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Bladder Cancer

Bladder cancer is a disease in which malignant cells arise in the bladder. Symptoms can include blood in the urine, pain during urination, increased frequency of passing urine, or feeling the need to urinate but with nothing coming out. The bulk of bladder cancers are histlogically classed as transitional cell carcinomas which arise in the uroepithelium (lining of the bladder). Other types include squamous cell carcinomas, and adenocarcinomas. Treatment will depend on how far the tumour has invaded the surrounding tissues, and if it has spread to other parts of the body. World-wide about 260,000 people are diagnosed with bladder cancer each year.

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Molecular Biology of Bladder Cancer
Urinary System Cancers

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  • PubMed search for publications about Bladder Cancer - Limit search to: [Reviews]

    PubMed Central search for free-access publications about Bladder Cancer
    MeSH term: Urinary Bladder Neoplasms
    International US National Library of Medicine
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Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Pacella E, Ricci F, Colecchia M, et al.
Prostatic and urothelial metastasis in the same lymph node: a case report.
Anal Quant Cytopathol Histpathol. 2015; 37(2):139-43 [PubMed] Related Publications
BACKGROUND: Collision metastasis is a rare phenomenon in which metastases of carcinoma from 2 separate primary tumors occur in the same lymph node. We summarize here the clinical course and highlight the histological challenges in the diagnosis of this rare phenomenon.
CASE: A biopsy performed due to gross hematuria by endoscopic resection revealed an infiltrative high-grade urothelial carcinoma in a 75-year-old man receiving androgen deprivation therapy due to biopsy-proven high-grade prostate cancer. A radical cystectomy, with regional lymphadenectomy and prostatectomy, was performed. Three nodes appeared to have metastatic foci from both primary tumors: prostatic and urothelial cancer. The presence of the 2 tumor types colliding in the same lymph nodes was confirmed by immunohistochemical stains.
CONCLUSION: In a patient with simultaneous tumors it is important to remember that a part of lymph node metastases with histological polymorphic appearance may result from a collision metastasis. In light of the important therapeutic consequences, a differential diagnosis is needed, suggesting appropriate immunohistochemical investigations.

Milojevic B, Dzamic Z, Kajmakovic B, et al.
Urothelial carcinoma: Recurrence and risk factors.
J BUON. 2015 Mar-Apr; 20(2):391-8 [PubMed] Related Publications
Urothelial carcinomas are malignant tumors that arise from the urothelial epithelium and may involve the lower and upper urinary tract. They are characterized by multiple, multifocal recurrences throughout the genitourinary tract. Bladder tumors account for 90-95% of urothelial carcinomas and are the most common malignancies of the urinary tract. Upper urinary tract urothelial carcinomas (UTUC) are relatively rare, accounting for 5% of urothelial tumors. The incidence of subsequent bladder cancer after surgical treatment for UTUC is approximately 15-50%. In contrast, patients with a primary tumor of the bladder have a low risk (2-6%) the development of UTUC. Identification of prognostic factors and early detection of recurrent disease provide a better strategy for postoperative monitoring, surveillance, and potentially improve patient outcomes. In this review study we discuss the main risk factors for UTUC recurrence after radical cystectomy, and risk factors for intravesical recurrence after radical nephroureterectomy.

Baack Kukreja JE, Scosyrev E, Brasacchio RA, et al.
Bladder cancer incidence and mortality in patients treated with radiation for uterine cancer.
BJU Int. 2014; 114(6):844-51 [PubMed] Related Publications
OBJECTIVE: To estimate the effect of radiation therapy (RT) administered for uterine cancer (UtC) on bladder cancer (BC) incidence, tumour characteristics at presentation, and mortality.
PATIENTS AND METHODS: In this retrospective cohort study, records of 56 681 patients diagnosed with UtC as their first primary malignancy during 1980-2005 were obtained from the Surveillance, Epidemiology and End-Results (SEER) database. Follow-up for incident BC ended on 31 December 2008. Occurrences of BC diagnoses and BC deaths in patients with UtC managed with or without RT were summarised with counts and person-time incidence rates (counts divided by person-years of observation). Age adjustment of rates was performed by direct standardisation. Incident BC cases were described in terms of histological types, grades and stages.
RESULTS: With a mean follow-up of 15 years, BC was diagnosed in 146 (0.93%) of 15 726 patients with UtC managed with RT, and in 197 (0.48%) of 40 955 patients with UtC managed without RT, with an age-adjusted rate ratio of 2.0 (95% confidence interval [CI] 1.6-2.5). Fatal BC occurred in 39 (0.25%) and 36 (0.09%) of patients with UtC managed with vs without RT, respectively, with an age-adjusted rate ratio of 2.9 (95% CI 1.8-4.6). Incident BC cases diagnosed in patients with UtC managed with vs without RT had similar distributions of histological types, grades, and stages.
CONCLUSIONS: Use of RT for UtC is associated with increased BC incidence and mortality later in life. Heightened awareness should help identify women with new voiding symptoms or haematuria, all of which should be fully evaluated.

