Bacille Calmette-Guérin Instillation Research Articles

Clinical presentation of bacille Calmette-Guérin (BCG) infections after BCG instillation therapy.

To investigate the timing of the clinical presentation of various types of bacille Calmette-Guérin (BCG) infections in a Finnish population of patients with bladder cancer treated with BCG instillation therapy. We identified patients with a history of post-instillation BCG infection from 1996 to 2016 using the Finnish Cancer Registry and the Finnish National Infectious Diseases Registry. We categorised infections as systemic if the infection was found in the non-urogenital system and genitourinary (GU) if the infection affected the urogenital tract. We calculated the time interval between the last BCG instillation and the presentation of the infection. The infection was considered late if the time interval was ≥1 year. A total of 100 patients with BCG infection were identified during the study period. In all, 39 (39%) infections presented as systemic and 61 (61%) were in the GU tract. The majority of the systemic infections presented rapidly after the last instillation, while five (13%) presented after a latency of ≥1 year. The presentation of GU infections was more heterogeneous, with 12 (20%) presenting as late infections. This study confirms the concept of early and late infection types, especially among systemic infections. However, late infections appeared to be rarer than previously described. Urologists should be aware of the possibility of late BCG infection if patients develop symptoms even several years after the BCG regimen.

Association of Increased Age With Decreased Response to Intravesical Instillation of Bacille Calmette-Guérin in Patients With High-Risk Non-Muscle Invasive Bladder Cancer: Retrospective Multi-Institute Results From the Japanese Urological Oncology Research Group JUOG-UC-1901-BCG

ObjectiveTo compare the therapeutic effect of Bacille Calmette-Guérin (BCG) intravesical instillation in older and younger patients with high-risk non-muscle-invasive bladder cancer. The comparison was performed with propensity score matching (PSM) without terminating the death of the older patients using relatively large-scale retrospective data from multiple institutes in Japan. Materials and MethodsOverall, 3283 patients diagnosed with non-muscle-invasive bladder cancer treated with intravesical BCG instillation during 2000-2018 in 31 institutes were examined; 1437 and 602 patients with high-grade T1 and Tis tumors were divided into those aged ≥75 and <75 years. Multivariate analysis using the Fine–Gray competing risks regression model before PSM and survival analysis using the cumulative incidence method after PSM were performed. ResultsIn the pre-PSM series of high-grade T1 tumors, age ≥75 years was an independent prognostic factor for both recurrence and progression in multivariate analysis (P = .015 and P = .013). In the pre-PSM series with Tis tumor, no variables to predict recurrence and progression was found. In the post-PSM series of 870 high-grade T1 tumors, cumulative probability of recurrence after BCG intravesical instillation were significantly higher in patients aged ≥75 years than in those aged <75 years (P = .008). The frequency of discontinuation of BCG instillation in patients aged ≥75 years with high-grade T1 and Tis was not significantly different from those in patients aged <75 years (P = .564 and P = .869). ConclusionThe cumulative probability of recurrence after intravesical BCG instillation was significantly higher in older than in younger patients with high-grade T1 bladder cancer.

A0164 - Clinical presentation of Bacille Calmette-Guérin (BCG) infections following BCG instillation therapy of non-muscle invasive Bladder Cancer

A0164 - Clinical presentation of Bacille Calmette-Guérin (BCG) infections following BCG instillation therapy of non-muscle invasive Bladder Cancer

Low-dose versus standard-dose bacille Calmette-Guérin for non-muscle-invasive bladder cancer: Systematic review and meta-analysis of randomized controlled trials.

