HISTOPATHOLOGIC CHANGES IN SEPSIS

Teška sepsa i septički šok su ozbiljni globalni zdravstveni problem uz porast incidencije i visoku smrtnost. Najveći broj slučajeva septičnog šoka uzrokuju bolnički stečeni gram–negativni bacili ili gram–pozitivni koki. U dijagnostičkom algoritmu bolesnika u sepsi potrebno je učiniti mikrobiološku analizu tkiva i tjelesnih tekućina posebice u bolesnika s otprije poznatom infekcijom pojedinog organskog sustava. U slučaju kada su rezultati dijagnostičkih testova negativni ili se radi o teškoj kliničkoj slici bolesnika unatoč primijenjenim terapijskim postupcima moguće je učiniti i morfološku analizu uzoraka tkiva u dijagnostičke svrhe. Morfološke promjene koje se mogu vidjeti u bolesnika oboljelog od sepse uključuju reverzibilno i ireverzibilno stanično oštećenje, tj. nekrozu stanica, upalne i ostale patološke promjene koje dovode do funkcionalnog zatajenja organa. Analiza uzročnika moguća je pomoću specijalnih metoda, histokemijskog, imunohistokemijskog i imunofl uorescentnog bojanja. Analizu morfoloških promjena organa moguće je učiniti i u slučaju smrtnog ishoda bolesnika. Obdukcija je jedna od najpouzdanijih metoda u procjeni točnosti kliničkih dijagnoza. Morfološke promjene tkiva i organa koje se mogu analizirati u bolesnika oboljelih od sepse tijekom dijagnostičkog postupnika, te u slučaju smrtnog ishoda obdukcijom predstavljaju dijagnostičku i konačnu procjenu točnosti kliničkih dijagnoza. Kao takve izravno utječu na njegu i liječenje bolesnika te na poboljšanje kvalitete zdravstvene zaštite.Severe sepsis and septic shock are the major healthcare problem with high mortality and increasing incidence. Most cases of septic shock are caused by gram-negative bacilli or gram-positive cocci. In diagnostic algorithm, microbial culture and molecular analysis of tissue and body liquid should be obtained in patients with documented history of infection. Morphological analysis of tissue should be performed for diagnostic purpose in cases where the results of diagnostic tests are negative or when the patient clinically deteriorates despite standard therapeutic management of severe sepsis and septic shock. Morphological changes that can be found in a patient with sepsis include reversible and irreversible cell injury, cell necrosis, infl ammatory and other pathological changes that can cause functional organ failure. Analysis of infectious agents can be performed using special methods, histochemical, immunohistochemical and immunofl uorescence staining. Morphological analysis of pathological processes can be performed in cases of patient death. Autopsy is one of the most reliable methods to validate clinical diagnosis. In a patient with severe sepsis and septic shock, morphological analysis of tissue and organs, which can be performed during diagnostic algorithm, as well as on autopsy, presents diagnostic and fi nal validation of clinical diagnosis and contributes to appropriate patient care, therapy and improved health quality

