ADIOLOGY AND NCOLOGY March 2008 Vol. 42 No. 1 Ljubljana ISSN 1318-2099 BISTVENE INFORMACIJE IZ POVZETKA GLAVNIH ZNAČILNOSTI ZDRAVILA AROMASIN® 25 mg obložene tablete Sestava in oblika zdravila: obložena tableta vsebuje 25 mg eksemestana. Indikacije: adjuvantno zdravljenje žensk po menopavzi, ki imajo invazivnega zgodnjega raka dojke s pozitivnimi estrogenskimi receptorji in so se uvodoma vsaj 2 leti zdravile s tamoksifenom. Zdravljenje napredovalega raka dojke pri ženskah z naravno ali umetno povzročeno menopavzo, pri katerih je bolezen napredovala po antiestrogenski terapiji. Učinkovitost se ni bila dokazana pri bolnicah, pri katerih tumorske celice nimajo estrogenskih recep-torjev. Odmerjanje in način uporabe: 25 mg enkrat na dan, najbolje po jedi. Pri bolnicah z zgodnjim rakom dojke je treba zdravljenje nadaljevati do dopolnjenega petega leta adjuvantnega hormonskega zdravljenja oz. do recidiva tumorja. Pri bolnicah z napredovalim rakom dojke je treba zdravljenje nadaljevati, dokler ni razvidno napredovanje tumorja. Kontraindikacije: znana preobčutljivost na učinkovino zdravila ali na katero od pomožnih snovi, ženske pred menopavzo, nosečnice in doječe matere. Posebna opozorila in previdnostni ukrepi: predmenopavzni endokrini status, jetrna ali ledvična okvara, bolniki z redkimi prirojenimi motnjami, kot so fruktozna intoleranca, malabsorpcija glukoze-galaktoze ali insuficienca saharoze-izomaltase. Lahko povzroči alergijske reakcije ali zmanjšanje mineralne gostote kosti. Ženskam z osteoporozo ali tveganjem zanjo je treba izrecno izmeriti gostoto kosti s kostno denzitometrijo, in sicer na začetku zdravljenja in nato redno med zdravljenjem. Medsebojno delovanje z drugimi zdravili: sočasna uporaba zdravil - npr. rifampicina, antiepileptikov (npr. fenitoina ali karbamazepina) ali zeliščnih pripravkov s šentjaževko - ki inducirajo CYP 3A4, lahko zmanjša učinkovitost Aromasina. Uporabljati ga je treba previdno z zdravili, ki se presnavljajo s pomočjo CYP 3A4 in ki imajo ozek terapevtski interval. Kliničnih izkušenj s sočasno uporabo zdravila Aromasin in drugih zdravil proti raku ni. Ne sme se jemati sočasno z zdravili, ki vsebujejo estrogen, saj bi ta izničila njegovo farmakološko delovanje. Vpliv na sposobnost vožnje in upravljanja s stroji: po uporabi zdravila je lahko psihofizična sposobnost za upravljanje s stroji ali vožnjo avtomobila zmanjšana. Neželeni učinki: neželeni učinki so bili v študijah ponavadi blagi do zmerni. Zelo pogosti (> 10 %): vročinski oblivi, bolečine v sklepih, utrujenost, slabost, nespečnost, glavobol, močnejše znojenje, blago zvišanje alkalne fosfataze. Način in režim izdajanja: zdravilo se izdaja le na recept, uporablja pa se po navodilu in pod posebnim nadzorom zdravnika specialista ali od njega pooblaščenega zdravnika. Imetnik dovoljenja za promet: Pfizer Luksembourg SARL, 283, route d Arlon, L-8011 Strassen, Luksemburg. Datum zadnje revizije besedila: 9.12.2005 Pred predpisovanjem se seznanite s celotnim povzetkom glavnih značilnosti zdravila. Podrobnejše informacije o zdravilu so na voljo pri: Pfizer, podružnica za svetovanje s področja farmacevtske dejavnosti, Ljubljana, Letališka cesta 3c, 1000 Ljubljana 1\_ adiology a\and (Jncology Editorial office Radiology and Oncology Institute of Oncology Zaloska 2 SI-1000 Ljubljana Slovenia Phone: +386 1 5879 369 Phone/Fax: +386 1 5879 434 E-mail: gsersa@onko-i.si March 2008 Vol. 42 No. 1 Pages 1-49 ISSN 1318-2099 UDC 616-006 CODEN: RONCEM Aims and scope Radiology and Oncology is a journal devoted to publication of original contributions in diagnostic and interventional radiology, computerized tomography, ultrasound, magnetic resonance, nuclear medicine, radiotherapy, clinical and experimental oncology, radiobiology, radiophysics and radiation protection. Editor-in-Chief Gregor Sersa Ljubljana, Slovenia Executive Editor Viljem Kovac Ljubljana, Slovenia Deputy Editors Andrej Cor Ljubljana, Slovenia Igor Kocijančič Ljubljana, Slovenia Editorial Board Karl H. Bohuslavizki Hamburg, Germany Maja Čemažar Ljubljana, Slovenia Christian Dittrich Vienna, Austria Metka Filipič Ljubljana, Slovenia Tullio Giraldi Trieste, Italy Maria Godény Budapest, Hungary Vassil Hadjidekov Sofia, Bulgaria Marko Hočevar Ljubljana, Slovenia Maksimilijan Kadivec Ljubljana, Slovenia Miklos Kasler Budapest, Hungary Michael Kirschfink Heidelberg, Germany Janko Kos Ljubljana, Slovenia Tamara Lah Turnšek Ljubljana, Slovenia Damijan Miklavčič Ljubljana, Slovenia Luka Milas Houston, USA Damir Miletič Rijeka, Croatia Maja Osmak Zagreb, Croatia Branko Palčič Vancouver, Canada Dušan Pavčnik Portland, USA Geoffrey J Pilkington Portsmouth, UK Ervin B. Podgoršak Montreal, Canada Uroš Smrdel Ljubljana, Slovenia Primož Strojan Ljubljana, Slovenia Borut Štabuc Ljubljana, Slovenia Ranka Štern-Padovan Zagreb, Croatia Justin Teissie Tolouse, France Sandor Toth Oroshaza, Hungary Gillian M. Tozer Sheffield, UK Andrea Veronesi Aviano, Italy Branko Zakotnik Ljubljana, Slovenia Advisory Committee Marija Auersperg Ljubljana, Slovenia; Tomaž Benulič Ljubljana, Slovenia; Jure Fettich Ljubljana; Valentin Fidler Ljubljana, Slovenia; Berta Jereb Ljubljana, Slovenia; Vladimir Jevtič Ljubljana, Slovenia; Stojan Plesničar Ljubljana, Slovenia; Živa Zupančič Ljubljana, Slovenia Publisher Association of Radiology and Oncology Affiliated with Slovenian Medical Association - Slovenian Association of Radiology, Nuclear Medicine Society, Slovenian Society for Radiotherapy and Oncology, and Slovenian Cancer Society Croatian Medical Association - Croatian Society of Radiology Societas Radiologorum Hungarorum Friuli-Venezia Giulia regional groups of S.I.R.M.. (Italian Society of Medical Radiology) Copyright © Radiology and Oncology. All rights reserved. Reader for English Vida Kološa Key words Eva Klemenčič Secretary Mira Klemenčič Design Monika Fink-Serša Printed by Imprint d.o.o., Ljubljana, Slovenia Published quarterly in 600 copies Beneficiary name: DRUŠTVO RADIOLOGIJE IN ONKOLOGIJE Zaloška cesta 2, 1000 Ljubljana Slovenia Beneficiary bank account number: SI56 02010-0090006751 IBAN: SI56020100090006751 Our bank name: Nova Ljubljanska banka, d.d., Ljubljana, Trg republike 2, 1520 Ljubljana; Slovenia SWIFT: LJBASI2X Subscription fee for institutions EUR 100, individuals EUR 50 The publication of this journal is subsidized by the Slovenian Research Agency. Indexed and abstracted by: BIOMEDICINA SLOVENICA CHEMICAL ABSTRACTS EMBASE / Excerpta Medica Sci Base Scopus This journal is printed on acid- free paper Radiology and Oncology is available on the internet at: http://www.onko-i.si/radioloncol and http://www.versita.com ISSN 1581-3207 adiolqgy AND ncology Ljubljana, Slovenia ISSN 1318-2099 UDc 616-006 coDEN: RoNcEM March 2008 Vol. 42 No. 1 CONTENTS RADIOLOGY Treatment of complicated case with subclavia steal syndrome and stenosis of common iliac artery 1 Gjikolli B, Hadzihasanovic B, Jaganjac S, Herceglija E, Niksic M, Hadzimehmedagic A, Dilic M, Solakovic E, Merhemic Z, Beslic S, Lincender L, Miftari R0 IMAGES IN CLINICAL MEDICINE Planocellular carcinoma of the right cheek 13 Jančar B ONCOLOGY Radiation effects on skeletal muscle Jurdana M 15 Malignant spinal cord compression Rajer M in Kovač V 23 A method on theoretical simulation of chromosome breaks in cells exposed to heavy ions Yang J, Li W, Jing X, Wang Z, Gao Q 32 Solid tumors in young children in Moscow Region of Russian Federation 39 Kachanov DY, Dobrenkov KV, Shamanskaya TV, Abdullaev RT, Inushkina EV, Savkova RF, Varfolomeeva SR, Rumyantsev AG Current system of childhood cancer registration in Belarus 45 Savva NN, Zborovskaya AA, Aleinikova OV SLOVENIAN ABSTRACTS NOTICES VII Radiology and Oncology is covered in Biomedicina Slovenica, Chemical Abstracts, EMBASE / Excerpta Medica, Sci Base and Scopus Radiol Oncol 2008; 42(1): 1-12. doi:W.2478/vW019-007-0032-7 case report Treatment of complicated case with subclavia steal syndrome and stenosis of common iliac artery Bujar Gjikolli1, Besima Hadzihasanovic2, Suad Jaganjac3, Edin Herceglija4, Maida Niksic1, Amel Hadzimehmedagic5, Mirza Dilic6, Emir Solakovic7, Zulejha Merhemic1, Serif Beslic8, Lidija Lincender9, Rame Miftari10 Neuroradiology Department, Institute of Radiology, KCU Sarajevo, Bosnia and Herzegovina, 2Muskuloskeletal Department, Institute of Radiology, KCU Sarajevo, Bosnia and Herzegovina, 3Klinikum Eilbek Hamburg, Germany, 4 Vascular Department, Institute of Radiology, KCU Sarajevo, Bosnia and Herzegovina 5Clinic for Orthopedics and Traumatoology, KCU Sarajevo, Bosnia and Herzegovina, 6Clinic for Vascular Diseases, KCU Sarajevo, Bosnia and Herzegovina, 7Clinic for Vascular Surgery, KCU Sarajevo, Bosnia and Herzegovina, 8Thoracic Department, Institute of Radiology, KCU Sarajevo, Bosnia and Herzegovina, 9Abdominal Department, Institute of Radiology, KCU Sarajevo, Bosnia and Herzegovina, 10Institute of Radiology, Nuclear Medicine Dep., UCC of Kosova, Pristhine, Republic of Kosova Background. The aim of this case report is to describe the realization of complex radiological minimally invasive interventional procedures at the Institute of Radiology in KCU Sarajevo during which we treated a very complicated case with the left subclavia steal syndrome and the stenosis of the left common iliac artery. Case report. The patient was 57 years old with previous history of ischemic lesions in brain, with occlusion of the left arteria carotis communis (ACC) and stenosis of the right arteria carotis interna (ACI), with dizziness and inability to look upward. The patient was treated first with subintimal recanalization and introduction of self-expandable stent into the left subclavia artery to compensate for the very wide remnant of the occluded artery. After four months of follow up with no change, our team attempted to treat stenosis of the right ACI but failed to do so and during this procedure in-stent restenosis in the left subclavia artery was noted. After less than two weeks we performed balloon dilatation of in-stent restenosis of a previously installed stent into the left subclavia artery. The patient underwent CT and CT angiography (CTA), colour Doppler ultrasonography (CDUS), MRI and MR angiography (MRA) before and after the procedures. Conclusions. A follow up and, if needed, a balloon dilation are necessary to prevent the re-occlusion of the previously treated subclavia artery with stenting. Key words: subclavia steal syndrome; intentional subintimal recanalisation; restenosis; balloon dilation Received 13 August 2007 Accepted 21 August 2007 Correspondence to: Bujar Gjikolli M.D., Radiologist, Institute of Radiology, University Clinical Centre of Kosova, Pristine, Kosova; E-mail: bujargjikolli@yahoo. com Introduction Subclavia steal syndrome (SSS) is a group of signs and symptoms resulting from 2 Gjikolli B et al. / Subclavia steal syndrome and stenosis of common iliac artery steno-occlusive disease proximal to the origin of the vertebral artery, in which the arterial flow is reversed.1-4 It was described in 1960 for the first time, and the association between this phenomenon and neurologic symptoms was recognized in 1961.5'6, SSS refers to the retrograde vertebral artery flow associated with transient neurologic symptoms related to cerebral ischemia while subclavia steal phenomena (SSP) refer to the retrograde flow in the vertebral artery only. Stenosis or occlusion of the proximal subclavia artery causes a reversed vertebral flow with resulting decreased blood pressure in the arm distal to the steno-occlusive disease. A reduced blood pressure causes the ipsilateral vertebral artery blood flow alteration as a compensatory pathway through the arm, and this sign confirms subclavia disease proximal to the origin of the vertebral artery. Other potential collateral pathways include those between the external carotid artery (ECA) and the subclavia artery from occipital branches of ECA and the superior thyroid artery of ECA to the inferior thyroid artery branch of thyrocervical trunk. There are four types of subclavia steal, defined by territory from which blood is "stolen" in SSS: vertebro-vertebral, carotid-basilar, external carotid-vertebral, and carotid-subclavia.7 Based on vertebral hemodynamic changes, SSS has three defined stages: reduced antegrade vertebral flow (stage I), reversal of flow during reactive hyperemia testing of the arm (stage II), and permanent retrograde vertebral flow indicating subclavia artery occlusion (stage III).8 Arm symptoms can be provoked during arm exercise or peripheral reactive hyper-aemia, while neurological symptoms occur when compensatory flow to the subclavia artery from the vertebral artery diverts too much flow to the arm and away from brain. Neurologic symptoms result primarily from Radiol Oncol 2008; 42(1): 1-12. the insufficient intracranial circulation through circle of Willis mainly through the posterior communicating artery. Absence of a posterior communicating artery, extra cranial carotid artery stenosis and higher flow toward the arm can cause neurologic symptoms. The spontaneous resolution of vertebro-basilar symptoms may be related to the establishment of extra cranial collaterals to the subclavia circulation. Etiology of SSS is predominantly atherosclerotic in people older than fifty years of age. In Asians Takayasu arteritis as etiology can be seen in up to 36% of the population. Other causes of SSS include giant cell ar-teritis, tumour encasement, trauma, previous surgical procedure such as aortic stent-graft placement for thoracic dissection or aneurysm, coarctation of aorta with the ob-¡iteration of subclavia orifice, extra vascular obstruction, hypoplasia / atresia