адренокортикальный рак.

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. Â 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. Â
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
 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. Â
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
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