Malignant bone tumors are recognized as rare diseases following the already estimated incidence which is well known, with osteosarcoma as the most common bone tumor [1], [2]. Median incidence rate for malignant childhood tumors in Croatia is 163 new cases during period 1987–2014, age 0–19 according to Croatian National Cancer Registry (CNCR) data ([ Fig. 1 ]).

Maligne bolesti su jedan od vodecih uzroka smrti djece u Europi i Sjedinjenim Americkim Državama. Posljednjih desetak godina postignut je bitan napredak, kako u dijagnostici tako i njihovom lijecenju. Uvođenjem novih metoda lijecenja (nove kombinacije citostatika, zracenja, kirurskog zahvata, monoklonskih antitijela te transplantacije kostane srži) i u ovih je bolesnika danas moguce postici visoki postotak dugotrajnih remisija i izljecenja.

Maligne bolesti su jedan od najtežih problema suvremene medicine. Cesti su uzrok smrtnosti u djece do 14 godina života, te su na drugome mjestu iza nesretnih slucajeva. Maligne bolesti u djece cine hemoblastoze (leukemije i limfomi) i solidni tumori u približno podjednakom omjeru 50:50 %. Postoje brojne razlike između malignih bolesti u djece i onih u odraslih. Danas su pojedini tipovi malignih bolesti u djece (leukemije i solidni tumori) izljecivi, pa je iznimno važno malignu bolest rano prepoznati, dijagnosticirati i klasificirati, sto je preduvjet odabira ucinkovitih terapijskih protokola, a time i uspjeha terapije. Citologija se temelji na pretpostavci da svaki patoloski proces pa tako i tumorski ima svoje karakteristicne stanice pa se misljenje, a cesto i dijagnoza, donosi proucavanjem izgleda pojedinacnih stanica u nakupinama te međusobnog odnosa pojedinih stanicnih elemenata pregledom cijelog razmaza. Citodijagnostika je metoda pomocu koje se nastoji doci do dijagnoze proucavanjem morfologije pojedinih stanica u obojenim razmazima. Citodijagnostika ima velike prednosti u ranom otkrivanju i postavljanju dijagnoze, bilo hemoblastoza bilo solidnih tumora u djece. Razmazi dobiveni jednom od citodijagnostickih metoda mogu se upotrijebiti u analizi novih tehnickih mogucnosti u podrucju molekularne dijagnostike. U razdoblju od 1974. – 2008. godine u Klinici za djecje bolesti Zagreb postavljena je dijagnoza maligne bolesti u 1428-ero djece. Njih 480-ero su imali leukemiju, a 948-ero solidne maligne tumore. Jednom od citomorfoloskih metoda moguce je postaviti dijagnozu maligne bolesti u djece. Ova je metoda brza, jednostavna, relativno neopasna i bezbolna i moguce ju je primijeniti u vecini laboratorija. Uspotrebom ove metode moguce je pratiti dinamiku tumorskog procesa, uspjeh terapijskih protokola, rano otkriti recidiv tumora ili udaljene metastaze. Korelacija s patohistoloskom dijagnozom je visoka.

The paper presents the basic facts about therapy in the treatment of solid malignant tumors in childhood. Knowing the side effects of chemotherapy and various combinations of given drugs plays an important role in deciding how to treat a child with a malignant tumor

Wilmsov tumor je jedan od najcescih solidnih malignih tumora djecje dobi. Od prvih podataka o njegovu lijecenju iz 1923. godine do danas postotak izljecenja porastao je od 10% na 90%. U radu se prikazuju osnove epidemiologije, genetike, klinicke slike dijagnostickih postupaka, patohistologije, stadija bolesti, lijecenje, nuspojava i kasnih posljedica lijecenja. Iznose se spoznaje o hereditarnim i sporadicnim tumorima, udruženim kongenitalnim anomalijama i genetickim sindromima te mogucnosti da kromosomski markeri posluže kao faktor u ranom dijagnosticiranju Wilmsovog tumora, sto može biti presudan faktor u prognozi lijecenja. Tumor se najcesce javlja kao asimptomatska tumorska masa. Od dijagnostickih pretraganajznacajnije su intravenozna pijelografija, ultrazvuk abdomena, racunalna tomografija. Zavisno o patohistoloskoj podvrsti tumora (clear cel, rabdoidni) i stadiju, vezano za mogucnost metastaziranja, radi se scintigrafija kostiju, racunalna tomografija mozga, anmgiografija. U poglavlju o terapiji iznosi se znacenje smanjenja tumora preoperativnom kemoterapijom, sto omogucava radikalni operativni zahvat prijeko potreban za izljecenje. Od citostatika se u preoperacijskoj i postoperativnoj kemoterapiji primjenjuju Actinomycin D i Vincristin. Prema patohistoloskom nalazu i prosirenosti tumora primjenjuju se najcesce jos Adriamycin, Ifosfamid, Etoposid, Carboplatina. Samo u manjem broju slucajeva primjenjuje se i zracenjezbog mogucih kasnih posljedica, među kojima su najteže sekundarne neoplazme sto se javljaju 10-20 godina nakon zracenja.

