{"id":1972,"date":"2020-05-05T17:17:37","date_gmt":"2020-05-05T15:17:37","guid":{"rendered":"https:\/\/www.newslab.sk\/laboratorna-diagnostika-karcinoidov\/"},"modified":"2020-05-05T17:20:03","modified_gmt":"2020-05-05T15:20:03","slug":"laboratory-diagnosis-of-carcinoids","status":"publish","type":"post","link":"https:\/\/www.newslab.sk\/en\/laboratory-diagnosis-of-carcinoids\/","title":{"rendered":"Laboratory diagnosis of carcinoids"},"content":{"rendered":"

*<\/strong>All tables, charts, graphs and pictures that are featured in this article can be found in the .pdf attachment at the end of the paper.<\/strong><\/span><\/p>\n

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\u00davod<\/strong><\/p>\n

Karcinoidy predstavuj\u00fa svojr\u00e1zny typ n\u00e1dorov, ktor\u00e9 sa \u0161trukt\u00farou, histologicky aj biologick\u00fdm spr\u00e1van\u00edm l\u00ed\u0161ia od be\u017en\u00fdch epitelov\u00fdch n\u00e1dorov GIT-u. Patria medzi naj\u010dastej\u0161ie sa vyskytuj\u00face tumory zo skupiny neuroendokrinn\u00fdch n\u00e1dorov (NET). Incidencia t\u00fdchto n\u00e1dorov v posledn\u00fdch rokoch v\u00fdrazne st\u00fapa. Z h\u013eadiska svojej hormon\u00e1lnej aktivity tvoria ve\u013emi pestr\u00fa a heterog\u00e9nnu skupinu. Ich z\u00e1kladom s\u00fa neuroendokrinn\u00e9 enterochromafinn\u00e9 bunky (EC), ktor\u00e9 sa vyskytuj\u00fa v r\u00f4znych anatomick\u00fdch \u010dastiach tela, naj\u010dastej\u0161ie v\u0161ak v tr\u00e1viacom trakte vr\u00e1tane pankreasu, v p\u013e\u00facach, menej \u010dasto v ov\u00e1ri\u00e1ch \u010di \u0161t\u00edtnej \u017e\u013eaze. V\u00e4\u010d\u0161inou ide o pomaly rast\u00face n\u00e1dory. \u010casto b\u00fdvaj\u00fa diagnostikovan\u00e9 neskoro, v mnoh\u00fdch pr\u00edpadoch u\u017e ako diseminovan\u00e9 ochorenie. Karcinoidy m\u00f4\u017eu dlh\u0161\u00ed \u010das r\u00e1s\u0165 asymptomaticky, m\u00f4\u017eu sa manifestova\u0165 onkologick\u00fdmi pr\u00edznakmi alebo sa pri endokrinne funk\u010dn\u00fdch n\u00e1doroch manifestuj\u00fa karcinoidov\u00fdm syndr\u00f3mom. Klinick\u00e9 prejavy s\u00fa z\u00e1visl\u00e9 od typu spektra hormon\u00e1lne akt\u00edvnych substanci\u00ed. Diagn\u00f3za karcinoidov je zalo\u017een\u00e1 na pou\u017eit\u00ed zobrazovac\u00edch met\u00f3d pod\u013ea lokaliz\u00e1cie n\u00e1doru, tie\u017e na histologickom n\u00e1leze a z laborat\u00f3rnych vy\u0161etren\u00ed na stanoven\u00ed s\u00e9roton\u00ednu, chromogran\u00ednu A a neur\u00f3novej \u0161pecifickej enol\u00e1zy (NSE) v s\u00e9re a kyseliny 5-hydroxyindoloctovej (5-HIAA) v mo\u010di.<\/p>\n

Epidemiol\u00f3gia karcinoidov<\/h3>\n

Karcinoidy sa vyskytuj\u00fa v po\u010dte asi 1-2 pr\u00edpady na 100 000 obyvate\u013eov ro\u010dne. Tvoria len 0,49 % zo v\u0161etk\u00fdch malign\u00edt. Predominantne sa vyskytuj\u00fa u \u017eien, vrchol v\u00fdskytu je medzi 40. a\u017e 60. rokom veku. U det\u00ed nach\u00e1dzame karcinoidy zriedka, a to najviac v apendixe(1).<\/p>\n

Ke\u010f\u017ee n\u00e1dory vyrastaj\u00fa z neuroendokrinn\u00fdch buniek, frekvencia ich v\u00fdskytu koreluje s hustotou t\u00fdchto buniek. V najv\u00e4\u010d\u0161om endokrinnom org\u00e1ne \u010dloveka, v \u010dreve, sa nach\u00e1dza pribli\u017ene 60 % karcinoidov. Viac ako 25 % karcinoidov\u00fdch n\u00e1dorov rastie v bronchopulmon\u00e1lnom trakte(2).<\/p>\n

Karcinoidy b\u00fdvaj\u00fa najviac lokalizovan\u00e9 v tenkom \u010dreve. N\u00e1dory tenk\u00e9ho \u010dreva ak\u00e9hoko\u013evek druhu sa vyskytuj\u00fa zriedka a tvoria iba 1 % v\u0161etk\u00fdch n\u00e1dorov gastrointestin\u00e1lneho traktu. V tejto skupine v\u0161ak karcinoidy maj\u00fa v\u00fdznamn\u00e9 postavenie svoj\u00edm 50 % zast\u00fapen\u00edm medzi malignitami tenk\u00e9ho \u010dreva. Rast\u00fa ve\u013emi pomaly, rozmerovo s\u00fa pomerne mal\u00e9, preto b\u00fdvaj\u00fa \u010dasto diagnostikovan\u00e9 a\u017e v pokro\u010dilom \u0161t\u00e1diu. Nemusia ich sprev\u00e1dza\u0165 prakticky \u017eiadne pr\u00edznaky alebo s\u00fa ich pr\u00edznaky typick\u00e9 pre cel\u00fd rad in\u00fdch chor\u00f4b, preto odhalenie m\u00f4\u017ee trva\u0165 mesiace a\u017e roky. V\u00fdskyt karcinoidov pod\u013ea lokaliz\u00e1cie je uveden\u00fd v tabu\u013eke 1<\/em><\/strong>. Existuj\u00fa tie\u017e ve\u013emi neobvykl\u00e9 a extr\u00e9mne vz\u00e1cne lokaliz\u00e1cie prim\u00e1rneho v\u00fdskytu kar- cinoidov \u2013 \u017el\u010dn\u00edk a \u017el\u010dov\u00e9 cesty, vaje\u010dn\u00edky, semenn\u00edky, mo\u010dov\u00fd mech\u00far, prostata, mlie\u010dna \u017e\u013eaza, t\u00fdmus(3).<\/p>\n

