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Sample records for non-muscle-invasive bladder carcinoma

  1. Non-muscle-invasive bladder cancer

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    Malmström, Per-Uno; Agrawal, Sachin; Bläckberg, Mats

    2017-01-01

    The management of non-muscle-invasive bladder cancer (NMIBC) has evolved from the first reports on bladder endoscopy and transurethral resection to the introduction of adjuvant intravesical treatment. However, disease recurrence and progression remain an ongoing risk, placing a heavy burden on he...

  2. Gene expression signatures predict outcome in non-muscle invasive bladder carcinoma - a multi-center validation study

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    Andersen, Lars Dyrskjøt; Zieger, Karsten; Real, Francisco X.

    2007-01-01

    PURPOSE: Clinically useful molecular markers predicting the clinical course of patients diagnosed with non-muscle-invasive bladder cancer are needed to improve treatment outcome. Here, we validated four previously reported gene expression signatures for molecular diagnosis of disease stage and ca...

  3. Risk estimation of multiple recurrence and progression of non muscle invasive bladder carcinoma using new mathematical models.

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    Luján, S; Santamaría, C; Pontones, J L; Ruiz-Cerdá, J L; Trassierra, M; Vera-Donoso, C D; Solsona, E; Jiménez-Cruz, F

    2014-12-01

    To apply new mathematical models according to Non Muscle Invasive Bladder Carcinoma (NMIBC) biological characteristics and enabling an accurate risk estimation of multiple recurrences and tumor progression. The classical Cox model is not valid for the assessment of this kind of events becausethe time betweenrecurrencesin the same patientmay be stronglycorrelated. These new models for risk estimation of recurrence/progression lead to individualized monitoring and treatment plan. 960 patients with primary NMIBC were enrolled. The median follow-up was 48.1 (3-160) months. Results obtained were validated in 240 patients from other center. Transurethral resection of the bladder (TURB) and random bladder biopsy were performed. Subsequently, adjuvant localized chemotherapy was performed. The variables analyzed were: number and tumor size, age, chemotherapy and histopathology. The endpoints were time to recurrence and time to progression. Cox model and its extensions were used as joint frailty model for multiple recurrence and progression. Model accuracy was calculated using Harrell's concordance index (c-index). 468 (48.8%) patients developed at least one tumor recurrence and tumor progression was reported in 52 (5.4%) patients. Variables for multiple-recurrence risk are: age, grade, number, size, treatment and the number of prior recurrences. All these together with age, stage and grade are the variables for progression risk. Concordance index was 0.64 and 0.85 for multiple recurrence and progression respectively. the high concordance reported besides to the validation process in external source, allow accurate multi-recurrence/progression risk estimation. As consequence, it is possible to schedule a follow-up and treatment individualized plan in new and recurrent NMCB cases. Copyright © 2014 AEU. Published by Elsevier Espana. All rights reserved.

  4. Blue-light cystoscopy in the evaluation of non-muscle-invasive bladder cancer

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    Oude Elferink, P.; Witjes, J.A.

    2014-01-01

    Bladder carcinoma is the most common malignancy of the urinary tract. Two distinct groups can be identified: non-muscle-invasive bladder carcinoma (NMIBC) and muscle-invasive bladder carcinoma. At initial resection about 75-85% of the patients will be diagnosed with NMIBC. This subgroup has a

  5. Intravesical chemotherapy in non-muscle-invasive bladder cancer

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    Sima P Porten

    2015-01-01

    Full Text Available Non-muscle-invasive bladder cancer (NMIBC is characterized by a tendency for recurrence and capacity for progression. Intravesical instillation therapy has been employed in various clinical settings, which are summarized within this review. Several chemotherapeutic agents have shown clinical efficacy in reducing recurrence rates in the post-transurethral resection of bladder tumor (TURBT setting, including mitomycin C (MMC, doxorubicin, and epirubicin. Mounting evidence also supports the use of intravesical MMC following nephroureterectomy to reduce later urothelial bladder recurrence. In the adjuvant setting, bacillus Calmette-Guérin (BCG immunotherapy is an established first-line agent in the management of carcinoma in situ (CIS and high-grade non muscle invasive urothelial carcinoma (UC. Among high and intermediate-risk patients (based on tumor grade, size, and focality improvements in disease-free intervals have been seen with adjunctive administration of MMC prior to scheduled BCG dosing. Following failure of first-line intravesical therapy, gemcitabine and valrubicin have demonstrated modest activity, though valrubicin remains the only agent currently Food and Drug Administration (FDA-approved for the treatment of BCG-refractory CIS. Techniques to optimize intravesical chemotherapy delivery have also been explored including pharmacokinetic methods such as urinary alkalization and voluntary dehydration. Chemohyperthermia and electromotive instillation have been associated with improved freedom from recurrence intervals but may be associated with increased urinary toxicity. Improvements in therapeutic selection may be heralded by novel opportunities for genomic profiling and refinements in clinical risk stratification.

  6. Preoperative prognostic nutritional index and nomogram predicting recurrence-free survival in patients with primary non-muscle-invasive bladder cancer without carcinoma in situ

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    Cui J

    2017-11-01

    Full Text Available Jianfeng Cui,1,* Shouzhen Chen,1,* Qiyu Bo,2 Shiyu Wang,1 Ning Zhang,1 Meng Yu,1 Wenfu Wang,1 Jie Han,3 Yaofeng Zhu,1 Benkang Shi1 1Department of Urology, 2Department of First Operating Room, Qilu Hospital of Shandong University, 3Department of Radiation Oncology, Shandong Cancer Hospital and Institute Affiliated to Shandong University, Jinan, People’s Republic of China *These authors contributed equally to this work Background and objectives: Among the cancers of the urogenital system, bladder cancer is ranked second both in incidence and mortality, and hence, a more accurate estimate of the prognosis for individual patients with non-muscle-invasive bladder cancer (NMIBC is urgently needed. Prognostic nutritional index (PNI which is based on serum albumin levels and peripheral lymphocyte count has been confirmed to have prognostic value in various cancers. The aim of this study was to clarify the prognostic value of PNI in patients with NMIBC.Methods: Data of 329 patients with NMIBC were evaluated retrospectively. Recurrence-free survival (RFS was assessed using the Kaplan–Meier method, and the equivalences of survival curves were tested by log-rank tests. The univariate and multivariate analyses were performed using the Cox proportional hazards regression model. Discrimination of the nomogram was measured by the concordance index. A p-value of <0.05 was considered statistically significant.Results: In univariate analysis, age, tumor focality, tumor size, tumor grade, pathological T stage and preoperative PNI were significantly associated with RFS. Multivariate analysis identified PNI as an independent predictor of RFS in patients with NMIBC. According to these independent predictors, a nomogram for the prediction of recurrence was developed.Conclusion: PNI can be regarded as an independent prognostic factor for predicting RFS in NMIBC. The nomogram could be useful to improve personalized therapy for patients with NMIBC. Keywords: non-muscle-invasive

  7. Mitomycin C Intravesical Chemotherapy in Conjunction With Synergo® Radiofrequency-Induced Hyperthermia for Treatment of Carcinoma in Situ Non-Muscle Invasive Bladder Cancer Patients Unresponsive to Bacillus Calmette-Guérin, With or Without Papillary Tumors.

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    2018-03-20

    Bladder Cancer; Bladder Neoplasm; Bladder Tumors; Cancer of Bladder; Cancer of the Bladder; Malignant Tumor of Urinary Bladder; Neoplasms, Bladder; Urinary Bladder Cancer; Carcinoma in Situ of Bladder; Papillary Carcinoma of Bladder (Diagnosis); BCG-Unresponsive Bladder Cancer

  8. Interferon alfa in the treatment paradigm for non-muscle-invasive bladder cancer

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    Lamm, D.; Brausi, M.; O'Donnell, M.A.; Witjes, J.A.

    2014-01-01

    OBJECTIVES: In this article, we review the various options for and the potential role of interferon alfa (IFN-alpha) in the treatment of non-muscle-invasive bladder cancer (NMIBC). METHODS: PubMed was searched for journal articles on IFN-alpha use in treating bladder cancer. The references listed in

  9. Predictive Factors for Time to Progression after Hyperthermic Mitomycin C Treatment for High-Risk Non-Muscle Invasive Urothelial Carcinoma of the Bladder: An Observational Cohort Study of 97 Patients.

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    Sooriakumaran, Prasanna; Chiocchia, Virginia; Dutton, Susan; Pai, Aakash; Ayres, Benjamin E; Le Roux, Pieter; Swinn, Michael; Bailey, Michael; Perry, Matthew J A; Issa, Rami

    2016-01-01

    Hyperthermic mitomycin (HM) is a novel treatment modality for selected patients with high-risk non-muscle invasive bladder cancer (NMIBC). We sought to determine predictors of response to this therapy. A longitudinal, cohort study of 97 patients with high-risk NMIBC treated with ≥4 HM instillations on a prophylactic schedule was conducted. The primary outcome was time-to-progression survival; secondary outcomes were overall survival, cancer-specific survival, and adverse events. Descriptive statistics, Kaplan-Meier survival analyses, Cox proportional hazards modelling, and univariate and multivariable regression were performed. The presence of initial complete response (CR; no evidence of disease at first check video-cystoscopy and urine cytology) post-HM treatment was an independent predictor of good response to HM. Female patients and those without carcinoma in situ (CIS) also appeared to respond better to the intervention. The overall bladder preservation rate at a median of 27 months was 81.4%; 17/97 (17.5%) patients died during the course of the study. High-risk NMIBC patients can be safely treated with HM and have good oncological outcome. However, those without an initial CR have a poor prognosis and should be counselled towards adopting other treatment methodologies such as cystectomy. Female gender and lack of CIS may be good prognostic indicators for response to HM. © 2015 S. Karger AG, Basel.

  10. Transurethral en bloc resection with bipolar button electrode for non-muscle invasive bladder cancer.

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    Zhang, Junfeng; Wang, Longsheng; Mao, Shiyu; Liu, Mengnan; Zhang, Wentao; Zhang, Ziwei; Guo, Yadong; Huang, Bisheng; Yan, Yang; Huang, Yong; Yao, Xudong

    2018-04-01

    Transurethral resection of bladder tumor (TURBT) using a wire loop is considered the gold standard for staging and treating non-muscle invasive bladder cancer (NMIBC). TURBT is associated with serious disadvantages that facilitate tumor recurrence. The present study evaluated the safety and efficacy of the bipolar button electrode for en bloc resection of NMIBC. From January 2013 to July 2016, 82 consecutive patients newly diagnosed with NMIBC received transurethral en bloc resection with bipolar button electrode. Operative details, pathological result, and intraoperative and postoperative complications regarded as safety outcomes were documented. Each patient was followed up for ≥ 18 months. A total of 118 neoplasms were removed en bloc from 82 patients. The mean tumor diameter was 2.42 ± 1.34 cm. The average operation time was 35 ± 14 min. No complications such as bladder bleeding, vesicle perforation, and obturator nerve reflex occurred during the treatment. Pathological evaluations showed urothelial carcinoma with stage Ta low grade in 26 patients, T1 high grade in 51 patients, and T2 high grade in 5 patients. In addition, the bladder detrusor muscle layer was provided in all cases. The 18-month recurrence-free survival was 88.5% (23/26) and 74.5% (38/51) for Ta and T1 patients, respectively. The current results demonstrated that transurethral en bloc resection with bipolar button electrode is an effective, feasible, and safe treatment for NMIBC.

  11. Treatment Options Available for Bacillus Calmette-Guerin Failure in Non-muscle-invasive Bladder Cancer

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    Yates, D.R.; Brausi, M.A.; Catto, J.W.; Dalbagni, G.; Roupret, M.; Shariat, S.F.; Sylvester, R.J.; Witjes, J.A.; Zlotta, A.R.; Palou-Redorta, J.

    2012-01-01

    CONTEXT: Intravesical bacillus Calmette-Guerin (BCG) is a standard conservative treatment for patients with high-risk non-muscle-invasive bladder cancer (NMIBC). Many patients will experience recurrence or progression following BCG and are termed BCG failures. OBJECTIVE: To summarise the current

  12. BCG-unresponsive non-muscle-invasive bladder cancer: recommendations from the IBCG

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    Kamat, A.M.; Colombel, M.; Sundi, D.; Lamm, D.; Boehle, A.; Brausi, M.; Buckley, R.; Persad, R.; Palou, J.; Soloway, M.; Witjes, J.A.

    2017-01-01

    Intravesical immunotherapy with live attenuated BCG remains the standard of care for patients with high-risk and intermediate-risk non-muscle-invasive bladder cancer (NMIBC). Most patients initially respond, but recurrence is frequent and progression to invasive cancer is a concern. No established

  13. Fluorescence cystoscopy in patients with non-muscle invasive bladder cancer

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    I. G. Rusakov

    2015-01-01

    Full Text Available The main challenge of treating non-muscle invasive bladder cancer is multifocal tumors. Current methods of diagnosis are failed to detect all superficial flat tumor lesions in bladder mucosa. The use of fluorescence imaging with 5-aminolevulinic acid (5-ALA allows to improve the sensibility of routine cystoscopy, but low specificity decreases its diagnostic accuracy. The method of fluorescence imaging combined with local fluorescence spectroscopy developed in P.A. Herzen MCRI has been shown to increase the specificity from 71% to 84%. Thus, local fluorescence spectroscopy in visible fluorescence of 5-ALA-induced protoporphyrin allows to perform guided biopsy and decrease the rate of diagnostic mistakes. 

  14. INITIAL EXPERIENCE WITH ADJUVANT INTRAVESICAL THERMOCHEMOTHERAPY FOR NON-MUSCLE INVASIVE BLADDER CANCER

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    K. A. Pavlenko

    2011-01-01

    Full Text Available Objective: to reveal the benefits of adjuvant intravesical thermochemotherapy (TCT and to evaluate its efficiency in the treatment of moderateand high-risk non-muscle invasive bladder cancer (BC.Subjects and methods. In the period 2009 to 2010, the Urology Clinic, Federal Medical Biophysical Center, treated 21 patients with nonmuscle invasive BC, by using a Thermotron RF-8 clinical hyperthermal system. Intravesical TCT with mitomycin C 40 mg for 60–80 min was performed at 42 ± 2 °С as one session weekly for 6 weeks. Control cystoscopy was carried out every 3 months.Results. Of the 21 patients, 19 were found to tolerate the procedure well. No complications were recorded in these patients during the sessions and throughout the course of intravesical TCT. A recurrence was histologically verified in 2 patients at 6-month follow-up. There was no evidence suggesting a recurrence in 12 (57.14 % patients at one-year follow-up. The follow-up of the other patients is now less than 12 months.Conclusion. The proposed method of hyperthermia may be used as an alternative to the existing one of intracavitary hyperthermia to treat high- and moderate-risk BC and in case of inefficiency of other adjuvant therapy options for non-muscle invasive BC.

  15. Molecular markers increase precision of the European Association of Urology non-muscle invasive bladder cancer progression risk groups

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    Van Kessel, Kim E.; van der Keur, Kirstin A.; Dyrskjøt, Lars

    2018-01-01

    PURPOSE: The European Association of Urology (EAU) guidelines for non-muscle invasive bladder cancer (NMIBC) recommend risk stratification based on clinicopathological parameters. Our aim was to investigate the added value of biomarkers to improve risk stratification of NMIBC. EXPERIMENTAL DESIGN...

  16. Defining Priorities to Improve Patient Experience in Non-Muscle Invasive Bladder Cancer.

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    Garg, Tullika; Connors, Jill Nault; Ladd, Ilene G; Bogaczyk, Tyler L; Larson, Sharon L

    2018-01-20

    Although approximately 75% of bladder cancers are non-muscle invasive (NMIBC) at diagnosis, most research tends to focus on invasive disease (e.g., experiences related to radical cystectomy and urinary diversion). There is a lack of studies on quality of life, and especially qualitative research, in bladder cancer generally. As a result, relatively little is known about the experiences and needs of NMIBC patients. To understand patient experience, define care priorities, and identify targets for care improvement in NMIBC across the cancer continuum. Through focus groups, patients treated for NMIBC (stage influences on decision-making, and role of social support. Patients with NMIBC desired timely access to care and honest and caring provider communication. They described urinary function and emotional quality of life changes resulting from diagnosis and treatment. Avoiding cystectomy and being alive for family were the major decision influencers. In this qualitative study, we identified access to care, provider characteristics and communication, quality of life, values/influences on decision-making, and social support as priority areas to improve patient experience in NMIBC. Care redesign efforts should focus on improving access, enhancing provider communication, reducing side effects, and supporting caregiver roles.

  17. Managing Patients with Non-Muscle Invasive Bladder Cancer: Old Disease, New Ideas

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    Per-Uno Malmström

    2016-04-01

    Full Text Available Prof Per-Uno Malmström opened this symposium on non-muscle invasive bladder cancer (NMIBC by describing the medical and economic burden caused by the increasing incidence of bladder cancer and the lack of new therapeutic options available to address the challenges of the management of NMIBC. Prof Marko Babjuk followed with a presentation that demonstrated that risk stratification using European Organisation for Research and Treatment of Cancer (EORTC and Spanish Urological Club for Oncological Treatment (CUETO risk scores remains a useful tool for determining the best individual treatment options for patients. The next presentation, given by Dr Carsten Ohlmann, described the use of mitomycin C (MMC for low and intermediate-risk patients as per the European Association of Urology (EAU guidelines. However, despite a favourable safety profile, single case reports of severe adverse events following treatment with MMC should not be dismissed. MMC should therefore be given with care, with an emphasis on performing high quality transurethral resection of the bladder (TURB. Prof Bernard Malavaud then presented details of newer diagnostic methods, such as photodynamic diagnosis (PDD and narrow band imaging (NBI, which offer better optical tumour recognition for the surgeon than the old standard of white light cystoscopy. The uptake of PDD and NBI in the future will facilitate an increase in the quality of TURB. Finally, Prof Ashish Kamat explained that recurrence of bladder cancer after bacillus Calmette–Guérin (BCG treatment (‘BCG failure’ needs to be more clearly defined and stratified. He stated that optimal recognition of timing with relation to BCG immunotherapy is critical to determine the next steps. For example, in the past, patients with late recurrence who may have benefitted from challenge with BCG may have been overlooked.

  18. Reduction of recurrence in non-muscle invasive bladder cancer using photodynamic diagnosis and immediate post-TUR-B chemoprophylaxis

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    Risager, Malene Bøg

    2013-01-01

    Reduction of recurrence in non-muscle invasive bladder cancer using photodynamic diagnosis and immediate post-TUR-B chemoprophylaxis. Risager, Malene Bøg; Nielsen, Tommy Kjærsgaard; Ebbensgaard, Nanna Andersen; Zieger, Karsten. Department of Urology, Randers Regional Hospital, Randers, Denmark....... Background: Recurrences after non-muscle invasive bladder cancer (NMIBC) are common and a major burden for health care systems. Fluorescence-guided resection/ photodynamic diagnosis and immediate post-TUR-B chemoprophylaxis can improve recurrence free survival, but the further outcome and cost......-effectiveness of these interventions are a matter of current debate. This single-institution case-control study investigated these issues under routine conditions. Materials and Methods: Photodynamic diagnosis (PDD) using intravesical instillation of 85 mg hexaminolevulinate one hour before transurethral resection of bladder tumor...

  19. Quantitative genome-wide methylation analysis of high-grade non-muscle invasive bladder cancer.

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    Kitchen, Mark O; Bryan, Richard T; Emes, Richard D; Glossop, John R; Luscombe, Christopher; Cheng, K K; Zeegers, Maurice P; James, Nicholas D; Devall, Adam J; Mein, Charles A; Gommersall, Lyndon; Fryer, Anthony A; Farrell, William E

    2016-03-03

    High-grade non-muscle invasive bladder cancer (HG-NMIBC) is a clinically unpredictable disease with greater risks of recurrence and progression relative to their low-intermediate-grade counterparts. The molecular events, including those affecting the epigenome, that characterize this disease entity in the context of tumor development, recurrence, and progression, are incompletely understood. We therefore interrogated genome-wide DNA methylation using HumanMethylation450 BeadChip arrays in 21 primary HG-NMIBC tumors relative to normal bladder controls. Using strict inclusion-exclusion criteria we identified 1,057 hypermethylated CpGs within gene promoter-associated CpG islands, representing 256 genes. We validated the array data by bisulphite pyrosequencing and examined 25 array-identified candidate genes in an independent cohort of 30 HG-NMIBC and 18 low-intermediate-grade NMIBC. These analyses revealed significantly higher methylation frequencies in high-grade tumors relative to low-intermediate-grade tumors for the ATP5G2, IRX1 and VAX2 genes (P<0.05), and similarly significant increases in mean levels of methylation in high-grade tumors for the ATP5G2, VAX2, INSRR, PRDM14, VSX1, TFAP2b, PRRX1, and HIST1H4F genes (P<0.05). Although inappropriate promoter methylation was not invariantly associated with reduced transcript expression, a significant association was apparent for the ARHGEF4, PON3, STAT5a, and VAX2 gene transcripts (P<0.05). Herein, we present the first genome-wide DNA methylation analysis in a unique HG-NMIBC cohort, showing extensive and discrete methylation changes relative to normal bladder and low-intermediate-grade tumors. The genes we identified hold significant potential as targets for novel therapeutic intervention either alone, or in combination, with more conventional therapeutic options in the treatment of this clinically unpredictable disease.

  20. Guideline-based management of non-muscle invasive bladder cancer

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    Justin R Gregg

    2015-01-01

    Full Text Available Introduction: Non-muscle invasive bladder cancer (NMIBC represents a broad spectrum of disease, the hallmarks of which include disease recurrence and progression. Clinicians have a number of surgical and therapeutic options at their disposal when treating this disease, and the underlying evidence continues to evolve. A number of professional organizations have invested in the development of clinical practice guidelines to guide patient management. Materials and Methods: We review and summarize four major guidelines, the American Urological Association, the European Association of Urology, the International Consultation on Urological Disease and the National Comprehensive Cancer Network. Results: Guideline panels differed in their composition, methodological approach and structure of recommendations. Despite this, many recommendations were similar between various panels, although differences are present in panel recommendations related to initial diagnosis and treatment, adjuvant therapy and disease surveillance. Conclusions: Guideline recommendations are similar at many decision points that clinicians face when managing NMIBC, although they are far from uniform. While future prospective, well-designed studies will hopefully clarify NMIBC management, urologists ultimately must rely on a combination of evidence-based recommendations, which they should seek to integrate with patients' values and preferences and the individual circumstances to provide the best possible patient care.

  1. Prognostic factors in non-muscle-invasive bladder tumors - I. Clinical prognostic factors: A review of the experience of the EORTC genito-urinary group - II. Biologic prognostic markers

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    Kurth, Karl-Heinz; Sylvester, Richard J.

    2007-01-01

    Objectives: To summarize the most important clinical prognostic factors of non-muscle-invasive bladder cancer, as assessed by the European organization for Research and Treatment of Cancer (EORTC) Genito-Urinary Group, to present biologic markers involved in urothelial cell carcinoma, and to address

  2. Snail immunohistochemical overexpression correlates to recurrence risk in non-muscle invasive bladder cancer: results from a longitudinal cohort study.

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    Santi, Raffaella; Cai, Tommaso; Nobili, Stefania; Galli, Ilaria Camilla; Amorosi, Andrea; Comperat, Eva; Nesi, Gabriella

    2018-03-10

    The current WHO/ISUP classification and grading system subdivides urothelial tumours into prognostically distinct categories. Understanding the molecular pathways involved in bladder cancer development can improve patient stratification and management. This study aims to investigate the relationship between Snail, Slug and E-cadherin expressions and clinico-pathological features of non-muscle invasive bladder carcinoma (NMIBC). All patients attending the same urological centre from January to May 2002, who were pathologically diagnosed with NMIBC, were enrolled in this longitudinal cohort study. E-cadherin, Snail and Slug protein expressions were assessed by immunohistochemical analysis and compared with follow-up data. The main outcome measures were recurrence and progression rates. The cohort under investigation included 43 patients (38 men and 5 women, mean age 67.7 ± 10.6 years). High-grade (HG) carcinomas were 20/43, with 10 invasive cases (pT1). Low-grade (LG) carcinomas were 23/43, with no invasive cases (pTa). Among the eight HGpTa cases with recurrence, strong Snail expression was detected in six (75%). Out of the 17 LGpTa patients who experienced recurrence, 12 (70.6%) showed strong positivity for Snail. Among the 10 HGpT1 cases, recurrence was observed in 4, of which, 3 (75%) stained intensely for Snail. The Kaplan-Meier curves showed significantly different recurrence rates for patients with strong or weak Snail reactivity (p = 0.027). E-cadherin and Slug expression did not correlate with any of the parameters considered. On multivariate analysis, Snail expression was recognised as an independent prognostic factor for tumour recurrence (p = 0.003). In our study population, Snail immunohistochemical overexpression proved to be related to tumour recurrence in patients affected by NMIBC.

  3. Non-muscle invasive bladder cancer: Are epicrises the ‘Bermuda Triangle’ of information transfer?

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    May, Matthias; Wick, Anne-Kathrin; Roiner, Michael; Mathew, Marcella; Gilfrich, Christian; Schostak, Martin

    2017-01-01

    Introduction The aim of the study was to collect information regarding the quality of communication of risk-determining factors or risk profile, and the guideline conformity of recommendations for adjuvant treatment in patients with non-muscle invasive bladder cancer (NMIBC) between clinical and ambulatory urologists. Material and methods At three German urological clinics during the period between 2012-2014, epicrises of 1,033 NMIBC-patients were retrospectively summarised to 505 tumour episodes (tumour resection including any re-resections) and analysed regarding the endpoints 1) risk profile is explicitly named or recorded risk factors are sufficient for the determination of risk profile, and 2) guideline conformity of treatment recommendation. Independent factors influencing the endpoints were determined by means of multivariate logistic regression models. Results The risk profile was explicitly named for 3.6% of tumour episodes; for 68.9% a risk profile could be derived from the information in the epicrises. Treatment recommendations were given for 93.7% of tumour episodes, but only 17.8% were guideline compliant. 42.6% of the recommendations were not reliably effective; 33.1% and 0.2% resulted in under- and overtreatment respectively. Neither endpoint showed gender specific or regional differences, but both were considerably less likely to be achieved in case of recurrence. Conclusions The discrepancy between treatment recommendation (93.7%) and guideline compliance (17.8%) could indicate a lack of familiarity with guidelines. The quality of the epicrises of NMIBC-patients was poor and bore the potential risk of undertreatment. The results of this study are not necessarily applicable to other clinics, but could, however, prompt physicians to re-examine epicrises for the fulfillment of the quality criteria examined here. PMID:29104786

  4. Non-muscle invasive bladder cancer: Are epicrises the 'Bermuda Triangle' of information transfer?

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    Lebentrau, Steffen; May, Matthias; Wick, Anne-Kathrin; Roiner, Michael; Mathew, Marcella; Gilfrich, Christian; Schostak, Martin

    2017-01-01

    The aim of the study was to collect information regarding the quality of communication of risk-determining factors or risk profile, and the guideline conformity of recommendations for adjuvant treatment in patients with non-muscle invasive bladder cancer (NMIBC) between clinical and ambulatory urologists. At three German urological clinics during the period between 2012-2014, epicrises of 1,033 NMIBC-patients were retrospectively summarised to 505 tumour episodes (tumour resection including any re-resections) and analysed regarding the endpoints 1) risk profile is explicitly named or recorded risk factors are sufficient for the determination of risk profile, and 2) guideline conformity of treatment recommendation. Independent factors influencing the endpoints were determined by means of multivariate logistic regression models. The risk profile was explicitly named for 3.6% of tumour episodes; for 68.9% a risk profile could be derived from the information in the epicrises. Treatment recommendations were given for 93.7% of tumour episodes, but only 17.8% were guideline compliant. 42.6% of the recommendations were not reliably effective; 33.1% and 0.2% resulted in under- and overtreatment respectively. Neither endpoint showed gender specific or regional differences, but both were considerably less likely to be achieved in case of recurrence. The discrepancy between treatment recommendation (93.7%) and guideline compliance (17.8%) could indicate a lack of familiarity with guidelines. The quality of the epicrises of NMIBC-patients was poor and bore the potential risk of undertreatment. The results of this study are not necessarily applicable to other clinics, but could, however, prompt physicians to re-examine epicrises for the fulfillment of the quality criteria examined here.

  5. [Clinical Benefits of Transurethral Resection Under Narrow Band Imaging for Non-Muscle Invasive Bladder Cancer].

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    Mita, Koji; Kobatake, Kohei; Ohara, Shinya; Kato, Masao

    2018-01-01

    The aim of this study was to reveal the clinical benefits of transurethral resection (TUR) under narrow band imaging (NBI-TUR) for non-muscle-invasive bladder cancer (NMIBC) compared with conventional white light imaging TUR (WLI-TUR). The subjects were 172 patients with NMIBC who were followed for more than 1 year after undergoing TUR with no additional postoperative treatment. In the WLI-TUR group (n=101), lesions that were detected as positive after systematic intravesical observation under WLI were resected completely under WLI. In the NBI-TUR group (n=71), similar observations under WLI were followed by systematic intravesical observation under NBI. After multiple site biopsy under NBI, TUR was performed for all lesions that were detected as positive under NBI. The sensitivity was calculated based on the results of cystoscopy and pathology of multiple site biopsy samples under WLI and NBI in the NBITUR group. The tumor recurrence rate was analyzed in both groups. Background factors did not differ significantly between the two groups, except for the observation period (63.3 months in the WLI-TUR group vs 42.0 months in the NBI-TUR group, p<0.01). The procedure under NBI had significantly higher sensitivity (94.6% vs 75.0%, p<0.01) compared with that under WLI. The recurrence-free rate in the NBITUR group was significantly higher than that in the WLI-TUR group (p=0.013). The tumor recurrencefree rate of NBI-TUR is higher than that of conventional WLI-TUR for patients with NMIBC.

  6. Advantage of transurethral resection with narrow band imaging for non-muscle invasive bladder cancer

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    KOBATAKE, KOHEI; MITA, KOJI; OHARA, SHINYA; KATO, MASAO

    2015-01-01

    The aim of the present study was to compare the benefits of transurethral resection (TUR) under narrow band imaging (NBI-TUR) and TUR under conventional white light imaging (WLI-TUR) for non-muscle invasive bladder cancer (NMIBC). The study cohort consisted of 135 patients with NMIBC who were followed up for ≥1 year after TUR and who received no additional post-operative treatment. In the WLI-TUR group (n=78), systematic intravesical observation under WLI was followed by a multiple site biopsy (MSB), after which lesions detected as positive findings were resected completely under WLI. In the NBI-TUR group (n=57), similar observation under WLI was followed by systematic intravesical observation under NBI. Following MSB under NBI, TUR was performed for all lesions detected as positive findings under NBI. The sensitivity, specificity, positive-predictive value, negative-predictive value (NPV) and accuracy in the NBI-TUR group were calculated using results from the cystoscopical and pathological examinations of MSB samples under WLI and NBI. The tumor recurrence rate was analyzed in the two groups. Background factors did not differ significantly between the two groups, with the exception of the observation period (31.0 vs. 15.0 months; P<0.01). The procedure under NBI exhibited significantly higher sensitivity (95.0 vs. 70.0%; P<0.01) and NPV (97.1 vs. 86.8%; P<0.01) compared with the procedure under WLI. The 1-year recurrence rate in the NBI-TUR group was significantly lower than that in the WLI-TUR group (21.1 vs. 39.7%; P=0.016). In conclusion, the present study indicated that NBI-TUR is more advantageous than conventional WLI-TUR for patients with NMIBC. PMID:26622632

  7. Reducing recurrence in non-muscle-invasive bladder cancer using photodynamic diagnosis and immediate post-transurethral resection of the bladder chemoprophylaxis

    DEFF Research Database (Denmark)

    Risager, Malene Bøg; Nielsen, Tommy Kjærgaard; Zieger, Karsten Egbert Arnold

    2015-01-01

    Abstract Objective. The aim of this study was to evaluate the effect of fluorescence cystoscopy and immediate post-transurethral resection of the bladder (TURB) chemoprophylaxis on the risk of recurrence of non-muscle-invasive bladder cancer (NMIBC) under routine clinical conditions. Materials...

  8. Definitions, End Points, and Clinical Trial Designs for Non-Muscle-Invasive Bladder Cancer: Recommendations From the International Bladder Cancer Group

    NARCIS (Netherlands)

    Kamat, A.M.; Sylvester, R.J.; Bohle, A.; Palou, J.; Lamm, D.L.; Brausi, M.; Soloway, M.; Persad, R.; Buckley, R.; Colombel, M.; Witjes, J.A.

    2016-01-01

    PURPOSE: To provide recommendations on appropriate clinical trial designs in non-muscle-invasive bladder cancer (NMIBC) based on current literature and expert consensus of the International Bladder Cancer Group. METHODS: We reviewed published trials, guidelines, meta-analyses, and reviews and

  9. A new tool for distinguishing muscle invasive and non-muscle invasive bladder cancer: the initial application of flexible ultrasound bronchoscope in bladder tumor staging.

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    Chuanliang Xu

    Full Text Available OBJECTIVES: To validate the flexible ultrasound bronchoscope (FUB as a tool in distinguishing muscle invasive and non-muscle invasive bladder tumors. MATERIALS AND METHODS: From June 2010 to April 2012, 62 patients (11 female and 51 male with 92 bladder urothelial carcinoma were treated in our study. The mean (±SD patient age was 64.0±12.5 years old (ranged from 22 to 87. Clinical T stage was assessed by FUB at first in operating room, then immediately initial diagnostic transurethral resection (TUR was performed. A second TUR would be done 2-4 weeks after initial TUR when the latter was incomplete (in large and multiple tumours, no muscle in the specimen or when an exophytic high-grade and/or T1 tumour was detected. And radical cystectomy would be performed for the patients who were diagnosed with muscle-invasive tumors. FUB staging and initial TUR staging, final pathological results were compared. RESULTS: In ultrasonic images, the normal muscle layer of bladder wall could be clearly distinguished into three layers, which were hyperechogenic mucosa, hypoechogenic muscle and hyperechogenic serosal. For non-muscle invasive tumors, the muscle layers were continuous. And distorted or discontinuous muscle layers could be seen in muscle-invasive case. The overall accuracy (95.7% and the specificity of muscle invasion detection of FUB (98.8% were comparable to TUR (overall accuracy 90.2% and specificity 100%, but sensitivity of muscle invasion detection of FUB was significantly higher than initial TUR (72.7%VS18.2%. Moreover, the tumor's diameter could not affect the FUB's accuracy of muscle invasion detection. For tumors near the bladder neck, FUB also showed the similar validity as those far from bladder neck. CONCLUSIONS: To conclude, the flexible ultrasound bronchoscope is an effective tool for muscle invasion detection of bladder tumor with ideal ultrasonic images. It is an alternative option for bladder tumor staging besides TUR. It might

  10. Prognostic Impact of a 12-gene Progression Score in Non-muscle-invasive Bladder Cancer: A Prospective Multicentre Validation Study.

    Science.gov (United States)

    Dyrskjøt, Lars; Reinert, Thomas; Algaba, Ferran; Christensen, Emil; Nieboer, Daan; Hermann, Gregers G; Mogensen, Karin; Beukers, Willemien; Marquez, Mirari; Segersten, Ulrika; Høyer, Søren; Ulhøi, Benedicte P; Hartmann, Arndt; Stöhr, Robert; Wach, Sven; Nawroth, Roman; Schwamborn, Kristina; Tulic, Cane; Simic, Tatjana; Junker, Kerstin; Harving, Niels; Petersen, Astrid C; Jensen, Jørgen B; Keck, Bastian; Grimm, Marc-Oliver; Horstmann, Marcus; Maurer, Tobias; Steyerberg, Ewout W; Zwarthoff, Ellen C; Real, Francisco X; Malats, Núria; Malmström, Per-Uno; Ørntoft, Torben F

    2017-09-01

    Progression of non-muscle-invasive bladder cancer (NMIBC) to muscle-invasive bladder cancer (MIBC) is life-threatening and cannot be accurately predicted using clinical and pathological risk factors. Biomarkers for stratifying patients to treatment and surveillance are greatly needed. To validate a previously developed 12-gene progression score to predict progression to MIBC in a large, multicentre, prospective study. We enrolled 1224 patients in ten European centres between 2008 and 2012. A total of 750 patients (851 tumours) fulfilled the inclusion and sample quality criteria for testing. Patients were followed for an average of 28 mo (range 0-76). A 12-gene real-time qualitative polymerase chain reaction assay was performed for all tumours and progression scores were calculated using a predefined formula and cut-off values. We measured progression to MIBC using Cox regression analysis and log-rank tests for comparing survival distributions. The progression score was significantly (prisk score, and disease progression. Univariate Cox regression analysis showed that patients molecularly classified as high risk experienced more frequent disease progression (hazard ratio 5.08, 95% confidence interval 2.2-11.6; prisk factors (prisk factors, and may help in stratifying NMIBC patients to optimise treatment and follow-up regimens. Clinical use of a 12-gene molecular test for disease aggressiveness may help in stratifying patients with non-muscle-invasive bladder cancer to optimal treatment regimens. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  11. The 1973 WHO Classification is more suitable than the 2004 WHO Classification for predicting prognosis in non-muscle-invasive bladder cancer.

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    Zhongqing Chen

    Full Text Available BACKGROUND: Predicting the recurrence and progression of Non-muscle-invasive bladder cancer(NMIBC is critical for urologist. Histological grade provides significant prognostic information, especially for prediction of progression. Currently, the 1973 and the 2004 WHO classification co-exist. Which system is better for predicting rumor recurrence and progression still a matter for debate. METHODOLOGY/PRINCIPAL FINDINGS: 348 patients diagnosed with Non-muscle invasive bladder cancer were enrolled in our retrospective study. Paraffin sections were assessed by an experienced urological pathologist according to both the 1973 and 2004 WHO classifications. Tumor recurrence and progression was followed-up in all patients. During follow-up, corresponding 5-year recurrence-free survival rates of G1, G2 and G3 were 82.1%, 55.9%, 32.1% and the 5-year progression-free survival rates were 95.9%, 84.4% and 43.3%, respectively. The 5-year recurrence-free survival rates of papillary urothelial neoplasm of low malignant potential (PUNLMP, low-grade papillary urothelial carcinoma(LGPUC and high-grade papillary urothelial carcinoma (HGPUC were 69.8%, 67.1% and 42.0% respectively and the 5-year progression-free survival rates were 100%, 90.9% and 54.8% respectively. In multivariate analysis, the 1973 WHO classification significantly associated with both tumor recurrence and progression(p=0.010 and p=0.022, respectively; the 2004 WHO classification correlated with tumor progression(p=0.019, while was not proved to be a variable that can predict the risk of recurrence(p=0.547. Kaplan-Meier plots showed that both the 1973 WHO and the 2004 WHO classifications were significantly associated with progression-free survival (p<0.0001, log-rank test. For prediction of recurrence, significant differences were observed between the tumor grades classified using the 1973 WHO grading system (p<0.0001, log-rank test, while a significant overlap was observed between PUNLMP and LG

  12. Two-year follow-up of the phase II marker lesion study of intravesical apaziquone for patients with non-muscle invasive bladder cancer

    NARCIS (Netherlands)

    Hendricksen, Kees; van der Heijden, Antoine G.; Cornel, Erik B.; Vergunst, Henk; de Reijke, Theo M.; van Boven, Erika; Smits, Geert A. H. J.; Puri, Rajiv; Gruijs, Sigrid; Witjes, J. Alfred

    2009-01-01

    To study the time-to-recurrence and duration of response in non-muscle invasive bladder cancer (NMIBC) patients, with a complete ablative response after intravesical apaziquone instillations. Transurethral resection of bladder tumour(s) (TURBT) was performed in patients with multiple pTa-T1 G1-2

  13. Prognostic Performance and Reproducibility of the 1973 and 2004/2016 World Health Organization Grading Classification Systems in Non-muscle-invasive Bladder Cancer: A European Association of Urology Non-muscle Invasive Bladder Cancer Guidelines Panel Systematic Review.

    Science.gov (United States)

    Soukup, Viktor; Čapoun, Otakar; Cohen, Daniel; Hernández, Virginia; Babjuk, Marek; Burger, Max; Compérat, Eva; Gontero, Paolo; Lam, Thomas; MacLennan, Steven; Mostafid, A Hugh; Palou, Joan; van Rhijn, Bas W G; Rouprêt, Morgan; Shariat, Shahrokh F; Sylvester, Richard; Yuan, Yuhong; Zigeuner, Richard

    2017-11-01

    Tumour grade is an important prognostic indicator in non-muscle-invasive bladder cancer (NMIBC). Histopathological classifications are limited by interobserver variability (reproducibility), which may have prognostic implications. European Association of Urology NMIBC guidelines suggest concurrent use of both 1973 and 2004/2016 World Health Organization (WHO) classifications. To compare the prognostic performance and reproducibility of the 1973 and 2004/2016 WHO grading systems for NMIBC. A systematic literature search was undertaken incorporating Medline, Embase, and the Cochrane Library. Studies were critically appraised for risk of bias (QUIPS). For prognosis, the primary outcome was progression to muscle-invasive or metastatic disease. Secondary outcomes were disease recurrence, and overall and cancer-specific survival. For reproducibility, the primary outcome was interobserver variability between pathologists. Secondary outcome was intraobserver variability (repeatability) by the same pathologist. Of 3593 articles identified, 20 were included in the prognostic review; three were eligible for the reproducibility review. Increasing tumour grade in both classifications was associated with higher disease progression and recurrence rates. Progression rates in grade 1 patients were similar to those in low-grade patients; progression rates in grade 3 patients were higher than those in high-grade patients. Survival data were limited. Reproducibility of the 2004/2016 system was marginally better than that of the 1973 system. Two studies on repeatability showed conflicting results. Most studies had a moderate to high risk of bias. Current grading classifications in NMIBC are suboptimal. The 1973 system identifies more aggressive tumours. Intra- and interobserver variability was slightly less in the 2004/2016 classification. We could not confirm that the 2004/2016 classification outperforms the 1973 classification in prediction of recurrence and progression. This article

  14. Clinical significance of serum and urinary HER2/neu protein levels in primary non-muscle invasive bladder cancer

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    Ozgur Arikan

    2015-12-01

    Full Text Available Objective: We aimed to compare serum and urinary HER2/neu levels between healthy control group and patients with non-muscle invasive bladder cancer. Additionally, we evaluated relationship of HER2/neu levels with tumor stage, grade, recurrence and progression. Materials and Methods: Fourty-four patients with primary non-muscle invasive bladder tumors (Group 2 and 40 healthy control group (Group 1 were included the study. Blood and urinary samples were collected from all patients and HER2/neu levels were measured by ELISA method. Blood and urinary HER2/neu levels and additionally, ratio of urinary HER2/neu levels to urinary creatinine levels were recorded. Demographic data and tumor characteristics were recorded. Results: Mean serum HER2/neu levels were similar between two groups and statistically significant difference wasn't observed. Urinary HER2/neu levels were significantly higher in group 2 than group 1. Ratio of urinary HER2/neu to urinary creatinine was significantly higher in group 2 than group 1, (p=0,021. Serum and urinary HER2/ neu levels were not associated with tumor stage, grade, recurrence and progression while ratio of urinary HER2/neu to urinary creatinin levels were significantly higher in high-grade tumors. HER2/neu, the sensitivity of the test was found to be 20.5%, and the specificity was 97.5%, also for the urinary HER2/neu/urinary creatinine ratio, the sensitivity and specificity of the test were found to be 31.8% and 87.5%, respectively. Conclusions: Urinary HER2/neu and ratio of urinary creatinine urine were significantly higher in patients with bladder cancer compared to healthy subjects. Large series and controlled studies are needed for use as a tumor marker.

  15. Chronic kidney disease as a risk factor for recurrence and progression in patients with primary non-muscle-invasive bladder cancer.

    Science.gov (United States)

    Kobatake, Kohei; Hayashi, Tetsutaro; Black, Peter C; Goto, Keisuke; Sentani, Kazuhiro; Kaneko, Mayumi; Yasui, Wataru; Mita, Koji; Teishima, Jun; Matsubara, Akio

    2017-08-01

    To investigate the relationship between chronic kidney disease and primary non-muscle-invasive bladder cancer. Disease outcomes were analyzed in 418 patients treated with transurethral resection for primary non-muscle-invasive bladder cancer, and were correlated to traditional risk factors as well as chronic kidney disease stage according to estimated glomerular filtration rate: ≥60 (G1-2), 45-59 (G3a) or chronic kidney disease, respectively. T1 tumor was present in 29.6% of G1-2, 43.9% of G3a and 51.4% of G3b-5 chronic kidney disease (P = 0.004). The proportion of histological grade 3 non-muscle-invasive bladder cancer was higher in G3a and G3b-5 than G1-2 (P chronic kidney disease stage was associated with worse recurrence-free (P Chronic kidney disease stage was also strongly associated with the European Association of Urology bladder cancer risk groups (P Chronic kidney disease predicts the clinical outcome of primary non-muscle-invasive bladder cancer. Adding chronic kidney disease to the conventional risk factors might increase the accuracy of risk stratification. © 2017 The Japanese Urological Association.

  16. Analysis of molecular intra-patient variation and delineation of a prognostic 12-gene signature in non-muscle invasive bladder cancer; technology transfer from microarrays to PCR

    DEFF Research Database (Denmark)

    Andersen, Lars Dyrskjøt; Reinert, Thomas; Novoradovsky, A

    2012-01-01

    Background: Multiple clinical risk factors and genetic profiles have been demonstrated to predict progression of non-muscle invasive bladder cancer; however, no easily clinical applicable gene signature has been developed to predict disease progression independent of disease stage and grade. Meth...

  17. ROLE OF ADJUVANT INTRAVESICAL CHEMOTHERAPY IN THE COMBINED ORGAN-SPARING TREATMENT OF NON-MUSCLE-INVASIVE BLADDER CANCER

    Directory of Open Access Journals (Sweden)

    A. Yu. Zubko

    2014-01-01

    Full Text Available Objective: to enhance the efficiency of combined treatment for non-muscle-invasive bladder cancer ((NMIBC and to assess the results of its treatment using transurethral resection (TUR as monotherapy and in combination with intravesical adjuvant chemotherapy (CT.Subjects and methods. The results of treatment were analyzed in 59 patients with NMIBC. Twenty-two patients underwent TUR in Group 1; TUR and single intravesical injection of drugs were performed in 19 patients in Group 2; 18 patients had TUR and long-term intravesical CT.Results and discussion. The recurrence rates were 59.1, 57.9, and 38.89 % in Groups 1, 2, and 3, respectively. Intravesical CT was found to appreciably affect the prevention of recurrence in the area of resection. The rate of this recurrence was 31.81, 26.32, and 5.56 % in Groups 1, 2, and 3, respectively. Conclusion. Adjuvant intravesical chemotherapy CT is an effective method to prevent recurrent bladder cancer.

  18. Contemporary management of patients with high-risk non-muscle-invasive bladder cancer who fail intravesical BCG therapy.

    Science.gov (United States)

    Yates, D R; Rouprêt, M

    2011-08-01

    It is advocated that patients with high-risk non-muscle-invasive bladder cancer (NMIBC) receive an adjuvant course of intravesical Bacille Calmette-Guerin (BCG) as first-line treatment. However, a substantial proportion of patients will 'fail' BCG, either early with persistent (refractory) disease or recur late after a long disease-free interval (relapsing). Guideline recommendation in the 'refractory' setting is radical cystectomy, but there are situations when extirpative surgery is not feasible due to competing co-morbidity, a patient's desire for bladder preservation or reluctance to undergo surgery. In this review, we discuss the contemporary management of NMIBC in patients who have failed prior BCG and are not suitable for radical surgery and highlight the potential options available. These options can be categorised as immunotherapy, chemotherapy, device-assisted therapy and combination therapy. However, the current data are still inadequate to formulate definitive recommendations, and data from ongoing trials and maturing studies will give us an insight into whether there is a realistic efficacious second-line treatment for patients who fail intravesical BCG but are not candidates for definitive surgery.

  19. High-Risk Non-Muscle-Invasive Bladder Cancer-Therapy Options During Intravesical BCG Shortage.

    Science.gov (United States)

    Veeratterapillay, Rajan; Heer, Rakesh; Johnson, Mark I; Persad, Raj; Bach, Christian

    2016-09-01

    Bladder cancer is the second commonest urinary tract malignancy with 70-80 % being non-muscle invasive (NMIBC) at diagnosis. Patients with high-risk NMIBC (T1/Tis, with high grade/G3, or CIS) represent a challenging group as they are at greater risk of recurrence and progression. Intravesical Bacilli Calmette-Guerin (BCG) is commonly used as first line therapy in this patient group but there is a current worldwide shortage. BCG has been shown to reduce recurrence in high-risk NMIBC and is more effective that other intravesical agents including mitomycin C, epirubicin, interferon-alpha and gemcitabine. Primary cystectomy offers a high change of cure in this cohort (80-90 %) and is a more radical treatment option which patients need to be counselled carefully about. Bladder thermotherapy and electromotive drug administration with mitomycin C are alternative therapies with promising short-term results although long-term follow-up data are lacking.

  20. Genetic and immunologic determinants of intravesical BCG therapy in non-muscle-invasive urothelial bladder cancer

    Directory of Open Access Journals (Sweden)

    Wojciech Krajewski

    2014-03-01

    Full Text Available Bladder cancer (BCA is one of the most common cancers. In 2010 in Poland, 6296 people developed bladder cancer and 3110 people died of it. Immunotherapy with BCG (Bacillus Calmette-Guérin is by far the most effective adjuvant therapy. Noninfiltrating muscle membrane changes, that is, stages Ta, Tis and T1 qualify for BCG immunotherapy. BCG immunotherapy comprises series of bladder instillations, containing attenuated strain of Mycobacterium bovis. The effectiveness of immunotherapy in non-invasive bladder cancer is 70% 5-year survival without recurrence of the tumor. The treatment leads to a reduction of the residual tumor mass, but also to the delay and/or prevention of relapse, disease progression and ultimately death. Cytokines, as key mediators of immune response, play an important role in the pathogenesis of bladder cancer, which occurrence is stimulated by the inflammatory process. BCG immunotherapy provokes an intensive immunological response by the increase of cytokine production. Genetic variants determine inter-individual differences in the incidence of this cancer, as well as the response to the therapy. This is evidenced by the presence of differences in genetic variants of cytokines correlated with the varied risk of bladder cancer incidence. It is believed that concentrations of particular cytokines in urine after installation of BCG may indicate response to the therapy. Increased levels of Th1 cytokines – IFN-γ, IL-2 and TNF-α are correlated with longer survival time without recurrence, whereas high levels of Th2 cytokines such as IL-10, predict unsuccessful BCG therapy.

  1. A cocktail regimen of intravesical mitomycin-C, doxorubicin, and cisplatin (MDP) for non-muscle-invasive bladder cancer.

    Science.gov (United States)

    Chen, Chung-Hsin; Yang, Hung-Ju; Shun, Chia-Tung; Huang, Chao-Yuan; Huang, Kuo-How; Yu, Hong-Jeng; Pu, Yeong-Shiau

    2012-01-01

    To compare the efficacy and toxicity profiles of 3 intravesical regimens, including doxorubicin alone, bacillus Calmette-Guerin (BCG), and a cocktail regimen, in the prevention of bladder cancer recurrence. Two hundred ninety patients with newly diagnosed non-muscle-invasive bladder cancer treated with transurethral resection (TUR) between March 1996 and December 2004 were analyzed retrospectively. Each cycle of the cocktail regimen contained 30 mg each of sequential weekly intravesical mitomycin-C (MMC), doxorubicin, and cisplatin (MDP). Two cycles of MDP were given within the first 6 weeks of TUR, followed by 1 cycle each at 3, 6, and 12 months, and every 6 months until 36 months after a negative cystoscopy. Doxorubicin and BCG alone was given at similar time points as the MDP and BCG protocols. There were no demographic differences among the 3 groups. The median follow-up duration was 50 months. Dropout rates due to intolerance and/or poor compliance with the BCG, doxorubicin, and MDP protocols were 22.5%, 16.8%, and 11.0%, respectively. The MDP and BCG groups had similar bladder recurrence rates (37.9% vs. 33.9% at 5 years, respectively; P = 0.69). The doxorubicin group had significantly more recurrences than the BCG or MDP groups (HR = 1.9 (vs. BCG; P = 0.02) and 1.8 (vs. MDP; P = 0.01)). MDP was associated with less major adverse events than BCG (5.8% vs. 15.0%, respectively; P = 0.02). Compared with maintenance BCG, the MDP group had a similar recurrence rate but less side effects. Large randomized study is warranted to further determine the benefit of MDP adjuvant intravesical therapy. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Tumor associated macrophages polarization dictates the efficacy of BCG instillation in non-muscle invasive urothelial bladder cancer.

    Science.gov (United States)

    Suriano, Francesca; Santini, Daniele; Perrone, Giuseppe; Amato, Michela; Vincenzi, Bruno; Tonini, Giuseppe; Muda, Andrea; Boggia, Sara; Buscarini, Maurizio; Pantano, Francesco

    2013-11-05

    To evaluate the prognostic role of TAMs in patients affected by non-muscle invasive bladder cancer (NMIBC), undergone Trans Urethral Resection of Bladder (TURB) and Bacillus Calmette-Guerin (BCG) therapy. Data from 40 patients (36 men, 4 women), mean age 69 years (40-83 years), treated for NMIBC with TURB and BCG instillation were collected. Two different groups were considered: group with and group without bladder cancer recurrence. Correlations between immunofluorescence measured Mtot, M1 and M2 infiltration and clinicopathological parameters were evaluated using Spearman and Mann-Whitney methods. The recurrence-free survival rate was calculated using the Kaplan-Meier method. CD68 positive cells (Mtot) were observed in all specimens tested. High Mtot, M1 and M2 infiltration was observed in patients with disease recurrence, even before endovescical BCG instillation. Significant value for M2 infiltration (p = 0,042) was found calculating significativity between two group medians before BCG therapy. p = 0,072 and p = 0,180 were observed correlating median of Mtot and M1 between two groups of patients respectively. Values of p = 0,44, p = 0,23 and p = 0,64 from correlation between DFS and Mtot, M1 and M2 median in patients before endovescical BCG instillation, were calculated respectively. Comparing DFS and Mtot, M1 and M2 median in patients group after endovescical BCG instillation significant values were obtained (p = 0,020; p = 0,02; and p = 0,029 respectively). M2 tumor infiltration could be a prognostic value of recurrence in patients with NMIBC.

  3. Characterizing intermediate-risk non-muscle-invasive bladder cancer: Implications for the definition of intermediate risk and treatment strategy.

    Science.gov (United States)

    Matsumoto, Kazuhiro; Kikuchi, Eiji; Yanai, Yoshinori; Hayakawa, Nozomi; Ito, Yujiro; Maeda, Takahiro; Nagata, Hirohiko; Miyajima, Akira; Oya, Mototsugu

    2017-05-01

    Patients with intermediate-risk non-muscle-invasive bladder cancer have traditionally been defined as those not included in the low- or high-risk groups. Therefore, the intermediate-risk group consists of heterogeneous patients. We reviewed 326 patients diagnosed with intermediate-risk tumors. We subclassified these patients into 3 groups according to their clinical courses. Group A included patients with initial and multiple low-grade tumors (N = 170). Group B consisted of patients with a low-grade tumor that recurred after a low-risk tumor (N = 97), and Group C consisted of patients with a low-grade tumor that recurred after a high-risk tumor (N = 59). The 2-year recurrence-free survival rate was significantly lower in Group C (42%) than in Groups A (69%, Prisk tumors that recurred after a high-risk tumor (Group C) should be treated with adjuvant BCG therapy, owing to the high probability of subsequent recurrence. Furthermore, the definition of intermediate risk may include some BCG refractory cases. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Molecular Markers Increase Precision of the European Association of Urology Non-Muscle-Invasive Bladder Cancer Progression Risk Groups.

    Science.gov (United States)

    van Kessel, Kim E M; van der Keur, Kirstin A; Dyrskjøt, Lars; Algaba, Ferran; Welvaart, Naeromy Y C; Beukers, Willemien; Segersten, Ulrika; Keck, Bastian; Maurer, Tobias; Simic, Tatjana; Horstmann, Marcus; Grimm, Marc-Oliver; Hermann, Gregers G; Mogensen, Karin; Hartmann, Arndt; Harving, Niels; Petersen, Astrid C; Jensen, Jørgen B; Junker, Kerstin; Boormans, Joost L; Real, Francisco X; Malats, Núria; Malmström, Per-Uno; Ørntoft, Torben F; Zwarthoff, Ellen C

    2018-01-24

    Purpose: The European Association of Urology (EAU) guidelines for non-muscle-invasive bladder cancer (NMIBC) recommend risk stratification based on clinicopathologic parameters. Our aim was to investigate the added value of biomarkers to improve risk stratification of NMIBC. Experimental Design: We prospectively included 1,239 patients in follow-up for NMIBC in six European countries. Fresh-frozen tumor samples were analyzed for GATA2, TBX2, TBX3 , and ZIC4 methylation and FGFR3, TERT, PIK3CA , and RAS mutation status. Cox regression analyses identified markers that were significantly associated with progression to muscle-invasive disease. The progression incidence rate (PIR = rate of progression per 100 patient-years) was calculated for subgroups. Results: In our cohort, 276 patients had a low, 273 an intermediate, and 555 a high risk of tumor progression based on the EAU NMIBC guideline. Fifty-seven patients (4.6%) progressed to muscle-invasive disease. The limited number of progressors in this large cohort compared with older studies is likely due to improved treatment in the past two decades. Overall, wild-type FGFR3 and methylation of GATA2 and TBX3 were significantly associated with progression (HR = 0.34, 2.53, and 2.64, respectively). The PIR for EAU high-risk patients was 4.25. On the basis of FGFR3 mutation status and methylation of GATA2 , this cohort could be reclassified into a good class (PIR = 0.86, 26.2% of patients), a moderate class (PIR = 4.32, 49.7%), and a poor class (PIR = 7.66, 24.0%). Conclusions: We conclude that the addition of selected biomarkers to the EAU risk stratification increases its accuracy and identifies a subset of NMIBC patients with a very high risk of progression. Clin Cancer Res; 1-8. ©2018 AACR. ©2018 American Association for Cancer Research.

  5. Potential therapeutic strategies for non - muscle invasive bladder cancer based on association of intravesical immunotherapy with P-MAPA and systemic administration of cisplatin and doxorubicin

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    Queila Cristina Dias

    Full Text Available ABSTRACT The present study describes the histopathological and molecular effects of P-MAPA (Protein aggregate magnesium-ammonium phospholinoleate-palmitoleate anhydride intravesical immunotherapy combined with systemic doxorubicin or cisplatin for treatment of non-muscle invasive bladder cancer (NMIBC in an appropriate animal model. Our results showed an undifferentiated tumor, characterizing a tumor invading mucosa or submucosa of the bladder wall (pT1 and papillary carcinoma in situ (pTa in the Cancer group. The histopathological changes were similar between the combined treatment with intravesical P-MAPA plus systemic Cisplatin and P-MAPA immunotherapy alone, showing decrease of urothelial neoplastic lesions progression and histopathological recovery in 80% of the animals. The animals treated systemically with cisplatin or doxorubicin singly, showed 100% of malignant lesions in the urinary bladder. Furthemore, the combined treatment with P-MAPA and Doxorubicin showed no decrease of urothelial neoplastic lesions progression and histopathological recovery. Furthermore, Akt, PI3K, NF-kB and VEGF protein levels were significantly lower in intravesical P-MAPA plus systemic cisplatin and in intravesical P-MAPA alone treatments than other groups. In contrast, PTEN protein levels were significantly higher in intravesical P-MAPA plus systemic cisplatin and in intravesical P-MAPA alone treatments. Thus, it could be concluded that combination of intravesical P-MAPA immunotherapy and systemic cisplatin in the NMIBC animal model was effective, well tolerated and showed no apparent signs of antagonism between the drugs. In addition, intravesical P-MAPA immunotherapy may be considered as a valuable option for treatment of BCG unresponsive patients that unmet the criteria for early cystectomy.

  6. Clinical usefulness of random biopsies in diagnosis and treatment of non-muscle invasive bladder cancer: Systematic review and meta-analysis.

    Science.gov (United States)

    Subiela, J D; Palou, J; Esquinas, C; Fernández Gómez, J M; Rodríguez Faba, O

    2017-11-20

    This systematic review of the literature has been focused on determining the clinical usefulness of random bladder biopsies (RB) in the diagnosis of carcinoma in situ. A meta-analysis was performed to establish the clinic and pathological factors associated to positive biopsies. A systematic review was performed using Pubmed/Medline database according to the PRISMA guidelines. Thirty-seven articles were included, recruiting a total of 12,657 patients, 10,975 were submitted to RB. The overall incidence of positive RB was 21.91%. Significant differences were found in the incidence of positive RB when patients were stratified according to urine cytology result, tumor multiplicity, tumor appearance, stage and grade. The results of the meta-analysis revealed that the presence of positive cytology, tumor multiplicity, non-papillary appearance tumors, stage T1 and histological grades G2 and G3 represent the risk factors to predict abnormalities in RB. The incidence of positive RB in patients with non-muscle invasive bladder cancer was 21.91%. The maximum usefulness of RB was observed when these are performed in a standardized way. The results of the meta-analysis showed that besides positive cytology and non-papillary appearance tumors, tumor multiplicity and histological grades G2 and G3 represent risk factors associated to positive RB, suggesting that the use of RB might be extensive to the intermediate risk group of the European Organization for Research and Treatment of Cancer (EORTC). Copyright © 2017 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  7. Adverse reactions related to treatment compliance during BCG maintenance therapy for non-muscle-invasive bladder cancer.

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    Miyazaki, Jun; Hinotsu, Shiro; Ishizuka, Naoki; Naito, Seiji; Ozono, Seiichiro; Akaza, Hideyuki; Nishiyama, Hiroyuki

    2013-08-01

    The aim of the study was to investigate the factor of adverse reactions related to compliance with Mycobacterium bovis bacillus Calmette-Guérin maintenance therapy in patients with high-risk non-muscle-invasive bladder cancer. This study was a post hoc analysis using the database of a randomized controlled trial that examined the efficacy of bacillus Calmette-Guérin (Connaught strain) maintenance therapy. Among the 42 patients assigned to the bacillus Calmette-Guérin maintenance therapy group, six patients dropped out or withdrew consent before the bacillus Calmette-Guérin maintenance therapy. The adverse reactions and clinical backgrounds of the remaining 36 patients who underwent bacillus Calmette-Guérin maintenance therapy were compared between the two groups: the patients who completed the bacillus Calmette-Guérin maintenance therapy (the Completed group), and those who discontinued the bacillus Calmette-Guérin maintenance therapy (the Discontinued group). Of the 36 patients who underwent bacillus Calmette-Guérin maintenance therapy, 15 (41.7%) were in the Completed group and 21 (58.3%) were in the Discontinued group. Local adverse reactions (≥G2) were observed during maintenance therapy in 86.7% of the Completed group and 95.2% of the Discontinued group. As for adverse reactions during the induction therapy (bacillus Calmette-Guérin induction therapy), the frequencies of gross hematuria and systemic adverse reactions (any grade) tended to be higher in the Discontinued group than in the Completed group, although not significantly so. In the Cochran-Armitage trend test, the linear T trend (i.e. the trend in the risk of an increased rate of discontinuation according to gross hematuria and systemic adverse reactions with bacillus Calmette-Guérin induction therapy) was statistically significant (P = 0.0179). Most patients who completed bacillus Calmette-Guérin maintenance therapy experienced local adverse reactions (≥G2) during the maintenance

  8. Methylation status as a predictor of intravesical Bacillus Calmette-Guérin (BCG) immunotherapy response of high grade non-muscle invasive bladder tumor.

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    Husek, Petr; Pacovsky, Jaroslav; Chmelarova, Marcela; Podhola, Miroslav; Brodak, Milos

    2017-06-01

    Genetic and epigenetic alterations play an important role in urothelial cancer pathogenesis. Deeper understanding of these processes could help us achieve better diagnosis and management of this life-threatening disease. The aim of this research was to evaluate the methylation status of selected tumor suppressor genes for predicting BCG response in patients with high grade non-muscle-invasive bladder tumor (NMIBC). We retrospectively evaluated 82 patients with high grade non-muscle-invasive bladder tumor (stage Ta, T1, CIS) who had undergone BCG instillation therapy. We compared epigenetic methylation status in BCG-responsive and BCG-failure groups. We used the MS-MLPA (Methylation-Specific Multiplex Ligation-Dependent Probe Amplification probe sets ME001 and ME004. The control group was 13 specimens of normal urotel (bladder tissue)). Newly identified methylations in high grade NMIBC were found in MUS81a, NTRK1 and PCCA. The methylation status of CDKN2B (P=0.00312 ** ) and MUS81a (P=0.0191 * ) is associated with clinical outcomes of BCG instillation therapy response. CDKN2B and MUS81a unmethylation was found in BCG failure patients. The results show that the methylation status of selected tumor suppressor genes (TSGs) has the potential for predicting BCG response in patients with NMIBC high grade tumors. Tumor suppressor genes such as CDKN2b, MUS81a, PFM-1, MSH6 and THBS1 are very promising for future research.

  9. Construction of predictive models for recurrence and progression in >1000 patients with non-muscle-invasive bladder cancer (NMIBC) from a single centre.

    Science.gov (United States)

    Ali-El-Dein, Bedeir; Sooriakumaran, Prasanna; Trinh, Quoc-Dien; Barakat, Tamer S; Nabeeh, Adel; Ibrahiem, El-Housseiny I

    2013-06-01

    To construct predictive models based on the objectively calculated risks of progression and recurrence of non-muscle-invasive bladder cancer (NMIBC) in a large cohort of patients from a single centre. Between October 1984 and March 2009 a cohort of 1019 patients (877 males; 142 females; median age 44 years) with histologically confirmed NMIBC was included in this study. Among these patients, 74% received bacillus Calmette-Guérin (BCG)-based therapy. Complete transurethral resection of bladder tumour of all visible tumours was carried out in all patients, and the stage and grade were determined. Univariate analysis and multivariate Cox regression were used to identify predictors of recurrence and progression. The studied predictors included age, sex, stage, grade, associated carcinoma in situ, tumour size, multiplicity, macroscopic appearance of the tumour, history of recurrence and type of adjuvant intravesical therapy. Multivariate logistic regression models were used to develop the 12- and 60-month recurrence and progression predictive models. The predictive accuracy of the models was assessed for discrimination as well as calibration. The median (range) follow-up was 44 (6-254) months. On multivariate analysis, stage, multiplicity, history of recurrence and adjuvant intravesical therapy were significantly associated with recurrence, whereas for progression only tumour grade and size were significant independent predictors. The constructed nomograms had a 64.9% and 69.4% chance of correctly distinguishing between two patients, one destined to have a recurrence and one not at 12 and 60 months, respectively. The constructed nomograms had a 70.2% and 73.5% chance of correctly distinguishing between two patients, one destined to progress and one not at 12 and 60 months, respectively. All predictive models were well calibrated. Based on multivariate analysis of the studied prognostic factors nomograms for predicting recurrence and progression in NMIBC were

  10. Current clinical practice gaps in the treatment of intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC) with emphasis on the use of bacillus Calmette-Guerin (BCG): results of an international individual patient data survey (IPDS)

    NARCIS (Netherlands)

    Witjes, J.A.; Palou, J.; Soloway, M.; Lamm, D.; Kamat, A.M.; Brausi, M.; Persad, R.; Buckley, R.; Colombel, M.; Bohle, A.

    2013-01-01

    OBJECTIVES: To examine the management of intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC), particularly with regard to the use of bacillus Calmette-Guerin (BCG) therapy, in North America and Europe. To compare NMIBC management practices to European Association of Urology (EAU)

  11. An individual patient data meta-analysis of the long-term outcome of randomised studies comparing intravesical mitomycin C versus bacillus Calmette-Guerin for non-muscle-invasive bladder cancer.

    NARCIS (Netherlands)

    Malmstrom, P.U.; Sylvester, R.J.; Crawford, D.E.; Friedrich, M.; Krege, S.; Rintala, E.; Solsona, E.; Stasi, S.M. Di; Witjes, J.A.

    2009-01-01

    BACKGROUND: Patients with non-muscle-invasive bladder cancer with an intermediate or high risk need adjuvant intravesical therapy after surgery. Based largely on meta-analyses of previously published results, guidelines recommend using either bacillus Calmette-Guerin (BCG) or mitomycin C (MMC) in

  12. Prognostic factors and risk groups in T1G3 non-muscle-invasive bladder cancer patients initially treated with Bacillus Calmette-Guerin: results of a retrospective multicenter study of 2451 patients

    NARCIS (Netherlands)

    Gontero, P.; Sylvester, R.; Pisano, F.; Joniau, S.; Eeckt, K. Vander; Serretta, V.; Larre, S.; Stasi, S. Di; Rhijn, B. Van; Witjes, J.A.; Grotenhuis, A.J.; Kiemeney, L.A.L.M.; Colombo, R.; Briganti, A.; Babjuk, M.; Malmstrom, P.U.; Oderda, M.; Irani, J.; Malats, N.; Baniel, J.; Mano, R.; Cai, T.; Cha, E.K.; Ardelt, P.; Varkarakis, J.; Bartoletti, R.; Spahn, M.; Johansson, R.; Frea, B.; Soukup, V.; Xylinas, E.; Dalbagni, G.; Karnes, R.J.; Shariat, S.F.; Palou, J.

    2015-01-01

    BACKGROUND: The impact of prognostic factors in T1G3 non-muscle-invasive bladder cancer (BCa) patients is critical for proper treatment decision making. OBJECTIVE: To assess prognostic factors in patients who received bacillus Calmette-Guerin (BCG) as initial intravesical treatment of T1G3 tumors

  13. Copy Number Analysis of 24 Oncogenes: MDM4 Identified as a Putative Marker for Low Recurrence Risk in Non Muscle Invasive Bladder Cancer

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    Samanta Salvi

    2014-07-01

    Full Text Available Patients with non-muscle invasive bladder cancer (NMIBC generally have a high risk of relapsing locally after primary tumor resection. The search for new predictive markers of local recurrence thus represents an important goal for the management of this disease. We studied the copy number variations (CNVs of 24 oncogenes (MDM4, MYCN, ALK, PDGFRA, KIT, KDR, DHFR, EGFR, MET, SMO, FGFR1, MYC, ABL1, RET, CCND1, CCND2, CDK4, MDM2, AURKB, ERBB2, TOP2A, AURKA, AR and BRAF using multiplex ligation probe amplification technique to verify their role as predictive markers of recurrence. Formalin-fixed paraffin-embedded tissue samples from 43 patients who underwent transurethral resection of the bladder (TURB were used; 23 patients had relapsed and 20 were disease-free after 5 years. Amplification frequencies were analyzed for all genes and MDM4 was the only gene that showed significantly higher amplification in non recurrent patients than in recurrent ones (0.65 vs. 0.3; Fisher’s test p = 0.023. Recurrence-free survival analysis confirmed the predictive role of MDM4 (log-rank test p = 0.041. Our preliminary results indicate a putative role for the MDM4 gene in predicting local recurrence of bladder cancer. Confirmation of this hypothesis is needed in a larger cohort of NMIBC patients.

  14. Effects of programmed death-ligand 1 expression on OK-432 immunotherapy following transurethral resection in non-muscle invasive bladder cancer.

    Science.gov (United States)

    Liu, Zhi-Hua; Zheng, Fu-Fu; Mao, Yu-Ling; Ye, Lie-Fu; Bian, Jun; Lai, De-Hui; Ye, Yun-Lin; Dai, Yu-Ping

    2017-06-01

    The present study aimed to investigate the effect of the negative costimulatory molecule programmed death-ligand 1 (PD-L1) on immunotherapy with OK-432, following transurethral resection of bladder tumors in non-muscle invasive bladder cancer (NMIBC), and to elucidate the underlying mechanism. PD-L1 was detected by immunohistochemical staining in tumor specimens from 55 cases of NMIBC following postoperative immunotherapy with OK-432. The PD-L1 mRNA and protein expression levels were measured in the bladder cancer T24 cell line and the human uroepithelial SV-HUC-1 cell line, following treatment with interleukin (IL)-2, interferon (IFN)-α and IFN-γ, by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, respectively. PD-L1 was widely expressed in the NMIBC tumors, with 56.4% (31/55) of specimens exhibiting positive staining. When compared with PD-L1-negative patients, PD-L1-positive patients exhibited significantly increased recurrence [48.4% (15/31) vs. 16.7% (4/24)] and progression [16.1% (5/31) vs. 4.2% (1/24)] rates (POK-432 intravesical immunotherapy in patients with NMIBC. The results indicated that the involved mechanism occurred via upregulation of PD-L1 by immune cytokines, which in turn suppressed the antitumor effectiveness of the immune system, thereby promoting tumor recurrence and progression.

  15. Improving Access to Adjuvant Intravesical Therapy for Non-Muscle Invasive Bladder Cancer in a Community Hospital.

    Science.gov (United States)

    Carvalho, Dorothy R

    2015-01-01

    Relative to the high incidence of bladder cancer in Connecticut, an analysis of practice patterns in treatment of early stage bladder cancer was undertaken in a 275-bed community hospital, to determine if the practice patterns mirrored National Comprehensive Cancer Network guidelines. A nurse-led performance improvement project followed. Subsequently change in bladder cancer recurrence rates related to change in practice patterns was assessed.

  16. UroVysion compared with cytology and quantitative cytology in the surveillance of non-muscle-invasive bladder cancer.

    NARCIS (Netherlands)

    Moonen, P.M.J.; Merkx, G.F.M.; Peelen, P.; Karthaus, H.F.M.; Smeets, D.F.C.M.; Witjes, J.A.

    2007-01-01

    OBJECTIVES: The multitarget fluorescence in situ hybridization probe set Vysis UroVysion, consisting of probes for chromosomes 3, 7, and 17 and for the 9p21 band, was studied to evaluate its value in the follow-up of patients with bladder cancer. The results were compared with conventional cytology

  17. The Moreau Strain of Bacillus Calmette-Guerin (BCG) for High-Risk Non-Muscle Invasive Bladder Cancer: An Alternative during Worldwide BCG Shortage?

    Science.gov (United States)

    Hofbauer, Sebastian L; Shariat, Shahrokh F; Chade, Daher C; Sarkis, Alvaro S; Ribeiro-Filho, Leopoldo A; Nahas, Willian C; Klatte, Tobias

    2016-01-01

    Bacillus Calmette-Guerin (BCG) is the standard of care for adjuvant intravesical instillation therapy for intermediate- and high-risk non-muscle invasive bladder cancer (NMIBC) after complete transurethral resection. Increasing evidence suggests that there are marked differences in outcomes according to BCG substrains. BCG-Moreau was recently introduced to the European market to cover the issue of BCG shortage, but there are little data regarding the oncologic efficacy. We retrospectively analyzed 295 consecutive patients, who received adjuvant intravesical instillation therapy with BCG-Moreau for intermediate- and high-risk NMIBC between October 2007 and April 2013 at a single institution. The end points of this study were time to first recurrence and progression to muscle-invasive disease. Median age was 66 years (interquartile range 59-74, mean 65.9 years). According to the EAU risk group, 76 patients presented with intermediate-risk and 219 patients with high-risk NMIBC. The 5-year recurrence-free survival and progression-free survival rate was 64.8% (95% CI 52.8-74.4) and 81.4% (95% CI 65.2-90.2), respectively. BCG-Moreau is an effective substrain for adjuvant instillation therapies of NMIBC, and outcomes appear to be comparable to series using other substrains. During worldwide shortage of BCG-TICE, Connaught and RIVM, BCG-Moreau may serve as an equally effective alternative. © 2015 S. Karger AG, Basel.

  18. Predictive Effect of Preoperative Anemia on Long-Term Survival Outcomes with Non-Muscle Invasive Bladder Cancer.

    Science.gov (United States)

    Celik, Orcun; Akand, Murat; Keskin, Mehmet Zeynel; Ekin, Rahmi Gokhan; Yoldas, Mehmet; Ilbey, Yusuf Ozlem

    2016-01-01

    Anemia is the most common hematologic abnormality in bladder cancer (BC) patients. We evaluated the impact of preoperative anemia on oncologic outcomes in BC undergoing transurethral resection of a bladder tumor (TURBT) for the first time diagnosis. We retrospectively evaluated the data collected from 639 patients who underwent TURBT between January 2006 and September 2014 in our department. Of these patients, 320 qualified for inclusion in the study. The primary efficacy endpoint was the effect of preoperative anemia status on cancer-specific and overall survival. Independent t-test and chi-square analyses were performed to assess the effects of anemia on oncologic outcomes. Survival was estimated by using the Kaplan-Meier test. There were 118 (36.9%) and 202 (63.1%) patients in the anemia (Group-1) and non-anemia groups (Group-2), respectively. The median follow-up duration was 68 months. Anemia was associated with decreased overall survival (anemia status of BC patients according to World Health Organization classification is associated with decreased overall survival, but not with cancer-specific survival. We think that preoperative hemoglobin levels should be considered in patient counseling and decision-making for additional therapy.

  19. Recommended oral sodium bicarbonate administration for urine alkalinization did not affect the concentration of mitomycin-C in non-muscle invasive bladder cancer patients.

    Science.gov (United States)

    Seo, Ho Kyung; Kim, Sung Han; Ahn, Kyung-Ohk; Lee, Sang-Jin; Park, Weon Seo; Kim, Sohee; Hwang, Sang-Hyun; Lee, Do Hoon; Joung, Jae Young; Chung, Jinsoo; Joo, Jungnam; Jeong, Kyung-Chae

    2017-11-10

    Sodium bicarbonate has been reported to maximize the efficacy of intravesical instillation of mitomycin-C (IVI-MMC) therapy by urine alkalinization in non-muscle-invasive bladder cancer (NMIBC). This study aimed to analyze the changes in MMC concentration according to urinary pH and evaluate the efficacy of sodium bicarbonate to maintain the concentration of active form of MMC during IVI-MMC. We prospectively enrolled 26 patients with NMIBC after transurethral resection of bladder tumor. Patients with very high-risk and low-risk NMIBC were excluded. Urinary creatinine, volume, pH, and concentrations of MMC and its degraded form were measured immediately before and after IVI-MMC. The patients were administered 1.5 g of oral sodium bicarbonate during the preceding evening, in the morning, and immediately before the fourth cycle of the six-cycle IVI-MMC. The correlation between MMC concentration and urinary pH changes was explored with or without oral bicarbonate therapy. Recurrence without progression to muscle-invasive disease was noted in 4 of 26 patients in a 23.7-month follow-up. The mean urinary pH before and after the therapy increased from 6.03 to 6.50, and 6.46 to 7.24, without or with oral SB therapy, respectively. Despite this increase, the concentration of active form of MMC did not change significantly. No correlation was found between urinary pH and MMC concentration. Urine alkalinization by SB administration did not maintain the high concentration of urinary MMC. Urine alkalinization by sodium bicarbonate administration for IVI-MMC did not maintain the high concentration of active urinary MMC in NMIBC.

