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‹#› ------=_NextPart_01CA4838.DDEA2AC0 Content-Location: file:///C:/9D2D214F/Chemoprewencjarakagruczolukrokowego_pliki/master104.xml Content-Transfer-Encoding: quoted-printable Content-Type: text/xml; charset="utf-8" ------=_NextPart_01CA4838.DDEA2AC0 Content-Location: file:///C:/9D2D214F/Chemoprewencjarakagruczolukrokowego_pliki/pres.xml Content-Transfer-Encoding: quoted-printable Content-Type: text/xml; charset="utf-8" ------=_NextPart_01CA4838.DDEA2AC0 Content-Location: file:///C:/9D2D214F/Chemoprewencjarakagruczolukrokowego_pliki/slide0001.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="us-ascii" Chemoprewencja raka gruczołu krokowego
Chemoprewen= cja raka stercza
Andrzej Paradysz
Skupia= jąc się głównie na przeprowadzonych ostatnio badaniach z blokerami 5 alfa reduktazy.
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3DCroweFingers
Wczesna diagnostyka raka stercza<= /span>
nDRE – ognisko >0,2 ml
nPSA - ≥4ng/ml (≥2,5 ng/ml)
nTRUS
nBiopsja stercza
nPCA3 - nowy marker
n genetyczny w fazie badań
nBadania ERSPC i PLCO
Na szczęście nie jesteśmy bezsilni. Możemy przeprowadzić wczesną diagnostykęktóra obejmuje.
Rozpoc= zęte w latach dziwędziesiątych badania obejmujące prawie 200 ty&#= 347; mężczyzn potwierdzają spadek umieralności rzędu = 20% u osób objętych screeningiem lecz potwierdzają obawę przed rozpoznawaniem i leczeniem pacjentów z nieistotnym klinicznie rakiem stercza tzw „overtreatment”.  Programy badawcze mające ustalić czy testy screeningowe prowadzą do zmniejszenia śmiertelności w przebiegu raka stercza.

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Prewencja
nChemoprewencja to stosowanie farmakologicznych = lub naturalnych czynników = w celu zahamowania lub odwrócenia procesu kancerogenezy.
nPowinna poprzedzać proces kancerogenezy lub ingerować na etapie promocji - przeciętnie 20 lat.
nStosowanie określonych środków farmakologicznych wydaje się bardziej obiecujące niż efekty osiągane w wyniku stosowania coraz agresywniejszego screeningu i wynikającego z niego leczenia [1].
n
<= span style=3D'font-size:88%;text-shadow:auto;visibility:hidden'>n<= span style=3D'font-size:88%;text-shadow:auto;mso-special-format:lastCR;display:= none'>
1. Brawley OW, Barnes ST: Potential agents for prostate cancer chemoprevention. Epidemiol Rev 2001, 23, 1, 168-172.
Ale co= możemy zrobić oprócz screeningu.
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Naturalna prewencja raka prostaty=
<= span style=3D'font-size:75%;text-shadow:auto'>nSoja – fitoestrogen genisteina – redukuje poziom PSA
nPomidory – likopeny – naturalny antyoxydant zmniejszający ryzyko raka
<= span style=3D'font-size:75%;text-shadow:auto'>nKwasy tłuszczowe Omega 3 [1].
<= span style=3D'font-size:75%;color:red;text-shadow:auto'>nSelen
<= span style=3D'font-size:75%;color:red;text-shadow:auto'>nWitamina E =
<= span style=3D'font-size:75%;text-shadow:auto'>nWitamina D,
<= span style=3D'font-size:75%;text-shadow:auto'>nZielona herbata
nCzerwone wino – 4 kieliszki tygodniowo zmniejszają o 60 % ryzyko najbardziej agresywnych nowotworów prostaty
<= span style=3D'font-size:75%;text-shadow:auto'>nWarzywa – brokuły, kapusta, czosnek, cebu= la, szczypiorek
1. Brawley OW, Barnes ST: Poten= tial agents for prostate cancer chemoprevention. Epidemiol Rev 2001, 23, 1, 168-172.
1.Niek= tórzy autorzy dowodzą skuteczności stosowania genisteiny, głównego fitoestrogenu sojowego, który swoje prewencyj= ne działanie wywierać ma poprzez hamowanie kinazy tyrozynowej i wywieranie efektu antyestrogenowego. Skuteczność tego rodzaju preparatów testowana jest dotychczas jedynie na zwierzętach [= 4].
2.Uwa&= #380;a się, że zwiększona konsumpcja nasyconych kwasów tłuszczowych przy zmniejszonym spożyciu błonnika może powodować długotrwałą stymulację organizmu androgenami i przyczynić się do zwiększenia ryzyka wystąpienia raka stercza
3.Bada= nie SELECT (USA, Puerto Rico, Kanada) przeprowadzone od 2001-2008 roku wykazało że przyjmowanie 200mcg selenu i 400 IUs witaminy E nie działają prewencyjnie w stosunku do raka stercza. Co wiecej wstępne analizy wyników dowodzą że witamina E nieznacznie zwiększa ryzyko raka prostaty a selen w dawce 200mcg może zwiększać ryzyko cukrzycy typu drugiego.
------=_NextPart_01CA4838.DDEA2AC0 Content-Location: file:///C:/9D2D214F/Chemoprewencjarakagruczolukrokowego_pliki/slide0044.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="us-ascii" Chemoprewencja raka gruczołu krokowego
Naturalna prewencja raka prostaty=
nW 2003 roku Giles i wsp. <= /span>opisali zjawisko mniejszego współczynnika zapadalności na PCa u mężczyzn o większej, niż przeciętna, <= span style=3D'position:absolute;top:53.5%;left:9.92%;width:39.7%;height:5.25%'>= częstotliwości ejakulac= ji – = nie stwierdzono jednak przyczyn leżących u podłoża tej zależności [1].