Zadnjih desetak godina doslo je do bitnog napredka u medicini. Vecina autora se slaže da je bas najveci napredak nastao na podrucju pedijatrijske onkologije. Zlocudne bolesti djecje dobi koje su pred desetak godina bile neizljecive postale su danas izljecive u relativno visokom postotku. Tako se danas 5 godisnje preživljenje bez povratka bolesti postiže u 78% bolesnika ; u akutne limfaticke leukemije u 84%, u akutne mijeloicne leukemije 52%, u malignih limfoma (Hodgkin i non-Hodgkin) 91%, tumori mozga 69%, tumori simpatickog živcanog sistema 73%, retinoblastoma 99%, tumori bubrega 88%, tumori jetre 38%, tumori kosti 67%, sarkomi mekih tkiva 61%, tumori zametnog epitela 90%, karcinomi 73%, ostali rijeđi tumori 53%. Da bi se postigli tako dobri rezultati , visok postotak dugotrajnog preživljenja te izlijecenja potrebno je sto ranije postaviti preciznu (tocan podtip bolesti) dijagnozu, utvrditi prosirenost (stadij) bolesti, te primijeniti odgovarajucu terapiju koja se najcesce sastoji, ovisno o tipu zlocudne bolesti , od kemoterapije sa/ili bez kirurskog zahvata te radioterapije. Lijecenje je najcesce izrazito agresivno ( sto je bolest zlocudnija mora se primijeniti agresivnije lijecenje) te je praceno brojnim ranim te kasnim komplikacijama koje su cesto i po život opasne. Ukoliko se želi smanjiti postotak jatrogenih smrtnih ishoda potrebno je takvo intenzivno lijecenje sprovoditi u specijaliziranim centrima koji su adekvatno opremljeni te imaju veliko iskustvo u primjeni suvremene multimodalne terapije. Lijecenje je timsko ; u njemu sudjeluje veliki broj specijalista razlicitih specijalnosti od pedijatra onkologa, citologa, citogeneticara, patologa, radiologa, kirurga, neurokirurga, ortopeda, radioterapeuta itd. Lijecenje je izrazito skupo ali i izrazito efikasno, s obzirom da se vecina bolesnika danas može izlijeciti U radu se iznose danasnje mogucnosti dijagnostike i lijecenja kao i rezultati koji se postižu kod najcescih zlocudnih bolesti djecje dobi.

Background/Purpose: Intratumoral angiogenesis quantified by microvessel density (MVD) has been shown to be a strong prognostic indicator in a number of malignant tumors. Its association with prognosis in Ewing sarcoma has not been previously studied. The aim of our study was to investigate the relationship between angiogenesis and clinical outcome in Ewing sarcoma.Methods: Twenty-seven patients with Ewing sarcoma were included in a retrospective immunohistochemical study. Sections from diagnostic biopsies were immunostained using anti-von Willebrand factor antibody and microvessels were counted at 400x magnification on three microscopic fields per patient. Microvessel density was correlated with overall and disease-free survival as a continuous variable using univariate regression analysis and as a dichotomous variable by Kaplan-Meier and log-rank analysis. Correlation between clinicopathologic variables and the degree of angiogenesis was tested using chi(2) test.Results: Increasing MVD was not confirmed to be a poor prognostic factor in univariate analysis. Also, statistically significant difference was not found in overall survival or disease-free survival between patients with high (> 31.6 vessels per field) and low (<= 3 1.6 vessels per field) microvessel counts. Finally, there was no difference regarding the metastatic rate between patients with high and low microvessel counts.Conclusions: Our results did not confirm increasing angiogenesis quantified by MVD to be predictive of prognosis or pulmonary metastasis in Ewing sarcoma. The diffiuse pattern of distribution of microvessels found in Ewing sarcoma may be responsible for the observed lack of prognostic significance of angiogenesis. Future work is required to assess the prognostic importance of WD in this disease. (c) 2006 Elsevier Inc. All rights reserved.

