Intravesical BCG Instillation Research Articles

Recommandations en onco-urologie 2016-2018 du CCAFU : Tumeurs de la vessie

ObjectiveThe purpose of the guidelines national committee CCAFU on bladder cancer was to propose updated french guidelines for non-muscle invasive (NMIBC) and invasive (MIBC) bladder cancers. MethodsA Medline search was achieved between 2013 and 2016, as regards diagnosis, options of treatment and follow-up of bladder cancer, to evaluate different references with levels of evidence. ResultsDiagnosis of NMIBC (Ta, T1, CIS) is based on a complete deep resection of the tumour. The use of fluorescence and a second-look indication are essential to improve initial diagnosis. Risks of both recurrence and progression can be estimated using the EORTC score. A stratification of patients into low, intermediate and high risk groups is pivotal for recommending adjuvant treatment : instillation of chemotherapy (immediate post-operative, standard schedule) or intravesical BCG (standard schedule and maintenance). Cystectomy is recommended in BCG-refractory patients. Extension evaluation of MIBC is based on pelvic-abdominal and thoracic CT-scan; MRI and FDG-PET remain optional. Cystectomy associated with extensive pelvic lymph nodes resection is considered the gold standard for non metastatic MIBC. An orthotopic bladder substitution should be proposed to both male and female patients lacking any contraindications and in cases of negative frozen urethral samples. The interest of neoadjuvant chemotherapy is well known for all MIBC, wathever the stage. Thus, neoadjuvant chemotherapy is recommended for all eligible patients according PS (PS <2) and renal function (clearance > 60ml/mn). As regards metastatic MIBC, first-line chemotherapy using platin is recommended (GC or MVAC). In second line treatment, only chemotherapy using vinflunine has been validated to date, even if results of immunotherapy clinical trials are encouraging. ConclusionThese updated french guidelines will contribute to increase the level of urological care for the diagnosis and treatment for NMIBC and MIBC.© 2016 Elsevier Masson SAS. All rights reserved.

Abstract 1405: Vesigenurtacel-L stimulates tumor infiltration of unique polyclonal T cell clones in non-muscle invasive bladder cancer patients

Abstract Non-muscle invasive bladder cancer affects approximately 50,000 Americans each year, requires chronic medical management with a combination of surgical resection and intravesical BCG instillations for treatment. While BCG improves recurrence-free survival in this population, there remains a significant unmet medical need for therapeutics in patients who have a particularly high risk of recurrence and/or progression to muscle-invasive disease. Vesigenurtacel-L is an allogeneic, cell based, vaccine engineered to secrete the heat shock protein, gp96-Ig, which facilitates cross-presentation of cell-derived antigens on MHC I to activate CD8+ T cell responses across MHC barriers. We recently reported that in patients treated with Vesigenurtacel-L in a Phase I clinical trial, a minimum of 15 antigens were shared between the vaccine and individual patient tumors. Although no patient received a complete course of maintenance BCG, 70% of patients remained recurrence free beyond 12 months. Baseline biopsies were collected from all patients, and serial biopsies for several patients when clinically indicated. Analysis of these tissues by RNA Sequencing revealed that recurring patient tumors expressed higher levels of B7-H4, GITR and KIR3 at baseline, while non-recurring patient tumors expressed an immune profile consistent with an interferon defense signature. In addition, patients with progressive elimination of residual disease in repeat biopsies showed increased levels of CD3, CD8, IL-23A and OX40. Deep sequencing of peripheral blood T cells and total tumor DNA for T cell receptors was performed at baseline and at several post-treatment time points. These data demonstrated polyclonal expansion of TCR clones that were either absent, or present at low frequencies at baseline in the peripheral blood. Remarkably, approximately 40% of these clones could also be found expanded within the tumor. These data correlate positively with the absolute increase in tumor infiltrating lymphocyte percentages observed by immunohistochemistry. ELISPOT assays were performed to demonstrate the specificity of expanded T cell clones toward shared tumor antigens, since the antigens in both the patients tumors and Vesigenurtacel-L were known. These data provide exciting clinical evidence of patient benefit derived from an allogeneic immunotherapy vaccine and compelling evidence for a vaccine therapy converting ‘cold’ tumor to (predominantly CD8+) TIL-rich tumors, with a corresponding analysis of the antigenic determinants of the response. Citation Format: Taylor H. Schreiber, George Fromm, Xin Xu, Eric Yusko, Brandon Early, Melissa Price. Vesigenurtacel-L stimulates tumor infiltration of unique polyclonal T cell clones in non-muscle invasive bladder cancer patients. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1405.

