HIRURŠKA TERAPIJA KARCINOMA ŠTITASTE ŽLEZDE
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1 Edukativni rad DOI: /PI HIRURŠKA TERAPIJA KARCINOMA ŠTITASTE ŽLEZDE Ivan Paunović Centar za endokrinu hirurgiju, KC Srbije; Medicinski fakultet, Univerzitet u Beogradu Autor za korespondenciju: Ivan Paunović Centar za endokrinu hirurgiju, KC Srbije Medicinski fakultet, Univerzitet u Beogradu Koste Todorovića br. 8, Dr Subotica br Beograd Srbija prof.paunovic@med.bg.ac.rs; Prof.Paunovic55@gmail.com Prevoditeljica za engleski jezik: Kalina Mladenović-Paunović Lektorica za B/H/S jezik: Irma Grebović Sažetak Cilj: Adekvatan pristup hirurškom lečenju karcinoma štitaste žlezde još uvek nije dovoljno razjašnjen. Uvod: Karcinomi štitaste žlezde su najčešći karcinomi endokrinih organa, ali retki u poređenju sa karcinomima drugih lokalizacija. Operacija, za razliku od karcinoma drugih lokalizacija, karcinoma štitaste žlezde je inicijalno najbolji način lečenja, što znači da je karcinom štitaste žlezde hirurško oboljenje. Histopatološka i klinička klasifikacija karcinoma štitaste žlezde kao i tip operacije i praćenje zavise od porekla ćelija štitaste žlezde iz kojih nastaje karcinom. Dobro diferentovani (papilarni i folikularni karcinom) (DTC) i slabo doferentovani (anaplastični karcinom) (ATC) su karcinomi štitaste žlezde folikularnog porekla (tireocita). Medularni karcinom štitaste žlezde (MTC) porekla je C (kalcitonin stvarajućih ćelija) ćelija štitaste žlezde koje se još uvek pogrešno nazivaju parafolikularne ćelije i pored toga što se C ćelije mogu naći i intrafolikularno. Metod: Analizirani su literaturni podaci i poređeni sa ličnim iskustvom autora, a u vezi sa adekvatnim hirurškim lečenjem različitih vrsta karcinoma štitaste žlezde. Diskusija: Diskusija vezana za adekvatno hirurško lečenje DTC traje već trideset godina, a prema autorovom mišljenju trajaće i narednih trideset godina. Na osnovu svog tridesetgodišnjeg iskustva, autor smatra da svakom pacijentu sa preoperativno potvrđenom dijagnozom DTC ili suspektnim DTC treba pristupiti individualno. Tip operacije treba da zavisi od intraoperativnog nalaza, godina starosti, prisustva ili odsustva cervikalne limfonodopatije kao i prisustva ili odsustva udaljenih metastaza. U poređenu sa Tumori štitnjače u kliničkoj praksi 85
2 Posebna izdanja ANUBiH CLXVII, OMN 48, str DTC, jasno je da je u slučaju MTC totalna tiroidektomija sa centralnom disekcijom operacija izbora kako za sporadični tako i za nasledni MTC. Dijagnoza ATC se na osnovu autorovog iskustva u regionu Zapadnog Balkana najčešće postavlja kasno, kada je bolest uznapredovala i kada je jedino moguće redukcija tumora u cilju deliberacije traheje. S obzirom da se na ovim prostorima ATC najčešće javlja kod pacijenata koji su dugo godina imali polinodoznu strumu, savetuje se praćenje ovih pacijenata i hitna operacija u slučaju potvrđenog ATC aspiracionom biopsijom tankom iglom. Zaključak: Endokrini hirurg treba da razume prirodu oboljenja organa koji operiše, a da u slučaju karcinoma štitaste žlezde ima jasnu ideju šta planirana operacija donosi pacijentu koga operiše. Preoperativna i intraoperativna evaluacija hirurga kao i sposobnost hirurga da razume posebnost karcinoma štitaste žlezde u poređenju sa karcinomima drugih lokalizacija su kamen temeljac uspešne operacije karcinoma štitaste žlezde. Ključne riječi: dobro diferentovani karcinom (DTC), medularni karcinom (MTC), anaplastični karcinom, štitasta žlezda Uvod Karcinomi štitaste žlezde su načešći karcinomi endokrinih organa, ali retki u poređenju sa karcinomima drugih lokalizacija (1). Za razliku od karcinoma drugih lokalizacija operativno lečenje karcinoma štitaste žlezde je primarno najbolji način lečenja, što znači da je karcinom štitaste žlezde hirurško oboljenje. U našoj sredini u poređenju sa razvijenijim zemljama, još uvek ne postoje adekvatne analize o učestalosti karcinoma štitaste žlezde. Retrospektivne analize vezane su najčešće za iskustvo jedne ustanove, tako u Centru za endokrinu hirurgiju Kliničkog Centra Srbije u Beogradu, koji je jedina ustanova na području zapadnog Balkana koja se isključivo bavi hirurškim lečenjem oboljenja endokrinih organa, u periodu od do operisano je 898 pacijenata zbog karcinoma štitaste žlezde (Tabela 1). Tabela 1. Distribucija operisanih zbog karcinoma štitaste žlezde prema pato-histološkoj dijagnozi u Centru za endokrinu hirurgiju KC Srbije u periodu godina PATO-HISTOLOŠKI TIP KARCINOMA ŠTITASTE ŽLEZDE PAPILARNI KARCINOM FOLIKULARNI- HÜRTHLE CELL KARCINOM MEDULARNI KARCINOM ANAPLASTIČNI KARCINOM UKUPNO Veliki broj operisanih u ovoj tercijalnoj zdravstvenoj ustanovi može se objasniti sve većom primenom ultrasonografskog pregleda štitaste žlezde, aspiracione biospije tankom iglom, genetskim skriningom u dijagnostici nodusa u štitastoj žlezdi, kao i znanjem i iskustvom hirurga Centra za endokrinu hirurgiju u selekciji pacijenata za operaciju. 86 Tumori štitnjače u kliničkoj praksi
3 Ivan Paunović: Hirurška terapija karcinoma štitaste žlezde Poreklo ćelija štitaste žlezde iz kojih nastaje karcinom uslovljava pato-histološku i kliničku klasifikaciju karcinoma štitaste žlezde kao i postoperativno praćenje i lečenje. Karcinomi štitaste žlezde porekla folikulskih ćelija klasifikuju se kao dobro diferentovani (papilarni i folikularni karcinom) (DTC) i nediferentovani (anaplastični karcinom)(1). Medularni karcinom tiroideje (MTC) nastaje iz C (kalcitonin sekretujućih ćelija) ćelija štitaste žlezde koje se još uvek pogrešno nazivaju parafolikulske ćelije iako se C ćelije mogu naći i intrafolikularno (2). Danas, kao posebni pato-histološki entitet karcinoma štitaste žlezde opisuje se i slabo diferentovani karcinom štitaste žlezde koji po svojim kliničkim, pato-histološkim i prognostičkim osobinama predstavlja most između diferentovanih i nediferentovanih karcinoma štitaste žlezde (3). Najveća je učestalost DTC-a (75-80%) i oni u velikom broju slučajeva imaju povoljnu prognozu (4,5,6), MTC obuhvata 10% a anaplastični (nediferentovani) manje od 10% karcinoma štitaste žlezde (7,8). Dijagnoza Karcinom štitaste žlezde se najčešće otkriva kao palpabilni nodus (čvor) prilikom pregleda vrata. Ultrasonografki pregled štitaste žlezde i aspiraciona biopsija tankom iglom (FNB) su danas najefikasnije dijagnostičke procedure u primarnoj proceni malignosti nodusa štitaste žlezde (9). Citološki nalaz dobijen FNB najjednostavnije se može klasifikovati kao: benigni, maligni, nedijagnostički i neadekvatan (10). Sve veća primena genetskog testiranja, moguća u našim uslovima, omogućava da se posebno kod MTC-a, a sve više i kod papilarnog karcinoma štitaste žlezde (PTC), bolest otkrije u pretkliničkoj fazi kada nije došlo do pojave tumora i načini preventivna (profilaktička) operacija (2). Lečenje karcinoma štitaste žlezde Adekvatno lečenje dobro diferentovanih karcinoma štitaste žlezde (DTC), medularnog (MTC) i anaplasticnog karcinoma štitaste žlezde razlikuje se i može se podeliti u tri faze. U prvoj fazi na osnovu intraoperativnog i definitivnog pato-histološkog nalaza određuje se TNM klasifikacija i stadijum bolesti. U drugoj fazi, posebno za DTC i MTC, pacijent se primenom scintigrafije celog tela radioaktivnim jodom 131(WBS J 131 ), 99 mtc DMSA(Dimercaptosuccinic Acid), ultrasonografskim pregledom, kompjuterizovanom tomografijom, određivanjem tireoglobulina i kalcitonina prati u cilju otkrivanja recidiva bolesti i/ili limfogenih i hematogenih metastaza i potom adekvatno leči. U trećoj fazi visoko rizični pacijenti se u planiranim vremenskim periodima kontrolišu radi otkrivanja recidiva bolesti i ovo praćenje traje i do 30 god. od primarne (inicijalne) operacije. Tumori štitnjače u kliničkoj praksi 87