  20. Effect of Age on Outcome of High-Risk Non-Muscle-Invasive Bladder Cancer Patients Treated with Second Transurethral Resection and Maintenance Bacillus Calmette-Guerin Therapy

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    Sümer Baltacı

    2016-09-01

    Full Text Available Objective To determine the effect of age on recurrence and progression rates in a population of high-risk non-muscle invasive bladder cancer (NMIBC patients treated with a second transurethral resection (TUR and at least 1 year of maintenance Bacillus Calmette-Guerin (BCG therapy. Materials and Methods In this multicenter study, we reviewed the data of patients treated for high-risk NMIBC between 2005 and 2012. Patients without a muscle-invasive cancer on second TUR and received induction BCG and at least one year of maintenance BCG therapy and at least 12 months of follow-up after completion of maintenance BCG were included. Effect of age was analyzed both dichotomously (<70 or ≥70 years as well as by 10-year increments. Chi-square test, Student’s T-test and analysis of variance (ANOVA were used for comparison of the groups. Univariate and multivariate logistic regression analyses were performed to identify predictors of recurrence and progression. Results Overall, 242 eligible patients were included. Baseline parameters were similar. With a mean follow-up of 29.4±22.2 months, neither 3-year recurrence-free survival nor 3-year progression-free survival differed between the age groups when examined either dichotomously or by 10-year increments. Conclusion In high-risk NMIBC patients treated with a second TUR and received maintenance BCG therapy, age was not associated with increased rates of neither recurrence nor progression. Until a randomized prospective clinical trial assess the appropriate adjuvant intravesical therapy in the elderly, elderly patients should probably be treated in the same manner as younger patients.

  1. Determining optimal maintenance schedules for adjuvant intravesical bacillus Calmette-Guerin immunotherapy in non-muscle-invasive bladder cancer: a systematic review and network meta-analysis.

    Science.gov (United States)

    Huang, Zixiong; Liu, Huixin; Wang, Yizeng; Zhang, Chunfang; Xu, Tao

    2017-08-01

    To figure out optimal bacillus Calmette-Guerin (BCG) maintenance schedules for non-muscle-invasive bladder cancer (NMIBC) patients by comparing different schedules in a systematic review using conventional and network meta-analysis. Literature was searched in the databases of Medline, Embase, Cochrane library, Clinicaltrials.gov, Wanfang, CNKI and SinoMed in April 2016 and 9 randomized clinical trials comparing intravesical BCG maintenance therapy with BCG induction-only therapy or comparing different BCG maintenance schedules (induction-only, 1 year, 1.5 year, 2 year, 3 year maintenance) in NMIBC patients were included. Conventional and network meta-analyses within a Bayesian framework were performed to calculate odds ratios of tumor recurrence, progression and side effects (cystitis, hematuria, general malaise and fever). The surface under the cumulative ranking curve (SUCRA) mean ranking was used to obtain schedule hierarchy. Data from 1951 patients showed that longer-term maintenance BCG therapy does not significantly decrease tumor recurrence and progression rate of NMIBC compared to shorter-term maintenance BCG therapy. However, longer-maintenance therapy does not increase side effect incidence compared to induction-only therapy. According to SUCRA results, induction-only therapy has the highest probability of recurrence and progression but least probability of side effects. Longer BCG maintenance therapy (such as 3 years) is not superior to shorter maintenance therapy (such as 1 year). But maintenance therapy overall is better than induction-only BCG therapy while not increasing side effects. Though further evidence and clinical practice with balanced confounding factors (risk stratification and BCG strain) are wished for, the current study suggests the common use of 1 year intravesical BCG instillation for NMIBC patients.

  2. HumanMethylation450K Array–Identified Biomarkers Predict Tumour Recurrence/Progression at Initial Diagnosis of High-risk Non-muscle Invasive Bladder Cancer

    Science.gov (United States)

    Kitchen, Mark O; Bryan, Richard T; Emes, Richard D; Luscombe, Christopher J; Cheng, KK; Zeegers, Maurice P; James, Nicholas D; Gommersall, Lyndon M; Fryer, Anthony A

    2018-01-01

    Background: High-risk non-muscle invasive bladder cancer (HR-NMIBC) is a clinically unpredictable disease. Despite clinical risk estimation tools, many patients are undertreated with intra-vesical therapies alone, whereas others may be over-treated with early radical surgery. Molecular biomarkers, particularly DNA methylation, have been reported as predictive of tumour/patient outcomes in numerous solid organ and haematologic malignancies; however, there are few reports in HR-NMIBC and none using genome-wide array assessment. We therefore sought to identify novel DNA methylation markers of HR-NMIBC clinical outcomes that might predict tumour behaviour at initial diagnosis and help guide patient management. Patients and methods: A total of 21 primary initial diagnosis HR-NMIBC tumours were analysed by Illumina HumanMethylation450 BeadChip arrays and subsequently bisulphite Pyrosequencing. In all, 7 had not recurred at 1 year after resection and 14 had recurred and/or progressed despite intra-vesical BCG. A further independent cohort of 32 HR-NMIBC tumours (17 no recurrence and 15 recurrence and/or progression despite BCG) were also assessed by bisulphite Pyrosequencing. Results: Array analyses identified 206 CpG loci that segregated non-recurrent HR-NMIBC tumours from clinically more aggressive recurrence/progression tumours. Hypermethylation of CpG cg11850659 and hypomethylation of CpG cg01149192 in combination predicted HR-NMIBC recurrence and/or progression within 1 year of diagnosis with 83% sensitivity, 79% specificity, and 83% positive and 79% negative predictive values. Conclusions: This is the first genome-wide DNA methylation analysis of a unique HR-NMIBC tumour cohort encompassing known 1-year clinical outcomes. Our analyses identified potential novel epigenetic markers that could help guide individual patient management in this clinically unpredictable disease. PMID:29343995

  3. HumanMethylation450K Array-Identified Biomarkers Predict Tumour Recurrence/Progression at Initial Diagnosis of High-risk Non-muscle Invasive Bladder Cancer.

    Science.gov (United States)

    Kitchen, Mark O; Bryan, Richard T; Emes, Richard D; Luscombe, Christopher J; Cheng, K K; Zeegers, Maurice P; James, Nicholas D; Gommersall, Lyndon M; Fryer, Anthony A

    2018-01-01

    High-risk non-muscle invasive bladder cancer (HR-NMIBC) is a clinically unpredictable disease. Despite clinical risk estimation tools, many patients are undertreated with intra-vesical therapies alone, whereas others may be over-treated with early radical surgery. Molecular biomarkers, particularly DNA methylation, have been reported as predictive of tumour/patient outcomes in numerous solid organ and haematologic malignancies; however, there are few reports in HR-NMIBC and none using genome-wide array assessment. We therefore sought to identify novel DNA methylation markers of HR-NMIBC clinical outcomes that might predict tumour behaviour at initial diagnosis and help guide patient management. A total of 21 primary initial diagnosis HR-NMIBC tumours were analysed by Illumina HumanMethylation450 BeadChip arrays and subsequently bisulphite Pyrosequencing. In all, 7 had not recurred at 1 year after resection and 14 had recurred and/or progressed despite intra-vesical BCG. A further independent cohort of 32 HR-NMIBC tumours (17 no recurrence and 15 recurrence and/or progression despite BCG) were also assessed by bisulphite Pyrosequencing. Array analyses identified 206 CpG loci that segregated non-recurrent HR-NMIBC tumours from clinically more aggressive recurrence/progression tumours. Hypermethylation of CpG cg11850659 and hypomethylation of CpG cg01149192 in combination predicted HR-NMIBC recurrence and/or progression within 1 year of diagnosis with 83% sensitivity, 79% specificity, and 83% positive and 79% negative predictive values. This is the first genome-wide DNA methylation analysis of a unique HR-NMIBC tumour cohort encompassing known 1-year clinical outcomes. Our analyses identified potential novel epigenetic markers that could help guide individual patient management in this clinically unpredictable disease.

  4. The application of adjuvant autologous antravesical macrophage cell therapy vs. BCG in non-muscle invasive bladder cancer: a multicenter, randomized trial

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    Kiss Tamas

    2010-06-01

    Full Text Available Abstract Introduction While adjuvant immunotherapy with Bacille Calmette Guérin (BCG is effective in non-muscle-invasive bladder cancer (BC, adverse events (AEs are considerable. Monocyte-derived activated killer cells (MAK are discussed as essential in antitumoural immunoresponse, but their application may imply risks. The present trial compared autologous intravesical macrophage cell therapy (BEXIDEM® to BCG in patients after transurethral resection (TURB of BC. Materials and methods This open-label trial included 137 eligible patients with TaG1-3, T1G1-2 plurifocal or unifocal tumours and ≥ 2 occurrences within 24 months and was conducted from June 2004 to March 2007. Median follow-up for patients without recurrence was 12 months. Patients were randomized to BCG or mononuclear cells collected by apheresis after ex vivo cell processing and activation (BEXIDEM. Either arm treatment consisted of 6 weekly instillations and 2 cycles of 3 weekly instillations at months 3 and 6. Toxicity profile (primary endpoint and prophylactic effects (secondary endpoint were assessed. Results Patient characteristics were evenly distributed. Of 73 treated with BCG and 64 with BEXIDEM, 85% vs. 45% experienced AEs and 26% vs. 14% serious AEs (SAE, respectively (p Discussion This initial report of autologous intravesical macrophage cell therapy in BC demonstrates BEXIDEM treatment to be safe. Recurrence rates were significantly lower with BCG however. As the efficacy of BEXIDEM remains uncertain, further data, e.g. marker lesions studies, are warranted. Trial registration The trial has been registered in the ISRCTN registry http://isrctn.org under the registration number ISRCTN35881130.

  5. Difference in recurrence frequencies of non-muscle-invasive-bladder tumors depending on optimal usage of intravesical immunotherapy of bacillus Calmette-Guérin

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    Milošević Radovan

    2015-01-01

    Full Text Available Background/Aim. The therapy with intravesical instillation of bacillus Calmette-Guérin (BCG after transurethral resection (TUR of the tumor is the gold standard of treatment of non-muscle invasive bladder cancer (NMIBC. The aim of this study was to compare the frequencies of reccurence between a group of patients submitted to TUR + BCG therapy (group I and a group of patients submitted only to TUR (group II. Methods. The patients with NMIBC, a total of 899, treated in our Institution from January 1, 2007 to March, 2013, were included in this study and divided into two groups: group I and group II. These two groups were divided into three subgroups: solitary first diagnosed tumor ≤ 3 cm (SFDGT, solitary first diagnosed tumor > 3 cm and multiple first diagnosed tumors (MFDGT, and recedive tumors (RCT. Statistical analysis was performed by using χ2-test and Kolmogorov-Smirnov test. Results: In the group I a total of 133 cases had reccurence contrary to 75 in the group II, making a statistically highly significant difference. Analysis of recurrences through the subgroups revealed: in the group I SFDGT recurrence occured in 27 of the cases vs 9 cases in the group II; in the group I MFDGT recurrence occured in 49 of the cases vs 31 in the group II (p < 0.001, and finally, in the group I RCT recurrence occured in 57 cases vs 35 cases in the group II (p < 0.001. Conclusion. The obtained results indicate no difference in the frequency of reccurence between the group I and group II regarding SFDGT, but a very high significant difference regarding those with MFDGT and RCT. These results should be taken into consideration in everyday clinical practise.

  6. HumanMethylation450K Array–Identified Biomarkers Predict Tumour Recurrence/Progression at Initial Diagnosis of High-risk Non-muscle Invasive Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Mark O Kitchen

    2018-01-01

    Full Text Available Background: High-risk non-muscle invasive bladder cancer (HR-NMIBC is a clinically unpredictable disease. Despite clinical risk estimation tools, many patients are undertreated with intra-vesical therapies alone, whereas others may be over-treated with early radical surgery. Molecular biomarkers, particularly DNA methylation, have been reported as predictive of tumour/patient outcomes in numerous solid organ and haematologic malignancies; however, there are few reports in HR-NMIBC and none using genome-wide array assessment. We therefore sought to identify novel DNA methylation markers of HR-NMIBC clinical outcomes that might predict tumour behaviour at initial diagnosis and help guide patient management. Patients and methods: A total of 21 primary initial diagnosis HR-NMIBC tumours were analysed by Illumina HumanMethylation450 BeadChip arrays and subsequently bisulphite Pyrosequencing. In all, 7 had not recurred at 1 year after resection and 14 had recurred and/or progressed despite intra-vesical BCG. A further independent cohort of 32 HR-NMIBC tumours (17 no recurrence and 15 recurrence and/or progression despite BCG were also assessed by bisulphite Pyrosequencing. Results: Array analyses identified 206 CpG loci that segregated non-recurrent HR-NMIBC tumours from clinically more aggressive recurrence/progression tumours. Hypermethylation of CpG cg11850659 and hypomethylation of CpG cg01149192 in combination predicted HR-NMIBC recurrence and/or progression within 1 year of diagnosis with 83% sensitivity, 79% specificity, and 83% positive and 79% negative predictive values. Conclusions: This is the first genome-wide DNA methylation analysis of a unique HR-NMIBC tumour cohort encompassing known 1-year clinical outcomes. Our analyses identified potential novel epigenetic markers that could help guide individual patient management in this clinically unpredictable disease.

  7. The efficacy of BCG TICE and BCG Connaught in a cohort of 2,099 patients with T1G3 non-muscle-invasive bladder cancer.

    Science.gov (United States)

    Witjes, J Alfred; Dalbagni, Guido; Karnes, Robert J; Shariat, Shahrokh; Joniau, Steven; Palou, Joan; Serretta, Vincenzo; Larré, Stéphane; di Stasi, Savino; Colombo, Renzo; Babjuk, Marek; Malmström, Per-Uno; Malats, Nuria; Irani, Jacques; Baniel, Jack; Cai, Tommaso; Cha, Eugene; Ardelt, Peter; Varkarakis, John; Bartoletti, Riccardo; Spahn, Martin; Pisano, Francesca; Gontero, Paolo; Sylvester, Richard

    2016-11-01

    Potential differences in efficacy of different bacillus Calmette-Guérin (BCG) strains are of importance for daily practice, especially in the era of BCG shortage. To retrospectively compare the outcome with BCG Connaught and BCG TICE in a large study cohort of pT1 high-grade non-muscle-invasive bladder cancer patients. Individual patient data were collected for 2,451 patients with primary T1G3 tumors from 23 centers who were treated with BCG for the first time between 1990 and 2011. Using Cox multivariable regression and adjusting for the most important prognostic factors in this nonrandomized comparison, BCG Connaught and TICE were compared for time to recurrence, progression, and the duration of cancer specific survival and overall survival. Information on the BCG strain was available for 2,099 patients: 957 on Connaught and 1,142 on TICE. Overall, 765 (36%) patients received some form of maintenance BCG, 560 (59%) on Connaught and 205 (18%) on TICE. Without maintenance, Connaught was more effective than TICE only for the time to first recurrence (hazard ratio [HR] = 1.48; 95% CI: 1.20-1.82; PBCG significantly reduced the risk of recurrence, progression and death, both overall, and disease specific, for TICE, but not for Connaught. We found that BCG Connaught results in a lower recurrence rate as compared with BCG TICE when no maintenance is used. However, the opposite is true when maintenance is given. As there is currently a BCG shortage, information on the efficacy of different BCG strains is important. In this nonrandomized retrospective comparison in over 2,000 patients, we found that BCG Connaught reduces the recurrence rate compared to BCG TICE when no maintenance is used, but the opposite is true when maintenance is given. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Predictive Value of NRAMP1 and HGPX1 Gene Polymorphism for Maintenance BCG Response in Non-muscle-invasive Bladder Cancer.

    Science.gov (United States)

    Lenormand, Claire; Couteau, Jérôme; Nouhaud, François-Xavier; Maillet, Géraldine; Bou, Jacqueline; Gobet, Françoise; Pfister, Christian

    2016-04-01

    To assess the potential predictive value of natural resistance-associated macrophage protein 1 (NRAMP1) and human glutathione peroxidase 1 (hGPX1) polymorphism in non-muscle-invasive bladder cancer treated with bacillus Calmette-Guerin (BCG) instillation, we conducted an original ancillary multicenter study. We evaluated patients included in the multicenter URO-BCG 4 trial, who received three weekly instillations of one-third dose BCG every 6 months (group I) or two weekly instillations every 3 months (group II) for 3 years. For clinical evaluation we also evaluated tumor recurrence and muscle progression. NRAMP1 and hGPX1 polymorphism analyses were performed on blood DNA. NRAMP1 exon 15 and hGPX1 exon 1c were amplified using Type-it Microsatellite PCR Kit® for multiplex polymerase chain reaction. From June 2004 to April 2010, 146 randomized patients were included in this retrospective study. Blood samples were obtained from 107 patients. With 36 months of follow-up, 13.6% of patients had a tumor recurrence and muscle-invasive progression was observed in 4.3% of patients. Concerning NRAMP1 D543N polymorphism, patients with allele A had no tumor recurrence or muscle-invasive progression. No significant difference was observed in gene polymorphism distribution between groups I and II. Moreover, we did not observe any significant association of gene polymorphisms, tumor recurrence or muscle-invasive progression, event time and disease-free survival. Our results suggest that no significant difference was found for NRAMP1 and hGPX1 gene polymorphisms associated with recurrence time, muscle invasion frequency and disease-free survival, nevertheless, we observed that the NRAMP1 D543N GG genotype group had a shorter time to tumor recurrence. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  9. An open label, single-arm, phase II multicenter study of the safety and efficacy of CG0070 oncolytic vector regimen in patients with BCG-unresponsive non-muscle-invasive bladder cancer: Interim results.

    Science.gov (United States)

    Packiam, Vignesh T; Lamm, Donald L; Barocas, Daniel A; Trainer, Andrew; Fand, Benjamin; Davis, Ronald L; Clark, William; Kroeger, Michael; Dumbadze, Igor; Chamie, Karim; Kader, A Karim; Curran, Dominic; Gutheil, John; Kuan, Arthur; Yeung, Alex W; Steinberg, Gary D

    2017-07-26

    CG0070 is a replication-competent oncolytic adenovirus that targets bladder tumor cells through their defective retinoblastoma pathway. Prior reports of intravesical CG0070 have shown promising activity in patients with high-grade non-muscle invasive bladder cancer (NMIBC) who previously did not respond to bacillus Calmette-Guérin (BCG). However, limited accrual has hindered analysis of efficacy, particularly for pathologic subsets. We evaluated interim results of a phase II trial for intravesical CG0070 in patients with BCG-unresponsive NMIBC who refused cystectomy. At interim analysis (April 2017), 45 patients with residual high-grade Ta, T1, or carcinoma-in-situ (CIS) ± Ta/T1 had evaluable 6-month follow-up in this phase II single-arm multicenter trial (NCT02365818). All patients received at least 2 prior courses of intravesical therapy for CIS, with at least 1 being a course of BCG. Patients had either failed BCG induction therapy within 6 months or had been successfully treated with BCG with subsequent recurrence. Complete response (CR) at 6 months was defined as absence of disease on cytology, cystoscopy, and random biopsies. Of 45 patients, there were 24 pure CIS, 8 CIS + Ta, 4 CIS + T1, 6 Ta, 3 T1. Overall 6-month CR (95% CI) was 47% (32%-62%). Considering 6-month CR for pathologic subsets, pure CIS was 58% (37%-78%), CIS ± Ta/T1 50% (33%-67%), and pure Ta/T1 33% (8%-70%). At 6 months, the single patient that progressed to muscle-invasive disease had Ta and T1 tumors at baseline. No patients with pure T1 had 6-month CR. Treatment-related adverse events (AEs) at 6 months were most commonly urinary bladder spasms (36%), hematuria (28%), dysuria (25%), and urgency (22%). Immunologic treatment-related AEs included flu-like symptoms (12%) and fatigue (6%). Grade III treatment-related AEs included dysuria (3%) and hypotension (1.5%). There were no Grade IV/V treatment-related AEs. This phase II study demonstrates that intravesical CG0070 yielded an overall 47

  10. Effectiveness of transurethral resection under the control of photodynamic diagnosis and intravesical instillation of bacillus Calmette–Guérin in case of poorly differentiated non-muscle-invasive bladder cancer

    Directory of Open Access Journals (Sweden)

    A. I. Rolevich

    2016-01-01

    Full Text Available Background. High-grade non-muscle-invasive bladder cancer (NMIBC is characterized by a high rate of recurrence, progression, and mortality associated with this disease. Organ-preserving treatment by transurethral resection and immunotherapy with bacillus Calmette-Guerin (BCG is an initial approach to therapy in these patients. However, the efficacy of such therapy is limited. This justifies the use of other methods of treatment, such as TUR under the control of photodynamic diagnosis (PDD. Aim of this study was to evaluate the effectiveness of therapeutic interventions in patients with high-grade NMIBC.Materials and methods. We have retrospectively analyzed results of follow-up of patients with primary or recurrent high-grade transitional cell NMIBC, treatment by TUR in conjunction with BCG or without it N.N. Alexandrov National Cancer Centre in the period from 2004 to 2013. In total, the study included 113 patients (27 women and 86 men, in the median age of 72 years. We have evaluated 5-year recurrence- and progression-free survival, analyzed an influence of prognostic factors and methods of treatment on the risk of recurrence and progression with Cox model and Kaplan–Meier method.Results. With a median of follow up of 59 (12–116 months the rates of 5-year recurrence- and progression-free survival were respectively 42.5 and 71.6 %. Statistically significant association with the risk of recurrence was observed in multivariate Cox regression analysis for recurrent tumors (hazard ratio (HR 2.73; 95 % confidence interval (CI 1.61–4.62 and immunotherapy with BCG (HR 0.56; 95 % CI 0.31–0.99. BCG significantly increased recurrence-free survival in patients with both primary tumors, and with recurrent ones. Significant factors in the multivariate analysis with regard to the risk of progression were suspicion for muscle-invasive tumors according to the cystoscopic picture (HR 3.36; 95 % CI 1.09–10.4, abnormal tumor-free bladder mucosa

  11. A panel of prognostic protein markers for progression in non-muscle invasive bladder cancer - a multicenter tissue microarray validation study

    DEFF Research Database (Denmark)

    Fristrup, Niels; Birkenkamp-Demtröder, Karin; Ulhøi, Benedicte Parm

    2012-01-01

    Bladder cancer is the fifth most common cancer in the Western world. The histopathological parameters used in the clinic cannot precisely predict the individual disease course. Bladder cancer patients are therefore monitored thoroughly for disease recurrence and progression by urine and cystoscop...

  12. Tar, nicotine and carbon monoxide yield of UK cigarettes and the risk of non-muscle-invasive and muscle-invasive bladder cancer.

    NARCIS (Netherlands)

    van Osch, Frits H M; Pauwels, Charlotte G G M; Jochems, Sylvia H J; Fayokun, Ranti; James, Nicholas D; Wallace, D Michael A; Cheng, Kar-Keung; Bryan, Richard T; van Schooten, Frederik J; Zeegers, Maurice P

    2017-01-01

    Cigarette smoking is a major risk factor for bladder cancer (BC); however, the impact of cigarette content remains unclear. This study aims to investigate tar, nicotine and carbon monoxide (TNCO) yields of different filtered cigarettes in relation to BC risk. From the Bladder Cancer Prognosis

  13. BCG+MMC trial: adding mitomycin C to BCG as adjuvant intravesical therapy for high-risk, non-muscle-invasive bladder cancer: a randomised phase III trial (ANZUP 1301)

    International Nuclear Information System (INIS)

    Hayne, Dickon; Stockler, Martin; McCombie, Steve P.; Chalasani, Venu; Long, Anne; Martin, Andrew; Sengupta, Shomik; Davis, Ian D.

    2015-01-01

    Despite adequate trans-urethral resection of the bladder tumour (TURBT), non-muscle-invasive bladder cancer (NMIBC) is associated with high rates of recurrence and progression. Instillation of Bacillus Calmette-Guérin (BCG) into the urinary bladder after TURBT (adjuvant intravesical administration) reduces the risk of both recurrence and progression, and this is therefore the standard of care for high-risk tumours. However, over 30 % of people still recur or progress despite optimal delivery of BCG. Our meta-analysis suggests that outcomes might be improved further by using an adjuvant intravesical regimen that includes both mitomycin and BCG. These promising findings require corroboration in a definitive, large scale, randomised phase III trial using standard techniques for intravesical administration. The BCG + MMC trial (ANZUP 1301) is an open-label, randomised, stratified, two-arm multi-centre phase III trial comparing the efficacy and safety of standard intravesical therapy (BCG alone) against experimental intravesical therapy (BCG and mitomycin) in the treatment of adults with resected, high-risk NMIBC. Participants in the control group receive standard treatment with induction (weekly BCG for six weeks) followed by maintenance (four-weekly BCG for ten months). Participants in the experimental group receive induction (BCG weeks 1, 2, 4, 5, 7, and 8; mitomycin weeks 3, 6, and 9) followed by four-weekly maintenance (mitomycin weeks 13, 17, 25, 29, 37, and 41; BCG weeks 21, 33, and 45). The trial aims to include 500 participants who will be centrally randomised to one of the two treatment groups in a 1:1 ratio stratified by T-stage, presence of CIS, and study site. The primary endpoint is disease-free survival; secondary endpoints are disease activity, time to recurrence, time to progression, safety, health-related quality of life, overall survival, feasibility, and resource use

  14. Association Between Number of Endoscopic Resections and Utilization of Bacillus Calmette-Guérin Therapy for Patients With High-Grade, Non-Muscle-Invasive Bladder Cancer.

    Science.gov (United States)

    Lenis, Andrew T; Donin, Nicholas M; Litwin, Mark S; Saigal, Christopher S; Lai, Julie; Hanley, Jan M; Konety, Badrinath R; Chamie, Karim

    2017-02-01

    Bacillus Calmette-Guérin (BCG) is the reference standard treatment for patients with high-grade, non-muscle-invasive bladder cancer (NMIBC). We previously described noncompliance with guidelines for BCG use in patients with high-risk disease. In the current study, we sought to characterize how the number of endoscopic resections of bladder tumors affects BCG utilization using population-level data. We queried a Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database to evaluate claims records of 4776 patients diagnosed with high-grade NMIBC between 1992 and 2002 and followed until 2007, who survived for at least 2 years and who did not undergo definitive treatment with cystectomy, radiotherapy, or systemic chemotherapy. We stratified patients on the basis of the number of endoscopic resections of bladder tumors. We used chi-square analysis to compare number of resections to BCG utilization and multinomial logistic regression analysis to quantify BCG utilization by patient and tumor characteristics. Utilization of BCG increases with increasing endoscopic resections from 40% at diagnosis to 72% after 6 resections. The cumulative rate of at least an induction course of BCG plateaus after 3 resections. Lower BCG utilization was associated with advanced age (≥ 80 years), while increased utilization was associated with being married, higher disease stage (Tis and T1) and grade (undifferentiated), and increasing endoscopic resections. A significant fraction of patients with NMIBC do not receive induction BCG despite its proven benefit in minimizing recurrences. Most patients receive BCG only after multiple endoscopic resections. Strategies focused on earlier adoption of BCG to prevent recurrences instead of reacting to recurrences may limit progression and improve survival. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Treatment of non muscle invasive bladder tumor related to the problem of bacillus Calmette-Guerin availability. Consensus of a Spanish expert's panel. Spanish Association of Urology.

    Science.gov (United States)

    Fernández-Gómez, J M; Carballido-Rodríguez, J; Cozar-Olmo, J M; Palou-Redorta, J; Solsona-Narbón, E; Unda-Urzaiz, J M

    2013-01-01

    Since June 2012, the has been a worldwide lack of available of the Connaught strain. In December 2012, a group of experts met in the Spanish Association of Urology to analyze this situation and propose alternatives. To present the work performed by said committee and the resulting recommendations. An update has been made of the principal existing evidence in the treatment of middle and high risk tumors. Special mention has been made regarding the those related with the use of BCG and their possible alternative due to the different availability of BCG. In tumors with high risk of progression, immediate cystectomy should be considered when BCG is not available, with dose reduction or alternating with chemotherapy as methods to economize on the use of BCG when availability is reduced. In tumors having middle risk of progression, chemotherapy can be used, although when it is associated to a high risk of relapse, BCG would be indicated if available with the mentioned savings guidelines. BCG requires maintenance to maintain its effectiveness, it being necessary to optimize the application of endovesical chemotherapy and to use systems that increase its penetration into the bladder wall (EMDA) if they are available. Due to the scarcity of BCG, it has been necessary to agree on a series of recommendations that have been published on the web page of the Spanish Association of Urology. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

  16. Do Standardised Prognostic Algorithms Reflect Local Practice? Application of EORTC Risk Tables for Non-Muscle Invasive (pTa/pT1 Bladder Cancer Recurrence and Progression in a Local Cohort

    Directory of Open Access Journals (Sweden)

    Rajiv Pillai

    2011-01-01

    Full Text Available A risk calculator algorithm to allow prediction of probabilities of 1- and 5-year recurrence and progression rates in individuals with pTa/pT1 bladder cancer has been proposed by the European Organisation for Research and Treatment of Cancer (EORTC and was incorporated into the European Association of Urology guidelines in 2006. We attempted to validate this algorithm in a cohort of patients with known outcome. Prognostic data were collected from a consecutively presenting cohort of 109 patients with non-muscle invasive (pTa/pT1 transitional cell cancer (TCC at a single institution between 1983 and 1985. Using the same statistical models as in the EORTC original paper, predicted probabilities of 1- and 5-year recurrence and progression were calculated. Patients were divided into four risk groups for recurrence (Ir-IVr and progression (Ip-IVp, respectively, using six prognostic criteria. These were then compared to the probabilities predicted in the EORTC algorithm. The predicted 1- and 5-year probabilities of recurrence were significantly higher in the study population as compared to the original EORTC algorithm for all four risk groups. The predicted 1-year probabilities for progression in groups Ip/IIIp and at 5-years for groups Ip/IIp were in accordance with the original algorithm, but were higher for the other progression groups. The concordance for the model of prediction using the study group for recurrence at 1 and 5 years was 62 and 63%, respectively, and for progression was 65 and 67, respectively. We were unable to validate the proposed algorithm in our group of patients. Although our study has limitations that prevent firm conclusions on the validity of the algorithm, it does expose some of the drawbacks of standardised nomograms when applied to local clinical practice.

  17. The clinical course of non-muscle invasive bladder cancer after transuretral resection of the tumor with or without subsequent intravesical application of bacillus Calmette-Guérin: The influence of patients gender and age

    Directory of Open Access Journals (Sweden)

    Milošević Radovan

    2015-01-01

    Full Text Available Bacground/Aim. The therapy with intravesical instillation of bacillus Calmette-Guérin (BCG after transurethral resection (TUR of tumor is the gold standard of treatment of non-muscle invasive bladder cancer (NMIBC. The role and importance of BCG intravesical therapy in various shape of tumors, were confirmed by our previous investigation. The aim of this study was to examine whether incidence of recurrence and tumor regression differs depending on sex and age of patients. Methods. This study included a total of 899 patients suffering from NIMBC, treated at our institution from January 1, 2007 to March 1, 2013. Two groups of patients were formed: patients underwent TUR + BCG therapy (the group I and the group II with patients in whom TUR was performed as only therapy. These two groups of patients were divided into subgroups of respondents male and female, age 60 years or younger and older than 60 years. Statistical analysis was performed using χ2 test and the Kolmogorov-Smirnov test. Results. This research suggests that if the frequency of recurrence is seen as the only parameter, considering all the subjects, the lowest recurrence rate was determined in the male subjects, aged 60 years and younger who had received BCG after TUR. A high statistical significance was found in the incidence of recurrence in patients younger than 60 years, depending on the response to the therapy, while in those older than 60 years, the difference was at the level of statistical significance. This can be attributed to a certain degree of infravesical obstruction in older men. Conclusions. Sex and age of patients may have a significant influence on the course and outcome of NMIBC. The disease has the most malignant and most aggressive behavior when present in males older than 60 years.

  18. Maintenance versus non-maintenance intravesical Bacillus Calmette-Guerin instillation for non-muscle invasive bladder cancer: A systematic review and meta-analysis of randomized clinical trials.

    Science.gov (United States)

    Chen, Siteng; Zhang, Ning; Shao, Jialiang; Wang, Xiang

    2018-02-28

    It is not clear whether maintenance Bacillus Calmette-Guerin (BCG) is necessary for intermediate- or high-risk non-muscle-invasive bladder cancer (NMIBC). This systematic review and meta-analysis aimed to illustrate the effects of maintenance BCG for intermediate- or high-risk NMIBC. A comprehensive literature search of PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov databases and International Clinical Trials Register (ICTRP) Search was conducted to identify relevant randomized controlled trials (RCTs) that have assessed the efficacy of maintenance or non-maintenance BCG therapy for patients with NMIBC. The maintenance group first received induction BCG instillations, and subsequently received BCG intravesical instillations regularly for at least 1 year, while the control group only received induction BCG instillations. Systematic review and meta-analysis were performed according to Preferred Reporting Items for Systematic Reviews and Meta-analysis Criteria. Ten RCTs were eligible in this systematic review. The meta-analysis showed that induction BCG followed by maintenance BCG instillation after transurethral resection (TUR) could reduce the risk ratios of tumor recurrence by 21% (RR = 0.79; 95% CI 0.70-0.89; P maintenance BCG. It could also reduce the risk ratios of tumor progression (RR = 0.81; 95% CI 0.68-0.97; P = 0.02). However, these pooled results should be considered with caution since the quality of evidences for outcomes ranged low. Subgroup analysis implied that different durations of maintenance BCG instillations might be one of the sources of potential clinical heterogeneity of included studies. Begg's funnel plot and Egger's test did not reveal any evidence of publication bias in this meta-analysis. Induction BCG followed by maintenance BCG instillation after TUR, compared with induction BCG along, can reduce the risk ratios of tumor recurrence and tumor progression, and prolong RFS. However, these results with a lower level of

  19. Intravesical rAd-IFNα/Syn3 for Patients With High-Grade, Bacillus Calmette-Guerin-Refractory or Relapsed Non-Muscle-Invasive Bladder Cancer: A Phase II Randomized Study.

    Science.gov (United States)

    Shore, Neal D; Boorjian, Stephen A; Canter, Daniel J; Ogan, Kenneth; Karsh, Lawrence I; Downs, Tracy M; Gomella, Leonard G; Kamat, Ashish M; Lotan, Yair; Svatek, Robert S; Bivalacqua, Trinity J; Grubb, Robert L; Krupski, Tracey L; Lerner, Seth P; Woods, Michael E; Inman, Brant A; Milowsky, Matthew I; Boyd, Alan; Treasure, F Peter; Gregory, Gillian; Sawutz, David G; Yla-Herttuala, Seppo; Parker, Nigel R; Dinney, Colin P N

    2017-10-20

    Purpose Many patients with high-risk non-muscle-invasive bladder cancer (NMIBC) are either refractory to bacillus Calmette-Guerin (BCG) treatment or may experience disease relapse. We assessed the efficacy and safety of recombinant adenovirus interferon alfa with Syn3 (rAd-IFNα/Syn3), a replication-deficient recombinant adenovirus gene transfer vector, for patients with high-grade (HG) BCG-refractory or relapsed NMIBC. Methods In this open-label, multicenter (n = 13), parallel-arm, phase II study ( ClinicalTrials.gov identifier: NCT01687244), 43 patients with HG BCG-refractory or relapsed NMIBC received intravesical rAd-IFNα/Syn3 (randomly assigned 1:1 to 1 × 10 11 viral particles (vp)/mL or 3 × 10 11 vp/mL). Patients who responded at months 3, 6, and 9 were retreated at months 4, 7, and 10. The primary end point was 12-month HG recurrence-free survival (RFS). All patients who received at least one dose were included in efficacy and safety analyses. Results Forty patients received rAd-IFNα/Syn3 (1 × 10 11 vp/mL, n = 21; 3 × 10 11 vp/mL, n = 19) between November 5, 2012, and April 8, 2015. Fourteen patients (35.0%; 90% CI, 22.6% to 49.2%) remained free of HG recurrence 12 months after initial treatment. Comparable 12-month HG RFS was noted for both doses. Of these 14 patients, two experienced recurrence at 21 and 28 months, respectively, after treatment initiation, and one died as a result of an upper tract tumor at 17 months without a recurrence. rAd-IFNα/Syn3 was well tolerated; no grade four or five adverse events (AEs) occurred, and no patient discontinued treatment because of an adverse event. The most frequently reported drug-related AEs were micturition urgency (n = 16; 40%), dysuria (n = 16; 40%), fatigue (n = 13; 32.5%), pollakiuria (n = 11; 28%), and hematuria and nocturia (n = 10 each; 25%). Conclusion rAd-IFNα/Syn3 was well tolerated. It demonstrated promising efficacy for patients with HG NMIBC after BCG therapy who were unable or unwilling to

  20. Chromium in urothelial carcinoma of the bladder.

    Science.gov (United States)

    Golabek, Tomasz; Socha, Katarzyna; Kudelski, Jacek; Darewicz, Barbara; Markiewicz-Zukowska, Renata; Chlosta, Piotr; Borawska, Maria

    2017-12-23

    Many epidemiological and experimental studies report a strong role of chemical carcinogens in the etiology of bladder cancer. However, the involvement of heavy metals in tumourigenesis of urothelial carcinoma of the bladder has been poorly investigated. Therefore, the aim of this study was to examine the relationship between chromium (Cr) and bladder cancer. Chromium concentration in two 36-sample series of bladder cancer tissue and sera from patients with this neoplasm were matched with those of a control group. The amount of trace elements in every tissue sample was determined using atomic absorption spectrometry. This was correlated with tumour stage. While the median chromium concentration levels reached statistically higher values in the bladder cancer tissue, compared with the non-cancer tissue (99.632ng/g and 33.144ng/g, respectively; p<0.001), the median Cr levels in the sera of the patients with this carcinoma showed no statistical difference when compared to those of the control group (0.511μg/l and 0.710μg/l, respectively; p=0.408). The median levels of Cr in the bladder tissue, depending on the stage of the tumour, compared with the tissue without the neoplasm, observed the same relationship for both non-muscle invasive and muscle-invasive tumours (p<0.001 and p<0.01, respectively). This study shows that patients with urothelial carcinoma of the bladder had higher tissue Cr levels than people without tumour, while no difference was found in the Cr serum levels between the two groups of patients under investigation.

  1. UBC®Rapid Test for detection of carcinoma in situ for bladder cancer.

    Science.gov (United States)

    Ecke, Thorsten H; Weiß, Sarah; Stephan, Carsten; Hallmann, Steffen; Barski, Dimitri; Otto, Thomas; Gerullis, Holger

    2017-05-01

    UBC ® Rapid Test is a test that detects fragments of cytokeratins 8 and 18 in urine. We present results of a multicentre study measuring UBC ® Rapid Test in bladder cancer patients and healthy controls with focus on carcinoma in situ (CIS) and high-grade bladder cancer. From our study with N = 452 patients, we made a stratified sub-analysis for carcinoma in situ of the urinary bladder. Clinical urine samples were used from 87 patients with tumours of the urinary bladder (23 carcinoma in situ, 23 non-muscle-invasive low-grade tumours, 21 non-muscle-invasive high-grade tumours and 20 muscle-invasive high-grade tumours) and from 22 healthy controls. The cut-off value was defined at 10.0 µg/L. Urine samples were analysed by the UBC ® Rapid Test point-of-care system (concile Omega 100 POC reader). Pathological levels of UBC Rapid Test in urine are higher in patients with bladder cancer in comparison to the control group (p Rapid Test using the optimal threshold obtained by receiveroperated curve analysis was 0.75. Pathological values of UBC ® Rapid Test in urine are higher in patients with high-grade bladder cancer in comparison to low-grade tumours and the healthy control group. UBC ® Rapid Test has potential to be more sensitive and specific urinary protein biomarker for accurate detection of high-grade patients and could be added especially in the diagnostics for carcinoma in situ and non-muscle-invasive high-grade tumours of urinary bladder cancer.

  2. [Analysis of budgetary impact of moderate and high risk non muscle-invasive bladder cancer by means of neoadjuvant hyperthermia chemotherapy compared to the standard adjuvant treatment with BCG].

    Science.gov (United States)

    Sousa, Alejandro; Piñeiro, Idelfonso; Aparici, Vicente; Neira, Pilar; Monserrat, Víctor; Uribarri, Carlos

    2015-06-01

    To study the relationship between cost-effectiveness and budgetary impact the application of a neoadjuvant chemo-hyperthermia treatment on 15 patients with NMI multi-recurrent bladder cancer and/or whose risk of recurrence and progression is medium-high, compared with the standard neoadjuvant BCG treatment, has had on the Hospital Comarcal de Monforte de Lemos (Lugo). A model was designed from an SNS perspective with a temporary horizon of three years to compare the costs of applying neoadjuvant chemo-hyperthermia on the patients of the clinical test (8 instillations weekly of 80 mg Mitomycin C recirculating at 43 C for an hour prior to carrying out a transurethral resection of the bladder tumor) with the costs of treating 15 patients with the same risk profile with the standard adjuvant treatment of BCG (control group). The effective available costs corresponding to drugs, disposables and those relative to TURBT, cold biopsy and tumor relapse were included. The costs of diagnostic tests and follow-up were discarded from the model because they did not vary between groups. The model built with effective and published cost data establishes a favourable difference in favour of the neoadjuvant treatment with chemo hyperthermia in terms of 3 year costs with a minimum global savings of 10,300€ and 687€ per patient, together with an improvement in the effectiveness of the treatment. These values could reach a minimum savings of 25,960€ and 1,731€ per patient, if a change in protocol is made after the neoadjuvant treatment, which uses the cold biopsy to check the results. Of the 15 patients pre-treated with chemo-hyperthermia, 11 high-risk and 4 medium-risk, 9 have responded completely (absence of residual tumor) and 6 partially (shrinking of the tumor). The number of expected relapses has been reduced from 8 to 2 and progression from 3 to 0. The neoadjuvant treatment with chemo hyperthermia constitutes a cost-effective therapeutic strategy.

  3. Supplementary Material for: Promoter hypermethylation of HS3ST2, SEPTIN9 and SLIT2 combined with FGFR3 mutations as a sensitive/specific urinary assay for diagnosis and surveillance in patients with low or high-risk non-muscle-invasive bladder cancer

    KAUST Repository

    Roperch, Jean-Pierre

    2016-01-01

    Abstract Background Non-muscle-invasive bladder cancer (NMIBC) is a high incidence form of bladder cancer (BCa), where genetic and epigenetic alterations occur frequently. We assessed the performance of associating a FGFR3 mutation assay and a DNA methylation analysis to improve bladder cancer detection and to predict disease recurrence of NMIBC patients. Methods We used allele specific PCR to determine the FGFR3 mutation status for R248C, S249C, G372C, and Y375C. We preselected 18 candidate genes reported in the literature as being hypermethylated in cancer and measured their methylation levels by quantitative multiplex-methylation specific PCR. We selected HS3ST2, SLIT2 and SEPTIN9 as the most discriminative between control and NMIBC patients and we assayed these markers on urine DNA from a diagnostic study consisting of 167 NMIBC and 105 controls and a follow-up study consisting of 158 NMIBC at diagnosis time’s and 425 at follow-up time. ROC analysis was performed to evaluate the diagnostic accuracy of each assay alone and in combination. Results For Diagnosis: Using a logistic regression analysis with a model consisting of the 3 markers’ methylation values, FGFR3 status, age and known smoker status at the diagnosis time we obtained sensitivity/specificity of 97.6 %/84.8 % and an optimism-corrected AUC of 0.96. With an estimated BCa prevalence of 12.1 % in a hematuria cohort, this corresponds to a negative predictive value (NPV) of 99.6 %. For Follow-up: Using a logistic regression with FGFR3 mutation and the CMI at two time points (beginning of the follow-up and current time point), we got sensitivity/specificity/NPV of 90.3 %/65.1 %/97.0 % and a corrected AUC of 0.84. We also tested a thresholding algorithm with FGFR3 mutation and the two time points as described above, obtaining sensitivity/specificity/NPV values of, respectively, 94.5 %/75.9 %/98.5 % and an AUC of 0.82. Conclusions We showed that combined analysis of FGFR3 mutation and DNA

  4. Promoter hypermethylation of HS3ST2, SEPTIN9 and SLIT2 combined with FGFR3 mutations as a sensitive/specific urinary assay for diagnosis and surveillance in patients with low or high-risk non-muscle-invasive bladder cancer

    KAUST Repository

    Roperch, Jean-Pierre

    2016-09-02

    Background: Non-muscle-invasive bladder cancer (NMIBC) is a high incidence form of bladder cancer (BCa), where genetic and epigenetic alterations occur frequently. We assessed the performance of associating a FGFR3 mutation assay and a DNA methylation analysis to improve bladder cancer detection and to predict disease recurrence of NMIBC patients. Methods: We used allele specific PCR to determine the FGFR3 mutation status for R248C, S249C, G372C, and Y375C. We preselected 18 candidate genes reported in the literature as being hypermethylated in cancer and measured their methylation levels by quantitative multiplex-methylation specific PCR. We selected HS3ST2, SLIT2 and SEPTIN9 as the most discriminative between control and NMIBC patients and we assayed these markers on urine DNA from a diagnostic study consisting of 167 NMIBC and 105 controls and a follow-up study consisting of 158 NMIBC at diagnosis time\\'s and 425 at follow-up time. ROC analysis was performed to evaluate the diagnostic accuracy of each assay alone and in combination. Results: For Diagnosis: Using a logistic regression analysis with a model consisting of the 3 markers\\' methylation values, FGFR3 status, age and known smoker status at the diagnosis time we obtained sensitivity/specificity of 97.6 %/84.8 % and an optimism-corrected AUC of 0.96. With an estimated BCa prevalence of 12.1 % in a hematuria cohort, this corresponds to a negative predictive value (NPV) of 99.6 %. For Follow-up: Using a logistic regression with FGFR3 mutation and the CMI at two time points (beginning of the follow-up and current time point), we got sensitivity/specificity/NPV of 90.3 %/65.1 %/97.0 % and a corrected AUC of 0.84. We also tested a thresholding algorithm with FGFR3 mutation and the two time points as described above, obtaining sensitivity/specificity/NPV values of, respectively, 94.5 %/75.9 %/98.5 % and an AUC of 0.82. Conclusions: We showed that combined analysis of FGFR3 mutation and DNA methylation markers

  5. Non-muscle invasive bladder cancer risk stratification

    Directory of Open Access Journals (Sweden)

    Sumit Isharwal

    2015-01-01

    Conclusion: EORTC and CUETO risk tables are the two best-established models to predict recurrence and progression in patients with NMIBC though they tend to overestimate risk and have poor discrimination for prognostic outcomes in external validation. Future research should focus on enhancing the predictive accuracy of risk assessment tools by incorporating additional prognostic factors such as depth of lamina propria invasion and molecular biomarkers after rigorous validation in multi-institutional cohorts.

  6. Bioinformatic identification of FGF, p38-MAKP, and calcium signalling pathways associated with carcinoma in situ in the urinary bladder

    DEFF Research Database (Denmark)

    Herbsleb, Malene; Christensen, Ole F; Thykjaer, Thomas

    2008-01-01

    Background Carcinoma in situ (CIS) is believed to be a precursor of invasive bladder cancer. Identification of CIS is a valuable prognostic factor since radical treatment strategies can be offered these patients before the disease becomes invasive. Methods We developed a pathway based classifier...... approach to predict presence or absence of CIS in patients suffering from non muscle invasive bladder cancer. From Ingenuity Pathway Analysis we considered four canonical signalling pathways (p38 MAPK, FGF, Calcium, and cAMP pathways) with most coherent expression of transcription factors (TFs) across...

  7. Commentary on "Outpatient laser ablation of non-muscle-invasive bladder cancer: is it safe, tolerable and cost-effective?" Wong KA, Zisengwe G, Athanasiou T, O'Brien T, Thomas K, The Urology Centre, Guys and St. Thomas' NHS Foundation Trust.: BJU Int 2013; 112(5):561-7. doi:10.1111/bju.12216. [Epub 2013 Jul 2].

    Science.gov (United States)

    See, William A

    2014-11-01

    To evaluate the safety, tolerability and effectiveness of outpatient (office-based) laser ablation (OLA), with local anaesthetic, for non-muscle-invasive bladder cancer (NMIBC) in an elderly population with and without photodynamic diagnosis (PDD). To compare the cost-effectiveness of OLA of NMIBC with that of inpatient cystodiathermy (IC). We conducted a prospective cohort study of patients with NMIBC treated with OLA by one consultant surgeon between March 2008 and July 2011. A subgroup of patients had PDD before undergoing OLA. Safety and effectiveness were determined by complications (In the immediate post operative period, at three days and at three months), patient tolerability (visual analogue score) and recurrence rates. The long-term costs and cost-effectiveness of OLA and IC of NMIBC were evaluated using Markov modeling. A total of 74 OLA procedures (44 white-light, 30 PDD) were carried out in 54 patients. The mean (range) patient age was 77 (52-95) years. More than half of the patients had more than three comorbidities. Previous tumour histology ranged from G1pTa to T3. One patient had haematuria for 1 week which settled spontaneously and did not require hospital admission. There were no other complications. The procedure was well tolerated with pain scores of 0-2/10. Additional lesions were found in 21% of patients using PDD that were not found using white light. At 3 months, the percentage of patients who had recurrence after OLA with white light and OLA with PDD were 10.6 and 4.3%, respectively. At 1 year, 65.1% and 46.9% of patients had recurrence. The cost of OLA was found to be much lower than that of IC (£ 538 vs £ 1474), even with the addition of PDD (£ 912 vs £ 1844). Over the course of a patient's lifetime, OLA was more clinically effective, measured in quality-adjusted life-years (QALY), than IC (0.147 [sd 0.059]) and less costly (£ 2576.42 [sd £ 7293.07]). At a cost-effectiveness threshold of £ 30,000/QALY, as set by the National

  8. Intravesical therapy for urothelial carcinoma of the urinary bladder: a critical review

    Directory of Open Access Journals (Sweden)

    Daher C. Chade

    2009-12-01

    Full Text Available The management of non-muscle-invasive urothelial carcinoma of the bladder (UCB is a challenge for physicians and patients alike. This is largely due to the heterogeneous natural history of this disease, in which tumors range from indolent to rapidly progressive and eventually fatal. Moreover, the high rate of recurrence and progression cause significant morbidity, expense, and detriment to quality of life. The advent of effective and safe intravesical therapies has improved the management of non-muscle-invasive UCB. Nevertheless, despite over 30 years of research and clinical experience, the mechanism, risks, benefits, and optimal regimens and treatment algorithms remain unclear. Although immunotherapy with bacillus Calmette-Guerin (BCG has been the mainstay of intravesical treatment and represents a significant advance in the interaction of immunology and oncology, its clinical effectiveness is accompanied by a wide range of adverse events. Here, we review the literature on intravesical immunotherapy and chemotherapy with the aim of evaluating the clinical utility of the different treatments and providing recommendations. Many studies over the years have compared efficacy and toxicities of different agents and regimens, and certain conclusions are now well supported by high-level evidence. Future perspectives and promising advances in drug development are discussed and areas of improvement are identified in order to promote better cancer control and decrease the rate and severity of side-effects.

  9. Bioinformatic identification of FGF, p38-MAPK, and calcium signalling pathways associated with carcinoma in situ in the urinary bladder

    International Nuclear Information System (INIS)

    Herbsleb, Malene; Christensen, Ole F; Thykjaer, Thomas; Wiuf, Carsten; Borre, Michael; Ørntoft, Torben F; Dyrskjøt, Lars

    2008-01-01

    Carcinoma in situ (CIS) is believed to be a precursor of invasive bladder cancer. Identification of CIS is a valuable prognostic factor since radical treatment strategies can be offered these patients before the disease becomes invasive. We developed a pathway based classifier approach to predict presence or absence of CIS in patients suffering from non muscle invasive bladder cancer. From Ingenuity Pathway Analysis we considered four canonical signalling pathways (p38 MAPK, FGF, Calcium, and cAMP pathways) with most coherent expression of transcription factors (TFs) across samples in a set of twenty-eight non muscle invasive bladder carcinomas. These pathways contained twelve TFs in total. We used the expression of the TFs to predict presence or absence of CIS in a Leave-One-Out Cross Validation classification. We showed that TF expression levels in three pathways (FGF, p38 MAPK, and calcium signalling) or the expression of the twelve TFs together could be used to predict presence or absence of concomitant CIS. A cluster analysis based on expression of the twelve TFs separated the samples in two main clusters: one branch contained 11 of the 15 patients without concomitant CIS and with the majority of the genes being down regulated; the other branch contained 10 of 13 patients with concomitant CIS, and here genes were mostly up regulated. The expression in the CIS group was comparable to the expression of twenty-three patients suffering from muscle-invasive bladder carcinoma. Finally, we validated our results in an independent test set and found that prediction of CIS status was possible using TF expression of the p38 MAPK pathway. We conclude that it is possible to use pathway analysis for molecular classification of bladder tumors

  10. Sperm associated antigen 9 plays an important role in bladder transitional cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Deepika Kanojia

    Full Text Available BACKGROUND: Majority of bladder cancer deaths are caused due to transitional cell carcinoma (TCC which is the most prevalent and chemoresistant malignancy of urinary bladder. Therefore, we analyzed the role of Sperm associated antigen 9 (SPAG9 in bladder TCC. METHODOLOGY AND FINDINGS: We examined SPAG9 expression and humoral response in 125 bladder TCC patients. Four bladder cancer cell lines were assessed for SPAG9 expression. In addition, we investigated the effect of SPAG9 ablation on cellular proliferation, cell cycle, migration and invasion in UM-UC-3 bladder cancer cells by employing gene silencing approach. Our SPAG9 gene and protein expression analysis revealed SPAG9 expression in 81% of bladder TCC tissue specimens. High SPAG9 expression (>60% SPAG9 positive cells was found to be significantly associated with superficial non-muscle invasive stage (P = 0.042 and low grade tumors (P = 0.002 suggesting SPAG9 putative role in early spread and tumorigenesis. Humoral response against SPAG9 was observed in 95% of patients found positive for SPAG9 expression. All four bladder cancer cell lines revealed SPAG9 expression. In addition, SPAG9 gene silencing in UM-UC-3 cells resulted in induction of G0-G1 arrest characterized by up-regulation of p16 and p21 and consequent down-regulation of cyclin E, cyclin D and cyclin B, CDK4 and CDK1. Further, SPAG9 gene silencing also resulted in reduction in cellular growth, and migration and invasion ability of cancer cells in vitro. CONCLUSIONS: Collectively, our data in clinical specimens indicated that SPAG9 is potential biomarker and therapeutic target for bladder TCC.

  11. Bladder carcinoma. Apport MR imaging

    International Nuclear Information System (INIS)

    Roy, C.; Spittler, G.; Jacqmin, D.; Morel, M.

    1991-01-01

    Bladder carcinoma is the second most commun cause of urogenital tumor. It is suspected by abdominal ultrasound and prouved by cystoscopy with biopsy. At present, MR Imaging is the most accurate diagnostic modality for loco-regional staging. Urography is still useful to appreciate urinary tract [fr

  12. NEOADJUVANT RADIOTHERAPY FOR BLADDER CARCINOMA IN ...

    African Journals Online (AJOL)

    Objective To evaluate the impact of preoperative accelerated hyperfractionated radiotherapy in the management of bladder carcinoma in Egyptian patients. Patients and Methods Between December 1996 and February 2000, 104 Egyptian patients with pathologically proven infiltrative bladder carcinoma were enrolled in ...

  13. Clinical significance of T-bet, GATA-3, and Bcl-6 transcription factor expression in bladder carcinoma.

    Science.gov (United States)

    Bahria-Sediki, Islem Ben; Yousfi, Nadhir; Paul, Catherine; Chebil, Mohamed; Cherif, Mohamed; Zermani, Rachida; El Gaaied, Amel Ben Ammar; Bettaieb, Ali

    2016-05-30

    The aim of this study was to investigate the clinical significance of three immune cell-related transcription factors, T-bet, GATA-3 and Bcl-6 in bladder cancer in Tunisian patients. Expression of T-bet, GATA-3 and Bcl-6 genes was assessed using RT-qPCR in 65 bladder cancers from patients: 32 being diagnosed as low- and medium-grade, 31 as high-grade, 25 as muscle invasive stage and 39 as non-muscle invasive stage. Gene expression was statistically correlated according to the grade, the stage, tobacco consumption, the BCG response and disease severity. T-bet levels in patients with high-grade bladder cancer were significantly elevated compared to patients with low- or medium-grade bladder cancer (p = 0.005). In invasive carcinoma (T2-T4), the T-bet levels were significantly higher than in superficial non-invasive bladder tumors (Tis, Ta, and T1) (p = 0.02). However, T-bet is predictive of the response to BCG. Its expression is high in good responders to BCG (p = 0.02). In contrast, the expression of GATA-3 and Bcl-6 in non-invasive carcinoma (p = 0.008 and p = 0.0003) and in patients with low- and medium-grade cancers (p = 0.001 and p T-bet expression. Our results suggest that T-bet expression in bladder tumors could be a positive prognostic indicator of BCG therapy, even if high levels are found in high-grade and stage of the disease. However, GATA-3 and Bcl-6 expression could be considered as predictive factors for good patient survival.

  14. Squamous cell carcinoma in bladder extrophy

    OpenAIRE

    Cabral-Ribeiro, J; Silva, C; Sousa, L; Pérez García, D; Ribeiro dos Santos, A

    2005-01-01

    Bladder extrophy is a rare congenital malformation that nowadays is surgically corrected in neonatal period. We present a case report of a 71-year-old male with a verrucous squamous cell carcinoma arising in a classical uncorrected form of bladder extrophy.

  15. Analysis of intravesical recurrence after bladder-preserving therapy for muscle-invasive bladder cancer

    International Nuclear Information System (INIS)

    Onozawa, Mizuki; Miyanaga, Naoto; Hinotsu, Shiro

    2012-01-01

    The aim of the present study was to analyze the pattern of recurrences after bladder-preserving therapy for muscle-invasive bladder cancer. The subjects were 77 patients with T2-3N0M0 bladder cancer whose bladder was preserved by intra-arterial chemotherapy and radiation. The patterns of the first recurrences were retrospectively analyzed. With a median follow-up of 38.5 months, 17 patients (22.1%) experienced intravesical recurrence without metastasis, 14 (82.4%) of which were cases of non-muscle-invasive bladder cancer recurrence and 3 (17.6%) of which were muscle-invasive bladder cancer recurrences. Muscle-invasive bladder cancer recurred at the same site as the initial tumor site in all three cases, whereas non-muscle-invasive bladder cancer recurred at different sites in 64% of the patients in that group. The peak hazard of the non-muscle-invasive bladder cancer recurrence was observed at around a year after treatment. Recurrent non-muscle-invasive bladder cancer was of a significantly lower histological grade with lower Ki-67-labeling indices than the initial muscle-invasive bladder cancer. Twelve (85.7%) of 14 patients with non-muscle-invasive bladder cancer recurrence achieved disease-free status. The multivariate analysis revealed that multiplicity, grade and tumor size were significantly correlated with the recurrence (P=0.0001, 0.0442 and 0.0412, respectively). Most of the recurrences after bladder-preserving therapy were cases of non-muscle-invasive bladder cancer. The recurrence pattern and characteristics of the tumors did not differ from those of primary non-muscle-invasive bladder cancer. Patients with high-risk factors would be candidates for prophylactic intravesical therapy for non-muscle-invasive bladder cancer recurrence. (author)

  16. Oncolytic Viruses in the Treatment of Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Kyle G. Potts

    2012-01-01

    Full Text Available Bladder carcinoma is the second most common malignancy of the urinary tract. Up to 85% of patients with bladder cancer are diagnosed with a tumor that is limited to the bladder mucosa (Ta, T1, and CIS. These stages are commonly termed as non-muscle-invasive bladder cancer (NMIBC. Although the treatment of NMIBC has greatly improved in recent years, there is a need for additional therapies when patients fail bacillus Calmette-Guérin (BCG and chemotherapeutic agents. We propose that bladder cancer may be an ideal target for oncolytic viruses engineered to selectively replicate in and lyse tumor cells leaving normal cells unharmed. In support of this hypothesis, here we review current treatment strategies for bladder cancer and their shortcomings, as well as recent advancements in oncolytic viral therapy demonstrating encouraging safety profiles and antitumor activity.

  17. Recurrent dermatomyositis manifesting as a sign of recurrent transitional cell carcinoma of urinary bladder: Long-term survival

    Directory of Open Access Journals (Sweden)

    John Fitzpatrick

    2014-01-01

    Full Text Available The association between urological malignancies and paraneoplastic syndromes has been well documented. We report a case of recurrent dermatomyositis manifesting as a sign of metastatic recurrence of non-muscle-invasive transitional cell carcinoma of the bladder, a relationship which has only been referred to in a few reports. The case highlights a few important clinical challenges; firstly, the importance of thorough investigation for underlying malignancy in patients with dermatomyositis, as successful treatment of such malignancy can lead to resolution of paraneoplastic symptoms, and secondly, a high index of suspicion of recurrence in cases where paraneoplastic manifestations recur. Metastatic pulmonary recurrence without local evidence of disease at a follow-up of 4 years makes this case unique. Moreover, in the light of our experience and reported literature, a framework is suggested to approach such a diagnostic dilemma in the future. Description of the case will guide clinicians in the future, in case they encounter such an unusual clinical scenario. This could also serve as a hypothesis-generating source for designing future research as well.

  18. Carcinoma Gall Bladder: Past, Present, and Future

    Directory of Open Access Journals (Sweden)

    Ghosh Y

    2014-12-01

    Full Text Available Carcinoma gall bladder is a very aggressive disease with poor outcomes. Despite achievements in the field of advanced imaging techniques, there is a very high mortality rate of the disease Cancer is the second most common disease in India responsible for maximum mortality with about 0.3 million deaths per year. The magnitude of cancer problem in the Indian Sub-continent (sheer numbers is increasing due to poor to moderate living standards and inadequate medical facilities. Women are more commonly affected than men. The peak incidence occurs in people in their 60s, but the disease age range is from 29 to 90 years of age and there is great geographic and ethnic variation. Carcinoma gall bladder, a disease of old age, is now found in the younger age group and presents with greater ferocity.

  19. Pathologic Pattern of Invasive Bladder Carcinoma: Impact of ...

    African Journals Online (AJOL)

    Objective: To describe the pathologic pattern of invasive bladder carcinoma in cystectomy specimens in relation to bilharziasis. Patients and Methods: Between April 2002 and October 2006, 148 consecutive patients with invasive bladder cancer were subjected to radical cystectomy and orthotopic sigmoid bladder ...

  20. Urinary bladder carcinoma with divergent differentiation featuring small cell carcinoma, sarcomatoid carcinoma, and liposarcomatous component.

    Science.gov (United States)

    Yasui, Mariko; Morikawa, Teppei; Nakagawa, Tohru; Miyakawa, Jimpei; Maeda, Daichi; Homma, Yukio; Fukayama, Masashi

    2016-09-01

    Both small cell carcinoma and sarcomatoid carcinoma of the urinary bladder are highly aggressive tumors, and a concurrence of these tumors is extremely rare. We report a case of urinary bladder cancer with small cell carcinoma as a predominant component, accompanied by sarcomatoid carcinoma and conventional urothelial carcinoma (UC). Although the small cell carcinoma component had resolved on receiving chemoradiotherapy, rapid growth of the residual tumor led to a fatal outcome. A 47-year-old man presented with occasional bladder irritation and had a 2-year history of asymptomatic hematuria. Cystoscopy revealed a huge mass in the urinary bladder, and transurethral resection was performed. Microscopically, small cell carcinoma was detected as the major tumor component. Spindle-shaped sarcomatoid cells were also observed that were intermingled with small cell carcinoma and conventional UC. In addition, a sheet-like growth of the lipoblast-like neoplastic cells was observed focally. Initially, by providing chemoradiotherapy, we achieved a marked tumor regression; however, the tumor rapidly regrew after the completion of chemoradiotherapy, and the patient underwent radical cystectomy. Only conventional UC and sarcomatoid carcinoma were identified in the cystectomy specimen. The patient died of the disease 4 months after cystectomy. Urinary bladder cancer may include a combination of multiple aggressive histologies as in the present case. Because the variation in the tumor components may affect the efficacy of therapy, a correct diagnosis of every tumor component is necessary. Copyright © 2016 Elsevier GmbH. All rights reserved.

  1. Is radical cystectomy mandatory in every patient with variant histology of bladder cancer

    Directory of Open Access Journals (Sweden)

    Ofer N Gofrit

    2011-04-01

    Full Text Available Urothelial carcinomas have an established propensity for divergent differentiation. Most of these "variant tumors" are muscle invasive but not all. The response of non muscle invasive variant tumors to intravesical immunotherapy with BCG is not established in the literature, and is reported here. Between June 1995 and December 2007, 760 patients (mean age of 67.5 years underwent transurethral resection of first time bladder tumors in our institution. Histologically variant tumors were found in 79 patients (10.4%, 57 patients (72% of them had muscle-invasive disease or extensive non-muscle invasive tumors and 22 patients (28% were treated with BCG immunotherapy. These included 7 patients with squamous differentiation, 4 with glandular, 6 with nested, 4 with micropapillary and 1 patient with sarcomatoid variant. The response of these patients to immunotherapy was compared with that of 144 patients having high-grade conventional urothelial carcinomas. Median follow-up was 46 months. The 2 and 5-year progression (muscle-invasion free survival rates were 92% and 84.24% for patients with conventional carcinoma compared to 81.06% and 63.16% for patients with variant disease (p=0.02. The 2 and 5-year disease specific survival rates were 97% and 91.43% for patients with conventional carcinoma compared to 94.74 % and 82% for patients with variant disease (p=0.33. 5 patients (22.7% of variant group and 13 patients (9.03% of conventional group underwent cystectomy during follow-up (p=0.068. Patients with non-muscle invasive variants of bladder cancers can be managed with intra-vesical immunotherapy if tumor is not bulky (>4cm. Although progression to muscle invasive disease is more common than in conventional group and occurs in about 40% of the patients. Life expectancy is similar to patients with conventional high-grade urothelial carcinomas provided that follow-up is meticulous.

  2. Outpatient diagnostic of bladder tumours in flexible cystoscopes

    DEFF Research Database (Denmark)

    Hermann, Gregers G; Mogensen, Karin; Toft, Birgitte Grønkær

    2012-01-01

    The aim of this study was to evaluate photodynamic diagnosis (PDD) in flexible cystoscopes and the diagnostic quality of biopsies for diagnosis of non-muscle-invasive bladder cancer in the outpatients department (OPD).......The aim of this study was to evaluate photodynamic diagnosis (PDD) in flexible cystoscopes and the diagnostic quality of biopsies for diagnosis of non-muscle-invasive bladder cancer in the outpatients department (OPD)....

  3. Using Copy Number Alterations to Identify New Therapeutic Targets for Bladder Carcinoma

    Directory of Open Access Journals (Sweden)

    Donatella Conconi

    2016-02-01

    Full Text Available Bladder cancer represents the ninth most widespread malignancy throughout the world. It is characterized by the presence of two different clinical and prognostic subtypes: non-muscle-invasive bladder cancers (NMIBCs and muscle-invasive bladder cancers (MIBCs. MIBCs have a poor outcome with a common progression to metastasis. Despite improvements in knowledge, treatment has not advanced significantly in recent years, with the absence of new therapeutic targets. Because of the limitations of current therapeutic options, the greater challenge will be to identify biomarkers for clinical application. For this reason, we compared our array comparative genomic hybridization (array-CGH results with those reported in literature for invasive bladder tumors and, in particular, we focused on the evaluation of copy number alterations (CNAs present in biopsies and retained in the corresponding cancer stem cell (CSC subpopulations that should be the main target of therapy. According to our data, CCNE1, MYC, MDM2 and PPARG genes could be interesting therapeutic targets for bladder CSC subpopulations. Surprisingly, HER2 copy number gains are not retained in bladder CSCs, making the gene-targeted therapy less interesting than the others. These results provide precious advice for further study on bladder therapy; however, the clinical importance of these results should be explored.

  4. Consistent genomic alterations in carcinoma in situ of the urinary bladder confirm the presence of two major pathways in bladder cancer development

    DEFF Research Database (Denmark)

    Zieger, Karsten; Marcussen, Niels; Borre, Michael

    2009-01-01

    examined 48 high-risk non-muscle-invasive bladder cancers using SNP microarrays to reveal characteristic changes correlated with the CIS-phenotype. DNA copy-number changes were further validated using QPCR in 77 independent tumor samples. CIS was found to be chromosomal unstable in 8 of 12 cases....... Characteristic chromosomal changes were copy number gains of chromosomes 5p, 6p22.3, 10p15.1 and losses/LOH of chromosome 5q and 13q13-q14. Tumor samples with these alterations were significantly associated with CIS. Using FGFR3 mutations as markers of the opposing papillary phenotype, we found 5p gains and FGFR......3 mutations mutually exclusive. No FGFR3 mutations were found in 23 CIS and dysplasia samples. Based on this, we classified high-risk non-muscle-invasive bladder tumors according to FGFR3 mutations and chromosomal changes into papillary and CIS-type tumors with high correlation to CIS status (p = 0...

  5. Radionuclide targeting with particular emphasis on urinary bladder carcinoma

    CERN Document Server

    Sjöström, A

    2001-01-01

    primary bladder carcinoma tumours was investigated. Both receptors were expressed in the majority of metastases and primary tumours. Targeting the EGF receptor and/or HER-2 in urinary bladder carcinoma is an exciting new concept The incidence of urinary bladder carcinoma is increasing and many patients die every year of this disease despite assumed radical therapy. Thus, there is a need for improved methods of diagnosis and therapy. Radionuclide targeting is based on achieving specific delivery of radioactive nuclides to tumour cells with minimal damage to surrounding normal tissues. Two possible target structures are the epidermal growth factor (EGF) receptor and the related receptor HER-2. Cellular binding and retention of sup 1 sup 2 sup 5 I-EGF-dextran conjugates was investigated in two bladder carcinoma cell lines. The conjugate bound specifically to the EGF receptor with delayed maximum binding, limited intracellular degradation and prolonged cellular retention compared to sup 1 sup 2 sup 5 I-EGF. EGF w...

  6. Transitional Cell Carcinoma within a Portion of Inguinally Herniated Bladder

    Directory of Open Access Journals (Sweden)

    Matthew A. Uhlman

    2013-01-01

    Full Text Available Bladder herniation within the inguinal canal is a relatively uncommon finding. We report an even less-common occurrence of transitional cell carcinoma located within a portion of inguinally herniated bladder. Fewer than 20 reports exist in the literature describing this scenario.

  7. Thin-section CT with air insufflation technique for bladder carcinoma: CT findings of superficial bladder carcinoma

    International Nuclear Information System (INIS)

    Kim, Hyun; Song, Ha Hun; Kim, Mi Hye; Lee, Eun Ja; Kim, Young Sin; Kang, Si Won; Shinn, Kyung Sub

    1994-01-01

    The staging of bladder carcinoma is a major determinant of operative management CT of bladder carcinoma has been widely used to diagnose external extension (pT3b and over), but tumors confined to the bladder wall (from pT1 to pT3a) are poorly delineated. The authors describe CT findings of the superficial bladder carcinoma (below T1, stage A) in thin-section CT with air insufflation technique (air insufflation-CT) to facilitate early detection and to aid correct staging of the superficial bladder carcinoma. The materials consisted of proved 24 cases (19 patients, single tumor: 16 patients, multiple tumors: 3 patients) of stage A bladder carcinomas. Air insufflation-CT was performed by the infusion of approximately 200 mL of air into the bladder via a Foley catheter. After the routine pelvic CT, bladder tumors were re-scanned with 1.5 to 5 mm thickness and intervals. The superficial bladder carcinoma were detected as nodular(5 cases, 20.8%), papillary(15 cases, 62.5%), pyramida(2 cases, 8.3%), and domed(2 cases, 8.3%) forms on air insufflation-CT. These tumors were classified into three types according to the size of the tumoral neck: type I(pedundulated polypoid tumor: 4 cases, 16.6%), type II(polypid tumor with short neck: 13 cases, 54.2%), and type III(sessile tumor: 7 cases, 29.2%). The mean size(tumoral width x height x base c neck/stalk) of the tumors was 22 x 20 x 16mm. The average tumoral sizes according to each type of the superficial tumors were type I: 22 x 25 x 6mm, type II: 23 x 22 x 18mm, and type III: 18 x 15 x 18mm. The mean width of the type I-II tumoral necks was 15mm. The mean length of the type I tumoral neck(pedicle) was 2.5mm. Papillary fronds of the tumors were seen in 10 cases(41.7%) of 24 superficial tumors. Outer margin of the involved bladder wall was smooth in all cases. Thin-section CT with air insufflation technique for bladder carcinoma was useful in tumoral demonstration, and characteristics of the superficial bladder carcinomas were

  8. BCG Induced Necrosis of the Entire Bladder Urothelium

    Directory of Open Access Journals (Sweden)

    Malte Krönig

    2015-09-01

    Full Text Available Instillation therapy with attenuated tuberculosis bacteria (BCG can significantly reduce rates of recurrence of non-muscle invasive bladder cancer. Local and systemic side effects such as dysuria, irritative voiding symptoms or partial bladder contracture and systemic inflammation were reported. A 75 year-old male patient with recurrent non muscle invasive bladder cancer developed necrosis of the entire bladder urothelium more than six years after BCG instillation immunotherapy. The resulting irritative voiding symptoms and low bladder capacity required radical cystectomy. BCG instillation can cause severe side effects, which develop gradually and eventually need radical surgical therapy such as cystectomy without tumor recurrence.

  9. Pure Lymphoepithelioma-Like Carcinoma Originating from the Urinary Bladder

    Directory of Open Access Journals (Sweden)

    Takashi Nagai

    2016-03-01

    Full Text Available Lymphoepithelioma-like carcinoma of the urinary bladder (LELCB is a rare variant of infiltrating urothelial carcinoma. We report a case of LELCB in a 43-year-old man. Ultrasonography and cystoscopy revealed two bladder tumors, one on the left side of the trigone and the other on the right side of the trigone. Transurethral resection of the bladder tumors was performed and pathological analysis revealed undifferentiated carcinoma. We therefore performed radical cystectomy and urinary diversion. Immunohistochemically the tumor cells were positive for cytokeratin, but negative for Epstein-Barr virus-encoded small RNA in situ hybridization as found for previous cases of LELCB. The final pathological diagnosis was a lymphoepithelioma-like variant of urothelial carcinoma with perivesical soft tissue invasion. For adjuvant systemic chemotherapy, three courses of cisplatin were administered. The patient subsequently became free of cancer 72 months postoperatively. Based on the literature, pure or predominant LELCB types show favorable prognoses due to their sensitivity to chemotherapy or radiotherapy. An analysis of the apparent diffusion coefficient (ADC values of bladder tumors examined in our institution revealed that the ADC value measured for this LELCB was relatively low compared to conventional urothelial carcinomas. This suggests that measuring the ADC value of a lymphoepithelioma-like carcinoma prior to operation may be helpful in predicting LELCB.

  10. SOX4 expression in bladder carcinoma

    DEFF Research Database (Denmark)

    Aaboe, Mads; Birkenkamp-Demtroder, Karin; Wiuf, Carsten

    2006-01-01

    The human transcription factor SOX4 was 5-fold up-regulated in bladder tumors compared with normal tissue based on whole-genome expression profiling of 166 clinical bladder tumor samples and 27 normal urothelium samples. Using a SOX4-specific antibody, we found that the cancer cells expressed...... in the clinical bladder material and a small subset of the genes showed a high correlation to SOX4 expression. The present data suggest a role of SOX4 in the bladder cancer disease....... the SOX4 protein and, thus, did an evaluation of SOX4 protein expression in 2,360 bladder tumors using a tissue microarray with clinical annotation. We found a correlation (P bladder cell line HU609, SOX4...

  11. Urology and nephrology update: bladder and kidney cancer.

    Science.gov (United States)

    Fiore, David C; Fox, Cara-Louise

    2014-01-01

    It has been estimated that bladder and kidney cancers would be diagnosed in approximately 140,000 Americans in 2013, with approximately 30,000 dying from these cancers. Urinary tract cancers affect men more commonly than they do women, and the median age at diagnosis is 65 years. Major risk factors for these cancers include tobacco smoking, certain chemical exposures, family history, age, and obesity. Unexplained hematuria in adults should be evaluated to exclude bladder and kidney cancer. Staging of bladder and kidney cancer should be based on the TNM staging system, which, along with tumor grade, provides important treatment and prognostic information. Urothelial cell carcinoma is the most common type of bladder cancer; it also can occur in the kidneys or ureters. Renal cell carcinoma is the most common type of kidney cancer. Treatment options for bladder cancer vary widely, depending on the grade of the cancer. Early non-muscle-invasive bladder cancer may be removed cystoscopically and/or treated with intravesical immunotherapy or chemotherapy, whereas patients with muscle-invasive bladder tumors typically require surgery. Management of kidney cancer is almost always surgical, unless the patient is too ill to undergo surgery or chooses palliative care. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

  12. Contemporary management of low-risk bladder cancer

    NARCIS (Netherlands)

    Falke, J.; Witjes, J.A.

    2011-01-01

    Bladder cancer comprises a heterogeneous group of tumors, the majority of which are non-muscle-invasive bladder cancer (NMIBC) at initial presentation. Low-risk bladder cancer--defined as pTa low-grade papillary tumors--is the type of NMIBC with the most favorable oncologic outcome. Although the

  13. Pure primary small cell carcinoma of urinary bladder: A rare diagnostic entity

    Directory of Open Access Journals (Sweden)

    Sonia Gon

    2013-01-01

    Full Text Available Small cell carcinoma of the bladder is a rare, aggressive, poorly differentiated neuroendocrine neoplasm accounting for only 0.3-0.7% of all bladder tumors. Since the tumor is very rare, pathogenesis is uncertain. Small cell carcinomas of the urinary bladder are mixed with classic urothelial carcinomas or adenocarcinomas of the bladder in 68% cases, making pure primary small cell carcinoma even a rarer entity. The unknown etiology and natural history of small cell carcinoma of the urinary bladder represent a challenge both to the pathologist and urologists for its diagnosis and treatment, respectively.

  14. Isolated Meningeal Recurrence of Transitional Cell Carcinoma of the Bladder

    Directory of Open Access Journals (Sweden)

    Catherine Butchart

    2010-06-01

    Full Text Available Meningeal carcinomatosis occurs in 1–18% of patients with solid tumours, most commonly carcinomas of the breast and lung or melanomas. There are relatively few reports of meningeal carcinomatosis in transitional cell carcinoma of the bladder. Isolated meningeal recurrence is particularly uncommon, and we present an unusual case of this in a 58-year-old man. The case was further complicated by the somewhat atypical presentation with a confirmed ischaemic stroke. The patient died one month after presentation.

  15. Transitional cell carcinoma developing in a bladder diverticulum ...

    African Journals Online (AJOL)

    Computed tomography confirmed a left-sided narrow neck urinary bladder diverticulum, with wall thickening, in a 56-year-old man. These findings were initially detected on ultrasonographic investigation. Transitional cell carcinoma was confirmed histologically. There is an increased incidence of neoplastic transformation in ...

