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464 Cost comparison for different medical treatments in conservative — expulsive therapy of distal ureteral stones
461 PROSTATE CYTOMETRY
STEM
CELL
ISOLATION
USING
HOECHST
Gilmore P.t, Bhatt R.2, Hart C.‘, Ramani V.3, George N.?, Brown GU Cancer Research Group, Manchester, United Kingdom
33342
FLOW
M.‘, Clarke N.3, ProMPT
‘Cancer Research UK Paterson Institute, Department Kay Kendall, Manchester, Umted Kingdom, ZHope Hospital, Department of Urology, Manchester, United Kingdom, 3Cluistie Hospital, Department of Urology, Manchester, United Kingdom, YSouth Manchester University Hospital, Department of Urology, Manchester, United Kingdom & OBJECTIVES: It has been proposed that prostate cancer originates from prostate stem cells with a potentially inexhaustible capacity for proliferation, differentiation and self-renewal. Their isolation has proved elusive although encouraging results have been reported using basal marker expression and binding characteristics to isolate cells with the differentiation/ proliferative properties of stem cells. We have adapted the Hoechst 33342 flow cytometry based dye efflux assay used for the isolation of haematopoietic stem cells to isolate prostate epithelial cells. We have character&d these using immunohistochemistry, and proliferation and differentiation assays.
INTRODUCTION
8-z METHODS: CD45 depleted prostate epithelial cells from benign and malignant prostates were incubated with Hoechst 33342 dye prior to FACS Vantage SE flow cytometry. A stem cell enriched side population (SP) and non-SP control (Body) were isolated. Immunofluorescent phenotyping used basal and luminal cell cytokeratins 5114 and X/18, primitive cell marker ~63, proposed stem cell markers ~27~‘p’, ~21~~~“~‘p’ , Notch 1, Cleaved Notch, Musashi 1 and was viewed by confocal microscopy. 3-D SP co-cultures were grown as spheroids in M&gel with a ST0 feeder layer. These were fixed and sectioned before immunohistochemistry and microscopy as above.
MATERIAL
The CD45 depleted Hoechst 33342 FACS profiles of both benign and malignant epithelia (n=25) showed the proportion of SP cells was 0.83 + 0.095%. SP cells showed increased expression of cytokeratins 5 (p=O.O14, n=X) and 14 (p=O.O003, n=8), p63 (p=O.O24, n=3), Musashi 1 (p=O.O28, n=lO), p21wAF”c’p’ (p=O.OOlS, n=14) and ~27~‘“’ (p=O.OOOS, n=ll) and decreased expression of PSA (p=O.O032, n=6) when compared to cells in the Body part of the FACS profile. Malignant SP showed diminished p21WAF”C’p’ expression (p=O.O045, n=6) compared to benign. In addition malignant SP S Cat&n expression was enhanced when compared to corresponding Body cells (p=O.O04, n=6). 3-D culture of SP cells in M&gel produced ‘Spheroid” structures with duct-like formation inter-linking individual cell regions in a manner consistent with stem cell behaviour. These expressed a basal phenotype of high cytokeratin 5 and low 18 with an outer layer high in p63 and inner layer surrounding a lumen.
RESULTS:
The Hoechst 33342 FACS based dye eMux assay is applicable to prostate epithelia enabling isolation of a side population with a similar profile to haematopoietic SPistem cell populations. Characterisation depicts a stem cell like phenotype with increased expression of stem cell markers includmg the CDK inhibitor p21 wAF”c’p’, which is lost in the malignant SP.
