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Naše dosedanje izkušnje in izkušnje drugod jasno utemeljujejo potrebo dosmrtnega spremljanja bolnikov, ozdravelih od raka v otroštvu. Glede na to, da se enake težave in posledice zdravljenja raka verjetno pojavljajo tudi pri drugih bolnikih, ki imajo pred seboj še dolgo življenje, je potrebno dosmrtno spremljanje vseh nekdanjih bolnikov, ki so zboleli v mladosti.

Obsevanje je utečen in uspešen način zdravljenja možganskih tumorjev, vendar moramo vedeti, da ima poleg akutnih neželenih učinkov lahko tudi pozne posledice, ki se pokažejo šele leta po končanem zdravljenju. Med največkrat na ta način okvarjenimi organi so endokrine žleze, predvsem hipotalamus in hipofiza. Na podlagi kliničnega primera želimo pokazati, da bolniki po obsevanju glave nujno potrebujejo tudi redno endokrinološko testiranje in po potrebi ustrezno hormonsko nadomestno zdravljenje. Radiotherapy is a proven and successful way of treating brain tumors. One should be aware, however, of its acute side effects as well as late consequences, often only apparent years after concluded treatment. The endocrine glands, primarily the hypothalamus and pituitary gland, are the most commonly affected organs. We present a clinical case to illustrate that, after irradiation of the head, patients should have periodic endocrinological testing and adequate hormonal substitution, when necessary.

A 27-year-old male was treated for medulloblastoma with complete removal of tumor, postoperative RT to CNA with 36 Gy and boost to the posterior fossa 16 Gy. Nine years later, a suprasellar recurrence was treated with Carboplatin and Vepezid and 33 Gy to the tumor bed. Three years later he complained about headaches, periodic loss of conciousness and progressively showed bizarre behavior. He was referred to psychiatrist. No recurrence was found. He did not appear on the day of follow-up appointment. He died at home, at the age of 43 years, 16 years after the first treatment. The cause of death determined by forensic autopsy : anemic subacute infarction in the left cerebellum

Pri bolnikih, ki so se zdravili zaradi raka v otroštvu, so okvare kardiovaskularnega sistema med poglavitnimi vzroki pozne umrljivosti, ki je sedem-krat večja kot pri splošni populaciji. Najpogostejši vzrok komplikacij na srcu pri bolnikih z rakom so antraciklini ki sodijo med najučinkovitejša zdravila neoplastičnih bolezni. Pri opisu primera našega bolnika želimo opozoriti na napredujočo okvaro srčne mišice po zdravljenju ne-Hodgkinovega limfoma s kemoterapijo, ki je vsebovala antracikline in alkilirajoče agense, in je 28 let po končanem zdravljenju privedla do odpovedi srca, zaradi katere je bila potrebna transplantacija srca. Pri bolnikih, zdravljenih z antracikini, je zelo pomembno doživljenjsko sledenje funkcije srca, da vsako motnjo (tudi klinično nemo) na srcu čim prej odkrijemo in ustrezno zdravimo. Ehokardiografija je najpogosteje uporabljena diagnostična metoda za ocenjevanje delovanja srca v okviru sledenja poznih posledic zdravljenja s citostatiki in/ali obsevanjem. Zelo pomembno je morebitne okvare najti v fazi, ko je bolnik še asimptomatski, saj lahko z ustreznim zdravljenjem (predvsem ACE inhibitorji in beta-blokatorji) in ustreznim načinom življenja in zmanjševanjem drugih dejavnikov tveganja za razvoj kardiovaskularnih obolenj preprečimo oz. upočasnimo razvoj življenje ogrožujoče okvare srca. In patients, who have received cancer treatment in childhood, the damages of the cardiovascular system are among the primary causes for later mortality, which is seven times higher than in general population. The most frequent cause for heart complications in cancer patients are anthracycline, which are the most effective medications for neoplastic diseases. In our patient case report we wish to draw attention to the advanced heart muscle defect after treatment of nonHodgkin’s lymphoma with chemotherapy, which included anthracyclines and alkaline agents, after 28 years resulted in heart failure and required a heart transplant. In patients treated with anthracyclines, lifetime active monitoring of their cardiac function is crucial, so that any heart disturbances (also clinically silent) are discovered as soon as possible and treated accordingly. Echocardiography is the most frequently used diagnostic method for heart function evaluation within the scope of monitoring subsequent consequences of cytostatic treatment and/or radiation. It is very important that any potential defects are discovered at a stage when the patient is still asymptomatic, because appropriate treatment (mainly ACE inhibitors and beta blockers), appropriate lifestyle, as well as minimising other risks for developing cardiovascular disease can prevent or delay the development of a life-threatening heart defect.

