Molecular genetics of bladder cancer: Emerging mechanisms of tumor initiation and progression.

Urothelial cancer has served as one of the most important sources of information about the mutational events that underlie the development of human solid malignancies. Although "field effects" that affect the entire bladder mucosa appear to initiate disease, tumors develop along 2 distinct biological "tracks" that present vastly different challenges for clinical management. Recent whole genome methodologies have facilitated even more rapid progress in the identification of the molecular mechanisms involved in bladder cancer initiation and progression.

A multiplexed, particle-based flow cytometric assay identified plasma matrix metalloproteinase-7 to be associated with cancer-related death among patients with bladder cancer.

Background: The current study was conducted to demonstrate the utility of a multiplexed, particle-based flow cytometric assay for the simultaneous analysis of a panel of matrix metalloproteinases (MMPs) using small volumes of plasma samples from patients with bladder cancer. In addition, the authors attempted to test the hypothesis that plasma levels of MMPs are associated with time to cancer-related death.

Methods: Plasma MMP concentrations (MMP-1, -2, -3, -7, -8, -9, and -12) in 135 patients presenting with high-grade≥T1 bladder cancer were measured.

Incidence of downstaging and complete remission after neoadjuvant chemotherapy for high-risk upper tract transitional cell carcinoma.

Background: The authors evaluated the incidence of pathologic downstaging and complete remission (CR) in patients with high-grade ureteral and renal pelvic transitional cell carcinoma (TCC) (upper tract TCC) who received neoadjuvant chemotherapy followed by surgery.

Methods: The study group comprised patients with biopsy-demonstrated, high-grade disease who received neoadjuvant chemotherapy followed by nephrouterectomy from 2004 to 2008, during which time patients uniformly were considered for neoadjuvant chemotherapy. The control group comprised patients with biopsy-demonstrated, high-grade disease who underwent initial nephroureterectomy from 1993 to 2004, when patients uniformly underwent initial surgery.

Genetic variations of the PI3K-AKT-mTOR pathway and clinical outcome in muscle invasive and metastatic bladder cancer patients.

The phosphoinositide-3 kinase (PI3K)-AKT- mammalian target of rapamycin (mTOR) pathway is an important cellular pathway controlling cell growth, tumorigenesis, cell invasion and drug response. We hypothesized that genetic variations in the PI3K-AKT-mTOR pathway may affect the survival in muscle invasive and metastatic bladder cancer (MiM-BC) patients. We conducted a follow-up study of 319 MiM-BC patients to systematically evaluate 289 single-nucleotide polymorphisms (SNPs) of 20 genes in the PI3K-AKT-mTOR pathway as predicators of survival.

Validating bladder cancer xenograft bioluminescence with magnetic resonance imaging: the significance of hypoxia and necrosis.

Objective: To assess the correlation in orthotopic bladder xenografts of bioluminescence imaging (BLI) with tumour volume as determined by magnetic resonance imaging (MRI), and to define the potential role of hypoxia and necrosis in the relationship between BLI and tumour volume at autopsy.

Materials And Methods: Orthotopic bladder tumours were established in nude mice with KU7 and 253J B-V cells expressing luciferase. BLI and MRI were performed weekly.

Age and body mass index are independent risk factors for the development of postoperative paralytic ileus after radical cystectomy.

Objectives: To identify the risk factors that would aid in the identification of patients at the greatest risk of developing postoperative paralytic ileus (POI). POI is a common complication after radical cystectomy and can result in a prolonged hospital stay and delayed recovery.

Methods: A retrospective cohort study design was used to analyze data from consecutive patients presenting to our institution for radical cystectomy with pelvic nodal dissection.

The role of radical cystectomy in patients with clinical T4b bladder cancer.

Objectives: Patients with clinical T4b bladder cancer (extension to pelvic wall and/or adjacent organs other than prostate, vagina, or uterus) are commonly considered unresectable. We hypothesized that select patients might achieve durable benefit from multiagent chemotherapy and extirpative surgery.

Methods: We identified patients with clinical T4bN0 bladder cancer from our IRB-approved database of patients undergoing radical cystectomy (n = 1,194).

BCAN Think Tank session 1: Overview of risks for and causes of bladder cancer.

This article reviews the proceedings of the cause and risk session of the recently held BCAN Bladder Think Tank in 2009. Understanding associations between specific genetic changes and development of particular forms of bladder cancer, whether low-grade or more invasive forms, may justify screening programs for earlier detection. A fundamental epidemiological issue is causation.

Soft tissue surgical margin status is a powerful predictor of outcomes after radical cystectomy: a multicenter study of more than 4,400 patients.

Purpose: We evaluated the association of soft tissue surgical margins with characteristics and outcomes of patients treated with radical cystectomy for urothelial carcinoma of the bladder.

Materials And Methods: We retrospectively collected the data of 4,410 patients treated with radical cystectomy and pelvic lymphadenectomy without neoadjuvant chemotherapy at 12 academic centers in the United States, Canada and Europe. A positive soft tissue surgical margin was defined as presence of tumor at inked areas of soft tissue on the radical cystectomy specimen.