Karcinoidy apendixu b\u00fdvaj\u00fa zo v\u0161etk\u00fdch t\u00fdchto n\u00e1dorov najmenej zhubn\u00e9, len zriedka vzdialene metast\u00e1zuj\u00fa. B\u00fdvaj\u00fa diagnostikovan\u00e9 n\u00e1hodne pri chirurgickom v\u00fdkone pre apendicit\u00eddu (asi 1\/200 \u2013 300 pr\u00edpadov) a okolo 87 % \u013eud\u00ed s takto diagnostikovan\u00fdm a odstr\u00e1nen\u00fdm n\u00e1dorom pre\u017e\u00edva dlh\u0161ie ako 5 rokov. Druh\u00fa skupinu s dobrou progn\u00f3zou tvoria karcinoidy rekta s 5-ro\u010dn\u00fdm pre\u017e\u00edvan\u00edm v 72 %. Ak s\u00fa v\u0161ak v \u010dase stanovenia diagn\u00f3zy pr\u00edtomn\u00e9 vzdialen\u00e9 metast\u00e1zy a pacient sa nelie\u010di, kles\u00e1 5-ro\u010dn\u00e9 pre\u017eitie na hodnotu 27 %(3).<\/p>\n

Etiol\u00f3gia karcinoidov je prakticky nezn\u00e1ma. Vo v\u00e4\u010d\u0161ine pr\u00edpadov sa vyskytuj\u00fa sporadicky. Famili\u00e1rny v\u00fdskyt je ve\u013emi zriedkav\u00fd, menej ako 1 % pacientov s karcinoidom m\u00e1 pozit\u00edvnu rodinn\u00fa anamn\u00e9zu. Relat\u00edvne riziko vzniku karcinoidu po\u010das \u017eivota u pokrvn\u00e9ho pr\u00edbuzn\u00e9ho je 3,6 %(4).<\/p>\n

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Rozdelenie karcinoidov<\/h3>\n

Doned\u00e1vna bola pou\u017e\u00edvan\u00e1 sch\u00e9ma rozdelenia karcinoidov pod\u013ea klasifik\u00e1cie Williamsa a Sandlera z roku 1963, ktor\u00e1 sa opierala o rozdelenie n\u00e1dorov pod\u013ea r\u00f4znych \u00fasekov embryon\u00e1lneho \u010dreva a poukazovala na vz\u0165ah morfol\u00f3gie a topografie ich v\u00fdskytu(5).<\/p>\n

Toto delenie sa pri s\u00fa\u010dasn\u00fdch poznatkoch jav\u00ed ako prekonan\u00e9, je v\u0161ak jednoduch\u00e9, zrozumite\u013en\u00e9, a preto sa aj dnes s vedom\u00edm ur\u010ditej nepresnosti pou\u017e\u00edva v literat\u00fare. T\u00e1to klasifik\u00e1cia del\u00ed karcinoidy na tri skupiny \u2013 karcinoidy vych\u00e1dzaj\u00face z predn\u00e9ho \u00faseku embryon\u00e1lneho \u010dreva (foregut karcinoidy), karcinoidy zo stredn\u00e9ho \u00faseku (midgut karcinoidy) a karcinoidy zo zadn\u00e9ho \u00faseku embryon\u00e1lneho \u010dreva (hindgut karcinoidy)(1) (tabu\u013eka 2)<\/em><\/strong>.<\/p>\n

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Karcinoidy \u017eal\u00fadka<\/h3>\n

Predstavuj\u00fa asi 2 \u2013 4 % zo v\u0161etk\u00fdch karcinoidov GIT-u a iba 0,3 % mal\u00edgnych n\u00e1dorov \u017eal\u00fadka(6). Vznik \u017eal\u00fado\u010dn\u00e9ho karcinoidu sa d\u00e1va do s\u00favislosti s in\u00fdm ochoren\u00edm \u017eal\u00fadka, pri ktorom doch\u00e1dza k zv\u00fd\u0161enej produkcii gastr\u00ednu. Ide predov\u0161etk\u00fdm o chronick\u00fa atrofick\u00fa gastrit\u00eddu spojen\u00fa s enter\u00e1lnou metapl\u00e1ziou \u017eal\u00fado\u010dnej sliznice. Naj\u010dastej\u0161ia lokaliz\u00e1cia je fundus \u017eal\u00fadka(3).<\/p>\n

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Bronchopulmon\u00e1lne karcinoidy<\/h3>\n

Vyskytuj\u00fa sa v 1 \u2013 6 % zo v\u0161etk\u00fdch prim\u00e1rnych p\u013e\u00facnych neopl\u00e1zi\u00ed. Predstavuj\u00fa 10 \u2013 12 % v\u0161etk\u00fdch karcinoidov. Vych\u00e1dzaj\u00fa z neuroendokrinn\u00fdch buniek lokalizovan\u00fdch v bronchi\u00e1lnej sliznici. Naj\u010dastej\u0161ie sa vyskytuje u mu\u017eov \u2013 2,5\/100 000. Z h\u013eadiska biologick\u00fdch vlastnost\u00ed zah\u0155\u0148aj\u00fa ben\u00edgnej\u0161ie formy v podobe typick\u00fdch karcinoidov a\u017e po mal\u00edgne atypick\u00e9 formy. Malobunkov\u00fd p\u013e\u00facny karcinoid je najmal\u00edgnej\u0161ou formou. Metast\u00e1zuje v region\u00e1lnych mediastin\u00e1lnych lymfatick\u00fdch uzlin\u00e1ch, v pe\u010deni, vz\u00e1cne v kostiach a ko\u017ei. Pri produkcii ACTH doch\u00e1dza k rozvoju Cushingovho syndr\u00f3mu(7).<\/p>\n

