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Treatment of postprostatectomy incontinence -3 years experience using a new minimal invasive technique
605 TREATMENT OF POSTPROSTATECTOMY YEARS EXPERIENCE USING A NEW TECHNIQUE
INCONTINENCE -3 MINIMAL INVASIVE
Van Poooel H.‘, Bolla M.~. Van Cangh P... Vckemans K:, Rigatti P.‘, De Reijke T.“, Verbacps A.-, Van Velthoven R.“, Mar&ha1 J.“, Haustermans K.‘“. Scalliet P.“. Collette L.“, Pierart M.”
Schlarn O.M., Hiibner W.A KH Komeuburg,
Urology, Komeuburg,
606 HOW SEVERE IS ACUTE AND LATE TOXICITY OF POSTOPERATIVE RADIATION TREATMENT FOR PT3NO PROSTATE CANCER? EORTC TRIAL 22911
Austria
INTRODUCTION & OBJECTIVES: Effort incontinence after radical Prostatectomy occurs in 5 to 20% of cases. Treatment options were mainly implantation of a hydraulic sphincter or the use of bulky agents. We present an entirely new approach, which can be performed as an outpatient procedure. MATERIAL & METHODS: The PRO ACT device (Adjustable Continence Therapy) consists of two balloons, which are implanted periurethrally through a perineal approach. The balloon volume can be adjusted any time after implantation via a tubing conduit and a titanium port, which is placed subcutaneously into the scrotum in a minimal invasive procedure. We report on long- term continence rate and patient satisfaction in men treated for urinary Incontinence after prostatectomy with the implantation of this device. With a computer database, the implant reports of 52 consecutive patients who had the PRO ACT device implanted from Sept. 99 to Aug. 2002 were collected. The medical records of these patients, including cystometry, Valsalva leak point pressure measurement, were reviewed, and a quality of life questionnaire (Elli Lilly 1996) was evaluated at baseline and follow up investigations. RESULTS: 18 of 52 (34%) had a failed bulking agents therapy prior to PRO ACT implantation. After a mean follow up of 8,57 months (range l-31), 32 patients were dry, 15 improved, 5 did not improve. Av. 4 adjustments (2-9) were necessary to achieve these results. The number of daily used pads decreased from av. 4 to av. 0,5. Valsalva LPP increased from av. 28,9 to av. 67,0 cm H,O. The Quality of life score obtained from the questionnaire increased subsequently from av. 50,6 (Range 23-89 Max. available:1 IO) to av. 86 (36-106) after 12 months. 16 patients experienced complications, such as: intraoperative perforation of the bladder or urethra 9x, loss of balloon volume 10x, balloon migration 8x. There were no long-time complications. Operation time decreased from initially av. 45 minutes to av. 25. CONCLUSIONS: PRO ACT is very well accepted by patients and their treating urologists. The surgical procedure is easy and has a short learning curve. The long-term results are better compared to other minimal invasive procedures and offer the opportunity to treat postprostatectomy incontinence effectively. P33 TESTISCANCER Satufi%y,hch 15,07.45-09.15hrs,RoomN104 ANGIOGENETIC PROTOONCOGEN ETS-1 NEOVASCULARIZATION IS INVOLVED IN THE PROCESS OF TESTICULAR GERM CELL TUMOURS
,University Hospitals of KULeuven, Urology, Leuven, Belgium, ‘CHR &-&noble. Radiotherapy, Grenoble, France, ‘Cliniques Univeraitaires St. Luc, Urology, Brusselr. Belgium, ‘Virga Jesse Hospital, Urology. Hasselt, Belgium, ‘San R&Ye, Urology, Milano. Italy, ‘AMC, Urology, Amsterdam, The Netherlands, ‘Umversiry Hospital, Urology, Ghent, Belgium, “Institut Jules Bordet, Urology, Brussels, Belgium, ‘HBpital Edouard Herriot, Urology, Lyon, France, ‘YJniversity Hosptial of KULeuven, Radiotherapy, Leuven, Belgium, “Cliniques Universitaires St. Luc, Radiotherapy, Brussels, Belgium, “EORTC Data Center, Statistician, Bmssels, Belgium, “EORTC Data Center. Datamanager, Brussels.
Belgium INTRODUCTION & OBJECTIVES: 1005 panems with pT3NO prostate cancer that underwent radical prostatectomy between II11992 and 1l/2001 were random&d in EORTC-trial 22911. 503 patients had no adJuvant treatment and 502 had 60 Gy immediate post-operative MATERIAL
irradiation within 16 weeks.