Guo LS, Li HX, Li CY, et al.
Vitamin D3 enhances antitumor activity of metformin in human bladder carcinoma SW-780 cells.
Pharmazie. 2015; 70(2):123-8 [PubMed] Related Publications
OBJECTIVE: To study the effects of vitamin D3 combined with metformin on the proliferation and apoptosis in human bladder cancer cell line SW-780 and its possible mechanism.
METHODS: MTT assay and fluorescence microscope observations were used to study the effects of vitamin D3 combined with metformin on the proliferation and apoptosis of SW-780 cells in vitro. Western blot was used to detect the expression of apoptosis-related proteins p-Bcl-2, Bax, Cyclin D1, c-Myc and related signaling pathways activated proteins p-IGF-IR, p-mTOR, p-P70S6K, p-S6.
RESULTS: MTT results showed that 320 μg/ml vitamin D3 combined with 620 μg/ml metformin acting on cells for 48h had a significant synergistic effect on proliferation. Fluorescence microscope observations showed that compared with negative control group and monotherapy treatment group, the apoptosis features of combination treatment group were obvious and the apoptosis rate increased greatly. Western blot showed that compared with the negative control group and monotherapy treatment group, the expression levels of p-Bcl-2, Cyclin D1 and c-Myc in combination treatment group significantly decreased, whereas the expression level of Bax significantly increased, and the expression levels of p-IGF-IR, p-mTOR, p-P70S6K and p-S6 in combination treatment group significantly decreased.
CONCLUSION: Vitamin D3 combined with metformin exhibited obvious inhibitory effects on the cell proliferation and apoptosis induction in SW-780 cells. The underlying anti-tumor mechanism might be related to inhibiting the expressions of p-Bcl-2, Cyclin D1, c-Myc, p-IGF-IR, p-mTOR, p-P70S6K, p-S6 and activating the expression of Bax.

El-Gamal EM, Gouida MS
Flow cytometric study of cell cycle and DNA ploidy in bilharzial bladder cancer.
Clin Lab. 2015; 61(3-4):211-8 [PubMed] Related Publications
BACKGROUND: Tumor grade and stage are currently the most important prognostic variables in bladder cancer but establishing additional criteria is still needed for effective treatment. In this study, we analyzed DNA ploidy and the cell cycle: gap one stage (GO/1), synthesis stage (S-phase%), and gap two stage (G2/M) in urine and blood cells of bilharzial bladder cancer patients.
METHODS: The cell cycle and DNA ploidy were investigated using a flow cytometric technique for 150 bilharzial bladder cancer patients and 60 healthy normal controls.
RESULTS: This study demonstrated that GO/1 levels were significantly decreased in urine and blood cells of bladder cancer patients compared to controls and these decreases were significant in urine cells compared to blood cells and at high grade and stage. In contrast, S-phase%, G2/M, coefficient variation (CV), and DNA index (DI) levels were increased in urine and blood cells of patients compared to those of controls. These levels were significantly increased in urine patients compared to their blood. Finally, the undetectable DNA aneuploidy in control cells was significantly increased in urine cells of patients compared to their blood cells at higher grade and stage.
CONCLUSIONS: Taken together, the cell cycle and DNA aneuploidy analysis especially in urine cells of bilharzial bladder cancer patients may help in diagnosis, prognosis, and clinical treatment and can be considered as an additional marker for bladder cancer.

Milošević R, Milović N, Aleksić P, et al.
Difference in recurrence frequencies of non-muscle-invasive-bladder tumors depending on optimal usage of intravesical immunotherapy of bacillus Calmette-Guérin.
Vojnosanit Pregl. 2015; 72(3):241-6 [PubMed] Related Publications
BACKGROUND/AIM: The therapy with intravesical instillation of bacillus Calmette-Guérin (BCG) after transurethral resection (ITJR) 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.