Zlocudne su bolesti nakon nesretnih slucajeva vodeci uzrok smrti djece u Evropi i Americi. Nove metode dijagnostike i lijecenja znacajno su poboljsale rezultate tako da se danas petogodisnje preživljenje djece sa zlocudnim bolestima postiže u 78% bolesnika. Detaljnije su prikazane neuroblastom, leukemije i tumori bubrega.

AIM Almost 20 different prognostic factors have so far been investigated in childhood bone tumors, but apart from clinical stage the results have been inconclusive. We evaluated possible prognostic factors of malignant bone tumors in children and adolescents. METHODS Seventy children and adolescents, who have been treated for bone sarcomas (36 with osteosarcoma and 34 with Ewing's sarcoma) at the Children's Hospital in Zagreb and the Orthopedic Clinic of the Zagreb University School of Medicine were included in the study. We analyzed 9 variables: clinical stage, patient age and sex, tumor size and location, location of metastases, chemotherapy response, concentration of lactate dehydrogenase (LDH) and erythrocyte sedimentation rate (ESR), and chondroid differentiation in osteosarcoma. RESULTS The clinical stage was the most important prognostic factor for both type of tumors. Lactate dehydrogenase in patients with Ewing's sarcoma (p=0.033) and in patients with osteosarcoma (p=0.015) as well as erythrocyte sedimentation rate (p<0.001 and p=0.014, respectively) may also be of predictive value. CONCLUSION Elevated erythrocyte sedimentation rate and high LDH concentration seem to be of importance in both Ewing's sarcoma and osteosarcoma, regardless of their different pathogenesis or pathohistology.

Intratumoral angiogenesis quantified by microvessel density (MVD) has been shown to be a strong prognostic indicator in a number of malignant tumors. Its association with prognosis in bone sarcomas has been subject to less extensive research. The aim of this study was to investigate prognostic significance of angiogenesis in osteosarcoma. Thirty-nine patients with osteosarcoma were included in a retrospective immunohistochemical study. Sections from diagnostic biopsies were immunostained using anti-von Willebrand factor antibody and microvessels were counted at 400 x magnification on 3 microscopic fields per patient. MVD was correlated with overall and disease-free survival by Kaplan-Meier and log-rank analysis. Correlation between clinicopathological variables and the degree of angiogenesis was tested using a chi 2 test. Significant statistical difference was found regarding overall survival and disease-free survival between patients with high (> 32.3 vessels/field) and low (< or = 32.3 vessels/field) microvessel counts (log-rank test p = .0196 and p = .0147, respectively). The rate of metastasis was significantly higher in patients with high microvessel counts (p = .042). These findings strongly suggest that angiogenesis quantified by microvessel density is predictive of metastasis and poor prognosis in osteosarcoma.

Objective. Evaluation of toxic episodes in children who were treated with HD Methotrexate(8-12g/m2) along with supportive therapy in this cases. Patients. Among 1993-2002 we have treated 46 pts (26 boys, 20 girls) diagnosed with osteosarcoma. They had received high dose of Methotrexate with Leucovorin during preoperative therapy. Results. In our group of patients, 30 had some degree of mucositis, 24 had mild elevation od hepatic enzyms and 3 of them had high elevation of hepatic enzyms, 3 patients with high elevated hepatic enzymes had exanthema, mucositis, oliguria and high value of serum methotrexate. One patient had hypertension. Non of our patients had to have hemodialiysis. 7 patients had positive Candida spp. in mouth or stool and 2 patients had positive hemoculture. As supportive therapy they have received adequate hidration, urine alkalisation, fursemide, djustment of leucovorine dose and nifedipin (boy with hypertension). Mouth and skin hygiene has been taken care of with special attenstion as well as the adequate food preparation. Conclusion. methotrexate intoxiation is treatable revesible complication during preoperative chemotherapy in children with osteosarcoma.

Kirurski zahvat kod djeteta u terminalnom stadiju bolesti cesto je potreban radi ublažavanja boli ili uklanjanja funkcionalnih abnormalnosti cime se poboljsava kvaliteta života pacijenta sa zlocudnim tumorom. Najcesce primjenjivani zahvati su palijativno odstranjenje voluminoznog ulceriranog tumora, amputacija, zaobilazne crijevne anastomoze, anus praeter, gastrostoma, jejunostoma, zahvat urinarne diverzije - implantacija uretera u crijevo, traheostoma, drenaža pleure, debridement dekubitusa. Kod patoloskih fraktura potrebna je ponekad operativna fiksacija. Za primjenu lijekova za uklanjanje boli i ostale terapije od znacaja može biti ugradnja trajnih endovenoznih kaketera tipa Broviac-Hickmann ili Port a cath.