[Paratestikularni žlezni rak - neobičajna oblika zasevka raka trebušne slinavke]

Background. Metastatic paratesticular adenocarcinoma from the pancreatic cancer is very rare. To our knowledge, there are less than 20 cases published in the literature. Case report. We experienced a case of paratesticular adenocarcinoma from the primary pancreatic cancer. A 42-year-old man was presented with locoregionally advanced carcinoma of the tail of the pancreas with intraoperatively found liver metastases and with a tumour in the right hemi-scrotum. Ultrasound of the scrotum revealed a paratesticular tumour. A fine needle aspiration biopsy (FNAB) confirmed a poorly differentiated adenocarcinoma and it was in concordance with the diagnosis of the primary tumour. The patient started treatment with chemotherapy with gemcitabine. Unfortunately, he progressed one month later and the treatment was discontinued. Conclusions. Outcome in the adenocarcinoma of the pancreas is dismal. The only possible treatment option for metastatic disease is systemic therapy but the results are disappointing, as in the present case

Malignant melanoma : awareness of malignant melanoma, risk factors and related behavior towards them among adolescents in Slovenia

Incidenca malignega melanoma v Sloveniji v zadnjih desetletjih strmo narašča, poznavanje malignega melanoma in dejavnikov tveganja pa je med populacijo še vedno vprašljivo in malo raziskano. Najpomembnejši dejavnik tveganja za nastanek bolezni je delovanje ultravijoličnih žarkov, pred katerimi se je treba fizično zaščititi in uporabljati sredstva za zaščito pred soncem, predvsem v mladosti. Namen raziskave je bil pridobiti podatke o poznavanju malignega melanoma, dejavnikov tveganja in odnosu do njih ter primerjava odgovorov med študenti Medicinske fakultete in študenti treh ostalih fakultet. V presečno in anketno raziskavo so bili vključeni študentje štirih fakultet Univerze v Ljubljani: Medicinske fakultete, Fakultete za elektrotehniko, Fakultete za farmacijo ter Fakultete za matematiko in fiziko, ki so prek spletne povezave odgovarjali na anonimni vprašalnik. Odgovori 66,3 odstotka študentov Medicinske fakultete in 33,7 odstotka študentov ostalih fakultet kažejo, da je poznavanje malignega melanoma boljše med študenti Medicinske fakultete, razlika je statistično značilna (p = 0,0001). Študenti se v poznavanju dejavnikov tveganja statistično značilno razlikujejo le v pogostnosti uporabe zaščite pred soncem (p = 0,0001) in uporabljenem zaščitnem faktorju (p = 0,015). Študenti medicine s svetlimi tipi kože se pred soncem zaščitijo pogosteje, obstaja statistično značilna razlika (p = 0,001). Študenti Medicinske fakultete statistično značilno bolje prepoznavajo maligni melanom kot nevarno obliko kožnega raka. Pogosteje se tudi zaščitijo pred ultravijoličnimi žarki in uporabljajo višje zaščitne faktorje kot študenti ostalih fakultet. Kljub zelo visokem vedenju o škodljivosti izpostavljanja UV-žarkom med mlado slovensko populacijo je ukrepanje bistveno slabše.Malignant melanoma in Slovenia continues to increase rapidly in incidence over the last decades. Knowledge and risk factors amongst the population is still questionable and poorly investigated. Exposure to ultraviolet radiation is the leading risk factor for melanoma development, therefore physical protection and use of sunscreens with sun protection factors is crucial. The study aimed to investigate awareness of melanoma, risk factors and related behavior towards them among students of four faculties of University of Ljubljana: Faculty of Medicine, Faculty of Electrical Engineering, Faculty of Pharmacy and Faculty of Mathematics and Physics and to compare the answers between medical students and students of the other three faculties. The study was cross-sectional and survey-based. Students answered an anonymous questionnaire, which was sent to them through a website link. Answers obtained by 66.3% medical students and 33.7% students of other three faculties showed that medical students have statistically significant better knowledge about melanoma, (p=0.0001). It has also been found that there was statistical difference in frequency of protecting themselves from the sun (p=0.0001) and in used sun protection factor (p=0.015). Medical students with fair skin types more frequently used some means of protection from ultraviolet radiation, the measured difference was statistically significant (p=0.001). Medical students significantly better recognize malignant melanoma as the most threatening type of skin cancer. They also protect themselves from the sun more often and use higher sun protection factors. Slovenian adolescent population has high knowledge about harmful effects of exposure to ultraviolet radiation, but responds poorly to it

