Therapy For Superficial Bladder Cancer Research Articles

Recurrent Sigmoid Diverticulitis After Intravesical Bacillus Calmette-Guérin (BCG) Immunotherapy for Bladder Cancer

Bacillus Calmette-Guerin (BCG), a live attenuated strain of Mycobacterium bovis, is a popular adjunctive therapy for superficial bladder cancer as it triggers local immune response. Localized cystitis is a common complication, but systemic infections or sepsis is rare. Diverticulitis has never been reported as a complication of intravesical BCG use. We report two episodes of sigmoid diverticulitis in a patient with urinary bladder papillary urothelial carcinoma after each intravesical BCG treatment, which subsided after the BCG treatment was discontinued. This case report raises awareness of acute diverticulitis as a potential side effect of intravesical BCG therapy for superficial bladder cancer. The use of antibiotics in concurrence with intravesical BCG therapy should be used with caution as evidence is not sufficient to evaluate the effect of antibiotics on BCG. Therefore, a change in therapy is warranted if recurrence of diverticulitis occurs and requires antibiotic therapy.

A CASE OF RUPTURED MYCOTIC ANEURYSM AFTER DISSEMINATED MYCOBACTERIUM BOVIS INFECTION

SESSION TITLE: Medical Student/Resident Critical Care Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Dissemination is a rare complication of intravesical bacille Calmette-Guerin (BCG) therapy for bladder malignancy. CASE PRESENTATION: An 86 year-old male with medical history of atrial fibrillation, cerebrovascular accident, and bladder carcinoma treated with intravesical BCG who initially presented with worsening lower back pain. A contrast CT showed left psoas abscess abutting posterior and left lateral wall of the infrarenal abdominal aorta without evidence of aneurysm formation or contrast extravasation. Culture from the left psoas abscess aspirate returned positive for mycobacterium tuberculosis complex with a monoresistance pattern for Pyrazinamide consistent with the diagnosis of Mycobacterium Bovis(M.Bovis). He was started on a multidrug antitubercular regimen with a plan for close-follow up with serial imaging. After 3 months, he developed worsening back pain and was brought to the emergency room with increasing somnolence. Vitals were remarkable for hypotension and tachycardia. On physical examination, the patient was disoriented and had mild abdominal tenderness. Rest of the exam was unremarkable. His blood work revealed hemoglobin 6.2mg/dl and creatinine 2.2mg/dl. Abdominal CT angiography showed large left retroperitoneal hematoma and contained rupture of the infrarenal aortic aneurysm. He was resuscitated with blood products and anticoagulation was held. He underwent emergent endovascular aneurysm repair. His postoperative period was complicated by the deterioration of renal functions resulting in anuric renal failure. He was transitioned to hospice as hemodialysis was not consistent with his goals of care. DISCUSSION: BCG contains a weak strain of M. Bovis which is used as a vaccination against mycobacterium tuberculosis infection in some parts of the world and also as intravesical immunotherapy for the treatment of bladder cancer. Common side effects of intravesical BCG treatment include transient fever, fatigue, dysuria, or hematuria. Rarely, it can lead to disseminated infection leading to pneumonitis, prostatitis, hepatitis, or endovascular involvement. The pathogenesis of endovascular invasion by BCG is unclear but it is postulated to be associated with instrumentation of the bladder. Presentation of endovascular involvement may be subtle and is usually discovered after the development of complications like a ruptured aneurysm. Mycotic aneurysm related to disseminated BCG infection should be suspected based on relevant history. Diagnosis requires imaging as well as a specimen collection for microscopic analysis and culture. Mycobacterium Bovis isolates are inherently resistant to pyrazinamide. On biopsy, there is usually evidence of granulomatous inflammation. Management involves multidrug antitubercular regimen and surgical repair of the aneurysm. CONCLUSIONS: Physicians should be aware of late complications of intravesicular BCG administration. Reference #1: A. Steg, S. Adjiman, B. Debre BCG therapy in superficial bladder tumors—complications and precautions Eur Urol, 21 (suppl 2) (1992), pp. 35-40 Reference #2: J.M. LaBerge, R.K. Kerlan Jr, L.M. Reilly, T.A. Chuter Diagnosis please: Case 9: mycotic pseudoaneurysm of the abdominal aorta in association with mycobacterial psoas abscess—a complication of BCG therapy Radiology, 211 (1999), pp. 81-85 Reference #3: D.L. Lamm, P.M. van der Meijden, A. Morales, S.A. Brosman, W.J. Catalona, H.W. Herr, et al. Incidence and treatment of complications of bacillus Calmette-Guerin intravesical therapy in superficial bladder cancer J Urol, 147 (1992), pp. 596-600 DISCLOSURES: No relevant relationships by Shahrukh Arif, source=Web Response No relevant relationships by Firas Jafri, source=Web Response

