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NAFLD je najčešća kronična bolest jetre u odrasloj populaciji, koja se sastoji od entiteta s različitom prognozom: obične steatoze, koja ima benignu prognozu, i NASH-a, koji ima potencijalno progresivni tijek. Razlikovanje ovih entiteta trenutno je definitivno moguće jedino biopsijom jetre. Selekcija bolesnika za biopsiju podložna je znatnim varijacijama ovisno o određenoj sredini i pojedinom liječniku. Najčešće se povišena vrijednost ALT uzima kao najpouzdaniji marker moguće prisutnosti NASH-a ili neke druge ozbiljne kronične bolesti jetre, te povišene vrijednosti ALT često usmjeravaju odluku prema izvođenju biopsije. Međutim, više studija pokazalo je da cijeli spektar NAFLD uključujući steatohepatitis i uznapredovalu fibrozu može biti prisutan i kod bolesnika s normalnim vrijednostima ALT. S druge strane, primijetili smo da je kod bolesnika kod kojih postoji sumnja na NAFLD vrijednost GGT znatno češće povišena od ostalih jetrenih biokemijskih testova, a u kliničkoj praksi i u znanstvenoj literaturi vezanoj za NAFLD vrijednosti GGT relativno često se ne uzimaju u razmatranje, što nema opravdanje u dosad objavljenim studijama. Naprotiv, u pojedinim studijama upravo je GGT pokazao najbolju korelaciju s određenim značajkama patohistološki izraženije bolesti. Cilj našeg istraživanja bio je dokazati da je GGT kod bolesnika s NAFLD znatno češće povišen od ALT i da je patohistološka težina bolesti jednaka kod bolesnika s izolirano povišenim GGT i onih kod kojih je povišen ALT, te ispitati da li GGT ujedno i bolje korelira s patohistološkom težinom bolesti od ALT. Usporedbu prevalencije povišenosti pojedinih enzima ispitali smo u populaciji bolesnika s dijabetesom tipa 2, koja uz populaciju pretilih predstavlja skupinu s najznačajnijim rizičnim faktorom za NAFLD i izrazito visokom prevalencijom NAFLD (do 70%). U analiziranoj populaciji od 892 bolesnika koju smo obuhvatili istraživanjem prikazana je relativno visoka učestalost povišenih vrijednosti jetrenih biokemijskih testova, a učestalost povišenog GGT bila je znatno viša od učestalosti povišenog ALT ili AST (33.4% prema 16.1% odnosno 10.5%). U prospektivnom dijelu istraživanja, uključeno je 98 bolesnika koji su bioptirani pod sumnjom na NAFLD, koji je dokazan kod njih 84. U detaljnoj usporedbi bolesnika s izolirano povišenim GGT i onih s povišenim ALT, skupine su imale gotovo identičnu učestalost i izraženost većine patohistoloških značajki, a nisu se razlikovale ni u težini metaboličkog sindroma. Skupina s izolirano povišenim GGT imala je nešto izraženiju lobularnu upalu, dok je uznapredovala fibroza bila nešto češća kod bolesnika s povišenim ALT. Nije postojala nikakva značajna razlika u učestalosti NASH-a, kao ni u raspodjeli bolesnika prema semikvantitativnim stupnjevima nekroinflamatorne aktivnosti i stadijima fibroze, ili prema vrijednostima NAFLD Activity Score (NAS). Ovime je dokazano da nema razlike u težini bolesti, histološkom spektru i pojedinim značajkama bolesti kod bolesnika s NAFLD kod kojih su izolirano povišene vrijednosti GGT u odnosu na bolesnike kod kojih su povišene vrijednosti ALT. U ispitivanju koreliranja, ni vrijednosti GGT niti ALT nisu pokazale korelaciju sa stupnjem nekroinflamatorne aktivnosti, stadijem fibroze, ili vrijednostima NAS. Bila je vidljiva tendencija da uznapredovaliju fibrozu prati viša vrijednost AST, a AST je bio jasno povezan s vrijednosti NAS. Broj sastavnica metaboličkog sindroma najbolje je korelirao sa stupnjem nekroinflamatorne aktivnosti i vrijednostima NAS. U zaključku, prevalencija izolirano povišenog GGT je visoka, a obzirom da su histološki uznapredovaliji oblici bolesti jednako zastupljeni kod bolesnika s takvim nalazom, on se ne bi trebao zanemarivati. Nadalje, kod 3 od ukupno 24 bolesnika s izolirano povišenim GGT i sumnjom na NAFLD biopsija jetre je u konačnici uputila na autoimunu bolest jetre kao uzrok povišenja enzima, iako je sva prethodno učinjena serologija bila negativna. Taj podatak dodatno naglašava važnost pažljivog pristupa bolesnicima kod kojih su vrijednosti GGT izolirano povišene., In NAFLD, the only method that distinguishes between simple steatosis (benign prognosis) and NASH (potentially progressive course) is liver biopsy. Patient selection for biopsy varies significantly. ALT is often considered the most reliable marker of potential NASH or other serious liver disease, and it often influences the decision to perform biopsy. However, several studies have demonstrated that the full spectrum of NAFLD can be present with normal ALT. On the other hand, we have noticed that patients in whom NAFLD is suspected have elevated GGT more often than other enzymes, while in clinical as well as scientific practice GGT levels are often disregarded – an attitude which isn't backed by any evidence. Indeed, some studies have demonstrated GGT to best correlate with pathohistological disease severity. Aim of our study was to prove that GGT is significantly more often elevated than ALT in patients with NAFLD and that pathohistological disease severity is the same in patients with isolated GGT elevation and those with elevated ALT. We also wanted to test if GGT correlates better with pathohistological severity than ALT. Prevalence of elevation of liver enzymes was analyzed in a population of type 2 diabetics, which has the highest NAFLD prevalence (up to 70%). In the 892 patients included in the study, prevalence of enzyme elevation was high, and GGT was significantly more frequently elevated than ALT or AST (33.4% vs. 16.1% vs. 10.5%). In the prospective part of our study, we included 98 patients who underwent liver biopsy with suspicion of NAFLD, and NAFLD was proved in 84 of them. In the detailed comparison of patients with isolated GGT elevation and those with elevated ALT, there was no difference in severity, histological spectrum or individual characteristics of the disease. In the analysis of the correlation, neither GGT nor ALT demonstrated the correlation with necroinflammatory activity grade, fibrosis stage, or NAS values. AST demonstrated a tendency of correlation with fibrosis stage, and it was clearly associated with NAS values. Number of metabolic syndrome components correlated best with necroinflammatory grade and NAS values. In conclusion, prevalence of isolated GGT elevation is high, and it should definitely not be disregarded.