MP13-04 CONCENTRATION OF MITOMYCIN-C IN URINE ACCORDING TO URINE PH AFTER INTRAVESICAL INSTILLATION OF MITOMYCIN-C IN NON-MUSCLE INVASIVE BLADDER CANCER PATIENTS

Aim of this study was to evaluate HRQoL of patients affected by NMIBC underwent intravesical instillations of Bacillus Calmette-Gu erin (BCG) or Mytomicin C (MMC) with a short-term follow-up. METHODS: From December 2011 to December 2014 we recruited 108 consecutive patients in a single academic center with a first-time diagnosis of NMIBC at intermediate or high risk. The median age was 73 years (38-94) and 55.3% (N 57) patients underwent BCG and 44.7% (N 46) patients underwent MMC after TURBT respectively. The assessment of HRQoL was performed using two questionnaires from EORTC: QLQ-C30 and QLQ-BLS24 specific for NMIBC. Patients self-completed the questionnaires in three different times: T0 (before intravesical instillation), T1 (after intravesical instillation), T2 (at three months after last instillation). The above analysis was stratified by gender, age (?70 years and >70 years), tumour degree risk (intermediate and high risk) and type of intravesical therapy (MMC and BCG). Wilcoxon two sample test was used to verify differences. Statistical significance was achieved if pvalue was 1⁄40.05 (two-sides). RESULTS: Treatment was well tolerated in both groups of patients underwent intravesical instillations of BCG and MMC respectively. Grade I and II side effects, as CTCAE classification, were reported by 46.6% of patients at T1 and 47.5% at T2. 5 patients dropped out of the study (3 lost in follow-up and 2 developed side effects of BCG). At T1 we founded a drop in QoL, with reference to Physical, Role, Emotional and Social functioning domains and a worsening of urinary bladder symptoms with a generally decrease of Global Quality of Life Score. The sexual sphere was affected by adjuvant therapy with persistence or worsening of sexual disorders. At T2 patients showed a progressive return to baseline QoL, in particular in the Social and clinical symptoms domains. Male gender, age>70 years, high-risk tumours and BCG seem to be the factors that worsening HRQoL of these patients. CONCLUSIONS: Intravesical instillations seem to modify the HRQoL of these patients with a return at 3 months to baseline conditions.

Évaluation des effets indésirables des instillations endovésicales par BCG : implication potentielle de la souche utilisée ?

Intravesical instillations of BCG represent an established treatment of high-risk non-muscle-invasive bladder cancer but also carry considerable toxicity. The aim of this work was to identify adverse effects, their impact on the treatment and the possible involvement of the BCG strain used. To evaluate adverse events in terms of incidence, severity and moment of occurrence, we performed a retrospective analysis of all patients treated with BCG in our institution from 1998 to 2012. One hundred and forty-six patients were retained for analysis, 140 (95.9%) finished their first induction cycle. Thirty patients (20.6%) had to stop the treatment because of BCG-related adverse events, 80% of which happened during the first 3 BCG cycles (12 instillations). The strain used may have had a significant impact: 16 out of 42 patients (38.1%) treated with Connaught (Immucyst®) and 14 out of 104 patients (13.5%) treated with Tice (Oncotice®) had to stop treatment because of BCG related adverse events (P=0.0019) with an odds ratio of 2.83 (IC 95%: 1.52-5.23). BCG-related adverse events generally occur at the beginning of the treatment and therefore do not limit the use of BCG maintenance therapy. Good instillation practice and, in our series, the shift from Connaught to Tice strain enabled to significantly reduce BCG-related adverse events through time. The potential implication of the BCG strain used should be evaluated in prospective trials.

