Prognostička vrijednost tumorskog biljega CEA u bolesnika s kolorektalnim karcinomom (CRC)

Cilj istraživanja 1. Utvrditi preoperativne koncentracije tumorskog biljega CEA u serumu. 2. Ispitati povezanost razine CEA kod bolesnika s kolorektalnim karcinomom s ishodom liječenja, te s ostalim, do sada prihvaćenim prognostičkim čimbenicima za rak debelog crijeva. Ispitanici i metode Ova retrospektivna studija provedena je na uzorku od 101-og bolesnika koji su započeli liječenje zloćudnog tumora debelog crijeva na Zavodu za onkološku kirurgiju, Klinike za tumore, KBC "Sestre milosrdnice" tijekom 2006., 2007. i 2008. godine. U studiju su uključeni bolesnici sa stadijem zloćudnog tumora od A - C prema Dukes klasifikaciji. Koncentracija tumorskog biljega CEA u serumu mjerena je imunokemijskom metodom čije se načelo mjerenja temelji na principu kemiluminiscencije. Svi dobiveni podaci su tablično pohranjeni i statistički obrađeni. Rezultati Prosječna dob bolesnika bila je 63,98 godina. Prema Dukes klasifikaciji ustanovljeno je 19 bolesnika sa statusom Dukes A, 45 bolesnika Dukes B i 37 bolesnika u statusu Dukes C. Najveći broj pacijenata (n=50) imao je dubinu prodora tumora T3, u 29 bolesnika ustanovljena je dubina prodora T2, kod 10 bolesnika dubina prodora T4, a kod 12 pacijenata je tumor otkriven u početnoj fazi i tumor je bio ograničen na submukozu (T1). Većina bolesnika (n=63) ima negativne limfne čvorove, 28 sudionika studije imalo je 1-3 limfna čvora zahvaćena metastazama (N1), dok je njih 10 imalo 4 ili više pozitivna limfna čvora (N2). U vrijeme dijagnoze udaljene metastaze pronađene su u uznapredovanoj bolesti kod 19 pacijenata, a njih 82 je bilo je bez metastaza. Ustanovljena je statistički značajna razlika koncentracije tumorskog biljega CEA u odnosu na stadij tumora Dukes A, B ili C (p=0,000). Dubina prodora tumora također je povezana s povišenim vrijednostima CEA. Bolesnici s tumorom T3 i T4 imali su značajno više razine CEA (median: 5,3 Ęg/L; 10,45 Ęg/L) u odnosu na dubinu prodora tumora T1 i T2, čije su vrijednosti bile oko 1,5 Ęg/L. Pozitivni limfni čvorovi i udaljene metastaze u vrijeme dijagnoze statistički značajno koreliraju s vrijednostima CEA (p=0,000). Kod stadija limfnih čvorova N1 ustanovljen je CEA = 6,00 Ęg/L, a u stadiju N2 median vrijednost bio je 7,3 Ęg/L. U bolesnika s udaljenim metastazama median vrijednosti CEA iznosio je 28,9 Ęg/L. Bolesnici sa smrtnim ishodom liječenja imali su statistički značajno povišenu koncentraciju CEA (7,00 Ęg/L) u odnosu na skupinu bolesnika koji su preživjeli, čiji je median vrijednosti bio CEA = 1,75 Ęg/L. Kao značajni prediktori preživljenja prema Cox-ovoj regresijskoj analizi pokazali su se samo metastaze i lokalni recidiv. Varijable kao što su dob, spol, Dukes status, veličina tumora, status limfnih čvorova i vrijednost tumorskog biljega CEA u odnosu na preživljenje nisu se pokazale kao statistički značajne varijable za preživljenje. Zaključak Povišene preoperativne vrijednosti tumorskog biljega CEA povezane su s dubinom prodora tumora, te metastazama u limfnim čvorovima i udaljenim metastazama. Bolesnici s povišenim vrijednostima tumorskog biljega i prisutnim metastazama u vrijeme dijagnoze imaju lošiju prognozu preživljenja.Study goal 1. To determine the preoperative serum CEA marker levels. 2. To establish correlation between the CEA level in colorectal cancer patients and treatment outcomes, and other prognostic factors in colon cancer accepted so far. Patients and methods This retrospective study was conducted on a sample of 101 patients who started their malignant colon cancer treatment at Department of Oncologic Surgery, University Hospital for Tumours, "Sestre milosrdnice" Clinical Hospital Center in 2006, 2007 and 2008. The study included patients with malignant tumour stage A-C acc. to Dukes classification. The CEA marker concentration was measured in serum by immunochemistry assays. The measurement was based on using chemoluminiscence principle. All data obtained is stored in spreadsheets and statistically analysed. Results The average age of patients was 63.98 years. According to the Dukes classification, 19 patients were determined Dukes A, 45 patients Dukes B and 37 patients Dukes C status. The tumour degree of invasion in majority of patients (n=50) was T3, in 29 patients T2 , in 10 patients T4, and only 12 patients were detected tumours in early stage that were confined to submucosa (T1). Lymph nodes in majority of patients (n=63) were negative, 28 patients participating in the study had metastases present in 1-3 lymph nodes (N1), while 10 patients had 4 or more positive lymph nodes (N2). At the time of diagnostic procedure, distant metastases were detected in advanced disease stage in 19 patients, while 82 were free of metastases. Correlation between the CEA marker level and tumour stage Duke's A, B or C is statistically significant (p=0.000). The tumour degree of invasion is also related to increased CEA levels. The CEA levels in patients with tumour stage T3 and T4 were significantly higher (median: 5,3 and 10,45 μg/L ) as compared to the degree of invasion of tumours T1 and T2, with median values close to 1,5 μg/L. Positive lymph nodes and distant metastases at the time the diagnosis was made have significant statistical correlations with the CEA levels (p=0.000). A median level was determined for lymph node stage N1, CEA= 6,00 μg/L, and for stage N2, CEA= 7,30 μg/L. ln patients with distant metastases a median CEA level s was 28,90 μg/L. Patients with fatal outcome of treatment had statistically significant increased CEA level (median: 7,00 μg/L), with regard to a group of patients who survived whose median level was 1,75 μg/L. The only significant survival predictors according to the Cox regression analysis were metastases and local recurrence. Variables such as age, sex, Dukes status, tumor size, lymph node status, and the value of tumor markers CEA compared to survival have not proven as significant variables for survival. Conclusion Increased preoperative values of CEA marker are correlated with the tumour degree of invasion and metastases to lymph nodes and distant metastases. Survival of patients with increased marker levels and presence of metastases at the time of diagnosis is poor