Tekuća biopsija omogućava nov neinvazivan pristup u molekularnom profiliranju tumora uključujući kolorektalni karcinom (CRC). Cirkulirajuća tumorska DNA (ctDNA) jedan je od obećavajućih biomarkera za probir, praćenje odgovora na terapiju, procjenu progresije i ishoda bolesti. Kako je rukovanje uzorcima tekuće biopsije zahtjevno, a nije standardizirano, prikazana je optimizacija metode za genotipizaciju JAK2 V617F u uzorcima ctDNA dobivenih tekućom biopsijom pacijenata s CRC-om. U sklopu projekta HRZZ IP- 2019-04-4624 prikupljena je periferna venska krv u epruvete CellSave (Menarini Silicon Biosistems) pri +4 °C od 25 pacijenata s CRC te je isti dan odvojena plazma i pohranjena na –20 °C. ctDNA je izdvojena u duplikatu iz 1–1, 5 mL plazme pomoću kompleta QIAamp ccfDNA/RNA Kit (Qiagen). Koncentracije ctDNA određene su fluorimetrijski pomoću uređaja DS-11 FX (DeNovix) i reagensa Qubit dsDNA HS Assay (Thermo Fisher Scientific). Genotipizacija JAK2 V617F u uzorcima ctDNA provedena je na uređaju 7500 Real-Time PCR System (Applied Biosystems) metodom alelne diskriminacije nakon lančane reakcije polimerazom u stvarnom vremenu (qPCR) uz komplet početnica i sondi TaqMan Digital PCR Liquid Biopsy Assay (Applied Biosystems) i uz dva isprobana reagensa za umnažanje TaqMan Genotyping PCR Master Mix i TaqMan Universal PCR Master Mix (Applied Biosystems). Kao kontrolni uzorci korišteni su uzorci genomske DNA iz leukocita genotipizirani akreditiranom metodom. Utvrđene su koncentracije ctDNA u rasponu od 0, 002 do 0, 993 ng/μL. Početno ispitivanje umnažanja i uspješnosti genotipizacije dalo je zadovoljavajuće rezultate za kontrolne uzorke ; vidljivo je umnažanje do 30. ciklusa, a očekivana diskriminacija alela nakon 40 ciklusa umnažanja bez obzira na korišteni reagens. Za uzorke ctDNA nije dobiveno uspješno umnažanje pa je ono nastavljeno tijekom još 20 ciklusa. Nakon 60 ciklusa umnažanja uspješno je očitan rezultat genotipizacije u uzorcima ctDNA umnoženih pomoću TaqMan Universal PCR Master Mix-a, dok reagens TaqMan Genotyping PCR Master Mix i dalje nije dao zadovoljavajuće umnažanje. Opisanom metodom uspješno je provedena genotipizacija JAK2 V617F za 24 od 25 prikupljenih uzoraka ctDNA iz periferne krvi pacijenata s CRC- om, iako prisutnost mutacije nije utvrđena niti u jednom uzorku. Dobiveni rezultati usporedit će se s rezultatima genotipizacije DNA izdvojene iz tumorskog tkiva i tako pridonijeti daljnjem profiliranju CRC-a korištenjem tekuće biopsije.

Exosomes, extracellular vesicles, and their cargo, such as microRNAs, are among the most promising emerging biomarkers of various diseases, including colorectal cancer (CRC). Since their handling and isolation are not standardised, in this study we aimed to evaluate the performance of two different methods for isolation of microRNA from CRC patients' exosomes. Exosomes and exosomal microRNA were isolated from peripheral blood of 11 CRC patients using miRCURY Exosome Serum/Plasma kit and miRNeasy Serum/Plasma Advanced kit (Qiagen) or Total Exosome isolation reagent and Total Exosome RNA and Protein isolation kit (Invitrogen). Concentration of microRNA was determined using DS- 11 spectrophotometer (Denovix), and quality of the samples was determined on Bioanalyzer 2100 (Agilent). cDNA for microRNA expression analysis was obtained using miRCURY RT LNA kit (Qiagen), while expressions of mir-103a-3p and mir-19a-3p were assessed with miRCURY LNA SYBR GREEN PCR system (Qiagen) on 7500 Real-Time PCR System (Applied Biosystems) with UniSp6 as internal control. Wilcoxon matched pairs test was used for statistical analysis in GraphPad Prism 6.01 software. There was no significant difference in RNA concentrations between the two methods (P=0.102), and both methods isolated RNAs less than 200 nt in size. ΔCt (corrected to UniSp6) for mir-103a-3p (P=0.123) and mir-19a-3p (P=0.413) was similar between the two methods. mir-19a-3p was also corrected to mir-103a-3p (usually used as reference gene) and we found no difference between the used methods (P=0.083). We concluded that both assessed methods showed similar performance and could be used for determination of microRNA expression from CRC patients' exosomes.

Eozinofilni ezofagitis je kronična bolest posredovana putem Th2 obrasca imunosne reakcije, karakterizirana prisutnošću predominatno eozinofilnih upalnih promjena u jednjaku. Bolest je posredovana imuno/antigenim patofizološkim putem, a za definiciju bolesti potrebno je prisustvo kliničkih simptoma i histoloških elemenata bolesti. Unatrag desetak godina bilježi se porast incidencije i prevalencije EoE, gdje prevalencija EoE varira, te u općoj populaciji iznosi 0,2–4/1000 u asimptomatskih bolesnika, dok kod simptomatskih bolesnika ona iznosi 5–6%. Smatra se da prevalencija u općoj populaciji iznosi 43 do 52/100000. Patofiziološki riječ je o poligenskoj bolesti u kojoj određeni citokini (IL-4, IL-5,IL-13, IL-14, TGF-β) igraju ključnu ulogu aktivirajući eotaksin-3 u sluznici jednjaka. Eotaksin-3 snažno privlači eozinofile u sluznicu jednjaka, a tako aktivirani eozinofili dovode do privlačenja drugih upalnih stanica, oslobađanja medijatora i nastanka bolesti. Histološki kriterij dijagnoze EoE je prisutnost više od 15 eozinofila prisutnih u vidnom polju bioptata sluznice jednjaka. Klinički, bolest se može manifestirati spektrom simptoma, od akutne impakcije hrane, disfagije, boli u žličici i žgaravice, a i nespecifični simptomi poput inapetencije ili povraćanja također se javljaju kod ovih bolesnika. Osnova liječenja ovih bolesnika temelji se na medikamentnom liječenju, dijetalnim preporukama i endoskopskoj dilataciji. Cilj ovih kliničkih smjernica jest prikazati preporučeni algoritam dijagnostike i liječenja eozinofilnog ezofagitisa., Eosinophilic esophagitis is a chronic, Th2-mediated disease characterized by the presence of predominantly eosinophilic inflammation in the esophagus. The disease is mediated by an immune or antigenic pathophysiological background, and the definition of the disease requires the presence of clinical symptoms and histological elements of the disease. Over the past ten years, there has been an increase in the incidence and prevalence of EoE, where the prevalence of EoE varies, and in the general population is 0.2–4 / 1000 in asymptomatic patients, while in symptomatic patients it is 5–6%. The prevalence in the general population is considered to be 43 to 52/100000. Pathophysiologically, it is a polygenic disease in which certain cytokines (IL-4, IL-5, IL-13, IL-14 and TGF-β) play a key role by activating eotaxin-3 in the esophageal mucosa. Eotaxin-3 strongly attracts eosinophils into the esophageal mucosa, and thus activated eosinophils lead to the attraction of other inflammatory cells, the release of mediators and the onset of disease. The histological criterion for the diagnosis of EoE is the presence of more than 15 eosinophils present in the visual field of esophageal mucosal biopsies. Clinically, the disease can manifest itself by a spectrum of symptoms, from acute food impaction, dysphagia, epigastric pain and heartburn, and nonspecific symptoms such as incontinence or vomiting also occur in these patients. The basis of treatment of these patients is based on drug therapy, dietary recommendations and endoscopic dilatation. Thea im of these clinical recommendations is to present the pathway of diagnosis and therapy of eosinophilic esophagitis.

Liquid biopsy offers a promising non-invasive approach for determination of the molecular profile of various tumours, including colorectal cancer (CRC). Exosomal microRNA represents one of most promising biomarkers for diagnostic screening, as well as for determining a response to therapy and evaluating disease progression and outcome. Since handling of liquid biopsy specimens is demanding and nonstandardized, in this study we aim to evaluate and optimise a method for determining selected microRNAs expression in exosome-derived microRNA samples from CRC patients. Exosomal microRNA was isolated from peripheral blood liquid biopsy samples obtained from 18 CRC patients using miRCURY Exosome Serum/Plasma kit and miRNeasy Serum/Plasma Advanced kit (Qiagen). cDNA was obtained using miRCury RT LNA kit (Qiagen) while expression of eight selected microRNAs was assessed with miRCURY LNA SYBR GREEN PCR system (Qiagen) on 7500 Real- Time PCR System (Applied Biosystems) with UniSp6 as internal control. Initial examination of expression of three microRNAs with four different starting sample volumes showed satisfactory results with the starting microRNA volume of 2 µl. miR-103a-3p was shown to be the best reference microRNA candidate, with Ct values ranging from 27.40 to 36.05 and ΔCt (corrected to UniSp6) from 13.36 to 22.31, since miR-1228-3p and miR-520d-3p were not detected. miR-125-3p was detected in three samples with Ct ranging from 33.58 to 35.86, and ΔCt from 20.01 to 22.40 ; miR-193a-3p was detected in seven samples with Ct ranging from 36.13 to 42.17, and ΔCt from 21.15 to 27.70 ; miR- 210-3p was detected in 14 samples with Ct ranging from 31.15 to 42.91 and ΔCt from 17.71 to 29.18, whereas miR-19a-3p and miR-92a-3p were detected in all samples with Ct ranging from 32.20 to 32.67 and 23.87 to 31.96, and ΔCt ranging from 9.90 to 16.74 and 10.35 to 16.97, respectively. The described optimisation of the method for the detection of selected exosomal microRNAs in samples obtained by the peripheral blood biopsy will contribute to the further profiling of CRC utilizing liquid biopsy through comparison with expression in tumour tissue samples.

