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ID naloge: 158    Letnik: 2003    Predmet: interna medicina

KORELACIJA MED REZULTATOM KLASICNE CITOLOGIJE IN KVANTITATIVNE CITOLOGIJE INDUCIRANEGA IZPLJUNKA PRI BOLNIKIH S PLJUCNIM RAKOM V VSEH ŠTIRIH STADIJIH BOLEZNI
Avtor: Blaž Vrhnjak, Nina Zadravec
Mentor: prof. dr. Andreja Kocijancic
Somentor: asist. dr. Marjeta Tercelj-Zorman


IZHODIŠCE: Pljucni rak je najpogostejša rakava bolezen v svetu, Evropi in Sloveniji. Pojavnost raste in je leta 1998 predstavljala 19% vseh rakavih obolenj v Sloveniji. Skupno petletno preživetje je 10-15%, v stadiju I pa lahko tudi do 80%. Ker je pljucnega raka v zgodnjih stadijih zelo težko odkriti, ostaja smrtnost še vedno visoka. Zgodnje odkrivanje pljucnega raka je kljuc do zvišanja preživetja teh bolnikov. Presejanje populacije z rentgenogramom oz. pregledovanjem izkašljajev s klasicno citologijo sta se izkazali kot neuspešni metodi. Prva predvsem zaradi nizke specificnosti, druga pa zaradi nizke obcutljivosti. Kvantitativna citometrija je metoda, katere osnova je merjenje razlicnih spremenljivk v jedru, tudi do 147 razlicnih znacilnosti, ki prevedeni v številcno vrednost kot celota napovedujejo, kolikšna je verjetnost prisotnosti pljucnega raka pri bolniku.
NAMEN: Namen raziskave je ovrednotiti novo metodo presejalnega testa za zgodnejše odkrivanje pljucnega raka iz izkašljaja (AQC izkašljaja, Automated Quantitative Cytometry sputum test). Primerjali bomo metodo klasicne citologije sputuma z metodo kvantitativne citometrije v vseh stadijih pljucnega raka, s poudarkom na zgodnjih stadijih.
HIPOTEZA: Avtomatizirana kvantitativna citometrija je bolj ucinkovita metoda kot presejalni test za pljucnega raka v primerjavi s klasicno citologijo.
METODE: V študijo je bilo vkljucenih 380 pacientov, od tega je bilo 170-im z biopsijo predhodno diagnosticiran pljucni rak, 210 oseb pa predstavlja visoko rizicne posameznike, brez malignih sprememb.
Pri našem delu je bil uporabljen popolnoma avtomatiziran kvantitativni test, ki temelji na avtomatiziranem, visoko locljivem digitalnem slikovnem citometru (CytoSavant ®). Metoda obsega merjenje vec tisoc celicnih jeder v vsakem vzorcu. Izbrane jedrne spremenljivke se nato uporabijo za oceno verjetnosti prisotnosti pljucnega raka.
Isti vzorci so bili pregledani dvakrat, enkrat klasicno citološko, drugic pa z metodo AQC. Rezultate smo razvrstili v tabele ter izracunali obcutljivost in specificnost obeh metod.
REZULTATI: Rezultati kvantitativne citologije so pokazali veliko zvišanje obcutljivosti (35 - 60%, odvisno od stadija in tipa pljucnega raka), v primerjavi z rezultati klasicne citologije (1 - 25%), ob sprejemljivem nivoju specificnosti, to je 90% pri kvantitativni proti 98% klasicni citologiji.
ZAKLJUCEK: Z AQC je bilo odkritih 52.4% pljucnih rakov z obcutljivostjo 58.2%. To je znatno vec kot odstotek s klasicno citologijo odkritih pljucnih rakov (2.9%), ampak še premalo za uporabo te metode kot diagnosticni test. Rezultati AQC pa kažejo na možnost uporabe kot presejalni test, namenjen odkrivanju pljucnega raka v zgodnjih stadijih pri posameznikih s povišanim tveganjem. Ce je pljucni rak odkrit v zgodnjih stadijih (O in I), sta preživetje in kakovost življenja po zdravljenju znatno vecja.




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[Abstract / English version]
KORELACIJA MED REZULTATOM KLASICNE CITOLOGIJE IN KVANTITATIVNE CITOLOGIJE INDUCIRANEGA IZPLJUNKA PRI BOLNIKIH S PLJUCNIM RAKOM V VSEH ŠTIRIH STADIJIH BOLEZNI
Author: Blaž Vrhnjak, Nina Zadravec
Mentor: prof. dr. Andreja Kocijancic
Co-mentor: asist. dr. Marjeta Tercelj-Zorman


BACKGROUND: Lung cancer is the most common of all cancers in the world, Europe and Slovenia. Its incidence is increasing and in 1998 it was 19% for Slovenia. Mortality remains high with 5-year survival 10-15% overall but possibly up to 80% in stage I. Clearly, a chance for improvement lies in successful early detection and screening programmes. Screening with periodic chest radiography has not proven successful, mainly due its low specificity nor has screening with sputum cytology, due to its low sensitivity. Quantitative cytology is a method relying on measuring multiple features of nuclei (as many as 147) in the cells of the sample which taken together as a numerical value point to the probability of the presence of cancer in the patient.
AIM: The aim of our study was to evaluate this new method as a screening test in early sputum lung cancer detection (AQC, Automated Quantitative Cytometry sputum test). We also wanted to determine the differences between classical sputum cytology and AQC in all stages, particularly in the early stages of the disease, when clinical symptoms are absent.
HYPOTHESIS: AQC is more efficient as screening test in early lung cancer detection compared to classical cytology.
METHODS: In this study, sputum samples were collected from 380 patients of whom 170 had previously histopathologically diagnosed lung cancer. Approximately half of the lung cancers were of an early stage (stage 0 or stage I) and 210 subjects present matching (high-risk) population with no known malignancy.
AQC has been used, basing on a fully automated high resolution image cytometer (CytoSavant®) for early lung cancer detection. The AQC involves measurements of several thousand cell nuclei per sputum sample. Selected nuclear texture features are then used to estimate the probability of lung cancer presence.
All samples were examined twice. The sample was examined first by a cytologist, using the conventional cytology. Then the sample was examined by AQC. Results, specificity and sensitivity of both methods were compared.
RESULTS: The results of AQC test from sputum cells show a several-fold increase of sensitivity (35-60% depending on the lung cancer stage and type, over those 1-25% by conventional cytology) at acceptably reduced specificity level (90% vs. 98% for AQC and conventional cytology, respectively).
CONCLUSIONS: 52.4% of lung cancers have been detected by AQC with the specificity of 58.2%. This is far better than with conventional cytology, but too low for this method to be used as a diagnostic test. Its possible use as a screening test intended for high-risk individuals might be considered. Survival and quality of life are reasonably better when lung cancer is detected early.



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