Bladder Cancer
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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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Information for Patients and the Public
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Latest Research Publications
Molecular Biology of Bladder Cancer
Urinary System Cancers

Information Patients and the Public (16 links)

Information for Health Professionals / Researchers (8 links)

Latest Research Publications

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

Allchorne P, Lamb BW, Kinsella J, et al.
Initial experience of intravesical gemcitabine for patients with high-risk superficial transitional cell carcinoma of the bladder following BCG failure.
Urol Nurs. 2014 Mar-Apr; 34(2):95-9 [PubMed] Related Publications
This study reports the use of intravesical gemcitabine in managing patients with high-risk bladder cancer, refractory to Bacillus Calmette-Guerin (BCG). Patients were given gemcitibine; treatment response was evaluated by fluorescence-cystoscopy biopsy and urine cytology. Time to reoccurrence increased with instillation time.

Related: Transitional Cell Cancer of the Renal Pelvis and Ureter Gemcitabine

Dai J, Caldamone AA, Ellermeier CJ, Ellsworth P
A case report and review of transitional cell carcinoma in children.
Urol Nurs. 2014 Mar-Apr; 34(2):75-82 [PubMed] Related Publications
Transitional cell carcinoma (TCC) is a rare cause of hematuria in children. This type of urothelial bladder tumor is typically low grade and carries a good prognosis. In this article, a case report is presented along with a review of the literature on TCC in children.

Related: Transitional Cell Cancer of the Renal Pelvis and Ureter

Cormio L, Sanguedolce F, Massenio P, et al.
Osseous metaplasia within a urothelial bladder cancer nodal metastasis: a case report.
Anal Quant Cytol Histol. 2014; 36(2):117-9 [PubMed] Related Publications
BACKGROUND: Osseous metaplasia within bladder cancer is extremely rare and, to our knowledge, has not been previously reported within a urothelial bladder carcinoma (UBC) nodal metastasis.
CASE: A 78-year-old man underwent radical cystoprostatectomy because of high-grade pT2 UBC. Pathology revealed a high-grade pT4aN2 UBC with osseous metaplasia into a massively metastatic lymph node but not into the primary bladder tumor.
CONCLUSION: Based independently on its location, this finding warrants a careful differential diagnosis with sarcomatoid bladder tumors and is likely to be a marker of tumor aggressiveness, thus recommending aggressive treatment.

Haghighitalab A, Matin MM, Bahrami AR, et al.
In vitro investigation of anticancer, cell-cycle-inhibitory, and apoptosis-inducing effects of diversin, a natural prenylated coumarin, on bladder carcinoma cells.
Z Naturforsch C. 2014 Mar-Apr; 69(3-4):99-109 [PubMed] Related Publications
Chemotherapy is one of the main strategies for reducing the rate of cancer progression or, in some cases, curing the tumour. Since a great number of chemotherapeutic agents are cytotoxic compounds, i. e. similarly affect normal and neoplastic cells, application of antitumour drugs is preferred in cancer management and therapy. In this study, the cytotoxicity of diversin was evaluated in 5637 cells, a transitional cell carcinoma (TCC) subline (bladder carcinoma), and normal human fibroblast cells using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Chromatin condensation and DNA damage induced by diversin were also determined by means of 4',6-diamidino-2-phenylindole (DAPI) staining and the comet assay, respectively. In addition, the mechanism of action of diversin was studied in more detail by the caspase 3 colourimetric assay and flow cytometry-based cell-cycle analyses (PI staining). Our results revealed that diversin has considerable cytotoxic effects in 5637 cells, but not on HFF3 (human foreskin fibroblast) and HDF1 (human dermal fibroblast) cells. Further studies showed that diversin exerts its cytotoxicity via induction of chromatin condensation, DNA damage, and activation of caspase 3 in 5637 cells. In addition, flow cytometric analyses revealed that 5637 cells are mostly arrested at the G2 phase of the cell cycle in the presence of diversin.

Related: Apoptosis

Pendse AA, Edgerly CH, Fedoriw Y
Hemolytic anemia and metastatic carcinoma: case report and literature review.
Lab Med. 2014; 45(2):132-5 [PubMed] Related Publications
Hemolytic anemia can complicate the development of a variety of solid tumors and hematologic malignancies. Although patients may have an established diagnosis with documented metastases, microangiopathic hemolytic anemia (MAHA) can be a presenting feature of an occult malignancy. Prompt diagnosis is essential because conditions that mimic the symptoms of MAHA, including thrombotic thrombocytopenic purpura, have different prognoses and therapeutic options. Although the exact pathogenesis is not yet delineated, we present herein a case of cancer-associated MAHA and discuss the known pathways that can contribute to the initiation and propagation of hemolytic anemia in patients with cancer. The patient is a 69-year-old woman with breast carcinoma that had metastasized to her rectum, urinary bladder, and brain. She eventually developed progressive decline in her functional status, with intermittent epistaxis and melena. The results of laboratory studies revealed hemolytic anemia and thrombocytopenia; results of a bone-marrow biopsy confirmed the involvement by metastatic carcinoma. The patient received red blood cell and platelet transfusions and was discharged to hospice care after clinical stabilization. She died soon thereafter.