  16. Angiogenesis in urinary bladder carcinoma as defined by ...

    African Journals Online (AJOL)

    Background: Among the patients with bladder cancer, a group is still at risk of disease recurrence, progression, and death from their cancer after curative treatment. Angiogenesis is a crucial pathogenic mechanism for this type of urothelial carcinoma and is a potential therapeutic target. Objectives: To quantify tumor ...

  17. Management of transitional cell carcinoma of the urinary bladder at ...

    African Journals Online (AJOL)

    Management of transitional cell carcinoma of the urinary bladder at Kenyatta National Hospital, Nairobi. C G Waihenya, P N Mungai. Abstract. No Abstract. East African Medical Journal Vol. 83 (12) 2006: pp. 679-683. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL ...

  18. Carcinoma of Urinary Bladder in a Region of Low Schistosomiasis ...

    African Journals Online (AJOL)

    Aim: To study the geographical pathology of carcinoma of the urinary bladder as regards both its association with endemic schistosomiasis and the variable proportions of its histological types. Methods: A 30-year retrospective analysis was carried out with regard to Igbo patients who inhabit a region of low incidence of ...

  19. Aggressive bladder carcinoma in an HIV-positive man with tetraplegia and neurogenic bladder.

    Science.gov (United States)

    Benabdallah, Justin O; Collins, Clinton W; Carucci, Laura R; Moores, Kenneth E; Gater, David R; Klausner, Adam P

    2011-01-01

    Patients with neurogenic bladder secondary to spinal cord injury who are managed long term with an indwelling catheter are known to be at increased risk for transitional cell carcinoma of the bladder. Immunosuppression is a known risk factor for malignancies that often are more aggresSive than those seen in normal populations. Case report and discussion of management recommendations. We summarize the case of a 44-year-old HIV-positive C5-C6 incomplete tetraplegic male (date of injury 1980), who was diagnosed with transitional cell carcinoma of the bladder and succumbed to disease within 6 months of diagnosis. The patient was a non-smoker who was never managed with an indwelling catheter. There has been no such case reported in the literature. HIV infection in the presence of a neurogenic bladder may carry an increased risk of aggressive bladder malignancy. More studies are warranted to determine whether routine annual screening with cystoscopy in all patients with HIV and neurogenic bladder is indicated.

  20. Computed tomography in staging of bladder carcinoma (Prospective study)

    International Nuclear Information System (INIS)

    Lee, Kyung Soo; Choi, Byung Ihn; Han, Man Chung

    1985-01-01

    Staging of carcinoma of the urinary bladder is important for the choice of therapy and also has prognostic implications. Hitherto the staging has been based upon cystoscopy with biopsy, transurethral resection, and palpation with complementary radiographic examinations such as cystography, urography, lymphangiography, ultrasound and angiography. However, with all these methods, the staging of bladder carcinomas still uncertain and inferior to CT. Authors analyzed CT staging of bladder cancers and compared with pathologic staging of laparotomy results. The results are as following: 1. Overall accuracy of CT staging in bladder carcinoma was 72 percent. 2. Overstaging was 20 percent (5/25) and understaging was 8 percent (2/25). 3. All of CT stage B cancers were proven to be stage B, pathologically. 4. In 6 cases of CT static cancers, only one was correct, 3 were overstaged and 2 were understaged. 5. In 7 cases of CT stage D cancers, 5 were correct and 2 were overstaged. 6. CT detected only 2 cases of pelvic lymph node involvement in 4 of pathologically proven lymphadenopathy

  1. The efficacy of Apaziquone in the treatment of bladder cancer

    NARCIS (Netherlands)

    Caramés Masana, Francisco; de Reijke, Theo M.

    2017-01-01

    Bladder cancer is nowadays a common tumor. Non-muscle invasive bladder cancer (NMIBC) has still chances of recurrence and progression in spite of surgery and adjuvant treatments. New therapies are being developed to reduce these percentages with less adverse effects - Apaziquone (EO9) is an example.

  2. PDT-induced apoptosis in bladder carcinoma cells

    Science.gov (United States)

    Bachor, Ruediger; Reich, Ella D.; Kleinschmidt, Klaus; Repassy, Denes; Hautmann, Richard E.

    1999-02-01

    Photodynamic therapy (PDT) is a highly efficient inducer of apoptosis in EY-28 bladder carcinoma cells, resulting in extensive DNA fragmentation. Bladder carcinoma cells EY-28 (Tumorbank Heidelberg, Germany) were incubated for 1 h with 1 (mu) g AamTPPn/ml or 2 (mu) g AamTPPn/ml. After incubation cells were refed with complete medium and irradiated with 0.75 J/cm2. To identify apoptotic cells, a in situ cell death detection kit POD (Boehringer Mannheim, Germany) was used. The chromatin condensation characteristic to apoptotic cells was detected by transmission electron microscopy. Using 1 (mu) g AamTPPn/ml and 2 (mu) g AamTPPn/ml (9-Acetamido-2,7,12,17- tetra-n-Porpylporphycene), respectively, and irradiation at 0.75 J/cm2, a percentage of 36.9% and 54.7%, respectively, of apoptotic cells was detected.

  3. Trastuzumab therapy in metastatic bladder carcinoma: The proof of concept

    Directory of Open Access Journals (Sweden)

    Moussaid Y

    2014-08-01

    Full Text Available About 10% of metastatic urothelial carcinoma overexpress oncogenic HER2/neu receptor. Recent preliminary data suggest that patients with this particular molecular subset could benefit from trastuzumab therapy, which specifically targets the receptor and thus inhibits downstream activation pathway. Here we report a case illustrating this clinical benefit, with complete response reported as third line therapy in a heavily pretreated patient with diffuse metastatic urothelial carcinoma of the bladder. It also highlights the usefulness of 18-Fluorodeoxyglucose Positron Emission Tomography (18-FDG PET as a biomarker for response to trastuzumab.

  4. A rare bladder cancer - small cell carcinoma: review and update

    Directory of Open Access Journals (Sweden)

    Ismaili Nabil

    2011-11-01

    Full Text Available Abstract Small cell carcinoma of the bladder (SCCB is rare, highly aggressive and diagnosed mainly at advanced stages. Hematuria is the main symptom of this malignancy. The origin of the disease is unknown; however the multipotent stem cell theory applies best to this case. Histology and immunohistochemistry shows a tumour which is indistinguishable from small cell lung carcinoma (SCLC. Coexistence of SCCB with other types of carcinoma is common. The staging system used is the TNM-staging of bladder transitional cell carcinoma. The treatment is extrapolated from that of SCLC. However, many patients with SCCB undergo radical resection which is rarely performed in SCLC. Patients with surgically resectable disease ( or = cT4bN+M+ should be managed with palliative chemotherapy based on neuroendocrine type regimens comprising a platinum drug (cisplatin in fit patients. The prognosis of the disease is poor mainly in the case of pure small cell carcinoma. Other research programs are needed to improve the outcome of SCCB.

  5. [Neuroendocrine carcinoma of the urinary bladder. A case report].

    Science.gov (United States)

    Aragón-Tovar, Anel Rogelio; Pineda-Rodríguez, Marco Elí; Puente-Gallegos, Francisco Edgardo; Zavala-Pompa, Angel

    2014-01-01

    Small cell carcinoma of the urinary bladder is an infrequent lesion. We present the case of a 68-year-old male who arrived at the emergency room with a history of 24-h gross hematuria. Imaging studies show a urinary bladder tumor with a 218 cc volume that during a 20-day period increased to 426 cc. Histopathological images with hematoxylin-eosin show an infiltrating solid mass with uneven borders. It is composed of neoplastic cells with evident nuclei predominance and scant cytoplasm (small cells). Chromogranin immunohistochemical staining shows a diffusely positive cytoplasmic granular pattern on neoplastic cells. High molecular weight cytokeratin staining shows a negative pattern on neoplastic cells along with a positive pattern on reporsurrounding normal urothelium. Tumoral mass is positive for synaptophysin and CD-56 and negative for CK-7 and CK-20. Patient therapy was based on radiation plus chemotherapy. Small cell carcinoma of the urinary bladder represents 0.35-0.70% of urinary bladder tumors. Histological and immunohistochemical identification are key elements in the diagnosis. Treatment approach is based on cisplatin-based chemotherapy plus radical cystectomy, except when metastatic disease is present.

  6. Bladder hemorrhage after radiotherapy for carcinoma of the cervix uteri

    International Nuclear Information System (INIS)

    Matsuyama, Toshitake; Tsukamoto, Naoki; Sugimori, Hajime; Yoshino, Teruo; Kashiwamura, Masamichi.

    1979-01-01

    The relationship among the incidence, the time of occurrence, and radiation dose was studied in regard to hemorrhagic cystitis after radiotherapy for carcinoma of the cervix uteri. Of 1004 patients with carcinoma of the cervix uteri observed between 1961 and 1974, 28 (2.8%) had bladder hemorrhage seemingly due to radiation injury (0.7% were serious). Incidences varied every year. The radiation dose was increased from 4000 to 6000 rad after 1971. In addition to this external dose, because the depth-dose has also increased, the rate of bladder hemorrhage has become high. Seven patients with serious bladder hemorrhage were exposed to more than 5000 rad of 60 Co. Bladder hemorrhage occurred comparatively frequently in patients in whom two hila were irradiated. It usually occurred a few years after irradiation (about 1 year after initial rectal hemorrhage). It continued for approximately 1 year in 21 patients, for approximately 3 years in 4 patients, and for approximately 4 years in 3 patients. Adrenochrome (a hemostatic agent) and antiplasmin were used as therapeutic agents. Serious patients improved remarkably when a large amount of diluted formaline solution or conjugated estrogen was administered intravenously. (Namekawa, K.)

  7. Urine cytology of micropapillary carcinoma of the urinary bladder.

    Science.gov (United States)

    Sakuma, Takahiko; Furuta, Michiko; Mimura, Akihiro; Tanigawa, Naoto; Takamizu, Ryuichi; Kawano, Kiyoshi

    2011-11-01

    A case of micropapillary carcinoma (MPC) of urinary bladder is presented, in which the urine smear was studied in detail in an attempt to better characterize the cytologic findings of MPC. When the voided urine was examined in low power, cancer cells were scattered in the specimens as compact papillary/spheroidal clusters composed of pleomorphic cancer cells. Solitary carcinoma cells were occasionally observed. High power view of the smear revealed that the papillae/spheroids consisted of high-grade urothelial carcinoma cells. The cancer cells had pleomorphic nuclei with coarsely granular chromatin and thickened, irregular nuclear membrane, and thick cytoplasm. Histologically, the tumor in the resected bladder appeared as small nests with surrounding hallo both in the luminal surface and in the site of wall involvement. These tightly bound papillary/spheroidal clusters comprised of highly atypical cancer cells were the most specific cytologic finding in the urine of MPC, which were considered as a key diagnostic clue of MPC. The background of the urine smear showed numerous granulocytes and bacilli compatible with cystitis, which is a previously known complication of MPC. Differential diagnoses of MPC from those with pertinent cytologic findings such as conventional UC (including glandular differentiation), and primary/secondary adenocarcinoma of urinary bladder are discussed with a brief review of literature. Copyright © 2010 Wiley-Liss, Inc.

  8. Gall bladder carcinoma with ampullary carcinoma: A rare case of double malignancy

    Directory of Open Access Journals (Sweden)

    Praveer Rai

    2013-01-01

    Full Text Available Simultaneous double cancers in the biliary system are rare. Most are associated with pancreaticobiliary maljunction (PBM. However, it can occur in patients without PBM. Differentiation between these events is important since these two mechanistic origins imply different stages of disease, as well as different subsequent treatments and prognoses. Herein, we report a case of ampullary carcinoma associated with gall bladder carcinoma diagnosed nonoperatively and palliated with biliary metal stenting.

  9. Urothelial Carcinoma of the Urinary Bladder in Young Adults — Clinical Experience at Taipei Veterans General Hospital

    Directory of Open Access Journals (Sweden)

    Yu-Ching Wen

    2005-06-01

    Conclusion: Urothelial carcinoma of the urinary bladder in young adults is usually associated with low grade and low stage. Invasive bladder cancer had no worse a survival rate than superficial bladder cancer.

  10. [Disseminated BCG infection in patients with urinary bladder carcinoma].

    Science.gov (United States)

    Korać, Milos; Milosević, Branko; Lavadinović, Lidija; Janjić, Aleksandar; Brmbolić, Branko

    2009-01-01

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

  11. Researchers studying alternative to bladder removal for bladder cancer patients | Center for Cancer Research

    Science.gov (United States)

    A new phase I clinical trial conducted by researchers at the Center for Cancer Research (CCR) is evaluating the safety and tolerability, or the degree to which any side effects can be tolerated by patients, of a two-drug combination as a potential alternative to bladder removal for bladder cancer patients. The trial targets patients with non-muscle invasive bladder cancer (NMIBC) whose cancers have stopped responding to traditional therapies. Read more...

  12. Long intergenic non-coding RNA TUG1 is overexpressed in urothelial carcinoma of the bladder.

    Science.gov (United States)

    Han, Yonghua; Liu, Yuchen; Gui, Yaoting; Cai, Zhiming

    2013-04-01

    Long intergenic non-coding RNAs (lincRNAs) are a class of non-coding RNAs that regulate gene expression via chromatin reprogramming. Taurine Up-regulated Gene 1 (TUG1) is a lincRNA that is associated with chromatin-modifying complexes and plays roles in gene regulation. In this study, we determined the expression patterns of TUG1 and the cell proliferation inhibition and apoptosis induced by silencing TUG1 in urothelial carcinoma of the bladder. The expression levels of TUG1 were determined using Real-Time qPCR in a total of 44 patients with bladder urothelial carcinomas. Bladder urothelial carcinoma T24 and 5637 cells were transfected with TUG1 siRNA or negative control siRNA. Cell proliferation was evaluated using MTT assay. Apoptosis was determined using ELISA assay. TUG1 was up-regulated in bladder urothelial carcinoma compared to paired normal urothelium. High TUG1 expression levels were associated with high grade and stage carcinomas. Cell proliferation inhibition and apoptosis induction were observed in TUG1 siRNA-transfected bladder urothelial carcinoma T24 and 5637 cells. Our data suggest that lincRNA TUG1 is emerging as a novel player in the disease state of bladder urothelial carcinoma. TUG1 may have potential roles as a biomarker and/or a therapeutic target in bladder urothelial carcinoma. Copyright © 2012 Wiley Periodicals, Inc.

  13. Proteomics research on muscle-invasive bladder transitional cell carcinoma

    Directory of Open Access Journals (Sweden)

    Cao Yan

    2011-06-01

    Full Text Available Abstract Background Aimed to facilitate candidate biomarkers selection and improve network-based multi-target therapy, we perform comparative proteomics research on muscle-invasive bladder transitional cell carcinoma. Laser capture microdissection was used to harvest purified muscle-invasive bladder cancer cells and normal urothelial cells from 4 paired samples. Two-dimensional liquid chromatography tandem mass spectrometry was used to identify the proteome expression profile. The differential proteins were further analyzed using bioinformatics tools and compared with the published literature. Results A total of 885/890 proteins commonly appeared in 4 paired samples. 295/337 of the 488/493 proteins that specific expressed in tumor/normal cells own gene ontology (GO cellular component annotation. Compared with the entire list of the international protein index (IPI, there are 42/45 GO terms exhibited as enriched and 9/5 exhibited as depleted, respectively. Several pathways exhibit significantly changes between cancer and normal cells, mainly including spliceosome, endocytosis, oxidative phosphorylation, etc. Finally, descriptive statistics show that the PI Distribution of candidate biomarkers have certain regularity. Conclusions The present study identified the proteome expression profile of muscle-invasive bladder cancer cells and normal urothelial cells, providing information for subcellular pattern research of cancer and offer candidate proteins for biomarker panel and network-based multi-target therapy.

  14. Vinorelbine rescue therapy for dogs with primary urinary bladder carcinoma.

    Science.gov (United States)

    Kaye, M E; Thamm, D H; Weishaar, K; Lawrence, J A

    2015-12-01

    The goal of this study was to evaluate the anti-tumour activity and toxicoses of vinorelbine as a palliative rescue therapy for dogs with primary urinary bladder carcinoma. Thirteen dogs refractory to prior chemotherapeutics and one dog naïve to chemotherapeutic treatment were enrolled. Vinorelbine (15 mg m(-2) IV) was administered intravenously along with concurrent oral anti-inflammatory drugs, if tolerated. A median of six doses of vinorelbine (range: 1-16) was administered. Two dogs (14%) had partial responses, and eight (57%) experienced stable disease. Subjective improvement in clinical signs was noted in 11 dogs (78%). Adverse events were mild and primarily haematological in nature. Median time to progression was 93 days (range: 20-239 days). Median survival time for all dogs was 187 days; median survival for 13 pre-treated dogs was 207 days. Vinorelbine may have utility in the management of canine primary urinary bladder carcinoma and should be evaluated in a prospective study. © 2013 John Wiley & Sons Ltd.

  15. Low ANXA10 expression is associated with disease aggressiveness in bladder cancer

    DEFF Research Database (Denmark)

    Munksgaard, P P; Mansilla, F; Brems Eskildsen, A-S

    2011-01-01

    Markers for outcome prediction in bladder cancer are urgently needed. We have previously identified a molecular signature for predicting progression in non-muscle-invasive bladder cancer. ANXA10 was one of the markers included in the signature and we now validated the prognostic relevance of ANXA...

  16. OPIUM USE IN TRANSITIONAL CELL CARCINOMA OF THE URINARY BLADDER

    Directory of Open Access Journals (Sweden)

    A. Nourbakhsh

    2006-08-01

    Full Text Available Opium use is one of the most common forms of substance abuse in Iran and there are some evidence indicating it is a risk factor of transitional cell carcinoma (TCC of the urinary bladder. The majority of opium users are also cigarette smokers, so consideration of the high prevalence of smoking which is the most important risk factor of TCC of the urinary bladder among opium users is essential to assess the role of opium use as a possible risk factor of TCC. This study was done to evaluate the role of opium as a risk factor of TCC. A case-control study was performed on 255 individuals diagnosed with TCC of the urinary bladder by pathologic light microscopic examination of the tumor biopsies. Control population was chosen from individuals who had no history or presenting signs or symptoms of urinary problems. Case and control groups were matched by sex and age and also by cigarette smoking habits. Forty-one (18.1% of the cases and 12 (5% of controls were recognized to be opium users. Mantel-Haenszel analysis showed an odds ratio of 3.88, with 95% confidence interval of 1.99-7.57 and P value of < 0.001. Results indicate that opium use is a risk factor for TCC. The majority of opium users are also cigarette smokers, which is another important risk factor for TCC. Routine urine cytology and early evaluation in the patients presenting with any of the symptoms of urinary bladder malignancy by means of cystoscopy and urine cytology are highly recommended.

  17. Urine and bladder washing cytology for detection of urothelial carcinoma: standard test with new possibilities

    International Nuclear Information System (INIS)

    Flezar, Margareta Strojan

    2010-01-01

    Light microscopic evaluation of cell morphology in preparations from urine or bladder washing containing exfoliated cells is a standard and primary method for the detection of bladder cancer and also malignancy from other parts of the urinary tract. The cytopathologic examination is a valuable method to detect an early recurrence of malignancy or new primary carcinoma during the follow-up of patients after the treatment of bladder cancer. Characteristic cellular and nuclear signs of malignancy indicate invasive or in situ urothelial carcinoma or high-grade papillary urothelial carcinoma. However, low sensitivity of the method reflects the unreliable cytopathologic diagnosis of low-grade urothelial neoplasms as cellular and nuclear signs of malignancy in these neoplasms are poorly manifested. Many different markers were developed to improve the diagnosis of bladder carcinoma on urinary samples. UroVysion™ test is among the newest and most promising tests. By the method of in situ hybridization one can detect specific cytogenetic changes of urothelial carcinoma

  18. Role of hexaminolevulinate-guided fluorescence cystoscopy in bladder cancer

    DEFF Research Database (Denmark)

    Malmström, Per-Uno; Grabe, Magnus; Haug, Erik Skaaheim

    2012-01-01

    Hexaminolevulinate (HAL) is an optical imaging agent used with fluorescence cystoscopy (FC) for the detection of non-muscle-invasive bladder cancer (NMIBC). Guidelines from the European Association of Urology (EAU) and a recent, more detailed European expert consensus statement agree that HAL-FC ...

  19. Developments in diagnosis and prognosis of superficial bladder cancer.

    NARCIS (Netherlands)

    Moonen, P.M.J.

    2007-01-01

    Non-muscle invasive bladder encompasses the relatively innocent low risk tumours, but also the potentially lethal high risk tumours. Low risk tumours have a high chance of recurrence, but high risk tumours have both a high risk of recurrence and progression. Progression to muscle-invasive disease

  20. Surgical management of bladder transitional cell carcinoma in a vesicular diverticulum: case report.

    LENUS (Irish Health Repository)

    Raheem, Omer A

    2012-02-01

    We report a case of primary transitional cell carcinoma (TCC) of a bladder diverticum along with a literature review. A 55-year-old male presented with painless gross hematuria. A histological diagnosis of TCC within a bladder diverticulum was made following cystoscopical examination. Initially transurethral resection of bladder tumour with subsequent intravesical chemotherapy followed. As a result of recurrence and in view of bladder-sparing therapy, a distal partial cystectomy was performed. This report demonstrates that conservative bladder-sparing treatment can be achieved and subsequently followed by vigilant cystoscopy.

  1. Surgical management of bladder transitional cell carcinoma in a vesicular diverticulum: case report.

    LENUS (Irish Health Repository)

    Raheem, Omer A

    2011-08-01

    We report a case of primary transitional cell carcinoma (TCC) of a bladder diverticum along with a literature review. A 55-year-old male presented with painless gross hematuria. A histological diagnosis of TCC within a bladder diverticulum was made following cystoscopical examination. Initially transurethral resection of bladder tumour with subsequent intravesical chemotherapy followed. As a result of recurrence and in view of bladder-sparing therapy, a distal partial cystectomy was performed. This report demonstrates that conservative bladder-sparing treatment can be achieved and subsequently followed by vigilant cystoscopy.

  2. The Impact of Blue Light Cystoscopy with Hexaminolevulinate (HAL) on Progression of Bladder Cancer - A New Analysis

    NARCIS (Netherlands)

    Kamat, A.M.; Cookson, M.; Witjes, J.A.; Stenzl, A.; Grossman, H.B.

    2016-01-01

    Background: The International Bladder Cancer Group (IBCG) recently proposed a new definition of disease progression in non-muscle invasive bladder cancer (NMIBC), including change in T-stage, change to T2 or higher or change from low to high grade. Objective: To establish whether blue light

  3. Transitional cell carcinoma of the bladder in childhood: radiological findings and differential diagnosis

    International Nuclear Information System (INIS)

    Casado, L.; Mansilla, F.; Mansilla, M.D.; Marin, A.

    1998-01-01

    We present a case of transitional cell carcinoma of the bladder in an 11-year-old boy. The rarity of these tumors during childhood is pointed out. The radiological and ultrasonographic findings are described and the differential diagnosis is discussed with respect to other bladder tumors occurring in childhood. (Author) 11 refs

  4. Urothelial carcinoma of urinary bladder with exclusive heterologous component of epithelioid rhabdomyosarcoma at metastatic site.

    Science.gov (United States)

    Agarwal, Poojan; Pasricha, Sunil; Gupta, Gurudutt; Sharma, Anila; Mehta, Anurag

    2018-01-01

    Urothelial carcinoma of urinary bladder with divergent differentiation into rhabdomyosarcoma (RMS) is an extremely uncommon aggressive phenomenon. We present a case of a 74-year-old male with bladder carcinoma which metastasized to the abdominal wall as epithelioid RMS. To the best knowledge of our literature searches, an oligometastasis of exclusive heterologous component has not been described before. The clinical, radiological, and immunohistochemistry profile of the patient supported the monoclonal nature of the tumor.

  5. Experimental Treatment of Bladder Cancer with Bi-213-anti-EGFR MAb

    International Nuclear Information System (INIS)

    Seidl, Christof; Pfost, Birgit; Müller, Felix

    2013-01-01

    Therapy of non-muscle-invasive bladder cancer (carcinoma in situ) comprises transurethral resection of the tumour and subsequent instillation of the chemotherapeutic drug mitomycin C in order to eradicate remaining tumour cells. Yet 15 – 40% of treated patients relapse within 5 years. Therefore, new therapeutic strategies to combat tumour recurrence are needed. Alpha-particle emitting radionuclides efficiently kill single tumour cells or small tumour cell clusters. Because the epidermal growth factor receptor (EGFR) is overexpressed on bladder cancer cells, conjugates composed of the alpha-emitter Bi-213 and the anti-EGFR antibody matuzumab should provide a powerful drug to eliminate disseminated bladder cancer cells. Therefore, the aims of our study were (i) to analyse the cytotoxic effects of Bi-213-anti-EGFR radioimmunoconjugates at the cellular level, (ii) to evaluate therapeutic efficacy of intravesically applied Bi-213- anti-EGFR-Mab in a nude mouse model with intravesical human bladder cancer xenografts, (iii) to compare Bi- 213-anti-EGFR-Mab efficacy with chemotherapy using mitomycin C and (iv) to demonstrate that radioimmunotherapy is not toxic to cells of the bladder wall and of the kidneys

  6. Response and toxicity of photodynamic therapy for canine bladder carcinoma

    International Nuclear Information System (INIS)

    Beck, E.R.; Dunstan, R.W.

    1992-01-01

    This investigation was to determine PDT efficacy and tolerance (both short term and long term) in dogs with spontaneously occurring transitional cell carcinoma of the urinary bladder. All patients were T2-T3, N x , M o . 27 dogs were given Photofrin II at 3.0 mg/kg IV, and 72 hours later doses of 632 nm light from 5-25 J/cm 2 . In 25/27 dogs, PDT resulted in complete remission of stranguria, hematuria and pollackiuria within one week of treatment. Gross hematuria increased in 7 dogs for the first 2 days following treatment, but then disappeared completely. Duration of clinical remission varied from 5-25 weeks after single treatment, within a median duration of 10 weeks. Doses of light from 5-10 J/cm 2 were well tolerated, with only mild toxicity for 1-3 days. Moderate toxicity showed in some dogs given 10-15 J/cm 2 . In all dogs given 25 J/cm 2 and 46% of those given 15 J/cm 2 , severe abdominal cramping, fecal incontinence, perforations and sepsis was seen. A second PDT treatment of 10-15 J/cm 2 following recurrence of clinical signs was administered to 9 dogs, without an increase in toxicity beyond that seen following the first treatment. Median duration of this second remission was 8 weeks, with a range of 5-12 weeks. 4-5 multiple PDT treatments were given to 4 dogs without any clinical symptoms of decreased bladder function. Each treatment produced an additional remission of variable length. (author). 14 refs., 1 fig., 1 tab

  7. A rare case of synchronous renal cell carcinoma of the bladder presenting with gross hematuria

    Directory of Open Access Journals (Sweden)

    Stephan Kruck

    2013-05-01

    Full Text Available A 57-year old man was referred to the Urology Department due to gross hematuria; abdominal ultrasound revealed an unspecific solid tumor of the left bladder wall. Ultrasound, transurethral resection of the bladder mass with subsequent histological analysis, thoracic and abdominal computed tomography-scan and brain magnetic resonance imaging were performed. He was diagnosed with a bladder metastasis of clear cell renal cell carcinoma (RCC with concomitant bone, pulmonary, and cerebral metastatic disease of a primary RCC of the right kidney. Management: Transurethral resection of the bladder mass, cerebral and bone radiotherapy, removal of the primary tumor, targeted systemic therapy with mTOR followed by tyrosine kinase inhibition.

  8. Expression of RFC/SLC19A1 is associated with tumor type in bladder cancer patients.

    Directory of Open Access Journals (Sweden)

    Alyaa M Abdel-Haleem

    Full Text Available Urinary bladder cancer (UBC ranks ninth in worldwide cancer. In Egypt, the pattern of bladder cancer is unique in that both the transitional and squamous cell types prevail. Despite much research on the topic, it is still difficult to predict tumor progression, optimal therapy and clinical outcome. The reduced folate carrier (RFC/SLC19A1 is the major transport system for folates in mammalian cells and tissues. RFC is also the primary means of cellular uptake for antifolate cancer chemotherapeutic drugs, however, membrane transport of antifolates by RFC is considered as limiting to antitumor activity. The purpose of this study was to compare the mRNA expression level of RFC/SLC19A1 in urothelial and non-urothelial variants of bladder carcinomas. Quantification of RFC mRNA in the mucosa of 41 untreated bladder cancer patients was performed using RT-qPCR. RFC mRNA steady-state levels were ∼9-fold higher (N = 39; P<0.0001 in bladder tumor specimens relative to normal bladder mRNA. RFC upregulation was strongly correlated with tumor type (urothelial vs. non-urothelial; p<0.05 where median RFC mRNA expression was significantly (p<0.05 higher in the urothelial (∼14-fold compared to the non-urothelial (∼4-fold variant. This may account for the variation in response to antifolate-containing regimens used in the treatment of either type. RFC mRNA levels were not associated with tumor grade (I, II and III or stage (muscle-invasive vs. non-muscle invasive implying that RFC cannot be used for prognostic purposes in bladder carcinomas and its increased expression is an early event in human bladder tumors pathogenesis. Further, RFC can be considered as a potential marker for predicting response to antifolate chemotherapy in urothelial carcinomas.

  9. Diagnosis of Bladder Cancer Recurrence Based on Urinary Levels of EOMES, HOXA9, POU4F2, TWIST1, VIM, and ZNF154 Hypermethylation

    DEFF Research Database (Denmark)

    Reinert, Thomas; Borre, Michael; Christiansen, Anders

    2012-01-01

    Non muscle invasive bladder cancer (NMIBC) has the highest recurrence rate of any malignancy and as many as 70% of patients experience relapse. Aberrant DNA methylation is present in all bladder tumors and can be detected in urine specimens. Previous studies have identified DNA methylation markers...

  10. Expression profiles of variation integration genes in bladder urothelial carcinoma.

    Science.gov (United States)

    Wang, J M; Wang, Y Q; Gao, Z L; Wu, J T; Shi, B K; Yu, C C

    2014-04-30

    Bladder cancer is a common cancer worldwide and its incidence continues to increase. There are approximately 261,000 cases of bladder cancer resulting in 115,000 deaths annually. This study aimed to integrate bladder cancer genome copy number variation information and bladder cancer gene transcription level expression data to construct a causal-target module network of the range of bladder cancer-related genomes. Here, we explored the control mechanism underlying bladder cancer phenotype expression regulation by the major bladder cancer genes. We selected 22 modules as the initial module network to expand the search to screen more networks. After bootstrapping 100 times, we obtained 16 key regulators. These 16 key candidate regulatory genes were further expanded to identify the expression changes of 11,676 genes in 275 modules, which may all have the same regulation. In conclusion, a series of modules associated with the terms 'cancer' or 'bladder' were considered to constitute a potential network.

  11. Types of HLA in the bladder transitional cell carcinoma (TCC).

    Science.gov (United States)

    Yılmaz, Erkan; Uğur Özalp, Ali; Cekmen, Arman; Eren, Bülent; Onal, Bülent; Akkuş, Emre; Erdoğan, Ergun

    2013-02-01

    HLA plays a complementary role in the interaction between tumor and body immunology. The aim of this study was to determine the existence of the association between the HLA system and transitional cell carcinoma (TCC). Using standard micro-lymphocytotoxic method of Terasaki, HLA-A, B, DR and DQ antigen types of 30 patients with TCC of the bladder were compared with the control group (30 healthy people). In the TCC patient group, HLA -DQ6(1) and HLA -DQ7(3) antigens were detected with a significantly higher frequency than in the control group (p=0.018 and p=0.038, respectively), whereas HLA-A10, B4, DR53 and DQ1 antigens were detected with significantly higher frequency in the control group (p less 0.05 in all). It suggests that patients who had the antigens detected were at higher risk of TCC, and the ones who had the antigens displaying protective features as were detected in the control group, were at lesser risk.

  12. Circular RNA expression is abundant and correlated to aggressiveness in early-stage bladder cancer

    DEFF Research Database (Denmark)

    Okholm, Trine Line Hauge; Nielsen, Morten Muhlig; Hamilton, Mark

    2017-01-01

    The functions and biomarker potential of circular RNAs (circRNAs) in various cancer types are a rising field of study, as emerging evidence relates circRNAs to tumorigenesis. Here, we profiled the expression of circRNAs in 457 tumors from patients with non-muscle-invasive bladder cancer (NMIBC). We...

  13. Urothelial carcinoma with prominent squamous differentiation in the setting of neurogenic bladder: role of human papillomavirus infection.

    Science.gov (United States)

    Blochin, Elen B; Park, Kay J; Tickoo, Satish K; Reuter, Victor E; Al-Ahmadie, Hikmat

    2012-11-01

    Squamous cell carcinomas of the urinary bladder are rare in the Western world; the majority of cases are reported in countries endemic to Schistosoma parasitic infections. Unlike squamous tumors of the uterine cervix or oropharynx, the human papillomavirus (HPV) is not commonly associated with bladder squamous cell carcinomas. We report on two cases of HPV-positive urothelial carcinomas of the urinary bladder with extensive squamous differentiation showing the typical basaloid, poorly differentiated morphology of HPV-associated tumors. These occurred in patients with neurogenic bladders who had long-standing histories of self-catheterization with tumors that tested positive for HPV by in situ hybridization. A retrospective review of our institutional database revealed four additional patients with bladder tumors showing squamous differentiation arising in the setting of neurogenic bladder. Review of these cases showed the more common well-differentiated keratinizing appearance of squamous cell carcinomas of the bladder. These tumors showed only patchy positivity for p16 immunohistochemical stain (not the diffuse strong staining seen in HPV-positive tumors), and the one tested case was negative for HPV by in situ hybridization. HPV infection and neurogenic bladder have been independently associated with increased risk of developing carcinoma in the urinary bladder; however, this is the first report of squamous tumors arising in the setting of concurrent neurogenic bladder and HPV infection. The morphology of these tumors is similar to that of other high-risk HPV-associated squamous carcinomas with a basaloid, poorly differentiated appearance and little to no keratin formation.

  14. [Micropapillary carcinoma of the bladder: case report and review of the literature].

    Science.gov (United States)

    Ripa Saldías, L; Guarch Troyas, R; Hualde Alfaro, A; De Pablo Cárdenas, A; Pinós Paul, M; Santiago González de Garibay, A

    2005-04-01

    Micropapillary carcinoma is an uncommon pathologic variant of bladder carcinoma with aggressive behavior. Its usual presentation is like a high grade and high stage carcinoma and associated with other histologic types in different proportion. It doesn't differ clinically from normal transitional cell carcinoma of the bladder. Studies of molecular markers are still contradictories. Treatment should be early and aggresive, based on surgical therapy as radiotherapy and chemotherapy have shown limited results. We report a 72 year old man suffering from low urinary tract symptoms for years and recently presented gross hematuria. He was diagnosed as high stage micropapillary carcinoma. One year after radical cystectomy and subsequent chemotherapy based on carboplatin and gemcitabine, progression of the disease was shown on CT and the patient died 14 months after the diagnosis.

  15. Primary enteric-type adenocarcinomas of the urinary bladder are histogenetically analogous to colorectal carcinomas: Immunohistochemical evaluation of 109 cases

    Directory of Open Access Journals (Sweden)

    Saad S. Eissa

    2010-04-01

    In conclusion, primary non-urachal enteric-type adenocarcinoma of the urinary bladder is morphologically and immunophenotypically similar – if not identical – to colonic adenocarcinoma. The frequent association of enteric carcinomas of the urinary bladder with intestinal metaplasia and/or colonic-type adenomas with dysplasia suggests possible carcinogenetic pathways similar to that observed in colorectal carcinomas.

  16. Small cell carcinoma of the urinary bladder diverticulum: A case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Wu Xu Dong

    2013-01-01

    Full Text Available Small cell carcinoma of the urinary bladder is very rare. Small cell carcinoma of the urinary bladder is a mass with swiftly aggressive and metastatic, and with a poor prognosis. Due to its scarcity, no forward-looking researches assessing the most effective treatment have been issued in the medical literature. It can happen either in connection with urothelial (transitional cell carcinoma or in a pure form. Its treatment should include surgery, chemotherapy and radiotherapy. In this article,we report a case occurring in a mixed form in the urinary bladder diverticulum and we concisely review the published literature with respect to the clinical manifestation, pathology,differential diagnosis, treatment and prognosis.

  17. Analysis of failure following definitive radiotherapy for invasive transitional cell carcinoma of the bladder

    International Nuclear Information System (INIS)

    Mameghan, Hedy; Fisher, Richard; Mameghan, Jill; Brook, Susan

    1995-01-01

    Purpose: To assess prognostic factors for bladder relapse and distant failure following definitive radiotherapy for invasive transitional cell carcinoma (TCC) of the bladder. Methods and Materials: Retrospective review of patients treated in the period 1977 to 1990 by definitive radiotherapy. The factors studied included age, sex, T stage, histological grade, tumor multiplicity, ureteric obstruction, total radiation dose, and use of neoadjuvant chemotherapy. The endpoints studied were bladder relapse and distant failure. Results: There were 342 patients with a mean follow-up time of 7.9 years. Bladder relapse was observed in 159 patients. The overall actuarial bladder relapse rate at 5 years was 55% (SE = 3%). Prognostic factors for a higher bladder relapse rate were: tumor multiplicity (p < 0.001), presence of ureteric obstruction (p = 0.001), and higher T stage (p 0.044). Distant failure occurred in 39 patients. The overall actuarial distant failure rate at 5 years was 28% (SE = 3%). Prognostic factors for a higher distant failure rate were: ureteric obstruction (p = 0.003) and higher T stage (p = 0.030). Conclusion: In our study, patients with invasive bladder TCC fell into distinct prognostic groups determined by the three independent factors, ureteric obstruction, tumor multiplicity, and T stage. These factors provided estimated risks of bladder relapse by 5 years which ranged from 34% to 91%. Knowledge of these prognostic factors can help in the selection of patients more suited for bladder preservation by definitive radiotherapy

  18. Small cell carcinoma of the urinary bladder without gross hematuria: a case report.

    Science.gov (United States)

    Huang, Wanqiu; Luan, Yang; Jin, Lu; Wang, Tao; Chen, Ruibao; Liu, Zheng; Chen, Zhiqiang; Lan, Ruzhu

    2015-09-01

    Small cell carcinoma of the urinary bladder (SCCB) is a rare and aggressive form of bladder cancer with poor prognosis. Hematuria is the main symptom of this malignancy, and most patients have a history of smoking. The disease incidence of malignant bladder tumors in China is approximately 0.74%. Early and accurate diagnosis of SCCB can ensure timely and appropriate treatment of this malignant disease. Oncologic surgery is the standard treatment; however, it may not be a curative approach. Chemotherapy and/or radiotherapy should be performed following surgical removal. This case report describes a patient with a single neoplasm diagnosed as SCCB that arose because of recurrence of bladder cancer after bladder tumor resection. In contrast to previously reported cases, this patient had no gross hematuria and no history of smoking.

  19. Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder

    DEFF Research Database (Denmark)

    Gui, Yaoting; Guo, Guangwu; Huang, Yi

    2011-01-01

    frequently in tumors of low stages and grades, highlighting its potential role in the classification and diagnosis of bladder cancer. Our results provide an overview of the genetic basis of TCC and suggest that aberration of chromatin regulation might be a hallmark of bladder cancer.......Transitional cell carcinoma (TCC) is the most common type of bladder cancer. Here we sequenced the exomes of nine individuals with TCC and screened all the somatically mutated genes in a prevalence set of 88 additional individuals with TCC with different tumor stages and grades. In our study, we...

  20. Bacillus Calmette-Guérin (BCG) Treatment Failures with Non-Muscle Invasive Bladder Cancer: A Data-Driven Definition for BCG Unresponsive Disease.

    Science.gov (United States)

    Steinberg, Ryan L; Thomas, Lewis J; Mott, Sarah L; O'Donnell, Michael A

    2016-04-27

    Objective: To create the first data-driven definition for those unlikely to benefit from further BCG treatment. Materials and Methods: The database created for the Phase 2 BCG-Interferon- α 2B (IFN) study was queried and BCG failure patients were identified ( n  = 334). Full study protocols have previously been published. Separate models were constructed for analysis of patients with any CIS (pure or concomitant) and pure papillary disease. Variables considered included age, gender, stage, grade, tumor size and focality (for papillary only), number of prior BCG courses, and prior BCG failure interval. Results: Patients with recurrent CIS within 6 months of their most recent prior BCG course (HR 2.56, p  disease within 6 months (HR 1.82, p  = 0.02), ≥2 BCG failures (HR 1.54, p  = 0.03), and multifocal disease (HR 2.05, p  disease remained disease free in 38% of cases (24-51% 95% CI) at 2 years with low rates of progression. Conclusions: Patients who fail two courses of BCG with either persistent or recurrent multifocal papillary disease within 6 months or CIS within 12 months of their prior BCG should be considered BCG unresponsive. Recurrent T1 disease respond reasonably well to another course with low progression rates but further investigation is warranted.

  1. Anti-angiogenic effects of the superantigen staphylococcal enterotoxin B and Bacillus Calmette-Guerin immunotherapy in the non-muscle invasive bladder cancer

    OpenAIRE

    Leonardo Oliveira Reis

    2011-01-01

    Resumo: O tratamento do câncer de bexiga urotelial não músculo invasivo (CBNMI) com Bacilo Calmette-Guerin (BCG) tem efeito comprovado na redução de recidiva tumoral, embora ocorram efeitos colaterais de intensidades variadas, desde sintomas irritativos leves até reação sistêmica grave e o impacto na progressão tumoral seja controverso. Neste cenário a enterotoxina B do Staphylococcus aureus (EBS) destaca-se como alternativa promissora na terapêutica do CBNMI. Assim, os objetivos principais d...

  2. The efficacy of BCG TICE and BCG Connaught in a cohort of 2,099 patients with T1G3 non-muscle-invasive bladder cancer

    NARCIS (Netherlands)

    Witjes, J.A.; Dalbagni, G.; Karnes, R.J.; Shariat, S.; Joniau, S.; Palou, J.; Serretta, V.; Larre, S.; Stasi, S. Di; Colombo, R.; Babjuk, M.; Malmstrom, P.U.; Malats, N.; Irani, J.; Baniel, J.; Cai, T.; Cha, E.; Ardelt, P.; Varkarakis, J.; Bartoletti, R.; Spahn, M.; Pisano, F.; Gontero, P.; Sylvester, R.

    2016-01-01

    BACKGROUND: Potential differences in efficacy of different bacillus Calmette-Guerin (BCG) strains are of importance for daily practice, especially in the era of BCG shortage. OBJECTIVE: To retrospectively compare the outcome with BCG Connaught and BCG TICE in a large study cohort of pT1 high-grade

  3. Vaginal metastasis of bladder urothelial carcinoma: Description of a case and revision of literature.

    Science.gov (United States)

    Di Franco, Carmelo A; Porru, Daniele; Giliberto, Giovanni; Viglio, Alessandra; Rovereto, Bruno

    2017-06-30

    Vaginal metastases from urothelial cancer are a rare entity and in literature, few cases are described. We report a case of a 68 year-old woman with history of bladder urothelial carcinoma underwent to radical cystectomy who came in our department after 5 months for pelvic pain and vaginal bleeding. Objective examination revealed an ulcerative, solid vaginal lesion in the upper vaginal wall. We performed a vaginal biopsy that showed urothelial carcinoma compatible with the primitive bladder cancer. The patient underwent to surgery and was sent to oncological evaluation.

  4. Artificial intelligence and bladder cancer arrays.

    Science.gov (United States)

    Wild, P J; Catto, J W F; Abbod, M F; Linkens, D A; Herr, A; Pilarsky, C; Wissmann, C; Stoehr, R; Denzinger, S; Knuechel, R; Hamdy, F C; Hartmann, A

    2007-01-01

    Non-muscle invasive bladder cancer is a heterogenous disease whose management is dependent upon the risk of progression to muscle invasion. Although the recurrence rate is high, the majority of tumors are indolent and can be managed by endoscopic means alone. The prognosis of muscle invasion is poor and radical treatment is required if cure is to be obtained. Progression risk in non-invasive tumors is hard to determine at tumor diagnosis using current clinicopathological means. To improve the accuracy of progression prediction various biomarkers have been evaluated. To discover novel biomarkers several authors have used gene expression microarrays. Various statistical methods have been described to interpret array data, but to date no biomarkers have entered clinical practice. Here, we describe a new method of microarray analysis using neurofuzzy modeling (NFM), a form of artificial intelligence, and integrate it with artificial neural networks (ANN) to investigate non-muscle invasive bladder cancer array data (n=66 tumors). We develop a predictive panel of 11 genes, from 2800 expressed genes, that can significantly identify tumor progression (average Logrank p = 0.0288) in the analyzed cancers. In comparison, this panel appears superior to those genes chosen using traditional analyses (average Logrank p = 0.3455) and tumor grade (Logrank, p = 0.2475) in this non-muscle invasive cohort. We then analyze panel members in a new non-muscle invasive bladder cancer cohort (n=199) using immunohistochemistry with six commercially available antibodies. The combination of 6 genes (LIG3, TNFRSF6, KRT18, ICAM1, DSG2 and BRCA2) significantly stratifies tumor progression (Logrank p = 0.0096) in the new cohort. We discuss the benefits of the transparent NFM approach with respect to other reported methods.

  5. Local control rate and prognosis after sequential chemoradiation for small cell carcinoma of the bladder

    International Nuclear Information System (INIS)

    Meijer, Richard P.; Meinhardt, Wim; Poel, Henk G. van der; Rhijn, Bas W. van; Kerst, J. Martijn; Pos, Floris J.; Horenblas, Simon; Bex, Axel

    2013-01-01

    The objectives of this study were to assess the long-term outcome and the risk for local recurrence of patients with small cell carcinoma of the bladder (SCCB) treated with neoadjuvant chemotherapy followed by external beam radiotherapy (sequential chemoradiation). All consecutive patients with primary small cell carcinoma of the bladder (n=66), treated in our institution between 1993 and 2011 were retrospectively evaluated from an institutional database. Only patients with limited disease (Tx-4N0-1M0) small cell carcinoma of the bladder treated with sequential chemoradiation (n=27) were included in this study. Recurrence rates, overall survival and cancer-specific survival were analyzed using the Kaplan-Meier method. Median time to recurrence was 20 months, median overall survival 26 months, 5-year overall survival 22.2%, median cancer-specific survival 47 months and 5-year cancer-specific survival 39.6%. For complete responders after neoadjuvant chemotherapy (n=19), median cancer-specific survival was 52 months with a 5-year cancer-specific survival 45.9% versus a median cancer-specific survival of 22 months and 5-year cancer-specific survival 0.0% for incomplete responders (n=8; P=0.034). Eight patients (29.6%) underwent transurethral resections (TUR-BT) for local recurrences in the bladder. At the end of follow up, four patients had undergone cystectomy for recurrence of disease resulting in a bladder-preservation rate of 85.2%. Median time to local recurrence was 29 months and median time to distant recurrence was 10 months. Sequential chemoradiation for limited disease small cell carcinoma of the bladder results in a reasonable outcome with a high bladder preservation rate. Response to neoadjuvant chemotherapy represents a significant prognostic factor in this patient population. (author)

  6. Autopsy findings in surgical-radiotherapeutically treated bladder carcinoma - conclusions for optimization of radiotherapy

    International Nuclear Information System (INIS)

    Fueller, J.; Kob, D.; Fritzsche, V.

    1989-01-01

    Autopsy findings in patients with bladder carcinoma, treated by combined operation and radiotherapy, revealed tendencies of tumor spread as well as complications and late effects of radiotherapy. In 24.5% of the cases tumor tissue was found within the bladder and in 30.5% within the minor pelvis. Metastases were found in 24.1% in iliac lymph nodes, in 21.3% in abdominal lymph nodes. Liver, lungs, bones, and kidneys are main organs for hematological metastasizing. Little or undifferentiated carcinomas and squamous cell carcinomas showed a greater tendency to metastasize than highly and medium-differentiated ureteral carcinomas. The least radiotherapeutical complications and late effects were found in a fractionation with daily 1.5 Gy and a total dose of 60 Gy. (author)

  7. Expression of RFC/SLC19A1 is associated with tumor type in bladder cancer patients.

    Science.gov (United States)

    Abdel-Haleem, Alyaa M; El-Zeiry, Maha I; Mahran, Laila G; Abou-Aisha, Khaled; Rady, Mona H; Rohde, Jan; Mostageer, Marwa; Spahn-Langguth, Hilde

    2011-01-01

    Urinary bladder cancer (UBC) ranks ninth in worldwide cancer. In Egypt, the pattern of bladder cancer is unique in that both the transitional and squamous cell types prevail. Despite much research on the topic, it is still difficult to predict tumor progression, optimal therapy and clinical outcome. The reduced folate carrier (RFC/SLC19A1) is the major transport system for folates in mammalian cells and tissues. RFC is also the primary means of cellular uptake for antifolate cancer chemotherapeutic drugs, however, membrane transport of antifolates by RFC is considered as limiting to antitumor activity. The purpose of this study was to compare the mRNA expression level of RFC/SLC19A1 in urothelial and non-urothelial variants of bladder carcinomas. Quantification of RFC mRNA in the mucosa of 41 untreated bladder cancer patients was performed using RT-qPCR. RFC mRNA steady-state levels were ∼9-fold higher (N = 39; PRFC upregulation was strongly correlated with tumor type (urothelial vs. non-urothelial; pRFC mRNA expression was significantly (pRFC mRNA levels were not associated with tumor grade (I, II and III) or stage (muscle-invasive vs. non-muscle invasive) implying that RFC cannot be used for prognostic purposes in bladder carcinomas and its increased expression is an early event in human bladder tumors pathogenesis. Further, RFC can be considered as a potential marker for predicting response to antifolate chemotherapy in urothelial carcinomas.

  8. Carcinoma of Gall bladder with distant metastasis to breast parenchyma. Report of a case and review of literature

    International Nuclear Information System (INIS)

    Kumaran, D.; Anamalai, M.; Velu, U.; Julka, P.K.; Nambirajan, A.

    2016-01-01

    Background: Gall bladder carcinoma is one of the most common cancers in India. Gall bladder cancer with metastasis to the breast is very rare. Herein we intend to report a case of carcinoma gall bladder with breast metastasis and a short review of the literature. Methods: This report describes an interesting and unusual case of gall bladder carcinoma presenting with breast metastasis. Case report: A 38-year lady presented with complaints of right abdominal pain. Bilateral breast examination showed 2 2 cm palpable lump in the upper outer quadrant of the left breast. Contrast-enhanced CT of the abdomen and pelvis showed circumferential thickening of gall bladder with the loss of fat plane with the adjacent liver parenchyma. Biopsy from the breast lump was reported as metastatic adenocarcinoma compatible with primary in the gall bladder. Whole body PET-CT showed gall bladder mass with abdominal and pelvic nodes with metastasis to liver, left breast, C7 vertebral body and left supra-clavicular node. She was diagnosed to have disseminated carcinoma gall bladder with liver, breast and supraclavicular nodal metastasis. She received palliative chemotherapy with gemcitabine and carboplatin and radiotherapy to C7 vertebra. After receiving 3 cycles of chemotherapy, chemotherapy was changed to the second line with single agent capecitabine. In spite of two lines of chemotherapy, she succumbed to disease progression and expired. Conclusion: There are limited examples of gall bladder adenocarcinoma with simultaneous metastasis to breast in the English literature. Our case showed an unusual dissemination of gall bladder cancer

  9. Human papillomavirus-related basaloid squamous cell carcinoma of the bladder associated with genital tract human papillomavirus infection.

    Science.gov (United States)

    Ginori, Alessandro; Barone, Aurora; Santopietro, Rosa; Barbanti, Gabriele; Cecconi, Filippo; Tripodi, Sergio Antonio

    2015-02-01

    Basaloid squamous cell carcinoma is a biologically aggressive neoplasm mainly found in the head and neck region. Recently, four cases of basaloid squamous cell carcinoma of the bladder have been reported, and three of them occurred in patients with neurogenic bladder, repeated catheterizations and human papillomavirus infection of the urinary tract. To the best of our knowledge, none of the patients affected by basaloid squamous cell carcinoma of the bladder described in the literature had documented genital involvement by human papillomavirus. Herein, we describe the case of a woman with neurogenic bladder affected by basaloid squamous cell carcinoma of the bladder and by a concomitant genital tract human papillomavirus infection. © 2014 The Japanese Urological Association.

  10. Appraisal of diagnostic ability of UCA1 as a biomarker of carcinoma of the urinary bladder.

    Science.gov (United States)

    Srivastava, A K; Singh, P K; Rath, S K; Dalela, D; Goel, M M; Bhatt, M L B

    2014-11-01

    Initial diagnosis of carcinoma of the urinary bladder remains to be a challenge. Urine cytology, as an adjunct to cystoscopy, is less sensitive for low-grade tumors. Urothelial cancer associated 1 (UCA1) is a novel non-coding RNA gene, which plays a pivotal role in bladder cancer progression. Our aim is to investigate the significance of urinary UCA1 for the non-invasive diagnosis of transitional cell carcinoma (TCC) of the urinary bladder. We examined UCA1 expression in a bladder cancer cell line (T24) and in urine of 28 healthy individuals, 46 patients of non-malignant disorders, and 117 cases (69 primary and 48 recurrent cases) of histologically proven TCC prior to transurethral resection by using real-time PCR and compared it with voided urinary cytology. UCA1 expression was found in T24 cell line and also found to be significantly higher in the cancer group as compared to the controls (p0.05). UCA1 can be used as a non-invasive diagnostic biomarker for TCC bladder as an adjunct to cytology in the early diagnosis of primary urinary bladder cancer.

  11. Status of Her2 over expression in muscle invasive urothelial bladder carcinoma: Report of 21 cases

    Directory of Open Access Journals (Sweden)

    Nesrine Mejri

    2014-01-01

    Four patients died from disease, one of them had Her2 3+ score. Conclusion: Her2 overexpression can be observed in muscle invasive urothelial bladder carcinoma in an important number of patients. Evaluation criteria must be standardized, especially with heterogeneous cases. Metastases tests can also readdress the expression of Her2, which gives the patient a supplementary therapeutic tool.

  12. Expression of cathepsin D in bladder carcinoma: correlation with pathological features and serum cystatin C levels.

    Science.gov (United States)

    Tokyol, Cidğem; Köken, Tülay; Demirbas, Murat; Dilek, Fatma Hüsniye; Yörükoglu, Kutsal; Mungan, Ugur; Kirkali, Ziya

    2006-01-01

    The aim of this study is to evaluate the expression of cathepsin D in primary bladder cancer and to determine its relationship with conventional pathological features and serum cystatin C levels. The immunohistochemical cathepsin D expression and staining patterns of epithelial and stromal cells were investigated in 21 patients with primary bladder carcinoma. Serum cystatin C levels were determined by immunoturbidimetry and compared with matched controls. There were 7 papillary neoplasms of low malignant potential, 7 low-grade and 7 high-grade carcinomas. Six tumors were invasive. Statistical analysis showed a significant inverse relationship between cathepsin D expression of the tumor cells and tumor grade and stage (P = 0.018 and P = 0.046, respectively). Serum cystatin C levels of the controls and patients varied between 0.39 mg/L and 1.99 mg/L (P > 0.05). There was no significant relation between cathepsin D expression in tumor tissue and serum cystatin C levels. Loss of cathepsin D expression in bladder carcinomas may be associated with high-grade and invasive tumors. Thus, increased cathepsin D expression by tumor cells may be related to local tumor invasion at an early stage, but it seems that extracellular cystatin C is not affected by cathepsin D expression of tumor or stromal cells, and cystatin C concentrations are not directly correlated with the progression of primary bladder carcinomas.

  13. Sarcomatoid urothelial carcinoma of the bladder: a contemporary clinicopathologic analysis of 37 cases.

    Science.gov (United States)

    Fatima, Nazneen; Canter, Daniel J; Carthon, Bradley C; Kucuk, Omer; Master, Viraj A; Nieh, Peter T; Ogan, Kenneth; Osunkoya, Adeboye O

    2015-06-01

    Sarcomatoid urothelial carcinoma is a dedifferentiated biphasic tumor that exhibits morphological and/or immunohistochemical evidence of epithelial and mesenchymal differentiation. In this series, we analyzed the clinicopathologic features of this rare variant of urothelial carcinoma. A search was made through our surgical pathology files and consultation files of the senior author for cases of sarcomatoid urothelial carcinoma of the bladder from 2005-2014. All the slides were retrieved and re-reviewed, and clinical data was also obtained including follow up. Thirty-seven cases of sarcomatoid urothelial carcinoma of the bladder were identified. Mean patient age was 71 years (range: 51 to 88 years). Twenty-six of 37 (70%) patients were male and 11/37 (30%) patients were female. Twenty-five cases were from cystectomy/cystoprostatectomy specimens, 8 cases from transurethral resection of bladder tumor specimens and 4 cases were from biopsy specimens. The mean tumor size was 5 cm (range: 1.4 cm to 13.0 cm). Four of 37 (10%) cases had focal heterologous components; 1 case with both chondroid and osteoid, 2 cases with chondroid and 1 case rhabdoid elements. Twenty-one of 37 (56%) patients died within a year of presentation. Sarcomatoid urothelial carcinoma of the bladder is more prevalent in males, with the mean age of 71 years in our series. Smoking is an important risk factor. Sarcomatoid urothelial carcinoma is an aggressive variant of urothelial carcinoma which commonly presents at an advanced stage, and over 50% of patients in our series died of disease within 1 year of presentation.

  14. Squamous Cell Carcinoma of the Bladder Mimicking Interstitial Cystitis and Voiding Dysfunction

    Directory of Open Access Journals (Sweden)

    Colton Prudnick

    2013-01-01

    Full Text Available Squamous cell carcinoma (SCC of the bladder is a relatively uncommon cause of bladder cancer accounting for <5% of bladder tumors in the western countries. SCC has a slight male predominance and tends to occur in the seventh decade of life. The main presenting symptom of SCC is hematuria, and development of this tumor in the western world is associated most closely with chronic indwelling catheters and spinal cord injuries. A 39-year-old Caucasian female presented with bladder and lower abdominal pain, urinary frequency, and nocturia which was originally believed to be interstitial cystitis (IC but was later diagnosed as SCC of the bladder. Presentation of SCC without hematuria is an uncommon presentation, but the absence of this symptom should not lead a practitioner to exclude the diagnosis of SCC. This case is being reported in an attempt to explain the delay and difficulty of diagnosis. Background on the risk factors for SCC of the bladder and the typical presenting symptoms of bladder SCC and IC are also reviewed.

  15. Lymphoepithelioma-like carcinoma of the urinary bladder: A case report.

    Science.gov (United States)

    Laforga, Juan B; Gasent, Joan M

    We report a case of lymphoepithelioma-like carcinoma of the urinary bladder in an elderly female patient. A 97-year old woman presented with hematuria, and an ultrasonographic urinary study showed a localized tumor in the trigone region of the urinary bladder. A transurethral resection revealed a mixed tumor formed by high-grade transitional carcinoma and lymphoepithelioma-like carcinoma that had infiltrated into the muscular propria. We describe the clinicopathological, morphological and immunohistochemical features of this tumor and briefly discuss its differential diagnosis and biological behavior. Copyright © 2016 Sociedad Española de Anatomía Patológica. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. Spontaneous rupture of bladder diverticulum after postoperative radiotherapy for carcinoma of the uterine cervix. A case report

    Energy Technology Data Exchange (ETDEWEB)

    Nishimura, Tetsuo; Suzuki, Kazunori; Iijima, Mitsuharu; Nozue, Masashi; Imai, Michiko; Suzuki, Sachiko; Sakahara, Harumi; Ohta, Nobutaka; Kasami, Masako [Hamamatsu Univ. School of Medicine, Shizuoka (Japan)

    2000-08-01

    We present a case of spontaneous rupture of bladder diverticulum three years after postoperative whole pelvic irradiation (50.4 Gy) for carcinoma of the uterine cervix. The patient had suffered from a neurogenic bladder after hysterectomy, but excretory urography revealed no abnormalities. Bladder diverticulum was found two years later. Spontaneous rupture of the urinary bladder is one of the late complications associated with radiotherapy, although it is very rare. Postoperative neurogenic bladder may also be associated with rupture. We should be aware of this rare complication in patients who receive pelvic irradiation. (author)

  17. Bladder Carcinoma Data with Clinical Risk Factors and Molecular Markers: A Cluster Analysis

    Directory of Open Access Journals (Sweden)

    Enrique Redondo-Gonzalez

    2015-01-01

    Full Text Available Bladder cancer occurs in the epithelial lining of the urinary bladder and is amongst the most common types of cancer in humans, killing thousands of people a year. This paper is based on the hypothesis that the use of clinical and histopathological data together with information about the concentration of various molecular markers in patients is useful for the prediction of outcomes and the design of treatments of nonmuscle invasive bladder carcinoma (NMIBC. A population of 45 patients with a new diagnosis of NMIBC was selected. Patients with benign prostatic hyperplasia (BPH, muscle invasive bladder carcinoma (MIBC, carcinoma in situ (CIS, and NMIBC recurrent tumors were not included due to their different clinical behavior. Clinical history was obtained by means of anamnesis and physical examination, and preoperative imaging and urine cytology were carried out for all patients. Then, patients underwent conventional transurethral resection (TURBT and some proteomic analyses quantified the biomarkers (p53, neu, and EGFR. A postoperative follow-up was performed to detect relapse and progression. Clusterings were performed to find groups with clinical, molecular markers, histopathological prognostic factors, and statistics about recurrence, progression, and overall survival of patients with NMIBC. Four groups were found according to tumor sizes, risk of relapse or progression, and biological behavior. Outlier patients were also detected and categorized according to their clinical characters and biological behavior.

  18. Carcinoma Of The Urinary Bladder In Maiduguri, Nigeria: A ...

    African Journals Online (AJOL)

    Simple statistical analysis was used in analyzing the cases. RESULTS: Squamous cell carcinoma was the commonest tumour and accounted for 70% of the cases. Transitional cell carcinoma constituted 22%. The least common tumours were embryonal rhabdomyosarcoma and carcinosarcoma contributing one case each.

  19. Evaluation of the Efficacy of the H. pylori Protein HP-NAP as a Therapeutic Tool for Treatment of Bladder Cancer in an Orthotopic Murine Model.

    Science.gov (United States)

    Codolo, Gaia; Munari, Fabio; Fassan, Matteo; de Bernard, Marina

    2015-05-29

    Bladder cancer is one of the most common malignancies of the urogenital tract. Intravesical injection of Bacillus Calmette-Guérin (BCG) is the gold standard treatment for the high-grade non-muscle invasive bladder cancer (NMIBC). However, since the treatment-related side effects are relevant, newer biological response modifiers with a better benefit/side effects ratio are needed. The tumour microenvironment can influence both tumour development and therapy efficacy. In order to obtain a good model, it is desirable to implant tumour cells in the organ from which the cancer originates. In this protocol, we describe a method for establishing a tumour in the bladder cavity of female mice and subsequent delivery of therapeutic agents; the latter are exemplified by our use of Helicobacter pylori neutrophil activating protein (HP-NAP). A preliminary chemical burn of the mucosa, followed by the injection of mouse urothelial carcinoma cell line MB49 via urethral catheterization, enables the cells to attach to the bladder mucosa. After a period, required to allow an initial proliferation of the cells, mice are treated with HP-NAP, administrated again via catheterization. The anti-tumour activity of HP-NAP is evaluated comparing the tumour volume, the extent of necrosis and the degree of vascularization between vehicle- and HP-NAP-treated animals.

  20. Secondary hematologic neoplasm after intravesical chemotherapy for superficial bladder carcinoma

    NARCIS (Netherlands)

    Sonneveld, P.; Kurth, K. H.; Hagemeyer, A.; Abels, J.

    1990-01-01

    Two cases are reported of patients who developed a hematologic malignancy several years after intravesical chemotherapy of superficial bladder cancer with etoglucid, doxorubicin, and mitomycin C. In one patient, karyotypic abnormalities (-5, 7q-) typical of a therapy induced malignancy were

  1. Seminal vesicle cyst associated with ipsilateral renal agenesis and papillary carcinoma of the bladder

    Energy Technology Data Exchange (ETDEWEB)

    Gorrea, M.; Lorente, R.; Roel, J. [Dept. of Radiology, Hospital Gomez Ulla, Madrid (Spain)

    2001-12-01

    We report a case of seminal vesicle cyst associated with ipsilateral renal agenesis in a 37-year-old patient with papillary carcinoma of the bladder. Ultrasonography showed absence of the right kidney, a bladder tumour and a round retrovesical hypoechogenic mass with posterior acoustic enhancement. It showed low attenuation on CT, low signal intensity on T1-weighted MR images and high signal intensity on T2-weighted MR images. Intravenous urography (IVU) and cystoscopy were also performed. After surgery, it proved to be a seminal vesicle cyst. The embryology, imaging characteristics and differential diagnosis of seminal vesicle cysts are discussed. Associated findings are also described. (orig.)

  2. Forced diuresis 18F-fluorodeoxyglucose positron emission tomography/contrast enhanced in detection of carcinoma of urinary bladder diverticulum

    International Nuclear Information System (INIS)

    Soundararajan, Ramya; Singh, Harmandeep; Arora, Saurabh; Nayak, Brusabhanu; Shamim, Shamim Ahmed; Bal, Chandrasekhar; Kumar, Rakesh

    2015-01-01

    Urinary bladder diverticular carcinomas are uncommon with a lesser incidence of 0.8–10% and its diagnosis still remains a challenge. Cystoscopy is the most reliable method, but evaluating diverticulum with narrow orifices is difficult. Before the initiation of appropriate treatment, proper detection of bladder diverticular carcinoma and its locoregional and distant sites of involvement is necessary. Here, we present a case of 48-year-old male with urinary bladder diverticular carcinoma detected by forced diuretic 18 F-fluorodeoxyglucose positron emission tomography/computerized tomography ( 18 F-FDG PET/CT). This case also highlights the significance of forced diuretic 18 F-FDG PET/CT in the detection, staging, and response evaluation of bladder diverticular carcinoma

  3. Selective arterial embolization for control of haematuria secondary to advanced or recurrent transitional cell carcinoma of the bladder.

    LENUS (Irish Health Repository)

    Halpenny, D

    2014-05-02

    Haematuria is a common symptom in patients with advanced transitional cell carcinoma of the bladder. We report our experience of selective pelvic embolization using gelfoam as an embolic agent to treat intractable haematuria in these patients.

  4. Animal model of naturally occurring bladder cancer: Characterization of four new canine transitional cell carcinoma cell lines

    OpenAIRE

    Rathore, Kusum; Cekanova, Maria

    2014-01-01

    Background Development and further characterization of animal models for human cancers is important for the improvement of cancer detection and therapy. Canine bladder cancer closely resembles human bladder cancer in many aspects. In this study, we isolated and characterized four primary transitional cell carcinoma (K9TCC) cell lines to be used for future in vitro validation of novel therapeutic agents for bladder cancer. Methods Four K9TCC cell lines were established from naturally-occurring...

  5. A case of brain and leptomeningeal metastases from urothelial carcinoma of the bladder.

    Science.gov (United States)

    Erhamamcı, S; Reyhan, M; Altinkaya, N

    2014-01-01

    Brain metastases are unusual from urethelial carcinoma of bladder and particularly the occurrence of leptomeningeal metastases is extremely rare, with few cases described in the literature. We present a case of a 45-year-old man with a rare brain metastases as the first metastatic manifestation secondary to urethelial carcinoma of bladder followed by leptomeningeal metastases without any other organ involvement. Eleven months after the diagnosis of high-grade urethelial carcinoma of bladder (T2N0M0), the patient was detected having brain metastases by MRI. FDG PET/CT images for the metastatic evaluation showed no abnormal FDG uptake elsewhere in the body except the brain. Histopathology examination from brain lesion demonstrated the cerebral lesion to be a metastatic urothelial carcinoma. Two months later, the patient was diagnosed to have leptomeningeal metastases by MRI. Our patient's condition gradually worsened, and he died 3 months after the diagnosis of leptomeningeal metastases. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.

  6. Risk factors for transitional cell carcinoma of urinary bladder: a hospital based study

    International Nuclear Information System (INIS)

    Fayyaz, A.; Ilyas, M.; Qayyum, A.

    2011-01-01

    Objective: The objective of the study was to determine the role of various known risk factors for the development of Transitional cell carcinoma (TCC) of urinary bladder in our set up. Study design: Case control study Place and duration of the study: Department of Radiology CMH Rawalpindi, from March 2007 to December 2007. Material and methods: 70 patients with TCC urinary bladder were included in the study. 70 controls were included. The patients were enquired about the risk factors. The data was analysed on SPSS version 12. Odds ratio for each factor was carried out. p value of < 0.05 was considered statistically significant. Results: Smoking was the most important factor in the development of TCC of urinary bladder with odds ratio of 3:1. Driving was the next common factor. Low socioeconomic conditions appear to be an important factor in our set up. The role of chemicals in industrial work could not be established. Conclusion: Differences from the West exist regarding the etiological factors for the development of TCC of urinary bladder. Males outnumber the females by a significant ratio. Smoking is an important factor in the development of TCC of urinary bladder. Most bladder cancers arise in low socioeconomic group in our set up. (author)

  7. Non-invasive prediction of recurrence in bladder cancer by detecting somatic TERT promoter mutations in urine.

    Science.gov (United States)

    Descotes, Françoise; Kara, Norelyakin; Decaussin-Petrucci, Myriam; Piaton, Eric; Geiguer, Florence; Rodriguez-Lafrasse, Claire; Terrier, Jean E; Lopez, Jonathan; Ruffion, Alain

    2017-08-08

    Urothelial bladder cancer (UBC) is characterised by a high risk of recurrence. Patient monitoring is currently based on iterative cystoscopy and on urine cytology with low sensitivity in non-muscle-invasive bladder cancer (NMIBC). Telomerase reverse transcriptase (TERT) is frequently reactivated in UBC by promoter mutations. We studied whether detection of TERT mutation in urine could be a predictor of UBC recurrence and compared this to cytology/cystoscopy for patient follow-up. A total of 348 patients treated by transurethral bladder resection for UBC were included together with 167 control patients. Overall sensitivity was 80.5% and specificity 89.8%, and was not greatly impacted by inflammation or infection. TERT remaining positive after initial surgery was associated with residual carcinoma in situ. TERT in urine was a reliable and dynamic predictor of recurrence in NMIBC (P<0.0001). In univariate analysis, TERT positive-status after initial surgery increased risk of recurrence by 5.34-fold (P=0.0004). TERT positive-status was still associated with recurrence in the subset of patients with negative cystoscopy (P=0.034). TERT mutations in urine might be helpful for early detection of recurrence in UBC, especially in NMIBC.

  8. Bladder Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology.

    Science.gov (United States)

    Spiess, Philippe E; Agarwal, Neeraj; Bangs, Rick; Boorjian, Stephen A; Buyyounouski, Mark K; Clark, Peter E; Downs, Tracy M; Efstathiou, Jason A; Flaig, Thomas W; Friedlander, Terence; Greenberg, Richard E; Guru, Khurshid A; Hahn, Noah; Herr, Harry W; Hoimes, Christopher; Inman, Brant A; Jimbo, Masahito; Kader, A Karim; Lele, Subodh M; Meeks, Joshua J; Michalski, Jeff; Montgomery, Jeffrey S; Pagliaro, Lance C; Pal, Sumanta K; Patterson, Anthony; Plimack, Elizabeth R; Pohar, Kamal S; Porter, Michael P; Preston, Mark A; Sexton, Wade J; Siefker-Radtke, Arlene O; Sonpavde, Guru; Tward, Jonathan; Wile, Geoffrey; Dwyer, Mary A; Gurski, Lisa A

    2017-10-01

    This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Bladder Cancer focuses on systemic therapy for muscle-invasive urothelial bladder cancer, as substantial revisions were made in the 2017 updates, such as new recommendations for nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab. The complete version of the NCCN Guidelines for Bladder Cancer addresses additional aspects of the management of bladder cancer, including non-muscle-invasive urothelial bladder cancer and nonurothelial histologies, as well as staging, evaluation, and follow-up. Copyright © 2017 by the National Comprehensive Cancer Network.

  9. Clear cell urothelial carcinoma of the urinary bladder: a case report and review of the literature.

    Science.gov (United States)

    Knez, Virginia M; Barrow, Willis; Lucia, M Scott; Wilson, Shandra; La Rosa, Francisco G

    2014-08-14

    The occurrence of clear cell tumors in the bladder is not uncommon. Clear cell dysplasia is well-described and characterized by focal replacement of transitional mucosa by cells with abundant clear cytoplasm, nuclear enlargement, and a granular chromatin pattern. Clear cells can also be seen in clear cell adenocarcinoma, which is rare, comprising 0.5% to 2.0% of the reported bladder carcinomas. Other clear cell tumors found in the bladder to be considered in the differential diagnosis are tumors of Müllerian origin and metastatic lesions, such as renal cell carcinoma, clear cell sarcoma, and malignant melanoma. Clear cell urothelial carcinoma is exceedingly rare, with only nine clinical cases described in the literature. We report the case of a 75-year-old Caucasian man who presented with intermittent hematuria, in whom a bladder tumor was identified. A final histopathology examination of a cystoprostatectomy specimen revealed a pT3b, G3 urothelial carcinoma of clear cell type (>90% clear cells) and a prostatic adenocarcinoma of Gleason grade 3+3 (score=6). The bladder tumor consisted of sheets of malignant cells with severe nuclear atypia and abundant clear cytoplasm; no glandular or tubular structures were identified. Tumor cells were periodic acid-Schiff positive and negative after diastase treatment; additional mucicarmine and oil red O stains were negative. Immunohistochemical stains showed the tumor cells positive for cytokeratin 7 (CK7), p63 (>80% nuclei), p53 (about 30% nuclei), vimentin, E-cadherin, cluster of differentiation (CD10), and Ki-67 (>70% nuclei). Stains for cell adhesion molecule 5.2 (CAM 5.2), CD117, cytokeratin 20 (CK20), human melanoma black 45 (HMB-45), paired box protein (PAX 8), placental alkaline phosphatase (PLAP), prostate specific antigen (PSA), renal cell carcinoma (RCC), cancer antigen 25 (CA25), leukocyte common antigen (LC), S-100 protein, and uroplakin III were all negative. The tumor marker profile was consistent with clear

  10. Carcinoma-in-situ bladder -an early indication for cystectomy?

    Directory of Open Access Journals (Sweden)

    V Kumar

    2002-01-01

    All patients diagnosed to have CIS bladder histolo-gically in Harrogate District Hospital from August 94 to August 99 were included in the study. All data con-cerning the management, treatment and subsequent fol-low-up were collected from the patients′ records and analysed in a systematic way. A total of 20 patients were included in the study. Analysis showed that there was no age or sex predilection and the age group ranged from 36 to 75. It occurs either alone or with papillary bladder tumour. It is found to be poor prognostic indi-cator for subsequent ttunour recurrence. Mitomvcin was the least effective and BCG is the most effective form of intravesical treatment. Failure on BCG therapy is an earlvpredictorforaggressive treatment i.e. Radical Cys-tectomy. Eventually 1/3 of all patients diagnosed to have CIS progressed to muscle invasive disease requiring radical treatment.

  11. Clinical significance of the VEGF level in urinary bladder carcinoma.

    Science.gov (United States)

    Sankhwar, Monica; Sankhwar, Satya Narayan; Abhishek, Amar; Rajender, Singh

    2015-01-01

    To investigate the correlation of Vascular Endothelial Growth Factor (VEGF) and micro-vessel density (MVD) with urinary bladder tumor and its stage. The study was conducted between January 2010 and December 2012. The study included screening of 122 patients at elevated risk for bladder cancer, of which 35 patients were finally enrolled in the study. Diagnosis was made on the basis of urine cytology, radiological investigation (ultrasound KUB, and CT-scan) and histopathology. Thirty-five normal cancer-free individuals were enrolled as controls. Human VEGF levels were measured using an enzyme linked immunoassay and protein content (pg/mg protein) by Lowry method. SPSS for Windows version 10.0.7 (SPSS, Chicago, IL, USA) was used for statistical analysis of the data. Mean urine VEGF level in the cases was significantly higher in comparison to the control group. There was a direct correlation between VEGF level and tumor stage. Mean urine VEGF values were minimum in the control group (22.75 ± 15.41 pg/mg creatinine) and maximum in stage IV patients (180.15 ± 75.93 pg/mg creatinine). Tissue VEGF levels also showed a similar trend of increase with increase in stage. Urine VEGF level also showed a correlation with tissue VEGF level. Similarly, MVD showed a significant increase with increase in tumor stage. A correlation between bladder cancer and MVD and VEGF suggest that the latter can serve as markers for therapeutic guidance. This is the first study from India on clinical and pathological correlation among urine VEGF, tumor tissue VEGF levels, and Micro Vessel Density (MVD) in urinary bladder cancer patients.

  12. IFN Alfa-2B and BCG Therapy Is An Effective Method In Superficial Bladder Carcinoma

    Directory of Open Access Journals (Sweden)

    Ahmet Ozdemir

    2012-04-01

    Full Text Available Aim: The initial therapy for superficial bladder carcinoma is the transurethral resection of the tumor. In spite of successful resections, there are 60-79% recurrence and 15% progression rates. Additional therapies are suggested for the treatment of superficial bladder carcinoma. We compared the efficacy of interferon alfa-2b monotherapy with interferon alfa-2b plus Bacillus Calmette Guerin (BCG combination therapy with urine interleukin (IL 2, 6 and 10 levels of patients with superficial bladder carcinoma. Material and Method: The patients who underwent TUR-BT for superficial bladder tumor (pathological staging Ta-T1 between 2004 and 2007 at our hospital included in this prospective study. Intravesical immunotherapy was administered once a week for 6 weeks and there after a month for 6 months, starting 4 weeks after TUR-BT. IL levels were measured. Results: IL-2, IL-6 and IL- 10 levels in urine samples were taken at 2nd and 4th hours of intravesical therapy. A statistically significant difference was observed between mean urine IL-2 levels of patients treated with IFN%u03B1-2b monotherapy and IFN%u03B1- 2b plus BCG combination both at 2nd and 4th hours. (p=0.05 In IFN%u03B1-2b plus BCG combination group, there was a statistical significant difference between stages regarding IL-2 and IL-6 levels (p=0.05. Among patients with G3 tumors, IL-2 levels were higher at 2 and 4 hours (p=0.05 but there was no significant difference in IL-6 and IL-10 levels in this group of patients regardless of intravesical therapy received (p=0.05. Discussion: IFN%u03B1-2b and BCG combination therapy is a reliable and effective therapy in the management of superficial bladder tumors.

  13. Simultaneous Penile and Signet Ring Cell Bladder Carcinoma in Renal Transplant Recipient: A First Case

    Directory of Open Access Journals (Sweden)

    Francesca Manassero

    2009-01-01

    Full Text Available The incidence and prevalence of cancer increase with time after transplantation. Therefore, a risk-adapted screening process is very important in order to identify low-grade malignancies early in their development. This provides the opportunity to initiate appropriate immunosuppressive regimens depending on the tumor type and stage of development. The first case presented is one of a 65-year-old patient with a double genitourinary carcinoma (penis and bladder. The patient received kidney transplantation 7 years prior to this event. After adequate surgical treatment (partial amputation of the penis for squamous cell carcinoma and complete transurethral resection of bladder adenocarcinoma, the patient was noted to be free of tumor recurrence and had functioning renal graft with a 2-year follow-up.