<= span style=3D'font-size:75%;text-shadow:auto;visibility:hidden'>n<= span style=3D'font-size:75%;text-shadow:auto;mso-special-format:lastCR;display:= none'>
3Dprostate-779018
1.Giles GG, Severi G, English DR i wsp. Sexual fac= tors and prostate cancer. BJU Int. 2003 Aug;92(3):2116.
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Chemoprewencja - sele= ktywne inhibitory 5α-reduktazy
nTestosteron        = ;            &n= bsp;     dihydrotestosteron
Finasteryd - PCPT
Dutasteryd - REDUCE
   5 α reduktaza
Inhibi= tory 5α-reduktazy powodują obniżenie stężenia dihydrotestosteronu i nieco podnoszą poziom testosteronu w obrę= bie gruczołu krokowego [3,6]. Pierwszy z nich, finasteryd, powoduje selektywne hamowanie 5α-reduktazy typu 2, natomiast dutasteryd jest inhibitorem obu typów 1 i 2 tego enzymu. Oba leki zarejestrowane zostały w leczeniu łagodnego rozrostu stercza, z oboma też wiąże się nadzieje w odniesieniu do chemoprewencji raka gruczołu krokowego [6,7,8]. Dutasteryd pozostaje przedmiotem bada= 24; klinicznych, spośród których najlepiej znanym jest bad= anie REDUCE (Reduction by Dutasteride of Prostate Cancer Events), które= go wyniki poznamy w następnych latach [9,10].


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PCPT
nProstate Cancer Prevention Trial – USA 1996-2003.
nGrupa badana - 18 882 mężczyzn
n>55 rok życia
nPSA <3 ng/ml
nBrak odchyleń w badaniu per rectum
= nmężczyźni otrzymywali placebo (N=3D94= 59) lub f= inasteryd w dziennej dawce 5 mg (N=3D9423) przez siedem lat.
By = 2;o to pierwsze prospektywne, randomizowane, badanie chemoprewencji raka prostat= y. Badanie przerwanow marcu 2003 roku, dalsze dane spływały do cze= rwca ostatecznie w grupie leczonej finasterydem znalazło się 4251 mężczyzn a w grupie placebo 4576.
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Wyniki
Z 18882 badanie zakończyło 15990 mężczyzn
(9060)
(6930)
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Wyniki
Finasteryd
Placebo
Rak prostaty
16,6%
22,9%
High grade
(Gleeson>7)
5,8%
4,8%
Ró= ;żnice istotne statystycznie
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Wnioski -  2003 rok
nfinasteryd zmniejsza ryzyko wystąpienia raka stercza o 25%.
nczęsts= ze występowanie raka stercza o wyższym stopniu złośliwości (high-grade - Gleason score 7) u mężczyzn zażywających finasteryd [1]. =
n
1. Scardino PT: The prevention = of prostate cancer-the dilemma continues. N Engl J Med 2003, 349, 297-299.
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1. Czy rzeczywiście stosowanie finasterydu sprzyja rozwijaniu się = nowotworu o wyższym = stopniu złośliwoś= ci?
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Czy finasteryd sprzyja rozwojowi raka stercza o wysokim stopniu złośliwości?
nOszacowanie częstości występowania raka stercza u = uczestników badania przy założ= eniu, że każdy z nich spełnił kryteria końcowe protokołu.
nWspółzmienne poddane regresji logistycznej: 
nkierunek leczenia,
nwiek,
nprzynależność etniczna/rasa, = 3;
nstężenie PSA
nwywiad rodzinny w kierunku występowania ra= ka prostaty.
n =
n
<= o:OLEObject Type=3D"Embed" ProgID=3D"MSGraph.Chart.8" ShapeID=3D"Object_x0020_5" DrawAspect=3D"Content" ObjectID=3D"2">
Przepr= owadzono 3 analizy statystyczne:
Oszaco= wanie częstości występowania raka stercza u uczestników badania przy założeniu, że każdy z nich spełni&#= 322; kryteria końcowe protokołu
Oszaco= wanie częstości występowania raka stercza typu high-grade z wykorzystaniem danych uzyskanych po wykonaniu pięciuset prostatektom= ii radykalnych u uczestników badania
Dokona= nie oceny wpływu czułości biopsji stercza na częstość wykrywania raka tego narządu [4,18].
Oszaco= wanie częstości występowania raka stercza typu high-grade na podstawie prostatektomii
Ocena = wpływu czułości biopsji stercza na częstość wykrywania = raka tego narządu [4,18].
4.Redm= an MW, Tangen CM, Goodman PJ et al: Finasteride does not increase the risk of high-grade prostate cancer, a bias-adjusted modeling approach. Cancer Prev Res 2008, Online First 2008, 10.1158/1940-6207. CAPR-08-0092.
18.Log= othetis CJ, Schellhammer PF: High-grade prostate cancer and the Prostate Cancer Prevention Trial. Cancer Prev Res 2008, Online First 2008, 10.1158/1940-6207.CAPR-08-0085.

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Wyniki
Finasteryd
Placebo
16,6% (5,8%)
22,9% (4,8%)
= Powtórna analiza
14,7% (4,8%)
21,1% (4,2%)
Ryzyko raka stercza Ryzyko raka typu high-grade
Różnica istotna statystycznie Różnica nieistotna statystycznie
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2. Czy nowotwory, któ= rych = ryzyko wystąpienia jest zmniejszone przez finasteryd = mają znaczenie kliniczne?