4 Posebna izdanja ANUBiH CLXVII, OMN 48, str Praćenje pacijenta s karcinomom štitaste žlezde zahteva multidisciplinarni pristup u koji su uključeni specijalisti endokrine hirurgije, endokrinologije, nuklearne medicine, pato-histologije i onkologije. Pacijenti s karcinomom štitaste žlezde dele se u rizične grupe prema godinama starosti, veličini i proširenosti tumora, tipu operacije, postojanju regionalnih (cervikalnih) metastaza u limfne noduse, kao i prisutnim ili odsutnim udaljenim metastazama. Dobro diferentovani karcinom štitaste žlezde (DTC) Papilarni karcinom štitaste žlezde (PTC) PTC se u najvećem broju slučajeva klinički manifestuje kao solitarni nodus u štitastoj žlezdi ili kao nodus u okviru polinodozno izmenjene štitaste žlezde (6). PTC najčešće metastazira u limfne noduse vrata, ponekad najpre se uoče uvećani metastatski izmenjeni limfni nodusi na vratu, a potom se dijagnostikuje PTC. Manje od 5% pacijenata sa PTC-om na inicijalnoj operaciji ima udaljene metastaze, najčešće u pluća posebno u dečijem uzrastu (11). Folikularni karcinom (FTC) i Hürthle ov (HTC) karcinom štitaste žlezde Palpatorno mek, solitarni i inkapsulirani nodus najčešće su karakteristične kliničke osobine FTC-a. Javlja se češće u područjima sa smanjenim unosom joda u vodi i hrani. Ne postoji nasledna forma bolesti (12). Za razliku od PTC-a FTC retko metastazira limfogeno već hematogeno u kosti, pluća i centralni nervni sistem. HTC je za sada prema klasifikaciji Svetske zdravstvene organizacije podvarijanta FTC-a, čini 3-5% karcinoma štitaste žlezde, ima agresivnije biološko ponašanje u odnosu na FTC (13). Hirurško lečenje DTC-a Lečenje DTC je uvek hirurško, ali rasprava o adekvatnom obimu operacije DTC-a pogotovu kod pacijenata sa tumorom manjim od 1 cm, koji nije probio (infiltrisao) kapsulu tiroideje i bez potvrđenog postojanja cervikalne limfonodopatije traje poslednjih 30 godina, po našem mišljenju trajaće i narednih 30 godina. Pojedini hirurzi u ovom slučaju predlažu kao optimalnu operaciju hemitiroidektomiju, posebno za tumore manje od 1 cm (14,15), drugi (6) totalnu tiroidektomiju, a neki čak i totalnu tiroidektomiju sa profilaktičkom disekcijom centralne grupe limfnih nodusa sa argumentacijom da se na ovaj način smanjuje procenat recidiva PTC-a (16,17). Naše iskustvo je da svakom pacijentu kod koga je preoperativno potvrđen karcinom štitaste žlezde ili kod koga je postavljena sumnja na karcinom štitaste žlezde treba pristupiti individualno i samim tim tako planirati operaciju, a u zavisnosti od lokalnog nalaza, godina starosti, prisustva ili odsustva cervikalne limfonodopatije, 88 Tumori štitnjače u kliničkoj praksi