Ni abstrakta.

Akutne in kronične okvare pljuč po zdravljenju raka v otroštvu so po sodobnem zdravljenju redke in običajno brez kliničnih znakov ter simptomov. Pri bolnici, ki je bila v otroštvu zdravljena zaradi Hodgkinovega limfoma z obsevanjem vratu, supraklavikularnih bezgavk in mediastinuma ter s kemoterapijo, so kvarne posledice verjetna kombinacija neugodnih učinkov tega zdravljenja na srce in pljuča. Pri naši bolnici je glede na potek in napredovanje pljučne prizadetosti v ospredju vaskularna prizadetost - pljučna vaskulopatija, ki je bila s histološkim pregledom bioptata pljučnega tkiva tudi potrjena. Pri opisu želimo opozoriti na kroničen ter progredienten potek bolezni, ki terja zahtevno obravnavo specialistov in 22 let po zdravljenju povzroča težko invalidnost. Acute and chronic defects following childhood cancer treatment are rare with modern treatment techniques and usually without any clinical signs and symptoms. In a patient who was treated for childhood Hodgkin's lymphoma with irradiation to the neck, supraclavicular lymph nodes and mediastinum and chemotherapy, the consequences include a probable combination of adverse effects of this treatment on the lungs and heart. Considering the course and progression of lung impairment, vascular impairment - pulmonary vasculopathy was found to be at the forefront in our patient, which was confirmed by histological examination of the lung-tissue bioptat. By describing this case, we wish to point to the chronic and progredient course of the disease which requires complex management by specialists and causes severe disability 22 years after treatment.

Z izboljšanjem zdravljenja malignomov pri otrocih se je izboljšalo njihovo preživetje, vendar se po ozdravitvi sčasoma lahko razvijejo škodljive pozne posledice zdravljenja. Te spremembe, ki so pogosto asimptomatske, lahko pravočasno odkrijemo le, če bolnike redno spremljamo tudi po končanem zdravljenju. V prispevku predstavljamo primer bolnika, ki je bil v otroštvu obsevan in zdravljen s kemoterapijo, umrl pa je mlad z znaki srčne okvare, h kateri je verjetno prispevalo onkološko zdravljenje. Spremembe na srcu je pokazala šele obdukcija. Advances in the treatment of malignancies in children have improved their survival rates. However, the recovery may eventually be followed by the development of adverse late effects of treatment. These changes, which are often asymptomatic, may be detected on time only if the patients are monitored regularly even after they have completed their treatment. The article presents a case of a patient who was irradiated in childhood and treated with chemotherapy, dying at a young age with signs of cardiac dysfunction, which was most likely a result of cancer treatment. Cardiac changes were diagnosed only at autopsy.