  14. [Small cell bladder carcinoma in age extremes: Report of two cases.

    Science.gov (United States)

    Vallejo-Benítez, Ana; Rodríguez-Zarco, Enrique; Pabón-Carrasco, Sara; Espinal, Paula Sofía

    2018-03-01

    We report 2 cases of small cell neuroendocrine carcinomas (CCP) of the urinary bladder in patients aged 37 and 80 years. CCP is a malignancy with poor prognosis. We review the literature, under the current WHO classification (2016). Paraffin blocks were cut for HE staining and immunohistochemistry to analyze the expression of neuroendocrine differentiation. The main diagnosis was based on histopathologic features, which revealed a diffuse growth pattern of small cells with scant cytoplasm and hyperchromatic nuclei. The result of the additional technical immunoreaction was positive for synaptophysin and CD56. Our cases have been reviewed with the literature to discuss the evolution and differential diagnosis of small cell carcinoma of the urinary bladder. This is a rare tumor with very aggressive behavior and its diagnosis lies in its morphology, and immunohistochemical profile.

  15. [Transitional cell carcinoma of the bladder in adolescents: a diagnosis to bear in mind].

    Science.gov (United States)

    Ruiz, Eduardo; Alarcón Caba, Martín; Toselli, Luzia; Moldes, Juan; Ormaechea, María; de Badiola, Francisco; Christiansen, Silvia

    2009-02-01

    Transitional cell carcinoma of the bladder has a high incidence in adults, but it is uncommon in children and adolescents. Hematuria is the most common symptom of presentation and vesical ecography the preferred diagnostic method. The diagnosis and treatment is performed with cystoscopy and endoscopic resection. We describe two patients: an 18 years old male, who presented with a pediculated tumor on the posterior bladder wall and a 15 years old female with a 1 cm long tumor on the posterior wall too; both were removed under endoscopic control. In both patients superficial transitional cell carcinoma was the final diagnosis and are disease free 3 and 5 years later. A review of the available literature was performed to clarify if this type of tumors must be considered malignant and try to define how long and by which way these patients must be controlled.

  16. Metastatic Transitional Cell Carcinoma of the Bladder to the Testis: A Case Report

    Directory of Open Access Journals (Sweden)

    Gregory N. Kozak

    2012-01-01

    Full Text Available An 84-year-old gentleman presented with onset of gross hematuria in September 2010. Follow-up investigations revealed T1 superficially invasive, poorly differentiated, papillary urothelial carcinoma. He subsequently had GreenLight laser for BPH and bladder neck contracture on two occasions. He developed a right hydrocele 16 months after initial presentation and during his hydrocelectomy, a rock-hard right epididymis and testicle were discovered. Pathology revealed metastatic urothelial carcinoma replacing nearly the entire testis with lymphovascular invasion.

  17. Evaluation of her-2/neu expression by immunohistochemistry in urothelial carcinoma of urinary bladder

    International Nuclear Information System (INIS)

    Nasim, A.; Salim, B.; Niazi, S.; Fatima, N.

    2015-01-01

    The objective of this study is to determine the HER-2/NEU expression by immunohistochemistry in Urothelial carcinoma of urinary bladder. Study Design: Cross sectional study. Place and Duration of Study: Department of Histopathology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, from 15th August 2011 to 14th August 2012. Patients and Methods: Bladder cancer tissue specimens from 70 patients were selected in one year as per the inclusion criterion. Immunohistochemistry results were interpreted on light microscope using high power field objective and Her 2/ neu expression was recorded. Mean and standard deviation were calculated for quantitative variables. Frequencies and percentages were calculated for qualitative variables. Results: Out of 70 cases of urothelial carcinoma, Her 2/ neu expression was found to be positive in 24 cases, out of which 5 were of low grade and 19 were of high grade while 16 were invasive and 8 were non invasive. The expression of Her 2/neu was detected in 16 out of 33 cases of invasive carcinoma (48.4%) and in 8 out of 37 cases of non invasive carcinoma (21.6%). As far as grade is concerned, Her 2/ neu was found to be positive in 5 out of 30 cases of low grade carcinoma (16.6%) and 19 out of 40 cases of high grade carcinoma (47.5%). Conclusion: The expression of Her 2/neu has been shown to be related to the stage and grade of urothelial carcinoma. Her 2/neu expression is increased in high grade and invasive urothelial carcinoma. Molecular targeted therapy targeting Her 2/neu can be beneficial in patients after assessment of Her 2/neu expression. (author)

  18. The value of bladder mapping and prostatic urethra biopsies for detection of carcinoma in situ (CIS).

    Science.gov (United States)

    Gudjónsson, Sigurdur; Bläckberg, Mats; Chebil, Gunilla; Jahnson, Staffan; Olsson, Hans; Bendahl, Pär-Ola; Månsson, Wiking; Liedberg, Fredrik

    2012-07-01

    It is well known that CIS is a major risk factor for muscle-invasive bladder cancer and that this entity can be difficult to diagnose. Taking cold-cup mapping biopsies from different areas of the bladder (BMAP) is commonly used in patients at risk of harbouring CIS. The diagnostic accuracy of this approach has not been assessed until now. By using the CIS found in the cystoprostatectomy specimen as an indicator of the true occurrence of CIS and comparing that with the findings of BMAP, it is clear that the sensitivity of BMAP to detect CIS when present is low and that negative findings should be considered unreliable. To assess the value of bladder mapping and prostatic urethra biopsies for detection of urothelial carcinoma in situ (CIS). CIS of the urinary bladder is a flat high-grade lesion of the mucosa associated with a significant risk of progression to muscle-invasive disease. CIS is difficult to identify on cystoscopy, and definite diagnosis requires histopathology. Traditionally, if CIS is suspected, multiple cold-cup biopsies are taken from the bladder mucosa, and resection biopsies are obtained from the prostatic urethra in males. This approach is often called bladder mapping (BMAP). The accuracy of BMAP as a diagnostic tool is not known. Male patients with bladder cancer scheduled for cystectomy underwent cold-cup bladder biopsies (sidewalls, posterior wall, dome, trigone), and resection biopsies were taken from the prostatic urethra. After cystectomy, the surgical specimen was investigated in a standardised manner and subsequently compared with the BMAP biopsies for the presence of CIS. The histopathology reports of 162 patients were analysed. CIS was detected in 46% of the cystoprostatectomy specimens, and multiple (≥2) CIS lesions were found in 30%. BMAP (cold-cup bladder biopsies + resection biopsies from the prostatic urethra) provided sensitivity of 51% for any CIS, and 55% for multiple CIS lesions. The cold-cup biopsies for CIS in the bladder

  19. Chemotherapy by M-VAC protocol in progressive bladder carcinoma treatment.

    Science.gov (United States)

    Janicic, A; Tulic, C; Radosevic-Jelic, Lj; Dzamic, Z; Acimovic, M; Hadzi-Djokic, J

    2007-01-01

    Treatment of invasive bladder carcinoma is complex therapy procedure which means surgical and non-surgical treatment appliance. In spite of radical surgical treatment conduction, the gold standard in invasive bladder tumor therapy, about 30-40% patients spread metastasis in further disease course. The system chemotherapy in invasive bladder tumors treatments is marked with accent. Its fundamental aim is to correct results of surgical treatment. This therapy option very often means the only modality in bladder carcinoma treatment, for instance, in the diseminal disease faze. The adjuvant chemotherapy imposes a task to correct surgical treatments results in case where the high risk of recidive breaking out exists. As risks for recidive breaking out cite are: a) lymphatic and vascular invasion into the primary tumor; b) extravezical tumor extension-T3b; c) tumor invasion neighboring structures-T4; d) positive lgl findings-N+. After radical cystectomy caused by high level malignancy tumors - T3b,T4, is founded frequency of positive IgI of about 40-60%. Patients with positive lgl have badly prognosis. Only 17% they survive longer than two years, and 7% have surviving of five years.

  20. Dynamic contrast enhanced MRI-derived parameters are potential biomarkers of therapeutic response in bladder carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Chakiba, Camille [Department of Medical Oncology, Bergonié Cancer Institute, Bordeaux (France); Cornelis, François [Department of Radiology, Pellegrin Hospital, Bordeaux (France); Descat, Edouard [Department of Radiology, Saint-Augustin Clinic, Bordeaux (France); Gross-Goupil, Marine [Department of Medical Oncology, Bergonié Cancer Institute, Bordeaux (France); Sargos, Paul [Department of Radiotherapy, Bergonié Cancer Institute, Bordeaux (France); Roubaud, Guilhem [Department of Medical Oncology, Bergonié Cancer Institute, Bordeaux (France); Houédé, Nadine, E-mail: nadine.houede@chu-nimes.fr [Department of Medical Oncology, Bergonié Cancer Institute, Bordeaux (France); Department of Medical Oncology, Nimes University Hosptital, Nîmes (France)

    2015-06-15

    Highlights: • DCE-MRI parameters could be useful biomarker for patients with localized bladder carcinoma. • Rate of relapse is lower for good responders assessed by DCE-MRI. • The use of DCE-MRI parameters may improve the standardization of patients’ selection before surgery. - Abstract: Objectives: To evaluate the performance of dynamic contrast enhanced (DCE) magnetic resonance (MR) imaging to assess the histological response after chemotherapy on bladder carcinoma. Methods: From 2008 to 2010, 12 patients presenting localized urothelial carcinoma of the bladder were prospectively evaluated by DCE-MR imaging before and after two courses of cisplatin-based neoadjuvant chemotherapy. Size and thickness of tumours were measured. Relative enhancement at the arterial (rSI{sub 35s}) and venous phases (rSI{sub 80s}) of each tumour was obtained. Histological response was assessed and outcomes were recorded. Results: Histological examination after neoadjuvant chemotherapy concluded as pathological complete response (pCR) for 6 out of 12 patients. Five patients developed recurrences (4/6 no pCR and 1/6 pCR). Significant differences, between before and after treatment, were found for patients with complete pathological response after chemotherapy for all MR quantitative values. Tumours decreased in size and thickness (both P = 0.03). After treatment, rSI{sub 80s} was significantly different between pCR and non-pCR patients (P = 0.04) with a cut-off value of 40%. For this cut-off, sensitivity, specificity and accuracy were 83.33%. Similar recurrence free survivals were obtained if applying the MR cut-off value or the histopathological findings. Conclusion: Our results suggest that DCE-MR imaging may be a useful biomarker for patients with localized bladder carcinoma, improving selection before surgery.

  1. Small cell carcinoma of the urinary bladder: KIT and PDGFRA gene mutations

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    Nuket Eliyakin

    2015-12-01

    Full Text Available Primary small cell carcinoma of the urinary bladder is very rare. A 72-year-old was admitted to our hospital because of hematuria and dysuria. Cystoscopy revealed a bladder full of multiple, solid and papillary tumors. Biopsies from the deep and papillary tumors were taken. Histologically, tumor was pure small cell carcinoma. Immunohistochemically, the tumor cells were positive for cytokeratin, chromogranin, synaptophysin, neuron-specific enolase, CD56, CD117 and Ki67 (labeling 70%. The tumor cells were negative for CK7, CK20, CD3, CD20, LCA, CDX2, uroplakin, thyroid transcription factor 1, PSA and p63. Metastatic workup was performed an no primary or metastatic lung lesions were noted. Due to the clinical, radiologic and immunohistochemical findings, the patient was diagnosed as primary small cell carcinoma of bladder. A molecular genetic analysis for KIT (exons 9, 11, 13 and 17 and PDGFRA (exons 12 and 18 genes was performed, in paraffin micro dissection specimens, by the PCR-direct sequencing method. According to the sequencing analyses, two mutations were found at positions 558 (p.K558N and 562 (p.E562D in KIT gene exon 11 in our case. The another hand the same case presented two mutations in PDGFRA gene exon 14 at position 631 (p.P631A and 638 (p.638Q_639AinsC. The disease process was fulminant and the patient was lost due to several complications prior to any chemotherapy.

  2. An updated review on primary signet-ring cell carcinoma of the urinary bladder and report of a case

    DEFF Research Database (Denmark)

    Lendorf, Maria Elisabeth; Dohn, Line Hammer; Á Dunga, Bara

    2018-01-01

    OBJECTIVE: The aim of the present study was to emphasize the critical importance of the clinician's awareness of signet-ring cell carcinoma (SRCC) of the urinary bladder, a rare and aggressive disease entity. MATERIALS AND METHODS: A review of the current literature was conducted and a classic case...... of advanced SRCC of the urinary bladder is reported, clearly demonstrating the severity of this disease and the imperative need for standardized recommendations for the diagnostic work-up and management of urinary bladder SRCC. RESULTS: The prognosis for patients with SRCC of the urinary bladder is poor...

  3. A Case of Early Stage Bladder Carcinosarcoma in Late Recurrence of Urothelial Carcinoma after Transurethral Resection

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    Daisaku Hirano

    2018-01-01

    Full Text Available Carcinosarcomas of the urinary bladder are rare biphasic neoplasms, consisting of both malignant epithelial and malignant mesenchymal components, and the prognosis of this tumor is unfavorable in most patients with even possibility of resection of disease. A 77-year-old male with a history of transurethral resection (TUR of urothelial carcinoma (UC of the bladder and adjuvant intravesical chemotherapy with pirarubicin 10 years ago revisited our department with a gross hematuria. Cystoscopy demonstrated an approximately 2.5 cm nonpapillary tumor on the right wall of the bladder. Pelvic MRI showed the tumor without extending the base of the bladder wall. The tumor could be completely removed with TUR. The malignant epithelial elements consisted of high-grade UC and the majority of mesenchymal components were fibrosarcomatous differentiation based on immunohistochemical studies. The tumor could be pathologically also suspected to be an early stage on TUR specimens. Although he has received no additional intervention due to the occurrence of myocardial infarction at three weeks after the TUR, he has been alive with no evidence of recurrence of the disease 27 months after the TUR. Some early stages of bladder carcinosarcoma might have a favorable prognosis without aggressive treatments.

  4. Prognostic factors in invasive bladder carcinoma treated by combined modality protocol (organ-sparing approach)

    International Nuclear Information System (INIS)

    Matos, Tadeja; Cufer, Tanja; Cervek, Jozica; Borstnar, Simona; Kragelj, Borut; Zumer-Pregelj, Mirjana

    2000-01-01

    Purpose: The results of bladder sparing approach for the treatment of muscle-invasive bladder cancer, using a combination of transurethral resection (TUR), chemotherapy, and radiotherapy, are encouraging. The survival of patients treated by this method is similar to the survival of patients treated by radical cystectomy. The aim of our study was to find out which pretreatment characteristics influence the survival of patients treated by organ sparing approach that would enable us to identify the patients most suitable for this type of treatment. Methods and Materials: The prognostic value of different factors, such as age, gender, performance status, hemoglobin level, clinical stage, histologic grade, presence of obstructive uropathy, and completeness of TUR, has been studied in 105 patients with invasive bladder cancer, who received a bladder sparing treatment in the period from 1988 to 1995. They were treated with a combination of TUR, followed by 2-4 cycles of methotrexate, cisplatinum, and vinblastine polychemotherapy. In complete responders the treatment was completed by radiotherapy (50 Gy to the bladder and 40 Gy to the regional lymph nodes), whereas nonresponders underwent cystectomy whenever feasible. Results: Our study has confirmed an independent prognostic value of performance status, histologic grade, and obstructive uropathy, for the disease-specific survival (DSS) of bladder cancer patients treated by a conservative approach. We believe that performance status best reflects the extent of disease and exerts significant influence on the extent and course of treatment, while obstructive uropathy is a good indicator of local spread of the disease, better than clinical T-stage. Our finding that histologic grade is one of the strongest prognostic factors shows that tumor biology also is a very important prognostic factor in patients treated by conservative approach. Conclusion: Patients with muscle-invasive bladder cancer who are most likely to benefit

  5. Independent predictors of metachronous bladder transitional cell carcinoma (TCC) after nephroureterectomy for TCC of the upper urinary tract.

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    Novara, Giacomo; De Marco, Vincenzo; Dalpiaz, Orietta; Gottardo, Fedra; Bouygues, Vianney; Galfano, Antonio; Martignoni, Guido; Patard, Jean Jacques; Artibani, Walter; Ficarra, Vincenzo

    2008-06-01

    To identify the prognostic factors predictive of metachronous bladder transitional cell carcinoma (TCC) in a multi-institutional dataset of patients who had undergone nephroureterectomy (NU) for nonmetastatic upper urinary tract (UUT) TCC. The clinical and pathological data of 231 patients who had had NU for UUT-TCC from 1989 to 2005 in three European centres were collected retrospectively, and analysed for clinical and pathological variables. The median follow-up was 38 months; during the follow-up, bladder TCC was detected in 109 patients (47.2%), and was significantly more common in patients who had UUT-TCC after previous bladder TCC (P TCC (P = 0.017). On multivariate analysis, a previous history of bladder TCC was the only independent predictor of metachronous bladder TCC (hazard ratio 2.825; P TCC was 45.5%. A history of bladder TCC (P TCC (hazard ratio 2.226; P TCC (1.562; P = 0.036) were independent predictors of the probabilities of being free from metachronous bladder TCC. In this multi-institutional study of patients who had had NU for UUT-TCC, a history of bladder TCC was the only independent predictor of metachronous bladder TCC, while both a history of bladder TCC and the presence of ureteric tumours were predictive of the probabilities of being free from metachronous bladder TCC.

  6. Metastasis of Gastric Signet-Ring Cell Carcinoma to the Urinary Bladder: A Case Report and Review of the Literature

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    Kerem Okutur

    2015-01-01

    Full Text Available Although signet-ring cell (SRC adenocarcinoma is commonly seen in the stomach, it is a very rarely seen histologic entity in the bladder. It is difficult to distinguish primary SRC adenocarcinoma of the bladder from bladder metastasis of SRC carcinoma of the stomach only based on histological findings. In such cases, clinical findings and immunohistochemical studies may be helpful. We present here a 48-year-old male patient presenting with hematuria and abdominal pain. Computerised tomography of the patient revealed a gastric mass, peritoneal involvement, and thickening of the bladder wall, and histopathological analysis revealed SRC adenocarcinoma in both of the endoscopic biopsies taken from the stomach and bladder. Immunohistochemical analyses confirmed the diagnosis of SRC adenocarcinoma of the bladder secondary to gastric cancer.

  7. External Beam Radiotherapy for Focal Lymphoepithelioma-Like Carcinoma in the Urinary Bladder: A Case Report and Literature Review

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    Nobuhiro Kushida

    2015-01-01

    Full Text Available Lymphoepithelioma is a malignant epithelial tumor in the nasopharynx characterized by prominent lymphoid infiltration. Carcinomas that resemble lymphoepitheliomas have been called lymphoepithelioma-like carcinomas and have been reported in other organs. A tumor in the bladder is categorized by the percentage of the total area occupied by the lymphoepithelioma-like carcinoma pattern, with the prognosis dependent on the percentage. We present an 81-year-old man with stage 3 chronic obstructive pulmonary disease and a history of aortic aneurysm repair. The computed tomography scans indicated thickening and irregularity of the bladder wall, with left external iliac lymph node metastasis. His diagnosis was bladder cancer, and the clinical stage was evaluated as T3N1M0. Transurethral resection of the bladder tumor was performed, and the pathological specimen showed that the tumor was composed of undifferentiated malignant cells with sheets and nests arranged in a syncytial pattern, as well as an urothelial carcinoma lesion. A prominent lymphoid reaction accompanied the tumor. The pathological diagnosis was focal-type lymphoepithelioma-like carcinoma containing a component of urothelial carcinoma G3>G2. His general condition was such that he could not tolerate radical cystectomy or systemic chemotherapy. External beam radiotherapy (total 60 Gy was given to the bladder, including the lymph node metastatic lesion. No cancer recurrence was detected by regular follow-up computed tomography and cystoscopy. He eventually died of other causes 48 months later. Although treatment for focal lymphoepithelioma-like carcinoma generally requires multifocal therapies, in the present case, the bladder became tumor free. We also summarize previously reported lymphoepithelioma-like carcinoma cases treated with radiotherapy.

  8. The nested variant of bladder transitional cell carcinoma: Review of 12 cases and review of the literature.

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    Carrion-Ballardo, C J; Gala-Solana, L; Portillo-Martin, J A; Azueta-Etxebarria, A; Truan-Cacho, D; Campos-Juanatey, F

    2015-01-01

    The nested variant of bladder transitional cell carcinoma is extremely rare and has a different biological behavior to other bladder tumors. The aim of this study is to analize if their behavior is as aggressive as has been described in the literature. Review of 12 diagnosed cases with nested variant of bladder transitional cell carcinoma and analysis of demographic characteristics, clinical presentation, tumor characteristics, treatment options, analysis of recurrence and cancer-specific survival between January 1997 and December 2010 in our hospital. 50% of the cases had a pathologic stage ≥T2, with grade of differentiation G2 (50%) or G3 (50%). After the pathological result of the TUR (transurethral resection) Bladder, 5 cases underwent radical cystoprostatectomy, 3 a second TUR bladder and 4 cases with treatment chemotherapy and/or radiotherapy (RT). Five out of 12 cases (41.7%) died due to bladder cancer and 3 died (25%) of other causes (urinary sepsis, respiratory failure, renal failure). With a median follow up of 40 months, the overall survival was 50% and cancer-specific survival of 65.6%. The nested variant of bladder transitional cell carcinoma is a disease with an advanced-stage presentation, with high recurrence and mortality rates despite the use of different treatments. So far there is not a clinical practice guideline for this variety of urothelial tumor. Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  9. Clinical evaluation of intra-operative radiotherapy combined with subtotal cystectomy for invasive bladder carcinoma

    International Nuclear Information System (INIS)

    Ozawa, Kazunori; Nakagomi, Kazuaki; Yonese, Junzi

    1996-01-01

    From 1981 to 1994, intra-operative radiotherapy after subtotal cystectomy was performed on 22 patients with invasive bladder carcinoma on whom radical cystectomy could not be recommended because of old age or condition. All the patients received 25 to 30 Gy of radiotherapy focused on trigonum and internal urethral orifice after subtotal cystectomy with uretero-cutaneostomy. Of 22 patients, 15 patients died. Five patients died of bladder cancer, one died of gastic cancer, one died of rectal cancer and the others died of pneumonia, heart failure, sepsis and senility. The five-year survival rate was 41% and the cause-specific five-year survival rate was 75%. Local recurrence was seen only in one patient, who received second intra-operative radiotherapy and recovered well in complete remission. We believe that intra-operative radiotherapy after subtotal cystectomy is useful for patients with invasive bladder carcinoma on whom radical cystectomy could not be recommended because of old age or condition. (author)

  10. Evaluation of Bladder Carcinoma Risk of the Workers Exposed to Industrial Chemicals

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    Serpil Oguztuzun

    2010-12-01

    Full Text Available AIM: The aim of this study is to evaluate the ratios of bladder carcinoma of workers exposed to industrial chemicals in Kirikkale, Turkey by urinary cytology method. METHOD: Urinary cytology preparations for a total of 63 workers in the gun powder production plant was prepared using Papanicolaou staining and evaluated by light microscopy. The relationship between Papanicolaou staining results and workers’ exposure time to chemicals was evaluated statistically by Post Hoc Test method. RESULTS: For the cytological diagnoses of voided urine in all 63 workers, 16 workers as control group had negative cytologic findings. 47 workers exposed to industrial chemicals more than 20 years had two metaplasic and two dysplasic cells in their urine cytology samples. Moreover, a worker exposed to industrial chemicals more than 30 years had urothelial carcinoma cells. CONCLUSION: That the workers’ risk of developing bladder carcinoma increases with their exposure time to chemicals in their work environment has been found statistically significant (p<0,05. [TAF Prev Med Bull 2010; 9(6.000: 597-604

  11. Assessment of angiogenic factor, vascular endothelial growth factor, serum and urine level changes in superficial bladder tumor immunotherapy by intravesical Bacillus Calmette-Guerin

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    Kerigh Behzad

    2010-01-01

    Full Text Available Background and Aim: Bladder tumor is one of the most common genitourinary tumors. Management of non-muscle invasive (NMI bladder tumors is primarily by transurethral resection (TURBT followed by intravesical immunotherapy or chemotherapy. Bacillus Calmette-Guerin (BCG is the most effective adjuvant therapy in NMI bladder tumor. Since angiogenesis is an essential factor in solid tumor progression and vascular endothelial growth factor (VEGF is an important factor in angiogenesis, the aim of this study is the assessment of angiogenic factor, VEGF, serum and urine level changes in superficial bladder tumor immunotherapy by intravesical BCG. Materials and Methods: A total of 23 patients with bladder transitional cell carcinoma (TCC in stage Ta/T1 or carcinoma insitu (CIS, low or high grade, which passed a 2-4 week period from TURBT participated in this study. Blood and urine samples were obtained at first and sixth sessions before instillation of BCG. Enzyme-linked immunosorbent assay (ELISA method was used to obtain VEGF level in samples. Results: Urine and serum VEGF levels did not change significantly before and after BCG therapy. Changes in VEGF level were significantly different neither in low grade against high grade tumors nor in stage T1 against stage Ta tumors. A significant difference in VEGF level was seen between low grade and high grade tumors in serum after BCG therapy (P=0.007; but not in urine samples. Conclusion: Although intravesical BCG possesses anti-angiogenic activity, it seems that it exerts its effect through pathways other than VEGF, especially in low grade tumors.

  12. Incidental Detection of Perinephric Urinary Leak on Bone Scintigraphy in a Patient with Urinary Bladder Carcinoma.

    Science.gov (United States)

    Vadi, Shelvin Kumar; Dasagrandhi, Vaishnavi; Bhattacharya, Anish; Singh, Shrawan Kumar; Mittal, Bhagwant Rai

    2018-01-01

    A 71-year-old male patient with urothelial carcinoma of the bladder was referred for 99m Tc-methylene diphosphonate bone scintigraphy to assess for skeletal metastasis. While the bone scan showed no abnormal skeletal uptake, tracer activity was detected in the extrarenal region of the left renal fossa on the planar image; single photon emission computed tomography-computed tomography (CT) demonstrated tracer pooling in the perirenal collection. In addition, the CT detected nontracer-avid parenchymal lung nodules and hypodense liver lesions consistent with metastatic disease. The perinephric urinary leak was drained by percutaneous drainage, confirmed by diuretic renography the following day.

  13. Pathogenic and Diagnostic Potential of BLCA-1 and BLCA-4 Nuclear Proteins in Urothelial Cell Carcinoma of Human Bladder

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    Matteo Santoni

    2012-01-01

    Full Text Available Transitional cell carcinoma (TCC of the bladder is one of the most common malignancies of genitourinary tract. Patients with bladder cancer need a life-long surveillance, directly due to the relatively high recurrence rate of this tumor. The use of cystoscopy represents the gold standard for the followup of previously treated patients. Nevertheless, several factors, including cost and invasiveness, render cystoscopy not ideal for routine controls. Advances in the identification of specific alterations in the nuclear structure of bladder cancer cells have opened novel diagnostic landscapes. The members of nuclear matrix protein family BLCA-1 and BLCA-4, are currently under evaluation as bladder cancer urinary markers. They are involved in tumour cell proliferation, survival, and angiogenesis. In this paper, we illustrate the role of BLCA-1 and BLCA-4 in bladder carcinogenesis and their potential exploitation as biomarkers in this cancer.

  14. Commentary on: "Comprehensive transcriptional analysis of early-stage urothelial carcinoma." Hedegaard J, Lamy P, Nordentoft I, Algaba F, Høyer S, Ulhøi BP, Vang S, Reinert T, Hermann GG, Mogensen K, Thomsen MB, Nielsen MM, Marquez M, Segersten U, Aine M, Höglund M, Birkenkamp-Demtröder K, Fristrup N, Borre M, Hartmann A, Stöhr R, Wach S, Keck B, Seitz AK, Nawroth R, Maurer T, Tulic C, Simic T, Junker K, Horstmann M, Harving N, Petersen AC, Calle ML, Steyerberg EW, Beukers W, van Kessel KE, Jensen JB, Pedersen JS, Malmström PU, Malats N, Real FX, Zwarthoff EC, Ørntoft TF, Dyrskjøt L. Cancer Cell. 2016 Jul 11;30(1):27-42.

    Science.gov (United States)

    Lee, Byron H

    2017-09-01

    Non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease with widely different outcomes. We performed a comprehensive transcriptional analysis of 460 early-stage urothelial carcinomas and showed that NMIBC can be subgrouped into 3 major classes with basal- and luminal-like characteristics and different clinical outcomes. Large differences in biological processes such as the cell cycle, epithelial-mesenchymal transition, and differentiation were observed. Analysis of transcript variants revealed frequent mutations in genes encoding proteins involved in chromatin organization and cytoskeletal functions. Furthermore, mutations in well-known cancer driver genes (e.g., TP53 and ERBB2) were primarily found in high-risk tumors, together with APOBEC-related mutational signatures. The identification of subclasses in NMIBC may offer better prognostication and treatment selection based on subclass assignment. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Studies on the cellular immune response in patients with upper urinary tract carcinoma compawed with those in patients with bladder carcinoma and it's postoperative change

    International Nuclear Information System (INIS)

    Sakai, Shunsuke

    1980-01-01

    Non-specific cellular immunity of patients with upper urinary tract carcinoma was studied by PPD reaction (in vivo or in vitro), lymphocytes subpopulation and macrophage migration inhibition test and the results were compared with those of patients with bladder carcinoma or benign urological diseases. 1) The preoperative cellular immunity of the malignant tumor group gave low values as compared to that in the benign disease group. Although the cellular immunity of patients with renal cell carcinoma showed no difference in the points of their grade and stage, significant differences were noted in patients with bladder carcinoma. The patients with renal pelvic and ureter carcinoma appeared to be similar to the patients with bladder carcinoma in the aspects of immune reactions. 2) In the majority of patients with upper urinary tract and bladder carcinoma, the cellular immunity after complete removal of the carcinoma gave an increased value of each marker as compared to the preoperative value. 3) The cellular immunity after irradiation decreased in the majority of the cases in terms of PPD reaction and T-cell ratio in lymphocyte subpopulation. Irradiation of 4000 - 6000 Rad. showed greater influence on T-cell than on B-cell, but influence of irradiation on cellular immunity was not different by irradiation dose. 4) The cellular immunity indicated decreased values for one to two months after discontinuation of irradiation, but then it showed a tendency to increase in terms of PPD and lymphocytes subpopulation in the patients with satisfactory postoperative courses. 5) Through the pre and postoperative courses, the immunity of the carcinomatous stage seems to be reflected better by the T-cell ratio than by the absolute number of T-cell. It is likely that macrophage migration inhibition test shows much sharper reaction than PPD reaction. (author)

  16. The economics of bladder cancer: costs and considerations of caring for this disease.

    Science.gov (United States)

    Svatek, Robert S; Hollenbeck, Brent K; Holmäng, Sten; Lee, Richard; Kim, Simon P; Stenzl, Arnulf; Lotan, Yair

    2014-08-01

    Due to high recurrence rates, intensive surveillance strategies, and expensive treatment costs, the management of bladder cancer contributes significantly to medical costs. To provide a concise evaluation of contemporary cost-related challenges in the care of patients with bladder cancer. An emphasis is placed on the initial diagnosis of bladder cancer and therapy considerations for both non-muscle-invasive bladder cancer (NMIBC) and more advanced disease. A systematic review of the literature was performed using Medline (1966 to February 2011). Medical Subject Headings (MeSH) terms for search criteria included "bladder cancer, neoplasms" OR "carcinoma, transitional cell" AND all cost-related MeSH search terms. Studies evaluating the costs associated with of various diagnostic or treatment approaches were reviewed. Routine use of perioperative chemotherapy following complete transurethral resection of bladder tumor has been estimated to provide a cost savings. Routine office-based fulguration of small low-grade recurrences could decrease costs. Another potential important target for decreasing variation and cost lies in risk-modified surveillance strategies after initial bladder tumor removal to reduce the cost associated with frequent cystoscopic and radiographic procedures. Optimizing postoperative care after radical cystectomy has the potential to decrease length of stay and perioperative morbidity with substantial decreases in perioperative care expenses. The gemcitabine-cisplatin regimen has been estimated to result in a modest increase in cost effectiveness over methotrexate, vinblastine, doxorubicin, and cisplatin. Additional costs of therapies need to be balanced with effectiveness, and there are significant gaps in knowledge regarding optimal surveillance and treatment of both early and advanced bladder cancer. Regardless of disease severity, improvements in the efficiency of bladder cancer care to limit unnecessary interventions and optimize effective

  17. Rare Association of Anti-Hu Antibody Positive Paraneoplastic Neurological Syndrome and Transitional Cell Bladder Carcinoma

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    S. Lukacs

    2012-01-01

    Full Text Available Introduction. Paraneoplastic encephalomyelitis (PEM and subacute sensory neuronopathy (SSN are remote effects of cancer, usually associated with small-cell lung carcinoma and positive anti-Hu antibody. We describe the rare association of bladder transitional cell carcinoma (TCC with anti-Hu antibody positivity resulting in this paraneoplastic neurological syndrome. Patient. A 76-year-old female presented with bilateral muscle weakness and paraesthesia of the upper and lower limbs in a length-dependent “glove and stocking” distribution. Central nervous system symptoms included cognitive problems, personality change, and truncal ataxia. Case notes and the literature were reviewed. Result. Autoantibody screening was positive for anti-Hu antibody (recently renamed antineuronal nuclear antibody 1, ANNA-1. The diagnosis of PEM and SSN was supported by MRI and lumbar puncture results. A superficial bladder TCC was demonstrated on CT and subsequently confirmed on histology. No other primary neoplasm was found on full-body imaging. The neurological symptoms were considered to be an antibody-mediated paraneoplastic neurological syndrome and improved after resection of the tumour. Discussion. The association of anti-Hu positive paraneoplastic neurological syndrome and TCC has not been described in the literature previously. We emphasize the need for detailed clinical examination and the importance of a multidisciplinary thought process and encourage further awareness of this rare association.

  18. Pseudoaneurysm embolization and vasopressin infusion for lower gastrointestinal bleeding due to recurrence of urinary bladder carcinoma.

    Science.gov (United States)

    Kakizawa, Hideaki; Toyota, Naoyuki; Mita, Koji; Fujimura, Yoshio; Hieda, Masashi; Hirai, Nobuhiko; Tachikake, Toshihiro; Ito, Katsuhide

    2006-05-01

    We report a case that was successfully treated for massive lower gastrointestinal (LGI) bleeding due to a recurrent urinary bladder carcinoma. Treatment consisted of combination therapy including embolization of an inferior gluteal artery (IGA) pseudoaneurysm and low-dose arterial vasopressin infusion via a sigmoid artery (SA). A 57-year-old man presented with life-threatening sudden, massive LGI bleeding due to an obturator lymph node (LN) metastasis from a urinary bladder carcinoma. Computed tomography showed that the LN recurrence had invaded all the way to the sigmoid colon, and there was a pseudoaneurysm with extravasation inside the recurrence. An angiogram revealed a left IGA pseudoaneurysm. We therefore excluded the pseudoaneurysm by embolization with microcoils. Following this treatment the bleeding decreased, but intermittent LGI bleeding continued. Endoscopic examination showed the tumor with a huge ulcer inside the colonic lumen, and continuous oozing was confirmed. A second angiogram showed no recurrence of the IGA pseudoaneurysm and no apparent findings of bleeding. Then a 3F microcatheter was placed in the SA selectively using a coaxial catheter system, and vasopressin was infused at a rate 0.05 U/min for 12 h. Bleeding completely ceased 2 days later. There were no signs of ischemic gastrointestinal complications. Massive LGI bleeding has not recurred in 5 months.

  19. Management of transitional cell carcinoma of the urinary bladder in dogs: a review.

    Science.gov (United States)

    Fulkerson, Christopher M; Knapp, Deborah W

    2015-08-01

    Transitional cell carcinoma (TCC), also referred to as urothelial carcinoma, is the most common form of urinary bladder cancer in dogs, affecting tens of thousands of dogs worldwide each year. Canine TCC is usually a high grade invasive cancer. Problems associated with TCC include urinary tract obstruction, distant metastases in >50% of affected dogs, and clinical signs that are troubling both to the dogs and to their owners. Risk factors for TCC include exposure to older types of flea control products and lawn chemicals, obesity, female sex, and a very strong breed-associated risk. This knowledge is allowing pet owners to take steps to reduce the risk of TCC in their dog. The diagnosis of TCC is made by histopathology of tissue biopsies obtained by cystoscopy, surgery, or catheter. Percutaneous aspirates and biopsies should be avoided due to the risk of tumor seeding. TCC is most commonly located in the trigone region of the bladder precluding complete surgical resection. Medical treatment is the mainstay for TCC therapy in dogs. Although TCC is not usually curable in dogs, multiple drugs have activity against it. Approximately 75% of dogs respond favorably to TCC treatment and can enjoy several months to a year or more of good quality life. Many promising new therapies for TCC are emerging and with the close similarity between TCC in dogs and high grade invasive bladder cancer in humans, new treatment strategies found to be successful in canine studies are expected to help dogs and to be subsequently translated to humans. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Characteristics of Patients With Transitional Cell Carcinoma of the Urinary Bladder in Kermanshah Province, Iran.

    Science.gov (United States)

    Payandeh, Mehrdad; Sadeghi, Masoud; Sadeghi, Edris

    2015-12-01

    In Iran, bladder cancer is one of the most common malignancy sites among men, ranking as the fifth with age-specific incidence rate of about 11.2 per 100,000 males. It causes 8% of all malignancies in men and 3% of all malignancies in women. The aim of this study was to report the epidemiological, clinical, and pathological features of bladder cancer in Western Iran compared to other studies. This is a retrospective study between 2003 and 2014 when forty-four patients with bladder cancer referred to Hematology Clinic of Kermanshah, Kermanshah, Iran. Transitional cell carcinoma (TCC) was in 39 patients. In the patients with TCC, the mean age in diagnosis for them was 65.43 years (± 11.64), range of age 42 to 88 years , thirty-three patients (84.6%) were male, and six patients (15.4%) were female. Of 39 patients with TCC, 16 patients (41%) had metastasis. 21 patients (53.8%) were smoker and 16 patients (41%) had muscle invasive. 35 patients (89.7%) were histological high grade and the rest of patients were low grade. In the TCC patients with increasing age, metastasis and muscle invasive increased. The age presentation of TCC in West Iran was similar to other studies. Percentage of patients with high grade is more than other studies, and also the number of patients with bladder cancer has increased during last 4 years. For better results, studies must be conducted with more patients in this area, and other areas of Iran with checking of genetics, race and environmental factors.

  1. Immunohistochemical Expression of Cyclooxygenase-2 in Urinary Bladder Transitional Cell Carcinomas

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    F Niki

    2012-07-01

    Full Text Available Background: Transitional Cell Carcinoma (TCC is the most common type of urinary bladder cancer. Cyclooxygenase-2 (COX-2, a key enzyme in prostaglandins biosynthesis, has been introduced as a new candidate for targeted therapy in this cancer. In this study, we investigated the expression of COX-2 in urinary bladder TCCs and its relationship with clinicopathological parameters such as tumor grade and stage. Methods: This cross-sectional study was performed in the Pathology department of Sina Hospital in Tehran, Iran during 2006-2011. Pathology reports of patients with definite diagnosis of urinary bladder TCCs who had undergone Transurethral Resection (TUR were reviewed and 40 cases were selected. Subsequently, COX-2 expression was assessed immunohistochemically by the examination of paraffin embedded tissue blocks. Staining in more than 5% of tumor cells was considered as positive expression. Results: COX-2 was expressed in 52.5% of the patients. High-grade tumors revealed a higher (87.5% COX-2 expression versus other grades of the lesions and there was a statistically significant difference in COX-2 expression between them (P<0.001. Patients age was also related to the expression of this marker (P=0.03. In contrast, this marker did not correlate with other characteristics including gender, lymphatic invasion or tumor stage. In addition, perineurial or vascular invasions were not detected in any of the patients. Conclusion: COX-2 expression was seen in more than half of our patients and it had a marked relation to tumor differentiation. Accordingly, this molecule may be a useful tumor marker in the assessment of urinary bladder cancers.

  2. Primary signet-ring cell carcinoma of the urinary bladder successfully managed with cisplatin and gemcitabine: a case report

    Directory of Open Access Journals (Sweden)

    El Ammari Jalal Eddine

    2013-02-01

    Full Text Available Abstract Introduction Primary signet-ring cell carcinoma of the urinary bladder is a rare variant of mucus-producing adenocarcinoma constituting approximately 0.5% to 2.0% of all primary carcinomas of the bladder. This tumor initially presents as a high-grade, high-stage lesion and diffusely invades the bladder wall without forming intraluminal growth. The patients have no specific symptoms, which leads to delayed diagnosis and poor prognosis. Case presentation We report the case of a 51-year-old Moroccan Berber man consulting for gross hematuria. Ultrasonography and a computed tomography scan found a bladder tumor diffusely invading the bladder wall. A histopathological examination of the tumor chips from a transurethral resection of the bladder revealed signet-ring cell adenocarcinoma. The gastrointestinal tract exploration did not reveal any other tumor localization. A radical cystectomy and adjuvant cisplatin and gemcitabine chemotherapy were therefore performed resulting in 18 months of survival without metastasis and a good quality of life within that time. Conclusion The rarity and the successful management with carboplatin and gemcitabine as adjuvant chemotherapy of this entity, which is rarely reported in the literature, are two remarkable characteristics described in this case report.

  3. Qualitative and quantitative histopathology in transitional cell carcinomas of the urinary bladder. An international investigation of intra- and interobserver reproducibility

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt; Sasaki, M; Fukuzawa, S

    1994-01-01

    BACKGROUND: Histopathologic, prognosis-related grading of malignancy by means of morphologic examination in transitional cell carcinomas of the urinary bladder (TCC) may be subject to observer variation, resulting in a reduced level of reproducibility. This may confound comparisons of treatment r...

  4. MORPHOMETRY, DENSITOMETRY AND PATTERN-ANALYSIS OF PLASTIC-EMBEDDED HISTOLOGIC MATERIAL FROM UROTHELIAL CELL-CARCINOMA OF THE BLADDER

    NARCIS (Netherlands)

    VANDERPOEL, HG; BOON, ME; KOK, LP; VANDERMEULEN, EA; VANCAUBERGH, RD; DEBRUIJN, WC; DEBRUYNE, FMJ

    1991-01-01

    An image analysis method of grading histologic sections of bladder carcinoma was tested. The method was new in four respects. First, fixation of the biopsies a coagulant fixative was used. Second, 2-mu-m plastic sections were used to ensure the reproductibility of nuclear imaging. Third, a new

  5. Total cystectomy for treatment of transitional cell carcinoma of the urethra and bladder trigone in a dog.

    Science.gov (United States)

    Boston, Sarah; Singh, Ameet

    2014-03-01

    To report total cystectomy with reimplantation of the ureters in the proximal aspect of the vagina. Case report. An 11-year-old female spayed Vizsla with spontaneously occurring transitional cell carcinoma of the urethra and bladder. After initial treatment for transitional cell carcinoma of the bladder trigone with urethral stent placement and chemotherapy, the dog developed urinary incontinence 2 months after stent placement. Eleven months after initial diagnosis, the dog developed pulmonary metastasis and local progression, leading to bilateral ureteral dilatation. After palliative radiation, total cystectomy was performed. The owners elected euthanasia 442 days after original presentation and 92 days after total cystectomy. Euthanasia was unrelated to the surgical procedure, but was related to the primary disease. Total cystectomy is a technically feasible procedure that should be considered for the treatment of bladder cancer in dogs. © Copyright 2014 by The American College of Veterinary Surgeons.

  6. Lymphoepithelioma-like carcinoma of the urinary bladder: A case report and review of systemic treatment options

    Directory of Open Access Journals (Sweden)

    Nicholas M Pantelides

    2012-01-01

    Full Text Available Lymphoepithelioma-like carcinoma (LELC of the urinary bladder is a rare variant, which can occur in a pure form or in conjunction with transitional cell carcinoma. Owing to the scarcity of reported cases, the optimum treatment is yet to be defined, although the benefits of chemotherapy are increasingly recognised. We present a case of a 64-year-old man with pure LELC, treated with trans-urethral resection of the bladder tumor (TURBT and primary gemcitabine and platinum-based chemotherapy. He remained free of disease at six-month follow-up cystoscopy. The case adds to the growing evidence for the efficacy of chemotherapy, coupled with TUR, as part of a bladder-preserving treatment option for LELC.

  7. Contrast-enhanced computed tomography of the primary tumor in muscle invasive carcinoma of the urinary bladder

    International Nuclear Information System (INIS)

    Sager, E.M.

    1991-01-01

    Patients with muscle invasive carcinoma of the urinary bladder were examined with contrast-enhanced CT of the primary tumor. A specially designed technique was developed to increase the diagnostic potential of CT. The most important points about the technique were controlled filling of the bladder, the use of thin slices, series of scans before and after intravenous injection of contrast medium, and long scanning times in the precontrast series. The absorbed dose to the patient resulting from the new technique was found to be within the range of the dose from urography or barium enema. This dose was considered to be acceptable given the diagnostic gain of the procedure. Features of irradiated bladder tumors were analysed to find which parameter correlated with persistent malignancy. High contrast enhancement of a tumor relative to the bladder wall was found to be the best indicator of a malignant tumour after irradiation. 127 refs

  8. Clinical significance of determination of changes of serum SE-cad, SF and TSGF levels after operation in patients with carcinoma of urinary bladder

    International Nuclear Information System (INIS)

    Zhang Jibang; Qin Wenjing

    2008-01-01

    Objective: To explore the clinical significance of changes of serum SE-cad, SF and TSGF levels after operation in patients with carcinoma of urinary bladder. Methods: Serum SE-cad ( with ELISA), SF (with RIA) and TSGF levels (with biochemistry) levels were measured in 36 patients with carcinoma of urinary bladder both before and 3 months after operation as well as in 30 controls. Results: Before operation, in the patients, the serum SE-cad, SF and TSGF levels were significantly higher than those in the controls (P 0.05). Conclusion: Serum SE-cad, SF and TSGF were useful markers for detection of carcinoma of urinary bladder. (authors)

  9. Lectin immunohistochemical evaluation of human bladder carcinomas. A comparison of Carnoy's and formalin fixation.

    Science.gov (United States)

    Okamura, T; Ueda, K; Ohtaguro, K; Inoue, K; Washida, H; Mori, M; Tatemoto, Y; Fukushima, S

    1993-10-01

    A lectin immunohistochemical analysis of 51 human bladder carcinomas, including 44 cases of transitional cell carcinoma (TCC) (G1, 15 cases; G2, 17 cases; G3, 12 cases) and 7 cases of squamous cell carcinoma (SCC), was performed. Tissues were obtained by cold punch biopsies, fixed in Carnoy's or 10% formalin solution, stained for binding of 10 different lectins, and evaluated under the light microscope. The lectins used were concanavalin agglutinin (Con A), soybean agglutinin (SBA), Lotus tetragonolobus agglutinin (LTA), Dolichos biflorusa agglutinin (DBA), peanut agglutinin (PNA), Ricinus communis agglutinin I (RCA1), Ulex europaeus agglutinin I, II (UEA-I, II), wheat germ agglutinin (WGA), and Pisum sativum agglutinin (PEA). TCC prepared with Carnoy's fixation tended to show moderately positive Con A, UEA-I, and WGA reactions for G1, and strongly positive reactions for G2 and G3 lesions. UEA-II was mainly negative in G1, but tended to increase to become moderate in G3. DBA tended to show a moderately positive reaction in G1 and G2, but was mainly negative in G3. With formalin fixation, only RCA1 demonstrated grade specific variation, tendency to react moderately in the G1 and G2 cases, and strongly in G3. There were no further differences among the histopathological grades of TCC for other lectins. Thus, Carnoy's fixation appears superior for distinguishing between grades of lesions. SCC tended to react more strongly than TCC with all the various lectins except PEA, independent of fixation.

  10. Clear-cell variant urothelial carcinoma of the bladder: a case report and review of the literature

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    Hossein Tezval

    2012-10-01

    Full Text Available Clear cell variants of transitional cell carcinomas (TCC of the bladder are extremely rare tumors. Only 6 cases have been reported until now. We report of a 67 year old man who presented with fast growing tumor disease. While initial diagnosis showed localized bladder tumor, final histopathology revealed pT4, G3, L1 urothelial carcinoma with clear cell differentiation. No more than 14 weeks after initial diagnosis the patient died from multi-organ failure after unsuccessful salvage laparotomy which showed massive tumor burden within the pelvis and peritoneal carcinosis. This case demonstrated an extremely fast tumor growth. Therefore, patients with clear cell urothelial carcinoma should be treated vigorously and without time delay. We present a case of clear cell variant of TCC which exhibited an extremely aggressive behavior. To our knowledge this is the fifth report of this rare disease.

  11. Rhodamine dyes as potential agents for photochemotherapy of cancer in human bladder carcinoma cells

    International Nuclear Information System (INIS)

    Shea, C.R.; Chen, N.; Wimberly, J.; Hasan, T.

    1989-01-01

    The phototoxicity in vitro of rhodamine 123 and tetrabromo rhodamine 123 (TBR) was compared, in order to assess their photochemotherapeutic potential. Exposure to 514.5-nm radiation from an argon ion laser caused phototoxicity in MGH-U1 bladder carcinoma cells previously treated with either dye at 10 microM for 30 min. As assessed by colony formation and cellular morphology, TBR was markedly more phototoxic than rhodamine 123, reflecting increased intersystem crossing of TBR to the triplet manifold via spin-orbital coupling induced by the heavy bromine atoms. Photoreactions of TBR very efficiently generated singlet oxygen ( 1 O 2 ) in solution; furthermore, irradiation of TBR-treated cells was significantly more toxic when performed in the presence of deuterium oxide, an enhancer of damage caused by 1 O 2 . Retention of fluorescence in TBR-treated cells was enhanced by irradiation, indicating that a stable photoproduct may be formed in reaction with cellular components

  12. New therapeutic targets in the management of urothelial carcinoma of the bladder

    Science.gov (United States)

    Sverrisson, Einar F; Espiritu, Patrick N; Spiess, Philippe E

    2013-01-01

    Urothelial carcinoma of the bladder, despite the myriad of treatment approaches and our progressively increasing knowledge into its disease processes, remains one of the most clinically challenging problems in modern urological clinical practice. New therapies target biomolecular pathways and cellular mediators responsible for regulating cell growth and metabolism, both of which are frequently overexpressed in malignant urothelial cells, with the intent of inducing cell death by limiting cellular metabolism and growth, creating an immune response, or selectively delivering or activating a cytotoxic agent. These new and novel therapies may offer a potential for reduced toxicity and an encouraging hope for better treatment outcomes, particularly for a disease often refractory or not amenable to the current therapeutic approaches. PMID:24400235

  13. Quantitative histopathology in the prognostic evaluation of patients with transitional cell carcinoma of the urinary bladder

    DEFF Research Database (Denmark)

    Sasaki, M; Sørensen, Flemming Brandt; Fukuzawa, S

    1993-01-01

    BACKGROUND: Morphologic grading of malignancy is considered to be of prognostic value in patients with transitional cell carcinomas of the urinary bladder (TCC). This qualitative approach is, however, associated with low reproducibility. Grading of malignancy can be carried out on a reproducible......, quantitative scale. METHODS: A retrospective, prognostic study of 110 patients treated for TCC in clinical Stages Ta-T4 (median follow-up time, 6 years) was performed, evaluating various grading techniques. Unbiased estimates of the volume-weighted mean nuclear volume (nuclear vV), nuclear volume fraction......, estimates of nuclear mean profile area (aH(nuc)), nuclear profile density index (NI), and mitotic profile density index (MI) were obtained by stereologic and morphometric techniques. RESULTS: The T-stage and morphologic grade of malignancy were closely cross-correlated (+0.63

  14. Quantitative histopathology in the prognostic evaluation of patients with transitional cell carcinoma of the urinary bladder

    DEFF Research Database (Denmark)

    Sasaki, M; Sørensen, Flemming Brandt; Fukuzawa, S

    1993-01-01

    BACKGROUND: Morphologic grading of malignancy is considered to be of prognostic value in patients with transitional cell carcinomas of the urinary bladder (TCC). This qualitative approach is, however, associated with low reproducibility. Grading of malignancy can be carried out on a reproducible......, quantitative scale. METHODS: A retrospective, prognostic study of 110 patients treated for TCC in clinical Stages Ta-T4 (median follow-up time, 6 years) was performed, evaluating various grading techniques. Unbiased estimates of the volume-weighted mean nuclear volume (nuclear vV), nuclear volume fraction...... of nuclear vV are prognostically superior to morphologic grading of malignancy in noninvasive TCC, whereas both morphologically and quantitatively based malignancy grading are without prognostic value in invasive TCC....

  15. New therapeutic targets in the management of urothelial carcinoma of the bladder

    Directory of Open Access Journals (Sweden)

    Sverrisson EF

    2013-03-01

    Full Text Available Einar F Sverrisson, Patrick N Espiritu, Philippe E SpiessDepartment of Genitourinary Oncology, H Lee Moffitt Cancer Center, Tampa, FL, USAAbstract: Urothelial carcinoma of the bladder, despite the myriad of treatment approaches and our progressively increasing knowledge into its disease processes, remains one of the most clinically challenging problems in modern urological clinical practice. New therapies target biomolecular pathways and cellular mediators responsible for regulating cell growth and metabolism, both of which are frequently overexpressed in malignant urothelial cells, with the intent of inducing cell death by limiting cellular metabolism and growth, creating an immune response, or selectively delivering or activating a cytotoxic agent. These new and novel therapies may offer a potential for reduced toxicity and an encouraging hope for better treatment outcomes, particularly for a disease often refractory or not amenable to the current therapeutic approaches.Keywords: targeted therapy, intravesical agents, systemic therapies

  16. Positive Correlation between Matrix Metalloproteinases and Epithelial-to-Mesenchymal Transition and its Association with Clinical Outcome in Bladder Cancer Patients.

    Science.gov (United States)

    Singh, R; Mandhani, A; Agrawal, V; Garg, Minal

    2018-01-18

    Involvement of matrix metalloproteinases (MMPs) in the pathogenesis of urothelial carcinoma elects them to be sensitive marker for clinical and prognostic implications. MMPs regulate tumor growth and invasion by inducing epithelial-to-mesenchymal transition (EMT) which is characterized by the complex reprogramming of epithelial cells and ultimately bring about major changes in the structural organization of bladder urothelium. The present study has been undertaken to evaluate the clinical relevance of MMPs in two distinct types of bladder cancer disease. Expression analysis of MMPs namely MMP-2, MMP-7, MMP-9 and EMT markers including epithelial marker, E-cadherin; mesenchymal markers, N-cadherin and Vimentin; and EMT-activating transcriptional factors (EMT-ATFs), Snail, Slug, Twist and Zeb was done in 64 cases of bladder tumor tissues [{Non-muscle invasive bladder cancer (NMIBC): 35 cases} and {Muscle invasive bladder cancer (MIBC): 29 cases}] by real-time quantitative polymerase chain reaction (RT-qPCR). Immunohistochemistry (IHC) staining was done in matched bladder tumor tissues to evaluate the protein expression and localization of E-cadherin, N-cadherin, Vimentin, Snail, and Slug. Our data showed overexpression of MMP-2, MMP-7 and MMP-9 at transcriptome level in 32.8%, 25% and 37.5% bladder tumor cases respectively. These tumor tissues were examined for higher expression of mesenchymal markers (N-cadherin and Vimentin) at mRNA and protein level and exhibited statistical association with tumor stage and tumor grade (p = 0.02, p = 0.04, Mann-Whitney test). Significant statistical correlation in tumor tissues with overexpressed MMPs has also been observed between gain of transcriptional factors and weak expression of E-cadherin with tumor stage, grade, gender, presence of hematuria and smoking history of the patients. Gene expression patterns of EMT markers in bladder tumors with overexpressed MMPs and their significant association with clinical profile

  17. Metabolic syndrome and the risk of urothelial carcinoma of the bladder: a case-control study

    International Nuclear Information System (INIS)

    Montella, Maurizio; Di Maso, Matteo; Crispo, Anna; Grimaldi, Maria; Bosetti, Cristina; Turati, Federica; Giudice, Aldo; Libra, Massimo; Serraino, Diego; La Vecchia, Carlo; Tambaro, Rosa; Cavalcanti, Ernesta; Ciliberto, Gennaro; Polesel, Jerry

    2015-01-01

    The Metabolic syndrome (MetS) is an emerging condition worldwide, consistently associated with an increased risk of several cancers. Some information exists on urothelial carcinoma of the bladder (UCB) and MetS. This study aims at further evaluating the association between the MetS and UCB. Between 2003 and 2014 in Italy, we conducted a hospital-based case-control study, enrolling 690 incident UCB patients and 665 cancer-free matched patients. The MetS was defined as the presence of at least three of the four selected indicators: abdominal obesity, hypercholesterolemia, hypertension, and diabetes. Odds ratios (ORs) and corresponding 95 % confidence intervals (CIs) for MetS and its components were estimated through multiple logistic regression models, adjusting for potential confounders. Patients with MetS were at a 2-fold higher risk of UCB (95 % CI:1.38–3.19), compared to those without the MetS. In particular, ORs for bladder cancer were 2.20 (95 % CI:1.42–3.38) for diabetes, 0.88 (95 % CI: 0.66-1.17) for hypertension, 1.16 (95 % CI: 0.80-1.67) for hypercholesterolemia, and 1.63 (95 % CI:1.22–2.19) for abdominal obesity. No heterogeneity in risks emerged across strata of sex, age, education, geographical area, and smoking habits. Overall, 8.1 % (95 % CI: 3.9-12.4 %) of UCB cases were attributable to the MetS. This study supports a positive association between the MetS and bladder cancer risk

  18. Loss of MTUS1/ATIP expression is associated with adverse outcome in advanced bladder carcinomas: data from a retrospective study

    International Nuclear Information System (INIS)

    Rogler, Anja; Lehmann, Jan; Petsch, Sabrina; Hartmann, Arndt; Stoehr, Robert; Hoja, Sabine; Giedl, Johannes; Ekici, Arif B; Wach, Sven; Taubert, Helge; Goebell, Peter J; Wullich, Bernd; Stöckle, Michael

    2014-01-01

    Seventy percent of all bladder tumours tend to recur and need intensive surveillance, and a subset of tumours progress to muscle-invasive and metastatic disease. However, it is still difficult to find the adequate treatment for every individual patient as it is a very heterogeneous disease and reliable biomarkers are still missing. In our study we searched for new target genes in the critical chromosomal region 8p and investigated the potential tumour suppressor gene candidate MTUS1/ATIP in bladder cancer. MTUS1 was identified to be the most promising deleted target gene at 8p in aCGH analysis with 19 papillary bladder tumours. A correlation with bladder cancer was further validated using immunohistochemistry of 85 papillary and 236 advanced bladder tumours and in functional experiments. Kaplan-Meier analysis and multivariate Cox-regression addressed overall survival (OS) and disease-specific survival (DSS) as a function of MTUS1/ATIP expression. Bivariate correlations investigated associations between MTUS1/ATIP expression, patient characteristics and histopathology. MTUS1 expression was analysed in cell lines and overexpressed in RT112, where impact on viability, proliferation and migration was measured. MTUS1 protein expression was lost in almost 50% of all papillary and advanced bladder cancers. Survival, however, was only influenced in advanced carcinomas, where loss of MTUS1 was associated with adverse OS and DSS. In this cohort, there was also a significant correlation of MTUS1 expression and histological subtype: positive expression was detected in all micropapillary tumours and aberrant nuclear staining was detected in a subset of plasmocytoid urothelial carcinomas. MTUS1 was expressed in all investigated bladder cell lines and overexpression in RT112 led to significantly decreased viability. MTUS1 is a tumour suppressor gene in cultured bladder cancer cells and in advanced bladder tumours. It might represent one new target gene at chromosome 8p and can be

  19. Total retroperitoneal laparoscopic nephroureterectomy with bladder-cuff resection for upper urinary tract transitional cell carcinoma.

    Science.gov (United States)

    Fang, Zhenqiang; Li, Longkun; Wang, Xiangwei; Chen, Wei; Jia, Weisheng; He, Fan; Shen, Chongxing; Ye, Gang

    2014-12-01

    Open nephroureterectomy (ONU) and bladder cuff resection (ONU-BCR) has been the gold standard of surgical treatment for upper urinary tract transitional cell carcinoma (UUT-TCC). The aim of this study is to introduce a modified total retroperitoneal laparoscopic nephroureterectomy (LNU) with bladder-cuff resection (LNU-BCR) method for treating UUT-TCC and compare its clinical efficacy with ONU-BCR. Sixty-five patients with UUT-TCC, who underwent ONU-BCR (n = 36) or LNU-BCR (n = 29) between January 2008 and June 2012, were analyzed in this retrospective study. Perioperative data as well as incidence of disease recurrence at the primary site or distant metastasis was compared in patients with at least 6 months follow-up. As compared with patients with ONU-BCR, the patients with LNU-BCR had significantly shorter operative time, lower estimated blood loss, shorter time to oral intake, lower analgesic dose, shorter duration of analgesic use, shorter duration of incision drainage tube, shorter time to ambulation out of bed and reduced postoperative hospital stay (all, p ONU-BCR with the advantages of reduced invasiveness, bleeding and hospitalization.

  20. Regorafenib Induces Apoptosis and Inhibits Metastatic Potential of Human Bladder Carcinoma Cells.

    Science.gov (United States)

    Hsu, Fei-Ting; Sun, Cho-Chin; Wu, Chia-Hsing; Lee, Yen-Ju; Chiang, Chih-Hung; Wang, Wei-Shu

    2017-09-01

    The aim of the present study was to verify the effects of regorafenib on apoptosis and metastatic potential in TSGH 8301 human bladder carcinoma cells in vitro. Cells were treated with different concentration of regorafenib for different periods of time. Effects of regorafenib on cell viability, apoptosis pathways, metastatic potential, and expression of metastatic and anti-apoptotic proteins were evaluated with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay, flow cytometry, cell migration and invasion assay, and western blotting. We found regorafenib significantly reduced cell viability, cell migration and invasion, and expression of metastatic and anti-apoptotic proteins. In addition, regorafenib significantly induced accumulation of sub-G 1 phase cells, loss of mitochondrial membrane potential, and expression of active caspase-3 and caspase-8. These results show that regorafenib not only induces apoptosis, but also inhibits metastatic potential in bladder cancer TSGH 8301 cells in vitro. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  1. Blood tests and prognosis in bladder carcinomas treated with definitive radiotherapy

    International Nuclear Information System (INIS)

    Hannisdal, E.; Fossa, S.D.; Host, H.

    1993-01-01

    The value of some commonly recorded blood tests as prognostic factors in patients with bladder carcinomas treated with definitive radiotherapy has been assessed. This study included 202 consecutive patients (T2, n=46; T3, n=82 and T4, n=74) treated during the period 1980-1987. The median total dose received was 56 Gy [50-67] and the median cumulative radiation effect was 1750 reu (radiation effect unit) (1515-1823). The blood tests examined in survival analyses were erythrocyte sedimentation rate (ESR), hemoglobin (Hb), leucocyte and thrombocyte count, alkaline phosphatase (ALP), γ-glutamyltransferase (GT), lactate dehydrogenase (LD), creatinine and albumin. In the univariate survival analyses six blood tests were significant prognostic factors (ESR, albumin, creatinine, Hb, ALP and GT). In the multivariate analysis of all 202 patients, the following five variables were significantly associated with shorter survival: T4 tumors, ESR > 30 mm/h, albumin 400 U/I and age >75 years. Our conclusion is that several commonly recorded blood tests are powerful prognostic factors in bladder cancer treated with definitive radiotherapy. These tests can replace other more expensive laboratory investigations used for prognostication. (author). figs. tabs

  2. High frequency of tumor cells with nuclear Egr-1 protein expression in human bladder cancer is associated with disease progression

    International Nuclear Information System (INIS)

    Egerod, Frederikke Lihme; Bartels, Annette; Fristrup, Niels; Borre, Michael; Ørntoft, Torben F; Oleksiewicz, Martin B; Brünner, Nils; Dyrskjøt, Lars

    2009-01-01

    Egr-1 (early growth response-1 transcription factor) has been proposed to be involved in invasion and metastasis processes of human bladder cancer, but Egr-1 protein expression levels in human bladder cancer have not been investigated. In the present study we investigated the expression levels of Egr-1 protein in early stages of human bladder cancer and correlated it to later progression. Expression of Egr-1 protein in human bladder cancer was examined by immunohistochemistry, on a tissue microarray constructed from tumors from 289 patients with non-muscle invasive urothelial bladder cancer. The frequency of tumor cells with nuclear Egr-1 immunolabelling correlated to bladder cancer stage, grade and to later progression to muscle-invasive bladder cancer (T2-4). Stage T1 tumors exhibited significantly higher frequencies of tumor cells with nuclear Egr-1 immunolabelling than Ta tumors (P = 0.001). Furthermore, Kaplan-Meier survival analysis showed that a high frequency of tumor cells with nuclear Egr-1 immunolabelling was significantly associated with a higher risk of progression to stage T2-4 (log-rank test, P = 0.035). Tumor cells with nuclear Egr-1 immunolabelling were found to localize at the tumor front in some of the tumor biopsies. The results from this study support a potential involvement of Egr-1 in the progression from non-muscle invasive bladder cancers to muscle invasive bladder cancer

  3. Role of Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Diagnostic Evaluation of Carcinoma Urinary Bladder: Comparison with Computed Tomography

    International Nuclear Information System (INIS)

    Chakraborty, Dhritiman; Mittal, Bhagwant Rai; Kashyap, Raghava; Mete, Utham Kumar; Narang, Vikram; Das, Ashim; Bhattacharya, Anish; Khandelwal, Niranjan; Mandal, Arup K.

    2014-01-01

    Bladder carcinoma is the most frequent tumor of the urinary tract and accounts 7% of all malignancies in men and 2% of all malignancies in women. This retrospective study was carried out to assess the diagnostic utility of F18-fludeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in the imaging evaluation of bladder carcinoma. Seventy-seven consecutive patients diagnosed to have carcinoma urinary bladder referred for F18-FDG PET/CT were included in this study. Thirty-four patients were for initial staging after transurethral biopsy and remaining 43 patients were for restaging. All patients also underwent CT scan of the abdomen and pelvis. PET/CT findings were correlated with diagnostic CT scan and histopathological findings. In 30 of the 34 patients for initial staging, both PET/CT and CT confirmed the primary lesion in the bladder. Histopathology report was available in 23 patients. Lymph nodes FDG uptake reported to be metastatic in 10/23 patients while CT detected lymph node metastasis in 12 patients. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy have been calculated to be 87.5%, 80%, 70%, 92%, 82% for PET/CT and 66%, 57%, 50%, 72%, 60% for CT respectively. PET/CT detected metastatic disease in 8 patients whereas CT detected in 4 patients. Of the 43 patients for restaging, local recurrence was detected in 24 patients on both PET/CT and CT. Histopathology report was available in 17 patients. Sensitivity, specificity, PPV, NPV and accuracy were 85%, 60%, 60%, 85%, 70% for PET/CT and 80%, 50%, 40%, 85%, 58% for CT respectively. Nineteen patients were detected to have metastatic disease by PET/CT, whereas CT detected metastases in 11 patients. F-18 FDG PET/CT is a very useful modality in pre-operative staging and monitoring after surgery, chemotherapy or radiotherapy of patients with carcinoma urinary bladder

  4. The efficacy of Apaziquone in the treatment of bladder cancer.

    Science.gov (United States)

    Caramés Masana, Francisco; de Reijke, Theo M

    2017-11-01

    Bladder cancer is nowadays a common tumor. Non-muscle invasive bladder cancer (NMIBC) has still chances of recurrence and progression in spite of surgery and adjuvant treatments. New therapies are being developed to reduce these percentages with less adverse effects - Apaziquone (EO9) is an example. Areas covered: A literature search has been performed using Pubmed, UpToDate and Google verified information (mainly from Food and Drug Administration and Spectrum Pharmaceutics websites). We have included data from the most representative clinical trials and reviews published. Expert opinion: Apaziquone is considered a promising chemical agent if applied intravesically due mainly to its pharmacodynamics and safety profile. There is evidence for this with respect to adjuvant chemo ablative therapy and as a post-transurethral resection of bladder (TURB) single-dose regimen. As a result, new clinical phase III trials are needed both to evaluate its efficacy as an adjuvant therapy in the spectrum from intermediate- to high-risk non-muscle invasive bladder cancer and to select the most appropriate candidates and treatment schedule. As a conclusion, Apaziquone is a good candidate to become a better alternative as an adjuvant therapy for the treatment of NMIBC in the near future.

  5. Bladder transitional cell carcinoma: correlation of contrast enhancement on computed tomography with histological grade and tumour angiogenesis

    International Nuclear Information System (INIS)

    Xie, Q.; Zhang, J.; Wu, P.-H.; Jiang, X.-Q.; Chen, S.-L.; Wang, Q.-L.; Xu, J.; Chen, G.-D.; Deng, J.-H.

    2005-01-01

    AIM: To investigate the correlation between the degree of contrast enhancement of bladder cancer in the early enhanced phase of helical computed tomography (CT) and microvessel density (MVD), vascular endothelial growth factor (VEGF) and histological grade. MATERIALS AND METHODS: Sixty-five patients with transitional cell carcinoma of the bladder were examined by incremental unenhanced CT and helical CT at 40-45 s after initiation of intravenous administration of contrast medium before surgery. The CT density in Hounsfield units of bladder carcinomas were measured in the middle of the maximum diameter section of the cancer lesions on unenhanced and enhanced CT. The degree of contrast enhancement of the tumour was determined as the absolute increase in Hounsfield units. Histological grade, VEGF and MVD were analysed for each cancer. The Pearson and Spearman correlation tests were used to determine the strength of the relationships between CT enhancement and histological grade, VEGF expression and MVD. RESULTS: Different degrees of enhancement were observed in 91 cancers during the early enhanced phase of helical CT. Mean MVDs and mean CT enhancing values of different histological grade groups were statistically different (p<0.001). A positive correlation was found in the CT-enhancing value of bladder cancer and MVD (Pearson correlation test; r=0.938, p<0.001) and histological grade (Spearman rank correlation; r=0.734, p<0.001). VEGF of bladder cancer did not correlate with the change in CT attenuation (Spearman rank correlation; r=0.087, p=0.410) and MVD (Spearman rank correlation, r=0.103, p=0.330). CONCLUSION: In bladder cancer, the degree of contrast enhancement during the early enhanced helical CT is correlated with the MVD and histological grade of tumour. It is possible that MVD is the histopathological basis of early contrast enhancement of bladder cancer

  6. Bladder Cancer Stem-Like Cells: Their Origin and Therapeutic Perspectives

    Directory of Open Access Journals (Sweden)

    Tomokazu Ohishi

    2015-12-01

    Full Text Available Bladder cancer (BC, the most common cancer arising from the human urinary tract, consists of two major clinicopathological phenotypes: muscle-invasive bladder cancer (MIBC and non-muscle-invasive bladder cancer (NMIBC. MIBC frequently metastasizes and is associated with an unfavorable prognosis. A certain proportion of patients with metastatic BC can achieve a remission with systemic chemotherapy; however, the disease relapses in most cases. Evidence suggests that MIBC comprises a small population of cancer stem cells (CSCs, which may be resistant to these treatments and may be able to form new tumors in the bladder or other organs. Therefore, the unambiguous identification of bladder CSCs and the development of targeted therapies are urgently needed. Nevertheless, it remains unclear where bladder CSCs originate and how they are generated. We review recent studies on bladder CSCs, specifically focusing on their proposed origin and the possible therapeutic options based on the CSC theory.

  7. CYTOKINE PRODUCTION BY THE HUMAN BLADDER-CARCINOMA CELL-LINE T24 IN THE PRESENCE OF BACILLUS-CALMETTE-GUERIN (BCG)

    NARCIS (Netherlands)

    de Reijke, T. M.; Vos, P. C.; de Boer, E. C.; Bevers, R. F.; de Muinck Keizer, W. H.; Kurth, K. H.; Schamhart, D. H.

    1993-01-01

    The study was initiated as an in vitro approach to the situation existing during intravesical bacillus Calmette-Guerin (BCG) instillation in patients with superficial bladder cancer. Cytokine secretion of a human bladder carcinoma cell line T 24 treated with BCG was investigated. A 24-h treatment of

  8. Resolution of hypercalcemia of malignancy following radical cystectomy in a patient with paraneoplastic syndrome associated with urothelial carcinoma of the bladder

    Directory of Open Access Journals (Sweden)

    Alfredo Harb-De La Rosa

    2015-01-01

    Full Text Available Hypercalcemia of malignancy is a common finding associated with different types of cancers; however, its association with urothelial carcinoma of the bladder is rare. We report a case of a 69-year-old male with nonmetastatic urothelial carcinoma of the bladder who developed hypercalcemia that failed to respond to medical management, but resolved completely after undergoing resection of the tumor through radical cystectomy.

  9. Hypofractionated Whole-Brain Radiotherapy for Multiple Brain Metastases From Transitional Cell Carcinoma of the Bladder

    International Nuclear Information System (INIS)

    Rades, Dirk; Meyners, Thekla; Veninga, Theo; Stalpers, Lukas J.A.; Schild, Steven E.

    2010-01-01

    Purpose: Brain metastases in bladder cancer patients are extremely rare. Most patients with multiple lesions receive longer-course whole-brain radiotherapy (WBRT) with 10 x 3 Gy/2 weeks or 20 x 2 Gy/4 weeks. Because its radiosensitivity is relatively low, metastases from bladder cancer may be treated better with hypofractionated radiotherapy. This study compared short-course hypofractionated WBRT (5 x 4 Gy/1 week) to longer-course WBRT. Methods and Materials: Data for 33 patients receiving WBRT alone for multiple brain metastases from transitional cell bladder carcinoma were retrospectively analyzed. Short-course WBRT with 5 x 4 Gy (n = 12 patients) was compared to longer-course WBRT with 10 x 3 Gy/20 x 2 Gy (n = 21 patients) for overall survival (OS) and local (intracerebral) control (LC). Five additional potential prognostic factors were investigated: age, gender, Karnofsky performance score (KPS), number of brain metastases, and extracranial metastases. The Bonferroni correction for multiple tests was used to adjust the p values derived from the multivariate analysis. p values of <0.025 were considered significant. Results: At 6 months, OS was 42% after 5 x 4 Gy and 24% after 10 x 3/20 x 2 Gy (p = 0.31). On univariate analysis, improved OS was associated with less than four brain metastases (p = 0.021) and almost associated with a lack of extracranial metastases (p = 0.057). On multivariate analysis, both factors were not significant. At 6 months, LC was 83% after 5 x 4 Gy and 27% after 10 x 3/20 x 2 Gy (p = 0.035). Improved LC was almost associated with a KPS of ≥70 (p = 0.051). On multivariate analysis, WBRT regimen was almost significant (p = 0.036). KPS showed a trend (p = 0.07). Conclusions: Short-course WBRT with 5 x 4 Gy should be seriously considered for most patients with multiple brain metastases from bladder cancer, as it resulted in improved LC.

  10. Responses of NBT-II bladder carcinoma cells to conditioned medium from normal fetal urogenital sinus.

    Science.gov (United States)

    Rowley, D R; Tindall, D J

    1987-06-01

    In vitro studies were conducted to determine whether conditioned medium from rat fetal urogenital sinus explants would affect phenotypic characteristics of NBT-II urinary bladder carcinoma cells in culture. NBT-II cells were exposed to medium (30%, v/v) conditioned for 48 h by intact urogenital sinus explants derived from 18-day fetal rats. Upon exposure for 23 h the [3H]thymidine incorporation by NBT-II cells was decreased by 40.3% relative to control cultures. This effect was paralleled by a similar decrease in proliferation. NBT-II cultures decreased in cell number by 32.1 and 45.8% on days 2 and 4, respectively, after exposure to conditioned medium. Although cell proliferation was inhibited, conditioned medium acted to induce an increase in protein secretion. An increase of 18.6% was observed in the incorporation of [35S]methionine into newly synthesized, secreted proteins by NBT-II cells exposed to conditioned medium for 23 h. Morphologically the NBT-II cells exposed to conditioned medium were larger, more spread out, and exhibited a greater array of lamellipodia and filopodia, although [35S]methionine incorporation into cellular proteins was decreased by 11.1%. These results suggest that diffusable factors produced by fetal urogenital sinus explants can induce changes in proliferation, protein synthesis, protein secretion, and phenotypic morphology of NBT-II carcinoma cells in culture.

  11. Initial Results of Bladder Preserving Approach by Chemo-Radiotherapy in Patients with Muscle Invading Transitional Cell Carcinoma

    International Nuclear Information System (INIS)

    Aboziada, M.A.; Hamza, H.; Abdlrahem, A.M.

    2009-01-01

    This study was conducted to test the efficacy and tolerability of trimodality treatment for invasive bladder cancer and to test the possibility of bladder sparing. Methods: This study had been carried out on 50 patients with transitional cell carcinoma (TCC) stage T2- T3 tumors with adequate performance status and renal function. All patients were subjected to maximum transurethral resection of bladder tumors (TURBT). Patients were then subjected to chemo-radiation that was executed in two treatment phases. Phase I was external radiotherapy in the form of 46 Gy /23 fractions /5 weeks to whole pelvis with concurrent cisplatin 40 mg/m 2 weekly. Phase II was 20 Gy /10 fractions /2 weeks to the bladder tumor with concurrent cisplatin 40 mg/m2 weekly. After phase I, patients who had complete response (CR) or partial response (PR) were subjected to phase II and patients who had stationary disease (SD) were subjected to salvage cystectomy. After the end of treatment, patients who had CR were subjected to bladder preservation. Radiological and cystoscopic reevaluation was done to assess the tumor response after phase I and phase II. After completion of the scheduled treatment, patients were under follow up for clinical examination, radiological, and cystoscopic assessment. Results: The treatment schedule was tolerable and was associated with infrequent incidence of moderate toxicity that was easily controlled without interruption of treatment. Bladder preservation was achieved in 72% of patients. The actuarial relapse free survival and overall survival at a median follow up 18 months for patients who were candidate for bladder preservation were 81% and 100%; respectively. Invasive recurrence (16%) sal-Jvaged with cystectomy and superficial recurrence (6%) successfully treated with Bacilles bilie de Calmette- Guerin. Conclusions: This study indicates that in spite of a relatively small number of patients and short follow-up period; the trimodality treatment could be an

  12. The forecasting of radiation injuries of the urinary bladder and rectum in patients with uterine cervix carcinoma

    International Nuclear Information System (INIS)

    Zharinov, G.M.; Gabelov, A.A.