Mycotic aortic aneurysms post-Intravesical BCG treatment for early-stage bladder carcinoma

BackgroundIntravesicular Bacillus Calmette-Guérin (BCG) is an effective adjunctive therapy for superficial bladder cancer that has been shown to delay recurrence and progression of disease. Serious side effects are relatively rare but are difficult to diagnose and are often overlooked. Vascular complications are particularly rare.Case presentationWe report two cases of mycotic aortic aneurysms secondary to BCG treatment, one managed with endovascular stent-graft placement and the other with open surgical repair. The present understanding of disseminated BCGosis, including a literature review, will be discussed.ConclusionThe incidence of mycotic aneurysms from BCG treatment is rare and very few cases have been reported in the literature. These cases further expand the current knowledge on vascular complications related to BCG treatment. In the absence of formal guidelines, we recommend a multidisciplinary approach involving vascular surgery, diagnostic and interventional radiology, and infectious disease to manage these patients.

Pott’s Disease Caused by Mycobacterium bovis Following Intravesical BCG Therapy for Bladder Cancer

BackgroundBacillus Calmette-Guerin (BCG) are attenuated strains of Mycobacterium bovis, which is part of the Mycobacterium tuberculosis complex. BCG is used for bladder cancer therapy.Case/Methods80 year old man presented with severe back pain, paraplegia, urine retention. Past history included rheumatoid arthritis, bladder cancer. He was diagnosed with recurrent bladder cancer (T1, high grade lamina propria superficial invasion) in June 2016 (previously diagnosed 14 years ago, treated with BCG). Patient had transurethral resection of tumor in August 2016, after which he got 6 weekly cycles of intravesical BCG. He underwent cystoscopies with no evidence of residual disease. No history of concurrent illness during therapy.He was initially admitted 1 month ago with back pain: MRI showed thoracic (T6-T7) epidural abscess, vertebral osteomyelitis/diskitis; he underwent T6-T7 hemilaminectomies, drainage of abscess, cord decompression. Operative cultures were initially negative. He was discharged with empiric broad spectrum antibiotics. Repeat MRI during this admission showed extensive inflammation at T6-T7: diskitis, osteomyelitis, epidural abscess, more non enhancing material in the disc space, progressive edema in pedicles and lamina, worse cord compression. Neurosurgery evaluated patient: deemed to be poor surgical candidate given his extensive comorbidities, advanced age. His operative AFB cultures turned positive 4 weeks after surgery (MTB complex by DNA probe). Therapy started with Isoniazid, Rifampin, Ethambutol, Pyridoxine, Dexamethasone. The isolate was sent to state lab: whole genome sequencing showed M. bovis BCG strain. Susceptibility testing is pending.Discussion/ResultsBCG therapy of superficial bladder cancer is a recommended treatment modality. Early infectious complications occur within 3 months, late infections after 1 year. In >2000 patients treated with BCG, infectious complications occurred in <5%. Potts disease following BCG therapy is rare but has been described; the time of onset can be from 14 days to 12 years after therapy.ConclusionIn patients treated with BCG for bladder cancer, clinicians must have a high index of suspicion for infectious complications, as early initiation of therapy yields better outcomes.Disclosures All authors: No reported disclosures.

Healthcare-Associated Mycobacterium bovis-Bacille Calmette-Guérin (BCG) Infection in Cancer Patients Without Prior BCG Instillation.

