Superficial Bladder Carcinoma Research Articles

Frequency of Tumor Recurrence: A Strong Predictor of Stage Progression in Initially Diagnosed Nonmuscle Invasive Bladder Cancer

Patients with nonmuscle invasive bladder cancer usually experience multiple instances of tumor recurrence until stage progression occurs. However, it has not yet been fully evaluated whether the timing and/or pattern of tumor recurrence could affect subsequent stage progression. We examined whether the frequency of tumor recurrence provides additional predictive information concerning stage progression. A total of 484 patients with initially diagnosed nonmuscle invasive bladder cancer were identified between 1985 and 2006 at our institution. Median followup was 7.2 years. Frequency of tumor recurrence was analyzed to determine if it affected subsequent stage progression. Of these patients 40 (8.3%) experienced stage progression during followup. Using Kaplan-Meier analysis subsequent stage progression could be most strongly predicted in patients with a recurrence rate of 1 or more per year during the first 2 years, although similar results were observed for various cutoff periods and recurrence rates. The 10-year progression-free survival rate was 58.0% in patients with a recurrence rate of 1 or more per year and 93.3% in their counterparts (p <0.001). Multivariate analysis demonstrated that the appearance of tumor grade 3 (p = 0.027, risk ratio 2.36), carcinoma in situ (p = 0.045, risk ratio 2.44) and a recurrence rate of 1 or more per year during the first 2 years (p <0.001, risk ratio 7.40) were independent risk factors for subsequent stage progression. Frequency of tumor recurrence is a strong predictor of subsequent stage progression in patients initially diagnosed with nonmuscle invasive bladder cancer. More appropriate followup and aggressive treatment due to a higher malignant potential for stage progression might be recommended in patients with a recurrence rate of 1 or more per year during the first 2 years.

Recurrences of Superficial Bladder Carcinoma are Associated with a Raise of CD8high&gt;CD57+ and CD8low T Lymphocytes in Peripheral Blood

Immunotherapy with BCG is effective in patients with recurrent superficial bladder carcinoma. This therapy involves Interleukin-2 (IL-2), but little is known about the immunological parameters involved in superficial bladder carcinoma. We have monitored immunological parameters in twenty patients with superficial bladder carcinoma treated with transurethral resection (TUR) followed by IL-2 instillation. Cell numbers of peripheral blood leukocyte subpopulations were counted before surgery and during follow-up after surgery. During follow-up, we compared the cell counts in patients with and without a recurrent tumour. We used the values of healthy matched controls as a reference. Recurrent disease in patients corresponded with a significant increase in CD8+ lymphocytes, and especially the CD8highCD57+ and CD8low subpopulations. The phenotype of these T lymphocytes belongs to cells with an immunosuppressive function. We hypothesize that these peripheral immune suppressive cells facilitate tumour recurrences or that tumour recurrences cause an increase in peripheral immune suppressive lymphocytes.

Tuberkulose durch Bacillus-Calmette-Guérin-Instillation bei Blasenkarzinom und Hypertonie

A 71-year-old patient with a superficial carcinoma of the urinary bladder and high risk of recurrence was treated with intravesical instillation of Bacillus Calmette-Guérin (BCG) after transurethral resection. As a complication of the catheterization during BCG-instillation therapy the patient suffered from tuberculosis. The patient received a tuberculosis triple-therapy including rifampicin 600 mg once daily, isoniazid 300 mg once daily and ethambutol 400 mg thrice daily. The existing arterial hypertension had successfully been controlled by 3.75 mg bisoprolol medication once daily for the last 15 years. An increase of blood pressure and cardiac arrhythmia were seen after combining the β (1)-receptor blocker treatment with the triple-therapy. The blood pressure was 160 / 90 mmHg. The heart rate reflected a value of 98 beats per minute. In the resting ECG monotopic ventricular extrasystoles could be diagnosed. The dosage of bisoprolol was changed to 3.75 mg in the morning and additional 1.875 mg in the evening. Due to this increase of dosage the blood pressure could be controlled sufficiently. Rifampicin is one of the best known potent enzyme inducing drugs. It strongly induces the expression of cytochrome P450 3A4 in the liver. The enzyme induction enhance the hepatic bisoprolol metabolism, hence the metabolic clearance of the drug increased. The maximal plasma level of bisoprolol decrease and in our use the arterial hypertension could not be treated sufficiently. It is well known that half the dose of bisoprolol undergoes oxidative metabolism in the liver and the rest eliminated unchanged in the kidney. A dosage adjustment of bisoprolol is necessary if the clinical status of the patient requires treatment with the antituberculosis drug rifampicin.