Related: Breast Cancer

de Haas RJ, Steyvers MJ, Fütterer JJ
Multiparametric MRI of the bladder: ready for clinical routine?
AJR Am J Roentgenol. 2014; 202(6):1187-95 [PubMed] Related Publications
OBJECTIVE: In this article, we describe the fundamentals of multiparametric MRI in bladder cancer and provide an overview of the currently available data concerning this new imaging technology. Urinary bladder cancer is a relatively common malignancy, especially in elderly patients. Treatment outcome and prognosis are strongly related to adequate local and regional tumor staging. Unfortunately, clinical understaging frequently occurs, which negatively influences prognosis. Therefore, advanced imaging techniques are needed to adequately stage bladder cancer patients. MRI is currently the best imaging technique for local and nodal staging in bladder cancer patients because of its superior soft-tissue contrast without exposure to ionizing radiation. Important improvements in MRI technology have led to the introduction of multiparametric MRI, combining anatomic and functional sequences.
CONCLUSION: The first results of multiparametric MRI seem promising, especially in detection, staging, and follow-up of bladder cancer. However, more studies are needed with larger study populations to define the exact place of multiparametric MRI in bladder cancer patients.

King K, Steggall M
Haematuria: from identification to treatment.
Br J Nurs. 2014 May 8-21; 23(9):S28-32 [PubMed] Related Publications
Haematuria has a prevalence of 0.1% to 2.6%. Potential diagnoses may include infection, kidney stones, trauma, exercise or spurious causes, such as foods, drugs or menstruation, and a tumour. Approximately 20% of patients with haematuria have a urological tumour, with a further 20% found to have a significant underlying pathology. Haematuria is subsequently known as the 'classic presentation' of bladder cancer with 70-80% of patients experiencing painless, gross (visible) haematuria. However, in all cases of visible haematuria, a tumour should be suspected until proven otherwise. A patient with visible haematuria requires urgent, stringent investigation, warranting specialist assessment and subsequent selective referral through a series of patient-centred investigations at a haematuria clinic. One-stop clinics have been shown to improve the patient experience in early diagnosis of potentially life-threatening conditions. Yet despite morbidity and mortality from bladder cancer increasing, the haematuria service has remained largely unchanged for several decades. This paper will discuss the tests and investigations that need to be undertaken in an individual with either visible or non-visible haematuria, and outline the care that is needed to support patients through the investigation process, with special focus on bladder tumour.

Cho SK, Emoto K, Su LJ, et al.
Functionalized gold nanorods for thermal ablation treatment of bladder cancer.
J Biomed Nanotechnol. 2014; 10(7):1267-76 [PubMed] Related Publications
Nanomaterial-directed, photothermal ablation is a practical future approach for the treatment of early-stage bladder cancer. Using a new PEGylation technique with bi-functional nitrophenyl carbonate PEG (bi-NPC-PEG) that promotes uniform suspension of the nanomaterial in solution, we have shown that gold nanorods conjugated to an anti-EGFR antibody (nano-alphaEGFR) bind effectively to EGFR-expressing bladder cancer cells. The subsequent application of infrared light, specifically tuned to the plasmon resonance of the nanorods used in this work, allows for the specific heating of nano-alphaEGFR to the point of localized cellular death. Such an approach, administering nano-alphaEGFR intravesically via a urinary catheter and infrared light via a modified cystoscope, represents a novel, future clinical application of this technology, which avoids the problem of systemic exposure and clearance of nanoparticles from body.

Zhao M, Williamson SR, Sun K, et al.
Benign perivascular myoid cell tumor (myopericytoma) of the urinary tract: a report of 2 cases with an emphasis on differential diagnosis.
Hum Pathol. 2014; 45(5):1115-21 [PubMed] Related Publications
Myopericytoma is a benign mesenchymal neoplasm thought to comprise part of a spectrum of perivascular myoid cell neoplasms with myofibroma, angioleiomyoma, and glomus tumor. We describe 2 such neoplasms involving the urinary tract: 1 incidentally identified in the kidney of a 59-year-old woman and 1 in the urinary bladder of a 52-year-old woman who presented with urinary frequency and dysuria. Histologically, the bladder tumor was composed of numerous blood vessels surrounded by plump perivascular myoid cells, as in subcutaneous myopericytoma. The renal tumor showed similar morphology centrally and a symplastic glomus tumor-like growth pattern at the periphery. Immunohistochemically, both tumors were reactive for markers of smooth muscle differentiation, such as smooth muscle actin and caldesmon/calponin but negative for CD34, cathepsin K, and S100 protein. Both patients are free of disease 14 and 39 months after resection, respectively. Our findings broaden the morphologic spectrum of myopericytoma.

