Martin Adamson AS Ida-Tallinna Keskhaigla Üld- ja onkoloogilise kirurgia keskus

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1 Martin Adamson AS Ida-Tallinna Keskhaigla Üld- ja onkoloogilise kirurgia keskus

2 Peritoneaalsed metastaasid

3 Peritoneaalsed siirded

4 Ussripikuvähi suurrasviku metastaasid

5 Definitsioon Peritoneumi ehk kõhukelme haaratust pahaloomulise kasvaja siiretest nimetatakse peritoneaalseks metastaseerumiseks. Peritoneaalne metastaseerumine = peritoneaalkülv = peritoneaalne kartsinomatoos haiguse terminaalstaadium parim toetav ravi

6 Hematogeenne metastaseerumine Lümfogeenne metastaseerumine Peritoneaalne metastaseerumine Kombineeritud metastaseerumine

7 Peritoneum

8 Sagedamini metastaseeruvad peritoneumile seedetraktist lähtuvad kasvajad Käär- ja pärasoolevähk Ussripikuvähk Maovähk Peritoneaalne metastaseerumine on iseloomulik ka munasarjavähile, mesotelioomile, peritoneumi pseudomüksoomile ning sarkoomidele (P. Sugarbaker 1998).

9 Parim toetav ravi maovähk/kolorektaalvähk B. Sadeghi, et al. Results of the EVOCAPE 1 Multicentric Prospective Study. Cancer 2000;88:358 63

10 Palliatiivne ravi (maovähk) Palliatiivse raviga on peritoneaalsele metastaseerunud maovähihaigete keskmiseks elulemuseks 4,0-6,5 kuud (B. Sadeghi jt 2000; P.C. Thuss-Patience, 2011) % maovähi surmajuhtudest on põhjustatud peritoneaalsest kartsinomatoosist (Y. Yonemura, 2009; F. Coccolini, 2013) Peritoneaalsete siiretega maovähi tsüstoreduktiivse operatsiooniga (kombineeritud intraperitoneaalse hüpertermilise keemiaraviga) on patsientide 5 aasta elulemuseks % (O. Glehen, 2010)

11 Palliatiivne ravi (kolorektaalvähk) Palliatiivse raviga on peritoneaalsele metastaseerunud kolorektaalvähi haigete keskmine elulemus 6,9 kuud (B. Sadeghi, 2000); väikestes uuringutes kaasaegse keemiaraviga ka 12 kuud ning bioloogilise ravi lisamisega kuni 22,4 kuud (Y.L. Klaver, 2013) Tsütoreduktiivne kirurgia ja intraperitoneaalse hüpertermilise keemiaravi kombinatsiooniga on patsientide 5 aasta elulemus % (D. Elias, 2010).

12 Kombineeritud ravi Tsütoreduktsioon nähtava kasvajakoe maksimaalne kirurgiline eemaldamine HIPEC hüpertermiline intraperitoneaalne keemiaravi Paikne kasvajavastane ravim Tsütoreduktiivne kirurgia Temperatuur Kasvaja

13 Tsütoreduktsioon/HIPEC karakteristikud PCI - peritoneaalse kartsinomatoosi indeks (Sugarbaker s Peritoneal Carcinomatosis Index). Maksimaalne skooring = 39 Mida väiksem on PCI, seda tulemuslikum on kombineeritud ravi

14 Tsütoreduktsioon/HIPEC karakteristikud Kirurgilise tsütoreduktsiooni kvaliteeti määratakse CC - skooringuga (Completeness of Cytoreduction Score, astmed: 0 3) Võtab aluseks jääk-kasvaja üksikkolde suuruse On näidatud seost peritoneaalse leviku ulatuse (PCI), tsütoreduktsiooni kvaliteedi (CC) ja elulemuse vahel (P. Jacquet jt 1996; J. Esquivel, 2007; B. Moran, 2008). CC-skooring on kõige olulisem prognostiline näitaja

15 Tsütoreduktsiooni kvaliteet CC-0 nähtav jääk-kasvaja puudub CC-1 jääk-kasvaja sõlmed < 2.5 mm (= ravimi penetratsioon-võime piir) CC-2 jääk-kasvaja sõlmed 2.5 mm cm CC-3 jääk-kasvaja sõlmed > 2.5 cm

16

17 Kompuutertomograafia KT on pahaloomulise kasvaja staadiumi (TNM) määramise nurgakivi KT-l jääb % peritoneaalsetest siiretest ja maksametastaasidest märkamata (Ziegler jt 1993; Oñate- Ocaña jt 2001; Nieveen van Dijkum jt 1997). Mitteinvasiivsete uuringumeetodite (UH, EUH, KT, FDG- PET) diagnostiline väärtus ei ole peritoneaalse kartsinomatoosi tuvastamiseks küllaldane (Z. Wang, 2011)

18 KT tundlikkus peritoneaalsete metastaaside diagnoosimisel Archer AG, Sugarbaker PH and Jelinek JS. Radiology of peritoneal carcinomatosis. In Sugarbaker PH (ed); Peritoneal Carcinomatosis, Principles of Management. Kluwer Academic Publishers, Boston, pp

19 Diagnostiline laparoskoopia Mini-invasiivne meetod Peritoneumi seisundi vahetu visuaalne hindamine. Võimaldab tuvastada kliiniliselt mitte avalduva väheulatusliku peritoneaalkülvi. Laparoskoopia ja KT-uuringu alusel määratud vähkkasvaja staadium lahknes 52 % patsientidest (V.G. Shelat, 2012) 2013 ITK uurija algatatud uuring: laparoskoopia KTnegatiivsetel järelkontrolli patsientidel.