Tveganje za nastanek sekundarnega raka debelega črevesja je pri bolnikih, ki so se zdravili zaradi raka v otroštvu, večje od tistega v splošni populaciji in strmo narašča s časom opazovanja ter s povečano dozo obsevanja v predelu trebuha. Pri bolniku, ki je bil v starosti 12 let uspešno zdravljen zaradi Hodgkinove bolezni s kemoterapijo in obsevanjem prizadetih regij, vključno paraaortnih bezgavk, je bila 27 let po zdravljenju ugotovljena mikrocitna hipohromna anemija. Sum, da gre za gastrointestinalno krvavitev z enkratno preiskavo blata, ni bil potrjen. Pol leta kasneje je bil ugotovljen metastatski adenokarcinom debelega črevesja. Zdravljen je bil operativno, s sistemskim zdravljenjem in paliativnim obsevanjem spinalnih ter možganskih metastaz. Leto in pol po začetku zdravljenja sekundarnega tumorja je bolnik v starosti 40 let umrl. Pri bolnikih, zdravljenih zaradi raka v otroštvu, so pozne posledice številne. Sekundarni maligni tumorji so drugi najpogostejši vzrok smrti, takoj za recidivom bolezni. Zato je zelo pomembno, da jih pravočasno odkrijemo in ustrezno zdravimo. Od leta 2014 je za bolnike, ki so prejeli 30 Gy ali več na predel trebuha, v mednarodnih smernicah priporočeno spremljanje s kolonoskopijo. Enkratna preiskava blata na kri in UZ trebuha nista zanesljivi metodi za odkrivanje raka debelega črevesja. The risk of developing secondary colon cancer is larger in patients treated for childhood cancer than in the general population, and it is rapidly increasing with observation time and increased radiation dose to the abdominal area. A patient, who was successfully treated for Hodgkin’s disease at the age of 12 with chemotherapy and radiation of the affected regions, including para-aortic lymph nodes, was diagnosed with microcytic hypochromic anaemia 27 years after treatment. A suspicion that this is gastrointestinal haemorrhage was not confirmed by a single-stool examination. Half a year later, the patient was found with metastatic adenocarcinoma of the colon and was treated operatively with systemic treatment and palliative radiation of spinal and brain metastases. A year and a half after the start of treatment of secondary tumour, the patient died at the age of 40 years. Patients treated for childhood cancer experience several late consequences. Secondary malignant tumours are the second most common cause of death, right after disease recurrence. Therefore, timely detection and appropriate treatment are of utmost importance. Since 2014, the international guidelines recommend that patients receiving 30 Gy or more to the abdominal region are monitored by colonoscopy. A single-stool examination for occult blood and US of the abdomen are not reliable methods for detecting colon cancer.

zhodišča: Nevroblastom je maligni tumor simpatičnega živčevja in predstavlja približno 5 odstotkov malignomov v otroški dobi. Namen raziskave je bil primerjati preživetje bolnikov z nevroblastomom, zdravljenih v Sloveniji od leta 1994 do 2007, s preživetjem bolnikov z nevroblastomom, ki so se zdravili med letoma 1980 in 1993, ter analizirati vpliv različnih dejavnikov na preživetje. Hipoteza je bila, da se je preživetje otrok, zdravljenih v obdobju 1994%2007, izboljšalo. Metode: V retrospektivno raziskavo je bilo vključenih 78 bolnikov z nevroblastomom, ki so se zdravili na Univerzitetni pediatrični kliniki in Onkološkem inštitutu v Ljubljani od leta 1980 do 2007. Seznam in osnovni podatki bolnikov so bili pridobljeni iz Registra raka Republike Slovenije. Podatki o bolnikih, značilnostih tumorjev in poteku zdravljenja so bili zbrani s pregledom popisov bolezni. Rezultati: Od 78 otrok z nevroblastomom vključenih v raziskavo, je živih 39 (50%%) oseb. Umrlo je 39 (50%%) bolnikov, od tega 23 (29,5%%) bolnikov med primarnim zdravljenjem, 15 (19,2%%) ob recidivu bolezni, pri enem (1,3%%) bolniku pa vzrok smrti ni znan. Preživetje glede na stadij bolezni, umeščenost in velikost primarnega tumorja se je v obdobju 1994%2007 v primerjavi z obdobjem 1980%1993 izboljšalo, medtem ko se preživetje glede na starost ob diagnozi in obseg operacije v obeh obdobjih ni statistično značilno razlikovalo. Zaključek: Raziskava je pokazala, da se je po letu 1994 preživetje bolnikov z nevroblastomom v primerjavi z zdravljenimi pred tem, izboljšalo. Najpomembnejši napovedni dejavniki so bili v obeh obdobjih stadij bolezni, starost bolnika in velikost tumorja ob diagnozi.

