Context: Renal cell carcinoma (RCC) accounts for 2-3% of adult malignancies. There remain uncertainties over the oncological outcomes for the surgical management of localised RCC. Objective: To systematically review relevant literature comparing oncological outcomes of surgical management of localised RCC (T1-2N0M0). Evidence Acquisition: Relevant databases including MEDLINE, Embase and the Cochrane Library were searched up to October 2010, and an updated scoping search was performed up to January 2012. Randomised or quasi-randomised controlled trials (RCTs), prospective observational studies with controls, retrospective matched-pair studies, and comparative studies from well defined registries/databases were included. The main outcomes were overall survival, cancer-specific survival, recurrence and metastases. The Cochrane risk of bias (RoB) tool was used to assess RCTs and an extended version was used to assess Non Randomised Studies (NRS). The quality of evidence was assessed using GRADE. Evidence Synthesis: 4580 abstracts and 389 full text articles were assessed. 34 studies met the inclusion criteria (6 RCTs and 28 NRSs). Meta-analyses were planned but were deemed inappropriate due to data heterogeneity. There were high risks of bias and low quality evidence across the evidence base. Open radical nephrectomy and open partial nephrectomy showed similar cancer-specific and overall survival, but when both open and laparoscopic approaches are considered together the evidence showed improved survival for partial nephrectomy for tumours ≤4cm.Overall, the evidence suggests either equivalent or better survival with partial nephrectomy. Laparoscopic radical nephrectomy offered equivalent survival to open radical nephrectomy, and all laparoscopic approaches achieved equivalent survival. Open and laparoscopic partial nephrectomy achieved equivalent survival. The issue of ipsilateral adrenalectomy or complete lymph node dissection with radical nephrectomy or partial nephrectomy remains unresolved. Conclusions: The evidence base suggests localised RCC are best managed by nephron sparing surgery where technically feasible. However, the current evidence base has significant limitations due to studies of low methodological quality marked by high risks of bias.

The epithelial-mesenchymal transition (EMT) contributes to cancer metastasis. Two ZEB family members, ZEB1 and ZEB2(SIP1), inhibit transcription of the E-cadherin gene and induce EMT in vitro. However, their relevance to human cancer is insufficiently studied. Here, we performed a comparative study of SIP1 and ZEB1 proteins in cancer cell lines and in one form of human malignancy, carcinoma of the bladder. Whereas ZEB1 protein was expressed in all E-cadherin-negative carcinoma cell lines, being in part responsible for the high motility of bladder cancer cells, SIP1 was hardly ever detectable in carcinoma cells in culture. However, SIP1 represented an independent factor of poor prognosis (P ‫؍‬ 0.005) in a series of bladder cancer specimens obtained from patients treated with radiotherapy. In contrast, ZEB1 was rarely expressed in tumor tissues; and E-cadherin status did not correlate with the patients' survival. SIP1 protected cells from UV-and cisplatin-induced apoptosis in vitro but had no effect on the level of DNA damage. The anti-apoptotic effect of SIP1 was independent of either cell cycle arrest or loss of cell-cell adhesion and was associated with reduced phosphorylation of ATM/ATR targets in UV-treated cells. The prognostic value of SIP1 and its role in DNA damage response establish a link between genetic instability and metastasis and suggest a potential importance for this protein as a therapeutic target. In addition, we conclude that the nature of an EMT pathway rather than the deregulation of E-cadherin per se is critical for the progression of the disease and patients' survival. E pithelial mesenchymal transition (EMT) is a genetic program controlling cell migration during embryonic development and in wound healing (1, 2). Aberrant activation of EMT programs occurs in cells of epithelial tumors and contributes to the formation of cancer stem cells and metastasis (1-4). EMT is characterized by the loss of epithelial and the acquisition of mesenchymal features. EMT programs are controlled by several master regulators including TWIST, SNAIL (SNAI1 and SNAI2), and ZEB (ZEB1/␦EF1/TCF8 and SIP1/ZEB2) protein family members. These proteins act downstream in EMTinducing signal transduction pathways activated by growth factors, integrin engagement and hypoxia (1-3). Their expression is tightly regulated at the posttranscriptional level. Recent reports highlighted the importance of miR-200 microRNA family in the regulation of ZEB1 and SIP1 protein expression (5). ZEB proteins bind proximal E-boxes within the E-cadherin gene (cdh1) promoter and repress transcription by recruiting corepressor complexes (6). Likewise, they directly repress numerous genes encoding components of the epithelial junctional complex and cell polarity factors (7,8). The relevance of ZEB proteins to tumor progression has been studied in several forms of human cancer. Expression of ZEB1 correlated with the aggressive phenotype in various histological types of endometrial carcinoma and was detected in sarcomatous compartment of endometri...

