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ASSOCIATION BETWEEN TUMOUR NECROSIS AND USUAL PROGNOSTIC PARAMETERS IN RENAL CELL CARCINOMA
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326
ERECTILE FUNCTIONS AND NOCTURNAL PENILE TUMESCENCE AND RIGIDITY MONITORING IN MEN WITH LOWER URINARY TRACT SYMPTOMS
APOLIPOPROTEIN E KNOCKOUT MICE AS A NEW MODEL OF HYPERCHORESTOROLAEMIA AND ATHEROSCLEROSISASSOCIATED ERECTILE DYSFUNCTION
Jakubczyk T., Kryst P., Pych K., Dybowski B., Hanecki R., Gugala A., Borkowski A.
Behr-Roussel D.1, Darblade B.1, Oudot A.1, Compagnie S.1, Bernabé J.1, Alexandre L.1, Giuliano F.2
Department of Urology, Medical University of Warsaw, Poland INTRODUCTION & OBJECTIVES: Erectile functions may be affected by lower urinary tract symptoms (LUTS). The reasons of erectile dysfunction (ED) in men with LUTS include ageing with its related organic risk factors, co-morbidities and their treatment, as well as psychological issues related to LUTS. Nocturnal penile tumescence and rigidity (NPTR) monitoring is a valuable tool in diagnostic evaluation of men with ED. However data on NPTR monitoring in patients with LUTS and their correlation with self-assessment of erectile function are lacking. Our objective was to analyze urinary symptoms, self-assessed sexual functions and NPTR monitoring in men with LUTS. MATERIAL & METHODS: Intensity of LUTS was assessed by IPSS, erectile functions by erectile domain of IIEF questionnaire (IIEF-ED). Subsequently all patients underwent NPTR monitoring during 2 consecutive nights. Time of rigidity exceeding 60%, rigidity activity units (RAU), tumescence activity units (TAU) separately at base and tip, number of erectile events per hour and total events time during the night with better erections were recorded. Average rigidity and tumescence at tip and base during the best erectile event were also analysed. RESULTS: Twenty men aged 38-75 (mean – 61, 6; SD 11, 68) presenting with LUTS was evaluated. Average IPSS was 17, 35 (7-32; SD 7, 44), quality of life 3, 4 (1-5; SD 1, 43) frequency of sexual activity 4, 45 per month (2-11; SD 2, 42), IIEF-ED 22, 1 (6-29; SD 5, 82). NPTR recording revealed 0, 45 erections per hour of sleep (0, 11-0, 72; SD 0, 16), with total erections time 54 minutes (11-110; SD 31, 47). Time of rigidity exceeding 60% at tip and base were 18,65 (0-90; SD 24,62) and 36,78 (0-94, SD 30,96) minutes, average best event rigidity respectively 51,65% (23-84; SD 18,51) and 68,4% (18-98; SD 19,18), while tumescence 8,85 (0-13; SD 2,68) and 9,55 (0-14; SD 2,74) cm. RAU at the tip and base reached 22,05 (0-73; SD 20,40) and 33,7 (0-85; SD 26,07), while TAU 15,8 (0-56; SD 14,49) and 19,3 (0-75; SD 18,02) respectively. Intensity of LUTS was correlated only with quality of life, frequency of sexual activity, tip RAU and TAU and base rigidity, but not with IIEF-ED neither majority of NPTR parameters. IIEF-ED was not correlated with any of the NPTR parameters. Age was correlated with number and time of erections, tumescence, and TAU both at tip and base, while with time of rigidity exceeding 60% and RAU only at base. CONCLUSIONS: LUTS was correlated with frequency of sexual activity, but not IIEFED, neither the majority of NPTR parameters. There was no correlation between IIEF-ED and NPTR findings. Only ageing was correlated with the decrease in the majority of NPTR parameters; however it did not influenced self-assessment of erectile function.