5 Ivan Paunović: Hirurška terapija karcinoma štitaste žlezde prisutnih ili odsutnih udaljenih metastaza. Najmanje totalna tiroidektomija je, u svakom slučaju, po našem mišljenju operacija izbora za hirurško lečenje DTC. Kada je načinjena operacija manja od totalne tiroidektomije, a postoji tzv. histološko iznenađenje (ex tempore biosijom nije dijagnostikovan karcinom štitaste žlezde) dok je na definitivnom pato-histološkom pregledu potvrđen karcinom štitaste žlezde, treba ordinirati l- thyroxin (LT 4 ) i posle tri meseca kompletirati totalnu tiroidektomiju. Najmanje totalna tiroidektomija kao optimalna metoda lečenja DTC-a je u visoko specijalizovanim hirurškim ustanovama, kao što je Centar za endokrinu hirurgiju KC Srbije, povezana sa jedne strane sa malim rizikom nastanka specifičnih postoperativnih komplikacija (hipoparatiroidizam, paraliza donjeg laringealnog nerva), a sa druge strane omogućava mnogo bolje praćenje pacijenata primenom scintigrafije celog tela radioaktivnin jodom 131(J 131 WBS) i određivanjem tireoglobulina (Tg) u svrhu otkrivanja recidiva karcinoma. U svakom slučaju, bez obzira koji tip operacije je načinjen (hemi ili totalna tiroidektomija), supresione doze LT 4 treba ordinirati s obzirom da je DTC kao i normalno tiroidno tkivo TSH (tireostimulišući hormon) senzitivno (18). Postoperativno praćenje i lečenje DTC Postoperativna adjuvantna terapija DTC J 131 moguća je samo kod onih pacijenata kod kojih je načinjena totalna tiroidektomija. Postoje autori (19) koji smatraju ovu terapiju obligatornom bez obzira na rizičnu grupu i rezultat preuzimanja J 131 i WBS. Drugi autori (20) su, što je i naš stav, za selektivniji pristup koji se sastoji u tome da je svim DTC pacijentima visoko rizične grupe potrebna ablativna doza J 131, dok DTC pacijentima nisko rizične grupe treba savetovati praćenje određivanjem Tg u pravilnim vremenskim intervalima i tek u slučaju povišenih vrednosti Tg-a primeniti ablativnu dozu J 131. Pacijentima s DTC iz nisko rizične grupe s posebnim pato-histoloskim varijantama DTC (insularni tip, slabo diferentovani tip, tip visokih ćelija, Hürthle -ov karcinom) potrebna je odmah postoperativno ablativna doza J 131. J 131 destruira normalno tiroidno tkivo, rezidualne ćelije DTC i prikazuje postojanje udaljenih metastaza. S obzirom da je štitasta žlezda jedini izvor Tg-a posle terapije J 131 povećava se senzitivnost određivanja Tg u detekciji rekurentnog ili rezidualnog DTC-a. Supresivna terapija DTC-a LT 4 je neophodna s obzirom da je DTC TSH senzitivan. Adekvatna terapija LT 4 podrazumeva da su vrednosti TSH između 0.1 i 0.4 miu/l. Vrednosti TSH u visoko rizičnih pacijenata kao i pacijenata s perzistentnom i/ili rekurentnom bolešću treba da budu veoma niske tj. manje od 0.1 miu/l ili nemerljive. Nisko rizični DTC pacijenti kao i oni koji se prate već duži niz godina i kod kojih nije potvrđeno postojanje perzistentne ili rekurentne bolesti treba da imaju vrednosti TSH između 0.5 i 1.0 miu/l. Evaluaciju vrednosti TSH i slobodnog T4 treba u prvoj godini posle operacije određivati svakih 8 nedelja, a potom tromesečno. Kod svih DTC pacijenata visoko rizične grupe treba načiniti WBS (18,19). Tumori štitnjače u kliničkoj praksi 89
6 Posebna izdanja ANUBiH CLXVII, OMN 48, str Adekvatno preuzimanje J 131 moguće je tek ako su vrednosti TSH preko 30 miu/l i postiže se ili prekidom terapije LT 4 4 do 6 nedelja ili primenom rekombinantnog ljudskog TSH (rhtsh) (18,19). U cilju praćenja i detekcije recidiva najbolje je odrediti Tg posle prekida terapije LT 4 ili posle WBS uz upotrebu rhtsh (18,19). Na dobijene vrednosti Tg-a može da utiče prisustvo anti Tg antitela tako da je i njihovo određivanje neophodno prevashodno u cilju tumačenja lažno niskih vrednosti Tg-a (18,19). Vrednosti Tg-a posle totalne tiroidektomije i terapije J 131 treba da budu manje od 1.0 miu/l ili nemerljive. Stepen proširenosti lokalnog recidiva ili prisustvo metastaza u limfnim nodusima vrata koji su dijagnostikovani WBS, Tg i UZ pregledom