UTJECAJ RATA NA OBOLIJEVANJE OD KARCINOMA
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1 2012; 7(1): 9 14 UDK: (497.6); (497.6) ISSN X Originalni nau~ni rad Rusmir Arslanagi}, 1 Selma Arslanagi}, 1 Naima Arslanagi} 2 UTJECAJ RATA NA OBOLIJEVANJE OD KARCINOMA Primljen/Received: god. Sa`etak: Cilj ovog istra`ivanja bio je ispitati kako su ratna de{avanja utjecala na pojavu karcinoma {titne `lijezde. Ovo je retrospektivno ispitivanje koje je obuhvatilo desetogodi{nji period istra`ivanja. Jedan petogodi{nji period obuhvatio je period nakon rata, period od 1. januara do 31. decembra godine, a drugi period je prijeratni period, period od 1. januara do 31. decembra godine. U istra`ivanju su kori{teni arhivirani podaci histopatolo{kih analiza tkivnih uzoraka {titne `lijezde Instituta za Patolo{ku anatomiju Medicinskog fakulteta u Sarajevu. Ovo istra`ivanje pokazalo je da je u postratnom periodu do{lo do porasta morbiditeta od karcinoma {titne `lijezde u odnosu na predratni period. Nakon rata do{lo je i do promjene u morbiditetu u odnosu na histopatolo{ki tip karcinoma {titnja~e. U predratnom periodu, najzastupljeniji histopatolo{ki tip karcinoma {titnja~e je folikularni karcinom, dok je u postratnom periodu papilarni karcinom najzastupljeniji. Karcinomi {titnja- ~e u postratnom periodu ~e{}e su verificirani u starijem dobnom uzrastu u odnosu na predratni su ~e{}e obolijevale od karcinoma {titnja~e u odnosu na mu- {karce, u oba analizirana perioda, ali je evidentan porast oboljelih mu{karaca od karcinoma {titnja~e u postratnom periodu, u odnosu na predratni period. Rezultati istra`ivanja upu}uju na mogu}u ulogu rata i ratnih zbivanja na izmjenu morbiditeta od karcinoma {titne `lijezde. Klju~ne rije~i: rat, karcinomi {titnja~e, dob i spol bolesnika. UVOD Agresija i rat, pored enormnog psihi~kog, a ~esto i enormnog fizi~kog stresa, uvijek imaju za posljedicu 1 Klinika za bolesti uha, grla i nosa, Klini~ki centar Univerziteta Sarajevo, BiH 2 Klinika za ko`ne i veneri~ne bolesti, Klini~ki centar Univerziteta Sarajevo, BiH Prihva}en/Accepted: god. ote`anu, lo{u ili nikakvu zdravstvenu za{titu, ote`anu, lo{u ili nikakvu mogu}nost dijagnostike i terapije oboljenja. ^etverogodi{nja agresija i rat u BiH imali su za posljedicu enormno stradanje i obolijevanje civilnog stanovni{tva, sa ote`anom ili nikakvom mogu}nosti dijagnostike i terapije oboljenja op}enito, pa tako i oboljenja {titne `lijezde. Zato je cilj ovog istra`ivanja bio ispitati kako su ratna de{avanja utjecala na pojavu karcinoma {titne `lijezde, na osnovu histopatolo{kih analiza tkivnih uzoraka {titne `lijezde. Podatke o utjecaju rata, u nama dostupnoj literaturi, na{li smo samo u istra`ivanjima autora iz Hrvatske (1). To je bio razlog vi{e da se odlu~imo na ovo istra`ivanje. MATERIJAL I METOD RADA Ovo retrospektivno ispitivanje, u kojem su kori- {teni arhivirani podaci histopatolo{kih analiza tkivnih uzoraka {titne `lijezde Instituta za Patolo{ku anatomiju Medicinskog fakulteta u Sarajevu, obuhvatilo je desetogodi{nji period istra`ivanja. Jedan petogodi{nji period obuhvatio je period nakon rata, period od 1. januara do 31. decembra godine. U tom periodu karcinom {titne `lijezde histopatolo{ki je potvr en kod ukupno 73 oboljele osobe i to kod 19 mu{karaca i 54 `ene. Srednja dob oboljelih je 51 godina. Najmla a oboljela osoba bila je djevoj~ica stara 13 godina, a najstarija osoba mu{karac star 74 godine. Drugi period je prijeratni period, istovremeno kontrolna skupina histopatolo{kih analiza, obuhvatio je period od 1. januara do 31. decembra godine. U tom periodu karcinom {titnja~e histopatolo{ki je potvr en ukupno kod 40 bolesnika i to kod 5 mu{karaca i 35 `ena. Srednja dob oboljelih bila je 45,9 godina. Najmla a oboljela osoba bila je `ena stara 19 godina, a najstarija oboljela osoba bila je `ena stara 69 godina.
