BCG Instillation Research Articles

Résultats oncologiques de la cystectomie pour carcinome urothélial résistant au BCG comparés aux tumeurs invasives d’emblée

BCG therapy deeply modified prognosis of high-risk non muscle invasive (NMI) urothelial carcinomas. However, these tumors remain potentially lethal. The objective of this study was to compare oncological outcome of radical cystectomy (RC) for BCG failure to primary invasive (PI) tumors. RC performed between 2001 and 2011 were retrospectively reviewed. Clinicopathological and follow-up data were compared between RC performed for: NMI high-grade recurrence under BCG therapy (ReNMI); MI recurrence (≥ T2) under BCG therapy (ReMI); primary invasive tumors (PI). The three groups were defined according to tumor status on last TUR before RC. All NMI high-grade bladder tumors at diagnosis had maintenance BCG immunotherapy. Two hundred patients were included, 155 PI, 21 ReNMI et 24 ReMI. Median follow up was 42 months (1.74-135.9). Mean BCG instillations number was 8 ± 4.2 versus 9.5 ± 4.3 for ReNMI and ReMI respectively (P=0.24). Upstaging (≥ pT2) occurred in 33% of ReNMI. The rate of pN+ was 24%, 42% and 30% for the ReNMI, ReMI et PI respectively (P=0.39). No differences were observed between the groups for lymphovascular invasion, extracapsular extension if pN+, soft tissue surgical margins and adjuvant chemotherapy. 5-year cancer specific survival (CSS) was 48% for the ReNMI, 18% for the ReMI and 47% for the PI (P=0.02). Progression to muscle invasion under BCG therapy was an independent pejorative prognostic factor for CSS (P=0.05). BCG failure led to poor prognosis, particularly when tumors progressed to muscle invasion. Recurrent NMI high-grade tumors seemed to have comparable prognosis than PI tumors because of the high amount of upstaging and nodal invasion. BCG failure is a therapeutic emergency.

390 ROLE OF KI-67 PROLIFERATION MARKER IN PREDICTING RECURRENCE OF HIGH GRADE TA & T1 BLADDER TRANSITIONAL CELL CARCINOMA

You have accessJournal of UrologyUrothelial Cancer: Natural History, Markers & Pathophysiology1 Apr 2013390 ROLE OF KI-67 PROLIFERATION MARKER IN PREDICTING RECURRENCE OF HIGH GRADE TA & T1 BLADDER TRANSITIONAL CELL CARCINOMA Mohamed Abdallah, Ahmed Abdelhalim, Hala Said, Tarek Abdelbakey, Nancy Assad, and Abdelaliem Eldorey Mohamed AbdallahMohamed Abdallah Quesna, Egypt More articles by this author , Ahmed AbdelhalimAhmed Abdelhalim Shibin Elkom, Macedonia More articles by this author , Hala SaidHala Said shibin elkom, Egypt More articles by this author , Tarek AbdelbakeyTarek Abdelbakey shibin elkom, Egypt More articles by this author , Nancy AssadNancy Assad shibin elkom, Egypt More articles by this author , and Abdelaliem EldoreyAbdelaliem Eldorey shibin elkom, Egypt More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.1779AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Ki-67, an established proliferation marker expressed in G1, S, G2, M phases of cell cycle. We previously found an association between Ki-67 index & urothelial tumor grade, muscle invasion & positive lymph nodes. In this study, we focused on high grade non-muscle invasive urothelial tumor to predict recurrence after complete TURBT with 1 year follow up. This can aid decision of urologist either to follow up or to schedule his patient for radical cystectomy. METHODS 87 patients with high grade non-muscle invasive TCC did complete TURBT with immediate intravesical instillation of Epirubicin® 50 mg, Ki-67 index was estimated using purified rabbit polyclonal antibody raised against the C-terminal fragment of the human Ki67 nuclear antigen (Lab vision, USA). Intravesical immunotherapy by instillation of BCG & follow up cystoscopy & immunohistochemical determination of Ki-67 index at 3, 6, 9 & 12 months. RESULTS The Age of the patients (Range, Mean ± SD)45-60, 56.72 ± 4.81. The gender (Male%, Female%)86.1, 13.9.The Ki-67 index was(Range, Median)30-90,70.The table shows the recurrence rates. CONCLUSIONS The higher the Ki-67 index, the higher the probability of recurrence of high grade Ta & T1 transitional cell carcinoma of bladder with 56% recurrence with Ki-67 index 81-90% at 1 year follow up. New recurrence at 3 months 6 months 9 months 12 months total Ki-67 index 30-40% (N=15) 0 (0%) 0 (0%) 0 (0%) 2 (13.33%) 2 (13.33%) Ki-67 index 41-60% (N=21) 0 (0%) 0 (0%) 4 (19.05%) 4 (19.05%) 8 (38.1%) Ki-67 index 61-80% (N=26) 1 (3.85%) 1 (3.85%) 4 (15.38%) 4 (30.77%) 10 (38.46%) Ki-67 index 81-90% (N=25) 2 (8.0%) 4 (16%) 2 (8.0%) 6 (24.0%) 14 (56.0%) Overall recurrence at 1 year 34 (39.08%) © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e158 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mohamed Abdallah Quesna, Egypt More articles by this author Ahmed Abdelhalim Shibin Elkom, Macedonia More articles by this author Hala Said shibin elkom, Egypt More articles by this author Tarek Abdelbakey shibin elkom, Egypt More articles by this author Nancy Assad shibin elkom, Egypt More articles by this author Abdelaliem Eldorey shibin elkom, Egypt More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