vrata određuje da li je potrebna reoperacija ili terapija J 131. Prema pojedinim autorima, a u cilju dugoročnog praćenja DTC pacijenta potrebno je jednom godišnje uraditi WBS, Tg i UZ pregled vrata kao i TSH i Tg (18). Naše je mišljenje da je TSH i Tg potrebno češće određivati, u cilju dugoročnog praćenja, najmanje jednom u 6 meseci pogotovu zbog toga što je u našim uslovima cena ovih analiza prihvatljiva. Lokalni recidiv u loži tiroideje ili velike meta promene na vratu treba svakako operisati i operaciju pažljivo planirati pogotovu ako je DTC pacijent primarno operisan u drugoj zdravstvenoj ustanovi. U slučaju udaljenih (hematogenih) metastaza treba primeniti terapiju J 131 ili transkutanu zračnu terpiju (21). Medularni karcinom štitaste žlezde (MTC) MTC nastaje iz C ćelija štitaste žlezde (2). Približno 75% MTC-a su sporadični, preostalih 25% su hereditarni po tipu autosomno-dominantnog nasleđivanja (Multipla endokrina neoplazija tip 2A, Multipla endokrina neoplazija tip 2B i u nasledni non-men MTC/FMTC/) (2,22). MTC je conditio sine qua non za sve navedene kliničke forme. Mulligan i sar. (23) kao i druge grupe istraživača (24,25) su godine, dokazali da su karakteristične mutacije jednog gena na hromozomu 10, ret proto onkogena, odgovorne za nasledni oblik MTC-a. Rutinska primena genetskog skrininga, posebno u razvijenim zemljama, smanjila je učestalost sporadične forme na 56%. (26) Postojanje metastaza u limfnim nodusim kod obe kliničke forme MTC-a na operaciji značajno utiče na prognozu bolesti (2). MTC najčešće daje udaljene metastaze u kosti, pluća, jetru i centralni nervni sistem (2). U slučaju hereditarne forme MTC-a treba prvo operisati feohromocitom nadbubrega (2). Minimalni standard operacije MTC-a je totalna tiroidektomija i disekcija VI i VII grupe limfonodusa vrata. Postoperativne vrednosti kalcitonina treba odrediti 8-12 nedelja posle operacije. U slučaju da je na primarnoj operaciji postojala limfonodopatija u više grupa limfnih nodusa vrata tada se ne može očekivati da postoperativne vrednosti kalcitonina budu u opsegu normalnih (2). C ćelije nisu TSH senzitivne i zato MTC pacijenti postoperativno treba da dobiju supstitucionu, a ne supresionu terapiju LT 4 (2). 90 Tumori štitnjače u kliničkoj praksi
7 Ivan Paunović: Hirurška terapija karcinoma štitaste žlezde Postoje autori, a to je i naše mišljenje, koji svim MTC pacijentima posle primarne operacije savetuju preventivnu (profilaktičku) transkutanu zračnu terapiju regije vrata i medijastinuma (2,27), iako je MTC radiorezistentan tumor, osim za metastaze u kostima. Hemioterapija, za sada, nije efikasna u lečenju MTC-a. Danas postoje lekovi koji daju nadu da će lečenje recidiva MTC biti u budućnosti uspešno. Sada su u završnoj fazi ispitivanja: Vandetanib mali molekul inhibitor VEGF (Vascular endothelial growth factor), PDGF ( platelet-derived growth factor) i EGF (epidermal growth factor), kao i XL-184 mali molukalrni inhibitor RET (RET proto-oncogene), MET (MET proto-oncogene, receptor tyrosine kinase ), VEGF (Vascular endothelial growth factor) i KIT (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog) (28,29). Anaplasticni karcinom štitaste žlezde (ATC) ATC po svom biološkom potencijalu predstavlja jedan od najmalignijih tumora, karakterišu ga nediferentovane ćelije i ima sklonost da brzo raste i urasta u okolne vitalne strukture vrata (30). Klinički se mainfestuje kao veoma čvrst tumor, nepokretan prilikom akta gutanja i sa prisutnim intratumorskim poljima nekroze i krvavljenja (30). ATC se najčešće javlja u osoba starijih od 65 godina. U našim