Neočekivani ishod kod liječene bolesnice s gonadnom disgenezom

Hormone replacement therapy is mandatory to maintain quality of life and bone mineralization status in patients with gonadal dysgenesis. Occasionally, these patients need higher than recommended estrogen dosage to prevent signs and symptoms of hypoestrogenic state. Our 18-year-old female patient with XY sex reversal syndrome was gonadectomized and administered conventional hormone replacement therapy. Gonadoblastoma was found in the excised streak gonad. Five years after continuous replacement therapy, the patient reported unexpectedly hot flushes and amenorrhea in spite of regular hormone intake. Severe osteopenia was also detected. Unconventionally high estrogen dose was given with additional daily vitamin D and calcium supplement. Dual energy x-ray absorptiometry revealed lesser but evident osteopenia and the patient reported repeated bleeding without hot flushes on the new hormone regimen. Individualized dosage of estrogen is essential for these patients according to their bone status and subjective symptoms. Early therapy initiation along with continuous and frequent evaluation of bone status and quality of life is advised.U bolesnica s disgenezom gonada liječenje hormonskom nadomjesnom terapijom potrebno je kako bi se očuvala kvaliteta života te primjerena mineralizacija koštanog tkiva. U liječenju je ponekad potrebno primijeniti višu dozu estrogena od preporučene kako bi se spriječili znaci i simptomi hipoestrogenemije. Prikazuje se osamnaestgodišnja bolesnica s čistom disgenezom gonada, liječena standardnom hormonskom nadomjesnom terapijom u koje je učinjena gonadektomija. Unutar fibrotičnog gonadnog tračka nađen je gonadoblastom. Bolesnica je liječena kontinuiranom hormonskom nadomjesnom terapijom pet godina, nakon čega je naglo razvila amenoreju te valove vrućine. Denzitometrijom se dokazala teška osteopenija. Bolesnica je potom liječena visokim dozama estrogena uz dodatak vitamina D i kalcija svakodnevno. Denzitometrijom se i dalje verificirala postojana osteopenija, ali manje izražena. Uspostavljena su redovita krvarenja bez valova vrućine tek uz tromjesečni režim hormonske terapije (estradiol 3 mg/3 mjeseca i didrogesteron 10 mg/posljednjih 14 dana). U bolesnica s čistom disgenezom gonada uputno je rano započeti s hormonskim liječenjem uza stalne i česte kontrole statusa koštanog tkiva i kvalitete života. Nužan je individualni pristup hormonskom nadomjesnom liječenju ovisno o subjektivnim smetnjama i statusu koštanog tkiva

Metastasis of endometrial cancer in ovary or synchronous primary cancers of endometrium and ovary – case report

Primarni karcinom endometrija najčešća je maligna neoplazma ženskoga spolnog sustava. Prvotni simptomi, kada se i dijagnosticira u početnom stadiju bolesti, jesu nepravilna i/ili produljena krvarenja u premenopauzi ili krvarenja u postmenopauzi. Ostali su simptomi boli u zdjelici ili abdomenu ili abnormalni Papanicolaouov test. Bolesnice su najčešće u postmenopauzalnom razdoblju, ali ni žene generativne dobi nisu isključene. Radovi su pokazali da žene generativne dobi s dijagnosticiranim karcinomom endometrija imaju povišen rizik i od istodobne bolesti karcinoma jajnika i nasljednoga nepolipoznog karcinoma kolona. Upravo je entitet istodobnoga primarnog karcinoma endometrija i jajnika velika dijagnostička zamka jer ne postoje jedinstveni histološki algoritam ni kirurški postupnik, a potrebno ga je odvojiti od primarnog karcinoma jajnika i metastatskog širenja karcinoma endometrija u jajnik radi povoljnije prognoze i mogućnosti poštednijega kirurškog zahvata u mlađih bolesnica te očuvanja fertiliteta. U radu prikazujemo bolesnicu u dobi od 49 godina, s anamnestičkim podacima o obilnijim krvarenjima i postojanju ciste na jajniku, kod koje se nakon intenzivnih i naglih boli te zbog sumnje na rupturu ciste pristupilo hitnom laparoskopskom zahvatu. Zbog intraoperativnoga citološkog nalaza sa sumnjom na maligni proces i pozitivnoga patohistološkog nalaza operacija je konvertirana u laparotomiju. Detaljnom patohistološkom analizom uz imunohistokemijsku dopunu dijagnosticirana je rasadnica (metastaza) endometrioidnog adenokarcinoma endometrija.Primary endometrial cancer is the most common malignant neoplasm of the female reproductive system. It is most commonly detected in the first stage of the disease. The most frequent initial symptoms are irregular or prolonged bleeding in premenopausal or bleeding in postmenopausal women. Other symptoms are pain in the pelvis or abdomen, or abnormal Pap smear. Patients are most often in postmenopausal period of life but women in generative age are not excluded. Different researches have shown that women of generative age with endometrial cancer have an increased risk of the synchronous disease of ovarian cancer and hereditary non-polypoid colon cancer. This is exactly corroborated by the fact that primary cancer in the reproductive system of women may occur at the same time, especially in endometrial cancer and in ovarian cancer. The entity of the synchronous primary cancer of endometrium and ovary is a large diagnostic trap because there is no unique histological algorithm or unique attitude for surgical procedure. However,, it is necessary to separate this entity from primary ovarian cancer and metastatic endometrial cancer in the ovary because of its better prognosis and possibility for less aggressive surgery in younger patients with preservation of fertility. We present a 49-year-old patient with history data on abundant bleeding and the existence of ovarian cyst. After intense and severe pain, and because of the suspicion of the rupture of the cyst, the emergency laparoscopic surgery was done. Intraoperative cytological analysis raised doubt about malignant process. Intraoperative histological finding was positive for endometrioid malignant process. Operation was converted to laparotomy. Detailed histopathological analysis, complemented with immunohistochemical procedure, diagnosed metastasis of endometrioid adenocarcinoma of endometrium