Related: Kidney Cancer

Ringel J, Erdmann K, Hampel S, et al.
Carbon nanofibers and carbon nanotubes sensitize prostate and bladder cancer cells to platinum-based chemotherapeutics.
J Biomed Nanotechnol. 2014; 10(3):463-77 [PubMed] Related Publications
Recent data suggest that carbon nanomaterials can act as antitumor agents themselves by increasing the efficiency of cytotoxic agents when applied in combination. Here, carbon nanofibers (CNFs) and multi-walled carbon nanotubes (CNTs) were investigated regarding their impact on cellular function, cellular uptake and ability to sensitize cancer cells of urological origin to the conventional chemotherapeutics cisplatin and carboplatin. CNFs and CNTs (1-200 microg/ml) showed a low to moderate impairment of cellular function with CNFs being more deleterious than CNTs. Inhibition of cellular viability by the nanomaterials was about 20% at most. In combinatory treatments, CNFs and CNTs markedly enhanced the effects of cisplatin and carboplatin on cellular viability by 1.2- to 2.8-fold in prostate, bladder and cisplatin-resistant prostate cancer cells in comparison to the individual effects of the chemotherapeutics. Particularly the cell viability-diminishing effect of CNFs alone and in combination with the chemotherapeutics was more pronounced with dispersions prepared with human serum albumin than with phospholipid-polyethylene glycol. Albumin might mediate the cellular uptake of carbon nanomaterials which was underlined by the co-localization of albumin and carbon nanomaterials along the cellular surface as evidenced by fluorescence microscopy. Transmission electron microscopy revealed that both carbon nanomaterials were internalized by cancer cells, thereby possibly leading to an enhanced accumulation of the chemotherapeutic drugs. In fact, CNFs enhanced the cellular accumulation of carboplatin by 28% as compared to the single treatment with carboplatin. In conclusion, carbon nanomaterial-based applications could present a new strategy to overcome chemoresistance by sensitizing cancer cells to conventional chemotherapeutics.

Related: Cisplatin Prostate Cancer

Sun C, Xu S, Guo J, et al.
The inhibitory and apoptotic effects of docetaxel-loaded mesoporous magnetic colloidal nanocrystal clusters on bladder cancer T24 cells in vitro.
J Biomed Nanotechnol. 2014; 10(3):455-62 [PubMed] Related Publications
Mesoporous magnetic colloidal nanocrystal clusters (MCNCs) are featured with high magnetization, adequate surface area, excellent colloidal stability, good biocompatibility, and acid degradability. It is thus highly anticipated that MCNCs can serve as vehicles for target drug delivery. Herein, the mesoporous MCNCs stabilized by poly(gamma-glutamic acid) (PGA) were fabricated by the modified solvothermal route, showing a high specific surface area (126.4 m2/g), strong magnetic response (63 emu/g) and appropriate mesoporosity including a large pore volume (0.27 cm3/g) and accessible pore size (8.1 nm). Docetaxel (DOC) was then loaded in the resultant MCNCs using the nanoprecipitation method, and a high drug loading capacity was achieved up to 24 wt%. The chemotherapeutic effect and mechanism of DOC-MCNC conjugates in bladder cancer was evaluated in vitro. A series of analyses for cell uptake, cell viability, cell cycle, cell apoptosis and some cell proteins were performed by transmission electron microscopy, MTT assay, flow cytometry, cell nuclei staining, Annexin V staining assay, western blot assay and caspase-3 activity assay, respectively. The results demonstrated that DOC-MCNC conjugates enhanced the inhibitory effect by hampering mitoschisis and increased the apoptotic effect by changing the expression of apoptosis-related proteins in T24 cells, substantially proving their remarkable efficiency in treatment of bladder cancer.

Related: Apoptosis Docetaxel

Jallad S, Goubet S, Symes A, et al.
Prognostic value of inflammation or granuloma after intravesival BCG in non-muscle-invasive bladder cancer.
BJU Int. 2014; 113(5b):E22-7 [PubMed] Related Publications
OBJECTIVE: To evaluate the prognostic value of inflammation or granuloma after intravesical bacille Calmette-Guérin (BCG) treatment in non-muscle-invasive bladder cancer (NMIBC).
MATERIALS AND METHODS: Patients with NMIBC treated with intravesical BCG over a 5-year period were identified. The correlations between histopathological results and disease recurrence and progression were assessed, with survival analysis performed using the Kaplan-Meier method. Other relevant variables were also evaluated using univariate and multivariate analysis. A log-rank test was performed to compare time-to-event between groups.
RESULTS: A total of 215 patients were treated with BCG for NMIBC and the median follow-up was 32 months. Granuloma was identified in 60 patients and inflammation in 125 patients. In 18 patients there was no evidence of either (normal histology group). A total of 12 patients did not have biopsies and were subsequently excluded. The mean recurrence-free survival rate was significantly higher in the granuloma and inflammation groups (65 months [95% CI: 58-72] and 56 months [95% CI: 49-63], respectively) than in the normal histology group (20 months [95% CI: 6-34]; log-rank P < 0.001). On the multivariate analysis, the absence of inflammation/granuloma was significantly associated with recurrence (log-rank P < 0.001). The progression-free survival rate was higher in the granuloma and inflammation groups (75 months [95% CI: 71-79] and 82 months [95% CI: 78-86], respectively) compared with the normal histology group (33 months [95% CI: 17-48]; log-rank P < 0.001). On multivariate analysis, the absence of inflammation/granuloma was significantly associated with recurrence (log-rank P < 0.001).
CONCLUSION: Inflammation or granuloma in histology samples after intravesical BCG treatment for NMIBC are positive markers of response and their absence increases the risk of recurrence and progression.

Klipfel JM, Carolan BJ, Brytowski N, et al.
Patient safety improvement through in situ simulation interdisciplinary team training.
Urol Nurs. 2014 Jan-Feb; 34(1):39-46 [PubMed] Related Publications
In situ simulation is an education strategy that promotes patient safety and enhances interdisciplinary teamwork. When a patient is experiencing an acute health status change or a rapidly emerging condition, teamwork is necessary to adequately and appropriately provide treatment. A unit-based quality improvement project was designed to enhance these skills. In situ simulation was used as the training venue for nurses and physicians to practice the techniques recommended in the evidence-based team-building model, TeamSTEPPS.