Results of long-term follow-up of patients with superficial bladder carcinoma treated with intravesically applied bacillus Calmette-Guerin vaccine according to the schedule of 6 weekly + 6 monthly instillations

BackgroundThe efficacy of bacillus Calmette-Guerin (BCG) immunotherapy in the prevention of local recurrence and disease progression in patients with superficial bladder cancer is very well documented. This study reports the effect of BCG on disease-specific and overall survival. Patients and methodsIn this retrospective trial, we have analyzed 170 patients with stage Ta and T1 superficial bladder cancer. Patients in the control group (87 patients) we followed-up only (median follow-up of 119 months) and treated surgically or with other oncologic modalities when progression of disease was diagnosed. The BCG group consisted of 83 patients treated with 6 weekly followed by 6 monthly instillations, and they have been followed-up of median 124 months. ResultsPatients receiving BCG had statistically significant better 10-year disease specific survival (83% vs. 69%, P = 0.03). At the same time point, the local recurrence rate was 48 % and the progression rate 19% for patients treated with BCG, while 77% (P < 0.001) and 38% (P = 0.007) were results in control group. Despite numerically better in the BCG group, overall survival is not significantly different in the 2 groups (P = 0.14). ConclusionBCG immunotherapy significantly increases the disease-specific survival in patients with superficial bladder carcinoma.

Diagnostik und Therapie des Harnblasenkarzinoms

Forty percent of patients with superficial bladder carcinoma progress towards muscle-invasive carcinoma despite initial therapy. Emergent technologies in the diagnostics and therapy of superficial bladder carcinoma including fluorescence cystoscopy are able to reduce recurrence and progression rates. Nevertheless to date no trial was able to show a benefit with regard to cancer-specific and overall survival using these new technologies. Lymph vessel invasion has been introduced as a new prognostic marker in muscle-invasive bladder carcinoma that can be easily incorporated into routine clinical practice. Furthermore adjuvant chemotherapy has been identified along with lymph node density as a statistically significant marker for survival in muscle-invasive bladder carcinoma which should be investigated in prospective clinical trials. In metastatic bladder carcinoma, vinflunine was approved as second-line chemotherapy for patients who failed cisplatin-based chemotherapy. This article critically reviews the emergent developments of the last 12-15 months and comments on their clinical efficacy for the treatment of bladder carcinoma.

Effect of mitomycin C on concentrations of vascular endothelial growth factor and its receptors in bladder cancer cells and in bladders of rats intravesically instilled with mitomycin C

