Displaying publications 21 - 40 of 61 in total

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  1. Lin C, Travis RC, Appleby PN, Tipper S, Weiderpass E, Chang-Claude J, et al.
    Int J Cancer, 2018 Nov 15;143(10):2351-2358.
    PMID: 29971779 DOI: 10.1002/ijc.31650
    Previous in vitro and case-control studies have found an association between the insulin-like growth factor (IGF)-axis and bladder cancer risk. Circulating concentrations of IGF-I have also been found to be associated with an increased risk of several cancer types; however, the relationship between pre-diagnostic circulating IGF-I concentrations and bladder cancer has never been studied prospectively. We investigated the association of pre-diagnostic plasma concentrations of IGF-I with risk of overall bladder cancer and urothelial cell carcinoma (UCC) in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 843 men and women diagnosed with bladder cancer between 1992 and 2005 were matched with 843 controls by recruitment centre, sex, age at recruitment, date of blood collection, duration of follow-up, time of day and fasting status at blood collection using an incidence density sampling protocol. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression with adjustment for smoking status. No association was found between pre-diagnostic circulating IGF-I concentration and overall bladder cancer risk (adjusted OR for highest versus lowest fourth: 0.91, 95% CI: 0.66-1.24, ptrend = 0.40) or UCC (n of cases = 776; 0.91, 0.65-1.26, ptrend = 0.40). There was no significant evidence of heterogeneity in the association of IGF-I with bladder cancer risk by tumour aggressiveness, sex, smoking status, or by time between blood collection and diagnosis (pheterogeneity > 0.05 for all). This first prospective study indicates no evidence of an association between plasma IGF-I concentrations and bladder cancer risk.
    Matched MeSH terms: Urinary Bladder Neoplasms/blood*; Urinary Bladder Neoplasms/epidemiology
  2. Foth M, Ismail NFB, Kung JSC, Tomlinson D, Knowles MA, Eriksson P, et al.
    J Pathol, 2018 Nov;246(3):331-343.
    PMID: 30043421 DOI: 10.1002/path.5143
    Recent studies of muscle-invasive bladder cancer show that FGFR3 mutations are generally found in a luminal papillary tumour subtype that is characterised by better survival than other molecular subtypes. To better understand the role of FGFR3 in invasive bladder cancer, we examined the process of tumour development induced by the tobacco carcinogen OH-BBN in genetically engineered models that express mutationally activated FGFR3 S249C or FGFR3 K644E in the urothelium. Both occurrence and progression of OH-BBN-driven tumours were increased in the presence of an S249C mutation compared to wild-type control mice. Interestingly, at an early tumour initiation stage, the acute inflammatory response in OH-BBN-treated bladders was suppressed in the presence of an S249C mutation. However, at later stages of tumour progression, increased inflammation was observed in S249C tumours, long after the carcinogen administration had ceased. Early-phase neutrophil depletion using an anti-Ly6G monoclonal antibody resulted in an increased neutrophil-to-lymphocyte ratio at later stages of pathogenesis, indicative of enhanced tumour pathogenesis, which supports the hypothesis that suppression of acute inflammation could play a causative role. Statistical analyses of correlation showed that while initial bladder phenotypes in morphology and inflammation were FGFR3-dependent, increased levels of inflammation were associated with tumour progression at the later stage. This study provides a novel insight into the tumour-promoting effect of FGFR3 mutations via regulation of inflammation at the pre-tumour stage in the bladder. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
    Matched MeSH terms: Urinary Bladder Neoplasms
  3. Fahmy O, Khairul-Asri MG, Schubert T, Renninger M, Malek R, Kübler H, et al.
    Urol Oncol, 2018 02;36(2):43-53.
    PMID: 29102254 DOI: 10.1016/j.urolonc.2017.10.002
    OBJECTIVE: This study aimed to comprehensively analyze the oncological long-term outcomes of trimodal therapy (TMT) and radical cystectomy (RC) for the treatment of muscle-invasive bladder cancer (BC) with or without neoadjuvant chemotherapy (NAC).

    PATIENTS AND METHODS: A systematic search was conducted according to the PRISMA guidelines for studies reporting on outcomes after TMT and RC. A total of 57 studies including 30,293 patients were included. The 10-year overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) rates for TMT and RC were assessed.