Bacille Calmette-Guérin (BCG), an attenuated strain of Mycobacterium bovis, is widely used as adjunctive therapy for superficial bladder cancer. Intravesical administration of BCG has been associated with systemic infection. Disseminated infection due to M. bovis is otherwise uncommon. After identification of 3 patients with healthcare-associated BCG infection who had never received intravesical BCG administration, an epidemiologic study was performed. All patients with healthcare-associated BCG infection in the Barcelona tuberculosis (TB) program were reviewed from 1 January 2005 to 31 December 2015, searching for infections caused by M. bovis-BCG. Patients with healthcare-associated BCG infection who had not received intravesical BCG instillation were selected and the source of infection was investigated. Nine oncology patients with infection caused by M. bovis-BCG were studied. All had permanent central venous catheters. Catheter maintenance was performed at 4 different outpatient clinics in the same room in which other patients underwent BCG instillations for bladder cancer without required biological precautions. All patients developed pulmonary TB, either alone or with extrapulmonary disease. Catheter-related infection was considered the mechanism of acquisition based on the epidemiologic association and positive catheter cultures for BCG in patients in whom mycobacterial cultures were performed. Physicians should be alerted to the possibility of TB due to nosocomially acquired, catheter-related infections with M. bovis-BCG in patients with indwelling catheters. This problem may be more common than expected in centers providing BCG therapy for bladder cancer without adequate precautions.

Mycotic Aneurysm after Bacillus Calmette-Guérin Treatment: Case Report and Review of the Literature

Background. Intravesicular Bacillus Calmette-Guérin (BCG) is an effective adjunctive therapy for superficial bladder cancer that has been shown to delay recurrence and progression of disease. Serious side effects are relatively rare but are difficult to diagnosis and commonly overlooked. Case Presentation. We report the case of a patient who was found to have mycotic aortic aneurysms secondary to treatment with BCG after a prolonged course with multiple intervening hospitalizations. Conclusion. Through this report, we discuss our present understanding of BCG infection following treatment and review the literature regarding this particular rare manifestation.

Anti-tumor effect of Radix Paeoniae Rubra extract on mice bladder tumors using intravesical therapy.

Radix Paeoniae Rubra (RPR) is the dried root of Paeonia lactiflora Pallas and Paeonia veitchii Lynch, and is a herbal medicine that is widely used in traditional Chinese medicine for the treatment of blood-heat and blood-stasis syndrome, similarly to Cortex Moutan. The present study identified the same three components in RPR and Cortex Moutan extracts. In addition, it has been reported that RPR has an anti-cancer effect. Bladder cancer is the seventh most common type of cancer worldwide. Due to the high recurrence rate, identifying novel drugs for bladder cancer therapy is essential. In the present study, RPR extract was evaluated as a bladder cancer therapy in vitro and in vivo. The present results revealed that RPR extract reduced the cell viability of bladder cancer cells with a half maximal inhibitory concentration of 1–3 mg/ml, and had an extremely low cytotoxic effect on normal urothelial cells. Additionally, RPR decreased certain cell cycle populations, predominantly cells in the G1 phase, and caused a clear sub-G increase. In a mouse orthotopic bladder tumor model, intravesical application of RPR extract decreased the bladder tumor size without altering the blood biochemical parameters of the mice. In summary, the present results demonstrate the anti-proliferative properties of RPR extract on bladder cancer cells, and its anti-bladder tumor effect in vivo. Compared to Cortex Moutan extract, RPR extract may provide a more effective alternative therapeutic strategy for the intravesical therapy of superficial bladder cancer.

First multicenter experience with thermotherapy and mitomycin of high risk NMIBC with a new recirculation system (COMBAT).

