Meta-analysis of the prevalence of renal cancer detected by abdominal ultrasonography.

BACKGROUND: The potential for an ultrasound-based screening programme for renal cell carcinoma (RCC) to improve survival through early detection has been the subject of much debate. The prevalence of ultrasound-detected asymptomatic RCC is an important first step to establishing whether a screening programme may be feasible. METHODS: A systematic search of MEDLINE and Embase was performed up to March 2016 to identify studies reporting the prevalence of renal masses and RCC. Two populations of patients were chosen: asymptomatic individuals undergoing screening ultrasonography and patients undergoing ultrasonography for abdominal symptoms not related to RCC. A random-effects meta-analysis was performed. Study quality was evaluated using a validated eight-point checklist. RESULTS: Sixteen studies (413 551 patients) were included in the final analysis. The pooled prevalence of renal mass was 0·36 (95 per cent c.i. 0·23 to 0·52) per cent and the prevalence of histologically proven RCC was 0·10 (0·06 to 0·15) per cent. The prevalence of RCC was more than double in studies from Europe and North America than in those from Asia: 0·17 (0·09 to 0·27) versus 0·06 (0·03 to 0·09) per cent respectively. Data on 205 screen-detected RCCs showed that 84·4 per cent of tumours were stage T1-T2 N0, 13·7 per cent were T3-T4 N0, and only 2·0 per cent had positive nodes or metastases at diagnosis. CONCLUSION: At least one RCC would be detected per 1000 individuals screened. The majority of tumours identified are early stage (T1-T2).

Identification of a hypoxia-regulated miRNA signature in bladder cancer and a role for miR-145 in hypoxia-dependent apoptosis.

BACKGROUND: Hypoxia leads to the stabilisation of the hypoxia-inducible factor (HIF) transcription factor that drives the expression of target genes including microRNAs (miRNAs). MicroRNAs are known to regulate many genes involved in tumourigenesis. The aim of this study was to identify hypoxia-regulated miRNAs (HRMs) in bladder cancer and investigate their functional significance. METHODS: Bladder cancer cell lines were exposed to normoxic and hypoxic conditions and interrogated for the expression of 384 miRNAs by qPCR. Functional studies were carried out using siRNA-mediated gene knockdown and chromatin immunoprecipitations. Apoptosis was quantified by annexin V staining and flow cytometry. RESULTS: The HRM signature for NMI bladder cancer lines includes miR-210, miR-193b, miR-145, miR-125-3p, miR-708 and miR-517a. The most hypoxia-upregulated miRNA was miR-145. The miR-145 was a direct target of HIF-1α and two hypoxia response elements were identified within the promoter region of the gene. Finally, the hypoxic upregulation of miR-145 contributed to increased apoptosis in RT4 cells. CONCLUSIONS: We have demonstrated the hypoxic regulation of a number of miRNAs in bladder cancer. We have shown that miR-145 is a novel, robust and direct HIF target gene that in turn leads to increased cell death in NMI bladder cancer cell lines.

Hypoxia regulates FGFR3 expression via HIF-1α and miR-100 and contributes to cell survival in non-muscle invasive bladder cancer.

BACKGROUND: Non-muscle invasive (NMI) bladder cancer is characterised by increased expression and activating mutations of FGFR3. We have previously investigated the role of microRNAs in bladder cancer and have shown that FGFR3 is a target of miR-100. In this study, we investigated the effects of hypoxia on miR-100 and FGFR3 expression, and the link between miR-100 and FGFR3 in hypoxia. METHODS: Bladder cancer cell lines were exposed to normoxic or hypoxic conditions and examined for the expression of FGFR3 by quantitative PCR (qPCR) and western blotting, and miR-100 by qPCR. The effect of FGFR3 and miR-100 on cell viability in two-dimensional (2-D) and three-dimensional (3-D) was examined by transfecting siRNA or mimic-100, respectively. RESULTS: In NMI bladder cancer cell lines, FGFR3 expression was induced by hypoxia in a transcriptional and HIF-1α-dependent manner. Increased FGFR3 was also in part dependent on miR-100 levels, which decreased in hypoxia. Knockdown of FGFR3 led to a decrease in phosphorylation of the downstream kinases mitogen-activated protein kinase (MAPK) and protein kinase B (PKB), which was more pronounced under hypoxic conditions. Furthermore, transfection of mimic-100 also decreased phosphorylation of MAPK and PKB. Finally, knocking down FGFR3 profoundly decreased 2-D and 3-D cell growth, whereas introduction of mimic-100 decreased 3-D growth of cells. CONCLUSION: Hypoxia, in part via suppression of miR-100, induces FGFR3 expression in bladder cancer, both of which have an important role in maintaining cell viability under conditions of stress.

