A series of 78 patients with metastatic bone disease from prostate cancer underwent iliac crest biopsy, enabling histomorphometric quantification of eroded bone surface and bone volume in both tumour-free and metastatic bone tissue. Eroded surfaces in tumour-free specimens were high in patients with active compared to stable disease but bone volume was maintained in both groups, whilst in bone surrounding micrometastases (n = 8) eroded surfaces were further increased and bone volume reduced. Eroded surfaces within metastases were greater still but were associated with increased bone volume due to replacement of the existing trabecular tissue with abnormal woven bone, giving an overall appearance of sclerosis. These results show that the effect of prostate cancer on bone tissue is complex, involving differential disturbance of bone formation and resorption within metastases, in bone surrounding tumour invasion and in the tumour-free skeleton.

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The second commonest cause of cancer death in the Western world is attributed to prostate cancer (Jensen et al, 1990). It is well documented that prostatic carcinoma shows a predilection to metastasize to the bone marrow (Jacobs, 1983). Metastatic prostate cancer remains an incurable disease and as such, is a massive clinical problem. There is clearly a need to elucidate the factors underlying the spread of prostate cancer, particularly to the skeleton.It has been suggested that the bone marrow microenvironment is conducive to the growth of prostate cancer cells, which nonselectively enter the bone marrow from the circulation (Galasko, 1981;Jacobs, 1983;Paget, 1989;Body, 1992). However, the strikingly consistent pattern of prostate metastasis within the red marrow suggests that this process may in fact be regulated (Fidler et al, 1978). The mechanism of metastasis is a complex multi-step process that is not fully understood. One critical step in this mechanism may be the attachment to and extravasation through endothelial barriers by malignant cells possibly leading to selective metastatic sites. Tumour cell binding to endothelium involves two distinct steps, an initial docking step mediated via lectin-carbohydrate interactions followed by an integrin-mediated locking step (Honn and Tang, 1992). Several endothelial and tumour adhesion molecules have been associated with metastasis. In particular the integrins β1, α2 and α5 have been shown to be expressed by prostate epithelial cells and bone marrow cells (Soligo et al, 1990;Nagle et al, 1994;Rokhlin and Cohen, 1995). The carbohydrate sialyl Lewis X has also been associated with breast and lung cancer metastasis and its ligand P selectin is found on endothelial cells (Soligo et al, 1990). Some lung, brain, liver and ovary metastatic tumour cells have been demonstrated to bind selectively to endothelial cells isolated from lung, brain, liver and ovary respectively (Nicolson and Winkelhake, 1975;Auerbach et al, 1987). These studies suggest an active regulatory role for the endothelium in metastasis (Zetter, 1990).We have shown previously that primary prostatic epithelia from both benign and malignant tissue show an accelerated growth rate within bone marrow stroma compared to control stroma (Lang et al, 1998) and also that integrin α2β1 is a major contributor to the binding of primary prostatic epithelial cells to bone marrow stroma (Lang et al, 1997). This pattern of primary prostatic epithelial cell adhesion (α2β1) is mimicked by the prostate cell line, PC3 (Kostenuik et al, 1996) and our experiments were therefore conducted with this cell line. These studies have now been extended to develop a model to investigate the interactions of prostatic epithelial cells (primary and cell lines) with the bone marrow endothelium. MATERIALS AND METHODS MaterialsGeneral chemicals were purchased from Sigma (Poole, UK). Tissue culture media and supplements were obtained from Gibco Summary Prostate cancer shows a propensity to form secondary tumours within the bone marrow. Such ...

and conclusions Fifty-five consecutive male patients aged 18-77 with chronic retention of urine were investigated urodynamically. All were shown to have obstructed micturition. Inflow cystometry defined two groups, one with highpressure and one with low-pressure filling. Recent-onset enuresis and upper-tract dilatation as seen on radiography were significantly associated with high-pressure bladder filling. Postoperative studies showed that patients with high-pressure filling on preoperative cystometry had a better response to outflow-tract surgery. The poor response of the patients with low-pressure filling was due to a high incidence of inadequate detrusor contraction leading to persistent residual urine. Thus urodynamic studies may be used to indicate which patients are likely to benefit from prostatectomy and, after the operation, whether the obstruction has been relieved.