Malignant gliomas

Malignant (high-grade) gliomas are rapidly progressive brain tumours with very high morbidity and mortality. Until recently, treatment options for patients with malignant gliomas were limited and mainly the same for all subtypes of malignant gliomas. The treatment included surgery and radiotherapy. Chemotherapy used as an adjuvant treatment or at recurrence had a marginal role. Conclusions. Nowadays, the treatment of malignant gliomas requires a multidisciplinary approach. The treatment includes surgery, radiotherapy and chemotherapy. The chosen approach is more complex and individually adjusted. By that, the effect on the survival and quality of life is notable higher

Cytostatic and Targeted Drug-Induced Skin Toxicities

Zdravljenje s citostatiki povzroča številne neželene učinke, med katerimi jih kar nekaj prizadene tudi kožo in sluznice, saj so v njih celice, ki se hitro delijo in prav na te celice citostatiki najmočneje vplivajo. Kožna toksičnost se ob zdravljenju s citostatiki lahko izraža kot sindrom roka – noga, dermatitis, eksantem, eritroderma, hiperpigmentacija. Paleta neželenih učinkov na kožo pri uporabi tarčnih zdravil pa je razen sindroma roka – noga ob multitarčnih zdravilih nekoliko drugačna. Pri uporabi zaviralcev EGFR je pogosto izražena kožna toksičnost, najpogosteje akniformni izpuščaj. Kseroze, ekceme, poke kože, teleangiektazije, spremembe nohtov in paronihijo opažamo pri nekaterih bolnikih, hiperpigmentacije kože pa so redkejše. Obvladovanje kožnih sprememb pomaga bolnikom prebroditi neželene učinke, pri čemer je izredno pomembno sodelovanje bolnikov. Kožna toksičnost je navadno obvladljiva s topično ali sistemsko uporabo zdravil, včasih pa je treba zmanjšati odmerek citostatika ali tarčnega zdravila oz. prilagoditi shemo zdravljenja. Poduk bolnikov pred zdravljenjem in hitro ukrepanje ob prvih znakih kožne toksičnosti sta ključna za uspeh.The patients treated with cytostatic drugs may experience many side-effects, among them also skin and mucosal side-effects because skin and mucosal cells rapidly divide and are therefore most sensitive to cytostatics. The most common skin side-effects are hand-foot syndrome, eczema, erythroderma, hyperpigmentation. Skin toxicity of targeted drugs is different with the exception of hand-foot syndrome. EGFR-inhibitors often cause skin toxicity, most frequently acneiform eruption. Xerosis, eczema, fissures, teleangiectasias, nail changes and paronychia can be seen in some cases, rarely hyperpigmentation. Management of the skin toxicity helps patients to overcome cytostatics- and EGFR- inhibitors associated skin toxicity and is of great importance for patients’ compliance. It is generally manageable with standard topical or systemic antibiotics and anti-inflammatory agentsIn some cases, it is nevertheless necessary to reduce doses of the drugs. Education of patients prior to beginning the therapy and proactive intervention at the first signs of skin toxicity are keys to successful management