He H, Zhang Z, Ge J, Zhou W
Leukemoid reaction associated with transitional cell carcinoma: a case report and literature review.
Niger J Clin Pract. 2014 May-Jun; 17(3):391-4 [PubMed] Related Publications
The goal of this article was to investigate the diagnosis, treatment and mechanisms of the leukemoid reaction (LKR) 14 15 associated with transitional cell carcinoma. A 64-year-old male patient presented with anuria. Color ultrasound imaging 15 16 revealed a large bladder tumor. Digital radiography and computerized tomography of the chest, abdomen and pelvis 16 17 revealed only bilateral hydronephrosis, but did not reveal any metastasis. The pre-operative white blood cell count in 17 18 the peripheral blood consistently increased to 58,400/mm3 while neutrophil granulocyte count was 54,900/mm3, without 18 19 fever. Radical cystectomy and construction of bilateral cutaneous ureterostomy was performed. The histological diagnosis 19 20 was transitional cell carcinoma, Grade 3. Granulocyte colony-stimulating factor (G-CSF) staining was positive in tumor 20 21 cells. Results: After surgery, the leukocyte value became nearly normal. At 3 months later, patient was admitted to our 21 22 hospital with the complaints of the left leg edema, diagnosed as pelvic lymph node metestasis. Patient died of systemic 22 23 metastasis within 6 months after the cystectomy. Bladder cancer associated with LKR, though rare, is considered highly 23 24 malignant, difficult to diagnose and as having poor prog.

Related: Transitional Cell Cancer of the Renal Pelvis and Ureter

Dutton TJ, Daugherty MO, Mason RG, McGrath JS
Implementation of the Exeter enhanced recovery programme for patients undergoing radical cystectomy.
BJU Int. 2014; 113(5):719-25 [PubMed] Related Publications
OBJECTIVES: To describe our experience with the implementation and refinement of an enhanced recovery programme (ERP) for radical cystectomy (RC) and urinary diversion. To assess the impact on length of stay (LOS), complication and readmission rates.
PATIENTS AND METHODS: In all, 165 consecutive patients undergoing open RC (ORC) and urinary diversion between January 2008 and April 2013 were entered into an ERP. A retrospective case note review was undertaken. Outcomes recorded included LOS, time to mobilisation, complication rates within the first 30 days (Clavien-Dindo classification) and readmissions.
RESULTS: All patients were successfully entered into the ERP. As enhanced recovery principles became embedded in the unit, LOS reduced from a mean of 14 days over the initial year of the ERP to a mean of 9.2 days. The complication rate was 6.6% for Clavien ≥3, and 43.5% for Clavien ≤2. The 30-day mortality rate was 1.2%. The 30-day readmission rate was 13.9%. In the most contemporary subset of 52 patients: the median time after ORC to sit out of bed, mobilise and open bowels was day 1, 2 and 6, respectively.
CONCLUSIONS: The ERP described for patients undergoing ORC appears to be safe. Benefits include early feeding, mobilisation and hospital discharge. The ERP will continue to develop with the incorporation of advancing evidence and technology, in particular the introduction of robot-assisted RC.

Related: USA

Guin S, Pollard C, Ru Y, et al.
Role in tumor growth of a glycogen debranching enzyme lost in glycogen storage disease.
J Natl Cancer Inst. 2014; 106(5) [PubMed] Related Publications
BACKGROUND: Bladder cancer is the most common malignancy of the urinary system, yet our molecular understanding of this disease is incomplete, hampering therapeutic advances.
METHODS: Here we used a genome-wide functional short-hairpin RNA (shRNA) screen to identify suppressors of in vivo bladder tumor xenograft growth (n = 50) using bladder cancer UMUC3 cells. Next-generation sequencing was used to identify the most frequently occurring shRNAs in tumors. Genes so identified were studied in 561 patients with bladder cancer for their association with stratification of clinical outcome by Kaplan-Meier analysis. The best prognostic marker was studied to determine its mechanism in tumor suppression using anchorage-dependent and -independent growth, xenograft (n = 20), and metabolomic assays. Statistical significance was determined using two-sided Student t test and repeated-measures statistical analysis.
RESULTS: We identified the glycogen debranching enzyme AGL as a prognostic indicator of patient survival (P = .04) and as a novel regulator of bladder cancer anchorage-dependent (P < .001), anchorage-independent (mean ± standard deviation, 180 ± 23.1 colonies vs 20±9.5 in control, P < .001), and xenograft growth (P < .001). Rescue experiments using catalytically dead AGL variants revealed that this effect is independent of AGL enzymatic functions. We demonstrated that reduced AGL enhances tumor growth by increasing glycine synthesis through increased expression of serine hydroxymethyltransferase 2.
CONCLUSIONS: Using an in vivo RNA interference screen, we discovered that AGL, a glycogen debranching enzyme, has a biologically and statistically significant role in suppressing human cancer growth.