Xu C, Zeng XT, Liu TZ, et al.
Fruits and vegetables intake and risk of bladder cancer: a PRISMA-compliant systematic review and dose-response meta-analysis of prospective cohort studies.
Medicine (Baltimore). 2015; 94(17):e759 [PubMed] Related Publications
Clinical practice recommends eating ≥2.5 cups of fruits and vegetables (FVs) each day for cancer prevention, in which the evidence from epidemiological studies for the association between FVs intake and bladder cancer (BC) prevention is inconsistent.We searched the PubMed, Embase, and Willy online Library for relevant studies published up to September 27, 2014. Prospective cohort studies investigated FVs intake, and the risk of BC with ≥3 categories of exposure was included. A dose-response meta-analysis was carried out to evaluate the association between FVs intake and risk of BC.Fourteen cohorts with 17 studies including 9447 cases were identified. No evidence of nonlinear association was examined between FVs intake and risk of BC. The summarized relevant risk (RR) of every 0.2 serving increment a day was 1.00 (95%CI: 0.99, 1.00; P = 0.17; I = 41.7%; n = 14) for total fruits; 0.99 (95%CI: 0.96, 1.01; P = 0.28; I = 37.0%; n = 13) for total vegetables; and 0.99 (95%CI: 0.97, 1.01; P = 0.24; I = 57.5%; n = 8) for both FVs. In further analysis, we observed inverse association between every 0.2 serving increment of green leafy vegetables intake a day and risk of BC (RR = 0.98, 95%CI: 0.96, 0.99; I = 0.0%; P < 0.01; Power = 0.76; n = 6), but neither for cruciferous vegetables (RR = 0.97, 95%CI: 0.93, 1.01; P = 0.19; I = 55.8%; n = 8) nor for citrus (RR = 1.00, 95%CI: 1.00, 1.00; P = 0.83; I = 0.0%; n = 7). Subgroup analysis showed consistent results.Little evidence supports a beneficial effect for total fruits, vegetables, both FVs, and citrus intake against bladder cancer. Green leafy vegetables may help prevent bladder cancer.

Wang X, Zhang L, Ding N, et al.
Identification and characterization of DNAzymes targeting DNA methyltransferase I for suppressing bladder cancer proliferation.
Biochem Biophys Res Commun. 2015; 461(2):329-33 [PubMed] Related Publications
Epigenetic inactivation of genes plays a critical role in many important human diseases, especially in cancer. A core mechanism for epigenetic inactivation of the genes is methylation of CpG islands in genome DNA, which is catalyzed by DNA methyltransferases (DNMTs). The inhibition of DNMTs may lead to demethylation and expression of the silenced tumor suppressor genes. Although DNMT inhibitors are currently being developed as potential anticancer agents, only limited success is achieved due to substantial toxicity. Here, we utilized a multiplex selection system to generate efficient RNA-cleaving DNAzymes targeting DNMT1. The lead molecule from the selection was shown to possess efficient kinetic profiles and high efficiency in inhibiting the enzyme activity. Transfection of the DNAzyme caused significant down-regulation of DNMT1 expression and reactivation of p16 gene, resulting in reduced cell proliferation of bladder cancers. This study provides an alternative for targeting DNMTs for potential cancer therapy.

Jordan EJ, Iyer G
Targeted therapy in advanced bladder cancer: what have we learned?
Urol Clin North Am. 2015; 42(2):253-62, ix [PubMed] Related Publications
Despite advances in the treatment of other genitourinary malignancies, no novel therapies have been approved by the US Food and Drug Administration for urothelial carcinoma (UC) in the last 20 years. To date, no clinical trials of targeted agents in UC have led to improvements in survival compared with cytotoxic therapy. This article outlines representative trials of targeted therapies in UC and discusses the significance of genetic preselection in trial design as a method to optimize responses to these agents, thus, hopefully expanding the armamentarium of treatment options against this lethal disease.

Johnson DC, Greene PS, Nielsen ME
Surgical advances in bladder cancer: at what cost?
Urol Clin North Am. 2015; 42(2):235-52, ix [PubMed] Related Publications
Bladder cancer is the most expensive cancer to treat from diagnosis to death. Frequent disease recurrence, intense follow-up, and expensive, invasive techniques for diagnosis and treatment drive these costs for non-muscle invasive bladder cancer. Fluorescence cystoscopy increases the detection of superficial bladder cancer and reduces costs by improving the quality of resection and reducing recurrences. Radical cystectomy with intestinal diversion is the mainstay of treatment of invasive disease; however it is associated with substantial cost and morbidity. Increased efforts to improve the surgical management of bladder cancer while reducing the cost of treatment are increasingly necessary.

Lucca I, de Martino M, Klatte T, Shariat SF
Novel biomarkers to predict response and prognosis in localized bladder cancer.
Urol Clin North Am. 2015; 42(2):225-33, ix [PubMed] Related Publications
This review summarizes recent developments in diagnostic and prognostic biomarkers for nonmuscle invasive bladder cancer (NMIBC). Although the number of new biomarkers increases continuously, none are included in practice guidelines. Most NMIBC biomarkers show a higher sensitivity than urinary cytology, but lower specificity. Some protein and chromosome markers have been approved for screening and follow-up of patients in combination with cystoscopy. The long interval required for validation, testing, and approval of the assays and the lack of standardization could explain present issues in biomarker research. To enhance the development of new biomarkers, a more structured approach is required.