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Karcinoidy tenk\u00e9ho \u010dreva<\/h3>\n

Karcinoidy tenk\u00e9ho \u010dreva predstavuj\u00fa najpo\u010detnej\u0161iu sku- pinu (asi 50 %) gastrointestin\u00e1lnych karcinoidov. Vzh\u013eadom na to, \u017ee adenokarcin\u00f3my tenk\u00e9ho \u010dreva sa vyskytuj\u00fa vz\u00e1cne, karcinoidy patria k naj\u010dastej\u0161\u00edm mal\u00edgnym n\u00e1dorom vyskytuj\u00facim sa v tejto lokaliz\u00e1cii (60 %). Naj\u010dastej\u0161ie s\u00fa lokalizovan\u00e9 v ileu(8).<\/p>\n

Biologick\u00e9 vlastnosti karcinoidov tenk\u00e9ho \u010dreva s\u00fa dan\u00e9 predov\u0161etk\u00fdm ich ve\u013ekos\u0165ou a sp\u00f4sobom rastu. N\u00e1dory men\u0161ie ako 1 cm metast\u00e1zuj\u00fa iba v 2 %, zatia\u013e \u010do n\u00e1dory v\u00e4\u010d\u0161ie ako 2 cm metast\u00e1zuj\u00fa v 80 %(7).<\/p>\n

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Karcinoidy apendixu<\/h3>\n

Zvl\u00e1\u0161tnu skupinu karcinoidov\u00fdch n\u00e1dorov GIT-u predstavuj\u00fa karcinoidy apendixu. S\u00fa relat\u00edvne \u010dast\u00e9, tvoria 34 % v\u0161etk\u00fdch karcinoidov GIT-u a s\u00fa naj\u010dastej\u0161\u00edmi epitelov\u00fdmi n\u00e1dormi apendixu (90 %). Incidencia kulminuje u \u017eien vo veku 15 \u2013 19 rokov a u mu\u017eov vo veku 20 \u2013 24 rokov. M\u00f4\u017eu sa objavi\u0165 aj u det\u00ed(3).<\/p>\n

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Klinick\u00e9 prejavy karcinoidov<\/h3>\n

Klinick\u00e9 prejavy s\u00fa z\u00e1visl\u00e9 od lokaliz\u00e1cie prim\u00e1rneho n\u00e1doru, rozsahu ochorenia a spektra hormon\u00e1lnej produkcie n\u00e1dorom. Karcinoidy maj\u00fa v\u00e4\u010d\u0161inou mal\u00e9 rozmery, b\u00fdvaj\u00fa dlho asymptomatick\u00e9, m\u00f4\u017eu sa manifestova\u0165 v\u0161eobecne onkologick\u00fdmi pr\u00edznakmi alebo sa pri endokrinne funk\u010dn\u00fdch n\u00e1doroch manifestuj\u00fa karcinoidov\u00fdm syndr\u00f3mom(1).<\/p>\n

Pri p\u013e\u00facnych tumoroch b\u00fdva klinick\u00fdm prejavom sk\u00f4r ka\u0161e\u013e, d\u00fdchavi\u010dnos\u0165, hemopt\u00fdza alebo boles\u0165 na hrudn\u00edku vypl\u00fdvaj\u00faca z lokaliz\u00e1cie tumoru(1).<\/p>\n

Karcinoidy \u017eal\u00fadka a \u010driev sa m\u00f4\u017eu prejavi\u0165 krv\u00e1can\u00edm, a to okultn\u00fdm s postupnou anemiz\u00e1ciou alebo manifestn\u00fdm vo forme hematem\u00e9zy \u010di mel\u00e9ny. N\u00e1dory \u010dreva m\u00f4\u017eu vies\u0165 k ob\u0161trukcii alebo enteror\u00e1gii. Tumory v duod\u00e9ne \u010di pankrease m\u00f4\u017eu sp\u00f4sobova\u0165 ob\u0161truk\u010dn\u00fd ikterus(1).<\/p>\n

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Karcinoidov\u00fd syndr\u00f3m<\/h3>\n

Karcinoidov\u00fd syndr\u00f3m sa m\u00f4\u017ee vyvin\u00fa\u0165 u 10 a\u017e 18 % pacientov s karcinoidov\u00fdm n\u00e1dorom. Klasick\u00fd karcinoidov\u00fd syndr\u00f3m typicky zah\u0155\u0148a vazomotorick\u00e9, kardi\u00e1lne a gastrointestin\u00e1lne pr\u00edznaky. Naj\u010dastej\u0161\u00edmi prejavmi s\u00fa flush, hna\u010dka, kardi\u00e1lne po\u0161kodenie, bronchi\u00e1lna astma, hypotenzia alebo hypertenzia. Ku klinicky manifestn\u00fdm prejavom syndr\u00f3mu doch\u00e1dza v pr\u00edtomnosti metast\u00e1z v pe\u010deni alebo ak je n\u00e1dor lokalizovan\u00fd mimo gastrointestin\u00e1lneho traktu a uvo\u013e\u0148ovan\u00e9 hormon\u00e1lne l\u00e1tky s\u00fa vyplavovan\u00e9 priamo do cirkul\u00e1cie \u2013 napr\u00edklad pri n\u00e1doroch lokalizovan\u00fdch v ov\u00e1riu, v testes alebo v p\u013e\u00facach(9).<\/p>\n