    1984-01-01

    The frequency and degree of severity of radiation in unjuries of the urinary bladder and rectum after combined treatment of 725 patients with uterine cercix carcigoma are analysed. A quantitative index was worked out permi-- tting one to give an ob ective evaluation of the degree of early radiation reactions of the ad acent organs. The determination of the ''radiation injuries prognosis index'' (RIPI) makes it possible to forecast the occurence and degree of severity of late radiation injuries of the urinary bladder and rectum. The evaluation of RIPI mean values in the patients' groups provides an opportunity to oompare the damaging effect of different methods and regiment directly in the process of radiation therapy. The above method improves the potentialities of the forecasting of radiation injuries of the urinary bladder and rectum in patients with uterine cervix carcinoma

  13. Spinal tuberculosis with severe neurological symptoms as a complication of intravesical BCG therapy for carcinoma of the bladder.

    Science.gov (United States)

    Białecki, Jerzy; Nowak-Misiak, Mirosława; Rąpała, Kazimierz; Marczyński, Wojciech; Suchodolski, Gracjan; Truszczyńska, Aleksandra

    2016-01-01

    Non-invasive bladder cancer is effectively treated with intravesical BCG therapy. The administration of the BCG vaccine is to destroy the neoplastic lesion or prevent further recurrences. The activity of the vaccine involves boosting the immune system through the stimulation of the inflammation in the bladder. Adverse reactions after this immunotherapy are rare. The aim of the study was to present complications in the form of spinal tuberculosis and serious neurological symptoms that occurred during intravesical BCG immunotherapy for carcinoma of the bladder. The manuscript also describes a method for neurosurgical spinal cord decompression of the thoracic spine. In the first patient, aged 66, after intravesical BCG therapy for bladder carcinoma, back pain and spastic paralysis of the lower limbs were observed. The MRI and CT revealed destruction of the intervertebral disc and vertebral endplates Th11-Th12. Mycobacterium tuberculosis complex bacilli were cultured from the material obtained by puncture aspiration. In the second patient, aged 35 years, during intravesical BCG immunotherapy for carcinoma of the bladder, girdle thoracic spine pain was observed. The MRI and CT of the spine showed visible lesions characteristic of tuberculosis. Immobilization in a plaster corset and implementation of antituberculous treatment resulted in quick relief of the pain and healing of the tuberculosis focus in the spine. The cases described in the work are the first documented reports in the Polish literature of spinal tuberculosis which occurred as a complication of intravesical administration of bacilli Calmette-Guérin. The diagnosis was based on the finding of BCG vaccine bacillus with molecular methods or PCR. Full antimycobacterial treatment was implemented. Copyright © 2015 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  14. Late effects of radiation therapy for prostate carcinoma: The patient's perspective of bladder, bowel and sexual morbidity

    International Nuclear Information System (INIS)

    Franklin, C.I.V.; Parker, C.A.; Morton, K.M.

    1998-01-01

    The patients' perceptions of the late effects of radiation therapy for carcinoma of the prostate on bladder, bowel and sexual function were determined by using a self-administered questionnaire (included as an appendix) which was posted in June 1996 to patients who had been treated for carcinoma of the prostate between February 1993 and April 1994 at the Herston centre of the Queensland Radium Institute. The questions were based on the SOMA-LENT subjective scales. Moderate bladder morbidity was reported by 15% of patients, with 2% reporting major morbidity. Moderate bowel morbidity was reported by 19% of patients with 2% reporting major morbidity, the major symptoms being bowel urgency and mucus discharge. Sexual function was a problem, with 72% of patients reporting dissatisfaction with their current level of sexual activity. Copyright (1998) Blackwell Science Pty Ltd

  15. Gene expression in the urinary bladder: a common carcinoma in situ gene expression signature exists disregarding histopathological classification

    DEFF Research Database (Denmark)

    Andersen, Lars Dyrskjøt; Kruhøffer, Mogens; Andersen, Thomas Thykjær

    2004-01-01

    The presence of carcinoma in situ (CIS) lesions in the urinary bladder is associated with a high risk of disease progression to a muscle invasive stage. In this study, we used microarray expression profiling to examine the gene expression patterns in superficial transitional cell carcinoma (s...... in mTCC samples. We used a supervised learning approach to build a 16-gene molecular CIS classifier. The classifier was able to classify sTCC samples according to the presence or absence of surrounding CIS with a high accuracy. This study demonstrates that a CIS gene expression signature is present...

  16. Stereological estimates of nuclear volume in the prognostic evaluation of primary flat carcinoma in situ of the urinary bladder

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt; Jacobsen, F

    1991-01-01

    bladder biopsies from 22 patients with primary flat carcinoma in situ (Bergkvist grades III-IV). On average, nuclear vv was 77 microns 3 in nine biopsies with morphologically normal urothelium, 292 microns 3 in 56 isolated primary lesions and 266 microns 3 in lesions of luminal urothelium in 13 biopsies...... carcinoma in situ (nuclear vv = 261 microns 3), the survival was the same in patients with nuclear vv above and below the cut-off point (2P = 0.16). However, the survival curves showed a tendency to differ in the first 2-8 years of observation. Stereological estimates of nuclear vv provide objective...

  17. Genomic predictors of survival in patients with high-grade urothelial carcinoma of the bladder.

    Science.gov (United States)

    Kim, Philip H; Cha, Eugene K; Sfakianos, John P; Iyer, Gopa; Zabor, Emily C; Scott, Sasinya N; Ostrovnaya, Irina; Ramirez, Ricardo; Sun, Arony; Shah, Ronak; Yee, Alyssa M; Reuter, Victor E; Bajorin, Dean F; Rosenberg, Jonathan E; Schultz, Nikolaus; Berger, Michael F; Al-Ahmadie, Hikmat A; Solit, David B; Bochner, Bernard H

    2015-02-01

    Urothelial carcinoma of the bladder (UCB) is genomically heterogeneous, with frequent alterations in genes regulating chromatin state, cell cycle control, and receptor kinase signaling. To identify prognostic genomic markers in high-grade UCB, we used capture-based massively parallel sequencing to analyze 109 tumors. Mutations were detected in 240 genes, with 23 genes mutated in ≥5% of cases. The presence of a recurrent phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutation was associated with improved recurrence-free survival (RFS) (hazard ratio [HR]: 0.35; p=0.014) and improved cancer-specific survival (CSS) (HR: 0.35; p=0.040) in patients treated with radical cystectomy (RC). In multivariable analyses controlling for pT and pN stages, PIK3CA mutation remained associated with RFS (HR: 0.39; p=0.032). The most frequent alteration, TP53 mutation (57%), was more common in extravesical disease (69% vs 32%, p=0.005) and lymph node-positive disease (77% vs 56%, p=0.025). Patients with cyclin-dependent kinase inhibitor 2A (CDKN2A)-altered tumors experienced worse RFS (HR: 5.76; pHR: 2.94; p=0.029) in multivariable analyses. Mutations in chromatin-modifying genes were highly prevalent but not associated with outcomes. In UCB patients treated with RC, PIK3CA mutations are associated with favorable outcomes, whereas TP53 and CDKN2A alterations are associated with poor outcomes. Genomic profiling may aid in the identification of UCB patients at highest risk following RC. Using next-generation sequencing, we identified genomic subsets of high-grade urothelial bladder cancer associated with favorable and unfavorable outcomes. These findings may aid in the selection of patients most likely to benefit from novel combined modality approaches. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  18. Identification of key pathways and genes influencing prognosis in bladder urothelial carcinoma

    Directory of Open Access Journals (Sweden)

    Ning X

    2017-03-01

    Full Text Available Xin Ning, Yaoliang Deng Department of Urology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, People’s Republic of China Background: Genomic profiling can be used to identify the predictive effect of genomic subsets for determining prognosis in bladder urothelial carcinoma (BUC after radical cystectomy. This study aimed to investigate potential gene and pathway markers associated with prognosis in BUC.Methods: A microarray dataset of BUC was obtained from The Cancer Genome Atlas database. Differentially expressed genes (DEGs were identified by DESeq of the R platform. Kaplan–Meier analysis was applied for prognostic markers. Key pathways and genes were identified using bioinformatics tools, such as gene set enrichment analysis, gene ontology, the Kyoto Encyclopedia of Genes and Genomes, gene multiple association network integration algorithm (GeneMANIA, Search Tool for the Retrieval of Interacting Genes/Proteins, and Molecular Complex Detection.Results: A comparative gene set enrichment analysis of tumor and adjacent normal tissues suggested BUC tumorigenesis resulted mainly from enrichment of cell cycle and DNA damage and repair-related biological processes and pathways, including TP53 and mitotic recombination. Two hundred and fifty-six genes were identified as potential prognosis-related DEGs. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that the potential prognosis-related DEGs were enriched in angiogenesis, including the cyclic adenosine monophosphate biosynthetic process, cyclic guanosine monophosphate-protein kinase G, mitogen-activated protein kinase, Rap1, and phosphoinositide-3-kinase-AKT signaling pathway. Nine hub genes, TAGLN, ACTA2, MYH11, CALD1, MYLK, GEM, PRELP, TPM2, and OGN, were identified from the intersection of protein–protein interaction and GeneMANIA networks. Module analysis of protein–protein interaction and GeneMANIA networks mainly showed

  19. Characterization of HGF/Met Signaling in Cell Lines Derived From Urothelial Carcinoma of the Bladder

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Young H. [Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Apolo, Andrea B. [Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Agarwal, Piyush K.; Bottaro, Donald P., E-mail: dbottaro@helix.nih.gov [Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)

    2014-11-25

    There is mounting evidence of oncogenic hepatocyte growth factor (HGF)/Met signaling in urothelial carcinoma (UC) of the bladder. The effects of three kinase inhibitors, cabozantinib, crizotinib and EMD1214063, on HGF-driven signaling and cell growth, invasion and tumorigenicity were analyzed in cultured UC cell lines. SW780 xenograft growth in SCID and human HGF knock-in SCID (hHGF/SCID) mice treated with cabozantinib or vehicle, as well as tumor levels of Met and pMet, were also determined. Met content was robust in most UC-derived cell lines. Basal pMet content and effector activation state in quiescent cells were low, but significantly enhanced by added HGF, as were cell invasion, proliferation and anchorage independent growth. These HGF-driven effects were reversed by Met inhibitor treatment. Tumor xenograft growth was significantly higher in hHGF/SCID mice vs. SCID mice and significantly inhibited by cabozantinib, as was tumor phospho-Met content. These studies indicate the prevalence and functionality of the HGF/Met signaling pathway in UC cells, suggest that paracrine HGF may contribute to UC tumor growth and progression, and that support further preclinical investigation of Met inhibitors for the treatment of UC is warranted.

  20. The response of variant histology bladder cancer to intravesical immunotherapy compared to conventional cancer

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    Ofer Nathan Gofrit

    2016-03-01

    Full Text Available Background: High-grade urothelial carcinomas (UC often show foci of variant differentiation. There is limited information in the literature about the response of these variant urothelial tumors to immunotherapy with Bacillus Calmette Guerin (BCG. We compared the response to treatment with BCG of UC containing glandular, squamous, nested and micropapillary types of differentiation to response of conventional non-muscle invasive high-grade urothelial carcinoma. Methods: A total of 100 patients were diagnosed with variant histology urothelial cancer between June 1995 and December 2013. 41 patients with Ta or T1, confirmed by 2nd look biopsies, received immunotherapy with BCG. Fourteen patients in this group were diagnosed with micropapillary differentiation 13 patients with squamous differentiation, in 9 patients glandular differentiation was seen and in 7 patients nested variant. The control group included 140 patients with conventional high-grade UC. Both groups have been treated and followed similarly. Findings: Patients with variant tumors had similar clinical features to patients with conventional disease including: age, males to female ratio, stage, presence of Tis and median follow-up. Patients with variant tumors had a significantly worse prognosis compared to patients with conventional high-grade UC including: 5-year recurrence-free survival (63.5% Vs. 71.5%, p=0.05, 5-year progression to≥T2 -free survival (60% Vs. 82.5%, p=0.002, 5-year disease-specific survival (73% Vs. 92.5%, p=0.0004 and overall survival (66% Vs. 89.5%, 0.05. Interpretation: A patient with variant bladder cancer treated with intra-vesical immunotherapy has a 27% chance of dying from this disease within 5-years compared to 7.5% for a patient with conventional high-grade UC.

  1. Concomitant carcinoma in situ is a feature of aggressive disease in patients with organ-confined TCC at radical cystectomy.

    Science.gov (United States)

    Shariat, Shahrokh F; Palapattu, Ganesh S; Karakiewicz, Pierre I; Rogers, Craig G; Vazina, Amnon; Bastian, Patrick J; Schoenberg, Mark P; Lerner, Seth P; Sagalowsky, Arthur I; Lotan, Yair

    2007-01-01

    Carcinoma in situ (CIS) is a nonpapillary, high-grade, potentially aggressive, and unpredictable manifestation of transitional cell carcinoma (TCC) of the bladder. The aim of this study was to assess whether presence of concomitant CIS has a detrimental effect on cancer control after radical cystectomy. The records of 812 consecutive patients who underwent radical cystectomy and pelvic lymphadenectomy for bladder TCC at three US academic centres were reviewed. Ninety-nine of 812 (12%) patients had CIS only at radical cystectomy and were excluded from the analyses. Three hundred thirty of the 713 (46.3%) patients had concomitant CIS at radical cystectomy. Patients with TCC involvement of the urethra were more likely to have concomitant CIS than not (61% vs. 40%, p=0.018). Concomitant CIS was significantly more common in patients with lower cystectomy stages and higher tumour grades. In univariate, but not multivariate, analysis, patients with concomitant CIS versus those without were at increased risk of disease recurrence (p=0.0371). In patients with organ-confined disease, concomitant CIS was an independent predictor of disease recurrence (p=0.048 and p=0.012, respectively) but not bladder cancer-specific mortality (p=0.160 and p=0.408, respectively) after adjusting for the effects of standard postoperative features. Concomitant CIS in the cystectomy specimen is common, and patients with concomitant CIS are at increased risk of urethral TCC involvement. The presence of concomitant CIS appears to confer a worse prognosis in patients with non-muscle-invasive TCC treated with radical cystectomy.

  2. Tumour front inflammation and necrosis are independent prognostic predictors in high-grade urothelial carcinoma of the bladder.

    Science.gov (United States)

    Hodgson, Anjelica; Xu, Bin; Satkunasivam, Raj; Downes, Michelle R

    2018-02-01

    Inflammation and necrosis have been associated with prognosis in multiple epithelial malignancies. Our objective was to evaluate inflammation and necrosis in a cohort of patients with high-grade urothelial carcinomas of the bladder to determine their association with pathological parameters and their prognostic effect on relapse-free and disease-specific survival. A retrospective cohort that underwent radical cystectomy for urothelial carcinomas (n=235) was evaluated for invasive front and central inflammation using the Klintrup-Makinen assessment method. Necrosis was scored using a four-point scale. The relationship of inflammation and necrosis with stage, nodal status, carcinoma in situ, tumour size, margin status and vascular space invasion and the impact on relapse-free and disease-specific survival were calculated using appropriate statistical tests. On multivariate analysis, invasive front inflammation (p=0.003) and necrosis (p=0.000) were independent predictors of relapse-free survival. Both invasive front inflammation (p=0.009) and necrosis (p=0.002) again were independent predictors of disease-specific survival. For pathological features, low invasive front inflammation was associated with lymphovascular space invasion (p=0.008), a positive soft tissue margin (p=0.028) and carcinoma in situ (p=0.042). Necrosis was statistically associated with tumours >3 cm in size (p=0.013) and carcinoma in situ (pinflammation are additional histological variables with independent prognostic relevance in high-grade urothelial carcinoma of the bladder. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  3. Can Bcl-XL expression predict the radio sensitivity of Bilharzial-related squamous bladder carcinoma? a prospective comparative study

    Directory of Open Access Journals (Sweden)

    Kamel Nermen A

    2011-01-01

    Full Text Available Abstract Background Local pelvic recurrence after radical cystectomy for muscle invasive bilharzial related squamous cell carcinoma accounts for 75% of treatment failures even in organ confined tumors. Despite the proven value of lymphadenectomy, up to 60% of patients undergoing cystectomy do not have it. These factors are in favor of adjuvant radiotherapy reevaluation. objectives: to evaluate the effect of adjuvant radiotherapy on disease free survival in muscle invasive bilharzial related squamous cell carcinoma of the urinary bladder and to test the predictability of radio-sensitivity using the anti apoptotic protein Bcl-XL. Methods The study prospectively included 71 patients, (47 males, 24 females with muscle invasive bilharzial related squamous cell carcinoma of the bladder (Stage pT2a-T3N0-N3M0 who underwent radical cystectomy in Assiut university hospitals between January 2005 and December 2006. Thirty eight patients received adjuvant radiotherapy to the pelvis in the dose of 50Gy/25 fractions/5 weeks (Group 1, while 33 patients did not receive adjuvant radiotherapy (group 2. Immunohistochemical characterization for bcl-xL expression was done. Follow up was done every 3 months for 12 to 36 months with a mean of 16 ± 10 months. All data were analyzed using SPSS version 16. Three years cumulative disease free survival was calculated and adjusted to Bcl-XL expression and side effects of the treatment were recorded. Results The disease free cumulative survival was 48% for group 1 and 29% for group 2 (log rank p value 0.03. The multivariate predictors of tumor recurrence were the positive Bcl-XL expression (odd ratio 41.1, 95% CI 8.4 - 102.3, p Conclusions Adjuvant radiotherapy for muscle invasive bilharzial related squamous cell carcinoma of the urinary bladder has potential effectiveness and minor side effects. Moreover, Bcl-XL expression is a valuable tool for predicting those who might not respond to this adjuvant treatment.

  4. Inhibiting Invasion into Human Bladder Carcinoma 5637 Cells with Diallyl Trisulfide by Inhibiting Matrix Metalloproteinase Activities and Tightening Tight Junctions

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    Yung Hyun Choi

    2013-10-01

    Full Text Available Diallyl trisulfide (DATS, an organosulfur compound in garlic, possesses pronounced anti-cancer potential. However, the anti-invasive mechanism of this compound in human bladder carcinoma is not fully understood. In this study, we evaluated the anti-invasive effects of DATS on a human bladder carcinoma (5637 cell line and investigated the underlying mechanism. The results indicated that DATS suppressed migration and invasion of 5637 cells by reducing the activities and expression of matrix metalloproteinase (MMP-2 and MMP-9 at both the protein and mRNA levels. DATS treatment up-regulated expression of tissue inhibitor of metalloproteinase (TIMP-1 and TIMP-2 in 5637 cells. The inhibitory effects of DATS on invasiveness were associated with an increase in transepithelial electrical resistance and repression of the levels of claudin family members. Although further studies are needed, our data demonstrate that DATS exhibits anti-invasive effects in 5637 cells by down-regulating the activity of tight junctions and MMPs. DATS may have future utility in clinical applications for treating bladder cancer.

  5. Transurethral resection versus open bladder cuff excision in patients undergoing nephroureterectomy for upper urinary tract carcinoma: Operative and oncological results.

    Science.gov (United States)

    Fragkoulis, Charalampos; Pappas, Athanasios; Papadopoulos, Georgios I; Stathouros, Georgios; Fragkoulis, Aristodimos; Ntoumas, Konstantinos

    2017-03-01

    To evaluate the impact of distal ureter management on oncological results after open nephroureterectomy (ONU) comparing transurethral resection of the intramural ureter to conventional open excision, as controversy still exists about the method of choice for managing the distal ureter and bladder cuff during ONU. We retrospectively collected data from 378 patients who underwent ONU for upper urinary tract transitional cell carcinoma (UUT-TCC) from 1988 to 2009. Patients were divided into two subgroups according to the type of operation performed. Group A comprised 192 patients who had ONU with open resection of the bladder cuff from 1988 to 1997. Group B comprised 186 patients in whom transurethral resection of the intramural ureter plus single incision ONU was performed between 1998 and 2009. The mean operative time, hospital stay, duration of catheterisation, bladder recurrence rates, and cancer-specific survival (CSS) were assessed. The total operative time was statistically significantly less in the endoscopic group (Group B). For catheterisation, patients treated with an open approach (Group A) had a statistically significantly shorter duration of postoperative catheterisation. There was no statistical difference between Groups A and B for the bladder recurrence rate (Group A 24% vs 27% in Group B, P  = 0.51). There was no difference in CSS at the 5-year follow-up. ONU with transurethral resection of the intramural ureter up to the extravesical fat followed by ureter extraction is an oncologically safe and technically feasible operation.

  6. Photochemical internalization in bladder cancer - development of an orthotopic in vivo model.

    Science.gov (United States)

    Gederaas, Odrun A; Johnsson, Anders; Berg, Kristian; Manandhar, Rojlina; Shrestha, Chetana; Skåre, Daniel; Ekroll, Ingvild Kinn; Høgset, Anders; Hjelde, Astrid

    2017-11-08

    The possibility of using photochemical internalization (PCI) to enhance the effects of the cytotoxic drug bleomycin is investigated, together with photophysical determination and outlines of a possible treatment for intravesical therapy of bladder cancer. In vitro experiments indicated that the employment of PCI technology using the novel photosensitizer TPCS 2a ® can enhance the cytotoxic effect of bleomycin in bladder cancer cells. Furthermore, experiments in an orthotopic in vivo bladder cancer model show an effective reduction in both the necrotic area and the bladder weight after TPCS 2a based photodynamic therapy (PDT). The tumor selectivity and PDT effects may be sufficient to destroy tumors without damaging the detrusor muscle layer. Our results present a possible new treatment strategy for non-muscle invasive bladder cancer, with the intravesical instillation of the photosensitizer and bleomycin followed by illumination through an optic fiber by using a catheter.

  7. Long-term prognostic value of the combination of EORTC risk group calculator and molecular markers in non-muscle-invasive bladder cancer patients treated with intravesical Bacille Calmette-Guérin

    Directory of Open Access Journals (Sweden)

    Sultan S Alkhateeb

    2011-01-01

    Conclusion: Molecular markers have a long-term prognostic value when combined with EORTC scoring system and they may be used to improve the predictive accuracy of currently existing scoring system. Larger series are needed to confirm these findings.

  8. Incidental Diagnosis of Carcinoma of the Bladder Due to Uptake of {sup 99m}Tc-MDP

    Energy Technology Data Exchange (ETDEWEB)

    Damle, Nishikant A; Pandey, Dinesh Chand; Gautam, Awadhesh Kumar; Subbarao, Kiran; Singh, Prabhjot [All India Institute of Medical Sciences, New Delhi (India); Mishra, Rohini; Das, Nitendra Lal; Pandey, Dinesh Chand; Gautam, Awadhesh Kumar [B. L. Kapur Memorial Hospital, New Delhi (India)

    2012-06-15

    A bone scan was per-formed using 740 MBq (29 mCi) {sup 99}mTc-MDP. Whole-body planar images were acquired 3 h after injection (Fig. 1). Soft tissue uptake of {sup 99}mTc-MDP is described in various benign and malignant conditions. It is known to accumulate in adenocarcinoma of lung, primary breast cancer, and colonic carcinoma among others. The postulated causes of {sup 99}mTc-MDP uptake in extraosseous neoplasms are numerous and include tumor vascularity, inflammation, local pH factors, altered calcium metabolism, hormonal influences and cell wall damage. Our case shows that TCC of the bladder was incidentally diagnosed due to MDP uptake in multiple bladder polyps detected on a bone scan done for low backache in an 80-year-old man.

  9. Intravesical BCG therapy in bladder carcinoma. Effect on cytotoxicity, IL-2 production and phenotype of peripheral blood mononuclear cells

    DEFF Research Database (Denmark)

    Hermann, G G; Petersen, K R; Zeuthen, J

    1991-01-01

    The purpose of the study was to examine the effects of intravesical BCG treatment on the cytotoxicity, interleukin-2 (IL-2) production and distribution of the subsets of peripheral blood mononuclear cells (PBMC) in patients with carcinoma in situ of the bladder. Treatments were made in 6 patients...... during a conventional BCG treatment schedule. Four patients showed a complete response, one a partial response and one had a progressive disease after BCG treatment. Intravesical BCG did not induce significant changes in the cytotoxicity of PBMC. The distribution of NK-cells and T-cells also remained...... unchanged and so did the lectin induced production of IL-2. The results suggest that the effects of intravesical BCG on the immune system should be studied in lymphocytes isolated from the bladder....

  10. GSTO1*C/GSTO2*G haplotype is associated with risk of transitional cell carcinoma of urinary bladder.

    Science.gov (United States)

    Djukic, Tatjana; Simic, Tatjana; Radic, Tanja; Matic, Marija; Pljesa-Ercegovac, Marija; Suvakov, Sonja; Coric, Vesna; Pekmezovic, Tatjana; Novakovic, Ivana; Dragicevic, Dejan; Savic-Radojevic, Ana

    2015-04-01

    To clarify the role of genetic polymorphisms of GSTO1 (rs4925) and GSTO2 (rs156697) in individual susceptibility to urinary bladder cancer. Case-control study consisting of 187 patients with histologically confirmed transitional cell carcinoma (TCC) of urinary bladder and 140 age- and gender-matched cancer-free controls was carried out. Genotyping of GSTO1 and GSTO2 was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). We found that carriers of mutant GSTO2*G/G genotype were at increased risk of the development of TCC (OR 2.6, 95% CI 1.2-5.8, p = 0.041), while GSTO1 rs4925 polymorphism was not significantly associated with TCC risk (p = 0.450). According to smoking status, smokers with GSTO2*G/G genotype had significantly higher risk of TCC of urinary bladder (OR 4.3, 95% CI 1.6-11.2, p = 0.003) compared to wild-type carriers with no smoking history. We further analyzed the effects of GSTO1/GSTO2 haplotypes on TCC risk, based on the linkage disequilibrium found for GSTO1 (rs4925) and GSTO2 (rs156697) (D' = 0.309, p = 0.001). The study subjects with GSTO1*C/GSTO2*G (GSTO1 wild-type/GSTO2 mutant) haplotype were at the highest risk of the development of transitional cell carcinoma of urinary bladder (OR 2.8, 95% CI 1.5-5.2, p = 0.002). Our results indicate that GSTO1*C/GSTO2*G haplotype is associated with increased risk of TCC. The modifying effect of GSTO2*G/G genotype on individual susceptibility to TCC is more pronounced, when associated with smoking.

  11. [Influence of hepatocyte cell adhesion molecule on gene expression profile of human bladder transitional cell carcinoma cell line].

    Science.gov (United States)

    Wang, Qiu-ju; Lv, Chang-kun; Tao, Jia; Du, Hong-fei; Fan, Yan-ru; Song, Xue-dong; Luo, Chun-li

    2013-04-01

    To investigate the changes of gene expression file in transitional cell carcinoma of bladder after hepatocyte cell adhesion molecule(hepaCAM) overexpression. Affymetrix Human Genome U133 Plus 2.0 Array was used to investigate the changes of gene expression profile between adenovirus-green fluorescent protein(GFP) -hepaCAM group and GFP group in transitional cell carcinoma of bladder EJ cells.Significant Analysis of Microarray(SAM) was used to screen the differentially expressed genes, DAVID software was used to conduct gene ontology analysis and wikiPathway analysis based on the differentially expressed genes. Reverse transcription-polymerase chain reaction and Western blot were applied to verify microarray data. Compared with the GFP group, a total of 2469 genes were up-regulated or down-regulated by more than 2 times in the GFP-hepaCAM group. Among these genes, 1602 genes were up-regulated and 867 were down-regulated.Most of the differentially expressed genes were involved in the function of cell proliferation and cell cycle regulation. The mRNA expressions of nibrin, liver kinase B1, and cyclin D1 detected by reverse transcription-polymerase chain reaction in three different bladder cancer cell lines were consistent with the microarray data.The protein expressions of nibrin and liver kinase B1 in these three cell lines measured by Western blot were consistent with the mRNA expression. HepaCAM can alter the gene expression profile of bladder cancer EJ cells. The well-known anti-tumor effect of hepaCAM may be mediated by regulating the gene expression via multiple pathways.

  12. Analysis of Clinicopathological Features and Prognostic Factors in 39 Cases of Bladder Neuroendocrine Carcinoma.

    Science.gov (United States)

    Zhou, Hui-Hui; Liu, Li-Yan; Yu, Guo-Hua; Qu, Gui-Mei; Gong, Pei-You; Yu, Xiao; Yang, Ping

    2017-08-01

    Through analysis and summarization of clinicopathological features, immunohistochemical expression, pathological diagnostic criteria, prognostic and other factors in patients suffering from bladder neuroendocrine carcinoma (BNEC), a better understanding of BNEC could be achieved to provide solid evidence for clinicopathology and prognosis. The clinicopathological data of 39 cases of BNEC with up to 5-year follow-up data (median follow-up=650 days) were analyzed retrospectively based on immunohistochemical staining. Survival analyses were carried out using the Kaplan-Meier method and tested with the log-rank method. Multivariate Cox regression analysis was adopted to screen independent risk factors affecting patients' survival. In these 39 cases of BNEC, there were 26 cases of male patients, 13 female, with the proportion of male to female being 2:1. The ages of onset ranged from 44 to 86, with the median age being 62 and the average age 61.97 years, respectively. Histologically, referring to the WHO standard of neuroendocrine lung tumor classification, there were 7 cases of typical carcinoid tumors, 8 atypical carcinoid, 12 small-cell carcinomas and 12 large-cell carcinomas. In these cases there were 11 cases of featured urothelium carcinomas and 9 cases of adenocarcinomas. Immunohistochemical staining showed that, in these 39 cases of BNEC, the positive expression for the neuroendocrinic markers, including neural cell adhesion molecule 56 (CD56), synaptophysin (Syn), chromogranin A (CgA), neuron-specific enolase (NSE), thyroid transcription factor-1 (TTF-1), cytokeratin (CK) and cytokeratin 7 (CK7), accounted for 39/39, 27/39, 18/39, 39/39, 19/39, 10/39 and 8/39, respectively. In contrast, cytokeratin 20 (CK20), protein 63 (P63), human melanoma black 45 (HMB45), S-lfln protein 100 (S-100) and leukocyte common antigen (LCA) were all negatively expressed. During the follow-up period, 12 patients died. The 1-, 3- and 5-year overall survival (OS) rates were 76.92%, 74

  13. Molecular Characterization of Urothelial Carcinoma of the Bladder and Upper Urinary Tract

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    Ji Yun Lee

    2018-02-01

    Full Text Available PURPOSE: A better understanding of the molecular basis of urothelial carcinoma (UC is needed to refine the clinical decision-making process. METHODS AND MATERIALS: We performed next-generation sequencing to investigate the mutational and transcriptional profiles of commonly mutated genes in UC using Ampliseq v2. Copy number variations (CNVs were detected with nCounter assay. Genetic alterations between upper tract UC (UTUC and urinary bladder UC (UBUC were compared. RESULTS: Tumor samples from 31 UTUC and 61 UBUC patients were included in analysis. The two groups showed similar clinicopathologic features including tumor grade and stage. Median survival was longer in UTUC than UBUC patients, though this was statistically nonsignificant (59 vs 41 months, P = .137. In total, we found 982 genetic alterations from 92 samples: single nucleotide variants were the most common type of somatic mutation (479/508, 94.3%. Frequently detected somatic mutations included TP53 (68.5%, KDR (41.3%, and PIK3CA (17.4%. Notably, RB1 mutations were the only mutations significantly different between the UBUC and UTUC groups (19.7% vs. 0%, P = .020. The most common types of CNVs included amplifications (56/62, 90.3%: 17.7% of patients identified amplifications in NOTCH1. We also identified five translocations in the entire study population, including one case with FGFR3-TACC3 (Chr4 fusion. CONCLUSION: Within a small study population, we identified similar genetic alterations in both UTUC and UBUC patients, indicating a basis for similar management strategies.

  14. MDM2 SNP309 promoter polymorphism and p53 mutations in urinary bladder carcinoma stage T1

    Directory of Open Access Journals (Sweden)

    Olsson Hans

    2013-01-01

    Full Text Available Abstract Background Urinary bladder carcinoma stage T1 is an unpredictable disease that in some cases has a good prognosis with only local or no recurrence, but in others can appear as a more aggressive tumor with progression to more advanced stages. The aim here was to investigate stage T1 tumors regarding MDM2 promoter SNP309 polymorphism, mutations in the p53 gene, and expression of p53 and p16 measured by immunohistochemistry, and subsequently relate these changes to tumor recurrence and progression. We examined a cohort of patients with primary stage T1 urothelial carcinoma of the bladder and their tumors. Methods After re-evaluation of the original slides and exclusions, the study population comprised 141 patients, all with primary stage T1 urothelial carcinoma of the bladder. The hospital records were screened for clinical parameters and information concerning presence of histologically proven recurrence and progression. The paraffin-embedded tumor material was evaluated by immunohistochemistry. Any mutations found in the p53 gene were studied by single-strand conformation analysis and Sanger sequencing. The MDM2 SNP309 polymorphism was investigated by pyrosequencing. Multivariate analyses concerning association with prognosis were performed, and Kaplan-Meier analysis was conducted for a combination of changes and time to progression. Results Of the 141 patients, 82 had at least one MDM2 SNP309 G allele, and 53 had a mutation in the p53 gene, but neither of those anomalies was associated with a worse prognosis. A mutation in the p53 gene was associated with immunohistochemically visualized p53 protein expression at a cut-off value of 50%. In the group with p53 mutation Kaplan-Meier analysis showed higher rate of progression and shorter time to progression in patients with immunohistochemically abnormal p16 expression compared to them with normal p16 expression (p = 0.038. Conclusions MDM2 SNP309 promoter polymorphism and mutations in

  15. Radical Scavenging and Anti Proliferative Activity of Woodfordia Fruticosa Kurz on Human Bladder Carcinoma, 5637 Cell Lines

    OpenAIRE

    Manggau, Marianti; gemini, alam; Wahyudin, Elly; ulrike, lindequest

    2013-01-01

    Antiproliferative effect of ethanol extract from a plant used in folk medicine, Woodfordia fruticosa Kurz to human bladder carcinoma, 5637 cell lines. After incubation for 72 h with varying concentration of extract (0,343, 1,029, 3,086, 9.259, 27.78, 83.33 dan 250 mg/ml), anti proliferative effect was determined by the neutral red assay and reported in terms of cell viability. The ethanol extract, had a significant anti proliferation against 5637 cell lines with IC50 values of 10,8 mg/ml. A h...

  16. Combination of CK20 and Ki-67 immunostaining analysis predicts recurrence, progression, and cancer-specific survival in pT1 urothelial bladder cancer.

    Science.gov (United States)

    Bertz, Simone; Otto, Wolfgang; Denzinger, Stefan; Wieland, Wolf F; Burger, Maximilian; Stöhr, Robert; Link, Stefan; Hofstädter, Ferdinand; Hartmann, Arndt

    2014-01-01

    The prognostic value of CK20, Ki-67, and p53 has been investigated for non-muscle-invasive urothelial bladder cancers but not for the distinct and clinically challenging subset of pT1 bladder cancers. To evaluate the prognostic value of CK20, Ki-67, and p53 within the largest series of pT1 urothelial bladder cancers. Data from 309 patients with pT1 urothelial bladder cancer from one single urologic centre were collected. Adjuvant instillation of bacillus Calmette-Guérin was performed in each patient. A second resection was performed after 4-8 wk. A total of 76 patients underwent cystectomy. We conducted histomorphologic analysis; immunohistochemistry for CK20, Ki-67, and p53; and univariate and multivariate Cox regression models including recurrence-free survival (RFS), progression-free survival (PFS), and cancer-specific survival (CSS). At a median follow-up of 49 mo, we found recurrence and progression and disease-specific mortality rates of 22.7%, 20.1%, and 15.9%, respectively. CK20 expression was significantly correlated with RFS in multivariate analysis (hazard ratio [HR]: 5.89; 95% confidence interval [CI], 1.44-24.15; p=0.014). In multivariate analysis, Ki-67 was the only marker significantly correlated with PFS (HR: 2.80; 95% CI, 1.45-5.43, p=0.002). Ki-67 (HR: 3.83; 95% CI, 1.59-9.26; p=0.003), and CK20 (HR: 8.44; 95% CI,1.16-61.34; p=0.035) were significantly correlated with CSS in multivariate analysis. The combination of CK20 and Ki-67 showed significantly worse RFS (p=0.026), PFS (p=0.003), and CSS (plimitation of this study. Our present analysis of the largest series of patients with pT1 urothelial bladder cancer published to date found Ki-67 and CK20 to be potential prognostic markers improving the risk stratification of pT1 bladder tumours. They are reliable indicators of biologic aggressiveness and may contribute to decision making on therapeutic strategy for pT1 bladder carcinomas. Copyright © 2012 European Association of Urology. Published by

  17. Prophylactic yttrium 90 instillation in the case of bladder carcinomas Jewett 0

    International Nuclear Information System (INIS)

    Donn, F.; Becker, H.; Kaufmann, J.; Montz, H.R.

    1982-01-01

    We performed in a prospective pilot study the treatment of bladder cancer Jewett 0 by 90-Yttrium-instillation. The chief aim is to prevent recurrent tumour formation. Our technique delivers an average dose of ca. 3000 rad to the surface of the bladder. The complication rate was moderate. The results were encouraging because the recurrent tumour formation was distinctly reduced. (orig.) [de

  18. Cytologic diagnosis of transitional cell carcinoma of the urinary bladder. Comparison with endoscopical and pathological findings on 538 cases.

    Science.gov (United States)

    Raica, M; Minciu, R; Miclea, F; Botoca, M; Drăgan, P; Ioiart, I

    1997-01-01

    There were investigated 583 cases with tumors of the urinary bladder and 612 patients with non-malignant diseases of the urinary tract. Samples of voided urine were taken from all cases and direct smears fixed by drying were stained by rapid blue polychrome-tanin Drăgan method Cytological results were compared with endoscopical and pathological findings. The overall rate of real positive results was 91.7% and false negative results were noticed in 8.3% of cases. A direct relationship between real positive results and histological "G" was found. Causes for false negative results were: tumor developed in a bladder diverticulum, calcified tumor, irradiated tumor, insufficient quantity of voided urine, chronic urinary infections and underestimation of cytological criteria of cellular malignancy. There were 9 false positive results in patients with nonmalignant diseases, due to lithiasis, chronic renal failure and chronic urinary infections. The cytological grade of differentiation was performed by the method purposed by Friedman and Ash, and concordance with the standard histological finding was 76.4%. Urine cytology is thought to be a useful method in the primary diagnosis and recurrences of transitional cell carcinoma of the urinary bladder, in all patients with hematuria, recurrent infections of the urinary tract and neglected lithiasis.

  19. Clinical usefulness of CEA, CA19-9, and CYFRA 21-1 as tumor markers for urothelial bladder carcinoma.

    Science.gov (United States)

    Washino, Satoshi; Hirai, Masaru; Matsuzaki, Atsushi; Kobayashi, Yutaka

    2011-01-01

    To evaluate the usefulness of measuring serum CEA, CA19-9, and CYFRA 21-1 levels for the diagnosis and monitoring of bladder cancer. Serum levels of CEA, CA19-9, and CYFRA 21-1 were measured in 85 patients with bladder cancer. The absolute level of each marker and the positive rate were compared with the clinical stage and histological grade of the tumor. Changes of the markers were assessed in patients with or without disease progression, and the correlations between survival and positivity/negativity of these markers were also evaluated. A higher serum level of CYFRA 21-1 was significantly correlated with higher tumor stage (p CEA and CA19-9 levels did not differ significantly among each stage and grade. The CYFRA 21-1 level increased significantly along with disease progression (from 7.33 ± 13.3 to 55.9 ± 127 ng/ml, p marker of advanced- and high-grade urothelial carcinoma of the bladder. It is useful for monitoring this disease and for predicting the prognosis. In contrast, the clinical usefulness of CEA and CA19-9 as tumor markers was not demonstrated. Copyright © 2011 S. Karger AG, Basel.

  20. Image Analysis Based Grading of Bladder Carcinoma. Comparison of Object, Texture and Graph Based Methods and Their Reproducibility

    Directory of Open Access Journals (Sweden)

    Heung‐Kook Choi

    1997-01-01

    Full Text Available The possibility that computerized image analysis could increase the reproducibility of grading of bladder carcinoma as compared to conventional subjective grading made by pathologists was investigated. Object, texture and graph based analysis were carried out from Feulgen stained histological tissue sections. The object based features were extracted from gray scale images, binary images obtained by thresholding the nuclei and several other images derived through image processing operations. The textural features were based on the spatial gray‐tone co‐occurrence probability matrices and the graph based features were extracted from the minimum spanning trees connecting all nuclei. The large numbers of extracted features were evaluated in relation to subjective grading and to factors related to prognosis using multivariate statistical methods and multilayer backpropagation neural networks. All the methods were originally developed and tested on material from one patient and then tested for reproducibility on entirely different patient material. The results indicate reasonably good reproducibility for the best sets of features. In addition, image analysis based grading showed almost identical correlation to mitotic density and expression of p53 protein as subjective grading. It should thus be possible to use this kind of image analysis as a prognostic tool for bladder carcinoma.

  1. Disseminated Mycobacterium bovis Infection Complicating Intravesical BCG Instillation for the Treatment of Superficial Transitional Cell Carcinoma of the Bladder.

    Science.gov (United States)

    Elzein, Fatehi; Albogami, Nada; Saad, Mustafa; El Tayeb, Nazik; Alghamdi, Abdullah; Elyamany, Ghaleb

    2016-01-01

    Intravesical instillation of Bacillus Calmette-Guérin (BCG) remains a first-line treatment for superficial transitional cell carcinoma of the bladder. Although its use is relatively safe, severe complications such as granulomatous hepatitis, osteomyelitis, pneumonitis, and sepsis occur in few patients. Complications of intravesical instillation of BCG can be local or systemic, with early or late presentation. Here, we report an 88-year-old man who developed fever, rigors, and episodes of syncope following fourth intravesical BCG instillation for the treatment of superficial transitional cell carcinoma of the bladder. Pancytopenia, disseminated intravascular coagulation, ground glass appearance on computerized tomography of the chest scan in addition to multiple bone marrow granulomas, suggested the diagnosis of disseminated BCG infection. All these features recovered on antituberculosis treatment. Our case study highlights the importance of early recognition and prompt treatment of patients with disseminated BCG infection following intravesical instillation. Although isolation of mycobacterium is desirable to make the diagnosis, it is not unusual to have negative smears and cultures and this should not be used to dismiss the possibility of BCG infection.

  2. Alterations to the protein profile of bladder carcinoma cell lines induced by plant extract MINA-05 in vitro.

    Science.gov (United States)

    Nguyen-Khuong, Terry; White, Melanie Y; Hung, Tzong-Tyng; Seeto, Shona; Thomas, Melissa L; Fitzgerald, Anna M; Martucci, Carlos E; Luk, Sharon; Pang, Shiu-Fu; Russell, Pamela J; Walsh, Bradley J

    2009-04-01

    Bladder cancer (BLCa) is a severe urological cancer of both men and women that commonly recurs and once invasive, is difficult to treat. MINA-05 (CK Life Sciences Int'l, Hong Kong) is a derivative of complex botanical extracts, shown to reduce cellular proliferation of bladder and prostate carcinomas. We tested the effects of MINA-05 against human BLCa cell sublines, B8, B8-RSP-GCK, B8-RSP-LN and C3, from a transitional cell carcinoma, grade IV, to determine the molecular targets of treatment by observing the cellular protein profile. Cells were acclimatised for 48 h then treated for 72 h with concentrations of MINA-05 reflecting 1/2 IC(50), IC(50) and 2 x IC(50) (n = 3) or with vehicle, (0.5% DMSO). Dose-dependant changes in protein abundance were detected and characterised using 2-dimensional electrophoresis and MS. We identified 10 proteins that underwent changes in abundance, pI and/or molecular mass in response to treatment. MINA-05 was shown to influence proteins across numerous functional classes including cytoskeletal proteins, energy metabolism proteins, protein degradation proteins and tumour suppressors, suggesting a global impact on these cell lines. This study implies that the ability of MINA-05 to retard cellular proliferation is attributed to its ability to alter cell cycling, metabolism, protein degradation and the cancer cell environment.

  3. Recurrent bladder carcinoma: clinical and prognostic role of 18 F-FDG PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Alongi, Pierpaolo [San Raffaele G. Giglio Institute, Department of Radiological Sciences, Nuclear Medicine Unit, Cefalu (Italy); Caobelli, Federico [Basel University Hospital, Department of Nuclear Medicine, Basel (Switzerland); Gentile, Roberta; Baldari, Sergio [University of Messina, Nuclear Medicine Unit, Department of Biomedical Sciences and Morphological and Functional Images, Messina (Italy); Stefano, Alessandro; Russo, Giorgio; Gilardi, Maria Carla [IBFM-CNR, Cefalu (Italy); Albano, Domenico [Universita degli Studi di Palermo, DIBIMEF - Sezione di Scienze Radiologiche, Palermo (Italy); Midiri, Massimo [San Raffaele G. Giglio Institute, Department of Radiological Sciences, Nuclear Medicine Unit, Cefalu (Italy); Universita degli Studi di Palermo, DIBIMEF - Sezione di Scienze Radiologiche, Palermo (Italy)

    2017-02-15

    A small number of studies evaluated the detection rate of lesions from bladder carcinoma (BC) of 18 F-FDG PET/CT in the restaging process. However, the prognostic role of FDG PET/CT still remains unclear. The aim of the present study was to evaluate the accuracy, the effect upon treatment decision, and the prognostic value of FDG PET/CT in patients with suspected recurrent BC. Forty-one patients affected by BC underwent FDG PET/CT for restaging purpose. The diagnostic accuracy of visually interpreted FDG PET/CT was assessed compared to histology (n = 8), other diagnostic imaging modalities (contrast-enhanced CT in 38/41 patients and MRI in 15/41) and clinical follow-up (n = 41). Semiquantitative PET values (SUVmax, SUVmean, SUL, MTV, TLG) were calculated using a graph-based method. Progression-free survival (PFS) and overall survival (OS) were assessed by using Kaplan-Meier curves. The risk of progression (hazard ratio, HR) was computed by Cox regression analysis by considering all the available variables. PET was considered positive in 21 of 41 patients. Of these, recurrent BC was confirmed in 20 (95 %). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FDG PET/CT were 87 %, 94 %, 95 %, 85 %, 90 %. AUC was 0.9 (95 %IC 0.8-1). Bayesian positive and negative likelihood ratios were 14.5 and 0.13, respectively. FDG PET/CT findings modified the therapeutic approach in 16 patients (modified therapy in 10 PET-positive patients, watch-and-wait in six PET-negative patients). PFS was significantly longer in patients with negative scan vs. those with pathological findings (85 % vs. 24 %, p < 0.05; HR = 12.4; p = 0.001). Moreover, an unremarkable study was associated with a longer OS (88 % vs. 47 % after 2 years and 87 % vs. 25 % after 3 years, respectively, p < 0.05). Standardized uptake value (SUV)max > 6 and total lesion glycolysis (TLG) > 8.5 were recognized as the most accurate thresholds to predict PFS (2-year PFS 62 % for

  4. Identification of Apo-A1 as a biomarker for early diagnosis of bladder transitional cell carcinoma

    Directory of Open Access Journals (Sweden)

    Wang Shixin

    2011-04-01

    Full Text Available Abstract Background Bladder transitional cell carcinoma (BTCC is the fourth most frequent neoplasia in men, clinically characterized by high recurrent rates and poor prognosis. Availability of urinary tumor biomarkers represents a convenient alternative for early detection and disease surveillance because of its direct contact with the tumor and sample accessibility. Results We tested urine samples from healthy volunteers and patients with low malignant or aggressive BTCC to identify potential biomarkers for early detection of BTCC by two-dimensional electrophoresis (2-DE coupled with mass spectrometry (MS and bioinformatics analysis. We observed increased expression of five proteins, including fibrinogen (Fb, lactate dehydrogenase B (LDHB, apolipoprotein-A1 (Apo-A1, clusterin (CLU and haptoglobin (Hp, which were increased in urine samples of patients with low malignant or aggressive bladder cancer. Further analysis of urine samples of aggressive BTCC showed significant increase in Apo-A1 expression compared to low malignant BTCC. Apo-A1 level was measured quantitatively using enzyme-linked immunosorbent assay (ELISA and was suggested to provide diagnostic utility to distinguish patients with bladder cancer from controls at 18.22 ng/ml, and distinguish patients with low malignant BTCC from patients with aggressive BTCC in two-tie grading system at 29.86 ng/ml respectively. Further validation assay showed that Apo-A1 could be used as a biomarker to diagnosis BTCC with a sensitivity and specificity of 91.6% and 85.7% respectively, and classify BTCC in two-tie grading system with a sensitivity and specificity of 83.7% and 89.7% respectively. Conclusion Taken together, our findings suggest Apo-A1 could be a potential biomarker related with early diagnosis and classification in two-tie grading system for bladder cancer.

  5. Antiproliferative factor decreases Akt phosphorylation and alters gene expression via CKAP4 in T24 bladder carcinoma cells

    Directory of Open Access Journals (Sweden)

    Zhang Chen-Ou

    2010-12-01

    β-catenin changed in response to APF in these cells. In addition, the changes in cell proliferation, MMP2/p53 mRNA and protein expression, and Akt/GSK3β/β-catenin phosphorylation in response to APF treatment were all specifically abrogated following CKAP4 siRNA knockdown. Conclusions Synthetic as-APF inhibits cell proliferation in T24 bladder carcinoma cells via the CKAP4 receptor. The mechanism for this inhibition involves regulating phosphorylation of specific cell signaling molecules (Akt, GSK3β, and β-catenin plus mRNA and protein expression of p53 and MMP2.

  6. Urinary pH Levels are Strongly Associated with Bladder Recurrence After Nephroureterectomy in Upper Tract Urothelial Carcinoma Patients with a Smoking History.

    Science.gov (United States)

    Ide, Hiroki; Kikuchi, Eiji; Hagiwara, Masayuki; Hayakawa, Nozomi; Hongo, Hiroshi; Miyajima, Akira; Oya, Mototsugu

    2016-12-01

    Aromatic amines, well-known bladder carcinogens, derived from cigarette smoke are activated by acidic urine. We herein determined whether urinary pH levels are associated with bladder recurrence in upper tract urothelial carcinoma patients with a positive smoking history. A total of 256 upper tract urothelial carcinoma patients who were surgically treated at our institution between 1990 and 2013 were included. Urinary pH levels were defined as the median of at least two consecutive measurements within 1 month of surgery. Ninety-six patients (37.5 %) had pH pH ≥5.5, and urinary pH levels were identified as one of the significant predictors for bladder recurrence in univariate but not multivariate Cox regression analysis in overall. In patients with a positive smoking history among those without a history of bladder tumor (N = 110), the 5-year bladder recurrence-free survival rate was 52.5 % in patients with pH ≥5.5, which was significantly higher than that in those with pH pH pH pH for urine alkalization may prevent bladder recurrence.

  7. Recent advances in the diagnosis and treatment of bladder cancer

    Directory of Open Access Journals (Sweden)

    Cheung Grace

    2013-01-01

    Full Text Available Abstract Bladder cancer is the commonest malignancy of the urinary tract. In this review, we look at the latest developments in the diagnosis and management of this condition. Cystoscopy and urine cytology are the most important tools in the diagnosis and follow-up of bladder cancer. Various alternatives have been investigated, either to reduce the frequency of cystoscopy, or improve its sensitivity for detection of tumors. These include urine-based markers and point-of-care tests. Narrow-band imaging and photodynamic diagnosis/blue-light cystoscopy have shown promise in improving detection and reducing recurrence of bladder tumors, by improving the completion of bladder resection when compared with standard resection in white light. The majority of patients with a new diagnosis of bladder cancer have non-muscle-invasive bladder cancer, which requires adjuvant intravesical chemotherapy and/or immunotherapy. Recent developments in post-resection intravesical regimens are discussed. For patients with muscle-invasive bladder cancer, both laparoscopic radical cystectomy and robot-assisted radical cystectomy have been shown to reduce peri-operative morbidity, while being oncologically equivalent to open radical cystectomy in the medium term. Bladder-preserving strategies entail resection and chemoradiation, and in selected patients give equivalent results to surgery. The development, advantages, and disadvantages of these newer approaches are also discussed.

  8. Long-term survival after gemcitabine and cisplatin in patients with locally advanced transitional cell carcinoma of the bladder: focus on supplementary treatment strategies

    DEFF Research Database (Denmark)

    Als, Anne Birgitte; Sengelov, Lisa; von der Maase, Hans

    2007-01-01

    OBJECTIVE: The objective was to evaluate response and survival, as well as efficacy of subsequent supplementary treatment and follow-up strategy in patients with locally advanced transitional cell carcinoma of the bladder following combination chemotherapy with gemcitabine and cisplatin (GC...

  9. Association of PAX5 Expression with Clinical Outcome in Patients with TaT1 Transitional Cell Carcinoma of the Bladder

    Czech Academy of Sciences Publication Activity Database

    Babjuk, M.; Soukup, V.; Mareš, J.; Dušková, J.; Pecen, Ladislav; Pešl, M.; Pavlík, I.; Dvořáček, J.

    2006-01-01

    Roč. 67, č. 4 (2006), s. 756-761 ISSN 0090-4295 R&D Projects: GA MZd NR8095; GA MZd NR8934 Institutional research plan: CEZ:AV0Z10300504 Keywords : bladder carcinoma * PAX5 expression Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 2.130, year: 2006

  10. The Relationship between Bladder Cancer and Epigenetic Alterations

    Directory of Open Access Journals (Sweden)

    Ata Özen

    2017-03-01

    Full Text Available Bladder cancer is one of the most common cancers of urinary system and approximately 70% of the cases are low grade and non-muscle invasive. Because of the histological indicator inadequacy of heterogeneous tumors like bladder cancer, researchers tend to look into genetic and molecular markers. Furthermore, role of epigenetic changes in cancer biology to be more distinctive than other cellular changes was shown. Epigenetic changes include 3 main titles; DNA methylation, micro RNA regulation and histone modification. In the literature, many epigenetic changes were found to be associated with early detection of the disease, progression, patient prognosis, tumor recurrence, early relapse, higher pathologic stage, disease-specific survival. With the understanding of epigenetic changes better patient outcomes will be achieved in the future.

  11. Cohort profile: The Swedish National Register of Urinary Bladder Cancer (SNRUBC) and the Bladder Cancer Data Base Sweden (BladderBaSe)

    Science.gov (United States)

    Häggström, Christel; Liedberg, Fredrik; Hagberg, Oskar; Aljabery, Firas; Ströck, Viveka; Hosseini, Abolfazl; Gårdmark, Truls; Sherif, Amir; Malmström, Per-Uno; Garmo, Hans; Jahnson, Staffan; Holmberg, Lars

    2017-01-01

    Purpose To monitor the quality of bladder cancer care, the Swedish National Register of Urinary Bladder Cancer (SNRUBC) was initiated in 1997. During 2015, in order to study trends in incidence, effects of treatment and survival of men and women with bladder cancer, we linked the SNRUBC to other national healthcare and demographic registers and constructed the Bladder Cancer Data Base Sweden (BladderBaSe). Participants The SNRUBC is a nationwide register with detailed information on 97% of bladder cancer cases in Sweden as compared with the Swedish Cancer Register. Participants in the SNRUBC have registered data on tumour characteristics at diagnosis, and for 98% of these treatment data have been captured. From 2009, the SNRUBC holds data on 88% of eligible participants for follow-up 5 years after diagnosis of non-muscle invasive bladder cancer, and from 2011, data on surgery details and complications for 85% of participants treated with radical cystectomy. The BladderBaSe includes all data in the SNRUBC from 1997 to 2014, and additional covariates and follow-up data from linked national register sources on comorbidity, socioeconomic factors, detailed information on readmissions and treatment side effects, and causes of death. Findings to date Studies based on data in the SNRUBC have shown inequalities in survival and treatment indication by gender, regions and hospital volume. The BladderBaSe includes 38 658 participants registered in SNRUBC with bladder cancer diagnosed from 1 January 1997 to 31 December 2014. The BladderBaSe initiators are currently in collaboration with researchers from the SNRUBC investigating different aspects of bladder cancer survival. Future plans The SNRUBC and the BladderBaSe project are open for collaborations with national and international research teams. Collaborators can submit proposals for studies and study files can be uploaded to servers for remote access and analysis. For more information, please contact the corresponding

  12. Performance of Urinary Markers for Detection of Upper Tract Urothelial Carcinoma: Is Upper Tract Urine More Accurate than Urine from the Bladder?

    Directory of Open Access Journals (Sweden)

    Simone Bier

    2018-01-01

    Full Text Available Objectives. To assess the performance of urine markers determined in urine samples from the bladder compared to samples collected from the upper urinary tract (UUT for diagnosis of UUT urothelial carcinoma (UC. Patients and Methods. The study comprised 758 urine samples either collected from the bladder (n=373 or UUT (n=385. All patients underwent urethrocystoscopy and UUT imaging or ureterorenoscopy. Cytology, fluorescence in situ hybridization (FISH, immunocytology (uCyt+, and nuclear matrix protein 22 (NMP22 were performed. Results. UUT UC was diagnosed in 59 patients (19.1% (UUT urine and 27 patients (7.2% (bladder-derived urine. For UUT-derived samples, sensitivities for cytology, FISH, NMP22, and uCyt+ were 74.6, 79.0, 100.0, and 100.0, while specificities were 66.6, 50.7, 5.9, and 66.7%, respectively. In bladder-derived samples, sensitivities were 59.3, 52.9, 62.5, and 50.0% whereas specificities were 82.9, 85.0, 31.3, and 69.8%. In UUT-derived samples, concomitant bladder cancer led to increased false-positive rates of cytology and FISH. Conclusions. Urine markers determined in urine collected from the UUT exhibit better sensitivity but lower specificity compared to markers determined in bladder-derived urine. Concomitant or recent diagnosis of UC of the bladder can further influence markers determined in UUT urine.

  13. Schistosomiasis-induced squamous cell bladder carcinoma in an HIV-infected patient

    DEFF Research Database (Denmark)

    Marbjerg, Lis Høy; Øvrehus, Anne Lindebo Holm; Johansen, Isik Somuncu

    2015-01-01

    haematuria for more than a year. Investigations revealed invasive S. haematobium-associated squamous cell bladder cancer. If her origin had been taken into account, the diagnosis might have been made earlier. Awareness of the disease prevalence among HIV co-infected patients from endemic areas and timely...... screening of such patients is important for the early diagnosis of schistosomiasis and related complications, such as S. haematobium-associated squamous cell bladder cancer.......The burden of Schistosoma haematobium-associated bladder cancer is very high in Africa; nevertheless the disease can pose considerable diagnostic challenges in low prevalence countries. We present the case of a 40-year-old HIV co-infected woman, originally from Mozambique, who had persisting...

  14. Overview of bladder heating technology: matching capabilities with clinical requirements

    Science.gov (United States)

    Stauffer, Paul R.; van Rhoon, Gerard C.

    2016-01-01

    Moderate temperature hyperthermia (40–450°C for one hour) is emerging as an effective treatment to enhance best available chemotherapy strategies for bladder cancer. A rapidly increasing number of clinical trials have investigated the feasibility and efficacy of treating bladder cancer with combined intravesical chemotherapy and moderate temperature hyperthermia. To date, most studies have concerned treatment of non-muscle invasive bladder cancer (NMIBC) limited to the interior wall of the bladder. Following the promising results of initial clinical trials, investigators are now considering protocols for treatment of muscle invasive bladder cancer (MIBC). This paper provides a brief overview of the devices and techniques used for heating bladder cancer. Systems are described for thermal conduction heating of bladder wall via circulation of hot fluid, intravesical microwave antenna heating, capacitively coupled RF current heating, and radiofrequency phased array deep regional heating of the pelvis. Relative heating characteristics of the available technologies are compared based on published feasibility studies, and the systems correlated with clinical requirements for effective treatment of MIBC and NMIBC. PMID:26939993

  15. Short-term moderate dose pelvic radiotherapy of advanced bladder carcinoma

    International Nuclear Information System (INIS)

    Fossaa, S.D.; Hosbach, G.

    1991-01-01

    Thirty-nine patients with advanced bladder cancer received pelvic radiotherapy (3 Gyx10 during 2 weeks) with palliative aim. Except for improvement of urinary incontinence, no improvement regarding urinary symptoms or general well-being could be demonstrated in 19 completely evaluable patients who were assessed by a mailed questionnaire 3 months after treatment. The median survival for all 39 patients was 7.5 months. Other forms of palliative treatment (chemotherapy combined with radiotherapy or accelerated radiotherapy, palliative surgery) should be evaluated by randomized trials in these poor-prognosis bladder cancer patients. Self-administrated questionnaires seem to be useful for assessing the subjective morbidity of such patients. (orig.)

  16. Qualitative and quantitative histopathology in transitional cell carcinomas of the urinary bladder. An international investigation of intra- and interobserver reproducibility

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt; Sasaki, M; Fukuzawa, S

    1994-01-01

    .54). This can probably be related to the manual design of the sampling scheme and may be solved by introducing a motorized object stage in the systematic selection of fields of vision for quantitative measurements. However, the nuclear mean size estimators are unaffected by such sampling variability...... results. Using objective, unbiased stereologic techniques and ordinary histomorphometry, such problems may be solved. EXPERIMENTAL DESIGN: A study of 110 patients with papillary or solid transitional cell carcinomas of the urinary bladder in stage Ta through T4 was carried out, addressing reproducibility...... of both qualitative and quantitative grading methods. Grading of malignancy was performed by one observer in Japan (using the World Health Organization scheme), and by two observers in Denmark (using the Bergkvist system). A "translation" between the systems, grade for grade, and kappa statistics were...

  17. Effect of non-specific prophylaxis of thrombogenic complications on delayed results of combined treatment of bladder carcinoma

    International Nuclear Information System (INIS)

    Popov, A.I.

    1987-01-01

    Altogether 106 patients with bladder carcinoma (Stage T 3 N x M 0 ) after combined treatment were followed-up for 5 yrs. Nicotonic acid and aspirin at common doses were adminstrated to 51 patients (the 1st group) during pre- and postoperative radiation therapy. The other 55 patients (the 2nd group) did not receive these drugs. Relapses were noted in 33.3% of the patients of the 1st group and in 76.3% of the patients of the 2nd group. The 5-year survival in the 1st group was 72.5% and in the 2nd group 27.4%. The administration of nicotonic acid and aspirin to patients during pre- and postoperative γ-beam therapy was shown to raise the body antitumor resistance

  18. The natural history of bladder carcinoma in situ after initial response to bacillus Calmette-Gúerin immunotherapy.

    Science.gov (United States)

    Gofrit, Ofer N; Pode, Dov; Pizov, Galina; Zorn, Kevin C; Katz, Ran; Duvdevani, Mordechi; Shapiro, Amos

    2009-01-01

    To explore patterns of recurrence, muscle invasion, and disease specific mortality in patients with bladder carcinoma in situ (CIS) who responded to an induction course with intravesical bacillus Calmette-Gúerin (BCG) immunotherapy. Between June 1985 and December 2003, 104 patients (mean age 67 years) were diagnosed with either pure (38 patients) or concomitant (66 patients) CIS. Patients who responded to one (92 patients) or two (12 patients) induction courses of intravesical BCG instillation were included in the study. Response was determined and monitored by routine periodic bladder biopsies. Outcome of patients and the effect of various prognostic parameters were assessed after a median follow-up of 75 months. The 5- and 10-year recurrence-free survival rates were 63% and 54%, respectively. The 5- and 10-year muscle-invasive-free survival rates were 79% and 77%, and the 5- and 10-year disease-specific survival rates were 90.5 and 85.8%, respectively. Median time to recurrence, muscle invasion, and disease-specific mortality was 18, 19, and 40 months, respectively. Pure and concomitant CIS were associated with a similar outcome. The recurrence of nonmuscle-invasive tumor did not increase the risk for muscle invasion or mortality. Pure and concomitant bladder CIS share similar biologic behavior. Muscle-invasive disease is expected in about 25% of the BCG responders followed for long time periods and disease-specific mortality in 15%. Tumor recurrence, whether nonmuscle-invasive or muscle-invasive, follows a similar time table suggesting that these are not sequential but parallel and independent processes.

  19. The Prognostic Role of NEDD9 and P38 Protein Expression Levels in Urinary Bladder Transitional Cell Carcinoma

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    Ola A. Harb

    2017-01-01

    Full Text Available Background. The most common malignant tumor of the urinary bladder is transitional cell carcinoma (TCC. Neural precursor cell-expressed developmentally downregulated protein 9 (NEDD9 is found to be a cell adhesion mediator. P38 Mitogen-Activated Protein Kinase is a serine/threonine kinases member which can mediate carcinogenesis through intracellular signaling. Methods. To assess their prognostic role; NEDD9 and p38 protein were evaluated in sections from 50 paraffin blocks of TCC. Results. The high expressions of NEDD9 and p38 protein were significantly associated with grade, stage, distant metastasis (p<0.001, number of tumors, lymph node metastasis, and tumor size (p<0.001, 0.002; 0.018, <0.001; and 0.004, 0.007, respectively. High NEDD9 and p38 detection had a worse 3-year OS (p=0.041 and <0.001, respectively. By multivariate analysis the NEDD9 and p38 protein expression levels and various clinicopathological criteria including gender, grade, stage of the tumor, and regional lymph node involvement were independent prognostic parameters of TCC of the urinary bladder patients’ outcome. Conclusion. NEDD9 and p38 protein expressions were poor prognostic markers of TCC.

  20. Pattern and Risk Factors of Urinary Bladder Neoplasms in ...

    African Journals Online (AJOL)

    It poses biologic and clinical challenges. ... Conclusion: There is significant relationship between urinary schistosomal infestation and the development of squamous cell carcinoma of the urinary bladder among Sudanese patients. Keywords: Urinary Bladder, Transitional Cell Carcinoma, Squamous Cell Carcinoma

  1. Prognostic Value of Beta-Tubulin-3 and c-Myc in Muscle Invasive Urothelial Carcinoma of the Bladder

    Science.gov (United States)

    Massari, Francesco; Bria, Emilio; Ciccarese, Chiara; Munari, Enrico; Modena, Alessandra; Zambonin, Valentina; Sperduti, Isabella; Artibani, Walter; Cheng, Liang; Martignoni, Guido; Tortora, Giampaolo; Brunelli, Matteo

    2015-01-01

    Background To date, putative prognostic biomarkers have shown limited utility from the clinical perspective for bladder urothelial carcinoma. Herein, the expression of beta-tubulin-3 and c-Myc was evaluated to determine their prognostic potential. Methods In formalin fixed-paraffin embedded blocks, immunohistochemical expression of c-Myc and beta-tubulin-3 was evaluated. H score ranging from 0 to 300 was obtained by multiplying the percentage of positive cells by intensity (0–3); c-Myc and beta-tubulin-3 expression was defined: 0: negative, 1: weakly positive, 2: strongly positive. Results beta-tubulin-3 and c-Myc immunoexpression was available for 46 cases. At the univariate analysis, node-involvement, beta-tubulin-3 and c-Myc overexpression discriminate shorter DFS (HR 2.19, p = 0.043; HR 3.10, p = 0.24 and HR 3.05, p = 0.011, respectively); 2-yrs DFS log-rank analysis according to low versus high level of immunoexpression were statistically significant; beta-tubulin-3, 53% low vs 12.7% high (p = value 0.02) and c-Myc 28 low vs 8 high (p-value 0.007). Patients displaying negative beta-tubulin-3/c-Myc had statistically significant better 2-yrs DFS than those with mixed expression or double positivity (54.5% versus 18.7% versus 0%, log-rank p = 0.006). Conclusions c-Myc and beta-tubulin-3 show improvement for prognostic risk stratification in patients with muscle invasive bladder urothelial carcinoma. These molecular pathways may also be candidate to improve predictiveness to targeted therapies. PMID:26046361

  2. Prognostic Value of Beta-Tubulin-3 and c-Myc in Muscle Invasive Urothelial Carcinoma of the Bladder.

    Directory of Open Access Journals (Sweden)

    Francesco Massari

    Full Text Available To date, putative prognostic biomarkers have shown limited utility from the clinical perspective for bladder urothelial carcinoma. Herein, the expression of beta-tubulin-3 and c-Myc was evaluated to determine their prognostic potential.In formalin fixed-paraffin embedded blocks, immunohistochemical expression of c-Myc and beta-tubulin-3 was evaluated. H score ranging from 0 to 300 was obtained by multiplying the percentage of positive cells by intensity (0-3; c-Myc and beta-tubulin-3 expression was defined: 0: negative, 1: weakly positive, 2: strongly positive.beta-tubulin-3 and c-Myc immunoexpression was available for 46 cases. At the univariate analysis, node-involvement, beta-tubulin-3 and c-Myc overexpression discriminate shorter DFS (HR 2.19, p = 0.043; HR 3.10, p = 0.24 and HR 3.05, p = 0.011, respectively; 2-yrs DFS log-rank analysis according to low versus high level of immunoexpression were statistically significant; beta-tubulin-3, 53% low vs 12.7% high (p = value 0.02 and c-Myc 28 low vs 8 high (p-value 0.007. Patients displaying negative beta-tubulin-3/c-Myc had statistically significant better 2-yrs DFS than those with mixed expression or double positivity (54.5% versus 18.7% versus 0%, log-rank p = 0.006.c-Myc and beta-tubulin-3 show improvement for prognostic risk stratification in patients with muscle invasive bladder urothelial carcinoma. These molecular pathways may also be candidate to improve predictiveness to targeted therapies.

  3. Survival after primary and deferred cystectomy for stage T1 transitional cell carcinoma of the bladder

    Directory of Open Access Journals (Sweden)

    Bedeir Ali-El-Dein

    2011-01-01

    Conclusions: Cancer-specific survival is statistically comparable for primary and deferred cystectomy in T1 bladder cancer, although there is a non-significant difference in favor of primary cystectomy. In the deferred cystectomy group, the number of TURBTs beyond three is associated with lower survival. Conservative treatment should be adopted for most cases in this category.

  4. Tea (Camellia sinensis (L.)): a putative anticancer agent in bladder carcinoma?

    Science.gov (United States)

    Conde, Vanessa R; Alves, Marco G; Oliveira, Pedro F; Silva, Branca M

    2015-01-01

    The leaves of Camellia sinensis (L.) are the source of tea, the second most consumed beverage worldwide. Tea contains several chemical compounds such as polyphenols (mainly catechins), caffeine, theophylline, L-theanine, among many others. Polyphenolic compounds are mainly responsible for its significant antioxidant properties and anticarcinogenic potential. Bladder cancer is one of the most common types of cancer, and its progression and onset are thought to be controlled by dietary and lifestyle factors. Epidemiological studies showed that the regular consumption of tea can be a preventive factor for this type of cancer, and several in vivo and in vitro studies reported that tea and its components may interfere in the cancer cells' signaling, preventing the bladder tumor progression. The mechanisms responsible for this protection include deregulation of cell cycle, induction of apoptosis while protecting the surrounding healthy bladder cells, inhibition of metastization processes, among others. Herein, we discuss the potential beneficial effects of tea and tea components in bladder cancer prevention and/or treatment, and how they can be helpful in finding new therapeutic strategies to treat this type of cancer.

  5. Systemic BCG-osis following intravesical BCG instillation for bladder carcinoma.

    Science.gov (United States)

    Liaw, Frank; Tan, Yan Yu; Hendry, David

    2017-10-01

    Intravesical instillation of Bacillus Calmette-Guérin (BCG) has been shown to be an effective form of immunotherapy for bladder cancer. This case report describes a patient who develops systemic BCG-osis following intravesical BCG instillation and demonstrates the importance of being aware of more severe complications associated with BCG immunotherapy.

  6. Role of Aspirin in Patients with Bladder Cancer Receiving Intravesical Bacillus Calmette-Guerin: A Prospective, Observational Study

    Directory of Open Access Journals (Sweden)

    Rupesh Gupta

    2017-10-01

    Full Text Available Introduction: High-Risk Non-Muscle Invasive Bladder Cancers (HR NMIBC are prone to recur and progress even with intravesical Bacillus Calmette-Guerin (BCG therapy. Aim: To investigate the role of aspirin in prevention of early recurrence and progression in patients with HR NMIBC receiving intravesical BCG. Materials and Methods: This was a prospective, single centre, observational study that included patients with HR NMIBC {Ta, T1 or Carcinoma in situ (CIS} from February 2015 to January 2017. Patients were screened for eligibility based on clinical, radiological and risk factor profile assessment, history of treatment with aspirin and medical records. Eligible patients were grouped into Group 1 and Group 2 based on aspirin (for minimum of three months or non-aspirin consumption respectively. Both groups received similar induction, maintenance and intravesical BCG therapy; according to Southwest Oncology Group (SWOG protocol. Follow up cystoscopy was done every three months for up to two years. Results: A total of 152 patients were screened and 103 patients were included in the study (Group 1, n=15; Group 2, n=88. Binary progression analysis revealed that focality was the only significant predictor variable for the recurrence (OR, 5.064; p=0.001. Aspirin intake was not related to stage (p=0.595, grade (p=0.558, recurrence (p=0.508 and progression (p=0.621 of the tumour. Kaplan-Meier analysis showed that 12-month recurrence (64.2% versus 64.7%, p=0.566 and progression free survival rate (66.7% versus 57.3%, p=0.640 were same in both groups. Conclusion: Results showed that aspirin does not affect the recurrence and progression of HR NMIBC in patients receiving BCG therapy.

  7. Bladder Contracture – A Rare and Serious Side Effect of Intravesical Bacillus Calmette-Guérin Therapy

    Directory of Open Access Journals (Sweden)

    Cindy Garcia

    2016-01-01

    Full Text Available Instillation of intravesical bacillus Calmette-Guérin (BCG is an effective treatment for non-muscle invasive bladder cancer (NMIBC. The high incidence of side effects may limit its tolerability in patients. Local side effects including cystitis and hematuria are common but generally self-limiting. Bladder contractures are a rare but serious consequence of BCG treatment. In this case, an 82 year-old male developed BCG reactivation and subsequent bladder contractures following transurethral resection of the prostate (TURP three years post-BCG. To our knowledge, this is the first reported case of BCG reactivation post-TURP leading to the rare but serious effect of bladder contractures.

  8. Optimal Treatment for Intermediate- and High-Risk, Nonmuscle-Invasive Bladder Cancer

    Directory of Open Access Journals (Sweden)

    A.P.M. van der Meijden

    2006-01-01

    Full Text Available According to clinical and pathological factors the prognosis of a patient with non-muscle invasive bladder tumors can be assessed. The prognosis is determined by the likelihood of recurrence(30-70% and/or progression to muscle invasive bladder cancer(1-15%.Trans urethral resection of bladder tumors remains the initial therapy but adjuvant intravesical instillations are necessary.All patients benefit from a single immediate post operative instillation with a chemotherapeutic agent and for low risk tumors this is the optimal therapy.Patients with intermediate and high risk tumors need more intravesical chemo-or immunotherapy. Chemotherapy reduces recurrences but not progression. Intravesical immunotherapy(BCG prevents or delays progression. Patients at high risk for progression may need upfront cystectomy.

  9. Suppression of urinary bladder urothelial carcinoma cell by the ethanol extract of pomegranate fruit through cell cycle arrest and apoptosis.

    Science.gov (United States)

    Lee, Song-Tay; Lu, Min-Hua; Chien, Lan-Hsiang; Wu, Ting-Feng; Huang, Li-Chien; Liao, Gwo-Ing

    2013-12-21

    Pomegranate possesses many medicinal properties such as antioxidant, anti-inflammation and antitumor. It has been extensively used as a folk medicine by many cultures. Pomegranate fruit has been shown to have the inhibitory efficacy against prostate cancer and lung cancer in vitro and in vivo. It can be exploited in chemoprevention and chemotherapy of prostate cancer. In this study we examined the anti-cancer efficacy of pomegranate fruit grown in Taiwan against urinary bladder urothelial carcinoma (UBUC) and its mechanism of action. Edible portion of Taiwanese pomegranate was extracted using ethanol and the anti-cancer effectiveness of ethanol extract was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Flow cytometry and western immunoblotting were exploited to uncover the molecular pathways underlying anti-UBUC activity of Taiwanese pomegranate ethanol extract. This study demonstrated that Taiwanese pomegranate fruit ethanol extract (PEE) could effectively restrict the proliferation of UBUC T24 and J82 cells. Cell cycle analyses indicated that the S phase arrest induced by PEE treatment might be caused by an increase in cyclin A protein level and a decrease in the expression of cyclin-dependent kinase 1. The results of western immunoblotting demonstrated that PEE treatment could not only evoke the activation of pro-caspase-3, -8,-9 but also increase Bax/Bcl-2 ratio in T24 cells. The above observations implicated that PEE administration might trigger the apoptosis in T24 cells through death receptor signaling and mitochondrial damage pathway. Besides we found that PEE exposure to T24 cells could provoke intensive activation of procaspase-12 and enhance the expressions of CHOP and Bip, endoplasmic reticulum (ER) stress marker, suggesting that ER stress might be the cardinal apoptotic mechanism of PEE-induced inhibition of bladder cancer cell. The analytical results of this study help to provide insight into the molecular mechanism

  10. Delayed Cystectomy for T1G3 Transitional Cell Carcinoma (TCC) of the Urinary Bladder, NCI Retrospective Case Series.

    Science.gov (United States)

    Fakhr, Ibrahim; El-Hossieny, Hesham; Salama, Asmaa

    2008-12-01

    We aim to evaluate the National Cancer Institute (NCI) treatment protocol and its outcome regarding recurrence, progression and survival in patients with T1G3 urinary bladder transitional cell carcinoma. In a retrospective study, between January 2001 and December 2007, all 34 patients with T1G3 bladder transitional cell carcinoma (TCC), after complete transurethral resection (TURBT), received intravesical BCG as adjuvant therapy. A conservative approach was adopted, whereby those with superficial recurrences were eligible to TURBT, with delayed cystectomy for progression to muscle invasion. Overall, recurrence, and progression-free survival were analyzed. Thirty-three patients were included, 29 were males and 4 were females. The mean age was 61 years (range 35-89 years). Final analysis was made at median follow-up of 15 months (Range of 3-68 months, mean 18 months) for survival. Eleven (33.3%) patients had multifocal tumors. Associated schistosomiasis was present in 12 (36.6%) patients. Twenty-two (66.67%) patients showed recurrence. Eleven out of these 22 (50.0%) patients progressed to muscle invasion and underwent radical cystectomy. Ten out of 34 (30.3%) patients received postcystectomy radiotherapy. Two (20.0%) of them, were staged as TNM stage II, 6 (60.0%) as TNM stage III and 2 (20.0%) patients were TNM stage IV. Eight (72.7%) of these 11 patients had post-cystectomy radiotherapy alone; while the 2 (6.0%) other patients with stage IV had adjuvant concomitant Cisplatin and Gemcitabine chemotherapy. Five (14%) patients of those cystectomy patients died of TCC. Three (60%) patients died from metastatic disease (to lung, liver and bone), one patient died from advanced locoregional disease and another patient died from postoperative complications. Among those patients who received radiotherapy alone, 62.5% are alive. Although, we report a biologically more aggressive behavior of T1G3 than that reported by some authors, for this conservative approach, the overall

  11. Metastatic carcinoma of the urinary bladder in a 67-year-old female with underlying triple primary cancers

    Directory of Open Access Journals (Sweden)

    Chia-Yen Hung

    2016-06-01

    A 67-year-old Taiwanese female presented to our institution in November 1997 with gastric signet ring cell carcinoma, pT2N0M0, status post subtotal gastrectomy. In February 2003 she was diagnosed with left breast invasive lobular carcinoma status post modified radical mastectomy, pT2N2M0. Further examination in January 2005 revealed proximal transverse colon cancer, Dukes' C2, with status post right hemicolectomy. She achieved disease-free status from all three malignancies after surgical resection and adjuvant chemotherapy for breast and colon cancers sequentially. In November 2011, she complained about sudden onset of gross hematuria for several days. Diagnostic cystoscopy showed a mass lesion over her urinary bladder. Cystoscope-assisted biopsy showed metastatic poorly differentiated adenocarcinoma with signet ring appearance. Herein we have discussed the pathologic role in the diagnosis of metastatic tumor involving a patient with multiple primary cancers. We also explored the epidemiologic risk and potential causal mechanism of patients with multiple primary cancers.