1787 DIHYDROPYRIMIDINE DEHYDROGENASE IS ASSOCIATED WITH CLINICAL OUTCOME IN T1G3 BLADDER CANCER PATIENTS TREATED WITH BACILLUS CALMETTE-GUERIN

You have accessJournal of UrologyBladder Cancer: Superficial (II)1 Apr 20131787 DIHYDROPYRIMIDINE DEHYDROGENASE IS ASSOCIATED WITH CLINICAL OUTCOME IN T1G3 BLADDER CANCER PATIENTS TREATED WITH BACILLUS CALMETTE-GUERIN Hiroki Ide, Eiji Kikuchi, Shuji Mikami, Akira Miyajima, and Mototsugu Oya Hiroki IdeHiroki Ide Tokyo, Japan More articles by this author , Eiji KikuchiEiji Kikuchi Tokyo, Japan More articles by this author , Shuji MikamiShuji Mikami Tokyo, Japan More articles by this author , Akira MiyajimaAkira Miyajima Tokyo, Japan More articles by this author , and Mototsugu OyaMototsugu Oya Tokyo, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.2877AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Recently, it was reported that thymidylate synthase (TS), a target enzyme of 5-fluorouracil (5-FU), and dihydropyrimidine dehydrogenase (DPD), which degraded most of 5-FU, were significant prognostic factors for invasive bladder cancer. However, few studies that evaluated the roles of them in recurrence focused on non-muscle invasive bladder cancer, especially T1G3 tumors. In the present study, we used the Dannenberg tumor profile (DTP) method, which is a highly accurate method for the measurement of RNA that involves a special technique for its extraction from paraffin-embedded specimens, to evaluate the role of 5-FU related enzymes as predictive biomarkers in T1G3 tumors. METHODS The subjects were 45 patients with T1G3 tumors who were surgically treated at our institution. The median follow-up was 37 months (3 to 159 months). Twenty-eight patients received adjuvant BCG instillation. The mRNA levels of TS and DPD were analyzed using the DTP method. Recurrence-free survival (RFS) and progression-free survival (PFS) were evaluated by the Kaplan-Meier method. Cox proportional hazards regression analysis was used to assess the predictors for RFS and PFS. RESULTS Overall, the mean DPD and TS mRNA levels were 1.255±0.179 and 9.273±1.098, respectively. BCG instillation was significantly associated with RFS and an independent predictor for RFS (p<0.01). The TS and DPD mRNA levels were not significantly associated with RFS and PFS. Recurrence and progression were observed in 13 (46.4%) and 6 (21.4%) patients, respectively, among those treated with BCG. In patients treated with BCG, the mean DPD mRNA level with recurrence was 1,341±0.426, compared to 0.994±0.335 without it (p<0.05). On the other hand, no significant difference in TS level between patients with recurrence and without it was observed. In patients treated with BCG, DPD was significantly associated with PFS (p=0.047). Multivariate analysis revealed DPD (p=0.048, hazard ratio 4.759, 95%CI: 0.868-26.098) was an independent predictor for PFS. The 5-year PFS rate was 85.6% in patients with lower DPD compared to 63.5% in those with higher DPD. The mean DPD mRNA level with progression was 1.884±0.679, compared to 0.980±0.279 without it (p<0.05). Meanwhile, the TS mRNA level was not significantly associated with PFS. CONCLUSIONS DPD may be a key enzyme involved in recurrence and progression in T1G3 patients treated with BCG therapy. Combination therapy of BCG with a 5-FU-based agent having a strong DPD inhibitor such as S-1 might be a novel therapeutic strategy in T1G3 tumors. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e734 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hiroki Ide Tokyo, Japan More articles by this author Eiji Kikuchi Tokyo, Japan More articles by this author Shuji Mikami Tokyo, Japan More articles by this author Akira Miyajima Tokyo, Japan More articles by this author Mototsugu Oya Tokyo, Japan More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...

