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Izpis gradiva Pomoč

Naslov:Pomen vnetnih in atrofičnih sprememb v vzorcih igelne biopsije prostate pri oceni indolentnosti karcinoma prostate z gleason score 6
Avtorji:ID Zupančič, Marko (Avtor)
ID Hočevar, Marko (Mentor) Več o mentorju... Novo okno
ID Cerović, Snežana (Komentor)
Datoteke:.pdf DOK_Zupancic_Marko_2021.pdf (7,59 MB)
MD5: 6916261B95A394C2EC23C290C72C5AAA
PID: 20.500.12556/dkum/e6eba146-ecdb-4dcd-9c96-a46a9a50fa55
 
Jezik:Slovenski jezik
Vrsta gradiva:Doktorsko delo/naloga
Tipologija:2.08 - Doktorska disertacija
Organizacija:MF - Medicinska fakulteta
Opis:Namen: Namen raziskave je bil preveriti vpliv prisotnosti vnetja in/ali atrofije v vzorcih igelne biopsije prostate na oceno indolentnosti karcinoma prostate in tveganja za napredovanje karcinoma pri bolnikih z GS 3+3=6 ter morebitno povezanost obeh z aktivacijo NF-κB v citoplazmi in jedru karcinomskih celic. Raziskavo smo razširili še na analizo povezanosti pozitivne IHK reakcije na NF-κB p65 v citoplazmi in v jedru karcinomskih celic z biokemično ponovitvijo karcinoma pri obravnavanih bolnikih. Bolniki in metode: Raziskava je temeljila na retrospektivni analizi kliničnih podatkov bolnikov, ki so bili diagnosticirani, operativno operirani in vsaj 5 let po operaciji spremljani na Oddelku za urologijo v Splošni bolnišnici Slovenj Gradec. Vključitveni kriteriji za uvrstitev bolnikov v raziskavo so bili izhodiščni PSA ≤ 10,0 ng/ml, GS 3+3=6, število vzorcev igelne biopsije prostate ≥ 8, klinični stadij T1-2 ter dostopni podatki o kontrolnih vrednostih PSA 1, 6, 18, 30, 42, 54 in 66 mesecev po radikalni prostatektomiji. Vključenih je bilo 177 bolnikov. Pri 16 je bil ugotovljen GS 3+4=7, zato so bili izključeni iz nadaljnje raziskave. Glavni del študije je bil izveden na 161, od teh je bilo v del, ki se je nanašal na NF-κB, vključenih 123 bolnikov. V sklopu raziskave so bile na tkivnih vzorcih igelne biopsije prostate vključenih bolnikov, arhiviranih na Oddelku za patologijo iste bolnišnice, opravljene še dodatna patohistološka analiza prisotnosti vnetja in/ali atrofije, ocena odstotka zajetja vzorca s tumorjem pri bolnikih z ≤ 2 pozitivnima stebričkoma na igelni biopsiji ter imunohistokemična detekcija NF-κB v pozitivnih vzorcih biopsije. Izsledke teh analiz smo primerjali s klinično patološkimi dejavniki tveganja za ponovitev bolezni po radikalni prostatektomiji. Rezultati: Biokemično ponovitev karcinoma prostate z mejno vrednostjo PSA 0,05 ng/ml smo ugotovili pri 16,9 % bolnikov, z mejno vrednostjo 0,2 ng/ml pa pri 5,8 %. Manj kot 50 % s karcinomom zajetega tkiva v enem ali v obeh pozitivnih vzorcih igelne biopsije prostate je bilo pri 101 bolniku. Med 161 bolniki je bilo na preparatih igelne biopsije samo vnetje ugotovljeno pri 45 (27,9 %), samo atrofija pri 46 (28,6 %), vnetje in atrofija skupaj pa pri 23 (14,3 %). V analizo IHK reakcije na NF-κB p65 so bili vključeni 123 bolniki. Citoplazemska IHK reakcija je bila pozitivna pri 63 (51,2 %), jedrna pa pri 20 (16,3 %) bolnikih. V delu študije, ki se je nanašal na povezanost pozitivne IHK reakcije na NF-κB p65 z biokemično ponovitvijo bolezni je bilo vključenih 118 bolnikov. Po 66 mesecih spremljanja je do biokemične ponovitve bolezni (PSA ≥ 0,2 ng/ml) prišlo pri 6 (5,1%) bolnikih, od tega je pri 3 (50 %) šlo za GS 3+3=7, pri 3 (50%) pa za GS 3+4=7. V analizi povezanosti prisotnosti vnetja in/ali atrofije v vzorcih igelne biopsije prostate s klinično patološkimi dejavniki tveganja za napredovanje KP statistično značilne povezanosti nismo ugotovili. Prav tako prisotnost vnetja ni bila statistično povezana z biokemično ponovitvijo bolezni. Povezanosti IHK reakcije na NF-κB p65 s klinično patološkimi dejavniki tveganja za biokemično ponovitev bolezni po radikalni prostatektomiji v citoplazmi in v jedru smo statistično potrdili samo pri pozitivni IHK reakciji v citoplazmi v povezavi z NCCN tveganjem (P = 0,044). Citoplazemska IHK reakcija NF-κB je bila ob mejni vrednosti PSA ≥ 0,2 ng/ml statistično značilno povezana tudi s slabšim preživetjem bolnikov brez biokemične ponovitve bolezni (P = 0,013), med tem ko je bila pri bolnikih z mejno vrednostjo PSA ≥ 0,05 ng/ml ta povezava na meji statistične značilnosti (P = 0,057). Zaključek: Citoplazemsko izražanje NF-κB v vzorcih igelne biopsije prostate je povezano z večjo verjetnostjo biokemične ponovitve karcinoma prostate in bi lahko predstavljalo samostojen dejavnik tveganja za ponovitev bolezni po radikalni prostatektomiji. Za potrditev teh začetnih rezultatov bi bile potrebne dodatne študije na večjem številu bolnikov.
Ključne besede:vnetne spremembe prostate, atrofične spremembe prostate, igelna biopsija prostate, ocena indolentnosti karcinoma prostate, Gleason score 6, Nuklearni faktor-Kappa beta
Kraj izida:Maribor
Leto izida:2021
PID:20.500.12556/DKUM-78133 Novo okno
COBISS.SI-ID:60396035 Novo okno
NUK URN:URN:SI:UM:DK:9E2YY9LK
Datum objave v DKUM:20.04.2021
Število ogledov:1338
Število prenosov:70
Metapodatki:XML DC-XML DC-RDF
Področja:MF
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Licence