Karcinom Merklovih celic: novosti v sistemskem zdravljenju

Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine skin cancer with a poor prognosis in advanced stage. The incidence is increasing with some deviations between different geographic regions. The risk factors are advanced age, immunosuppression, and ultraviolet light exposure. There are associations between MCC and polyomavirus infection, but the exact mechanism that leads to carcinogenesis is yet to be fully understood. For localized disease (when feasible), surgery is the recommended treatment, followed by adjuvant radiation or chemoradiation. In the metastatic setting, chemotherapy has been the standard treatment, but durable responses are rare. As tumour oncogenesis is linked to Merkel cell polyomavirus integration and ultraviolet-radiation-induced mutations, there is rationale for treatment with immunotherapy antibodies that target the PD-L1/PD-1 pathway. However, recently published trials with immune checkpoint inhibitors in the first- and second-line showed promising results with a tolerable safety profile, and these are becoming the standard therapy, already included in international guidelines. The published data showed a high efficacy of avelumab in the metastatic setting.Karcinom Merklovih celic (KMC) je redek, agresiven nevroendokrini kožni rak s slabo prognozo, posebno, ko je v napredovalem stadiju. Incidenca na splošno narašča, čeprav podatki o incidenci kažejo na razlike med geografskimi področji. Med dejavnike tveganja štejemo starost, imunosupresijo in izpostavljenost ultravijoličnemu sevanju. Znana je povezava med MCC in okužbo s poliomavirusom, čeprav natančnega mehanizma, ki vodi v karcinogenezo, še ne razumemo v celoti. Pri lokalizirani bolezni je izbor zdravljenja kirurgija (ko je to mogoče), sledi mu dopolnilno obsevanje ali obsevanje v kombinaciji s kemoterapijo. Pri razsejani bolezni je bila doslej na voljo le kemoterapija, čeprav so dolgotrajni odgovori ob njej redki. Glede na to, da je onkogeneza tumorja povezana z integracijo poliomavirusa Merklovih celic in mutacijami, povzročenih z ultravijoličnim sevanjem, obstaja logična osnova za zdravljenje z imunoterapijo oz. protitelesi, ki ciljajo pot PD-L1/PD-1. Nedavno objavljene raziskave v prvem in drugem redu zdravljenja z inhibitorji imunskih stikal (anti-PD-1/PD-L1-protitelesi) kažejo obetajoče rezultate s sprejemljivim varnostnim profilom zdravljenja, zato tovrstno zdravljenje postaja standardno in je že priporočeno v mednarodnih smernicah za zdravljenje razsejanega raka Merklovih celic. Objavljeni podatki randomiziranih raziskav kažejo na obetajočo učinkovitost teh zdravil pri metastatski bolezni

Novosti v zdravljenju metastatskega raka debelega črevesa in danke

Metastatski rak debelega črevesa in danke je v večini primerov še vedno neozdravljiva bolezen, vendar pa sta se prognoza in preživetje teh bolnikov v zadnjih šestih letih močno izboljšala. Od srednjega desetmesečnega preživetja, ki smo ga dosegali z zdravljenjem s 5-fluorouracilom, ki je bilo še pred nekaj leti edino učinkovito zdravilo za zdravljenje teh bolnikov, smo prešli na preživetje, daljše od 20 mesecev, kar so omogočila nova zdravila. V zadnjih šestih letih je bilo registriranih pet novih zdravil za zdravljenje metastatskega raka debelega črevesa in danke: kapecitabin, irinotekan, oksaliplatin, cetuximab, bevacizumab. Kombinirano zdravljenje omogoča boljšo kakovost življenja in daljše remisije, s tem pa tudi daljše celokupno preživetje. V kombinaciji z operacijo pljučnih ali jetrnih zasevkov pa tovrstno zdravljenje omogoča tudi ozdravitve

Systemic treatment of hepatocellular carcinoma

Rak jetrnih celic - hepatocelularni karcinom (HCC) je pogost rak z omejenimi učinkovitimi možnostmi zdravljenja. Napredovali HCC se zdravi s sistemsko terapijo, ki je vrsto let bila omejena na eno samo učinkovino – tirizinkinazni inhibitor sorafenib. V zadnjih leti pa so potekale številne klinične raziskave, ki so prinesle več novih učinkovitih zdravljenj, tako da sodobno sistemsko zdravljenje vključuje peroralne zaviralce tirozin kinaze (TKI) in intravenske zaviralce imunskih nadzornih točk in zaviralce angiogeneze, seveda pod pogojem, da je delovanje jeter še zadovoljivo ohranjeno. V zadnjih 3 letih je bilo s strani EMA odobrenih večt novih učinkovin za zdravljenje HCC: kombinacija atezolozumaba in bevacizumaba, kakor tudi lenvatinib in durvalumab v prvi liniji ter regorafenib, nivolumab, pembrolizumab in kabozantinib kot druga linija zdravljenja. Dokazano je, da vse te terapije podaljšujejo skupno preživetje bolnikov in zdi se, da imajo razumen varnostni profil. Več potekajočih kliničnih raziskav proučuje različne kombinacije imunoterapij ali pa imunoterapiej v kombinaciji s tarčnimi zdravili. Rezultati teh raziskav bodo pomagali določiti optimalno izbiro, čas in pa tudi optimalno zaporedje učinkovin