- Email: [email protected]
Value of high-frequency doppler ultrasound for prostate cancer detection
302
301 THE INTEREST OF ENDORECTAL IMAGING IN THE LOCAL STAGING BEFORE RADICAL PROSTATECTOMY Palascak R.‘, Lang H.‘, Gome~-Ororco ‘HU Strasbourg, Urology, Strasbourg, France
MAGNETIC RESONANCE OF PROSTATIC CANCER
W.‘. Buy X.‘, Roy C.‘. Jacqmin D.’
Strasbourg.
France.
‘HU Strdsbourg.
Radiology.
INTRODUCTION & OBJECTIVES: To evaluate the accuracy of endorectal surface coil magnetic resonance imaging (MRI) to detect extracapsular extension (EC‘E) of prostatic carcinoma before radical prostatectomy. MATERIAL & METHODS: A retrospective study was done from March 00 to July 02 on 66 patients with mean age 63 years (range 43 to 74). who underwent radical prostatectomy for prostatic adenocarcinoma. The mean preoperative prostate-specific antigen level was 8.9 ngiml (range I,9 to 27.X). Endorectal surface coil MRI was performed before transrectal biopsies. A prostatic tumour in contact with capsule was not considered as an ECE. Histological examination was performed according to Stanford protocol. The results of MRI concerning the ECE and the tmnour stage (TNM classification) were statistIcally correlated with the histopathological findings. RESULTS: Of the 66 patients. 11 (I 6,O%) had stage T3 discasc by MRI and S5 (83%) stage T2 disease by MRI. llistopathological staging showed I3 patients ( 19.6 ?/II)with pT3 disease and 53 (80.3 ‘%) with pT? disease.
I
i MRI MRI
T3 T2
1 Prostatectomy pT3 6 7
j Prostatcctomy pT2 5 38
The sensitivity, specificity, positive predictive value and negative predictive value of MRI for ECE were respectively 4&l%, 90,5%, 54,5% and X7,5?& .Accuracy for differentiating a pT2 from pT3 tumour was 8 I .80/u. CONCLUSIONS: Results of this study indicate that the sensitivity of endorectal coil MRI for ECE is poor, but the specificity is much better. In our experience, the local staging ofprostatic carcinoma before radical prostatectomy by endorectal MRI reduce from 35”/0 to 20% the rate ofpatients with pT3 disease treated by surgery. The high accuracy and specificity of MRI should allow a better selection of patients for curative treatmcnr. P16 STONES:CALISESANDCOLlCS Friday,March 14,11.45-13.15 hrs, Room N106.
J.. Haulmann
trauscher F.‘. Halpcrn Ncdden D.’
of Ulm, Department
E.J.‘. Hominget-
W.‘. Klauser
ULTRASOUND A.
FOR
. Bartsch G.‘, Zur
University of Innsbruck. Radiology. Innsbruck. Austria, ‘Thomas Jeflerson University, Radiology, Philadelphia, United States of America. ’University of Innsbruck. Urology. Innsbruck, Austria INTRODUCTION & OBJECTIVES: To assess the value of high-frequency colour Doppler ultrasound (US) for prostate cancer detection. MATERIAL & METHODS: Fifty patients were prospectively evaluated with grey-scale, colour, and power Doppler transrectal US. For the colour Doppler examinations an endorectal probe operating at a Doppler frequency of 9.0 MH! was used. Up to five biopsies were obtained based on Doppler findings. Greyscale and Doppler findings were graded according to the follo\ving scale: 5. definitely abnormal (i.e., a focal hypocchoic mass was present on grey-scale images or obvious increase in flow was present on Doppler images); 4, probably abnormal (i.e.. a probable hypoechoic mass was present on grcy-scale images or a mild increase in flow was present on Doppler images); 3, indeterminate (i.e.. abnormal echotexture without definite mass was present on grey-scale images or subtle increase 1n flow was present on Doppler images); 2, probably normal (i.e.. heterogeneity on grey-scale Images or minimal asymmetry in tlow. which might \imply represent a normal variation. on Doppler images): and I _ dctinite1.y normal (i.e.. homogeneous appearance on grey-scale images and symmetric flow pattern on Doppler images). The cancer detection rate for high-frequency Doppler findings was compared with systematic IO core biopsy results. RESULTS: Cancer was detected in I5 (30%) patlents. including 10 patients in whom cancer was detected with both Doppler and grey-scale US, 4 in whom cancer was detected only with grey-scale US, and one in whom cancer was detected only with Doppler US. The odds ratio for cancer detection with Doppler US versus grey-scale US was 1.7. Receiver operating characteristic analysis demonstrated that overall identification of positive systematic biopsy sites was close to random chance for grcy-scale (area under the curve, 0.52), colour Doppler (area under the curve, 0.50), and power Doppler (area under the curve. 0.48) imaging. CONCLUSIONS: tllgh-tizqucncy colour or power I)oppler findIngs will rnl\a a substantial number ofprohlatc cancc~-s dcrected by systematic biopsy.