Is bladder tumor location associated with prostate cancer detection after intravesical bacillus Calmette-Guérin instillation?

ObjectivesThe aim of this study was to evaluate the effect of bladder tumor (BT) location on prostate cancer (PCa) detection in patients with elevated PSA levels after intravesical BCG instillation.MethodsBetween February 2004 and January 2013 prostate biopsies were performed in 59 non-muscle invasive bladder cancer (NMIBC) patients whose PSA level were elevated (≥3 ng/ml) after a 6 week course of intravesical BCG (Oncotice, 12.5 mg in 50 ml normal saline). Differences in PCa detection according to the BT location [bladder neck and/or trigone (Group 1, n = 22) vs. other locations (Group 2, n = 37)] were evaluated. The Fisher's exact test and the Mann-Whitney U test were used to evaluate the association between categorical and continuous variables, respectively.ResultsA total of 14 patients (23.7%) were diagnosed with PCa. The mean ± standard deviation (SD) PSA before intravesical BCG instillation and prostate biopsy were 1.36±1.04 ng/ml in Group 1 and 1.09±1.12 ng/ml in Group 2 (P = 0.633), and 6.05±3.57 ng/ml in Group 1 and 5.13±3.88 ng/ml in Group 2 (P = 0.378), respectively. Interestingly, whereas PCa was detected upon biopsy in only one patient in Group 1 (4.5%), 13 cases were detected in Group 2 (35.1%) (P = 0.009).ConclusionsPCa detection after intravesical BCG was highly associated with BT location. Prostate biopsy should therefore be considered when PSA level is elevated after BCG instillation and his BT is located far from the bladder neck.

Quelle place pour l’évaluation endoscopique avec fluorescence après traitement d’attaque par instillations endovésicales de BCG

The objective of this retrospective study was to assess the usefulness of fluorescence during cystoscopy after BCG-therapy in the management of non-invasive bladder tumors. Fifty-four patients were enrolled: Ta (15 cases), T1 (27 cases) carcinoma in situ (CIS) alone (12 cases) or associated (14 cases). Urine cytology was of high grade and a second look was systematically performed in case of lamina propria infiltration. Initial therapy with 6 intravesical BCG instillations (81 mg) was performed with histologic and endoscopic bladder evaluation 3 months after initial resection using hexylaminolevulinate fluorescence (Hexvix(®) 85 mg). Urine cytology was negative in 27 cases, suspicious in 12 cases and positive in 15 cases. With standard endoscopy under white light, mucosal bladder was normal in 32 cases, the use of fluorescence detected 8 tumour lesions confirmed with histology (CIS). When mucosal bladder was suspect under white light (22 patients), fluorescence was positive in 16 cases with 10 matching histological analysis (CIS and/or residual tumoral lesion). Therefore, despite high false positive rate with persistent mucosal bladder inflammation (38%), fluorescence guided endoscopy has allowed the diagnosis of suspect lesions not detected with white light with negative urine cytology. Hexvix(®) fluorescence after intravesical BCG instillations may improve persistent carcinoma in situ detection when performed 3 months after induction treatment. However, a multicenter prospective study will be necessary in future to confirm these preliminary results. 5.

A Case of Granulomatous Hepatitis and Pancytopenia Secondary to Bacillus Chalmette Guerin Immunotherapy (BCG)

We describe the case of a 69-year-old female who developed pancytopenia and acute hepatitis as a complication of intravesical BCG instillations for the treatment of bladder urothelial carcinoma. Liver and bone marrow biopsies revealed multinucleated giant epithelioid cells and non-caseating granulomas. Treatment with antituberculosis drugs achieved complete resolution. This case illustrates an infrequent but severe complication of intravesical BCG instillations, whichcan be successfully treated without steroids.