• To examine, using in vitro and in vivo models, the largely unexamined effect of mitomycin C (MMC), an effective intravesical treatment for superficial bladder cancer and carcinoma in situ, on expression of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor-2 (VEGFR-2), which mediates many of the angiogenic properties of VEGF. • To measure, as a positive control, concentrations of the inhibitor of apoptosis, survivin, as an assessment of MMC effectiveness. • To measure MMC-induced changes in proliferation in the presence and absence of VEGF-A small interfering RNA (siRNA). • After treatment with increasing MMC concentrations (5-200 µg/mL), we measured proliferation, as well as VEGF, survivin, VEGF receptor-1 (VEGFR-1) and VEGFR-2 concentrations in RT-4 and T-24 bladder cancer cells. • The effect of pre-treatment of VEGF siRNA and survivin siRNA on MMC-induced decreases in proliferation was measured. • Urinary VEGF concentrations and bladder and kidney concentrations of VEGF-A, VEGFR-1, VEGFR-2 and interleukin-6 (IL-6) mRNA were measured in rats intravesically instilled with saline or MMC (200 µg/mL). • Although MMC treatment inhibited cell proliferation and decreased survivin mRNA expression in T-24 and RT4 cells, MMC (12-50 µg/mL) increased VEGF-A mRNA and VEGFR-2 mRNA and protein expression. • Pre-treatment with VEGF-A siRNA or survivin siRNA before MMC treatment reduced proliferation more than MMC alone. • MMC-induced reductions in proliferation were reduced additively by pre-treatment with survivin siRNA, but were potentiated by pre-treatment with VEGF-A siRNA. • VEGFR-2 mRNA and protein concentrations and urinary VEGF concentrations were increased in bladders of rats instilled with MMC. • Intravesically instilled MMC increases urinary VEGF and bladder VEGFR-2 protein and mRNA in rats. • MMC increases VEGF mRNA and VEGFR-2 protein and mRNA concentrations in bladder cancer cells. Therefore, we speculate that MMC could increase the angiogenic potential of both cancer and normal cells. • In cancer cells this effect is largest at lower MMC concentrations. • Combining MMC with agents that reduce EGF concentrations could be of value in treatment of transitional cell carcinoma of the bladder (TCC).

Systemic granulomatous disease and syndrome of inappropriate antidiuretic hormone

A 71-year-old man was admitted with generalized tiredness, mild confusion and low-grade pyrexia following the fourth cycle of intravesical bacillus Calmette–Guérin instillation for the treatment of superficial bladder carcinoma. These symptoms were accompanied by some weight loss which was difficult to quantify. His past medical history included type 1 diabetes mellitus, chronic obstructive pulmonary disease and prostatic hyperplasia. He was a smoker and consumed a moderate amount of alcohol. Physical examination was unremarkable with the exception of confusion (abbreviated mental test score 7/10). Initial investigations showed low serum sodium of 122 mmol/litre with normal potassium, renal and thyroid functions. His liver functions were abnormal with aspartate transferase of 76 IU/litre and alkaline phosphatase 286 U/litre. Chest X-ray showed bilateral non-specific reticular changes suggestive of infection. Two sets of blood cultures showed no growth after 72 hours. Urine tests for legionella and pneumococcal antigen were negative. Computed tomography of the brain revealed deep white matter changes suggestive of small vessel disease. On further investigations urine osmolality was 546 mOsm/kg, serum osmolality 256 mOsm/kg, urine sodium 61 mmol/litre and the short Synacthen test was normal, confirming the diagnosis of syndrome of inappropriate antidiuretic hormone. After fluid restriction to 1 litre per day his sodium level started to improve slowly, but the patient's condition continued to deteriorate with ongoing low-grade pyrexia, confusion and lethargy. A repeat chest X-ray 5 days later (Figure 1) showed multiple small non-calcified nodules in both lungs raising the possibility of miliary tuberculosis. This was confirmed on high resolution computed tomography scan of the chest (Figure 2) as presence of bilateral diffuse miliary shadowing in keeping with a diagnosis of miliary tuberculosis. In view of his confusion, CSF examination was done to rule out CNS involvement, but this was normal. No endobronchial lesions were identified on bronchoscopy and bronchial washings were sent for analysis and cultures. The patient was started on anti-tuberculous treatment (isoniazid, rifampicin and ethambutol) as well as steroids and pyridoxine. Unfortunately, the patient suffered a cardiac arrest and died a week after starting the treatment. Cultures of bronchial lavage and CSF did not grow any mycobacterium. On post-mortem examination he was found to have multiple small whitish nodules in both lungs, with caseating granulomata, central areas of necrosis and multinucleated giant cells microscopically.