Vulvar Paget’s Disease – A Case Report

Vulvar Morbus Paget (MP) represents a rare intraepithelial adenocarcinoma. It accounts for less than 1% of all vulvar neoplasia and usually appears in postmenopausal women. Histologically it is analogous to Paget’s disease of the breast. The most common clinical symptom is pruritus. The lesion appears as an erythematous or as an eczematous lesion with islands of hyperkeratosis. Occasionally, single anaplastic Paget’s cells can be found on the vulvar smears which make cytological diagnosis of the disease possible. However, the disease can be diagnosed only by biopsy. We present a case of 49-year old woman with vulvar symptoms of pruritus, who had liver and kidney transplantation two years ago. During the standard gynecological examination the vulvar smear was taken for cytological evaluation. The smear was scanty, with inflammatory background, overloaded with squamae. There were two types of cells: dysplastic squamous cells from lower layer of the epithelium and the single, anaplastic cells with a high nuclear:cytoplasmic ratio who possessed eccentric, large nucleus. Nucleoli were rare. Cytoplasm varied from pale and delicate to densely basophilic. Accordingly, cytological diagnosis vulvar intraepithelial neoplasia (VIN III) with differential diagnosis of vulvar Paget’s disease was made. The pathological verification supported the diagnosis of MP and an immunohistochemistry panel confirmed type III of Paget’s disease and an evaluation of bladder was suggested

