Comprehensive profiling and localisation of the matrix metalloproteinases in urothelial carcinoma.

The matrix metalloproteinases (MMPs) are endopeptidases which break down the extracellular matrix and regulate cytokine and growth factor activity. Several MMPs have been implicated in the promotion of invasion and metastasis in a broad range of tumours including urothelial carcinoma. In this study, RNA from 132 normal bladder and urothelial carcinoma specimens was profiled for each of the 24 human MMPs, the four endogenous tissue inhibitors of MMPs (TIMPs) and several key growth factors and their receptors using quantitative real time RT-PCR. Laser capture microdissection (LCM) of RNA from 22 tumour and 11 normal frozen sections was performed allowing accurate RNA extraction from either stromal or epithelial compartments. This study confirms the over expression in bladder tumour tissue of well-documented MMPs and highlights a range of MMPs which have not previously been implicated in the development of urothelial cancer. In summary, MMP-2, MT1-MMP and the previously unreported MMP-28 were very highly expressed in tumour samples while MMPs 1, 7, 9, 11, 15, 19 and 23 were highly expressed. There was a significant positive correlation between transcript expression and tumour grade for MMPs 1, 2, 8, 10, 11, 12, 13, 14, 15 and 28 (P < 0.001). At the same confidence interval, TIMP-1 and TIMP-3 also correlated with increasing tumour grade. LCM revealed that most highly expressed MMPs are located primarily within the stromal compartment except MMP-13 which localised to the epithelial compartment. This work forms the basis for further functional studies, which will help to confirm the MMPs as potential diagnostic and therapeutic targets in early bladder cancer.

Percutaneous stone surgery in the obese: outcome stratified according to body mass index.

OBJECTIVE: To report our experience of percutaneous surgery for treating renal pelvicalyceal stones over 6 years, to show that this approach is feasible and safe in obese and morbidly obese patients, as the prevalence of obesity and stone disease has risen in the last 20 years. PATIENTS AND METHODS: We retrospectively reviewed the results of 223 percutaneous nephrolithotomies (PCNLs) by one urologist between 1995 and 2001. Patients were stratified into four groups according to the World Health Organization classification of body mass index (BMI), i.e. <25, 25-29.9 (overweight), 30-39.9 (obese) and > 40 kg/m(2) (morbidly obese). The outcomes of surgery in these four groups were compared. RESULTS: There were no statistically significant differences in operative duration, decrease in haemoglobin concentration, postoperative analgesic use, hospital stay and stone-free rates; nor was there a higher complication rate in patients who were obese. CONCLUSION: The outcome of PCNL is independent of the patients' BMI and results can be favourable in most patients. We therefore advocate treating obese patients with symptomatic stone disease based on individual status, using percutaneous surgery where appropriate.