    RESULTS: The mean 10-year OS was 30.9% for TMT and 35.1% for RC (P = 0.32). The mean 10-year DSS was 50.9% for TMT and 57.8% for RC (P = 0.26). NAC was administered before therapy to 453 (13.3%) of 3,402 patients treated with TMT and 812 (3.0%) of 27,867 patients treated with RC (P<0.001). Complete response (CR) was achieved in 1,545 (75.3%) of 2,051 evaluable patients treated with TMT. A 5-year OS, DSS, and RFS after CR were 66.9%, 78.3%, and 52.5%, respectively. Downstaging after transurethral bladder tumor resection or NAC to stage ≤pT1 at RC was reported in 2,416 (29.1%) of 8,311 patients. NAC significantly increased the rate of pT0 from 20.2% to 34.3% (P = 0.007) in cT2 and from 3.8% to 23.9% (P<0.001) in cT3-4. A 5-year OS, DSS, and RFS in downstaged patients (≤pT1) at RC were 75.7%, 88.3%, and 75.8%, respectively.

    CONCLUSION: In this analysis, the survival outcomes of patients after TMT and RC for MIBC were comparable. Patients who experienced downstaging after NAC and RC exhibited improved survival compared to patients treated with RC only. Best survival outcomes after TMT are associated with CR to this approach.

    Matched MeSH terms: Urinary Bladder Neoplasms/pathology; Urinary Bladder Neoplasms/therapy*
  4. Fahmy O, Khairul-Asri MG, Schubert T, Renninger M, Kübler H, Stenzl A, et al.
    Urol Oncol, 2018 02;36(2):54-59.
    PMID: 29196179 DOI: 10.1016/j.urolonc.2017.11.007
    PURPOSE: Currently, identified factors for urethral recurrence (UR) are based on individual reporting which has displayed controversy. In addition, risk of UR is one of the limiting factors to offer neobladder diversion during radical cystectomy (RC). We aim to systematically evaluate the incidence and risk factors of UR post-RC and its effect on survival.

    MATERIALS AND METHODS: A systematic online search was conducted according to PRISMA statement for publications reporting on UR after RC. From initial 802 results, 14 articles including 6169 patients were included finally after exclusion of ineligible studies.

    RESULTS: The incidence rate of UR was 4.4% (1.3%-13.7%). It was significantly lower with neobladder diversion (odds ratio = 0.44, 95% CI: 0.24-0.79, P = 0.006). Muscle invasion (hazard ratio = 1.18, 95% CI: 0.86-1.62, P = 0.31), carcinoma in situ (hazard ratio 0.97, 95% CI: 0.64-1.47, P = 0.88), prostatic stromal involvement (hazard ratio = 2.26, 95% CI: 0.01-627.75, P = 0.78), and prostatic urethral involvement (hazard ratio = 2.04, 95% CI: 0.20-20.80, P = 0.55) have no significant effect on UR. Men displayed tendency toward higher incidence of UR (odds ratio = 2.21, 95% CI: 0.96-5.06, P = 0.06). Absence of recurrence displayed tendency toward better disease specific survival, yet not significant (hazard ratio = 0.84, 95% CI: 0.66-1.08, P = 0.17). These results are limited by the retrospective nature of the included studies.

    CONCLUSION: Muscle invasion, carcinoma in situ and prostatic stromal or urethral involvement at time of RC have no significant effect on UR. Orthotopic neobladder is associated with a significant lower risk of UR after RC.

    Matched MeSH terms: Urinary Bladder Neoplasms/pathology; Urinary Bladder Neoplasms/surgery*
  5. Pedersen M, Stafoggia M, Weinmayr G, Andersen ZJ, Galassi C, Sommar J, et al.
    Eur Urol Focus, 2018 01;4(1):113-120.
    PMID: 28753823 DOI: 10.1016/j.euf.2016.11.008
    BACKGROUND: Ambient air pollution contains low concentrations of carcinogens implicated in the etiology of urinary bladder cancer (BC). Little is known about whether exposure to air pollution influences BC in the general population.

    OBJECTIVE: To evaluate the association between long-term exposure to ambient air pollution and BC incidence.