Licenca:CC BY-NC-ND 4.0, Creative Commons Priznanje avtorstva-Nekomercialno-Brez predelav 4.0 Mednarodna
Povezava:http://creativecommons.org/licenses/by-nc-nd/4.0/deed.sl
Opis:Najbolj omejujoča licenca Creative Commons. Uporabniki lahko prenesejo in delijo delo v nekomercialne namene in ga ne smejo uporabiti za nobene druge namene.
Začetek licenciranja:01.11.2020

Sekundarni jezik

Jezik:Angleški jezik
Naslov:Significance of inflammatory and atrophic changes on prostate needle biopsy samples in the evaluation of Gleason score 6 prostatic carcinoma indolence
Opis:Background: The goal of the study was to find out the impact of inflammation and/or atrophy in prostate needle biopsy samples on prostate cancer indolence and risk of cancer progression in patients with GS 3+3=6 and the possible association of both with NF-κB activation in cytoplasm and nucleus of cancer cells. The study was extended to the analysis of the association between a positive IHK response to NF-κB p65 in the cytoplasm and in the nucleus and biochemical recurrence of cancer. Patients and methods: The study was based on a retrospective analysis of clinical data of patients who were diagnosed, surgically treated and followed up at least 5 years after surgery at the Department of Urology in General Hospital Slovenj Gradec. The inclusion criteria were baseline PSA ≤ 10.0 ng / ml, GS 3+3=6, number of prostate needle biopsy samples ≥ 8, clinical stage T1-2, and available data on PSA control values 1, 6, 18, 30, 42, 54 and 66 months after radical prostatectomy. 177 patients were included. GS 3+4=7 was found in 16 and they were therefore excluded from further study. The main part of the study was conducted on 161 patients, of which 123 were included in the part related to NF-κB. On tissue samples of prostate needle biopsy archived in the Department of Pathology of the same hospital, an histopathology analysis of the presence of inflammation and/or atrophy was performed, as well as the assessment of the percentage of tumour tissue in patients with ≤ 2 positive cores and immunohistochemical detection of NF-κB in positive biopsy samples. The results of these analyses were compared with clinically pathological risk factors for disease recurrence after radical prostatectomy. Results: Biochemical recurrence with a PSA 0.05 ng/ml as cut-off point was found in 16.9% of patients and with 0.2 ng/ml in 5.8%. Less than 50% of cancer-covered tissue in one or both positive needle biopsy samples were found in 101 patients. Among 161 patients, in 45 (27.9%) inflammation only was found on needle prostate biopsy, atrophy only in 46 (28.6%) and inflammation and atrophy together in 23 (14.3%). 123 patients were included in the immunohistochemical reaction analysis on NF-κB p65. The cytoplasmic reaction was positive in 63 (51.2%) and nuclear in 20 (16.3%) patients. In the part of the study related to the association of a positive immunohistochemical reaction on NF-κB p65 with biochemical recurrence of the disease, 118 patients were included. After 66 months of follow-up, biochemical recurrence (PSA ≥ 0.2 ng/ml) occurred in 6 (5.1%) patients, of which 3 (50%) had GS 3+3=7 and 3 (50%) GS 3+4=7. In analysis of the possible association of the presence of inflammation and/or atrophy in needle biopsy samples with clinically pathological risk factors for prostate cancer progression, no statistically significant association was found. Also, the presence of inflammation was not statistically associated with biochemical recurrence of the disease. The association of the immunohistochemical response to NF-κB p65 with clinically pathological risk factors for biochemical recurrence after radical prostatectomy in the cytoplasm and in the nucleus was statistically confirmed only in the cytoplasmic positive reaction in association with NCCN risk (P = 0.044). The cytoplasmic response to NF-κB was also statistically significantly associated with poorer recurrent free survival (P = 0.013) at the PSA threshold ≥ 0.2 ng/ml, while in patients with a PSA threshold ≥ 0,05 ng/ml this association was at the limit of statistical significance (P = 0.057). Conclusions: Cytoplasmic expression of NF-κB in needle biopsy specimens of the prostate is associated with an increased risk of biochemical recurrence of prostate cancer and might be an independent prognostic factor for recurrence free survival after radical prostatectomy, but further studies including larger number of patients are needed to confirm these initial results.
Ključne besede:prostatic inflammatory changes, prostatic atrophic changes, prostate needle biopsy, prostatic carcinoma indolence evaluation, Gleason score6, Nuclear factor-Kappa Beta


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