Balar AV, Milowsky MI
Neoadjuvant therapy in muscle-invasive bladder cancer: a model for rational accelerated drug development.
Urol Clin North Am. 2015; 42(2):217-24, viii-ix [PubMed] Related Publications
Since the advent of cisplatin-based combination therapy in the management of muscle-invasive and advanced bladder cancer, there has been little progress in improving outcomes for patients. Novel therapies beyond cytotoxic chemotherapy are needed. The neoadjuvant paradigm lends to acquiring ample pretreatment and posttreatment tumor tissue as a standard of care, which enables comprehensive biomarker analyses to better understand mechanisms of both response and resistance, which will aid drug development. This article discusses the evolution of neoadjuvant therapy as standard treatment and the role it may serve toward the development of novel therapies.

Mitra AP, Lerner SP
Potential role for targeted therapy in muscle-invasive bladder cancer: lessons from the cancer genome atlas and beyond.
Urol Clin North Am. 2015; 42(2):201-15, viii [PubMed] Related Publications
The Cancer Genome Atlas project has identified and confirmed several important molecular alterations that form the basis for tumorigenesis and disease progression in muscle-invasive bladder cancer. Profiling studies also have reported on validated biomarker panels that predict prognosis and may be used to identify patients who require more aggressive therapy. This article describes the major molecular alterations in muscle-invasive urothelial carcinoma, and how several of these are being investigated as targets for novel therapeutics. It also highlights studies that identify biomarkers for platinum sensitivity, and efforts to integrate targeted therapeutics and companion theranostics for personalized treatment of muscle-invasive bladder cancer.

Cha EK, Donahue TF, Bochner BH
Radical transurethral resection alone, robotic or partial cystectomy, or extended lymphadenectomy: can we select patients with muscle invasion for less or more surgery?
Urol Clin North Am. 2015; 42(2):189-99, viii [PubMed] Related Publications
Improvements in the accuracy of clinical staging and refinements in patient selection may allow for improved outcomes of bladder-preservation strategies for muscle-invasive bladder cancer incorporating radical transurethral resection (TUR) and partial cystectomy (PC). Retrospective studies of patients treated with radical cystectomy and pelvic lymph node dissection have reported an association between greater extent of lymphadenectomy and improved clinical outcomes. However, there is no consensus regarding the optimal extent of lymphadenectomy, as there are currently no reports from prospective, randomized trials to address this issue in regards to cancer-specific and overall survival. Future advances in the understanding of the appropriate extent of lymphadenectomy requires well-designed prospective clinical trials that directly compare varying extents of surgery with their ability to provide local and distant disease control and disease-specific survival.

Sfakianos JP, Galsky MD
Neoadjuvant chemotherapy in the management of muscle-invasive bladder cancer: bridging the gap between evidence and practice.
Urol Clin North Am. 2015; 42(2):181-7, viii [PubMed] Related Publications
Although cisplatin-based chemotherapy followed by radical cystectomy is the standard treatment of muscle-invasive bladder cancer, population-based studies reveal that only a small fraction of patients actually receive such treatment. A comprehensive understanding of the reasons for this gap between efficacy and effectiveness is necessary to increase the likelihood of cure of all patients with muscle-invasive bladder cancer. These reasons include systems-, provider-, and patient-level barriers that are not amenable to a single solution. Tackling each barrier will ultimately be necessary to bridge the disconnect between what is achievable and what is actually achieved.

Premo C, Apolo AB, Agarwal PK, Citrin DE
Trimodality therapy in bladder cancer: who, what, and when?
Urol Clin North Am. 2015; 42(2):169-80, vii [PubMed] Article available free on PMC after 01/05/2016 Related Publications
Radical cystectomy is a standard treatment of nonmetastatic, muscle-invasive bladder cancer. Treatment with trimodality therapy consisting of maximal transurethral resection of the bladder tumor followed by concurrent chemotherapy and radiation has emerged as a method to preserve the native bladder in highly motivated patients. Several factors can affect the likelihood of long-term bladder preservation after trimodality therapy and therefore should be taken into account when selecting patients. New radiation techniques such as intensity modulated radiation therapy and image-guided radiation therapy may decrease the toxicity of radiotherapy in this setting. Novel chemotherapy regimens may improve response rates and minimize toxicity.

Boehm BE, Svatek RS
Novel therapeutic approaches for recurrent nonmuscle invasive bladder cancer.
Urol Clin North Am. 2015; 42(2):159-68, vii [PubMed] Related Publications
This article summarizes strategies being investigated in patients with nonmuscle invasive bladder cancer. Progress has been made toward improving the delivery method of intravesical agents. Intravesical therapy is limited by the amount of time that the agent remains in contact with the bladder. Bladder cancer is considered to be responsive to immune therapy. Thus, many novel approaches are immune-based therapies and include cancer vaccines, use of Bacillus Calmette-Guérin (BCG) subcomponents, and checkpoint inhibitors. Finally, access to bladder mucosa via direct catheterization into the bladder via the urethra has enabled unique strategies for delivery of cancer therapy including viral- or plasmid-based gene therapy.