    DESIGN, SETTING, AND PARTICIPANTS: We obtained data from 15 population-based cohorts enrolled between 1985 and 2005 in eight European countries (N=303431; mean follow-up 14.1 yr). We estimated exposure to nitrogen oxides (NO2 and NOx), particulate matter (PM) with diameter <10μm (PM10), <2.5μm (PM2.5), between 2.5 and 10μm (PM2.5-10), PM2.5absorbance (soot), elemental constituents of PM, organic carbon, and traffic density at baseline home addresses using standardized land-use regression models from the European Study of Cohorts for Air Pollution Effects project.

    OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We used Cox proportional-hazards models with adjustment for potential confounders for cohort-specific analyses and meta-analyses to estimate summary hazard ratios (HRs) for BC incidence.

    RESULTS AND LIMITATIONS: During follow-up, 943 incident BC cases were diagnosed. In the meta-analysis, none of the exposures were associated with BC risk. The summary HRs associated with a 10-μg/m3 increase in NO2 and 5-μg/m3 increase in PM2.5 were 0.98 (95% confidence interval [CI] 0.89-1.08) and 0.86 (95% CI 0.63-1.18), respectively. Limitations include the lack of information about lifetime exposure.

    CONCLUSIONS: There was no evidence of an association between exposure to outdoor air pollution levels at place of residence and risk of BC.

    PATIENT SUMMARY: We assessed the link between outdoor air pollution at place of residence and bladder cancer using the largest study population to date and extensive assessment of exposure and comprehensive data on personal risk factors such as smoking. We found no association between the levels of outdoor air pollution at place of residence and bladder cancer risk.

    Matched MeSH terms: Urinary Bladder Neoplasms/etiology; Urinary Bladder Neoplasms/epidemiology*
  6. Rosmazihana Mat Lazim, Raizulnasuha Ab Rashid, Wan Nordiana Rahman, Binh. T.T. Pham, Brian S. Hawkett, Moshi Geso
    MyJurnal
    Therapeutic application of metallic nanoparticles such as gold nanoparticles have been extensively investigated and intriguing finding have been reported. Superparamagnetic iron oxide nanoparticles (SPION) could also potentially have therapeutic properties that can be exploited to enhance radiotherapy outcome. In this study, investigations on the dose enhancement effects inflicted by SPIONs under irradiation with megavoltage photon beam radiotherapy were conducted. T24 human bladder cancer cell lines were pretreated with 1 mMol/L of SPION and irradiated with 6 MV and 10 MV photon beam at different doses.The non-treated cells irradiation was used as a control. Clonogenic assay was performed to determine the cell survival. Linear quadratic (LQ) model are used as fitting curve and does enhancement factors (DEF) were extrapolated from the curves. The cytotoxicity indicated cell growth normally after 72 hours and no long term cytotoxicity effects of SPIONs towards the cells were observed. The dose enhancement effects were observed for both 6 MV and 10 MV photon beam with DEF obtained 1.71 and 2.50, respectively. This reduction of cell colonies growth could be resulted from the interaction that induced free radical and reactive oxygen species (ROS) by megavoltage photon beams. The SPIONs were therefore act as multifunction nanoparticle both in diagnostic agent and radiotherapy as radiation dose enhancer, thus clearly qualified as future theranostic agents.
    Matched MeSH terms: Urinary Bladder Neoplasms
  7. Hata S, Ise K, Azmahani A, Konosu-Fukaya S, McNamara KM, Fujishima F, et al.
    Life Sci, 2017 Dec 01;190:15-20.
    PMID: 28947209 DOI: 10.1016/j.lfs.2017.09.029
    AIMS: Bladder urothelial carcinoma is increasing in incidence with age and its prognosis could become worse when accompanied with metastasis. Effective treatment of these advanced patients is required and it becomes important to understand its underlying biology of this neoplasm, especially with regard to its biological pathways. A potential proposed pathway is androgen receptor (AR)-mediated intracellular signaling but the details have remained relatively unexplored.

    MAIN METHODS: The expression of AR, 5α-reductase type1 (5αR1) and 5α-reductase type2 (5αR2) were examined in the bladder cancer cell line T24 and surgical pathology specimens. We also evaluated the status of androgen related cell proliferation and migration using the potent, non-aromatizable androgen agonist 5α-dihydrotestosterone (DHT).