PurposeIntravesical BCG (bacille Calmette–Guérin) instillation in patients with non-muscle-invasive bladder cancer decreases the risk for tumor recurrence and progression. After one BCG product was discontinued, a chronic global BCG shortage occurred. We focused on identifying a reduced dose of BCG that could maintain efficacy and reduce adverse effects.Materials and MethodsWe conducted a comprehensive literature search of PubMed, Embase, the Cochrane Library, CINAHL, Web of Science, and Scopus to identify randomized controlled trials through April 2021. The odds ratios (ORs) and 95% confidence intervals (CIs) for the low and standard doses in nine studies were compared. A low dose was defined as a low volume of BCG compared with the standard BCG dose (Armand Frappier, 120 mg; Connaught, 81 mg; Danish 1331, 120 mg; modified Danish 1331, 120 mg; Tokyo 172, 80 mg).ResultsThe low-dose group experienced aggravated recurrence (OR, 1.45; 95% CI, 1.09–1.94; p=0.01) but similar progression (OR, 1.11; 95% CI, 0.76–1.62; p=0.59), similar cancer-specific survival (OR, 1.02; 95% CI, 0.60–1.75; p=0.93), similar overall survival (OR, 1.09; 95% CI, 0.76–1.56; p=0.65), favorable adverse effects (OR, 0.41; 95% CI, 0.28–0.62; p<0.0001), and favorable withdrawal (OR, 0.42; 95% CI, 0.25–0.71; p=0.001).ConclusionsLow-dose BCG had more unfavorable outcomes than did standard-dose BCG in terms of recurrence. Tumor progression, cancer-specific survival, and overall survival were similar between the doses. Low-dose BCG improved adverse effects and withdrawal. In the setting of BCG shortage, low-dose BCG may have strong potential as an alternative.

Incidence of and mortality from Bacille Calmette-Guérin (BCG) infections after BCG instillation therapy.

To investigate the incidence of and mortality associated with Bacille Calmette-Guérin (BCG) infections in a Finnish population of patients with bladder cancer treated with BCG instillations. We conducted a nationwide register study and identified patients with BCG infections in Finland during 1996 to 2016 using the Finnish Cancer Registry and the Finnish National Infectious Diseases Register. We estimated the number of patients treated with BCG instillations based on data on national consumed BCG doses used to treat patients with bladder cancer, and calculated the annual incidence proportion of BCG infections. We further performed a detailed medical chart review to describe the clinical features and outcomes of the treated BCG infections. In total, 87 patients with BCG infection after BCG treatment of bladder cancer were identified. The incidence proportion increased gradually, yielding a cumulative incidence proportion of 2.5% during the latter half of the study period. BCG infections led to significant mortality, with 10% overall mortality and 17.5% mortality from systemic infections, which is notably higher than previously reported. The incidence proportion of BCG infections among bladder cancer patients treated with BCG has increased in Finland up to 2.5% at a nationwide level, with a notably higher mortality rate than previously reported.

Efficacy and toxicity in scheduled intravesical gemcitabine versus Bacille Calmette-Guérin for Ta and T1 bladder cancer: a systematic review and meta-analysis.

BackgroundWe conducted a meta-analysis to compare the efficacy and toxicity of scheduled intravesical gemcitabine (GEM) and Bacille Calmette-Guérin (BCG) for Ta and T1 non-muscle invasive bladder cancer (NMIBC).MethodsThe database search was performed in Ovid Medline, Embase, Web of Science, Cochrane Library from the commencement of the database to July 7, 2020. Trials using immediate instillation were excluded and we present the included studies in accordance with the PRISMA 2020 reporting checklist. The data extracted was analyzed using Stata 11.0 software.ResultsSix studies of 466 patients comparing GEM and BCG were finally included. No significant difference was detected between GEM and BCG group in recurrence free survival [hazard ratio (HR) =0.80, 95% confidence interval (95% CI), 0.46–1.37, P=0.410], progression free survival (HR =0.82, 95% CI, 0.38–1.77, P=0.621), and total adverse events [odds ratio (OR) =0.70, 95% CI, 0.38–1.29, P=0.253). However, patients receiving GEM treatment are less likely to develop urinary adverse events, such as dysuria (OR =0.50, 95% CI, 0.29–0.87) and hematuria (OR =0.40, 95% CI, 0.18–0.91). We performed subgroup analysis and found that the effects of GEM and BCG were similar even on patients with high recurrence risk tumor. Sensitivity analysis showed the robustness of the results.DiscussionScheduled intravesical GEM instillation has a similar effect with BCG instillation in preventing NMIBC recurrence and progression, but GEM therapy causes a lower incidence of dysuria and hematuria than BCG. GEM may be an alternative therapy for BCG. However, the results should be treated with caution due to the low to moderate quality of the included studies.

