Demografska i kliničko-patološka obilježja bolesnica s primarnim rakom dojke liječenih u razdoblju od 1997. do 2010. godine: iskustvo jedne klinike

Breast cancer accounted for 28% of all new cancers and 18% of female cancer deaths in Europe in 2010. It is the most common type of cancer in women in Croatia, with an incidence rate of 56.9/100 000 in the year 2010, and the highest number of newly diagnosed women aged between 60 and 64. Multiple factors are associated with an increased risk of breast cancer: advancing age, family history, exposure to endogenous and exogenous reproductive hormones, dietary factors, benign breast disease, and environmental factors. To assess demographic and clinicopathologic features of primary breast cancer, we retrospectively analyzed 870 patients treated in our institution between 1997 and 2010. Data were obtained from medical documentation and a printed questionnaire regarding life habits. Most of our patients presented with a breast lump and were self-diagnosed by breast examination. This fact highlights the need of regular breast self-examination, although it should also be taken into account that most of our patients did not attend regular mammography screening (only 31%). One of the most concerning facts is that the mean time from observing the first symptom to visiting a physician was 4 months. Previous studies have identified ignorance, fear and fatalistic attitudes, poor socioeconomic conditions, and illiteracy as important factors resulting in delay. Considering these facts, education and raising awareness about the disease in the general population is one of the key weapons for lowering breast cancer mortality.U europskoj populaciji rak dojke činio je 2010. godine 28% svih novodijagnosticiranih zloćudnih tumora te bio uzrokom smrti u 18% žena oboljelih od raka. Prvi je po učestalosti zloćudni tumor u žena u Hrvatskoj, s incidencijom od 56,9/100.000 (2010. godine), a najveći broj bolesnica dijagnosticira se u dobi između 60 i 64 godine. Rizični čimbenici za rak dojke su višestruki: dob, pozitivna obiteljska anamneza, izloženost endogenim i egzogenim hormonima, prehrana, dobroćudna bolest dojke te okolišni čimbenici. Radi procjene demografskih i kliničko-patoloških značajka primarnog raka dojke retrospektivno smo analizirali 870 bolesnica koje su liječene u našoj ustanovi između 1997. i 2010. godine. Podaci su prikupljeni iz medicinske dokumentacije te formuliranog upitnika koji se odnosio na životne navike. U većine bolesnica se bolest prezentirala kao čvor u dojci te su bolest dijagnosticirale same. Ova činjenica naglašava potrebu redovitog samopregleda, iako također treba uzeti u obzir činjenicu da je tek manji broj bolesnica redovito pohađao kontrolne mamografske preglede (31%). Zabrinjava podatak da je prosječno vrijeme od prvog simptoma bolesti do javljanja liječniku bilo čak 4 mjeseca. Prema ranijim studijama najvažniji razlozi odgode javljanja liječniku su neznanje, strah i fatalistički odnos prema bolesti, niži socioekonomski status te nepismenost. U skladu s dobivenim rezultatima, izobrazba i podizanje svijesti o bolesti u općoj populaciji među ključnim su metodama za snižavanje smrtnosti od raka dojke