W celu wyjaśnienia tych zagadnień dokonano w ostatnim roku ponownej oc= eny histopatologicznej preparatów biopsyjnych uzyskanych od uczestników badania. Oceniono również i porówna= no z preparatami biopsyjnymi materiały tkankowe uzyskane z prostatektomii radykalnych, wykonanych u tych uczestników badania, u który= ch wykryto nowotwór gruczołu krokowego.
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<= ![if !vml]>
Nowotwór nieistotny klinic= znie:
1.Lucia MS, Darke AK, Goodm= an PJ et al: Pathologic characteristics of cancers detected in the prostate cancer prevention tri= al, implications for prostate cancer detection and chemoprevention. Cancer Prev Res 2008, Online First 2008, 10.= 1158/1940-6207.CAPR-08-0078.
2. Luci= a MS, Darke AK, Goodman PJ et al: Pathologic characteristics of cancers detected= in the prostate cancer prevention trial, implications for prostate cancer detection and chemoprevention. Cancer Prev Res 2008, Online First 2008, 10.1158/1940-6207.CAPR-08-0078. &= #13;
3. Logothetis CJ, Schellhammer = PF: High-grade prostate cancer and the Prostate Cancer Prevention Trial. Cancer Prev Res 2008, Online First 2008, 10.1158/1940-6207.CAPR-08-0085.
placebo
Finasteryd
<T1c, gęstość PSA <0,15 ng= /ml, gleason <6
27,7 %
19,9 %<= b>[2,3]
wykryty w mniej niż trz= ech skrawkach biopsyjnych i zajmujący do 50% objętości lub mniej niż 3 mm jakiegokolwiek skrawka [1]
30, 5%
21,4 %<= b>[2,3]
Stosuj= ąc kryteria pierwszej definicji oceniono, że 27,7% preparatów uzyskanych od mężczyzn zażywających placebo oraz 19,9% preparatów z grupy przyjmującej finasteryd należy zakwalifikować do raków nieistotnych klinicznie.
Wed= 22;ug kryteriów drugiej definicji nieistotnymi klinicznie okazało się 30,5% raków wykrytych u mężczyzn, którym podawano placebo, i 21,4% raków stwierdzonych u chorych leczonych finasterydem [17,18].

Dane t= e są porównywalne do większości serii uzyskanych po prostatektomii (u chorych niebędących uczestnikami badania PCPT= ) i przeczą zarzutom o większym odsetku nieistotnych klinicznie nowotworów, które miałyby być wykrywane u chorych leczonych finasterydem.

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3. Oszacowanie częstości występowania raka stercza typu high-grade z wykorzystaniem = danych uzyskanych po wykonaniu pięciuset prostatektomii = radykalnych u uczestników = = badania.
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Wyniki
nNa podstawie 500 prostatektomii wykonano analizę regresji logistycznej 2017 badanych z dodatnią biopsją:
<= span style=3D'font-size:75%;text-shadow:auto;visibility:hidden'>n<= span style=3D'font-size:75%;text-shadow:auto;display:none'> <= /div>
nPrzy założeniu, że prostatektomię wykonano by u wszystkich z dodatnią biopsją wykryt= oby <= b>658 przypadków raka typu high= -grade (Gleason >7)w grupie z p= lacebo (8,2%) i t= ylko <= b>478 przypadków tego typu raka w grupie stosujących finasteryd (6%) a także <= b>27%; (p<0,02) redukcję ryzyk= a w grupie finasterydu.
nFinasteryd redukuje także ry= zyko wystąpienia raka o niższym stopniu zaawansowania (Gleason ≤6) – o <= b>34%; (p≤0,0001)
<= span style=3D'font-size:75%;text-shadow:auto;visibility:hidden'>n<= span style=3D'font-size:75%;text-shadow:auto;display:none'> <= /div>
<= span style=3D'font-size:75%;text-shadow:auto;visibility:hidden'>n<= span style=3D'font-size:75%;text-shadow:auto;mso-special-format:lastCR;display:= none'>
Celem = drugiej analizy było oszacowanie częstości występowania raka = typu high-grade przy założeniu, że wszyscy chorzy, u któ= rych w czasie biopsji wykryto raka stercza, zostaliby poddani operacji wycięcia gruczołu krokowego.
wyst&#= 281;powanie raka typu high-grade przy założeniu, że wszyscy chorzy, u których w czasie biopsji wykryto raka stercza, zostaliby poddani operacji wycięcia gruczołu krokowego.
Ocenio= no, że przy takim założeniu wykryto by 658 przypadków raka typu high-grade w grupie z placebo (8,2%) i tylko 478 przypadków tego t= ypu raka w grupie stosujących finasteryd (6%).
Oszaco= wano, że stosowanie finasterydu zmniejsza ryzyko wystąpienia raka w każd= ym zakresie skali Gleasona: w przypadku niższych stopni (Gleasona Ͱ= 4;6) – o 34%; (p≤0,0001) zaś dla stopni wyższych (Gleaso= na ≥7) – o 27 %; (p=3D0,02) [4,18].

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4. = Ocena wpływu czułości
biopsji stercza na częstość wykrywania
raka tego narządu.
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Większa czułość biopsji w grupie leczonych finasterydem [1,2].
<= span style=3D'font-size:88%;text-shadow:auto;visibility:hidden'>n<= span style=3D'font-size:88%;text-shadow:auto;display:none'> <= /div>
nzmniejszenie się objętości gruczołu krokowego
n - średnio o 24%
n
<= span style=3D'text-shadow:auto'>nzwięks= zenie gęstości pobieranych próbek
n - średnio o 27%<= /div>
= 1.Redman MW, Tangen CM, Goodman PJ et al: Finasteride does not increase the risk of high-grade prostate = cancer, a bias-adjusted modeling approach. Cancer Prev Res 2008, Online First 2008, 10.1158/1940-6207. = CAPR-08-0092.