Uvod: Egzosomi su izvanstanične vezikule promjera 30-150 nm, bogate proteinima, RNA molekulama i dijelovima genomske DNA. Egzosomi imaju važnu ulogu u dijagnostici tumorskih bolesti primjenom tekuće biopsije, ali nanometarska veličina otežava njihovu izolaciju i karakterizaciju. Cilj ovoga rada bio je uspostaviti metodu za izolaciju egzosoma iz plazme bolesnika s kolorektalnim karcinomom (CRC). Materijali i metode: Plazma je dobivena centrifugiranjem pune krvi 11 bolesnika s CRC-om. Izolacija egzosoma provedena je korištenjem dva komercijalno dostupna kompleta, miRCURY Exosome Serum/Plasma Kit (Qiagen, Njemačka) ili Invitrogen Total Exosome Isolation Kit (from plasma) (ThermoFisher Scientific, SAD). Egzosomi su lizirani RIPA puferom i sonikacijom. Koncentracija proteina utvrđena je kolorimetrijskom metodom s bicinkoniničnom kiselinom ili mjerenjem apsorbancije na 280 nm korištenjem DS-11 spektrofotometra (DeNovix, SAD). Uzorci egzosoma pripremljeni su za SDS-PAGE miješanjem s puferom za pripremu uzoraka (s ili bez β-merkaptoetanola). Karakterizacija je provedena Western blot metodom uz upotrebu mišjih monoklonskih antitijela za CD9, HSC70, aktin i kalneksin (Invitrogen, SAD). Rezultati: Određivanjem koncentracije proteina kolorimetrijskom metodom dobivena je zadovoljavajuća preciznost u seriji (7, 91 %), točnost (96, 53 %) i linearnost (r = 0, 9964), dok rezultati dobiveni mjerenjem apsorbancije na 280 nm nisu bili prihvatljivi zbog nemogućnosti otklanjanja interferencije RIPA pufera. Sveukupni rezultati volumena i broja egzosoma te određivanja koncentracije proteina u egzosomima i njihovim vizualnim očitanjem na gelu za SDS-PAGE razvidno je da Qiagenov komplet daje bolji prinos egzosoma od ThermoFisherovog kompleta. U svim je uzorcima egzosoma Western blotom dokazana prisutnost njihovog biljega CD9, uz nereducirajuće uvjete (bez β-merkaptoetanola). U pojedinim je uzorcima dobiven signal za HSC70, a niti u jednom uzroku nije dokazan aktin. Odsutnost endoplazmatskog retikula u uzorcima dokazana je izostankom vrpce karakteristične za kalneksin. Zaključak: Pokazano je da je za izolaciju egzosoma primjeren Qiagenov komplet, a za određivanje koncentracije proteina u uzorcima egzosoma s RIPA puferom kolorimetrijska metoda s bicinkoniničnom kiselinom.

Drug-specific therapeutic approaches for colorectal cancer (CRC) have contributed to a significant improvement in the health status of patients. However, a great need to improve personalization of treatments based on genetic and epigenetic tumor profiles to maximize quality and efficacy while limiting cytotoxicity remains. Currently, CEA and CA 19- 9 are the only validated blood biomarkers in clinical practice. For this reason, laboratories are trying to identify new specific prognostic and, more importantly, predictive biomarkers for CRC patient profiles. Thus, the unique landscape of personalized biomarker data should have a clinical impact on CRC treatment strategies and molecular genetic screening tests should become the standard method for CRC diagnosis, as well as detection of disease progression.

Purpose: Hypomagnesemia contributes to morbidity in a significant proportion of hospitalized and severely ill patients, but it could also have beneficial anticancer effects. Alimentary tract mucositis is a frequent complication of cytotoxic chemotherapy. The aim of this study was to determine frequency and severity of hypomagnesemia in patients with different grades of chemotherapy- induced alimentary tract mucositis and to assess its clinical manifestations. Methods: Multicentric observational study included 226 adult patients with alimentary mucositis treated at 3 different institutions. Patients were evaluated for severity of mucositis and the presence of hypomagnesemia, symptoms associated with hypomagnesemia, hypocalcemia, ECG changes and granulocytopenia. Subgroup analysis related to mucositis severity and presence of hypomagnesemia was performed. Results: Patients with grade 3 or 4 alimentary mucositis expectedly had more frequent and more severe granulocytopenia than patients with milder mucositis (49.6% vs. 35.4%, P = 0.043), but there were no differences in rate of hypomagnesemia (24.8% vs. 26.5%). When compared to patients with normal magnesium levels, patients with hypomagnesemia had higher rates of hypocalcemia (50.0% vs. 32.7%, P = 0.026), QTc prolongation (15.5% vs. 3.0%, P = 0.002) and granulocytopenia (77.6% vs. 39.9%, P < 0.001), while there was no difference in symptoms or other ECG features among these subgroups. Conclusions: Hypomagnesaemia is not associated with the severity of chemotherapy- induced mucositis. However, hypomagnesaemia was associated with higher rates of granulocytopenia and hypocalcemia. Our study failed to identify the link between hypomagnesaemia and chemotherapy- induced mucositis.

Introduction: The aim of this study was to compare peptic ulcer bleeding (PUB) with upper gastrointestinal tumor bleeding (UGITB) while placing special emphasis on the incidence, outcomes including thirty-day re-bleeding rate, mortality and the need for blood transfusion. Aims & Methods: A total of 2198 patients referred to our Emergency Department with upper gastrointestinal bleeding (UGIB) were included in this prospective study during 5 years (from January 2008 till December 2012) ; 796 with PUB and 61 with UGITB, found during urgent upper GI endoscopy performed within 24 hours of admission. Results: Cumulative incidence of UGIB was 126/100000 in a 5-year period. 796(36.2%) patients had PUB and 61 (2.8%) patients had UGITB. UGITB was most often found in the stomach (58/95%) ; the tumors were dominantly malignant (55/90%), most of them adenocarcinoma (48/87.3%). Median age for PUB was 67, and for UGITB 76 years(p50.01). PUB and UGITB were more common in men (62.3% and 52.5%). Re-bleeding occurred more often in patients with UGITB(19.7% vs 9.7%, p50.01), but a higher number of patients with PUB required surgical intervention due to uncontrolled bleeding (5.9% vs 3.3% p50.01). Thirty-day mortality showed no difference between the two groups (5.2% vs 7.2%). Transfusion of red blood cells was administered more often in patients with UGITB (75.4% vs 49.5%, p50.01), while patients with PUB received comparably higher volumes of transfused red blood cells. Conclusion: Patients with UGITB have higher re-bleeding rates, require surgical intervention less often, and are more often treated with blood transfusion than PUB.