uslovima, dijagnoza ATC-a se postavlja kasno kada radikalno operativno lečenje nije moguće, kada tumor obuhvata vrat kao kragna. Operacija je u ovim slučajevima neophodna samo u cilju deliberacije traheje tj. disajnog puta. Pokušaji radikalnog hirurškog lečenja (resekcija traheje, ezofagusa) ovih pacijenata povezani su sa visokim postoperativnim mortalitetom (31). Preživljavanje ATC pacijenata poboljšava se primenom transkutane zračne terapije u kombinaciji sa hemioterapijom. Nadu da će ATC, jedan od najmalignijih tumora čoveka, moći u budućnosti da se leči, daju lekovi koji su sada u III fazi kliničkih ispitivanja: Carboplatinum/Taxol +/- Combretastatin, Avastin + Doxorubicin, Axitinib (AG013736), itd...(32) S obzirom da se ATC najčešće javlja kod pacijenata koji su dugo godina imali polinodoznu strumu najbolji način lečenja ovog tumora po našem mišljenju je stalna kontrola ovih pacijenata od strane hirurga i hitna operaciju u slučaju da se FNB biopsijom postavi dijagnoza ATC-a. Zaključak Od samih početaka endokrine hirurgije do današnjih dana znanje, iskustvo i operativna veština hirurga određivali su ishod lečenja. Razvoj lokalizacionih i funkcionalnih dijagnostičkih metoda omogućio nam je prikaz morfoloških promena unutar žlezde i praćenje poremećaja njene funkcije. Razvojem imunohistohemije i genetike dobili smo mogućnost identifikacije hormona, markera različite prirode i gena čime je dalje unapređeno razumevanje bolesti endokrinih organa. Međutim, preoperativna Tumori štitnjače u kliničkoj praksi 91
8 Posebna izdanja ANUBiH CLXVII, OMN 48, str i intraoperativna procena hirurga i sposobnost hirurga da razume posebnosti karcinoma žlezde odnosu na karcinome drugih lokalizacija još uvek čine osnovu uspeha hirurškog lečenja. Literatura 1. Živaljević V, Paunović I, Diklić A, Krgović K, Živić R, Kažić M, Kalezić N, Božić V, Tatić S, Havelka M. Klasifikacija, stepenovanie, prognostički faktori i faktori rizika kod karcinoma štitaste žlezde. Acta Chirurgica Iugoslavica 2003,50(3): Paunovic I. Hirurške, pato-histološke i imunohistohemijske karakteristike medularnog karcinoma štitaste žlezde. Doktorska disertacija. Medicinski fakultet u Beogradu; Marco V, Paola C, Yuri N, Atsuhiko S, Kennichi K, Ryohei K. et al. Poorly Differentiated Thyroid Carcinoma: The Turin Proposal for the Use of Uniform Diagnostic Criteria and an Algorithmic Diagnostic Approach. Am J Clin Pathol 2007;31(8): LiVolsi VA. Papillary neoplasms of the thyroid.pathologic and prognostic features. Am J Clin Pathol 1992;(97): Mazzaferi EYR. Papillary thyroid carcinoma: a 10-year follow-up report of the impact of therapy in 576 patients. Am J Med 1981;(70): Krgović K, Paunović I, Diklić A, Živaljević V, Tatić S, Havelka M, Todorović-Kažić M, Kalezić N, Božić V, Papilarni karcinom štitaste žlezde. Acta Chirurgica Iugoslavica 2003;50(3): Paunović I, Diklić A, Krgović K, Živaljević V, Tatić S,Havelka M, Kalezić N, Todorović- Kažić M, Božić V, Medularni karcinom štitaste žlezde (sporadični, familijarni). Acta Chirurgica Iugoslavica 2003;50(3): Živaljević V, Diklić A, Paunović I, Krgović K, Živić R, Kažić M, Kalezić N, Božić V, Tatić S, Havelka M, Anaplastični karcinom štitaste žlezde. Acta Chirurgica Iugoslavica 2003;50(3): Paunović I, Diklić A,Krgović K,Živaljević V,Tatić S,Havelka M,Kalezić N,Todorović- Kažić M,Božić V. Racionalna dijagnoza i hirurško lečenje solitarnog nodusa štitaste žlezde. Acta Chirurgica Iugoslavica 2003;50(3): Busseniers EA, Silver AS. Fine-needle Aspiration Cytology of the Thyroid. Oertli D, Udelsman R, editors. Surgery of the Thyroid and Parathyroid