1789 FOLLOWUP AFTER A CONSERVATIVE APPROACH OF LOW GRADE UPPER URINARY TRACT TOMOURS: CHANGING THE PATTERNS

and 2009 archived at our institution. A total of 330 patients with initially diagnosed NMIBC were identified. The use of antihypertensive drugs at TUR-BT was reviewed focusing on the use of RAS inhibitors and other agents (calcium-channel blockers, ƒA-blockers, and diuretics). We retrospectively investigated the clinical outcomes following TUR-BT in patients who did or did not administer RAS inhibitors. The median follow-up period was 4.1 years. RESULTS: A total of 128 patients (38.8%) experienced subsequent tumor recurrence during follow-up. One hundred sixteen patients (35.2%) received medications for hypertension at TUR-BT. Fifty-one patients (15.5%) had received ACEI or ARB administration. Multivariate analysis demonstrated that tumor multiplicity, the absence of BCG instillation, and no ACEI or ARB administration (P 0.010 HR 2.26) were independent risk factors for subsequent tumor recurrence. The 5-year recurrence-free survival rate was 78.4% in patients administered ACEIs or ARBs, and 53.3% in their counterparts (p 0.011). CONCLUSIONS: The absence of RAS inhibitor administration was an independent risk factor for subsequent tumor recurrence in patients with initially diagnosed NMIBC. Our data supports further investigation of the RAS inhibitors as a potential therapy to decrease tumor recurrence in NMIBC.

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 ...

1621 ONCOLOGICAL OUTCOME OF RADICAL CYSTECTOMY FOR BCG FAILURE COMPARED TO PRIMARY INVASIVE DISEASE

You have accessJournal of UrologyBladder Cancer: Invasive (II)1 Apr 20131621 ONCOLOGICAL OUTCOME OF RADICAL CYSTECTOMY FOR BCG FAILURE COMPARED TO PRIMARY INVASIVE DISEASE Alexandra Masson-Lecomte, Dimitri Vordos, René Yiou, Yves Allory, Claude Abbou, Alexandre de la Taille, and Laurent Salomon Alexandra Masson-LecomteAlexandra Masson-Lecomte Creteil, France More articles by this author , Dimitri VordosDimitri Vordos Créteil, France More articles by this author , René YiouRené Yiou Créteil, France More articles by this author , Yves AlloryYves Allory Créteil, France More articles by this author , Claude AbbouClaude Abbou Créteil, France More articles by this author , Alexandre de la TailleAlexandre de la Taille Créteil, France More articles by this author , and Laurent SalomonLaurent Salomon Créteil, France More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.3171AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES BCG therapy deeply modified prognosis of high risk non muscle invasive (NMI) urothelial carcinomas. However, these tumors remain potentially lethal. The objective of this study was to compare oncological outcome of radical cystectomy (RC) for BCG failure to primary invasive(PI) tumors. METHODS RC performed between 2001 and 2011 were retrospectively reviewed. Clinico-pathological and follow up data were compared between RC performed for (i) NMI high grade recurrence under BCGtherapy (ReNMI) (ii), MI recurrence (ÂiÝT2) under BCGtherapy (ReMI) (iii) Primary Invasive tumors (PI). The three groups were defined according to tumor status on last TUR before RC. All NMI high grade bladder tumors at diagnosis had maintenance BCG immunotherapy. RESULTS 200 patients were included, 155 PI, 21 ReNMI et 24 ReMI. Median follow up was 42 months (1.74-135.9). Mean BCG instillations number was 8±4.2 vs 9.5±4.3 for ReNMI and ReMI respectively (p=0.24). Upgrading (ÂiÝpT2) occurred in 33% of ReNMI. The rate of pN+ was 24%, 42% and 30% for the ReNMI, ReMI et PI respectively (p=0.39). No differences were observed between the groups for lymphovascular invasion, extracapsular extension if pN+, soft tissue surgical margins and adjuvant chemotherapy. 5-year cancer specific survival (CSS) was 48% for the ReNMI, 18% for the ReMI and 47% for the PI (p=0.02) (Figure). Progression to muscle invasion under BCG therapy was an independent pejorative prognostic factor for CSS (p=0,05). CONCLUSIONS BCG failure leads to poor prognosis, particularly when tumors progress to muscle invasion. Recurrent NMI high grade tumors seem to have comparable prognosis than PI tumors because of the high amount of upstaging and nodal invasion. BCG failure is a therapeutic emergency. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e666 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alexandra Masson-Lecomte Creteil, France More articles by this author Dimitri Vordos Créteil, France More articles by this author René Yiou Créteil, France More articles by this author Yves Allory Créteil, France More articles by this author Claude Abbou Créteil, France More articles by this author Alexandre de la Taille Créteil, France More articles by this author Laurent Salomon Créteil, France More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