2 10 Rusmir Arslanagi}, Selma Arslanagi}, Naima Arslanagi} Histopatolo{ke analize karcinoma {titne `lijezde, u postratnom periodu, analizirani su prema vrsti karcinoma, spolu, dobnom uzrastu i srednjim godinama oboljelih i upore eni sa istim takvim podacima prijeratnog perioda, kao kontrolnom grupom. STATISTI^KA ANALIZA Prikupljeni podaci dobiveni ovim istra`ivanjem su analizirani statisti~kim metodama. Svi podaci predstavljeni su tabelarno i grafi~ki. Osim grafikona strukture, kru`nih i {tapi}astih, kori{teni su i box-plot dijagrami kod prikaza parametara histopatolo{kih analiza za dva analizirana perioda. Za svaku kontinuiranu varijablu izra~unati su osnovni statisti~ki pokazatelji univarijantne analize. Statisti~ka obrada podataka ra ena je metodom deskriptivne statistike (aritmeti~ka sredina, standardna devijacija, standardna gre{ka aritmeti~ke sredine, raspon i koeficijent varijacije). Za svaku kvantitativnu, kontinuiranu varijablu procjenjen je i oblik distribucije. Vrijednost p < 0,05 je smatrana zna~ajnom. Statisti~ka zna~ajnost razlike u pojedina~nom broju histopatolo{kih analiza za petogodi{nje periode, je u zavisnosti od odre ene distribucije rezultata, testirana razli~ito. Kod normalnih distribucija testiranje je vr{eno Studentovim t-testom, a od neparametrijskih testova primjenjen je X 2 -test gdje je to bilo potrebno. Pri izra~unavanju X 2 testa u tablicama 2 x 2 koristili smo Yatesov test korekcije, dok smo kod testiranja malog broja frekvencija izvr{ili spajanje susjednih }elija da bi zadovoljili kriterije upotrebe ovog testa. Vrijednost p < 0,05 se smatrala zna~ajnom. REZULTATI ISTRA@IVANJA Najve}i procenat oboljelih od karcinoma {titne `lijezde, 37,5%, u predratnom periodu, je dobnog uzrasta od godine `ivota. U dobnom uzrastu od god. `ivota neoplazije {titnja~e potvr ene su kod 21,5% histopatolo{kih analiza {titnja~e. Papilarni karcinom u predratnom periodu naj~e- {}e je verificiran u dobnom uzrastu od godine `ivota, a folikularni karcinom u mla em dobnom uzrastu, od godine `ivota, kao i medularni i anaplasti~ni karcinomi. Na Grafikonu 1 prikazane su maligne neoplazije {titne `lijezde, prema dobnom uzrastu oboljelih i tipu karcinoma, u predratnom periodu. Najve}i procenat histopatolo{ki potvr enih neoplazija {titnja~e, 31,5%, u periodu izme u i god. verificiran je kod bolesnika dobnog uzrasta izme u godine starosti. U postratnom periodu i papilarni i folikularni karcinomi su naj~e{}e verificirani u dobnom uzrastu izme u 51. i 60. godine `ivota. Grafikon 1. Maligne neoplazije {titne `lijezde prema dobnom uzrastu i tipu karcinoma u periodu god. Maligne neoplazije {titnja~e, prema dobnom uzrastu i tipu karcinoma, u postratnom periodu, prikazane su na Grafikonu 2. Grafikon 2. Maligne neoplazije {titne `lijezde prema dobnom uzrastu i tipu karcinoma u periodu godine Analiza frekvencije obolijevanja od malignih neoplazija {titne `lijezde prema dobnom uzrastu u predratnom i postratnom periodu prikazana je na Grafikonu 3. U oba perioda najve}i broj histopatolo{ki verificiranih malignih neoplazija bio je kod oboljelih dobnog uzrasta od 51. do 60. godine `ivota. Grafikon 3. Broj malignih neoplazija {titne `lijezde prema dobnom uzrastu: u odnosu na godine Srednja dob obolijevanja od malignih neoplazija {titnja~e u periodu od do godine bila je 45,9 godina. Najmla a bolesnica imala je 19 godina, a najstarija bolesnica 69 godina. U postratnom periodu ve}ina bolesnika obolijevala je u starijem `ivotnom dobu. Srednja dob obolijevanja od neoplazija {titnja~e u periodu od godine, bila je 51 godina.