or isolation of subclavia artery with the anomalous aortic arch, vascular ring, ligation for the correction of tetralogy of Fallot or co-arcta-tion of aorta.9 The risk of stroke seems low10 but patients with SSS can be severely debilitated by arm and intracranial ischemia symptoms. As many as 15% of initially asymptomatic patients can experience vertebro-basilar transient ischemic attacks during two years of follow up.11 SSS is more frequent in males than females with incidence 1.5-2:1 while Takayasu arteritis is more common in females. SSS has a left-sided to right-sided ratio of 3-4:1 as a result of turbulence-related atherosclerosis of the acutely angled left subclavia artery. Symptoms include dizziness, unsteadiness, vertigo, vision changes, arm ischemia causing arm claudication and rest pain, focal sensory or motor loss, dysphasia, and unilateral visual disturbances. Symptoms may develop during the exercise of the upper limbs, when blood is deviated from the vertebro-basilar system to the upper limb. 9 Gjikolli B et al. / Subclavia steal syndrome and stenosis of common iliac artery A reduced blood pressure with change of >20 mm Hg when compared with contra lateral arm, weak or absent radial and ulnar pulse are other signs suggesting SSS. Colour Doppler US is the preferred examination.12 CT visualizes calcifications related to atheroma. Contrast enhanced CT angiography (CTA) can visualize the degree of subclavia artery stenosis or occlusion, including other changes in the arteries; mural thrombus, ulceration, and arterial wall calcification can be evaluated. MRI and contrast enhanced 3-D MR an-giography (MRA) after localizing 2-dimen-sional time-of-flight can also confirm SSP. Phase-contrast MRA measures the vertebral artery flow direction and velocity.13-15 SSS can be treated with minimally invasive radiological procedures of percutaneous transluminal angioplasty and stenting if angioplasty fails, using balloon-expandable stents or in some cases self expandable stents.16-22 Vertebro-basilar stroke during interventional procedures is rare due to the delayed establishment of the ante grade flow in the vertebral artery after the angi-oplasty/stenting. A distal protection may be useful especially in cases with thrombosis/unstable plaque. KCUS Saraievo I 1950 Jan GI M 11Î59 Acc 2ÛIJ5 NOV 50 tcffTnr 14 09 25 394030 Additionally SSS can be treated with surgical revascularization using either synthetic graft or saphenous vein grafts. Invasive options include carotid-subclavia bypass (CSB), carotid-subclavia transposition (CST), and axillo-axillary bypass.23-26 With this presentation we would like to describe the realization of complex radiological interventional therapeutic procedures of treating subclavia steal syndrome and stenosis of the left common iliac artery, at the institute of Radiology KCUS under the supervision of a Bosnian expert Dr. Suad Jaganjac working at the Hamburg Klinik Eilbek in Germany. Case report A 57-year-old male patient had complained of multiple symptoms, including weakness, dizziness, inability to look upward, speech difficulties and difficulties in using his left hand, in the five years following cerebral vascular insult. In 2002 he was admitted to the vascular surgery hospital KCUS because of atherosclerotic changes with stenosis of arteria carotis communis (ACC) and arteria carotis Figure 1 (a, b). CT angiography (CTA) maximum intensity projection (MIP) reformats show the occlusion of the left subclavian artery and the left brachial artery receiving blood from the left vertebral artery- steal syndrome. Radiol Oncol 2008; 42(1): 1-12. 4 Gjikolli B et al. / Subclavia steal syndrome and stenosis of common iliac artery interna (ACI) in the left side. In 2003 he was hospitalized in the clinic for cardiovascular diseases in UCC Tuzla where surgeons confirmed stenosis of the right ACI but did not intervene in the artery. The patient also complained for claudi- Figure 2 (a, b, c, d). CTA reconstructed images show the occlusion of left common carotid artery (ACC) less than 1 cm from the aortic arch with the reconstruction of left internal carotid artery (ACI) through collaterals coming from left external carotid artery (ACE). The occlusion of the left subclavia artery approximately 1 cm from its origin with its reconstruction in the level of origin of the vertebral artery and severe stenosis of right ACI in its initial part. Radiol Oncol 2008; 42(1): 1-12. cating pain in his legs after 20 meters of walking. He had high blood pressure and increased triglycerides in blood but was not diabetic. He quit smoking in 2002 after more than 40 years of 1-1.5 packages of cigarettes per day. 5 Gjikolli B et al. / Subclavia steal syndrome and stenosis of common iliac artery 35t7S«8-«-2S-5 et - SP 6 12VAS Ml U KCUSllütllijt 14 ftSMùiiTl1« 3,5cm .'14H* TIS 0,2 29,122006 03:57;30PM ftirwty SP612.VAS Mi 1.2 HCUS «icttiri io «idiakiijijii S.Scih'flHf H» 09,01,ÎOfli «MfcttPM J PS-'j 7.42 c m/s ! Il I rj~ «7 i ft m -îtûffe f ; f I ; f ft «Ci j Figure 3 (a, b). Colour Doppler ultrasound (CD US) showing flow in the left internal carotid artery (ACI) and ACE above the occluded left common carotid artery (ACC). In November 2005, the patient complained of ongoing symptoms and underwent CTA at our institute (Figure 1). The occlusion of left ACC and left subclavia steal syndrome was diagnosed but no interventions were performed. In December 2006 the patient was referred for CTA again and the occlusion of left ACC and left subclavia artery reconstructed through the left vertebral artery was shown. The remnant subclavia artery below the occlusion was measured at 1.11 cm. High grade stenosis of right ACI has been shown too. Left ACI was reconstructed through collaterals coming mainly through arteria carotis externa (ACE) branches (Figure 2). During discussion, the patient mentioned physicians' previous difficulties doctors had accessing his femoral artery for diagnostic digital subtraction angiography (DSA). Additional CTA of abdominal aorta and the upper part of his lower extremities confirmed mild stenosis of the right femoral artery and significant stenosis of the left common iliac artery. Additionally colour Doppler ultrasound (CD US) confirmed the changes seen in the CTA: the disturbance of the flow and the steal syndrome in the left side (Figures 3, 4). Left ACC showed maximum diameter of 6.5 mm without detectable flow while in ACI and ACE portion there was flow detectable coming from surrounding collaterals. Right ACC had maximum diameter of 7 mm with intima medial thickness of 1.3 mm with laminar flow and Peak Systolic »175-06.12-?».5 PwflOft* a ® ■■ WW 1 »Ott; ■■ SV Amjli» (ifi ■ Hill ?.ûmm ■ Ml 1.2 MCuS UISWMl Ii naihowtrtu Tis OS 29,12-ÄÖJß «MttOGP« PI Oisl fCA-PS 2S<0?i™/s I PU DitL ICA-EO 45.24em/S ' RI Oi*t (CA-ftt 0 82' rUDisLICA-n l.?Z' R1 Oi=t fCA-S/O 5,62 ' Rl oisl. rCA' TAtniM 121.48i:m/* 1 Figure 4 (a, b). Colour Doppler ultrasound (CD US) images showing stenosis of the initial part in the right arteria carotis interna (ACI) and its increased spectral values. Radiol Oncol 2008; 42(1): 1-12. 6 Gjikolli B et al. / Subclavia steal syndrome and stenosis of common iliac artery Figure 5 (a, b, c, d, e). Steps of the procedure performed. Subintimal recanalization, pre stenting balloon dilation, introduction of the stent with additional balloon dilatation giving the final result and preserving the vertebral artery which fills with contrast immediately after filling the aortic arch. Radiol Oncol 2008; 42(1): 1-12. 7 Gjikolli B et al. / Subclavia steal syndrome and stenosis of common iliac artery Figure 6 (a, b, c). Stenosis of the left iliac artery before stenting and result gained after stenting. Velocity (PSV) 91.43 cm/s and End Diastolic Velocity (EDV) 21.33 cm/s in its proximal part and turbulent flow with PSV 79.49 cm/s, EDV 32.56 cm/s in its distal part. The dorsal part of the bifurcation and the initial part of the right ACI showed partly hyperand partly hypo-echogenic plaque inside the lumen, reducing its width 3.5 mm with increase of PSV to 254.02 cm/s and EDV 45.24 cm/s. After analyzing all imaging procedures performed, we decided to offer the patient treatment of subclavia syndrome while avoiding treating the stenosis of the right ACI as the only big artery supplying his brain with blood. He agreed and the procedure was performed in January 10, 2007 at the Institute of Radiology - KCU Sarajevo. We used a left brachial approach and a hydrophilic guiding wire to perform Bolia's intentional subintimal recanalization. After reaching the aorta the guiding wire was pulled out with a goose neck snare from the introducer in the left femoral artery. Meanwhile this introducer was installed to confirm the position of the guide wire in n : %: ml., %'Yi ! i'V' '^fsjpv jijfc w f^vfi m m ! r\ - 'ISP • m * a it. ê m # • • # m it a t # |B 1 Figure 7 (a, b). Diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) images show old ischemic lesions and no new ischemic lesions at all. Radiol Oncol 2008; 42(1): 1-12. 8 Gjikolli B et al. / Subclavia steal syndrome and stenosis of common iliac artery Figure 8 (a, b). Maximum intensity projection (MIP) MR reconstructions after stenting showing position and the patency of the left subclavian and left vertebral arteries. the right lumen inside aorta. With a 3x120 mm balloon, we dilated the recanalized subclavia artery to create space for passing the stent. We used a self expandable stent to address both the wide proximal portion of the left subclavia artery and its narrow distal part. After introducing a self expandable stent, size 10 x 44 mm, the ad- O.OT MRC23749 Ex: 1 l Pwr 36« t7<*A (Ml 8 __ WMF 190 Hi I SVAngl» -60 ■! •IT« ?,0niiii I SP6-12iVAS MJ t2 HCUS-tmtrlui it RaiMto^fil 3.5CIH I 7HI TteO,* 3SJ3SJOIH 0335:17 PM ; Vtts-PS ' ; V«t^D O-Uttcrt/» > V«a-ftl 1,00 • 1_J Vos-HI 1.18 ' ' / Vos-TAmax ' 3SI754I743-30-2 172 / 4 (equ. 6) Where Numbercells is the number of cells grow in culture dish, Scell the area of single cell vertically faced to ion beams, nty1 /4 the inner area of culture dish. At various phases of cell cycle, the chromosome agglomeration status and the content are different. Though it is not so well impacting the physical density of cells, the cross-section of the interaction between cells and ions closely linked with it. Chromosome in G2 phase, is of better configuration, which is selected to analyze chromatid breaks, K3 was denoted as g0+g1 + g2+s+m = Gn Where G0, G1, G2> S, Mwere respectively the content percent of each phase cell number in all cells which were detected. This percent could be measured by flow cy-tometer (FCM). In a word, considered these external factors, the simulation of chromatid breaks to predict the radiosensitivity in heavy ion radiotherapy project is of great possibility and feasibility. Conclusions Chemically induced PCC technique can be used to analyze chromatid breaks induced by heavy ion, the radiation induced by initial chromatid/isochromatid breaks can be regarded as a possible good sign of intrinsic radiosensitivity of cells exposed to heavy charged ions, the theoretical simulation of radiation induced by chromatid breaks was a simple and convenient and safe approach to measure the radiosensitivity. Acknowledgements We would express our thanks to all of the workers in the HIRFL. This work was jointly supported by the National Natural Science Foundation Committee (Grant No. 10335050), Sciences and Technology Ministry of People's Republic of China (Grant No. 2003CCB00200), K. C. Wong Ed ucation Foundation, Hong Kong.(Grant No. 20060037) and China Postdoctoral Science Foundation (Grant No. 20060400686). Radiol Oncol 2008; 42(1): 32-8. 38 Yang J et al. / Theoretical simulation of chromosome breaks 38 References 1 Kraft G. Tumor therapy with heavy charged particles. Prog Part Nucl Phys 2000; 45: 473-544. 2 Kawata T, Gotoh E, Durante M, Wu H, George K, FurusawaY, et al. High-LET radiation-induced aberrations in prematurely condensed G2 chromosome of human fibroblasts. Int J Radiat Biol 2000; 76: 929-37. 3 Kawata T, Durante M, Frusawa Y, George K, Takai N, Wu H, et al. Dose-response of initial G2-chromatid breaks induced in normal human fibroblasts by heavy ions. 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Biomed Res 1995; 16: 638. 9 Murakami M, Minamihisamatsu M, Sato K, I Hayata. Structural analysis of heavy ion radiation-induced chromosome aberrations by atomic force microscopy. J Biochem Biophys Methods 2001; 48: 293-301. 10 Girinsky T, Bernheim A, Lubin R, Tavakolirazavi T, Baker F, Janot F, et al. In vitro parameters and treatment outcome in head and neck cancers treated with surgery and /or radiation: cell characterization and correlation with local control and overall survival. Int J Radia Oncol Biol Phys 1994; 30: 789-94. 11 West CM, Davidson SE, Burt PA, Hunter RD. The intrinsic radios ens itivity of cervical carcinoma: correlations with clinical data. Int J Radiat Oncol Biol Phys 1995; 31: 841-6. 12 West CM, Davidson SE, Roberts SA Hunter RD. The independence of intrinsic radiosensitivity as a prognostic factor for patient response to radiotherapy of carcinoma of cervix. Br J Cancer 1997; 76: 1184-90. 13 Rosenblum ML, Knebel KD, Wheeler KT, Barker M Wilson CB. Development of an in vitro colony formation assay for the evaluation of in vivo chemotherapy of a rat brain tumor. In Vitro 1975; 11: 264-73. 14 Eastham AM, Atkinson J, West CM. Relationship between clonogenic cell survival, DNA damage and chromosomal radiosensitivity in nine human cervix carcinoma cell lines. Int J Radiat Biol 2001; 77: 295-302. 