.     

Oral or intravesical bacillus Calmette-Guerin immunoprophylaxis in bladder carcinoma

A total of 71 patients with superficial transitional cell carcinoma underwent transurethral resection of bladder tumor. All patients had stage pTa or pT1 transitional cell carcinoma or carcinoma in situ without other concurrent malignancies. The patients were assigned to 3 treatment groups: control group--transurethral resection discontinued within the study, oral bacillus Calmette-Guerin (BCG) group--transurethral resection of bladder tumor plus BCG (Moreau) and intravesical BCG group--transurethral resection of bladder tumor plus BCG. Of 9 patients in the control group 8 (89%) experienced tumor recurrence during a mean followup of 20 months. Of the 28 patients in the oral BCG group 11 (39.3%) had recurrence during a mean followup of 36 months. Of the 34 patients in the intravesical group 6 (18%) had recurrence in a 24-month mean followup. The incidence of complications was higher in the intravesical (41.2%) than in the oral BCG group (28.5%). These results show that intravesical BCG is a more effective immunotherapy; however, oral BCG can be used in patients who do not accept intravesical BCG administration.     

Surgical site infection by bacillus Calmette-Guerin (BCG) after radical cystectomy, occurring after intravesical bcg therapy: a case report

A 51-year-old man received 2 courses of intravesical bacillus Calmette-Guerin (BCG) therapy for carcinoma in situ of the bladder. Two years after the therapy, he underwent left radical nephroureterectomy, cystectomy, urethrectomy and construction of an ileal conduit because of left renal pelvic cancer and severe atrophic bladder. The histopathological diagnosis was carcinoma in situ of the left pelvis and ureter, and epithelioid cell granuloma of left kidney, prostate and bladder. After the operation, he developed extensive surgical site infection (SSI) by BCG, the diagnosis of which was delayed. He recovered from the SSI soon after anti-tuberculosis chemotherapy was begun. We discuss the requirements for more prompt diagnosis of SSI by BCG by analysis of this case.     

Reiter syndrome after intravesical Bacillus Calmette-Guerin (BCG) immunotherapy: a case report

A 56-year-old man who had previously undergone transurethral resection and intra-arterial chemotherapy for bladder cancer developed irritable bladder, bilateral conjunctivitis and arthritis including the knees, ankles and sacroiliac joints after starting intravesical Calmette-Guerin bacillus (BCG) immunotherapy. These symptoms were in agreement with the features of Reiter syndrome. One month after cessation of the intravesical BCG immunotherapy and initiation of the treatment with a non-steroidal anti-inflammatory drug (NSAID), he was not complaining of symptoms. Reiter syndrome is an uncommon complication after intravesical BCG immunotherapy. Nevertheless, since the prolonged arthritis has a possibility to cause joint deformity, we must pay serious attention to this side effect.     

Choice of an optimal diluent for intravesical bacillus Calmette-Guerin administration

The physical conditions, including diluent pH, salt concentration and duration of bacillus Calmette-Guerin attachment, were determined in in vitro binding assays for soluble and matrix fibronectin. Since soluble fibronectin may block attachment of bacillus Calmette-Guerin to matrix fibronectin in the bladder, the optimal conditions were determined under which matrix fibronectin-bacillus Calmette-Guerin binding was maximal and soluble fibronectin-bacillus Calmette-Guerin binding was minimal. These conditions, which were confirmed in vivo in the murine bladder model, included use of normal saline, pH 7 as diluent for bacillus Calmette-Guerin organisms, with retention of the bacillus Calmette-Guerin suspension for 2 hours.     

Clinical evidence of systemic persistence of bacillus Calmette-Guerin: long-term pulmonary bacillus Calmette-Guerin infection after intravesical therapy for bladder cancer and subsequent cystectomy.

A patient with urothelial bladder carcinoma is reported who suffered from culture proved pulmonary bacillus Calmette-Guerin (BCG) infection 14 months after a single course of intravesical BCG and 11 months after subsequent radical cystectomy for progressive cancer. This unusual case raises the question of the ultimate fate of intravesically instilled BCG and the possible persistence of these mycobacteria in remote organs. Systemic spread and dormant survival at least in some cases are suggested, and therapeutic and diagnostic consequences are discussed.     

Immune response following intravesical bacillus Calmette-Guerin instillations in superficial bladder cancer: a review

Local immunotherapy with bacillus Calmette-Guerin (BCG) can prevent recurrences and progression of superficial bladder cancer, but the antitumoral mechanism of BCG is still unclear. The first event seems to be binding of BCG to urothelial cells via fibronectin, and processing of mycobacterial antigens by antigen-presenting cells. Experimental data suggest that bacterial antigens can also be processed by urothelial cells. CD4 lymphocytes subsequently recognize antigenic peptides presented by HLA class II molecules. The most common profile of urinary cytokines is interleukin-2 and interferon-gamma, suggesting the predominant involvement of the Th1 lymphocyte subpopulation. Natural killer cells, lymphocyte-activated killer cells, BCG-activated killer cells and macrophages are able to kill bladder tumor cells in vitro, but there is no evidence that a major histocompatibility complex (MHC)-restricted specific T cytotoxic response is involved in BCG antitumor activity. Received: 11 October 1996 / Accepted: 15 May 1997