Recommandations en onco-urologie 2013 du CCAFU : Tumeurs de la vessie

The objective was to update the guidelines of the French Urological Association Cancer Committee for non invasive (NMIBC) and invasive bladder cancer (MIBC). A Medline search was performed between 2010 and 2013, as regards diagnosis, options of treatment and follow-up of bladder cancer, to evaluate different references with levels of evidence. Diagnosis of NMIBC (Ta, T1, CIS) depends on cystoscopy and complete deep resection of the tumour. The use of fluorescence and a second-look indication are essential to improve initial diagnosis. Risks of both recurrence and progression can be estimated using the EORTC score. A stratification of patients into low, intermediate and high groups is pivotal for recommending adjuvant treatment: instillation of chemotherapy (immediate post-operative, standard schedule) or intravesical BCG (standard schedule and maintenance). Cystectomy is recommended in BCG-refractory patients. Extension evaluation of MIBC is based on pelvic-abdominal and thoracic CT-scan, MRI and FDGPET remain optional. Cystectomy associated with extensive lymph nodes resection is considered the gold standard for non metastatic MIBC. An orthotopic bladder substitution should be proposed to both male and female patients lacking any contraindications and in cases of negative frozen urethral samples, otherwise trans-ileal ureterostomy is recommended as urinary diversion. The interest of neoadjuvant chemotherapy is well known for advanced MIBC as T3-T4 and/or N1-3. As regards metastatic MIBC, first-line chemotherapy using platin is recommended (GC or MVAC), when status (PS<1) and renal function (creatinine clearance > 60 ml/min) permits (only in 50% of cases). In second line treatment, only chemotherapy using vinfluvine has been validated to date. Conclusion.-These new guidelines will hopefully contribute not only to improve patient management, but also diagnosis and treatment for NMIBC and MIBC.

Klebsiella pneumoniae invasive infection in an immunocompetent patient

Immunotherapywith BCG, a live attenuated strain ofMycobacterium bovis, is a well known and effective therapy in the treatment of superficial bladder cancer. Although considered a relatively safe treatment, local and systemic complications may occur. Late disseminated infection manifested 1 year or more after the first BCG intravesical instillation is rare, occurring in 1% of the patients. There are less than 50 cases of late-presentation infection described in the literature. The authors present the case of an 80 year-old male patient with a known diagnosis of bladder carcinoma. Two years earlier he underwent transurethral resection of the bladder tumor followed by intravesical BCG instillation therapy. His past medical history was remarkable for several comorbidities namely chronic kidney disease on hemodialysis treatment. The patient presented with asthenia, occasional low grade fever and night sweats for the last 12 months. These complaints were attributable to urinary tract infections and the patient was started on quinolones for several times for the last months. An isolated generalized seizure was reported during a previous hospital course 1 month earlier. His bladder cancer remained in remission. On physical examination the patient was cachectic and had no adenopathies or meningeal signs. Laboratory investigation showed pancytopenia. Computed tomography scan of the abdomen revealed hepatomegaly, splenomegaly and several abdominal aorta aneurysms. The bone marrow biopsy showed noncaseating granulomas. A lumbar puncture was made and the cerebrospinal fluid analysis revealed pleocytosis with a lymphocyte predominance, diminished glucose levels and elevated protein levels and adenosine deaminase. M. bovis was isolated in the bone marrow and bronchoalveolar lavage cultures by polymerase chain reaction assay was performed confirming the diagnosis of M. bovis disseminated infection. The patient died 2 weeks after antituberculous therapy was started. This case illustrates a rare late complication of intravesical BCG instillation. We highlight the multisystemic infection involvement (meninges, lung, bone marrow and abdominal aorta walls) and the isolation of M. bovis in two distinct locations (lung and bone marrow). We assumed that the insidious clinical presentation could be due to the anti-bacilar activity of quinolones prescribed for several times prior to hospital admission.