3 UTJECAJ RATA NA OBOLIJEVANJE OD KARCINOMA 11 Slika 1 pokazuje box plotove rezultata statisti~ke analize srednjih vrijednosti godina obolijevanja od malignih neoplazija {titne `lijezde u periodu od god. i perioda od godine. Analizom svakog pojedinog karcinoma, u predratnom periodu, dokazali smo da su `ene vi{e od pet puta ~e{}e obolijevale od papilarnog karcinoma, ~etiri puta ~e{}e od follikularnog karcinoma i da su samo `ene obolijevale od medularnog i anaplasti~nog karcinoma. Histopatolo{ka klasifikacija karcinoma {titnja~e prema spolu u predratnom periodu prikazana je na Grafikonu 4. Slika 1. Statisti~ka analiza srednjih vrijednosti godina oboljelih od malignih neoplazija {titne `lijezde A Srednje vrijednosti godina oboljelih od malignih neoplazija u periodu B Srednje vrijednosti godina oboljelih od malignih neoplazija u periodu Statisti~kom analizom srednjih godina oboljelih od papilarnog karcinoma, u dva posmatrana perioda, nismo dokazali statisti~ki signifikantnu razliku. Rezultati statisti~ke analize prikazani su u Tabeli 1. Statisti~kom analizom srednjih godina obolijevanja od folikularnog karcinoma u dva ispitivana perioda, dokazali smo da su u postratnom periodu oboljeli od folikularnog karcinoma {titnja~e bili statisti~ki signifikantno starijeg `ivotnog doba. Rezultati statisti~ke analize oboljelih od folikularnog karcinoma prikazani su u Tabeli su sedam puta ~e{}e obolijevale od karcinoma {titnja~e u odnosu na mu{karce u predratnom periodu. Grafikon 4. Histopatološka klasifikacija karcinoma {titne `lijezde prema spolu u periodu: godine U postratnom periodu `ene su 2,7 puta ~e{}e obolijevale od karcinoma {titnja~e u odnosu na mu{karce. U postratnom periodu `ene 3,5 puta ~e{}e obolijevaju od papilarnog karcinoma, 2,2 puta ~e{}e od folikularnog karcinoma, od medularnog karcinoma podjednako su obolijevali mu{karci i `ene, a od anaplasti~nog karcinoma isklju~ivo su obolijevale `ene. B }elijski limfom podjednako je prisutan, kod jednog mu{karca i jedne `ene. Histopatolo{ka klasifikacija malignih neoplazija {titnja~e, prema spolu, u postratnom periodu, prikazana je na Grafikonu 5. Broj histopatolo{ki verificiranih malignih neoplazija {titnja~e signifikantno je ve}i u periodu od 1998 Vremenski period ispitivanja Xmin Xmax prosjek X 95%CI standardna devijacija (+/ ) medijana ,1 33,7 48, p > 0, ,7 43,2 52, r.n.s Tabela 1. Statisti~ka analiza srednjih vrijednosti godina oboljelih od papilarnih karcinoma {titne `lijezde Vremenski period ispitivanja Xmin Xmax prosjek X 95%CI standardna devijacija (+/ ) Tabela 2. Statisti ka analiza srednjih vrijednosti godina medijana signifikantnost signifikantnost ,6 41,3 51,7 9,9 50 p < 0, ,9 50,8 58,9 9,3 57 r.s
4 12 Rusmir Arslanagi}, Selma Arslanagi}, Naima Arslanagi} Grafikon 5. Histopatolo{ka klasifikacija karcinoma i limfoma {titne `lijezde prema spolu u periodu: godine godine u odnosu na predratni period od godine. Rezultati statisti~ke analize prikazani su na Grafikonu 6. Grafikon 6. Statisti~ka analiza broja oboljelih od malignih neoplazija {titne `lijezde: u odnosu na godinu DISKUSIJA Ovo je prva detaljna studija histopatolo{kih analiza karcinoma {titnja~e, na podru~ju BiH, koja analizira kretanje morbiditeta u predratnom periodu, neposredno pred rat, period od do godine u odnosu na period od do godine, period neposredno poslije rata. Najve}i broj histopatolo{ki potvr enih karcinoma {titne `lijezde, u