2.D’Amico AV, Barry MJ: Prostate cancer prevent= ion and finasteride. J Urol 2006, 176, 5, 2010-2013.
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5. Czy wartość odcięcia dla PSA 4ng/ml jest wystarczająca?<= /span>
3D"stockmarket(AR=3D"
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PSA 4ng/ml czy mniej?
n = 3;
n48,4% mężczyzn, u których wykryto obecność raka, nie miało stwierdzanych = nieprawidłowości w bada= niu per rectum ani wartości PSA przekraczających 4 ng/ml.
nu chorych z PSA <1 ng/ ml aż u 15,6% pacjentów wykryto raka osiągającego ≥7 punktó= ;w = w skali Gleasona.
 Lucia M= S, Darke AK, Goodman PJ et al: Pathologic characteristics of cancers detected= in the prostate can= cer prevention trial, implications for prostate cancer detection and chemoprevention. Cancer Prev Res 200= 8, Online First 2008, 10.1158/1940-6207.CAPR-08-0078.
<= ![if !vml]>
PSA [ng/ml]
0-1
1,1-2,5
= 2,6-4,0
4,1-10
Nieistotne klinicznie
51,7%
33,7%
= 17,8%
11,7%
High grade
15,6%
37,9%
= 49,1%
52,4%
ocenio= ny w poszczególnych przedziałach PSA wynosił: 51,7% (PSA, 0-1 ng/ml), 33,7% (PSA, 1,1-2,5 ng/ml), 17,8% (PSA, 2,6- 4,0 ng/ml) or= az 11,7% (PSA, 4,1-10 ng/ml).
ryzyko wystąpienia raka o dużym stopniu złośliwości (high-grade) ocenione zostało w poszczególnych grupach odpowiednio na: 15,6%, 37,9%, 49,1% oraz 52,4% [1]

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Podsumowanie
nStosowanie finasterydu nie zwiększa ryzyka wystąpienia raka gruczołu krokowego o wysokim stopniu złośliwości.
nStosowanie finasterydu nie zwiększa ryzyka wystąpienia nowotworu nieistotnego klinicznie.
nStosowanie finasterydu zmniejsza ryzyko wystąpienia raka w każdym zakresie skali Gleasona.
n
n
n
n
n
n
------=_NextPart_01CA4838.DDEA2AC0 Content-Location: file:///C:/9D2D214F/Chemoprewencjarakagruczolukrokowego_pliki/slide0042.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="us-ascii" Chemoprewencja raka gruczołu krokowego
Podsumowanie
nStosowanie finasterydu powoduje znamienny spadek ryzyka wystąpienia raka gruczoł= ;u = krokowego niezależnie od czynników = ryzyka i wyjściowych wartości PSA.
nStosowanie finasterydu zwiększa czułość biopsji stercza.
<= span style=3D'text-shadow:auto'>nSugeruje si= ę obniżenie stężenia PSA do
n 2,5 ng/ml jako wartości progowej dla wykonania diagnostycznej biopsji stercza.
<= span style=3D'text-shadow:auto;visibility:hidden'>n
n
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Podsumowanie
nBadacze dokonujący powyż= ;szych ocen przekonują, że pacjenci powinni być = informowani o możliwości zmniejszenia ryzyka zachorowania o co najmniej 25% przy zastosowaniu finasterydu= w dziennej dawce 5 mg. Podkreślają, że lek ten wywiera inne, wcześn= iej dowiedzione, pozytywne działania na układ moczowy zmniejszając:
<= span style=3D'font-size:67%;text-shadow:auto'>Øliczbę parć naglących
<= span style=3D'font-size:67%;text-shadow:auto'>Øczęstość oddawania moczu
<= span style=3D'font-size:67%;text-shadow:auto'>Øobjętość zalegającego moczu
<= span style=3D'font-size:67%;text-shadow:auto'>Øobjawy zapalenia gruczołu krokowego.
nPamiętać jednak należy o objawach ubocznych, spośród których obserwowane były najczęściej:
<= span style=3D'font-size:67%;text-shadow:auto'>Øzaburzenia wzwodu
<= span style=3D'font-size:67%;text-shadow:auto'>Øobniżenie libido =
<= span style=3D'font-size:67%;text-shadow:auto'>Øzmniejszenie objętości ejakulatu
<= span style=3D'font-size:67%;text-shadow:auto'>Øginekomastia
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Dziękuję za uwagę
3D"prostate
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Skupiaj= 61;c się głównie na przeprowadzonych ostatnio badaniach z blokerami 5 alfa reduktazy.
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Na szczęście nie jesteśmy bezsilni. Możemy przeprowadzi&#= 263; wczesną diagnostykęktóra obejmuje. 
Rozpocz= 81;te w latach dziwędziesiątych badania obejmujące prawie 200 ty= 47; mężczyzn potwierdzają spadek umieralności rzędu 20% u osób objętych screeningiem lecz potwierdzają obawę przed rozpoznawaniem i leczeniem pacjentów z nieistotnym klinicznie rakiem stercza tzw „overtreatment”.&= nbsp; Programy badawcze mające ustalić czy testy screeningowe prowadzą do zmniejszenia śmiertelności w przebiegu raka stercza.
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Ale co mo&= #380;emy zrobić oprócz screeningu.
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1.Niekt&oa= cute;rzy autorzy dowodzą skuteczności stosowania genisteiny, głównego fitoestrogenu sojowego, który swoje prewencyjne działanie wywierać ma poprzez hamowanie kinazy tyrozynowej i wywieranie efektu antyestrogenowego. Skuteczność tego rodzaju preparatów testowana jest dotychczas jedynie na zwierzętach [4].