Karcinomi želuca i jednjaka u cijelom svijetu spadaju među vodeće uzročnike smrti, pa tako i u Hrvatskoj. Budući da su klinički simptomi oba karcinoma slabo izraženi, u trenutku otkrivanja bolest je najčešće već metastazirala ili se barem lokalno ili regionalno proširila. Zbog toga je preživljenje za oba karcinoma vrlo loše diljem svijeta. Karcinom želuca zauzima peto mjesto po incidenciji i četvrto po mortalitetu u skupini malignih bolesti. Godišnje se otkrije preko milijun novih slučajeva, a zabilježise preko sedamsto tisuća smrti. Adenokarcinom želuca je najčešći histološki tip. Karcinom jednjaka je osmi najčešći karcinom na svijetu s preko petsto tisuća novih slučajeva i preko petsto tisuća smrti godišnje. Planocelularni karcinom jednjaka je globalno najzastupljeniji, ali u zadnjim desetljećima adenokarcinom zauzima prvo mjesto u zemljama Zapada. I adenokarcinom želuca i adenokarcinom jednjaka nastaju progresijom iz premalignih stanja koja su ograničena na sluznicu i koja se mogu iskoristiti za pravodobno prepoznavanje i liječenje malignih lezija čime bi se značajno poboljšalo preživljenje. Premaligna stanja želuca su kronični atrofični gastritis, intestinalna metaplazija i displazija. Infekcija bakterijom Helicobacter pylori se smatra glavnim uzrokom koji pokreće kaskadu premalignih promjena koje u konačnici dovode do razvoja karcinoma. Barrettov jednjak je jedina poznata premaligna lezija jednjaka. Karakteriziran je metaplazijom višeslojnog pločastog epitela jednjaka u cilindrični do koje dolazi uslijed gastroezofagealne refluksne bolesti. Preko intestinalne metaplazije i displazije, Barrettov jednjak dovodi do razvoja adenokarcinoma. Praćenje bolesnika s premalignim stanjima želuca i jednjaka se temelji na endoskopskom pregledu sa ili bez biopsija, a eriod praćenja se određuje na temelju stupnja izraženosti premaligne lezije. Endoskopska resekcija je metoda izbora za liječenje premalignih lezija s obzirom na to da su promjene ograničene na sluznicu. U državama Zapada ne postoji organizirani probir kojim bi se otkrila premaligna stanja jednjaka i želuca s obzirom na lošu isplativost uslijed nedovoljnog poznavanja rizičnih čimbenika koji bi odredili populaciju koja je pod najznačajnijim rizikom., Carcinomas of the stomach and oesophagus are among the leading causes of death worldwide. Given that the clinical symptoms of both carcinomas are weakly expressed, at the time of detection the disease has most often already metastasized or at least spread locally or regionally leading to poor survival worldwide. Stomach carcinoma ranks fifth in terms of incidence and fourth in terms of mortality in the group of malignant diseases. Over a million new cases are discovered annually, and over seven hundred thousand deaths are recorded. Gastric adenocarcinoma is the most common histological type. Oesophageal carcinoma is the eighth most common carcinoma in the world with over five hundred thousand new cases and over five hundred thousand deaths annually. Squamous cell carcinoma is the most prevalent type globally, but in recent decades adenocarcinoma has taken the first place in the West. Both adenocarcinomas develop from premalignant conditions limited to the mucosa and could be used for timely recognition and treatment of malignant lesions. Premalignant conditions of the stomach are chronic atrophic gastritis, gastric intestinal metaplasia and dysplasia. Helicobacter pylori infection is considered the main cause that initiates a cascade of premalignant changes that ultimately lead to the development of carcinoma. Barrett's oesophagus is the only known premalignant lesion of the oesophagus. It is characterized by metaplasia of the multi-layered squamous epithelium of the oesophagus into a cylindrical one, which occurs due to gastroesophageal reflux disease. Through intestinal metaplasia and dysplasia, Barrett's oesophagus leads to the development of adenocarcinoma. Management of patients is based on endoscopic examination with random biopsies, and the follow-up period is determined based on the stage of the lesion. Endoscopic resection is the method of choice given that the changes are limited to the mucosa. There is no organized screening in the West given the poor cost-effectiveness due to insufficient knowledge of the risk factors that would determine the population that is most at risk.

Polipi želuca pronalaze se u 1-8 % endoskopija gornjeg gastrointestinalnog trakta, najčešće kao slučajan nalaz. Hiperplastični polipi želuca (HPŽ) čine 30-93% otkrivenih polipa, čest su nalaz u zemljama s visokom prevalencijom H.pylori infekcije. Procjenjuje se da je rizik za neoplastičnu transformaciju unutar polipa u rasponu od 1,5 do 4,5 %, pri čemu je prevalencija nastanka adenokarcinoma izvan HPŽ veće nego unutar polipa (6% vs. 2%). U ovoj retrospektivnoj studiji koristili smo uvid u medicinsku dokumentaciju, nalaze endoskopske obrade i biopsije u 36 pacijenata koji su u periodu od 2012. do 2021. hospitalizirani na Zavodu za gastroenterologiju KBCSM zbog resekcije HPŽ. Cilj studije bio je prikazati trendove recidiviranja i pojave karcinoma unutar HPŽ, rizične čimbenike u nastanku i transformaciji, te pokušati definirati preporuku o resekciji i praćenju ovih polipa. U inicijalnoj obradi identificirano je 36 bolesnika sa 144 polipa od čega je resecirano 98 HPŽ. Više su bili zastupljeni muškarci (63,9%), medijan dobi bio je 71,5, a prosječan broj polipa po pacijentu 3,8. Polipi su bili smješteni antralno u 75% pacijenata, a simptome je imalo 58,3% bolesnika. Primarni recidiv HPŽ zabilježen je kod 50% pacijenata nakon inicijalne resekcije. U univarijatnoj analizi statistički značajnim za recidiv pokazao se broj reseciranih polipa (RR 5,14 uz CI 95% 1,17-22,48 p=0,03), te ne uzimanje ASK (0,18 uz CI 95% 0,040-0,820, p=0,027). Faktori ipak nisu značajni u multivarijatnoj analizi. Tijekom perioda praćenja, neoplastičnu transformaciju HPŽ zabilježi se u 19,4% svih sudionika, od čega je adenokarcinom utvrđen u 5,5% sudionika. Medijan perioda praćenja do pojave displazije je 9,5 mjeseci, dok je u slučaju recidiva 7,5. Na temelju Kaplan-Meierovih krivulja preživljenja, optimalni period za praćenje da bi se otkrili recidivi i displazija je procjenjen na 12 mjeseci. Dobivena učestalost recidiviranja i neoplastične transformacije u grupi pacijenata, ako se podaci obrađuju kao pacijent-slučaj, veća je od opisane u literaturi. Kao optimalni period praćenja nakon resekcije HPŽ, procjenjuje se na 12 mjeseci zbog toga se otkriva većina recidiva i displazija u HPŽ., Gastric polips are an incidental finding in 1 to 8 % upper GIT endoscopies and hyperplastic gastric polyps (HGP) account for 30 to 93% of cases. The incidince is higher in countries with high H. pylori infection prevalence, but as the eradication strategies progress, the rate of HGP is falling. Studies estimate that the overall risk for neoplastic transformation in the polyp to be 1,5 – 4,5%. It is considered that the risk for adenocarcinoma development is higher in the adjacent mucosa than in the polyp itself (6% vs 2%). In this retrospective study an analysis of medical records, endoscopy and biopsy results of 36 patients that were reffered to KBCSM Gastroenterology department for endoscopic GHP removal from 2009 to 2021 was conducted. The aim od this study is to define the trends and risk factors for HGP reccurence and neoplastic transformation in our patient group, as well as to review the resection and follow-up protocols. A number of 36 patients, initially presented with 144 HGP of which 98 were resected endoscopically. The HGP in our patients are situated antrally (75%), multiple in number (3,8 per person), tend to occur in men (63,9%) and the average patients' age was 71,5 years. Symptoms were described in 58,3% of the patients with HGP. After iniatial resection, 50% of our patients with HGP had a primary reccurence. A univariant analysis found the number of resected polyps (RR 5,14,CI 95% 1,17-22,48 p=0,03) and not belonging to the acetylsalicyc acid therapy group(RR 0,18,CI 95% 0,040-0,820, p=0,027) as factors that are statistically significant for recurrence, but multivariant analysis did not follow through. During the follow up, 19,4% of the patients developed neoplastic changes in HGP, but no risk factors were proven significant in an univariate analysis. The median reccurence period is 6,5 months, while neplastic change was discovered after a median of 9,5 months since resection of GHP. The period of 12 months is consider to be the cut-off point to discover most recurrences and neoplastic changes. Finally, this study did show that the rates of recurrence and neoplastic transformation to be higher than expected in the literatureAlso, a follow up period of 12 months after the resection was confirmed to be the best option for follow-up and early neoplastic change detection.