oba analizirana perioda, bio je kod bolesnika dobnog uzrasta od godine `ivota. Ipak, u postratnom periodu karcinomi {titnja~e histopatolo- {ki su potvr eni kod bolesnika starijeg `ivotnog doba. Kod papilarnog karcinoma nije bilo signifikantne razlike u srednjim godinama obolijevanja u dva analizirana perioda. Oboljeli od folikularnog karcinoma u postratnom periodu bili su starije srednje `ivotne dobi u odnosu na predratni period. U postratnom periodu, kao i u predratnom periodu, `ene vi{e obolijevaju od karcinoma {titnja~e, ali je odnos ne{to umanjen, jer se pove}ao broj oboljelih mu- {karaca od karcinoma {titnja~e u postratnom periodu. Odnos oboljelih mu{karaca prema oboljelim `enama u postratnom periodu je 1 : 2,84. Podaci iz literature o ujecaju rata i ratnih stradanja na obolijevanje od karcinoma {titnja~e su veoma oskudni. U nama dostupnoj literaturi na{li smo sli~no ispitivanje u susjednoj Hrvatskoj. [imunovi} D. i sar. (1) u Hrvatskoj proveli su istra`ivanje o utjecaju rata na epidemiologiju karcinoma {titnja~e. Autori nisu na{li signifikantan porast incidencije karcinoma {titnja~e kada su poredili predratni sa poslijeratnim periodom, za razliku od na{ih istra`ivanja koja su pokazala signifikantno pove}anje morbiditeta od karcinoma {titne `lijezde u postratnom periodu. Rezultati istra`ivanja u Hrvatskoj sli~ni su na{im rezultatima o spolnoj zastupljenosti karcinoma {titnja~e. Naime, i oni su na{li da su `ene ~e{}e oboljevale od karcinoma {titnja~e i u predratnom i u postratnom periodu. U istra`ivanjima [imunovi}a D. i sar., vrijeme dijagnosticiranja karcinoma {titnja~e pomjeralo se prema starijem `ivotnom dobu, naro~ito u periodu poslije rata, {to autori tuma~e utjecajem ratnih de{avanja i konsekventnih lo{ih socioekonomskih uvjeta `ivota, ali autori ne isklju~uju i mogu}nost slu- ~ajne koincidencije. Za razliku od na{ih ispitivanja koja su pokazala da su karcinomi {titnja~e u postratnom periodu dijagnosticirani u starijem dobu, srednja dob obolijevanja bila je 51 godina, u odnosu na predratni period kada je bila 45,9 godina, statisti~kom analizom srednje `ivotne dobi oboljelih, autori iz Hrvatske su do{li do podataka da je srednja dob obolijevanja za sve tipove karcinoma pokazala tendenciju opadanja, odnosno, najve}i broj osoba su obolijevale u mla em `ivotnom dobu, osim za anaplasti~ni karcinom od kojeg su uglavnom obolijevale osobe starijeg `ivotnog doba. U istra`ivanjima [imunovi}a D. i sar. papilarni karcinom bio je naju~estaliji karcinom i u predratnom i u postratnom periodu, sa tendencijom rasta, za razliku od na{ih istra`ivanja koja su pokazala da je u predratnom periodu folikularni karcinom bio naju~estaliji karcinom, a u postratnom periodu naju~estaliji karcinom je papilarni karcinom. Za razliku od na{eg istra`ivanja, koje je dokazalo da je u BiH poslije rata do{lo do porasta obolijevanja od karcinoma {titnja~e, zaklju~ak istra`ivanja [imunovi}a i sar. jeste da u postratnom periodu u Hrvatskoj nije do{lo do porasta morbiditeta od karcinoma {titnja~e, ali su se karcinomi {titnja~e dijagnosticirali u vi{e uznapredovalim stadijima. U BiH do{lo je, u periodu poslije rata, do promjene u morbiditetu od pojedinih tipova karcinoma {titnja~e. U postratnom periodu papilarni karcinom je naju~estaliji me u neoplazijama {titnja~e i ovi podaci se sla`u sa podacima drugih autora, koji bilje`e porast obolijevanja od papilarnog karcinoma.