15 Guo GZ, Sasai K, Oya N, Shibata T, Shibuya K, Hiraoka M. A significant correlation between clonogenic radiosensitivity and the simultaneous assessment of micronucleus and apoptotic cell frequencies. Int J Radiat Biol 1999; 75: 857-64. 16 Yang JS, Li WJ, Zhou GM, Jin XD, Xia JG, Wang JF, et al. Comparative study on radiosensitivity of various tumor cells and human normal liver cells. World J Gastroenterol 2005; 11: 4098-101. 17 Yang JS, Li WJ, Jin XD, Jing XG, Guo CL, Wei W, et al. Radiobiological response on human hepatoma and normal liver cells exposed to carbon ions generated by Heavy Ion Research Facility in Lanzhou. Sci China Ser G 2006; 49: 72-6. 18 Ziegler JF, Biersack JP Littmark U. The stopping and range of ions in solids. Oxford: Pergamon Press; 1985. 19 Savage JRK. Classification and relationships of induced chromosomal structural changes. J Med Gene, 1976; 13: 103-22. 20 Nasonova E, Gudowska E, Ritter S Kraft G. Analysis of Ar-ion and X-ray-induced chromatin breakage and repair in V79 plateau-phase cells by the premature chromosome condensation technique. Int J Radiat Biol 2001; 77: 59-70. 21 Yang JS, Jing XG, Li WJ, Wang ZZ, Zhou GM, Wang JF, et al. Correlation between initial chro-matid damage and survival of various cell lines exposed to heavy charged particles. Radiat Environ Bioph 2006; 45: 261-6. Radiol Oncol 2008; 42(1): 32-8. Radiol Oncol 2008; 42(1): 39-44. doi:10.2478/v10019-007-0037-2 Solid tumors in young children in Moscow Region of Russian Federation Denis Y Kachanov1,2, Konstantin V Dobrenkov2, Tatyana V Shamanskaya1,2, Ruslan T Abdullaev1,2, Evgueniya V Inushkina1,2, Rimma F Savkova1, Svetlana R Varfolomeeva2, Alexander G Rumyantsev2 1Moscow regional oncological hospital, Balashiha, Russian Federation; 2Federal Clinical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation Background. The aim of the study was to assess the main epidemiologic characteristics of solid tumours in young children. Methods. The data were retrieved from the Childhood Cancer Registry of Moscow Region, Russian Federation. Children aged 0-4 years with solid tumours diagnosed in 2000-2006 were included in the analysis. Results. The data on total 142 children with solid tumours were analyzed. The average number of annually registered cases was 5.9 ± 1.1 in infants and 14 ± 1.8 in older children with male-to-female ratio 1.1:1 and 0.92:1, respectively. The average incidence rate (IR) of all solid tumours was 10.6 per 100.000 children/ year in infants and 7.35 per 100.000 children/year in children 1-4 years old. The prevalent types of solid tumours in infants were hepatic (IR 2.46) and renal (IR 2.26) tumours. In children aged 1-4 years the following IRs for certain malignancies were found: CNS tumours 1.70, renal tumours 1.76, sympathetic nervous system tumours 1.73, retinoblastoma 0.87, soft tissue sarcomas 0.70, germ-cell tumours 0.19, hepatic tumours 0.14, and bone tumours 0.13. Conclusions. The lower IR of CNS tumours can be explained by under-reporting of this cancer type in Moscow region as a result of patient scattering through non-oncological hospitals. As compared to the data from cancer registries of the most European countries and US, lower IR of sympathetic nervous system tumours and retinoblastoma and higher IR of liver tumours and soft tissue sarcomas in infants were revealed in this study. Key words: solid tumors; epidemiology; children. Note: DY Kachanov and KV Dobrenkov contributed equally to this work. Paper was presented at the 27th Conference of International Association of Cancer Registries, Ljubljana, Slovenia, 17-20 September 2007. Received 10 December 2007 Accepted 17 December 2007 Correspondence to: Konstantin Dobrenkov M.D., Ph.D., Department of Pediatric Oncology, Federal Clinical Research Center of Pediatric Hematology, Oncology and Immunology, Leninskiy Prosp., 117, Moscow, Russian Federation; Email: dobrenkov@hotmail.com Introduction Solid tumours represent about 50% of all malignant neoplasms in children aged less than 15 years.1,2 The incidence and histo-logical type of solid tumours is age-dependent. They make up more than 80% of all malignancies in infants.3 The solid tumours to leukemias ratio is 2:1 in children aged 1-14 but 5:1 in infants less than 1 year. The 40 Dobrenkov K / Solid tumours in children in Moscow Region rate for neuroblastoma is four times higher in infants as compared to children of 1-14 years old.4 Other embryonal tumors, e.g. Wilms', heptoblastoma and retinoblastoma also show higher rates in infants. The accurate statistic data on children with solid tumours have been lacking until recently in Russian Federation. The nationwide cancer registration in the USSR was initiated in 1953. New cancer cases were registered by hospitals and were annually reported to Gertsen Oncological Institute in Moscow. The first population-based adulthood cancer registry (CR) was established in Saint-Petersburg in 1993. Despite of the earlier attempts to initiate registry for children with cancer in several regions, the first comprehensive childhood population-based CR was set up in Moscow Region (MR) in 2000. The information for this registry is collected from 10 different hospitals, which carry out an anti-cancer treatment in children residing in MR. This registry is maintained by the devoted cancer registry staff. Local paediatricians actively participate in data reporting, that allows for a more accurate and rapid registration. The aim of this study was to assess the main epidemiologic characteristics of malignant solid tumours in young children in Moscow Region. MR is located in the central part of Russian Federation and occupies 46 thousand sq. km. Its total population is 6.6 million (2006). MR is divided in 72 municipal districts (okrug) which are clustered in 12 medical districts. Moscow city is not an administrative part of the region and its territory is not covered by MR cancer registry. Patients and methods The data on patients were collected pro-spectively starting from 01. 01. 2000 until 31.12.2006 (72 months). Children less than four years old residing in MR with an estab- Kadiol Oncol 2008; 42(1): 39-44. lished diagnosis of malignant solid tumour during the given period of time were included in this study. The stratification was based on the International Classification of Childhood Cancer (ICCC), 2nd edition.5 The following types of cancer were included in the analysis: III - CNS and miscellaneous intracranial and intraspinal neoplasms, IV - Sympathetic nervous system tumours, V - retinoblastoma, VI - renal tumours, VII - hepatic tumours, VIII - malignant bone tumours, IX - Soft-tissue sarcomas, X - germ-cell, trophoblastic, other gonadal tumours, XII - carcinomas, other malignant epithelial tumours, XIII - Other and unspecified malignant neoplasms. The data were collected using both an active search and a passive retrieval. All hospitals in the region which carried out the treatment of children with cancer were visited by the CR personnel. The oncologists from the municipal districts of MR were required to send a special notification on every child with malignant neoplasm to the CR. The paediatricians annually informed the CR about all the children followed by them after the end of the anticancer treatment. Data were also routinely collected from pathology laboratories in the region. None of the cases were registered from death certificate only. For each registered case, the data comprised civil status items (name, surname, gender, date of birth, address at the time of cancer diagnosis), and disease items (incidence date, primary site and histology, diagnostic basis). The localization of the primary tumour and histological type were allocated in accordance with the International Classification of Diseases for Oncology (ICD-O), 2nd edition.6 The data on multiple primary tumours occurring in the same patient were registered separately. All malignancies with an ICD-O behaviour code of ''/3'' were included in this study. Benign tumours, tumours of uncertain ma- 41 Dobrenkov K / Solid tumours in children in Moscow Region lignancy, or in situ carcinomas (ICD-O morphology behaviour code "/0," "/1," or ''/2'') were excluded. The exception was ''Central nervous system and miscellaneous intracranial and intraspinal neoplasms'' (ICCC group III). In line with the international recommendations all types of tumours were registered irrespective of the behaviour code.5 Annual population estimates in MR were based on the data of the population census of Russian Federation in 2002 and were received from Moscow Regional Committee of Federal State Statistics Service. The average annual population in the given period was 53,880 ± 2,564 for infants and 196,519 ± 6,105 for children aged 1-4 years. Age-standardized annual incidence rates (IR) were calculated using the direct method for infants and children of 1-4 years old. The IR was expressed as means ± SD per 100,000 children of the corresponding age group. The male to female (F/M) ratio was calculated as a number of solid tumour cases in males divided by that in females. Statistica 6.0 software was used for the statistical analyses. Results A total of 142 cases of solid tumours in children aged 0-4 years were registered in Moscow Region over the period 2000-2006. Forty one case (28.9%) was recorded for infants and 101 cases (71.1%) in children aged 1-4 years. The average number of annually registered cases of solid tumours in infants was 5.9 ± 1.1 (range 2-11) with F/M ratio 1.1 : 1 and 14±1.8 (range 10-22) with F/M ratio 0.92 : 1 in older children. Frequencies and annual incidence rates per 100,000 children by age group and tumour type are summarized in Table 1. The average annual age-standardized IRs in infants was 10.6 ± 1.7. In this age group Table 1. Frequencies, annual incidence rates (IR) per 100.000 children and F/M ratios by age group over 2006 registration period the 2000- Tumour type < n 1 year IR old M:F 1-4 n years IR old M:F III. Central nervous system tumours 3 0.79 0.5:1 24 1.70 0.9:1 IV. Sympathetic nervous system tumours 4 0.95 3:1 24 1.73 1.2:1 V. Retinoblastoma 3 0.80 2:1 12 0.87 0.7:1 VI. Renal tumours 9 2.26 0.8:1 24 1.76 0.8:1 VII. Hepatic tumours 10 2.46 2.3:1 2 0.14 1:1 VIII. Malignant bone tumours 0,0 0.0 0.0 2 0.13 1:1 IX. Soft-tissue sarcomas 6 1.69 1:1 9 0.70 1.3:1 X. Germ-cell, trophoblastic, other gonadal tumours 5 1.25 0.7:1 3 0.19 0.0 XI. Carcinomas, other malignant epithelial tumours 1 0.30 - 1 0.07 - XII. Other and unspecified malignant neoplasms 0 - - 0 - - All tumours 41 10.55 1.1:1 101 7.35 0.9:1 Kadiol Oncol 2008; 42(1): 39-44. 42 Dobrenkov K / Solid tumours in children in Moscow Region Table 2. Incidence Rates per 100.000 children in Moscow Region (MR) in 2000-2006 as compared to the data from cancer registries of the European Union (ACCISS, 1978-1997) and US (SEER, 1975-2001) for infants and children aged 1-5 years1,9,11-15 Tumour type < 1 year 1-4 years MR Europe US MR Europe US III. Central nervous system tumours 0.79 2.85 2.95 1.70 3.39 3.51 IV. Sympathetic nervous system tumours 0.95 5.26 6.30 1.73 1.81 2.00 V. Retinoblastoma 0.80 2.04 2.70 0.87 0.75 0.82 VI. Renal tumours 2.26 1.89 2.01 1.76 1.81 1.89 VII. Hepatic tumours 2.46 0.72 0.94 0.14 0.22 0.35 IX. Soft-tissue sarcomas 1.69 1.45 1.41 0.70 1.11 0.97 the most common type of cancer were hepatic tumours: 10 cases (24.3%), followed by renal tumours - 9 cases (21.9%) and soft tissue sarcomas - 6 cases (14.6%). The average annual age-standardized IRs in children age 1-4 years was 7.4 ± 0.9. CNS tumours, sympathetic nervous system tumours and renal tumours represented the most common malignancies in this age (24 cases or 23.7% for the each cancer group). Embryonal solid tumours were prevalent in children younger than 4 years old. Among sympathetic nervous system tumours neurob-lastoma was the most common histological type representing 82.2% (23 cases), followed by ganglioneuroblastoma - 17.8% (5 cases). Hepatoblastoma was the only hepatic tumour in this cohort of patients. Wilms tumour was the most common entity among renal tumours representing 84.9% (28 cases) of diagnoses followed by clear cell sarcoma of the kidney (3 cases, 9,1%), renal-cell carcinoma (1 case, 3,0%) and malignant rhabdoid tumour of the kidney (1 case, 3,0%). Rhabdomyosarcoma was the prevalent histological type in children with soft tissue sarcoma comprising of 80% of diagnosis (12 cases). Discussion The present study was the first that analyzed incidence rates of solid tumours in children in Moscow Region of Russian Federation. It was also the first study on the comparison of statistical data on solid tumours in young children in the country with international data. We have shown that the incidence rate of solid tumours in infants was higher than in 1-4 years age group, and was comparable with the data from cancer registries of the industrialized countries.1-3 The overall incidence rate in the both age groups was lower than in European countries and in the USA (Table 2). It can be attributed, first of all, to under-reporting of patients with CNS and sympathetic nervous system tumours that are the most frequent tumour types for the given age group. CNS tumours represent considerable challenges for registration. As some of the patients with CNS tumours can be treated in neurological departments of non-oncological hospitals and further they do not receive any cancer-specific treatment (i.e. chemotherapy, radiotherapy), the information on them is not transmitted to the childhood cancer registry. The low rate of registration has been also observed in other countries. For example, the incidence rate for childhood CNS tumours in the 1980's in Germany was considerably lower than the median incidence rate for the world's largest registries. This lower incidence has been explained by under-reporting of CNS tumours in Germany. A more complete reg- Kadiol Oncol 2008; 42(1): 39-44. 