Medzi hlavn\u00e9 prejavy karcinoidov\u00e9ho syndr\u00f3mu patr\u00ed ko\u017en\u00fd flush<\/strong>. Vyskytuje sa v 25 \u2013 73 % pr\u00edpadov metast\u00e1zuj\u00faceho karcin\u00f3mu. V typickej podobe sa prejavuje n\u00e1hlym vznikom \u010derven\u00e9ho alebo \u010dervenofialov\u00e9ho eryt\u00e9mu hornej \u010dasti tela, hlavne na tv\u00e1ri a na krku. Pacient ho vn\u00edma ako pocit hor\u00fa\u010davy a svrbenia. \u010cast\u00fdmi sprievodn\u00fdmi pr\u00edznakmi s\u00fa hna\u010dka, b\u00fa\u0161enie srdca, slzenie, opuch tv\u00e1re alebo spojoviek(7).<\/p>\n

Prv\u00e9 ataky flushu v skor\u00fdch f\u00e1zach ochorenia s\u00fa prchav\u00e9, trvanie nepresahuje 5 min\u00fat. Nesk\u00f4r je ich v\u00fdskyt prolongovan\u00fd, trv\u00e1 aj hodiny. Pri pokro\u010dilej\u0161\u00edch ochoreniach m\u00f4\u017ee by\u0165 flush aj fixovan\u00fd, permanentne hnedo\u010derven\u00fd a pacient nepoci\u0165uje \u017eiadne subjekt\u00edvne pr\u00edznaky(7).<\/p>\n

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Karcinoidov\u00e9\u00a0 po\u0161kodenie srdca<\/h3>\n

Vyskytuje sa v 10 \u2013 50 % pr\u00edpadov karcinoidov\u00e9ho syndr\u00f3mu. Patogen\u00e9za postihnutia srdca nie je doposia\u013e celkom jasn\u00e1, ale ur\u010dit\u00fa \u00falohu hr\u00e1 vylu\u010dovanie s\u00e9roton\u00ednu a in\u00fdch vazoakt\u00edvnych l\u00e1tok n\u00e1dorov\u00fdmi bunkami, ktor\u00e9 vedie k po\u0161kodeniu endokardu. D\u00f4le\u017eit\u00fdm faktorom je nielen absol\u00fatne mno\u017estvo s\u00e9roton\u00ednu, ale tie\u017e d\u013a\u017eka expoz\u00edcie(10). Postihnutie srdca je charakterizovan\u00e9 fibr\u00f3zou endokardu, ktor\u00e1 vytv\u00e1ra plaky porcel\u00e1nov\u00e9ho vzh\u013eadu v dutin\u00e1ch prav\u00e9ho srdca a \u010dasto sp\u00f4sobuje retrakciu a fix\u00e1ciu c\u00edpov trikuspid\u00e1lnej a pulmon\u00e1lnej chlopne. Tri naj\u010dastej\u0161ie chlop\u0148ov\u00e9 po\u0161kodenia s\u00fa tvoren\u00e9 trikuspid\u00e1lnou insuficienciou, pulmon\u00e1lnou insuficienciou a trikuspid\u00e1lnou sten\u00f3zou. Kardi\u00e1lne pr\u00edznaky sa objavuj\u00fa v pokro\u010dil\u00fdch f\u00e1zach ochorenia a zmeny s\u00fa ireverzibiln\u00e9. A\u017e polovica pacientov s karcinoidov\u00fdm syndr\u00f3mom zomiera na pravostrann\u00e9 srdcov\u00e9 zlyhanie(9).<\/p>\n

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Laborat\u00f3rna diagnostika<\/h3>\n

Karcinoid predstavuje\u00a0 z\u00a0 h\u013eadiska\u00a0 diagnostiky\u00a0 zlo\u017eit\u00fd\u00a0 a komplexn\u00fd probl\u00e9m. Vypl\u00fdva to v podstate z jeho biolo- gick\u00fdch vlastnost\u00ed. Na rozdiel od klasicky hormon\u00e1lnych akt\u00edvnych tumorov vych\u00e1dzaj\u00facich z dif\u00fazneho endokrinn\u00e9ho syst\u00e9mu, kde klinicky maj\u00fa prevahu prejavy hypersekr\u00e9cie jedn\u00e9ho konkr\u00e9tneho horm\u00f3nu, pod\u013ea ktor\u00e9ho sa n\u00e1dor ozna\u010duje (gastrin\u00f3m, inzulin\u00f3m, somatostatin\u00f3m, glukagon\u00f3m, vip\u00f3m at\u010f.), pri karcinoide je situ\u00e1cia odli\u0161n\u00e1. Klasick\u00fd karcinoid produkuje hlavne s\u00e9roton\u00edn, prostagland\u00edny a za ur\u010dit\u00fdch okolnost\u00ed cel\u00fd rad tzv. gastrointestin\u00e1lnych horm\u00f3nov, napr. gastr\u00edn, somatostat\u00edn, vazoakt\u00edvny intestin\u00e1lny peptid (VIP), taktie\u017e peptidov\u00e9 a prote\u00ednov\u00e9 l\u00e1tky, napr. ACTH(3).<\/p>\n

Medzi hormon\u00e1lne akt\u00edvne l\u00e1tky, ktor\u00e9 naj\u010dastej\u0161ie stanovujeme pri diagnostike karcinoidu v na\u0161om laborat\u00f3riu, patria: s\u00e9roton\u00edn, NSE, chromogran\u00edn A v s\u00e9re a 5-HIAA v mo\u010di.<\/p>\n

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S\u00e9roton\u00edn<\/h3>\n

S\u00e9roton\u00edn \u00a0(5-hydroxytryptam\u00edn, \u00a05-HT) \u00a0je \u00a0biologicky \u00a0akt\u00edvna l\u00e1tka, ktor\u00e1 sa vyskytuje v trombocytoch, v bunk\u00e1ch GIT-u a v men\u0161ej miere aj v CNS. Vznik\u00e1 synt\u00e9zou z aminokyseliny L-tryptof\u00e1nu (obr\u00e1zok 1)<\/em><\/strong>.<\/p>\n