Disseminated Mycobacterium bovis infection: Late complication of intravesical instillation of Bacillus Calmette-Guérin

Immunotherapywith BCG, a live attenuated strain ofMycobacterium bovis, is a well known and effective therapy in the treatment of superficial bladder cancer. Although considered a relatively safe treatment, local and systemic complications may occur. Late disseminated infection manifested 1 year or more after the first BCG intravesical instillation is rare, occurring in 1% of the patients. There are less than 50 cases of late-presentation infection described in the literature. The authors present the case of an 80 year-old male patient with a known diagnosis of bladder carcinoma. Two years earlier he underwent transurethral resection of the bladder tumor followed by intravesical BCG instillation therapy. His past medical history was remarkable for several comorbidities namely chronic kidney disease on hemodialysis treatment. The patient presented with asthenia, occasional low grade fever and night sweats for the last 12 months. These complaints were attributable to urinary tract infections and the patient was started on quinolones for several times for the last months. An isolated generalized seizure was reported during a previous hospital course 1 month earlier. His bladder cancer remained in remission. On physical examination the patient was cachectic and had no adenopathies or meningeal signs. Laboratory investigation showed pancytopenia. Computed tomography scan of the abdomen revealed hepatomegaly, splenomegaly and several abdominal aorta aneurysms. The bone marrow biopsy showed noncaseating granulomas. A lumbar puncture was made and the cerebrospinal fluid analysis revealed pleocytosis with a lymphocyte predominance, diminished glucose levels and elevated protein levels and adenosine deaminase. M. bovis was isolated in the bone marrow and bronchoalveolar lavage cultures by polymerase chain reaction assay was performed confirming the diagnosis of M. bovis disseminated infection. The patient died 2 weeks after antituberculous therapy was started. This case illustrates a rare late complication of intravesical BCG instillation. We highlight the multisystemic infection involvement (meninges, lung, bone marrow and abdominal aorta walls) and the isolation of M. bovis in two distinct locations (lung and bone marrow). We assumed that the insidious clinical presentation could be due to the anti-bacilar activity of quinolones prescribed for several times prior to hospital admission.

Antigen-Specific CD4 T Cells Are Induced after Intravesical BCG-Instillation Therapy in Patients with Bladder Cancer and Show Similar Cytokine Profiles as in Active Tuberculosis

Specific T cell immunity in patients with active tuberculosis is associated with a decrease in multifunctionality. However, it is unknown whether cytokine profiles differ in patients with primary infection and those with prior contact. We therefore used intravesical immunotherapy with attenuated live Bacille Calmette–Guérin (BCG) in patients with urothelial carcinoma as a model to characterise the induction of systemic immunity towards purified protein derivate (PPD) and to study whether cytokine profiles differ depending on pre-existing immunity. Eighteen patients with non-muscle invasive bladder cancer were recruited during the BCG-induction course. Fifty-four healthy individuals served as controls. Interferon (IFN)-γ and interleukin (IL)-2 producing PPD-specific CD4 T cells were analysed longitudinally before each instillation using a rapid flow-cytometric whole blood immunoassay. Baseline levels of IFN-γ producing PPD-specific T cells were comparable to controls. T cells showed a 5-fold increase to 0.23% by week 2/3, and further increased 8-fold by week 4/5 (to 0.42%, p=0.0007). Systemic immunity was induced in all patients, although the increase was less pronounced in patients with pre-existing immunity. As in active TB, cytokine profiling during therapy revealed a lower percentage of multifunctional IFN-γ/IL-2 double-positive T cells compared to controls (60.2% vs. 71.9%, p=0.0003). Of note, when comparing patients with and without pre-existing immunity, cytokine profiles in patients with primary immunity were shifted towards IL-2 single producing T cells (p=0.02), whereas those in patients with pre-existing immunity were shifted towards IFN-γ single-positivity (p=0.01). In conclusion, systemic T cell responses were induced after BCG-therapy, and their kinetics and cytokine profile depended on pre-existing immunity. Decreased functionality is a typical feature of specific immunity in both patients with active tuberculosis and BCG-therapy. Among patients with active infection, a shift towards IL-2 or IFN-γ single-positive cells may allow distinction between patients with primary infection and cases with boosted immunity after prior contact, respectively.