304 EFFECTS OF OXALATE FIBROBLASTS
ON
RENAL
EPITHELIAL
CELLS
AND
R.t . Hraendlc E Unlvcrslty
Um>crsity ( icrmany
DOPPLER
303
THE IMPACT OF CARBONIC ANHYDRASE ON THE REGULATION OF TRANSCELLULAR OXAI,ATE TRANSPORT IN THE PROXIMAL TL’BULE: Slraub M.. H&lo-l:lo
VALUE OF HIGH-FREQUENCY PROSTATE CANCER DETECTION
of llrology
and Paediatric
lirology.
Ulm.
INTRODUCTION & OBJECTI\‘ES: Elc\ated urinary oxalate Ie\cls amplify the risk of calcium oxalate stone formation. In previous studies WCcharacterized the carrier mechanisms of transcellular oxalate transport at the renal proximal tubule. Moreover, we found evidence for a link between oxalate excretion and renal acidification mechanisms. Carbonic anhydrase is an important factor for the acid-base-equilibrium in the proximal tubule and may hence regulate oxalate excretion. MATERIAL & METHODS: Clearance studies were carried out in male Sprague-Dawley rats. First, the animals underwent implantation of a jugular vein and a suprapubic bladder catheter. Then, saline solution (0.90/u) was perfused continuously. After I hour of cquilibrdtion 2 control pcrlods followed. Intravenous bolus administration of aceta7olamidc (ACA, 2 mg) was followed by 5 clearance periods, 15 minutes each. To assess kidney function and the lumindl oxalate carriers l4C-oxalate, 35S-sulf’dte, 14C-formatc and 3H-inulin was added to the solution. Renal fractionel clearances and excretion rates forl4C-oxalate, 3SS-sulfate, l4C-formate we investigated.
tlospital
Mannhelm,
Department
of Urology. Mannheim.
Germany
INTRODUCTION Sr OBJECTI\‘ES: Meal rcnnl stones In humans arc composed of calcium oxalate. An incrcasc in urinary oxalatc levels has been +own to result in renal epithclial cell damage and crystal retention However, the underlying mechanisms are unclear. Which cell type plays the pivotal role m stone formation remains unknown. but renal epithelial cells and as well interstitial cells seem to be involved in this process leading to interstitial calcifications. Aim of this study was to evaluate the effects of oxalatc on distinct renal cpithelial cells and fibroblaals. MATERIAL & >lETHODS: LLCPKI, MDCK and renal tibroblast cell lines (ECACC) were cultured in DMEM under standard conditions. The pH was adjusted to 7.4. Part I: cells were grown in T-75 flasks until confluent layers were achieved. Ammonium oxalate was added at tinal concentrations of I, 2 and 1 mM. The free oxalate concentrations were obtained by EQUIL program After I. 2 and 4 hours cell survival was assc\sed microscopically by trypan blue slaining. The influence of oxalatc on proliferation (Proliferation Assay. Promo&en, Germany) and apoptosis induction (Annexin Assay Roche, (iermany; Cisplatin used as positive control) was additionally examined. Part 2: MDCK and LLCPKI cells were grown in 6-well plates until confluent layers were achieved. Ammonium oxalate was then added to this two-compartment model in same amounts as in pan I, either on apical or basolateral side, plain medium wab added on the other. The further protocol was identical to part I.