CONCLUSIONS:
P26
STONE DISEASE:MEDlCALMANAGEMENTANDRESEARCH Friday, 26 March, 14.00-15.30, Hall Fl-F2/Yellow level
NIFEDIPINE VERSUS TAMSULOSIN LOWER URETERAL STONES Poroiglia F., Ghignone Scarpa R.M. San Luigi Hospital,
IN
THE
G., Fiori C., Ten-one C., Scoffone
Urology,
Orbassano
Torino,
462 MANAGEMENT
OF
C., Ragni F., Guercio
Italy
INTRODUCTION & OBJECTIVES: The aim of this study is to evaluate and to compare the effectiveness of two different medical therapies during watchful waiting in patients with lower ureteral stones. & METHODS: Eighty-six patients with stones < lcm in size located in the lower ureter (juxtavesical or intramural tract) were enrolled in this study and were randomly divided into three groups. Patients of group A (11~30) received a daily oral treatment with 30 mg of a corticosteroid agent (deflazacort, for a maximum of 10 days) plus 30 mg of nifedipine slow-release (for a maximum of 28 days); patients of group B (n=28) received a daily oral treatment with 30 mg of deflazacort (for a maximum of 10 days) plus 0.4 mg of tamsulosin (for a maximum of 28 days), patients of group C were used as the control group (only symptomatic therapy). Patients of group A and B were also treated with gastroprotective therapy. All patients were required to drink a minimum of 2 litres of water day and were allowed to use a symptomatic therapy with injections of 75 mg (3 ml) diclofenac on demand. Statistical analyses were performed using Student’s test, chi square test, and Fisher’s exact test. MATERIAL
The average stone size was 4.7 mm +1.47 for group A, 5.42 mm *I .54 for group B and 5.35 mm tl.49 for group C without statistical difference (P=NS). Expulsion was observed in 24130 patients of group A (80%), 24/28 patients of group B (85%) and 12/28 patients of group C (43%). No statistical difference was noted in expulsion rate between group A and B; whereas the difference of both A and B with respect to group C was highly significant (p
The results of this study indicate that stones in the lower tract of ureter can be treated with an expulsive medical therapy in patients when a watchful waiting approach can be chosen. In our study, medical treatments with nifedipine and tamsulosin proved to be safe and effective as demonstrated by the low incidence of side effects and the increased stone expulsion rate. Moreover medical therapy, particularly as far as concern the use of tamsulosin, seems to reduce the expulsion time.
CONCLUSIONS:
463 A DOUBLE-BLINDED TRIAL ASSESSING AGENTS FOR EXTRACORPOREAL Beiko D.’ Watterson -> H.3, Denstedt J.3
PROSPECTIVE RANDOMIZED CONTROLLED THE SAFETY AND EFFICACY OF INTRAVESICAL URETERAL STENT SYMPTOMS FOLLOWING SHOCK WAVE LITHOTRIPSY J.2, Knudsen
t Queen’s University, Urology, Ottawa, Canada, 3University
B.3, Nott
Kingston, of Western
L.3, Pautler
Canada, Ontario,
S.3, Brock
G.3, Razvi
2University of Ottawa, Urology, Urology, London, Canada
INTRODUCTION & OBJECTIVES: Ureteral stems are a significant source of pain and discomfort for many urologic patients. A novel approach to addressing this problem is the intravesical instillation of a selected pharmacologic agent following stent insertion. The purpose of this study was to assess the safety and efficacy of intravesical instillation of various agents in reducing ureteral stentassociated discomfort in patients requiring a stent for extracorporeal shock wave lithotripsy. MATERIAL & METHODS: In this double-blinded prospective trial, 42 patients were randomized to receive intravesical instillation of one of three selected agents (oxybutynin, alkalinized lidocaine or ketorolac) or a control solution (0.9% sodium chloride) immediately following stent insertion at time of extracorporeal shock wave lithotripsy. Preoperative, intraoperative and postoperative data were prospectively collected and statistically analyzed. The primary outcome measure was reduction in ureteral stent symptoms and the secondary outcome measure was determination of safety of intravesical instillation of each agent through assessment of drug-related adverse events in each group of patients. RESULTS: The four groups of patients were demographically similar. There were no intraoperative or postoperative complications, nor were there any serious side effects attributable to any of the inhavesically-instilled agents. There was a statistically significant decrease in stent-related discomfort at the one-hour time point in the group of patients who received intravesical ketorolac when compared with the control group. CONCLUSIONS: Intravesical instillation represents a novel approach to addressing the problem of ureteral stent-related discomfort. We have established that intravesical instillation of ketorolac is safe in humans. Based on our results, ketorolac appears to be the most effective intravesical agent in reducing stentrelated patient discomfort. European