miR-210 is a target of hypoxia-inducible factors 1 and 2 in renal cancer, regulates ISCU and correlates with good prognosis.

BACKGROUND: Clear cell renal cancer frequently harbours von Hippel-Lindau (VHL) gene mutations, leading to stabilisation of the hypoxia-inducible factors (HIFs) and expression of their target genes. We investigated HIF-1 and HIF-2 in the regulation of microRNA-210 (miR-210), and its clinical relevance in renal tumours. METHODS: RCC4 and 786-O renal cancer cell lines transfected with either an empty vector or functional VHL and incubated in normoxia or hypoxia were examined for miR-210 expression. Hypoxia-inducible factor siRNAs were used to examine their regulation of miR-210. Seventy-one clear cell renal tumours were sequenced for VHL mutations. Expression of miR-210, VHL, CA9, ISCU and Ki-67 were determined by immunohistochemistry and qRT-PCR. RESULTS: In addition to HIF-1 regulating miR-210 in renal cancer, HIF-2 can regulate this microRNA in the absence of HIF-1. MicroRNA-210 is upregulated in renal cancer compared with normal renal cortex tissue. MicroRNA-210 correlates negatively with its gene target ISCU at the protein and mRNA level. MicroRNA-210 correlated with positive outcome variables and negatively with Ki-67. CONCLUSION: We provide further evidence of miR-210 activity in vivo, and show that high miR-210 expression is associated with better clinico-pathological prognostic factors.

The diagnostic value of abdominal ultrasound, urine cytology and prostate-specific antigen testing in the lower urinary tract symptoms clinic.

INTRODUCTION: Lower urinary tract symptoms (LUTS) affect 18-26% of men aged 40-79 years, many of whom present with a fear of having cancer. Current guidelines for the assessment of LUTS focus mainly upon benign prostatic hypertrophy. It has been our practice to perform an abdominal ultrasound scan (USS), a prostate-specific antigen (PSA) blood test and urine cytology during the assessment of males presenting with LUTS to investigate the alternative potentially life-threatening causes for LUTS. We report on the added value of these tests during the assessment of men with LUTS. RESULTS: A total of 263/3976 (6.6%) patients investigated for LUTS were found to have incidental urological malignancies, urinary tract calculi or abdominal aortic aneurysms (AAA). Abdominal USSs resulted in the incidental diagnosis of four renal carcinomas (0.1%), 45 AAAs (incidence = 1.1%) and 44 urinary tract calculi (1.1%). Urine cytology testing and bladder USSs helped diagnose 17 new bladder cancers (0.4%), five of which did not present with haematuria. Patients found to have an elevated age-specific PSA had a 23.6% chance of being diagnosed with prostate cancer (3.8%). CONCLUSION: The addition of abdominal ultrasound scanning, urine cytology and PSA testing as part of an LUTS assessment protocol can help to diagnose significant, potentially life-threatening conditions in up to 6.6% of patients. While the pick up rate of each individual condition is not higher in the LUTS patient than in the general population, the combined pick up rate may justify these additional investigations.

Anaplastic, T-cell, non-Hodgkin's Lymphoma presenting with haematuria.

Non-Hodgkin's lymphoma (NHL) represents about 3% of new cancer cases[1]. Bladder involvement has been found in approximately 3-13% of NHL patients when studied at postmortem[2]. Although accounting for only 0.2% of all primary bladder tumours, the majority of bladder lymphomas are B-cell lymphomas. T-cell lymphoma of the bladder is incredibly rare. We describe a case of anaplastic, T-cell lymphoma presenting with haematuria and loin pain, with unilateral upper tract obstruction.