    KEY FINDINGS: DHT treatment significantly increased AR mRNA expression level, but not those of 5αR1 and 5αR2 in T24 cells. DHT also suppressed cellular migration with weaker and opposite effects on cell proliferation. A significant inverse correlation was detected between pT stage and AR, 5αR1 and 5αR2 immunoreactivity.

    SIGNIFICANCE: Inverse correlations detected between tumor grade and AR/androgen metabolizing enzyme also suggested that the loss of AR and androgen-producing enzymes could be associated with tumor progression. Effects of DHT on cells also suggest that androgens may regulate cellular behavior.

    Matched MeSH terms: Urinary Bladder Neoplasms/genetics*; Urinary Bladder Neoplasms/pathology
  8. Md Akhir MKA, Hussin H, Veerakumarasivam A, Choy CS, Abdullah MA, Abd Ghani F
    Malays J Pathol, 2017 Dec;39(3):227-234.
    PMID: 29279584 MyJurnal
    Urothelial carcinoma is a common malignant neoplasm that has a poor prognosis and a high frequency of recurrence and metastasis. Constant disease surveillance with periodic and long term cystoscopy examination is necessary for management of the disease. However, the monitoring and therapy regimen is expensive, incurring a massive burden to patients and the government. Therefore, the development of specific biomarkers for urothelial carcinoma at an early stage and recurrence detection becomes a priority. Homeobox genes are a family of genes that are involved in tumourigenesis. They might be potential prognostic markers for urothelial carcinoma. The study investigated the expression pattern of NANOG which is one of a homeobox gene in different stages and grades of urothelial carcinoma. NANOG expressions were also correlated with patient demographic factors and clinicopathological parameters. The expression of NANOG in 100 formalin-fixed paraffin-embedded urothelial carcinoma tissues was determined by immunohistochemistry. Immunohistochemistry showed positive expression of NANOG in all specimens with detection in the cytoplasm, nuclei and the nuclear membrane of the cancer cells. The immunohistochemical expression of NANOG increased across stages and grades of the tumour. The expression of NANOG was not significantly associated with demographic factors; gender (p = 0.376), race (p = 0.718) and age (p = 0.058) as well as with most of the clinicopathological parameters; pathological stage (p = 0.144), grade (p = 0.625), lymph node involvement (p = 0.174) and distant metastasis (p = 0.228). However, NANOG expression showed significant correlation with tumour invasion (p = 0.019). We concluded that NANOG might be a potential biomarker for early diagnosis of urothelial carcinoma of the bladder.
    Matched MeSH terms: Urinary Bladder Neoplasms/pathology*
  9. Ng KL, Chua CB
    Asian J Surg, 2017 Apr;40(2):163-165.
    PMID: 25183290 DOI: 10.1016/j.asjsur.2014.01.016
    Intravesical Bacillus Calmette-Guérin (BCG) has been a proven and effective immunotherapy treatment for superficial transitional cell carcinoma (TCC) of the bladder, especially for high-grade tumors and carcinoma in situ. Nevertheless, significant side effects are associated with BCG instillations, including fever, myalgia, malaise, dysuria, hematuria, and irritable lower urinary tract symptoms. We herein report the case of a patient who developed Reiter's syndrome following intravesical BCG instillations. A 39-year-old Chinese man presented with a 3-week history of dysuria, suprapubic pain, and pain at the tip of the penis postmicturition. Initial investigations revealed that he had microhematuria, and an ultrasound with computed tomography scan of the abdomen showed a bladder mass. Transurethral resection of the bladder tumor was performed and the patient received a single dose of intravesical mitomycin postoperatively. Results of histopathological examination revealed high-grade bladder TCC (G3pT1), and the patient was managed with intravesical BCG for 2 weeks following the surgery. Four weekly cycles of BCG were administered uneventfully; however, before the fifth instillation, the patient complained of urethral discharge, bilateral conjunctivitis, and low back pain. Reiter's syndrome was diagnosed as a rare but known complication of BCG instillation and the BCG immunotherapy was withheld. The patient was treated with nonsteroidal antiinflammatory drugs (for back pain) and eye ointment (for conjunctivitis) and his condition improved. This case report of Reiter's syndrome should be highlighted as a rare but significant complication of BCG immunotherapy and urologists should have a high index of suspicion to diagnose this rare complication.
    Matched MeSH terms: Urinary Bladder Neoplasms/drug therapy*; Urinary Bladder Neoplasms/pathology; Urinary Bladder Neoplasms/surgery
  10. Ismail AF, Oskay Halacli S, Babteen N, De Piano M, Martin TA, Jiang WG, et al.
    Biochem. J., 2017 Mar 24;474(8):1333-1346.
    PMID: 28232500 DOI: 10.1042/BCJ20160875
