- Email: [email protected]
536Rechallenging non-responders to tadalafil and vardenafil: A real-life study
533
534
PROOF
O F H U M A N E P A P I L O M A V I R U S E S (HPV) I N B L A D D E R B I O P S I E S
COMPARATIVE ASSESSMENT OF MAXIMAL BLADDER CAPACITY, 0 . 9 % N A C L VS. 0.2 M K C L B E F O R E AND A F T E R T H E R A P Y F O R INTERSTITIAL CYSTITIS
Loch A. t, Stein U. 2, Loch T. t
Daha L. t , Riedl C ? , Lazar D. t , Hohlbrugger G. 3, Pfl/iger H. t
tDiakonissenkrankenhaus, Urology, Ftensburg, Germany, 2University, Pathology,
tHospital Lainz, Urology, Vienna, Austria, 2Hospital Baden, Urology, Baden, Austria, 3Hospital Innsbruck, Urology, Innsbruck, Austria
I N T E R S T I T I A L C Y S T I T I S (IC): I M M U N E H I S T O C H E M I C A L
Homburg, Germany I N T R O D U C T I O N & O B J E C T I V E S : There are still many questions concerning the etiology of the symptom complex IC. Mast cells play a key role b y degranulating different vasoactive and nociceptive substances that keep the inflammatory process active. The triggers of mast cell secretion are cytokines, hormones, cationic peptides, bacterial toxins and viruses. We investigated whether human papiloma virus (HPV) mediates mast cell activity in our study population. M A T E R I A L & M E T H O D S : We examined 40 women and 3 men with symptoms of IC defined by the national instituted o f diabetes, digestive and kidney diseases (NIDDK). All underwent systematic bladder biopsies with a cold loop, In 34 cases a significant mast cell density was found in the sub epithelium by GIEMSAstaining. In addition a nerve fiber sprouting in the tissue samples b y S 100 immune histochemistry. These 34 cases were further analyzed by immune histochemistry for HPV (type 11,6,18) activity. R E S U L T S : In 70% of the study population a HPV activity was found. The highest activity was found in the mast cells. Controls o f 12 unspecific cystitis, 18 cystectomy specimens of bladder cancer, 10 vaginal samples as well as 9 other mastocytosis sample were so far negative for HPV. C O N C L U S I O N S : HPV (type 11, 6, 18) seems to be present in the mast cells of IC. The next step is a molecular biological test, in order to define the detailed role of HPV as possible trigger in the ethologic cascade of IC.
535 THE INTRAVESICAL HEPARIN AND PERIPHERAL
NEUROMODU-
L A T I O N ON I N T E R S T I T I A L C Y S T I T I S
I N T R O D U C T I O N & O B J E C T I V E S : For diagnosis of increased potassimn sensitivity in patients with interstitial cystitis (IC) comparative assessment of maximal bladder capacity (CAMBC) with a 0.9% NaCI solution vs. a 0.2 M KC1 solution is a well tolerated alternative to the 0.4M potassium sensitivity test (PST) (Daha et al., J.Urol., 165, Supp: A 280, 2001). In the present study comparative assessment of maximal bladder capacity was performed before and after GAG substitution therapy to asses the post therapeutic changes in potassium sensitivity. M A T E R I A L & M E T H O D S : The study comprised a total of 20 volunteers with IC who showed increased potassium sensitivity (reduction of maximal bladder capacity > 30% with 0.2MKC1 vs. saline). All patients were treated with weekly with 50cc of 40 mg Hyaluronic acid for 10 weeks. Eight patients who showed no improvement after 5 weeks of therapy had an additive intravesical treatment with 200mg Pentosanpolysulfate (PPS) instillations three times weekly for 5 weeks. After this treatment period C A M B C was repeated. R E S U L T S : Patients were separated into 2 groups according to their response to therapy. Symptom improvement was observed in 12 patients (Group I). In this group average maximal bladder capacity was 249.5 cc with saline solution and 153.4 cc with 0.2M KC1 solution before therapy. After therapy maximal bladder capacity increased to 360.6 cc (+44 %) with a saline solution and 286.6 cc (+86%) with a 0.2M KC1 solution. Maximal bladder capacity reduction with KCI ranged from 0% (4 patients) to 20% (1 patient) and averaged 1 1 % . 8 Patients had no improvement after therapy (Group II). In this group average maximal bladder capacity was 232.5 cc with saline solution and 153.4 cc with 0.2M KC1 solution before therapy. After therapy maximal bladder capacity was reduced to 184 cc (- 2 1 % ) with a saline solution and 144 cc (- 13 %) with a 0.2M KC1 solution. C O N C L U S I O N S : Patients who c l i n i c a l l y respond to intravesical G A G substitution therapy show an increase of bladder capacity and a normal posttherapeutic CAMBC, whereas patients without symptom improvement have a reduction of all bladder capacity parameters after therapy. These data demonstrate that G A G substitution responders also show improvement of bladder function, suggesting correction of increased urothelial permeability in these cases.