Loss of Heterozygosis on IFN-α Locus is a Prognostic Indicator of Bacillus Calmette-Guerin Response for Nonmuscle Invasive Bladder Cancer

We evaluated the role of loss of heterozygosity on the interferon-alpha locus to predict the response to bacillus Calmette-Guerin therapy in patients with nonmuscle invasive bladder cancer. A total of 117 consecutive patients were selected, including 77 with nonmuscle invasive bladder cancer and 40 controls. Loss of heterozygosity on the interferon-alpha locus (chromosome 9p21) was assessed in blood and urine samples before transurethral resection. All patients underwent transurethral resection and then 6 weekly bacillus Calmette-Guerin instillations. Those with nonmuscle invasive bladder cancer were assigned to groups 1 and 2 with and without loss of heterozygosity on the interferon-alpha locus, respectively. Of the 77 patients with nonmuscle invasive bladder cancer 39 (50.6%) had loss of heterozygosity on the interferon-alpha locus (group 1) and 38 (49.4%) had no alteration (group 2). Only 1 of 40 controls showed loss of heterozygosity on the interferon-alpha locus. At the end of followup 13 patients in group 1 and 27 in group 2 were alive without recurrence. We noted a significant difference between loss of heterozygosity on interferon-alpha and followup status (dF 01, LR 11.252, p = 0.003). Kaplan-Meier analysis revealed a significant difference in recurrence probability (response to bacillus Calmette-Guerin) and loss of heterozygosity on interferon-alpha (p <0.0001). On multivariate analysis loss of heterozygosity (HR 4.09, 95% CI 2.59-6.28, p = 0.002), grade (grade 3 HR 3.31, 95% CI 1.38-3.35, p = 0.03) and the number of lesions (3 or greater HR 2.31, 95% CI 1.38-3.25, p = 0.03) were independent predictors of the bacillus Calmette-Guerin response. This study highlights the predictive value of loss of heterozygosity analysis on interferon-alpha in patients with nonmuscle invasive bladder cancer treated with bacillus Calmette-Guerin.

Should Patients With Primary Upper Urinary Tract Cancer Receive Prophylactic Intravesical Chemotherapy After Nephroureterectomy?

We assessed the efficacy of prophylactic intravesical chemotherapy for primary upper urinary tract urothelial cancer after nephroureterectomy during long-term followup. From January 1985 to June 2007, 196 patients with primary upper urinary tract urothelial cancer were included in this study. Patients were divided into group 1-31 who received intravesical epirubicin instillation, group 2-27 who received intravesical mitomycin C instillation and group 3-138 who did not receive prophylactic instillation after nephroureterectomy. We compared the bladder tumor recurrence rate, number of recurrence episodes, time to first bladder tumor recurrence, tumor type, percent of patients with cystectomy and percent who died of urothelial cancer, and the recurrence-free survival rate. Of the 196 patients 73 had subsequent bladder recurrence at a mean followup of 55.6 months. There were no significant differences in recurrence type, mean number of bladder tumor recurrences, percent of patients with cystectomy and the cancer specific survival rate. The bladder recurrence rate was lower in group 1 and 2 than in group 3. Mean time to first bladder tumor recurrence was longer in groups 1 and 2. Kaplan-Meier curves of recurrence-free survival rates were significantly increased in groups 1 and 2. Intravesical instillation of epirubicin or mitomycin C appears to be well tolerated and effective for preventing bladder recurrence and prolonging time to first bladder recurrence. Patients should receive prophylactic intravesical chemotherapy after nephroureterectomy.