    Urothelial bladder cancer is a major cause of morbidity and mortality worldwide, causing an estimated 150 000 deaths per year. Whilst non-muscle-invasive bladder tumours can be effectively treated, with high survival rates, many tumours recur, and some will progress to muscle-invasive disease with a much poorer long-term prognosis. Thus, there is a pressing need to understand the molecular transitions occurring within the progression of bladder cancer to an invasive disease. Tumour invasion is often associated with a down-regulation of E-cadherin expression concomitant with a suppression of cell:cell junctions, and decreased levels of E-cadherin expression have been reported in higher grade urothelial bladder tumours. We find that expression of E-cadherin in a panel of bladder cancer cell lines correlated with the presence of cell:cell junctions and the level of PAK5 expression. Interestingly, exogenous PAK5 has recently been described to be associated with cell:cell junctions and we now find that endogenous PAK5 is localised to cell junctions and interacts with an E-cadherin complex. Moreover, depletion of PAK5 expression significantly reduced junctional integrity. These data suggest a role for PAK5 in maintaining junctional stability and we find that, in both our own patient samples and a commercially available dataset, PAK5mRNA levels are reduced in human bladder cancer compared with normal controls. Taken together, the present study proposes that PAK5 expression levels could be used as a novel prognostic marker for bladder cancer progression.
    Matched MeSH terms: Urinary Bladder Neoplasms/enzymology; Urinary Bladder Neoplasms/metabolism*; Urinary Bladder Neoplasms/pathology
  11. Md Noh MS, Abdul Aziz AF, Mohd Ghani KA, Lee Kheng Siang C, Yunus R, Mohd Yusof M
    Am J Case Rep, 2017 Mar 01;18:212-216.
    PMID: 28246375
    BACKGROUND Intradiverticular bladder tumors are rare. This renders diagnosis of an intradiverticular bladder tumor difficult. Imaging plays a vital role in achieving the diagnosis, and subsequently staging of the disease. CASE REPORT A 74-year-old male presented to our center with a few months history of constitutional symptoms. Upon further history, he reported hematuria two months prior to presentation, which stopped temporarily, only to recur a few days prior to coming to the hospital. The patient admitted to having lower urinary tract symptoms. However, there was no dysuria, no sandy urine, and no fever. Palpation of his abdomen revealed a vague mass at the suprapubic region, which was non tender. In view of his history and the clinical examination findings, an ultrasound of the abdomen and computed tomography (CT) was arranged. These investigations revealed a giant tumor that seemed to be arising from a bladder diverticulum, with a mass effect and hydronephrosis. He later underwent operative intervention. CONCLUSIONS Intradiverticular bladder tumors may present a challenge to the treating physician in an atypical presentation; thus requiring a high index of suspicion and knowledge of tumor pathophysiology. As illustrated in our case, CT with its wide availability and multiplanar imaging capabilities offers a useful means for diagnosis, disease staging, operative planning, and follow-up.
    Matched MeSH terms: Urinary Bladder Neoplasms/pathology*; Urinary Bladder Neoplasms/surgery
  12. Vasudevan G, Bishnu A, Singh BMK, Nayak DM, Jain P
    J Clin Diagn Res, 2017 Mar;11(3):ER01-ER04.
    PMID: 28511402 DOI: 10.7860/JCDR/2017/24590.9536
    Primary urinary Bladder Adenocarcinoma (PBA) is an uncommon neoplasm and can cause diagnostic difficulties due to histologic similarities with adenocarcinomas of adjacent structures like Gastrointestinal Tract (GIT) and prostate, since involvement of the bladder by metastasis or direct spread can occur. Seven cases of bladder adenocarcinomas were diagnosed during a period of four years in a tertiary care hospital. Patient's age ranged from 26-78 years with a male predilection. Three cases were signet ring type adenocarcinomas, two cases were subtyped as enteric variant, one as mucinous variant and one as adenocarcinoma Not Otherwise Specified (NOS) variant. One case showed urachal involvement. Common site of involvement was the base and posterior wall of the bladder. Three cases had prior history of GIT malignancy. No morphologic difference was identified to differentiate primary from secondary adenocarcinomas. Bladder adenocarcinoma is rare tumours. Primary and secondary adenocarcinomas cannot be distinguished from each other on morphologic grounds. Ancillary studies may have limited role in distinguishing between the two. Hence, clinical correlation has a major role in their evaluation.
    Matched MeSH terms: Urinary Bladder Neoplasms
  13. Fahmy O, Khairul-Asri MG, Schubert T, Renninger M, Stenzl A, Gakis G
    J Urol, 2017 02;197(2):385-390.
    PMID: 27569436 DOI: 10.1016/j.juro.2016.08.088
    PURPOSE: There is controversy in the literature about the oncologic significance of incidental prostate cancer detected at radical cystoprostatectomy for bladder cancer.