Wang L, Mudaliar K, Mehta V, et al.
Seeking a standard for adequate pathologic lymph node staging in primary bladder carcinoma.
Virchows Arch. 2014; 464(5):595-602 [PubMed] Related Publications
The purposes of this study are to evaluate the adequacy of pathologic lymph node (LN) staging in radical cystectomy specimens from patients with urothelial carcinoma of the bladder and to analyze the frequency of LN metastases among different anatomic regions. All radical cystectomies performed for primary urothelial bladder cancer over a 5-year period (January 2007-September 2012) at a single institution were reviewed. Particular attention was paid to the total number of LNs examined, the number and location of LNs with metastases (positive LNs), and the presence or absence of extranodal tumor extension and/or lymphovascular invasion in the cystectomy specimen. Results and data were analyzed with Origin 6.0 and Microsoft Office Excel 2007 software. A total of 248 radical cystectomies with 8,432 LNs were reviewed. A total of 60 (24 %) cases, with 274 positive LNs out of the 1,982 total (13.8 %), were identified with a male to female ratio of 6.5:1 (52 male, 8 female patients). The average number of LNs examined in each case was 33.0 ± 20.9 (range 5-112). The average number of positive LNs identified in each case was 4.5 ± 4.8 (range 1-26). Among all of the LNs, the hypogastric/obturator (internal iliac) LNs were the most commonly submitted (35.2 %) and also yielded the highest number of positive LNs (46.0 %). On average, for cases staged pN1 and pN2, there was one positive LN per 17.8 and 8.9 LNs examined from the primary drainage LNs, respectively. For pN3 cases, one out of 4.4 secondary drainage LNs was found to be positive. Similarly, one out of 4.0 distant LNs was found to be positive in cases with pM1 staging. Our study suggests that, on average, 23 LNs (including 18 primary drainage LNs and five secondary drainage LNs) should be submitted for optimal pN staging. For adequate pM1 staging, an average of four distal LNs should be evaluated. In total, an average of 27 LNs (23 for pN staging and 4 for pM staging) should be examined in radical cystectomy specimens. We also propose to stratify the number of positive LNs according to the drainage area.

Related: Transitional Cell Cancer of the Renal Pelvis and Ureter

Manny TB, Hemal AK
Fluorescence-enhanced robotic radical cystectomy using unconjugated indocyanine green for pelvic lymphangiography, tumor marking, and mesenteric angiography: the initial clinical experience.
Urology. 2014; 83(4):824-9 [PubMed] Related Publications
OBJECTIVE: To describe the initial feasibility of fluorescence-enhanced robotic radical cystectomy (FERRC) using real-time cystoscopic injection of unconjugated indocyanine green (ICG) for tumor marking and identification of sentinel lymphatic drainage with additional intravenous injection for mesenteric angiography.
METHODS: Ten patients with clinically localized high-grade bladder cancer underwent FERRC. Before robot docking, rigid cystoscopy was performed, during which a 2.5-mg/mL ICG solution was injected in the bladder submucosa and detrusor circumferentially around the tumor. After robot docking, parameters describing the time course of tissue fluorescence and pelvic lymphangiography were systematically recorded. Lymphatic packets containing fluorescent lymph nodes were considered the sentinel drainage. Eight patients underwent intracorporeal ileal conduit urinary diversion, during which an additional 2-mL ICG solution was given intravenously for mesenteric angiography, allowing maximal preservation of bowel vascularity to the conduit and remaining bowel segments.
RESULTS: Bladder tumor marking and identification of sentinel drainage were achieved in 9 of 10 (90%) patients. The area of bladder tumor was identified at a median of 15 minutes after injection, whereas sentinel drainage was visualized at a median of 30 minutes. Mesenteric angiography was successful in 8 of 8 (100%) patients at a median time of <1 minutes after intravenous injection and enabled identification of bowel arcades before intracorporeal bowel stapling.
CONCLUSION: FERRC using combined cystoscopic and intravenous injection of ICG is safe and feasible. FERRC allows for reliable bladder tumor marking, identification of sentinel lymphatic drainage, and identification of mesenteric vasculature in most patients.

Related: Transitional Cell Cancer of the Renal Pelvis and Ureter

Radosavljevic V, Belojevic G
Shortcomings in bladder cancer etiology research and a model for its prevention.
Tumori. 2014 Jan-Feb; 100(1):1-8 [PubMed] Related Publications
AIMS AND BACKGROUND: Bladder cancer (BC) is the most expensive cancer to treat. Its incidence and mortality have not decreased in the last three decades. Numerous uncertainties are still surrounding the etiology of BC. There is a need for a low-cost screening test for BC that would be applicable for early detection in asymptomatic persons, a test that would preferably be noninvasive and have satisfactory sensitivity and specificity.
METHODS AND STUDY DESIGN: The first part of this paper addresses critical issues in the research into BC etiology, which we classified as entrances, toxicity and metabolism, amounts, and duration of exposure to carcinogens in the bladder. In the second part, based on the proven risk factors for BC, we present a simple scoring system as part of a new BC screening method.
RESULTS: The heterogeneous results of studies on BC etiology are largely due to a lack of research into the compounds (and their mutual interactions) present in the urinary bladder, carcinogens absorbed through the skin and/or inhaled, and the daily dynamics of exposure to exogenous risk factors. We have calculated a score for BC screening which is an integral component of a new, four-level system of BC prevention.
CONCLUSIONS: Interactions of carcinogens and their daily dynamics deserve more attention in further clarifying BC etiology. New attempts in BC screening should be focused on urine content analyses (carcinogens, antioxidants, vitamins, minerals) and not only on hematuria and currently used biomarkers. We propose a score for BC pre-evaluation and recruitment for screening and a new model of BC prevention.