425 Background: At a temperature of 43° (109°F) cytotoxicity of mitomycin increases 10 fold to tumor cells if used for instillation therapy of superficial bladder cancer (NMIBC).In the last years high organ preservation rates were reported for high risk NMIBC after radiofrequency induced hyperthermia and mitomycin (Synergo System).Unfortunately side effects were frequent and discontinuitation of 40% were reported with this method thus thermotherapy combined with instillation this therapy has not been very common.We here report about the first experience with a newly developed device using a recirculation heating system (COMBAT). Methods: After diagnosis by complete TUR/ReTUR patients received 40 mg mitomycin (mito-extra,medac) via transurethral catheter for 1 h heated up to constant 43° by a circulation pump system (COMBAT). Side effects were recorded pprospectively before and after each teratment and during follow up and success was validated by TUR/biopsy if possible. Results: A total of 20 patients were treated from 11/14-9/15 in 5 institutions. Follow up until now is 1-10 month (mean 8 m). All patients had high risk NMIBC including BCG failures. Therapy must be abondened in 1 patient after the 5th treatment, 50% had dysuria during treatment but symptoms decreased after the last treatment in all patients. 2 patients experienced mild allergic reaction also seen under conventional instillation therapy with mitomycin and were treated by corticosteroids. ReTUR was performed in 17/20 patients and revealed a persistent/recurrent tumor pTa GIII in 1 out of 20 patients. Conclusions: Compared to the microwave driven heating system the new device with recirculation of heated mitomycin seems to have less side effects without major complications. Treatment discontinuitation was recorded in 1/20 patients. Given the assumption that this system has the same high rate of organ preservation as the Synergo System at even much lower costs, it may alter the therapy algorythm in high risk NMIBC. Despite our first promising oncological results further research with longer follow up is necessary.Two prospective randomized studies are now underway in England and Spain and first results are awaited in 2 years.

Granulomatous Hepatitis as a Consequence of Disseminated Mycobacterium bovis (M. bovis)

A 77 year-old male with history of transitional bladder cell carcinoma diagnosed 12 years ago, presented for further evaluation of recurrent fever, night sweats and weight loss of 1-month duration. Previously he was treated with 3 transurethral tumor resections (TUR) over 7 years and 18 intravesicular Bacillus Calmette-Guerin (BCG) doses. His cancer recurred recently and he underwent a TUR 2 months prior to presentation followed by 2 intravesicular BCG doses, last dose 1 day prior to fever. An extensive infectious work up in the form of blood, urine, and radiographic evaluation was obtained and was negative. Blood and urine cultures were negative. He was empirically treated for BCG cystitis with an antimycobacterial (anti-TB) regimen consisting of isoniazid (INH), rifampin (R), ethambutol and vitamin B6 (B6). His fevers resolved on this regimen and he was discharged on this regimen. He was readmitted 10 days later with fevers. Repeat blood and urine cultures had no growth. In addition, he had mildly elevated transaminases, which were attributed to the R and was substituted with ciprofloxacin. With persistently elevated transaminases, a liver biopsy was done showing granulomatous hepatitis with non-necrotizing granulomas and negative acid-fast bacilli (AFB) stain. Due to BCG therapy, this histologic finding is most consistent with BCG-associated granulomatous hepatitis confirming the diagnosis of disseminated BCG. He was restarted on anti-TB therapy with INH, levofloxacin and B6. His fevers improved 5 days after initiation of therapy. He was discharged on these medications for a 6-month course. Surprisingly, 6 weeks later, initial blood and urine cultures grew M bovis. BCG is a live attenuated strain of M bovis. Intravesicular administration of BCG is commonly used as an adjuvant therapy in superficial bladder cancer. Disseminated BCG is a very rare complication following intravesicular BCG therapy. The prevalence of granulomatous hepatitis in disseminated BCG is 0.7%. Of patients with BCG-associated granulomatous hepatitis, only 10% of patients have tissue that test positive for AFB stains showing mycobacterial organisms. The mechanism by which BCG therapy can cause disseminated M bovis is not clearly understood. One thought is a Th1-mediated hypersensitivity reaction since a number of case reports demonstrated disseminated granulomas with negative AFB and no isolated organism. Our patient did have evidence of disseminated granulomas with negative AFB, but the organism was later isolated in his urine and blood, hence raising the hypothesis that the organism itself also can access the blood stream via uroepithelial cells and disseminate to other organs. In these cases, multi drug anti-TB therapy is recommended for three to six months with or without the addition of glucocorticoids.

Is the calcified lesion of bladder wall after intravesical mitomycin-c therapy for superficial bladder cancer should be resected?

Is the calcified lesion of bladder wall after intravesical mitomycin-c therapy for superficial bladder cancer should be resected?