& METHODS: the 423 eheible
Acute and late toxlcny of the combined treatment arm &as oatlents entered m the srudv hefore Januarv 2001 and was assessed in graded according to the_WHb and RTOG scales respect&y. The 3-y& mcidence rates were estimated usmg the Kaplan-Mew method. RESULTS: The median age of the patients was 65.3 (range: 47.2-75.8). The pre-opcratlbe T stage (TNM 19X3) was cTl 19% cT2 63 % and cT3 18%. WHO histopathological grade
was 1 (15%). II (62%). III (23%). and pathologically there was capsule perforation m 75%, invasion of the seminal vesicles m 26% and positive surgical margins in 63%. The medmn radiotherapy dose was 60 Gy delivered in a me&an of 30 fractions. Early toxicity: 1 I patients (3%) stopped radiotherapy because of grade 2-3 diarrhoea (6). cystitis (1). rectitis (3) and bladder frequency (1). WHO acute diarrhoea G3 was reported in 5% of the patients, G3-4 bladder frequency in 3.3%, G3 dysuria in 1.2”/. Skin toxicity G3 was observed in 2 patients (0.5%). Late toxicity: after median follow-up of 3.8 years, no grade 4 late complications have been reported and grade 3 late complications were reported m 11 patients (2.6O$ IO GU and I GI). G3 late complications were urethral stricture in 6 patients. incontinence m 6 and small bowel obstruction in 1. The 3-year GU late toxicity rate was 2.8% (95% Cl: 1.1 4.5%) for grade 3 and 14.7% (95% Cl: 11.0 18.5%) for G2-3. The only grade 3 late GI toxicity was observed after 3 years, and the 3-year G2 GI toxwuy rate nils 2.5”h (95”/, Cl: 0.9 4.5%).
CONCLUSIONS: With a median follow-tip of 3.8 years. acute and late toxicity of early post-operatwe external madiatlon of .p73NO prostate cancer patients are low wnh on/v . 2.8 % incidence of grade 3 late toxicity at 3 years. The combined treatment rnodahty see& safe and the final results of the trial should show whether oost-onerative irradiation should systematically be offered to patients at high risk of local relapse. 1
.
607 INDUCED METASTATIC
Adam M.‘, Schtmdt 0.‘. Wardclmann E.‘, Wemert N.‘, Albers P.’ ‘University of Bonn, Urology, Bonn, Germany, ‘Universny of Bonn. Pathology, Bonn. Germany
608 FLUORESCENT MICROSATELLITE ANALYSIS (MSA) D382447AS A NEW SEMINOMA SPECIFIC MARKER Ohlmann C., Rappenherg Philipps-iiniversity,
IDENTIFIES
D.. Konrad L.. Hofmann R.. Heidenreich
Department
A.
of Urology. Marburg, Germany
INTRODUCTION & OBJECTIVES: Induction of angiogenesis is csscntial for tumour growth and metastasis. The role of angiogenetic factors and corresponding microvessel density in the development of metastasis of testicular germ cell turnours (GCT’s) is not clearly defined. Aim of the study was to gain new insights in the expression of the above described factors in different subtypes of metastatic and nonmetastatic GCT’s.
INTRODUCTION & OBJECTIVES: Molecular events triggering the malignant transformation of primordial germ cell to testicular intraepithelial neoplasia and being involved in the progression of TIN to locally invasive GCT arc still unknown. Amplification of the chromosomal subregion 12pl l.2-~12.1 represents a characteristic finding in >90% of all GCT, but no specific genes have been identified. Purpose of our study was to identify new chromosomal regions potentially being involved in the pathogenesis of GCT.
MATERIAL & METHODS: Paraffin embedded tissues of 39 GCT’s (19 organ confined CiCT’s, pathological stage 1 and 20 GCT’s with metastasis, pathological stage IIA or IIB) were immunohistochemical stained with antibodies for VEGF, flt, flk, ets-I as well as for endothelial markers CD34 and CDl05. Areas representative of the invasive tumour were selected and the different histological subtypes were microdissected. For each subtype immunohistochemical expression in metastatic and organ-confined turnours was assessed. Addinonally, neovascularization was investigated by microvessel density and correlated to the markers of angiogenesis. For positive control expression of VEGF in Leydig and Sertoli cells was determined.
MATERIAL & METHODS: Fresh specimens of tumour & normal parenchyma were collected in 44 TGCT and IO healthy controls. DNA was extracted by phenol-chloroform method from both tissue and blood samples. Eor MSA. 21 polymorphic markers on 9 chromosomal arms were analysed. Following PCR amplification detection of allelic imbalance (Al), LOH, deletion, amplification (AMP) was carried out using an automated laser sequencer. With regard to 12pl1.2.p 12. I the encoded genes SOX5. JAW I and K-ras were analysed by RT-PCR and Southern Blot.
