14 ÝÍÄÎÊÐÈÍÍÀß ÕÈÐÓÐÃÈß ¹ 1(4) 2009 ÀÄÐÅÍÎÊÎÐÒÈÊÀËÜÍÛÉ ÐÀÊ. Áåëüöåâè÷ Ä.Ã., Êóçíåöîâ Í.Ñ., Âàíóøêî Â.Ý. Ýíäîêðèíîëîãè÷åñêèé íàó÷íûé öåíòð Ðîñìåäòåõíîëîãèé. Àäðåíîêîðòèêàëüíûé ðàê (ÀÊÐ) – ðåäêîå çàáîëåâàíèå, äî íàñòîÿùåãî ìîìåíòà õàðàêòåðèçóþùååñÿ ïîçäíèì ñðîêîì âûÿâëåíèÿ è íåáëàãîïðèÿòíûì ëå÷åáíûì ïðîãíîçîì. Ýïèäåìèîëîãèÿ Åæåãîäíîå âûÿâëåíèå ÀÊÐ ñîñòàâëÿåò 0.5-2 ñëó÷àåâ íà ìèëëèîí íàñåëåíèÿ, ÷òî ñîñòàâëÿåò 0.04-0.2% â ñòðóêòóðå îíêîëîãè÷åñêîé ñìåðòíîñòè (Crucitti F. è ñîàâò.1996). Ýïèäåìèîëîãè÷åñêèì èñêëþ÷åíèåì ÿâëÿåòñÿ Þæíàÿ Áðàçèëèÿ, ãäå âûÿâëÿåìîñòü ïðèáëèçèòåëüíî â 10 ðàç âûøå, ÷åì â ëþáîì äðóãîì ìåñòå ìèðà. Âûÿâëåíèå ÀÊÐ èìååò 2 ñòàòèñòè÷åñêèõ âîçðàñòíûõ ïèêà: íà ïÿòîé äåêàäå æèçíè è ó äåòåé îò 5 äî 10 ëåò. ÝÍÄÎÊÐÈÍÍÀß ÕÈÐÓÐÃÈß ÐÅÄÀÊÖÈÎÍÍÛÅ ÊËÈÍÈ×ÅÑÊÀß ËÅÊÖÈß ÌÀÒÅÐÈÀËÛ Ýòèîëîãèÿ Îïèñàíû äâà ñèíäðîìà, èçâåñòíûì êîìïîíåíòîì êîòîðûõ ÿâëÿåòñÿ ÀÊÐ.  ðàìêàõ îáîèõ ñèíäðîìîâ îòìå÷àåòñÿ íèçêàÿ ôåíîòèïè÷åñêàÿ ïåíåòðàíòíîñòü, â ñâÿçè ñ ÷åì ïðîñëåäèòü íàñëåäñòâåííûé õàðàêòåð àíàìíåñòè÷åñêè äîñòàòî÷íî ñëîæíî. Ñèíäðîì ËèÔðàóìåíè (Li-Fraumeni) ñâÿçàí ñ íåàêòèâíîé ìóòàöèåé â TP53-ãåíå-ñóïðåññîðå îïóõîëåâîãî ðîñòà, õàðàêòåðèçóåòñÿ ñàðêîìîé ìÿãêèõ òêàíåé, ðàêîì ìîëî÷íîé æåëåçû, íîâîîáðàçîâàíèÿìè ìîçãà è ÀÊÐ. Èíòåðåñíî, ÷òî ìóòàöèè â TP53 ÿâëÿþòñÿ ïðè÷èíîé âûñîêîé âûÿâëÿåìîñòè ÀÊÐ â Þæíîé Áðàçèëèè, ïîòîìó ÷òî ó íå èìåþùèõ ðîäñòâåííîé ñâÿçè ïàöèåíòîâ ýòîãî ðåãèîíà îïðåäåëÿåòñÿ R337H ìóòàöèÿ â TP53. ÀÊÐ - òàêæå êîìïîíåíò ñèíäðîìà Áåêâèòà-Âàéäåìàíà (Beckwith-Wiedemann), êîòîðûé ïðîÿâëÿåòñÿ ìàêðîãëîññèåé, äåôåêòàìè áðþøíîé ñòåíêè (ýìáðèîíàëüíàÿ ïóïî÷íàÿ ãðûæà), ãåìèãèïåðòðîôèåé, íåôðî-, ãåïàòîáëàñòîìîé è ÀÊÐ. Íà