Time interval from transurethral resection of bladder tumour to bacille Calmette-Guérin induction does not impact therapeutic response.

To investigate bacille Calmette-Guérin (BCG) tolerability and response with respect to the timing of BCG administration after transurethral resection of bladder tumour (TURBT) in patients with non-muscle-invasive bladder cancer (NMIBC). A review of patients with NMIBC at our institution managed with at least 'adequate BCG' (defined by the United States Food and Drug Administration as at least five of six induction instillations, with two additional instillations comprising either maintenance or repeat induction) at our institution from 2000 to 2018 was performed. Time from TURBT to first instillation of induction BCG was stratified by quartile and analysed as a continuous variable. Kaplan-Meier and log-rank tests analysed differences in recurrence-free (RFS) and progression-free survival (PFS). Cox proportional hazards regression models identified associations between risk factors and survival outcomes. A total of 518 patients received adequate BCG at a median (range) of 26(6-188)days from TURBT. Overall, 45 patients (9%) developed BCG intolerance at a median (range) 12 (7-33) instillations. When time from TURBT to BCG was stratified into quartiles, there was no difference with respect BCG intolerance (P=0.966), RFS (P=0.632) or PFS (P = 0.789). On both uni- and multivariate regression analysis for RFS and PFS, time from TURBT to BCG was not a significant predictor when analysed by quartile or as a continuous variable (the hazard ratio for RFS was 1.00, 95% confidence interval [CI] 0.99-1.00, P=0.449; and for PFS was 0.99, 95% CI 0.98-1.00, P=0.074). The rates of tolerability and response to adequate BCG are not predicated by the timing of induction BCG instillation after TURBT. Early administration in properly selected patients is safe and delays do not affect therapeutic response.

BCG Therapy of Bladder Cancer Stimulates a Prolonged Release of the Chemoattractant CXCL10 (IP10) in Patient Urine.

Background: Intra-vesical instillation of Bacille Calmette–Guérin (BCG), an attenuated strain of Mycobacterium bovis, is an effective therapy for high-grade non-muscle invasive bladder cancer (NMIBC), which provokes a local immune response resulting in 70% of patients free of relapse after three years. Because non-responder patients usually have a bad prognosis, the early identification of treatment failure is crucial. We hypothesized that, if an effective immune response was taking place in the bladder, soluble factors would be released to the urine many days after BCG instillations. Methods: An extensive panel of cytokines and chemokines released into the urine seven days after every BCG instillation was screened in a cohort of NMIBC patients over three years. Results: The determinations of the urinary concentrations of cytokines, chemokines, and creatinine showed that increasing concentrations of C-X-C motif chemokine 10 (CXCL10) also known as interferon-inducible protein 10 (IP10) could be detected during the six-week induction cycle of BCG-treated patients released into the urine by CD14+ cells. In vitro, CXCL10 facilitated the recruitment of effector immune cells after the BCG-mediated upregulation of CXCR3 in both T- and natural killer (NK)-cells. Conclusions: The high concentrations of chemokine detected one week after the encounter with mycobacteria suggest that the CXCL10 axis might be related to the intensity of the immune anti-tumor response.

The epidemiology of bacille Calmette-Guérin infections after bladder instillation from 2002 through 2017: a nationwide retrospective cohort study.

