Search

Tumor recurrence develops in 45-80% of patients after liver surgery for colorectal liver metastases. To assess the significance of preoperative tumor marker levels for disease free interval (DFI) and patient survival (PS) after liver surgery.Preoperative serum levels of carcinoembryonic antigen--CEA, CA 19-9, CA 72-4, thymidine kinase (TK), tissue polypeptide antigen (TPA) and tissue polypeptide specific antigen (TPS) were evaluated in 173 patients operated on for colorectal liver metastases (CLM). Liver resection was performed on 114 patients and radiofrequency ablation on 59 patients.Preoperative serum levels of TPA (cut off level = 53 IU/L, Hazard ratio = 4.5, Wilcoxon test: p0.01, Log-Rank test: p0.03) and TPS (cut off level = 81 IU/L, Hazard ratio = 5.1, Wilcoxon test: p0.007, Log-Rank test: p0.009) were important for PS and DFI after liver resection (TPA: cut off level = 53 IU/L, Hazard ratio = 3.5, Wilcoxon test: n.s., Log-Rank test: n.s.; TPS: cut off level = 81 IU/l, Hazard ratio = 2.6, Wilcoxon test: p0.02, Log-Rank: p0.06). TPA serum levels were important for PS (Wilcoxon test--p0.003, Log-Rank test--p0.0002) and DFI after RFA (Wilcoxon test--p0.001, Log-Rank Test--p0.0001). TPS serum levels also correlated with PS (Wilcoxon test--p0.005, Log-Rank test--p0.003) and DFI after RFA (Wilcoxon test--p0.001, Log-Rank Test--p0.0001).TPA and TPS are important predictive markers for PS and DFI after liver resections and radiofrequency ablations for CLM.

Destruction of the extracellular matrix is a necessary precondition for metastasis and invasion of tumour cells. Metalloproteinases (MMPs) are involved in this process, matrilysin being one of them (MMP-7). The results of our pilot study with patients operated on for non-small cell lung carcinoma (NSCLC), with the assessment of MMP-7 and the tissue inhibitor of matrix metalloproteinase (TIMP-1), are presented here.The group consisted of 34 patients who had been operated on in the course of 2005. Messenger RNA MMP- 7 and TIMP-1 were assessed in 20 cases (58%). Tissue samples were frozen to -70 degrees C, total RNA was subsequently isolated and a reverse transcription was performed from it. The quantitative assessment itself was performed using a real-time PCR method. The resulting expression level was determined as the expression ratio of the assessed gene and the housekeeping gene, glyceraldehyde-3-phosphate dehydrogenase (GAPDH).A higher expression of mRNA MMP-7 was found in the NSCLC tissue than in non-tumourous lung tissue. On the other hand, a higher expression of mRNA TIMP-1 in the non-tumourous surrounding lung tissue was demonstrated. The expression of mRNA MMP-7 and TIMP-1 was higher in adenocarcinoma than in the epidermoid form of NSCLC.The value of our results should not be overestimated since we had only a small group of patients and assessed only one of the whole range of metalloproteinases (MMP-7). We consider the assessment and ratio quantification of metallorpoteinases in normal lung and NSCLC to be the first step in a further application of these parameters.

Thymidine kinase (TK) plays an essential role in the processing of thymidine within the cell and therefore it is an important marker of proliferation, particularly in tumor cells. The aim of our study was to determine the diagnostic, prognostic and predictive importance of TK measurement in cancer.TK was measured using radioreceptor analysis (RRA) with Immunotech assay kits. The serum level of TK was measured in 1087 patients with malignant disease (355 patients with hematology malignancies and 732 patients with solid tumors).Serum levels of TK were significantly elevated in inflammatory and immunological diseases in comparison with healthy individuals. Malignant diseases were associated with elevated serum levels of TK only in particular cases (e.g. hematological malignancies, cervical cancer). This marker has a high sensitivity for use as a primary diagnostic tool. It also has a high sensitivity during the follow-up period in breast and colorectal cancer for the prediction of relapse at the time of primary diagnosis and 3 months earlier than the diagnosis of relapse by imaging methods.TK represents a secondary tumor marker which is particularly useful for cancer disease monitoring. Interpretation of this marker must be performed only in association with evaluation of clinical status since all other possible non-specific causes (inflammatory or immunological diseases) of elevated serum levels must be excluded.