  12. Analysis of prognostic factors in patients with transitional cell carcinoma of the bladder treated with radical cystectomy

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    Antunes Alberto A.

    2006-01-01

    Full Text Available OBJECTIVE: To analyze the results of the treatment of transitional cell carcinoma (TCC of the bladder with radical cystectomy and determine which prognostic factors can be utilized as disease-free survival and cancer-specific survival independent variables. MATERIALS AND METHODS: Medical records of 113 patients submitted to radical cystectomy and bilateral iliac lymphadenectomy between 1993 and 2005 were reviewed. The risk factors analyzed were age, sex, pathological stage, tumor grade, presence of carcinoma in situ and the presence of lymph nodes involvement. RESULTS: After a mean follow-up of 31.7 ? 28.5 months, 46 patients (40.7% presented recurrence and 24 patients (21.2% died due to cancer. Only pathological stage and the lymph nodes involvement became independent variables for recurrence and survival. Patients with T4 stage presented 9.6 times the risk of recurrence of the disease when compared with stage T0 patients (p = 0.010 and the patients with lymph node involvement presented 2.5 times the risk of recurrence (p = 0.047 and 3.1 times the risk of death (p = 0.022 when compared to patients without lymph nodes involvement. CONCLUSIONS: Pathological stage and the involvement of lymph nodes represented more important prognostic variables, and in the presence of advanced stage tumors (T3/T4 and involvement of lymph nodes, the institution of adjuvant treatment should be considered.

  13. Usefulness of the UBCTM (urinary bladder cancer) test compared to urinary cytology for transitional cell carcinoma of the bladder in patients with hematuria

    International Nuclear Information System (INIS)

    Gil, Myung Cheol; Kang, Do Young; Seong, Youl Koon

    2001-01-01

    Urinary cytology and cystoscopic exam are effective methods for diagnosis of transitional cell carcinoma (TCC). But the former shows drawbacks such as the need for a well-trained examiner, and wide imprecision related to the variability of microscopic exam; the latter is a invasive method. UBC TM test detects the epitope on specific cytokeratin fragments released from epithelium of bladder cancer by immunoradiometric assay. We compared UBC TM test with urinary cytology for diagnosis of TCC to evaluate the utility of UBC TM test. Eighty-four patients with hematuria were included in our study, UBC TM tests (IDL Biotech, Sweden) were assayed in mid-stream urine according to the ordinary assay protocol. Nineteen patients were confirmed as TCC by cystoscopic examination and underwent transurethral resection (Group A). Other patients had various benign urinary tract conditions (Group B). Samples were considered positive as the UBC TM concentration was greater than 12 μg/L. UBC TM levels were significantly different between group A (95.9 ±166.4 μg/L) and group B (19.2 ± 85.6 μg/L)(p TM test and 100% (65/65) in cytology. UBC TM test was significantly more sensitive in stage Ta, T 1 tumors (84.6 vs 38.5%, p TM test showed a tendency to be more sensitive as the grade was higher (83.3% in Grade 1, 90% in Grade II and 100% in Grade III). UBC TM test could be a useful method in distinguishing TCC from other benign genitourinary diseases. Moreover, UBC TM test could be an especially valuable marker for diagnosis of TCC in patients with early TCC of low grade TCC compared to urinary cytology. Therefore, mbined use of UBC TM test in association with cytology is helpful to overcome the limited sensitivity of cytology

  14. Chemoradiotherapy for muscle invading bladder carcinoma. final report of a single institutional organ-sparing program

    International Nuclear Information System (INIS)

    Arias, Fernando; Dominguez, Miguel A.; Martinez, Enrique; Illarramendi, Jose J.; Miquelez, Santiago; Pascual, Ignacio; Marcos, Marta

    2000-01-01

    Purpose: Chemoradiotherapy is becoming an alternative to radical cystectomy among patients with muscle invading bladder cancer. We began a prospective study in 1988 to determine the possibilities of conservative treatment and aiming to improve the results obtained by cystectomy alone in invasive bladder cancer. A combination of methotrexate, vinblastine, adriamycin, and cisplatin (M-VAC), followed by radiotherapy and concomitant cisplatin was used. Methods: Fifty patients with good performance status and with stages T2 to T4 operable untreated invasive bladder cancer were entered in the study. Treatment protocol was as follows: (i) cytoreductive transurethral resection; (ii) two cycles of M-VAC chemotherapy; (iii) radiotherapy, 45 Gy on pelvic volume and, at the same time, 20 mg/m 2 cisplatin on days 1 to 5. Cystoscopic evaluation: if there was a complete response, radiotherapy was completed up to 65 Gy; if there was not a complete response, a cystectomy was performed. Median follow-up of the series was 73 months (18-180 m). Results: Tumor response was as follows: 34 complete responses (68%), 9 partial responses (18%), and 7 nonresponses (14%) were observed. The 5-year overall survival and local control were 48% and 47%, respectively. For the complete responder patient, 5-year survival and local control were 65% and 70%, respectively. Severe toxicity was uncommon. The most frequent were leucopenia and cystitis. No treatment-related deaths occurred with either treatment protocol. Conclusions: Conservative combination treatment may be an acceptable alternative to immediate cystectomy in selected patients with bladder cancer, although a randomized clinical trial would be required to produce definitive results

  15. Impact of lymphovascular invasion on recurrence and progression rates in patients with pT1 urothelial carcinoma of bladder after transurethral resection

    Directory of Open Access Journals (Sweden)

    Sha N

    2015-11-01

    Full Text Available Nan Sha,* Linguo Xie,* Tao Chen,* Chen Xing, Xiaoteng Liu, Yu Zhang, Zhonghua Shen, Hao Xu, Zhouliang Wu, Hailong Hu, Changli Wu Department of Urology, Tianjin Key Laboratory of Urology, Tianjin Institute of Urology, Second Hospital of Tianjin Medical University, Tianjin, People’s Republic of China *These authors contributed equally to this work Objective: To evaluate the clinical significance of lymphovascular invasion (LVI on recurrence and progression rates in patients with pT1 urothelial carcinoma of bladder after transurethral resection.Methods: This retrospective study was performed with 155 patients with newly diagnosed pT1 urothelial carcinoma of bladder who were treated with transurethral resection of bladder tumor at our institution from January 2006 to January 2010. The presence or absence of LVI was examined by pathologists. Chi-square test was performed to identify the correlations between LVI and other clinical and pathological features. Kaplan–Meier method was used to estimate the recurrence-free survival (RFS and progression-free survival curves and difference was determined by the log-rank test. Univariate and multivariate analyses were performed to determine the predictive factors through a Cox proportional hazards analysis model.Results: LVI was detected in a total of 34 patients (21.9%. While LVI was associated with high-grade tumors (P<0.001 and intravesical therapy (P=0.009. Correlations with age (P=0.227, sex (P=0.376, tumor size (P=0.969, tumor multiplicity (P=0.196, carcinoma in situ (P=0.321, and smoking (P=0.438 were not statistically significant. There was a statistically significant tendency toward higher recurrence rate and shorter RFS time in LVI-positive patients. However, no statistically significant differences were observed in progression rate between the two groups. Moreover, multivariate Cox proportional hazards analysis revealed that LVI, tumor size, and smoking were independent prognostic predictors of

  16. Urothelial carcinoma associated 1 is a hypoxia-inducible factor-1α-targeted long noncoding RNA that enhances hypoxic bladder cancer cell proliferation, migration, and invasion.

    Science.gov (United States)

    Xue, Mei; Li, Xu; Li, Zhengkun; Chen, Wei

    2014-07-01

    Urothelial carcinoma associated 1 (UCA1) has been identified as an oncogenic long noncoding RNA (lncRNA) that is involved in bladder cancer progression and acts as a diagnostic biomarker for bladder carcinoma. Here, we studied the expression and function of lncRNA-UCA1 in the hypoxic microenvironment of bladder cancer. The expression and transcriptional activity of lncRNA-UCA1 were measured by quantitative real-time polymerase chain reaction and luciferase assays. Cell proliferation and apoptosis were evaluated by MTT assays and flow cytometry. Cell migration and invasion were detected by wound healing, migration, and invasion assays. The binding of hypoxia-inducible factor-1α (HIF-1α) to hypoxia response elements (HREs) in the lncRNA-UCA1 promoter was confirmed by electrophoretic mobility shift assay and chromatin immunoprecipitation. HRE mutations were generated by using a site-directed mutagenesis kit, and HIF-1α knockdown was mediated by small interfering RNA. The effect of HIF-1α inhibition by YC-1 on lncRNA-UCA1 expression was also examined. LncRNA-UCA1 was upregulated by hypoxia in bladder cancer cells. Under hypoxic conditions, lncRNA-UCA1 upregulation increased cell proliferation, migration, and invasion and inhibited apoptosis. The underlying mechanism of hypoxia-upregulated lncRNA-UCA1 expression was that HIF-1α specifically bound to HREs in the lncRNA-UCA1 promoter. Furthermore, HIF-1α knockdown or inhibition could prevent lncRNA-UCA1 upregulation under hypoxia. These findings revealed the mechanism of lncRNA-UCA1 upregulation in hypoxic bladder cancer cells and suggested that effective blocking of lncRNA-UCA1 expression in the hypoxic microenvironment of bladder cancer could be a novel therapeutic strategy.

  17. Needle tract implantation after fine needle aspiration biopsy (FNAB) of transitional cell carcinoma of the urinary bladder and adenocarcinoma of the lung.

    Science.gov (United States)

    Vignoli, M; Rossi, F; Chierici, C; Terragni, R; De Lorenzi, D; Stanga, M; Olivero, D

    2007-07-01

    This paper reports three clinical cases of needle tract implantation of neoplastic cells on the abdominal and thoracic wall after ultrasound (US) fine needle aspiration biopsy (FNAB). Primary tumors were two transitional cell carcinomas of the urinary bladder (2 dogs) and one pulmonary adenocarcinoma (1 cat). All three masses grew up along the needle tract. To our knowledge, the seeding of pulmonary adenocarcinoma cells after FNAB on the thoracic wall has never been reported in veterinary medicine.

  18. Plasmacytoid urothelial carcinoma of the bladder with extensive scrotal wall invasion

    Directory of Open Access Journals (Sweden)

    Yong Gang Wang

    2016-01-01

    Full Text Available Plasmacytoid urothelial carcinoma (PUC is an extremely rare and aggressive variant of urothelial carcinoma. We report a case of a 62-year-old male who presented with a rapid spread of PUC to involve his entire scrotal wall after failed surgery and chemotherapy. The second course of chemotherapy was effective in providing symptom control. We believe this is the first case report of PUC causing such rapid and extensive scrotal invasion. This case highlights the important features of PUC including the pattern of tumor spread along fascial planes, the tendency for initial understaging, and the rapid recurrence after initially response to chemotherapy.

  19. Does phosphorylation of cofilin affect the progression of human bladder cancer?

    International Nuclear Information System (INIS)

    Chung, Hong; Kim, Hong Sup; Kim, Bokyung; Jung, Seung-Hyo; Won, Kyung-Jong; Jiang, Xiaowen; Lee, Chang-Kwon; Lim, So Dug; Yang, Sang-Kuk; Song, Ki Hak

    2013-01-01

    We determined the differently expressed protein profiles and their functions in bladder cancer tissues with the aim of identifying possible target proteins and underlying molecular mechanisms for taking part in their progression. We examined the expression of proteins by proteomic analysis and western blot in normal urothelium, non-muscle-invasive bladder cancers (NMIBCs), and muscle-invasive bladder cancers (MIBCs). The function of cofilin was analyzed using T24 human bladder cancer cells. The expression levels of 12 proteins were altered between bladder cancers and normal bladder tissues. Of these proteins, 14-3-3σ was upregulated in both NMIBCs and MIBCs compared with controls. On the other hand, myosin regulatory light chain 2, galectin-1, lipid-binding AI, annexin V, transthyretin, CARD-inhibitor of NF-κB-activating ligand, and actin prepeptide were downregulated in cancer samples. Cofilin, an actin-depolymerizing factor, was prominent in both NMIBCs and MIBCs compared with normal bladder tissues. Furthermore, we confirmed that cofilin phosphorylation was more prominent in MIBCs than in NMIBCs using immunoblotting and immunohistochemcal analyses. Epidermal growth factor (EGF) increased the phosphorylation of cofilin and elevated the migration in T24 cells. Knockdown of cofilin expression with small interfering RNA attenuated the T24 cell migration in response to EGF. These results demonstrate that the increased expression and phosphorylation of cofilin might play a role in the occurrence and invasiveness of bladder cancer. We suspected that changes in cofilin expression may participate in the progression of the bladder cancer

  20. G9a Inhibition Induces Autophagic Cell Death via AMPK/mTOR Pathway in Bladder Transitional Cell Carcinoma.

    Directory of Open Access Journals (Sweden)

    Feng Li

    Full Text Available G9a has been reported to highly express in bladder transitional cell carcinoma (TCC and G9a inhibition significantly attenuates cell proliferation, but the underlying mechanism is not fully understood. The present study aimed at examining the potential role of autophagy in the anti-proliferation effect of G9a inhibition on TCC T24 and UMUC-3 cell lines in vitro. We found that both pharmaceutical and genetical G9a inhibition significantly attenuated cell proliferation by MTT assay, Brdu incorporation assay and colony formation assay. G9a inhibition induced autophagy like morphology as determined by transmission electron microscope and LC-3 fluorescence assay. In addition, autophagy flux was induced by G9a inhibition in TCC cells, as determined by p62 turnover assay and LC-3 turnover assay. The autophagy induced positively contributed to the inhibition of cell proliferation because the growth attenuation capacity of G9a inhibition was reversed by autophagy inhibitors 3-MA. Mechanically, AMPK/mTOR pathway was identified to be involved in the regulation of G9a inhibition induced autophagy. Intensively activating mTOR by Rheb overexpression attenuated autophagy and autophagic cell death induced by G9a inhibition. In addition, pre-inhibiting AMPK by Compound C attenuated autophagy together with the anti-proliferation effect induced by G9a inhibition while pre-activating AMPK by AICAR enhanced them. In conclusion, our results indicate that G9a inhibition induces autophagy through activating AMPK/mTOR pathway and the autophagy induced positively contributes to the inhibition of cell proliferation in TCC cells. These findings shed some light on the functional role of G9a in cell metabolism and suggest that G9a might be a therapeutic target in bladder TCC in the future.

  1. Transitional cell carcinoma of urinary bladder with metastasis in lumbar vertebrae and spinal cord compression in an ocelot(Leopardus pardalis

    Directory of Open Access Journals (Sweden)

    Karen Y.R. Nakagaki

    2015-01-01

    Full Text Available This paper reports a case of nonpapillary and infiltrative transitional cell carcinoma (TCC of the urinary bladder with metastasis of lumbar vertebrae and spinal cord compression in an adult female ocelot (Leopardus pardalis, from the Mato Grosso state, Brazil. The ocelot had pelvic limb paralysis and skin ulcers in the posterior region of the body and was submitted to euthanasia procedure. At necropsy was observed a multilobulated and irregular shaped, yellowish to white nodule in the urinary bladder. The nodule had a soft consistency and arised from the mucosa of the urinary bladder extending throughout the muscular layers and the serosa. Nodules of similar appearance infiltrating the vertebral column the at L6 and L7 vertebrae with corresponding spinal canal invasion were also observed. The histological evaluation showed epithelial neoplastic proliferation in the urinary bladder with characteristics of nonpapillary and infiltrative TCC, with positive immunohistochemical staining for pancytokeratin, and strong immunostaining for cytokeratin of low molecular weight, and weak or absent labeling for high molecular weight cytokeratin. This is the first report of TCC of urinary bladder in ocelot in Brazil.

  2. Small Cell Carcinoma of the Urinary Bladder: A Retrospective, Multicenter Rare Cancer Network Study of 107 Patients.

    Science.gov (United States)

    Pasquier, David; Barney, Brandon; Sundar, Santhanam; Poortmans, Philip; Villa, Salvador; Nasrallah, Haitam; Boujelbene, Noureddine; Ghadjar, Pirus; Lassen-Ramshad, Yasmin; Senkus, Elżbieta; Oar, Andrew; Roelandts, Martine; Amichetti, Maurizio; Vees, Hansjoerg; Zilli, Thomas; Ozsahin, Mahmut

    2015-07-15

    Small cell carcinomas of the bladder (SCCB) account for fewer than 1% of all urinary bladder tumors. There is no consensus regarding the optimal treatment for SCCB. Fifteen academic Rare Cancer Network medical centers contributed SCCB cases. The eligibility criteria were as follows: pure or mixed SCC; local, locoregional, and metastatic stages; and age ≥18 years. The overall survival (OS) and disease-free survival (DFS) were calculated from the date of diagnosis according to the Kaplan-Meier method. The log-rank and Wilcoxon tests were used to analyze survival as functions of clinical and therapeutic factors. The study included 107 patients (mean [±standard deviation, SD] age, 69.6 [±10.6] years; mean follow-up time, 4.4 years) with primary bladder SCC, with 66% of these patients having pure SCC. Seventy-two percent and 12% of the patients presented with T2-4N0M0 and T2-4N1-3M0 stages, respectively, and 16% presented with synchronous metastases. The most frequent curative treatments were radical surgery and chemotherapy, sequential chemotherapy and radiation therapy, and radical surgery alone. The median (interquartile range, IQR) OS and DFS times were 12.9 months (IQR, 7-32 months) and 9 months (IQR, 5-23 months), respectively. The metastatic, T2-4N0M0, and T2-4N1-3M0 groups differed significantly (P=.001) in terms of median OS and DFS. In a multivariate analysis, impaired creatinine clearance (OS and DFS), clinical stage (OS and DFS), a Karnofsky performance status <80 (OS), and pure SCC histology (OS) were independent and significant adverse prognostic factors. In the patients with nonmetastatic disease, the type of treatment (ie radical surgery with or without adjuvant chemotherapy vs conservative treatment) did not significantly influence OS or DFS (P=.7). The prognosis for SCCB remains poor. The finding that radical cystectomy did not influence DFS or OS in the patients with nonmetastatic disease suggests that conservative treatment is appropriate in this

  3. Small Cell Carcinoma of the Urinary Bladder: A Retrospective, Multicenter Rare Cancer Network Study of 107 Patients

    Energy Technology Data Exchange (ETDEWEB)

    Pasquier, David, E-mail: d-pasquier@o-lambret.fr [Academic Radiation Oncology Department, Centre Oscar Lambret, Lille (France); Barney, Brandon [Mayo Clinic, Rochester, Minnesota (United States); Sundar, Santhanam [Department of Oncology, Nottingham University Hospitals National Health Service Trust, Nottingham (United Kingdom); Poortmans, Philip [Department of Radiation Oncology, Radboud university medical center, Nijmegen (Netherlands); Villa, Salvador [Radiation Oncology, Catalan Institute of Oncology, H. Universitari Germans Trías, Badalona, Barcelona (Spain); Nasrallah, Haitam [Division of Oncology, Rambam Health Care Campus and Faculty of Medicine, Technion-Israel Institute of Technology, Haifa (Israel); Boujelbene, Noureddine [Department of Radiation Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne (Switzerland); Ghadjar, Pirus [Department of Radiation Oncology, Bern University Hospital, Bern (Switzerland); Lassen-Ramshad, Yasmin [Department of Oncology, Aarhus University Hospital, Aarhus (Denmark); Senkus, Elżbieta [Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk (Poland); Oar, Andrew [Genesis Cancer Care, Southport (Australia); Roelandts, Martine [Institut Jules Bordet, Brussels (Belgium); Amichetti, Maurizio [Provincial Agency for Proton Therapy, Trento (Italy); Vees, Hansjoerg [Department of Radiation Oncology, Hopital de Sion, Sion (Switzerland); Zilli, Thomas [Department of Radiation Oncology, Geneva University Hospital, Geneva (Switzerland); Ozsahin, Mahmut [Department of Radiation Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne (Switzerland)

    2015-07-15

    Purpose: Small cell carcinomas of the bladder (SCCB) account for fewer than 1% of all urinary bladder tumors. There is no consensus regarding the optimal treatment for SCCB. Methods and Materials: Fifteen academic Rare Cancer Network medical centers contributed SCCB cases. The eligibility criteria were as follows: pure or mixed SCC; local, locoregional, and metastatic stages; and age ≥18 years. The overall survival (OS) and disease-free survival (DFS) were calculated from the date of diagnosis according to the Kaplan-Meier method. The log-rank and Wilcoxon tests were used to analyze survival as functions of clinical and therapeutic factors. Results: The study included 107 patients (mean [±standard deviation, SD] age, 69.6 [±10.6] years; mean follow-up time, 4.4 years) with primary bladder SCC, with 66% of these patients having pure SCC. Seventy-two percent and 12% of the patients presented with T2-4N0M0 and T2-4N1-3M0 stages, respectively, and 16% presented with synchronous metastases. The most frequent curative treatments were radical surgery and chemotherapy, sequential chemotherapy and radiation therapy, and radical surgery alone. The median (interquartile range, IQR) OS and DFS times were 12.9 months (IQR, 7-32 months) and 9 months (IQR, 5-23 months), respectively. The metastatic, T2-4N0M0, and T2-4N1-3M0 groups differed significantly (P=.001) in terms of median OS and DFS. In a multivariate analysis, impaired creatinine clearance (OS and DFS), clinical stage (OS and DFS), a Karnofsky performance status <80 (OS), and pure SCC histology (OS) were independent and significant adverse prognostic factors. In the patients with nonmetastatic disease, the type of treatment (ie radical surgery with or without adjuvant chemotherapy vs conservative treatment) did not significantly influence OS or DFS (P=.7). Conclusions: The prognosis for SCCB remains poor. The finding that radical cystectomy did not influence DFS or OS in the patients with nonmetastatic disease

  4. Computed tomographic diagnosis of a primary carcinoma in a bladder diverticulum

    International Nuclear Information System (INIS)

    Woo, Seong Ku; Kim, Ok Bae; Zeon, Seok Kil; Joo, Yang Goo

    1987-01-01

    Primary neoplasms arising within vesical diverticular are rare but present special problem in diagnosis and treatment. Authors have experienced a case of primary carcinoma arising in vesical diverticulum i a 57 year old male patient, demonstrated by CT, and reported with brief review of literature.

  5. The effect of photochemical internalization of bleomycin in the treatment of urothelial carcinoma of the bladder: an in vitro study.

    Science.gov (United States)

    Arentsen, Harm C; Falke, Johannes; Høgset, Anders; Oosterwijk, Egbert; Alfred Witjes, J

    2014-01-01

    In this in vitro study, we determined whether meso-tetraphenyl chlorin disulphonate (TPCS2a)-based photochemical delivery of bleomycin was able to potentiate the cytotoxicity of bleomycin on bladder cancer cells. The human RT4, RT112, 253J, T24, and rat AY-27 urothelial carcinoma cell lines were used. Cells were seeded in 96-well plates. TPCS2a was added to the growth medium and the plates were incubated overnight. Cells were then resuspended in TPCS2a-free culture medium and incubated for 3 hours. Subsequently, cells were treated for 60 minutes with increasing doses of epirubicin, gemcitabine, mitomycin C, or bleomycin followed by illumination for different periods. Cell viability was measured with a colorimetric assay after 72 hours. For the single treatments, in all 5 cell lines a dose-dependent inhibition of cell proliferation was observed. This was seen both after treatment with TPCS2a-based photodynamic therapy (PDT), as well as after treatment with either bleomycin or one of the control chemotherapeutic agents. After treatment with PDT (240-s illumination), bleomycin 9.0 µM, and the combination of these treatments, relative survival percentages were 89.2 ± 13.0, 70.2 ± 8.9, and 30.5 ± 6.1, respectively, in the T24 cell line. After treatment with PDT (120-s illumination), bleomycin 27 µM and the combination of these treatments, relative survival percentages were 93.6 ± 15.7, 74.7 ± 9.6, and 30.0 ± 11.1, respectively, in the AY-27 cell line. In both cell lines, PDT combined with bleomycin showed significantly (Pinternalization effect. TPCS2a-based photochemical internalization of bleomycin showed a significant, at least, additive antiproliferative activity against human and rat urothelial carcinoma cells in vitro. Thus, photochemical internalization may have therapeutic potential as an intravesical strategy against bladder cancer. As the effect is heterogeneous, biomarker studies are warranted to be able to predict the effects of a photochemical

  6. A Novel Risk Stratification to Predict Local-Regional Failures in Urothelial Carcinoma of the Bladder After Radical Cystectomy

    International Nuclear Information System (INIS)

    Baumann, Brian C.; Guzzo, Thomas J.; He Jiwei; Keefe, Stephen M.; Tucker, Kai; Bekelman, Justin E.; Hwang, Wei-Ting; Vaughn, David J.; Malkowicz, S. Bruce; Christodouleas, John P.

    2013-01-01

    Purpose: Local-regional failures (LF) following radical cystectomy (RC) plus pelvic lymph node dissection (PLND) with or without chemotherapy for invasive urothelial bladder carcinoma are more common than previously reported. Adjuvant radiation therapy (RT) could reduce LF but currently has no defined role because of previously reported morbidity. Modern techniques with improved normal tissue sparing have rekindled interest in RT. We assessed the risk of LF and determined those factors that predict recurrence to facilitate patient selection for future adjuvant RT trials. Methods and Materials: From 1990-2008, 442 patients with urothelial bladder carcinoma at University of Pennsylvania were prospectively followed after RC plus PLND with or without chemotherapy with routine pelvic computed tomography (CT) or magnetic resonance imaging (MRI). One hundred thirty (29%) patients received chemotherapy. LF was any pelvic failure detected before or within 3 months of distant failure. Competing risk analyses identified factors predicting increased LF risk. Results: On univariate analysis, pathologic stage ≥pT3, <10 nodes removed, positive margins, positive nodes, hydronephrosis, lymphovascular invasion, and mixed histology significantly predicted LF; node density was marginally predictive, but use of chemotherapy, number of positive nodes, type of surgical diversion, age, gender, race, smoking history, and body mass index were not. On multivariate analysis, only stage ≥pT3 and <10 nodes removed were significant independent LF predictors with hazard ratios of 3.17 and 2.37, respectively (P<.01). Analysis identified 3 patient subgroups with significantly different LF risks: low-risk (≤pT2), intermediate-risk (≥pT3 and ≥10 nodes removed), and high-risk (≥pT3 and <10 nodes) with 5-year LF rates of 8%, 23%, and 42%, respectively (P<.01). Conclusions: This series using routine CT and MRI surveillance to detect LF confirms that such failures are relatively common in

  7. Telomerase Activity Detected by Quantitative Assay in Bladder Carcinoma and Exfoliated Cells in Urine

    Directory of Open Access Journals (Sweden)

    Roberta Fedriga

    2001-01-01

    Full Text Available Early diagnosis is one of the most determining factors for patient survival. The detection of telomerase activity is a potentially promising tool in the diagnosis of bladder and other types of cancer due to the high expression of this enzyme in tumor cells. We carried out a quantitative evaluation of telomerase activity in urine samples in an attempt to determine a cut-off capable of identifying cancer patients. Telomerase activity was quantified by fluorescence TRAP assay in urine from 50 healthy volunteers and in urine and bioptic tumor samples from 56 previously untreated bladder cancer patients and expressed in arbitrary enzymatic units (AEU. Telomerase activity in urine ranged from 0 to 106 AEU (median 0 in healthy donors and from 0 to 282 AEU (median 87 in patients with cancer. A telomerase expression higher than the cut off value determined by receiver operating characteristic (ROC analysis was observed in 78% of cases, regardless of tumor grade and in 71% (15/21 of cases of nonassessable or negative cytology. The quantitative analysis of telomerase activity in urine enabled us to define cut-off values characterized by different sensitivity and specificity. Cytologic and telomerase determination, used sequentially, enabled us to detect about 90% of tumors.

  8. Molecular markers in transitional cell carcinoma of the bladder: New insights into mechanisms and prognosis

    Directory of Open Access Journals (Sweden)

    Behfar Ehdaie

    2008-01-01

    Full Text Available Urothelial carcinoma is potentially life-threatening and expensive to treat since for many patients, the diagnosis entails a lifetime of surveillance to detect recurrent disease. Advancements in technology have provided an understanding of the molecular mechanisms of carcinogenesis and defined distinct pathways in tumorigenesis and progression. At the molecular level, urothelial carcinoma is being seen as a disease with distinct pathways of carcinogenesis and progression and thus markers of these processes should be used as both diagnostics and predictors of progression and patient outcome. Herein we present a selective overview of the molecular underpinning of urothelial carcinogenesis and progression and discuss the potential for proteins involved in these processes to serve as biomarkers. The discovery of biomarkers has enabled the elucidation of targets for novel therapeutic agents to disrupt the deregulation underlying the development and progression of urothelial carcinogenesis.

  9. Bladder squamous cell carcinomas express psoriasin and externalize it to the urine

    DEFF Research Database (Denmark)

    Celis, J E; Rasmussen, H H; Vorum, H

    1996-01-01

    of SCCs obtained immediately after surgery were analyzed by two-dimensional gel electrophoresis and Coomassie blue staining. Protein identity was determined by microsequencing and immunoblotting. Protein expression in cryosections was studied by immunofluorescence. RESULTS: Four patients with SCC were...... were confined chiefly to the "squamous pearls." The presence of psoriasin in the urine of the 4 SCC patients was demonstrated by two-dimensional gel immunoblotting. Similar analysis of 43 urines from patients with bladder tumors other than SCC revealed 7 positives, some of which may reflect squamous...... differentiation. Analysis of the urine of 13 control individuals (12 males matched by age and a 42-year-old female) revealed 2 positives. Immunoblotting of the SCC patients' serum proteins with psoriasin antibodies failed to reveal the protein. CONCLUSION: The results point towards psoriasin, alone or as part...

  10. Crude mortality and loss of life expectancy of patients diagnosed with urothelial carcinoma of the urinary bladder in Norway.

    Science.gov (United States)

    Andreassen, Bettina K; Myklebust, Tor Å; Haug, Erik S

    2017-02-01

    Reports from cancer registries often lack clinically relevant information, which would be useful in estimating the prognosis of individual patients with urothelial carcinoma of the urinary bladder (UCB). This article presents estimates of crude probabilities of death due to UCB and the expected loss of lifetime stratified for patient characteristics. In Norway, 10,332 patients were diagnosed with UCB between 2001 and 2010. The crude probabilities of death due to UCB were estimated, stratified by gender, age and T stage, using flexible parametric survival models. Based on these models, the loss in expectation of lifetime due to UCB was also estimated for the different strata. There is large variation in the estimated crude probabilities of death due to UCB (from 0.03 to 0.76 within 10 years since diagnosis) depending on age, gender and T stage. Furthermore, the expected loss of life expectancy is more than a decade for younger patients with muscle-invasive UCB and between a few months and 5 years for nonmuscle-invasive UCB. The suggested framework leads to clinically relevant prognostic risk estimates for individual patients diagnosed with UCB and the consequence in terms of loss of lifetime expectation. The published probability tables can be used in clinical praxis for risk communication.

  11. Defect in lectin-induced interleukin 2 production by peripheral blood lymphocytes of patients with invasive urinary bladder carcinoma

    DEFF Research Database (Denmark)

    Bubeník, J; Kieler, J; Tromholt, V

    1988-01-01

    The production of interleukin 2 (IL-2) by phytohaemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC) from 21 patients with transitional cell carcinoma of the urinary bladder (BTCC) and 16 control blood donors was measured with a solid phase enzyme immunoassay based on the dual...... antibody immunometric sandwich principle. PBMC from patients with invasive BTCC (grade III-IV) showed a defect in the production of IL-2. The concentration of IL-2 in the supernatants of PBMC cultures from these patients was substantially lower (0.4 +/- 0.1 U/ml) than that observed in the supernatants...... of PBMC cultures from patients with non-invasive BTCC, grade II (1.5 +/- 0.7 U/ml), and from tumour-free controls (1.4 +/- 0.8 U/ml). These results suggest an immune dysfunction based on quantitatively impaired IL-2 production in patients with invasive BTCC and indicate that exogenous IL-2 could be used...

  12. Expression of KAI1/CD82 and MRP-1/CD9 in transitional cell carcinoma of bladder.

    Science.gov (United States)

    Ai, Xing; Zhang, Xu; Wu, Zhun; Ma, Xin; Ju, Zhenghua; Wang, Baojun; Shi, Taoping

    2007-02-01

    The expression of KAI1/CD82 and MRP-1/CD9 in transitional cell carcinoma of bladder (TCCB) and its clinical significance were investigated. Immunohistochemistry was used to detect KAI1/CD82 and MRP-1/CD9 protein expression in 52 TCCB specimens. Correlation between the expression of KAI1/CD82 and MRP-1/CD9 to clinicopathologic factors was statistically analyzed. The results showed that the positive rate of KAI1/CD82 and MRP-1/CD9 in TCCB was 50% and 61.5%, respectively. The MRP-1/CD9 and KAI1/CD82 expression was significantly associated with grade of TCCB (PMRP-1/CD9 or KAI1/CD82 expression and clinical stage of TCCB (P>0.05). The expression level of MRP-1/CD9 and KAI1/CD82 in recurrent TCCB samples was lower than that in non-recurrent samples (PMRP-1/CD9 expression was statistically significant (r=0.316, PMRP-1/CD9 expression may be important prognostic indicators and potentially useful for assessing the biological behavior of TCCB.

  13. Preoperative anemia is associated with adverse outcome in patients with urothelial carcinoma of the bladder following radical cystectomy.

    Science.gov (United States)

    Gierth, M; Mayr, R; Aziz, A; Krieger, S; Wullich, B; Pycha, A; Lodde, M; Salvadori, U; Bründl, J; Fritsche, H M; Hofstädter, F; Pawlik, M T; Otto, W; May, M; Burger, M; Denzinger, S

    2015-10-01

    Radical cystectomy (RC) can be associated with significant blood loss, whereas many patients are presenting with anemia preoperatively. To date, there is a lack of data addressing the impact of preoperative anemia (PA) on survival of patients undergoing RC for urothelial carcinoma of the bladder (UCB). This retrospective multicenter study includes 684 patients with UCB undergoing RC with pelvic lymph node dissection. The median follow-up was 50 (IQR 29,78) months. Anemia was defined in line with the WHO classification (hemoglobin (Hb): male ≤13 g/dL, female ≤12 g/dL) and based on contemporary gender- and age-adjusted classification (Hb: white male aged classification versus contemporary classification. Age, increased ECOG performance status, advanced tumor stages, lymph node metastasis, positive surgical margin and anemia were associated with disease recurrence (DR), cancer-specific mortality (CSM) and all-cause mortality (ACM). In multivariable analysis, anemia was an independent predictor of DR, CSM and ACM (WHO and/or contemporary classification). Blood transfusion was significantly associated with ACM in both classifications of anemia. PA is significantly associated with worse oncological outcome in patients undergoing RC. Based on the additional unfavorable influence of blood transfusion, this emphasizes the importance of early diagnosis and correction of anemia and implementation of alternative methods of blood volume management.

  14. Developments in bladder cancer

    International Nuclear Information System (INIS)

    Denis, L.; Niijima, T.; Prout, G.; Schroder, F.H.

    1986-01-01

    This book contains 20 selections. Some of the titles are: Guidelines for Radiation Therapy in Clinical Research on Bladder Cancer; Transitional Cell Carcinoma in Situ; Policy on Monitoring and Reporting Results; Standardization of Protocol Formnd The Role of Cytology in the Diagnosis, Detection and Follow-up of Bladder Cancer

  15. Intravenous urography for diagnosing synchronous upper-tract tumours in patients with newly diagnosed bladder carcinoma can be restricted to patients with high-risk superficial disease.

    Science.gov (United States)

    Bajaj, A; Sokhi, H; Rajesh, A

    2007-09-01

    To determine the incidence of synchronous upper-tract transitional cell carcinomas (TCCs) in patients with newly diagnosed bladder cancer and to evaluate the need for performing intravenous urography (IVU) in these patients. Imaging data on 330 consecutive patients who were diagnosed with TCC of the bladder over a 2-year period were retrospectively reviewed. Only 233 out of the 330 patients had IVU at presentation. The IVU results were recorded as normal, abnormal, or equivocal. The follow-up radiological or urological investigations in the patients who had an equivocal IVU were reviewed. Clinical follow-up data on all 330 patients were also recorded. Only 233 out of the 330 patients had an IVU at presentation. Four of these (1.7%) patients were found to have synchronous upper-tract tumours. Twenty-two patients were reported to have equivocal findings on IVU. Nine of these patients had follow-up imaging [computed tomography (CT)=5, IVU=4], which were reported as normal. Retrograde urography was performed in two patients, which was normal. The remaining 11 patients did not have any evaluation of the upper tracts despite the equivocal findings on IVU, but routine clinical follow-up did not reveal any significant disease. Three patients with high-risk superficial disease developed upper-tract tumours that were detected on follow-up. IVU for diagnosing synchronous upper-tract tumours in patients with newly diagnosed bladder carcinoma can be restricted to patients with high-risk superficial disease.

  16. Fatores de risco em carcinomas de células transicionais da bexiga: risk factors Transitional cell carcinoma of the bladder

    Directory of Open Access Journals (Sweden)

    Ricardo Brianezi Tiraboschi

    2002-01-01

    Full Text Available OBJETIVO: Investigar alguns dados epidemiológicos do câncer vesical bem como fatores de risco. MÉTODOS: Foram selecionados 125 pacientes atendidos no período 1980-2002, com idade média de 63,6±11,3 anos, sendo 97 (77,6% homens e 28 (22,4% mulheres. As proporções de tumores G1, G2 e G3 foram: 48%, 35,2% e 16,8%. As proporções dos estádios da lesão primária foram: pTa-1 - 85 ( 68% e pT2-4 - 40 ( 32%. Entre os pacientes com tumores superficiais houve recidiva em 41 (48,2%. RESULTADOS: O grau da lesão primária mostrou relação com o estádio T (pOBJECTIVE: To analyse some epidemiological data of patients with transitional cell carcinoma of the bladder (TCC and the predictive value of conventional risk factors. METHODS: From 1980 to 2002, 125 patients were treated at our hospital and selected retrospectively for this study. The series mean age was 63,6±11,3 years, being 77.6% males and 22.4% females. The proportions of G!, G2 and G3 TCC were: 48%, 35.2% and 16.8%. The T stage was: pTa-1 - 85 (68% and pT2-4 - 40 (32%. Superficial tumors were treated by TUR alone or plus BCG (>G1, and the invasives ones by radical cystectomy. The vesical reccurence rate of superficial TCC was 48.2%. RESULTS: TCC grade showed a positive association with T stage (p<0.0001 and patient survival (p<0.0001, but not with local bladder reccurence of superficial tumors (p=0.72. The T stage also showed a strong correlation with patient survival (p<0.0001. CONCLUSION: The TCC is more common in male than in female with mean age of 63.2 years. The tumor grading and staging exhibited as strong predictive value for disease progression and patient survival.

  17. Vulvar Metastasis from Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Fouad Aoun

    2015-01-01

    Full Text Available Vulvar metastasis of urothelial carcinoma of the bladder is a very rare entity; few cases are reported in the English literature. In this paper, we describe the clinical and pathological characteristics, evolution, and treatment of a patient with vulvar metastasis of urothelial carcinoma of the bladder followed by a brief review of the reported cases in the literature.

  18. Study of false positives in 5-ALA induced photodynamic diagnosis of bladder carcinoma

    Science.gov (United States)

    Draga, Ronald O. P.; Grimbergen, Matthijs C. M.; Kok, Esther T.; Jonges, Trudy G. N.; Bosch, J. L. H. R.

    2009-02-01

    Photodynamic diagnosis (PDD) is a technique that enhances the detection of tumors during cystoscopy using a photosensitizer which accumulates primarily in cancerous cells and will fluoresce when illuminated by violetblue light. A disadvantage of PDD is the relatively low specificity. In this retrospective study we aimed to identify predictors for false positive findings in PDD. Factors such as gender, age, recent transurethral resection of bladder tumors (TURBT), previous intravesical therapy (IVT) and urinary tract infections (UTIs) were examined for association with the false positive rates in a multivariate analysis. Data of 366 procedures and 200 patients were collected. Patients were instilled with 5-aminolevulinic acid (5-ALA) intravesically and 1253 biopsies were taken from tumors and suspicious lesions. Female gender and TURBT are independent predictors of false positives in PDD. However, previous intravesical therapy with Bacille Calmette-Guérin is also an important predictor of false positives. The false positive rate decreases during the first 9-12 weeks after the latest TURBT and the latest intravesical chemotherapy. Although shortly after IVT and TURBT false positives increase, PDD improves the diagnostic sensitivity and results in more adequate treatment strategies in a significant number of patients.

  19. Simultaneous metastases of clear cell renal cell carcinoma to the urinary bladder and left retroperitoneal space: A case report and review of the literature.

    Science.gov (United States)

    Li, Hengping; Wang, Jianzhong; Wei, Qiang; Wang, Huan

    2016-07-01

    The present study describes an extremely rare case of simultaneous metastases of clear cell renal cell carcinoma (ccRCC) to the urinary bladder and left retroperitoneal space, occurring subsequent to an open radical nephrectomy. A review of the literature is also considered. A 70-year-old man presenting with diabetes mellitus and hypertension was referred to West China Hospital (Chengdu, China) with constant left flank pain that had been apparent for 2 months. Ultrasonography identified a heterogeneous tumor with a solid component measuring 4.4×3.4×5.0 cm, and computed tomography (CT) revealed a circumscribed and contrast-enhanced tumor in the left kidney. Subsequent pathological analysis of the specimen, obtained from an open radical nephrectomy, confirmed the presence of ccRCC. At 1 month after the radical nephrectomy, an abdominopelvic CT scan identified tumors located on the posterior bladder wall and also in the left retroperitoneal space, forming due to hematuria and acute urinary clot retention. There was no evidence of metastasis to the lungs, bones or other organs. A transurethral resection of the bladder tumor was performed and pathological analysis of the bladder specimen demonstrated metastatic ccRCC. Extensive hydrothorax and general anasarca presented half a month after the transurethral resection, with the patient subsequently succumbing 15 days later.

  20. MicroRNA profiling of dogs with transitional cell carcinoma of the bladder using blood and urine samples.

    Science.gov (United States)

    Kent, Michael S; Zwingenberger, Allison; Westropp, Jodi L; Barrett, Laura E; Durbin-Johnson, Blythe P; Ghosh, Paramita; Vinall, Ruth L

    2017-11-15

    Early signs of canine transitional cell carcinoma (TCC) are frequently assumed to be caused by other lower urinary tract diseases (LUTD) such as urinary tract infections, resulting in late diagnosis of TCC which could be fatal. The development of a non-invasive clinical test for TCC could dramatically reduce mortality. To determine whether microRNAs (miRNAs) can be used as non-invasive diagnostic biomarkers, we assessed miRNA expression in blood and/or urine from dogs with clinically normal bladders (n = 28), LUTD (n = 25), and TCC (n = 17). Expression levels of 5 miRNA associated with TCC pathophysiology (miR-34a, let-7c, miR-16, miR-103b, and miR-106b) were assessed by quantitative real-time PCR. Statistical analyses using ranked ANOVA identified significant differences in miR-103b and miR-16 levels between urine samples from LUTD and TCC patients (miR-103b, p = 0.002; and miR-16, p = 0.016). No statistically significant differences in miRNA levels were observed between blood samples from LUTD versus TCC patients. Expression levels of miR-34a trended with miR-16, let-7c, and miR-103b levels in individual normal urine samples, however, this coordination was completely lost in TCC urine samples. In contrast, co-ordination of miR-34a, miR-16, let-7c, and miR-103b expression levels was maintained in blood samples from TCC patients. Our combined data indicate a potential role for miR-103b and miR-16 as diagnostic urine biomarkers for TCC, and that further investigation of miR-103b and miR-16 in the dysregulation of coordinated miRNA expression in bladder carcinogenesis is warranted.

  1. Advanced small cell carcinoma of the bladder: clinical characteristics, treatment patterns and outcomes in 960 patients and comparison with urothelial carcinoma

    International Nuclear Information System (INIS)

    Geynisman, Daniel M.; Handorf, Elizabeth; Wong, Yu-Ning; Doyle, Jamie; Plimack, Elizabeth R.; Horwitz, Eric M.; Canter, Daniel J.; Uzzo, Robert G.; Kutikov, Alexander; Smaldone, Marc C.

    2015-01-01

    To describe the clinical characteristics, treatment patterns and outcomes in advanced small cell bladder cancer (aSCBC) patients and compare to those with urothelial carcinoma (UC). Individuals in the National Cancer Data Base with a diagnosis of either nodal (TxN+M0) or distant metastatic (TxNxM1) disease were identified from 1998 to 2010. We assessed the relationships between stage, treatment modalities and survival in the aSCBC cohort and compared these to UC patients. In the 960 patient aSCBC cohort (62% M1), 50% received palliative therapy alone, 68% in M1 versus 21% in M0 groups (P < 0.0001). Single modality local therapy (15%) and surgical (21%) or radiation-based (14%) multimodal therapy (MMT) were used in the other 50%. Cystectomy-based MMT was utilized in 45% of N+M0 versus 6.4% of NxM1 patients (P < 0.0001). Median overall survival (OS) for aSCBC patients was 8.6 months; 13.0 months in N+M0 versus 5.3 months in NxM1 patients (P < 0.0001). Survival was similar between TxN1M0 and TxN2-3M0 patients (14.8 months vs. 12.1 months, P = 0.15). Urothelial carcinoma patients (n = 27,796, 45% M1) lived longer compared to aSCBC patients in the N+M0 group (17.3 months vs. 13.0 months, P = 0.0007). There were not clinically significant differences in OS between UC and aSCBC patients in the M1 group. Advanced SCBC is a rare disease with a poor survival and palliative therapy is common, especially in M1 patients. In comparison to UC, the outcomes for aSCBC patients are worse in those with lymph node only involvement but similar in those with distant disease

  2. Reduced immunohistochemical PTEN staining is associated with higher progression rate and recurrence episodes in non-invasive low-grade papillary urothelial carcinoma of the bladder.

    Science.gov (United States)

    Kulac, Ibrahim; Arslankoz, Sehbal; Netto, George J; Ertoy Baydar, Dilek

    2018-01-24

    Non-invasive low-grade papillary urothelial carcinoma (NILGPUC) of the bladder is regarded as a relatively indolent disease. However, its propensity for frequent recurrences constitutes a major clinical problem. Additionally, there is a progression risk of 10-15% to either a higher grade and/or a higher stage disease in these tumors. The molecular factors that will predict recurrence and progression in low-grade pTa bladder carcinoma have not yet been elucidated. Herein, we investigated the association of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) alterations with recurrence and progression in NILGPUC using immunohistochemistry. Eighty-one cases of bladder cancer initially diagnosed as NILGPUC in a single institution with follow-up were encountered after searching medical records. Tissue microarrays (TMA) that contained both tumor and non-neoplastic mucosa from each case were constructed using paraffin blocks of transurethral resections. Sections from TMA blocks were stained immunohistochemically for PTEN protein and were evaluable in 76 cases. Any absence of staining was recorded and correlated with clinical findings. Ten patients (13.2%) showed progression and 41 (53.9%) showed recurrence. Reduced PTEN expression was observed in 29 cases (38.1%). Cases with reduced PTEN had higher progression rate compared to cases with intact PTEN (p = 0.026). Tumor relapse was more frequent in cases with reduced PTEN (65.5 vs 46.8%), but this difference was not statistically significant (p = 0.112). On the other hand, decreased PTEN expression was associated with higher number of recurrence episodes (p = 0.002). PTEN seems to have a link with the disease course in NILGPUC of the bladder.

  3. Loss of prostasin (PRSS8 in human bladder transitional cell carcinoma cell lines is associated with epithelial-mesenchymal transition (EMT

    Directory of Open Access Journals (Sweden)

    Chai Karl X

    2009-10-01

    Full Text Available Abstract Background The glycosylphosphatidylinositol (GPI-anchored epithelial extracellular membrane serine protease prostasin (PRSS8 is expressed abundantly in normal epithelia and essential for terminal epithelial differentiation, but down-regulated in human prostate, breast, and gastric cancers and invasive cancer cell lines. Prostasin is involved in the extracellular proteolytic modulation of the epidermal growth factor receptor (EGFR and is an invasion suppressor. The aim of this study was to evaluate prostasin expression states in the transitional cell carcinomas (TCC of the human bladder and in human TCC cell lines. Methods Normal human bladder tissues and TCC on a bladder cancer tissue microarray (TMA were evaluated for prostasin expression by means of immunohistochemistry. A panel of 16 urothelial and TCC cell lines were evaluated for prostasin and E-cadherin expression by western blot and quantitative PCR, and for prostasin gene promoter region CpG methylation by methylation-specific PCR (MSP. Results Prostasin is expressed in the normal human urothelium and in a normal human urothelial cell line, but is significantly down-regulated in high-grade TCC and lost in 9 (of 15 TCC cell lines. Loss of prostasin expression in the TCC cell lines correlated with loss of or reduced E-cadherin expression, loss of epithelial morphology, and promoter DNA hypermethylation. Prostasin expression could be reactivated by demethylation or inhibition of histone deacetylase. Re-expression of prostasin or a serine protease-inactive variant resulted in transcriptional up-regulation of E-cadherin. Conclusion Loss of prostasin expression in bladder transitional cell carcinomas is associated with epithelial-mesenchymal transition (EMT, and may have functional implications in tumor invasion and resistance to chemotherapy.

  4. Multiplex PCR and Next Generation Sequencing for the Non-Invasive Detection of Bladder Cancer.

    Directory of Open Access Journals (Sweden)

    Douglas G Ward

    Full Text Available Highly sensitive and specific urine-based tests to detect either primary or recurrent bladder cancer have proved elusive to date. Our ever increasing knowledge of the genomic aberrations in bladder cancer should enable the development of such tests based on urinary DNA.DNA was extracted from urine cell pellets and PCR used to amplify the regions of the TERT promoter and coding regions of FGFR3, PIK3CA, TP53, HRAS, KDM6A and RXRA which are frequently mutated in bladder cancer. The PCR products were barcoded, pooled and paired-end 2 x 250 bp sequencing performed on an Illumina MiSeq. Urinary DNA was analysed from 20 non-cancer controls, 120 primary bladder cancer patients (41 pTa, 40 pT1, 39 pT2+ and 91 bladder cancer patients post-TURBT (89 cancer-free.Despite the small quantities of DNA extracted from some urine cell pellets, 96% of the samples yielded mean read depths >500. Analysing only previously reported point mutations, TERT mutations were found in 55% of patients with bladder cancer (independent of stage, FGFR3 mutations in 30% of patients with bladder cancer, PIK3CA in 14% and TP53 mutations in 12% of patients with bladder cancer. Overall, these previously reported bladder cancer mutations were detected in 86 out of 122 bladder cancer patients (70% sensitivity and in only 3 out of 109 patients with no detectable bladder cancer (97% specificity.This simple, cost-effective approach could be used for the non-invasive surveillance of patients with non-muscle-invasive bladder cancers harbouring these mutations. The method has a low DNA input requirement and can detect low levels of mutant DNA in a large excess of normal DNA. These genes represent a minimal biomarker panel to which extra markers could be added to develop a highly sensitive diagnostic test for bladder cancer.

  5. Combined effects of extracellular matrix and growth factors on NBT-II rat bladder carcinoma cell dispersion.

    Science.gov (United States)

    Tucker, G C; Boyer, B; Valles, A M; Thiery, J P

    1991-10-01

    Using the rat bladder carcinoma cell line NBT-II we showed that collagens but not laminin and fibronectin were able to induce cell scattering. Acidic fibroblast growth factor and transforming growth factor alpha also promoted NBT-II cell dispersion on glass or tissue culture plastic. We have now further analysed the scatter response to these two growth factors in the presence of extracellular matrix molecules. In the presence of growth factors, no peripheral single-cell dispersion occurred on fibronectin and laminin, although time-lapse video analyses revealed intense cell mingling and motility inside the monolayer forming around NBT-II aggregates. Patterns of strings or files of cells protruding from the monolayer were often observed. The presence of a scattering activity in the complex acellular extracellular matrix deposited by NBT-II cells themselves strongly suggested that substratum conditioning was responsible for this effect. On the other hand, the two growth factors accelerated collagen-mediated NBT-II individual cell dispersion and locomotion in a reversible way. As a marker of cell dissociation, we studied desmosome distribution in aggregate cultures: desmosomes were present in aggregates formed in suspension even in the presence of growth factors, whereas internalization occurred after cell-to-substratum contact. On laminin or fibronectin and in the presence of growth factors, peripheral cells inside the halo of NBT-II aggregates did not exhibit desmosome linkages. These observations suggest that scatter effects per se are dependent on the composition of the extracellular matrix. In particular, on a substratum nonpermissive for direct cell translocation, individual cell dispersion can be replaced by en bloc patterns of migration following substratum conditioning by the cells.

  6. Collecting and Studying Blood and Tissue Samples From Patients With Locally Recurrent or Metastatic Prostate or Bladder/Urothelial Cancer

    Science.gov (United States)

    2017-12-04

    Healthy Control; Localized Urothelial Carcinoma of the Renal Pelvis and Ureter; Metastatic Malignant Neoplasm in the Bone; Metastatic Malignant Neoplasm in the Soft Tissues; Metastatic Urothelial Carcinoma of the Renal Pelvis and Ureter; Recurrent Bladder Carcinoma; Recurrent Prostate Carcinoma; Recurrent Urothelial Carcinoma of the Renal Pelvis and Ureter; Stage IV Bladder Cancer; Stage IV Bladder Urothelial Carcinoma; Stage IV Prostate Cancer

  7. Low circulating serum levels of second mitochondria-derived activator of caspase (Smac/DIABLO) in patients with bladder cancer.

    Science.gov (United States)

    Mizutani, Yoichi; Katsuoka, Yoji; Bonavida, Benjamin

    2012-04-01

    Smac/DIABLO promotes apoptosis by antagonizing inhibitor of apoptosis proteins. The expression of Smac/DIABLO in tissues has been reported in various cancers; however, little is known about circulating levels of Smac/DIABLO. The present study was designed to first determine if Smac/DIABLO can be detected in the serum and then assess whether the circulating levels of Smac/DIABLO are of prognostic significance in patients with bladder cancer. The levels of Smac/DIABLO in the sera of 173 patients with bladder cancer and 36 normal donors were determined by using an enzyme-linked immunosorbent assay. The mean serum level of Smac/DIABLO in patients with bladder cancer was approximately 2-fold lower than that in normal donors. The mean level of serum Smac/DIABLO in patients with muscle-invasive bladder cancer was lower than that in patients with non-muscle invasive cancer. In addition, the mean serum Smac/DIABLO level in patients with T4 muscle-invasive bladder cancer was lower than that in patients with T2 and T3 cancers. The mean serum level of Smac/DIABLO in patients with Grade 3 bladder cancer was lower than that in patients with Grade 1 and Grade 2 cancers. Analysis by Kaplan-Meier revealed that patients with Ta and T1 non-muscle invasive bladder cancer with high level of serum Smac/DIABLO (more than mean value) had a longer post-operative tumor-free interval than those with low level (less than mean value) in the 3-year follow-up. Furthermore, patients with T2-T4 muscle-invasive bladder cancer with high serum Smac/DIABLO level (more than mean value) had a higher post-operative disease-free rate when compared with patients with low level (less than mean value) in the 5-year follow-up. The present study is the first to analyze circulating levels of Smac/DIABLO in the serum. The findings demonstrate that the mean serum level of Smac/DIABLO was downregulated in patients with bladder cancer compared to control healthy individuals, especially high grade muscle

  8. Low-level Ki-67 expression as an independent predictor of bladder tumour recurrence in patients with primary upper tract urothelial carcinoma after radical nephroureterectomy.

    Science.gov (United States)

    Wu, Pengjie; Liu, Shengjie; Zhang, Wei; Zhang, Yaoguang; Zhu, Gang; Wei, Dong; Wan, Ben; Wang, Jianye

    2015-12-01

    To evaluate the association of molecular markers and conventional clinicopathological factors with bladder tumour recurrence in patients with primary upper tract urothelial carcinoma after radical nephroureterectomy. The expressions of Ki-67 and P53 were measured by immunohistochemical staining prospectively in 115 consecutive patients with primary upper tract urothelial carcinoma from March 2004 to February 2014. The Cox proportional hazards regression model was used to identify independent predictors. The association between Ki-67 expression and clinicopathological variables was assessed by the χ(2) test. Intravesical recurrence occurred in 13 out of 115 (11.3%) patients with a mean follow-up of 54.2 months (range: 7-130). Low-level Ki-67 expression (P = 0.010), older age (>65, P = 0.040) and lower ureter tumour (P = 0.001) were independent predictors of bladder tumour recurrence in Cox regression analysis. Ki-67 expression was elevated with the progression of tumour grade (P = 0.004) but not with stage (P = 0.186). Ki-67 overexpression was also significantly higher in aggressive pathological types (P = 0.008), but only shows an inclination towards poor oncologic outcomes in the cancer-specific survival rate (P = 0.107) and the overall survival rate (P = 0.063). Low-level Ki-67 expression was an independent predictor for bladder tumour recurrence, while Ki-67 overexpression was associated with adverse clinicopathological parameters and poor prognosis in patients with primary upper tract urothelial carcinoma after radical nephroureterectomy. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. Comparison of 18F fluoride PET/CT and 99mTc-MDP bone scan in the detection of skeletal metastases in urinary bladder carcinoma.

    Science.gov (United States)

    Chakraborty, Dhritiman; Bhattacharya, Anish; Mete, Uttam Kumar; Mittal, Bhagwant Rai

    2013-08-01

    The aim of this study was to compare (18)F-fluoride PET/CT and (99m)Tc-MDP bone scintigraphy in the detection of skeletal metastases in urinary bladder carcinoma. In this prospective study, 48 patients with urinary bladder carcinoma (44 male and 4 female patients, aged 35-80 years) underwent (99m)Tc-MDP planar and SPECT/CT bone scan (BS) followed by (18)F-fluoride PET/CT within 48 hours. Skeletal metastasis diagnosed on each of these techniques was compared against a final diagnosis based on contrast-enhanced CT, MRI, skeletal survey, clinical follow-up, and histological correlation. (18)F-fluoride PET/CT identified bony metastases and changed the management in 17 of 48 patients (35%). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of (99m)Tc-MDP planar BS were 82.35%, 64.51%, 56%, 86.95%, and 70.83%; of (99m)Tc-MDP SPECT/CT were 88.23%, 74.19%, 65.21%, 92%, and 79.16%; and of (18)F-fluoride PET/CT were 100%, 87.09%, 80.95%, 100%, and 91.66%, respectively. Fair agreement between (99m)Tc-MDP planar BS and F-fluoride PET/CT (κ = 0.42) and excellent agreement between SPECT/CT and (18)F-fluoride PET/CT (κ = 0.74) were found. ( 18)F-fluoride PET/CT has higher sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in detecting bone metastases in urinary bladder carcinoma than conventional (99m)Tc-MDP planar BS. SPECT/CT improves all these parameters compared with planar BS and may serve as a cost-effective screening procedure for the detection of skeletal metastases in high-risk patients.

  10. Long non-coding RNA urothelial carcinoma-associated 1 as a tumor biomarker for the diagnosis of urinary bladder cancer.

    Science.gov (United States)

    Wang, Zichun; Wang, Xiaoxiong; Zhang, Daming; Yu, Yongchun; Cai, Licheng; Zhang, Cheng

    2017-06-01

    To investigate the diagnostic value of urothelial carcinoma-associated 1 as a urine biomarker in urinary bladder cancer patients by performing a comprehensive meta-analysis. A comprehensive literature search was conducted by the databases PubMed, Embase, Cochrane Library, China Knowledge Resource Integrated, and Web of Science. The quality of eligible studies was scored with the Quality Assessment of Diagnostic Accuracy Studies. The bivariate meta-analysis model was used to pool the sensitivity, specificity, likelihood ratio, and diagnostic odds ratio. Receiver operating characteristic curves and hierarchical summary receiver operating characteristic models were employed to check the overall test performance in this meta-analysis. Seven publications involving 678 patients and 563 controls were included in this meta-analysis. The pooled sensitivity was 0.84 (95% confidence interval: 0.80-0.88), specificity was 0.87 (95% confidence interval: 0.75-0.94), positive likelihood ratio was 6.5 (95% confidence interval: 3.10-13.62), negative likelihood ratio was 0.18 (95% confidence interval: 0.13-0.25), and diagnostic odds ratio was 36 (95% confidence interval: 13-99). The area under the summary receiver operating characteristic curve was 0.89 (95% confidence interval: 0.86-0.91). Our results indicated that urothelial carcinoma-associated 1 was a potential diagnostic biomarker with good specificity and sensitivity in urinary bladder cancer. Further prospective studies with larger cohorts are necessary to evaluate the diagnostic accuracy of urothelial carcinoma-associated 1 for urinary bladder cancer.

  11. Immediate versus deferred chemotherapy after radical cystectomy in patients with pT3-pT4 or N+ M0 urothelial carcinoma of the bladder (EORTC 30994)

    DEFF Research Database (Denmark)

    Sternberg, Cora N; Skoneczna, Iwona; Kerst, J Martijn

    2015-01-01

    carcinoma of the bladder. METHODS: This intergroup, open-label, randomised, phase 3 trial recruited patients from hospitals across Europe and Canada. Eligible patients had histologically proven urothelial carcinoma of the bladder, pT3-pT4 disease or node positive (pN1-3) M0 disease after radical cystectomy......; all analyses were by intention to treat. The trial was closed after recruitment of 284 of the planned 660 patients. This trial is registered with ClinicalTrials.gov, number NCT00028756. FINDINGS: From April 29, 2002, to Aug 14, 2008, 284 patients were randomly assigned (141 to immediate treatment...

  12. Human bladder cancer diagnosis using multiphoton microscopy

    Science.gov (United States)

    Mukherjee, Sushmita; Wysock, James S.; Ng, Casey K.; Akhtar, Mohammed; Perner, Sven; Lee, Ming-Ming; Rubin, Mark A.; Maxfield, Frederick R.; Webb, Watt W.; Scherr, Douglas S.

    2009-02-01

    At the time of diagnosis, approximately 75% of bladder cancers are non-muscle invasive. Appropriate diagnosis and surgical resection at this stage improves prognosis dramatically. However, these lesions, being small and/or flat, are often missed by conventional white-light cystoscopes. Furthermore, it is difficult to assess the surgical margin for negativity using conventional cystoscopes. Resultantly, the recurrence rates in patients with early bladder cancer are very high. This is currently addressed by repeat cystoscopies and biopsies, which can last throughout the life of a patient, increasing cost and patient morbidity. Multiphoton endoscopes offer a potential solution, allowing real time, noninvasive biopsies of the human bladder, as well as an up-close assessment of the resection margin. While miniaturization of the Multiphoton microscope into an endoscopic format is currently in progress, we present results here indicating that Multiphoton imaging (using a bench-top Multiphoton microscope) can indeed identify cancers in fresh, unfixed human bladder biopsies. Multiphoton images are acquired in two channels: (1) broadband autofluorescence from cells, and (2) second harmonic generation (SHG), mostly by tissue collagen. These images are then compared with gold standard hematoxylin/eosin (H&E) stained histopathology slides from the same specimen. Based on a "training set" and a very small "blinded set" of samples, we have found excellent correlation between the Multiphoton and histopathological diagnoses. A larger blinded analysis by two independent uropathologists is currently in progress. We expect that the conclusion of this phase will provide us with diagnostic accuracy estimates, as well as the degree of inter-observer heterogeneity.

  13. Genetic susceptibility of methylenetetrahydrofolate reductase (MTHFR) gene C677T, A1298C, and G1793A polymorphisms with risk for bladder transitional cell carcinoma in men.

    Science.gov (United States)

    Safarinejad, Mohammad Reza; Shafiei, Nayyer; Safarinejad, Shiva

    2011-12-01

    We performed a case-control study of 158 bladder transitional cell carcinoma (TCC) cases and 316 controls to investigate the association between methylenetetrahydrofolate reductase (MTHFR) C677T, A1298G, and G1793A polymorphisms and bladder cancer susceptibility by polymerase chain reaction restriction fragment length polymorphism (PCR-RLFP) technique. The controls were frequency-matched to the cases by age (± 5 years), ethnicity, and smoking status. We also measured serum levels of total homocysteine (tHcy), folate, and vitamin B12. It was found that the 1298AC (odds ratio, OR = 3.74; 95% confidence interval, CI = 2.34-5.47; P = 0.001) and 1298CC (OR = 3.46, 95% CI = 2.37-5.52; P = 0.001) genotypes of MTHFR A1298C were significantly associated with increased risk of bladder TCC. The MTHFR C677T and G1793A polymorphisms were not associated with bladder TCC. After stratification for grade and stage, we observed that the 677TT (OR = 4.47, 95% CI = 2.74-6.72; P = 0.001) and MTHFR 1298CC (OR = 4.78, 95% CI = 2.82-6.89; P = 0.001) genotypes of MTHFR were associated with increased risk of muscle-invasive bladder TCC. We also found that the MTHFR 677CT+1298AA genotypes were associated with an approximately 70% reduction in risk of bladder cancer (OR = 0.31; 95% CI = 0.15-0.68) compared to the combined referent genotype. There were 8 haplotypes and 16 haplotype genotypes based on these three variants. When we used the haplotypes and assumed that the 677T, 1298C, and 1793G alleles were risk alleles, the adjusted odds ratios increased as the number of risk alleles increased: 1.00 for 0-1 variant, 1.88 (1.4-2.7) for any two risk alleles and 2.07 (1.6-2.8) for any three risk alleles. Serum tHcy levels were significantly higher in carriers of the 677T, 1298C, and 1793G alleles compared to noncarriers (all P < 0.01). There was no significant correlation between serum levels of tHcy and folate and bladder cancer risk. Further studies in larger samples size and different

  14. TOLERABILITY AND TUMOR RESPONSE OF A NOVEL LOW-DOSE PALLIATIVE RADIATION THERAPY PROTOCOL IN DOGS WITH TRANSITIONAL CELL CARCINOMA OF THE BLADDER AND URETHRA.

    Science.gov (United States)

    Choy, Kevin; Fidel, Janean

    2016-05-01

    Previously reported radiation protocols for transitional cell carcinoma of the canine lower urinary tract have been ineffective or associated with increased side effects. Objectives of this retrospective, cross-sectional study were to describe safety of and tumor responses for a novel palliative radiation protocol for transitional cell carcinoma in dogs. Included dogs had cytologically or histologically confirmed transitional cell carcinoma of the bladder or urethra, and were treated with 10 once-daily fractions (Monday-Friday) of 2.7 Gy. Thirteen dogs were sampled, with six treated using radiation as first-line (induction) therapy and seven treated using radiation as rescue therapy after failing previous chemotherapy. Within 6 weeks of radiation, 7.6% (1/13) dogs had a complete response, 53.8% (7/13) partial response, 38.5% (5/13) stable disease, and none had progressive disease. Three patients presenting with urethral obstruction had spontaneous micturition restored during the treatment protocol. A single patient with unilateral ureteral obstruction was patent at recheck examination. Median survival time from time of initial diagnosis was 179 days. Median survival time from start of radiation was 150 days. Acute radiation side effects occurred in 31% (4/13) patients and were classified as grade 1 or 2. No significant late side radiation side effects were reported. No variables examined were identified as prognostic factors. Findings indicated that the reported radiation protocol was safe in this sample of dogs with bladder and urethral transitional cell carcinoma. Future prospective studies are needed to determine utility of this treatment as a rescue therapy in patients with complete urinary tract obstruction. © 2016 American College of Veterinary Radiology.

  15. SU-F-J-05: The Effect of Air Pockets in the Urinary Bladder During Bladder Hyperthermia Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Schooneveldt, G.; Kok, H.P.; Bakker, A.; Geijsen, E.D.; Reijke, T.M. de; Crezee, J. [Academisch Medisch Centrum / Universiteit van Amsterdam, Amsterdam (Netherlands)

    2016-06-15

    Purpose: Hyperthermia combined with Mitomycin C is used for the treatment of non-muscle invasive bladder cancer (NMIBC), using a phased array system of microwave antennas for bladder heating. Often some air is present in the bladder, which effectively blocks the microwave radiation, potentially preventing proper treatment of that part of the bladder. Air can be a relevant fraction of the bladder content and large air pockets are expected to have a noticeable influence on achieved temperatures. Methods: We analysed 14 NMIBC patients treated at our institute with our AMC-4 hyperthermia device with four 70MHz antennas around the pelvis. A CT scan was made after treatment and a physician delineated the bladder on the CT scan. On the same scan, the amount of air present in the bladder was delineated. Using our in-house developed hyperthermia treatment planning system, we simulated the treatment using the clinically applied device settings. We did this once with the air pocket delineated on the CT scan, and once with the same volume filled with bladder tissue. Results: The patients had on average 4.2ml (range 0.8–10.1ml) air in the bladder. The bladder volume was delineated by the physician, that is including air pocket and bladder wall, was on average 253ml (range 93–452ml). The average volume in which changes exceeded 0.25°C was 22ml (range 0–108 ml), with the bladder being up to 2°C cooler when an air pocket was present. Except for extreme cases, there was no evident relation between the quantity of air and the difference in temperature. Conclusion: The effect of an air pocket in the bladder during bladder hyperthermia treatment varies strongly between patients. Generally, this leads to lower temperatures in the bladder, potentially affecting treatment quality, and suggesting that care need be taken to minimise the size of air pockets during hyperthermia treatments. The KWF Dutch Cancer Society financially supported this work, grant UVA 2012-5539.

  16. Clinical Significance of ErbB Receptor Family in Urothelial Carcinoma of the Bladder: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Yuh-Shyan Tsai

    2012-01-01

    Full Text Available The prognostic importance of examining ErbB receptor family expression in human bladder cancer remains uncertain. Using published evidence, we examined the clinical value and the updated results of clinical trials targeting ErbB receptor family members. Twenty-seven articles from 65 references related to ErbB receptor expression assessment in bladder cancer were reviewed. The estimates included the association significance, hazard ratios, and 95% confidence intervals (CIs from actuarial curves and survival analyses. A meta-analysis was done on those reports using univariate log-rank tests or a Cox-regression model. The methods of analysis and study subjects chosen varied widely among studies. The overall risks of disease progression for patients with EGFR or ErbB2 overexpression were 4.5 (95% CI: 2.5–8.4 and 1.1 (95% CI: 0.6–1.9, and the risks of mortality were 3.0 (95% CI: 1.6–5.9 and 1.1 (95% CI: 1.0–1.2, respectively. However, the significance of coexpression patterns of the ErbB receptor family remains controversial. None of six clinical trials yielded convincing results for blockading ErbB receptor signaling in urothelial carcinoma. The results of this analysis suggest that assessing co-expression patterns of the ErbB family may provide better prognostic information for bladder cancer patients.

  17. Cohort profile: The Swedish National Register of Urinary Bladder Cancer (SNRUBC) and the Bladder Cancer Data Base Sweden (BladderBaSe).

    Science.gov (United States)

    Häggström, Christel; Liedberg, Fredrik; Hagberg, Oskar; Aljabery, Firas; Ströck, Viveka; Hosseini, Abolfazl; Gårdmark, Truls; Sherif, Amir; Malmström, Per-Uno; Garmo, Hans; Jahnson, Staffan; Holmberg, Lars

    2017-09-27

    To monitor the quality of bladder cancer care, the Swedish National Register of Urinary Bladder Cancer (SNRUBC) was initiated in 1997. During 2015, in order to study trends in incidence, effects of treatment and survival of men and women with bladder cancer, we linked the SNRUBC to other national healthcare and demographic registers and constructed the Bladder Cancer Data Base Sweden (BladderBaSe). The SNRUBC is a nationwide register with detailed information on 97% of bladder cancer cases in Sweden as compared with the Swedish Cancer Register. Participants in the SNRUBC have registered data on tumour characteristics at diagnosis, and for 98% of these treatment data have been captured. From 2009, the SNRUBC holds data on 88% of eligible participants for follow-up 5 years after diagnosis of non-muscle invasive bladder cancer, and from 2011, data on surgery details and complications for 85% of participants treated with radical cystectomy. The BladderBaSe includes all data in the SNRUBC from 1997 to 2014, and additional covariates and follow-up data from linked national register sources on comorbidity, socioeconomic factors, detailed information on readmissions and treatment side effects, and causes of death. Studies based on data in the SNRUBC have shown inequalities in survival and treatment indication by gender, regions and hospital volume. The BladderBaSe includes 38 658 participants registered in SNRUBC with bladder cancer diagnosed from 1 January 1997 to 31 December 2014. The BladderBaSe initiators are currently in collaboration with researchers from the SNRUBC investigating different aspects of bladder cancer survival. The SNRUBC and the BladderBaSe project are open for collaborations with national and international research teams. Collaborators can submit proposals for studies and study files can be uploaded to servers for remote access and analysis. For more information, please contact the corresponding author. © Article author(s) (or their employer

  18. Transurethral Resection of Bladder Tumor (TUR-BT) then Concomitant Radiation and Cisplatin Followed by Adjuvant Gemcitabine and Cisplatin in Muscle Invasive Transitional Cell Carcinoma (TCC) of the Urinary Bladder.

    Science.gov (United States)

    Ibrahim, Salwa M; Abd El-Hafeez, Zeinab M; Mohamed, Ehab M; Elsharawy, Iman A; Kamal, Khaled M

    2007-03-01

    To evaluate the efficacy, safety, and tolerance of bladder preservation trimodality protocol combining maximal transurethral resection of bladder tumor (TURBT) with concomitant chemoradiation (CCRT) followed by adjuvant chemotherapy in patients with muscle invasive transitional cell carcinoma (TCC) of the bladder. Between January 2004 and May 2006, 40 patients with invasive TCC (T2-T4a) presented to the Radiation Oncology and Urosurgery departments - Ain Shams University hospitals and were enrolled in this prospective phase II study. Patients were treated using concurrent cisplatin and 45Gy radiotherapy (induction phase) after maximal TUR-BT. Patients were reevaluated 2 weeks after induction CCRT, by cystoscopy, repeated biopsy and urine cytology. Those with complete pathologic response (CR) received consolidation CCRT to 64.8Gy. Patients with less than CR were advised to undergo radical cystectomy (RC). Four cycles of adjuvant gemcitabine 1250mg/m2 on days 1 and 8 and cisplatin 70mg/m2 on day 1, repeated every 3 weeks, were given following definitive therapy. Twenty-four patients achieved CR after initial 45Gy CCRT, 22 of them received additional consolidation CCRT. Eight of 14 patients who did not achieve CR after induction CCRT underwent RC. A total of 30 patients (75%) received adjuvant chemotherapy. Twenty percent (20%) and 13.7% of patients experienced at least one severe (grade 3) toxicity during induction and consolidation phase of CCRT, respectively, mainly neutropenia, cystitis, proctatitis and nausea and vomiting, while 46% experienced at least one severe (grade 3 or 4) toxicity during adjuvant chemotherapy, mainly neutropenia (32%), thrombocytopenia (11%) and nausea and vomiting (29%). Local and/or regional failure was recorded in 40% of patients and distant metastasis was reported in 25%. Eighteen patients (45%) retained functioning and healthy urinary bladder at the end of follow-up. The 2-year actuarial survival and progression free survival (PFS

  19. Summary of the 8th Annual Bladder Cancer Think Tank: Collaborating to move research forward.

    Science.gov (United States)

    Apolo, Andrea B; Hoffman, Vanessa; Kaag, Matthew G; Latini, David M; Lee, Cheryl T; Rosenberg, Jonathan E; Knowles, Margaret; Theodorescu, Dan; Czerniak, Bogdan A; Efstathiou, Jason A; Albert, Matthew L; Sridhar, Srikala S; Margulis, Vitaly; Matin, Surena F; Galsky, Matthew D; Hansel, Donna; Kamat, Ashish M; Flaig, Thomas W; Smith, Angela B; Messing, Edward; Zipursky Quale, Diane; Lotan, Yair

    2015-02-01

    The 8th Annual Bladder Cancer Think Tank (BCAN-TT) brought together a multidisciplinary group of clinicians, researchers, and patient advocates in an effort to advance bladder cancer research. With the theme of "Collaborating to Move Research Forward," the meeting included three panel presentations and seven small working groups. The panel presentations and interactive discussions focused on three main areas: gender disparities, sexual dysfunction, and targeting novel pathways in bladder cancer. Small working groups also met to identify projects for the upcoming year, including: (1) improving enrollment and quality of clinical trials; (2) collecting data from multiple institutions for future research; (3) evaluating patterns of care for non-muscle-invasive bladder cancer; (4) improving delivery of care for muscle-invasive disease; (5) improving quality of life for survivors; (6) addressing upper tract disease; and (7) examining the impact of health policy changes on research and treatment of bladder cancer. The goal of the BCAN-TT is to advance the care of patients with bladder cancer and to promote collaborative research throughout the year. The meeting provided ample opportunities for collaboration among clinicians from multiple disciplines, patients and patient advocates, and industry representatives. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Tertiary Lymphoid Structures Associate with Tumour Stage in Urothelial Bladder Cancer.

    Science.gov (United States)

    Koti, Madhuri; Xu, Amanda Shou; Ren, Kevin Yi Mi; Visram, Kash; Ren, Runhan; Berman, David M; Siemens, D Robert

    2017-10-27

    Urothelial bladder cancer (UBC) is a highly prevalent disease in North America, however its optimal management remains elusive. The contribution of B cell associated responses is poorly understood in bladder cancer. Lymphoid neogenesis is a hallmark of an active immune response at tumor sites that sometimes leads to formation of tertiary lymphoid structures (TLS) that resemble germinal centers formed in secondary lymphoid organs. This study was conducted with an aim to investigate the presence and characteristics of TLS in UBC with a focus to compare and contrast the TLS formation in treatment naive low grade non-muscle invasive (NMIBC) and muscle invasive bladder cancers (MIBC). The study cohort consisted of transurethral bladder resection tumour (TURBT) specimens from 28 patients. Sections showing lymphoid aggregates in hematoxylin and eosin (H&E) stained TURBT specimens were further subjected to multi-color immunohistochemistry using immune cell markers specific to CD20 + B cells, CD3 + and CD8 + T cells, PNAd + high endothelial venules, CD208 + mature dendritic cells, CD21 + follicular dendritic cells to confirm the hallmarks of classical germinal centers. Our pilot study investigating the presence of TLS in bladder cancer patients is the first to demonstrate that well-formed TLS are more common in aggressive high grade MIBC tumors compared to low grade NIMBC. These novel findings suggest B cell mediated anti-tumour humoral immune responses in bladder cancer progression.