Failure of Bacillus Calmette Guerin (BCG) therapy for the treatment of bladder cancer: Al-Azhar experience

To determine the failure rate of intravesical Bacillus Calmette Guerin (BCG) instillation following complete transurethral resection of superficial transitional cell carcinoma (TCC) of the urinary bladder at the Urology Department, Al-Azhar University, Cairo, Egypt. A prospective analysis of 160 patients with superficial TCC of the urinary bladder treated by transurethral resection of the bladder tumor (TURT) and adjuvant intravesical BCG instillation was performed at the Urology Department, Al-Azhar University, Cairo, between 2002 and 2008. The mean follow-up was 37 ± 4 (range 3 to 64) months. After the initiation of BCG treatment 12 patients (7.5%) were lost to follow-up, 6 (3.8%) stopped BCG due to side-effects and were subsequently treated with intravesical chemotherapy, while another 5 (3.1%) died during BCG therapy due to tumor-unrelated causes. The overall survival rate at 3 years was 90.4%. At a mean follow-up period of 37 ± 4 months, 70.4% of the patients showed no tumor recurrence and 82% no tumor progression. BCG failure was significantly observed in cases with stage T1, or grade-3 tumors or in cases associated with carcinoma in situ. TURT with adjuvant intravesical BCG therapy is considered the first treatment option in high and intermediate risk patients with superficial TCC. Failure of BCG treatment is mainly observed in stage T1 or grade-3 tumors. Different treatment modalities can be used after a second tumor recurrence or progression according to the tumor aggressiveness and the patient’s preference.

S2 Evaluation of the clinical value of urinary NMP22 as a marker in the surveillance of superficial transitional cell carcinoma of the urinary bladder

S2 Evaluation of the clinical value of urinary NMP22 as a marker in the surveillance of superficial transitional cell carcinoma of the urinary bladder

Drug eruption due to intravesical instillations of both epirubicin and mitomycin C

We present the first patient to develop drug eruption due to intravesical instillations of both epirubicin and mitomycin C. A 58-year-old-man underwent transurethral resection (TUR) for superficial bladder carcinoma followed by instillations of intravesical chemotherapy. Immediately after TUR, the first instillation of epirubicin was performed. Two days after the first instillation, the patient developed generalized erythema of the face, trunk, upper and lower limbs. Two days after the second instillation, the patient developed severe generalized erythema and was diagnosed as having drug eruption due to intravesical instillations of epirubicin by the dermatologist. Instead of epirubicin, mitomycin C was instilled 2 weeks postoperatively. Two days after the first instillation of mitomycin C, the patient again developed severe generalized erythema and was diagnosed as having drug eruption due to intravesical instillation of mitomycin C. Drug eruption after the first instillation of epirubicin might have been due to drug toxicity of the agent. However, drug eruptions after the second instillation of epirubicin and the first instillation of mitomycin C might have been due to allergic reactions to the drugs. The patient has not received any further intravesical chemotherapy and has not demonstrated any such a drug eruption again.

Results at 5 years of intra vesical gemcitabine (G) single agent as adjuvant chemotheray in superficial transitional cell carcinoma (TCC) of the bladder

e16087 Background: Systemic intravenous gemcitabine is usually used in advanced bladder carcinoma, intravesical G is a novel treatment approach for TCC. In this study we evaluate the efficacy of intravesical Gemcitabine in patients (pts) with superficial bladder carcinoma. Methods: From February 2003 to June 2004, 60 pts (57M/3F) were enrolled in the study (M/F = 57/3). The median age was 59,5 years old (24–84). Nine pts had a carcinoma in situ (Cis) and 51 had pT1 lesions. Three weeks after a total transurethral resection (TUR), patients receive intravesical instillation of 2000 mg G every week for 6 weeks, than every month for six months. They received a total of 720 instillations, Follow up was with cystoscopy and urine cytology every six months. Results: At a median follow-up time 60 months, all patients were evaluable for tumor response: 23(38, 3%) patient had a persistant complete remission after treatment, 26 patients (43,3%) had a superficial relapse of TCC, six patients (10%) had progressive disease: four with muscle invasion and two with distant metastasis. Conclusions: Intravesical therapy with gemcitabine is active and well tolerated treatment in patients with superficial TCC carcinoma of the bladder. A phase III trial comparing GEM with intravesical BCG or MMC is warranted No significant financial relationships to disclose.