Urology
Supplements
3 (2004)
No. 2, pp. 118
S.,
464 COST COMPARISON FOR DIFFERENT MEDICAL TREATMENTS CONSERVATIVE - EXPULSIVE THERAPY OF DISTAL URETERAL STONES Milanese
G., Dellabella
A.O. Umberto
M., Muzzonigro
1 st, University
of Ancona,
IN
G Institute
of Urology,
Ancona,
Italy
INTRODUCTION & OBJECTIVES: During past years only a few studies have proposed different medical treatments in conservative-expulsive therapy of distal ureteral stones greater than 4mm. These treatments offer better expulsion rates then observational approaches, but are obviously more costly, because of various pharmacological associations. Our objective was to determine which of these strategies could be most cost-effective. MATERIAL & METHODS: From review in literature articles on the natural history and medical expulsive treatment of distal ureteral stones, we abstracted the following data: success rates, duration of therapy until expulsion or treatment failure. We individualised 4 types of treatment: a) Observational (OBS), b) Anticholinergic drug + deflazacort (AD), c) Nifedipine + Deflazacort (ND), d) Tamsulosin + Deflazacort (TD). The daily cost for each treatment was calculated on the basis of Italian drug prices. The cost of ureteroscopy (URS) was calculated via the mean cost published in articles over the last 5 years (2644.50 e). Decision tree analysis models were designed to estimate the cost of each treatment using the DATA program (TreeAge software 3.5). Sensitivity analysis evaluated the effect of each treatment’s variables on cost. The base case was a patient affected by ureteral colic pain due to a distal ureteral stone. We assumed that the failure of each treatment strategy was always followed by URS. RESULTS: The mean cost was 0.67 e (O-2.88 e) for OBS approach, 15.98 e (2.8630.24 e) for AD, 22.36 e (6.36-29.22 8) for ND and 13.83 e (3.66-52.38 e) for TD. Using the decision tree analysis and taking into account treatment costs and success rates, the rank order of treatment costs was: TD (290 e +806), ND (665 f? il128), AD (1198 f? *1308) and OBS (1573 e +1303). In one-way sensitivity analysis, varying the success rate TD remains the most cost effective treatment. This result was also confirmed by two-way sensitivity analysis. CONCLUSIONS: Extracorporeal lithotripsy and ureteroscopy are widely accepted as the first-choice treatment for distal ureteral calculi with a great impact on cost, whereas medical therapy is not considered enough. Using decision tree analysis, the association Tamsulosin + Deflaracort results in the most cost-effective choice in conservative-expulsive therapy of distal ureteral stones, This conservative approach could have a predominant role as first line treatment of distal ureteral stones, also as alternative of ureteroscopy, both for the success rate and for the cost containment.
STEM
CELL
ISOLATION
USING
HOECHST
Gilmore P.t, Bhatt R.2, Hart C.‘, Ramani V.3, George N.?, Brown GU Cancer Research Group, Manchester, United Kingdom
33342
FLOW
M.‘, Clarke N.3, ProMPT
‘Cancer Research UK Paterson Institute, Department Kay Kendall, Manchester, Umted Kingdom, ZHope Hospital, Department of Urology, Manchester, United Kingdom, 3Cluistie Hospital, Department of Urology, Manchester, United Kingdom, YSouth Manchester University Hospital, Department of Urology, Manchester, United Kingdom & OBJECTIVES: It has been proposed that prostate cancer originates from prostate stem cells with a potentially inexhaustible capacity for proliferation, differentiation and self-renewal. Their isolation has proved elusive although encouraging results have been reported using basal marker expression and binding characteristics to isolate cells with the differentiation/ proliferative properties of stem cells. We have adapted the Hoechst 33342 flow cytometry based dye efflux assay used for the isolation of haematopoietic stem cells to isolate prostate epithelial cells. We have character&d these using immunohistochemistry, and proliferation and differentiation assays.
INTRODUCTION
8-z METHODS: CD45 depleted prostate epithelial cells from benign and malignant prostates were incubated with Hoechst 33342 dye prior to FACS Vantage SE flow cytometry. A stem cell enriched side population (SP) and non-SP control (Body) were isolated. Immunofluorescent phenotyping used basal and luminal cell cytokeratins 5114 and X/18, primitive cell marker ~63, proposed stem cell markers ~27~‘p’, ~21~~~“~‘p’ , Notch 1, Cleaved Notch, Musashi 1 and was viewed by confocal microscopy. 3-D SP co-cultures were grown as spheroids in M&gel with a ST0 feeder layer. These were fixed and sectioned before immunohistochemistry and microscopy as above.