ãåíåòè÷åñêîì óðîâíå ýòîò ñèíäðîì âûçâàí èçìåíåíèÿìè â 11p15, ãåíåòè÷åñêîå ìåñòîïîëîæåíèå âêëþ÷àåò IGF-2, H19, è CDKN1C (p57Kip2) ãåíû. Âîçìîæíà ñâÿçü ÀÊÐ ñ ñèíäðîì Ãàðäíåðà (àäåíîìàòîçíûé ïîëèïîç êèøêè), êîòîðûé âûçâàí ìóòàöèåé APC-ãåíà-ñóïðåññîðà îïóõîëåâîãî ðîñòà (APC – îò adenomatosis polyposis coli). Ïðè ãåíåòè÷åñêîì èññëåäîâàíèè îïóõîëåé íàäïî÷å÷íèêîâ ó áîëüíûõ ñ ñèíäðîìîì Ãàðäíåðà âûÿâëÿåòñÿ äåëåöèÿ íîðìàëüíîé APC-àëëåëè â îïóõîëåâûõ õðîìîñîìàõ. Ñèíäðîì ÌÝÍ 1 òèïà ðàíåå ñâÿçûâàëè ñ äîáðîêà÷å ñòâåííûìè, ãîðìîíàëüíî-íåàêòèâíûìè îïóõîëÿìè íàäïî÷å÷íèêîâ, êîòîðûå îòìå÷àëèñü â 20-40 % íàáëþäåíèé ÌÝÍ1. Íåäàâíèå èññëåäîâàíèÿ ïîêàçàëè, ÷òî ïðè ñèíäðîìå ÌÝÍ 1 òèïà ãîðìîíàëüíî-àêòèâíûé ÀÊÐ íå ÿâëÿåòñÿ ðåäêîñòüþ (Langer P, 2002). Ó áîëüíûõ ñ êîìïëåêñîì Êàðíè (Carney) èëè ñèíäðîìîì ÌàêÊüþí-Àëáðàéò (McCune-Albright) ìîãóò áûòü âûÿâëåíû îïóõîëè íàäïî÷å÷íèêà ñ îòñóòñòâèåì èëè íàëè÷èåì ãîðìîíàëüíîé àêòèâíîñòè. Îäíàêî î çëîêà÷åñòâåííîì õàðàêòåðå ýòèõ îáðàçîâàíèé íå ñîîáùàëîñü. Ãåíåòè÷åñêèå äåôåêòû äëÿ ýòèõ äâóõ áîëåçíåé îáóñëîâëåíû àêòèâàöèåé ö-ÀÌÔ-çàâèñèìîé ïðîòåèíêèíàçû.  ðÿäå èññëåäîâàíèé (Gicquel C. è äð. 1994, 1997, 2001) ïðîàíàëèçèðîâàíû ÄÍÊ íàäïî÷å÷íèêîâûõ îïóõîëåé ïðè ñïîðàäè÷åñêîì ÀÊÐ â ó÷àñòêàõ 17p (ñîäåðæàùåì TP53ãåí) è â 11p15 (ñîäåðæàùèì IGF-2/CDKN1C) . Ïîëó÷åííûå ðåçóëüòàòû ñðàâíèëè ñ ìîðôîëîãè÷åñêèì òèïîì îïóõîëåé. Âûÿâëåíî, ÷òî äåëåöèÿ â 17p è ñòðóêòóðíàÿ ïåðåñòàíîâêà 11p15 (è, êàê ðåçóëüòàò — ïîâûøåííàÿ ýêñïðåññèÿ IGF-II ) áûëà îáëèãàòíî ñâÿçàíà ñî çëîêà÷åñòâåííîé ñòðóêòóðîé îïóõîëè. Àâòîðû ïðåäëàãàþò èñïîëüçîâàòü ýòîò òåñò ïðè äèôôåðåíöèðîâàíèè äîáðîêà÷åñòâåííûõ è çëîêà÷åñòâåííûõ îïóõîëåé íàäïî÷å÷íèêà (36). Êëèíè÷åñêèå ïðîÿâëåíèÿ Êëèíè÷åñêèå ïðîÿâëåíèÿ â ðàçíûõ âîçðàñòíûõ ãðóïïàõ íåñêîëüêî îòëè÷àþòñÿ. 