    MATERIALS AND METHODS: An online search was done for studies reporting incidental prostate cancer in cystoprostatectomy specimens. After following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines we identified a total of 34 reports containing 13,140 patients who underwent radical cystoprostatectomy for bladder cancer with no previous history of prostate cancer. A cumulative analysis was performed on the available data regarding prevalence, clinicopathological features and oncologic outcomes. RevMan, version 5.3 was used for data meta-analysis.

    RESULTS: Of the 13,140 patients incidental prostate cancer was detected in 3,335 (24.4%). Incidental prostate cancer was significantly associated with greater age (Z = 3.81, p = 0.0001, d = 0.27, 95% CI -0.14-0.68), lymphovascular invasion of bladder cancer (Z = 2.07, p = 0.04, r = 0.14, 95% CI 0.09-0.18) and lower 5-year overall survival (Z = 2.2, p = 0.03). Among patients with clinically significant and insignificant prostate cancer those with clinically significant prostate cancer significantly more frequently showed a positive finding on digital rectal examination (Z = 3.12, p = 0.002, r = 0.10, 95% CI 0-0.19) and lower 5-year overall survival (Z = 2.49, p = 0.01) whereas no effect of age was observed (p = 0.15). Of 1,320 patients monitored for biochemical recurrence prostate specific antigen recurrence, defined as prostate specific antigen greater than 0.02 ng/ml, developed in 25 (1.9%) at between 3 and 102 months.

    CONCLUSIONS: This meta-analysis suggests that incidental prostate cancer detected during histopathological examination of radical cystoprostatectomy specimens might be linked with adverse characteristics and outcomes in patients with invasive bladder cancer.

