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.     

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.     

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.     

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.     

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.     

Mycotic vascular infections of large arteries with Mycobacterium bovis after intravesical bacillus Calmette-Guérin therapy: Case report

Disseminated infection after intravesical bacille Calmette-Guérin instillation for bladder cancer is a rare but potential complication. Vascular infection is an additional serious complication but is seldom reported. We present the first report of a small series of patients with vascular infections after intravesical bacille Calmette-Guérin instillation, and we review the related literature. (J Vasc Surg 1999;29:377-81.)     

Evolution of the urothelial bladder field after intravesical Bacille Calmette-Guérin therapy.

After transurethral resection (T.U.R) and open surgery of 178 patients with superficial bladder tumors (pTa, pT1) we applied intravesical Romanian (modified Pasteur strain) Bacille Calmette-Guérin therapy. An introduction phase consisting of 8 weekly instillations was followed by a maintenance phase of instillations monthly for 10 months and then 3 monthly for 2 years. Two cases with primary Carcinoma in situ (Cis) were treated with the same protocol. The random urothelial biopsies (4 quadrant) showed before immunotherapy 105 cases (58.33%) with simple (36 cases), medium (36 cases), severe (13 cases) dysplasia and Cis (20 cases) and after 3 years of treatment we found 37 cases (20.55%) with simple (14 cases), medium (14 cases), severe (9 cases) dysplasia and two cases with invasive stage after Cis. The response rate was 75, 55% at 3 years. The mean period of follow up was 50 months. The complications of this therapy were frequent but mild. These results demonstrated the dynamic evolution of the urothelial bladder field after "long-course treatment" with intravesical BCG.     

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.     

Effect of advanced age on the development of complications from intravesical bacillus Calmette-Guérin therapy

PURPOSE: Advanced age is considered a risk factor for complications in patients receiving intravesical bacillus Calmette-Guérin (BCG) therapy. However, there is no clear delineation of BCG-related complication rates relative to patient age. MATERIALS AND METHODS: We reviewed the clinical course of 58 consecutive men receiving maintenance BCG therapy from December 1999 to July 2004 for transitional cell carcinoma. Patients ranged in age from 51 to 92 years (mean 72.4). Age and BCG-related complications warranting discontinuance of therapy were documented. RESULTS: In our patient population, 22 of 58 (37.9%) patients experienced complications. The complication rate for patients <70 years old on intravesical BCG maintenance therapy was 17.6%. Patients >or=70 years old had a complication rate of 48.6%. Excluding patients taking anticoagulants, the complication rate in patients age 70 and older was 53.3%. Patients who had complications (mean age 76.0 years) were significantly older than those who had no complications (mean age 70.3 years) (P < 0.00001). The peak incidence of complications occurred with the third BCG course. CONCLUSIONS: Maintenance BCG therapy should be given with caution in patients over age 70 and should be avoided in patients over age 80. Elderly patients at high risk for TCC recurrence and progression may be better served with a single 6-week course of BCG or alternative intravesical agents. Anticoagulants may be somewhat protective against complications in elderly patients but have been shown to significantly decrease the effectiveness of intravesical BCG, further supporting the consideration of alternative agents.     

Vesicoureteral reflux after intravesical instillation of bacillus Calmette-Guérin against carcinoma in situ of the bladder

We report a case of vesicoureteral reflux (VUR) 3 years after intravesical instillation of bacillus Calmette-Guérin (BCG, Tokyo 172 strain) against carcinoma in situ of the bladder. The present case suggests that a long-term careful follow-up is needed to detect not only tumor recurrences but also VUR as a late complication after intravesical BCG instillation.     

Increased urinary albumin indicating urothelial leakage following intravesical bacillus Calmette-Guérin therapy for superficial bladder cancer

Summary This study on the increase in albumin in the urine of patients with superficial bladder cancer after intravesical bacillus Calmette-Guérin (BCG) treatment was initiated on the basis of two facts. First, extravasation of serum albumin could be expected as a result of the BCG-induced delayed-type hypersensitivity reaction in the bladder wall. Second, appearance of albumin in the urine was a possibility as cytokines also appear in the urine, although probably after being produced suburothelially by infiltrating leukocytes. Albumin and the cytokines interleukin (IL) 1, IL2, IL6, and tumor necrosis factor alpha (TNF) were determined in urine from 20 patients treated with 6 weekly intravesical BCG instillations, collected prior to each instillation and 2, 4, 6, 8, 12, and 24h thereafter. The mean concentration of albumin in pre-therapy specimens was 112±118 (range 2–432) g albumin/ml urine, approximating 14±14 g/ mol creatinine (creat) (n=15), which was comparable to the mean pre-instillation value of 16±32 g/mol creat (n=96). A significant increase in urinary albumin during the 6 weeks of BCG treatment was observed (P<0.001). However, a large variation existed between individual patients and in some patients no reaction was seen. Maximum albumin concentrations were observed after instillations 3–6. A significant correlation between albumin and concentration of the cytokines IL1, IL2, IL6, and TNF was found (P<0.01), correlation coefficients (r) being 0.56, 0.56, 0.67, and 0.71 (n=418), respectively. During the first 24h after instillation cytokines and albumin peaked in the following order: TNFIL2albuminIL6IL1. TNF peaked most frequently after 2–4h and IL1 after 6h, while IL2, albumin, and IL6 peaked between these time points. In conclusion, the presence of albumin in urine indicates a leakiness of the bladder wall after repeated BCG instillations. Since albumin was shown to be stable in urine and the assay is relatively simple and cheap, it may be performed in most hospitals. This will allow largescale investigations of the correlation between elevation of urinary albumin and (tumor) response on BCG therapy.     