P20 KIDNEY TUMOURS: DIAGNOSIS AND STAGING II Thursday, 6 April, 12.15-13.45, Room Maillot / Level 2 327 ASSOCIATION BETWEEN TUMOUR NECROSIS AND USUAL PROGNOSTIC PARAMETERS IN RENAL CELL CARCINOMA Rioux-leclercq N.1, Fergelot P.2, Bensalah K.3, Lobel B.3, Guille F.3, Manunta A.3, Vincendeau S.3, Patard J.J.3 1
Rennes University Hospital, Pathology, Rennes, France, 2Université De Rennes 1, Umr 60-61, Rennes, France, 3Rennes University Hospital, Urology, Rennes, France INTRODUCTION & OBJECTIVES: Tumour necrosis is emerging as a potentially important prognostic parameter in Renal Cell Carcinoma (RCC). The aim of this study was to compare tumour necrosis to other important clinical or pathological variables in RCC. MATERIAL & METHODS: Pathological slides from 275 patients who underwent a partial or a radical nephrectomy for RCC in our department were retrospectively reviewed by a single pathologist. Tumour stage and nuclear grade were determined according to the 2002 TNM classification and to the Fuhrman grading system respectively. Histological subtype was established according to the 1997 UICC classification and the presence or absence of tumour necrosis was systematically recorded. Age, sex, tumour size, symptoms at presentation, ECOG performance status and clinical outcome were also noted. Qualitative and quantitative variables were compared by using Chi-square (Fischer exact test) and Student t tests, respectively. RESULTS: There were 173 males (62.9%) and 102 females (37.1%). Median age was 65 years (27-88). Median tumour size was 7cm (1-20). Tumour stage and Fuhrman grade were >= 3 in 52.3% and 66.8% of the cases respectively. Positive lymph nodes and distant metastases were present in 11% and 19.3% of the cases. Tumour necrosis was present in 151 cases (54.9%). Mean tumour size was significantly different according to the presence or absence of tumour necrosis (9.4 vs. 5.7 cm, p:0.0001). Tumour necrosis was also strongly associated with symptoms at presentation, T Stage, Fuhrman grade, ECOG (p:0.0001), N Stage (p :0.003) and M Stage (p :0.002). However no association was found between tumour necrosis and histological subtype. The presence of tumour necrosis was found in 54.5%, 52.2% and 50% of clear cell, papillary and chromophobe carcinomas respectively. Finally, 9% of the tumours without tumour necrosis caused the death of the patient compared to 27% when tumour necrosis was noted (p:0.0001). CONCLUSIONS: Tumour necrosis is potentially associated with important biological mechanisms such as hypoxia and stimulation of angiogenesis. Our data show that tumour necrosis is associated with the most important clinical and pathological prognostic variables in RCC. The presence or absence of tumour necrosis should be systematically recorded on pathological reports and its independent prognostic value should be further evaluated through large series.