Related: Cancer Screening and Early Detection

Bacillus Calmette-Guerin and bladder cancer: helpful packaging.
Prescrire Int. 2014; 23(146):41-2 [PubMed] Related Publications
There are no randomised controlled trials comparing the BCG RIVM strain (BCG-medac) versus the BCG Connaught strain (Immucyst), but the packaging of BCG-medac is far more complete than that of immucyst.

Jing Y, Cui D, Guo W, et al.
Activated androgen receptor promotes bladder cancer metastasis via Slug mediated epithelial-mesenchymal transition.
Cancer Lett. 2014; 348(1-2):135-45 [PubMed] Related Publications
Androgen receptor (AR) has been indicated to be involved in bladder cancer progression. We showed androgen induced epithelial-mesenchymal transition (EMT) in AR-positive bladder cancer cells and promoted tumor metastasis in xenograft models. We subsequently identified that Slug was the mediator of EMT induced by androgen. Furthermore, upregulation of Slug was due to activation of Wnt/β-catenin signaling in response to androgen. Finally, expression of AR showed strong correlation with loss of E-cadherin, higher expression of Slug and nuclear accumulation of β-catenin in bladder tumor tissues. Taken together, our results suggest AR signaling promotes bladder cancer metastasis through Slug mediated EMT.

Related: AR: androgen receptor

Li C, Li H, Zhang T, et al.
Discovery of Apo-A1 as a potential bladder cancer biomarker by urine proteomics and analysis.
Biochem Biophys Res Commun. 2014; 446(4):1047-52 [PubMed] Related Publications
Bladder cancer is clinically characterized by high recurrent rate and poor prognosis and thereby patients need regular re-examinations which are invasive, unpleasant, and expensive. A noninvasive and less expensive method for detecting and monitoring bladder cancer would thus be advantageous. In this study, by using the two-dimensional electrophoresis (2-DE) approach with subsequent mass spectrometry (MS), we demonstrated the increased expression of apolipoprotein-A1 (Apo-A1) in individual urine from patients with bladder cancer, which was confirmed by Western blot results. A further analysis of the urinary Apo-A1 levels by an enzyme-linked immunosorbent assay yielded results that were consistent with the Western blot, and suggested Apo-A1 could provide diagnostic utility to distinguish patients with bladder cancer from healthy controls at 19.21 ng/ml. Further validation assay in a larger number of urine samples (n=379) showed that Apo-A1 could be used as a biomarker to diagnosis bladder cancer with a sensitivity and specificity of 89.2% and 84.6% respectively. Moreover, the application of exfoliative urinary cytology in combination with the urine Apo-A1 detection could significantly increased the sensitivity in detecting bladder cancer. Our data showed a significant relationship of expressed Apo-A1 was established between bladder cancer and normal controls. Apo-A1 could be a potential biomarker for the diagnosis of bladder cancer.

Gray PJ, Lin CC, Jemal A, et al.
Clinical-pathologic stage discrepancy in bladder cancer patients treated with radical cystectomy: results from the national cancer data base.
Int J Radiat Oncol Biol Phys. 2014; 88(5):1048-56 [PubMed] Related Publications
PURPOSE: To examine the accuracy of clinical staging and its effects on outcome in bladder cancer (BC) patients treated with radical cystectomy (RC), using a large national database.
METHODS AND MATERIALS: A total of 16,953 patients with BC without distant metastases treated with RC from 1998 to 2009 were analyzed. Factors associated with clinical-pathologic stage discrepancy were assessed by multivariate generalized estimating equation models. Survival analysis was conducted for patients treated between 1998 and 2004 (n=7270) using the Kaplan-Meier method and Cox proportional hazards models.
RESULTS: At RC 41.9% of patients were upstaged, whereas 5.9% were downstaged. Upstaging was more common in females, the elderly, and in patients who underwent a more extensive lymphadenectomy. Downstaging was less common in patients treated at community centers, in the elderly, and in Hispanics. Receipt of preoperative chemotherapy was highly associated with downstaging. Five-year overall survival rates for patients with clinical stages 0, I, II, III, and IV were 67.2%, 62.9%, 50.4%, 36.9%, and 27.2%, respectively, whereas those for the same pathologic stages were 70.8%, 75.8%, 63.7%, 41.5%, and 24.7%, respectively. On multivariate analysis, upstaging was associated with increased 5-year mortality (hazard ratio [HR] 1.80, P<.001), but downstaging was not associated with survival (HR 0.88, P=.160). In contrast, more extensive lymphadenectomy was associated with decreased 5-year mortality (HR 0.76 for ≥10 lymph nodes examined, P<.001), as was treatment at an National Cancer Institute-designated cancer center (HR 0.90, P=.042).
CONCLUSIONS: Clinical-pathologic stage discrepancy in BC patients is remarkably common across the United States. These findings should be considered when selecting patients for preoperative or nonoperative management strategies and when comparing the outcomes of bladder sparing approaches to RC.