Na na\u0161om pracovisku sa stanovuje s\u00e9roton\u00edn v s\u00e9re HPLC pomocou HPLC analyz\u00e1tora Agilent 1200.<\/p>\n

Odber treba realizova\u0165 do \u0161tandardnej biochemickej sk\u00famavky so separa\u010dn\u00fdm g\u00e9lom. Referen\u010dn\u00e9 hodnoty s\u00fa u oboch pohlav\u00ed 667 <\/strong>\u2013 1 097 nmol\/l<\/strong>.<\/p>\n

Nev\u00fdhodou vy\u0161etrenia je kol\u00edsanie hladiny po\u010das d\u0148a v s\u00e9re, z d\u00f4vodu kr\u00e1tkeho biologick\u00e9ho pol\u010dasu s\u00e9roton\u00ednu. Preto je z\u00e1kladn\u00fdm postupom laborat\u00f3rnej diagnostiky karcinoidu vy\u0161etrovanie denn\u00e9ho odpadu jeho hlavn\u00e9ho metabolitu, kyseliny 5-hydroxyindoloctovej, v mo\u010di za 24 hod\u00edn(11).<\/p>\n

 <\/p>\n

5-hydroxyindoloctov\u00e1 kyselina (5-HIAA)<\/h3>\n

Pri podozren\u00ed na karcinoid sa pou\u017e\u00edva ako jedna z prv\u00fdch laborat\u00f3rnych met\u00f3d vy\u0161etrenie 5-hydroxyindoloctovej kyse- liny (5-HIAA) v mo\u010di. 5-HIAA je v\u00fdznamn\u00fd metabolit s\u00e9roton\u00ednu, vznik\u00e1 oxida\u010dnou deamin\u00e1ciou enz\u00fdmom monooxid\u00e1za a vylu\u010duje sa do mo\u010du(7) (obr\u00e1zok 2)<\/em><\/strong>.<\/p>\n

Vy\u0161etrenie 5-HIAA v mo\u010di za dodr\u017eania podmienok zberu mo\u010du je prakticky 100 % \u0161pecifick\u00e9. Mo\u010d sa zbiera 24 hod\u00edn do tmavej n\u00e1doby s pridan\u00edm 10 ml 25 % HCl. 5-HIAA v mo\u010di sa stanovuje HPLC met\u00f3dou pomocou HPLC analyz\u00e1tora Agilent 1200(12).<\/p>\n

Referen\u010dn\u00e9 hodnoty s\u00fa u oboch pohlav\u00ed 10,5 <\/strong>\u2013 <\/strong>47,1 \u03bcmol\/ 24 hod<\/strong>.<\/p>\n

Pred vy\u0161etren\u00edm 5-HIAA v mo\u010di je nutn\u00e9 dodr\u017ea\u0165 2-3-d\u0148ov\u00fa di\u00e9tu z vyl\u00fa\u010den\u00edm potrav\u00edn, ktor\u00e9 by falo\u0161ne zvy\u0161ovali hladinu s\u00e9roton\u00ednu a n\u00e1sledne 5-HIAA v mo\u010di(11) (tabu\u013eka 3)<\/em><\/strong>.<\/p>\n

Okrem potrav\u00edn obsahuj\u00facich s\u00e9roton\u00edn patria medzi interferuj\u00face faktory r\u00f4zne lieky a ochorenia, ktor\u00e9 v\u00fdznam- ne ovplyv\u0148uj\u00fa hladinu s\u00e9roton\u00ednu a odpad 5-HIAA v mo\u010di(11) (tabu\u013eka 4)<\/em><\/strong>.<\/p>\n

V pr\u00edpadoch v\u00fdznamn\u00e9ho zv\u00fd\u0161enia hodn\u00f4t odpadov 5-HIAA v mo\u010di existuje pozit\u00edvna korel\u00e1cia medzi hmotnos\u0165ou n\u00e1doru a hladinou 5-HIAA v mo\u010di. Vy\u0161etrenie sl\u00fa\u017ei i na monitorovanie priebehu a efektivity lie\u010dby, pr\u00edpadnej poopera\u010dnej recid\u00edvy alebo progresie po predch\u00e1dzaj\u00facej \u00faspe\u0161nej odpovedi na konzervat\u00edvnu terapiu. K najbe\u017enej\u0161\u00edm<\/p>\n

biochemick\u00fdm vy\u0161etreniam pri karcinoidoch doteraz patr\u00ed 24-hodinov\u00fd zber mo\u010du na vy\u0161etrenie 5-HIAA(11).<\/p>\n

Na na\u0161om pracovisku (Medirex, a. s.) okrem \u0161pecifick\u00fdch markerov pre diagnostiku karcinoidov (s\u00e9roton\u00edn a 5-HIAA) stanovujeme aj ne\u0161pecifick\u00e9 n\u00e1dorov\u00e9 markery. Tieto markery s ve\u013ekou pravdepodobnos\u0165ou signalizuj\u00fa pr\u00edtomnos\u0165 NET, ale samy osebe nepod\u00e1vaj\u00fa bli\u017e\u0161iu inform\u00e1ciu o vlastnos- tiach vy\u0161etrovan\u00e9ho NET(11). K ne\u0161pecifick\u00fdm markerom patria NSE, chromogran\u00edn A, gastr\u00edn a kalciton\u00edn.<\/p>\n