Mitral and tricuspid valvuloplasty in a patient with myelodysplastic syndrome

Mijelodisplastični sindrom (MDS) klonska je bolest matične hematopoetske stanice, koja se očituje poremećenom proliferacijom, diferencijacijom i sazrijevanjem hematopoeze te displastičnim promjenama u koštanoj srži. U kliničkoj slici i laboratorijskim nalazima bolesnika s MDS-om dominira anemija, nešto rjeđe neutropenija ili trombocitopenija različitih stupnjeva težine. Kardiokirurški zahvat u bolesnika s MDS-om velik je izazov jer su neutropenija i trombocitopenija vodeći uzroci infekcija i krvarenja tijekom operacije. Malen je broj izvješća u literaturi koja opisuju kardiokirurški zahvat u bolesnika s MDS-om. Prikazujemo 66-godišnju bolesnicu s MDS-om kod koje je uspješno izvedena rekonstrukcija mitralnog i trikuspidalnoga srčanog zalistka. Bolesnica se javila u hitnu službu zbog otežanog disanja, opće slabosti i znakova srčanog popuštanja. Radiološkom obradom verificirani su obostrani pleuralni izljev, izraženije lijevo, i povećana sjena srca s naglašenim vaskularnim hilusima. Daljnjom obradom dokazane su mitralna i trikuspidalna insuficijencija teškog stupnja pa je bolesnica operirana, a pet godina nakon zahvata ima dobru kvalitetu života. Multidisciplinarnom suradnjom kardiologa, hematologa, anesteziologa i kardiokirurga u bolesnice je uspješno izveden kirurški zahvat rekonstrukcije mitralne i trikuspidalne valvule. Ovaj prikaz bolesnice upućuje na važnost multidisciplinarnog pristupa specifičnoj i ranjivoj grupi bolesnika s MDS-om i kardiovaskularnim komorbiditetima.Myelodysplastic syndrome (MDS) is a clonal disease of mutated hematopoietic stem cells characterized by abnormal hematopoietic differentiation and dysplastic bone marrow changes. MDS usually tends to present with anemia, less often with neutropenia and thrombocytopenia of varying degrees. Cardiac surgery in MDS patients is a major challenge because neutropenia and thrombocytopenia are the leading causes of infection and bleeding during the procedure. There are only a few reports of cardiovascular surgery in patients with MDS. We are presenting a 66-year-old MDS patient with a successful reconstruction of the mitral and tricuspid heart valve. The patient presented in the Emergency department with weakness and dyspnea. Radiological workup verified 3rd stage heart failure. Severe mitral and tricuspid insufficiency was verified, after which the patient underwent cardiac surgery, and five years after the procedure has good quality of life. Through the multidisciplinary collaboration of cardiologists, hematologists and cardiac surgeons an operative reconstruction of mitral and tricuspid valve was successfully performed. This case indicates the need for multidisciplinary care for the specific and vulnerable group of MDS patients with cardiovascular comorbidities

CROATIAN GUIDELINES FOR GASTRIC CANCER PREVENTION BY ERADICATION OF HELICOBACTER PYLORI INFECTION

Želučani je rak četvrti po učestalosti karcinom u svijetu i drugi po učestalosti uzrok mortaliteta izazvanog malignim bolestima. Iako je etiologija tog karcinoma multifaktorska, infekcija Helicobacterom pyloriizrazito je povezana sa želučanom karcinogenezom. Na karcinogenezu utječu i neki čimbenici okoliša, kao i genska raznolikost, koji mogu dovesti do različitih upalnih odgovora te time utjecati na klinički ishod bolesti. Kronični gastritis izazvan infekcijom Helicobacterom pylori najjači je poznati čimbenik rizika od razvoja adenokarcinoma distalnog dijela želuca premda učinak bakterijske eradikacije na samu karcinogenezu ostaje zasad nedovoljno istražen. Iako se čini da eradikacija infekcije Helicobacterom pylori smanjuje rizik od nastanka želučanog karcinoma, više novijih terapijskih pokušaja prevencije nastanka tog tumora eradikacijom infekcijeHelicobacterom pylori postiglo je razočaravajuće rezultate. U pokušaju razjašnjenja tog problema u populacijama s visokim rizikom istraživači su započeli provoditi prospektivne randomizirane, dvostruko slijepe populacijske studije. Rezultati prethodnih studija upozorili su na važnost dugotrajnog i pomnog praćenja bolesnika nakon provedene eradikacijske terapije. Čini se da je eradikacija infekcije u svrhu prevencije želučanog karcinoma djelotvorna samo onda kada se provede prije razvoja premalignih promjena/lezija: atrofije, metaplazije i displazije želučane sluznice. Osim toga, značajna učinkovitost izlječenja uočena u mlađih bolesnika sugerira potrebu provođenja eradikacije infekcije Helicobacterom pylori što je moguće ranije.Gastric cancer is the fourth most common type of cancer and the second leading cause of cancer-related death in the world. Although gastric cancer has a multifactorial etiology, infection with Helicobacter pyloriis highly associated with gastric carcinogenesis. Carcinogenesis is also influenced by some environmental factors and host genetic diversity, which engenders differential host inflammatory responses that can influence clinical outcome. Chronic gastritis induced by H. pylori is the strongest known risk factor for adenocarcinoma of the distal stomach, but the effects of bacterial eradication on carcinogenesis have remained unclear up to now. Although eradication of H. pylori infection appears to reduce the risk of gastric cancer, several recent controlled interventional trials by H. pylori eradication to prevent gastric cancer have yielded disappointing results. To clarify this problem in a high-risk population, the investigators conducted a prospective, randomized, double-blind, placebo-controlled, population-based studies. The results of previous studies highlight the importance of longer and careful follow-up after eradication therapy. It seems that eradication treatment is effective in preventing gastric cancer if it is given before preneoplastic conditions/lesions, gastric atrophy, metaplasia, and dysplasia, have had time to develop. Furthermore, the significant efficacy of treatment observed in younger patients suggests the need to eradicate H. pylori as early as possible. This consensus aimed to propose guidelines for the diagnosis, management and control of individuals with chronic gastritis, atrophy, intestinal metaplasia, or dysplasia

