Maligne bolesti u bolesnika s celijakijom

master's thesis

• Title (english): Malignant disease in coeliac patients
• Author: Mirta Rode
• Mentor: Silvija Čuković-Čavka (mentor)
• Committee member: Marko Brinar (predsjednik povjerenstva)
• Committee member: Jasenka Markeljević (član povjerenstva)
• Committee member: Silvija Čuković-Čavka (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Internal Medicine); Zagreb
• Defense date and country: 2019-07-12, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Internal Medicine

Abstract

Celijakija je kronična bolest koja se javlja u oko 1% populacije. Maligne bolesti su ozbiljna komplikacija celijakije, s vrlo lošom prognozom. Najčešće neoplazme povezane s celijakijom su non-Hodgkinovi limfomi, adenokarcinom tankog crijeva i karcinom jednjaka. Nije potpuno razjašnjeno postoje li zajednička etiološka podloga između celijakije i maligniteta, ali pretpostavlja se da je patogeneza ovih tumora u bolesnika s celijakijom drugačija nego u opće populacije. Posebno se razmatra povezanost raka dojke i celijakije, budući da je incidencija ovog maligniteta u osoba s celijakijom snižena. Vrsta non-Hodgkinovog limfoma koja pokazuje najveću incidenciju u ovih bolesnika je T-stanični limfom povezan s enteropatijom. To je rijetka agresivna neoplazma, primarno sijelo joj je gotovo uvijek u tankom crijevu, te ima specifičan imunofenotip po kojem se razlikuje od ostalih ekstranodalnih limfoma. Najveću učestalost pokazuje u osoba s tipom 2 refraktorne celijakije. Refraktorna celijakija je oblik celijakije koji ne reagira na bezglutensku dijetu, karakteriziran proliferacijom intraepitelnih limfocita. Dijeli se na tip 1 i tip 2, koji se međusobno razlikuju po vrsti, tj. imunofenotipu intraepitelnih limfocita. Abnormalni intraepitelni limfociti u tipu 2 vrlo su slični limfocitima nađenim u T-staničnom limfomu povezanom s enteropatijom, zbog čega se refraktorna celijakija tipa 2 smatra premalignom lezijom ovog limfoma. Postavljanje dijagnoze može biti vrlo zahtjevno, pogotovo s obzirom da klasičnim dijagnostičkim metodama nije moguće vizualizirati tanko crijevo koje je najčešće sijelo malignih lezija. Patohistološka analiza bioptata crijeva ili kirurškog materijala pruža konačnu dijagnozu. Zakašnjela dijagnoza je glavni čimbenik koji pogoršava mortalitet i ograničava terapijske mogućnosti. Celijakija se često otkriva tek istovremeno s malignitetom. S obzirom da bolesnici koji se striktno pridržavaju bezglutenske dijete nemaju povećan rizik od malignih bolesti, te da rano uvođenje bezglutenske dijete smanjuje rizik od razvoja komplikacija celijakije, rano prepoznavanje bolesti i početak terapije ključni su u poboljšanju preživljenja ovih bolesnika.

Abstract (english)

Coeliac disease is a chronic disease which occurs in about 1% of population. Malignant diseases are a severe complication of coeliac disease with a very poor prognosis. Most common malignancies associated with coeliac disease are non-Hodgkin lymphomas, small bowel adenocarcinoma and oesophageal carcinoma. It is not clear whether there is a joint aetiologic background between coeliac disease and malignancies, but it is presumed that the pathogenesis of these tumours in coeliac patients differs from the general population. The correlation between coeliac disease and breast cancer is specific, considering the lower incidence of this malignancy in coeliac patients. Although all types of non-Hodgkin lymphomas occur more often in coeliac patients, the risk is higher for T-cell lymphomas and intestinal lymphomas compared to B-cell and extraintestinal lymphomas. Enteropathy associated T-cell lymphoma is a rare and aggressive type of non-Hodgkin lymphoma, which shows the strongest correlation with coeliac disease. It is typically located in the small intestine and has a specific immunophenotype that distinguishes it from other extranodal lymphomas. Most commonly, it affects patients with type 2 refractory coeliac disease. Refractory coeliac disease is a non-reactive type of coeliac disease, in which the patient’s condition does not improve despite adherence to a gluten-free diet for more than a year. It is further divided into type 1 or 2, based on the whether the intraepithelial lymphocytes are phenotypically normal or abnormal. The immunophenotype of abnormal intraepithelial lymphocytes in type 2 shows a high resemblance to that in enteropathy associated T-cell lymphoma, therefore type 2 refractory coeliac disease is considered a premalignant lesion of this lymphoma. Diagnosing these patients tends to be very complicated, since most localizations of lesions are difficult to reach using standard diagnostic methods. Pathohistological analysis enables the final diagnosis. Diagnostic delay increases mortality as well as limits the therapeutic options. Coeliac disease is often discovered simultaneously with malignancy. Considering the fact that patients who adhere to a gluten-free diet do not have an increased risk of malignant diseases, and that early introduction of gluten-free diet reduces the risk of developing complications, early recognition and treatment of coeliac disease are crucial in improving survival of these patients.

• Keywords: celijakija; limfom; karcinom; refraktorna celijakija
• Keywords (english): coeliac disease; lymphoma; carcinoma; refractory coeliac disease
• Language: croatian
• URN:NBN: urn:nbn:hr:105:302574
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2020-02-17 16:11:46