 <\/p>\n

Neur\u00f3nov\u00e1 \u0161pecifick\u00e1 enol\u00e1za<\/h3>\n

Neur\u00f3nov\u00e1 \u0161pecifick\u00e1 enol\u00e1za (NSE) je jeden z 5 izoenz\u00fdmov glykolytick\u00e9ho enz\u00fdmu enol\u00e1zy (2-fosfo-D-glycer\u00e1thydrol\u00e1za). Vyskytuje sa v r\u00f4znych dimerick\u00fdch izoform\u00e1ch zahr\u0148uj\u00facich 3 imunologicky odli\u0161n\u00e9 podjednotky \u03b1, \u03b2, \u03b3 \u2013 \u03b1podjednotka enol\u00e1zy sa vyskytuje v rozli\u010dn\u00fdch typoch tkan\u00edv cicavcov, zatia\u013e \u010do \u03b2podjednotka sa nach\u00e1dza predov\u0161etk\u00fdm v srdci a prie\u010dne pruhovan\u00fdch svaloch. Izoformy enol\u00e1zy \u03b1\u03b3 a \u03b3\u03b3, ktor\u00e9 s\u00fa ozna\u010dovan\u00e9 ako neur\u00f3nov\u00e1 \u0161pecifick\u00e1 enol\u00e1za (NSE) alebo tie\u017e \u03b3enol\u00e1za, sa vyskytuj\u00fa vo vysok\u00fdch koncentr\u00e1ci\u00e1ch v neur\u00f3noch a neuroendokrinn\u00fdch bunk\u00e1ch alebo v tumoroch z nich vzniknut\u00fdch(13).<\/p>\n

Hodnoty NSE stanovujeme met\u00f3dou ECLIA pomocou analyz\u00e1tora cobas 8000 modul e 801.<\/p>\n

Odber treba realizova\u0165 do \u0161tandardnej biochemickej sk\u00famavky so separa\u010dn\u00fdm g\u00e9lom. Referen\u010dn\u00e9 hodnoty s\u00fa u oboch pohlav\u00ed 0 <\/strong>\u2013 16,3 \u03bcg\/l<\/strong>.<\/p>\n

Medzi interferencie, ktor\u00e9 ovplyv\u0148uj\u00fa hodnotu NSE, patr\u00ed hemol\u00fdza s\u00e9ra.<\/p>\n

NSE sa pou\u017e\u00edva ako imunohistochemick\u00fd a s\u00e9rov\u00fd marker, m\u00f4\u017ee sl\u00fa\u017ei\u0165 aj ako prediktor odpovede na lie\u010dbu. Nebol pre- uk\u00e1zan\u00fd vz\u0165ah medzi rozsahom n\u00e1doru a stup\u0148om zv\u00fd\u0161enej hladiny NSE, na rozdiel od s\u00e9rov\u00e9ho chromogran\u00ednu A (CgA), kde tak\u00fdto vz\u0165ah bol preuk\u00e1zan\u00fd. Tieto rozdiely CgA a NSE sa vysvet\u013euj\u00fa odli\u0161nou intracelul\u00e1rnou lokaliz\u00e1ciou. CgA je lokalizovan\u00fd v neurosekre\u010dn\u00fdch granul\u00e1ch a NSE je cytoplazmatick\u00fd enz\u00fdm. Preto elev\u00e1cia NSE sa objavuje pri poru\u0161enej integrite bunkovej membr\u00e1ny, zv\u00fd\u0161en\u00e9 hodnoty NSE treba preto o\u010dak\u00e1va\u0165 sk\u00f4r pri agres\u00edvnej\u0161\u00edch, r\u00fdchlo rast\u00facich a menej diferencovan\u00fdch form\u00e1ch NET, ktor\u00e9 \u010dasto podliehaj\u00fa rozpadu<\/p>\n

buniek a nekr\u00f3zam. Falo\u0161ne vy\u0161\u0161ie hodnoty b\u00fdvaj\u00fa pri ren\u00e1l- nej insuficiencii, pri p\u013e\u00facnych a pe\u010de\u0148ov\u00fdch ochoreniach. Pre diagnostiku NET v\u0161ak enz\u00fdm nevykazuje vysok\u00fd stupe\u0148 diag- nostickej presnosti, a preto sa vyu\u017e\u00edvaj\u00fa z onkomarkerov iba CgA a 5-HIAA(11).<\/p>\n

 <\/p>\n

Chromogran\u00edn A<\/h3>\n

Chromogran\u00edn A (CgA) je kysl\u00e1 bielkovina zlo\u017een\u00e1 zo 439 aminokysel\u00edn s molekulovou hmotnos\u0165ou 48 kDa. Je produkovan\u00fd a secernovan\u00fd endokrinn\u00fdmi a neuroendokrinn\u00fdmi bunkami spolu s peptidov\u00fdmi horm\u00f3nmi a neurotransmitermi, predov\u0161etk\u00fdm so s\u00e9roton\u00ednom a s glukag\u00f3nmi. CgA je s\u00fa\u010das\u0165ou mnoh\u00fdch intracelul\u00e1rnych a extracelul\u00e1rnych procesov. Je lokalizovan\u00fd v denzn\u00fdch sekre\u010dn\u00fdch granul\u00e1ch skladuj\u00facich peptidov\u00e9 horm\u00f3ny a vo vezikul\u00e1ch obsahuj\u00facich katecholam\u00edny. Nach\u00e1dza sa v neur\u00f3noch, v CNS a perif\u00e9rnych sympatick\u00fdch neur\u00f3noch. In\u00e9 org\u00e1ny bohat\u00e9 na CgA s\u00fa napr. pri\u0161t\u00edtne telieska, p\u013e\u00faca, exokrinn\u00e9 bunky pankreasu, bunky produkuj\u00face inzul\u00edn a glukag\u00f3n. Hlavn\u00fd zdroj sekr\u00e9cie CgA je dre\u0148 nadobli\u010diek(11).<\/p>\n

Hodnoty CgA stanovujeme met\u00f3dou ELISA pomocou analyz\u00e1tora Dynex DSX.<\/p>\n

Odber treba realizova\u0165 do \u0161tandardnej biochemickej sk\u00famavky so separa\u010dn\u00fdm g\u00e9lom. Referen\u010dn\u00e9 hodnoty s\u00fa u oboch pohlav\u00ed 0 <\/strong>\u2013 100 \u03bcg\/l<\/strong>.<\/p>\n