MATERIAL
The CD45 depleted Hoechst 33342 FACS profiles of both benign and malignant epithelia (n=25) showed the proportion of SP cells was 0.83 + 0.095%. SP cells showed increased expression of cytokeratins 5 (p=O.O14, n=X) and 14 (p=O.O003, n=8), p63 (p=O.O24, n=3), Musashi 1 (p=O.O28, n=lO), p21wAF”c’p’ (p=O.OOlS, n=14) and ~27~‘“’ (p=O.OOOS, n=ll) and decreased expression of PSA (p=O.O032, n=6) when compared to cells in the Body part of the FACS profile. Malignant SP showed diminished p21WAF”C’p’ expression (p=O.O045, n=6) compared to benign. In addition malignant SP S Cat&n expression was enhanced when compared to corresponding Body cells (p=O.O04, n=6). 3-D culture of SP cells in M&gel produced ‘Spheroid” structures with duct-like formation inter-linking individual cell regions in a manner consistent with stem cell behaviour. These expressed a basal phenotype of high cytokeratin 5 and low 18 with an outer layer high in p63 and inner layer surrounding a lumen.
RESULTS:
The Hoechst 33342 FACS based dye eMux assay is applicable to prostate epithelia enabling isolation of a side population with a similar profile to haematopoietic SPistem cell populations. Characterisation depicts a stem cell like phenotype with increased expression of stem cell markers includmg the CDK inhibitor p21 wAF”c’p’, which is lost in the malignant SP.
CONCLUSIONS:
P26
STONE DISEASE:MEDlCALMANAGEMENTANDRESEARCH Friday, 26 March, 14.00-15.30, Hall Fl-F2/Yellow level
NIFEDIPINE VERSUS TAMSULOSIN LOWER URETERAL STONES Poroiglia F., Ghignone Scarpa R.M. San Luigi Hospital,
IN
THE
G., Fiori C., Ten-one C., Scoffone
Urology,
Orbassano
Torino,
462 MANAGEMENT
OF
C., Ragni F., Guercio
Italy
INTRODUCTION & OBJECTIVES: The aim of this study is to evaluate and to compare the effectiveness of two different medical therapies during watchful waiting in patients with lower ureteral stones. & METHODS: Eighty-six patients with stones < lcm in size located in the lower ureter (juxtavesical or intramural tract) were enrolled in this study and were randomly divided into three groups. Patients of group A (11~30) received a daily oral treatment with 30 mg of a corticosteroid agent (deflazacort, for a maximum of 10 days) plus 30 mg of nifedipine slow-release (for a maximum of 28 days); patients of group B (n=28) received a daily oral treatment with 30 mg of deflazacort (for a maximum of 10 days) plus 0.4 mg of tamsulosin (for a maximum of 28 days), patients of group C were used as the control group (only symptomatic therapy). Patients of group A and B were also treated with gastroprotective therapy. All patients were required to drink a minimum of 2 litres of water day and were allowed to use a symptomatic therapy with injections of 75 mg (3 ml) diclofenac on demand. Statistical analyses were performed using Student’s test, chi square test, and Fisher’s exact test. MATERIAL
The average stone size was 4.7 mm +1.47 for group A, 5.42 mm *I .54 for group B and 5.35 mm tl.49 for group C without statistical difference (P=NS). Expulsion was observed in 24130 patients of group A (80%), 24/28 patients of group B (85%) and 12/28 patients of group C (43%). No statistical difference was noted in expulsion rate between group A and B; whereas the difference of both A and B with respect to group C was highly significant (p
The results of this study indicate that stones in the lower tract of ureter can be treated with an expulsive medical therapy in patients when a watchful waiting approach can be chosen. In our study, medical treatments with nifedipine and tamsulosin proved to be safe and effective as demonstrated by the low incidence of side effects and the increased stone expulsion rate. Moreover medical therapy, particularly as far as concern the use of tamsulosin, seems to reduce the expulsion time.