2.Uważ= ;a się, że zwiększona konsumpcja nasyconych kwasów tłuszczowych przy zmniejszonym spożyciu błonnika może powodować długotrwałą stymulację organizmu androgenami i przyczynić się do zwiększenia ryzyka wyst= 1;pienia raka stercza
3.Badanie = SELECT (USA, Puerto Rico, Kanada) przeprowadzone od 2001-2008 roku wykazało że przyjmowanie 200mcg selenu i 400 IUs witaminy E nie działaj&#= 261; prewencyjnie w stosunku do raka stercza. Co wiecej wstępne analizy wy= ników dowodzą że witamina E nieznacznie zwiększa ryzyko raka pros= taty a selen w dawce 200mcg może zwiększać ryzyko cukrzycy typu drugiego. 
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Inhibitory 5α-reduktazy powodują obniżenie stężenia dihydrotestosteronu i nieco podnoszą poziom testosteronu w obręb= ie gruczołu krokowego [3,6]. Pierwszy z nich, finasteryd, powoduje selektywne hamowanie 5α-reduktazy typu 2, natomiast dutasteryd jest inhibitorem obu typów 1 i 2 tego enzymu. Oba leki zarejestrowane zostały w leczeniu łagodnego rozrostu stercza, z oboma też wiąże się nadzieje w odniesieniu do chemoprewencji raka gruczołu krokowego [6,7,8]. Dutasteryd pozostaje przedmiotem bada = 4; klinicznych, spośród których najlepiej znanym jest bada= nie REDUCE (Reduction by Dutasteride of Prostate Cancer Events), którego wyniki poznamy w następnych latach [9,10].
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Było = to pierwsze prospektywne, randomizowane, badanie chemoprewencji raka prostaty. Badanie przerwanow marcu 2003 roku, dalsze dane spływały do czer= wca ostatecznie w grupie leczonej finasterydem znalazło się 4251 m&#= 281;żczyzn a w grupie placebo 4576. 
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Przeprowad= zono 3 analizy statystyczne:
Oszacowanie częstości występowania raka stercza u uczestników badania przy założeniu, że każdy z nich spełni= 22; kryteria końcowe protokołu
Oszacowanie częstości występowania raka stercza typu high-grade z wykor= zystaniem danych uzyskanych po wykonaniu pięciuset prostatektomii radykalnych u uczestników badania
Dokonanie = oceny wpływu czułości biopsji stercza na częstość wykrywania raka tego narządu [4,18].
Oszacowanie częstości występowania raka stercza typu high-grade na pods= tawie prostatektomii
Ocena wp&#= 322;ywu czułości biopsji stercza na częstość wykrywania r= aka tego narządu [4,18].
4.Redman M= W, Tangen CM, Goodman PJ et al: Finasteride does not increase the risk of high-grade prostate cancer, a bias-adjusted modeling approach. Cancer Prev= Res 2008, Online First 2008, 10.1158/1940-6207. CAPR-08-0092.
18.Logothe= tis CJ, Schellhammer PF: High-grade prostate cancer and the Prostate Cancer Preven= tion Trial. Cancer Prev Res 2008, Online First 2008, 10.1158/1940-6207.CAPR-08-= 0085.
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W celu wyjaśnienia tych zagadnień dokonano w ostatnim roku ponownej oce= ny histopatologicznej preparatów biopsyjnych uzyskanych od uczestników badania. Oceniono również i porównan= o z preparatami biopsyjnymi materiały tkankowe uzyskane z prostatektomii radykalnych, wykonanych u tych uczestników badania, u których wykryto nowotwór gruczołu krokowego.
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Stosuj= 1;c kryteria pierwszej definicji oceniono, że 27,7% preparatów uzy= skanych od mężczyzn zażywających placebo oraz 19,9% preparatów z grupy przyjmującej finasteryd należy zakwalifikować do raków nieistotnych klinicznie.
Według kryteriów drugiej definicji nieistotnymi klinicznie okazało się 30,5% raków wykrytych u mężczyzn, którym podawano placebo, i 21,4% raków stwierdzonych u chorych leczonych finasterydem [17,18].
Dane te s&= #261; porównywalne do większości serii uzyskanych po prostatekt= omii (u chorych niebędących uczestnikami badania PCPT) i przeczą zarzutom o większym odsetku nieistotnych klinicznie nowotworów, które miałyby być wykrywane u chorych leczonych finasterydem.
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Celem drug= iej analizy było oszacowanie częstości występowania raka t= ypu high-grade przy założeniu, że wszyscy chorzy, u których w czasie biopsji wykryto raka stercza, zostaliby poddani operacji wycięcia gruczołu krokowego.
wystę= powanie raka typu high-grade przy założeniu, że wszyscy chorzy, u k= tórych w czasie biopsji wykryto raka stercza, zostaliby poddani operacji wyci= 1;cia gruczołu krokowego.
Oceniono, = że przy takim założeniu wykryto by 658 przypadków raka typu high-grade w grupie z placebo (8,2%) i tylko 478 przypadków tego ty= pu raka w grupie stosujących finasteryd (6%).
Oszacowano, że stosowanie finasterydu zmniejsza ryzyko wystąpienia raka w ka= żdym zakresie skali Gleasona: w przypadku niższych stopni (Gleasona ≤= ;6) – o 34%; (p≤0,0001) zaś dla stopni wyższych (Gleasona ≥= ;7) – o 27 %; (p=3D0,02) [4,18].
