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C A Hulsbergen

Publications and source records attributed to C A Hulsbergen.

3 recordsLinked to original sources

Does the tertiary Gleason pattern influence the PSA progression-free interval after retropubic radical prostatectomy for organ-confined prostate cancer?

INTRODUCTION: The Gleason sum is an important prognostic parameter for patients treated with radical prostatectomy for localized prostate cancer. However, frequently more than two predominant Gleason patterns are present in one specimen. In this study we investigated the prognostic significance of tertiary Gleason patterns in radical prostatectomy specimens. PATIENTS AND METHODS: Between 1994 and 2001, 277 patients underwent radical retropubic prostatectomy (RRP) for clinically localised prostate cancer in our institute. We collected information on Gleason score and cancer volume (CV) for all tumour localizations, clinical and pathological stage, seminal vesicle invasion (SVI) and extra capsular extension (ECE). In case one pattern was seen in more than 95% of the tumour, this pattern was used both for the primary and secondary Gleason pattern, and any other pattern (actually the secondary pattern) was called tertiary. Charts were examined retrospectively for clinical follow up. PSA progression was defined as two subsequent rising PSA measurements above 0.10 ng/ml. Kaplan-Meier time to PSA progression was compared between patients with and without a tertiary pattern. RESULTS: Overall, of the 223 patients, 106 (48%) were found to have a tertiary pattern, which on average, was 7% of the total tumour volume. Patients with a tertiary pattern had a 5-year risk of PSA progression of 37.3% versus 12.6% in case no tertiary Gleason pattern was present (log rank p=0.0002). There was no prognostic difference between patients with a higher-grade tertiary pattern as compared to those with a lower grade tertiary pattern. CONCLUSIONS: If present, a tertiary Gleason pattern, whether better or worse than the primary or secondary pattern, is an indication for a worse outcome, as indicated by a shorter time to PSA progression. This suggests that tumour multifocality, rather than the presence of a higher-grade tertiary Gleason pattern has prognostic value.

Biomarkers, Tumor↗

A rabbit model to tissue engineer the bladder.

A rabbit model was used for the evaluation of a collagen-based biomatrix of small intestinal submucosa (SIS, COOK) in comparison to a biochemically reconstructed biomatrix for bladder tissue regeneration. Rabbits underwent partial cystectomy and cystoplasty with SIS patch graft or with a biochemically defined collagen biomatrix. The grafts of the regenerated bladder wall were harvested at different intervals and tissue regeneration was evaluated. The results of the SIS and biochemically defined biomatrix grafts were comparable. At harvesting, we found five bladder stones and encrustation of the biomatrix in 21/56 animals. No stone formation was observed in the control group. The results of the molecularly defined biomatrix are thus far comparable to SIS. Both matrices show good epithelialization and ingrowth of smooth muscle cells. Both biomatrices show considerable encrustation, which appears to disappear in time. The rabbit model is suitable for bladder tissue engineering studies as it is an easy model to use. In this model, besides tissue regeneration, also some of the clinical problems are seen such as encrustation of foreign body material in the bladder. These aspects are subject for further pre-clinical studies in this animal model.

Absorbable Implants↗

Rabbit urethra replacement with a defined biomatrix or small intestinal submucosa.

OBJECTIVE: The evaluation of collagen-based biomatrix (SIS COOK((R))) in comparison to a biochemically reconstructed biomatrix for replacement of the urethra in a rabbit model as a preclinical model. MATERIAL AND METHODS: Rabbits underwent partial urethra replacement (resection of 0.5 to 1.0 cm segment of the urethra), which was replaced with 1 or 4 layers Small Intestinal Submucosa (SIS COOK) patch grafts or with a biochemically defined collagen biomatrix, partly sutured with unresolvable sutures for future reference. Six animals underwent a sham control operation. The grafts of regenerated urethras were harvested at 1, 3 and 9 months after implantation. Urethrography was performed pre-operatively and before sacrificing. The animals were evaluated macroscopically and by routine histology and immunohistochemistry. RESULTS: At 1 month after implantation, the biomatrices (1 layer, 4 layers and our biochemically defined biomatrix) were well distinguishable from the normal surrounding tissues and showed blood vessels at the periphery. Macroscopically, the unresolvable reference sutures were easy to find at all time points. At 3 months the graft was still distinguishable in the 4 layers SIS group. In the 1 layer and the defined biomatrix group a good regeneration of the urethra within the graft was seen with some central fibrosis. Histological and immunohistochemical evaluation showed urothelium regeneration on the 1 layer and on biochemically defined biomatrix with decreasing number of inflammatory cells from 1 month on. In the group treated with 4 layers SIS the urothelium was completely regenerated at 3 months. Histologically, the regeneration of muscle cells in the three biomatrices was comparable. The smooth muscle cells regenerated very slowly as 1 month after implantation no muscle cells were detectable within the grafts. At 3 months a few muscle cells were present in the graft, but cell density did not increase in the following 6 months. Strictures were not observed on control urethrography pre-operatively in the animals. In one case slight narrowing of the urethra on urethrography was seen, but apparently without causing voiding problems. One rabbit developed a fistula near the operation site. CONCLUSION: The biomatrices investigated are feasible scaffolds to repair urethral lesions. The results with our biochemically defined biomatrix are comparable to one layer Small Intestinal Submucosa. Almost no smooth muscle cells population was observed after nine months for the three biomatrices. We conclude that an improved molecularly defined biomatrix focussed on stimulation of smooth muscle cell growth may be necessary to obtain optimal cellular grafting results.

Animals↗