40% âçðîñëûõ ñ ÀÊÐ èìåþò ãîðìîíàëüíî-íåàêòèâíóþ îïóõîëü, îáíàðóæåííóþ ñëó÷àéíî èëè â ðåçóëüòàòå äèàãíîñòèêè ýêñòðààäðåíàëîâûõ çàáîëåâàíèé. 60 % âçðîñëûõ èìåþò ãîðìîíàëüíî-àêòèâíóþ îïóõîëü. Èç íèõ, ñèíäðîì ñìåøàííîé ãîðìîíàëüíîé ïðîäóêöèè (ãèïåðêîðòèöèçì è âèðèëèçàöèÿ) îòìå÷àåòñÿ ó 30-40 %, èçîëèðîâàííûé ñèíäðîì Êóøèíãà ó 25-35%, è èçîëèðîâàíàÿ ãèïåðïðîäóêöèÿ àíäðîãåíîâ îòìå÷àåòñÿ ó 20 % áîëüíûõ. Èçîëèðîâàííûå ýñòðîãåí — è àëüäîñòåðîíïðîäóöèðóþùèå îïóõîëè ÿâëÿþòñÿ ðàðèòåòîì, ñîñòàâëÿþò ìåíåå 2%. Ïîâûøåííàÿ ïðîäóêöèÿ àëüäîñòåðîíà îòìå÷àåòñÿ íåñêîëüêî ÷àùå â ðàìêàõ ñìåøàííîé ãîðìîíàëüíîé ïðîäóêöèè. Ó äåòåé ãîðìîíàëüíàÿ àêòèâíîñòü ÀÊÐ âûÿâëÿåòñÿ ÷àùå, ÷åì ó âçðî ñëûõ è ñî ñò àâëÿåò 87-95%. Ïðåîáëàäàþùåå áîëüøèíñòâî îïóõîëåé èçîëèðîâàííî ñåêðåòèðóåò àíäðîãåíû (55 %), èëè àíäðîãåíû â êîìáèíàöèè ñ êîðòèçîëîì (30%). Èçîëèðîâàííûé ãèïåðêîðòèöèçì âñòðå÷àåòñÿ ðåæå — ìåíåå 5 % íàáëþäåíèé. Äðóãèå âàðèàíòû ãîðìîíàëüíîé àêòèâíîñòè â äåòñêîì âîçðàñòå ìîæíî ñ÷èòàòü êàçóèñòè÷åñêèìè. Íà ìîìåíò âûÿâëåíèÿ ñðåäíèé ðàçìåð îïóõîëè ó âçðîñëûõ ïðèáëèçèòåëüíî 10 ñì, ïðè ýòîì ó 30-40 % ïàöèåíòîâ èìåþòñÿ îïðåäåëÿåìûå ìåòàñòàçû (Dackiw A.P. è äð.,2001, Libertino J.M. è äð. 2003). Îïóõîëü ëåãêî âûÿâëÿåòñÿ ïðè ÊÒ è ÌÐÒ è îíêîëîãè÷å ñêàÿ íàñòîðîæåííîñòü â îòíîøåíèè ÀÊÐ ÿâëÿåòñÿ ñåðüåçíûì ïîêàçàíèåì äëÿ óäàëåíèÿ èíöèäåíòàëîìû íàäïî÷å÷íèêîâ. Ïðè îïóõîëÿõ çíà÷èòåëüíîãî ðàçìåðà ïðè îòñóòñòâèè ãîðìîíàëüíîé àêòèâíîñòè íåîáõîäèìî âûïîëíåíèå ÓÇÈ äëÿ èñêëþ÷åíèÿ ìèåëîëèïîìû è êèñòû íàäïî÷å÷íèêà.  