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oceniony w poszczególnych przedziałach PSA wynosił: 51,7% (PSA, 0-1 = ng/ml), 33,7% (PSA, 1,1-2,5 ng/ml), 17,8% (PSA, 2,6- 4,0 ng/ml) oraz 11,7% (PSA, 4,1-10 ng/ml).
ryzyko wystąpienia raka o dużym stopniu złośliwości (high-grade) ocenione zostało w poszczególnych grupach odpowie= dnio na: 15,6%, 37,9%, 49,1%= oraz 52,4% [1]
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FULLSCR_HREF = : FULLSCR_HREF+"#"+GetHrefObj(gCurSld).mSldHref; if(PPTNav.event.ctrlKey) { var w =3D (window.screen.availWidth * 1.0) / 2.0 var h =3D w * (PPTSld.g_origH * 1.0) / PPTSld.g_origW win =3D window.open( MHTMLPrefix+href,null,"toolbar=3D0,resizable=3D1,top= =3D0,left=3D0," + "width=3D"+ w + ",height=3D" + h ); if( win.document.body && PPTSld.g_animUseRuntime ) win.document.body.PPTSldFrameset=3Dwindow; } else { win =3D window.open( MHTMLPrefix+href,null,"fullscreen=3Dyes" ); if( win.document.body && PPTSld.g_animUseRuntime ) win.document.body.PPTSldFrameset=3Dwindow; } } function ToggleVNarration() { rObj=3DPPTSld.document.all("NSPlay") if( rObj && !PPTSld.g_animUseRuntime ) { if( (rObj.playState =3D=3D 1)||(rObj.playState =3D=3D 0) ) rObj.Play() else if( rObj.playState =3D=3D 2 ) rObj.Pause() else return; } else if( PPTSld.g_animUseRuntime ) { narObj =3D PPTSld.document.all("narrationID") if( narObj ) narObj.togglePause() } } function GetCurSldNum() { obj=3DGetHrefObj(gCurSld) if( obj.mOrigVis =3D=3D 1 ) return obj.mSldIdx else return gCurSld } function GetNumSlds() { if( GetHrefObj(gCurSld).mOrigVis =3D=3D 1 ) return GetSldList().mNumVisSlds; else return GetSldList().mList.length } function GetSldNum( href ) { for(ii=3D0; ii 1 ) PopSldList(); else if( !IsFramesMode() ) { if( gLoopCont ) GoToFirst() else EndShow() } } function GoToPrevSld() { ii=3DgCurSld-1 if( ii > 0 ) { obj=3DGetHrefObj(ii) while ( obj && ( obj.mVis =3D=3D 0 ) && ( ii>0 ) ) obj=3DGetHrefObj(--ii) if( ii =3D=3D 0 ) ii=3D1 GoToSldNum(ii) } } function GoToFirst(){ GoToSld( GetHrefObj(1).mSldHref ) } function GoToLast() { ii=3DGetSldList().mList.length if( ii !=3D gCurSld ) GoToSld( GetHrefObj(ii).mSldHref ) } function GoToSldNum( num ) { if( PPTSld.event ) PPTSld.event.cancelBubble=3Dtrue obj =3D GetHrefObj( num ) obj.mVis=3D1 gPrevSld=3DgCurSld gCurSld =3D num; PPTSld.location.replace(MHTMLPrefix+obj.mSldHref) if( IsFramesMode() ) { UpdNavPane(); UpdOtlPane(); UpdNtsPane() } } function GoToSld( href ) { if( PPTSld.event ) PPTSld.event.cancelBubble=3Dtrue GetHrefObj( GetSldNum(href) ).mVis=3D1 PPTSld.location.replace(MHTMLPrefix+href) } function SldUpdated( id ) { if( id =3D=3D GetHrefObj(gCurSld).mSldHref ) return gPrevSld=3DgCurSld gCurSld=3DGetSldNum(id) if( IsFramesMode() ) { UpdNavPane(); UpdOtlPane(); UpdNtsPane() } } function PrevSldViewed(){ GoToSld( GetHrefObj(gPrevSld).mSldHref ) } function HasPrevSld() { return ( gIsEndShow || ( gCurSld !=3D 1 && GetHrefO= bj( gCurSld-1 ).mVis =3D=3D 1 )||( GetCurSldNum() > 1 ) ) } function HasNextSld() { return (GetCurSldNum() !=3D GetNumSlds()) } function CloseWindow() { if( HideMenu() ) return; var event =3D PPTSld.event; if( !IsFramesMode() && event && (event.keyCode=3D=3D27 || event.keyCode=3D= =3D32 || event.type=3D=3D"click" ) ) window.close( self ); CatchNumKeys( self, event ); } function Unload() { gIsEndShow=3D0; } function SetupEndShow() { gIsEndShow=3D1; PPTSld.document.body.scroll=3D"no"; PPTSld.document.onkeypress=3DCloseWindow; PPTSld.document.onclick=3DCloseWindow; PPTSld.document.oncontextmenu=3D_CM; } function EndShow() { if( IsFramesMode() ) return if( PPTSld.event ) PPTSld.event.cancelBubble=3Dtrue doc=3DPPTSld.document var dir =3D doc.body.dir if( dir !=3D "rtl" ) dir =3D "ltr"; doc.open() doc.writeln('


' + ENDSHOW_MESG + '