CONCLUSIONS:
463 A DOUBLE-BLINDED TRIAL ASSESSING AGENTS FOR EXTRACORPOREAL Beiko D.’ Watterson -> H.3, Denstedt J.3
PROSPECTIVE RANDOMIZED CONTROLLED THE SAFETY AND EFFICACY OF INTRAVESICAL URETERAL STENT SYMPTOMS FOLLOWING SHOCK WAVE LITHOTRIPSY J.2, Knudsen
t Queen’s University, Urology, Ottawa, Canada, 3University
B.3, Nott
Kingston, of Western
L.3, Pautler
Canada, Ontario,
S.3, Brock
G.3, Razvi
2University of Ottawa, Urology, Urology, London, Canada
INTRODUCTION & OBJECTIVES: Ureteral stems are a significant source of pain and discomfort for many urologic patients. A novel approach to addressing this problem is the intravesical instillation of a selected pharmacologic agent following stent insertion. The purpose of this study was to assess the safety and efficacy of intravesical instillation of various agents in reducing ureteral stentassociated discomfort in patients requiring a stent for extracorporeal shock wave lithotripsy. MATERIAL & METHODS: In this double-blinded prospective trial, 42 patients were randomized to receive intravesical instillation of one of three selected agents (oxybutynin, alkalinized lidocaine or ketorolac) or a control solution (0.9% sodium chloride) immediately following stent insertion at time of extracorporeal shock wave lithotripsy. Preoperative, intraoperative and postoperative data were prospectively collected and statistically analyzed. The primary outcome measure was reduction in ureteral stent symptoms and the secondary outcome measure was determination of safety of intravesical instillation of each agent through assessment of drug-related adverse events in each group of patients. RESULTS: The four groups of patients were demographically similar. There were no intraoperative or postoperative complications, nor were there any serious side effects attributable to any of the inhavesically-instilled agents. There was a statistically significant decrease in stent-related discomfort at the one-hour time point in the group of patients who received intravesical ketorolac when compared with the control group. CONCLUSIONS: Intravesical instillation represents a novel approach to addressing the problem of ureteral stent-related discomfort. We have established that intravesical instillation of ketorolac is safe in humans. Based on our results, ketorolac appears to be the most effective intravesical agent in reducing stentrelated patient discomfort. European
Urology
Supplements
3 (2004)
No. 2, pp. 118
S.,
464 COST COMPARISON FOR DIFFERENT MEDICAL TREATMENTS CONSERVATIVE - EXPULSIVE THERAPY OF DISTAL URETERAL STONES Milanese
G., Dellabella
A.O. Umberto
M., Muzzonigro
1 st, University
of Ancona,
IN
G Institute
of Urology,
Ancona,
Italy
INTRODUCTION & OBJECTIVES: During past years only a few studies have proposed different medical treatments in conservative-expulsive therapy of distal ureteral stones greater than 4mm. These treatments offer better expulsion rates then observational approaches, but are obviously more costly, because of various pharmacological associations. Our objective was to determine which of these strategies could be most cost-effective. MATERIAL & METHODS: From review in literature articles on the natural history and medical expulsive treatment of distal ureteral stones, we abstracted the following data: success rates, duration of therapy until expulsion or treatment failure. We individualised 4 types of treatment: a) Observational (OBS), b) Anticholinergic drug + deflazacort (AD), c) Nifedipine + Deflazacort (ND), d) Tamsulosin + Deflazacort (TD). The daily cost for each treatment was calculated on the basis of Italian drug prices. The cost of ureteroscopy (URS) was calculated via the mean cost published in articles over the last 5 years (2644.50 e). Decision tree analysis models were designed to estimate the cost of each treatment using the DATA program (TreeAge software 3.5). Sensitivity analysis evaluated the effect of each treatment’s variables on cost. The base case was a patient affected by ureteral colic pain due to a distal ureteral stone. We assumed that the failure of each treatment strategy was always followed by URS. RESULTS: The mean cost was 0.67 e (O-2.88 e) for OBS approach, 15.98 e (2.8630.24 e) for AD, 22.36 e (6.36-29.22 8) for ND and 13.83 e (3.66-52.38 e) for TD. Using the decision tree analysis and taking into account treatment costs and success rates, the rank order of treatment costs was: TD (290 e +806), ND (665 f? il128), AD (1198 f? *1308) and OBS (1573 e +1303). In one-way sensitivity analysis, varying the success rate TD remains the most cost effective treatment. This result was also confirmed by two-way sensitivity analysis. CONCLUSIONS: Extracorporeal lithotripsy and ureteroscopy are widely accepted as the first-choice treatment for distal ureteral calculi with a great impact on cost, whereas medical therapy is not considered enough. Using decision tree analysis, the association Tamsulosin + Deflaracort results in the most cost-effective choice in conservative-expulsive therapy of distal ureteral stones, This conservative approach could have a predominant role as first line treatment of distal ureteral stones, also as alternative of ureteroscopy, both for the success rate and for the cost containment.