To describe incidence and clinical characteristics of bacille Calmette-Guérin (BCG) infections after BCG bladder instillation amongst patients with non-muscle-invasive bladder cancer in Denmark. We conducted a nationwide register-based cohort study in Denmark between 2002 through 2017. Patients with BCG infection were identified by cross-linking data from the Danish National Hospital Registry on patients treated with BCG instillations and patients diagnosed with tuberculosis according to the International Classification of Diseases 10, and data obtained from International Reference Laboratory of Mycobacteriology. Hospital records were reviewed for clinical information. During the study period, 6753 patients (5281 men; mean [SD] age 71.1(0.1)years) received BCG instillations, of which 66 patients (1%) developed BCG infections. There were no differences in age or Charlson Comorbidity Index between the patients in the study population stratified by BCG infection. The median (interquartile range) time from first BCG instillation until symptoms of BCG infection was 169.5(38-585)days. Extrapulmonary localisation of BCG infections (37 patients, 56.1%) was significantly more frequent than pulmonary BCG infections (20 patients, 30.3%; P<0.001). The most common extrapulmonary localisation was the genitourinary tract (29 patients, 78.4%). BCG infections after bladder instillation are rare, mainly affect male patients, and are most frequently extrapulmonary. BCG infections should be suspected despite a long time span between occurrence of symptoms and prior bladder instillation.

Urine cytology is a feasible tool for assessing erythematous bladder lesions after bacille Calmette-Guérin (BCG) treatment.

To investigate the need to biopsy erythematous lesions of the bladder after bacille Calmette-Guérin (BCG) treatment as well as the diagnostic value of voided urine cytology in the detection of recurrence. Data on 206 consecutive patients with non-muscle-invasive bladder cancer treated with one or more BCG instillations in the period 2009-2015 at Satakunta Central Hospital and Turku University Hospital were reviewed. Biopsy histology was pooled according to lesion cystoscopy appearance regarding growth pattern and presence of erythema. Voided urine cytology grading before resection was reviewed. We correlated the cystoscopy findings with histology and calculated the sensitivity, specificity, and positive (PPV) and negative predictive value (NPV) for voided urine cytology. In total, 159 patients with a median follow-up of 35 months were included in the study. Altogether, 367 biopsies were analysed. In the case of papillary or flat tumours, 76% of biopsies showed malignant histology and the diagnostic value of cytology was very limited (sensitivity 33%, specificity 84%). Erythematous lesions constituted 57% of all biopsy targets, with the majority being either chronic non-specific inflammation or granulomatous inflammation; 10% of erythematous lesions were malignant at pathological examination. In contrast to papillary and flat tumours, cytology proved to be more accurate in the case of erythematous lesions with a sensitivity, specificity, PPV and NPV of 59%, 76%, 23% and 94%, respectively. Bladder lesions after BCG instillations pose a challenge during follow-up and the appropriate management strategy is not clear. Lesions should not be overlooked as being BCG-induced irritation because they may harbour significant malignancies. The presence of papillary or flat tumour always warrants a biopsy or resection. In the case of erythematous lesions, our results suggest that biopsy may be avoided if voided urine cytology is negative.

A Case of Epididymo-orchitis after intravesical bacille Calmette-Guérin therapy for superficial bladder carcinoma in a patient with latent tuberculosis infection.

BackgroundIntravesical instillation of bacille Calmette-Guérin (BCG) has been established as efficient therapy for superficial bladder carcinoma. Overall, intravesical BCG is well tolerated and results in complications of less than 5 %. However, adverse effects such as granulomatous prostatitis, pneumonitis, hepatitis, sepsis, and hypersensitivity reactions may occur. The reported rate for tuberculous orchitis after BCG intravesical therapy is 0.4 %.FindingsWe report a case of monolateral tuberculous orchitis occurring one month after the second course of intravescical instillation of bacille Calmette-Guérin in a patient with proven superficial bladder carcinoma and latent tuberculosis infection.ConclusionsIn our opinion intravesical instillation of BCG should be considered on an individual patient basis, with full patient disclosure of the potentially significant risks. A screening with an intradermal Mantoux before starting the first cycle of BCG instillation should be recommended and isoniazid would be indicated as the treatment for latent tuberculosis infection.