702 Is there any influence on the real number of BCG instillations applied on the outcome of high-grade non-muscle-invasive bladder cancer (NMIBC)?

702 Is there any influence on the real number of BCG instillations applied on the outcome of high-grade non-muscle-invasive bladder cancer (NMIBC)?

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.

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.

Systemic granulomatous reaction secondary to treatment of bladder cancer with Bacillus Calmette-Guerin

Intravesical instillation of Bacillus Calmette-Guérin is the elective treatment for transitional cell and in situ bladder carcinoma. Severe complications occur very seldom, but must be known and promptly recognized. We describe the case of a 48-year-old man, treated with chemo-immunotherapy ten years before for a follicular lymphoma, who developed a systemic granulomatous reaction after his twelfth intravescical BCG instillation for bladder cancer.

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.

Empfehlungen zur Therapie, Chemoprävention und Chemoprophylaxe der Tuberkulose im Erwachsenen- und Kindesalter

Several new international recommendations have been published since the German Central Committee against Tuberculosis (DZK) published its recommendations for drug treatment of tuberculosis (TB) in 2001 and for chemoprevention of latent tuberculosis infection (LTBI) in 2004. These international publications have been integrated in the present new recommendations which describe both the treatment of active TB and preventive treatment, pointing out specific adaptations for Germany. Separate sections deal with the current management of mono-, poly-, and multiresistance or drug intolerance, of TB in children, of different forms of extrapulmonary TB, of LTBI and of special situations such as HIV infection, renal or hepatic insufficiency, infection following BCG instillation in bladder cancer or in case of adverse drug reactions. The following aspects differ from the previous recommendations: A three-drug regimen for the so-called fully susceptible minimal TB is no longer recommended in adults. A dosage of 15 mg/kg body weight of ethambutol for adults is regarded as sufficient. Four secondline drugs (supplemented by pyrazinamide, where appropriate) are recommended for multidrug-resistant tuberculosis (MDR-TB). MDR-TB should be treated over a period of at least 20 months, with an injectable drug administered for a minimum of 8 months (initial phase). Ciprofloxacine and ofloxacine are no longer used to treat TB. It is also recommended to offer an HIV test to all TB patients to complement antiretroviral therapy, if necessary, and to adapt the antituberculous therapy accordingly.

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.

Treatment changes and long‐term recurrence rates after hexaminolevulinate (HAL) fluorescence cystoscopy: does it really make a difference in patients with non‐muscle‐invasive bladder cancer (NMIBC)?