Zlatev DV, Altobelli E, Liao JC
Advances in imaging technologies in the evaluation of high-grade bladder cancer.
Urol Clin North Am. 2015; 42(2):147-57, vii [PubMed] Article available free on PMC after 01/05/2016 Related Publications
Bladder cancer ranges from a low-grade variant to high-grade disease. Assessment for treatment depends on white light cystoscopy, however because of its limitations there is a need for improved visualization of flat, multifocal, high-grade, and muscle-invasive lesions. Photodynamic diagnosis and narrow-band imaging provide additional contrast enhancement of bladder tumors and have been shown to improve detection rates. Confocal laser endomicroscopy and optical coherence tomography enable real-time, high-resolution, subsurface tissue characterization with spatial resolutions similar to histology. Molecular imaging offers the potential for the combination of optical imaging technologies with cancer-specific molecular agents to improve the specificity of disease detection.

Mata DA, Groshen S, Von Rundstedt FC, et al.
Variability in surgical quality in a phase III clinical trial of radical cystectomy in patients with organ-confined, node-negative urothelial carcinoma of the bladder.
J Surg Oncol. 2015; 111(7):923-8 [PubMed] Related Publications
BACKGROUND AND OBJECTIVES: Previous studies have shown that variability in surgical technique can affect the outcomes of cooperative group trials. We analyzed measures of surgical quality and clinical outcomes in patients enrolled in the p53-MVAC trial.
METHODS: We performed a post-hoc analysis of patients with pT1-T2N0M0 urothelial carcinoma of the bladder following radical cystectomy (RC) and bilateral pelvic and iliac lymphadenectomy (LND). Measures of surgical quality were examined for associations with time to recurrence (TTR) and overall survival (OS).
RESULTS: We reviewed operative and/or pathology reports for 440 patients from 35 sites. We found that only 31% of patients met all suggested trial eligibility criteria of having ≥15 lymph nodes identified in the pathologic specimen (LN#) and having undergone both extended and presacral LND. There was no association between extent of LND, LN#, or presacral LND and TTR or OS after adjustment for confounders and multiple testing.
CONCLUSIONS: We demonstrated that there was substantial variability in surgical technique within a cooperative group trial. Despite explicit entry criteria, many patients did not undergo per-protocol LNDs. While outcomes were not apparently affected, it is nonetheless evident that careful attention to study design and quality monitoring will be critical to successful future trials.

Huang YL, Chen J, Yan W, et al.
Diagnostic accuracy of cytokeratin-19 fragment (CYFRA 21-1) for bladder cancer: a systematic review and meta-analysis.
Tumour Biol. 2015; 36(5):3137-45 [PubMed] Related Publications
Previous studies have evaluated the accuracy of serum and urinary measurements of cytokeratin-19 fragment (CYFRA 21-1) for the diagnosis of bladder cancer; however, the results have been inconsistent. The aim of this study was to evaluate the overall accuracy of CYFRA 21-1 for the diagnosis of bladder cancer. We performed a search for English-language publications reporting on the detection of CYFRA21-1 levels for the diagnosis of bladder cancer through November 2, 2014, using public medical databases, including EMBASE, Web of Science, and Medline. The quality of the studies was assessed by revised QUADAS tools. The performance characteristics were pooled and analyzed using a bivariate model. Publication bias was explored with the Deek's test. Sixteen studies, with a total 1,262 bladder-cancer patients and 1,233 non-bladder-cancer patients, were included in the study. The pooled sensitivities for serum and urine CYFRA 21-1 were 0.42 (95 % confidence interval (CI), 0.33-0.51) and 0.82 (95 % CI, 0.70-0.90), respectively. The corresponding specificities were 0.94 (95 % CI, 0.90-0.96) and 0.80 (95 % CI, 0.73-0.86), respectively. The areas under the summary receiver-operating-characteristic curves for serum and urine CYFRA 21-1 were 0.88 (95 % CI, 0.85-0.91) and 0.87 (95 % CI, 0.84-0.90), respectively. The major design deficiencies of the included studies were participant-selection bias, potential review, and verification bias. Therefore, we concluded that both serum and urine CYFRA 21-1 served as efficient indexes for bladder-cancer diagnosis. Additional, well-designed studies should be performed to rigorously evaluate the diagnostic value of CYFRA 21-1 for bladder cancer.