Nevaricealno krvarenje iz gornjeg gastrointestinalnog trakta spada u skupinu čestih hitnih stanja s visokim razinama mortaliteta i morbiditeta. Krvarenje se najčešće razvija u području jednjaka, želuca ili proksimalnog duodenuma, a prezentira se predominantno pojavom hematemeze, melene i/ili hematokezije u slučajevima masivnog krvarenja. Peptička ulkusna bolest nameće se kao glavni uzrok krvarenja, iako doživljava pad u incidenciji uslijed razvoja terapije eradikacije Helicobacter pylori. Liječenje je složeno i može se podijeliti u tri faze: pre-endoskopsku, endoskopsku i post-endoskopsku obradu pacijenta. U sklopu pre-endoskopske obrade, nakon stratifikacije rizika primjenom alata poput Glasgow-Blatchford skale, moguća je upotreba transfuzije koncentrata eritrocita za određene skupine pacijenata, kao i pre-endoskopska medikamentna terapija eritromicinom i inhibitorima protonske pumpe u visokim dozama. Vrijeme od prezentacije simptoma do početka zahvata endoskopije važan je faktor endoskopske obrade, koja kao takva ima svoju ne samo terapijsku već i dijagnostičku ulogu. Preporuke govore u prilog rane (, Non-variceal upper gastrointestinal bleeding (NVUGIB) is a common emergency with a high rate of mortality and morbidity. Hemorrhage usually develops in the esophagus, stomach, or proximal duodenum while the presentation predominantly includes hematemesis, melena and hematochezia in the case of a massive bleeding. Peptic ulcer disease is regarded as the leading cause of hemorrhage, although the incidence is in decline due to the developments in the Helicobacter pylori eradication therapy. NVUGIB treatment is complex and can be divided into three stages: pre-endoscopy, endoscopy, post-endoscopy. During the pre-endoscopy stage, following the risk stratification using tools such as the Glasgow-Blatchford score, a red-blood cell transfusion can be considered with the specific groups of patients alongside with the pre-endoscopic use of erythromycin and high-dose PPI medication. Timing of the endoscopy is an important factor during the endoscopic stage. Endoscopy itself has both therapeutic and diagnostic role. The early form (

Celijakija i necelijačne preosjetljivosti na gluten spadaju u skupinu poremećaja povezanih s glutenom. Gluten i njemu slični proteini nalaze se u pšenici, raži, ječmu i zobi. Celijakija je autoimuna bolest koja nastaje kod genetski predisponiranih osoba nakon konzumacije glutena. Tipični simptomi celijakije su dijareja s ili bez steatoreje, gubitak na težini i usporen rast i razvoj. Za postavljanje dijagnoze koristi se kombinacija seroloških testova i endoskopskog pregleda uz uzimanje biopsije i patohistološku analizu. Patohistološki celijakiju karakterizira atrofija resica i hipertrofija kripti te porast broja intraepitelnih limfocita. Trenutno jedina dostupna terapija jest strogo pridržavanje bezglutenskoj dijeti. Refraktorna celijakija je oblik celijakije u kojem ne dolazi do poboljšanja simptoma unatoč prehrani bez glutena tijekom najmanje 12 mjeseci. Razlikuju se tip I i tip II koji se smatra pre-limfomom zbog visokog rizika od transformacije u s enteropatijom udružen T-stanični limfom. Necelijačna preosjetljivost na gluten (NCGS) prezentira se sličnim simptomima kao i celijakija. Postavljanje sigurne dijagnoze NCGS je otežano jer trenutno ne postoje osjetljivi i specifični biomarkeri. Kao i kod celijakije jedina terapija jest prehrana bez glutena., Celiac disease and non-celiac gluten sensitivity are a part of gluten-related disorders. Gluten and gluten alike proteins are found in wheat, rye, barley and oats. Celiac disease is an autoimmune disorder that develops in genetically predisposed individuals after gluten consumption. Typical symptoms are diarrhea with or without steatorrhea, weight loss and failure to thrive. A combination of serology and endoscopy with biopsy and pathohistological analysis is used to establish the diagnosis. Pathohistological findings characteristic of celiac disease are villous atrophy, crypt hyperplasia and increased density of intraepithelial lymphocytes. Currently, the only available treatment is strict adherence to a gluten-free diet. Refractory celiac disease is a form of celiac disease characterized by persisting symptoms despite adhering to the gluten-free diet for at least 12 months. Two types of refractory celiac disease are recognized, type I and type II, which is also considered pre-lymphoma due to a high risk of transformation into enteropathy-associated T cell lymphoma. Non-celiac gluten sensitivity (NCGS) presents with similar symptoms as celiac disease. Due to the lack of sensitive and specific biomarkers, establishing a clear NCGS diagnosis is difficult. As with celiac disease, the only available treatment is strict adherence to a gluten-free diet.

Varikoziteti jednjaka i želuca uzrokuju krvarenje iz gornjeg gastrointestinalnog sustava u 13 – 25% slučajeva. Varikoziteti jednjaka i želuca posljedica su portalne hipertenzije, čiji je najčešći uzrok ciroza jetre. Na varikozitete jednjaka treba sumnjati kod pacijenata s krvarenjem iz gornjeg probavnog trakta koji uz to imaju cirozu jetre ili bilo kakvu drugu bolest koja može uzrokovati portalnu hipertenziju. Znakovi i simptomi krvarenja gornjeg probavnog sustava su hematemeza, melena, abdominalna bol, vrtoglavica i sinkopa. Zlatni standard pri postavljanju dijagnoze varikoziteta jednjaka i želuca je endoskopija gornjeg probavnog sustava – ezofagogastroduodenoskopija. Čimbenici koji mogu pomoći u procjeni rizika krvarenja iz varikoziteta su: lokalizacija variksa, veličina variksa, izgled variksa, kliničke značajke pacijenta i intravaricealni tlak. Profilaksa je izrazito važna kako bi se smanjila ukupna smrtnost kod pacijenata s cirozom jetre. Razlikujemo primarnu i sekundarnu profilaksu. Primarnom preveniramo inicijalno krvarenje iz varikoziteta, dok sekundarnom preveniramo ponovne epizode krvarenja u pacijenata koji su već doživjeli hemoragiju. Neselektivni beta blokatori i endoskopska ligacija varikoziteta metode su izbora u primarnoj i sekundarnoj profilaksi krvarenja srednjih i velikih varikoziteta jednjaka. Pacijentima koji akutno krvare iz varikoziteta jednjaka i želuca potrebno je osigurati hemodinamsku stabilnost nadoknadom tekućine, ordinirati antibiotsku profilaksu i primjenom vazoaktivnih lijekova smanjiti portalni tlak. Varicealno krvarenje zbrinjava se endoskopski. Endoskopska ligacija varikoziteta smatra se prvom linijom liječenja krvarenja varikoziteta jednjaka i gastroezofagealnih varikoziteta tip 1, dok je endoskopska terapija tkivnim ljepilima, primarno cijanoakrilatom, prva linija terapije za zbrinjavanje gastroezofagealnih varikoziteta tip 2, izoliranih varikoziteta želuca tip 1 i izoliranih varikoziteta želuca tip 2., Gastrointestinal bleeding is divided into bleeding from the upper gastrointestinal system and bleeding from the lower gastrointestinal system, depending on whether the bleeding is proximal or distal to the duodenojejunal junction (Treitz ligament). Approximately 80% of gastrointestinal bleeding originates from the upper gastrointestinal tract. Esophageal and gastric varices cause upper gastrointestinal bleeding in 13 - 25% of cases. Esophageal and gastric varices develop as a consequence of portal hypertension, the most common cause of which is cirrhosis of the liver. Esophageal varices should be suspected in patients with upper gastrointestinal bleeding who have cirrhosis of the liver or any other disease that may cause portal hypertension. Signs and symptoms of upper gastrointestinal bleeding include haematemesis, melena, abdominal pain, dizziness, and syncope. The initial evaluation of a patient with a suspected clinically significant acute upper GI bleed includes a history, physical examination, and laboratory tests. The gold standard in diagnosis of esophageal and gastric varices is endoscopy of the upper gastrointestinal system - esophagogastroduodenoscopy. Factors that may help assess the risk of variceal bleeding include: localization of the varices, size of the varices, appearance of the varices, clinical features of the patient, and intravariceal pressure. Prophylaxis is extremely important to reduce overall mortality in patients with cirrhosis of the liver. We distinguish between primary and secondary prophylaxis. The primary prevents initial bleeding from varices, while the secondary prevents recurrent bleeding episodes in patients who have already experienced hemorrhage. Nonselective beta blockers and endoscopic variceal ligation are the methods of choice in primary and secondary prophylaxis of bleeding of medium and large esophageal varices. Patients who bleed from esophageal and gastric varices should be provided with hemodynamic stability by fluid replacement, antibiotic prophylaxis should be administered, and vasoactive drugs should be used to reduce portal pressure. Varicose bleeding is managed endoscopically. Endoscopic variceal ligation is considered the first line of treatment for bleeding esophageal varices and gastroesophageal varices type 1, while endoscopic tissue adhesive therapy, primarily cyanoacrylate, is the first line therapy for gastroesophageal varices type 2, isolated gastric varices type 1 and isolated gastric varices type 2.