RESULTS: Highest VEGF expression was seen in teratoma components (100% in metastatic, 86% in organ confined turnours). @here was no significant difference in the expression of VEGF, flt or flk in metastatic vs. organ-confined tumours and their different histological subtypes seen. Only the expression of ets-I differed significantly in all different histological tumour subtypes between and metastatic and non-metastatic turnours. In addition, using CD105 a significantly higher microvessel density was observed in stage II tumours and in GCT’s positive for e&-l.
RESULTS: No DNA alterations were detected in normal tissue samples of controls; at least I molecular event (LOW, AI, AMP) was identified in 41144 (93.2%) TGCT. Most frequently tumour associated LOH/AI were detected for DlSl656 (41%), D3S2447 (42%), D9S1748 (53%). DllS1978 (42%), Dl7S799 (37%). Alterations for D3S2447 were only demonstrated in seminomas and associated TIN but not in nonseminomas; amplifications of Dl7S799 were only detected in seminomas. SOX5, JAW I and K;ras did not demonstrate TGCT-specific alterations.
CONCLUSIONS: Higher expression of VEGF was seen in better-differentiated tumour components such as teratoma. VEGF and its receptors flt and flk seem not bc involved in the progress of metastatic development of GCT’s. Only ets-1, a protooncogene involved in tumour angiogenesis, showed a significantly higher expression in metastatic GCT’s. A difference in microvessel density between tumour stages could only be observed if the specific CD105 antibody was used, in contrast no different distribution of microvessels in histological subtypes or tumour stage was seen if the pan-endothelial marker CD34 was used. Conclusively, ets-1 together with microvessel density determined by CD105 may have prognostic value m the multistep event of carcinogenesis.
European
Urology Supplements 2 (2003) No. 1, pp. 154
CONCLUSIONS: For the first time, D3S2447 was identified as a new seminoma specific chromosomal marker. D3S2447 encodes for the DAZL-1 gene and the expression of the protein product has also only been found in seminomas. The seminoma specific amplification of Dl73799 might contribute to the progression of TIN into locally invasive seminomas. JAWl, SOX5 and Kras arc not involved in the pathogenesis of TGCT. Grant of Kempkes Stiftung Marburg, Germany.
INCONTINENCE -3 MINIMAL INVASIVE
Van Poooel H.‘, Bolla M.~. Van Cangh P... Vckemans K:, Rigatti P.‘, De Reijke T.“, Verbacps A.-, Van Velthoven R.“, Mar&ha1 J.“, Haustermans K.‘“. Scalliet P.“. Collette L.“, Pierart M.”
Schlarn O.M., Hiibner W.A KH Komeuburg,
Urology, Komeuburg,
606 HOW SEVERE IS ACUTE AND LATE TOXICITY OF POSTOPERATIVE RADIATION TREATMENT FOR PT3NO PROSTATE CANCER? EORTC TRIAL 22911
Austria
INTRODUCTION & OBJECTIVES: Effort incontinence after radical Prostatectomy occurs in 5 to 20% of cases. Treatment options were mainly implantation of a hydraulic sphincter or the use of bulky agents. We present an entirely new approach, which can be performed as an outpatient procedure. MATERIAL & METHODS: The PRO ACT device (Adjustable Continence Therapy) consists of two balloons, which are implanted periurethrally through a perineal approach. The balloon volume can be adjusted any time after implantation via a tubing conduit and a titanium port, which is placed subcutaneously into the scrotum in a minimal invasive procedure. We report on long- term continence rate and patient satisfaction in men treated for urinary Incontinence after prostatectomy with the implantation of this device. With a computer database, the implant reports of 52 consecutive patients who had the PRO ACT device implanted from Sept. 99 to Aug. 2002 were collected. The medical records of these patients, including cystometry, Valsalva leak point pressure measurement, were reviewed, and a quality of life questionnaire (Elli Lilly 1996) was evaluated at baseline and follow up investigations. RESULTS: 18 of 52 (34%) had a failed bulking agents therapy prior to PRO ACT implantation. After a mean follow up of 8,57 months (range l-31), 32 patients were dry, 15 improved, 5 did not improve. Av. 4 adjustments (2-9) were necessary to achieve these results. The number of daily used pads decreased from av. 4 to av. 0,5. Valsalva LPP increased from av. 28,9 to av. 67,0 cm H,O. The Quality of life score obtained from the questionnaire increased subsequently from av. 50,6 (Range 23-89 Max. available:1 IO) to av. 86 (36-106) after 12 months. 