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Vpliv kirurškega zdravljenja in obsevanja na imunski status, stanje prehranjenosti ter vnetni odziv pri bolnikih z rakom ustne votline
Dovšak, Tadej Peter (Author), Ihan Hren, Nataša (Mentor) More about this mentor... This link opens in a new window

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Abstract
UVOD: Raka ustne votline zdravimo kirurško, z obsevanjem, kemoterapijo in kombinacijo naštetega. Poleg alkohola in tobaka je vse več dokazov, da tudi imunski status bolnikov vpliva na pojavnost raka ustne votline. Bolniki z rakom ustne votline imajo v primerjavi z zdravimi posamezniki znižane vrednosti posameznih limfocitnih populacij. Vsaka terapija, ki jo izvajamo s ciljem ozdravitve bolezni, pa začetno stanje le še poslabša, kar lahko vpliva na izid zdravljenja. NAMEN: Želeli smo ugotoviti vpliv kirurškega zdravljenja in obsevanja na določene imunske kazalce, na osnovne vrednosti hemograma in prehransko stanje bolnikov z rakom ustne votline. METODA: V prospektivno raziskavo smo vključili 110 bolnikov, pri katerih je bil rak ustne votline prvi do tedaj ugotovljeni malignom in zanj še niso bili zdravljeni. Bolnike smo razdelili na tiste, ki so bili zdravljeni le z operacijo, in na tiste, ki so bili operirani in so zdravljenje nadaljevali z obsevanjem. Vzorce periferne krvi smo odvzeli pred vsakim zdravljenjem in leto dni po končanem zdravljenju ter opredelili vpliv zdravljenja na merjene parametre. Za vse v študiji sodelujoče bolnike smo izračunali preživetje in opredelili napovedne dejavnike. REZULTATI: Povprečne vrednosti merjenih parametrov pri bolnikov pred začetkom zdravljenja niso odstopale od referenčnih vrednosti. Operacija je povzročila statistično značilno anemijo, levkocitozo, trombocitozo in dvig C reaktivnega proteina. Leto dni po končanem kirurškem zdravljenju se je večina merjenih parametrov vrnila na predoperativno raven, izstopale so višje vrednosti celic naravnih ubijalk. Pri bolnikih, ki so bili tudi obsevani, je to povzročilo dodaten statistično značilen padec v vrednostih levkocitov, B-limfocitov, T-limfocitov, celic T-pomagalk, citotoksičnih T-limfocitov, spominskih in naivnih T-limfocitov. Indeks CD4/CD8 se je prepolovil. Leto dni po obsevanju so vrednosti spominskih T-limfocitov, naivnih T-limfocitov, citotoksičnih T-limfocitov, celic T-pomagalk in indeksa CD4/CD8 ostale nespremenjene glede na vrednosti po obsevanju. Skupno petletno preživetje bolnikov v študiji je bilo 56-odstotno, za bolezen značilno petletno preživetje pa 81-odstotno. Univariatna Coxova analiza je pokazala statistično značilen vpliv predoperativnih vrednosti eritrocitov, CRP, sedimentacije eritrocitov (ESR) in albuminov na preživetje, od patohistoloških kriterijev pa so na preživetje vplivali stadij bolezni, število pozitivnih bezgavk na vratu, prodor prek kapsule bezgavke (ECS) in perinevralna invazija. V multivariatni analizi se je omenjeni vpliv izgubil in je bil vpliv na preživetje le pri razmerju pozitivnih bezgavk glede na vse odstranjene bezgavke. ZAKLJUČEK: Pri le operiranih bolnikih je operacija povzročila kratkotrajen dvig parametrov akutnega vnetnega odziva, ki so se leto dni po zdravljenju vrnili na izhodiščne vrednosti. Pri bolnikih, ki so bili dodatno tudi obsevani, so se po obsevanju statistično značilno znižale vse subpopulacije T-limfocitov in B-limfociti, indeks CD4/CD8 je ostal prepolovljen glede na izhodiščne vrednosti. Po letu dni so bile vrednosti še vedno statistično značilno znižane glede na vrednosti pred začetkom zdravljenja. Pomemben vpliv na preživetje imajo stadij bolezni, perivaskularna in perinevralna invazija ter prodor tumorskih celic prek kapsule bezgavk, od merjenih krvnih parametrov pa predoperativne vrednosti albuminov, CRP, ESR in vrednost eritrocitov.