1704 THE EFFECT OF REPEAT TRANSURETHRAL RESECTION ON RECURRENCE RATES IN PATIENTS WITH NON MUSCLE INVASIVE BLADDER CANCER WHO RECEIVED INTRAVESICAL BACILLUS CALMETTE-GUERIN

You have accessJournal of UrologyBladder Cancer: Superficial (I)1 Apr 20131704 THE EFFECT OF REPEAT TRANSURETHRAL RESECTION ON RECURRENCE RATES IN PATIENTS WITH NON MUSCLE INVASIVE BLADDER CANCER WHO RECEIVED INTRAVESICAL BACILLUS CALMETTE-GUERIN John P. Sfakianos, Philip H. Kim, and Harry W. Herr John P. SfakianosJohn P. Sfakianos New York, NY More articles by this author , Philip H. KimPhilip H. Kim New York, NY More articles by this author , and Harry W. HerrHarry W. Herr New York, NY More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.3014AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The standard of care for non muscle invasive bladder cancer (NMIBC) is transurethral resection (TUR) with or without adjuvant intravesical therapy. A repeat TUR has been associated with a decreased risk of recurrence and progression, likely due to improved staging and therapeutic intervention. We sought to identify if repeat resection prior to initiation of intravesical BCG improved recurrence free rates. METHODS We retrospectively analyzed 1021 patients with NMIBC treated with intravesical BCG at our institution. All patients underwent a second resection, except for those who were already undergoing BCG treatment at consultation or refused a repeat resection. Repeat resections were performed within 2-6 weeks after the initial procedure (patients upstaged to pT2 were excluded). All patients were followed every 3 to 6 months for a minimum of 5 years. Recurrence was assessed at 3, 6 and 12 months with office cystoscopy, cytology and resection of bladder tumors when indicated. RESULTS Of 1021 patients who underwent initial TUR of their tumor, 127 (12.5%) had only a single TUR while 894 (87.5%) had a repeat TUR before intravesical BCG instillation. The median age of our cohort was 63, with 756 (74%) males. At initial presentation we identified 612 (59.9%) and 409 (40.1%) pTa and pT1 tumors, respectively. 769 (75.3%) were high-grade tumors and CIS was found in 629 (61.6%). At repeat TUR, 421 (41.2%) were found to be free of tumor, while 109 (10.7%), 211 (20.7%), 138 (13.5%), and 142 (13.9%) and were found to have papilloma, pTis only, pTa, and pT1 respectively. On univariate analysis, tumor grade, presence of CIS on initial TUR, tumor present on repeat TUR and having a single TUR were predictors of recurrence at 3 and 6 months (all p <0.003). Grade, presence of tumor on repeat TUR and a single TUR were also predictors of recurrence at 12 months (all p <0.001). On multivariate analysis presence of tumor on repeat TUR (OR 5.6 95% CI 3.0, 10.2; p <0.001) and a single TUR (OR 4.4% CI 2.8, 6.9; p <0.001) were predictors of recurrence at 3 months. On Kaplan-Meier analysis, time to recurrence for a single TUR was significantly decreased compared to those receiving a repeat TUR (median 22 months versus 36 months, p <0.001). CONCLUSIONS Repeat resection prior to initiation of intravesical BCG therapy decreased recurrence rates at 3, 6 and 12 months. We believe repeat resection should therefore be performed prior to initiating BCG therapy for superficial bladder cancer. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e701 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information John P. Sfakianos New York, NY More articles by this author Philip H. Kim New York, NY More articles by this author Harry W. Herr New York, NY More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Traitement d’entretien par BCG-thérapie des tumeurs de vessie n’infiltrant pas le muscle (TVNIM) : résultats à un an de l’étude multicentrique URO-BCG-4