Related: USA

Hansen C, Becker CD, Montet X, Botsikas D
Diagnosis of urothelial tumors with a dedicated dual-source dual-energy MDCT protocol: preliminary results.
AJR Am J Roentgenol. 2014; 202(4):W357-64 [PubMed] Related Publications
OBJECTIVE: The purpose of this study was to evaluate the diagnostic performance of a dedicated dual-source dual-energy MDCT (DECT) protocol for the detection of urothelial tumors.
MATERIALS AND METHODS: A DECT protocol including furosemide and split-bolus contrast injection was used in 69 consecutive patients with suspected abnormalities of the urinary system. Thirteen patients were excluded because there was no follow-up available. In 56 patients, the final diagnosis was proven with endoscopy, biopsy, or follow-up and included urothelial tumors (n = 37) in 16 patients, other urinary tract pathologies (n = 9) in eight patients, and absence of lesions of the collecting system in 32 patients. The image series consisted of a dual-energy true unenhanced series, 35-second arterial phase, and 8-minute nephrographic-excretory phase and were analyzed retrospectively. True enhancement of all detected lesions was measured. On the basis of the DECT data of the contrast-enhanced images, virtual unenhanced series were created and iodine concentration was calculated using commercially available software. The attenuation difference between virtual unenhanced and contrast-enhanced images (virtual enhancement) was measured. CT findings were compared with the final diagnosis.
RESULTS: Urothelial tumors were identified on 35-second series, 8-minute series, and both series combined, with sensitivity of 91.9% (95% CI, 78.1-98.2%), 83.4% (68.0-93.8%), and 97.3% (85.8-100%), respectively. Urothelial tumors showed stronger virtual enhancement (p = 0.02) and higher iodine concentration (p = 0.03) than lesions of other origin. Distinction between urothelial tumors and nontumoral lesions was possible with sensitivity of 91.9% (78.1-98.2%) when using a threshold concentration of at least 1.0 mg I/mL.
CONCLUSION: Dual phase DECT with virtual unenhanced imaging and iodine concentration measurement appears to be a useful diagnostic test for urothelial tumors.

Antunes D, Padrão AI, Maciel E, et al.
Molecular insights into mitochondrial dysfunction in cancer-related muscle wasting.
Biochim Biophys Acta. 2014; 1841(6):896-905 [PubMed] Related Publications
Alterations in muscle mitochondrial bioenergetics during cancer cachexia were previously suggested; however, the underlying mechanisms are not known. So, the goal of this study was to evaluate mitochondrial phospholipid remodeling in cancer-related muscle wasting and its repercussions to respiratory chain activity and fiber susceptibility to apoptosis. An animal model of urothelial carcinoma induced by exposition to N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) and characterized by significant body weight loss due to skeletal muscle mass decrease was used. Morphological evidences of muscle atrophy were associated to decreased respiratory chain activity and increased expression of mitochondrial UCP3, which altogether highlight the lower ability of wasted muscle to produce ATP. Lipidomic analysis of isolated mitochondria revealed a significant decrease of phosphatidic acid, phosphatidylglycerol and cardiolipin in BBN mitochondria, counteracted by increased phosphatidylcholine levels. Besides the impact on membrane fluidity, this phospholipid remodeling seems to justify, at least in part, the lower oxidative phosphorylation activity observed in mitochondria from wasted muscle and their increased susceptibility to apoptosis. Curiously, no evidences of lipid peroxidation were observed but proteins from BBN mitochondria, particularly the metabolic ones, seem more prone to carbonylation with the consequent implications in mitochondria functionality. Overall, data suggest that bladder cancer negatively impacts skeletal muscle activity specifically by affecting mitochondrial phospholipid dynamics and its interaction with proteins, ultimately leading to the dysfunction of this organelle. The regulation of phospholipid biosynthetic pathways might be seen as potential therapeutic targets for the management of cancer-related muscle wasting.

Related: Apoptosis Mitochondrial Mutations in Cancer

Thiel T, Ryk C, Chatzakos V, et al.
Secondary stimulation from Bacillus Calmette-Guérin induced macrophages induce nitric oxide independent cell-death in bladder cancer cells.
Cancer Lett. 2014; 348(1-2):119-25 [PubMed] Related Publications
The anti-tumour mechanisms following Bacillus Calmette-Guérin (BCG) treatment of bladder-cancer remain largely unknown. Previous studies have shown involvement of nitric-oxide (NO) formation in the BCG-mediated effect. We analyzed the effects of macrophage secreted factors (MSFs) from BCG-stimulated RAW264.7 cells on the bladder-cancer cell line MBT2. Direct treatment with BCG did not induce NO in MBT2-cells whereas supernatant from BCG-stimulated macrophages increased NOS2 mRNA and protein expression, NO concentrations and cell-death. Blocking NO-synthesis with the NOS-inhibitor L-NAME did not affect levels of cell-death suggesting cytotoxic pathways involving other signalling molecules than NO. Several such candidate genes were identified in a microarray.