  1. Paclitaxel-hyaluronic acid for intravesical therapy of bacillus Calmette-Guérin refractory carcinoma in situ of the bladder: results of a phase I study.

    Science.gov (United States)

    Bassi, P F; Volpe, A; D'Agostino, D; Palermo, G; Renier, D; Franchini, S; Rosato, A; Racioppi, M

    2011-02-01

    Carcinoma in situ represents high grade anaplasia of the bladder mucosa. Intravesical immunotherapy with bacillus Calmette-Guérin is the gold standard treatment for patients with carcinoma in situ. Patients with carcinoma in situ refractory to bacillus Calmette-Guérin are candidates for major surgery such as radical cystectomy. We identified the maximum tolerated dose and the recommended dose, and evaluated the safety profile of paclitaxel-hyaluronic acid bioconjugate given by intravesical instillation to patients with carcinoma in situ refractory to bacillus Calmette-Guérin. A total of 16 patients with carcinoma in situ refractory to bacillus Calmette-Guérin were enrolled in a phase I, open label, single institution study. A minimum of 3 eligible patients were included per dose level. Paclitaxel-hyaluronic acid solution (ONCOFID-P-B™) was administered for 6 consecutive weeks. The primary objective was to identify the maximum tolerated dose and the recommended dose. As secondary objectives the safety profile of ONCOFID-P-B, the pharmacokinetic profile after each instillation and the tumor response were also evaluated. No dose limiting toxicity occurred at any drug level evaluated. The plasma levels of the study drug were always below the lower limit of quantification at all tested doses after each instillation. A total of 11 adverse events were reported by 7 patients and 9 (60%) showed complete treatment response. Intravesical instillation of ONCOFID-P-B for carcinoma in situ refractory to bacillus Calmette-Guérin showed minimal toxicity and no systemic absorption in the first human intravesical clinical trial to our knowledge. Finally, satisfactory response rates were observed. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  2. Long-term outcomes in patients with muscle-invasive bladder cancer after selective bladder-preserving combined-modality therapy: a pooled analysis of Radiation Therapy Oncology Group protocols 8802, 8903, 9506, 9706, 9906, and 0233.

    Science.gov (United States)

    Mak, Raymond H; Hunt, Daniel; Shipley, William U; Efstathiou, Jason A; Tester, William J; Hagan, Michael P; Kaufman, Donald S; Heney, Niall M; Zietman, Anthony L

    2014-12-01

    Multiple prospective Radiation Therapy Oncology Group (RTOG) protocols have evaluated bladder-preserving combined-modality therapy (CMT) for muscle-invasive bladder cancer (MIBC), reserving cystectomy for salvage treatment. We performed a pooled analysis of long-term outcomes in patients with MIBC enrolled across multiple studies. Four hundred sixty-eight patients with MIBC were enrolled onto six RTOG bladder-preservation studies, including five phase II studies (RTOG 8802, 9506, 9706, 9906, and 0233) and one phase III study (RTOG 8903). Overall survival (OS) was estimated using the Kaplan-Meier method, and disease-specific survival (DSS), muscle-invasive and non-muscle-invasive local failure (LF), and distant metastasis (DM) were estimated by the cumulative incidence method. The median age of patients was 66 years (range, 34 to 93 years), and clinical T stage was T2 in 61%, T3 in 35%, and T4a in 4% of patients. Complete response to CMT was documented in 69% of patients. With a median follow-up of 4.3 years among all patients and 7.8 years among survivors (n = 205), the 5- and 10-year OS rates were 57% and 36%, respectively, and the 5- and 10-year DSS rates were 71% and 65%, respectively. The 5- and 10-year estimates of muscle-invasive LF, non-muscle-invasive LF, and DM were 13% and 14%, 31% and 36%, and 31% and 35%, respectively. This pooled analysis of multicenter, prospective RTOG bladder-preserving CMT protocols demonstrates long-term DSS comparable to modern immediate cystectomy studies, for patients with similarly staged MIBC. Given the low incidence of late recurrences with long-term follow-up, CMT can be considered as an alternative to radical cystectomy, especially in elderly patients not well suited for surgery. © 2014 by American Society of Clinical Oncology.

  3. Problems in early diagnosis of bladder cancer in a spinal cord injury patient: Report of a case of simultaneous production of granulocyte colony stimulating factor and parathyroid hormone-related protein by squamous cell carcinoma of urinary bladder

    Directory of Open Access Journals (Sweden)

    Singh Gurpreet

    2002-08-01

    Full Text Available Abstract Background Typical symptoms and signs of a clinical condition may be absent in spinal cord injury (SCI patients. Case presentation A male with paraplegia was passing urine through penile sheath for 35 years, when he developed urinary infections. There was no history of haematuria. Intravenous urography showed bilateral hydronephrosis. The significance of abnormal outline of bladder was not appreciated. As there was large residual urine, he was advised intermittent catheterisation. Serum urea: 3.5 mmol/L; creatinine: 77 umol/L. A year later, serum urea: 36.8 mmol/l; creatinine: 632 umol/l; white cell count: 22.2; neutrophils: 18.88. Ultrasound: bilateral hydronephrosis. Bilateral nephrostomy was performed. Subsequently, blood tests showed: Urea: 14.2 mmol/l; Creatinine: 251 umol/l; Adjusted Calcium: 3.28 mmol/l; Parathyroid hormone: A repeat ultrasound scan demonstrated a tumour arising from right lateral wall; biopsy revealed squamous cell carcinoma. In view of persistently high white cell count and high calcium level, immunohistochemistry for G-CSF and PTHrP was performed. Dense staining of tumour cells for G-CSF and faintly positive staining for C-terminal PTHrP were observed. This patient expired about five months later. Conclusion This case demonstrates how delay in diagnosis of bladder cancer could occur in a SCI patient due to absence of characteristic symptoms and signs.

  4. Labelling of anti-human bladder tumor chimeric antibody with 99Tcm and radioimmunoimaging of bladder carcinoma xenograft in nude mice

    International Nuclear Information System (INIS)

    Zhang Chunli; Wang Rongfu; Fu Zhanli; Bai Yin; Ding Yi; Yu Lizhang

    2003-01-01

    Objective: To study the in vitro immunoreactivity and in vivo tissue distribution, tumor targeting property of anti-human bladder tumor human-murine chimeric antibody (ch-BDI) labeled with 99 Tc m and to investigate its possibility for being used in guiding diagnosis and guiding therapy of bladder cancer. Methods: The ch-BDI was labeled with 99 Tc m by improved Schwarz method and the labeled antibody was purified by Sephadex G-50. Labeling yield and radiochemical purity were measured by paper chromatography. The immunoreactive fraction and association constant (K a ) were measured by Lindmo method and Scatchard analysis, respectively. 11.1 MBq (30 μg) 99 Tc m -ch-BDI was intravenously injected into nude mice bearing human bladder cancer xenografts in the right thigh and radioimmunoimaging (RII) was performed 2, 6, 20 and 24 h postinjection. The images were processed by region of interest (ROI) method to acquire the counts of whole body and the tumor and the counts ratios of tumor to contralateral normal tissue or to tissues of other non-tumor bearing organs. The mice were killed after 24 h postinjection imaging and tissue distribution was measured. %ID/g and target to nontarget (T/NT) ratios were calculated. Results: The labeling yield and radiochemical purity of 99 Tc m -ch-BDI were (66.5±7.3)% and >90%, respectively. The immunoreactive fraction was 76% and K a was 3.56 x 10 9 L/mol. RII showed that the tumor was clearly visualized 6 h postinjection and becoming clearer along with time prolonging. The radioactivity of whole body decreased rapidly with time, whereas the radioactivity of the tumor decreased slowly. The T/NT ratios was increased with time. Biodistribution results showed that tumor uptake was 17.4%ID/g 24 h postinjection. T/NT ratios were very high except for the kidney. T/NT ratios for brain, muscle, intestinal wall, bone and heart wall were 136.0, 55.1, 39.3, 29.7 and 27.9, respectively. Conclusion: 99 Tc m -ch-BDI exhibits excellent

  5. In vivo 31P magnetic resonance spectroscopy and 1H magnetic resonance imaging of human bladder carcinoma on nude mice: effects of tumour growth and treatment with cis-dichloro-diamine platinum

    DEFF Research Database (Denmark)

    De Certaines, J D; Albrectsen, J; Larsen, V A

    1992-01-01

    In vivo 31P NMR spectroscopy and 1H NMR imaging were used to examine the bladder T24B carcinoma in nude mice during untreated growth and in response to chemotherapy by Cis-dichloro-diammine-platinum (CDDP) at a dose of 8 mg/kg i.p. Untreated growth was associated with an increase of inorganic pho...

  6. Clinical implications in the shift of syndecan-1 expression from the cell membrane to the cytoplasm in bladder cancer

    International Nuclear Information System (INIS)

    Miyake, Makito; Lawton, Adrienne; Dai, Yunfeng; Chang, Myron; Mengual, Lourdes; Alcaraz, Antonio; Goodison, Steve; Rosser, Charles J

    2014-01-01

    To determine the diagnostic and prognostic capability of urinary and tumoral syndecan-1 (SDC-1) levels in patients with cancer of the urinary bladder. SDC-1 levels were quantitated by enzyme-linked immunosorbent assay (ELISA) in 308 subjects (102 cancer subjects and 206 non-cancer subjects) to assess its diagnostic capabilities in voided urine. The performance of SDC-1 was evaluated using the area under the curve of a receiver operating characteristic curve. In addition, immunohistochemical (IHC) staining assessed SDC-1 protein expression in 193 bladder specimens (185 cancer subjects and 8 non-cancer subjects). Outcomes were correlated to SDC-1 levels. Mean urinary levels of SDC-1 did not differ between the cancer subjects and the non-cancer subjects, however, the mean urinary levels of SDC-1 were reduced in high-grade compared to low-grade disease (p < 0.0001), and in muscle invasive bladder cancer (MIBC) compared to non-muscle invasive bladder cancer (NMIBC) (p = 0.005). Correspondingly, preliminary data note a shift from a membranous cellular localization of SDC-1 in normal tissue, low-grade tumors and NMIBC, to a distinctly cytoplasmic localization in high-grade tumors and MIBC was observed in tissue specimens. Alone urinary SDC-1 may not be a diagnostic biomarker for bladder cancer, but its urinary levels and cellular localization were associated with the differentiation status of patients with bladder tumors. Further studies are warranted to define the potential role for SDC-1 in bladder cancer progression

  7. Immunogenic Human Papillomavirus Pseudovirus-Mediated Suicide-Gene Therapy for Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Rim Hojeij

    2016-07-01

    Full Text Available Bladder cancer is the second most common urological malignancy in the world. In 70% of cases it is initially diagnosed as non-muscle-invasive bladder cancer (NMIBC and it is amenable to local treatments, with intravesical (IVES Bacillus-Calmette-Guerin (BCG immunotherapy being routinely used after transurethral resection of the lesion. However, this treatment is associated with significant side-effects and treatment failures, highlighting the necessity of novel strategies. One potent approach is the suicide-gene mediated therapy/prodrug combination, provided tumor-specificity can be ensured and anti-tumor immune responses induced. Using the mouse syngeneic orthotopic MB49-bladder tumor model, here we show that IVES human papillomavirus non-replicative pseudovirions (PsV can pseudoinfect tumors with a ten-fold higher efficacy than normal bladders. In addition, PsV carrying the suicide-gene herpes-simplex virus thymidine kinase (PsV-TK combined to Ganciclovir (GCV led to immunogenic cell-death of tumor cells in vitro and to MB49-specific CD8 T-cells in vivo. This was associated with reduction in bladder-tumor growth and increased mice survival. Altogether, our data show that IVES PsV-TK/GCV may be a promising alternative or combinatory treatment for NMIBC.

  8. Summary of the 6th Annual Bladder Cancer Think Tank: new directions in urologic research.

    Science.gov (United States)

    Svatek, Robert S; Rosenberg, Jonathan E; Galsky, Matthew D; Lee, Cheryl T; Latini, David M; Bochner, Bernard H; Weizer, Alon Z; Apolo, Andrea B; Sridhar, Srikala S; Kamat, Ashish M; Hansel, Donna; Flaig, Thomas W; Smith, Norm D; Lotan, Yair

    2013-10-01

    The 6th Annual Bladder Cancer Think Tank brought together a multidisciplinary group of clinicians, researchers, and representatives from the National Cancer Institute and Industry in an effort to advance bladder cancer research efforts. This year's meeting comprised panel discussions and research involving 5 separate working groups, including the Survivorship, Clinical Trials, Standardization of Care, Data Mining, and Translational Science working groups. In this manuscript, the accomplishments and objectives of the working groups are summarized. Notable efforts include: (1) the development of a survivorship care plan for early and late-stage bladder cancer; (2) the development of consensus criteria for eligibility and endpoints for bladder cancer clinical trials; (3) an improved understanding of current practice patterns regarding the use of perioperative chemotherapy in an effort to standardize care; (4) creation of a comprehensive handbook to assist researchers with developing bladder cancer databases; and (5) identification of response to therapy of high-grade non muscle invasive disease through a collaborative exchange of expertise and resources. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Intraoperative photodynamic therapy of bladder cancer with alasens (results of multicenter trial

    Directory of Open Access Journals (Sweden)

    E. V. Filonenko

    2014-01-01

    Full Text Available The results of multicenter prospective trial for efficacy of combined modality treatment: transurethral resection (TUR + photodynamic therapy (PDT with alasens for bladder cancer are represented in the article. Trials were organized by Research Institute of Organic Intermediates and Dyes and conducted according to clinical protocol approved by Ministry of Health of Russia, at the sites of leading Russian cancer clinical centers. The trial included 45 subjects with verified diagnosis of non-muscle-invasive bladder cancer. Patients underwent TUR of bladder with simultaneous PDT as anti-relapse treatment. Alasens was administered to patients as intravesicular instillation of 3% solution in volume of 50 ml with 1.5–2h exposure (prior to TUR. TUR was performed after instillation. PDT session was conducted immediately after the completion of TUR on a single occasion by means of combined local irradiation on tumor bed with diffuse irradiation on whole urinary bladder mucosa (light dose of local irradiation – 100 J/cm2, diffuse irradiation – 20 J/cm2. Good tolerance of the treatment was noticed, there were no complications. Among 45 patients included in the trial, 35 (78% completed 12 month protocol follow-up without relapse. The recurrence of bladder tumor was registered in 10 (22% cases 6–12 months after TUR+PDT including 3 patients with recurrence 6 months after treatment, 3–9 months and 4–12 months. These patients underwent repeated TUR, whereafter their follow-up in the settings of the clinical trial was disposed. Thus, PDT with alasens after TUR allowed to decrease the recurrence rate of non-muscle-invasive bladder cancer for 1st year after treatment to 22% versus 40–80% for TUR as monotherapy according to literature data. The obtained results were comparable by efficiency with TUR combined with methods of adjuvant treatment for bladder tumors (the recurrence rates for 1-year follow-up after TUR+chemotherapy – 36–44%, after TUR

  10. Assessment of range of uric and serum biomarkers in determination of bladder cancer severity

    Directory of Open Access Journals (Sweden)

    Popkov V.M.

    2013-12-01

    Full Text Available Purpose: to establish efficiency of a range of uric and serum biomarkers of bladder cancer for diagnostics and the prognosis of risk of development of disease recurrence. Material and methods: TPA and TPS, VEGF level research in blood serum, UBC in urine in 176 people, among which 135 patients with bladder cancer (RMP have been conducted. Group of comparison has included16 patients (patients with cystitis. The control group has been made of 25 almost healthy men. 75 patients had non-muscle invasive RMP (Ta-1N0M0. Results. It has been statistically determined that reliable growth of of TPA, TPS in blood serum and UBC in urine in patients with non-muscle invasive RMP in comparison with patients in groups of control and comparison has been established. The increase of UBC in urine of patients of this group with recurrence of tumoral growth within a year has been noted. In comparison with cytological research of urine sedimentation, molecular markers of RMP (the uric UBC and serum TPA, TPS possess diagnostic sensitivity, allow to confirm the presence of disease, to carry out diagnostics of stages of organ and extra invasion. RMP is possible to consider as an additional prognostic serum marker increase in the VEGF level in blood serum. Conclusion. Inclusion in diagnostic process in the clinical research of biomarkers showed that identification of NMIRMP increased from 18,1% in 2006 to 55,6% in 2011. The chosen volume of complex treatment allowed to reduce recurrence and lethality in the first two years from 32 to 15,5%.

  11. Therapeutic effect of intravesical administration of paclitaxel solubilized with poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate) in an orthotopic bladder cancer model

    International Nuclear Information System (INIS)

    Tamura, Koetsu; Kikuchi, Eiji; Konno, Tomohiro; Ishihara, Kazuhiko; Matsumoto, Kazuhiro; Miyajima, Akira; Oya, Mototsugu

    2015-01-01

    To evaluate the effects of intravesical administration of paclitaxel (PTX-30W), which was prepared by solubilization with a water-soluble amphiphilic polymer composed of PMB30W, a copolymer of 2-methacryloyloxyethyl phosphorylcholine and n-butyl methacrylate, in an orthotopic bladder cancer model. The cytotoxicities of PMB30W were examined in MBT-2 cell cultures and the results were compared with those of the conventional paclitaxel solubilizer Cremophor. In an orthotopic MBT-2 bladder cancer model, the effect of intravesical administration of PTX-30W was compared with that of paclitaxel solubilized with Cremophor (PTX-CrEL). The paclitaxel concentration in bladder tumors after the intravesical treatment was also evaluated using liquid chromatography tandem mass spectrometry (LC-MS/MS) system. In vitro, Cremophor exhibited dose-dependent cytotoxicity towards MBT-2 cells, whereas no cytotoxicity was observed with PMB30W. In the orthotopic bladder cancer model, intravesical administration of PTX-30W resulted in a significant reduction of bladder wet weight compared with that of PTX-CrEL. The paclitaxel concentration in bladder tumors after the intravesical treatment was significantly higher in PTX-30W treated mice than in PTX-CrEL treated mice. Intravesically administered PTX-30W can elicit stronger antitumor effects on bladder tumors than conventional paclitaxel formulated in Cremophor, presumably because of its better penetration into tumor cells. PTX-30W might be a promising antitumor agent for intravesical treatment of non-muscle invasive bladder cancer

  12. The association of ABO blood type with disease recurrence and mortality among patients with urothelial carcinoma of the bladder undergoing radical cystectomy.

    Science.gov (United States)

    Gershman, Boris; Moreira, Daniel M; Tollefson, Matthew K; Frank, Igor; Cheville, John C; Thapa, Prabin; Tarrell, Robert F; Thompson, Robert Houston; Boorjian, Stephen A

    2016-01-01

    To evaluate the association of ABO blood type with clinicopathologic outcomes and mortality among patients with urothelial carcinoma of the bladder treated with radical cystectomy (RC). We identified 2,086 consecutive patients who underwent RC between 1980 and 2008. Postoperative recurrence-free survival (RFS) and cancer-specific survival (CSS) were estimated using the Kaplan Meier method and compared with the log-rank test. Cox proportional hazards regression models were used to evaluate the association of ABO blood type with outcomes. A total of 913 (44%), 881 (42%), 216 (10%), and 76 (4%) patients had blood type O, A, B, and AB, respectively. Median postoperative follow-up among survivors was 11.0 years (interquartile range: 7.7-15.9y). Overall, 1,561 patients died, with 770 deaths attributable to bladder cancer. Non-O blood type was associated with significantly worse 5-year RFS (65% vs. 69%; P = 0.04) and/or CSS (64% vs. 70%; P = 0.02). In particular, among patients with≤pT2N0 disease, the 5-year RFS for those with non-O vs. O blood type was 75% vs. 82%, respectively (P = 0.002), whereas the 5-year CSS was 77% vs. 85%, respectively (P = 0.001). Moreover, on multivariable analysis, blood type A remained independently associated with an increased risk of cancer-specific mortality (hazard ratio = 1.22; P = 0.01). Non-O blood type, particularly blood type A, is associated with a significantly increased risk of death from bladder cancer among patients undergoing RC. If validated, the utility of a multimodal therapy approach, including perioperative chemotherapy, or more frequent postoperative surveillance in this cohort warrants further study. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Is beta-human chorionic gonadotrophin production by transitional cell carcinoma of the bladder a marker of aggressive disease and resistance to radiotherapy?

    International Nuclear Information System (INIS)

    Moutzouris, G.; Yannopoulos, D.; Barbatis, C.; Zaharof, A.; Theodorou, Ch.; Red Cross Hospital, Athens

    1993-01-01

    The biopsies from 75 patients with transitional cell carcinoma of the bladder (25 Ta-T1; 45 T2-T4, 5M) were studied immunohistochemically for the expression of beta-human chorionic gonadotrophin (β-HCG). Only 5 Ta-T1 tumours contained a small number of β-HCG positive cells but 24 invasive tumours and all patients with metastases showed increased numbers of positive cells. A significant correlation was found between β-HCG immunoreactivity and tumour category. In 30 patients with muscle-invasive disease (T2-T4,NO,MO) who were treated with radical radiotherapy a significant correlation was observed between response to treatment and β-HCG expression; β-HCG positive tumours did not respond to treatment. A difference in survival was found between patients with tumours negative for β-HCG compared with patients with positive tumours, all treated with radical radiotherapy. The results indicate that β-HCG expression increases with tumour invasiveness and the use of immunohistochemistry may prove a useful means of identifying radioresistant and aggressive forms of bladder cancer. (Author)

  14. ABO Blood Group and Rhesus Factor Are Not Associated with Outcomes After Radical Cystectomy for Non-metastatic Urothelial Carcinoma of the Bladder.

    Science.gov (United States)

    D'Andrea, David; Moschini, Marco; Soria, Francesco; Gust, Kilian M; Briganti, Alberto; Karakiewicz, Pierre I; Rouprêt, Morgan; Shariat, Shahrokh F

    2017-10-01

    To investigate the role of ABO blood group and Rhesus factor as a predictor of outcome in patients undergoing radical cystectomy (RC) for non-metastatic urothelial carcinoma of the bladder. Data of 463 consecutive patients treated with RC between 1988 and 2003 were retrospectively analyzed. The effect on recurrence-free survival, and cancer-specific and overall mortality were assessed using the Kaplan-Meier and multivariable Cox regression methods. Overall, 185 (41.3%), 190 (42.4%), 46 (10.3%) and 27 (6%) patients expressed O, A, B and AB phenotypes, respectively; 65 (14.5%) were Rhesus-negative. Median follow-up was 14.2 years (interquartile range=10.2-17.1 years). No individual blood group was associated with any clinicopathological characteristics whereas Rhesus-positive patients had a higher rate of pT4 disease (11% vs. 22%; p=0.02). ABO blood groups were not associated with outcomes. Rhesus-positive patients had an increased risk of shorter recurrence-free survival, and of cancer-specific and overall mortality compared to Rhesus-negative patients (all pABO blood group nor Rhesus factor are associated with oncological outcomes. The clinical relevance of blood groups and Rhesus factor in bladder cancer remains questionable. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  15. Knockdown of long non-coding RNA Taurine Up-Regulated 1 inhibited doxorubicin resistance of bladder urothelial carcinoma via Wnt/β-catenin pathway.

    Science.gov (United States)

    Xie, Dalong; Zhang, Hui; Hu, Xuanhao; Shang, Chao

    2017-10-24

    In genitourinary system, bladder cancer (BC) is the most common and lethal malignant tumor, which most common type is bladder urothelial carcinoma (BUC). Long non-coding RNA (lncRNA) Taurine Up-Regulated 1 (TUG1) gene is high-expressed in several malignant tumors, including BC. In this study, over-expression of TUG1 was found in BUC tissues and cell line resistant to doxorubicin (Dox). Knockdown of TUG1 inhibited the Dox resistance and promoted the cytotoxicity induced by Dox in T24/Dox cells. TUG1 knockdown also depressed the Wnt/β-catenin pathway, and the activation the Wnt/β-catenin pathway partly reversed the inhibitory effects of TUG1 knockdown on Dox resistance in T24/Dox cells. In conclusion, up-regulation of lncRNA TUG1 was related with the poor response of BUC patients to Dox chemotherapy, knockdown of TUG1 inhibited the Dox resistance of BUC cells via Wnt/β-catenin pathway. These findings might assist in the discovery of novel potential diagnostic and therapeutic target for BUC, thereby improve the effects of clinical treatment in patients.

  16. Differential gene expression profiling in aggressive bladder transitional cell carcinoma compared to the adjacent microscopically normal urothelium by microdissection-SMART cDNA PCR-SSH.

    Science.gov (United States)

    Wang, H T; Ma, F L; Ma, X B; Han, R F; Zhang, Y B; Chang, J W

    2006-01-01

    Identifying novel and known genes that are differentially expressed in aggressive bladder transitional cell carcinoma (BTCC) has important implications in understanding the biology of bladder tumorigenesis and developing new diagnostic and therapeutic agents. In this study we identified the differential gene expression profiles comparing tumor to the adjacent microscopically normal mucosa by manual microdissection on frozen sections. The RNAs extracted from microdissected tissues were amplified by SMART cDNA PCR technology to generate forward subtractive cDNA library by suppressive subtractive hybridization (SSH). We obtained 376 positive clones, one hundred clones of aggressive BTCC subtracted cDNA library were selected at random and inserts were reamplified by PCR. After differential screening by reverse dot blotting, 73 positive clones, that contend inserts putatively upregulated in aggressive BTCC, were further analysed by DNA sequencing, GenBank and EST database searching. Sequencing results showed that 66 clones stand for 23 known genes and 7 clones for three new EST (Genbank number: DN236875, DN236874 and DN236873). In conclusion, microdissection-SMART cDNA PCR-SSH allowed for an efficient way to identify aggressive BTCC-specific differential expressed genes that may potentially be involved in the carcinogenesis and/or progression of aggressive BTCC. These differentially expressed genes may be of potential utility as therapeutic and diagnostic targets for aggressive BTCC.

  17. Expression of cell cycle regulators, 14-3-3σ and p53 proteins, and vimentin in canine transitional cell carcinoma of the urinary bladder.

    Science.gov (United States)

    Suárez-Bonnet, Alejandro; Herráez, Pedro; Aguirre, Maria; Suárez-Bonnet, Elena; Andrada, Marisa; Rodríguez, Francisco; Espinosa de Los Monteros, Antonio

    2015-07-01

    The study of the expression of 14-3-3σ, p53, and vimentin proteins in canine transitional cell carcinoma (TCC) evaluating differences with normal bladder tissues, and the association with clinicopathological variables. We analyze by immunohistochemistry in 19 canine TCCs the expression of 14-3-3σ, p53, and vimentin using monoclonal antibodys. A semiquantitative scoring method was employed and statistical analysis was performed to display relationships between variables. In contrast to normal urinary bladder epithelium, which showed high levels of 14-3-3σ, its expression was decreased in 53% of the studied tumors (P = 0.0344). The 14-3-3σ protein was expressed by neoplastic emboli and by highly infiltrative neoplastic cells. The p53 protein was expressed in 26% of TCCs, but no significant association between 14-3-3σ and p53 was detected. Neoplastic epithelial cells displayed vimentin immunoreactivity in 21% of TCCs, and a positive correlation with mitotic index was observed (P = 0.042). Coexpression of vimentin and 14-3-3σ by highly infiltrative neoplastic cells was also observed. 14-3-3σ is deregulated in canine TCCs and its expression by highly infiltrative tumor cells may be related to the acquisition of aggressive behavior. Furthermore, this article reinforce the role of canine TCC as relevant model of human urothelial carcinoma and we suggest 14-3-3σ as a potential therapeutic target. Further studies are necessary to clarify the role of 14-3-3σ in canine TCC. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Decreased expression of protein tyrosine phosphatase non-receptor type 12 is involved in the proliferation and recurrence of bladder transitional cell carcinoma

    Science.gov (United States)

    PIAO, YONGRUI; LIU, XIANKUI; LIN, ZHENHUA; JIN, ZHEHU; JIN, XUANSHUN; YUAN, KUICHANG; WU, WENYUAN

    2015-01-01

    Protein tyrosine phosphatase non-receptor type 12 (PTPN12) has been shown to be involved in the development of a number of types of carcinoma. However, the effect of PTPN12 on the proliferation and recurrence of human bladder transitional cell carcinoma (TCC) is unclear. The present study aimed to investigate the expression and function of PTPN12 in human TCC. Samples from 164 patients with TCC, in addition to 146 patients undergoing bladder surgery for indications other than TCC, were examined. PTPN12 protein expression was examined using immunohistochemistry and western blotting, and PTPN12 mRNA expression was examined using reverse transcription-quantitative polymerase chain reaction. PTPN12 expression was increased following transfection with the PTPN12-expressing, pcDEF3 vector, and PTPN12 expression was decreased by RNA interference, in four TCC cell lines. The proliferation of TCC cells was analyzed by a WST-1 assay and in xenografts on BALB/C nude mice. The effect of PTPN12 on tumor recurrence was analyzed by adhesion, migration and invasion assays in TCC cell lines. PTPN12 expression was significantly decreased in TCC tissues compared with that in normal urothelium, and the level of PTPN12 expression was negatively correlated with tumor size, pathological grade, clinical stage and tumor recurrence. Furthermore, decreased expression of PTPN12 significantly enhanced the proliferation of TCC cells in vitro and in vivo. TCC cells with lower levels of PTPN12 exhibited greater adhesion, migration and invasion. In conclusion, PTPN12 expression is downregulated in human TCC. Restoring PTPN12 activity may represent a novel therapeutic strategy for this disease. PMID:26622721

  19. The effect of photochemical internalization of bleomycin in the treatment of urothelial carcinoma of the bladder: an in vitro study

    NARCIS (Netherlands)

    Arentsen, H.C.; Falke, J.; Hogset, A.; Oosterwijk, E.; Witjes, J.A.

    2014-01-01

    OBJECTIVES: In this in vitro study, we determined whether meso-tetraphenyl chlorin disulphonate (TPCS2a)-based photochemical delivery of bleomycin was able to potentiate the cytotoxicity of bleomycin on bladder cancer cells. MATERIALS AND METHODS: The human RT4, RT112, 253J, T24, and rat AY-27

  20. Orthotopic genital sparing radical cystectomy in pre-menopausal women with muscle-invasive bladder carcinoma: A prospective study

    Science.gov (United States)

    Moursy, Essam ElDin S.; Eldahshoursy, Mohammed Z.; Gamal, Wael M.; Badawy, Abdelbasset A.

    2016-01-01

    Introduction: Invasive cancer bladder is a life-threatening disease that is best treated with radical cystectomy and a suitable urinary diversion. The aim of this study was to evaluate the oncological outcome, voiding and sexual functions after genital sparing radical cystectomy with orthotopic bladder reconstruction in pre-menopausal women with bladder cancer. Materials and Methods: 18 pre-menopausal women who underwent radical cystectomy and orthotopic urinary diversion with preservation of genital organs were included for this study. The patients were followed-up clinically and radiologically to assess their oncological outcome in addition to their voiding and sexual function. Results: Mean age of the patients was 37.8 years, and the median follow-up after surgery was 70 months. One patient was lost to follow-up at 12 months post-operatively. The surgery was completed as planned in all patients, with a mean operative time of 290 min and an average blood loss of 750 mL. 14 patients were able to void satisfactorily, being continent day and night, while four patients needed clean intermittent catheterization. Sexual life remained unchanged in 15 cases, while three patients reported dysparunea. Till the last follow-up, there was no local recurrence while distant metastases were detected in three cases, two of whom died. Conclusions: Genital sparing cystectomy is a valid option for managing carefully selected women with muscle-invasive bladder cancer with good functional and sexual outcomes. PMID:26941498

  1. Deregulation of HOX B13 expression in urinary bladder cancer progression.

    Science.gov (United States)

    Marra, L; Cantile, M; Scognamiglio, G; Perdonà, S; La Mantia, E; Cerrone, M; Gigantino, V; Cillo, C; Caraglia, M; Pignata, S; Facchini, G; Botti, G; Chieffi, S; Chieffi, P; Franco, R

    2013-02-01

    Urinary bladder cancer is a common malignancy in industrialized countries. More than 90% of bladder cancer originates in the transitional cells. Bladder transitional cancer prognosis is, according to the most recent definition related to the level of tumor infiltration, characterized by two main phenotypes, Non Muscle Invasive Bladder Transitional Cancer (NMIBC) and Muscle Invasive Bladder Transitional Cancer (MIBC). The genetic profile and the clinical course of the two subtypes are completely different, however among NMIBC the prognosis is not completely predictable, since 20% of the cases experience a relapse, even in the form of MIBC. It has recently been reported that the chromosomal region 12q13-15, containing crucial cancer genes such as MDM2, CDK4, GLI and an entire cluster of HOX genes, is amplified in bladder cancer. HOX genes codify for transcriptionl factor, involved in embryonal development and cancer progression, with main nuclear expression. Particularly it was also described the strong involvement of HOX B13 in several tumors of urogenital system. In this study we have been investigated, by immunohistochemisty and quantitative Real Time PCR, the HOX B13 expression in bladder cancer evolution and progression, evaluating its ability to discriminate between NMIBC and MBCI phenotypes. Cytoplasmic HOX B13 delocalization significantly relates with muscle invasion (p 0.004). In addition in the series of NMIBC nuclear HOX B13 expression loss is significantly associated to shorter disease free survival (p-value=0.038) defining a potential prognostic role. Overexpression of HOX B13 in more aggressive phenotype is also demonstrate at gene level by quantitative RT-PCR. The de-regulation and delocalization of HOX B13 in urinary bladder cancer supports again the important role of HOX genes in tumor evolution and represents a starting point to establish an integrated analysis, in which HOX genes represent important prognostic and predictive markers for bladder

  2. Confocal Laser Endomicroscopy for the Diagnosis of Urothelial Carcinoma in the Bladder and the Upper Urinary Tract: Protocols for Two Prospective Explorative Studies.

    Science.gov (United States)

    Liem, Esmee Iml; Freund, Jan Erik; Baard, Joyce; de Bruin, D Martijn; Laguna Pes, M Pilar; Savci-Heijink, C Dilara; van Leeuwen, Ton G; de Reijke, Theo M; de la Rosette, Jean Jmch

    2018-02-07

    Visual confirmation of a suspicious lesion in the urinary tract is a major corner stone in diagnosing urothelial carcinoma. However, during cystoscopy (for bladder tumors) and ureterorenoscopy (for tumors of the upper urinary tract) no real-time histopathologic information can be obtained. Confocal laser endomicroscopy (CLE) is an optical imaging technique that allows for in vivo high-resolution imaging and may allow real-time tumor grading of urothelial lesions. The primary objective of both studies is to develop descriptive criteria for in vivo CLE images of urothelial carcinoma (low-grade, high-grade, carcinoma in situ) and normal urothelium by comparing CLE images with corresponding histopathology. In these two prospective clinical trials, CLE imaging will be performed of suspicious lesions and normal tissue in the urinary tract during surgery, prior to resection or biopsy. In the bladder study, CLE will be performed in 60 patients using the Cystoflex UHD-R probe. In the upper urinary tract study, CLE will be performed in 25 patients during ureterorenoscopy, who will undergo radical treatment (nephroureterectomy or segmental ureter resection) thereafter. All CLE images will be analyzed frame by frame by three independent, blinded observers. Histopathology and CLE-based diagnosis of the lesions will be evaluated. Both studies comply with the IDEAL stage 2b recommendations. Presently, recruitment of patients is ongoing in both studies. Results and outcomes are expected in 2018. For development of CLE-based diagnosis of urothelial carcinoma in the bladder and the upper urinary tract, a structured conduct of research is required. This study will provide more insight in tissue-specific CLE criteria for real-time tumor grading of urothelial carcinoma. Confocal Laser Endomicroscopy: ClinicalTrials.gov NCT03013894; https://clinicaltrials.gov /ct2/show/NCT03013894?term=NCT03013894&rank=1 (Archived by WebCite at http://www.webcitation.org/6wiPZ378I); and Dutch Central

  3. Expression microarray meta-analysis identifies genes associated with Ras/MAPK and related pathways in progression of muscle-invasive bladder transition cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Jonathan A Ewald

    Full Text Available The effective detection and management of muscle-invasive bladder Transition Cell Carcinoma (TCC continues to be an urgent clinical challenge. While some differences of gene expression and function in papillary (Ta, superficial (T1 and muscle-invasive (≥T2 bladder cancers have been investigated, the understanding of mechanisms involved in the progression of bladder tumors remains incomplete. Statistical methods of pathway-enrichment, cluster analysis and text-mining can extract and help interpret functional information about gene expression patterns in large sets of genomic data. The public availability of patient-derived expression microarray data allows open access and analysis of large amounts of clinical data. Using these resources, we investigated gene expression differences associated with tumor progression and muscle-invasive TCC. Gene expression was calculated relative to Ta tumors to assess progression-associated differences, revealing a network of genes related to Ras/MAPK and PI3K signaling pathways with increased expression. Further, we identified genes within this network that are similarly expressed in superficial Ta and T1 stages but altered in muscle-invasive T2 tumors, finding 7 genes (COL3A1, COL5A1, COL11A1, FN1, ErbB3, MAPK10 and CDC25C whose expression patterns in muscle-invasive tumors are consistent in 5 to 7 independent outside microarray studies. Further, we found increased expression of the fibrillar collagen proteins COL3A1 and COL5A1 in muscle-invasive tumor samples and metastatic T24 cells. Our results suggest that increased expression of genes involved in mitogenic signaling may support the progression of muscle-invasive bladder tumors that generally lack activating mutations in these pathways, while expression changes of fibrillar collagens, fibronectin and specific signaling proteins are associated with muscle-invasive disease. These results identify potential biomarkers and targets for TCC treatments, and

  4. Methylation of a CpG Island within the Uroplakin Ib Promoter: A Possible Mechanism for Loss of Uroplakin lb Expression in Bladder Carcinoma

    Directory of Open Access Journals (Sweden)

    Andrea E. Varga

    2004-03-01

    Full Text Available Uroplakin Ib is a structural protein on the surface of urothelial cells. Expression of uroplakin Ib mRNA is reduced or absent in many transitional cell carcinomas (TCCs but molecular mechanisms underlying loss of expression remain to be determined. Analysis of the uroplakin Ib promoter identified a weak CpG island spanning the proximal promoter, exon 1, and the beginning of intron 1. This study examined the hypothesis that methylation of this CpG island regulates uroplakin Ib expression. Uroplakin Ib mRNA levels were determined by reverse transcription polymerase chain reaction and CpG methylation was assessed by bisulfite modification of DNA, PCR, and sequencing. A correlation was demonstrated in 15 TCC lines between uroplakin Ib mRNA expression and lack of CpG methylation. In support of a regulatory role for methylation, incubating uroplakin Ib-negative lines with 5-aza-2′ -deoxycytidine reactivated uroplakin Ib mRNA expression. A trend between uroplakin Ib mRNA expression and CpG methylation was also observed in normal urothelium and bladder carcinomas. In particular, loss of uroplakin Ib expression correlated with methylation of a putative Spi/NFκB binding motif. The data are consistent with the hypothesis that methylation of specific sites within the uroplakin Ib promoter may be an important factor in the loss of uroplakin Ib expression in TCCs.

  5. BK virus-associated urinary bladder carcinoma in transplant recipients: report of 2 cases, review of the literature, and proposed pathogenetic model.

    Science.gov (United States)

    Alexiev, Borislav A; Randhawa, Parmjeet; Vazquez Martul, Eduardo; Zeng, Gang; Luo, Chunqing; Ramos, Emilio; Drachenberg, Cinthia B; Papadimitriou, John C

    2013-05-01

    Despite strong experimental evidence, BK polyomavirus involvement in human cancers has been controversial. We report 2 cases of kidney ± pancreas transplant recipients with evidence of BK polyomavirus reactivation, who developed aggressive urinary bladder urothelial carcinomas with adenocarcinomatous and/or micropapillary differentiation. Diffuse strong nuclear positivity for viral T antigen, p53, Ki-67, and p16 was observed in both malignancies. The BK polyomavirus role in promoting urothelial neoplasia in transplant recipients may be partly indirect, based on the demonstration by polymerase chain reaction in both tumors of BK polyomavirus with intact open reading frames and close phylogenetic clustering with known replication-competent strains, and viral capsid protein VP1 messenger RNA and intranuclear virions by electron microscopy in 1 tumor. No unique cancer-associated mutations were found, but some viral T antigen mutations were potentially associated with increased rate of viral replication and risk for "rare" carcinogenic events. The BK polyomavirus-induced profound effects on cell activation, cell cycle shift to proliferation, and apoptosis inhibition, in the context of marked immunosuppression, constitute a potentially ideal background for malignant transformation. The long time lapse between transplantation and tumor manifestation, 7 and 11 years, respectively, further supports the concept of multistep carcinogenesis cascade and long-term risk for these patients. We propose a model of changes ranging from viral reactivation to dysplasia to invasive carcinoma. Clinical vigilance is warranted for early diagnosis of BK polyomavirus-related urothelial malignancies in transplant recipients. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Image-Guided Radiation Therapy for Muscle-Invasive Carcinoma of the Urinary Bladder with Cone Beam CT Scan: Use of Individualized Internal Target Volumes for a Single Patient

    Directory of Open Access Journals (Sweden)

    Gagan Saini

    2012-09-01

    Full Text Available Introduction: While planning radiation therapy (RT for a carcinoma of the urinary bladder (CaUB, the intra-fractional variation of the urinary bladder (UB volume due to filling-up needs to be accounted for. This internal target volume (ITV is obtained by adding internal margins (IM to the contoured bladder. This study was planned to propose a method of acquiring individualized ITVs for each patient and to verify their reproducibility. Methods: One patient with CaUB underwent simulation with the proposed ‘bladder protocol’. After immobilization, a planning CT scan on empty bladder was done. He was then given 300 ml of water to drink and the time (T was noted. Planning CT scans were performed after 20 min (T+20, 30 min (T+30 and 40 min (T+40. The CT scan at T+20 was co-registered with the T+30 and T+40 scans. The bladder volumes at 20, 30 and 40 min were then contoured as CTV20, CTV30 and CTV40 to obtain an individualized ITV for our patient. For daily treatment, he was instructed to drink water as above, and the time was noted; treatment was started after 20 min. Daily pre- and post-treatment cone beam CT (CBCT scans were done. The bladder visualized on the pre-treatment CBCT scan was compared with CTV20 and on the post-treatment CBCT scan with CTV30. Results: In total, there were 65 CBCT scans (36 pre- and 29 post-treatment. Individualized ITVs were found to be reproducible in 93.85% of all instances and fell outside in 4 instances. Conclusions: The proposed bladder protocol can yield a reproducible estimation of the ITV during treatment; this can obviate the need for taking standard IMs.

  7. Nano-BCG: A Promising Delivery System for Treatment of Human Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Julieti Huch Buss

    2018-01-01

    Full Text Available Mycobacterium bovis bacillus Calmette–Guerin (BCG remains at the forefront of immunotherapy for treating bladder cancer patients. However, the incidence of recurrence and progression to invasive cancer is commonly observed. There are no established effective intravesical therapies available for patients, whose tumors recur following BCG treatment, representing an important unmet clinical need. In addition, there are very limited options for patients who do not respond to or tolerate chemotherapy due to toxicities, resulting in poor overall treatment outcomes. Within this context, nanotechnology is an emergent and promising tool for: (1 controlling drug release for extended time frames, (2 combination therapies due to the ability to encapsulate multiple drugs simultaneously, (3 reducing systemic side effects, (4 increasing bioavailability, (5 and increasing the viability of various routes of administration. Moreover, bladder cancer is often characterized by high mutation rates and over expression of tumor antigens on the tumor cell surface. Therapeutic targeting of these biomolecules may be improved by nanotechnology strategies. In this mini-review, we discuss how nanotechnology can help overcome current obstacles in bladder cancer treatment, and how nanotechnology can facilitate combination chemotherapeutic and BCG immunotherapies for the treatment of non-muscle invasive urothelial bladder cancer.

  8. MEK inhibition enhances efficacy of bacillus Calmette-Guérin on bladder cancer cells by reducing release of Toll-like receptor 2-activated antimicrobial peptides.

    Science.gov (United States)

    Whang, Young Mi; Jin, Su Bin; Park, Serk In; Chang, In Ho

    2017-08-08

    Bacillus Calmette-Guérin (BCG) is one of the standard treatment options for non-muscle-invasive bladder cancer. The details of the biological defense mechanisms against BCG remain unclear. Here, we investigated whether BCG-induced release of antimicrobial peptides (AMPs; e.g., human β-defensin-2, -3, and cathelicidin) is involved with mitogen-activated protein kinase (MAPK) pathways, and investigated the enhanced anticancer effect of BCG through the down-regulation of Toll-like receptors (TLRs) and MAPK pathways in bladder cancer cells. BCG-infected bladder cancer cells produced AMPs as a defense mechanism against BCG, which were reduced by MEK inhibitors by blocking phosphorylation of extracellular signal-regulated kinase (ERK1/2 or MEK) and c-Jun. MEK inhibitors enhanced inhibition of bladder cancer cell growth by decreased binding of c-Jun, p65 and Pol II to the activated protein-1 promoter. Knockdown of TLR2 and TLR4 reduced ERK phosphorylation. Knockdown of TLR 2 decreased release of AMPs, which was similar to the efficacy of MEK inhibitor on BCG-infected cells. BCG-infected bladder cancer cells were more prone to induction of AMP release following TLR2 activation via ERK and c-Jun pathway mediators. In conclusion, our data suggest that the BCG-induced release of AMPs in bladder cancer cells is a promising molecular target for enhancing the immunotherapeutic efficacy of BCG in bladder cancer patients.

  9. Bladder Management

    Science.gov (United States)

    ... Catheterization • Urinary Tract Infections: Indwelling (Foley) Catheter Bladder Management [ Download this pamphlet: "Bladder Management" - (PDF, 499KB) ] The ... and medication or surgery may be helpful. Bladder Management Foley or Suprapubic Catheter A tube is inserted ...

  10. Neurogenic bladder

    Science.gov (United States)

    ... your bladder at all Have signs of a bladder infection (fever, burning when you urinate, frequent urination) Urinate small amounts, frequently Alternative Names Neurogenic detrusor overactivity; NDO; Neurogenic bladder sphincter dysfunction; NBSD ...

  11. Bladder Cancer

    Science.gov (United States)

    ... organ in your lower abdomen that stores urine. Bladder cancer occurs in the lining of the bladder. It ... urinate Low back pain Risk factors for developing bladder cancer include smoking and exposure to certain chemicals in ...

  12. Correlation between Urothelial Differentiation and Sensory Proteins P2X3, P2X5, TRPV1, and TRPV4 in Normal Urothelium and Papillary Carcinoma of Human Bladder

    Directory of Open Access Journals (Sweden)

    Igor Sterle

    2014-01-01

    Full Text Available Terminal differentiation of urothelium is a prerequisite for blood-urine barrier formation and enables normal sensory function of the urinary bladder. In this study, urothelial differentiation of normal human urothelium and of low and high grade papillary urothelial carcinomas was correlated with the expression and localization of purinergic receptors (P2X3, and P2X5 and transient receptor potential vanilloid channels (TRPV1, and TRPV4. Western blotting and immunofluorescence of uroplakins together with scanning electron microscopy of urothelial apical surface demonstrated terminal differentiation of normal urothelium, partial differentiation of low grade carcinoma, and poor differentiation of high grade carcinoma. P2X3 was expressed in normal urothelium as well as in low grade carcinoma and in both cases immunolabeling was stronger in the superficial cells. P2X3 expression decreased in high grade carcinoma. P2X5 expression was detected in normal urothelium and in high grade carcinoma, while in low grade carcinoma its expression was diminished. The expression of TRPV1 decreased in low grade and even more in high grade carcinoma when compared with normal urothelium, while TRPV4 expression was unchanged in all samples. Our results suggest that sensory proteins P2X3 and TRPV1 are in correlation with urothelial differentiation, while P2X5 and TRPV4 have unique expression patterns.

  13. Bladder Diseases

    Science.gov (United States)

    ... frequent, urgent urination Bladder cancer Doctors diagnose bladder diseases using different tests. These include urine tests, x- ... National Institute of Diabetes and Digestive and Kidney Diseases

  14. Variations in the Spatial Distribution of Gall Bladder Cancer: A Call ...

    African Journals Online (AJOL)

    which is second to the highest (Chile) in the world and AAR of carcinoma gall bladder is 7.4/100,000 male population, the AAR of carcinoma gall bladder in males is highest in the country.[1,2] Nandakumar et al. had identified this part of the country as a geographically high risk area for carcinoma of the gall bladder.

  15. mTOR inhibitors in urinary bladder cancer.

    Science.gov (United States)

    Pinto-Leite, R; Arantes-Rodrigues, R; Sousa, Nuno; Oliveira, P A; Santos, L

    2016-09-01

    Despite the great scientific advances that have been made in cancer treatment, there is still much to do, particularly with regard to urinary bladder cancer. Some of the drugs used in urinary bladder cancer treatment have been in use for more than 30 years and show reduced effectiveness and high recurrence rates. There have been several attempts to find new and more effective drugs, to be used alone or in combination with the drugs already in use, in order to overcome this situation.The biologically important mammalian target of rapamycin (mTOR) pathway is altered in cancer and mTOR inhibitors have raised many expectations as potentially important anticancer drugs. In this article, the authors will review the mTOR pathway and present their experiences of the use of some mTOR inhibitors, sirolimus, everolimus and temsirolimus, in isolation and in conjunction with non-mTOR inhibitors cisplatin and gemcitabine, on urinary bladder tumour cell lines. The non-muscle-invasive cell line, 5637, is the only one that exhibits a small alteration in the mTOR and AKT phosphorylation after rapalogs exposure. Also, there was a small inhibition of cell proliferation. With gemcitabine plus everolimus or temsirolimus, the results were encouraging as a more effective response was noticed with both combinations, especially in the 5637 and T24 cell lines. Cisplatin associated with everolimus or temsirolimus also gave promising results, as an antiproliferative effect was observed when the drugs were associated, in particular on the 5637 and HT1376 cell lines. Everolimus or temsirolimus in conjunction with gemcitabine or cisplatin could have an important role to play in urinary bladder cancer treatment, depending on the tumour grading.

  16. Deletion/duplication mutation screening of TP53 gene in patients with transitional cell carcinoma of urinary bladder using multiplex ligation-dependent probe amplification.

    Science.gov (United States)

    Bazrafshani, Mohammad Reza R; Nowshadi, Pouriaali A; Shirian, Sadegh; Daneshbod, Yahya; Nabipour, Fatemeh; Mokhtari, Maral; Hosseini, Fatemehsadat; Dehghan, Somayeh; Saeedzadeh, Abolfazl; Mosayebi, Ziba

    2016-02-01

    Bladder cancer is a molecular disease driven by the accumulation of genetic, epigenetic, and environmental factors. The aim of this study was to detect the deletions/duplication mutations in TP53 gene exons using multiplex ligation-dependent probe amplification (MLPA) method in the patients with transitional cell carcinoma (TCC). The achieved formalin-fixed paraffin-embedded tissues from 60 patients with TCC of bladder were screened for exonal deletions or duplications of every 12 TP53 gene exons using MLPA. The pathological sections were examined by three pathologists and categorized according to the WHO scoring guideline as 18 (30%) grade I, 22 (37%) grade II, 13 (22%) grade III, and 7 (11%) grade IV cases of TCC. None mutation changes of TP53 gene were detected in 24 (40%) of the patients. Furthermore, mutation changes including, 15 (25%) deletion, 17 (28%) duplication, and 4 (7%) both deletion and duplication cases were observed among 60 samples. From 12 exons of TP53 gene, exon 1 was more subjected to exonal deletion. Deletion of exon 1 of TP53 gene has occurred in 11 (35.4%) patients with TCC. In general, most mutations of TP53, either deletion or duplication, were found in exon 1, which was statistically significant. In addition, no relation between the TCC tumor grade and any type of mutation were observed in this research. MLPA is a simple and efficient method to analyze genomic deletions and duplications of all 12 exons of TP53 gene. The finding of this report that most of the mutations of TP53 occur in exon 1 is in contrast to that of the other reports suggesting that exons 5-8 are the most (frequently) mutated exons of TP53 gene. The mutations of exon 1 of TP53 gene may play an important role in the tumorogenesis of TCC. © 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  17. Comparative Gene Expression Analyses Identify Luminal and Basal Subtypes of Canine Invasive Urothelial Carcinoma That Mimic Patterns in Human Invasive Bladder Cancer.

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    Deepika Dhawan

    Full Text Available More than 160,000 people are expected to die from invasive urothelial carcinoma (iUC this year worldwide. Research in relevant animal models is essential to improving iUC management. Naturally-occurring canine iUC closely resembles human iUC in histopathology, metastatic behavior, and treatment response, and could provide a relevant model for human iUC. The molecular characterization of canine iUC, however, has been limited. Work was conducted to compare gene expression array results between tissue samples from iUC and normal bladder in dogs, with comparison to similar expression array data from human iUC and normal bladder in the literature. Considerable similarities between enrichment patterns of genes in canine and human iUC were observed. These included patterns mirroring basal and luminal subtypes initially observed in human breast cancer and more recently noted in human iUC. Canine iUC samples also exhibited enrichment for genes involved in P53 pathways, as has been reported in human iUC. This is particularly relevant as drugs targeting these genes/pathways in other cancers could be repurposed to treat iUC, with dogs providing a model to optimize therapy. As part of the validation of the results and proof of principal for evaluating individualized targeted therapy, the overexpression of EGFR in canine bladder iUC was confirmed. The similarities in gene expression patterns between dogs and humans add considerably to the value of naturally-occurring canine iUC as a relevant and much needed animal model for human iUC. Furthermore, the finding of expression patterns that cross different pathologically-defined cancers could allow studies of dogs with iUC to help optimize cancer management across multiple cancer types. The work is also expected to lead to a better understanding of the biological importance of the gene expression patterns, and the potential application of the cross-species comparisons approach to other cancer types as well.

  18. Tumor-infiltrating CD8+ lymphocytes predict different clinical outcomes in organ- and non-organ-confined urothelial carcinoma of the bladder following radical cystectomy.

    Science.gov (United States)

    Zhang, Shiqiang; Wang, Jun; Zhang, Xinyu; Zhou, Fangjian

    2017-01-01

    Tumor-infiltrating lymphocytes (TILs) are associated with better clinical outcomes in many tumors. TILs represent a cell-mediated immune response against the carcinoma. CD8+ TILs are a crucial component of cell-mediated immunity. The significance of CD8+ TILs has not been reported respectively in organ- and non-organ-confined urothelial carcinoma (UC) of the bladder. We explored the prognostic value of CD8+ TILs in the two groups. The presence of CD8+ TILs was assessed by immunohistochemical staining of whole tissue sections from 75 organ and 51 non-organ-confined disease patients with long-term follow-up, and its correlation with clinicopathological features and overall survival (OS) was determined. The CD8+ TIL immunohistochemical staining score was 0 (CD8 negative if the score was 0. There were no associations between CD8+ TILs and age, sex, nuclear grade, and adjuvant or neoadjuvant chemotherapy in organ- and non-organ-confined disease. The presence of CD8+ TILs was seen more frequently in pTa- 1 than pT 2 stage ( p  = 0.033) in organ-confined disease. No associations between CD8+ TILs and pT stage, pN stage were found in non-organ-confined disease. CD8+ TILs were associated with better OS (log-rank test, P  = 0.036) in non-organ-confined disease, but with poorer OS (log-rank test, P  = 0.040) in organ-confined disease by the Kaplan-Meier method. In multivariate analysis, CD8+ TILs were an independent favorable prognostic factor in non-organ-confined disease, but were an independent unfavorable prognostic factor in organ-confined disease. These results suggest that CD8+ TILs have clinically significant anti-tumor activity in non-organ-confined disease, but may have pro-tumor activity in organ-confined disease. Therefore, we should be cautious if CD8+ TILs are aimed to be exploited in the treatment of bladder cancer.

  19. A Multimodal Imaging Approach for Longitudinal Evaluation of Bladder Tumor Development in an Orthotopic Murine Model.

    Directory of Open Access Journals (Sweden)

    Chantal Scheepbouwer

    Full Text Available Bladder cancer is the fourth most common malignancy amongst men in Western industrialized countries with an initial response rate of 70% for the non-muscle invasive type, and improving therapy efficacy is highly needed. For this, an appropriate, reliable animal model is essential to gain insight into mechanisms of tumor growth for use in response monitoring of (new agents. Several animal models have been described in previous studies, but so far success has been hampered due to the absence of imaging methods to follow tumor growth non-invasively over time. Recent developments of multimodal imaging methods for use in animal research have substantially strengthened these options of in vivo visualization of tumor growth. In the present study, a multimodal imaging approach was addressed to investigate bladder tumor proliferation longitudinally. The complementary abilities of Bioluminescence, High Resolution Ultrasound and Photo-acoustic Imaging permit a better understanding of bladder tumor development. Hybrid imaging modalities allow the integration of individual strengths to enable sensitive and improved quantification and understanding of tumor biology, and ultimately, can aid in the discovery and development of new therapeutics.

  20. Efficacy of voided urinary cytology and ultrasonography compared to cystoscopy in the detection of urinary bladder cancer

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    N. Kumar

    2017-09-01

    Conclusions: Voided urinary cytology can be omitted as a screening test. Ultrasonography can be recommended as the initial imaging investigation for detection of bladder carcinoma in patients presenting with hematuria and for follow up of bladder carcinoma patients.

  1. Primary combined carcinoid and adenocarcinoma of the ileum associated with transitional carcinoma of the bladder. Single case report Causa infrecuente de disfagia en el postoperatorio tardío de la cirugía de la hernia de hiato

    Directory of Open Access Journals (Sweden)

    I. D. Venizelos

    2007-03-01

    Full Text Available Composite neoplasms, carcinoid and adenocarcinoma have been reported to occur in several parts of the body, including the stomach, ampulla of Vater, large bowel, lung, and urinary bladder. Here we report a case of a 74-year-old male with a composite carcinoid-adenocarcinoma of the ileum associated with a transitional cell carcinoma of the bladder. The microscopical examination of the composite tumor showed an admixture of typical carcinoid tumor and moderately a differentiated adenocarcinoma. Immunohistochemically, the two components showed clear-cut differentiations. A review of the literature revealed that this is the first reported case of composite carcinoid-adenocarcinoma of the ileum associated with transitional cell carcinoma of the urinary bladder.Las neoplasias compuestas, el carcinoide y el adenocarcinoma se ha observado que aparecen en varias partes del organismo, como el estómago, la ampolla de Vater, el intestino grueso, el pulmón y la vejiga urinaria. Publicamos aquí el caso de un varón de 74 años con un tumor compuesto de tipo carcinoide-adenocarcinoma del íleon asociado a un carcinoma vesical de células transicionales. El examen macroscópico del tumor compuesto mostró una mezcla de tumor carcinoide típico y adenocarcinoma moderadamente diferenciado. Desde el punto de vista inmunohistoquímico, los dos componentes estaban claramente diferenciados. Una revisión de la bibliografía reveló que este es el primer caso que se publica de un tumor compuesto de tipo carcinoide-adenocarcinoma del íleon asociado a un carcinoma de células transicionales de la vejiga urinaria.

  2. Orthotopic AY-27 rat bladder urothelial cell carcinoma model presented an elevated methemoglobin proportion in the increased total hemoglobin content when evaluated in vivo by single-fiber reflectance spectroscopy

    Science.gov (United States)

    Sun, Tengfei; Davis, Carole A.; Hurst, Robert E.; Slaton, Joel W.; Piao, Daqing

    2017-02-01

    In vivo single-fiber reflectance spectroscopy (SfRS) was performed on an orthotopic AY-27 rat bladder urothelial cell carcinoma model to explore potential spectroscopic features revealing neoplastic changes. AY-27 bladder tumor cells were intravesically instilled in four rats and allowed to implant and grow for one week, with two additional rats as the control. A total of 107 SfRS measurements were taken from 27 sites on two control bladders and 80 from four AY-27 treated bladders. The spectral profiles obtained from AY-27 treated bladders revealed various levels of a methemoglobin (MetHb) characteristic spectral feature around 635nm. A multisegment spectral analysis method estimated concentrations of five chromophore compositions including oxyhemoglobin, deoxyhemoglobin, MetHb, lipid and water. The total hemoglobin concentration ([HbT]), the MetHb proportion in the total hemoglobin and the lipid volume content showed possible correlations. The 80 measurements from the AY-27 treated bladders could separate to three sub-sets according to the MetHb proportion. Specifically, 72 were in subset 1 with low proportion (5.3%30%). When grouped according to [MetHB], the [HbT] increased from 368 μM of subset 1 to 488 μM of subset 2 to 541 μM of subset 3, in comparison to the 285 μM of the control. The increased total hemoglobin and the elevation of MetHb proportion may signify angiogenesis and degradation in hemoglobin oxygen-transport. Additionally, the lipid volume content decreased from 2.58% in the control to <0.2% in the tumor groups, indicating disruption of subepithelium tissue architecture.

  3. A combination therapy of selective intraarterial anti-cancer drug infusion and radiation therapy for muscle-invasive bladder cancer

    International Nuclear Information System (INIS)

    Okuno, Yumiko; Zaitsu, Masayoshi; Mikami, Koji; Takeuchi, Takumi; Matsuda, Izuru; Arahira, Satoko

    2017-01-01

    The gold standard for the treatment of muscle-invasive bladder cancer Without metastasis is radical cystectomy. However, there increase patients very elderly and with serious complications. They are not good candidates for invasive surgical operation. Intraarterial infusion of 70 mg/m 2 of cisplatin and 30 mg/m 2 of pirarubicin into bilateral bladder arteries was conducted for 5 patients diagnosed with muscle invasive bladder cancers without distant metastasis. Right and left distribution of anti-cancer drugs was determined based on the location of bladder tumor(s). External beam radiation therapy was commenced immediately following intraarterial infusion. The patients were followed up with clinical and radiographic investigations and bladderbiopsy was performed as needed. Patients were all males who are smoking or with smoking history ranging from 73 to 85 years of age (median 82). The duration between transurethral resection of bladder tumors (TUR-Bt) and intraarterial infusion of anti-cancer drugs was 47.4 days (range 26-68), the median follow-up period after intraarterial infusion was 21.5 months (range 87-547) without death. Total radiation dose was 59.2 ±3.0 Gy. Complete remission was accomplished in all cases. One patient showed intravesical recurrence of non muscle-invasive tumors 45.8 months following intraarterial infusion and underwent TUR-Bt. Two cases underwent bladder biopsies showing no tumors. All patients but one case with bladder recurrence were free of tumor recurrence with radiographic investigation. For adverse events, acute renal failure was in one case and leukocytopenia was in all 5 cases, Grade 2 for one and Grade 3 for 4 cases. Follow-up periods are not long enough, but early results of a combination therapy of selective intraarterial anti-cancer drug infusion and radiation therapy for muscle-invasive bladder cancer were good. (author)

  4. Microsatellite instability in bladder cancer

    DEFF Research Database (Denmark)

    Gonzalez-Zulueta, M; Ruppert, J M; Tokino, K

    1993-01-01

    Somatic instability at microsatellite repeats was detected in 6 of 200 transitional cell carcinomas of the bladder. Instabilities were apparent as changes in (GT)n repeat lengths on human chromosome 9 for four tumors and as alterations in a (CAG)n repeat in the androgen receptor gene on the X...... or larger (> 2 base pairs) alterations in repeat length. All six tumors were low stage (Ta-T1), suggesting that these alterations can occur early in bladder tumorigenesis....

  5. Intravesical BCG+interferon-α-2b in prevention of recurrence in transitional cell carcinoma of urinary bladder

    Directory of Open Access Journals (Sweden)

    Nayan K Mohanty

    2000-01-01

    Between Jan. ′94 to Dec. ′98, 100 patients with super-ficial TCC (Ta, TI of urinary bladder with or without Tis after transurethral resection of tumor underwent intra-vesical instillation of BCG (70 ing + Interferon-α-2b (5-million IU weekly for 8 weeks, fortnightly for 8 weeks, monthly . for 8 weeks . followed by maintenance dose at the end of 9th, 12th, 18th & 24th months with follow-up for 60 months. Results: At the end of 60 months of follow-up 36 pa-tients (36% showed complete response, 44 patients (44% showed partial response, resulting in a total response rate of 80% while 20% progressed to higher stage & grade. Patients′ tolerance was good and adverse reaction was low 19%. Conclusion: This study has shown that a low dose com-bined therapy with BCG and Interferon is not only safe, well tolerated, cost effective but also highly efficient in preventing recurrences in 36%, maintaining superficial nature of the disease in another 44% with a disease pro-gression free interval of 5 years in 80% of cases.

  6. Current clinical practice gaps in the treatment of intermediate- and high-risk non-muscleinvasive bladder cancer (NMIBC) with emphasis on the use of bacillus Calmette- Guérin (BCG): results of an international individual patient data survey (IPDS)

    Science.gov (United States)

    Witjes, J Alfred; Palou, Joan; Soloway, Mark; Lamm, Donald; Kamat, Ashish M; Brausi, Maurizio; Persad, Raj; Buckley, Roger; Colombel, Marc; Böhle, Andreas

    2013-01-01

    Objectives To examine the management of intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC), particularly with regard to the use of bacillus Calmette-Guérin (BCG) therapy, in North America and Europe. To compare NMIBC management practices to European Association of Urology (EAU) and American Urological Association (AUA) guideline recommendations for the management of intermediate- and high-risk NMIBC. Patients and Methods In all, 102 urologists from Europe and North America participated in this retrospective on-line chart review, which was conducted between 1 April 2011 and 30 April 2012. Participants selected the charts of the first 10 intermediate- (defined as multiple or recurrent low-grade tumours) or high-risk (defined as any T1 and/or high-grade/G3 tumours and/or carcinoma in situ) patients who underwent transurethral resection of bladder tumour in 2009. Physicians retrospectively reviewed the charts and completed an on-line survey consisting of questions related to diagnosis, planned treatment, treatment status and follow-up. In all, 971 patients (197 intermediate-risk; 774 high-risk) were included in the analysis; frequency counts and associated percentages were used to analyse treatment variables. Results In all, 47% of intermediate-risk patients received EAU or AUA guideline-recommended intravesical therapy: intravesical chemotherapy, BCG induction therapy or BCG induction plus maintenance. Of the high-risk patients, 50% received maintenance BCG as recommended by the EAU and the AUA; although not recommended for high-risk NMIBC, 12.5% received intravesical chemotherapy. Of patients prescribed maintenance BCG, 93% were scheduled for at least 1 year of therapy. Notably, only 15% discontinued BCG maintenance and, of these discontinuations, 65% were due to reasons unrelated to BCG-associated adverse events. Conclusions There is significant non-adherence to EAU and AUA guideline recommendations for BCG use in intermediate- and high

  7. Imaging of urinary bladder tumors

    International Nuclear Information System (INIS)

    Hadjidekov, G.

    2015-01-01

    Full text: Primary bladder neoplasms account for 2%-6% of all tumors, with urinary bladder cancer ranked as the fourth most common cancer in males. Transitional cell carcinoma (TCC) is the most common subtype of urothelial tumour accounting for approximately 90% of all urothelial cancers. It is typically observed in men aged 50-70 years with history of smoking or occupational exposure to carcinogens. Most urothelial neoplasms are low-grade papillary tumors, with high incidence of recurrence, requires rigorous follow-up but have a relatively good prognosis. Other bladder neoplasm include squamous cell carcinoma accounts for 2%-15% mainly according to geographic location; adenocarcinoma - less than 2% /both occurring in the context of chronic bladder infection and irritation/; mesenchymal tumors in 5%, with the most common examples being rhabdomyosarcoma in children and leiomyosarcoma in adults. More rare mesenchymal tumors include paraganglioma, lymphoma, leiomyoma and solitary fibrous tumor which have no specific typical imaging findings to be differentiated. Multidetector computed tomography urography is an efficient tool for diagnosis and follow-up in patients with transitional cell carcinoma and it can be considered the primary radiologic method for detection, staging and assessment of the entire urothelium regarding the multicentric nature of TCC. MRI is rapidly expanding modality of choice especially in locally staging the tumor and in controversies. Accurate TNM staging is primordial in choosing treatment and prognosis for patients with bladder carcinoma. Correct interpretation and classification of the tumour is helpful for the urologists to determine further management in these cases. The learning objectives of the presentation are: to illustrate the spectrum of CT and MRI findings and to assess their clinical value in patients with transitional cell carcinoma and some other bladder neoplasm; to discuss the TNM staging based on the imaging findings; to be

  8. Apoptosis, proliferation and p53, cyclin D1, and retinoblastoma gene expression in relation to radiation response in transitional cell carcinoma of the bladder

    International Nuclear Information System (INIS)

    Moonen, Luc; Ong, Francisca; Gallee, Maarten; Verheij, Marcel; Horenblas, Simon; Hart, Augustinus A.M.; Bartelink, Harry

    2001-01-01

    Purpose: To determine whether the apoptotic index, the Ki67 index, and the expression of the p53, cyclin D1, and retinoblastoma genes correlate with local control, overall survival, and time to distant metastases in invasive bladder cancer treated with external beam radiation. Methods and Materials: Paraffin-embedded pretreatment biopsies from 83 patients with invasive transitional cell carcinoma of the bladder were scored morphologically for apoptosis and immunohistochemically for Ki67, p53, cyclin D1, and retinoblastoma gene expression. Survival analysis methods were used to assess overall survival, local control, and freedom from distant metastases. A multiple proportional hazard (PH) regression analysis was performed to study the prognostic value of the above mentioned biologic parameters (all divided into two categories, except Ki67) in addition to classical prognostic factors such as T stage, histologic grade, multifocality of the tumor, and completeness of transurethral resection. All patients were treated with external beam radiation as sole treatment. Median follow-up for the 19 patients still living was 7.5 years. Results: Apoptotic index varied from 0% to 3.4% with a mean of 0.8% and a median of 0.6%. Ki67 index varied from 0% to 60% with a mean of 14% and a median of 12%. P53 protein was detectable in 61% of the tumors. Overexpression of cyclin D1 was observed in 39% of the tumors and loss of retinoblastoma protein in 23% of the tumors. High Ki67 index was found to be significantly associated with p53 expression (p=0.04) and cyclin D1 overexpression (p=0.023). Cyclin D1 overexpression was found more often in Rb-positive tumors than in Rb-negative tumors (p=0.006). Other associations between the markers are less clear. Biologic markers were not correlated with T stage or grade. In the PH analysis local control was found to be significantly better for tumors with wild-type p53 (p=0.028). Also, tumors with an apoptotic index above the median value (0

  9. Effects of YC-1 on hypoxia-inducible factor 1 alpha in hypoxic human bladder transitional carcinoma cell line T24 cells.

    Science.gov (United States)

    Li, Yangle; Zhao, Xiaokun; Tang, Huiting; Zhong, Zhaohui; Zhang, Lei; Xu, Ran; Li, Songchao; Wang, Yi

    2012-01-01

    It was the aim of this study to explore the effects of 3-(5'-hydroxymethyl-2'-furyl)-l-benzyl indazole (YC-1) on transcription activity, cell proliferation and apoptosis of hypoxic human bladder transitional carcinoma cells (BTCC), mediated by hypoxia-inducible factor 1α (HIF-1α). BTCC cell line T24 cells were incubated under normoxic or hypoxic conditions, adding different doses of YC-1. The protein expression of HIF-1α and HIF-1α-mediated genes was detected by Western blotting. RT-PCR was used to detect HIF-1α mRNA expression. Cell proliferation, apoptosis and migration activity were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry and transwell migration assay. The cells were pretreated by two ERK/p38 MAPK pathway-specific inhibitors, PD98059 or SB203580, and then incubated with YC-1 treatment under hypoxic condition. HIF-1α protein expression was detected by Western blotting. Hypoxic T24 cells expressed a higher level of HIF-1α, vascular endothelial growth factor, matrix metalloproteinases-2, B-cell lymphoma/leukemia-2 protein and HIF-1α mRNA compared with normoxic controls, in which the above-mentioned expression was downregulated by YC-1 in a dose-dependent manner. Cell proliferation and migration activity were inhibited while apoptosis was induced by YC-1 under hypoxic condition. Moreover, YC-1-downregulated HIF-1α expression was reversed by PD98059 and SB203580, respectively. YC-1 inhibits HIF-1α and HIF-1α-mediated gene expression, cell proliferation and migration activity and induces apoptosis in hypoxic BTCC. The ERK/p38 MAPK pathway may be involved in YC-1-mediated inhibition of HIF-1α. Copyright © 2011 S. Karger AG, Basel.

  10. Gender-specific differences in cancer-specific survival after radical cystectomy for patients with urothelial carcinoma of the urinary bladder in pathologic tumor stage T4a.

    Science.gov (United States)

    May, Matthias; Bastian, Patrick J; Brookman-May, Sabine; Fritsche, Hans-Martin; Tilki, Derya; Otto, Wolfgang; Bolenz, Christian; Gilfrich, Christian; Trojan, Lutz; Herrmann, Edwin; Moritz, Rudolf; Tiemann, Arne; Müller, Stefan C; Ellinger, Jörg; Buchner, Alexander; Stief, Christian G; Wieland, Wolf F; Höfner, Thomas; Hohenfellner, Markus; Haferkamp, Axel; Roigas, Jan; Zacharias, Mario; Nuhn, Philipp; Burger, Maximilian

    2013-10-01

    Bladder cancer (UCB) staged pT4a show heterogeneous outcome after radical cystectomy (RC). No risk model has been established to date. Despite gender-specific differences, no comparative studies exist for this tumor stage. Cancer-specific survival (CSS) of 245 UCB patients without neoadjuvant chemotherapy staged pT4a, pN0-2, M0 after RC were analyzed in a retrospective multi-center study. Seventeen patients were excluded from further analysis due to carcinoma in situ (CIS) of the prostatic urethra and/or positive surgical margins. Average follow-up period was 30 months (IQR: 14-45). The influence of different clinical and histopathologic variables on CSS was determined through uni- and multivariate Cox regression analyses. Two risk groups were generated using factors with independent effect in multivariate models. Internal validity of the prediction model was evaluated by bootstrapping. Eighty-four percent of the patients (n = 192) were male; 72% (n = 165) showed lymphovascular invasion (LVI). The 5-year CSS rate was 31%, and significantly different between male and female (35% vs. 15%, P = 0.003). Multivariate Cox regression modeling, female gender (HR = 1.83, P = 0.008), LVI (HR = 1.92, P = 0.005), and absence of adjuvant chemotherapy (HR = 0.61, P = 0.020) significantly worsened CSS. Two risk groups were generated using these 3 criteria, which differed significantly between each other in CSS (5-year-CSS: 46% vs. 12%, P < 0.001). The c-index value of the risk model was 0.61 (95% CI: 0.53-0.68, P < 0.001). Prognosis in UCB staged pT4a is heterogeneous. Female gender and LVI are adverse factors. Adjuvant chemotherapy seems to improve outcome. The present analysis establishes the first risk model for this demanding tumor stage. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. In vivo 31P magnetic resonance spectroscopy and 1H magnetic resonance imaging of human bladder carcinoma on nude mice: effects of tumour growth and treatment with cis-dichloro-diamine platinum

    DEFF Research Database (Denmark)

    De Certaines, J D; Albrectsen, J; Larsen, V A

    1993-01-01

    In vivo 31P NMR spectroscopy and 1H NMR imaging were used to examine the bladder T24B carcinoma in nude mice during untreated growth and in response to chemotherapy by Cis-dichloro-diammine-platinum (CDDP) at a dose of 8 mg/kg i.p. Untreated growth was associated with an increase of inorganic......, as early as 6 hours after treatment. Although necrotic area was clearly visible in MRI, no treatment effect could be detected on the images of treated tumours....

  12. Re-examination of the Natural History of High-grade T1 Bladder Cancer using a Large Contemporary Cohort

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    Daniel J. Canter

    2014-04-01

    Full Text Available IntroductionHigh-grade T1 (HGT1 bladder cancer represents a clinical challenge in that the urologist must balance the risk of disease progression against the morbidity and potential mortality of early radical cystectomy and urinary diversion. Using two non-muscle invasive bladder cancer (NMIBC databases, we re-examined the rate of progression of HG T1 bladder cancer in our bladder cancer populations.Materials and MethodsWe queried the NMIBC databases that have been established independently at the Atlanta Veterans Affairs Medical Center (AVAMC and the University of Pennsylvania to identify patients initially diagnosed with HGT1 bladder cancer. Demographic, clinical, and pathologic variables were examined as well as rates of recurrence and progression.ResultsA total of 222 patients were identified; 198 (89.1% and 199 (89.6% of whom were male and non-African American, respectively. Mean patient age was 66.5 years. 191 (86.0% of the patients presented with isolated HG T1 disease while 31 (14.0% patients presented with HGT1 disease and CIS. Induction BCG was utilized in 175 (78.8% patients. Recurrence occurred in 112 (50.5% patients with progression occurring in only 19 (8.6% patients. At a mean follow-up of 51 months, overall survival was 76.6%. Fifty two patients died, of whom only 13 (25% patient deaths were bladder cancer related.ConclusionsIn our large cohort of patients, we found that the risk of progression at approximately four years was only 8.6%. While limited by its retrospective nature, this study could potentially serve as a starting point in re-examining the treatment algorithm for patients with HG T1 bladder cancer.

  13. 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.

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    Julia Elsäßer

    Full Text Available 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

  14. Modulation of intra-epithelial expansion of human T24 bladder-carcinoma cells in murine urothelium by growth factors and extracellular-matrix components

    NARCIS (Netherlands)

    J.M.J. Rebel (Annemarie); C.D.E.M. Thijssen (C. D E M); M. Vermey; E.C. Zwarthoff (Ellen); Th.H. van der Kwast (Theo)

    1995-01-01

    textabstractThe high recurrence rate of bladder cancer is probably due to an efficient repopulation of the bladder by residual transformed cells after resection of the tumour. However, the regenerating capacity of the normal urothelial cells is very high. To study the balance between regenerating

  15. BCG-mediated bladder cancer immunotherapy: identifying determinants of treatment response using a calibrated mathematical model.

    Directory of Open Access Journals (Sweden)

    Cyrill A Rentsch

    Full Text Available Intravesical Bacillus Calmette Guérin (BCG immunotherapy is considered the standard of care for treatment of non-muscle invasive bladder cancer; however the treatment parameters were established empirically. In order to evaluate potential optimization of clinical parameters of BCG induction therapy, we constructed and queried a new mathematical model. Specifically, we assessed the impact of (1 duration between resection and the first instillation; (2 BCG dose; (3 indwelling time; and (4 treatment interval of induction therapy - using cure rate as the primary endpoint. Based on available clinical and in vitro experimental data, we constructed and parameterized a stochastic mathematical model describing the interactions between BCG, the immune system, the bladder mucosa and tumor cells. The primary endpoint of the model was the probability of tumor extinction following BCG induction therapy in patients with high risk for tumor recurrence. We theoretically demonstrate that extending the duration between the resection and the first BCG instillation negatively influences treatment outcome. Simulations of higher BCG doses and longer indwelling times both improved the probability of tumor extinction. A remarkable finding was that an inter-instillation interval two times longer than the seven-day interval used in the current standard of care would substantially improve treatment outcome. We provide insight into relevant clinical questions using a novel mathematical model of BCG immunotherapy. Our model predicts an altered regimen that may decrease side effects of treatment while improving response to therapy.