Eur Urol Suppl 2006;5(2):104
1 Pelvipharm, Pelvipharm, Gif Sur Yvette, France, 2AP-HP Raymond Poincaré Hôspital, Neurourology Unit, Garches, France
INTRODUCTION & OBJECTIVES: Erectile dysfunction (ED) and cardiovascular diseases share the same risk factors including hypercholesterolemia and atherosclerosis, but there are few available animal models allowing studying hypercholesterolemia-associated ED. Although the use of hypercholesterolemic rabbit models has proven to be useful to illustrate the link between ED and hypercholesterolemia, the cost of daily maintenance of the animals and necessity for important amounts of drug in view of proof of concept studies to prevent or slow down these disorders have limited their use. Thus, we aimed to develop a new model of atherosclerosis-associated ED in a well-known experimental model of atherosclerosis, the ApoE KO mice. MATERIAL & METHODS: Simultaneous computerised measures of mean arterial blood pressure (MAP) and intracavernous pressure (ICP) were performed. Erectile function was evaluated by recording frequency-dependent increase in intracavernosal pressure (ICP) following electrical stimulation of the cavernous nerve (square-wave pulses 6 V, 0.3ms pulse duration for 30 s, 0 to 15 Hz frequency), expressed as ΔICP/MAP (%), in 26, 32, and 38 weeksold ApoE KO fed with a western-type diet from 4 weeks of age (n=9, 13, and 11 respectively) and age-matched C57BL6/J anesthetized mice (n=9, 14, and 18 respectively). Atherosclerotic lesions were evaluated by planimetry in Oil Red O stained aortas. RESULTS: We found that in contrast to C57BL6/J mice, ApoE mice displayed atherosclerotic lesions covering 22% of the aortic luminal surface at 26 weeks of age and increasing to 27% and 35% at 32 weeks and 38 weeks of age respectively. The amplitude of erectile responses to electrical stimulation of the cavernous nerve was markedly impaired in 26 weeks-old ApoE KO mice as compared to age-matched C57BL6/J mice (up to 30% impairment at 10 Hz stimulation frequency). Impairment in erectile function was maintained in ApoE KO mice of 32 and 38 weeks of age (20% and 32% impairment at 10 Hz at respectively 32 and 38 weeks-old as compared to age-matched C57BL6/J. CONCLUSIONS: The ApoE KO mouse, a well-characterized model to study disorders associated with hypercholesterolemia and atherosclerosis in cardiovascular research could therefore be used to investigate disease modifying effects of new therapeutic strategies aiming to target both atherosclerosis and ED as early as 26 weeks of age.
328 DIAGNOSTIC AND EVOLUTIVE PATTERNS OF RENAL CELL CARCINOMA IN ADULTS 40 YEARS OR LESS: COMPARATIVE STUDY VERSUS OLDER PATIENTS Taccoen X.1, Valeri A.1, Descotes J.L.2, Morin V.1, Stindel E.3, Doucet L.4, Bocqueraz F.2, Coulange C.5, Rambeaud J.J.2, Fournier G.1, Mejean A.6 1
University Hospital of Brest, Urology, Brest, France, 2University Hospital of Grenoble, Urology, Grenoble, France, 3University Hospital of Brest, Statistics, Brest, France, 4University Hospital of Brest, Pathology, Brest, France, 5University Hospital of Marseille-Salvador, Urology, Marseilles, France, 6University Hospital of Paris-Necker, Urology, Paris, France INTRODUCTION & OBJECTIVES: Renal cell carcinoma (RCC) is uncommon in young adults. Based on the rare studies published to date, it is difficult to determine whether this tumour has a particular progression pattern. We aimed to compare diagnostic and progression patterns of RCC in young patients (≤40 years) versus those in older patients. MATERIAL & METHODS: Between 1988 and 2000, 1233 patients, 93 young and 1140 old (mean ages: 34.2 and 61.9 years, respectively) underwent surgery for RRC in four university hospitals. Their clinical and biological parameters at diagnosis were compared and subjected to uni- and multivariate analyses to study survival. Mean survival lasted 49.1 (± 38.1) months for young and 44.3 (± 36.4) months for older patients. RESULTS: Comparing younger to older patients, respectively, they had: lower M/F ratio (1.2 versus 2.5), lower stage (86.5% versus 67.5% pT1–pT2N0M0; P=0.001), fewer clear cell carcinomas (71.3% versus 82%) but more papillary carcinomas (20.4% versus 11.4%; P=0.01), better 5-year specific survival (90.8% versus 78.3%; P=0.05). Independent prognostic factors for survival, in the order of decreasing impact, were: tumour stage (P<0.0001), Fürhman nuclear grade (P<0.0001) and age ≤40 years at diagnosis (P<0.05). Young patients tended to have better 5-year progression-free survival (80.5% versus 70.7%; P=0.05). CONCLUSIONS: RCC in young adults was more often localised at diagnosis and had a better prognosis than that of older subjects. Age ≤40 years old was an independent prognostic factor for survival.