Related: Signal Transduction

Szarvas T, Reis H, Kramer G, et al.
Enhanced stromal syndecan-1 expression is an independent risk factor for poor survival in bladder cancer.
Hum Pathol. 2014; 45(4):674-82 [PubMed] Related Publications
In this study, we assessed the changes and prognostic relevance of syndecan-1 (SDC1) tissue and serum levels in bladder cancer (BC). SDC1 levels were analyzed in 213 samples (119 paraffin-embedded and 79 serum samples of BC patients and 15 controls) using immunohistochemistry and enzyme-linked immunosorbent assay. Results were correlated with clinicopathological characteristics and follow-up data, as well as previously determined serum levels of angiogenic factors (basic fibroblast growth factor, endostatin, angiostatin, angiopoietin, vascular endothelial growth factor, Tie2 and MMP-7). SDC1 staining was present in the cell membrane of normal bladder epithelium and non-muscle-invasive BC cells but was absent in a significant proportion of muscle-invasive carcinomas (P < .001). In contrast, stromal SDC1 expression was enhanced in muscle-invasive compared to non-muscle-invasive BCs (P = .001). Serum concentrations of the SDC1 ectodomain were higher in muscle-invasive BCs compared to controls or non-muscle-invasive carcinomas (P < .001 each). Lymph node-positive cases had the highest SDC1 serum concentrations (P < .001). SDC1 expression in stromal cells was independently associated with survival (hazard ratio = 2.034, 95% confidence interval 1.176-3.519, P = .011). SDC1 serum concentrations correlated with those of endostatin and matrix metalloproteinase 7. Loss of SDC1 in tumor cells and the parallel increase of serum SDC1 ectodomain concentration in high-stage, high-grade BCs suggest the involvement of SDC1 shedding in BC progression. In addition, high preoperative SDC1 serum levels may help to identify patients with lymph node metastases, supporting therapeutic decision-making. Presence of SDC1 in tumor stroma is an independent risk factor for patient survival and may therefore be used to select patients for more aggressive therapy.

Related: SDC1

Logan JK, Walton-Diaz A, Rais-Bahrami S, et al.
Changes observed in multiparametric prostate magnetic resonance imaging characteristics correlate with histopathological development of chronic granulomatous prostatitis after intravesical Bacillus Calmette-Guerin therapy.
J Comput Assist Tomogr. 2014 Mar-Apr; 38(2):274-6 [PubMed] Article available free on PMC after 01/03/2015 Related Publications
Administration of Bacillus Calmette-Guerin (BCG) has been shown to cause granulomatous prostatitis, a rare inflammatory process that can be mistaken for prostate cancer. We present a case of a 78-year-old man on active surveillance for prostate cancer with a subsequent diagnosis of high-grade urothelial carcinoma. After intravesical BCG therapy, he developed chronic granulomatous prostatitis. We present serial magnetic resonance imaging and biopsy data demonstrating the time interval between BCG administration and the manifestation of chronic granulomatous prostatitis.

Related: Transitional Cell Cancer of the Renal Pelvis and Ureter Prostate Cancer

DeSouza K, Chowdhury S, Hughes S
Prompt diagnosis key in bladder cancer.
Practitioner. 2014; 258(1767):23-7, 3 [PubMed] Related Publications
Bladder cancer is the most frequently diagnosed cancer involving the urinary tract and is the seventh most common cancer in the UK. Delayed diagnosis is associated with high-grade muscle invasive disease which has the potential to progress rapidly, metastasise and is often fatal. Urothelial cancer (transitional cell carcinoma) is the predominant histological subtype in Europe, where it accounts for 90% of all bladder cancers. Haematuria, which is typically intermittent, frank, painless and at times present throughout micturition, is the classical and most common presentation of bladder cancer. However, irritative symptoms such as dysuria, urgency, urge incontinence and frequency as well as obstructive symptoms can also be experienced. Fatigue; weight loss; anorexia; renal failure; respiratory symptoms and a suprapubic palpable mass are usually signs of advanced or metastatic malignancy. Cigarette smokers have up to four times the risk of bladder cancer compared with non-smokers. Other risk factors include: exposure to aniline dyes; use of cyclophosphamide; history of pelvic radiation; exposure to chemical carcinogens associated with certain industries; spinal cord injuries requiring long-term indwelling catheters; type 2 diabetes treated with pioglitazone and condylomata acuminata. Frank haematuria has a high diagnostic yield for malignancies involving the urinary tract and initial routine tests should be directed towards identifying a variety of potential non-malignant causes. A thorough physical examination should be undertaken to identify evidence of bleeding diathesis and metastatic malignancy. Suggested laboratory investigations include FBC, coagulation, creatinine and PSA. The diagnosis of bladder cancer is based on urine cytology, cystoscopy and pathological assessment of the bladder biopsy.

Spina B, Pacella E, Introini C, et al.
Primary bladder angiosarcoma with no apparent previous exposure to carcinogens: a case report.
Anal Quant Cytol Histol. 2013; 35(6):349-52 [PubMed] Related Publications
BACKGROUND: Angiosarcomas are rare vascular neoplasms, and visceral involvement is quite uncommon. Predisposing factors that are thought to contribute to the development of angiosarcomas include ionizing radiation and chemical agents. Particularly, the association of angiosarcomas with therapeutic radiation has been previously emphasized. Nonurothelial bladder tumors are quite rare, too. Sarcomas represent the most common mesenchymal tumors of the bladder and generally share an extremely aggressive biologic behavior.
CASE: A 67-year-old, white woman presented with primary angiosarcoma of the bladder and with no apparent risk factors or previous exposure to the carcinogens typically related to such neoplasms. A biopsy performed due to gross hematuria by endoscopic resection revealed an infiltrative, poorly differentiated neoplasm that was interpreted as high grade papillary urothelial carcinoma. A radical cystectomy, with regional lymphadenectomy and bilateral hysterosalpingo-oophorectomy, was performed. The pathological examination revealed a voluminous and extensively necrotic mass, histologically compatible with an angiosarcoma of the bladder. Despite a multimodal therapeutic approach, the patient died within a short time. This report summarizes the clinical course and highlights the histological features of this tumor.
CONCLUSION: This case falls within the limited group of primary angiosarcoma of the bladder with very aggressive clinical features in a patient without recognized risk factors.

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