Energy balance, the PI3K-AKT-mTOR pathway genes, and the risk of bladder cancer.

We evaluated the association between energy balance and risk of bladder cancer and assessed the joint effects of genetic variants in the mammalian target of rapamycin (mTOR) pathway genes with energy balance. The study included 803 Caucasian bladder cancer patients and 803 healthy Caucasian controls matched to cases by age (+/-5 years) and gender. High energy intake [odds ratio, 1.

International validation of the prognostic value of lymphovascular invasion in patients treated with radical cystectomy.

Objective: To externally validate the prognostic value of lymphovascular invasion (LVI) in a large international cohort of patients treated with radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB).

Patients And Methods: We collected data from 4257 patients treated with RC and pelvic lymphadenectomy for UCB, without neoadjuvant chemotherapy, at 12 centres. LVI was defined as presence of nests of tumour cells within an endothelium-lined space.

Risk factor analysis in a contemporary cystectomy cohort using standardized reporting methodology and adverse event criteria.

Purpose: Adverse event reporting is poorly classified and nonstandardized in the urological literature. We report adverse event data and associated risk factors using standardized reporting methods and Common Terminology Criteria for Adverse Events, version 3.0 to minimize interpretation bias and allow reliable comparisons with other populations.

Management of metastatic urothelial cancer: the role of surgery as an adjunct to chemotherapy.

Metastatic or unresectable disease is identified in approximately 20% of patients presenting with invasive urothelial cancer. In addition, up to 50% of patients will develop metastases following radical cystectomy for clinically localized disease. Multiagent cisplatin-based chemotherapy is considered standard first-line treatment for these patients.

Role of epithelial-to-mesenchymal transition (EMT) in drug sensitivity and metastasis in bladder cancer.

Epithelial-to-mesenchymal transition (EMT) is a process that plays essential roles in development and wound healing that is characterized by loss of homotypic adhesion and cell polarity and increased invasion and migration. At the molecular level, EMT is characterized by loss of E-cadherin and increased expression of several transcriptional repressors of E-cadherin expression (Zeb-1, Zeb-2, Twist, Snail, and Slug). Early work established that loss of E-cadherin and increased expression of MMP-9 was associated with a poor clinical outcome in patients with urothelial tumors, suggesting that EMT might also be associated with bladder cancer progression and metastasis.

Management of urethral recurrence after orthotopic urinary diversion.

Study Type: Therapy (case series) Level of Evidence 4 OBJECTIVE To evaluate our experience with urethral recurrences in patients treated by radical cystectomy(RC) and orthotopic neobladder urinary diversion for carcinoma of the bladder.

Patients And Methods: We retrospectively reviewed the records of patients treated with RC and orthotopic urinary diversion between January 1980 and July 2004.

Results: In all, 260 patients underwent RC with a Studer or Hautmann orthotopic urinary diversion; the median (range) follow-up was 5.

The molecular, the bad, and the ugly: preventing bladder cancer via mTOR inhibition.

This perspective on Seager et al. (beginning on p. 1008) considers an important advance in the effort to control bladder cancer.

Characteristics and outcomes of patients with pT4 urothelial carcinoma at radical cystectomy: a retrospective international study of 583 patients.

Purpose: We describe cancer specific outcomes in patients with pT4 bladder urothelial carcinoma at radical cystectomy in a large international cohort.

Materials And Methods: We reviewed the records of 4,257 patients treated with radical cystectomy for bladder urothelial carcinoma at 12 centers. No patient received any preoperative systemic chemotherapy or radiotherapy.

Cytoplasmic mislocalization of the orphan nuclear receptor Nurr1 is a prognostic factor in bladder cancer.

Background: Nurr1 belongs to a novel class of orphan nuclear receptors (the NR4A family). The authors have previously shown that Nurr1 is important in carcinogenesis. In the current study, they examined the clinicopathologic relevance of expression patterns of Nurr1 in bladder tumors.

Genetic variations in PI3K-AKT-mTOR pathway and bladder cancer risk.

Genetic variations in phosphoinositide-3 kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) pathway may affect critical cellular functions and increase an individual's cancer risk. We systematically evaluate 231 single-nucleotide polymorphisms (SNPs) in 19 genes in the PI3K-AKT-mTOR signaling pathway as predictors of bladder cancer risk. In individual SNP analysis, four SNPs in regulatory associated protein of mTOR (RAPTOR) remained significant after correcting for multiple testing: rs11653499 [odds ratio (OR): 1.

The stabilization and targeting of surfactant-synthesized gold nanorods.

The strong cetyltrimethylammonium bromide (CTAB) surfactant responsible for the synthesis and stability of gold nanorod solutions complicates their biomedical applications. The critical parameter to maintain nanorod stability is the ratio of CTAB to nanorod concentration. The ratio is approximately 740,000 as determined by chloroform extraction of the CTAB from a nanorod solution.