09 PB~BMA6OTHEPAP~FOBERECTILED¥$NNCTION : RECHALLENGING NON-RESPONDERS VARDENAFIL: A REAL-LIFE STUDY
TO
: TADALAFIL
AND
HatzimouraddisK., MoysidisK., BekosA., TsimtsiouZ., IoannidisE., HatzichristouD. Baykal K., Senkul T., Sen B., Alp B.F., Karademir K., Adayener C.
AristotleUniversity,2nd Dep. of Urology,Thessalothki,Greece
Gata Haydarpasa Training Hospital, Urology, Istanbul, Turkey
INTRODUCTION & OBJECTIVES: To rechallengenon-respondersED patients treated with the new PDE5 inhibitors,tadalafiland vardenafil.
INTRODUCTION
& O B J E C T I V E S : We wanted to evaluate the therapeutic
effect of the intravesical heparin and peripheral neuromodulation on patients with interstitial cystitis. M A T E R I A L & M E T H O D S : From March 2002 to M a y 2004, 12 female and 2 male subjects conform to the N I D D K criteria and not responsive to the previous conventional treatments were included in the study. Wisconsin pain scores, m a x i m a l cystometric capacities, night and day voiding frequencies were determined and these studies were repeated in the 2nd and 12th months of the treatment with 10.000 units intravesical heparin and peripheral nenromodulation. Frequency of the treatment was once a week during first 8 weeks, once in two weeks in following 8 weeks, and once in 3 weeks as four times. Then, it was decreased once in a month.
MATERIAL& METHODS: The study comprisedof 2 groups,the tadalafil-treated(T) and the vardenafiltreated (V) group; all patients had previouslyused the maximumdose of 20 mg for at least 4 attempts, according to the manufacturer's instructionsunsuccessfully.All patients underwent typical work-up and completedthe IIEF and a questionnaireregardingthe previoususe of the PDE5 inhibitor.New insWactions were givento both groupsin termstimingof intercoursefor the T group(at least2h beforesexualintercourse) and food restrictionsfor the V group(use only fasted).Those stillnot respondingto the new instructionswere rechallengedwith continuoustreatment (everydayuse of 20rag of vm-denafil,and 20mg of tadalafilevery other day respectively).Clinicalefficacywas re~evalustedin a scheduledfollow-upvisit. RESULTS: "['adatafilGroup: Mean patient age was 48 ± 12.8 (range: 23-65) years, mean durationof ED 2.2 ± 5.1 (range: 0.3-7) years, mean EF Domain Score of the llEF was 16 ± 6.4 (range 7-25) while risk factors for ED were recognizedin 44 patients. Of the 86 non-responders,32 (37.2%) responded having intercourse between 2-36 hours after the dose intake (table 1). Of the 54 still non-responders, 34 (63%) accepted the continuous every other day administrationand 6 (17.6%) responded (t~ble 2). The overall salvagerate of the presentedtreatmentstrategywas 38/86 (44.2%). Vardenafil Group: Mean patient age was 52 ± 16.6 (range: 28~72) years, mean duration of ED 2.5 ± 7.I (range: 0.3-11) years, mean EF DomainScore of the IIEF was 15 ~ 7.1 (range 5-24), while risk factors for ED were recognizedin 56 patients. Of the 88 uon-responders,22 (25%)respondedwhen the dose was taken in the fasted state (table 1). Of the 66 still non-responders, 32 (48.5%) acceptedthe continuousevery day administrationand 12 (37.5%) responded (table 2). The overall salvage rate of the presented treatment strategywas 34/88 (38.6%). Table 1. Retrialwith new instructionsfor tadalafiland vardenafil Tadalafil
Vardenafil
86 32 (37.2%) NA
88 NA 22 (25%)