Role of oral pentosan polysulphate in the reduction of local side effects of BCG therapy in patients with non-muscle-invasive bladder cancer: a pilot study.

To assess the role of oral pentosan polysulphate (PPS) in the reduction of bacille Calmette-Guérin (BCG)-related local side effects in patients with high grade Ta/T1 non-muscle-invasive bladder cancer (NMIBC). A total of 32 symptomatic patients receiving BCG instillation were randomized into three groups: group A received placebo (vitamin B complex tablet) thrice daily; group B received PPS 100mg thrice daily; and group C received PPS 100mg once daily and placebo (vitamin B complex tablet) twice daily for 6weeks. A visual analogue scale (VAS) score for bladder pain, Overactive Bladder-Validated 8 Question Screener (OAB-V8) scores and dysuria were evaluated in the three groups before and during each weekly visit for BCG instillation. The mean ± sd post-treatment VAS scores were significantly lower in groups B (4.4 ± 1.2) and C (5.8 ± 0.8) than in group A (8 ± 0.4). In addition, the post-treatment VAS score was significantly lower in group B than in group C (P<0.01). The mean post-treatment OAB-V8 score was significantly lower only in group B (decreased from 15.5 to 9.7). Dysuria decreased in groups B and C but persisted in group A. The present study shows that oral PPS (100mg) thrice daily is effective in relieving BCG-related local side effects.

A comparative study between full-dose and half-dose intravesical immune bacille Calmette–Guérin injection in the management of superficial bladder cancer

ObjectivesTo determine whether a half-dose of bacille Calmette–Guérin (BCG) can reduce toxicity without affecting its efficacy in the management of non-muscle-invasive bladder cancer. Patients and methodsFrom January 2012 to January 2014, 80 patients with superficial bladder cancer and in the intermediate-risk group were simply randomised to receive two different doses of BCG, i.e., a full dose of 90mg (group A) or a half-dose of 45mg (group B). There were no significant differences in clinical and pathological characteristics between the groups. At completion of the study, 40 patients could be evaluated in each group. ResultsAll patients were evaluated for a follow-up of 12months after treatment. There was no significant difference in recurrence rate (15 patients, 38%, in group A and 16, 40%, in group B) in the two groups, and no difference in progression rate of the disease, at eight patients (20%) in each group. There were significant differences between groups A and B in toxicity (grade 1 adverse events, 70% vs. 60%; grade 2, 18% vs. 7.5%, respectively). Grade 3 adverse events were only reported in group A (2.5%). ConclusionThe half dose of intravesical BCG instillation can reduce the toxicity and side-effects that are associated with the treatment of superficial bladder cancer, without affecting the efficacy of therapy.

Penile Tuberculosis After Intravesical Bacille Calmette-Guérin Immunotherapy

Immunotherapy with bacille Calmette-Guérin (BCG) is widely used for treatment of superficial urothelial cancer. Complications associated with BCG treatment are common. The most common are minor reactions as cystitis, hematuria, fever, malaise. We report an unusual case of granulomatous balanoposthitis as a complication of intravesical BCG instillation therapy. To our knowledge, only a few reports of BCG-related penile or urethralgranulomatous infection have been previously published in the literature.