16 patients experienced complications, such as: intraoperative perforation of the bladder or urethra 9x, loss of balloon volume 10x, balloon migration 8x. There were no long-time complications. Operation time decreased from initially av. 45 minutes to av. 25. CONCLUSIONS: PRO ACT is very well accepted by patients and their treating urologists. The surgical procedure is easy and has a short learning curve. The long-term results are better compared to other minimal invasive procedures and offer the opportunity to treat postprostatectomy incontinence effectively. P33 TESTISCANCER Satufi%y,hch 15,07.45-09.15hrs,RoomN104 ANGIOGENETIC PROTOONCOGEN ETS-1 NEOVASCULARIZATION IS INVOLVED IN THE PROCESS OF TESTICULAR GERM CELL TUMOURS
,University Hospitals of KULeuven, Urology, Leuven, Belgium, ‘CHR &-&noble. Radiotherapy, Grenoble, France, ‘Cliniques Univeraitaires St. Luc, Urology, Brusselr. Belgium, ‘Virga Jesse Hospital, Urology. Hasselt, Belgium, ‘San R&Ye, Urology, Milano. Italy, ‘AMC, Urology, Amsterdam, The Netherlands, ‘Umversiry Hospital, Urology, Ghent, Belgium, “Institut Jules Bordet, Urology, Brussels, Belgium, ‘HBpital Edouard Herriot, Urology, Lyon, France, ‘YJniversity Hosptial of KULeuven, Radiotherapy, Leuven, Belgium, “Cliniques Universitaires St. Luc, Radiotherapy, Brussels, Belgium, “EORTC Data Center, Statistician, Bmssels, Belgium, “EORTC Data Center. Datamanager, Brussels.
Belgium INTRODUCTION & OBJECTIVES: 1005 panems with pT3NO prostate cancer that underwent radical prostatectomy between II11992 and 1l/2001 were random&d in EORTC-trial 22911. 503 patients had no adJuvant treatment and 502 had 60 Gy immediate post-operative MATERIAL
irradiation within 16 weeks.
& METHODS: the 423 eheible
Acute and late toxlcny of the combined treatment arm &as oatlents entered m the srudv hefore Januarv 2001 and was assessed in graded according to the_WHb and RTOG scales respect&y. The 3-y& mcidence rates were estimated usmg the Kaplan-Mew method. RESULTS: The median age of the patients was 65.3 (range: 47.2-75.8). The pre-opcratlbe T stage (TNM 19X3) was cTl 19% cT2 63 % and cT3 18%. WHO histopathological grade
was 1 (15%). II (62%). III (23%). and pathologically there was capsule perforation m 75%, invasion of the seminal vesicles m 26% and positive surgical margins in 63%. The medmn radiotherapy dose was 60 Gy delivered in a me&an of 30 fractions. Early toxicity: 1 I patients (3%) stopped radiotherapy because of grade 2-3 diarrhoea (6). cystitis (1). rectitis (3) and bladder frequency (1). WHO acute diarrhoea G3 was reported in 5% of the patients, G3-4 bladder frequency in 3.3%, G3 dysuria in 1.2”/. Skin toxicity G3 was observed in 2 patients (0.5%). Late toxicity: after median follow-up of 3.8 years, no grade 4 late complications have been reported and grade 3 late complications were reported m 11 patients (2.6O$ IO GU and I GI). G3 late complications were urethral stricture in 6 patients. incontinence m 6 and small bowel obstruction in 1. The 3-year GU late toxicity rate was 2.8% (95% Cl: 1.1 4.5%) for grade 3 and 14.7% (95% Cl: 11.0 18.5%) for G2-3. The only grade 3 late GI toxicity was observed after 3 years, and the 3-year G2 GI toxwuy rate nils 2.5”h (95”/, Cl: 0.9 4.5%).
CONCLUSIONS: With a median follow-tip of 3.8 years. acute and late toxicity of early post-operatwe external madiatlon of .p73NO prostate cancer patients are low wnh on/v . 2.8 % incidence of grade 3 late toxicity at 3 years. The combined treatment rnodahty see& safe and the final results of the trial should show whether oost-onerative irradiation should systematically be offered to patients at high risk of local relapse. 1
.