Pacienti po zdravljenju raka v otroštvu so glede samomorilnosti izrazito občutljiva skupina. Pri njih sta povišana tako razmišljanje o samomoru kot tudi dejanski samomor. V slovenskem prostoru sicer ne beležimo povišane stopnje samomora pri tej skupini pacientov. Od 1.647 pacientov, ki so bili v otroštvu zdravljeni za rakom, so zaradi samomora umrli trije. V pričujočem članku so predstavljeni vsi trije pacienti, ki so storili samomor. Iz podatkov, ki so nam na voljo, smo sklepali na sorodnosti in različnosti, ki so botrovale razvoju samomorilnosti pri vsakem od njih. Ugotovimo lahko, da je bilo kljub razlikam v poteku in zdravljenju bolezni skupno vsem trem pacientom to, da niso bili deležni polne strokovne psihološke pomoči, ki naj bi bila namenjena pacientom po zdravljenju raka v otroštvu. Razvoj dobre strokovne mreže na tem področju bi lahko omogočil vključitev večjega števila pacientov, da bi lahko spregovorili o svojih psihičnih težavah. S tem bi lahko pomembno prispevali k preprečevanju samomora pri tej ranljivi skupini pacientov. Patients treated for childhood cancer are particularly vulnerable to suicide. There is increased suicidal ideation and a high incidence of suicide among them. In Slovenia, we have recorded no increase in the suicide rate in this group of patients. Out of 1,647 patients who were treated for cancer in childhood, only three died by suicide. The following article presents all three patients who committed suicide. With the help of the available data, we established the similarities and differences that contributed to the development of suicidal behaviour in each of these three patients. We can find that despite the differences in the course and treatment of the disease, all three patients had one thing in common: none of them received professional psychological help intended for patients after childhood cancer treatment. The development of a well-functioning professional network in this field would enable the inclusion of a larger number of patients, allowing them to speak out about their psychological problems. By doing so, we would contribute significantly to preventing suicide in this vulnerable group of patients.

Po zdravljenju Hodgkinove bolezni z obsevanjem in kemoterapijo v otroštvu se lahko šele čez leta pojavijo posledice na srcu. Pri predstavljenem bolniku smo 25 let po zdravljenju ugotovili spremembe na srcu, ki so se med desetletnim opazovanjem stopnjevale. Ugotovili smo prizadetost diastolične funkcije levega srčnega prekata, fibrozo na aortni in mitralni zaklopki ter zadebelitev osrčnika. Pri mladostnikih, ki so se v otroštvu zdravili zaradi raka, je potrebno sledenje poznih posledic do konca življenja. Večino neugodnih posledic na srcu lahko odkrijemo z neinvazivno ehokardiografsko preiskavo. Cardiac damage can develop many years after treatment of Hodgkin’s disease with irradiation and chemotherapy. In the presented case, we found cardiac damage 25 years after treatment. In the last decade, it has been severily escalating. The patient was diagnosed with the diastolic dysfunction of the left ventricle, fibrosis of the aortic and mitral valves and thickening of the pericardium. In childhood cancer survivors, lifelong follow-up is necessary. The majority of cardiac late effects can be discovered with non invasive ultrasound examination.