5 UTJECAJ RATA NA OBOLIJEVANJE OD KARCINOMA 13 Na{a istra`ivanja sli~na su istra`ivanjima do kojih su do{li Furlan J. i sar (2), Scheiden R. i sar. (3), Omur O. i sar. (4), Enwold L. i sar (5) i drugi autori koji su istra`ivali prisustvo malignih tumora u tkivu {titnja~e. Tako je u istra`ivanju koje su proveli Furlan J. i sar. (2), od 350 oboljelih od karcinoma {titnja~e, najzastupljeniji bio papilarni karcinom. Sli~no kao i u na{em istra`ivanju, koje je pokazalo da i u postratnom periodu `ene ~e{}e obolijevaju od karcinoma {titnja~e, i u istra`ivanju Furlan J. i sar., `ene su ~e{}e obolijevale. Srednja dob obolijevanja u istra`ivanju Furlan J. i sar. bila je 44 godine, {to je pribli`no srednjim godina oboljelih u na{em istra`ivanju u predratnom periodu. U studiji koja su proveli Scheiden R. i sar. (3) u Luksemburgu, na osnovu podataka prikupljenih u Nacionalnom registru za tumor, za period od godine papilarni karcinom bio je zastupljen sa 80%. I u njihovom istra`ivanju `ene su ~e{}e obolijevale od karcinoma {titnja~e. Srednja dob obolijevanja bila je 48,3 godine, a te godine su vi{e u odnosu na na{e istra`ivanje u predratnom periodu, i ne{to ni`e u odnosu na na{e istra- `ivanje u postratnom periodu. I ovi autori su na{li evidentan porast morbiditeta od papilarnog karcinoma. Me u brojnim autorima koji su na{li da je papilarni karcinom naj~e{}i karcinom {titnja~e je i Omur O. i sar. (4), zatim Envold L. i sar. (5). Envold L. i sar. (5), u periodu od godine, analizirali su pacijenta sa karcinomom {titnja~e. Papilarni karcinom je bio jedini histopatolo- {ki tip karcinoma {titnja~e koji je imao konstantan porast incidencije, naro~ito me u `enama. Izme u i godine, incidencija papilarog karcinoma pove}ana je skoro 100% kod `ena, a samo za 20 50% kod mu{karaca. Porasla je naro~ito incidencija manjih tumora, ali i tumora u uznapredovalom stadiju. U periodu od godine polovina broja papilarnih karcinoma bili su papilarni karcinomi manji ili jednako 1 cm, 30% karcinomi od 1,1 2 cm i 20% karcinomi ve}i od 2 cm. Me u bjelkinjama stepen pove}anja incidencije papilarnih karcinoma ve}ih od 5 cm bio je jednak obolijevanju od papilarnih karcinoma manjeg promjera. Hundhal Sa i sar. (6) analizom pacijenata sa karcinomima {titnja~e, kod 78% su na{li papilarni karcinom, kod 13% folikularni karcinom, medularni kod 4% i anaplasti~ni kod 2% pacijenata, {to je pribli- `no rezultatima na{ih istra`ivanja. I drugi autori, sli~no na{im istra`ivanjima, registruju porast morbiditeta od papilarnog karcinoma, kao na primer Jung KW i sar. u Koreji (7). Navedeni autori, u periodu od godine, na{li su kontinuirani porast incidencije karcinoma {titnja~e i kolorektalog karcinoma kod oba spola, a naro~ito kod `ena, dok smo mi u na{im istra`ivanjima na{li porast morbiditeta karcinoma {titne `lijezde kod mu{karaca, mada `ene u ukupnom morbiditetu ipak preovladavaju. Va`no je ista}i da podaci koji su dobiveni ovim istra`ivanjem, na osnovu histopatolo{kih analiza tkivnih preparata {titnja~e, ne moraju reflektovati stanje u op- }oj populaciji BiH. Mada, obzirom da su sve histopatolo{ke analize isklju~ivo sa teritorije BiH i da su do godine, svi histopatolo{ki nalazi sa podru~ja Federacije BiH uglavnom histopatolo{ki verificirani na Institutu za Patolo{ku anatomiju Medicinskog fakulteta u Sarajevu, ovi rezultati bi sa puno prava mogli reflektovati stanje u op}oj populaciji. ZAKLJU^AK U postratnom periodu do{lo je do porasta morbiditeta od karcinoma {titne `lijezde u odnosu na predratni period. Nakon rata do{lo je do promjene u morbiditetu u odnosu na histopatolo{ki tip karcinoma {titnja~e. U predratnom periodu, najzastupljeniji