íàñòîÿùåå âðåìÿ ïðè ïðèìåíåíèè òîïè÷åñêèõ ìåòîäîâ âûäåëÿþò õàðàêòåðèñòèêè, ïðè êîòîðûõ âûñîêà âåðîÿòíîñòü äîáðîêà÷åñòâåííûõ èçìåíåíèé â íàä- ÝÍÄÎÊÐÈÍÍÀß ÕÈÐÓÐÃÈß ¹ 1(4) 2009 Õèðóðãè÷åñêîå ëå÷åíèèå ÀÊÐ Îñíîâíûì ëå÷åíèåì ÀÊÐ â íàñòîÿùåå âðåìÿ ÿâëÿåòñÿ ïîëíîå õèðóðãè÷åñêîå óäàëåíèå îïóõîëè ñðàçó ïîñëå åå îáíàðóæåíèÿ. Àêöåíò íà ñðî÷íîñòè îïåðàòèâíîãî âìåøàòåëüñòâà ñâÿçàí ñ áûñòðûì ïðîãðåññèðîâàíèåì ðàçìåðîâ îïóõîëè è âûñîêîé âåðîÿòíîñòüþ ìåòàñòàçèðîâàíèÿ. Åñëè íà ìîìåíò îáíàðóæåíèÿ îïóõîëè ìåòàñòàçû íå âûÿâëÿþòñÿ, òî âûãîäà îïåðàöèè î÷åâèäíà, ò.ê. íàöåëåíà íà ïîëíîå èçëå÷åíèå. Ñðåäè íàèáîëåå ÷àñòûõ ïðîáëåì, âîçíèêàþùèõ ïðè ïðîâåäåíèè îïåðàòèâíîãî ëå÷åíèÿ ïî ïîâîäó ÀÊÐ: — êîìïðåññèÿ íèæíåé ïîëîé âåíû, èíôèëüòðàöèÿ ñòåíêè íèæíåé ïîëîé âåíû îïóõîëüþ. Êëèíè÷åñêè âûðàæåííîãî ñèíäðîìà íèæíåé ïîëîé âåíû, êàê ïðàâèëî, íå îòìå÷àåòñÿ â ñâÿçè ñ ïîñòåïåííîé àäàïòàöèåé ê âåíîçíîé ãèïåðòåíçèè ñèñòåìû êàâàïîðòàêàâàëüíûõ àíàñòîìîçîâ. Äîïîëíèòåëüíûìè äèàãíîñòè÷åñêèìè ìåòîäàìè ÿâëÿþòñÿ âîñõîäÿùàÿ êàâàãðàôèÿ, äîïïëåðîãðàôè÷åñêîå èññëåäîâàíèå êðîâîòîêà â êðóïíûõ âåíîçíûõ ñîñóäàõ. Èñõîäîì îïåðàöèè ìîæåò ñòàòü ïåðåâÿçêà íèæíåé ïîëîé âåíû èëè åå ïðîòåçèðîâàíèå; — èíâàçèâíûé îïóõîëåâûé ðîñò â íèæíþþ ïîâåðõíîñòü ïå÷åíè, ïå÷åíî÷íî-12-òèïåðñòíóþ ñâÿçêó, ïîäæåëóäî÷íóþ æåëåçó, ïî÷êó. Ïðîáëåìà ñîïðÿæåíà ñ âîçìîæíûì ðàñøèðåíèåì îáúåìà îïåðàöèè äî ðåçåêöèè ïå÷åíè, íåîáõîäèìîñòüþ íàðóæíîãî èëè âíóòðåííåãî æåë÷åîòâåäåíèÿ, ðåçåêöèè ïîäæåëóäî÷íîé æåëåçû, ñïëåíýêòîìèè, íåôðýêòîìèè èëè ðåçåêöèè âåðõíåãî ïîëþñà ïî÷êè; — âûñîêàÿ âåðîÿòíîñòü ýìáîëè÷åñêèõ îñëîæíåíèé. ßâëÿåòñÿ îñíîâíîé ïðè÷èíîé èíòðàîïåðàöèîííîé è ðàííåé ïîñëåîïåðàöèîííîé ñìåðòíîñòè ó áîëüíûõ ÀÊÐ. Ýìáîëèÿ ìîæåò