RESULTS: Carbonic anhydrase inhibition increased the renal oxalate excretion rate (control: 43.47i4.34 vs. ACA: 62.15*2.81, p< 0.001) significantly. The activity of luminal Na+-(S04)2-(oxalate) cotransport was reduced while CI/oxalate(formate) exchange rose. Carrier activity was measured by the fractional clearances of l4C-oxalate (control: I .38*0.06 vs. ACA: 1.6210.04, py 0.002), 35S-sulfate (control: 0. I3+0.02 vs. ACA: 0.09*0.0 I, p= 0.056) and 14C-formatc (control: 0.04iO.00 vs. ACA: 0.06~tO.00, p’ 0.001).
RESULTS: I : Oxalate led to a time- and concentration-dependent decrease in cell survival that was most prominent the in LLCPKI and tibroblast groups. This was reflected by significant impairment in cell proliferation. No induction of apoptosis was observed in any cell lint. 2: Both cell lines were m&c vulnerable to oxalate on basolateral side. This effect was more pronounced in LLCPKI cells.
CONCLUSIONS: Renal oxalate excretion depends on the activity of the carbonic anhydrase in the proximal tubule. Additionally, our results demonstrate, for the first time, in a whole animal model that carbonic anhydrasc exerts influence on both luminal oxalate carriers. The local control of tubular oxalate excretion by carbonic anhydrase aeemu to he an interesting target for a new pharmacological approach in the treatment of calcium oxalatc stones.
CONCLUSIONS: Our results show that oxalate has a negative effect on growth and survival of renal epithelial cells as well as on fibroblasts. As no induction of apoptotic pl-ocesses was observed, this might be due to a direct toxic effect on cells. LLCPKI cells and fibroblasts are most vulnerable. We also demonstrated that this noxious effect is related to cell polarity. Cells arc apparently more rccis;tant on the apical (-tubular) side.
European
Urology
Supplements
2 (2003)
No. 1, pp. 78
301 THE INTEREST OF ENDORECTAL IMAGING IN THE LOCAL STAGING BEFORE RADICAL PROSTATECTOMY Palascak R.‘, Lang H.‘, Gome~-Ororco ‘HU Strasbourg, Urology, Strasbourg, France
MAGNETIC RESONANCE OF PROSTATIC CANCER
W.‘. Buy X.‘, Roy C.‘. Jacqmin D.’
Strasbourg.
France.
‘HU Strdsbourg.
Radiology.
INTRODUCTION & OBJECTIVES: To evaluate the accuracy of endorectal surface coil magnetic resonance imaging (MRI) to detect extracapsular extension (EC‘E) of prostatic carcinoma before radical prostatectomy. MATERIAL & METHODS: A retrospective study was done from March 00 to July 02 on 66 patients with mean age 63 years (range 43 to 74). who underwent radical prostatectomy for prostatic adenocarcinoma. The mean preoperative prostate-specific antigen level was 8.9 ngiml (range I,9 to 27.X). Endorectal surface coil MRI was performed before transrectal biopsies. A prostatic tumour in contact with capsule was not considered as an ECE. Histological examination was performed according to Stanford protocol. The results of MRI concerning the ECE and the tmnour stage (TNM classification) were statistIcally correlated with the histopathological findings. RESULTS: Of the 66 patients. 11 (I 6,O%) had stage T3 discasc by MRI and S5 (83%) stage T2 disease by MRI. llistopathological staging showed I3 patients ( 19.6 ?/II)with pT3 disease and 53 (80.3 ‘%) with pT? disease.