Liver surgery for colorectal liver metastases (CLM) is very often followed by recurrence. The prediction of early relapse of CLM is important for successful treatment, long disease free period and for long survival of patients, because it could help us to choose adequate surgical and oncological treatment. The authors present contemporary overview of the prognostic factors of early CLM recurrence and their possible use in prognostic scoring systems. These could be very helpful in clinical practice.

In the period of November 1999 - June 2003 78 patients with colorectal liver metastases (CLM) were operated at Department of Surgery, University Hospital in Pilsen. In multifactorial analysis there were evaluated these clinical parametres: age of patient, sex, localisation of primary tumor, Dukes classification, grading, staging and histology of primary tumor, histologicaly free resection margin, chemotherapy or actinotherapy after colorectal operation, type of liver resection, complications after liver surgery, radicality of liver surgery, lateralisation of liver metastatic process, number of metastases, blood transfusions, repeated liver surgery, volume of metastases. Kaplan-Meier method was used for evaluation of survival rate and disease free interval (DFI). Statistical analysis of studied clinical parametres was performed by Log-rank test and Wilcoxon test. The medium DFI after liver surgery was 16 months for all the patients (range 0-55 months), the medium DFI for patients after radical surgery was 18 months. The medium survival time after liver surgery for all the patients was 30 months (range 1-57 months), for patients after radical surgery it was 32 months, and for patients after palliative surgery the medium disease free interval was 29 months (range 5-30 months). The 4-year survival rate after the liver surgery was for all the patients 37%. The factors statistically significant for a disease free interval after liver surgery were bilaterality of metastatic process, the microscopically free resection line, radical surgical treatment versus RFA and unilaterality of metastatic process. The authors proved followed factors as statistically significant for survival rate: grading of colorectal cancer and age of patients. The prediction of early recurrence enables us to choose adequate surgical therapy or its extension by oncological therapy. More thorough follow up of patients with tendency to early recurrence of CLM helps to early diagnosis of relaps and it increases the posssibility of repeated liver surgery.

An essential step in the process of tumor invasion and metastasis involves the degradation of tissue barriers in the extracellular matrix (ECM), particularly in the basal membrane (BM). Matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs), in particular MMP-2, MMP-7, TIMP-1 and TIMP-2, play an important role in the process of ECM and BM degradation in connection with tumor invasion. The aim of our study was to assess the levels of MMP-2, MMP-7, TIMP-1 and TIMP-2 mRNA expression in colorectal carcinoma tissue samples and to correlate them with the stage of the disease.The study included samples of tumor tissue of 38 patients with colorectal carcinoma and samples of tissue of 11 patients with benign disease. The expression levels of mRNA MMP-2, MMP-7, TIMP-1, TIMP-2 and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), as housekeeping gene, were quantified in tissue samples using the method of reverse transcription real-time PCR.The levels of mRNA expression of MMP-2, MMP-7 and TIMP-1 were significantly higher in tumor tissue samples that in the control tissue (p0.0005, p0.0007 and p0.0004). In addition the presence of mRNA MMP-2, MMP-7, TIMP-1 and TIMP-2 in tumor tissue samples in these parameters was significantly higher than in the control tissue (p0.003, p0.0001, p0.0001 and p0.05).This pilot study demonstrated that a significant difference in the level and in the presence of mRNA MMP-2, MMP-7 and TIMP-1 expressions between tumor colorectal and control colorectal tissues might be helpful for the prognosis of colorectal cancer.