Endoskopske metode gastrointestinalnog sustava uključuju ezofagogastroduodenoskopiju, kolonoskopiju, perkutanu endoskopsku gastrostomiju (PEG), endoskopsku retrogradnu kolangiopankreatografiju (ERCP) te endoskopski ultrazvuk. Ove invazivne metode, koje vizualiziraju pojedine dijelove probavnog sustava, nose sa sobom određeni rizik pojave neželjenih događaja. S modernizacijom korištenih uređaja i napretkom ovih tehnika, rizik za pojavu komplikacije znatno se smanjio u odnosu na početke primjene istih. Priprema pacijenta prije izvođenja pojedinog zahvata izuzetno je bitna kako bi zahvat bio uspješan, a rizik pojave komplikacije minimalan. Glavne i najučestalije komplikacije svih endoskopskih zahvata u probavnom sustavu jesu perforacija i krvarenje. Neovisno o vrsti tehnike, postojeća koagulopatija ili primjena antikoagulantnih lijekova povećava rizik pojave krvarenja, dok perforaciji pogoduju loša priprema bolesnika, patološka stanja stijenke probavnog sustava kao i izvođenje terapijskih zahvata prilikom endoskopije. Ovisno o težini komplikacije i zdravstvenom stanju pacijenta odabire se modalitet liječenja koji može uključivati primjenu konzervativne terapije, ponovljene endoskopske tehnike pa sve do hitnog kirurškog liječenja. Endoskopičari tako moraju imati na umu moguću pojavu uobičajenih komplikacija, ali i onih iznimno rijetkih i specifično vezanih uz određenu tehniku. Neke od mogućih specifičnih komplikacija su ozljeda slezene i postpolipektomijski sindrom vezan uz kolonoskopiju, pojava post ERCP pankreatitisa nakon ERCP-a te „buried bumper“ sindroma uz primjenu PEG-a. Na posljetku, tijekom svih ovih postupaka moguća je i pojava općih komplikacije poput infektivnih, kardiovaskularnih ali i nuspojava intravenske sedacije ili anestezije. Temeljita preoperativna obrada pacijenta uz pažljivi monitoring tijekom zahvata ove bi neželjene događaje trebala svesti na minimum., Gastrointestinal endoscopic procedures include esophagogastroduodenoscopy, colonoscopy, percutaneous endoscopic gastrostomy, endoscopic retrograde cholangiopancreatography and endoscopic ultrasound. Mentioned invasive methods that visualize individual parts of the digestive system, carry a certain risk of adverse events. Using modern devices and more advanced techniques, the risk of complications has significantly decreased compared to the beginnings of their application. Preparing the patient before performing a particular procedure is extremely important for the procedure to be successful, but also to minimize the risk of complications. The main and most common complications of all gastrointestinal endoscopic procedures are perforation and bleeding. Regardless of the type of technique, the existing coagulopathy or the use of anticoagulant drugs increases the risk of bleeding, while perforation is contributed by poor preoperative preparation, pathology of the wall of the digestive system as well as performing therapeutic endoscopy procedures. The choice of treatment modalities depends on the severity of the complication and the health status of the patient. It may include the use of conservative therapy, repeated endoscopic techniques and in the most severe conditions, emergency surgery. Endoscopists must thus keep in mind the possibility of common complications, but also those that are extremely rare and specifically related to a particular technique. Some of possible specific complications are splenic injury and post-polypectomy syndrome associated with colonoscopy, the occurrence of post-ERCP pancreatitis after ERCP and buried bumper syndrome with the use of PEG. Finally, infectious complications, side effects of intravenous sedation or anesthesia as well as cardiovascular complications are possible with these invasive methods as well as any other procedure. Thorough preoperative treatment and careful monitoring during the procedure should minimize these adverse events.

Fekalna ili crijevna mikrobiota obuhvaća sve mikroorganizme koji žive u čovjekovu crijevu. Glavnina ljudske mikrobiote smještena je upravo u gastrointestinalnom traktu, a od toga najveći dio u kolonu. Obuhvaća bakterije, arheje i gljive. Najveći udio ipak čine crijevne bakterije čije su funkcije i najviše proučavane u znanstvenim istraživanjima. Crijevne bakterije imaju opsežnu metaboličku ulogu u razgradnji prehrambenih vlakana, sintezi vitamina K, proizvodnji kratkolančanih masnih kiselina, metabolizmu žučnih kiselina te proizvode razne druge metabolite kojim utječu na cjelokupni metabolizam ugljikohidrata, bjelančevina i lipida. Nadalje, komenzalne crijevne bakterije sprječavaju kolonizaciju crijeva patogenim bakterijama te tako sudjeluju u obrani organizma od infekcija. Budući da je za vrijeme trudnoće probavni sustav djeteta gotovo sterilan, crijevne bakterije su nakon rođenja djeteta važne za sazrijevanje imunosnog sustava te i kasnije tijekom života imaju veliki utjecaj na imunitet i autoimunost. Fekalna mikrobiota je i u bliskom kontaktu s enteričkim živčanim sustavom te tako utječe na osovinu crijevo – mozak. Promjene fekalne mikrobiote (disbioze) u vidu prekomjerne proliferacije određenih bakterija ili pak smanjenja raznolikosti cjelokupne mikrobiote povezane su s bolestima poput proljeva uzrokovanog s C.difficile, pretilošću, dijabetesom tipa 2, upalnim bolestima crijeva, autoimunim bolestima, neuropsihijatrijskim bolestima i dr. Saznanjima o povezanosti tih promjena i navedenih bolesti pokušava se terapijski utjecati na fekalnu mikrobiotu te su neke od metoda utjecaja na fekalnu mikrobiotu već u rutinskoj primjeni u brojnim zemljama. Ovaj rad donosi pregled različitih uloga crijevnih mikroorganizama u zdravlju i bolesti te mogućeg terapijskog učinka aktivnim utjecanjem na fekalnu mikrobiotu., Fecal or gut microbiota includes all microorganisms that are living in human intestine. The majority of whole human microbiota is located in gastrointestinal system, with the largest share being in colon. It encompasses bacteria, archea and fungi. The biggest part of gut microbiota consists of gut bacteria whose functions are also most thoroughly researched. Gut bacteria have extensive metabolic function in digestion of dietary fiber, vitamin K synthesis, production of short-chain fatty acids, bile acids metabolism and they produce various metabolites which affect complete carbohydrate, protein and lipid metabolism. Furthermore, commensal gut bacteria are preventing the colonization of gut by pathogenic bacteria and thereby defending the organism from infections. Considering the fact that the gastrointestinal system of an infant in utero is almost sterile, gut bacteria is important for maturation of innate immune system and have long term impact on immune system and autoimmunity. Fecal microbiota is also in close contact with enteric nerve system and affects gut-brain axis. Changes of fecal microbiota (dysbiosis) in the form of excessive proliferation of certain bacteria or decreasing of microbiota diversity are associated with diseases such as: diarrhea caused by C.difficile, obesity, type 2 diabetes, inflammatory bowel diseases, autoimmune diseases, neuropsychiatric diseases and other. The knowledge of this links to therapeutic efforts that are aimed to change harmful changes of fecal microbiota. Some of those therapeutic efforts are routinely applied in many countries. This paper reviews the role of gut microorganisms in health and disease and possible therapeutic effects on fecal microbiota.