Intravesical instillations of BCG remains the gold standard for intermediate and high risk NMIBC management. Maintenance treatment is recommended, however, the frequency of side effects responsible for the discontinuation of maintenance therapy over four out of five patients before the third year suggest a reduction or even spacing instillations. The objective of the study URO-BCG-4 was the evaluation of a new maintenance schedule by intravesical instillations of BCG combined reduced dose (third dose) and a decrease number of instillations per cycle (two or three).Multicenter study of the French Association Oncologic Committee (12 university hospital centers), randomized, prospective, comparing reference diagram of BCG maintenance therapy one third of usual dose (group I) to a regimen combining third dose and decrease the number of instillations per cycle (two instead of three) (group II). We present the preliminary results at 1year of this Program of Clinical Research (CHU Rouen Promoter 2003-081).The rate of recurrence was respectively 9 and 7% (P=0.678) in groups I and II. The rate of tumor progression are 3 and 2.8% in groups I and II (P=1). Tolerance of intravesical instillations of BCG scored according to the WHO classification (Geneva 1979) was similar in the two groups.The decrease in the BCG dose (third dose) and the changes in the number and rate of instillations did not alter free tumor recurrence survival. The toxicity of intravesical instillations of BCG was identical in both groups. The use of the WHO classification has shown its limitations in the study of side effects of BCG as too complex and often not exhaustive. The rate of increase muscle was comparable in the two groups; however, a larger clinical experience is required.

卡介苗治疗反复复发性膀胱癌3例临床体会

目的：探讨卡介苗膀胱灌注对保留膀胱术后反复复发的膀胱移行细胞癌患者预防复发和进展的疗效。方法：对3例膀胱癌患者进行卡介苗灌注治疗的临床资料进行回顾性分析。结果：3例患者保留膀胱术后经卡介苗膀胱灌注治疗，复发率明显降低，进展减缓。结论：卡介苗膀胱灌注能够有效预防膀胱癌术后复发和进展。 Objective: To study the curative effect of intravesical instillation of BCG on patients with transitional cell carcinoma recurrence and progression and recurrence of bladder preservation of the bladder after surgery. Methods: The clinical data of 3 cases of patients with bladder cancer receiving BCG therapy were retrospectively analyzed. Re- sults: After 3 cases of patients with preservation of the bladder underwent intravesical instillation of BCG therapy, recurrence rate reduced obviously and the progression slowed down. Conclusion: Intravesical instillation of BCG can be used as an effective treatment in the prevention of postoperative recurrence and progression of bladder cancer.

Intravesical BCG causing bilateral panuveitis and optic neuritis

We are reporting an interesting case of bilateral panuveitis with optic neuritis, after intravesical instillation of BCG. A 70 years old female developed eye changes post maintenance BCG for her Bladder cancer (Carcinoma in situ). After discussion with pulmonary team, it was decided not to start anti-TB medications and to treat her with oral steroids and topical steroids. There was a dramatic improvement in her vision six weeks after the treatment.These patients may have a good visual outcome, as long as the diagnosis and treatment are not delayed.

Aorto-enteric fistula development secondary to mycotic abdominal aortic aneurysm following intravesical bacillus Calmette–Guerin (BCG) treatment for transitional cell carcinoma of the bladder

INTRODUCTIONIntravesical BCG-instillation for bladder cancer is considered safe but is not without risk. While most side-effects are localised and self-limiting, the development of secondary vascular pathology is a rare but significant complication. PRESENTATION OF CASEA 77-year-old male presented with a mycotic abdominal aortic aneurysm and associated aorto-enteric fistula 18 months after receiving intravesical BCG-instillations for early stage transitional cell carcinoma. DISCUSSIONResponse rates to intravesical BCG for early stage transitional cell carcinoma are high. The procedure produces a localised inflammatory response in the bladder but the exact mechanism of action is unclear. The treatment is generally well tolerated but BCG-sepsis and secondary vascular complications have been documented.Mycotic abdominal aortic aneurysm with associated aorto-enteric fistula secondary to BCG is very rare. Few examples have been documented internationally and the extent of corresponding research and associated management proposals is limited.Surgical options include in situ repair with prosthetic graft, debridement with extra-anatomical bypass and, occasionally, endovascular stent grafting. Recommended medical therapy for systemic BCG infection is Isoniazid, Rifampicin and Ethambutol. CONCLUSIONCurrent screening methods must be updated with clarification regarding duration of anti-tuberculous therapy and impact of concomitant anti-tuberculous medication on the therapeutic action of intravesical BCG. Long-term outcomes for patients post graft repair for mycotic aneurysm are unknown and more research is required regarding the susceptibility of vascular grafts to mycobacterial infection.Recognition of the risks associated with BCG-instillations, even in immunocompetent subjects, is paramount and must be considered even several months or years after receiving the therapy.