Cigarette Smoking and Drinking Water Source: Correlation with Clinical Features and Pathology of Superficial Bladder Carcinoma

Objective: Water source and cigarette smoking are related to clinical characteristics and pathology of superficial transitional cell carcinoma of the bladder. Methods: Tumor number, dimension, G-grade, T-stage, recurrences, cigarette smoking and water supply were recorded in patients harboring Ta–T1 G1–3 transitional cell carcinoma of the bladder. Results: Of 577 patients, 61% had multiple and 36% recurrent tumors. Two hundred and forty-one patients (42%) were current smokers and 188 (33%) were former smokers. Bottled water was the only drinkable source for 249 (45%) patients, municipal water supply for 177 (32%), artesian wells for 38 (7%), spring water for 7 (1%) and mixed source for 89 (16%). By adopting a cut-off of 30 years of smoking, patients affected by recurrent tumors varied from 22 to 43% (p = 0.0001). T1 tumors were more frequent in patients drinking nonbottled water (p = 0.03). Nonbottled supply was more frequent in never smokers (p = 0.015) and could represent a weak risk factor not detectable in smokers. Conclusions: Cigarette smoking correlates with the number of recurrences. T1 tumors were statistically more frequent in patients taking nonbottled drinking water. Chlorinated water supply was more frequent among patients who did not present cigarette smoking as a risk factor.

Bladder outlet obstruction accelerates bladder carcinogenesis

To examine the correlation between partial bladder outlet obstruction (PBOO) and bladder carcinogenesis. Female Wistar rats (6 weeks old) were divided into three groups of 10 each: group 1 was exposed to n-butyl-n-butanol nitrosamine (BBN, a carcinogen) in drinking water for 8 weeks; group 2 had PBOO induced surgically after exposure to BBN for 8 weeks; group 3 had a sham operation and the rats drank normal water (control group). After 20 weeks, all of the rats were killed humanely and their bladders analysed. There were no significant differences in body weight among the groups. The bladder weight of group 2 was significantly greater than either group 1 or group 3. Histopathologically, bladder smooth muscle hypertrophy was the major cause of the increased bladder weight for group 2. In group 2 there were increases in bladder wall thickness and many nipple-shaped urothelial tumours. Basic fibroblast growth factor and hypoxia-inducible factor-1alpha expression were significantly greater in group 2 than in groups 1 and 3. Exposure of the bladder to carcinogens during bladder hyperplasia and hypertrophy induced by PBOO results in a greater incidence of superficial bladder carcinoma.

Research Highlights

Research Highlights

The accuracy of ultrasonography in the diagnosis of superficial bladder tumors in patients presenting with hematuria

Ultrasonography has been proposed as the initial test for detection of bladder carcinomas in patients presenting with hematuria, but the accuracy of transabdominal ultrasonography in the diagnosis of superficial bladder carcinoma has not been assessed. We prospectively evaluated 173 patients presenting to the outpatient department with painless hematuria by transabdominal ultrasound and cystoscopy. The tolerability of cystoscopy was also assessed. Of 148 patients who met the inclusion criteria, 39 with bladder carcinoma were identified by cystoscopy as having bladder carcinoma, while 34 were identified by ultrasonography. For ultrasonography, the sensitivity (87.1%), specificity (98.1%), positive predictive value (94.4%) and negative predictive value (95.4%) were good but not as good as cystoscopy. While the tolerability of cystoscopy is relatively low, it is still superior to ultrasonography in the evaluation of the bladder as a possible source of hematuria.