FRI-10 MITOMYCIN-C: HISTORICAL ASPECTS OF THE DISCOVERY OF MOST COMMONLY USED CHEMOTHERAPY AGENT IN UROLOGY

You have accessJournal of UrologyHistory of Urology Forum I1 Apr 2015FRI-10 MITOMYCIN-C: HISTORICAL ASPECTS OF THE DISCOVERY OF MOST COMMONLY USED CHEMOTHERAPY AGENT IN UROLOGY Hemant Nemade, Hussein Tukmatchy, and Peter Thompson Hemant NemadeHemant Nemade More articles by this author , Hussein TukmatchyHussein Tukmatchy More articles by this author , and Peter ThompsonPeter Thompson More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.488AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Although urology is primarily a surgical speciality, evolution of pharmacotherapy over time has revolutionised the treatment of certain disorders. Endoscopic resection was the only treatment that was available for superficial bladder tumours, till the development of intravesical instillation of chemotherapeutic agents. The discovery and introduction of mitomycin C into urological field is researched in this presentation. METHODS Material per taining to early treatment of bladder cancer was reviewed. Correspondences with Japanese companies where the discovery was made also contributed immensely to the research. RESULTS The mitomycins are a family of aziridine-containing products isolated from Streptomyces species. After discovery of penicillin by Fleming, there was an interest in isolating substances from microorganisms that were capable of killing other bacteria. Japan, after its defeat in the WWII, was keen to be a frontrunner in development of newer antibiotics. Dr. Kitasato founder of Kitasato Institute laid the foundation of early development of microbiology and pharmacology. Dr Toju Hata (1908-2004), after serving in the army during the War, joined Kitasato Institute to pursue his interest in microbiology. His hard work paid results as in 1953, he discovered the antibiotic Leucomycin. In 1956, Hata isolated mitomycin-A & mitomycin-B from Steptomyces caespitosus that had antibiotic & antitumour activities. Dr Hata along with Dr Shigetoshi Wakagi from Kyowa Hakko Kogyo company later reported the isolation of mitomycin-C from the same fermentation broth at a higher pH and that this compound had much higher antitumour activity. After the success of intravesical therapy using Thiotepa in 1961 by Jones and Swinney, Dr Shida and his colleagues reported in a Japanese journal the use of mitomycin C. Because of lesser side-effects and its efficacy, mitomycin-C became the most popular agent for intravesical therapy for superficial bladder cancer. CONCLUSIONS The discovery of mitomycin C is interesting as it was being isolated as an antibiotic but found to have antineoplastic properties. Its success in reducing the recurrence had made it the most commonly used chemotherapeutic agent in urology. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e585 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hemant Nemade More articles by this author Hussein Tukmatchy More articles by this author Peter Thompson More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Histopathology of Disseminated Mycobacterium bovis Infection Complicating Intravesical BCG Immunotherapy for Urothelial Carcinoma

Intravesical instillation of Bacillus Calmette-Guérin (BCG) is a mainstay of adjunctive therapy for superficial bladder cancer. Disseminated BCG infection ("BCG-osis") after this therapy is rare and potentially life-threatening; only isolated case reports detail the histopathologic findings thereof, few of which had a diagnosis confirmed by molecular testing. We report 3 additional cases of BCG-osis complicating BCG therapy, all confirmed by cultures and molecular assays, including the first cases of wedge biopsy-confirmed BCG pneumonia and BCG olecranon bursitis. When suggested by a relevant clinical history, recognition of randomly distributed granulomas in any organ should prompt consideration of BCG-osis and liberal performance of AFB stains, aided by targeted molecular assays. Physicians should maintain a high index of suspicion when miliary infiltrates arise after intravesical BCG instillation, and close multidisciplinary communication is essential. Pathologist awareness of this rare cause of granulomatous inflammation aids recognition of BCG-osis and facilitates prompt initiation of antimycobacterial therapy.

Peritoneal tuberculosis presenting as recurrent peritonitis secondary to treatment with intravesical Bacillus Calmette-Guérin in a patient receiving peritoneal dialysis.