• To evaluate in a prospective, randomized study the impact of hexaminolevulinate blue-light cystoscopy (HAL-BLC) on the diagnostic accuracy and treatment changes in cases of non-muscle invasive bladder cancer (NMIBC) compared with standard white-light cystoscopy (WLC). • To compare the long-term recurrence rates in the two study arms. • In all, 362 patients suspected of NMIBC were included in the trial based on positive urinary cytology and/or ultrasonographic suspicion of bladder tumours and underwent transurethral resection of bladder tumours. • A single postoperative mytomicin-C instillation was performed in all cases, intravesical chemotherapy for intermediate-risk patients and BCG instillations for high-risk cases. • The follow-up protocol consisted of urinary cytology and WLC every 3 months for 2 years. • Only first-time recurrences after the initial diagnosis were considered. • In the 142 patients with NMIBC in the HAL-BLC series, tumour detection rates significantly improved for carcinoma in situ, pTa andoverall cases. • In 35.2% of the cases, additional malignant lesions were found by HAL-BLC and consequently, the recurrence- and progression-risk categories of patients and subsequent treatment improved in 19% of the cases due to fluorescence cystoscopy. • In all, 125 patients in the HAL-BLC group and 114 of the WLC group completed the follow-up. • The recurrence rate at 3 months was lower in the HAL-BLC series (7.2% vs 15.8%) due to fewer 'other site' recurrences when compared with the WLC series (0.8% vs 6.1%). • The 1 and 2 years recurrence rates were significantly decreased in the HAL-BLC group compared with the WLC group (21.6% vs 32.5% and 31.2% vs 45.6%, respectively). • HAL-BLC was better than WLC for detecting NMIBC cases and improved tumour detection rates. • HAL-BLC significantly modified the postoperative treatment of cases. • The 3 months, 1 and 2 years recurrence rates were significantly improved in the HAL-BLC arm.

Sensitivity to Isoniazid of Mycobacterium bovis BCG Strains and BCG Disseminated Disease Isolates

Intravesical Mycobacterium bovis BCG instillation therapy is commonly used to prevent recurrences of carcinoma in situ (CIS) and/or Ta/T1 papillary tumors of the urinary bladder (8). A rare and serious complication associated with BCG treatment of bladder cancer is the development of disseminated BCG disease (1, 6). Current recommendations for bladder cancer patients (being treated with BCG) who develop persistent fever or experience an acute febrile illness consistent with a mycobacterial infection include administration of combination therapy with two or more antimycobacterial agents (3). Recently, U.S. federal public health authorities were notified of two cases of disseminated BCG disease resulting after bladder cancer therapy with BCG Connaught. Drug sensitivity testing (DST) of these strains suggested that both of these strains were resistant to low concentrations of isoniazid (0.2 μg/ml isoniazid [INH]), the primary drug used to treat Mycobacterium tuberculosis complex infections. These DST results raised concerns about acquired resistance in vivo or the generation of drug-resistant bacteria during manufacturing. Interpretation of the DST data was confounded because the levels of sensitivity to INH for many BCG strains were poorly defined. To address these concerns, the sensitivities to INH of 13 different BCG strains were determined using the standard proportion method (7). DST analysis showed that four of the BCG strains (Tokyo, Moreau, Russia, and Sweden) and two M. tuberculosis controls were extremely sensitive to INH at the 0.05-μg/ml level (Table 1). In contrast, the other 9 BCG strains tested (including BCG Connaught) consistently had 2- to 4-fold-higher MICs for INH. For these BCG strains, the MICs ranged from 0.1 to 0.2 μg/ml INH. Importantly, the MICs of INH for the patient isolates and the parental BCG Connaught strain were essentially identical. Table 1. Drug sensitivity testing of M. bovis BCG strains Interestingly, our DST analysis of the different BCG strains indicated that all BCG strains obtained by international public health officials from the Pasteur Institute after 1926 had moderately elevated levels of resistance to INH (Table 1). Following the original attenuation of BCG at the Pasteur Institute from 1908 to 1921, BCG strains were maintained by serial propagation in different laboratories (1921 to 1961) until frozen seed lot systems were developed. Behr et al. have reported that all BCG strains obtained from the Pasteur Institute after 1926 had a point mutation in the mma3 gene which resulted in impaired methoxy mycolic acid production (2). Since the target for INH antituberculosis activity is the mycolic acid biosynthetic pathway, it has been speculated that this mutation would cause decreased sensitivity to INH for BCG strains obtained after 1926. These data support this hypothesis since every strain obtained from the Pasteur Institute after 1926 has a modestly elevated MIC for INH. The increasing frequency of drug-resistant M. tuberculosis disease worldwide has enhanced public health concerns about the adequacy of antituberculosis therapeutic regimens and the overall effectiveness of tuberculosis control programs (4, 5). Within this environment, the identification of two BCG isolates with apparent increased resistance to INH from patients with disseminated mycobacterial disease was worrisome. However, these DST data suggest that the decreased sensitivity to INH seen in the patient isolates (relative to that seen in sensitive M. tuberculosis strains) was likely not caused by acquired resistance in vivo or a genotypic modification during the manufacturing process. The modestly decreased sensitivity to INH seen in these BCG strains likely resulted from a mutation in a gene involved in mycolic acid biosynthesis which occurred more than 8 decades ago.