ObjectivesThe aim of this study was to assess the test performance and clinical effectiveness of photodynamic diagnosis (PDD) compared with white light cystoscopy (WLC) in people suspected of new or recurrent bladder cancer. MethodsA systematic review of randomised controlled trials (RCTs), non-randomised comparative studies or diagnostic cross-sectional studies comparing PDD with WLC. Fifteen electronic databases and websites were searched (last searches April 2008).For clinical effectiveness only RCTs were considered. ResultsTwenty-seven studies (2949 participants) assessed test performance. PDD had higher sensitivity than WLC (92%, 95% CI 80 to 100% versus 71%, 95% CI 49 to 93%) but lower specificity (57%, 95% CI 36 to 79% versus 72%, 95% CI 47 to 96%). For detecting higher risk tumours, median sensitivity of PDD (89% (6 to 100%)) was higher than WLC (56% (0 to 100%)) whereas for lower risk tumours it was broadly similar (92% (20 to 95%) versus 95% (8 to 100%)). Four RCTs (709 participants) using 5-aminolaevulinic acid (5-ALA) as the photosensitising agent reported clinical effectiveness. Using PDD at transurethral resection of bladder tumour (TURBT) resulted in fewer residual tumours at check cystoscopy (relative risk (RR) 0.37, 95% CI 0.20 to 0.69) and longer recurrence-free survival (RR 1.37, 95% CI 1.18 to 1.59), compared with WLC. 4 ConclusionsPDD detects more bladder tumours than WLC, including more high risk tumours.Based on four RCTs reporting clinical effectiveness, 5-ALA mediated PDD at TURBT facilitates a more complete resection and prolongs recurrence-free survival.

Partial nephrectomy results in significantly better preservation of renal function over radical nephrectomy. For tumours where partial nephrectomy is not technically feasible, there is no evidence that alternative procedures or techniques are better than LRN in terms of perioperative or QoL outcomes. In making treatment decisions, perioperative and QoL outcomes should be considered in conjunction with oncological outcomes. Overall, there was a paucity of data regarding QoL outcomes, and when reported, both QoL and perioperative outcomes were inconsistently defined, measured, or reported. The current evidence base has major limitations due to studies of low methodological quality marked by high risks of bias.

Summary More than 350,000 new cases of bladder cancer are diagnosed worldwide each year; the vast majority (> 90%) of these are transitional cell carcinomas (TCC). The most important risk factors for the development of bladder cancer are smoking and occupational exposure to toxic chemicals. Painless visible haematuria is the most common presenting symptom of bladder cancer; significant haematuria requires referral to a specialist urology service. Cystoscopy and urine cytology are currently the recommended tools for diagnosis of bladder cancer. Excluding muscle invasion is an important diagnostic step, as outcomes for patients with muscle invasive TCC are less favourable. For non‐muscle invasive bladder cancer, transurethral resection followed by intravesical chemotherapy (typically Mitomycin C or epirubicin) or immunotherapy [bacillus Calmette‐Guérin (BCG)] is the current standard of care. For patients failing BCG therapy, cystectomy is recommended; for patients unsuitable for surgery, the choice of treatment options is currently limited. However, novel interventions, such as chemohyperthermia and electromotive drug administration, enhance the effects of conventional chemotherapeutic agents and are being evaluated in Phase III trials. Radical cystectomy (with pelvic lymphadenectomy and urinary diversion) or radical radiotherapy are the current established treatments for muscle invasive TCC. Neoadjuvant chemotherapy is recommended before definitive treatment of muscle invasive TCC; cisplatin‐containing combination chemotherapy is the recommended regimen. Palliative chemotherapy is the first‐choice treatment in metastatic TCC.

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S100A4 (also known as Mts1, metastasin, p9Ka, pEL98, CAPL, calvasculin, Fsp-1, placental calcium-binding protein) belongs to the family of EF-hand calcium-binding proteins, whose expression is elevated in a number of pathological conditions. Although it is well documented that S100A4 is expressed in cancer cells and contributes to tumor cell motility and metastatic progression, the exact underlying mechanisms remain elusive. An important characteristic feature of S100 proteins is their dual function, inside and outside the cell. In this review, we focus on the intracellular function of S100A4. The review contains structural analysis of S1004 in comparison with other members of S100 proteins. Possible modes of the interaction of S100 proteins with targets are described. Several examples of best-studied molecular interactions involving S100A4 with heavy chain of nonmuscle myosin IIA, LAR-interacting protein liprin beta1 and tumor suppressor protein p53 are provided. We suggest that the binding of S100A4 to these molecules is critical for the S100A4 function. Further studies of the implications of these interactions in different molecular pathways may shed additional light on the role of S100A4 protein in the control of tumor cell motility and migration. We discuss the approaches for down-regulation of S100A4 expression and their potential for application in the clinics.

Background There is no effective intravesical second-line therapy for non-muscle invasive bladder cancer (NMIBC) when bacillus Calmette-Guérin (BCG) fails. Objective To compare disease-free survival time (DFS) between radiofrequency-induced thermo-chemotherapy effect (RITE) and institutional standard second-line therapy (control) in NMIBC patients with recurrence following induction/ maintenance BCG. Design, settings, and participants Open-label, phase III randomised controlled trial accrued across 14 centres between May 2010 and July 2013 [HYMN (ClinicalTrials.gov: NCT01094964)].