Intravesical Bacillus Calmette-Guérin (BCG) is an established treatment for high-risk superficial bladder cancer [Morales A, Eidinger D, Bruce AW. Intracavitary Bacillus Calmette-Guérin in the treatment of superficial bladder tumors.1976. J Urol 2002; 167: 891–893, Lamm DL, van der Meijden APM, Morales A et al. Incidence and treatment of complications of Bacillus Calmette-Guérin intravesical therapy in superficial bladder cancer. J Urol 1992; 147: 596–600]. We describe a patient receiving peritoneal dialysis (PD), who developed peritoneal tuberculosis following treatment of bladder cancer with intravesical BCG instillations. To the best of our knowledge, this is the first case of peritoneal tuberculosis following intravesical BCG treatment in which the mycobacterium has been typed and confirmed as a BCG strain with genetic analysis.

Anti-cancer properties of gastropodan hemocyanins in murine model of colon carcinoma.

BackgroundVarious immunotherapeutic approaches have been used for the treatment of cancer. A number of natural compounds are designed to repair, stimulate, or enhance the immune system response. Among them are the hemocyanins (Hcs) - extracellular copper proteins isolated from different arthropod and mollusc species. Hcs are oxygen transporter molecules and normally are freely dissolved in the hemolymph of these animals. Hemocyanins are very promising class of anti-cancer therapeutics due to their immunogenic properties and the absence of toxicity or side effects. KLH (Megathura crenulata hemocyanin) is the most studied molecule of this group setting a standard for natural carrier protein for small molecules and has been used in anti-tumor clinical trials.ResultsThe Hcs isolated from marine snail Rapana thomasiana (RtH) and the terrestrial snail Helix pomatia (HpH) express strong in vivo anti-cancer and anti-proliferative effects in the developed by us murine model of colon carcinoma. The immunization with RtH and HpH prolonged the survival of treated animals, improve humoral anti-cancer response and moderate the manifestation of C-26 carcinoma symptoms as tumor growth, splenomegaly and lung metastasis appearance.ConclusionHemocyanins are used so far for therapy of superficial bladder cancer and murine melanoma models. Our findings demonstrate a potential anti-cancer effect of hemocyanins on a murine model of colon carcinoma suggesting their use for immunotherapy of different types of cancer.

Functionalized mesoporous silica nanoparticles with mucoadhesive and sustained drug release properties for potential bladder cancer therapy.

The synthesis of a series of β-cyclodextrin modified mesoporous silica nanoparticles with hydroxyl, amino, and thiol groups was described. A comparison of their mucoadhesive properties and potential as a drug delivery system for superficial bladder cancer therapy was made. The thiol-functionalized nanoparticles exhibit significantly higher mucoadhesivity on the urothelium as compared to the hydroxyl- and amino-functionalized nanoparticles. This is attributed to the formation of disulfide bonds between the thiol-functionalized nanoparticles and cysteine-rich subdomains of mucus glycoproteins. An anticancer drug, doxorubicin, was loaded into the mesopores of the thiol-functionalized nanoparticles, and sustained drug release triggered by acidic pH was achieved. The present study demonstrates that thiol-functionalized mesoporous silica nanoparticles are promising as a mucoadhesive and sustained drug delivery system for superficial bladder cancer therapy.

P011 Monthly intravesical bacillus Calmette-Guérin maintenance therapy for superficial bladder cancer: A single instituition experience

P011 Monthly intravesical bacillus Calmette-Guérin maintenance therapy for superficial bladder cancer: A single instituition experience

Cost-Effectiveness of Fluorescence In Situ Hybridization in Patients with Atypical Cytology for the Detection of Urothelial Carcinoma