Dell'Atti L
Relevance of prostate cancer in patients with synchronous invasive bladder urothelial carcinoma: a monocentric retrospective analysis.
Arch Ital Urol Androl. 2015; 87(1):76-9 [PubMed] Related Publications
OBJECTIVES: We retrospectively reviewed data of patients with incidental prostate cancer (PCa) who underwent radical cystoprostatectomy (RCP) for invasive bladder cancer and we analyzed their features with regard to incidence, pathologic characteristics, clinical significance, and implications for management.
MATERIAL AND METHODS: Clinical data and pathological features of 64 patients who underwent standard RCP for bladder cancer were included in this study. Besides the urothelial carcinoma of the urinary bladder, the location and tumor volume of the PCa, prostate apex involvement, Gleason score, pathological staging and surgical margins were evaluated. Clinically significant PCa was defined as a tumor with a Gleason 4 or 5 pattern, stage ≥ pT3, lymph node involvement, positive surgical margin or multifocality of three or more lesions. Postoperative follow-up was scheduled every 3 months in the first year, every 6 months in the second and third year, annually thereafter.
RESULTS: 11 out of 64 patients (17.2%) who underwent RCP had incidentally diagnosed PCa. 3 cases (27.3%) were diagnosed as significant PCa, while 8 cases (72.7%) were clinically insignificant. The positive surgical margin of PCa was detected in 1 patient with significant disease. The prostate apex involvement was present in 1 patient of the significant PCa group. Median follow-up period was 47.8 ± 29.2 (range 4-79). During the follow-up, biochemical recurrence occurred in 1 patient (9%). Concerning the cancer specific survival there was no statistical significance (P = 0.326) between the clinically significant and clinical insignificant cancer group.
CONCLUSIONS: In line with published studies, incidental PCa does not impact on the prognosis of bladder cancer of patients undergoing RCP.

Fonseka T, Ahmed K, Froghi S, et al.
Comparing robotic, laparoscopic and open cystectomy: a systematic review and meta-analysis.
Arch Ital Urol Androl. 2015; 87(1):41-8 [PubMed] Related Publications
OBJECTIVE: To conduct a systematic review and meta-analysis comparing outcomes between Open Radical Cystectomy (ORC), Laparoscopic Radical Cystectomy (LRC) and Robot-assisted Radical Cystectomy (RARC). RARC is to be compared to LRC and ORC and LRC compared to ORC.
MATERIAL AND METHODS: A systematic review of the literature was conducted, collating studies comparing RARC, LRC and ORC. Surgical and oncological outcome data were extracted and a meta-analysis was performed.
RESULTS: Twenty-four studies were selected with total of 2,104 cases analyzed. RARC had a longer operative time (OPT) compared to LRC with no statistical difference between length of stay (LOS) and estimated blood loss (EBL). RARC had a significantly shorter LOS, reduced EBL, lower complication rate and longer OPT compared to ORC. There were no significant differences regarding lymph node yield (LNY) and positive surgical margins (PSM.) LRC had a reduced EBL, shorter LOS and increased OPT compared to ORC. There was no significant difference regarding LNY.
CONCLUSION: RARC is comparable to LRC with better surgical results than ORC. LRC has better surgical outcomes than ORC. With the unique technological features of the robotic surgical system and increasing trend of intra-corporeal reconstruction it is likely that RARC will become the surgical option of choice.

Tadin T, Sotosek S, Rahelić D, Fuckar Z
Diagnostic accuracy of ultrasound T-staging of the urinary bladder cancer in comparison with histology in elderly patients.
Coll Antropol. 2014; 38(4):1123-6 [PubMed] Related Publications
Urinary bladder cancer (UBC) is dominantly the cancer of the elderly occurring primarily in the 6h, 7!h and 81h decade of life. The aim of this study was to evaluate diagnostic accuracy of ultrasound T-staging (UTS) of UBC in dhe group of elderly patients. In 152 elderly patients referred to transabdominal ultrasound examination in two different facilities (76 each) due to various symptoms (primarily painless gross or microscopic haematuria) UBC was diagnosed. Initial UTS at the moment of detection was performed and compared with final histological T-staging (HTS). A high level of conformity between UTS and HTS was detected. In a total of 152 patients with UBC there were 115 (75.66%) patients with complete match between the UTS and HTS, 24 (15.79%) patients with minimal variation within one stage, and 13 (8.55%) patients with one stage difference between the UTS and HTS. The best result was established for the stage T1, where the accuracy was 94.5%. In other stages the accuracy was between 84.9% and 91.8%. The Youden's index for all the stages was over 0.6. UTS has a high diagnostic accuracy, especially for stages T1 and T2. It is extremely useful tool in differentiating the superficial UBC from the muscle-invasive one, being of significant importance in planning the further treatment of elderly patients and having important role in choosing appropriate surgical approach.