Pancreatic cancer represents a group of cancers with the worst prognosis. There exists only one method of successful therapy--radical surgery, i.e. the complete resection of the tumor. However, only 5% of cases are diagnosed in the early stage. More than 60% are recognised in the period of advanced disease. For those patients only palliative treatment can be used. Only early diagnosis can ensure better therapy results. Possibility of early diagnosis based on imaging and endoscope methods is at present very limited due to the anatomical location of pancreas. Serum tumor markers assessment might represent one of the possibilities of early detection of the pancreatic cancer. Review summarizes current knowledge on the use of tumor markers for diagnosis, prognosis and therapy monitoring of pancreatic exocrine adenocarcinomas with respect to the clinical use at the daily routine practice.

The aim of study was to reveal the relationship between metabolic syndrome and depression in a population sample, based on clinical and metabolic parameters.We tried to estimate depression (or other psychopathologies) prevalence in a randomly chosen population sample of the Pilsen city, using special questionnaires. Further, we estimated metabolic syndrome of insulin resistance risk factors and we looked for the relationship between these two disorders. Mental state of object was classified according to the questionnaires results, currently evaluated by the psychiatrist. Metabolic syndrome of insulin resistance was diagnosed as a presence of 3 of the 5 following factors: Triglyceridesor = 1.7 mmol/l, HDL cholesterol1.0 mmol/l in males or1.3 mmol/l in females, blood pressureor = 130/85 mmHg (and/or antihypertensive medication), fasting plasma glucoseor = 6.1 mmol/l, waist circumference102 cm in males or88 cm in females. Depressive syndrome diagnosed by Zungs scale is present in 31% of the Pilsen population, in 38% females and 31% males (n = 340). In the group of depressive objects, characteristics of metabolic syndrome of insulin resistance were two times higher than in the control group. Differences in resting heart rate, triglycerides level and fasting C-peptid were significantly higher in the depressive subjects. After the corrections considering age, sex and treatment adjustment, the waist to hip ratio was in the depressive subjects statistically higher as well as the 24 hour excretion of urine cortisone. In persons with metabolic syndrome of insulin resistance the prevalence of depression and anxiety was significantly higher.Our results show a possible relationship between depressive disorder and risk factors of the syndrome of insulin resistance. The question remains if the depression treatment can correct some of the metabolic syndrome risk factors.

In the group of 450 patients operated in the Cardiosurgical Department of the Faculty Hospital in Plzen during the period from III/2003 till XI/2003, 1451 samples were collected to examine the following-procalcitonin levels (PCT), white blood cell counts (Leu) and C-reactive protein levels (CRP). The findings were assessed with respect to the respective patient's clinical status, and any correlation between procedures with extracorporeal circulation (MO), signs of inflammation, septic and non-septic serious complications and between the above mentioned markers levels, was searched. It was detected, that the PCT levels correlated well with the clinical signs of inflammation and sepsis, as well as with the non-inflammatory complications. The CRP and Leu changes were not statistically significant and their levels are commonly increased by the surgical procedure itself.

The significance of CEA, CA19-9 and CA72-4 was evaluated the for early detection of disease recurrence, on the basis of retrospective evaluation of routine data in patients with colorectal carcinoma. They also considered the dependence of the results of these data analyses on the definition of groups of patients, both with no evidence of disease (NED) and with recurrence of disease (RD).From January 1994 to March 1999 serum levels of CEA, CA19-9 and CA72-4 were determined in the follow-up of 517 patients with colorectal cancer and compared with the retrospectively confirmed clinical status of the patients.CEA and CA19-9 showed comparable sensitivities in the detection of locoregional recurrence of colorectal carcinoma, whilst the sensitivity of CA72-4 was considerably lower. CEA is an optimal marker for detecting distant metastases, in particular liver metastases, since its sensitivity considerably exceeds the sensitivities of the other two monitored markers.Using routine data required detailed analysis and clear definitions of groups of patients with NED and RD. The following conclusions for the evaluation of data were drawn from this analysis: a) Tumor marker cut-off values and sensitivities related to 95% specificity of remission values depended strongly on the given definition of the groups of patients with NED and RD. b) The patient group with NED is best characterized as the group of patients who never developed progression and where all the values which were assessed within a period shorter than six months from the end of therapy and follow-up, or less than six months before progression, death, or before the last marker assessment in the patient, were excluded. c) For the optimal characterisation of the group of patients with RD it is recommended only to consider values obtained during the first progression, after the period of complete post-operative or post-therapeutic remission. d) These conclusions refer not only to routine data, where this correction represents a condition for reliable evaluation, but also to any research done, since they ensure complete homogeneity of the group and mutual comparability of the results.

