Proliferative response of human prostate tumour xenografts to surgical trauma and the transurethral resection of the prostate controversy

Abstract

Summary Transurethral resection of the prostate (TURP) as an excisional procedure involving multiple incisions into the prostate does not differentiate between palpably benign prostate tissue and microscopic foci of well-differentiated adenocarcinoma. The impact of TURP on the progression of such 'latent' or 'incidental' tumours unique to the prostate gland has been a focal point of a continuing controversy. In studies designed to develop preclinical evidence that would lend support to, or detract from, either side of the TURP controversy, surgical trauma-induced stimulation of in situ tumour growth was extended to include human prostate tumour tissue PC-3, DU-145 and H-1579, albeit (Coplen et al., 1991). An astonishingly high prevalence of what pathologists have interpreted as microscopic foci of well-differentiated adenocarcinoma has been found at autopsy in serial sections of prostate glands considered to be normal from men over the age of 50. Every decade of ageing nearly doubles the incidence of such tumours -from 10% in men in their 50s to 70% in men in their 80s (Scott et al., 1969;Sheldon et al., 1980). Such a prevalence of 'latent' or 'incidental' tumours appears to be unique to the prostate gland (Silverberg and Lubera, 1989). The biological potential of focal low-grade, incidentally discovered prostatic cancer (stage Al) has generally been believed to be relatively innocuous, although this view has been challenged in recent years by several groups who have found a 16-27% rate of disease progression in patients followed for extended periods (Blute et al., 1986;Epstein et al., 1986). The phenomenon of tumour cell dissemination by surgical manipulation has been investigated with various surgical procedures and tumour types and is hardly a fresh topic. It has, however, become an important concept for exploration with regard to prostatic carcinoma, considering both the incidence of this particular tumour and the frequency with which TURP has been performed for obstructive symptoms. The actual impact of TURP on the development of metastases, however, is not well defined. McGowan (1980) has reported that the 5 year actuarial disease-free survival of patients with clinical stage B and C tumours treated by radiation therapy is significantly lower for patients who have undergone prior TURP compared with patients who have not undergone prior TURP. Further, it has been speculated that the relatively poor prognosis of patients with stage A2 prostatic tumours may be related to tumour dissemination during TURP (Walsh, 1980 al., 1983) or to the possibility that the patients who were selected for TURP had a higher incidence of clinically occult metastases before the procedure bears upon the influences of the method of diagnosis (TURP vs needle biopsy) on patient outcome, which is also controversial (Hanks et al., 1986;Kuban et al., 1987;McGowan, 1988).In a retrospective analysis of 225 patients with localised adenocarcinoma of the prostate who were treated with continuous-course external-beam radiation therapy, A...

High-Resolution Ultrasound Allows Percutaneous Initiation and Surveillance of Prostate Cancer in an Orthotopic Murine Model

“…It is already known that surgically traumatized animals show an increased proliferative response in human prostate tumor xenografts, possibly due to blood-borne growth factors [19]. This may explain our finding that the tumors induced through open surgery were bigger than those inoculated percutaneously.…”

Proliferative response of human and animal tumours to surgical wounding of normal tissues: onset, duration and inhibition

“…With a more complex description of the various growth factors, it is increasingly apparent that the same mediators of cell growth and stromal synthesis are involved in malignancy, fetal growth and wound healing. In our own studies, surgical traumatization (wounding) of normal connective tissues, such as excision of a segment of skin or abrasion of subcutaneous fascia, induced a significant proliferative response of human prostate tumour xenografts implanted in athymic nude mice (Bogden et al, 1996). Application of a somatostatin analogue, a neuroendocrine antisecretagogue, to the wound had an inhibitory effect on the proliferative response, suggesting the surgical wound as a source of tumour-stimulatory factors.…”

“…We had also observed that LAN applied topically to the surgical wound appears to inhibit the release of these factors, inducing a therapeutic tumour-inhibitory effect in surgically treated animals (Bogden et al, 1996). The following studies were designed to confirm the British Journal of Cancer (1997) 75 (7), 1021-1027 findings described above and to test the antisecretagogue activity of LAN further by treating the surgical wound only during the critical first 2-3 days after traumatization.…”

“…The feasibility of inducing a therapeutic tumour-inhibitory effect by inhibiting the phenomenon with a somatostatin analogue augers for a post-operative treatment modality as wound breaking strength assays indicate that somatostatin analogues do not significantly affect wound healing in normal rats (Abribat et al, 1992;Bogden et al, 1996).…”

Early Events of Hepatic Metastasis Formation in Mice: Role of Kupffer and NK-Cells in Natural and Interferon-γ-Stimulated Defense

“…Surgical manipulation of the tumor may result in an increased influx of tumor cells to the blood, which in turn may result in saturation of the tumoricidal capacity of the host [4,6]. This condition has been shown to increase the formation of metastases in experimental models [9,53,55,56].…”