Abstract 2697: Enhanced antitumor effect of combination intravesical BCG plus Docetaxel therapy in an orthotopic bladder cancer model

Abstract Introduction and Objective: Little progress in the management of non-muscle invasive bladder cancer (NMIBC) has been made. We explored the combination of intravesical BCG plus Doc in an orthotopic model. Methods: An orthotopic murine bladder cancer model was used. To assess the antitumoral effect of Doc, intravesical Doc therapy was administered at various dose-escalating concentrations: 0 μg (control: PBS), 25 μg, 50 μg and 100 μg (n = 12 for each group; total of 4 groups). Next, a comparative evaluation of tumor growth among the control group, the BCG-alone group, the Doc-alone group, and three combined BCG + Doc groups (a coincident group [CO] and two sequential groups) was performed (n = 12 for each group; total of 6 groups). The sequential combined groups consisted of SA group (SA; Doc administration followed by BCG administration on the next day) and an SB group (SB; BCG administration followed by Doc administration on the next day). Intravesical therapy was administered at 3-day intervals starting on day 5 and was repeated 5 times. To evaluate proliferation, T cell infiltration and apoptosis among the different groups, the tumor cells in the animal model were stained for Ki-67, CD8 and Cleaved caspase 3 after 4 instillations performed every 3 days. Results: In the Doc groups (12 mice each) treated with a dose of 0 μg (survival period: 32.3 ± 9.4 days), 25 μg (36.8 ± 11.4), 50 μg (38.1 ± 11.0) or 100 μg (40.0 ± 12.7), one, two, two and three mice failed to develop tumors and survived, respectively. The survival advantage for intravesical Doc in the 100 μg administration group was statistically significant when compared with that in the control group (p = 0.04). Out of the 12 mice in each group treated with control, Doc-alone, BCG-alone or combined Doc + BCG (CO, SA, SB), 1, 2, 1, 4, 4 and 1 mice failed to develop tumors and survived, respectively. Significant survival advantages were observed in the combined BCG + Doc group (CO: 50.7 ± 9.0, SA: 51.5 ± 6.9) compared with that in the BCG-alone group (33.1 ± 10.4) and the Doc-alone group (38.8 ± 11.5). The Ki-67 index of the cancer cells was significantly lower in the combined group, compared with that in the BCG-alone group (p &amp;lt; 0.0001), the Doc-alone group (p &amp;lt; 0.05) and the control group (p &amp;lt; 0.0001). BCG-alone significantly increased the number of CD8+ T cells (p &amp;lt; 0.05), while Doc-alone reduced the number of CD8+ T cells (p &amp;lt; 0.05), compared with that in the control. Apoptosis was significantly increased when Doc was administrated to the animals irrespective of the presence (p &amp;lt; 0.05) or absence (p &amp;lt; 0.05) of BCG instillation. Conclusions: Our results suggested that the combination of BCG and Doc treatment decreased the tumor appearance rate and improved the survival period. The enhancement in tumor growth inhibition enabled by combination regimens was presumably associated with a reduction in the tumor proliferation rate and might not depend on either CD8+ T cells or apoptosis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2697. doi:10.1158/1538-7445.AM2011-2697