Glands. Berlin Heidelberg NewYork: Springer; p Brink J, vanheerden AJ, Brzan M, Salomao RD, Farley RD, Grant SC. et al. Papillary thyroid cancer with pulmonary metastases in children: Long-term prognosis.surgery 2000;128(6): Krgović K, Paunović I, Diklić A, Živaljević V, Tatić S, Havelka M, Todorović-Kažić M, Kalezić N, Božić V, Folikularni karcinom štitaste žlezde. Acta Chirurgica Iugoslavica 2003;50(3): Paunovic I, Krgovic K, Tatic S, Diklic A, Zivaljevic V, Kalezic N, Havelka M. Surgery for thyroid Hurthle cell tumours-a single institution experience. European Journal of Surgical Oncology 2006;32(4): Hay ID, Grant CS, Bergstralh EJ, et al. Unilateral total lobectomy: is it sufficient surgical treatment for patients with AMES low-risk papillary thyroid carcinoma? Surgery 1998;124 (6): Tumori štitnjače u kliničkoj praksi
9 Ivan Paunović: Hirurška terapija karcinoma štitaste žlezde 15. Dralle H, Musholt JT, Schabram J, Steinmüller T, Frilling A, Simon D et al. German Association of Endocrine Surgeons practice guideline for the surgical management of malignant thyroid tumors. Langenbecks Arch Surg 2013; (398): Barczynski M, Konturek A, Stopa M, Nowak W. Prophylactic central neck dissection for papillary thyroid cancer. Br J Surg 2013; 100(3): Sancho JJ, Lennard TW, Paunovic I, Triponez F, Sitges-Serra A. Prophylactic central neck disection in papillary thyroid cancer: a consensus report of the European Society of Endocrine Surgeons (ESES).Langenbecks Arch Surg 2014; 399(2): Sipos AJ, Mazzaferri LE. Papillary thyroid cancer. Gregory W.Randolph editor, Surgery of thyroid and parathyroid glands, 2nd edition. Philadelphia: Elsevier Saunders:2013.p Sawka AM, Brierley JD, Tsang RW et al. An updated systematic review and commentary examining the effectiveness of radioactive iodine remnant ablation in well-differentiated thyroid cancer. Endocrinol Metab Clin North Am 2008;( 37): Lundgren CI, Hall P, Dickman PW, et al. Influence of surgical and postoperative treatment on survival in differentiated thyroid cancer. Br J Surg 2007; (94): Chow SM et al. Local and regional control in patients with papillary thyroid carcinoma: specific indications of external radiotherapy and radioactive iodine according to T and N categories in AJCC 6th edition. Endocr Relat Cancer 2006; 13(4): Moley FJ. Sporadic medullary thyroid cancer. Gregory W.Randolph editor, Surgery of thyroid and parathyroid glands, 2nd edition. Philadelphia: Elsevier Saunders:2013.p Mulligan LM, Kwok JBJ, Healey CS et al. Germline mutations of the ret protooncogene in multiple endocrine neoplasia type 2A.Nature 1993; (363): Donis-Keller H, Dou S, Chi D et al. Mutations in the ret protooncogene are associated with MEN 2A and FMTC.Human Mol Genet 1993; (2): Hofstra RMW, Landsvater RM, Ceccherini I et al. A mutation in the ret proto-oncogene associated with multiple endocrine neoplasia type 2B and sporadic medullary thyroid carcinoma.nature 1994; (367): Kebebew E, Ituarte PH, Siperstein AE et al. Medullary thyroid carcinoma:clinical cha racteristics,treatment,prognostic factors and a comparasion of staging systems. Cancer 2000;88(5): Brierley J, et al. Medullary thyroid cancer: analyses of survival and prognostic factors and the role of radiation therapy in local control.thyroid 1996; 6(4): Wells Jr SA et al. Vandetanib for the treatment of patients with locally advanced or metastatic hereditary medullary thyroid cancer. J Clin Oncol 2010; 28(5): Wedge SR. et al. ZD6474 inhibits vascular endothelial growth factor signaling, angiogenesis, and tumor growth following oral administration. Cancer