326
ERECTILE FUNCTIONS AND NOCTURNAL PENILE TUMESCENCE AND RIGIDITY MONITORING IN MEN WITH LOWER URINARY TRACT SYMPTOMS
APOLIPOPROTEIN E KNOCKOUT MICE AS A NEW MODEL OF HYPERCHORESTOROLAEMIA AND ATHEROSCLEROSISASSOCIATED ERECTILE DYSFUNCTION
Jakubczyk T., Kryst P., Pych K., Dybowski B., Hanecki R., Gugala A., Borkowski A.
Behr-Roussel D.1, Darblade B.1, Oudot A.1, Compagnie S.1, Bernabé J.1, Alexandre L.1, Giuliano F.2
Department of Urology, Medical University of Warsaw, Poland INTRODUCTION & OBJECTIVES: Erectile functions may be affected by lower urinary tract symptoms (LUTS). The reasons of erectile dysfunction (ED) in men with LUTS include ageing with its related organic risk factors, co-morbidities and their treatment, as well as psychological issues related to LUTS. Nocturnal penile tumescence and rigidity (NPTR) monitoring is a valuable tool in diagnostic evaluation of men with ED. However data on NPTR monitoring in patients with LUTS and their correlation with self-assessment of erectile function are lacking. Our objective was to analyze urinary symptoms, self-assessed sexual functions and NPTR monitoring in men with LUTS. MATERIAL & METHODS: Intensity of LUTS was assessed by IPSS, erectile functions by erectile domain of IIEF questionnaire (IIEF-ED). Subsequently all patients underwent NPTR monitoring during 2 consecutive nights. Time of rigidity exceeding 60%, rigidity activity units (RAU), tumescence activity units (TAU) separately at base and tip, number of erectile events per hour and total events time during the night with better erections were recorded. Average rigidity and tumescence at tip and base during the best erectile event were also analysed. RESULTS: Twenty men aged 38-75 (mean – 61, 6; SD 11, 68) presenting with LUTS was evaluated. Average IPSS was 17, 35 (7-32; SD 7, 44), quality of life 3, 4 (1-5; SD 1, 43) frequency of sexual activity 4, 45 per month (2-11; SD 2, 42), IIEF-ED 22, 1 (6-29; SD 5, 82). NPTR recording revealed 0, 45 erections per hour of sleep (0, 11-0, 72; SD 0, 16), with total erections time 54 minutes (11-110; SD 31, 47). Time of rigidity exceeding 60% at tip and base were 18,65 (0-90; SD 24,62) and 36,78 (0-94, SD 30,96) minutes, average best event rigidity respectively 51,65% (23-84; SD 18,51) and 68,4% (18-98; SD 19,18), while tumescence 8,85 (0-13; SD 2,68) and 9,55 (0-14; SD 2,74) cm. RAU at the tip and base reached 22,05 (0-73; SD 20,40) and 33,7 (0-85; SD 26,07), while TAU 15,8 (0-56; SD 14,49) and 19,3 (0-75; SD 18,02) respectively. Intensity of LUTS was correlated only with quality of life, frequency of sexual activity, tip RAU and TAU and base rigidity, but not with IIEF-ED neither majority of NPTR parameters. IIEF-ED was not correlated with any of the NPTR parameters. Age was correlated with number and time of erections, tumescence, and TAU both at tip and base, while with time of rigidity exceeding 60% and RAU only at base. CONCLUSIONS: LUTS was correlated with frequency of sexual activity, but not IIEFED, neither the majority of NPTR parameters. There was no correlation between IIEF-ED and NPTR findings. Only ageing was correlated with the decrease in the majority of NPTR parameters; however it did not influenced self-assessment of erectile function.