Ruptured mycotic abdominal aortic aneurysm secondary to Mycobacterium bovis after intravesical treatment with bacillus Calmette-Guérin

Bacillus Calmette-Guérin (BCG) is a live attenuated strain of Mycobacterium bovis that has proven effective in the treatment of early-stage bladder cancer. Although intravesical therapy with BCG is generally considered safe, serious complications including hematuria, granulomatous pneumonitis, hepatitis, and life-threatening BCG sepsis are well known. BCG-related vascular infections are rarely reported. We present a case of a ruptured abdominal aortic aneurysm secondary to M bovis infection 2 years after intravesical instillation of BCG and review the related literature.     

A case of tuberculous epididymitis after Bacillus Calmette-Guérin intravesical instillation therapy for bladder cancer

A 65-year-old male had undergone transurethral resection of bladder tumor (TUR-Bt) four times for recurrent bladder cancer, and each histopathological examination revealed non-invasive urothelial carcinoma, pTa, G2. To prevent further recurrence, he received eight weekly intravesical instillations of Bacillus Calmette-Guérin (BCG). Four months after the BCG therapy, he underwent cystoscopy. One week after the cystoscopy, he developed a painful and swollen left scrotum. Treatment with levofloxacin for acute epididymitis reduced the scrotal pain initially, but the pain increased and 3 months later, a fistula with suppurative discharge appeared at the bottom of the scrotum. A smear of the discharge revealed Gaffky 2, and a culture showed tubercle bacillus. Incisional drainage of the abscess and anti-tuberculosis chemotherapy for 2 months to treat tuberculous epididymitis was not completely effective. We performed a left orchiectomy with resection of the infected scrotal skin. Histopathological examination showed tuberculous epididymitis consisting of a caseating granuloma with epithelioid cells and Langhans giant cells. He received anti-tuberculosis chemotherapy for 4 months postoperatively and had no sign of recurrence 1 year postoperatively.     

Does switching the bacillus Calmette-Guérin strain affect clinical outcome in patients with recurrent non–muscle-invasive bladder cancer after initial bacillus Calmette-Guérin therapy?

Purpose

It is still unknown whether switching the bacillus Calmette-Guérin (BCG) strain at the second induction course of BCG therapy has a therapeutic benefit in patients with tumor recurrence after the initial BCG therapy (BCG-relapsing tumor).

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.     

Pharmacokinetic study of intravesical gemcitabine in carcinoma in situ of the bladder refractory to bacillus Calmette-Guérin therapy

INTRODUCTION: Gemcitabine, a chemotherapeutic agent, has been shown to be active against transitional cell cancer of the bladder. The aim of the study was to determine the pharmacokinetic profile of gemcitabine, administered intravesically in patients with carcinoma in situ(CIS). MATERIAL AND METHODS: Nine patients with CIS refractory to intravesical bacillus Calmette-Guérin (BCG) therapy were enrolled. Gemcitabine was given in 50 ml 0.9% NaCl by catheterization and held in the bladder for 1 h, once weekly for 6 consecutive weeks. The pharmacokinetics for gemcitabine metabolites were performed in plasma and serum. Dose levels were: 1,000, 1,250, and 1,500 mg. Clinical evaluation was repeated 4 weeks after therapy and thereafter every 6 months. RESULTS: Grade-1 neutropenia was observed only in 1 patient. Grade-1 urinary frequency and hematuria were observed in 1 and 3 patients, respectively. No grade 2-4 toxicity or clinically relevant myelosuppression were observed. Gemcitabine was detectable in serum, but with an irrelevant pharmacological effect, in only 1 patient treated with 1,500 mg of gemcitabine. With regard to activity, after 6 instillations of this drug, 4 complete responses were observed. CONCLUSION: Intravesical gemcitabine is well tolerated and safe. No systemic absorption with a clinical or pharmacological effect was detected and only slightly irritative bladder symptoms were observed. These results warrant further investigation in phase-II trials.