Res 2002;62(16): Živaljević V, Diklić A, Paunović I, Krgović K, Živić R, Kažić M, Kalezić N, Božić V, Tatić S, Havelka M, Anaplastični karcinom štitaste žlezde. Acta Chirurgica Iugoslavica 2003;50(3): Machens A, Hinze R, Lautenschlager C, Thomusch O, Dunst J, Dralle H. Extended surgerz and early postoperative radiotherapy for undifferentiated thyroid carcinoma. Thyroid 2001;(11): Houvras Y, Shah HM. Medical treatment for metastatic thyroid cancer. Gregory W.Randolph editor, Surgery of thyroid and parathyroid glands, 2nd edition. Philadelphia: Elsevier Saunders:2013.p Tumori štitnjače u kliničkoj praksi 93
10 Posebna izdanja ANUBiH CLXVII, OMN 48, str SURGICAL MANAGEMENT OF THYROID GLAND CARCINOMA Abstract Aim: There is still no clear solution for appropriate surgical management of thyroid gland carcinoma. Background: Thyroid gland carcinomas are most frequent carcinomas of endocrine organs, but rare comparing to the carcinomas of other localizations. Unlike other carcinomas, surgical treatment of thyroid carcinomas is primarily the best way of treatment, which means that the thyroid carcinomas are surgical disease. The origin of the cells of the thyroid gland from which the cancer arises determinates histopathological and clinical classification of the thyroid gland carcinomas as well as treatment and follow-up. Well-differentiated (papillary and follicular carcinoma) (DTC) and undifferentiated (anaplastic carcinoma) (ATC) are thyroid carcinomas of the follicular origin. Medullary thyroid carcinoma (MTC) arises from the C (calcitonin producing cells) cells of the thyroid gland, which are still incorrectly referred as parafollicular cells even though that C cell can be found intrafolliculary. Methods: The published studies were analyzed and compared with author s personal experience in connection with surgical management of different types of thyroid gland carcinomas. Discussion: In the field of thyroid surgery for DTC discussion about appropriate type of surgery for DTC lasted previous thirty years and from the author opinion will last next thirty years. The author s thirty year experience in the field of thyroid surgery is that every patient either with preoperative confirmed DTC, or patient with suspicious DTC should be approached individually. Type of the operation should depend of the local findings, age, presence or absence of cervical lymphonodopathy and presence or absence of distant metastases. Compared to DTC, there is no doubt that total thyroidectomy with central node dissection is appropriate surgical procedure both for sporadic and hereditary MTC. From author s experience ATC diagnosis in the region of Western Balkans is often established lately, when only tumor reduction in order to deliberate trachea is possible. Since, in this area, the ATC is commonly found with coexistent multinodular goiter in author s opinion, continuous control of these patients and emergency operation in case of FNB biopsy diagnosed ATC are highly recommended. Conclusion: Endocrine surgeon must always have a clear idea about surgical approach to the patient with thyroid gland carcinoma. Preoperative and intraoperative evaluation of the surgeon and the surgeon s ability to understand the unique characteristic of thyroid gland carcinomas compared to carcinomas of other localizations are still the basis of the successful operation. Key words: well differentiated carcinoma (DTC), medullary carcinoma (MTC), anaplastic carcinoma (ATC), thyroid gland 94 Tumori štitnjače u kliničkoj praksi
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