Stanovenie hodn\u00f4t CgA ako neuroendokrinn\u00e9ho s\u00e9rov\u00e9ho markera sa vyu\u017e\u00edva v diagnostike, v hodnoten\u00ed v\u00fdvoja ochorenia a odpovedi na lie\u010dbu. Pri v\u00e4\u010d\u0161ine n\u00e1dorov produkuj\u00facich CgA s\u00fa hladiny cirkuluj\u00faceho peptidu v\u00fdrazne nad hranicu normy a v\u00fdskyt falo\u0161ne pozit\u00edvnych a falo\u0161ne negat\u00edvnych v\u00fdsledkov neb\u00fdva \u010dast\u00fd. Naj\u010dastej\u0161\u00edm d\u00f4vodom falo\u0161ne pozit\u00edvnych n\u00e1lezov je ren\u00e1lna insuficiencia. Senzitivita CgA je pri neuroendokrinn\u00fdch tumoroch 70 \u2013 95 % a \u0161pecificita 70 \u2013 80 %. Vy\u0161etrenie je najpresnej\u0161ie pri n\u00e1doroch s intenz\u00edvnou sekre\u010dnou aktivitou, hlavne pri metast\u00e1zuj\u00facich midgut karcinoidoch a pri tumoroch pankreasu(11) (tabu\u013eka 5)<\/em><\/strong>.<\/p>\n

Existuje priama korel\u00e1cia medzi celkovou hmotnos\u0165ou n\u00e1doru a plazmatickou hladinou CgA. Taktie\u017e existuje vz\u0165ah k histologick\u00e9mu typu, kde najvy\u0161\u0161ie hodnoty exprimuje karcinoid, a to ston\u00e1sobne zv\u00fd\u0161en\u00e9 oproti norme. Vysok\u00e1 hladina CgA je nez\u00e1visl\u00fdm prognostick\u00fdm faktorom zlej progn\u00f3zy pri pokro\u010dil\u00fdch stavoch. Pri diagnostike a stanoven\u00ed hladiny CgA treba myslie\u0165 na faktory \u2013 interferencie sp\u00f4sobuj\u00face falo\u0161n\u00e9 zv\u00fd\u0161enie hladiny CgA. Mierne zv\u00fd\u0161enie bolo zisten\u00e9 u \u017eien v postmenopauz\u00e1lnom obdob\u00ed, hlavne v r\u00e1mci zv\u00fd\u0161enia gonadotrop\u00ednov. Vy\u0161\u0161ie hladiny CgA b\u00fdvaj\u00fa aj u zdrav\u00fdch tehotn\u00fdch \u017eien, kde CgA je produkovan\u00fd placentou. R\u00fdchly vzostup hladiny CgA sp\u00f4sob\u00ed taktie\u017e lie\u010dba n\u00edzkymi d\u00e1vkami omeprazolu. Falo\u0161ne pozit\u00edvne hodnoty CgA sa vyskytuj\u00fa tie\u017e u chor\u00fdch so z\u00e1palov\u00fdmi ochoreniami \u010driev, s atrofickou gastrit\u00eddou, s hepat\u00e1lnou a ren\u00e1lnou insuficienciou(11).<\/p>\n

 <\/p>\n

Z\u00e1ver<\/h3>\n

Karcinoidy patria do skupiny neuroendokrinn\u00fdch tumorov (NET) so \u0161irokou biologickou a klinickou charakteristikou a s relat\u00edvne n\u00edzkou incidenciou. Najvy\u0161\u0161\u00ed v\u00fdskyt karcinoidov je v oblasti gastrointestin\u00e1lneho traktu, a to hlavne v tenkom \u010dreve, v rekte a v \u017eal\u00fadku. Klinick\u00e9 prejavy n\u00e1doru z\u00e1visia od jeho prim\u00e1rnej lokaliz\u00e1cie a endokrinnej aktivity. Medzi naj\u010dastej\u0161ie prejavy patr\u00ed ka\u0161e\u013e, du\u0161nos\u0165, dyspepsia, abdomin\u00e1lne bolesti, obstip\u00e1cia, hna\u010dka. Vzh\u013eadom na to, \u017ee karcinoidy patria medzi endokrinne akt\u00edvne n\u00e1dory a produkuj\u00fa r\u00f4zne spektrum hormon\u00e1lne akt\u00edvnych substanci\u00ed, ve\u013emi d\u00f4le\u017eit\u00fa \u00falohu hr\u00e1 laborat\u00f3rna diagnostika dan\u00fdch parametrov. Medzi naj\u010dastej\u0161ie hormon\u00e1lne akt\u00edvne l\u00e1tky, ktor\u00fdch hodnotu stanovujeme, patr\u00ed s\u00e9roton\u00edn, NSE, CgA v s\u00e9re a 5-HIAA v mo\u010di. \u0160pecificita a senzitivita dan\u00fdch markerov s\u00fa ve\u013emi vysok\u00e9, pri niektor\u00fdch typoch NET-ov a karcinoidov skoro 100 %, a preto ve\u013emi potrebn\u00e1 pri v\u010dasnej diagnostike dan\u00fdch n\u00e1dorov.<\/p>\n

 <\/p>\n

Zoznam skratiek:<\/h3>\n

5-HIAA <\/strong>\u2013 kyselina 5-hydroxyindoloctov\u00e1 ACTH <\/strong>\u2013 adrenokortikotropn\u00fd horm\u00f3n CgA <\/strong>\u2013 chromogran\u00edn A<\/p>\n

CNS <\/strong>\u2013 centr\u00e1lny nervov\u00fd syst\u00e9m<\/p>\n

EC <\/strong>\u2013 enterochromafinn\u00e9 bunky<\/p>\n

ECLIA <\/strong>\u2013 ElectroChemiLuminiscen\u010dn\u00e1 Imuno Anal\u00fdza<\/p>\n

