The role of tumor markers and biomarkers in colorectal cancer.

A steady increase in colorectal cancer (CRC) incidence and mortality has been observed in Europe, despite the continuous advancement in diagnostic and therapeutic methods. Accordingly, further progress is very much desirable in non-invasive diagnostic methods to enable early diagnosis, preand postoperative staging, and to assist in selecting the most suitable neo-adjuvant and adjuvant therapeutic methods and post-treatment follow-up. This review summarizes the current state of knowledge about the role of tumor markers and biomarkers in CRC diagnosis, treatment and follow-up. New biomarkers which are absent in healthy persons and present in CRC are still being investigated, especially those that can be detected at early development stage of the disease and used in screening tests. Unfortunately, no molecule that would meet all of the foregoing criteria has been identified so far. Carcinoembryonic antigen still remains the only tumor marker of recognised efficacy in monitoring patients during and after CRC therapy. Clinical studies and retrospective analyses allowed to discover and introduce to the clinical practice several bioindicators that assist in selecting the proper chemotherapeutic drug. There are attempts to "personalise" chemotherapy based on presence or absence of specific biomarkers. Therapy with anti-EGFR antibodies is desirable in patients with advanced CRC and absence of KRAS or BRAF mutation. Defining tumor phenotype - microsatellite instability (MSI) or microsatellite stability (MSS) and testing for the presence or absence of 18q chromosome deletion is very much desirable in standard 5-FU-based therapy. Analysis of UGT1A1 alleles may be the basis for modified dosing and reducing the potential toxicity of irinotecan. Studies on CRC biomarkers need to continue to closely examine the relationship between therapy and CRC curability. Targeted therapy against membrane receptors appears to be the future of CRC therapy.

Serum cytokine concentration after liver lobe harvesting for transplantation.

OBJECTIVE: To investigate cytokine concentration after liver lobe harvesting for transplantation in order to prove that it is a relatively safe surgical procedure with limited tissue injury. MATERIAL AND METHODS: Study was performed in 17 healthy liver donors and 6 patients with benign liver tumors. Serum levels of IL-6, IL-1ra and sTNFRI were measured before surgery and on the days 1, 3 and 7 thereafter, by immunoassay (ELISA). RESULTS: There was a significant increase in serum concentrations of IL-6 on day 1-7 (from 2.4 pg/ml to 315.1 +/- 526, 47.3 +/- 48 and 15.3 +/- 15 pg/ml; p = 0.0002, p = 0.0006, p = 0.003), for IL-1ra on day 1-3 (from 472.5 +/- 436 pg/ml to 2072.6 +/- 3511 and 715.5 +/- 268 pg/ml; p = 0.001, p = 0.004), and for sTNFRI on day 1-3 (from 1075.7 +/- 338.0 pg/ml to 1601.4 +/- 317.0 and 1528.9 +/- 402.0 pg/ml; p = 0.0006, p = 0.003), following liver harvesting. No significant difference was observed between pre and postoperative IL-6 serum concentration, whereas IL-1ra and sTNFRI were elevated only on day 3 after liver resection (p = 0.02, p = 0.04). A significantly higher level of sTNFRI was seen in patients after liver resection, as compared to liver donors on day 1 (p = 0.01), 3 (p = 0.03) and 7 (p = 0.0006) after surgery, whereas on day 3 (p = 0.03) and 7 (p = 0.01) when IL-1ra was measured. CONCLUSION: The short period of elevated concentrations of IL6, sTNFRI and IL1ra after harvesting of lobes for transplantation and a relatively low serum level of these cytokines indicate that this type of procedure does not evoke any major postoperative SIRS-type reaction as seen not infrequently after resection of liver for primary or secondary liver pathology.

[Dynamic of IL-6 and IL-8 concentrations in patients after surgery treated with total parenteral nutrition]. / Dynamika zmian stezenia interleukin 6 i 8 u chorych po zabiegach chirurgicznych leczonych calkowitym zywieniem pozajelitowym.

Exaggerated cytokines productions and development of systemic inflammatory response (SIRS) is the most common cause of postoperative complications and death after major abdominal surgery. The present study was conducted to investigate alterations in systemic production of interleukin-6 (IL-6) and interleukin-8 (IL-8) after total parenteral nutrition (TPN) in surgical patients. Plasma concentrations of IL-6 and IL-8 were measured in 22 patients (10 treated with TPN and 12 without TPN) before major surgery and on the days 1, 3, 7, 10 and 14-16 after, by ELISA test (indications for surgery: stomach, pancreatic and colon carcinoma, complications of IBD and acute pancreatitis). There were no differences between preoperative levels of IL-6 and IL-8 in the examined groups of patients. The highest (on the days 1, 3, 7, 10: 268.3 (p = 0.002), 41.9 (p = 0.03), 122.6 (p = 0.009), 29.3 (p = 0.03) pg/ml respectively) and longer lasting significantly elevated level of IL-6 was observed in the group of patients after major surgery without TPN. In the group of patients received TPN (with glutamine) there was a significantly increased but in comparison with group of patients without TPN, significantly lower level of IL-6 on days 1 and 7 (103.4 and 34.7 pg/ml respectively, p = 0.01). There was no significant change in postoperative concentration of IL-8 after major surgery in the group of patients treated with TPN. The level of IL-8 was significantly elevated (p = 0.01) in the group of patients without TPN on day 1 and 3 following surgery. The IL-8 level in the TPN group vs. group of patients without TPN was significantly lower on day 1 after surgery. After TPN concentration of cholesterol was significantly higher and CRP level significantly lower. We conclude that TPN improved immunological response to major surgical trauma by reduction of the inflammatory response.