') doc.close() } function SetSldVisited(){ GetSldList().mList[gCurSld-1].mVisited=3Dtrue } function IsSldVisited(){ return GetSldList().mList[gCurSld-1].mVisited } function hrefList( sldHref, visible, advDelay, advClk ) { this.mSldHref=3D this.mNtsHref =3D sldHref this.mOrigVis=3D this.mVis =3D visible this.mVisited=3D false this.mAdvDelay=3D advDelay this.mAdvOnClk=3D advClk } function SldList(arr,curSld,fEnd) { this.mCurSld =3D curSld; this.mList =3D new Array(); var idx =3D 1; for(ii=3D0;ii 0) { PushSldList(sldList,fEnd); gCurSld =3D 1; } else if( PPTSld.event ) PPTSld.event.cancelBubble=3Dtrue } function PushSldList(arr,fEnd) { var ii =3D gSldStack.length; gSldStack[ii] =3D new SldList(arr,gCurSld,fEnd); GoToSld( gSldStack[ii].mList[0].mSldHref ); } function PopSldList() { if (gSldStack[gSldStack.length-1].fEndShow) EndShow() else { gCurSld =3D gSldStack[gSldStack.length-1].mCurSld; gSldStack[gSldStack.length-1] =3D null; gSldStack.length--; var sldList =3D gSldStack[gSldStack.length-1]; GoToSld( sldList.mList[gCurSld - 1].mSldHref ); } } var custShowList=3Dnew Array(); function ImgBtn( oId,bId,w,action ) { var t=3Dthis t.Perform =3D _IBP t.SetActive =3D _IBSetA t.SetInactive=3D _IBSetI t.SetPressed =3D _IBSetP t.SetDisabled=3D _IBSetD t.Enabled =3D _IBSetE t.ChangeIcon =3D null t.UserAction =3D action t.ChgState =3D _IBUI t.mObjId =3D oId t.mBorderId=3D bId t.mWidth =3D w t.mIsOn =3D t.mCurState =3D 0 } function _IBSetA() { if( this.mIsOn ) { obj=3Dthis.ChgState( gHiliteClr,gShadowClr,2 ) obj.style.posTop=3D0 } } function _IBSetI() { if( this.mIsOn ) { obj=3Dthis.ChgState( gFaceClr,gFaceClr,1 ) obj.style.posTop=3D0 } } function _IBSetP() { if( this.mIsOn ) { obj=3Dthis.ChgState( gShadowClr,gHiliteClr,2 ) obj.style.posLeft+=3D1; obj.style.posTop+=3D1 } } function _IBSetD() { obj=3Dthis.ChgState( gFaceClr,gFaceClr,0 ) obj.style.posTop=3D0 } function _IBSetE( state ) { var t=3Dthis GetObj( t.mBorderId ).style.visibility=3D"visible" if( state !=3D t.mIsOn ) { t.mIsOn=3Dstate if( state ) t.SetInactive() else t.SetDisabled() } } function _IBP() { var t=3Dthis if( t.mIsOn ) { if( t.UserAction !=3D null ) t.UserAction() if( t.ChangeIcon ) { obj=3DGetObj(t.mObjId) if( t.ChangeIcon() ) obj.style.posLeft=3Dobj.style.posLeft+(t.mCurState-4)*t.mWidth else obj.style.posLeft=3Dobj.style.posLeft+(t.mCurState-0)*t.mWidth } t.SetActive() } } function _IBUI( clr1,clr2,nextState ) { var t=3Dthis SetBorder( GetObj( t.mBorderId ),clr1,clr2 ) obj=3DGetObj( t.mObjId ) obj.style.posLeft=3Dobj.style.posLeft+(t.mCurState-nextState)*t.mWidth-obj= .style.posTop t.mCurState=3DnextState return obj } function TxtBtn( oId,oeId,action,chkState ) { var t=3Dthis t.Perform =3D _TBP t.SetActive =3D _TBSetA t.SetInactive=3D _TBSetI t.SetPressed =3D _TBSetP t.SetDisabled=3D _TBSetD t.SetEnabled =3D _TBSetE t.GetState =3D chkState t.UserAction =3D action t.ChgState =3D _TBUI t.mObjId =3D oId t.m_elementsId=3D oeId t.mIsOn =3D 1 } function _TBSetA() { var t=3Dthis if( t.mIsOn && !t.GetState() ) t.ChgState( gHiliteClr,gShadowClr,0,0 ) } function _TBSetI() { var t=3Dthis if( t.mIsOn && !t.GetState() ) t.ChgState( gFaceClr,gFaceClr,0,0 ) } function _TBSetP() { if( this.mIsOn ) this.ChgState( gShadowClr,gHiliteClr,1,1 ) } function _TBSetD() { this.ChgState( gFaceClr,gFaceClr,0,0 ) this.mIsOn =3D 0 } function _TBSetE() { var t=3Dthis if( !t.GetState() ) t.ChgState( gFaceClr,gFaceClr,0,0 ) else t.ChgState( gShadowClr,gHiliteClr,1,1 ) t.mIsOn =3D 1 } function _TBP() { var t=3Dthis if( t.mIsOn ) { if( t.UserAction !=3D null ) t.UserAction() if( !t.GetState ) return if( t.GetState() ) t.SetPressed() else t.SetActive() } } function _TBUI( clr1,clr2,lOffset,tOffset ) { SetBorder( GetObj( this.mObjId ),clr1,clr2 ) Offset( GetObj( this.m_elementsId ),lOffset,tOffset ) } function Offset( obj, top, left ){ obj.style.top=3Dtop; obj.style.left=3Dle= ft } function SetBorder( obj, upperLeft, lowerRight ) { s=3Dobj.style; s.borderStyle =3D "solid" s.borderWidth =3D 1 s.borderLeftColor =3D s.borderTopColor =3D upperLeft s.borderBottomColor=3D s.borderRightColor =3D lowerRight } function GetBtnObj(){ return gBtnArr[window.event.srcElement.id] } function BtnOnOver(){ b=3DGetBtnObj(); if( b !