Abstract | Tumorski rast povezan je sa znatnim metaboličkim promjenama koje vode nastanku
sindroma tumorske anoreksije i kaheksije. Značajan je uzrok morbiditeta i mortaliteta
koji se pojavljuje u čak do 80% pacijenata s uznapredovalim karcinomom i odgovoran
je za smrt oko 20% slučajeva. Tumorska keheksija je kompleksan poremećaj
karakteriziran progresivnim gubitkom tjelesne težine, povezan s anoreksijom,
astenijom, anemijom i promjenama imunološkog sustava. Dok anoreksiju definiramo
gubitkom želje za jelom, kaheksija je posljedica progresivnog gubitka mase skeletnih
mišića i smanjenja opsega masnog tkiva koji nastaju i prije nego gubitak tjelesne
težine postane očigledan. Nadalje, dok je u gladovanju jednak gubitak proteina
skeletnih mišića i visceralnih proteina, u kaheksiji su visceralni proteini uglavnom
očuvani. Ove promjene ne mogu se u potpunosti povezati s pratećom anoreksijom i
sama nutricionistička nadoknada ne može zaustaviti proces trošenja tijela. Unatoč
smanjenom kalorijskom unosu, pacijenti s kaheksijom redovito imaju povišen bazalni
metabolizam kao posljedicu povećane aktivnosti Corijevog ciklusa, kruženja glukoze i
slobodnih masnih kiselina te glukoneogeneze. Patogenetski mehanizam tumorske
kaheksije je multifaktorijalan, a upalni citokini koje sintetizira vlastiti imunološki sustav
i faktori podrijetlom tumorskih stanica imaju značajnu ulogu. Optimalan terapijski
pristup trebao bi se bazirati na dijetetskim mjerama kroz nutritivno savjetovanje i
terapiji lijekovima koji interferiraju s ekspresijom i aktivnosti citokina. Polinezasićena
masna kiselina, eikosapentaenska kiselina (EPA), atenuira aktivnost kataboličkih
faktora te stabilizira proces trošenja tkiva i energije. Od ključne je važnosti rano
prepoznati i liječiti tumorsku kaheksiju jer osim što smanjuje kvalitetu života, smanjuje
i očekivano trajanje života. Uz to, kahektični pacijenti imaju slabiji odgovor na
kemoterapiju i podložniji su neželjenim nuspojavama onkološkog liječenja. |
Abstract (english) | Tumor growth is associated with profound metabolic alterations, which can lead to
onset of anorexia-cachexia syndrome. It is a significant cause of morbidity and
mortality, occuring in up to 80% of patients with advanced cancer, and responsible
for death in up to 20% of cases. Cancer cachexia is a complex disorder characterized
by progressive loss of weight, in association with anorexia, asthenia, anaemia and
alterations in immune function. Anorexia is defined as the loss of desire to eat, while
cachexia results from progressive wasting of skeletal muscle mass and to a lesser
extent adipose tissue, occurring even before weight loss becomes apparent.
Furthermore, the protein loss that does occur in starvation is split equally between
skeletal muscle and visceral protein, whereas in cachexia, visceral protein is
relatively preserved. These changes cannot be fully explained by the accompanying
anorexia, and nutritional supplementation alone is unable to reverse the wasting
process. Despite a falling caloric intake, patients with cachexia frequently show an
elevated resting energy expenditure as a result of increase in Cory cycle activity,
glucose and triglyceride-fatty acid cycling, and gluconeogenesis. The pathogenic
machanisms of cachexia are multifactorial, but proinflammatory cytokines produced
by the host immune system and circulating tumour-derived catabolic factors play a
significant role. The optimal therapeutic approach should be based on both changes
in dietary habits, achieved via nutritional counseling and drug therapy, aimed at
interfering with cytokine expression or activity. A polyunsaturated fatty acid,
eicosapentaenoic acid, attenuates the action of such catabolic factors and has been
shown to stabilize the process of wasting and resting energy expenditure in patients
with cancer. It is significant to early recognize and treat cachexia in patients because
it is associated with both reduced quality of life and shortened life expectancy.
Additionally, cachectic patients also have a lower chance of responding to
chemotherapy and are more prone to toxic side effects. |