histopatolo- {ki tip karcinoma {titnja~e je folikularni karcinom, dok je u postratnom periodu papilarni karcinom najzastupljeniji. Karcinomi {titnja~e u postratnom periodu ~e{}e su verificirani u starijem dobnom uzrastu u odnosu na predratni ~e{}e obolijevaju od karcinoma {titnja~e u odnosu na mu{karce, ali je evidentan porast oboljelih mu- {karaca od karcinoma {titnja~e u postratnom periodu. U predratnom periodu karcinomi {titnja~e su sedam puta ~e{}e verificirani kod osoba `enskog spola. U postratnom periodu karcinomi {titnja~e su 2,84 puta ~e{}e verificiran kod `ena u odnosu na mu{karce. Summary EFFECTS OF WAR ON MORBIDITY OF THYROID CANCER Rusmir Arslanagi}, 1 Selma Arslanagi}, 1 Naima Arslanagi} 2 1 Clinic of Oto-Rhino-Laryngology, Clinical center University of Sarajevo, Bosnia and Herzegovina; 2 Dermatovenerology Clinic, Clinical center University of Sarajevo, Bosnia and Herzegovina The aim of this study was to examine how wartime events affected the occurrence of cancer of the thyroid gland. This is a retrospective trial, which included a ten-year period of research. A five-year period included a period after the war, the period from 1 st January 1998 th to 31 st December 2002 th and the second period of the prewar
6 14 Rusmir Arslanagi}, Selma Arslanagi}, Naima Arslanagi} period, the period from 1 st January 1987 th until 31 st December 1991 st year. The study used data archived histopathological analysis of tissue samples of the thyroid gland of the Institute of Pathological Anatomy, Medical Faculty in Sarajevo. This study showed that in the postwar period there was an increase in morbidity from cancer of the thyroid gland in relation to the pre-war period. After the war there was a change in morbidity compared to the histopathologic type of thyroid cancer. In the prewar period, the most common histopathologic type of cancer is follicular thyroid carcinoma, while in the postwar perodu papillary carcinoma of the most common. Thyroid cancers in the postwar period more often verified in the older age groups compared to pre-war period. Women are more often suffered from thyroid cancer compared to men in both periods analyzed, but there is an evident increase in men suffering from thyroid cancer in post-war period compared to pre-war period. Survey results indicate a possible role of war to change the morbidity of the thyroid gland carcinoma. Key words: war, thyroid cancer, age and sex of patients. LITERATURA 1. [imunovi} D, Cvjetko I, Gladi} V, et al. Possible effects of the war in Croatia on thyroid cancer epidemiology. Acta Clin Croat 2000; 39: Furlan J, Bedard Y, Rosen I, et al. Significance of Tumor Capsular Invasion in Well Differentiated Thyroid Carcinomas. American Surgeon 2007; 76(5): Scheiden R, Keips M, Bock C, et al. Thyroid cancer in Luxemburg: a national population-based data report ( ). BMC Cancer 2006; 6: Omur O, Ozcan Z, Yazici B, et al. Multiple primary tumor in differentiated thyroid carcinoma and relationship to thyroid cancer outcome. Endocrin J 2008; 52(2): Enewold L, Zhu K, Ron E, et al. Rising thyroid cancer incidence in the United States by demographic and tumor characteristics, Cancer Epidemiol Biomarkers Prev 2009; 18(3): Hundahl SA, Fleming ID, Fremgen AM, et al. A National Cancer Date Base report on cases of thyroid carcinoma treated in the U.S Cancer 1998; 83: Jung KW, Won YJ, Park S et al. Cancer statistics in Korea: incidence, mortality and survival in J Korean Med Sci 2009; 24: Correnspondence to/adresa za korenspodenciju Prof. dr Naima Arslanagi}, Medicinski fakultet Sarajevo prof.naima_arslanagicªyahoo.com
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