Language:Slovenian
Keywords:rak ustne, operacija, radioterapija, imunski status, prehranjenost
Work type:Doctoral dissertation (mb31)
Organization:MF - Faculty of Medicine
Year:2019
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Downloads:181
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Secondary language

Language:English
Title:Influence of surgery and radiotherapy on the immune status, nutritional status and systemic inflammatory response in patients with oral cancer
Abstract:
INTRODUCTION: Oral cavity cancer is treated surgically, with radiotherapy, chemotherapy, and a combination of all. There is increasing evidence of the impact that immunity status of patients, besides alcohol and tobacco, has on the incidence of oral cavity cancer. Compared to healthy individuals, patients with oral cavity cancer exhibit lower values of individual lymphocyte populations. However, each therapy applied to cure a disease, worsens the initial conditions, which can affect the outcome of the treatment. PURPOSE: Our intention was to establish the impact of surgical treatment and radiotherapy on specific immunity indicators, on the basic values of complete blood count, and on nutritional status of patients with oral cavity cancer. METHOD: 110 patients with oral cavity cancer as their first diagnosed and not yet treated malignoma were included in our prospective study. Patients were subsequently divided into those treated only surgically, and those who post-operatively received also radiotherapy. Samples of peripheral blood were taken prior to each treatment and a year after the completion of the treatment. The impact of treatment was defined in relation to the measured parameters. We calculated survival for all patients included in our study cohort and defined the prognostic factors. RESULTS: The average values of measured parameters in patients prior to the beginning of the treatment did not deviate from reference values. Surgical procedure caused statistically significant anaemia, leucocytosis, thrombocytosis, and an increase of reactive C protein (CRP). A year after the completed surgical treatment most of the measured parameters returned to pre-operative levels, with the exception of higher values in natural killer cells. In patients who were treated also with radiotherapy, this caused a statistically significant drop in the values of leucocytes; B lymphocytes, T lymphocytes, helper T cells, cytotoxic T lymphocytes, naïve and memory T lymphocytes. The CD4/CD8 index was halved. A year after the radiotherapy treatment, the values of memory T lymphocytes, naïve T lymphocytes, cytotoxic T lymphocytes, helper T cells and CD4/CD8 index remained unchanged relative to post-radiotherapy values. Overall 5 year survival of patients from the study cohort was 56%, and disease specific 5 year survival 81%. Univariate Cox regression analysis confirmed statistically significant impact of pre-operative values of erythrocytes, CRP, erythrocytes sedimentation rate (ESR) and albumins on survival, whereas the stage of disease, number of positive neck lymph nodes, penetration through lymph node capsule (ECS) and perineural invasion were confirmed as pathohystological criteria that impacted on survival. The mentioned impact was lost in multivariate regression analysis, which confirmed only the impact of the number of positive lymph nodes, relative to the total number of the dissected lymph nodes. CONCLUSION: In patients who were treated only surgically, the operative procedure caused a short-term increase of acute inflammatory response parameters, which returned to pre-operative values a year after the treatment completion. In patients who underwent additional radiotherapy, all subpopulations of T lymphocytes and B lymphocytes were lower for statistically significant values, and the CD4/CD8 index remained halved in relation to its initial values. A year after a statistically significant decrease of values in relation to the values prior to the treatment, remained. We have proven a significant impact of the following factors on survival: the stage of the disease, perivascular, perineural invasion, and the penetration of tumor cells through lymph node capsule. Among the measured blood parameters, the pre-operative values of albumins, CRP, ESR, and the total number of erythrocytes were proven to have impact on survival.

Keywords:oral cancer, operation, radiotherapy, immune status, nutritional status

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