Sustavna terapija raka debelog crijeva – pregled novih kliničkih studija

Colorectal cancer (CRC) is the most common malignancy of the gastrointestinal tract worldwide, and also one of the leading causes of cancer-related mortality, accounting for more than 600000 deaths every year. Depending on the stage of the disease some patients who were surgically treated for CRC with curative intent require adjuvant chemotherapy (fluorouracile-based), which reduces the risk of recurrence and death in patients with stage III CRC, but its role in stage II is still controversial. Pathogenesis of CRC is a result of two different genetic pathways: chromosomal instability (CIN), and inactivation of mismatch repair (MMR) genes. Stage II patients with deficient MMR tumor status do not benefit from adjuvant therapy and should receive surgery alone. For patients with metastatic CRC optimal sequence of chemotherapy regimens and targeted therapy is still debated. Epidermal growth factor receptor (EGFR) has been validated as a therapeutic target in several human tumors including CRC. Recently it has been reported that activating mutations in exons 2, 3, and 4 of both KRAS and NRAS all predict a lack of response to EGFR trageted agents. Recent studies suggest BRAF is another prognostic and potential predictive biomarker of CRC. It is necessary to indentify new prognostic and predictive markers, to acquire maximal benefit from every therapy line and to improve prognosis of these patients.Rak debelog crijeva (CRC) najučestalija je maligna neoplazma gastrointestinalnog trakta, te je sa preko 600.000 smrti godišnje jedan od vodećih uzroka smrtnosti od zloćudnih bolesti. Ovisno o stadiju bolesti, neki od bolesnika koji su kirurški liječeni radi raka debelog crijeva s ciljem izlječenja zahtijevaju primjenu adjuvantne kemoterapije (bazirane na fluorouracilu) koja smanjuje rizik povrata bolesti i smrti u III. stadiju bolesti, no njena uloga u stadiju II još je uvijek nedovoljno jasna. Patogeneza u CRC rezultat je dvaju različitih molekulsko-genskih mehanizama: kromosomske nestabilnosti (CIN) te inaktivacije gena koji sudjeluju u popravku pogrešno spojenih fragmenata DNA (MMR). Na temelju provedenih istraživanja, u bolesnika stadija II u kojih je prisutan deficijentan MMR status ne postoji dobit od primjene adjuvantne terapije te je u toj skupini bolesnika kirurško liječenje dostatno. U bolesnika s metatastatskim CRC još uvijek nema konsenzusa o optimalnom redoslijedu kemoterapijskih protokola i ciljane biološke terapije. Receptor za epidermalni čimbenik rasta (EGFR) potvrđen je kao terapijski cilj u više humanih tumora, uključujući CRC. Odnedavno, istraživanja su pokazala da aktivirajuće mutacije na eksonima 2, 3 i 4 KRAS i NRAS gena dovode do izostanka odgovora na ciljanu terapiju usmjerenu na EGFR. BRAF je još jedan od istraživanih biljega u raku debelog crijeva, te je pokazano da je povezan sa lošijom prognozom. Potrebna su daljnja istraživanja i identifikacija novih prognostičkih i prediktivnih biljega kako bi se postigla maksimalna učinkovitost svake terapijske linije te poboljšala prognoza ovih bolesnika

Ozračivanje slezene u bolesnika sa zloćudnim i drugim hematološkim bolestima – iskustva jedne bolničke ustanove

Splenic irradiation has long been known as a palliative treatment modality in patients with various malignant hematologic diseases aiming to ameliorate clinical symptoms of splenomegaly as well as clinical sequels of hypersplenism. It provides considerable effect with low toxicity although exact radiotherapy dose and fractionation schedule are not known. During the 1996-2010 period, eleven patients were treated at our institution with splenic irradiation. They received 16 courses of fractionated radiotherapy. There were six patients with non-Hodgkin’s lymphoma, four with chronic lymphocytic leukemia, and one patient with myelofibrosis. The median of the dose received was 7 Gy, while the median of dose received per fraction was 1 Gy. Both parallel opposed anterior-posterior fields and tangential fields were used. Due to the clinical target volume shrinkage, the treatment field was reduced in 44% of courses. Of the courses initiated for symptom control, 71% resulted in effective palliation, whereas of the courses started to treat hematologic sequels of hypersplenism 50% produced desirable effects. The most common side effects included thrombocytopenia and anemia. Splenic irradiation provides effective and low-toxic palliation of symptoms but it is much less successful in treating hematologic disorders caused by hypersplenism.Ozračivanje slezene je najstariji poznati način palijativnog liječenja bolesnika s različitim zloćudnim hematološkim bolestima. Ima za cilj umanjiti kliničke simptome splenomegalije, kao i posljedice hipersplenizma. Ozračivanje slezene ima značajan učinak uz nisku toksičnost, ali točna radioterapijska doza kao i način frakcioniranja nisu poznati. Između 1996. i 2010. godine 11 bolesnika je liječeno u našoj ustanovi ovim postupkom. Ti bolesnici su primili ukupno 16 aplikacija frakcioniranog zračenja. Šest bolesnika je imalo ne-Hodgkinov limfom, četiri kroničnu limfatičnu leukemiju, a jedan bolesnik je imao mijelofibrozu. Medijan aplicirane tumorske doze bio je 7 Gy, a medijan aplicirane doze po frakciji 1 Gy. Korištena su nasuprotna paralelna te tangencijska radioterapijska polja. Zbog smanjenja kliničkog ciljnog volumena terapijsko polje je tijekom postupka radioterapije smanjeno u 44% radioterapijskih aplikacija. Od radioterapijskih postupaka započetih s ciljem kontrole simptoma 71% ih je rezultiralo uspješnom palijacijom, dok je od postupaka koji su započeti radi popravka hematoloških posljedica hipersplenizma njih 50% izazvalo željeni učinak. Najčešće nuspojave bile su trombocitopenija i anemija. Ozračivanje slezene omogućuje učinkovitu i nisko toksičnu palijaciju simptoma, ali je manje uspješno u liječenju hematoloških poremećaja uzrokovanih hipersplenizmom