607 INDUCED METASTATIC
Adam M.‘, Schtmdt 0.‘. Wardclmann E.‘, Wemert N.‘, Albers P.’ ‘University of Bonn, Urology, Bonn, Germany, ‘Universny of Bonn. Pathology, Bonn. Germany
608 FLUORESCENT MICROSATELLITE ANALYSIS (MSA) D382447AS A NEW SEMINOMA SPECIFIC MARKER Ohlmann C., Rappenherg Philipps-iiniversity,
IDENTIFIES
D.. Konrad L.. Hofmann R.. Heidenreich
Department
A.
of Urology. Marburg, Germany
INTRODUCTION & OBJECTIVES: Induction of angiogenesis is csscntial for tumour growth and metastasis. The role of angiogenetic factors and corresponding microvessel density in the development of metastasis of testicular germ cell turnours (GCT’s) is not clearly defined. Aim of the study was to gain new insights in the expression of the above described factors in different subtypes of metastatic and nonmetastatic GCT’s.
INTRODUCTION & OBJECTIVES: Molecular events triggering the malignant transformation of primordial germ cell to testicular intraepithelial neoplasia and being involved in the progression of TIN to locally invasive GCT arc still unknown. Amplification of the chromosomal subregion 12pl l.2-~12.1 represents a characteristic finding in >90% of all GCT, but no specific genes have been identified. Purpose of our study was to identify new chromosomal regions potentially being involved in the pathogenesis of GCT.
MATERIAL & METHODS: Paraffin embedded tissues of 39 GCT’s (19 organ confined CiCT’s, pathological stage 1 and 20 GCT’s with metastasis, pathological stage IIA or IIB) were immunohistochemical stained with antibodies for VEGF, flt, flk, ets-I as well as for endothelial markers CD34 and CDl05. Areas representative of the invasive tumour were selected and the different histological subtypes were microdissected. For each subtype immunohistochemical expression in metastatic and organ-confined turnours was assessed. Addinonally, neovascularization was investigated by microvessel density and correlated to the markers of angiogenesis. For positive control expression of VEGF in Leydig and Sertoli cells was determined.
MATERIAL & METHODS: Fresh specimens of tumour & normal parenchyma were collected in 44 TGCT and IO healthy controls. DNA was extracted by phenol-chloroform method from both tissue and blood samples. Eor MSA. 21 polymorphic markers on 9 chromosomal arms were analysed. Following PCR amplification detection of allelic imbalance (Al), LOH, deletion, amplification (AMP) was carried out using an automated laser sequencer. With regard to 12pl1.2.p 12. I the encoded genes SOX5. JAW I and K-ras were analysed by RT-PCR and Southern Blot.
RESULTS: Highest VEGF expression was seen in teratoma components (100% in metastatic, 86% in organ confined turnours). @here was no significant difference in the expression of VEGF, flt or flk in metastatic vs. organ-confined tumours and their different histological subtypes seen. Only the expression of ets-I differed significantly in all different histological tumour subtypes between and metastatic and non-metastatic turnours. In addition, using CD105 a significantly higher microvessel density was observed in stage II tumours and in GCT’s positive for e&-l.
RESULTS: No DNA alterations were detected in normal tissue samples of controls; at least I molecular event (LOW, AI, AMP) was identified in 41144 (93.2%) TGCT. Most frequently tumour associated LOH/AI were detected for DlSl656 (41%), D3S2447 (42%), D9S1748 (53%). DllS1978 (42%), Dl7S799 (37%). Alterations for D3S2447 were only demonstrated in seminomas and associated TIN but not in nonseminomas; amplifications of Dl7S799 were only detected in seminomas. SOX5, JAW I and K;ras did not demonstrate TGCT-specific alterations.
CONCLUSIONS: Higher expression of VEGF was seen in better-differentiated tumour components such as teratoma. VEGF and its receptors flt and flk seem not bc involved in the progress of metastatic development of GCT’s. Only ets-1, a protooncogene involved in tumour angiogenesis, showed a significantly higher expression in metastatic GCT’s. A difference in microvessel density between tumour stages could only be observed if the specific CD105 antibody was used, in contrast no different distribution of microvessels in histological subtypes or tumour stage was seen if the pan-endothelial marker CD34 was used. Conclusively, ets-1 together with microvessel density determined by CD105 may have prognostic value m the multistep event of carcinogenesis.
European
Urology Supplements 2 (2003) No. 1, pp. 154
CONCLUSIONS: For the first time, D3S2447 was identified as a new seminoma specific chromosomal marker. D3S2447 encodes for the DAZL-1 gene and the expression of the protein product has also only been found in seminomas. The seminoma specific amplification of Dl73799 might contribute to the progression of TIN into locally invasive seminomas. JAWl, SOX5 and Kras arc not involved in the pathogenesis of TGCT. Grant of Kempkes Stiftung Marburg, Germany.