Akutni pankreatitis upalna je bolest nastala pretjeranom aktivacijom enzima gušterače, osobito tripsina, koja nastaje djelovanjem različitih etioloških čimbenika kod osoba s određenom genetskom predispozicijom. Iako je učestalost bolesti u porastu, posljednjih desetljeća smrtnost se smanjila uslijed brojnih napredaka u dijagnostičkom i terapijskom pristupu. Rutinska upotreba endoskopskog ultrazvuka dovela je do boljeg dijagnosticiranja etiologije, poboljšanog razumijevanja i klasificiranja peripankreatičnih kolekcija, te naročito razvoja endoskopskih, minimalno invazivnih metoda liječenja inficiranih nekrotičnih kolekcija, koje predstavljaju glavni uzrok odgođenog mortaliteta. Utjecaj na prognozu bolesti imali su i pomaci u konzervativnom liječenju, osobito vezano za enteralnu i parenteralnu prehranu, izbjegavanje rutinske, prijevremene primjene antibiotika i sprečavanje razvoja sindroma abdominalnog kompartmenta. Revidirana je klasifikacija peripankreatičnih kolekcija, a osim endoskopskih, razvijene su i minimalno invazivne, perkutane kirurške metode, koje su znatno smanjile smrtnost ranijih otvorenih kirurških zahvata. Prepoznata je važnost sustavnog pristupa liječenju ove bolesti u specijaliziranim jedinicama, te se najbolji rezultati postižu uz kvalitetnu multidisciplinarnu suradnju visokospecijaliziranih stručnjaka., Acute pancreatitis is an inflammatory disease caused by excessive activation of pancreatic enzymes, especially trypsin, which is caused by various etiological factors in people with a certain genetic predisposition. Although, there is a rising incidence of acute pancreatitis, during the last few decades mortality decreased due to better diagnostic and therapic procedures. Routine use of endoscopic ultrasound has led to better diagnosis of etiology, improved understanding and classification of peripancreatic collections, and especially to the development of endoscopic, minimally invasive methods of treating infected necrotic collections, which are a major cause of delayed mortality. Advances in conservative treatment, especially in enteral and parenteral nutrition, avoidance of routine premature administration of antibiotics and prevention of the development of abdominal compartment syndrome, also had an impact on the prognosis of the disease. The classification of peripancreatic collections has been revised, and besides endoscopic, minimally invasive, percutaneous surgical methods have been developed, which have significantly reduced the mortality of previously open surgical procedures. The importance of a systematic approach to the treatment of this disease in specialized units has been recognized, and the best results are achieved with quality multidisciplinary cooperation of highly specialized experts.

Ciroza je posljednji stadij kronične bolesti jetre, a poremećaji hemostaze koji nastaju u sklopu ovog stanja posljedica su smanjene sintetske funkcije jetre te portalne hipertenzije. U cirozi jetre snižene su koncentracije svih čimbenika zgrušavanja krvi i endogenih antikoagulansa uz iznimku faktora VIII koji se može naći u povišenim koncentracijama. Uspostavljena nova ravnoteža koja nastaje zbog relativnog manjka i čimbenika zgrušavanja krvi i prirodnih antikoagulansa u cirozi nije stabilna kao u fiziološkim uvjetima. Vrlo lako može doći do pomaka ravnoteže na stranu krvarenja ili tromboze, a što će prevagnuti ovisi o prisutnim rizičnim čimbenicima u pojedinog bolesnika (portalna hipertenzija, bakterijske infekcije, disfunkcija endotela, bubrežno zatajenje, uremija, varikoziteti jednjaka). Standardni testovi zgrušavanja krvi dobro koreliraju s težinom bolesti i mogu se koristiti za procjenu prognoze, no nažalost ne prikazuju dobro promjene u čitavom sustavu zgrušavanja krvi te ne mogu dobro procijeniti rizik za pojavu krvarenja ili tromboze u ove skupine pacijenata. Globalni viskoelastični testovi, poput tromboelastografije i rotacijske tromboelastometrije, omogućuju bolju procjenu sustava zgrušavanja krvi te se danas sve više koriste. Najčešća krvarenja su iz varikoziteta jednjaka te se smatraju posljedicom lokalnih promjena u području varikoziteta i portalne hipertenzije, a manje posljedicom samog poremećaja sustava zgrušavanja krvi. S druge strane portalna venska tromboza najčešći je trombotski događaj u pacijenata s cirozom jetre, a spori protok krvi u portalnom sustavu najznačajniji je čimbenik koji pridonosi riziku za trombozu. Odluke o terapijskim intervencijama potrebno je donositi individualno za svakog pacijenta, a često i u suradnji s hematologom., Liver cirrhosis presents an end stage of chronic liver disease and associated alterations in hemostasis result from an impaired synthetic function of the liver and portal hypertension. In cirrhosis levels of both procoagulants and anticoagulants are decreased, except for factor VIII which is increased. Consequently, the hemostasis in cirrhosis is rebalanced, because there is a relative deficit on both sides of the coagulation system, but this balance between the procoagulants and anticoagulants is not as stable as in physiological conditions. It can easily tip toward hemorrhage or thrombosis depending on the risk factors in each patient individually (portal hypertension, bacterial infections, endothelial dysfunction, renal failure, uremia, esophageal varices). Conventional coagulation tests are in good correlation with the severity of the disease and can be used as predicting factors, but they do not reflect all changes in the entire coagulation system and can not accurately predict the risk of bleeding or thrombosis in patients with liver cirrhosis. Global viscoelastic tests, such as thromboelastography and rotational thromboelastometry, enable better assessment of hemostatic balance and are being introduced into clinical practice. The most common bleeding event in patients with cirrhosis represents bleeding from ruptured esophageal varices, which develops as consequence of local vascular abnormalities as well as portal hypertension, while changes in hemostasis play a minor role in variceal bleeding. On the other hand, portal vein thrombosis is the most common thrombotic event in patients with liver cirrhosis and reduced portal blood flow represents the most important risk factor for portal vein thrombosis. Decisions on therapeutic interventions should be made individually for each patient and often in consultation with the hematologist.

Gastrointestinal bleeding remains a significant cause of morbidity and mortality worldwide, and contributes significantly to health care costs. GI bleeding can be life threatening, and treatment of this condition remains a significant challenge. Mortality rates have persisted stubbornly for decades; however recent advances in guidelines, pre-endoscopic management, and endoscopic therapies has decreased the death rate for this condition. Gastrointestinal bleeding is commonly divided into upper and lower GI bleeding based on the location of the bleed in relation to the ligament of Treitz. Although expansive, this review seeks to succinctly explain the causes, clinical manifestations, and management of both upper and lower gastrointestinal bleeding. A brief discussion of the challenges and uncertainties physicians continue to face concludes this review., Krvarenje iz probavnog trakta ostaje važan uzrok morbiditeta i mortaliteta diljem svijeta, te značajno doprinosi visokim troškovima zdravstvene skrbi. Ta vrsta krvarenja može često biti životno ugrožavajuća, a liječenje bolesnika s ovim stanjem ostaje i dalje značajan izazov. Stope smrtnosti su kod gastrointestinalnog krvarenja desetljećima uporno ostajale iste, no relativno recentnim pomacima u endoskopskom i medikamentoznom liječenju te razvojem smjernica prati se smanjenje mortaliteta kod ovih bolesnika. Krvarenje iz probavnog trakta obično se dijeli na krvarenje iz gornjeg i krvarenje iz donjeg trakta, na osnovu lokalizacije mjesta krvarenja u odnosu na Treitzov ligament. Iako opsežan, ovaj pregledni tekst nastoji sažeto obraditi uzroke, kliničke manifestacije i liječenje krvarenja iz oba dijela probavnog trakta. Pregled završava kratkom diskusijom o izazovima i nedoumicama s kojima se liječnici i dalje suočavaju pri zbrinjavanju ovih stanja.