voiding frequency were significantly better in the 2nd and in the 12th months,
Nonresponders Having sex >2h after administration Fasted
when compared to pre-treatment values. The percentage improvement on
Table 2. Scheduleddosingfor tadalafi[and vardenafil
R E S U L T S : The mean follow-up period was 20 months (12-25). Day and night
Wisconsin pain scores were 62.54-13.9% and 62.8=15.2% in the 2nd and the 12th months, respectively. The average increase in the m a x i m u m cystometric capacity was 54.8:k27.4% and 52.5:k31.6% in the 2nd and the 12th months, respectively. CONCLUSIONS:
Intravesical heparin
and
peripheral
neuromodulation
combination looks to be an alternative fur patients with interstitial cystitis not responsive to other treatments.
European Urology Supplements 4 (2005) No. 3, pp. 136
Nonresponders Accepted Response Selvage
Tadalafil
Vardenafil
54 34 (63%) 6 (17.6%) 52/100
66 32 (48.5%) 12 (37.5%) 54/100
CONCLUSIONS: Timingof intercourseand food instructionsmay play a significantrole in the responserate of ED patientsunder PDE5 inhibitorstreatment.Continuousadministrationschememay maximizeefficacy. Further research is urgently needed on the appmpftate dose and adverse events profile of the continuous administrationof these new drugs.
534
PROOF
O F H U M A N E P A P I L O M A V I R U S E S (HPV) I N B L A D D E R B I O P S I E S
COMPARATIVE ASSESSMENT OF MAXIMAL BLADDER CAPACITY, 0 . 9 % N A C L VS. 0.2 M K C L B E F O R E AND A F T E R T H E R A P Y F O R INTERSTITIAL CYSTITIS
Loch A. t, Stein U. 2, Loch T. t
Daha L. t , Riedl C ? , Lazar D. t , Hohlbrugger G. 3, Pfl/iger H. t
tDiakonissenkrankenhaus, Urology, Ftensburg, Germany, 2University, Pathology,
tHospital Lainz, Urology, Vienna, Austria, 2Hospital Baden, Urology, Baden, Austria, 3Hospital Innsbruck, Urology, Innsbruck, Austria
I N T E R S T I T I A L C Y S T I T I S (IC): I M M U N E H I S T O C H E M I C A L
Homburg, Germany I N T R O D U C T I O N & O B J E C T I V E S : There are still many questions concerning the etiology of the symptom complex IC. Mast cells play a key role b y degranulating different vasoactive and nociceptive substances that keep the inflammatory process active. The triggers of mast cell secretion are cytokines, hormones, cationic peptides, bacterial toxins and viruses. We investigated whether human papiloma virus (HPV) mediates mast cell activity in our study population. M A T E R I A L & M E T H O D S : We examined 40 women and 3 men with symptoms of IC defined by the national instituted o f diabetes, digestive and kidney diseases (NIDDK). All underwent systematic bladder biopsies with a cold loop, In 34 cases a significant mast cell density was found in the sub epithelium by GIEMSAstaining. In addition a nerve fiber sprouting in the tissue samples b y S 100 immune histochemistry. These 34 cases were further analyzed by immune histochemistry for HPV (type 11,6,18) activity. R E S U L T S : In 70% of the study population a HPV activity was found. The highest activity was found in the mast cells. Controls o f 12 unspecific cystitis, 18 cystectomy specimens of bladder cancer, 10 vaginal samples as well as 9 other mastocytosis sample were so far negative for HPV. C O N C L U S I O N S : HPV (type 11, 6, 18) seems to be present in the mast cells of IC. The next step is a molecular biological test, in order to define the detailed role of HPV as possible trigger in the ethologic cascade of IC.