    Matched MeSH terms: Urinary Bladder Neoplasms/surgery*
  14. Fahmy O, Khairul-Asri MG, Stenzl A, Gakis G
    Clin. Exp. Metastasis, 2016 10;33(7):629-35.
    PMID: 27380916 DOI: 10.1007/s10585-016-9807-9
    For many decades, no significant improvements could be achieved to prolong the survival in metastatic bladder cancer. Recently, systemic immunotherapy with checkpoint inhibitors (anti-PD-L1/anti-CTLA-4) has been introduced as a novel treatment modality for patients with metastatic bladder cancer. We conducted a systematic review according to the PRISMA statement for data published on the clinical efficacy of checkpoint inhibitors in metastatic bladder cancer. Clinical efficacy of anti PD-L1 therapy was investigated in prospective trials in a total of 155 patients. Patients with positive expression for PD-L1 tended towards better overall response rates (ORR) compared to those with negative expression (34/76 vs 10/73, 45 vs 14 %; p = 0.21). Among patients with PD-L1 positive tumors, those with non-visceral metastases exhibited significantly higher ORR compared to those with visceral metastases (82 vs 28 %; p = 0.001). For anti-CTLA4 therapy, there were no data retrievable on clinical efficacy. Although data on clinical efficacy of checkpoint inhibitors in metastatic bladder cancer are currently limited, the efficacy of these drugs might depend mainly on the metastatic volume and immune system integrity. Patients with PD-L1 positive tumors and non-visceral metastases seem to derive the highest benefit from therapy.
    Matched MeSH terms: Urinary Bladder Neoplasms/drug therapy*; Urinary Bladder Neoplasms/genetics; Urinary Bladder Neoplasms/pathology
  15. Gakis G, Fahmy O
    Bladder cancer (Amsterdam, Netherlands), 2016 Jul 27;2(3):293-300.
    PMID: 27500197
    Introduction: Although there is evidence that hexaminolevulinate (HAL)-based transurethral bladder tumor resection (TURBT) improves the detection of Ta-T1 non-muscle-invasive bladder cancer (NMIBC) as well as carcinoma in situ there is uncertainty about its beneficial effects on progression. Material and Methods: A systematic literature search was conducted according to the PRISMA statement to identify studies reporting on HAL- vs. white-light (WL-) based TUR-BT in non-muscle invasive bladder cancer between 2000 and 2016. A two-stage selection process was utilized to determine eligible studies. Of a total of 294 studies, 5 (4 randomized and one retrospective) were considered for final analysis. The primary objective was the rate of progression. Results: The median follow-up for patients treated with HAL- and WL-TURBT was 27.6 (1-55.1) and 28.9 (1-53) months, respectively. Of a total of 1301 patients, 644 underwent HAL- and 657 WL-based TURBT. Progression was reported in 44 of 644 patients (6.8%) with HAL- and 70 of 657 patients (10.7%) with WL-TURBT, respectively (median odds ratio: 1.64, 1.10-2.45 for HAL vs. WL; p = 0.01). Data on progression-free survival was reported in a single study with a trend towards improved survival for patients treated with HAL-TURBT (p = 0.05). Conclusions: In this meta-analysis the rate of progression was significantly lower in patients treated with HAL- vs. WL-based TURBT. These results support the initiation of randomized trials on HAL with progression as primary endpoint.
    Matched MeSH terms: Urinary Bladder Neoplasms
  16. Fahmy O, Khairul-Asri MG, Stenzl A, Gakis G
    Med Hypotheses, 2016 Jul;92:57-8.
    PMID: 27241256 DOI: 10.1016/j.mehy.2016.04.037
    Although intravesical instillation of Bacille-Calmette-Guerin (BCG) immunotherapy was approved many decades ago as a first line therapy for intermediate to high-risk non-muscle invasive bladder cancer, its long-term efficacy is still arguable as a proportion of up to 30-40% of patients will develop recurrence or progression of their disease. Based on currently available data on the clinical application of checkpoint inhibitors in solid tumors, the mucosa-associated lymphoid tissue seems to be a main target for anti-CTLA-4 antibodies. In this manuscript we hypothesize that the combination of anti-CTLA-4 therapy with BCG might enhance the immune activity in the bladder submucosal tissue, and subsequently, improve oncological outcomes of NMIBC.
    Matched MeSH terms: Urinary Bladder Neoplasms/immunology; Urinary Bladder Neoplasms/therapy*
  17. Figueroa JD, Middlebrooks CD, Banday AR, Ye Y, Garcia-Closas M, Chatterjee N, et al.
    Hum Mol Genet, 2016 Mar 15;25(6):1203-14.
    PMID: 26732427 DOI: 10.1093/hmg/ddv492