Diagnosis and treatment of superficial bladder caroinoma

Objective To investigate the diagnosis and treatment of superficial bladder carcinoma and its value of application.Methods Retrospective analysis of data of clinical 35cases from June,2000 to June,2008.The 35cases had intravesical instillation with 40ms Mitomycin C(MMC)in 24hours after electro resection.Afterwards performing once a week.continuing 6 weeks.Then once a month,continuing 1 year.Checking Cystoscopy every 3 months,continuing 2 years.Results Of all the 35cases during a follow-up study of 6～24 months,All the successful effects reach 85.71%(30/35),restore of 5cases was received the operation by electro resection again.Conclusions Transurethral electro resection and performed with MMC is the main and most effect ive method of treating superficial bladder carcinoma. Key words: Superficial bladder carcinoma; Transurethral electro resection; Mitomycin C(MMC)

Clinical Implications of the Expression of Survivin and p53 in Superficial Transitional Cell Carcinoma of the Bladder

Purpose: The prognostic value of p53 remains controversial in transitional cell carcinomas of the bladder. Survivin, an inhibitor of apoptosis, is expressed in many human cancers. Recent studies have reported increased expression of survivin in superficial transitional cell carcinomas of the bladder. We investigated the expression of survivin and p53 and the clinical implications of this expression in superficial transitional cell carcinomas of the bladder. Materials and Methods: Immunohistochemical staining of paraffin sections using a monoclonal antibody for survivin and p53 was performed in 82 cases of superficial transitional cell carcinomas of the bladder. Correlations between the expression of survivin and p53 and clinicopathological features, such as age, multiplicity of tumor, size, recurrence, and progression, were examined. Results: Among 82 cases, positive survivin expression (greater than 20%) was observed in 59 cases. Positive p53 expression (greater than 20%) was observed in 46 cases. There were no significant differences in age, gender, multiplicity, tumor size, tumor grade, pT stage, recurrence, or progression-free survival between p53-positive and p53-negative groups (p>0.05). Also, there were no significant differences in age, gender, multiplicity, tumor size, tumor grade, or pT stage between survivin-positive and survivinnegative groups (p>0.05). However, recurrent-free and progression-free survivals were significantly lower in the survivin-positive group than in the survivin-negative group (p<0.05). Conclusions: The expression of survivin can be recommended as a useful marker for predicting disease recurrence and progression. Survivin may be superior to p53 as a prognostic factor in superficial transitional cell carcinoma of bladder. (Korean J Urol 2009;50:12-17)

Disseminated BCG infection in patients with urinary bladder carcinoma

Bacillus Calmette-Guërin--a live, attenuated strain of Mycobacterium bovis has been used in immunotherapy of patients with superficial urinary bladder carcinoma. Some patients develop complications after intravesical instillation of BCG: high temperature followed by hematuria or granulomatous prostatits, epidydimoorchitis, urethral obstruction, and less than 1% have a systemic disease followed by dissemination of bacteria into other organs. A 50-year-old man underwent transurethral resection of a bladder tumor. One month after the operation BCG intravesical installations were administered for three weeks. After the fourth installation, our patient developed high fever, fatigue, vomiting, dark urine, light stools, and jaundice. On admission he was jaundiced with a high fever, enlarged liver and spleen and laboratory findings which included high erythrocyte sedimentation rate, pancytopenia, elevated liver enzymes, especially alkaline phosphatase and aminotranspherases. The bone-marrow biopsy showed granulomatous inflamation suggesting mycobacterial spread in the bone marrow, liver and spleen and sepsis. The patient was initially treated with antituberculous therapy, but his state did not improve until corticosteroids were added to the antituberculous treatment regimen. Although dissemination of BCG is a rare complication of intravesical BCG treatment of the bladder carcinoma, it may result in prolonged fever and granulomatous inflamation of the liver, spleen, lungs, bone marrow and BCG sepsis. Antituberclous agents in combination with corticosteroids comprise the treatment of choice for disseminated BCG infection.