535 THE INTRAVESICAL HEPARIN AND PERIPHERAL
NEUROMODU-
L A T I O N ON I N T E R S T I T I A L C Y S T I T I S
I N T R O D U C T I O N & O B J E C T I V E S : For diagnosis of increased potassimn sensitivity in patients with interstitial cystitis (IC) comparative assessment of maximal bladder capacity (CAMBC) with a 0.9% NaCI solution vs. a 0.2 M KC1 solution is a well tolerated alternative to the 0.4M potassium sensitivity test (PST) (Daha et al., J.Urol., 165, Supp: A 280, 2001). In the present study comparative assessment of maximal bladder capacity was performed before and after GAG substitution therapy to asses the post therapeutic changes in potassium sensitivity. M A T E R I A L & M E T H O D S : The study comprised a total of 20 volunteers with IC who showed increased potassium sensitivity (reduction of maximal bladder capacity > 30% with 0.2MKC1 vs. saline). All patients were treated with weekly with 50cc of 40 mg Hyaluronic acid for 10 weeks. Eight patients who showed no improvement after 5 weeks of therapy had an additive intravesical treatment with 200mg Pentosanpolysulfate (PPS) instillations three times weekly for 5 weeks. After this treatment period C A M B C was repeated. R E S U L T S : Patients were separated into 2 groups according to their response to therapy. Symptom improvement was observed in 12 patients (Group I). In this group average maximal bladder capacity was 249.5 cc with saline solution and 153.4 cc with 0.2M KC1 solution before therapy. After therapy maximal bladder capacity increased to 360.6 cc (+44 %) with a saline solution and 286.6 cc (+86%) with a 0.2M KC1 solution. Maximal bladder capacity reduction with KCI ranged from 0% (4 patients) to 20% (1 patient) and averaged 1 1 % . 8 Patients had no improvement after therapy (Group II). In this group average maximal bladder capacity was 232.5 cc with saline solution and 153.4 cc with 0.2M KC1 solution before therapy. After therapy maximal bladder capacity was reduced to 184 cc (- 2 1 % ) with a saline solution and 144 cc (- 13 %) with a 0.2M KC1 solution. C O N C L U S I O N S : Patients who c l i n i c a l l y respond to intravesical G A G substitution therapy show an increase of bladder capacity and a normal posttherapeutic CAMBC, whereas patients without symptom improvement have a reduction of all bladder capacity parameters after therapy. These data demonstrate that G A G substitution responders also show improvement of bladder function, suggesting correction of increased urothelial permeability in these cases.
09 PB~BMA6OTHEPAP~FOBERECTILED¥$NNCTION : RECHALLENGING NON-RESPONDERS VARDENAFIL: A REAL-LIFE STUDY
TO
: TADALAFIL
AND
HatzimouraddisK., MoysidisK., BekosA., TsimtsiouZ., IoannidisE., HatzichristouD. Baykal K., Senkul T., Sen B., Alp B.F., Karademir K., Adayener C.
AristotleUniversity,2nd Dep. of Urology,Thessalothki,Greece
Gata Haydarpasa Training Hospital, Urology, Istanbul, Turkey
INTRODUCTION & OBJECTIVES: To rechallengenon-respondersED patients treated with the new PDE5 inhibitors,tadalafiland vardenafil.