43 Dobrenkov K / Solid tumours in children in Moscow Region istration was achieved in particular by the organization of clinical trials for the given group of patients in the beginning of 90's.7 Under-reporting of neuroblastoma in children aged < 1 year was revealed in our study. Since neuroblastoma in infants can have less aggressive course as compared to older children, patients may remain asymptomatic while the tumour mature. Beyond the infancy these children undergo the surgical treatment for the non-malignant tumours (e.g. ganglioneuromas) in non-oncological hospitals and are not registered. The low level of registration of patients with sympathetic nervous system tumours was shown in epidemiologic studies in other regions of Russian Federation. The under-reporting rate was estimated as high as 30%.8 Spix et al.9 on behalf of Automated Childhood Cancer Information System project (ACCIS) analyzed the incidence of neuroblastoma in Europe over the period 1978-1997. As it was shown, the difference in overall incidence of neuroblastoma across five European regions was mainly the result of variations in incidence in children under 2 years of age, while the incidence at older ages was almost identical. Interestingly, the higher incidence rate (the overdiagno-sis phenomenon) was observed in regions with ongoing neuroblastoma screening programs (some countries in Western Europe). The authors suggested that the introduction of screening programs in a number of countries could make an indirect impact on the increased incidence as consequences of the increased awareness of paediatricians on the possibility of development of the given tumour. A wide implication of diagnostic ultrasound during the antenatal and perinatal period in the mid 1980's in Italy has led to the increased incidence of neurob-lastoma.10 Our own experience has shown that a potential improvement of registration quality in young children with solid tumours can be achieved by introducing of educational programs for paediatricians in the regional hospitals. These programs are aimed to increase the level of oncological awareness among paediatricians which can result in earlier diagnostics of tumours in young children, in particular neuroblas-toma. An interesting observation obtained from this study was the high incidence rate of hepatic tumours in infants (2.46 per 100,000 children) (Table 2). The highest incidence rate of hepatoblastoma in infants was noted in East European countries (1.18 per 100,000 children).11 The further studies are needed to investigate this difference. As compared to the data from cancer registries of the most European countries and US, lower IR of sympathetic nervous system tumours and retinoblastoma and higher IR of liver tumours and soft tissue sarcomas in infants were revealed in this study. These data reflect difficulties in registration of malignant solid tumours in children in one of the most populated regions of Russian Federation. The scattering of the patients through the different hospitals implies the scrupulous data retrieval by dedicated personnel. Nevertheless, the registry has proved its incremental role in the financial and administrative management in the region by providing accurate information for the evolving methodologies in cancer treatment and has become an integrative component of regional healthcare systems. References 1. Ries LAG, Eisner MP, Kosary CL, Hankey BF, Miller BA, Clegg LX, et al. SEER Cancer Statistics Review, National Cancer Institute, Bethesda, MD. http://seer. cancer.gov/csr/1975-2 001 [(eds)]. 2. Desandes E, Clavel J, Berger C, Bernard JL, Blouin P, de Lumley L, et al. Cancer incidence among children in France, 1990-1999. Pediatr Blood Cancer 2004; 43: 749-57. Kadiol Oncol 2008; 42(1): 39-44. 44 Dobrenkov K / Solid tumours in children in Moscow Region 3. Gurney JG, Smith MA, Ross JA. Cancer among infants. In: Ries LAG, Smith MA, Gurney JG, et al, editors. Cancer incidence and survival among children and adolescents: United States SEER Program 19751995. Bethesda: National Cancer Institute, SEER Program; 1999. p. 149-56. 4. Birch JM, Blair V. The epidemiology of infant cancers. Br J Cancer Suppl 1992; 18: S2-4. 5. Kramarova E, Stiller CA. The international classification of childhood cancer. Int J Cancer 1996; 68: 759-65. 6. Percy C, van Holten VCM, editors. International classification of childhood cancer. Second edition. Geneva; 1992. 7. Kaatsch P, Rickert CH, Kuhl J, Schuz J, Michaelis J. Population-based epidemiologic data on brain tumors in German children. Cancer 2001; 92: 315564. 8. Minaev SV. Incidence of childhood cancer in Stavropol territory, Russia. Med Pediatr Oncol 2001; 37:140-1. 9. Spix C, Pastore G, Sankila R, Stiller CA, Steliarova-Foucher E. Neuroblastoma incidence and survival in European children (1978-1997): report from the Automated Childhood Cancer Information System project. Eur J Cancer 2006; 42: 2081-91. 10. Dalmasso P, Pastore G, Zuccolo L, Maule MM, Pearce N, Merletti F, et al. Temporal trends in the incidence of childhood leukemia, lymphomas and solid tumors in north-west Italy, 1967-2001. A report of the Childhood Cancer Registry of Piedmont. Haematologica 2005; 90: 1197-204. 11. Stiller CA, Pritchard J, Steliarova-Foucher E. Liver cancer in European children: incidence and survival, 1978-1997. Report from the Automated Childhood Cancer Information System project. Eur J Cancer 2006; 42: 2115-23. 12. MacCarthy A, Draper GJ, Steliarova-Foucher E, Kingston JE. Retinoblastoma incidence and survival in European children (1978-1997). Report from the Automated Childhood Cancer Information System project. Eur J Cancer 2006; 42: 2092-102. 13. Pastore G, Peris-Bonet R, Carli M, Martinez-Garcia C, Sanchez de Toledo J, Steliarova-Foucher E. Childhood soft tissue sarcomas incidence and survival in European children (1978-1997): report from the Automated Childhood Cancer Information System project. Eur J Cancer 2006; 42: 2136-49. 14. Pastore G, Znaor A, Spreafico F, Graf N, Pritchard-Jones K, Steliarova-Foucher E. Malignant renal tumours incidence and survival in European children (1978-1997): report from the Automated Childhood Cancer Information System project. Eur J Cancer 2006; 42: 2103-14. 15. Peris-Bonet R, Martinez-Garcia C, Lacour B, Petrovich S, Giner-Ripoll B, Navajas A, et al. Childhood central nervous system tumours - incidence and survival in Europe (1978-1997): report from Automated Childhood Cancer Information System project. Eur J Cancer 2006; 42: 2064-80. Kadiol Oncol 2008; 42(1): 39-44. Radiol Oncol 2008; 42(1): 45-9. doi:10.2478/v10019-007-0038-1 Current system of childhood cancer registration in Belarus Natallia N. Savva, Anna A. Zborovskaya, Olga V. Aleinikova Belarusian Research Center for Pediatric Oncology and Hematology, Minsk, Belarus Background. The purpose of this article is to describe the current system of childhood cancer registration in Belarus and the main principles of organization of Childhood Cancer Sub-registry of Belarus including the retrospective and prospective (formalized and visualized) data collection. Conclusions. The use of visualized data of the initial diagnostic system not only helps to optimize the prospective recording in the cancer registry, but also contributes to the better verification of individual cases that is sometimes required in the retrospective research and in cases of changes in classification of malignant neoplasm. Key words: cancer registry; children Introduction A high quality population-based cancer registry approved by the government and a recognized international organization is foun-dational for any epidemiological study and worldwide acceptance of its results. A review of disputable cases by experts is a necessary step for the data input and for the retrospective and for the prospective cancer registry data base verification. The purpose of this article is to describe the current system of childhood cancer registration in Belarus Paper was presented at the 27th Conference of International Association of Cancer Registries, Ljubljana, Slovenia, 17-20 September 2007. Received 13 December 2007 Accepted 27 December 2007 Correspondence to: Natallia N. Savva, MD, PhD, Belarusian Research Centre for Paediatric Oncology and Haematology, Ministry of Health of Republic of Belarus, Lesnoe-2, 223040, Minsk region, Belarus; Phone: +375 17 265 48 61; Fax: +375-17-265-42-22; Email: nsavva@mail.ru, n_savva@yahoo.com and the main principles of organization of Childhood Cancer Sub-registry of Belarus including the retrospective and prospective (formalized and visualized) data collection. Retrospective data collection Previously, there were three main data bases for adult and childhood cancer in Belarus: Belarusian State Cancer Registry within the Belarusian Institute for Medical Technologies, Registry for Hemablastoses within the Research Institute for Hematology and Transfusiology, and Cancer-registry within the Research Institute for Oncology and Medical Radiology. These cancer registries had definite limitations in case verification and registration according to the modern classifications and standards used in childhood oncology. That is why the Childhood Cancer Subregistry was organized by the Ministry of Health of Belarus in 1999 based at the 46 Savva NN et al./ Childhood cancer registration in Belarus department for clinical and epidemiologi-cal research of the Belarusian (National) Research Center for Pediatric Oncology and Hematology (BRCPOH) in Minsk. This Center is responsible for diagnosing and treating all types of malignant neoplasm, except thyroid cancer, in children and adolescents of Belarus (all mentioned categories of patients from the entire country must be diagnosed there and most of them are treated at that Center). This fact contributes to the easier collection and verification of cases for the Childhood Cancer Sub-registry. The childhood Cancer Sub-registry of Belarus has been undertaking the prospective data collection since the August 1999. As a first step of the retrospective accumulation of cases, the data base for all cancer cases in children 0-14 years old had been actively collected with the help of the Belarusian State Cancer Registry back to 1989, and verified by the re-examination of slides, disease histories, death certificates etc. with the participation of oncologists, hematolo-gists and cytomorphologists from BRCPOH and the Research Institute for Oncology and Medical Radiology (Minsk, Belarus). In 2001 the official name 'Childhood Cancer Sub-registry of Belarus', designated and confirmed by certificate, was received (certificate #0170100025 in the state register of information resources of Belarus, in force from 12.12.2001). The leukemia's part of the automatic data base was subsequently extended back to 1986 with the additional collaboration of the Research Institute for Hematology and Blood Transfusion, which has a prospective database of hemablasto-sis registered according to the ICD-9 since 1979 and had performed leukemia studies previously published.1-4 Since 2004 the Childhood Cancer Sub-registry of Belarus prospectively collects the cancer cases in adolescents (15-19 years old) and extends the data bases for this age retrospectively. Principles of prospective data organization The nationwide Childhood Cancer Sub-registry of Belarus is a computerized system performing previously active data collection that is standardized according to the IARC recommendations5 with nearly 100% level of microscopically verified cancer cases diagnosed after 1990. Its main goal is to register all malignant neoplasm cases in children and adolescents in Belarus with the creation of the maximally verified data base of nosological/morphological forms and continued follow-up events for clinical and epidemiological studies. The registry staff is divided into a formalized data input group, a visualized data input group, a follow-up group, and a group for technical service and software assistance. Since the Childhood Cancer Sub-registry of Belarus is located in the BRCPOH (the only national center responsible for childhood cancer in Belarus), every cancer case is entered into the cancer registry immediately after establishing the diagnosis for more than 95% of cases, and less than 5% are collected actively during the calendar year. The following parameters are registered: personal data of patients (names, changed names during the life, passport identification number of a patient or his/her parents, date of birth, address at the diagnosis and other addresses changed during the follow-up), information about disease (date of disease, date of diagnosis, basis of diagnosis, stage, reference number, date and conclusion of cytomorphological examination, expert's name, the formalized and visualized data of primary diagnostic examinations); information about the treatment and remission status, date and status at follow-up, sources of information, date and cause of death by death certificate; time- and dis- Kadiol Oncol 2008; 42(1): 45-9. 47 Savva NN et al./ Childhood cancer registration in Belarus Disease Classification Scheme. Steep 1. 