I
i MRI MRI
T3 T2
1 Prostatectomy pT3 6 7
j Prostatcctomy pT2 5 38
The sensitivity, specificity, positive predictive value and negative predictive value of MRI for ECE were respectively 4&l%, 90,5%, 54,5% and X7,5?& .Accuracy for differentiating a pT2 from pT3 tumour was 8 I .80/u. CONCLUSIONS: Results of this study indicate that the sensitivity of endorectal coil MRI for ECE is poor, but the specificity is much better. In our experience, the local staging ofprostatic carcinoma before radical prostatectomy by endorectal MRI reduce from 35”/0 to 20% the rate ofpatients with pT3 disease treated by surgery. The high accuracy and specificity of MRI should allow a better selection of patients for curative treatmcnr. P16 STONES:CALISESANDCOLlCS Friday,March 14,11.45-13.15 hrs, Room N106.
J.. Haulmann
trauscher F.‘. Halpcrn Ncdden D.’
of Ulm, Department
E.J.‘. Hominget-
W.‘. Klauser
ULTRASOUND A.
FOR
. Bartsch G.‘, Zur
University of Innsbruck. Radiology. Innsbruck. Austria, ‘Thomas Jeflerson University, Radiology, Philadelphia, United States of America. ’University of Innsbruck. Urology. Innsbruck, Austria INTRODUCTION & OBJECTIVES: To assess the value of high-frequency colour Doppler ultrasound (US) for prostate cancer detection. MATERIAL & METHODS: Fifty patients were prospectively evaluated with grey-scale, colour, and power Doppler transrectal US. For the colour Doppler examinations an endorectal probe operating at a Doppler frequency of 9.0 MH! was used. Up to five biopsies were obtained based on Doppler findings. Greyscale and Doppler findings were graded according to the follo\ving scale: 5. definitely abnormal (i.e., a focal hypocchoic mass was present on grey-scale images or obvious increase in flow was present on Doppler images); 4, probably abnormal (i.e.. a probable hypoechoic mass was present on grcy-scale images or a mild increase in flow was present on Doppler images); 3, indeterminate (i.e.. abnormal echotexture without definite mass was present on grey-scale images or subtle increase 1n flow was present on Doppler images); 2, probably normal (i.e.. heterogeneity on grey-scale Images or minimal asymmetry in tlow. which might \imply represent a normal variation. on Doppler images): and I _ dctinite1.y normal (i.e.. homogeneous appearance on grey-scale images and symmetric flow pattern on Doppler images). The cancer detection rate for high-frequency Doppler findings was compared with systematic IO core biopsy results. RESULTS: Cancer was detected in I5 (30%) patlents. including 10 patients in whom cancer was detected with both Doppler and grey-scale US, 4 in whom cancer was detected only with grey-scale US, and one in whom cancer was detected only with Doppler US. The odds ratio for cancer detection with Doppler US versus grey-scale US was 1.7. Receiver operating characteristic analysis demonstrated that overall identification of positive systematic biopsy sites was close to random chance for grcy-scale (area under the curve, 0.52), colour Doppler (area under the curve, 0.50), and power Doppler (area under the curve. 0.48) imaging. CONCLUSIONS: tllgh-tizqucncy colour or power I)oppler findIngs will rnl\a a substantial number ofprohlatc cancc~-s dcrected by systematic biopsy.
304 EFFECTS OF OXALATE FIBROBLASTS
ON
RENAL
EPITHELIAL
CELLS
AND
R.t . Hraendlc E Unlvcrslty
Um>crsity ( icrmany
DOPPLER
303
THE IMPACT OF CARBONIC ANHYDRASE ON THE REGULATION OF TRANSCELLULAR OXAI,ATE TRANSPORT IN THE PROXIMAL TL’BULE: Slraub M.. H&lo-l:lo
VALUE OF HIGH-FREQUENCY PROSTATE CANCER DETECTION
of llrology
and Paediatric
lirology.
Ulm.