áûòü îáóñëîâëåíà íåñêîëüêèìè ôàêòîðàìè èëè èõ ñî÷åòàíèåì: à) íàëè÷èåì ãèïåðêîðòèöèçìà/ãèïåðàíäðîãåíèè, ñïîñîáñòâóþùèõ èñõîäíîé ãèïåðêîàãóëÿöèè; á) ìàññèâíîé èíòðà-îïåðàöèîííîé êðîâîïîòåðåé ñ îäíîìîìåíòíûì ïåðåëèâàíèåì áîëüøèõ îáúåìîâ êîìïîíåíòîâ êðîâè; â) íàëè÷èåì îïóõîëåâûõ òðîìáîâ; ã) îòñóòñòâèåì ïðåäîïåðàöèîííûõ ïðîôèëàêòè÷åñêèõ ìåðîïðèÿòèé, ñíèæàþùèõ ðèñê ýìáîëèè. Ñðåäè ïðîôèëàêòè÷åñêèõ ìåðîïðèÿòèé äîëæíû ðàññìàòðèâàòüñÿ ãåïàðèíî-ïðîôèëàêòèêà, óñòàíîâêà âåíîçíûõ òðîìáîóëàâëèâàþùèõ çîíäîâ. Ïîñëåäíåå ìîæåò áûòü çàòðóäíåíî èç-çà îïóõîëåâîé êîìïðåññèè íèæíåé ïîëîé âåíû. Õèìèîòåðàïèÿ ÀÊÐ Â òå÷åíèå äëèòåëüíîãî âðåìåíè ñ÷èòàëîñü, ÷òî ÀÊÐ ÿâëÿåòñÿ ñòîéêèì ê ñòàíäàðòíîé öèòîñòàòè÷åñêîé õèìèîòåðàïèè. Íà ìîëåêóëÿðíîì óðîâíå ïðè ÀÊÐ âûÿâëÿåòñÿ âûñîêèé óðîâåíü P-ãëèêîïðîòåèíà (â íåêîòîðûõ èñòî÷íèêàõ - MDR1), ñ êîòîðûì ñâÿçûâàþò ðåçèñòåíòíîñòü îïóõîëè ê õèìèîòåðàïåâòè÷åñêîìó âîçäåéñòâèþ. Ýòîò áåëîê ôóíêöèîíèðóåò êàê ATÔçàâèñèìàÿ ëåêàðñòâåííàÿ ïîìïà, òðàíñïîðòèðóþùàÿ èç êëåòêè ãèäðîôîáíûå öèòîñòàòè÷åñêèå ïðåïàðàòû. Íîðìàëüíàÿ òêàíü êîðû íàäïî÷å÷íèêà ïðîèçâîäèò áîëüøîå êîëè÷åñòâî P-ãëèêîïðîòåèíà (55,56), è ýòà ñåêðåöèÿ ñîõðàíÿåòñÿ â áîëüøèíñòâå ÀÊÐ (Cordon-Cardo è ñîàâò. 1990, Flynn è ñîàâò.1992, Goldstein è ñîàâò. 1989). Õîòÿ íàëè÷èå P-ãëèêîïðîòåèíà ÿâëÿåòñÿ âåðîÿòíîé è ñóùå ñòâåííîé ïðè÷èíîé ìóëüòèëåêàðñòâåííîé ðåçèñòåíòíîñòè â ÀÊÐ, òàêæå åñòü P-ãëèêîïðîòåèíí å ç à â è ñ è ì û å ì åõà í è çì û ì óë üò è ë å êà ð ñ ò â å í î é ðåçèñòåíòíîñòè, êîòîðûå ìîãóò îáúÿñíÿòü íåýôôåêòèâíîñòü íå òîëüêî ãèäðîôîáíûõ, íî è ãèäðîôèëüíûõ ëåêàðñòâåííûõ ñðåäñòâ òèïà öèñïëàòèíû (Fridborg è ñîàâò. 