1 ' Disease Class; Diagnostic group ICCC _ ims Leukemias, myeloproliferative disease«, and m y el * ICCC Lymphoma» and reticuloendothelial neoplasms Central Nervous System and Mixed Intracranial ar Neuroblastoma and other peripheral nervous cell Topography Morphology ICD- Retinoblastoma Renal tumors Morphology ICD- Hepatic tumors Malignant bone tumors Soft tissue and other extraosseous sarcomas Germ cell tumors, trophoblastic tumors, and neopl Other malignant epithelial neoplasms and maligna Cither and unspecified malignant neoplasms non-ICCC v MM .>/ Nosological group ICCC ICD-IO it— To trans< (la) Lymphoid leukemias A m 91 llal > X Cancel Mext » Figure 1. Classification algorithm using in the Childhood Cancer Sub-registry of Belarus. ease-relation of malignances (de novo, secondary, or multiple primaries). All cancer cases are coded according to ICCC-36 and ICD-O-3 (morphology and topography), and converted automatically to ICD-O-2 and ICD-10 (Figure 1). The sources of primary information are the following: hematological departments of regional clinics, hematological consultations, oncological dispensaries, specialized clinics, autopsy units and morphological laboratories. As the filling of the information about the primary established/suspected cancer cases and cancer deaths to Belarusian State Cancer Registry is mandatory for all medical institutions in Belarus, the Childhood Cancer Sub-registry of Belarus fulfils the annual verification of its database with the Belarusian State Cancer Registry using codes ICD-O-2 and ICD-10. Additionally, the Childhood Cancer Subregistry of Belarus verifies its data base on an ongoing basis with the clinical registries organized in BRCPOH for every nosological group and treatment protocol. Since 2004, the database of the Childhood Cancer Sub-registry has been also prospec-tively populated with the visualized data of morphological, immunological, cytogenetic and molecular-biological methods as well as computer tomography (CT) and ultrasound (US) examinations for the prospective and retrospective verification of cancer cases due to the creation of the computer-aided system for the registration and accumulation of the visualized and formalized Kadiol Oncol 2008; 42(1): 45-9. 48 Savva NN et al./ Childhood cancer registration in Belarus Figure 2. The information flows into the Childhood Cancer Sub-registry realized with help of the computer-aided system for formalized and visualized data of the primary diagnostic complex for patients with cancer inside the Belarusian Research Center for Pediatric Oncology and Hematology. data of the primary diagnostic complex for patients with cancer.7,8 This system includes the Clinical Base for Visualized and Formalized Data, where all information is accumulated from the automated (computer-aided) doctor's workplaces located in different laboratories (cytological, morphological, immunological, cytogenetical and molecular genetical) and in the departments for US and X-ray/CT diagnostics. The system of the data visualization also enables us to provide the distant consulting services as well as the weekly clinical conferences where all primary cancer cases are discussed before the input into the data base of the cancer registry (Figure 2). The short-term (within the first five years after the end of the anti-cancer treatment) and the long-term follow-up is implemented by active (including expeditions) and passive monitoring using the sources of the out-patient department of BRCPOH (information goes automatically into the registry data base), the Belarusian State Cancer Registry, autopsy units and morphological laboratories, medical institutions (clinics and territorial policlinics), registry offices and hospices. The short-term follow-up requires the update of the case's status as minimum as once a year, and long-term - as minimum as once a two years; and the registry's software alarms the necessity of updating and generates a list of cases. The system enables automatic calculation of incidence (crude, TASR - word and euro standard), overall survival and mortality rates for various nosological groups, ages, regions, and provides TERSON-code maps. The patient information and consent to registration and continued follow-up are requested to be signed at the time the personalized data are entered into the Childhood Cancer Sub-registry database. Kadiol Oncol 2008; 42(1): 45-9. 49 Savva NN et al./ Childhood cancer registration in Belarus Conclusions Timely and quality recording of childhood cancer at the national level and accumulation of verified information in the database of the automatic cancer registry not only supports a long-term epidemiologic and clinical research, but also enables experts to quickly obtain data on incidence, survival and death rate for a given span and undertake a prompt analysis of the existing trends, e.g. at request of the Ministry of Health for planning future action. In our opinion, the use of visualized data of the initial diagnostic system not only helps to optimize the prospective recording in the cancer registry, but also contributes to the better verification of individual cases that is sometimes required in the retrospective research and in cases of changes in classification of malignant neoplasm. Acknowledgements The programs for visualization of primary diagnostic complex and code-converting were created by specialists of United Institute for Informatics Problems of National Academy of Science of Belarus with the support of International Scientific Technical Center, (Project B-736, http:// tech-db.istc.ru/ISTC/sc.nsf/html/projects-all-by-number.htm?open&start=B). References 1. Ivanov E, Tolochko G, Lazarev V, Shuvaeva L. Child leukemia after Chernobyl (Scientific correspondence). Nature 1993; 365: 702. 2. Ivanov E, Tolochko G, Shuvaeva L, Becker S, Nekolla E, Kellerer A. Childhood leukemia in Belarus before and after the Chernobyl accident. Radiat Environ Biophys 1996; 35: 75-80. 3. Gapanovich V, laroshevich R, Shuvaeva L, Becker S, Nekolla E, Kellerer A. Childhood leukemia in Belarus before and after the Chernobyl accident: continued follow-up. Radiat Environ Biophys 2001; 40: 259-67. 4. Ivanov E, Tolochko G, Shuvaeva L, Ivanov V, laroshevich R, Becker S, et al. Infant leukemia in Belarus after the Chernobyl accident. Radiat Environ Biophys 1998; 37: 53-5. 5. IARC Scientific Publication No.95. In: Jensen OM, Parkin DM, MacLennan R, Muir CS, Skeet RG, editors. Cancer registration: principles and methods; 1991. 6. Steliarova-Foucher E, Stiller C, Lacour B, Kaatsch P. International classification of childhood cancer. Third edition. Cancer 2005; 103: 1457-67. 7. Khristich GA, Savva NN, Bydanov OI, Sergeev EA, Aleinikova OV, Anishchanka UV, et al. Computer-aided system for registration of formalized and visualized data for the primary diagnostic complex of the malignant neoplasm. In: Anishchanka UV, editor. Proceeding of the International Conference "Advanced information and telemedicine technologies for health, AITTH'2005". Minsk: UIIP; 2005. Vol. 2. p. 177-83. 8. Savva NN, Bydanov OI, Sergeev EA, Aleinikova OV, Anishchanka VV, Khristich GA. Computer-aided system for registration of the formalized and visualized data of patients, represented as one of the childhood cancer-register operation chains (abstract). In: Program and book of abstracts. Euroregional Conference on "Building Information Society in the Healthcare in Euroregion Niemen". Bialystok; 2005. p. 53-4. Kadiol Oncol 2008; 42(1): 45-9. Slovenian abstracts III Radiol Oncol 2008; 42(1): 12-31. Zdravljenje bolnika s subklavijskim sindromom kraje krvi ter zožitvijo skupne iliakalne arterije Gjikolli B, Herceglija E, Jaganjac S, Hadžihasanovic B, Nikšic M, Hadzimehmedagic A, Dilic M, Solakovic E, Merhemic Z, Bešlic Š, Lincender L, Myftary R Izhodišča. Namen članka je opisati bolnika s subklavijskim sindromom kraje krvi in zožitvijo skupne iliakalne arterije, pri katerem smo na Inštitutu za radiologijo UKc Sarajevo izvedli zapleteno interventno radiološko zdravljenje. Prikaz primera. Pri 57-letnem bolniku, ki se je predhodno že zdravil zaradi možganske ishe-mije, smo ugotovili okluzijo leve skupne karotidne arterije in stenozo desne interne karoti-dne arterije. Bolnik je imel vrtoglvico z moteno sposobnostjo pogleda navzgor. Najprej smo naredili rekanalizacijo in vstavili opornico v levo subklavijsko arterijo. Podobno smo zdravili zožitev desne interne karotidne arterije. Čez 4 mesece pa smo naredili balonsko dilatacijo, saj je prišlo do ponovne stenoze desne interne karotidne arterije. Pred in po interventnih radioloških posegih smo naredili preiskavo z računalniško tomografijo (CT), cT angiografijo, preiskavo z barvnim Doppler ultrazvokom in magnetno resonanco (MR) ter MR angiografijo. Zaradi anamnestičnega podatka, da je prišlo do težav pri femoralni digitalni subtrakcijski angiografiji, smo naredili CT angiografijo trebušne aorte in zgornjega dela spodnjih udov ter ugotovili zožitev leve skupne iliakalne arterije. Zaključki. Po zdravljenju žilne zožitve je potrebno skrbno sledenje bolnika, da bi lahko pravočasno preprečili žilno zaporo. Radiol Oncol 2008; 42(1): I-VI. II Slovenian abstracts III Radiol Oncol 2008; 42(1): 22-31. Radiacijake poškodbe skeletne mišice Jurdana M Izhodišča. odrasla skeletna mišica je odporna na ionizirajoče sevanje, razen pri uporabi večjih doz. To dejstvo lahko pripišemo manjšemu številu radiosenzibilnih proliferacijskih celic v odrasli dobi. Razvijajoča se skeletna mišica pa je izjemno senzibilna na ionizirajoče sevanje, poleg tega radioterapija v otroštvu lahko sproži mišično atrofijo. Sevanje preprečuje aktivacijo, proliferacijo in diferencijacijo mišičnih satelitskih celic ter vpliva na živčno-mi-šični stik, kjer privede do sprememb v propustnosti membrane, povezane z delovanjem Na+/K+ črpalke. Poleg tega sevanje preprečuje mišično rast v razvoju in po poškodbi. Zaključki. Rezultati raziskav po sevanju kažejo na značilne spremembe v aktivaciji satelitskih celic. Inhibitorji nekaterih beljakovin, podobnih citokinom v skeletni mišici, lahko sprožijo terapevtski učinek pri obolenjih, pri katerih je mišična masa omejena; izboljšajo dovzetnost za tumoralno terapijo ter povečajo življenjsko dobo pri bolnikih s kaheksijo. Radiol Oncol 2008; 42(1): I-VI. Slovenian abstracts III Radiol Oncol 2008; 42(1): 23-31. Metastatska vtesnitev hrbtenjače Rajer M, Kovač V Izhodišča. Metastatska vtesnitev hrbtenjače je urgentno stanje, ki zahteva takojšnjo diagnostiko in zdravljenje. Prizadane 5-14% vseh bolnikov z rakom. Vzrok za vtesnitev so bodisi osteolitični kostni zasevki v telesu vretenca, ki povzročijo patološki zlom in premik kostnih delcev v hrbtenični kanal, bodisi tumorske mase, ki rasejo v epiduralni prostor in vtisnjujejo hrbtenjačo. V hrbtenico najpogosteje zasevajo rak dojk in pljuč, sledijo jim limfom, mielom, rak prostate in sarkom. Zaključki. Najpogostejši simptom vtesnitve je bolečina, ki je lahko podobna bolečini pri degenerativni bolezni hrbtenice. ostali simptomi so mišična šibkost, vse do pareze ali paralize, ter avtonomne disfunkcije, kot so motnje odvajanja vode in blata, zlasti inkontinenca. Pri vseh bolnikih, pri katerih postavimo sum na maligno vtesnitev, je potrebno narediti MR preiskavo, v primeru kontraindikacij pa CT. odločitev o načinu zdravljenja je multi-disciplinarna in odvisna od nevroloških izpadov, narave tumorja, mehanične nestabilnosti hrbtenice in splošnega bolnikovega stanja. Bolnike lahko zdravimo z operacijo, kateri je dodano pooperativno obsevanje, ali samo z obsevanjem. Vsi bolniki pa potrebujejo dobro podporno zdravljenje, ki vključuje kortikosteroide in protibolečinsko zdravljenje. Kljub napredku diagnostike in terapije bolezni, je zdravljenje še vedno le paliativno. Preživetje je pri teh bolnikih kratkotrajno. Radiol Oncol 2008; 42(1): I-VI. IV Slovenian abstracts III Radiol Oncol 2008; 42(1): 32-31. Teoretična simulacija prelomov kromosomov v celicah, izpostavljenih težkim ionom Yang J, Li W, Jing X, Wang Z, Gao Q Izhodišča. Študija opisuje enostavno in hitro metodo za simulacijo kromosomskih prelomov v celicah po izpostavitvi težkim nabitim delcem. Metode. Izračunane teoretične vrednosti kromosomskih prelomov smo primerjali z eksperimentalnimi podatki predčasno kondenziranih kromosomov. Rezultati. Ugotovljena je bila dobra korelacija med teoretičnimi in eksperimentalnimi podatki. Podatki potrjujejo korelacijo med relativno biološko učinkovitostjo težkih nabitih delcev in njihovimi fizikalnimi karakteristikami. Zaključki. Ta metoda dobro in varno napoveduje kromosomske prelome v celicah, obsevanih z težkimi nabitimi delci. Radiol Oncol 2008; 42(1): I-VI. Slovenian abstracts III Radiol Oncol 2008; 42(1): 44-31. Solidni tumorji pri mlajših otrocih v Moskovski regiji Ruske federacije Kachanov DY, Dobrenkov KV, Shamanskaya TV, Abdullaev1 RT, Inushkina EV, Varfolomeeva SR, Rumyantsev AG Izhodišča. Namen raziskave je bil oceniti glavne epidemiološke značilnosti solidnih tumorjev pri mlajših otrocih. Metode. Podatke smo dobili iz otroškega registra raka Moskovske regije Ruske federacije. V analizo smo vključili mlajše otroke, stare od 1-4 leta, ki so jim v letih 2000-2006 odkrili solidni tumor. Rezultati. obravnavali smo podatke 101 otrok s solidnim tumorjem. Povprečno število letno ugotovljenih primerov raka je bilo 14,4 ± 1,8. Razmerje med dečki in deklicami je bilo 0,92:1. Povprečna letna incidenčna stopnja vseh solidnih tumorjev je bila 7,35 na 100.000 otrok. Našli smo naslednje letne incidenčne stopnje na 100.000 otrok za posamezne tumorje: tumorji centralnega živčnega sistema 1,70, ledvični tumorji 1,76, tumorji simpatičnega živčevja 1,73, retinoblastomi 0,87, sarkomi mehkih tkiv 0,70, germinalnocelični tumorji 0,19, jetrni tumorji 0,14 in kostni tumorji 0,13. Zaključki. Nižjo incidenčno stopnjo tumorjev centralnega živčnega sistema lahko razložimo z