INTRODUCTION & OBJECTI\‘ES: Elc\ated urinary oxalate Ie\cls amplify the risk of calcium oxalate stone formation. In previous studies WCcharacterized the carrier mechanisms of transcellular oxalate transport at the renal proximal tubule. Moreover, we found evidence for a link between oxalate excretion and renal acidification mechanisms. Carbonic anhydrase is an important factor for the acid-base-equilibrium in the proximal tubule and may hence regulate oxalate excretion. MATERIAL & METHODS: Clearance studies were carried out in male Sprague-Dawley rats. First, the animals underwent implantation of a jugular vein and a suprapubic bladder catheter. Then, saline solution (0.90/u) was perfused continuously. After I hour of cquilibrdtion 2 control pcrlods followed. Intravenous bolus administration of aceta7olamidc (ACA, 2 mg) was followed by 5 clearance periods, 15 minutes each. To assess kidney function and the lumindl oxalate carriers l4C-oxalate, 35S-sulf’dte, 14C-formatc and 3H-inulin was added to the solution. Renal fractionel clearances and excretion rates forl4C-oxalate, 3SS-sulfate, l4C-formate we investigated.
tlospital
Mannhelm,
Department
of Urology. Mannheim.
Germany
INTRODUCTION Sr OBJECTI\‘ES: Meal rcnnl stones In humans arc composed of calcium oxalate. An incrcasc in urinary oxalatc levels has been +own to result in renal epithclial cell damage and crystal retention However, the underlying mechanisms are unclear. Which cell type plays the pivotal role m stone formation remains unknown. but renal epithelial cells and as well interstitial cells seem to be involved in this process leading to interstitial calcifications. Aim of this study was to evaluate the effects of oxalatc on distinct renal cpithelial cells and fibroblaals. MATERIAL & >lETHODS: LLCPKI, MDCK and renal tibroblast cell lines (ECACC) were cultured in DMEM under standard conditions. The pH was adjusted to 7.4. Part I: cells were grown in T-75 flasks until confluent layers were achieved. Ammonium oxalate was added at tinal concentrations of I, 2 and 1 mM. The free oxalate concentrations were obtained by EQUIL program After I. 2 and 4 hours cell survival was assc\sed microscopically by trypan blue slaining. The influence of oxalatc on proliferation (Proliferation Assay. Promo&en, Germany) and apoptosis induction (Annexin Assay Roche, (iermany; Cisplatin used as positive control) was additionally examined. Part 2: MDCK and LLCPKI cells were grown in 6-well plates until confluent layers were achieved. Ammonium oxalate was then added to this two-compartment model in same amounts as in pan I, either on apical or basolateral side, plain medium wab added on the other. The further protocol was identical to part I.
RESULTS: Carbonic anhydrase inhibition increased the renal oxalate excretion rate (control: 43.47i4.34 vs. ACA: 62.15*2.81, p< 0.001) significantly. The activity of luminal Na+-(S04)2-(oxalate) cotransport was reduced while CI/oxalate(formate) exchange rose. Carrier activity was measured by the fractional clearances of l4C-oxalate (control: I .38*0.06 vs. ACA: 1.6210.04, py 0.002), 35S-sulfate (control: 0. I3+0.02 vs. ACA: 0.09*0.0 I, p= 0.056) and 14C-formatc (control: 0.04iO.00 vs. ACA: 0.06~tO.00, p’ 0.001).
RESULTS: I : Oxalate led to a time- and concentration-dependent decrease in cell survival that was most prominent the in LLCPKI and tibroblast groups. This was reflected by significant impairment in cell proliferation. No induction of apoptosis was observed in any cell lint. 2: Both cell lines were m&c vulnerable to oxalate on basolateral side. This effect was more pronounced in LLCPKI cells.
CONCLUSIONS: Renal oxalate excretion depends on the activity of the carbonic anhydrase in the proximal tubule. Additionally, our results demonstrate, for the first time, in a whole animal model that carbonic anhydrasc exerts influence on both luminal oxalate carriers. The local control of tubular oxalate excretion by carbonic anhydrase aeemu to he an interesting target for a new pharmacological approach in the treatment of calcium oxalatc stones.
CONCLUSIONS: Our results show that oxalate has a negative effect on growth and survival of renal epithelial cells as well as on fibroblasts. As no induction of apoptotic pl-ocesses was observed, this might be due to a direct toxic effect on cells. LLCPKI cells and fibroblasts are most vulnerable. We also demonstrated that this noxious effect is related to cell polarity. Cells arc apparently more rccis;tant on the apical (-tubular) side.
European
Urology
Supplements
2 (2003)
No. 1, pp. 78