Objective: To examine the natural history of patients identified with atypical urine cytology in the face of normal investigations, and thus provide guidance on the need for extended follow-up and investigation of such patients. Patients and methods: All patients identified over a 2-year period to have atypical urine cytology on Cytospin analysis and Papanicolaou staining were audited over a 5-year follow-up period. Clinical records, histopathology and radiology databases were independently searched. Patients were intensively investigated with cystoscopy and a range of upper tract imaging. Results: 126 patients were identified to have atypical urine cytology, and 77 of these had no urothelial tumour found. In these normal patients, only 12/48 who had further samples taken showed persistent atypia. 11/77 normal patients had another urological pathology which may have explained their atypical urine cytology. No patient presenting for the first time later went on to develop urothelial malignancy in the face of negative initial investigations. Conclusion: In the group of patients in which cystoscopy and urography show no urothelial malignancy, the finding of atypical urinary cytology does not predict the development of later urothelial tumour, and does not require prolonged follow-up, repeat cytological testing or further imaging.

Elevated thymidine phosphorylase has been shown to correlate with increased angiogenesis and poor prognosis in many cancers including transitional cell carcinoma of the bladder. In vitro studies have demonstrated that thymidine phosphorylase activity causes cellular oxidative stress and increases secretion of vascular endothelial growth factor. In this study, we show that thymidine phosphorylase activity also augments levels of the hypoxia-inducible factor-1α during in vitro hypoxia, and that thymidine phosphorylase activity and hypoxia act in concert to increase vascular endothelial growth factor (VEGF) secretion. We also demonstrate that thymidine phosphorylase overexpression confers tumorigenicity on an orthotopically implanted transitional cell carcinoma cell line. Administration of the antioxidant N-acetylcysteine together with a blocking anti-VEGF antibody abrogates the increase in tumorigenicity. Our results support the increased efficacy of combination approaches to antiangiogenic therapy.

Hypoxia-inducible genes have been linked to the aggressive phenotype of cancer. However, nearly all work on hypoxia-regulated genes has been conducted in vitro on cell lines. We investigated the hypoxia transcriptome in primary human bladder cancer using cDNA microarrays to compare genes induced by hypoxia in vitro in bladder cancer cell line EJ28 with genes upregulated in 39 bladder tumour specimens (27 superficial and 12 invasive). We correlated array mRNA fold changes with carbonic anhydrase 9 (CA IX) staining of tumours as a surrogate marker of hypoxia. Of 6000 genes, 32 were hypoxia inducible in vitro more than two-fold, five of which were novel, including lactate transporter SLC16A3 and RNAse 4. Eight of 32 hypoxia-inducible genes in vitro were also upregulated on the vivo array. Vascular endothelial growth factor mRNA was upregulated two-fold by hypoxia and 2–18-fold in 31 out of 39 tumours. Glucose transporter 1 was also upregulated on both arrays mRNA, and fold changes on the in vivo array significantly correlated with CA IX staining of tumours (P=0.008). However, insulin-like growth factor binding protein 3 mRNA was the most strongly differentially expressed gene in both arrays and this confirmed its upregulation in urine of bladder cancer patients (n=157, P<0.01). This study defines genes suitable for an in vivo hypoxia 'profile', shows the heterogeneity of the hypoxia response and describes new hypoxia-regulated genes.

OBJECTIVE:To determine the incidence of urological complications of renal transplantation at one institution, and relate this to donor and recipient factors.PATIENTS AND METHODS:A consecutive series of 1535 renal transplants were audited, and a database of donor and recipient characteristics created for risk-factor analysis. An unstented Leadbetter-Politano anastomosis was the preferred method of ureteric reimplantation.RESULTS:There were 45 urinary leaks, 54 primary ureteric obstructions, nine cases of ureteric calculi, three bladder stones and 19 cases of bladder outlet obstruction at some time after transplantation. The overall incidence of urological complications was 9.2%, with that for urinary leak or primary ureteric obstruction being 6.5%. One graft was lost because of complications, and there were three deaths associated directly or indirectly with urological complications. There was no association with recipient age, cadaveric vs living-donor transplants, or cold ischaemic times before organ reimplantation, although the donor age was slightly higher in cases of urinary leak. There was no association with kidneys imported via the UK national organ-sharing scheme vs the use of local kidneys. The management of these complications is discussed.CONCLUSION:The incidence of urological complications in this series has remained essentially unchanged for 20 years. The causes of these complications and techniques for their prevention are discussed.

Angiogenesis is the process by which tumours induce a blood supply, crucial for growth and metastasis. Evidence for its role in bladder carcinogenesis, its usefulness as a marker of patient prognosis, and potential anti-angiogenic therapies for future development are discussed in this chapter.

Angiogenesis is the process by which tumours induce a blood supply from their surrounding tissues and it has been shown to be necessary for tumour growth. Evidence is accumulating for both the prognostic usefulness of measures of angiogenesis and its potential as a target for anticancer therapy. This review discusses the evidence concerning the association between angiogenesis and bladder cancer, focusing on the mechanisms behind the angiogenic process and the quantification of factors believed to be involved, relating these clinically to their prognostic use and to the antiangiogenic strategies so far described in vitro and in vivo.