Background. Neoadjuvant chemotherapy (Cht) has changed the treatment of rhabdomyosarcoma (RMS) in children. The purpose of our study was to review thechildren treated for RMS between 1974 and 1996. Patients and methods. Fifty-one children, 1-15 years old, were included. Primary sites of tumour were: head and neck 15, orbit 6, genitourinary 12, extremity 9, torso 5 and paratesticular 4. Twelve patients were in stage 1, 10 in stage II, 26 in stage111 and 3 in stage IV. Of 43 histologically confirmed RMS 25 were embryonal, 13 alveolar, 1 botryoid, 1 spindle cell and 3 sarcoma NOS. In 8 patients, only fine needle aspiration biopsy (FNAB) was available. All patients had Cht, 29 neoadjuvant, 20 had surgery first, 40 had irradiation (RT), 2 stage IV patients had bone marrow transplant (ABMT). Multidrug Cht varied: VCR, AMD, and cyclophosphamide (VAC) were used in the 1970s, with Adriablastine (T2), methotrexat (MTX) and/or other drugs (T6, T11) in the 1980s; and in the 1990s, cyclophosphamide was replaced by ifosfamide (VAIA). The treatment was started with Cht in orbital and head and neck tumours and inthe majority of genitourinary tumours, but surgery was first in paratesticular and in the majority of extremity tumours. Results. The 3 patients with stage IV disease died. Of those with localised tumour, 34 (70%) were alive and well 5 years after treatment, 80% stage I, 75% stage II and 61%stage III. One patient died of heart failure, 3 of Cht toxicity and 1 of intereurrent disease. Conclusions. (Abstract truncated at 2000 characters) Izhodišča. Neoadjuvantna kemoterapija (KT) je spremenila način zdravljenja rabdomiosarkoma (RMS) otrok. Namen naše študije je bil analizirati rezultate zdravljenja pri otrocih, ki so bili zdravljeni v letih med 1974 in 1996. Bolniki in metode. V študijo smo vključili 51 otrok med enim in 15 letom starosti. Primarni tumorji so bili v področju glave in vratu pri 15, v orbiti pri 6, v genitourinskem področju pri 12, na udih pri 9, na trupu pri 5 in paratestikularno pri 4 bolnikih. Dvanajst bolnikov je imelo bolezen s stadijemI, 10 s stadijem II, 26 s stadijem III in 3 s stadijem IV. Med 43 histološko potrjenimi primeri RMS je imelo 25 bolnikov embrionalni podtip, 13 alveolarni, 1 botrioidni, 1 vretenastocelični in 3 sarkom brez nadalnje opredelitve. Pri 8 bolnikih je bila morfološka diagnoza opredeljena le iz vzorca aspiracijske biopsije s tanko iglo (ABTI). Vsi bolniki so prejeli KT, 29 neoadjuvantno, 20 je bilo najprej operiranih, 40 je bilo obsevanih (RT), 2 bonika z boleznijo v stadiju IV sta imela presaditev kostnega mozga. Kombinirana KT se je v različnih obdobjih razlikovala: z VRC, AMD in ciklofosfamidom (VAC) smo zdravili v 70-tih letih, kombinirano z tždriablastinom (T2), MTX in/ali drugimi kemoterapevtiki (T6, T11) v 80-tih letih, ciklofosfamid smo zamenjali z ifosfamidom v 90-tih letih (VAIA): S kemoterapijo smo pričeli pri tumorjih orbite, glave in vratu in pri večini tumorjev genitourinskega področja. Operacija je bila na prvem mestu pri paratestikularnih tumorjih in pri večini tumorjev na udih. Rezultati. Vsi trije bolniki z boleznijo v stadiju IV so umrli. Med bolniki z lokaliziranimi tumorji je bilo 34 (70 %) živih in brez znakov bolezni 5 let po pričetku zdravljenja: 80% bolnikov s stadijem I, 75 % s stadujem II in 61 % s stadijem III. En bolnik je umrl zaradi odpovedi srca, 3 zaradi posledic KT in eden zaradi spremljajoče bolezni. (Izvleček skrajšan pri 2000 znakih)

Introduction of cisplatin-based chemotherapy (ChT) improved the cure rate of patients with testicular cancer. Polyneuropathy, as the most common side effect of cisplatin, is observed in a high proportion of patients treated with PVB. Peripheral nerve damage of different grade, depending on the cumulative dose of the drug may last for many years after the conclusion of treatment. A large study on neuro-toxic symptoms in subjects treated with 6 cycles PVB is quoted. In the presented patient, neurologic symptoms appeared 11 years after the treatment with 3 cycles of PVB. The cause of his symptoms is not clear. Years ago, radiation was recognized as the most frequent cause of late effects, with chemotherapy recently increasing its role in this process. Careful life time follow-up by assorted specialists is necessary to gain further experience.

For resistant local recurrence, e.g. in breast cancer, or metastatic spread, local infiltration of IFN may be an interesting new approach. The aim of this study was to find out if intrapleurally administered interferon, in breast cancer patients with pleural carcinomatosis, can cause measurable serum concentrations and how soon after administration. Serum IFN concentrations were compared to those in the pleural fluid, and correlated with the presence of malignant cells in the pleural fluid.To uncover possible rhytmicity of serum interferon levels and its relationship to the timing of the therapy, natural leukocyte interferon was administered intrapleurally at 10 a.m. Data on pharmacokinetics were obtained from blood samples drawn at -2, 0, 2, 8, 14, 22 and 46 h during course of treatment. In contrast to our previous observations in healthy volunteers, levels of serum IFN before therapy had no circadian rhythmicity: Daily pharmacokinetic profile of individual patients on interferon therapy has shown that serum IFN peaks 8 h after intrapleurally administered IFN alpha. The peak depended on frequency and number of applied doses. During treatment with IFN alpha, malignant cells degenerated and finally disappeared from pleural fluid. At the same time reactive cells appeared. This effect is rather uniformly observed, but varies in degree. The number of patients is too small, however, to permitt conclusions in regard to correlation of this clinical effect and the levels of serum IFN alpha.