P20 KIDNEY TUMOURS: DIAGNOSIS AND STAGING II Thursday, 6 April, 12.15-13.45, Room Maillot / Level 2 327 ASSOCIATION BETWEEN TUMOUR NECROSIS AND USUAL PROGNOSTIC PARAMETERS IN RENAL CELL CARCINOMA Rioux-leclercq N.1, Fergelot P.2, Bensalah K.3, Lobel B.3, Guille F.3, Manunta A.3, Vincendeau S.3, Patard J.J.3 1
Rennes University Hospital, Pathology, Rennes, France, 2Université De Rennes 1, Umr 60-61, Rennes, France, 3Rennes University Hospital, Urology, Rennes, France INTRODUCTION & OBJECTIVES: Tumour necrosis is emerging as a potentially important prognostic parameter in Renal Cell Carcinoma (RCC). The aim of this study was to compare tumour necrosis to other important clinical or pathological variables in RCC. MATERIAL & METHODS: Pathological slides from 275 patients who underwent a partial or a radical nephrectomy for RCC in our department were retrospectively reviewed by a single pathologist. Tumour stage and nuclear grade were determined according to the 2002 TNM classification and to the Fuhrman grading system respectively. Histological subtype was established according to the 1997 UICC classification and the presence or absence of tumour necrosis was systematically recorded. Age, sex, tumour size, symptoms at presentation, ECOG performance status and clinical outcome were also noted. Qualitative and quantitative variables were compared by using Chi-square (Fischer exact test) and Student t tests, respectively. RESULTS: There were 173 males (62.9%) and 102 females (37.1%). Median age was 65 years (27-88). Median tumour size was 7cm (1-20). Tumour stage and Fuhrman grade were >= 3 in 52.3% and 66.8% of the cases respectively. Positive lymph nodes and distant metastases were present in 11% and 19.3% of the cases. Tumour necrosis was present in 151 cases (54.9%). Mean tumour size was significantly different according to the presence or absence of tumour necrosis (9.4 vs. 5.7 cm, p:0.0001). Tumour necrosis was also strongly associated with symptoms at presentation, T Stage, Fuhrman grade, ECOG (p:0.0001), N Stage (p :0.003) and M Stage (p :0.002). However no association was found between tumour necrosis and histological subtype. The presence of tumour necrosis was found in 54.5%, 52.2% and 50% of clear cell, papillary and chromophobe carcinomas respectively. Finally, 9% of the tumours without tumour necrosis caused the death of the patient compared to 27% when tumour necrosis was noted (p:0.0001). CONCLUSIONS: Tumour necrosis is potentially associated with important biological mechanisms such as hypoxia and stimulation of angiogenesis. Our data show that tumour necrosis is associated with the most important clinical and pathological prognostic variables in RCC. The presence or absence of tumour necrosis should be systematically recorded on pathological reports and its independent prognostic value should be further evaluated through large series.