nezadostnim poročanjem o tej vrsti raka v Moskovski regiji. Takšni bolniki so namreč zdravljeni tudi v neonkoloških bolnicah. Ko smo naše podatke primerjali s podatki registrov raka večine evropskih držav in iz Združenih držav Amerike, smo ugotovili nižjo incidenčno stopnjo tumorjev simpatičnega živčevja in retinoblastomov ter višjo incidenčno stopnjo jetrnih tumorjev in sarkomov mehkih tkiv. Radiol Oncol 2008; 42(1): I-VI. VI Slovenian abstracts III Radiol Oncol 2008; 42(1): 45-31. Beloruski register raka za otroke Savva NN, Zborovskaya AA, Aleinikova OV Izhodišča. Namen članka je opisati Beloruski register raka za otroke ter načela in organizacijo zajemanja podatkov otroškega raka v Belorusiji. Register vključujejo retrospektivno in prospektivno zbiranje podatkov. Zaključki. Sistem vidne predstavitve podatkov o začetnih diagnozah omogoča optimalno prospektivno beleženje podatkov v registru raka, hkrati pa pripomore k boljšemu preverjanju posamičnih primerov, ki je občasno potrebno pri retrospektivnih raziskavah in pri spremembah klasifikacije rakavih obolenj. Radiol Oncol 2008; 42(1): I-VI. VII Notices Notices submitted for publication should contain a mailing address, phone and/or fax number and/or e-mail of a Contact person or department. Lung cancer April 23-26, 2008 The first lung cancer conference in Europe will be held in Geneva, Switzerland. E-mail pia.hirsch@uchsc.edu Lung cancer April 24-26, 2008 The "IASLC/ESMO Lung Cancer Conference" will be offered in Geneva, Switzerland. See http://www.iaslc.org Lung cancer June 12-14, 2008 The "11th Central European Lung Cancer Conference" will be offered in Ljubljana, Slovenia. Contact Conference secretariat, Ms. Ksenia Potocnik, Department of Thoracic Surgery, Medical Centre Ljubljana, Slovenia; or call +386 1 522 2485; or fax +386 1 522 3968; or e-mail ksenia.potocnik @kclj.si; or see http://www.ce-lung2008.org/ Oncology October 9-10, 2008 The ''3rd Latin American Cancer Conference" will take place in Vina del Mar, Chile. E mail nisehy@uol.com.br or rodrigo.arriagada@ki.se Oncology November 13-15, 2008 The Chicago/IASLC/ASCO/ASTRO symposiums "Malignancies of the Chest and Head and Neck" will be offered in Chicago. E-mail: evokes@medicine.bsd.uchicago.edu Lung cancer August 21-24, 2009 The "13th World Conference on Lung Cancer" will be offered in San Francisco, USA. Contact Conference Secretariat; e-mail WCLC2007@ ncc.re.kr; or see http://www.iaslc.orgIumages/ 12worldconfannounce.pdf Oncology September 4-8, 2009 The "34th ESMO Congress" will take place in Vienna, Austria. Contact ESMO Head Office, Congress Department, Via La Santa 7, CH-6962 Viganello-Lugano, Switzerland; or +41 (0)91 973 19 19; or fax +41 (0)91 973 19 18; or email congress@esmo.org; or see http://www.esmo.org As a service to our readers, notices of meetings or courses will be inserted free of charge. Please send information to the Editorial office, Radiology and Oncology, Zaloska 2, SI-1000 Ljubljana, Slovenia. Radiol Oncol 2008; 42(1): VII. Fundacija dr. j. cholewa Fundacija "Docent dr. j. Cholewa" je neprofitno, neinstitucionalno in nestrankarsko združenje posameznikov, ustanov in organizacij, ki želijo materialno spodbujati in poglabljati raziskovalno dejavnost v onkologiji. Dunajska 106 1000 Ljubljana ŽR: 02033-0017879431 Fundacija dr. j. cholewa Activity of "Dr. J. Cholewa" Foundation for Cancer Research and Education - a report for the first quarter of 2008 The Dr. J. Cholewa Foundation for Cancer Research and Education continues to focus its activities and attention to cancer research and education in Slovenia and continues to deal carefully with the requests and proposals for research grants and scholarships. The Dr. J. Cholewa Foundation for Cancer Research and Education continues to support the regular publication of "Radiology and Oncology" international medical scientific journal in 2007. This journal is edited, published and printed in Ljubljana, Slovenia. The support for "Radiology and Oncology" emphasizes and addresses the need for the spread of information and knowledge about advances in cancer among professionals and too many interested individuals in lay public and others in Slovenia and elsewhere. "Radiology and Oncology" is an open access journal, available on its own website, thus allowing its users and readers to be freely access, use and re - use it. There are many professional and lay activities in connection with cancer research, cancer education and information presently taking place in Slovenia. As the public is gearing its attention towards newly established, extended and improved screening programs involving breast, cervical and colon cancers, the Foundation will probably support these activities in its own specific way. As the public and professional awareness of problems associated with these three very common types of cancer in Slovenia need to be improved, especially with regard to screening, there are ample opportunities for the Foundation to take part in promoting these activities. The Foundation continues to attach a large amount of importance to the support of the publication of the results from cancer research in Slovenia and from Slovenian authors in respectable international scientific journals and other means of communication worldwide. Borut Štabuc, MD, PhD Andrej Plesničar, MD Tomaž Benulič, MD SIEMENS Swm*ruM«d»calxonviincok>ay Siamen» oncology domntagrat0»r — wrrt* rjvf 100 yaa*i t»»»:o»v o' innov»»>or »n ">ad>ca< tachnotogv P"ov#« cfcraev »T^ttToea can he'o y (w to »c*>ava nwi VuCMttftfl outcoma« How' TlvwUgh mouiry-toc^noiogy. increased tvodjctivty ma«»ures tor nwmired ut'i'zat'O" uotantia) and DawM'tanHy öwi^gr and ieatu>a« o»v # tnp Un»ted State* »«one 29 000 canoe' oaten* ret*»v» 'ad-a'on t*e'apy de'veied bv Sauer-, ■nee« acee«e<«t»'f As cta«*) pfotoco* c«nvr>or. to nciui» 'MRT and 'CHT Sanies seamlessly mtetp*tps the d'agnos' t »<-d treatment modeMte« Tii#r* «v« call Besl Practise Oncology Caie Siemens edtcal S oluhons that help SEEK-FIND-ACT-F0LL0W - the Continuum of Oncology Care™ / Vse za rentgen dobite pri nas! • rentgenski filmi in kemikalije • rentgenska kontrastna sredstva • rentgenska zaščitna sredstva • aparati za rentgen, aparati za ultrazvočno diagnostiko in vsa ostala oprema za rentgen Sanolabor, d.d., Leskoškova 4, 1000 Ljubljana tel: 01 585 42 11, fax: 01 524 90 30 www. sanolabor.si © Sanolabor icoormED ZASTOPA PODJETJA: MENTOR Prsni vsadki napolnjeni s silikonskim gokjm, ekspandcijl In drugI pripomočki pri ne korist m let Í)1 dojk ^ líí 11 »im nn KtttermaÉÉ (nemi i ja): :üt)ordtüff]Skö pon.itvo, varnostne omare za tosfine, luge, topila, pline in strupe, ventilacijska tehnika i rt digestor]! Ctänqeiuj i/oni ^■tiiii ■i" *■* Angela ntoni selen tífica (Italija): 11 Milna tehnika In aparan za laboratorij, trariitijiijo, patologijo in sodno medicino CORNING Corning (Amerika): speoalna laboratorijska plastika ?a aplikacijo v imiunologifi, inilírotuologi)i, virotagiji, ipd., mehansko eno- in večkanalne pipete in nastavki V :V( MKHHia Micron ie (Nizozemska): stsfemi ra shranjevale vrorcev, ni pete, nastavki :a pipeto I^TÍ V V> KuMtt m ÜJKHIC Hlii Ammpe EW I m pla ntech (Amerika): oftwni In gluteal ni vsadti Bionorica (Amerika J: hitri lesti s j diagnostiko, EiA /RTA testi EHRET ehret (Nemčija); Lartiihar riaiv tehnika, inkubatorji, sušim*., suhi stcj-ilizatorji m np^ema zá íabora tor.jsko vzrejo živali - kletke a ko Pake (Danska): testi ¿a aplikacijo v imuneinstokemiji, patorogiji, mikrobiolngjji, virologiji, mono- In paNklonalna protitelesa Satura fin ote k (Evropa): aparati ?a priprauo hiscosoSkih preparatov: mi bra-inkrtjltofnl, za ii vali i, tkivnn prpcKorji, barvam, pokrivale! INTEGRA Integra Biosciíins (Švica): laboratorijska opnema ?a mikrobiologijo, biologijo celic, molekularno biologijo in biotehnologijo i k < i r uní uesici + f i ■ SpectrumDftsigns MEDICAL (Amerika): moíki pektoralm vsadki VUBfcflJ'tflly Byron (Amerika): liposuktorji In kanilo íu liposuk;;¡0 LA BOR MEO d,o.o. Beograjski dvor Pe rlíc va 29, ijubljana Tel.: £0)1 436 49 01 Fax: £0)1 436 49 OS t n f o @ I a b o r m e d , s i www.labormed.sl CETUKSIMAB ERBITUX - izbira za izboljšano učinkovitost Kolorektalni rak: učinkovitost dokazana v kombinaciji z irinotekanom Lokalno napredovali rak glave in vratu: signifikantno podaljšanje preživetja v kombinaciji z radioterapijo Merck Serono Onkologija / biološko zdravljenje za boljšo kakovost življenja jaj Erbitux 5 mg/ml raztopina za infundiranje (skrajšana navodila za uporabo) Cetuksimab je monoklonsko IgG1 protitelo, usmerjeno proti receptorju za epidermalni rastni faktor (EGFR). Terapevtske indikacije: Zdravilo Erbitux je v kombinirani terapiji z irinotekanom indicirano za zdravljenje bolnikov z metastatskim rakom debelega črevesa in danke in sicer po neuspešni citotoksični terapiji, ki je vključevala tudi irinotekan. Zdravilo Erbitux je v kombinaciji z radioterapijo indicirano za zdravljenje bolnikov z lokalno napredovalim rakom skvamoznih celic glave in vratu. Odmerjanje in način uporabe: Zdravilo Erbitux pri vseh indikacijah infundirajte enkrat na teden. Začetni odmerek je 400 mg cetuksimaba na m2 telesne površine. Vsi naslednji tedenski odmerki so vsak po 250 mg/m2. Kontraindikacije: Zdravilo Erbitux je kontraindicirano pri bolnikih z znano hudo preobčutljivostno reakcijo (3. ali 4. stopnje) na cetuksimab. Posebna opozorila in previdnostni ukrepi: Če pri bolniku nastopi blaga ali zmerna reakcija, povezana z infundiranjem, lahko zmanjšate hitrost infundiranja. Priporočljivo je, da ostane hitrost infundiranja na nižji vrednosti tudi pri vseh naslednjih infuzijah. Če se pri bolniku pojavi huda kožna reakcija (> 3. stopnje po kriterijih US National Cancer Institute, Common Toxicity Criteria; NCI-CTC), morate prekiniti terapijo s cetuksimabom. Z zdravljenjem smete nadaljevati le, če se je reakcija pomirila do 2. stopnje. Priporoča se določanje koncentracije elektrolitov v serumu pred zdravljenjem in periodično med zdravljenjem s cetuksimabom. Po potrebi se priporoča nadomeščanje elektrolitov. Posebna previdnost je potrebna pri oslabljenih bolnikih in pri tistih z obstoječo srčno-pljučno boleznijo. Neželeni učinki: Zelo pogosti (> 1/10): dispneja, blago do zmerno povečanje jetrnih encimov, kožne reakcije, blage ali zmerne reakcije povezane z infundiranjem, blag do zmeren mukozitis. Pogosti (> 1/100, < 1/10): konjunktivitis, hude reakcije povezane z infundiranjem. Pogostost ni znana: Opazili so progresivno zniževanje nivoja magnezija v serumu, ki pri nekaterih bolnikih povzroča hudo hipomagneziemijo. Glede na resnost so opazili tudi druge elektrolitske motnje, večinoma hipokalciemijo ali hipokaliemijo. Posebna navodila za shranjevanje: Shranjujte v hladilniku (2 °C - 8 °C). Ne zamrzujte. Vrsta ovojnine in vsebina: 1 viala po 20 ml ali 100 ml. Imetnik dovoljenja za promet: Merck KGaA, 64271 Darmstadt, Nemčija. Podrobne informacije o zdravilu so objavljene na spletni strani Evropske agencije za zdravila (EMEA) http://www.emea.europa.eu. I Dodatne informacije so vam na voljo pri: Merck, d.o.o., Dunajska cesta 119, 1000 Ljubljana, tel.: 01 560 3810, faks: 01 560 3831, el. pošta: info@merck.si I 1% J | L, LJI ; r' www.oncology.merck.de J TjTjllrin^ ■ bb KUIMU Epufen fentanil Nežen dotik skrije bolečino NOVO MATRIX oblika SKRAJŠAN POVZETEK GLAVNIH ZNAČILNOSTI ZDRAVILA Epufen 12,5, 25, 50 in 100 mikrogramov/uro transdermalni obliži SESTAVA: 1 transdermalni obliž vsebuje 2,89 mg, 5,78 mg 11,56 mg ali 23,12 mg fentanila. TERAPEVTSKE INDIKACIJE: Huda kronična bolečina, ki se lahko ustrezno zdravi le z opioidnimi analgetiki. ODMERJANJE IN NaČIN UPORABE: Odmerjanje je treba individualno prilagoditi ter ga po vsaki uporabi redno oceniti. Izbira začetnega odmerka: velikost odmerka fentanila je odvisna od predhod-ne uporabe opioidov, kjer se upošteva možnost pojava tolerance, sočasnega zdravljenja, bolnikovega splošnega zdravstvenega stanja in stopnje resnosti obolenja. Pri bolnikih, ki pred tem niso dobivali močnih opioidov, začetni odmerek ne sme preseči 12,5-25 mikrogramov na uro. Zamenjava opioidnega zdravljenja: pri zamenjavi peroralnih ali parenteralnih opioidov s fentanilom je treba začetni odmerek izračunati na osnovi količine analgetika, ki je bila potrebna v zadnjih 24 urah, jo pretvoriti v odgovarjajoči odmerek morfina s pomočjo razpredelnice in nato preračunati ustrezen odmerek fentanila, spet s pomočjo razpredelnice (glejte SmPC). Prvih 12 ur po prehodu na transdermalni obliž Epufen bolnik še vedno dobiva predhodni analgetik v enakem odmerku kot prej; v naslednjih 12 urah se ta analgetik daje po potrebi. Titracija odmerka in vzdrževalno zdravljenje: obliž je treba zamenjati vsakih 72 ur. Odmerek je treba titrirati individualno, dokler ni dosežen analgetični učinek. Odmerek 12,5 mikrogramov/uro je primeren za titriranje odmerka v manjšem odmernem območju. Če analgezija na koncu začetnega obdobja nošenja obliža ni zadostna, se lahko odmerek po 3 dneh zveča. Možno je, da bodo bolniki potrebovali občasne dodatne odmerke kratko delujočih analgetikov (npr. morfina) za prekinitev bole-čine. Sprememba ali prekinitev zdravljenja: vsaka zamenjava z drugim opioidom mora potekati postopoma, z majhnim začetnim odmerkom in počasnim zvečevanjem. Splošno veljavno pravilo je postopna ustavitev opioidne analgezije, da bi preprečili odtegnitvene simptome, kot so navzeja, bruhanje, diareja, anksioznost in mišični tremor. Uporaba pri starejših bolnikih: starejše in oslabljene bolnike je treba skrbno opazovati zaradi simptomov prevelikega odmerjanja ter odmerek po potrebi zmanjšati. Uporaba pri otrocih: transdermalni obliži Epufen se lahko uporabljajo le pri pediatričnih