ELISA <\/strong>\u2013 Enzyme-linked immunosorbent assay<\/p>\n

GIT <\/strong>\u2013 gastrointestin\u00e1lny trakt<\/p>\n

HCl <\/strong>\u2013 kyselina chlorovod\u00edkov\u00e1<\/p>\n

HPLC <\/strong>\u2013 (High Performance Liquid Chromatography) \u2013 vysoko\u00fa\u010dinn\u00e1 kvapalinov\u00e1 chromatografia<\/p>\n

NET <\/strong>\u2013 neuroendokrinn\u00e9 tumory<\/p>\n

NSE <\/strong>\u2013 neur\u00f3nov\u00e1 \u0161pecifick\u00e1 enol\u00e1za<\/p>\n

VIP <\/strong>\u2013 vazoakt\u00edvny intestin\u00e1lny peptid<\/p>\n

 <\/p>\n

LITERAT\u00daRA<\/strong><\/p>\n

    \n
  1. Barkmanov\u00e1 Karcinoidy. Onkologie 2009; 3(6): 336-342.<\/li>\n
  2. Cemp\u00edrkov\u00e1 V, Havr\u00e1nek P. Karcinoid. Vnit\u0159 L\u00e9k 2005; 51(9): 938-939.<\/li>\n
  3. Petru\u017eelka Karcinoid. Maxdorf 2003; 3-6.<\/li>\n
  4. Babovic-Vuksanovic D, Constantinou CL, Rubin J, et Familial occurrence of carcinoid tumors and association with other malignant neoplasms. Cancer Epidemiology, Biomarkers and Prevention 1999; 8(8): 715-719.<\/li>\n
  5. Williams ED, Sandler The classification of carcinoid tumors. The Lancet 1963; 281(1): 238-239.<\/li>\n
  6. Papotti M, Cassoni P, Volante M, et Ghrelin \u2013 Producing Endocrine Tumours of the Stomach and Intestine. The Journal of Endocrinology and Metabolism 2001; 86(10): 5052-5059.<\/li>\n
  7. Louthan Neuroendokrinn\u00ed n\u00e1dory. Klinick\u00e9 pohledy. Praha: Grada 2005; 344 s. ISBN 80-2471-16-21.<\/li>\n
  8. Sweeney JF, Rosemurgy Carcinoid Tumors of the Gut. Cancer Control Journal 1997; 4(1): 18-24.<\/li>\n
  9. Ki\u0148ov\u00e1 S, Kore\u0148 Neuroendokrinn\u00e9 n\u00e1dory v ambulancii praktick\u00e9ho lek\u00e1ra. Via practica 2014; 11(3-4): 118-121.<\/li>\n
  10. Talafa V, Pastucha D, Zeman K, a Karcinoid a jeho kardi\u00e1ln\u00ed manifestace. Vnit\u0159 L\u00e9k 2012; 58(11): 867-870.<\/li>\n
  11. Louthan Diagnostika neuroendokrinn\u00edch n\u00e1dor\u016f. Neuroendokrinn\u00ed n\u00e1dory 2012; 1-16.<\/li>\n
  12. Ki\u0148ov\u00e1 Neuroendokrinn\u00e9 tumory z poh\u013eadu internistu a endokrinol\u00f3ga. Onkol\u00f3gia 2011; 6(4): 194-198.<\/li>\n
  13. https:\/\/pimeservices.roche.com\/eLD_SF\/cz\/cs\/Documents\/GetDocument?documentId=9e848582-ff02-e611-e396-00215a9b3428<\/li>\n<\/ol>\n

     <\/p>\n

     <\/p>\n","protected":false},"excerpt":{"rendered":"

    *All tables, charts, graphs and pictures that are featured in this article can be found in the .pdf attachment at the end of the paper.   \u00davod Karcinoidy predstavuj\u00fa svojr\u00e1zny typ n\u00e1dorov, ktor\u00e9 sa \u0161trukt\u00farou, histologicky aj biologick\u00fdm spr\u00e1van\u00edm l\u00ed\u0161ia od be\u017en\u00fdch epitelov\u00fdch n\u00e1dorov GIT-u. Patria medzi naj\u010dastej\u0161ie sa vyskytuj\u00face tumory zo skupiny neuroendokrinn\u00fdch n\u00e1dorov<\/p>\n","protected":false},"author":7,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_mi_skip_tracking":false,"footnotes":""},"categories":[289],"tags":[1444,1449,1445,1447,1448],"class_list":["post-1972","post","type-post","status-publish","format-standard","hentry","category-biochemistry","tag-5-hiaa-en","tag-carcinoid","tag-cga-en","tag-nse-en","tag-serotonin-en","typ_clanku-review-article"],"acf":{"abstrakt":"

    Carcinoids are quite rare tumours. They belong to the group of neuroendocrine tumours, which originate from neuroendocrine tissue and have some common characteristics. They grow very slowly and are small. Therefore, they are often diagnosed in the late stage of the disease. In addition, there are no specific clinical signs, so to find a correct diagnosis may take months or even years. As they belong to the active neuroendocrine tumours and produce different hormonal active substances, laboratory diagnosis of these parameters is very important. To the most common hormonal active substances there belong parameters, which are analysed in our laboratory such as serotonin, NSE, CgA in serum and 5-HIAA in the urine. Specificity and sensitivity of these parameters are very high, in some cases of carcinoid around 100% and so their analysis is very important in the early diag- nosis of these tumours.<\/h4>\n

    Keywords: <\/strong>carcinoid, serotonin, NSE, CgA, 5-HIAA<\/p>\n","casopis":[{"ID":1893,"post_author":"7","post_date":"2020-05-05 11:32:54","post_date_gmt":"2020-05-05 09:32:54","post_content":"

      \r\n \t
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    • Molecular detection methods of mutations in the kinase domain of fusion gene bcr-abl1 in patients with chronic myelocyte leukemia<\/li>\r\n \t
    • The case report of toxoplasmic meningoencephalitis with fatal outcome in HIV patient<\/li>\r\n \t
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