Expression of micro RNAs (miRNAs) in myelodysplastic syndrome (MDS)

Sindrom mijelodisplazije ili mijelodisplastični sindrom (MDS) naziv je za skupinu heterogenih klonskih hematoloških poremećaja hematopoetskih matičnih stanica, praćenih neučinkovitom hematopoezom jedne ili više staničnih linija i pojavom posljedičnih citopenija s povišenim rizikom od progresije u akutnu mijeloičnu leukemiju (AML). Mikroglasničke ribonukleinske kiseline (miRNK; engl. Micro Messenger Ribonucleic Acid – miRNA) kratke su, nekodirajuće molekule RNK koje, osim što pridonose patogenezi MDS-a, djeluju i kao regulatori epigenetičkih mehanizama i potencijalni su prognostički biljezi za ranu dijagnostiku i klasifikaciju MDS-a. Cilj je rada bilo ispitivanje razine promjene genskih ekspresija specifičnih miRNK (hsa-miR-125a, hsa-miR-99b, hsa-miR 126 i hsa-miR-125b) u plazmi zdravih dobrovoljaca i ispitanika s dijagnozom MDS-a. Ispitivanje se provodilo u Kliničkom zavodu za medicinsku biokemiju i laboratorijsku medicinu Kliničke bolnice Merkur, akreditiranome prema normi EN ISO 15189:2012. Genske ekspresije navedenih, specifičnih miRNK određene su u uzorcima plazme zdravih dobrovoljaca (4) i ispitanika s MDS-om (33) kojima je on dijagnosticiran u Zavodu za hematologiju Klinike za unutarnje bolesti Kliničke bolnice Merkur, Referentnom centru Ministarstva zdravlja Republike Hrvatske za dijagnostiku i liječenje MDS-a. Statistički značajne razlike genske ekspresije specifičnih miRNK u zdravih dobrovoljaca u odnosu prema ispitanicima s MDS-om nisu nađene [P (hsa-miR-125a) = 0,398; P (hsa miR-99b) = 0,134; P (hsa-miR-126) = 0,305; P (hsa-miR-125b) = 0,079], a razina promjene genskih ekspresija miRNK (engl. miRNA ratios) hsa-miR-125a i hsa-miR-99b u ispitanika s MDS-om bila je gotovo dva puta viša u odnosu prema normaliziranim razinama genske ekspresije u zdravih dobrovoljaca (2,30 prema 1,90) i više od dva puta viša od razine promjene genske ekspresije miRNK hsa-miR-125b. Rezultati istraživanja upućuju na to da bi genske ekspresije miRNK hsa-miR-125a i hsa-miR-99b mogle biti regulirane istim mehanizmom i da bi mogle biti klinički važne u ispitanika s MDS-om.Myelodisplasia or myelodysplastic syndrome (MDS) is the name for a group of heterogeneous clonal hematological disorders of hematopoietic stem cells followed by ineffective hematopoesis of one or more cell lines and the emergence of consequent cytopenias with increased risk of progression to acute myelogenous leukemia (AML). Micro Messenger Ribonucleic Acids (miRNAs) are short, non-coding RNA molecules that, apart from contributing to MDS pathogenesis, act as regulators of epigenetic mechanisms and also are recognized as potential prognostic markers for early diagnosis and classification of MDS. The aim of the study was to examine the levels of gene expression of specific miRNAs (hsa-miR-125a, hsa-miR-99b, hsa-miR-126 and hsa-miR-125b) in healthy volunteers plasma and MDS diagnosed patients. Gene expressions of miRNAs were determined at the Clinical Institute of Medical Biochemistry and Laboratory Medicine, Merkur University Hospital, accredited according to EN ISO 15189:2012, in plasma samples of four healthy volunteers and 33 MDS patients diagnosed at the Institute of Hematology of the Clinic for Internal Diseases of Merkur University Hospital, Reference Center of the Ministry of Health of the Republic of Croatia for Diagnosis and Treatment of MDS. Statistically significant difference in gene expression of miRNA in healthy volunteers compared to the MDS patients was not found (P [hsa-miR- 125a] = 0.398; P [hsa-miR-99b] = 0.134; P [hsa- miR-126] = 0.305; P [hsa miR-125b] = 0.079). MiRNA ratios of hsa-miR-125a and hsa-miR-99b in MDS patients were almost twice as high compared to normalized levels of gene expression in healthy volunteers (2.30 versus 1.90), and the level of change of miRNAs hsa-miR-125 and hsa-miR-99b was more than two times higher than the level of change of miRNA hsa-miR-125b. Finally, the results of the research indicate that the gene expression of miRNAs hsa-miR-125a and hsa-miR-99b could be regulated by the same mechanism and could be clinically relevant in MDS patients