Eur Urol Suppl 2006;5(2):104
1 Pelvipharm, Pelvipharm, Gif Sur Yvette, France, 2AP-HP Raymond Poincaré Hôspital, Neurourology Unit, Garches, France
INTRODUCTION & OBJECTIVES: Erectile dysfunction (ED) and cardiovascular diseases share the same risk factors including hypercholesterolemia and atherosclerosis, but there are few available animal models allowing studying hypercholesterolemia-associated ED. Although the use of hypercholesterolemic rabbit models has proven to be useful to illustrate the link between ED and hypercholesterolemia, the cost of daily maintenance of the animals and necessity for important amounts of drug in view of proof of concept studies to prevent or slow down these disorders have limited their use. Thus, we aimed to develop a new model of atherosclerosis-associated ED in a well-known experimental model of atherosclerosis, the ApoE KO mice. MATERIAL & METHODS: Simultaneous computerised measures of mean arterial blood pressure (MAP) and intracavernous pressure (ICP) were performed. Erectile function was evaluated by recording frequency-dependent increase in intracavernosal pressure (ICP) following electrical stimulation of the cavernous nerve (square-wave pulses 6 V, 0.3ms pulse duration for 30 s, 0 to 15 Hz frequency), expressed as ΔICP/MAP (%), in 26, 32, and 38 weeksold ApoE KO fed with a western-type diet from 4 weeks of age (n=9, 13, and 11 respectively) and age-matched C57BL6/J anesthetized mice (n=9, 14, and 18 respectively). Atherosclerotic lesions were evaluated by planimetry in Oil Red O stained aortas. RESULTS: We found that in contrast to C57BL6/J mice, ApoE mice displayed atherosclerotic lesions covering 22% of the aortic luminal surface at 26 weeks of age and increasing to 27% and 35% at 32 weeks and 38 weeks of age respectively. The amplitude of erectile responses to electrical stimulation of the cavernous nerve was markedly impaired in 26 weeks-old ApoE KO mice as compared to age-matched C57BL6/J mice (up to 30% impairment at 10 Hz stimulation frequency). Impairment in erectile function was maintained in ApoE KO mice of 32 and 38 weeks of age (20% and 32% impairment at 10 Hz at respectively 32 and 38 weeks-old as compared to age-matched C57BL6/J. CONCLUSIONS: The ApoE KO mouse, a well-characterized model to study disorders associated with hypercholesterolemia and atherosclerosis in cardiovascular research could therefore be used to investigate disease modifying effects of new therapeutic strategies aiming to target both atherosclerosis and ED as early as 26 weeks of age.
328 DIAGNOSTIC AND EVOLUTIVE PATTERNS OF RENAL CELL CARCINOMA IN ADULTS 40 YEARS OR LESS: COMPARATIVE STUDY VERSUS OLDER PATIENTS Taccoen X.1, Valeri A.1, Descotes J.L.2, Morin V.1, Stindel E.3, Doucet L.4, Bocqueraz F.2, Coulange C.5, Rambeaud J.J.2, Fournier G.1, Mejean A.6 1
University Hospital of Brest, Urology, Brest, France, 2University Hospital of Grenoble, Urology, Grenoble, France, 3University Hospital of Brest, Statistics, Brest, France, 4University Hospital of Brest, Pathology, Brest, France, 5University Hospital of Marseille-Salvador, Urology, Marseilles, France, 6University Hospital of Paris-Necker, Urology, Paris, France INTRODUCTION & OBJECTIVES: Renal cell carcinoma (RCC) is uncommon in young adults. Based on the rare studies published to date, it is difficult to determine whether this tumour has a particular progression pattern. We aimed to compare diagnostic and progression patterns of RCC in young patients (≤40 years) versus those in older patients. MATERIAL & METHODS: Between 1988 and 2000, 1233 patients, 93 young and 1140 old (mean ages: 34.2 and 61.9 years, respectively) underwent surgery for RRC in four university hospitals. Their clinical and biological parameters at diagnosis were compared and subjected to uni- and multivariate analyses to study survival. Mean survival lasted 49.1 (± 38.1) months for young and 44.3 (± 36.4) months for older patients. RESULTS: Comparing younger to older patients, respectively, they had: lower M/F ratio (1.2 versus 2.5), lower stage (86.5% versus 67.5% pT1–pT2N0M0; P=0.001), fewer clear cell carcinomas (71.3% versus 82%) but more papillary carcinomas (20.4% versus 11.4%; P=0.01), better 5-year specific survival (90.8% versus 78.3%; P=0.05). Independent prognostic factors for survival, in the order of decreasing impact, were: tumour stage (P<0.0001), Fürhman nuclear grade (P<0.0001) and age ≤40 years at diagnosis (P<0.05). Young patients tended to have better 5-year progression-free survival (80.5% versus 70.7%; P=0.05). CONCLUSIONS: RCC in young adults was more often localised at diagnosis and had a better prognosis than that of older subjects. Age ≤40 years old was an independent prognostic factor for survival.