20 Maovähi peritoneaalse metastaseerumise T3 - T4 protsess > 6 cm kasvaja riskitegurid Madalat diferentseerunud kasvaja Difuusset tüüpi kasvaja Operatioonil on tuvastatud kasvajarakud peritoneaallavaaži vedelikus

21 T3 maovähk

22 Kolorektaalvähi peritoneaalse metastaseerumise riskitegurid Obstruktsiooni põhjustanud kolorektaalvähk Verejooksu põhjustanud kolorektaalvähk Perforeerunud kolorektaalvähk T4 protsess Munasarja metastaas

23 66-aastane naispatsient Kaasuvalt hüpertooniatõbi Varasemalt opereerimata Haigusjuht algusest kõhukinnisuse episoodid, subjektiivselt vähene nõrkus

24 Koloskoopial tegemist sigmakäärsoole kasvajaga Histoloogia tubulaarne adenokartsinoom G2 KT uuringul maksas 2 metastaasiks sobivat kollet, paremas munasarjas tsüst, mis tõenäoliselt samuti metastaas onkoloogilise konsiiliumi otsusega alustatud neoadjuvantse keemiaraviga

25 haigestub soolesulguse nähtududega ja pöördub EMO-sse erakorraliselt opereeritud tehtud Hartmanni tüüpi operatsioon (algkolde eemaldamine ja kolostoomi rajamine). Lisaks mõlemapoolne salpingo-ooforektoomia koos emaka supravaginaalse amputatsiooniga sünkroonsete munasarja-metastaaside tõttu

26 Histoloogia: tubulaarne adenokartsinoom, G2 pt3n2bm1 (HEP, OTH), IV st. Edasi onkoloogilise konsiiliumi otsusega jätkatakse keemiaravi

27 op.: kolostoomi likvideerimine ja maksa metastaasi eemaldamine Selle järgselt patsient keeldub keemiaravist KT uuringul näha väikesed metastaasikahtlased kolded kopsus ja kolle maksas. Onkoloogilise konsiiliumi otsusega näidustatud palliatiivne keemiaravi 4 kuuri

28 5 kuu möödudes teostatud KT uuringul kopsumetastaasid ei ilmestu Onkoloogilise konsiiliumi otsusega näidustatud maksa metastaasi kirurgiline ravi op.: proovilaparotoomia: lisaks maksametastaasile näha peritoneaalsed metastaasid, mis KT uuringul ei ilmestunud

29 op.- tsütoreduktsioon + HIPEC, maksa resektsioon metastaasi tõttu Sellele järgnevalt 5 kuuri palliatiivset keemiaravi

30 KT uuringul kasvaja retsidiivile viitavat ei ilmestu KT uuringul näha uued väikesed metastaasikahtlased kolded kopsus, kõhukoopas astsiit Onkoloogilise konsiiliumi otsusega näidustatud palliatiivne keemiaravi KT uuringul kopsu kolded dünaamikata, kõhukoopas vaba vedelikku ei esine (positiivne dünaamika)

31 Järeldused Sünkroonsete munasarja metastaaside olemasolu on peritoneaalse metastaseerumise riskitegur Erinevalt maksa- ja kopsumetastaasidest, peritoneaalsed metastaasid KT uuringul ei ilmestunud Agressiivne kombineeritud ravi parandab elulemust

32 Kokkuvõte Peritoneaalne metastaseerumine terminaalstaadium Peritoneaalne metastaseerumine on prognoositav Varajane avastamine parandab elulemust Mitte-invasiivsete uuringumeetodite diagnostiline väärtus ei ole peritoneaalse kartsinomatoosi tuvastamiseks küllaldane Kuldseks standardiks võiks olla diagnostiline laparoskoopia

33 Tänan!

34 Thermal enhancement of cytotoxicity increased drug uptake in malignant cells which is due to increased membrane permeability and improved membrane transport heat may alter cellular metabolism and change drug pharmacokinetics and excretion, both of which can increase the cytotoxicity of certain chemotherapeutic agents[22 increased drug penetration in tissue Temperaturedependent increases in drug action inhibition of repair mechanisms González-Moreno S et al. HIPEC: Rationale and Technique. World J Gastrointest Oncol 2010 February 15; 2(2): 68-75

35 IPKT mõjutavad tegurid Vasoaktiivsed jt. ained Temperatuur Kasvaja tundlikkus ravimile, jääk-kasvaja suurus Ravimi omadused, annus, manustamise aeg Ravimikandja omadused, kogus Ravimi jaotuvus kõhuõõnes TRO ja IPKT omavaheline ajastus

36 Peritoneaalse metastaseerumise diagnostika Kasvaja leviku ulatust ei saa algkolde iseloomu järgi hinnata Radioloogiliste uuringute tundlikkus sõltub kasvajakolde suurusest Kaudsed radioloogilised tunnused Diagnostiline laparoskoopia

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