Radiation Therapy in Treatment of Fibrodysplasia Ossificans Progressiva: A Case Report and Review of the Literature

Fibrodysplasia ossificans progressiva (FOP) is an extremely rare genetic disorder with diffuse extra-skeletal bone formation. The genetic mutation responsible for FOP has recently been discovered and is connected with excessive activation of bone morphogenetic protein receptor. This disease usually begins with typical ossification pattern in early childhood, causing increasing disability and making patients totally disabled by the age of 30. Ectopic ossification develops spontaneously and can be triggered by any trauma and even intramuscular injections. The symptoms of FOP are often misdiagnosed as cancer, causing unnecessary biopsies, which can precipitate further progressive heterotopic ossification. There is no effective treatment for this severe condition. Radiotherapy can be helpful in impeding ossification, although the strict evidence for that is lacking. There are only two reports in the literature referring to the use of radiotherapy in treatment of FOP. Herein, we present a 35-year-old patient successfully treated with small doses of fractionated radiotherapy in several courses. This case indicates that radiotherapy can be useful in treating patients with FO

Primarni fibrosarkom štitne žlijezde: prikaz slučaja

Due to progressive dyspnea, a male patient aged 59 underwent medical examination in 2003 in a local hospital. Neck ultrasound and fine-needle aspiration biopsy (FNAB) of a suspect lesion in the thyroid gland revealed the presence of a malignant neoplasm, i.e. mesenchymal tumor. Immunocytochemistry for epithelial membrane antigen, chromogranin A and leukocyte common antigen (CD45) was negative, while vimentin and S-100 were positive. The patient was referred to a university hospital center, where further oncologic work-up was done. Neck ultrasound revealed a tumor in the left lobe of the thyroid, with extension to the aortic arch. After repeated FNAB, cytologic diagnosis of primary thyroid fibrosarcoma was established. Due to the locally advanced and consequently inoperable disease, primary radiotherapy to the neck region (64 Gy in 32 fractions) was applied, followed by 6 cycles of chemotherapy with doxorubicin. After completion of therapy, computed tomography scan demonstrated significant regression of primary disease, but it was still not amenable to surgical treatment. Thus, the decision of the oncology board was active surveillance of the patient. During 9-year follow up, no signs of progression or activity of the disease were found.Bolesnik u dobi od 59 godina pregledan je zbog progresivne dispneje u lokalnoj bolnici. Ultrazvukom vrata te citološkom punkcijom suspektne lezije u štitnjači registrirana je maligna neoplazma, tj. mezenhimni tumor. Imunohistokemija je bila negativna na antigen epitelnih membrana, kromogranin A i CD45 te pozitivna na vimentin i S-100. Bolesnik je upućen u klinički bolnički centar, gdje je provedena daljnja onkološka obrada. Ultrazvukom vrata nađen je tumorski proces lijevoga režnja štitnjače sa širenjem na luk aorte. Nakon ponovljene citološke punkcije postavljena je dijagnoza primarnog fibrosarkoma štitnjače. Zbog lokalno uznapredovale i posljedično inoperabilne bolesti provedena je primarna radioterapija regije vrata (64 Gy u 32 frakcije), nakon čega je bolesnik primio 6 ciklusa kemoterapije doksorubicinom. Nakon završetka liječenja kontrolni CT pokazao je značajnu regresiju primarne bolesti koja je, međutim, i dalje bila inoperabilna. S obzirom na navedeno, odluka onkološkog konzilija bila je daljnje aktivno praćenje bolesnika. Tijekom 9 godina praćenja u bolesnika nisu nađeni znakovi progresije niti aktivnosti bolesti