1937 OFFICE-BASED ENDOUROLOGY USING FLUOROSCOPIC GUIDANCE: CLINICAL OUTCOMES AND COST-EFFECTIVENESS

You have accessJournal of UrologyStone Disease: New Technology/SWL, Ureteroscopic or Percutaneous Stone Removal1 Apr 20111937 OFFICE-BASED ENDOUROLOGY USING FLUOROSCOPIC GUIDANCE: CLINICAL OUTCOMES AND COST-EFFECTIVENESS Boris Gershman, Brian Eisner, and Dianne Sacco Boris GershmanBoris Gershman Boston, MA More articles by this author , Brian EisnerBrian Eisner Boston, MA More articles by this author , and Dianne SaccoDianne Sacco Boston, MA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.2118AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Endourologic procedures are increasingly being performed in the office. We examined the clinical outcomes and cost-effectiveness of endourologic procedures performed in the office using standard fluoroscopy under local anesthesia. METHODS We performed a retrospective review of all patients who underwent ureteral stent placement, ureteral stent exchange, or ureteral catheterization with retrograde pyeolography or BCG instillation in the office under topical anesthesia using fluoroscopic guidance from 9/2008 - 12/2009. Cost data was estimated from Medicare 2010 non-facility physician fees and Ambulatory Payment Classification (APC) reimbursements. RESULTS Procedures were attempted in 65 renal units in 38 patients (13 male, 25 female) with a mean age of 62.2 years (range 29.1–95.4 years). No procedure was terminated due to patient discomfort. Primary ureteral stent placement was successful in 23/24 (95.8%) renal units. Ureteral stent exchange was successful in 19/22 (86.4%) renal units. Ureteral catheterization with retrograde pyelography or BCG instillation was successful in 19/19 renal units. Indications for stent placement or exchange were ureteral stone (14/30, 46.7%), malignant extrinsic ureteral compression (8/30, 26.7%), benign extrinsic ureteral compression (3/30, 10%), ureteral stricture (2/30, 6.7%), ureteropelvic junction obstruction (2/30, 6.7%), and hydronephrosis of unknown etiology (1/30, 3.3%). The total cost of stent placement/stent exchange/retrograde pyelography is $599/$599/$346 when performed in the office compared with $2,306/$2,306/$2,279 when performed in the ambulatory surgical suite. The total cost savings for the 38 patients in this study was approximately $95,601, including excess cost from failure in the office. CONCLUSIONS Ureteral stent placement, exchange, and catheterization can be performed safely and effectively in the office in both men and women. This avoids general anesthesia, provides convenience to patient and clinician, and represents a substantial cost-savings for the healthcare system. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e775 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Boris Gershman Boston, MA More articles by this author Brian Eisner Boston, MA More articles by this author Dianne Sacco Boston, MA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

1938 RISK OF DIABETES MELLITUS AND HYPERTENSION AFTER EXTRACORPOREAL SHOCK WAVE (ESWL) THERAPY FOR URINARY STONE DISEASE

INTRODUCTION AND OBJECTIVES: Endourologic procedures are increasingly being performed in the office. We examined the clinical outcomes and cost-effectiveness of endourologic procedures performed in the office using standard fluoroscopy under local anesthesia. METHODS: We performed a retrospective review of all patients who underwent ureteral stent placement, ureteral stent exchange, or ureteral catheterization with retrograde pyeolography or BCG instillation in the office under topical anesthesia using fluoroscopic guidance from 9/2008 12/2009. Cost data was estimated from Medicare 2010 non-facility physician fees and Ambulatory Payment Classification (APC) reimbursements. RESULTS: Procedures were attempted in 65 renal units in 38 patients (13 male, 25 female) with a mean age of 62.2 years (range 29.1–95.4 years). No procedure was terminated due to patient discomfort. Primary ureteral stent placement was successful in 23/24 (95.8%) renal units. Ureteral stent exchange was successful in 19/22 (86.4%) renal units. Ureteral catheterization with retrograde pyelography or BCG instillation was successful in 19/19 renal units. Indications for stent placement or exchange were ureteral stone (14/30, 46.7%), malignant extrinsic ureteral compression (8/30, 26.7%), benign extrinsic ureteral compression (3/30, 10%), ureteral stricture (2/30, 6.7%), ureteropelvic junction obstruction (2/30, 6.7%), and hydronephrosis of unknown etiology (1/30, 3.3%). The total cost of stent placement/stent exchange/retrograde pyelography is $599/$599/$346 when performed in the office compared with $2,306/$2,306/$2,279 when performed in the ambulatory surgical suite. The total cost savings for the 38 patients in this study was approximately $95,601, including excess cost from failure in the office. CONCLUSIONS: Ureteral stent placement, exchange, and catheterization can be performed safely and effectively in the office in both men and women. This avoids general anesthesia, provides convenience to patient and clinician, and represents a substantial costsavings for the healthcare system.