Recommandations du comité de cancérologie de l’Association française d’urologie (CC-AFU) pour la bonne pratique des instillations endovésicales de BCG et de mytomycine C dans le traitement des tumeurs de la vessie n’envahissant pas le muscle (TVNIM)

Intravesical BCG immunotherapy and mitomycin C are considered as the standard treatment for non-muscle invasive bladder cancer. These guidelines aim to describe the optimal condition to perform intravesical instillation of BCG or mitomycin C in order to increase its oncologic efficiency and to decrease its morbidity.Online systematic literature search was performed on PubMed(®) until April 2010. Regulation texts, published guidelines and results of recent urologists practice study were taken into consideration. Level of evidence was assigned to each recommendation. A bibliographic research in French and English using Medline(®) and Embase(®) with the keywords "BCG", "mitomycin C", "bladder", "complication", "toxicity", "adverse reaction", "prevention" and "treatment" was performed.Patient information must be prior to the first intravesical instillation and should be given through a medical exam by the physician performing the procedure. The check for formal contra-indication to BCG is systematically mandatory by the physician during the medical exam. Intravesical instillation must be realized in a health center where urologic endoscopic procedures are made frequently. A recent urine culture has to be checked systematically before any instillation done either by the urologist or a specialized nurse. Contingent upon a bladder catheter has been inserted in the bladder without any injury of the lower urinary tract, the instillation can be done. The pharmaceutical agent needs to be kept two hours in the bladder. After instillation, the patient must be seated to void and also has to keep in mind that he needs to drink at least 2 liters of water per day for 2 days.To improve the oncologic performance and to reduce the risk of complication and adverse event, achievement of intravesical instillations of BCG and/or mitomycin C should follow a standardized procedure.

Added Value of Use of a Purified Protein Derivative-Based Enzyme-Linked Immunosorbent Spot Assay for Patients with Mycobacterium bovis BCG Infection after Intravesical BCG Instillations

In this case series, we describe four cases in which the use of gamma interferon release assays with purified protein derivative (PPD) as a stimulating antigen was able to demonstrate PPD-specific immune activation. This may help to improve the adequate diagnosis of (systemic) Mycobacterium bovis BCG infections after intravesical BCG instillations for bladder carcinoma.

BCG膀胱内注入療法後に生じた馬蹄腎結核の1例

A 63-year-old man with a horse shoe kidney was evaluated after an episode of asymptomatic gross hematuria. Cystoscopy revealed bladder tumor near the right ureteral orifice, and transurethral resection demonstrated high grade pT1 urothelial carcinoma. The patient was started on intravesical BCG instillation therapy at a dose of 81 mg weekly for 8 weeks without fever. 6 months later after the final BCG treatment, CT examination demonstrated a renal hypovascular tumor in an isthmus of a horseshoe kidney. We couldn't deny malignant tumor and tumorectomy was performed. Histological examination revealed epithelioid cell granulomas and no organisms were identified by Ziehl-Neelsen or Grocott-Gomori stains for acid-fast bacilli and fungi. We reported a rare case of renal tuberculosis in an isthmus of a horseshoe kidney after BCG therapy for bladder cancer that was considered due to vesicoureteral reflux.

Chest Wall Abscess Due to Mycobacterium bovis BCG after Intravesical BCG Therapy

We report a case of chest wall abscess caused by Mycobacterium bovis BCG that arose as a complication 1 year after intravesical BCG instillation. We identified M. bovis BCG Tokyo 172 in the abscess by PCR-based typing of Mycobacterium tuberculosis complex and analysis of variable number of tandem repeats data.