Patients with atypical cytology and equivocal or negative cystoscopy pose a challenge due to uncertainty about the presence of cancer. We determined the cost-effectiveness of using fluorescence in situ hybridization assays to determine the need for biopsy in patients with atypical cytology and equivocal or negative cystoscopy. Data from 2 large prospective studies evaluating the usefulness of fluorescence in situ hybridization in the setting of atypical cytology to detect urothelial carcinoma were combined. The data were used to calculate sensitivity and specificity for the UroVysion fluorescence in situ hybridization assay in various clinical scenarios. Cost data were obtained from our institution and Medicare reimbursement rates. Evaluations with or without bladder biopsy and with or without upper tract evaluation were considered. The study included 263 patients with atypical cytology and equivocal (62) or negative (201) cystoscopy. In patients with equivocal cystoscopy (assuming biopsy was performed in the operating room) biopsy based on fluorescence in situ hybridization results saved $1,740 per patient ($3,267 vs $1,527 per patient) and avoided 42 biopsies compared to biopsy in all patients. If office based biopsies were used then cost savings using fluorescence in situ hybridization results were $95 per patient. Among patients with negative cystoscopy biopsy based on fluorescence in situ hybridization resulted in costs savings of $2,241 per patient, avoiding 167 biopsies, compared to biopsy in all patients. Assuming office based biopsy, the cost savings were $216 per patient. The decision to perform biopsy based on fluorescence in situ hybridization assay in patients with atypical cytology and equivocal or negative cystoscopy was associated with a significant decrease in bladder cancer associated costs.

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 ...

Cortex Moutan Induces Bladder Cancer Cell Death via Apoptosis and Retards Tumor Growth in Mouse Bladders

Cortex Moutan is the root bark of Paeonia suffruticosa Andr. It is the herbal medicine widely used in Traditional Chinese Medicine for the treatment of blood-heat and blood-stasis syndrome. Furthermore, it has been reported that Cortex Moutan has anticancer effect. In this study, the Cortex Moutan extract was evaluated in bladder cancer therapy in vitro and in vivo. Cortex Moutan extract reduces cell viability with IC50 between 1~2 mg/ml in bladder cancer cells, and it has lower cytotoxicity in normal urotheliums. It arrests cells in G1 and S phase and causes phosphatidylserine expression in the outside of cell membrane. It induces caspase-8 and caspase-3 activation and poly(ADP-ribose) polymerase degradation. The pan caspase inhibitor z-VAD-fmk reverses Cortex Moutan-induced cell death. Cortex Moutan also inhibits cell invasion activity in 5637 cells. In mouse orthotopic bladder cancer model, intravesical application of Cortex Moutan decreases the bladder tumor size without altering the blood biochemical parameters. In summary, these results demonstrate the antiproliferation and anti-invasion properties of Cortex Moutan in bladder cancer cells and its antibladder tumor effect in vivo. Cortex Moutan may provide an alternative therapeutic strategy for the intravesical therapy of superficial bladder cancer.

Results of a Phase 1 Dose Escalation Study of Intravesical TMX-101 in Patients with Nonmuscle Invasive Bladder Cancer

Imiquimod, a toll like receptor 7 (TLR-7) agonist, is effective as a topical treatment for skin malignancies. TMX-101 is a liquid formulation of imiquimod. In this study we establish a safety profile of TMX-101 in patients with nonmuscle invasive bladder cancer. We conducted a multicenter phase 1 dose escalation study in patients with nonmuscle invasive bladder cancer. Patients were included in 1 of 4 dose groups (0.05%, 0.1%, 0.2% or 0.4%) and treated with 6 weekly instillations of TMX-101, starting 2 weeks after transurethral resection of bladder tumor. Patients were evaluated weekly, and pharmacokinetic and pharmacodynamic parameters were measured. A total of 16 patients were included in the study with 4 per dose group. Two patients dropped out after instillation 2 in dose groups 1 and 2. Overall, 88 instillations were administered without serious adverse events. There were 118 adverse events, of which 84 were related to the study drug. All adverse events were mild or moderate and number or severity was not correlated with dose group. Of the related adverse events 70% were confined to the genitourinary tract and resolved without intervention. There was a dose dependent systemic uptake with low plasma levels up to dose group 3 (0.2%, 100 mg). Maximum plasma concentration in dose group 4 (0.4%, 200 mg) was 71.7 ng/ml. This is below plasma concentrations of 123 and 128 ng/ml without significant side effects measured in healthy volunteers after subcutaneous (30 mg) or oral intake (100 mg) of imiquimod, respectively. Intravesical treatment with TMX-101 is safe. The side effects are common but mild and mostly limited to the genitourinary tract. There is a low systemic uptake.