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Title:Biološki dejavniki tveganja po operaciji jeter zaradi zasevkov raka debelega črevesa in danke
Authors:Ivanecz, Arpad (Author)
Potrč, Stojan (Mentor) More about this mentor... New window
Golouh, Rastko (Co-mentor)
Files:.pdf DR_Ivanecz_Arpad_2014.pdf (13,94 MB)
 
Language:Slovenian
Work type:Dissertation (m)
Organization:MF - Faculty of Medicine
Abstract:Izhodišče/cilji: Prizadevanja za prenos temeljnega znanja o bioloških označevalcih (BO) v klinično uporabo se nadaljujejo. Namen raziskave je bilo ugotoviti, ali lahko BO dopolnijo napovedno vrednost kliničnega točkovnega sistema tveganja (CRS) po zdravljenju jetrnih zasevkov raka debelega črevesa in danke (RDČD). Metode: Opravili smo retrospektivni pregled prospektivno vodene, računalniško podprte jetrne datoteke. Bolniki, izbrani za analizo, so bili zdravljeni na Oddelku za abdominalno in splošno kirurgijo Univerzitetnega kliničnega centra Maribor zaradi zasevkov RDČD s potencialno kurativno resekcijo jeter v obdobju od 1996 do 2011. Pri vseh bolnikih je bila s histopatološkim pregledom potrjena in postavljena dokončna diagnoza zasevkov adenokarcinoma RDČD v jetrih. Vključno s CRS smo skupaj analizirali 14 rutinsko razpoložljivih kliničnih dejavnikov tveganja. Izražanje p53, Ki-67 in timidilat-sintaze (TS) smo določali z imunohistokemijo na tkivnih mrežah. Izražanje p53 in Ki-67 smo ocenjevali s točkovanjem odstotka pozitivno obarvanih jeder malignih celic. Vzorec je bil ocenjen kot pozitiven na p53 in Ki-67, če je bilo obarvanih več kot 50 % tumorskih celic. Izražanje TS smo ocenjevali po intenziteti obarvanja citoplazme malignih celic. Intenzivnost obarvanja TS je bila določena z vizualno stopenjsko lestvico od 0 do 3. Stopnji 0 in 1 sta predstavljali nizko, stopnji 2 in 3 pa visoko intenzivnost obarvanja. Rezultate smo primerjali z aktualnim preživetjem, preživetjem brez bolezni ter preživetjem brez jetrne bolezni. Rezultati: Izmed 406 bolnikov jih je 98 (24 %) izpolnjevalo kriterije vključitve. Mediani čas sledenja preživelih bolnikov je bil 103 mesece (razpon 61–195 mesecev). Vsi bolniki so imeli CRS v razponu od 0 do 4, nihče ni imel CRS 5. Skupaj se je obarvalo pozitivno 52 (53 %) zasevkov na protein p53 in 27 (28 %) zasevkov na protein Ki-67. Intenziteta imunohistokemijskega barvanja za TS je bila nizka pri 29 (30 %) in visoka pri 69 (70 %) vzorcev. Statistična analiza s testom hi-kvadrat je razkrila korelacijo med prekomerno izraženim p53 in visokim CRS (P = 0,058). Aktualno petletno in pričakovano desetletno preživetje bolnikov je bilo 34,5 % oziroma 24,3 %, z medianim preživetjem 36 mesecev. Čeprav so bili vsi bolniki zdravljeni s potencialno kurativno resekcijo R0, se je pri 72 (73 % ) bolezen ponovila. Pri 20 izmed 72 bolnikov (28 %) je bila ponovitev bolezni omejena samo na jetra, pri 20 bolnikih (28 %) je bila prisotna izključno zunaj jeter, pri 32 (44 %) pa so bili zasevki prisotni tako v jetrih kakor tudi zunaj njih. Po multivariatni analizi je ostal samo visok CRS negativni napovedni dejavnik preživetja (P = 0,018), kazalec zgodnje ponovitve bolezni (P = 0,010) in hkrati tudi kazalec zgodnje ponovitve jetrne bolezni (P = 0,003). Med BO je po multivariatni analizi ostal pozitivni napovedni dejavnik preživetja samo prekomerno izraženi Ki-67 (P = 0,038). Zaključki: Razkrili smo korelacijo med prekomerno izraženim p53 in visokim CRS. Najpomembnejša ugotovitev dela je identifikacija prekomernega izražanja Ki-67 kot ugodnega napovednega dejavnika aktualnega preživetja po radikalni resekciji jetrnih zasevkov RDČD. TS ni dodala nobene klinične informacije. Samo CRS napoveduje neodvisno izid zdravljenja.
Keywords:rak debelega črevesa in danke, jetrni zasevki, kirurgija, napovedni dejavniki tveganja, biološki označevalci
Year of publishing:2014
Source:Maribor
COBISS_ID:4971071 Link is opened in a new window
NUK URN:URN:SI:UM:DK:DCWILKAU
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Downloads:273
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Secondary language