    Candidate gene and genome-wide association studies (GWAS) have identified 15 independent genomic regions associated with bladder cancer risk. In search for additional susceptibility variants, we followed up on four promising single-nucleotide polymorphisms (SNPs) that had not achieved genome-wide significance in 6911 cases and 11 814 controls (rs6104690, rs4510656, rs5003154 and rs4907479, P < 1 × 10(-6)), using additional data from existing GWAS datasets and targeted genotyping for studies that did not have GWAS data. In a combined analysis, which included data on up to 15 058 cases and 286 270 controls, two SNPs achieved genome-wide statistical significance: rs6104690 in a gene desert at 20p12.2 (P = 2.19 × 10(-11)) and rs4907479 within the MCF2L gene at 13q34 (P = 3.3 × 10(-10)). Imputation and fine-mapping analyses were performed in these two regions for a subset of 5551 bladder cancer cases and 10 242 controls. Analyses at the 13q34 region suggest a single signal marked by rs4907479. In contrast, we detected two signals in the 20p12.2 region-the first signal is marked by rs6104690, and the second signal is marked by two moderately correlated SNPs (r(2) = 0.53), rs6108803 and the previously reported rs62185668. The second 20p12.2 signal is more strongly associated with the risk of muscle-invasive (T2-T4 stage) compared with non-muscle-invasive (Ta, T1 stage) bladder cancer (case-case P ≤ 0.02 for both rs62185668 and rs6108803). Functional analyses are needed to explore the biological mechanisms underlying these novel genetic associations with risk for bladder cancer.
    Matched MeSH terms: Urinary Bladder Neoplasms/ethnology; Urinary Bladder Neoplasms/genetics*
  18. Fahmy O, Asri K, Schwentner C, Stenzl A, Gakis G
    J Surg Oncol, 2015 Sep;112(4):427-9.
    PMID: 26265262 DOI: 10.1002/jso.24007
    To investigate the current status and feasibility of robotic neobladder diversion after robotic assisted radical cystectomy. A Medline search was conducted resulting in identification of 423 articles. After exclusion of ineligible studies, 3 case series and 5 case reports were considered with a total number of reported cases of 203. Although robotic intracorporeal neobladder reconstruction is in its starting phase, initial perioperative results seem to be comparable to open series. However, randomized studies are needed to confirm non-inferiority.
    Matched MeSH terms: Urinary Bladder Neoplasms/surgery*
  19. Rashid Ali MR, Kannan KK
    J Bronchology Interv Pulmonol, 2015 Jan;22(1):66-8.
    PMID: 25590487 DOI: 10.1097/LBR.0000000000000128
    We report a case of a 52-year-old patient who had undergone a bladder resection and an ileal conduit for a transitional cell carcinoma. He then presented with a short history of hemoptysis 3 months later. Rigid bronchoscopy was performed revealing an endobronchial lesion, which was removed via laser and debulking method without complications. Histopathologic examination confirmed it to be a benign endobronchial glomus tumor. On the basis of our literature search, this is the 34th reported case of glomus tumor arising from the respiratory tract, seventh reported case of an endobronchial glomus tumor treated bronchoscopically, and the first possibly coincidental finding in relation to a patient with primary transitional bladder cell carcinoma.
    Matched MeSH terms: Urinary Bladder Neoplasms/pathology; Urinary Bladder Neoplasms/radiotherapy; Urinary Bladder Neoplasms/surgery
  20. Fu YP, Kohaar I, Moore LE, Lenz P, Figueroa JD, Tang W, et al.
    Cancer Res, 2014 Oct 15;74(20):5808-18.
    PMID: 25320178 DOI: 10.1158/0008-5472.CAN-14-1531
    A genome-wide association study (GWAS) of bladder cancer identified a genetic marker rs8102137 within the 19q12 region as a novel susceptibility variant. This marker is located upstream of the CCNE1 gene, which encodes cyclin E, a cell-cycle protein. We performed genetic fine-mapping analysis of the CCNE1 region using data from two bladder cancer GWAS (5,942 cases and 10,857 controls). We found that the original GWAS marker rs8102137 represents a group of 47 linked SNPs (with r(2) ≥ 0.7) associated with increased bladder cancer risk. From this group, we selected a functional promoter variant rs7257330, which showed strong allele-specific binding of nuclear proteins in several cell lines. In both GWASs, rs7257330 was associated only with aggressive bladder cancer, with a combined per-allele OR = 1.18 [95% confidence interval (CI), 1.09-1.27, P = 4.67 × 10(-5)] versus OR = 1.01 (95% CI, 0.93-1.10, P = 0.79) for nonaggressive disease, with P = 0.0015 for case-only analysis. Cyclin E protein expression analyzed in 265 bladder tumors was increased in aggressive tumors (P = 0.013) and, independently, with each rs7257330-A risk allele (P(trend) = 0.024). Overexpression of recombinant cyclin E in cell lines caused significant acceleration of cell cycle. In conclusion, we defined the 19q12 signal as the first GWAS signal specific for aggressive bladder cancer. Molecular mechanisms of this genetic association may be related to cyclin E overexpression and alteration of cell cycle in carriers of CCNE1 risk variants. In combination with established bladder cancer risk factors and other somatic and germline genetic markers, the CCNE1 variants could be useful for inclusion into bladder cancer risk prediction models.
    Matched MeSH terms: Urinary Bladder Neoplasms/genetics*; Urinary Bladder Neoplasms/pathology
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