1994, Haak è ñîàâò.,1993). Ñ öåëüþ óâåëè÷åíèÿ ýôôåêòèâíîñòè õèìèîòåðàïèè, äëÿ ñíèæåíèÿ ëåêàðñòâåííîé ðåçèñòåíòíîñòè ïðèìåíÿþòñÿ êîíêóðåíòîñïîñîáíûå èíãèáèòîðû MDR1çàâèñèìîîé ëåêàðñòâåííîé ïîìïû: D-âåðàïàìèë (â îòëè÷èå îò L-âåðàïàìèëà, íå ÿâëÿåòñÿ áëîêàòîðîì êàëüöèåâûõ êàíàëîâ) è ìèòîòàí. Èññëåäîâàíèå íåïîñðåäñòâåííîãî öèòîñòàòè÷åñêîãî âîçäåéñòâèÿ ýòèõ ïðåïàðàòîâ ïðîäåìîíñòðèðîâàëî íèçêóþ ýôôåêòèâíîñòü, îäíàêî óâåëè÷èâàåòñÿ ýôôåêòèâíîñòü ïðèìåíåíèÿ äðóãèõ öèòîñòàòèêîâ íà ôîíå MDR1-èíãèáèòîðîâ. Ñõîäíûå ðåçóëüòàòû ïîëó÷åíû ïðè èññëåäîâàíèè àíàëîãè÷íîãî ïðåïàðàòà âòîðîãî ïîêîëåíèÿ, èçâåñòíîãî êàê PSC833 – âàëñïîäàð (62). Íåñìîòðÿ íà îòñóòñòâèå çíà÷èòåëüíûõ ðåçóëüòàòîâ, ïîèñê áîëåå ìîùíûõ èíãèáèòîðîâ Pãëèêîïðîòåèíà ïðîäîëæàåòñÿ. Ïðîâîäèòñÿ èññëåäîâàíèå III ôàçû ýôôåêòèâíîñòè õèìèîòåðàïèè òàðèêâèäàðîì (XR9576) — íåêîíêóðåíòíîãî èíãèáèòîðà P-ãëèêîïðîòåèíîâîé ïîìïû òðåòüåãî ïîêîëåíèÿ (E.Fox, S.E Bates. 2007, Walker J è äð. 2004). Ðåçóëüòàòû ïðîâåäåíèÿ õèìèîòåðàïèè çàâèñÿò îò íåñêîëüêèõ ôàêòîðîâ: — îò îáúåìà õèðóðãè÷åñêîé àáëàöèè. Ó íåîïåðàáåëüíûõ áîëüíûõ ðàñøèðåííîå èñïîëüçîâàíèå öèòîñòàòè÷åñêîé õèìèîòåðàïèè, êàê ïðàâèëî, íå ïðèíîñèò óäîâëåòâîðèòåëüíîãî ðåçóëüòàòà (Dackiw A.P.è äð. 2001, Wooten M.D., King D.K. 1993); — îò èñïîëüçîâàíèÿ â ñîñòàâå õèìèîòåðàïèè ìèòîòàíà (ïðîèçâîäíîãî èíñåêòèöèäà o',p'-DDD) ïðè óñëîâèè äîñòèæåíèÿ â êðîâè åãî ýôôåêòèâíîé êîíòðîëèðóåìîé êîíöåíòðàöèè; — îò êîìáèíàöèè èíãèáèòîðîâ Ð-ãëèêîïðîòåèíà (ìèòîòàí, òàðèêâèäàð) ñ äðóãèìè ïðåïàðàòàìè öèòîñòàòè÷åñêîãî ðÿäà. Íåïîñðåäñòâåííî èíãèáèòîðû Ðãëèêîïðîòåèíà íå îáëàäàþò âûñîêîé ïðîòèâîîïóõîëåâîé àêòèâíîñòüþ, îäíàêî ïðåïàðàòû ñíèæàþò õèìèîðåçèñòåíòíîñòü îïóõîëè ïî