=3D null ) b.SetActive() } function BtnOnDown(){ b=3DGetBtnObj(); if( b !=3D null ) b.SetPressed() } function BtnOnOut(){ b=3DGetBtnObj(); if( b !=3D null ) b.SetInactive() } function BtnOnUp() { b=3DGetBtnObj() if( b !=3D null ) b.Perform() else Upd() } function GetNtsState(){ return parent.gNtsOpen } function GetOtlState(){ return parent.gOtlOpen } function GetOtlTxtState(){ return parent.gOtlTxtExp } function NtsBtnSetFlag( fVal ) { s=3Ddocument.all.item( this.m_flagId ).style s.display=3D"none" if( fVal ) s.display=3D"" else s.display=3D"none" } function _BSetA_Border(){ b =3D gBtnArr[this.mObjId]; if( b !=3D null ) b.S= etActive() } function _BSetI_Border(){ b =3D gBtnArr[this.mObjId]; if( b !=3D null ) b.S= etInactive() } function _BSetP_Border(){ b =3D gBtnArr[this.mObjId]; if( b !=3D null ) b.S= etPressed() } function _BSetA_BorderImg() { b =3D gBtnArr[this.mBorderId] if( b !=3D null && this.mIsOn && !b.GetState() ) { obj=3Dthis.ChgState( gHiliteClr,gShadowClr,2 ) obj.style.posTop=3D0 } } function _BSetI_BorderImg() { b =3D gBtnArr[this.mBorderId] if( b !=3D null && this.mIsOn && !b.GetState() ) { obj=3Dthis.ChgState( gFaceClr,gFaceClr,1 ) obj.style.posTop=3D0 } } var gHiliteClr=3D"THREEDHIGHLIGHT",gShadowClr=3D"THREEDSHADOW",gFaceClr=3D"= THREEDFACE" var gBtnArr =3D new Array() gBtnArr["nb_otl"] =3D new TxtBtn( "nb_otl","nb_otlElem",parent.ToggleOtlPan= e,GetOtlState ) gBtnArr["nb_otlElem"] =3D new TxtBtn( "nb_otl","nb_otlElem",parent.ToggleOt= lPane,GetOtlState ) gBtnArr["nb_nts"] =3D new ImgBtn( "nb_nts","nb_ntsBorder",10,parent.ToggleN= tsPane ) gBtnArr["nb_nts"].SetActive =3D _BSetA_BorderImg; gBtnArr["nb_nts"].SetInactive =3D _BSetI_BorderImg; gBtnArr["nb_ntsBorder"] =3D new TxtBtn( "nb_ntsBorder","nb_ntsElem",parent.= ToggleNtsPane,GetNtsState ) gBtnArr["nb_ntsElem"] =3D new TxtBtn( "nb_ntsBorder","nb_ntsElem",parent.To= ggleNtsPane,GetNtsState ) gBtnArr["nb_prevBorder"] =3D gBtnArr["nb_prev"]=3D new ImgBtn( "nb_prev","n= b_prevBorder",30,parent.GoToPrevSld ) gBtnArr["nb_nextBorder"] =3D gBtnArr["nb_next"]=3D new ImgBtn( "nb_next","n= b_nextBorder",30,parent.GoToNextSld ) gBtnArr["nb_sldshw"]=3D new ImgBtn( "nb_sldshw","nb_sldshwBorder",18,parent= .FullScreen ) gBtnArr["nb_sldshwBorder"] =3D new TxtBtn( "nb_sldshw","nb_sldshwBorder",pa= rent.FullScreen,null ) gBtnArr["nb_sldshwBorder"].SetActive =3D _BSetA_Border; gBtnArr["nb_sldshwBorder"].SetInactive =3D _BSetI_Border; gBtnArr["nb_sldshwText"] =3D new TxtBtn( "nb_sldshw","nb_sldshwText",parent= .FullScreen,null ) gBtnArr["nb_sldshwText"].SetActive =3D _BSetA_Border; gBtnArr["nb_sldshwText"].SetInactive =3D _BSetI_Border; gBtnArr["nb_voice"] =3D gBtnArr["nb_voiceBorder"] =3D new ImgBtn( "nb_voice= ","nb_voiceBorder",18,parent.ToggleVNarration ) gBtnArr["nb_otlTxtBorder"] =3D gBtnArr["nb_otlTxt"]=3D new ImgBtn( "nb_otlT= xt","nb_otlTxtBorder",23,parent.ToggleOtlText ) gBtnArr["nb_ntsBorder"].m_flagId=3D "nb_nts" gBtnArr["nb_ntsBorder"].SetFlag =3D NtsBtnSetFlag gBtnArr["nb_otlTxt"].ChangeIcon=3D GetOtlTxtState var sNext=3D"Dalej",sPrev=3D"Poprzedni",sEnd=3D"Zakończ pokaz",sFont= =3D"Arial",sArrow=3D"Strzałka",sFreeform=3D"Dowolny kształt",sRec= t=3D"Prostokąt",sOval=3D"Owal" function ShowMenu() { BuildMenu(); var doc=3DPPTSld.document.body,x=3DPPTSld.event.clientX+doc.scrollLeft,y= =3DPPTSld.event.clientY+doc.scrollTop m =3D PPTSld.document.all.item("ctxtmenu") m.style.pixelLeft=3Dx if( (x+m.scrollWidth > doc.clientWidth)&&(x-m.scrollWidth > 0) ) m.style.pixelLeft=3Dx-m.scrollWidth m.style.pixelTop=3Dy if( (y+m.scrollHeight > doc.clientHeight)&&(y-m.scrollHeight > 0) ) m.style.pixelTop=3Dy-m.scrollHeight m.style.display=3D"" } function _CM() { if( !parent.IsFullScrMode() ) return; 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