Šećerna bolest je heterogena skupina kroničnih metaboličkih poremećaja koji nastaju zbog apsolutnog ili relativnog nedostatka hormona inzulina i jedna je od najčešćih endokrinoloških bolesti u svijetu. Klasifikacija uključuje šećernu bolest tipa 1, šećernu bolest tipa 2, gestacijsku šećernu bolest te ostale, specifične tipove šećerne bolesti, a svima je zajednička hiperglikemija koja s vremenom dovodi do razvoja akutnih i kroničnih komplikacija. Šećerna bolest tipa 2 može se pojaviti u svim dobnim skupinama, a u njezinom nastanku sudjeluju nasljedni i okolišni čimbenici od kojih je jedan od najvažnijih povećana tjelesna masa definirana indeksom tjelesne mase većim od 25,0 kg/m2. Prema podacima Svjetske zdravstvene organizacije, povećana tjelesna masa uključena je u 10 vodećih čimbenika rizika za razvoj bolesti na globalnoj razini, a smatra se posljedicom suvremenih navika i načina života. U razvoju bolesti povezanih s debljinom, veći značaj se pridaje abdominalnom masnom tkivu koje je manje osjetljivo na inzulin te otpušta veće količine nekih adipokina. Česti komorbiditeti udruženi sa šećernom bolesti i debljinom su hipertenzija, dislipidemija i poremećaji prehrane od kojih je najčešći poremećaj prejedanja obilježen ponavljajućim epizodama prejedanja koje nisu praćene povraćanjem ili uporabom laksativa, emetika i diuretika. Saznanja o povezanosti antropometrijskih vrijednosti i prehrambenih navika u dijabetičara od iznimne su važnosti zbog planiranja terapije koja, osim farmakološke regulacije glukoze u plazmi, mora uključivati i promjene prehrambenih navika bolesnika, a po potrebi i suradnju s psihijatrom., Diabetes mellitus is a heterogeneous group of chronic metabolic disorders resulting from an absolute or relative lack of insulin and is one of the most common endocrine diseases in the world. Classification includes type 1 diabetes mellitus, type 2 diabetes mellitus, gestational diabetes and other, specific types of diabetes, all resulting in hyperglycemia, commonly associated with the development of acute and chronic complications. Type 2 diabetes mellitus may occur in all age groups, where inherited and environmental factors play a role in its emergence. One of them which is supposed to have the most impact is increased body mass defined by a body mass index greater than 25.0 kg/m2. According to World Health Organization data, increased body mass is included in the 10 leading risk factors for disease development globally and is considered a consequence of modern habits and lifestyles. The occurrence of diseases associated with obesity is due to the excess abdominal fat tissue that is less sensitive to insulin and releases larger amounts of some types of adipokines. Frequent comorbidities associated with diabetes mellitus and obesity are hypertension, dyslipidemia and eating disorders, the most common being Binge Eating Disorder, characterized by recurrent episodes of overeating without the use of laxatives, emetics and diuretics afterwards. Knowledge of the association of anthropometric data and dietary habits in diabetics is of great importance for planning a therapy that, besides pharmacological regulation of plasma glucose, should also involve changes in the dietary habits of patients and, if necessary, the co-operation with a psychiatrist.

Cistični tumori gušterače su epitelom omeđene tvorbe ispunjene tekućim sadržajem, a ovisno o vrsti epitela mogu imati benigni ili maligni potencijal. Smatra se da 1,2% populacije ima cistične lezije unutar parenhima gušterače od kojih 60% čine cistični tumori dok su ostatak pseudociste, kongenitalne i izvanpankreasne ciste te cistično degenerirani solidni tumori. Od svih tumora gušterače, cistični tumori su zastupljeni u 10-15% slučajeva. Na cistične tumore gušterače se najčešće posumnja na temelju slučajnog nalaza transabdominalnog ultrazvuka, CT-a ili MR-a koji se rade u sklopu obrade različitih bolesti probavnog sustava. Najčešći tip cističnih tumora je mucinozna cistična neoplazma koja je prisutna u 45% slučajeva, predominantno u mladih žena, te ima tendenciju maligne alteracije u 25% bolesnika. Nešto rjeđi tipovi cističnih tumora su: serozni cistadenom, intraduktalna papilarna mucinozna neoplazma, solitarna pseudopapilarna neoplazma i neuroendokrini tumori gušterače. Najosjetljivija dijagnostička metoda i zlatni standard u postavljanju dijagnoze malignih i benignih lezija gušterače je endoskopski ultrazvuk (EUZ). Osim mogućnosti detaljne vizualizacije, EUZ pruža i mogućnost uzimanja uzorka uz pomoć metode nazvane tankoiglena aspiracija pod kontrolom EUZ-a. EUZ-om se može prikazati cjelokupna struktura parenhima gušterače, ukupna veličina, lokalizacija i broj cista, komunikacija s glavnim ili postraničnim vodom, debljina stijenke, intracistične tvorbe poput septi, solidnih dijelova ili kalcifikata što sve pruža korisne informacije u procjeni malignog potencijala analizirane lezije. U vremenskom periodu od 2009. do 2018. godine na Zavodu za gastroenterologiju i hepatologiju KBC Sestre milosrdnice učinjeno je 5014 pregleda EUZ-om, a u 239 bolesnika je detektirano postojanje cističnog tumora gušterače. Cilj istraživanja je bio utvrditi dijagnostičku preciznost EUZ-a u dijagnostici i praćenju bolesnika s cističnim tumorima gušterače, te osjetljivost i specifičnost EUZ-FNA. Rezultati analize upućuju da dijagnostička preciznost EUZ-a iznosi 93.2%. Osjetljivost za detekciju malignog tumora iznosi 100%, a specifičnost 75.7%., Pancreatic cystic tumors are epithelium-bound formations filled with cystic content, and depending on the type of epithelium, can have a benign or malignant potential. 1,2% of population has cystic lesions within pancreatic parenchyma, of which 60% constitute cystic tumors. The rest are pseudocysts, congenital and non-pancreatic cysts, and cystically degenerate solid tumors. Cystic tumors are represented in 10-15% of cases and can be assessed with multiple imaging modalities, including transabdominal ultrasound, CT, MRI, EUS. They are usually accidentally diagnosed as part of the diagnosis of some other gastrointestinal diseases. The most common type of cystic tumor is mucinous cystic neoplasia which is present in 45% of cases, predominantly in young women, and has a tendency of malignant alteration in 25% of patients. Some rarer types of cystic tumors include: serous cysadenoma, intraductal papillary mucinous neoplasms, solitary pseudopapillar neoplasms and neuroendocrine pancreatic tumors. The most sensitive diagnostic method and the gold standard for malignant and benign lesions of the pancreas is endoscopic ultrasound. In addition to the possibility of visualization, the EUS provides the possibility of additional diagnostic procedure used to collect the sample of cystic cells which is called endoscopic ultrasound guided fine-needle aspiration. The EUS can show the overall structure of the pancreas parenchyma, the total size, the localization and the number of cysts, the communication with the main or branch duct, thickness of the wall, septa, intracystic solid parts and all of it provides useful informations in evaluating the malignancy of the analyzed lesion. In the period from 2009 to 2018, 5014 EUS procedures were performed at the Department of Gastroenterology and Hepatology, University Hospital Centre “Sestre milosrdnice”. In 239 participants was detected the existence of cystic pancreatic tumors. The aim of this study was to determine the diagnostic precision of the EUS in the diagnosis and monitoring of patients with pancreatic cystic tumors, and to investigate the sensitivity and and specificity of EUS-FNA. The results showed that the diagnostic precision of the EUS was 93,2% whereas the sensitivity of malignant tumor detection was 100% and specificity 75,7%.