îòíîøåíèþ ê äðóãèì, áîëåå ýôôåêòèâíûì öèòîñòàòèêàì. ÊËÈÍÈ×ÅÑÊÀß ËÅÊÖÈß ïî÷å÷íèêàõ. Íèçêàÿ íåóâåëè÷èâàþùàÿñÿ ïëîòíîñòü ñèãíàëà ïðè ÊÒ èëè áûñòðîå ñíèæåíèå èíòåíñèâíîñòè ñèãíàëà ïîñëå âíóòðèâåííîãî êîíòðàñòèðîâàíèÿ (AlHawary M.M. è ñîàâò, 2005, Hamrahian A.H. è ñîàâò., 2005, Korobkin M. È äð. 1996) õàðàêòåðíà äëÿ êîðêîâûõ àäåíîìû èëè ãèïåðïëàçèè. Îäíîðîäíàÿ ãèïåðýõîãåííàÿ ñòðóêòóðà îïóõîëè ïðè ÓÇÈ õàðàêòåðíà äëÿ ìèåëîëèïîìû.  íàñòîÿùèé ìîìåíò ðåêîìåíäîâàíî õèðóðãè÷åñêîå ëå÷åíèå ïðè îïóõîëÿõ áîëåå 5 ñì (èñêëþ÷àÿ êèñòû), íåñìîòðÿ íà òî, ÷òî â ýòèõ ñëó÷àÿõ 75 % îïóõîëåé ÿâëÿþòñÿ äîáðîêà÷åñòâåííûìè. 15 16 ÝÍÄÎÊÐÈÍÍÀß ÕÈÐÓÐÃÈß ¹ 1(4) 2009 Äî íàñòîÿùåãî âðåìåíè áûëè îòìå÷åíû ïðè ïðèìåíåíèè òàê íàçûâàåìîãî "èòàëüÿíñêîãî" ïðîòîêîëà: â êà÷åñòâå ñîñòàâëÿþùèõ èñïîëüçóþòñÿ ýòîïîçèä, äîêñîðóáèöèí è öèñïëàòèíà, ñ ïàðàëëåëüíûì íàçíà÷åíèåì ìèòîòàíà (ñõåìà EDP/M) (Berruti A. è äð.1998). Ó 28 ïàöèåíòîâ, ïîëó÷àþùèõ ýòîò ðåæèì, ïîëíîöåííûé îòâåò îòìå÷åí ó 53.5 %, õîòÿ ó çíà÷èòåëüíîãî áîëüøèíñòâà (13 èç 15) îòâåò áûë ÷àñòè÷íûì.  ýòîì èññëåäîâàíèè îñîáåííûé àêöåíò ñòàâèëñÿ íà ïîääåðæàíèå êîíöåíòðàöèè ìèòîòàíà â ñûâîðîòêå ìåæäó 14 è 20 ìã/äë, êîòîðàÿ îáóñëàâëèâàëà êëèíè÷åñêèé ýôôåêò ïðè ìèíèìàëüíîé òîêñè÷íîñòè (Terzolo M. è äð. 2003). Âòîðîé àêòèâíûé ðåæèì — êîìáèíàöèÿ ñòðåïòîçîòîöèíà è ìèòîòàíà (SO òåðàïèÿ) (Khan T.S. è äð. 2000). Ïðè èññëåäîâàíèè 40 ïàöèåíòîâ ñ ÀÊÐ, ïîëíûé èëè ÷àñòè÷íûé îòâåò áûë ïîëó÷åí ó 36.4 % èç 22 ïîëíîöåííî îáñëåäîâàííûõ áîëüíûõ. Íåïîñðåäñòâåííîå ñðàâíåíèå è îïðåäåëåíèå "îïòèìàëüíîé" òåðàïèè â íàñòîÿùåå âðåìÿ âûïîëíÿåòñÿ ñîâìåñòíîé ãðóïïîé ìåæäóíàðîäíûõ èññëåäîâàòåëåé ïî ÀÊÐ (ïåðâîå ìåæäóíàðîäíîå