[Value of chosen immunologic parameters in assessment of surgical trauma extent]. / Wartosc wybranych wskazników immunologicznych w ocenie wielkosci urazu operacyjnego.

The subject of study was to assess the sensitivity of chosen immunological parameters in the extension of the post operative trauma. Two groups of patients were studied: group I--12 patients underwent laparoscopic cholecystectomy (ChL), group II--18 patients underwent conventional cholecystectomy (ChK). We compared changes in the concentration of interleukin 1 receptor antagonist (IL-1ra) and interleukin 6 (IL-6) in blood. Blood tests were taken before operation and 1, 3, 7, 10 days after operation. Levels of IL-1ra and IL-6 were determined by ELISA. It was stated that cholecystectomy (ChK, ChL) evoked statistically significant changes in the value of chosen immunological parameters. In comparison with ChK the ChL evokes significant but smaller and shorter lasting changes in tested parameters of the immunological response that indicates that ChL is less invasive surgical procedure. The IL-1ra and IL-6 concentration changes constitute a very sensitive markers of immunological response to surgical trauma. The value of IL-1ra and IL-6 changes in immunological response monitoring, especially in the patients with postoperative complications requires further investigations.

[Postoperative monitoring of patients with gastric cancer]. / Monitorowanie pooperacyjne chorych na raka zoladka.

The problem of monitoring of patients after radical treatment because of gastric cancer is discussed. The purpose of postoperative follow-up is diagnosis of metastases or recurrence by means anamnesis, physical examination, laboratory studies, biochemical markers, double contrast x-ray, chest x-ray, CT scan, USG and gastroscopy.

[Usefulness of biochemical tumor markers (CEA, Ca 19-9, ferritin and sialic acid) in diagnosis and prognosis of colonic neoplasms]. / Przydatnosc biochemicznych markerów nowotworowych (CEA, Ca 19-9, ferrytyna i kwas sialowy) w diagnostyce i rokowaniu raka jelita grubego.

The aim of the study was: to determine the value of CEA, Ca 19-9, ferritin and sialic acid in diagnostics, to assess the prognostic role of serum CEA and Ca 19-9 levels before surgery and to evaluate their usefulness in diagnostics of recurrences. The study included 352 patients with colorectal carcinoma (adenocarcinoma). The preoperative level of CEA was elevated in 286 patients, Ca 19-9 in 108, ferritin in 60 and sialic acid in 58 patients. All of them are poor markers in diagnostics because of the low sensitivity, respectively 47.6%, 37.0%, 16.7% and 55.2%. Preoperative high, CEA and Ca 19-9 values are associated with a significantly poorer prognosis and with frequency of recurrences.

[Neoplasms of the large intestine in elderly patients]. / Rak jelita grubego u chorych w wieku podeszlym.

The aim of the study was to compare 2 groups of patients with colorectal cancer treated between 1985-1995. The analysed group consisted of 228 patients aged over 70. Reference group consisted of 330 younger ones. The stage of colorectal cancer (Dukes classification) was similar in both groups. Complications of the colorectal cancer often occurred in the elderly patients (21.9% vs. 10%, respectively). The incidence of associated diseases was also higher (70.6% vs. 59.1%). Operability was similar in both groups (93% vs. 98.8%) but resectability was lower in the elderly group (67.4% vs. 80.1%, respectively). Postoperative complications were observed in the similar percent of cases except those aged over 70 (17.5% vs. 4.9%), especially after emergency operations (31.6% vs. 4.7%, respectively).

[Sialic acid and carcinoembryonic antigen (CEA) as markers of colon cancer: Preliminary report]. / Kwas sialowy i antygen karcynoembrionalny jako markery raka jelita grubego. Doniesienie wstepne.

Tumor markers known to date are not sensitive and specific enough to detect malignant tumors. Therefore, attempts to find new markers have led to sialic acid assays in cancer patients. Serum sialic acid, CEA and ESR have been determined in 33 patients with the cancer of the colon. All patients have been divided into four groups, according to TNM cancer staging. Serum sialic acid levels have been increased by 100% of patients in groups I and IV. The most significant correlation was noted between sialic acid levels and ESR. No significant relationship between serum sialic acid and CEA have been noted. No correlation of the colon cancer stage, according to TNM staging, and sialic acid and CEA levels in the peripheral blood has been observed. It seems, however, that serum sialic acid assay may be useful auxiliary technique in the detection and monitoring of patients with colon cancer.