  16. Mycobacterium Brumae Extract Fractions with Potential Immunotherapeutic Activity for Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Zeliha Ertürk

    2017-09-01

    Full Text Available Objective: Immunotherapy with intravesical Bacillus Calmette-Guérin (BCG application is a gold standard treatment for high risk non-muscle invasive bladder cancer (NMIBC, despite its local and systemic side effects. We aimed to develop less toxic and more powerful therapeutic agents for the treatment of bladder cancer than live strain. Materials and Methods: Immunostimulated and non-pathogenic Mycobacterium brumae strains resembling BCG with cytotoxic activities were used. The bacteria were sonicated after heat treatment. Samples prepared by aqueous solution and acetone were subjected to high performance liquid chromatography on reverse phase and strong ion exchange columns. Tumour necrosis factor-α (TNF-α stimulating activities and the matrix-assisted laser desorption/ionization-mass spectroscopy findings of the samples were analysed. Results: As a result, it was revealed that two components, m/z ratios around 1800 and another around m/z 3600 could be responsible for TNF-α stimulating activity. Conclusion: These components have a potential to develop of new agents for NMIBC treatment.

  17. HP-NAP inhibits the growth of bladder cancer in mice by activating a cytotoxic Th1 response.

    Science.gov (United States)

    Codolo, Gaia; Fassan, Matteo; Munari, Fabio; Volpe, Andrea; Bassi, Piefrancesco; Rugge, Massimo; Pagano, Francesco; D'Elios, Mario Milco; de Bernard, Marina

    2012-01-01

    Intravesical Bacillus Calmette-Guérin (BCG) is the gold standard treatment for intermediate and high-risk non-muscle-invasive bladder cancer. BCG therapy is the most successful example of immunotherapy in cancer. Unfortunately, the treatment-related side effects are still relevant. Furthermore, non-responder patients are candidate to radical cystectomy in the absence of valuable alternative options. These aspects have prompted the search for newer biological response modifiers (BRM) with a better benefit/side effects ratio. The toll-like receptor (TLR) 2 ligand, Helicobacter pylori protein HP-NAP, has been shown to deserve a potential role as BRM. HP-NAP is capable of driving the differentiation of T helper (Th) 1 cells, both in vitro and in vivo, because of its ability to create an IL-12-enriched milieu. Herein, we report that local administration of HP-NAP decreases tumour growth by triggering tumour necrosis in a mouse model of bladder cancer implant. The effect is accompanied by a significant accumulation of both CD4+ and CD8+ IFN-γ-secreting cells, within tumour and regional lymph nodes. Noteworthy, HP-NAP-treated tumours show also a reduced vascularization due to the anti-angiogenic activity of IFN-γ induced by HP-NAP. Our findings strongly indicate that HP-NAP might become a novel therapeutic "bullet" for the cure of bladder tumours.

  18. Neurogenic Bladder

    Directory of Open Access Journals (Sweden)

    Peter T. Dorsher

    2012-01-01

    Full Text Available Congenital anomalies such as meningomyelocele and diseases/damage of the central, peripheral, or autonomic nervous systems may produce neurogenic bladder dysfunction, which untreated can result in progressive renal damage, adverse physical effects including decubiti and urinary tract infections, and psychological and social sequelae related to urinary incontinence. A comprehensive bladder-retraining program that incorporates appropriate education, training, medication, and surgical interventions can mitigate the adverse consequences of neurogenic bladder dysfunction and improve both quantity and quality of life. The goals of bladder retraining for neurogenic bladder dysfunction are prevention of urinary incontinence, urinary tract infections, detrusor overdistension, and progressive upper urinary tract damage due to chronic, excessive detrusor pressures. Understanding the physiology and pathophysiology of micturition is essential to select appropriate pharmacologic and surgical interventions to achieve these goals. Future perspectives on potential pharmacological, surgical, and regenerative medicine options for treating neurogenic bladder dysfunction are also presented.

  19. An evaluation of morphological and functional multi-parametric MRI sequences in classifying non-muscle and muscle invasive bladder cancer

    International Nuclear Information System (INIS)

    Panebianco, Valeria; Barchetti, Giovanni; Grompone, Marcello Domenico; Del Monte, Maurizio; Carano, Davide; Catalano, Carlo; De Berardinis, Ettore; Leonardo, Constantino; Simone, Giuseppe; Gallucci, Michele; National Cancer Insitute, Rome; Catto, James

    2017-01-01

    Our goal is to determine the ability of multi-parametric magnetic resonance imaging (mpMRI) to differentiate muscle invasive bladder cancer (MIBC) from non-muscle invasive bladder cancer (NMIBC). Patients underwent mpMRI before tumour resection. Four MRI sets, i.e. T2-weighted (T2W) + perfusion-weighted imaging (PWI), T2W plus diffusion-weighted imaging (DWI), T2W + DWI + PWI, and T2W + DWI + PWI + dif-fusion tensor imaging (DTI) were interpreted qualitatively by two radiologists, blinded to histology results. PWI, DWI and DTI were also analysed quantitatively. Accuracy was determined using histopathology as the reference standard. A total of 82 tumours were analysed. Ninety-six percent of T1-labeled tumours by the T2W + DWI + PWI image set were confirmed to be NMIBC at histopathology. Overall accuracy of the complete mpMRI protocol was 94% in differentiating NMIBC from MIBC. PWI, DWI and DTI quantitative parameters were shown to be significantly different in cancerous versus non-cancerous areas within the bladder wall in T2-labelled lesions. MpMRI with DWI and DTI appears a reliable staging tool for bladder cancer. If our data are validated, then mpMRI could precede cystoscopic resection to allow a faster recognition of MIBC and accelerated treatment pathways. (orig.)

  20. An evaluation of morphological and functional multi-parametric MRI sequences in classifying non-muscle and muscle invasive bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Panebianco, Valeria; Barchetti, Giovanni; Grompone, Marcello Domenico; Del Monte, Maurizio; Carano, Davide; Catalano, Carlo [Sapienza Univ. Rome (Italy). Dept. of Radiological Sciences, Oncology and Pathology; De Berardinis, Ettore; Leonardo, Constantino [Sapienza Univ. Rome (Italy). Dept. of Gynaecological-Obstetric and Urological Sciences; Simone, Giuseppe; Gallucci, Michele [' ' Regina Elena' ' National Cancer Insitute, Rome (Italy). Dept. of Urology; Catto, James [Sheffield Univ. (United Kingdom). Aademic Urology Unit

    2017-09-15

    Our goal is to determine the ability of multi-parametric magnetic resonance imaging (mpMRI) to differentiate muscle invasive bladder cancer (MIBC) from non-muscle invasive bladder cancer (NMIBC). Patients underwent mpMRI before tumour resection. Four MRI sets, i.e. T2-weighted (T2W) + perfusion-weighted imaging (PWI), T2W plus diffusion-weighted imaging (DWI), T2W + DWI + PWI, and T2W + DWI + PWI + dif-fusion tensor imaging (DTI) were interpreted qualitatively by two radiologists, blinded to histology results. PWI, DWI and DTI were also analysed quantitatively. Accuracy was determined using histopathology as the reference standard. A total of 82 tumours were analysed. Ninety-six percent of T1-labeled tumours by the T2W + DWI + PWI image set were confirmed to be NMIBC at histopathology. Overall accuracy of the complete mpMRI protocol was 94% in differentiating NMIBC from MIBC. PWI, DWI and DTI quantitative parameters were shown to be significantly different in cancerous versus non-cancerous areas within the bladder wall in T2-labelled lesions. MpMRI with DWI and DTI appears a reliable staging tool for bladder cancer. If our data are validated, then mpMRI could precede cystoscopic resection to allow a faster recognition of MIBC and accelerated treatment pathways. (orig.)

  1. INTRAVESICULAR IMMUNOTHERAPY WITH BCG VACCINE AND INTERFERON-αα2B FOR NON-INVASIVE CARCINOMA OF THE URINARY BLADDER: RESULTS OF PROSPECTIVE RANDOMIZED STUDY

    Directory of Open Access Journals (Sweden)

    A. A. Minich

    2009-01-01

    Full Text Available Background: Both bacillus Calmette-Gue’rin (BCG and interferon-alpha (IFN-α are active against urinary bladder cancer. In this studywe evaluate the therapeutic efficacy and toxicity of combined intravesical BCG plus IFN-α for treating non-invasive bladder cancer.Subjects and methods: A total of 149 patients (mean age 63.2 years were enrolled for the study. The inclusion criteria were histologically verifiednon-invasive transitional cell carcinoma with intermediate and high risks of recurrence and progression. After transurethral tumor resection, all thepatients were randomized in three groups. Group 1 (n=60 was treated with a 6-week course of BCG, 125 mg, starting 14 to 21 days after TUR, Group2 (n=60 patients received 6-week instillations of BCG, 125 mg, plus IFN-α, 6 million units, Group 3 patients (n = 29 had 4-month courses ofintravesical IFN-α, 6 million units, twice daily during 3 consecutive days. A response was assessed by cystoscopy every 3 months after treatment.Results: A median follow-up of 30.9 months revealed recurrences in 26 (43.3% patients in the BCG group, 8 (13.3% patients in the BCG + IFN-αgroup and 18 (62.1% patients in the IFN-α group. Progression to muscle invasion occurred in 12% and 7% in Groups 1 and 3, respectively, withno progression in Group 2 patients. Three-year relapse-free survival was higher in the BCG+IFN group (78.5% versus 62.6 and 40.2% in theBCG and IFN-α groups, respectively. There was no significant difference between the BCG groups in relapse-free survival. Monotherapy withIFN-α showed a significantly lower response rate than did BCG therapies (p = 0.007. Adverse reactions were observed in 25, 116, and 6.9% ofpatients from Groups 1, 2 and 3, respectively. Toxicity-related withdrawal and treatment delay were similar in both BCG groups. Comparison ofthe rate of adverse reactions revealed a significant difference between the BCG + IFN-α and BCG groups (p = 0.025. The respective rates ofmoderate

  2. INTRAVESICULAR IMMUNOTHERAPY WITH BCG VACCINE AND INTERFERON-αα2B FOR NON-INVASIVE CARCINOMA OF THE URINARY BLADDER: RESULTS OF PROSPECTIVE RANDOMIZED STUDY

    Directory of Open Access Journals (Sweden)

    A. A. Minich

    2014-07-01

    Full Text Available Background: Both bacillus Calmette-Gue’rin (BCG and interferon-alpha (IFN-α are active against urinary bladder cancer. In this studywe evaluate the therapeutic efficacy and toxicity of combined intravesical BCG plus IFN-α for treating non-invasive bladder cancer.Subjects and methods: A total of 149 patients (mean age 63.2 years were enrolled for the study. The inclusion criteria were histologically verifiednon-invasive transitional cell carcinoma with intermediate and high risks of recurrence and progression. After transurethral tumor resection, all thepatients were randomized in three groups. Group 1 (n=60 was treated with a 6-week course of BCG, 125 mg, starting 14 to 21 days after TUR, Group2 (n=60 patients received 6-week instillations of BCG, 125 mg, plus IFN-α, 6 million units, Group 3 patients (n = 29 had 4-month courses ofintravesical IFN-α, 6 million units, twice daily during 3 consecutive days. A response was assessed by cystoscopy every 3 months after treatment.Results: A median follow-up of 30.9 months revealed recurrences in 26 (43.3% patients in the BCG group, 8 (13.3% patients in the BCG + IFN-αgroup and 18 (62.1% patients in the IFN-α group. Progression to muscle invasion occurred in 12% and 7% in Groups 1 and 3, respectively, withno progression in Group 2 patients. Three-year relapse-free survival was higher in the BCG+IFN group (78.5% versus 62.6 and 40.2% in theBCG and IFN-α groups, respectively. There was no significant difference between the BCG groups in relapse-free survival. Monotherapy withIFN-α showed a significantly lower response rate than did BCG therapies (p = 0.007. Adverse reactions were observed in 25, 116, and 6.9% ofpatients from Groups 1, 2 and 3, respectively. Toxicity-related withdrawal and treatment delay were similar in both BCG groups. Comparison ofthe rate of adverse reactions revealed a significant difference between the BCG + IFN-α and BCG groups (p = 0.025. The respective rates ofmoderate

  3. Modeling correlation indices between bladder and Foley′s catheter balloon dose with CT-based planning using limited CT slices in intracavitary brachytherapy for carcinoma of cervix

    Directory of Open Access Journals (Sweden)

    Oinam Arun

    2008-01-01

    Full Text Available Purpose: To derive and validate an index to correlate the bladder dose with the catheter balloon dose using limited computed tomography (CT slices. Materials and Methods: Applicator geometry reconstructed from orthogonal radiographs were back-projected on CT images of the same patients for anatomy-based dosimetric evaluation. The correlation indices derived using power function of the catheter balloon dose and the bladder volume dose were validated in 31 patients with cervical cancer. Results: There was significant correlation between International Commission on Radiation Units (ICRU-38 balloon reference dose (Dr and the dose received by 25% bladder volume (D 25 (P < 0.0001. Significant correlation was also found between the reference dose of mid-balloon point (D rm and the dose to D 25 (P < 0.0001. Average percentage difference [100 x (observed index - expected index / expected index] of observed value of I′ 25 (index for the dose to D25 bladder with respect to mid-balloon reference point from that of expected value was 0.52%, when the index was modeled with reference dose alone. Similarly the average percentage difference for I′10cc (index for the dose to 10 cc volume of bladder with respect to mid balloon point was 0.84%. When this index was modeled with absolute bladder volume and reference dose, standard deviation of the percentage difference between observed and expected index for D rm reduced by approximately 2% when compared to D r . Conclusion: For clinical applications, correlation index modeled with reference dose and volume predicts dose to absolute volume of bladder. Correlation index modeled with reference dose gives a good estimate of dose to relative bladder volume. From our study, we found D rm to be a better indicator of bladder dose than D r .

  4. High Ki-67 Immunohistochemical Reactivity Correlates With Poor Prognosis in Bladder Carcinoma: A Comprehensive Meta-Analysis with 13,053 Patients Involved.

    Science.gov (United States)

    Luo, Yihuan; Zhang, Xin; Mo, Meile; Tan, Zhong; Huang, Lanshan; Zhou, Hong; Wang, Chunqin; Wei, Fanglin; Qiu, Xiaohui; He, Rongquan; Chen, Gang

    2016-04-01

    Ki-67 is considered as one of prime biomarkers to reflect cell proliferation and immunohistochemical Ki-67 staining has been widely applied in clinical pathology. To solve the widespread controversy whether Ki-67 reactivity significantly predicts clinical prognosis of bladder carcinoma (BC), we performed a comprehensive meta-analysis by combining results from different literature. A comprehensive search was conducted in the Chinese databases of WanFang, China National Knowledge Infrastructure and Chinese VIP as well as English databases of PubMed, ISI web of science, EMBASE, Science Direct, and Wiley online library. Independent studies linking Ki-67 to cancer-specific survival (CSS), disease-free survival (DFS), overall survival (OS), progression-free survival (PFS), and recurrence-free survival (RFS) were included in our meta-analysis. With the cut-off values literature provided, hazard ratio (HR) values between the survival distributions were extracted and later combined with STATA 12.0. In total, 76 studies (n = 13,053 patients) were eligible for the meta-analysis. It was indicated in either univariate or multivariate analysis for survival that high Ki-67 reactivity significantly predicted poor prognosis. In the univariate analysis, the combined HR for CSS, DFS, OS, PFS, and RFS were 2.588 (95% confidence interval [CI]: 1.623-4.127, P Asian and European-American patients (P Asian patients, for CSS, DFS, PFS, and RFS in European-American patients (P literature with low cut-off value (<20%) demonstrated that high Ki-67 reactivity predicted shorter DFS, PFS, and RFS in BC patients (P < 0.05). In the subgroup analysis of high cut-off value (≥20%), our meta-analysis indicated that high Ki-67 reactivity, in either univariate or multivariate analysis, significantly correlated with all five clinical outcomes in BC patients (P < 0.05). The meta-analysis indicates that high Ki-67 reactivity significantly correlates with deteriorated clinical outcomes

  5. Precystectomy serum levels of carbohydrate antigen 19-9, carbohydrate antigen 125, and carcinoembryonic antigen: prognostic value in invasive urothelial carcinoma of the bladder.

    Science.gov (United States)

    Ahmadi, Hamed; Djaladat, Hooman; Cai, Jie; Miranda, Gus; Daneshmand, Siamak

    2014-07-01

    To evaluate the prognostic value of precystectomy carbohydrate antigen 19-9 (CA 19-9), carbohydrate antigen 125 (CA 125), and carcinoembryonic antigen (CEA) levels in invasive urothelial carcinoma of the bladder (UCB). Preoperatively collected serum samples from patients with invasive UCB who underwent radical cystectomy between 2004 and 2009 were used to measure CA 19-9, CA 125, and CEA levels. Laboratory cutoff points were used to define elevated marker levels (CA 19-9>37 U/ml, CA 125>35 U/ml, and CEA>3.8 U/ml). The Cox regression model was used to identify independent predictors of recurrence-free survival (RFS) and overall survival (OS). A total of 186 patients with the mean age of 69 years (range: 36-89) and median follow-up of 4 years (range: 0.1-7.2) were included in the study. Overall, 94 (51%) patients had pathologic organ-confined disease (≤T2) and 92 (49%) had pathologic locally advanced UCB (pT3-T4 or positive lymph node or both). The mean CA 19-9, CA 125, and CEA levels were 11.6 U/ml (range:<0.6-111), 11.5 U/ml (range: 3-56), and 2.2 ng/ml (range: 0.3-30.2), respectively. Levels of CA 19-9, CEA, and CA 125 were elevated in 7 (3%), 25 (13%), and 3 (1%) patients, respectively. Median 3-year RFS and OS were 72%. Using the multivariate Cox regression model, elevated levels of CA 19-9 and CEA were found to be independent predictors of worse 3-year OS (hazard ratio [HR] = 2.7, P = 0.05 and HR = 2, P = 0.03, respectively), and an elevated level of CA 19-9 was an independent predictor of worse 3-year RFS (HR = 2.8, P = 0.05). Precystectomy CA 125 level was not associated with oncological outcome. Elevated precystectomy serum levels of CA 19-9 and CEA are independent predictors of worse oncological outcome in patients with invasive UCB. Further studies are needed to elucidate the role of these markers in the management of UCB. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Superficial Bladder Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Emmanuel Schenkman

    2004-01-01

    Full Text Available Bladder cancer treatment remains a challenge despite significant improvements in preventing disease progression and improving survival. Intravesical therapy has been used in the management of superficial transitional cell carcinoma (TCC of the urinary bladder (i.e. Ta, T1, and carcinoma in situ with specific objectives which include treating existing or residual tumor, preventing recurrence of tumor, preventing disease progression, and prolonging survival. The initial clinical stage and grade remain the main determinant factors in survival regardless of the treatment. Prostatic urethral mucosal involvement with bladder cancer can be effectively treated with Bacillus Calmette-Guerin (BCG intravesical immunotherapy. Intravesical chemotherapy reduces short-term tumor recurrence by about 20%, and long-term recurrence by about 7%, but has not reduced progression or mortality. Presently, BCG immunotherapy remains the most effective treatment and prophylaxis for TCC (Ta, T1, CIS and reduces tumor recurrence, disease progression, and mortality. Interferons, Keyhole-limpet hemocyanin (KLH, bropirimine and Photofrin-Photodynamic Therapy (PDT are under investigation in the management of TCC and early results are encouraging. This review highlights and summarizes the recent advances in therapy for superficial TCC.

  7. Bladder Cancer

    Science.gov (United States)

    ... Bladder cancer care at Mayo Clinic Symptoms Bladder cancer signs and symptoms may include: Blood in urine (hematuria) Painful urination Pelvic pain If you have hematuria, your urine may appear bright red or cola colored. Sometimes, urine may not look any different, ...

  8. Hypoxia regulates the expression and localization of CCAAT/enhancer binding protein α by hypoxia inducible factor-1α in bladder transitional carcinoma cells.

    Science.gov (United States)

    Xue, Mei; Li, Xu; Chen, Wei

    2015-08-01

    Hypoxia inducible factor-1α (HIF-1α) is overexpressed in various types of solid tumor in humans, including bladder cancer. HIF-1α regulates the expression of a series of genes, which are involved in cell proliferation, differentiation, apoptosis, angiogenesis, migration and invasion and represents a potential therapeutic target for the treatment of human cancer. Despite extensive investigation of the effects of HIF-1α in the progression and metastasis of bladder cancer, the possible regulatory mechanisms underlying the effects of HIF-1α on bladder cancer cell proliferation and differentiation remain to be elucidated. It has been suggested that the transcription factor CCAAT/enhancer binding protein α (C/EBPα) acts as a tumor suppressor in several types of cancer cell, which are involved in regulating cell differentiation, proliferation and apoptosis. The present study confirmed that, in bladder cancer cells, the expression and localization of C/EBPα was regulated by hypoxia through an HIF-1α -dependent mechanism, which may be significant in bladder cancer cell proliferation and differentiation. The 5637 and T24 bladder cancer cell lines were incubated under normoxic and hypoxic conditions. The expression levels of HIF-1α and C/EBPα were detected by reverse transcription-quantitative polymerase chain reaction, western blotting and immunofluorescence analysis. The results revealed that, under hypoxic conditions, the protein expression levels of HIF-1α were markedly upregulated, but the mRNA levels were not altered. However, the mRNA and protein levels of C/EBPα were significantly reduced. The present study further analyzed the subcellular localization of C/EBPα, which was markedly decreased in the nuclei under hypoxic conditions. Following HIF-1α small interference RNA silencing of HIF-1α, downregulation of C/EBPα was prevented in the bladder cancer cells cultured under hypoxic conditions. In addition, groups of cells treated with 3-(5'-hydroxymethyl

  9. NBI - plasma vaporization hybrid approach in bladder cancer endoscopic management.

    Science.gov (United States)

    Stănescu, F; Geavlete, B; Georgescu, D; Jecu, M; Moldoveanu, C; Adou, L; Bulai, C; Ene, C; Geavlete, P

    2014-06-15

    A prospective study was performed aiming to evaluate the surgical efficacy, perioperative safety profile, diagnostic accuracy and medium term results of a multi-modal approach consisting in narrow band imaging (NBI) cystoscopy and bipolar plasma vaporization (BPV) when compared to the standard protocol represented by white light cystoscopy (WLC) and transurethral resection of bladder tumors (TURBT). A total of 260 patients with apparently at least one bladder tumor over 3 cm were included in the trial. In the first group, 130 patients underwent conventional and NBI cystoscopy followed by BPV, while in a similar number of cases of the second arm, classical WLC and TURBT were applied. In all non-muscle invasive bladder tumors' (NMIBT) pathologically confirmed cases, standard monopolar Re-TUR was performed at 4-6 weeks after the initial intervention, followed by one year' BCG immunotherapy. The follow-up protocol included abdominal ultrasound, urinary cytology and WLC, performed every 3 months for a period of 2 years. The obturator nerve stimulation, bladder wall perforation, mean hemoglobin level drop, postoperative bleeding, catheterization period and hospital stay were significantly reduced for the plasma vaporization technique by comparison to conventional resection. Concerning tumoral detection, the present data confirmed the NBI superiority when compared to standard WLC regardless of tumor stage (95.3% vs. 65.1% for CIS, 93.3% vs. 82.2% for pTa, 97.4% vs. 94% for pT1, 95% vs. 84.2% overall). During standard Re-TUR the overall (6.3% versus 17.4%) and primary site (3.6% versus 12.8%) residual tumors' rates were significantly lower for the NBI-BPV group. The 1 (7.2% versus 18.3%) and 2 (11.5% versus 25.8%) years' recurrence rates were substantially lower for the combined approach. NBI cystoscopy significantly improved diagnostic accuracy, while bipolar technology showed a higher surgical efficiency, lower morbidity and faster postoperative recovery. The combined

  10. 4-Acetyl-12,13-epoxyl-9-trichothecene-3, 15-diol from Isaria japonica mediates apoptosis of rat bladder carcinoma NBT-II cells by decreasing anti-apoptotic Bcl-2 expression and increasing pro-apoptotic Bax expression.

    Science.gov (United States)

    Kim, Hyung-Jin; Jang, Seon Il; Kim, Young-Jun; Pae, Hyun-Ock; Won, Hae-Young; Hong, Kyung-Hwan; Oh, Hyuncheol; Kwon, Tae-Oh; Chung, Hun-Taeg

    2004-01-01

    We studied the effect of 4-acetyl-12,13-epoxyl-9-trichothecene-3, 15-diol (AETD) isolated from Isaria japonica, one of the most popular Chinese fungal medicines, on the induction of apoptosis in rat bladder carcinoma NBT-II cells. AETD was cytotoxic to NBT-II cells, and this cytotoxic effect appears to be attributed to its induction of apoptotic cell death, as AETD induced nuclear morphological changes and internucleosomal DNA fragmentation, and increased the proportion of hypodiploid cells and activity of caspase-3. AETD treatment also decreased the expression of the anti-apoptotic protein Bcl-2 and increased the expression of the pro-apoptotic protein Bax. These results provide important information in understanding the mechanism(s) of AETD-induced apoptosis.

  11. High risk bladder cancer: current management and survival

    Directory of Open Access Journals (Sweden)

    Anna M. Leliveld

    2011-04-01

    Full Text Available PURPOSE: To evaluate the pattern of care in patients with high risk non muscle invasive bladder cancer (NMIBC in the Comprehensive Cancer Center North-Netherlands (CCCN and to assess factors associated with the choice of treatment, recurrence and progression free survival rates. MATERIALS AND METHODS: Retrospective analysis of 412 patients with newly diagnosed high risk NMIBC. Clinical, demographic and follow-up data were obtained from the CCCN Cancer Registry and a detailed medical record review. Uni and multivariate analysis was performed to identify factors related to choice of treatment and 5 year recurrence and progression free survival. RESULTS: 74/412 (18% patients with high risk NMIBC underwent a transurethral resection (TUR as single treatment. Adjuvant treatment after TUR was performed in 90.7% of the patients treated in teaching hospitals versus 71.8 % in non-teaching hospitals (p 80 years OR 0.1 p = 0.001 and treatment in non-teaching hospitals (OR 0.25; p < 0.001 were associated with less adjuvant treatment after TUR. Tumor recurrence occurred in 191/392 (49% and progression in 84 /392 (21.4% patients. The mean 5-years progression free survival was 71.6% (95% CI 65.5-76.8. CONCLUSION: In this pattern of care study in high risk NMIBC, 18% of the patients were treated with TUR as single treatment. Age and treatment in non-teaching hospitals were associated with less adjuvant treatment after TUR. None of the variables sex, age, comorbidity, hospital type, stage and year of treatment was associated with 5 year recurrence or progression rates.

  12. Australian and New Zealand Faculty of Radiation Oncology Genito-Urinary Group: 2011 consensus guidelines for curative radiotherapy for urothelial carcinoma of the bladder

    International Nuclear Information System (INIS)

    Hindson, Benjamin R.; Turner, Sandra L.; Millar, Jeremy L.

    2012-01-01

    Curative radiotherapy, with or without concurrent chemotherapy, is recognized as a standard treatment option for muscle-invasive bladder cancer. It is commonly used for two distinct groups of patients: either for those medically unfit for surgery, or as part of a 'bladder preserving' management plan incorporating the possibility of salvage cystectomy. However, in both situations, the approach to radiotherapy varies widely around the world. The Australian and New Zealand Faculty of Radiation Oncology Genito-Urinary Group recognised a need to develop consistent, evidence-based guidelines for patient selection and radiotherapy technique in the delivery of curative radiotherapy. Following a workshop convened in May 2009, a working party collated opinions and conducted a wide literature appraisal linking each recommendation with the best available evidence. This process was subject to ongoing re-presentation to the Faculty of Radiation Oncology Genito-Urinary Group members prior to final endorsement. These Guidelines include patient selection, radiation target delineation, dose and fractionation schedules, normal tissue constraints and investigational techniques. Particular emphasis is given to the rationale for the target volumes described. These Guidelines provide a consensus-based framework for the delivery of curative radiotherapy for muscle-invasive bladder cancer. Widespread input from radiation oncologists treating bladder cancer ensures that these techniques are feasible in practice. We recommend these Guidelines be adopted widely in order to encourage a uniformly high standard of radiotherapy in this setting, and to allow for better comparison of outcomes.

  13. Histological grading of papillary urothelial carcinoma of the bladder: prognostic value of the 1998 WHO/ISUP classification system and comparison with conventional grading systems

    NARCIS (Netherlands)

    Oosterhuis, J. W. A.; Schapers, R. F. M.; Janssen-Heijnen, M. L. G.; Pauwels, R. P. E.; Newling, D. W.; ten Kate, F.

    2002-01-01

    AIM: To test the prognostic value of the 1998 WHO/ISUP (World Health Organisation/International Society of Urologic Pathology) consensus classification system in Ta papillary urothelial neoplasms of the bladder. METHODS: The histological slides of 322 patients with a primary Ta tumour were

  14. Increased accuracy of a novel mRNA-based urine test for bladder cancer surveillance.

    Science.gov (United States)

    Pichler, Renate; Fritz, Josef; Tulchiner, Gennadi; Klinglmair, Gerald; Soleiman, Afschin; Horninger, Wolfgang; Klocker, Helmut; Heidegger, Isabel

    2018-01-01

    To evaluate the diagnostic accuracy of the Xpert Bladder Cancer (BC) Monitor, compared with cystoscopy and cytology in the oncological follow-up of non-muscle-invasive bladder cancer (NMIBC). A total of 140 patients with a history of NMIBC undergoing routine surveillance at our institution were enrolled prospectively in this study (ISRCTN study registry number 37210907). Urine cytology was evaluated according to the Paris classification system. In addition, urinary specimens were analysed using the Xpert BC Monitor, which measures five target mRNAs (ABL1, CRH, IGF2, UPK1B, ANXA10) using real-time PCR. Descriptive analysis, diagnostic accuracy including sensitivity, specificity, positive (PPV) and negative predictive value (NPV), receiver-operating characteristic curve, and area under the curve (AUC) were calculated. The overall sensitivity (0.84) and NPV (0.93) of the Xpert BC Monitor were significantly superior to those of bladder washing cytology (0.33 and 0.76; P < 0.001). Subgroup analyses confirmed the high sensitivity of the Xpert BC Monitor even in low-grade (0.77) and pTa (0.82) disease compared with barbotage cytology (low-grade: 0.13; pTa: 0.21). The overall specificity of the Xpert BC Monitor and barbotage cytology was similar (0.91 vs 0.94; P = 0.41). Combining the Xpert BC Monitor with barbotage cytology (AUC = 0.85) did not enhance diagnostic performance compared with the performance of the Xpert BC Monitor alone (AUC = 0.87). In this study, we report for the first time that the Xpert BC Monitor, a new mRNA-based urine test, outperforms cytology with regard to sensitivity and NPV, even in low-grade and pTa tumours, with no reduction of specificity. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

  15. Asthma status is associated with decreased risk of aggressive urothelial bladder cancer.

    Science.gov (United States)

    Rava, Marta; Czachorowski, Maciej J; Silverman, Debra; Márquez, Mirari; Kishore, Sirish; Tardón, Adonina; Serra, Consol; García-Closas, Montse; Garcia-Closas, Reina; Carrato, Alfredo; Rothman, Nathaniel; Real, Francisco X; Kogevinas, Manolis; Malats, Núria

    2018-02-01

    Previous studies suggested an association between atopic conditions and specific cancers. The results on the association with urothelial bladder cancer (UBC) are scarce and inconsistent. To evaluate the association between asthma and risk of UBC, we considered 936 cases and 1,022 controls from the Spanish Bladder Cancer/EPICURO Study (86% males, mean age 65.4 years), a multicenter and hospital-based case-control study conducted during 1998-2001. Participants were asked whether they had asthma and detailed information about occupational exposures, smoking habits, dietary factors, medical conditions and history of medication was collected through face-to-face questionnaires performed by trained interviewers. Since asthma and UBC might share risk factors, association between patients' characteristics and asthma was studied in UBC controls. Association between UBC and asthma was assessed using logistic regression unadjusted and adjusted for potential confounders. The complex interrelationships, direct and mediating effect of asthma on UBC, were appraised using counterfactual mediation models. Asthma was associated with a reduced risk of UBC (odds ratio (OR) = 0.54, 95% confidence interval (CI) 0.37, 0.79) after adjusting for a wide range of confounders. No mediating effect was identified. The reduced risk associated with asthma was restricted to patients with high-risk non-muscle invasive (OR = 0.25, 95%CI 0.10, 0.62) and muscle invasive UBC (OR = 0.32, 95%CI 0.15, 0.69). Our results support that asthma is associated with a decreased risk of UBC, especially among aggressive tumors. Further work on the relationship between asthma and other atopic conditions and cancer risk should shed light on the relationship between immune response mechanisms and bladder carcinogenesis. © 2017 UICC.

  16. The prognostic value of family history among patients with urinary bladder cancer.

    Science.gov (United States)

    Egbers, Lieke; Grotenhuis, Anne J; Aben, Katja K; Alfred Witjes, J; Kiemeney, Lambertus A; Vermeulen, Sita H

    2015-03-01

    A history of urinary bladder cancer (UBC) in first-degree relatives increases UBC risk by twofold. The influence of positive family history on UBC prognosis is unknown. Here, we investigated association of first-degree UBC family history with clinicopathological characteristics and prognosis of UBC patients. Detailed clinical data of 1,465 non-muscle-invasive bladder cancer (NMIBC) and 250 muscle-invasive or metastatic bladder cancer (MIBC) patients, diagnosed from 1995 to 2010, were collected through medical file review. Competing risk analyses were used to compare recurrence-free survival (RFS) and progression-free survival (PFS) of NMIBC patients according to self-reported UBC family history. Overall survival in MIBC patients was estimated using Kaplan-Meier analysis. The added value of family history in prediction of NMIBC prognosis was quantified with Harrell's concordance-index. Hundred (6.8%) NMIBC and 14 (5.6%) MIBC patients reported UBC in first-degree relatives. Positive family history was statistically significantly associated with smaller tumor size and non-significantly with more favorable distribution of other tumor characteristics. In univariable analyses, positive family history correlated with longer RFS (p = 0.11) and PFS (p = 0.04). Hazard ratios for positive vs. negative family history after adjustment for clinicopathological characteristics were 0.75 (95% CI = 0.53-1.07) and 0.45 (95% CI = 0.18-1.12) for RFS and PFS, respectively. Five familial and 48 sporadic MIBC patients (Kaplan-Meier 10-year risk: 41% and 25%) died within 10 years. Family history did not improve the c-index of prediction models. This study shows that a first-degree family history of UBC is not clearly associated with NMIBC prognosis. Family history does not aid in prediction of NMIBC recurrence or progression. © 2014 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC.

  17. METASTATIC PENILE CARCINOMA: A STUDY OF NINE CASES AND

    African Journals Online (AJOL)

    9 55 bladder TCC total penectomy 21. TCC = transitional cell carcinoma, SCC = squamous cell carcinoma. The rarity of the event prompted this study which describes 9 metastatic penile carcinoma cases including 7 originating from the bladder and one each from the lung and the bone mar- row. PATIENTS AND METHODS.

  18. Expression of programmed cell death protein 4 (PDCD4) and miR-21 in urothelial carcinoma

    International Nuclear Information System (INIS)

    Fischer, Nicolas; Göke, Friederike; Splittstößer, Vera; Lankat-Buttgereit, Brigitte; Müller, Stefan C.; Ellinger, Jörg

    2012-01-01

    Highlights: ► The tumor suppressor gene PDCD4 is down-regulated in many tumorous entities. ► We investigate the impact of PDCD4 and its regulating factor miR-21 in urothelial carcinoma. ► We confirm PDCD4 as a tumor suppressor gene and it could be a diagnostic marker for this tumor. -- Abstract: Background: We investigated the role of the programmed cell death 4 (PDCD4) tumor suppressor gene in specimens of transitional cell carcinoma and of healthy individuals. Methods: PDCD4 immunohistochemical expression was investigated in 294 cases in histologically proven transitional cell carcinoma in different tumorous stages (28 controls, 122 non-muscle invasive urothelial carcinoma, stages Tis-T1, 119 invasive transitional cell carcinoma stages T2–T4 and 25 metastases). MiR-21 expression, an important PDCD4 regulator, was assessed with real-time PCR analysis and showed inverse correlation to tissue PDCD4 expression. Results: Nuclear and cytoplasmatic PDCD4 immunostaining decreased significantly with histopathological progression of the tumor (p < 0001). Controls showed strong nuclear and cytoplasmatic immunohistochemical staining. MiR-21 up regulation in tissue corresponded to PDCD4 suppression. Conclusions: These data support a decisive role for PDCD4 down regulation in transitional cell carcinoma and confirm miR-21 as a negative regulator for PDCD4. Additionally, PDCD4 immunohistochemical staining turns out to be a possible diagnostic marker for transitional cell carcinoma.

  19. Expression of programmed cell death protein 4 (PDCD4) and miR-21 in urothelial carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, Nicolas, E-mail: simplissimus@gmx.de [Department of Urology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn (Germany); Goeke, Friederike, E-mail: Friederike.goeke@ukb.uni-bonn.de [Department of Pathology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn (Germany); Splittstoesser, Vera, E-mail: Veri.sp@web.de [Department of Urology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn (Germany); Lankat-Buttgereit, Brigitte, E-mail: Lankatbu@staff.uni-marburg.de [Department of Internal Medicine, Philipps-University of Marburg, Baldingerstrasse, 35043 Marburg (Germany); Mueller, Stefan C., E-mail: Stefan.mueller@ukb.uni-bonn.de [Department of Urology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn (Germany); Ellinger, Joerg, E-mail: Joerg.ellinger@ukb.uni-bonn.de [Department of Urology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn (Germany)

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer The tumor suppressor gene PDCD4 is down-regulated in many tumorous entities. Black-Right-Pointing-Pointer We investigate the impact of PDCD4 and its regulating factor miR-21 in urothelial carcinoma. Black-Right-Pointing-Pointer We confirm PDCD4 as a tumor suppressor gene and it could be a diagnostic marker for this tumor. -- Abstract: Background: We investigated the role of the programmed cell death 4 (PDCD4) tumor suppressor gene in specimens of transitional cell carcinoma and of healthy individuals. Methods: PDCD4 immunohistochemical expression was investigated in 294 cases in histologically proven transitional cell carcinoma in different tumorous stages (28 controls, 122 non-muscle invasive urothelial carcinoma, stages Tis-T1, 119 invasive transitional cell carcinoma stages T2-T4 and 25 metastases). MiR-21 expression, an important PDCD4 regulator, was assessed with real-time PCR analysis and showed inverse correlation to tissue PDCD4 expression. Results: Nuclear and cytoplasmatic PDCD4 immunostaining decreased significantly with histopathological progression of the tumor (p < 0001). Controls showed strong nuclear and cytoplasmatic immunohistochemical staining. MiR-21 up regulation in tissue corresponded to PDCD4 suppression. Conclusions: These data support a decisive role for PDCD4 down regulation in transitional cell carcinoma and confirm miR-21 as a negative regulator for PDCD4. Additionally, PDCD4 immunohistochemical staining turns out to be a possible diagnostic marker for transitional cell carcinoma.

  20. Primary signet cell adenocarcinoma of bladder

    Directory of Open Access Journals (Sweden)

    Prateek Kinra

    2017-01-01

    Full Text Available Primary signet cell cancer of the urinary bladder is a relatively rare entity. Since there is no mucinous epithelium in the bladder, It is proposed that the tumor arises from metaplastic urothelium. Two thirds of the tumours are mucin secreting, in most of which the site of the deposition is either extracellular or intracellular displacing the nucleus to a peripheral crescent, giving the cells a signet ring appearance. The tumours are most often infiltrative and diffusely involving the majority of the bladder akin to its name sake in stomach. It is essential to distinguish this carcinoma from gastrointestinal metastases as different therapeutic strategies are often necessary.

  1. Activation by the protein-bound polysaccharide PSK (krestin) of cytotoxic lymphocytes that act on fresh autologous tumor cells and T24 human urinary bladder transitional carcinoma cell line in patients with urinary bladder cancer.

    Science.gov (United States)

    Mizutani, Y; Yoshida, O

    1991-05-01

    PSK, a protein-bound polysaccharide Kureha, was tested for its ability to modulate the cytotoxicity of lymphocytes that act on autologous tumor cells and T24 human urinary bladder tumor cells in urinary bladder cancer patients in a 6-h 51Cr release assay. In vitro treatment of peripheral blood lymphocytes (PBL) with PSK for 18 hours resulted in an augmentation or induction of cytotoxicity against relatively resistant T24 cells in previously reactive and nonreactive cases, respectively. The PSK-treated PBL were able to kill more effectively tumor cells that were freshly isolated from the same cancer patients than non-treated PBL. The effects of PSK were noted with PBL as well as tumor infiltrating lymphocytes (TIL) and with PSK at concentrations of 10 to 100 micrograms./ml., while PSK at higher doses reduced their lytic activities. The addition of PSK to the assay at the same concentrations also enhanced the cytotoxicities. Autologous tumor killing (ATK) activities of both large granular lymphocytes (LGL) and T lymphocytes were enhanced by PSK. Treatment of PBL with PSK did not effect on the proportion of PBL binding to the tumor cells, while it augmented the cytotoxic activity. Cell-free supernatant of PSK-stimulated lymphocyte culture did not contain any detectable amounts of interferon-alpha (IFN-alpha), interferon-gamma (IFN-gamma) and interleukin-2 (IL-2). In addition, anti-IFN-alpha monoclonal antibody (MAb), anti-IFN-gamma MAb and anti-IL-2 MAb did not inhibit PSK-induced augmentation of cytotoxicity against T24. Oral administration of PSK (three gm./day) to patients with urinary bladder cancer daily for seven days before operation resulted in an augmentation of the cytotoxicity against T24 cells in five out of 10 patients and no change of the cytotoxicity in the other five patients. ATK activity was also enhanced by oral administration of PSK in three out of five patients. These results indicate that the antitumor activity of PSK may be in part mediated

  2. Development and evaluation of a training program for therapeutic radiographers as a basis for online adaptive radiation therapy for bladder carcinoma

    International Nuclear Information System (INIS)

    Foroudi, Farshad; Wong, Jacky; Kron, Tomas; Roxby, Paul; Haworth, Annette; Bailey, Alistair; Rolfo, Aldo; Paneghel, Andrea; Styles, Colin; Laferlita, Marcus; Tai, Keen Hun; Williams, Scott; Duchesne, Gillian

    2010-01-01

    Aims: Online adaptive radiotherapy requires a new level of soft tissue anatomy recognition and decision making by therapeutic radiographers at the linear accelerator. We have developed a therapeutic radiographer training workshop encompassing soft tissue matching for an online adaptive protocol for muscle invasive bladder cancer. Our aim is to present the training program, and its evaluation which compares pre and post training staff soft tissue matching and bladder contouring using Cone Beam Computer Tomography (CBCT). Materials and Methods: Prior to commencement of an online adaptive bladder protocol, a staff training program for 33 therapeutic radiographers, with a separate ethics approved evaluation component was developed. A multidisciplinary training program over two days was carried out with a total of 11 h of training, covering imaging technology, pelvic anatomy and protocol specific decision making in both practical and theoretical sessions. The evaluation included both pre training and post training testing of staff. Results: Pre training and post training, the standard deviations in the contoured bladder between participants in left-right direction were 0.64 vs 0.59 cm, superior-inferior 0.89 vs 0.77 cm and anterior-posterior direction was 0.88 vs 0.52 cm respectively. Similarly the standard deviation in the volume contoured decreased from 40.7 cc pre training to 24.5 cc post training. Time taken in contouring was reduced by the training program (19.8 vs 17.2 min) as was the discrepancy in choice of adaptive radiotherapy plans. The greatest reduction in variations in contouring was seen in staff whose pre training had the largest deviations from the reference radiation oncologist contours. Conclusion: A formalized staff training program is feasible, well received by staff and reduces variation in organ matching and contouring. The improvement was particularly noticed in staff who pre training had larger deviations from the reference standard.

  3. [Bladder lithiasis].

    Science.gov (United States)

    Sylla, C; Fall, P A; Ndoye, A; Diao, B; Diallo, A B; Gueye, S M; Ba, M; Diagne, B A

    2001-01-01

    to study the particularities of the bladder lithiasis in our countries. This was a retrospective study of 94 cases (62 men and 32 women) of bladder lithiasis over a period of 13 years. The lithogenic factors; clinic, paraclinic and therapeutic aspects have been studied. Morphoconstitutional analysis has been carded out in collaboration with Cristal Laboratory (St Cloud hospital center in France). mean age was 24.2+/-20.7 years old. The principals mains of consultation were: dysuria (n =36), mictionnal pain (n = 28), hematuria (n = 15). Facilitating factors have been found in 27% of cases. In 10 cases, there was an association bladdder lithiasis and bladdder-vaginal fistula. Radiologic test was dominated by intraveinous urographic (53.19 of cases). The metabolic test showed hypercalcemia and cristalluria in 2 cases. In 7,45 % of cases, we have founding a renal failure. An urinary tract infection have been noticed in 42 % of cases. Open surgery has been the main treatement (96 %) associating in 15 % of cases the treatement of an uropathy. In one case the bladder lithiasis weighed 1120 g. The morphologic and spectrophotometric analysis of the lithiasis have been achieved in 13 % of cases showing the predominance of struvite. the bladder lithiasis is still common in our countries; it could be good for us to access endoorporeals and extracorporeals therapeutic equipements in orderto reduce the indications of open surgery.

  4. Preliminary report of a multicentric study on environmental risk factors in Ta-T1 transitional cell carcinoma of the bladder. A study from Gruppo Studi Tumori Urologici Foundation.

    Science.gov (United States)

    Serretta, V; Morgia, G; Altieri, V; Pavone-Macaluso, M; Scuto, F; Allegro, R; Di Lallo, A; Cindolo, L; Melloni, D

    2006-01-01

    The distribution of potential environmental risk factors among patients affected by superficial transitional cell carcinoma of the bladder (TCCB) has been analyzed. Patients affected by superficial TCCB underwent TUR and early intravesical chemotherapy. Detailed data about age, sex, residence, employment, active and passive cigarette smoking, water resource and hair dye use were centralized. Analysis has been conducted on 474 patients affected by Ta-T1 G1-2 TCCB at medium risk for recurrence. Patients with primary single Ta G1-2, Tis or T1G3 tumors were excluded from the present analysis. Over 80% of the patients lived in urban areas, 22% were employed in industries presumed at risk for bladder cancer, 8% used hair dye and 75% were smokers. Bottled water was the only water resource in 42% of the patients. Employment in industry at risk (p = 0.01) and cigarette smoking (p = 0.04) resulted in being statistically related to tumor multiplicity. Moreover, the period of cigarette smoking was significantly longer in patients with recurrent tumors (p = 0.026). The municipal water supply represented the main water source in never-smokers (p = 0.01) rather than in smokers and in patients harboring T1 rather than Ta tumors (p = 0.03). Employment in industry at risk and cigarette smoking resulted in being related to tumor multiplicity. The length of exposure to cigarette smoking was related to the natural history of the tumor. A drinkable water source emerged as a risk factor in absence of cigarette smoking.

  5. Destruction of the bladder by single dose Mitomycin C for low-stage transitional cell carcinoma (TCC)--avoidance, recognition, management and consent.

    Science.gov (United States)

    Elmamoun, Mamoun H; Christmas, Tim J; Woodhouse, Christopher R J

    2014-05-01

    To identify a cohort of patients under our care who have had significant and in some cases irreparable damage to their bladders after Mitomycin C (MMC) instillation. To highlight the importance of avoidance and recognition of bladder perforations during transurethral resection of bladder tumour (TURBT) and explore the issue of consent regarding MMC given the serious complications that may occur after its instillation. Patients referred to our tertiary centre for a second opinion to manage their complications after a suspected MMC leak was identified from the departmental database between January 2000 and December 2010. After collection of all the records, we established a cohort of six patients. All patients had their initial tumour resection elsewhere and were referred for specialist management thereafter. Details of the operating surgeon and cystoscopic findings were known only in half of the cases. Retrospective analysis of their notes including documentation from the referring centre was undertaken. This included a review of all the histology and imaging. All patients had immediate severe pelvic pain on instillation of the MMC. Four of the six continue to have chronic pelvic pain. Two patients had urinary retention and three had severe lower urinary tract symptoms. One patient developed a frozen pelvis. Initial treatment was with an indwelling catheter for a period of 2-52 weeks to aid healing. Two patients had reconstructive surgery, one with success and the other with failure, as an intestinal patch failed to close the fistula and he continues with a catheter. One patient had an ileal conduit. No patient was warned of such complications. Although rare, prophylactic MMC can have devastating consequences. Patients should be aware of such major risks. Strong emphasis should be placed on the quality of the initial TURBT coupled with the judgement of an experienced surgeon before to MMC instillation. The real clinical benefit could be reviewed and intravesical MMC

  6. Bladder carcinosarcoma: A case report with review of the literature

    Directory of Open Access Journals (Sweden)

    Ismail Basibuyuk

    2017-10-01

    Full Text Available Carcinosarcoma of the urinary bladder is a rare neoplasm that is histologically composed of malignant epithelial and mesenchymal components. The etiology of sarcomatoid tumors is unclear, but smoking and history of previous radiotherapy or chemotherapy may lead to bladder disorders and to the formation of sarcomatoid carcinoma. These neoplasms behave as highly aggressive tumors and optimal treatment is uncertain. Herein, we report a case of sarcomatoid carcinoma of urinary bladder presenting as a giant intravesical mass in a 61-year-old man complaining of macroscopic hematuria.

  7. Suppressions of Migration and Invasion by Cantharidin in TSGH-8301 Human Bladder Carcinoma Cells through the Inhibitions of Matrix Metalloproteinase-2/-9 Signaling

    Directory of Open Access Journals (Sweden)

    Yi-Ping Huang

    2013-01-01

    Full Text Available Cancer metastasis becomes an initial cause of cancer death in human population. In many cancers, it has been shown that the high levels of matrix metalloproteinase (MMP-2 and/or MMP-9 are associated with the invasive phenotypes of cancer cells. In this study, we investigated the effects of cantharidin, a derivative of blister beetles which is one of the traditional Chinese medicines, on the adhesion, migration, and invasion of human bladder cancer TSGH-8301 cells. Cantharidin effectively suppressed TSGH-8301 cell adhesion, migration, and invasion in a concentration-dependent manner. Results from Western blotting, RT-PCR, and gelatin zymography assays indicated that cantharidin blocked the protein levels, gene expression (mRNA, and activities of MMP-2 and -9 in TSGH-8301 cells. Cantharidin also significantly suppressed the protein expressions of p-p38 and p-JNK1/2 in TSGH-8301 cells. Taken together, cantharidin was suggested to present antimetastatic potential via suppressing the levels of MMP-2 and MMP-9 expression that might be mediated by targeting the p38 and JNK1/2 MAPKs pathway in TSGH-8301 human bladder cancer cells.

  8. The results of a series of 963 patients with transitional cell carcinoma of the urinary bladder primarily treated by radical megavoltage X-ray therapy

    International Nuclear Information System (INIS)

    Duncan, W.; Quilty, P.M.

    1986-01-01

    The results are reported of a large series of patients with transitional cell cancer of the bladder, treated in Edinburgh between 1971 and 1982. Analysis of pre-treatment characteristics for patients with transitional cell bladder cancer showed that tumour category was significantly associated with grade and tumour size. Complete local tumour regression at follow-up cystoscopy was achieved in 45.9% of patients who completed radical megavoltage X-ray therapy. Patients with grade 2 or 3 cancer, a solid cancer or a tumour of less than 8 cm in size had significantly improved complete regression rates. Lasting local tumour control after initial complete regression was better in patients with grade 3 cancer. Complete regression was associated with improved survival for all but patients with T1 cancer. The poorest survival rates were seen in patients over 79 years of age, those with T4 cancer, an ulcerated cancer, a grade 3 cancer or a tumour of more than 7 cm in size. Metastases were more often seen in patients with grade 3 or T3/T4 cancer. Severe late radiation-related complications were seen in 14.8% of patients. (Auth.)

  9. Cystocele (Prolapsed Bladder)

    Science.gov (United States)

    ... Navigation Bladder Control Problems in Women (Urinary Incontinence) Kegel Exercises Cystocele (Prolapsed Bladder) Cystocele (Prolapsed Bladder) What ... a vaginal pessary, or surgery. Pelvic floor, or Kegel, exercises involve strengthening pelvic floor muscles. Strong pelvic ...

  10. Bacillus Calmette Guerin induces fibroblast activation both directly and through macrophages in a mouse bladder cancer model.

    Directory of Open Access Journals (Sweden)

    Catalina Lodillinsky

    Full Text Available BACKGROUND: Bacillus Calmette-Guerin (BCG is the most effective treatment for non-muscle invasive bladder cancer. However, a failure in the initial response or relapse within the first five years of treatment has been observed in 20% of patients. We have previously observed that in vivo administration of an inhibitor of nitric oxide improved the response to BCG of bladder tumor bearing mice. It was described that this effect was due to a replacement of tumor tissue by collagen depots. The aim of the present work was to clarify the mechanism involved in this process. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrated that BCG induces NIH-3T3 fibroblast proliferation by activating the MAPK and PI3K signaling pathways and also differentiation determined by alpha-smooth muscle actin (alpha-SMA expression. In vivo, intratumoral inoculation of BCG also increased alpha-SMA and collagen expression. Oral administration of L-NAME enhanced the pro-fibrotic effect of BCG. Peritoneal macrophages obtained from MB49 tumor-bearing mice treated in vivo with combined treatment of BCG with L-NAME also enhanced fibroblast proliferation. We observed that FGF-2 is one of the factors released by BCG-activated macrophages that is able to induce fibroblast proliferation. The involvement of FGF-2 was evidenced using an anti-FGF2 antibody. At the same time, this macrophage population improved wound healing rate in normal mice and FGF-2 expression was also increased in these wounds. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that fibroblasts are targeted by BCG both directly and through activated macrophages in an immunotherapy context of a bladder murine model. We also described, for the first time, that FGF-2 is involved in a dialog between fibroblasts and macrophages induced after BCG treatment. The fact that L-NAME administration improves the BCG effect on fibroblasts, NO inhibition, might represent a new approach to add to the conventional BCG therapy.

  11. FLUORESCENCE DIAGNOSIS FOR RECURRENT BLADDER CANCER

    Directory of Open Access Journals (Sweden)

    R. V. Ulyanov

    2017-01-01

    Full Text Available The clinical case of successful use of local fluorescence spectroscopy combined with fluorescence imaging during cystoscopy for diagnosis of recurrent bladder cancer is represented in the article. Histological study of fluorescent foci confirmed tumor growth (urothelial carcinoma in all areas with high levels of diagnostic parameter. In the fluorescent focus with low diagnostic parameter inflammation was detected.

  12. Unusual presentation of metastatic gall bladder cancer

    Directory of Open Access Journals (Sweden)

    Piyush Shukla

    2014-01-01

    Full Text Available To report the first case of rare isolated breast metastasis from carcinoma gall bladder. Single patient case report. A 35-year-old pre-menopausal female presented with 2 FNx01 2 cm right upper outer quadrant breast lump. Post-mastectomy, histology confirmed it to be metastatic adenocarcinoma positive for both Cytokeratin (CK 7 and CK20. Past history as told by the patient revealed that 2 years back, cholecystectomy was performed for gall stones, of which no histology reports were present; she had a port site scar recurrence which showed it to be adenocarcinoma. Adjuvant chemotherapy and radiotherapy was advised which the patient did not complete. This is probably the first case reported of isolated breast metastasis from gall bladder carcinoma, diagnosed retrospectively. It also highlights the importance of adjuvant treatment in gall bladder malignancy.

  13. NMR imaging of bladder tumors in males. Preliminary clinical experience

    International Nuclear Information System (INIS)

    Sigal, R.; Rein, A.J.J.T.; Atlan, H.; Lanir, A.; Kedar, S.; Segal, S.

    1985-01-01

    Nuclear magnetic resonance (NMR) of the normal and pathologic bladder was performed in 10 male subjects: 5 normal volunteers, 4 with bladder primary carcinoma, 1 with bladder metastasis. All scanning was done using a superconductive magnet operating at 0.5 T. Spin echo was used as pulse sequence. The diagnosis was confirmed in all cases by NMR imaging. The ability of the technique to provide images in axial, sagital and coronal planes allowed a precise assessment of the morphology and the size of the tumors. The lack of hazards and the quality of images may promote NMR imaging to a prominent role in the diagnosis of human bladder cancer [fr

  14. Asymptomatic Bladder Metastasis from Breast Cancer

    Directory of Open Access Journals (Sweden)

    Luigi Cormio

    2014-01-01

    Full Text Available Introduction. Breast cancer is the most common nondermatologic cancer in women. Common metastatic sites include lymph nodes, lung, liver, and bone. Metastases to the bladder are extremely rare, with all reported cases presenting with urinary symptoms. Case Report. Herein, we report the first case of completely asymptomatic bladder metastasis from breast cancer, occasionally revealed, 98 months after the initial diagnosis of lobular breast carcinoma, by a follow-up computed tomography scanning showing thickening of left bladder wall and grade II left hydronephrosis. A positive staining for estrogen and progesterone receptors was confirmed by immunohistochemistry. Discussion. The reported case confirms that bladder metastases from breast cancer tend to occur late after the diagnosis of the primary tumor and, for the first time, points out they can be asymptomatic. Conclusion. Such data support the need for careful follow-up and early intervention whenever such clinical situation is suspected.

  15. Urokinase-type plasminogen activator receptor (uPAR) expression is associated with T-stage and survival in urothelial carcinoma of the bladder

    DEFF Research Database (Denmark)

    Dohn, Line Hammer; Illemann, Martin; Høyer-Hansen, Gunilla

    2015-01-01

    during cancer invasion and metastasis and is an established prognostic marker in cancer. The expression and localization of uPAR and its prognostic significance is only limitedly investigated in urothelial bladder neoplasia. MATERIALS AND METHODS: The expression-and localization pattern of u......PAR was investigated in formalin-fixed paraffin-embedded tumor tissue from 149 patients treated with radical cystectomy between 1988 and 2005. uPAR expression was determined by immunohistochemistry and scored as either negative or positive. Separate values were obtained for cancer cells, macrophages...... comparisons). In univariate analysis, the uPAR positive group had a shorter survival than the uPAR negative group (hazard ratio = 2.39; 95% CI: 1.15-5.01; P = 0.020). CONCLUSIONS: The expression of uPAR is a possible prognostic marker that could be useful in identification of patients with aggressive, highly...

  16. The potential effect of age on the natural behavior of bladder cancer: Does urothelial cell carcinoma progress differently in various age groups?

    Science.gov (United States)

    Gunlusoy, Bulent; Ceylan, Yasin; Degirmenci, Tansu; Aydogdu, Ozgu; Bozkurt, Ibrahim Halil; Yonguc, Tarik; Sen, Volkan; Kozacioglu, Zafer

    2016-05-01

    We aimed to evaluate the potential effect of age on the natural behavior of bladder cancer and to compare these findings between different age groups. The clinical and pathologic data of 239 patients treated at our institution between 1994 and 2014 were analyzed. The patients were classified into three groups according to age: ≤ 40 years (Group 1), 41-59 years (Group 2), and ≥ 60 years (Group 3). The following data were collected: characteristics of the patients, initial pathological findings after transurethral resection, tumor stage and grade, tumor size and multiplicity, and disease recurrence and progression. The mean age of the patients at initial diagnosis was 34.2±5.5 years, 53±5.1 years, and 71.1±7 years in Groups 1, 2, and 3, respectively. There were 207 (86.6%) patients with nonmuscle-invasive urothelial bladder cancer and 32 (13.4%) patients with muscle-invasive disease. Tumor recurrence was significantly lower in Group 1 than in Group 2 (p=0.001) and Group 3 (p=0.001). Although the time to tumor recurrence was significantly different between the three groups (p=0.001), no significant difference was noted in the time to progression (p=0.349). Patients with urothelial cancer younger than 40 years tend to have single and small tumors. The tumor recurrence rate is lower in the younger age group, but tumor progression is similar in older and younger patients. Therefore, the findings indicate that clinicians should be careful when assessing the invasiveness of urothelial tumors in younger patients and start treatment as soon as possible. Copyright © 2016. Published by Elsevier Taiwan.

  17. Direct FGF receptor 1 activation through an anti-idiotypic strategy mimicks the biological activity of FGF-2 and inhibits the progression of the bladder carcinoma derived from NBT-II cells.

    Science.gov (United States)

    Malavaud, Bernard; Pedron, Sandrine; Sordello, Sylvie; Mazerolles, Catherine; Billottet, Clotilde; Thiery, Jean-Paul; Jouanneau, Jacqueline; Plouët, Jean

    2004-09-02

    The hypothesis that tumor growth is angiogenesis-dependent has been documented by a considerable body of direct and indirect experimental data. Since the discovery of the vascular endothelial growth factor (VEGF), most attention has been focused on the VEGF system. Although fibroblast growth factors 1 and 2 (FGF-1 and FGF-2) can exert a strong angiogenic activity when they are supplied as a single pharmacological agent, their role in pathological angiogenesis in preclinical models remains controversial. To decipher the contribution of FGF receptors in various models of angiogenesis, we took advantage of the anti-idiotypic strategy to obtain circulating agonists specific for FGFR-1 and FGFR-2 (AIdF-1 and AIdF-2). They mimicked FGF-1 and FGF-2 for receptor binding, signal transduction, proliferation of endothelial cells and differentiation of the bladder carcinoma cell NBT-II which expresses FGFR-2b but not FGFR-1. The constitutive expression of FGFR-1 allowed binding of FGF-2 and AIdF-2 and inhibition of the proliferation of NBT-II cells. AIdF-1 and AIdF-2 induced angiogenesis in the corneal pocket assay. Although FGFR-1 dimerization achieved by AIdF-2 injection led to highly differentiated and smaller NBT-II tumors, no sign of reduction of tumor angiogenesis was observed, thus suggesting that endothelial cells are resistant to FGF.

  18. Thrombomodulin expression regulates tumorigenesis in bladder cancer

    International Nuclear Information System (INIS)

    Wu, Chun-Te; Chang, Ying-Hsu; Lin, Paul- Yang; Chen, Wen-Cheng; Chen, Miao-Fen

    2014-01-01

    The identification of potential tumor markers will help improve therapeutic planning and patient management. Thrombomodulin (TM) is a sensitive urothelial marker. TM was reported to be one of the endogenous anti-metastatic factors and has diagnostic and prognostic values for the progression of carcinoma. In the present study, we examine the role of TM in bladder cancer. We studied the role of TM in tumor behavior and related signaling pathways in vitro using the human bladder cancer cell lines HT1376, HT1197, J82 and T24, and in vivo using animal models. We also selected clinical specimens from 100 patients with bladder cancer for immunohistochemical staining to evaluate the predictive capacity of TM in tumor invasiveness. The data revealed that positive immunoreactivity for TM was inversely correlated with clinical stage and DNA methyltransferase 1 immunoreactivity. Decreased TM expression could predict the aggressive tumor growth and advanced clinical stage in bladder cancer. When TM was inhibited, tumor growth rate and invasion ability were augmented in vitro and in vivo. The underlying changes included increased cell proliferation, enhanced epithelial-mesenchymal transition (EMT) and angiogenesis. Moreover, inhibition of NF-κB activation significantly increased TM expression and attenuated tumor aggressiveness in bladder cancer. TM plays an important role in bladder cancer tumor aggressiveness in vitro and in vivo and is a clinically significant predictor that may represent a suitable therapeutic target for bladder cancer

  19. Bladder tumours in children: An interesting case report of TCC with a partial inverted growth pattern.

    Science.gov (United States)

    El Rahman, Davide Abed; Salvo, Giuseppe; Palumbo, Carlotta; Rocco, Bernardo; Rocco, Francesco

    2014-09-30

    Bladder urothelial carcinoma is typically a disease of older individuals and rarely occurs below the age of 40 years. There is debate and uncertainty in the literature regarding the clinicopathologic and prognostic characteristics of bladder urothelial neoplasms in younger patients compared with older patients, although no consistent age criteria have been used to define "younger" age group categories. We report on a 16 years old girl with transitional cell carcinoma of the bladder with a partial inverted growth pattern who presented with gross hematuria. Ultrasonography revealed a papillary lesion in the bladder; cystoscopic evaluation showed a 15 mm papillary lesion with a thick stalk located in the left bladder wall. Pathologic evaluation of the specimen was reported as "low grade transitional cell carcinoma of the bladder with a partial inverted growth pattern".

  20. Leukemoid reaction associated with transitional cell carcinoma: A ...

    African Journals Online (AJOL)

    Key words: Bladder cancer, immunohistochemistry, leukemoid reaction, lymphatic metastasis. Date of Acceptance: 28-Aug-2013. Address for correspondence: ..... bladder of a mouse in vivo tumor model and discovered that the morbidity of mice with bladder carcinoma treated with SA-GM-CSF decreased from 100% to ...

  1. Microsatellite instability in bladder cancer

    DEFF Research Database (Denmark)

    Gonzalez-Zulueta, M; Ruppert, J M; Tokino, K

    1993-01-01

    Somatic instability at microsatellite repeats was detected in 6 of 200 transitional cell carcinomas of the bladder. Instabilities were apparent as changes in (GT)n repeat lengths on human chromosome 9 for four tumors and as alterations in a (CAG)n repeat in the androgen receptor gene on the X...... chromosome for three tumors. Single locus alterations were detected in three tumors, while three other tumors revealed changes in two or more loci. In one tumor we found microsatellite instability in all five loci analyzed on chromosome 9. The alterations detected were either minor 2-base pair changes...... or larger (> 2 base pairs) alterations in repeat length. All six tumors were low stage (Ta-T1), suggesting that these alterations can occur early in bladder tumorigenesis....

  2. The paediatric neuropathic bladder

    African Journals Online (AJOL)

    A neurogenic bladder can be defined as a dysfunctinal urinary bladder caused by disease of the central nervous system or peripheral nerves involved in the control of micturition (urination). In pathophysiological terms, a neurogenic bladder is caused by a spinal reflex arc that occurs when the bladder becomes autonomous.

  3. TP53 modulating agent, CP-31398 enhances antitumor effects of ODC inhibitor in mouse model of urinary bladder transitional cell carcinoma.

    Science.gov (United States)

    Madka, Venkateshwar; Mohammed, Altaf; Li, Qian; Zhang, Yuting; Kumar, Gaurav; Lightfoot, Stan; Wu, Xueru; Steele, Vernon; Kopelovich, Levy; Rao, Chinthalapally V

    2015-01-01

    Mutations of the tumor suppressor p53 and elevated levels of polyamines are known to play key roles in urothelial tumorigenesis. We investigated the inhibition of polyamines biosynthesis and the restoration of p53 signaling as a possible means of preventing muscle invasive urothelial tumors using DFMO, an ODC-inhibiting agent, and CP-31398 (CP), a p53 stabilizing agent. Transgenic UPII-SV40T male mice at 6weeks age (n=15/group) were fed control diet (AIN-76A) or experimental diets containing DFMO (1000 and 2000 ppm) or 150 ppm CP or both. At 40 weeks of age, all mice were euthanized and urinary bladders were evaluated to determine tumor weight and histopathology. Low-dose DFMO had a moderate significant inhibitory effect on tumor growth (38%, P0.05). CP at 150 ppm alone had a strong inhibitory effect on tumor growth by 80% (PCP (150 ppm) led to significant decrease in tumor weight (70%, PCP and DFMO appears to be a promising strategy for urothelial TCC prevention.

  4. Proceedings of the 3rd Annual Albert Institute for Bladder Cancer Research Symposium.

    Science.gov (United States)

    Flaig, Thomas W; Kamat, Ashish M; Hansel, Donna; Ingersoll, Molly A; Barton Grossman, H; Mendelsohn, Cathy; DeGraff, David; Liao, Joseph C; Taylor, John A

    2017-07-27

    The Third Annual Albert Institute Bladder Symposium was held on September 8-10th, 2016, in Denver Colorado. Participants discussed several critical topics in the field of bladder cancer: 1) Best practices for tissue analysis and use to optimize correlative studies, 2) Modeling bladder cancer to facilitate understanding and innovation, 3) Targeted therapies for bladder cancer, 4) Tumor phylogeny in bladder cancer, 5) New Innovations in bladder cancer diagnostics. Our understanding of and approach to treating urothelial carcinoma is undergoing rapid advancement. Preclinical models of bladder cancer have been leveraged to increase our basic and mechanistic understanding of the disease. With the approval of immune checkpoint inhibitors for the treatment of advanced urothelial carcinoma, the treatment approach for these patients has quickly changed. In this light, molecularly-defined subtypes of bladder cancer and appropriate pre-clinical models are now essential to the further advancement and appropriate application of these therapeutic improvements. The optimal collection and processing of clinical urothelial carcinoma tissues samples will also be critical in the development of predictive biomarkers for therapeutic selection. Technological advances in other areas including optimal imaging technologies and micro/nanotechnologies are being applied to bladder cancer, especially in the localized setting, and hold the potential for translational impact in the treatment of bladder cancer patients. Taken together, advances in several basic science and clinical areas are now converging in bladder cancer. These developments hold the promise of shaping and improving the clinical care of those with the disease.

  5. Coordinated Increased Expression of Cyclooxygenase2 and Nuclear Factor B Is a Steady Feature of Urinary Bladder Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Stylianos Kontos

    2010-01-01

    Full Text Available Objectives. The inescapable relationship between chronic inflammation and carcinogenesis has long been established. Our objective was to investigate COX-2 and NF-B immunohistochemical expression in a large series of normal epithelium and bladder carcinomas. Methods. Immunohistochemical methodology was performed on formalin-fixed, paraffin-embedded sections from urinary bladder carcinomas of 140 patients (94 males and 46 females with bladder carcinomas. Results. COX-2 expression is increased in the cytoplasm of bladder cells, during loss of cell differentiation (s=0.61, -value<.001 and in muscle invasive carcinomas (-value<.001. A strong positive association between tumor grade and nuclear expression of NFB has been established. A positive correlation between COX-2 and nuclear NFB immunoreactivity was observed. Conclusions. The possible coordinated upregulation of NFB and COX-2, during bladder carcinogenesis, indicates that agents inhibitors of these two molecules may represent a possible new treatment strategy, by virtue of their role in bladder carcinogenesis.

  6. Nuclear E-cadherin expression is associated with the loss of membranous E-cadherin, plasmacytoid differentiation and reduced overall survival in urothelial carcinoma of the bladder.

    Science.gov (United States)

    Keck, Bastian; Wach, Sven; Kunath, Frank; Bertz, Simone; Taubert, Helge; Lehmann, Jan; Stöckle, Michael; Wullich, Bernd; Hartmann, Arndt

    2013-07-01

    Loss of E-cadherin represents a hallmark of plasmacytoid differentiation. We analyzed the effect of membranous E-cadherin loss and its nuclear accumulation in patients with locally advanced conventional urothelial carcinoma (UC) who were treated with radical cystectomy and adjuvant chemotherapy. A total of 247 formalin-fixed, paraffin-embedded tumor samples were reviewed to detect histological variants of UC. Immunohistochemical staining of E-cadherin was performed and analyzed for membranous and nuclear expression. The correlation between E-cadherin expression and histology was assessed, and overall survival (OS) was analyzed with univariate and multivariate Cox regression and Kaplan-Meier analyses. Correlation of nuclear E-cadherin to tumor stage (pT), lymph node metastasis (pN), histologic subtype, and chemotherapy was performed by Fisher's exact test. Membranous and nuclear E-cadherin expression was strongly correlated to plasmacytoid urothelial carcinoma (PUC) (p Nuclear accumulation was found in 47.6 % of PUCs, 10 % of MPCs, and 1.8 % of UCs. Sixty-two percent of all tumors with negative membranous E-cadherin expression and nuclear accumulation were PUCs (p = 0.035). In a Kaplan-Meier analysis, mean survival with nuclear E-cadherin expression was 31.9 months [95 % confidence interval (CI) 16.1-47.6] of patients without nuclear staining 61 months (95 % CI 53.5-67.7; p = 0.045). A univariate Cox regression analysis showed that nuclear E-cadherin accumulation was associated with a 2-fold increase in risk of death (95 % CI 1.03-4.06; p = 0.04). In multivariate Cox regression analysis adjusted to type of chemotherapy, tumor stage, and tumor grade, the hazard ratio for patients with nuclear E-cadherin was 2.03 (95 % CI 1.00-4.121; p = 0.050). Nuclear E-cadherin is associated with PUCs and is suggested to be an independent prognostic factor in advanced UC.

  7. Paraneoplastic retinopathy associated with occult bladder cancer

    DEFF Research Database (Denmark)

    Nivean, M; Muttuvelu, Danson V; Afzelius, Pia Maria Tullia

    2016-01-01

    The aim was to report the first case of cancer-associated retinopathy (CAR) presenting before bladder cancer diagnosis. A 71-year-old woman with a history of bilateral vision loss underwent subsequent complete ophthalmic examination include a fluorescein angiography, full-field electroretinogram...... (ERG), serology including serum antibodies for CAR, and positron emission tomography-computed tomography (PET-CT) scan. The patient was diagnosed with bladder carcinoma revealed by PET-CT. Timely recognition of this entity may be crucial for an increased patient survival thus adult onset progressive...

  8. Body Mass Index, Diet-Related Factors, and Bladder Cancer Prognosis: A Systematic Review and Meta-Analysis

    Science.gov (United States)

    Westhoff, Ellen; Witjes, J. Alfred; Fleshner, Neil E.; Lerner, Seth P.; Shariat, Shahrokh F.; Steineck, Gunnar; Kampman, Ellen; Kiemeney, Lambertus A.; Vrieling, Alina

    2018-01-01

    Background: Urologists are frequently confronted with questions of urinary bladder cancer (UBC) patients about what they can do to improve their prognosis. Unfortunately, it is largely unknown which lifestyle factors can influence prognosis. Objective: To systematically review the available evidence on the association between body mass index (BMI), diet, dietary supplements, and physical activity and UBC prognosis. Methods: We searched PubMed and Embase up to May 2017. We included thirty-one articles reporting on observational and randomized controlled trials investigating BMI, diet and dietary supplements in relation to recurrence, progression, cancer-specific or all-cause mortality in UBC patients. Results: In non-muscle invasive bladder cancer (NMIBC) patients, both overweight (3 studies, pooled hazard ratio (HR) 1.29, 95% CI 1.05–1.58, I2 = 0%) as well as obesity (3 studies, pooled HR 1.82, 95% CI 1.12–2.95, I2 = 79%) were associated with increased risk of recurrence when compared to normal weight. No association of BMI with risk of progression was found. Results for BMI and prognosis in muscle-invasive or in all stages series were inconsistent. Observational studies on diet and randomized controlled trials with dietary supplements showed inconsistent results. No studies on physical activity and UBC prognosis have been published to date. Conclusions: Evidence for an association of lifestyle factors with UBC prognosis is limited, with some evidence for an association of BMI with risk of recurrence in NMIBC. Well-designed, prospective studies are needed to develop evidence-based guidelines on this topic. PMID:29430510

  9. The pathologist's mean grade is constant and individualizes the prognostic value of bladder cancer grading.

    Science.gov (United States)

    van Rhijn, Bas W G; van Leenders, Geert J L H; Ooms, Bert C M; Kirkels, Wim J; Zlotta, Alexandre R; Boevé, Egbert R; Jöbsis, Adriaan C; van der Kwast, Theo H

    2010-06-01

    A new grading system for bladder cancer (BCa) was adopted in 2004 to reduce observer variability and provide better prognostic information. We compared the World Health Organization (WHO) 1973 and 2004 systems for observer variability and prognosis. Slides of 173 primary non-muscle-invasive BCa were reviewed two times by four pathologists. Intra- and interobserver variability were assessed using κ statistics. We determined the mean grade (eg, G1/low malignant potential is 1 grade point, G2/low grade is 2 grade points) of the pathologists per grading cycle. Kaplan-Meier analyses were applied for prediction of recurrence and progression. For WHO 2004 and 1973 grading, the agreement between the pathologists was 39-74% (κ: 0.14-0.58) and 39-64% (κ: 0.15-0.41), respectively. The intraobserver agreement varied from 71% to 88% (κ: 0.55-0.81). The mean grade of a pathologist was constant (difference below 0.1 grade point) irrespective of the grading system. Conversely, mean-grade differences among the pathologists were high, up to 0.7 grade point. The mean grades for the WHO 2004 system were 0.3-0.5 grade point higher than those of WHO 1973. Mean grade distinguished low and high graders among the pathologists and was strongly linked with risk of progression in each grade category. The variation in mean grade among individual pathologists exceeded the grade shift caused by WHO 2004 grading. Knowledge of the pathologist's mean grade allows a better assessment of the prognostic value of grading. Mean grade has the potential to become a tool for quality assurance in pathology. Copyright © 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  10. The Burden of Cystoscopic Bladder Cancer Surveillance: Anxiety, Discomfort, and Patient Preferences for Decision Making.

    Science.gov (United States)

    Koo, Kevin; Zubkoff, Lisa; Sirovich, Brenda E; Goodney, Philip P; Robertson, Douglas J; Seigne, John D; Schroeck, Florian R

    2017-10-01

    To examine discomfort, anxiety, and preferences for decision making in patients undergoing surveillance cystoscopy for non-muscle-invasive bladder cancer (NMIBC). Veterans with a prior diagnosis of NMIBC completed validated survey instruments assessing procedural discomfort, worry, and satisfaction, and were invited to participate in semistructured focus groups about their experience and desire to be involved in surveillance decision making. Focus group transcripts were analyzed qualitatively, using (1) systematic iterative coding, (2) triangulation involving multiple perspectives from urologists and an implementation scientist, and (3) searching and accounting for disconfirming evidence. Twelve patients participated in 3 focus groups. Median number of lifetime cystoscopy procedures was 6.5 (interquartile range 4-10). Based on survey responses, two-thirds of participants (64%) experienced some degree of procedural discomfort or worry, and all participants reported improvement in at least 2 dimensions of overall well-being following cystoscopy. Qualitative analysis of the focus groups indicated that participants experience preprocedural anxiety and worry about their disease. Although many participants did not perceive themselves as having a defined role in decision making surrounding their surveillance care, their preferences to be involved in decision making varied widely, ranging from acceptance of the physician's recommendation, to uncertainty, to dissatisfaction with not being involved more in determining the intensity of surveillance care. Many patients with NMIBC experience discomfort, anxiety, and worry related to disease progression and not only cystoscopy. Although some patients are content to defer surveillance decisions to their physicians, others prefer to be more involved. Future work should focus on defining patient-centered approaches to surveillance decision making. Published by Elsevier Inc.

  11. BCG strain S4-Jena: An early BCG strain is capable to reduce the proliferation of bladder cancer cells by induction of apoptosis

    Directory of Open Access Journals (Sweden)

    Hermann Inge-Marie

    2010-06-01

    Full Text Available Abstract Background Intravesical immunotherapy with Mycobacterium bovis bacillus Calmette-Guérin has been established as the most effective adjuvant treatment for high risk non-muscle-invasive bladder cancer (NMIBC. We investigated the differences between the S4-Jena BCG strain and commercially available BCG strains. We tested the genotypic varieties between S4-Jena and other BCG strains and analy