Wen J, Li HZ, Ji ZG, Jin J
Effects of sunitinib malate on growth of human bladder transitional cell line T24 in vitro.
Chin Med Sci J. 2015; 30(1):51-5 [PubMed] Related Publications
OBJECTIVE: To investigate the growth-inhibitory effect of sunitinib malate on human bladder transitional cell carcinoma (TCC) in vitro.
METHODS: Human bladder TCC cell line T24 was cultured and exposed to graded concentrations of sunitinib malate for 72 hours in vitro to determine the sensitivities to drug. Cell viability was measured by MTT assay. Cell apoptotic morphology was observed by fluorescence microscope following DAPI staining. Band expressions of Fas, Fas ligand, poly (ADP-ribose) polymerase (PARP) and β-actin were analyzed by Western blot. Wound healing process of T24 cells exposed to sunitinib malate was assayed.
RESULTS: Sunitinib malate exerted a concentration-dependent and time-dependent inhibitory effect on the T24 cell lines. Fluorescence microscopy showed that small vacuoles appeared in the nuclei of T24 cells and the vacuoles were bigger with higher drug concentrations. The expressions of Fas ligand and PARP in T24 cells treated with sunitinib malate exhibited a concentration-dependent increase. Moreover sunitinib malate suppressed the wound healing process in a concentration-dependent manner.
CONCLUSION: Sunitinib malate exerted marked inhibitory activity against bladder cancer cell line T24.

Seront E, Machiels JP
Molecular biology and targeted therapies for urothelial carcinoma.
Cancer Treat Rev. 2015; 41(4):341-53 [PubMed] Related Publications
Metastatic urothelial cancer (UC) is associated with poor prognosis. In the first-line setting, platinum-based chemotherapy is the standard of care but resistance rapidly occurs. With no validated treatment proven to increase survival after platinum failure, there is an urgent unmet medical need to develop new and efficacious cytotoxic agents. A better understanding of the molecular signaling pathways regulating UC has led to the development of new and innovative therapeutic strategies. Despite this, many recent drugs show only modest activity as single agents, and combining them with standard chemotherapy does not seem to enhance efficacy. Ongoing research is producing, however, a generation of new drugs that are showing promising results in clinical trials. This paper aims to review the most important mechanisms in bladder cancer tumorigenesis and describe the new therapeutic options currently undergoing evaluation in clinical trials.

Cheah MT, Chen JY, Sahoo D, et al.
CD14-expressing cancer cells establish the inflammatory and proliferative tumor microenvironment in bladder cancer.
Proc Natl Acad Sci U S A. 2015; 112(15):4725-30 [PubMed] Article available free on PMC after 01/05/2016 Related Publications
Nonresolving chronic inflammation at the neoplastic site is consistently associated with promoting tumor progression and poor patient outcomes. However, many aspects behind the mechanisms that establish this tumor-promoting inflammatory microenvironment remain undefined. Using bladder cancer (BC) as a model, we found that CD14-high cancer cells express higher levels of numerous inflammation mediators and form larger tumors compared with CD14-low cells. CD14 antigen is a glycosyl-phosphatidylinositol (GPI)-linked glycoprotein and has been shown to be critically important in the signaling pathways of Toll-like receptor (TLR). CD14 expression in this BC subpopulation of cancer cells is required for increased cytokine production and increased tumor growth. Furthermore, tumors formed by CD14-high cells are more highly vascularized with higher myeloid cell infiltration. Inflammatory factors produced by CD14-high BC cells recruit and polarize monocytes and macrophages to acquire immune-suppressive characteristics. In contrast, CD14-low BC cells have a higher baseline cell division rate than CD14-high cells. Importantly, CD14-high cells produce factors that further increase the proliferation of CD14-low cells. Collectively, we demonstrate that CD14-high BC cells may orchestrate tumor-promoting inflammation and drive tumor cell proliferation to promote tumor growth.

Barabás-Hajdu E, Maier A, Coroş F, Mártha O
Retrovesical hydatidosis associated with urinary tract pathology - case report.
Acta Microbiol Immunol Hung. 2015; 62(1):21-7 [PubMed] Related Publications
Cystic hydatidosis (CH) is a worldwide distributed parasitic zoonosis. It is considered one of the 17 neglected parasitic tropical diseases, among cysticercosis and soil transmitted helminthiases. CH is caused by the larval stage of Echinococcus granulosus, a tapeworm that usually infects dogs and other carnivorous animals as definitive hosts and herbivorous animals and rarely humans as intermediate hosts. Main primary localizations are the liver and the lung. In less than 3% they can primarily be present in the spleen. Treatment is mainly surgical, in some cases resulting in reoccurrence. In this paper we present the case of a male 55 years old patient who underwent a surgical intervention on his spleen for a solitary hydatid cyst as primary localization. Fifteen years after the operation the patient presented macroscopic haematuria; routine laboratory findings presented soft eosinophilia, 5%, without any other modification. There was found no palpable tumour in the pelvis by rectal examination. Abdominal ultrasound investigation revealed a 2×1 cm formation in the urinary bladder at the base of the left bladder-wall and a retrovesical, inhomogeneous 10×10 cm tumour with multiple septa and transonic zones. Computed tomography (CT) scan strongly suggested the presence of a bladder tumour and a hydatid cyst. The symptoms caused by the bladder tumour revealed the co-existing non-symptomatic retrovesical secondary CH, which is a rare complication of splenic Echinococcus granulosus infection. Close follow-up and a proper pre- and postoperative anti-parasitic medication of the patient could have prevented reoccurrence of CH.