bolnikih (starih od 2 do 16 let), ki tolerirajo opioide in peroralno že dobivajo opioide v odmerku, enakovrednemu najmanj 30 mg morfina na dan. Bolnik mora prvih 12 ur po prehodu na Epufen še vedno dobivati predhodni analgetik v enakem odmerku kot prej. V naslednjih 12 urah je treba ta analgetik dajati odvisno od kliničnih potreb. Titracija odmerka in vzdrževalno zdravljenje: če je analgetični učinek Epufena prešibak, je treba bolniku dodati morfin ali drugi opioid s kratkim delovanjem. Odvisno od dodatnih potreb po analgeziji in jakosti bolečine pri otroku se lahko uporabi več obližev. Odmerek je treba prilagajati korakoma, po 12,5 mikrogramov/uro. Uporaba pri bolnikih z jetrno ali ledvično okvaro: Zaradi možnosti pojava simptomov prevelikega odmerjanja je treba te bolnike skrbno spremljati in odmerek ustrezno zmanjšati. Uporaba pri bolnikih s povečano telesno temperaturo: Pri teh bolnikih bo morda treba prilagoditi odmerek. Način uporabe: transdermalni obliž Epufen je treba takoj po odprtju vrečke nalepiti na nerazdraženo, neobsevano kožo, na ravno površino prsnega koša, zgornjega dela hrbta ali nadlakti. Po odstranitvi zaščitne plasti je treba obliž trdno pritrditi na izbrano mesto in z dlanjo pritiskati približno 30 sekund, da se obliž popolnoma nalepi, še zlasti na robovih. Uporaba pri otrocih: pri mlajših otrocih je obliž priporočljivo nalepiti na zgornji del hrbta, ker je manjša verjetnost, da bi otrok odstranil obliž. Transdermalnega obliža se ne sme deliti, ker podatkov o tem ni na voljo. KONTRAINDIKACIJE: Preobčutljivost za zdravilno učinkovino, hidrogenirano kolofonijo, sojo, arašide ali katerokoli pomožno snov. Akutna ali pooperativna bolečina, ko v kratkem časovnem obdobju ni možno titriranje odmerka in obstaja verjetnost za življenjsko ogrožajočo respiratorno depresijo. Huda okvara osrednjega živčnega sistema. Sočasna uporaba MAO ali v obdobju 14 dni po prekinitvi jemanja zaviralcev MAO. POSEBNA OPOZORILA iN PREVIDNOSTNI UKREPI: Zaradi razpolovne dobe fentanila je treba bolnika v primeru pojava neželenega učinka opazovati še 24 ur po odstranitvi obliža. Pri nekaterih bolnikih, ki uporabljajo transdermalni obliž Epufen, se lahko pojavi respiratorna depresija. Epufen je treba previdno dajati: bolnikom s kronično pljučno boleznijo, zvišanim intrakranialnim tlakom, možganskim tumorjem, boleznimi srca, jeter in ledvic, tistim z zvišano telesno temperaturo, pri starejših bolnikih in otrocih, bolnikih z miastenijo gravis. Odvisnost od zdravila: kot posledica ponavljajoče se uporabe se lahko razvijeta toleranca na učinkovino ter psihična in/ali fizična odvisnost od nje. Ostali: lahko se pojavijo neepileptične (mio)klonične reakcije. MEDSEBOJNO DELOVANJE Z DRUGIMI ZDRAVILI IN DRUGE OBLIKE INTERAKCIJ: Derivati barbiturne kisline, opioidi, anksiolitiki in pomirjevala, hipnotiki, splošni anestetiki, fenotiazini, mišični relaksanti, sedativni antihistaminiki in alkoholne pijače, zaviralci MAO, itrakonazol, ritonavir, ketokonazol, nekateri makrolidni antibiotiki, pentazocin, buprenorfin. VPLIV NA SPOSOBNOST VOŽNJE IN UPRAVLJANJA S STROJI: Zdravilo ima močan vpliv na sposobnost vožnje in upravljanja s stroji. NEŽELENI UČINKI: Najbolj resen neželen učinek fentanila je respiratorna depresija. Zelo pogosti (> 1/10): dremavost, glavobol, navzeja, bruhanje, zaprtje, znojenje, srbenje, somnolenca. Pogosti (_ 1/100 do < 1/10): kserostomija, dispepsija, reakcije na koži na mestu aplikacije, sedacija, zmedenost, depresija, tesnoba, živčna napetost, halucinacije, zmanjšan apetit. Občasni (_ 1/1000 do < 1/100): tahikardija, bradikardija, tremor, parestezija, motnje govora, dispneja, hipoventilacija, diareja, zastajanje urina, izpuščaj, rdečina, hipertenzija, hipotenzija, evforija, amnezija, nespečnost, vznemirljivost. Nekateri od naštetih neželenih učinkov so lahko posledica osnovne bolezni ali drugih zdravljenj. Drugi neželeni učinki: odpornost, fizična in psihična odvisnost se lahko razvijejo med dolgotrajno uporabo fentanila. Pri nekaterih bolnikih se lahko pojavijo odtegnitveni simptomi, ko zamenjajo prejšnje opiodne analgetike s transdermalnim obilžem s fentanilom ali po nenadni prekinitvi zdravljenja. NAČIN IZDAJE: Samo na zdravniški recept. OPREMA: Škatle s 5 transdermalnimi obliži. IMETNIK DOVOLJENJA ZA PROMET: Lek farmacevtska družba, d.d., Verovškova 57, Ljubljana, Slovenija INFORMACIJA PRIPRAVLJENA: november 2007 lek član skupine Sandoz www.lek.si/vademekum . vedno svež vir informacij. ans9tno?ol Posodobili smo slovar Skrajšan povzetek glavnih značilnosti zdravila Arimidex 1 mg filmsko obložene tablete Sestava zdravila: Ena tableta vsebuje 1 mganastrozola. Indikacije: Adjuvantno zdravljenje žensk po menopavzi, ki imajo zgodnji invazivni rak dojke s pozitivnimi estrogenskimi receptorji. Adjuvantno zdravljenje zgodnjega raka dojke s pozitivnimi estrogenskimi receptorji pri ženskah po menopavzi, ki so se dve do tri leta adjuvantno zdravile s tamoksifenom. Zdravljenje napredovalega raka dojke pri ženskah po menopavzi. Učinkovitost pri bolnicah z negativnimi estrogenskimi receptorji ni bila dokazana razen pri tistih, ki so imele predhodno pozitiven klinični odgovor na tamoksifen. dmerja In način uporabe: Odrasle (tudi starejše) bolnice: l tableta po 1 mg peroralno, enkrat na dan. Odmerka zdravila ni treba prilagajati pri bolnicah z blago ali zmerno ledvično odpovedjo ali blagi m jetrnim odpovedovanjem. Pri zgodnjem raku je priporočljivo traja nje zdravljenja 5 let. Glavni neželeni učinki: Zelo pogosti (> 10 %): navali vročine, običajno blagi do zmerni. Pogosti (s 1 % in < 10 %): astenija, bolečine/okorelost v sklepih, suhost vagine, razredčenje las, izpuščaji, slabost, diareja, glavobol (vsi običajno blagi do zmerni) Posebna opozorila In previdnostni ukrepi: Uporabe Arimidexa ne priporočamo pri otrocih, ker njegova varnost in učinkovitost pri njih še nista raziskani. Menopavzo je potrebno biokemično določiti prt vseh bolnicah, kjer obstaja dvom o hormonskem statusu. Ni podatkov o varni uporabi Arimidexa pri bolnicah z zmerno ali hudo jetrno okvaro ali hujšo ledvično odpovedjo (očistek kreatinina manj kakor 20 ml/min (oziroma 0,33 ml/s)). Pri ženskah z osteoporozo ali pri ženskah s povečanim tveganjem za razvoj osteoporoze je treba določiti njihovo mineralno gostoto kosti z denzitometrijo, naprimersslikanjem DEXA na začetku zdravljenja, pozneje pa v redni h intervalih. Po potrebi Je treba začeti z zdravljenjem ali preprečevanjem osteoporoze ln to skrbno nadzorovati. NI podatkov o uporabi anastrozola z analogi LH RH. Arimidex znižuje nivo estrogena v obtoku, zato lahko povzroči zmanjšanje mineralne kostne gostote. Trenutno ni na voljo ustreznih podatkov o učinku bifosfonatov na izgubo mineralne kostne gostote, povzročene z anastrozolom, ali njihovi koristi, če se upora bij o preventivno. Zdravilo vsebuje laktozo. Kontraindikacije: Arimidex je kontraindiciran pri: ženskah pred menopavzo, nosečnicah in doječih materah, bolnicah s hujšo ledvično od povedjo (očistek kreatinina manj kot 20 ml/min (oziroma 0,33 ml/s)), bolnicah z zmernim do hudim jetrnim obolenjem, bolnicah, ki imajo znano preobčutljivostza anastrozol ali za katerokoli pomožno snov. Zdravila, ki vsebujejo estrogen, ne s mete dajati sočasno z Arimidexom, ker bi se njegovo farmakološko delovanje Izničilo. Sočasno zdravljenje s tamoksifenom. Medsebojno delovanje z drugimi zdravili In druge oblike Interak« Klinične raziskave o interakcijah z antlpirinom in cimetidinom kažejo, da pri sočasni uporabi Arimidexa in drugih zdravil klinično pomembne interakcije, posredovane s citokromom P450, niso verjetne. Pregled baze podatkov o varnosti v kliničnih preskušanjih pri bolnicah, ki so se zdravile z Arimidexom in sočasno jemale druga pogosto predpisana zdravila, ni pokazal klinično pomembnih interakcij. Imetnik dovoljenja za promet: AstraZeneca UK Limited, 15 Stanhope Gate, London, WIK 1LN, Velika Britanija Režim predpisovanja zdravila: Rp/Spec Datu m pri prave I nformaclje: april 2007 Pred predpisovanjem, prosimo, preberite celoten povzetek glavnih značilnosti zdravila. Dodatne informacije in literatura so na voljo pri: AstraZeneca UK Limited Podružnica vSIoveniji Verovškova ulica 55 1000 Ljubljana in na spletnih straneh: www.arimidex.net www.bco.org www.breastcancersource.com <4, AstraZeneca ^ adjuvant fae 'dzuv *nt] 1. adjective pomagljiv, /(pristen; ~ treatment TVitfl Sldjuvantno zdravljenje žtnskjpo menopaozi, ki imajo zgodnji irwazimi rak_dojke s pozitivnimi estrogenskimi receptorji. advanced[*dva:nst] 1. adjective napreden; zvišan (cene); to be ~ napredovati; ~ in years visoke starosti; treatment of ~ Breast cancer zvitfi Arimidex: ZdravCjenje napredovalega raka dojki pn ženskah po menopavzi. Učinkgvitost pri bolnicah z negativnim estrogenskimi receptorji ni bila dokazana razen pri tistih, ki so imele predhodno pozitiven klinični odgovor na tamoksifen. szifitcfi fszincj 1. transitive verß udariti, Bičati s šibo (z repom); šibati z, Hitro mahati z; naglo pograbiti; railway ranžirati, zapeljati (usmeriti) (vlak} na drug tir; electrical vključiti, vklopiti; spremeniti (pogovor), obrniti drugam (tokjmisli'); to ~ back, to figuratively (v mislih) vrniti se na; ~ tO ftrill I Adjuvantno zdravljenje zgodnjega raka dojkg s pozitivnimi estrogenskimi receptorji pri ženskah po menopaozi, ki so se dve do tri leta adjuvantno zdravile s tamoksifenom. Temodal 20 mg, 100 mg, 140mg, 180 mg, 250 mg. Sestava zdravila: Vsaka kapsula zdravila Temodal vsebuje 20 mg, 100 mg, 140 mg, 180 mg aH 250 mg temozolomida. Terapevtske indikacije Temodal kapsule so indicirane za zdravljenje bolnikov z: - za zdravljenje novo diagnosticiranega glioblastoma multiforme, sočasno z radioterapijo in kasneje kot monoterapija - malignim gliomom, na primer multiformnim glioblastomom ali anaplastičnim astrocitomom, ki se po standardnem zdravljenju ponovi ali napreduje. Odmerjanje in način uporabe Temodal smejo predpisati le zdravniki, ki imajo izkušnje z zdravljenjem možganskih tumorjev. Odrasli bolniki z novo diagnosticiranim glioblastomom multiforme Temodal se uporablja v kombinaciji z žariščno radioterapijo (faza sočasne terapije), temu pa sledi do 6 ciklov monoterapije z temozolomidom. Faza sočasne terapije Zdravilo Temodal naj bolnik jemlje peroralno v odmerku 75 mg/m2 na dan 42 dni, sočasno z žariščno radioterapijo (60 Gy, danih v 30 delnih odmerkih). Odmerka ne boste zmanjševali, vendar se boste vsak teden odločili o morebitni odložitvi jemanja temozolomida ali njegovi ukinitvi na podlagi kriterijev hematološke in nehematološke toksičnosti. Zdravilo Temodal lahko bolnik jemlje ves čas 42-dnevnega obdobja sočasne terapije do 49 dni, če so izpolnjeni vsi od naslednjih pogojev: absolutno število nevtrofilcev > 1,5 x 109/l, število trombocitov > 100 x 109/l, skupni kriteriji toksičnosti (SKT) za nehematološko toksičnost < 1. stopnje (z izjemo alopecije, slabosti in bruhanja). Med zdravljenjem morate pri bolniku enkrat na teden pregledati celotno krvno sliko. Faza monoterapije Štiri tedne po zaključku faze sočasnega zdravljenja z zdravilom Temodal in radioterapijo naj bolnik jemlje zdravilo Temodal do 6 ciklov monoterapije. V 1. ciklu (monoterapija) je odmerek zdravila 150 mg/m2 enkrat na dan 5 dni, temu pa naj sledi 23 dni brez terapije. Na začetku 2. cikla odmerek povečajte na 200 mg/m2, če je SKT za nehematološko toksičnost za 1. cikel stopnje <2 (z izjemo alopecije, slabosti in bruhanja), absolutno število nevtrofilcev (AŠN) > 1,5 x 109/l in število trombocitov > 100 x 109/l. Če odmerka niste povečali v 2. ciklusu, ga v naslednjih ciklusih ne smete povečevati. Ko pa odmerek enkrat povečate, naj ostane na ravni 200 mg/m2 na dan v prvih 5 dneh vsakega naslednjega ciklusa, razen če nastopi toksičnost. Med zdravljenjem morate pregledati celotno krvno sliko na 22. dan (21 dni po prvem odmerku zdravila Temodal). Ponavljajoči se ali napredujoči maligni gliom Odrasli bolniki Posamezen ciklus zdravljenja traja 28 dni. Bolniki, ki še niso bili zdravljeni s kemoterapijo, naj jemljejo Temodal peroralno v odmerku 200 mg/m2 enkrat na dan prvih 5 dni, temu pa naj sledi 23-dnevni premor (skupaj 28 dni). Pri bolnikih, ki so že bili zdravljeni s kemoterapijo, je začetni odmerek 150 mg/m2 enkrat na dan, v drugem ciklusu pa se poveča na 200 mg/m2 enkrat na dan 5 dni, če ni bilo hematoloških toksičnih učinkov (glejte poglavje 4.4). Pediatrični bolniki Pri bolnikih starih 3 leta ali starejših, posamezen ciklus zdravljenja traja 28 dni. Temodal naj jemljejo peroralno v odmerku 200 mg/m2 enkrat na dan prvih 5 dni, potem pa naj sledi 23-dnevni premor (skupaj 28 dni). Otroci, ki so že bili zdravljeni s kemoterapijo, naj prejmejo začetni odmerek 150 mg/m2 enkrat na dan 5 dni, s povečanjem na 200 mg/m2 enkrat na dan 5 dni v naslednjem ciklusu, če ni bilo hematoloških toksičnih učinkov (glejte poglavje 4.4). Bolniki z motnjami v delovanju jeter ali ledvic Pri bolnikih z blagimi ali zmernimi motnjami v delovanju jeter je farmakokinetika temozolomida podobna kot pri tistih z normalnim delovanjem jeter. Podatki o uporabi zdravila Temodal pri bolnikih s hudimi motnjami v delovanju jeter (razred III po Child-u) ali motnjami v delovanju ledvic niso na voljo. Na podlagi farmakokinetičnih lastnosti temozolomida obstaja majhna verjetnost, da bo pri bolnikih s hudimi motnjami v delovanju jeter ali ledvic potrebno zmanjšanje odmerka zdravila. Kljub temu je potrebna previdnost pri uporabi zdravila Temodal pri teh bolnikih. Starejši bolniki: Analiza farmakokinetike je pokazala, da starost ne vpliva na očistek temozolomida. Kljub temu je potrebna posebna previdnost pri uporabi zdravila Temodal pri starejših bolnikih. Način uporabe Temodal mora bolnik jemati na