Abernethy malformation as a rare indication for liver transplantation: Case report

Abernethyjeva malformacija ili kongenitalna ageneza portalne vene (KAPV) rijetka je malformacija abdominalnoga splanhničkog venskog sustava. Dijagnoza se najčešće postavlja u dječjoj dobi i često je povezana s drugim malformacijama poput srčanih grešaka i poremećaja skeletnog sustava, kao i s tumorima jetre. Sama malformacija može se manifestirati u dva oblika. Kod tipa I portalna krv potpuno zaobilazi jetru te se gornja mezenterijska vena i lijenalna vena odvojeno (tip Ia) ili zajedno (tip Ib) dreniraju u donju šuplju venu, a u jetri ne postoje intrahepatalni portalni venski ogranci. Kod tipa II prisutan je parcijalni portokavalni shunt i portalna krv djelomično opskrbljuje jetru. Nema jedinstvenoga terapijskog pristupa za sve bolesnike s Abernethyjevom malformacijom, međutim, kod bolesnika sa simptomima jetrene bolesti (encefalopatija, loša funkcija jetre) te onih s tumorima jetre preporučuje se transplantacija jetre. U ovom radu prikazujemo Abernethyjevu malformaciju tipa Ib u 17-godišnje bolesnice kod koje se obradom kronične malaksalosti praćene bolima pod desnim rebrenim lukom pronašao neresektabilni tumor jetre te joj je uspješno obavljena ortotopna transplantacija jetre.Abernethy malformation or congenital agenesis of the portal vein (CAPV) is a rare malformation of the abdominal splanchnic venous system. This malformation is commonly found in children and is often associated with other malformations such as congenital cardiac anomalies and skeletal system disorders, as well as liver tumors. There are two types of Abernethy malformation. In type I, portal blood bypasses the liver completely, with the superior mesenteric vein and the splenic vein draining into the inferior vena cava separately (type Ia), or together (type Ib). There are no intrahepatic portal vein branches in the liver. Type II is a partial portocaval shunt in which portal blood partially supplies the liver. There is no unified therapeutic approach for all patients with Abernethy malformation, however, liver transplantation is recommended in patients with liver disease (encephalopathy, poor liver function) and those with liver tumors. In this case report we present a case of Abernethy type Ib malformation in a 17-year-old patient with chronic malaise and uper abdominal pain. During diagnostic work-up, an unresectable liver tumor was found and the patient was successfully treated with orthotopic liver transplantation