Intravesical bacillus Calmette-Guérin and second primary malignancies

In an effort to answer the question, "Does intravesical bacillus Calmette-Guérin (BCG) therapy increase the incidence of second primary malignancies," the records of 153 patients treated with BCG for carcinoma in situ of the urinary bladder were reviewed. The weight of the available evidence suggests that intravesical BCG does not increase the incidence of second primary malignancies. While this question should be investigated, at the present time it appears that the advantage of intravesical BCG for high-risk patients with superficial bladder cancer outweighs the known disadvantages.     

Vitiligo--an autoimmune side-effect of intravesical bacillus Calmette-Guérin instillation?

We report a case of vitiligo in a 63-year-old man who had undergone intravesical bacillus Calmette-Guérin treatment following removal of a superficial transitional cell carcinoma in the bladder.     

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.     

Nephrogenic adenoma of the bladder after intravesical bacillus Calmette-Guérin treatment

A 60-year-old female patient was subjected to transurethral resection of transitional cell carcinoma of the bladder and was given intravesical bacillus Calmette-Guérin treatment for 6 weeks. The control cytoscopy performed after 6 months revealed a polypoid lesion at the trigon and the lesion was resected. The pathological examination of the specimen showed no evidence of cancer but the presence of a metaplastic lesion that was nephrogenic adenoma.     

Primary aortoenteric fistula following disseminated bacillus Calmette-Guérin infection: a case report

The aim of this paper is to illustrate a rare case of primary aortoenteric fistula in the presence of disseminated infection and review the critical decision-making process. A clinical case was reviewed for its initial presentation, planning of treatment strategy and outcome. A secondary literature search for discussion on current accepted recommendations for primary aortoenteric fistula was then completed. Aortoenteric fistulas are rare pathologies with highly morbid potential. Their diagnosis requires a high index of suspicion and prompt intervention is critical to patient survival. In conclusion, aortoenteric fistula most commonly arises from large atherosclerotic aneurysms but can be caused by systemic infection. In the case of the latter, extra-anatomic repair appears to be the treatment of choice.     

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.     

A case of interstitial pneumonitis caused by intravesical bacillus Calmette-Guérin instillation]

A 61-year-old man was referred to our hospital due to positive urine cytology. He underwent multiple cold punch biopsies of the bladder and the histopathological finding was transitional cell carcinoma (TCC), carcinoma in situ (CIS), grade 3. He was treated with 121.5 mg of bacillus Calmette-Guérin (BCG) (Connaught strain) suspended in 50 ml of saline instilled into the bladder at weekly intervals. After the third instillation he developed a fever up to 39 degrees C, pain on urination and an elevation of liver enzymes. Antituberculous drugs were administered and he was re-admitted for further evaluation. The chest radiograph showed diffuse extensive bilateral lung densities. His chest computed tomographic (CT) scan showed bilateral interstitial pneumonitis. All cultures from his blood, urine, sputum, and bronchoalveolar lavage remained negative for mycobacteria. He was diagnosed as having a hypersensitivity reaction of bilateral lung after immunotherapy with BCG. Pulse steroid therapy was done. The chest radiograph, findings improved and he was clinically asymptomatic after steroid therapy.     

Optimal treatment of systemic bacillus Calmette-Guérin infection: investigations in an animal model

PURPOSE: Hematogenous spread of bacillus Calmette-Guerin (BCG) after intravesical instillation for bladder cancer is rare but it may result in systemic infection and hypersensitivity reaction. We investigated fluoroquinolones and steroids in an animal model to improve the therapeutic options in local and systemic BCG infection. Furthermore, the antitumor effectiveness of intravesical BCG with simultaneous application of fluoroquinolones and/or steroids was tested. MATERIALS AND METHODS: Oral antimicrobial therapy with and without steroids was started immediately after intraperitoneal injection using fluoroquinolones or trimethoprim-sulfamethoxazole. To evaluate the therapeutic options against a hyperergic reaction after repeat systemic BCG infection re-challenge was performed with intraperitoneal BCG 7 days after primary infection and oral therapy was given with fluoroquinolones or trimethoprim-sulfamethoxazole with and without steroids. The influence of continuous oral fluoroquinolone therapy on the antitumor effect of BCG was also tested in the MB 49 orthotopic murine bladder tumor model. RESULTS: After primary systemic infection fluoroquinolone therapy alone led to significantly prolonged survival in mice (log rank test p = 0.041), whereas trimethoprim-sulfamethoxazole was ineffective. There was no additional effect of steroid administration. Steroids alone led to premature death (log rank test p = 0.022). After secondary BCG infection only steroid treated animals had prolonged survival (log rank test p = 0.032), whereas antimicrobials alone had no effect. The therapeutic efficacy of BCG in the orthotopic bladder tumor model was not affected by continuous oral fluoroquinolones in terms of survival (log rank test p = 0.001) or bladder weight (Wilcoxon test p = 0.001) compared with untreated controls. CONCLUSIONS: In a mouse model fluoroquinolones had a beneficial effect for primary systemic BCG infections, whereas the hyperergic reaction after repeat BCG infection was susceptible only to steroids. Administering fluoroquinolones during an intravesical treatment course does not affect the antitumor efficacy of BCG.     

Urinary fibronectin levels in patients treated with intravesical bacillus Calmette-Guérin for superficial bladder cancer

Intravesical bacillus Calmette-Guérin (BCG) has been shown to be an effective treatment for superficial transitional cell carcinoma (TCC) of the bladder, but the precise mechanism of action of BCG remains poorly understood. Fibronectin (FN), an important component of the extracellular matrix, has been found to play a role in BCG therapy. Some studies have shown that the soluble form of FN can compete efficiently with the matrix form of binding to the specific receptors on the bacteria and could consequently diminish the effect of BCG treatment. To evaluate a possible correlation between the urinary levels of FN and the efficacy of BCG therapy, we determined prospectively the urinary FN levels in 38 patients with TCC of the bladder and in 25 control subjects without malignancy matched for age and sex. All TCC patients were treated with transurethral tumor resection plus 6 weekly intravesical BCG instillations. After an average follow-up of 30 months, 8 patients (21.1%) had recurrent tumors, while 30 (78.9%) were free of tumor after intravesical BCG therapy. Urinary levels of FN in cancer patients have been shown to be significantly higher than controls (p < 0.001). These elevated levels were not decreased significantly after the operation (p > 0. 05). It was also found that the mean urinary FN levels were not statistically significant between patients with recurrence and complete remission. The data suggest that BCG-bladder tumor cell binding is not influenced by soluble fibronectin and urinary FN may not be a ideal marker for selecting patients to BCG therapy.     

Diffuse granulomatous mesenteric disease caused by intravesical bacillus Calmette-Guérin instillation masquerading as peritoneal carcinomatosis

Intravesical instillation with bacillus Calmette-Guérin is the most common therapy used for nonmuscle invasive bladder cancer in North America. Although local side effects are common, systemic side effects are rare when it is administered correctly. We present a case of diffuse mesenteric granulomatous disease resulting from inappropriate instillation of this agent. This patient was thought to have peritoneal carcinomatosis. One must be cognizant of the possibility when evaluating patients with similar findings and images after bacillus Calmette-Guérin therapy.     

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.     

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.