Dendritic cells in blood and urine samples from bladder cancer patients undergoing BCG immunotherapy

Immunotherapy with BCG (Bacille Calmette-Guérin) after transurethral resection of the bladder tumor represents a highly effective primary treatment for intermediate and high-risk superficial bladder cancer. The effectiveness of this therapy has been documented, but its mechanism of action is not clear yet. In the present study, we investigated the changes of dendritic cells (DC) numbers in peripheral blood and urine of patients with superficial bladder cancer undergoing BCG intravescical therapy. We have enumerated plasmacytoid and myeloid DCs in the peripheral blood and in the urine of patients with bladder cancer in order to clarify the role of these cells in the evolution of the disease and the effect of therapy. DCs in blood and urine samples were assessed using the single-platform TruCOUNT assay with monoclonal antibodies. The study population included 37 healthy donors and 13 patients with diagnosis of primitive superficial bladder cancer. At the time of diagnosis a reduction of blood DCs was found in patients as opposed to healthy donors, while DCs were not found in the urine in the same way as in healthy subjects. Six of these patients were followed before and after weekly and monthly instillations of BCG. In the peripheral blood, we observed an immunological recovery of DCs from the third weekly instillation up to the sixth. In the urine of patients, we didn't find mDCs or pDCs at T0, but we found a statistically significant change from the third instillation up to the sixth. On the contrary, we didn't find mDCs in urine during monthly instillation. DC Count could be used in the monitoring of patients undergoing BCG therapy. Immunological restoration of mDC numbers in peripheral blood and the efflux in urine could be important for confirming the effectiveness of BCG instillation.

Utility of 67Ga Scintigraphy in Disseminated Infection After BCG Instillation for Treatment of Bladder Carcinoma

Intravesical instillations of bacille Calmette-Guérin (BCG), an attenuated live strain of Mycobacterium bovis, is the treatment of choice for superficial bladder cancer. Local side effects are frequent, although adverse systemic reactions are uncommon, but more serious. We present 2 patients who developed disseminated M. bovis infection with multiorgan involvement after intravesical BCG therapy. (67)Ga scintigraphy was very helpful for the diagnosis as the only imaging tool with pathological findings.

Screening urine analysis before bacille Calmette‐Guérin instillation does not reduce the rate of infectious complications

Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Infectious complication is a risk of bacille Calmette-Guérin instillation. Urine analysis in asymptomatic patients has been used as a measure to reduce infections. This study suggests that screening urine analysis prior to bacille Calmette-Guérin instillation did not affect the rate of urinary tract infections. • To discover if the routine use of urine analysis decreases the rate of urinary tract infection (UTI) complications after bacille Calmette-Guérin (BCG) administration. • A retrospective review of the outcomes of 202 patients undergoing BCG treatment for bladder cancer at two medical centres with different pre-BCG screening strategies was performed. • The medical records of 100 patients who received BCG by one urologist at Memorial Sloan-Kettering Cancer Center (MSKCC) were reviewed. No patient received a urine analysis immediately prior to BCG treatment. • Similarly, 102 patients who received BCG at Northwestern Memorial Hospital (NMH) were reviewed. Patients at NMH were screened by urine analysis for pyuria and bacteriuria before BCG treatment, and, if clinically indicated, BCG instillation was delayed for the results of the urine culture. • If the urine culture confirmed infection, then the patient was treated before restarting BCG instillation. • At MSKCC, 100 patients underwent 600 BCG treatments. • After BCG administration, symptomatic UTI occurred in three patients (3%), successfully treated with antibiotics. • No patients developed BCG sepsis or required hospitalization due to infection. • At NMH, 102 patients underwent 612 BCG treatments. • Pre-BCG urine analysis was positive for pyuria (defined as white blood cells >5 per high-power field) in 27.8%, and positive for bacteriuria (defined as any bacteria on microscopy) in 18.1%. • Based on the results of pre-screening urine analysis, BCG instillation was delayed 15 times (2.5%). • Overall, three patients (3%) had culture-proven UTIs after BCG instillation. • No patients developed BCG sepsis or required hospitalization in either group and there were no significant differences in the frequency of UTIs. • Urine analysis can safely be omitted before administration of BCG in asymptomatic patients. • Omission of urine analysis could save time and expense during the office-based treatment of bladder cancer.