Palleschi G, Pastore AL, Ripoli A, et al.
Videourodynamic evaluation of intracorporeally reconstructed orthotopic U-shaped ileal neobladders.
Urology. 2015; 85(4):883-9 [PubMed] Related Publications
OBJECTIVE: To study the functional outcomes of 30 patients who had previously undergone laparoscopic radical cystectomy with intracorporeal orthotopic ileal neobladder reconstruction using videourodynamic (VUDM) assessment 180 days postoperatively.
METHODS: Between November 2010 and December 2013, 30 male patients had undergone laparoscopic radical cystectomy with bilateral standard pelvic lymphadenectomy and pure laparoscopic orthotopic ileal U-shaped neobladder diversion. The demographic data were as follows: median age, 67 years (range, 62-79); body mass index, 22.3 kg/m(2) (range, 16-26.1 kg/m(2)); and mean American Society of Anesthesiologists score 2.2 (range, 1-3). Functional outcomes were assessed performing a standard VUDM study combined with perineal floor electromyography 180 days postoperatively.
RESULTS: VUDM evaluations showed good functional outcomes of the reservoirs. Mean maximal neobladder capacity was 287 mL (range, 210-335 mL). Residual peristaltic activity was observed in all the individuals evaluated; however, only 9 of 30 individuals (30%) displayed severe peristaltic activity. Six of these 9 individuals (66.6%) experienced urinary leakage during these contractions. Mean postvoid residual volume was 44 mL (range, 0-105 mL), and peak flow rate was 13.9 mL/s (range, 9.7-29.2 mL/s). The Valsalva maneuver was positive in 5 of 30 subjects (17%). Bladder morphology assessed during contrast cystography showed the desired U-shape in all cases. Ureteral reflux was observed in 7 of 30 individuals (23.3%).
CONCLUSION: Based on VUDM, our study shows that U-shaped ileal neobladders achieved by a totally laparoscopic approach obtained good functional outcomes. These findings support the evidence that a minimally invasive approach does not impose technical limitations that negatively impact the surgical results.

Haddad AQ, Singla N, Gupta N, et al.
Association of distance to treatment facility on quality and survival outcomes after radical cystectomy for bladder cancer.
Urology. 2015; 85(4):876-82 [PubMed] Related Publications
OBJECTIVE: To examine the association of travel distance on quality and survival outcome measures for bladder cancer patients undergoing radical cystectomy for urothelial carcinoma.
METHODS: Four hundred eight patients who underwent radical cystectomy for bladder cancer at a single institution from 2007 to 2013 were included. Multivariate logistic regression was used to determine the association of distance from treatment facility with 90-day mortality and quality-of-care endpoints including neoadjuvant chemotherapy use and time to cystectomy. Survival was assessed by multivariate Cox regression.
RESULTS: Fifty-seven percent of patients lived within 50 miles of the treatment facility. There was no difference in time to cystectomy or the utilization of neoadjuvant chemotherapy between patients in different distance groups. On multivariate analysis, distance to treatment facility was the only predictor of 90-day mortality (odds ratio, 11.20; 95% confidence interval, 2.27-55.43; P = .003, for patients traveling >150 vs <50 miles). Although there was no difference in recurrence and cancer-specific survival between distance groups, greater distance was associated with worse overall survival on multivariate analysis (hazard ratio, 1.59; 95% confidence interval, 0.99-2.56; P = .05, for patients traveling >150 vs <50 miles).
CONCLUSION: Distance to treatment facility did not impact quality measures including time to cystectomy or use of neoadjuvant chemotherapy, and there was no difference in cancer-specific mortality between distance groups. There was a detrimental association of increased travel distance with 90-day mortality, which could reflect disparities in access to care after cystectomy.

de Souza D, Mariano DO, Nedel F, et al.
New organochalcogen multitarget drug: synthesis and antioxidant and antitumoral activities of chalcogenozidovudine derivatives.
J Med Chem. 2015; 58(8):3329-39 [PubMed] Related Publications
In this article we present the synthesis, characterization, and in vitro biological and biochemical activities of new chalcogenozidovudine derivatives as antioxidant (inhibition of TBARS in brain membranes and thiol peroxidase-like activity) as well as antitumoral agents in bladder carcinoma 5637. A prominent response was obtained for the selected chalcogenonucleosides, showing effective antioxidant and antitumoral activities.

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