Review Articles in 2011

Molecular biomarkers have been largely excluded from current management algorithms for urologic malignancies. This Review focuses on molecular biomarkers that could potentially be used to diagnose and prognose patients with bladder cancer, as well as markers with potential for forecasting and stratifying responses to emerging targeted therapies.

Detrusor smooth muscle (DSM) defects are responsible for some forms of bladder dysfunction, such as overactive bladder secondary to detrusor overactivity. In this Review, the author examines the role of K⁺channels in normal and dysfunctional DSM, the methods used to study their activity, and how these channels might be targeted therapeutically with the use of gene therapy approaches and specific inhibitors or activators.

Genitourinary tuberculosis (GUTB) is the second most common form of extrapulmonary TB, with more than 90% of cases occurring in developing countries. In this Review, Abbara and Davidson present the epidemiology and pathophysiology of TB and describe the diagnostic tests and imaging techniques. They also elucidate the sites of GUTB in men and women and explain the treatment options. Future challenges for the management of drug-resistant patients and those with HIV co-infections are also considered.

Asymptomatic bacteriuria (ABU) is defined by the presence of bacteria in the urine of a patient without signs or symptoms related to UTI. A common condition that is often treated unnecessarily with antibiotics, ABU should be detected and treated in pregnant women and patients undergoing urologic surgery, but in most other patient groups, treatment does not confer benefit and can be harmful. In this Review, Trautner discusses the science behind ABU, when it should be treated, and what is being done to change the prescribing behavior of physicians managing a patient with ABU.

The use of robot-assisted laparoscopic technology is rapidly expanding, with applicability in numerous disciplines of surgery. At present, there are very few published guidelines for the safe introduction of urologic robotic surgery (RS) at an institution. In this Review, Liberman and colleagues focus on some of the key aspects of postgraduate and residential RS training.

The hollow and mobile nature of the bladder leads to considerable variations in volume, shape and position of this organ over time, making delivery of radiation therapy to bladder tumors a challenging exercise in planning. In this Review, the authors describe the use of various imaging modalities to improve the accuracy and effectiveness of radiation therapy in patients with bladder cancer.

Radical cystectomy with subsequent urinary diversion has been assessed the most difficult surgical procedure in the field of urology. In this Review, the authors discuss the need for standardized reporting of complications after urinary diversion, and summarize our current knowledge of the complications associated with different diversion techniques.

Systemic inflammation has been linked with cancer development and progression. C reactive protein (CRP) is a useful marker of systemic inflammation. CRP levels could predict survival in patients with urological cancers, and the incorporation of CRP into prognostic models improves the models' predictive accuracy. The analysis of CRP kinetics could predict tumor aggressiveness and response to treatment. In this Review, Saito and Kihara discuss the usefulness of CRP as a prognostic biomarker in urological cancers, including renal cell carcinoma, bladder cancer and prostate cancer.

Wnt signaling is thought to have an important role in the development of several human cancers, but its role in renal cell carcinoma (RCC) seems to be distinct from other cancer types. In this Review, the authors describe our current understanding of Wnt signaling and the action of several endogenous Wnt antagonists in the context of RCC, and discuss how study of these proteins might lead to the development of effective new targeted therapies for patients with this malignancy.

Urothelial carcinoma of the bladder (UCB) is the fifth most common cancer in the USA; therefore, the identification of patients with high-risk disease is important for timely and appropriate treatment. UCB has two clinical manifestations: noninvasive lesions that recur but rarely progress, and muscle-invasive lesions that progress aggressively and are associated with poor outcome. In this Review, Prasad et al. define the high-risk UCB and the associated clinical, histological and genetic factors. They also describe the treatment options and provide a brief description of future efforts in bladder cancer research.

The authors discuss a novel strategy of increasing the elevated intracellular levels of reactive oxygen species, which result from aberrantly-regulated signaling pathways, to a lethal level in tumor cells only. The selective death of cancer cells might be exploited in order to develop highly effective and specific therapeutic strategies with minimal side effects for the treatment of urothelial carcinoma.

Although prolactin's action on the mammary gland is well known, it is also found in the circulation of males and its receptor (PRLR) is expressed in the prostate. Furthermore, studies have supported the contribution of the canonical PRLR-Jak2-Stat5a/b pathway to prostate cancer tumorigenesis and progression. In this Review, the authors discuss the data regarding the role of prolactin in the prostate and consider the therapeutic potential of targeting prolactin signaling pathways in the treatment of advanced prostate cancer.

Members of transient receptor potential (TRP) superfamily are expressed in lower urinary tract (LUT) tissues, where they are mainly involved in nociception and mechanosensory transduction and represent potential targets for treating LUT disorders. In this Review, the authors discuss the evidence for a pivotal role of TRPV1, TRPV2, TRPV4, TRPM8, and TRPA1 in normal and pathological LUT function and consider the therapeutic strategies that might arise from targeting these channels.

Ho and colleagues outline the requirements of focal therapy for prostate cancer and discuss the limitations of current imaging modalities and prostate biopsy techniques to meet them. They go on to describe how a robotic system might overcome these deficiencies and review the types of robotic prostate biopsy that have been reported.

Recent data indicate that sphingosine kinase 1 (SK1), a lipid enzyme with oncogenic properties, has a critical role in the progression of many cancers. In this Review, the authors describe the mechanisms of SK1 signaling and the molecular basis for targeting SK1 in cancer, with particular focus on prostate cancer.

The prostate gland expresses several components of the endocannabinoid system. In this Review, Díaz-Laviada outlines the anti-proliferative effect of cannabinoids on prostate cancer cells and the signaling pathways underlying cannabinoid action, before discussing the molecular targets and signaling pathways modulated by cannabinoids in prostate cancer cells.

Vesicoureteral reflux (VUR) a common urological anomaly in children, and can result in reflux-associated nephropathy, which is a major cause of childhood hypertension and chronic renal failure. In this Review, the authors discuss the pathogenesis of VUR, and consider genetic syndromes and gene loci that have been associated with the disorder.

Contemporary increase in the prescription of anticoagulant and antiplatelet drugs can increase the risk of TURP-related bleeding. Kavanagh et al. describe the commonly-prescribed prohemorrhagic medications that clinicians should be familiar with and discuss when it is safe to withhold them. They also discuss the medications and surgical techniques that can be used to minimize prostatic blood loss.

The metabolic syndrome comprises a number of disorders which predispose to cardiovascular disease, and is associated with a Western lifestyle. Urological diseases are emerging as possible constituents of the metabolic syndrome. In this Review, the authors discuss the evidence supporting the inclusion of urological diseases as part of the metabolic syndrome and consider the clinical implications of such data.

There is a need for new molecular markers to aid histopathological assessment in upper urinary tract urothelial carcinoma (UUT-UC). p53 is the most extensively investigated marker in this disease; however, the data is inconclusive. In this Review, the authors critically discuss the studies investigating p53 expression in UUT-UC, and consider whether there is any potential clinical application of this biomarker.