ðàíäîìèçèðîâàâøåå èñïûòàíèå ìåñòíîðàñïðîñòðàíåííûõ è ìåòàñòàòè÷åñêèõ ôîðì ÀÊÐ FIRM-ACT study; www.firm-act.org). Òàêèì îáðàçîì, ïðè ï ð è ì å í å í è è ñ î â ð å ì å í í û õ ï ð îò è âî î ï ó õîë å â û õ õèìèîòåðàïåâòè÷åñêèõ ñõåì âîçìîæíî äîñòèæåíèå ðåãðåññà îïóõîëåâûõ ïðîÿâëåíèé ÀÊÐ îò 35 äî 53% íàáëþäåíèé ïðîîïåðèðîâàííûõ áîëüíûõ. Õèìèîòåðàïèÿ «îò÷àÿíèÿ» ñ ïðèìåíåíèåì âèíêðèñòèíà, öèñïëàòèíû è öèêëîôîñôàìèäà ïðîâîäèòñÿ áîëüíûì, ó êîòîðûõ áûëà áåçóñïåøíà SO-òåðàïèÿ (Khan T.S. è äð., 2004). Ïðîãíîç Ïðè îòñóòñòâèè ïîëíîé õèðóðãè÷åñêîé àáëàöèè ÀÊÐ îñòàåòñÿ áîëåçíüþ ñ ïëîõèì ïðîãíîçîì, ñ íåáîëüøèìè ïîêàçàòåëÿìè 5-òèëåòíåãî âûæèâàíèÿ. Îïðåäåëåííûé îïòèìèçì ñâÿçàí ñ îïðåäåëåíèåì "ñòàíäàðòà" õèìèîòåðàïèè, è ðàçâèòèåì íîâûõ ïîäõîäîâ â õèìèîòåðàïèè (âîçäåéñòâèå íà îïóõîëåâûé àíãèîãåíåç, ïîÿâëåíèå íèçêîìîëåêóëÿðíûõ èíãèáèòîðîâ ôåðìåíòîâ, èììóííûå è ãåíåòè÷åñêèå ìåòîäû âëèÿíèÿ íà îïóõîëåâûé ðîñò). ÊËÈÍÈ×ÅÑÊÀß ËÅÊÖÈß Ëèòåðàòóðà 1. Crucitti F, Bellantone R, Ferrante A, Boscherini M, Crucitti P. — The Italian Registry for Adrenal Cortical Carcinoma: analysis of a multiinstitutional series of 129 patients. The ACC Italian Registry Study Group. - 1996 - Surgery 119:161-170 2. Dackiw AP, Lee JE, Gagel RF, Evans DB - Adrenal cortical carcinoma. – 2001 - World J Surg 25:914-926 3. Ng L, Libertino JM - Adrenocortical carcinoma: diagnosis, evaluation and treatment. – 2003 - J Urol 169:5-11 4. Al-Hawary MM, Francis IR, Korobkin M Non-invasive evaluation of the incidentally detected indeterminate adrenal mass. - 2005 - Best Pract Res Clin Endocrinol Metab 19:277-292. 5. 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