A unique case of a malignant Sertoli cell tumour with cutaneous metastasis.

Pure Sertoli cell tumours (SCTs) represent less than 1% of testicular neoplasms and malignant forms are rare. We present a unique case of a 69-year-old man who initially underwent inguinal orchidectomy for a malignant SCT. He then subsequently developed a paraumbilical cutaneous lesion which was histologically identical to the primary tumour. SCTs rarely metastasise. This is the first case of SCT with cutaneous metastasis described in the literature.

Bilateral renal angiomyolipomas with invasion of the renal vein: a case report.

An angiomyolipoma (AML) is usually a benign, rare, and, more commonly, a unilateral renal tumour. Bilateral tumours are very rare, particularly in the absence of tuberous sclerosis complex. Only in a few isolated cases have features of malignancy been associated with an AML. We present a unique case of bilateral AMLs mimicking invasive tumours in the absence of any other features of tuberous sclerosis complex.

The detection of patients with 'fragility fractures' in fracture clinic - an audit of practice with reference to recent British Orthopaedic Association guidelines.

INTRODUCTION: The British Orthopaedic Association published guidelines on the care of fragility fracture patients in 2003. A section of these guidelines relates to the secondary prevention of osteoporotic fractures. The objective of this audit was to compare practice in our fracture clinic to these guidelines, and take steps to improve our practice if required. PATIENTS AND METHODS: We retrospectively audited the treatment of all 462 new patients seen in January and February 2004. Using case note analysis, 38 patients who had sustained probable fragility fractures were selected. Six months' post-injury, a telephone questionnaire was administered to confirm the nature of the injury and to find out whether the patient had been assessed, investigated or treated for osteoporosis. A second similar audit was conducted a year later after steps had been taken to improve awareness amongst the orthopaedic staff and prompt referral. RESULTS: During the first audit period, only 5 of 38 patients who should have been assessed and investigated for osteoporosis were either referred or offered referral. This improved to 23 out of 43 patients during the second audit period. CONCLUSIONS: Improvements in referral and assessment rates of patients at risk of further fragility fractures can be achieved relatively easily by taking steps to increase awareness amongst orthopaedic surgeons, although additional strategies and perhaps the use of automated referral systems may be required to achieve referral rates nearer 100%.

Health-related quality of life after retroperitoneoscopic and hand-assisted laparoscopic nephrectomy.

BACKGROUND AND PURPOSE: The assessment of postoperative recovery typically involves the use of measures that are open to bias. Whilst there has been some work done on the short-term postoperative recovery comparison for hand-assisted laparoscopic nephrectomy (HALN) and retroperitoneoscopic nephrectomy (RPN), to our knowledge, this is the first study to look at long-term health outcomes for these two procedures. This study sought objectively to compare long-term postoperative health-related quality of life (HRQoL) after retroperitoneoscopic and hand-assisted transperitoneal laparoscopic nephrectomy undertaken for renal pathology. This was achieved by both reviewing perioperative data from medical records and by using the SF-36 questionnaire postoperatively. PATIENTS AND METHODS: Patients who had undergone elective retroperitoneoscopic (N = 19) or transperitoneal HALN (N = 32) between 2001 and 2004 at our institution underwent objective HRQoL assessment via a validated telephone questionnaire (SF-36) and by review of postoperative data from the medical records. This survey was administered between 3 and 6 months after surgery. The data then underwent statistical analysis using the paired Student's t-test. RESULTS: Perioperative data showed no significant difference in the postoperative complication rate in the two groups. The HRQoL scores gathered from the SF-36 questionnaire gave mean scores of 67.4 and 68.5 for the HALN and RPN groups, respectively (100 represents maximum quality of life). This difference was not statistically significant. CONCLUSIONS: This is the first study to look at long-term (mean follow-up 6 months) health outcomes for patients undergoing RPN and HALN. The results show no greater long-term health benefit for one procedure over the other. This finding supports the data in the literature on the benefits of HALN over RPN in terms of a less protracted learning curve, greater technical ease, fewer intraoperative complications, and consequently reduced operating times with no loss of the long-term health benefit that is traditionally associated with the standard laparoscopic technique.