tešče. Temodal kapsule mora bolnik pogoltniti cele s kozarcem vode in jih ne sme odpirati ali žvečiti. Predpisani odmerek mora vzeti v obliki najmanjšega možnega števila kapsul. Pred jemanjem zdravila Temodal ali po njem lahko bolnik vzame antiemetik Če po zaužitju odmerka bruha, ne sme še isti dan vzeti drugega odmerka. Kontraindikacije Temodal je kontraindiciran pri bolnikih, ki imajo v anamnezi preobčutljivostne reakcije na sestavine zdravila ali na dakarbazin (DTIC). Temodal je kontraindiciran tudi pri bolnikih s hudo mielosupresijo. Temodal je kontraindiciran pri ženskah, ki so noseče ali dojijo. Posebna opozorila in previdnostni ukrepi Pilotno preskušanje podaljšane 42-dnevne sheme zdravljenja je pokazalo, da imajo bolniki, ki so sočasno prejemali zdravilo Temodal in radioterapijo, še posebej veliko tveganje za nastanek pljučnice zaradi okužbe s Pneumocystis carinii (PCP). Profilaksa proti tovrstni pljučnici je torej potrebna pri vseh bolnikih, ki sočasno prejemajo zdravilo Temodal in radioterapijo v okviru 42-dnevne sheme zdravljenja (do največ 49 dni), ne glede na število limfocitov. Če nastopi limfopenija, mora bolnik nadaljevati s profilakso, dokler se limfopenija ne povrne na stopnjo < 1. Antiemetična terapija: Z jemanjem zdravila Temodal sta zelo pogosto povezana slabost in bruhanje. Laboratorijske vrednosti: Pred jemanjem zdravila morata biti izpolnjena naslednja pogoja za laboratorijske izvide: ANC mora biti > 1,5 x 109/l in število trombocitov > 100 x 109/l. Na 22. dan (21 dni po prvem odmerku) ali v roku 48 ur od navedenega dne, morate pregledati celotno krvno sliko in jo nato spremljati vsak teden, dokler ni ANC nad 1,5 x 109/l in število trombocitov nad 100 x 109/l. Če med katerimkoli ciklusom ANC pade na < 1,0 x 109/l ali število trombocitov na < 50 x 109/l, morate odmerek zdravila v naslednjem ciklusu zmanjšati za eno odmerno stopnjo. Odmerne stopnje so 100 mg/m2, 150 mg/m2 in 200 mg/m2. Najmanjši priporočeni odmerek je 100 mg/m2. Moški bolniki Temozolomid lahko deluje genotoksično, zato morate moškim, ki se zdravijo z temozolomidom svetovati, da naj ne zaplodijo otroka še šest mesecev po zdravljenju. Interakcije Sočasna uporaba zdravila Temodal in ranitidina ni povzročila spremembe obsega absorpcije temozolomida ali monometiltriazenoimidazol karboksamida (MTIc). Jemanje zdravila Temodal s hrano je povzročilo 33 % zmanjšanje Cmax in 9 % zmanjšanje površino pod krivuljo (AUC). Ker ne moremo izključiti možnosti, da bi bila sprememba Cmax lahko klinično pomembna, naj bolniki jemljejo zdravilo Temodal brez hrane. Analiza populacijske farmakokinetike v preskušanjih druge faze je pokazala, da sočasna uporaba deksametazona, proklorperazina, fenitoina, karbamazepina, ondansetrona, antagonistov receptorjev H2 ali fenobarbitala ne spremeni očistka temozolomida. Sočasno jemanje z valprojsko kislino je bilo povezano z majhnim, a statistično značilnim zmanjšanjem očistka temozolomida. Uporaba zdravila Temodal v kombinaciji z drugimi mielosupresivnimi učinkovinami la hko poveča verjetnost mielosupresije. Nosečnost Študij na nosečih ženskah ni bilo. Predklinične študije na podganah in kuncih z odmerkom 150 mg/m2 so pokazale teratogenost in/ali toksičnost za plod. Zato naj noseče ženske načeloma ne bi jemale zdravila Temodal. Če pa je uporaba v času nosečnosti nujna, morate bolnico opozoriti na možne nevarnosti zdravila za plod. Ženskam v rodni dobi svetujte, naj med zdravljenjem z zdravilom Temodal preprečijo zanositev. Dojenje Ni znano, ali se temozolomid izloča v materino mleko, zato ženske, ki dojijo ne smejo jemati zdravila Temodal. Neželeni učinki V kliničnih preskušanjih so bili najpogostnejši neželeni učinki, povezani z zdravljenjem, prebavne motnje, natančneje slabost (43 %) in bruhanje (36 %). Oba učinka sta bila ponavadi 1. ali 2. stopnje (od 0 do 5 epizod bruhanja v 24 urah) in sta prenehala sama, ali pa ju je bilo mogoče hitro obvladati s standardnim antiemetičnim zdravljenjem. Incidenca hude slabosti in bruhanja je bila 4 %. Laboratorijski izvidi: Trombocitopenija in. nevtropenija 3. in. 4. stopnje sta se pojavili pri 19 % in. 17 % bolnikov, zdravljenih zaradi malignega glioma. Zaradi njiju je bila potrebna hospitalizacija in/ali prekinitev zdravljenja z zdravilom Temodal pri 8 % in. 4 % bolnikov. Mielosupresija je bila predvidljiva (ponavadi se je pojavila v prvih nekaj ciklusih in je bila najizrazitejša med 21. in 28. dnem), okrevanje pa je bilo hitro, ponavadi v 1 do 2 tednih. Opazili niso nobenih dokazov kumulativne mielosupresije. Trombocitopenija lahko poveča tveganje za pojav krvavitev, nevtropenija ali levkopenija pa tveganje za okužbe. Imetnik dovoljenja za promet Sp Europe 73, rue de Stalle B-1180 Bruxelles Belgija. Način in režim izdaje Zdravilo se izdaja samo na recept, uporablja pa se pod posebnim nadzorom zdravnika specialista ali od njega pooblaščenega zdravnika. Datum priprave informacije oktober 2007. Schering-Plough Dunajska 22,1000 Ljubljana tel: 01 300 10 70 fax: 01 300 10 80 Resnični napredek Pri na novo odkritem glioblastomu multiforme in malignih gliomih, ki se ponovijo ali napredujejo. Poenostavljeno zdravljenje Z dvema novima jakostima 140 mg in 180 mg Temodal • Možnost prejemanja manjšega števila kapsul • Boljša sprejemljivost in sodelovanje bolnika • Natančno odmerjanje • Barvne kapsule za enostavnejšo dnevno uporabo J ^°NAVELBINE® vinorelbine Koncentrat za raztopino za infundiranje 10 mg/ml, 50 mg/5ml Novost za zdravljenje: nedrobnoceličnega raka pluč in napredovalega raka dojke Odlična učinkovitost v kombinaciji s cisplatinom ali kot monoterapija za bolnike, ki niso primerni za polikemoterapijo Dobra prenosljivost: - blaga alopecija - zelo nizka stopnja emetogenosti (<10 %) - ni kardiotoksičnosti - ni nevrotoksičnosti Premedikacija ni potrebna Sinergistično delovanje s tarčnim zdravilom trastuzumab Pred predpisovanjem zdravila Navelbine® preberite povzetek temeljnih značilnosti, ki ga dobite pri naših strokovnih sodelavcih. _ M E D 1 S I www.medis.si I onkologija@medis.si Radiology and Oncology Editorial policy Editorial policy of the journal Radiology and Oncology is to publish original scientific papers, professional papers, review articles, case reports and varia (editorials, reviews, short communications, professional information, book reviews, letters, etc.) pertinent to diagnostic and interventional radiology, computerized tomography, magnetic resonance, ultrasound, nuclear medicine, radiotherapy, clinical and experimental oncology, radiobiology, radiophysics and radiation protection. 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Y Vodilni Z GEMZARjem GEMZAR je indiciran za zdravljenje: nedrobnoceličnega karcinoma pljuč adenokarcinoma trebušne slinavke karcinoma sečnega mehurja , karcinoma dojke in ^ karcinoma ovarijev Utlrl^Alv [gemcitabin] Skrajšan povzetek glavnih značilnosti zdravila Gemzar 200 mg prašek za raztopino za infundiranje, Gemzar 1 g prašek za raztopino za infundiranje Sestava zdravila: 200 oz. 1 g gemci tabina, manitol, natrijev acetat, klorovodikova kislina in/ali natrijev hidroksid (za uravnavanje pH). Terapevtske indikacije: Lokalno napredovali ali metastatski karcinom sečnega mehurja, v kombinaciji z drugimi citostatičnimi zdravili. Lokalno napredovali ali metastatski nedrobnocelični karcinom pljuč, v kombinaciji z drugimi citostatičnimi zdravili. Lokalno napredovali ali metastatski adenokarcinom trebušne slinavke, pri bolnikih v dobrem splošnem stanju z zadostnimi rezervami kostnega mozga. Lokalno napredovali ali metastatski karcinom dojke v kombinaciji s paklitakselom pri bolnicah, pri katerih je prišlo do relapsa bolezni po predhodnem predoperativnem in/ali dopolnilnim zdravljenju s citostatiki. Predhodno zdravljenje mora vključevati antracikline, razen če so kontraindicirani. Lokalno napredovali ali metastatski epitelijski karcinom ovarijev, v kombinaciji s karbopla-tinom, pri bolnikih z relapsom bolezni po vsaj 6-mesečnem obdobju brez relapsa po zdravljenju prvega izbora na osnovi platine. Odmerjanje in način uporabe: Karcinom sečnega mehurja (v kombinaciji s cisplatinom 70 mg/m.?}, odrasli in starejši: Priporočeni odmerek gemcitabina je 1000 mg/m2, dan kot infuzija v 30 minutah. Odmerek dajemo 1., 8. in 15. dan vsakega 28-dnevnega ciklusa. Cisplatin dajemo v odmerku 70 mg/m2 2. dan vsakega 28-dnevnega ciklusa. Ta štiritedenski ciklus nato ponavljamo. Karcinom dojke (uporaba v kombinacijii), odrasli: Priporočamo uporabo gemcitabina v kombinaciji s paklitakselom, pakli taksel (175 mg/rn^ damo 1. dan preko približno 3 ur kot intravensko infuzijo, temu sledi gemctabin (1250 mgW) kot 30-minutna intravenska infuzija 1. in 8. dan vsakega 21-dnevnega ciklusa. Bolniki naj imajo pred uvedbo kombiniranega zdravljenja z gemcitabinom in paklitakselom absolutno koncentracijo gran ulocitov vsaj 1.500 (x 106/1). Nedrobnocelični kardnom pljuč (v kombinaciji s cispiatinom), odrasli in starejši: Pri zdravljenju po tritedenski shemi je priporočeni odmerek gemcitabina 1250 mg/m2 površine telesa, dan kot 30-minutna intravenska infuzija 1. in 8. dan ciklusa zdravlenja (21 dni). Odmerek lahko med tekočim ciklusom zdravlenja ali ob naslednjem ciklusu zdravljenja znižamo glede na individualno opazovano toksičnost. Pri zdravljenju po štiritedenski shemi je priporočeni odmerek gemcitabina 1000 mg/m2 površine telesa, dan kot 30-minutna intravenska infuzija 1., 8. in 15. dan ciklusa zdravljenja (28 dni). Karcinom jajčnika (uporaba v kombinaciji), odrasli: Priporočamo gemcitabin v kombinaciji s karboplatinom, z uporabo 1000 mg/mčgemcitabina 1. in 8. dan vsakega 21-dnevnega ciklusa, v obliki 30-minutne intravenske infuzij e. Po gemcitabinu 1. dan damo karboplatin, da dosežemo ciljno AUC 4,0 mg/ml x minuto. Karcinom trebušne slinavke, odrasli in starejši: Priporočeni odmerek gemcitabina je 1000 mg/m2 površine telesa, ki ga dajemo kot intravensko infuzijo v 30 minutah. To ponavljamo enkrat tedensko v obdobju do 7 tednov, ki mu dedi enotedenska prekinitev. V naslednjih ciklusih Gemzar dajemo enkrat tedensko v obdobju treh tednov, ki mu sledi enotedenska prekinitev. Odmerek lahko med tekočim ciklusom zdravljenja ali ob naslednjem ciklusu zdravljenja znižamo glede na individualno opazovano toksičnost. Odmerek lahko z vsakim ciklusom ali med tekočim ciklusom znižamo glede na toksičnost, izraženo pri bolniku. Kontraindikacije: Preobčutljivost za gemcitabin ali katero od pomožnih snovi. Bolnikom z zmerno do hudo okvarjenim jetrnim delovanjem ali hudo okvarjenim ledvičnim delovanjem Gemzarja ne smemo dajati. Posebna opozorila in previdnostni ukrepi: Podaljšanje časa infuzije in skrajšanje priporočenega intervala med odmerki povečujeta toksičnost. Gemcitabin moramo pri bolnikih z blago do zmerno okvarjenim ledvičnim delovanjem in pri bolnikih z blago okvarjenim jetrnim delovanjem uporabljati previdno. Ce se pojavijo kakršnikoli znaki mikroangiopatske hemolitične anemije je treba zdravljenje z Gemzarjem prekiniti. Dajanje gemcitabina bolnikom s sočasnimi jetrnimi zasevki ali hepatitisom, alkoholizmom ali jetrno cirozo v preteklosti lahko povzroči poslabšanje osnovnega popuščanja delovanja jeter. Pri bolnikih z okvarjenim delovanjem kostnega mozga je treba zdravljenje začeti previdno. Moškim, zdravljenim z Gemzarjem, odsvetujemo spočetje otroka med zdravljenjem in do 6 mesecev po njem. Pred vsakim odmerkom je treba preveriti koncentracije trombocitov, levkocitov in granulocitov. Tveganje za neželene učinke, povezane z dihali, je višje pri bolnikih s karcinomom pljuč in pljučnimi zasevki, kot pri drugih tipih tumorjev. V primeru intersticijskega pnevmonitisa skupaj s pljučnimi infiltrati ter hudih, redko smrtnih pljučnih neželenih učinkih, denimo pljučnem edemu, intersticijskem pnevmonitisu in sindromu akutne dihalne stiske je treba zdravljenje z Gemzarjem prekiniti. Gemcitabin so pri otrocih preučevali v omejenih preskušanjih faze 1 in 2 pri različnih tipih tumorjev. Te študije niso podale zadosti podatkov za zagotovitev učinkovitosti in varnosti gemcitabina pri otrocih. Interakcije: Ob sočasni radioterapiji (obsevanja istočasno ali v roku s 7 dni pred kemoterapijo ali po njej) gemcitabin deluje radio-senzitizirajoče, poročali pa so tudi o obsevalnih poškodbah na ciljnih tkivih. Neželeni učinki: Obseval na toksičnost in odpoklic obsevanja; Zelo pogosti: levkopenija, trombocitopenija, anemija, dispneja, slabost, bruhanje, povišane vrednosti AST, ALT in alkalne fosfataze, alergijski izpuščaj, pogosto s srbenjem, blaga proteniurija in hematurija, edem in periferni edem, gripi podobni simptomi, kašelj, rinitis, znojenje, motnje spanja, povišana temperatura in astenija; Pogosti: fe-brilna nevtropenija, anoreksija, glavobol, zaspanost, nespečnost, dia reja, zaprtje, stomatitis, povišane vrednosti bilirubina, znojenje, srbenje, alopecja, mialgija, bolečine v hrbtu, mrzlica, edem obraza; Manj pogosti: pljučni edem, bronhospazem, intersticijski pnevmo-nitis; Redki: miokardni ifarkt, popuščale srca, aritmija, hipotenzya, sindrom dihalne stiske pri odraslem, povišane vrednosti gama-GT, luščenje, tvorba mehurjev in razjed, odpoved ledvic, hemolitično-uremični sindrom; Zelo redki: trombocitoza, anafilaktoidna reakcija, klinični znaki perifernega vaskulitisa in gangrene, hude kožne reakcije, vključno z luščenjem in buloznimi vzbrstmi. Imetnik dovoljenja za promet: Eli Lilly Holdings Limited, Kingsclere Road, Basingstoke, Hampshire, RG21 6XA Velika Britanija Način in režim izdaje zdravila: H - Zdravilo se izdaja le na recept, uporablja pa se samo v bolnišnicah. Datum revizije besedila: 14.10.2006 Eli Lilly farmacevtska družba, d.o.o. Dunajska 156, 1000 Ljubljana, Slovenija Tel.: (01) 5800 010, faks: (01) 5691 705