UP-01.059 Evaluation of the Need for Transuretheral Biopsy at First Follow-Up After Intravesical BCG Therapy for Superficial Bladder Cancer

High risk non-muscle invasive superficial bladder cancer patients have life-long risk of progression and require particular attention. Bacille Calmette-Guérin (BCG) instillation is recommended as first-choice treatment to reduce the risk of progression of high-grade bladder cancer and carcinoma in situ (CIS). We tried to evaluate the need for routine transuretheral biopsy from the previous resection site at 3 months, after BCG instillation therapy, even if post-treatment urine cytology and cystoscopy were free.

Bilateral Panuveitis following Intravesical BCG Immunotherapy for Bladder Carcinoma

Purpose: To report a case of bilateral panuveitis following local treatment with Bacille Calmette-Guérin (BCG) immunotherapy for superficial bladder carcinoma.Design: Case report and literature review.Methods: A 70-year-old female presented with severe bilateral anterior chamber inflammation 5 days after intravesical BCG instillation. Despite topical steroids and mydriatics, inflammation worsened and bilateral optic nerve swelling developed.Results: Oral corticosteroids settled the ocular inflammation, and optic nerve function recovered. A trial of steroid cessation caused rebound uveitis, so she remains on maintenance doses of oral corticosteroid.Conclusions: Ocular inflammations following BCG therapy for bladder cancer are rare, and little is known about the management of such cases. This is the first report of bilateral panuveitis with optic nerve edema following such treatment.

Bacille Calmette-Guérin (BCG) Immunotherapy-Induced Celiac Crisis: A First Manifestation of Silent Celiac Disease in an Elderly Patient

Purpose: Introduction: Celiac disease (CD) is an immune-mediated glutensensitive enteropathy with various clinical presentations. BCG, in addition to its role as a vaccine against tuberculosis, has been used as an immunotherapeutic agent in patients with bladder cancer by intravesical instillation. We present an elderly patient with new onset of celiac disease after intravesical treatment with BCG, the first such report to our knowledge. Case Report: An 81-year-old woman with recently diagnosed superficial bladder cancer, treated with resection and intravesical BCG instillation, was seen because of multiple episodes of spurious non-bloody diarrhea for 3 days associated with colicky abdominal pain, nausea and non-bilious vomiting with no fever. On arrival, she was hypotensive requiring aggressive intravenous hydration. Physical examination was otherwise unremarkable. Similar episodes occurred twice 3 months ago, 2 weeks after her fourth BCG dose, requiring hospitalization and fluid resuscitation. At that time she was treated empirically for Clostridium difficile colitis and discharged without any definitive diagnosis. This admission, work up revealed normocytic anemia, +fecal WBC, and negative findings for C. difficile toxin and stool culture tests for cryptosporidia and ova and parasites. CT scan of the abdomen was unremarkable. Tissue transglutaminase antibody and gliadin IgG were mildly elevated. Endoscopy-guided small intestinal biopsy showed typical pathological characteristics of CD. The patient responded to a gluten-free diet with marked improvement in her symptoms. The diagnosis of latent CD was subsequently reconfirmed by genetic analysis. Discussion: The exact mechanism of BCG action is unknown, but intravesical instillation triggers a variety of local immune responses including stimulation of CD4 T cells, macrophages, cytokines and IFN-γ resulting in tumor destruction. The systemic response to intravesical BCG instillation has not been studied and has been thought to have only local effect. However, rare cases of BCG-induced HLA B27-positive arthritis have been reported. We propose that this new emergence of latent CD shortly after BCG therapy in our elderly patient is not just a coincidence. The impact of systemic immune response and possibly new onset of autoimmune disorders, such as CD, with intravesical BCG needs to be investigated. Clinicians should consider the diagnosis of activated CD (perhaps including other inflammatory bowel diseases) in patients with a new onset of unexplainable diarrhea after BCG therapy. More studies will need to be done to further validate this relationship, which suggests wider risks of activating remote immune reactions with BCG.