INTRODUCTION
& O B J E C T I V E S : We wanted to evaluate the therapeutic
effect of the intravesical heparin and peripheral neuromodulation on patients with interstitial cystitis. M A T E R I A L & M E T H O D S : From March 2002 to M a y 2004, 12 female and 2 male subjects conform to the N I D D K criteria and not responsive to the previous conventional treatments were included in the study. Wisconsin pain scores, m a x i m a l cystometric capacities, night and day voiding frequencies were determined and these studies were repeated in the 2nd and 12th months of the treatment with 10.000 units intravesical heparin and peripheral nenromodulation. Frequency of the treatment was once a week during first 8 weeks, once in two weeks in following 8 weeks, and once in 3 weeks as four times. Then, it was decreased once in a month.
MATERIAL& METHODS: The study comprisedof 2 groups,the tadalafil-treated(T) and the vardenafiltreated (V) group; all patients had previouslyused the maximumdose of 20 mg for at least 4 attempts, according to the manufacturer's instructionsunsuccessfully.All patients underwent typical work-up and completedthe IIEF and a questionnaireregardingthe previoususe of the PDE5 inhibitor.New insWactions were givento both groupsin termstimingof intercoursefor the T group(at least2h beforesexualintercourse) and food restrictionsfor the V group(use only fasted).Those stillnot respondingto the new instructionswere rechallengedwith continuoustreatment (everydayuse of 20rag of vm-denafil,and 20mg of tadalafilevery other day respectively).Clinicalefficacywas re~evalustedin a scheduledfollow-upvisit. RESULTS: "['adatafilGroup: Mean patient age was 48 ± 12.8 (range: 23-65) years, mean durationof ED 2.2 ± 5.1 (range: 0.3-7) years, mean EF Domain Score of the llEF was 16 ± 6.4 (range 7-25) while risk factors for ED were recognizedin 44 patients. Of the 86 non-responders,32 (37.2%) responded having intercourse between 2-36 hours after the dose intake (table 1). Of the 54 still non-responders, 34 (63%) accepted the continuous every other day administrationand 6 (17.6%) responded (t~ble 2). The overall salvagerate of the presentedtreatmentstrategywas 38/86 (44.2%). Vardenafil Group: Mean patient age was 52 ± 16.6 (range: 28~72) years, mean duration of ED 2.5 ± 7.I (range: 0.3-11) years, mean EF DomainScore of the IIEF was 15 ~ 7.1 (range 5-24), while risk factors for ED were recognizedin 56 patients. Of the 88 uon-responders,22 (25%)respondedwhen the dose was taken in the fasted state (table 1). Of the 66 still non-responders, 32 (48.5%) acceptedthe continuousevery day administrationand 12 (37.5%) responded (table 2). The overall salvage rate of the presented treatment strategywas 34/88 (38.6%). Table 1. Retrialwith new instructionsfor tadalafiland vardenafil Tadalafil
Vardenafil
86 32 (37.2%) NA
88 NA 22 (25%)
voiding frequency were significantly better in the 2nd and in the 12th months,
Nonresponders Having sex >2h after administration Fasted
when compared to pre-treatment values. The percentage improvement on
Table 2. Scheduleddosingfor tadalafi[and vardenafil
R E S U L T S : The mean follow-up period was 20 months (12-25). Day and night
Wisconsin pain scores were 62.54-13.9% and 62.8=15.2% in the 2nd and the 12th months, respectively. The average increase in the m a x i m u m cystometric capacity was 54.8:k27.4% and 52.5:k31.6% in the 2nd and the 12th months, respectively. CONCLUSIONS:
Intravesical heparin
and
peripheral
neuromodulation
combination looks to be an alternative fur patients with interstitial cystitis not responsive to other treatments.
European Urology Supplements 4 (2005) No. 3, pp. 136
Nonresponders Accepted Response Selvage
Tadalafil
Vardenafil
54 34 (63%) 6 (17.6%) 52/100
66 32 (48.5%) 12 (37.5%) 54/100
CONCLUSIONS: Timingof intercourseand food instructionsmay play a significantrole in the responserate of ED patientsunder PDE5 inhibitorstreatment.Continuousadministrationschememay maximizeefficacy. Further research is urgently needed on the appmpftate dose and adverse events profile of the continuous administrationof these new drugs.