Language:English
Title:The prognostic value of biological markers in patients undergoing liver resection of colorectal metastases
Abstract:Background/Aims: There is an ongoing effort to translate basic knowledge about biological markers (BM) into clinical use. The aim of this study was to assess whether BM can provide additional prognostic information to that supplied by clinical risk score (CRS) for colorectal liver metastases (CRLM). Methods: A retrospective review of a prospectively maintained database was conducted. Patients selected for this study were treated between 1996 and 2011 with potentially curative liver surgery at the Department of Abdominal and General Surgery, University Medical Center – Maribor. The diagnosis of CRLM was confirmed by histopathology. A total of 14 routinely available clinical variables were analysed, including a CRS. p53, Ki-67, and thymidylate synthase (TS) were assayed using immunohistochemical technique on tissue microarrays. Expressions of p53 and Ki-67 were evaluated by scoring the percentage of positively stained nuclei of the malignant cells. Specimens were considered positive for p53 and Ki-67 when more than 50% of tumor cells were stained. For TS, the intensity of cytoplasm staining of the malignant cells was studied. Definition of the TS staining intensity was based on a visual grading scale of 0-3. Intensity levels 0 and 1 were grouped together as representing low intensity staining; levels 2 and 3 were grouped as representing intermediate or high-intensity staining. The endpoints of the study were actual survival, disease-free survival and hepatic disease-free survival. Results: A total of 98 (24%) of 406 patients met the inclusion criteria. The median follow-up in surviving patients was 103 months (range: 65-195 months). All patients were found to have a CRS within the range of 0-4; no patient had a CRS of 5. A total of 52 (53%) metastases stained positive for p53 protein and 27 (28%) stained positive for Ki-67 protein. Immunostaining for TS was low in 29 (30%) and high in 69 (70%). Chi-squared analysis revealed a relationship between p53 protein positive staining and high CRS (P = 0.058). The actual 5-year and actuarial 10-year survival of patients were 34.5% and 24.3%, respectively, with median survival of 36 months. Although all patients underwent a potentially curative resection, 72 (73%) of them subsequently developed recurrent disease. The pattern of recurrence was as follows: in 20 (28%) patients, recurrence was confined to the liver; in 20 (28%) patients, recurrence was confined to an extrahepatic location only, and in 32 (44%) patients, intra- and extrahepatic metastases were present. Following multivariate analysis, only high CRS remained an independent negative prognostic predictor for survival (P = 0.018), indicator of early recurrence of disease (P = 0.010) as well as an indicator of early hepatic recurrence of disease (P = 0.003). Of the BM investigated, only Ki-67 overexpression was identified as a positive predictor of survival on multivariate analysis (P = 0.038). Conclusions: In CRLM a correlation between p53 protein overexpression and high CRS is established. The most important finding of the present study is the identification of Ki-67 overexpression as a positive predictor of survival. TS expression provides no clinical information. Only high CRS remaines an independent negative prognostic predictor.
Keywords:colorectal cancer, liver metastases, surgery, prognostic factors, biological markers


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