The matrix metalloproteinases (MMP) are a family of proteolytic enzymes involved in tumor growth and in the process of invasion. The aim of our study was to test the levels of MMP-2, MMP-7, and the MMP inhibitors TIMP-1 and TIMP-2 mRNA in colorectal carcinoma tissue samples with the clinicopathological status of the disease.Colorectal carcinoma tissue samples were obtained from 38 patients who underwent resection of colorectal carcinoma. The expression levels of mRNA of MMP-2, MMP-7, TIMP-1, TIMP-2 and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a housekeeping gene were quantified in these tissue samples using the method of reverse transcription real-time PCR.It was found that the levels of mRNA expression of MMP-2, TIMP-2, MMP-7 and TIMP-1 were significantly higher in tumor tissue samples than in the normal colorectal tissue (p0.0020, p0.0467, p0.0007 and p0.0003 respectively). The level of mRNA expression of MMP-2, MMP-7, TIMP-2 and TIMP-1 did not correlate with the stage of the disease, localization of the tumor, metastatic spread or with disease-free survival (DFI). We recorded a statistically significant inverse negative correlation (r = -0.85; p0.0001) between the levels of MMP-7 mRNA and TIMP-2 mRNA. Correlations between the values of mRNA MMP-7 vs. TIMP-1, MMP-2 vs. TIMP-2, MMP-2 vs. TIMP-1 and MMP-2 vs. MMP-7 were not statistically significant.We found that there were statistically significant differences in the levels of MMP-2, MMP-7, TIMP-1, TIMP-2 mRNA between normal colorectal tissue and tumor tissue, but we did not find any statistically significant correlation between mRNA levels of MMP-2, MMP-7, TIMP-1, TIMP-2 expression and localization of tumor, clinical stage or course of disease. We found an inverse negative statistically significant correlation between mRNA levels of MMP-7 and TIMP-2. On the basis of these results the clinical use of this approach to the determination of a prognosis is ambiguous.

Basic conventional prognostic factors for breast cancer include the age of the patient, tumor grade, regional lymph nodes status, and estrogen (ER) and progesterone (PR) receptor status. Positivity of the HER2 receptor (c-erbB-2) seems to be a new prognostic and predictive factor. Prognostic factors seem to be more important in the high-risk group of the premenopausal females. We evaluated individual prognostic factors (age, histology, TNM classification, ER, PR, CA 15-3, CEA, HER2) and their impact on disease-free survival (DFS) and overall survival (OS) during the 5-year follow-up period.Forty-two patients were monitored after standard oncology treatment for a period of at least 5 years. The statistical significance of the individual prognostic parameters was evaluated in relationship to the time to progression (DFS and OS).The following were evaluated as statistically significant prognostic parameters for DFS: PR positivity (p = 0.0036), proliferative marker MIB1 (p = 0.0108), pre-operative level of CA 15-3 (p = 0.0425), ER negativity (p = 0.0507). The following were evaluated as statistically significant prognostic parameters for OS: PR positivity (p = 0.0003), MIB1 (p = 0.0005), ER (p = 0.0440), pre-operative level of CEA (p = 0.0495). Positivity of immunohistochemically performed test of c-erbB-2 was not statistically significant for DFS os OS (p = 0.6361 and 0.9323, respectively).The statistically significant prognostic importance of the levels of tumor markers CA 15-3 and CEA for prognosis in breast cancer of premenopausal females was proven. So far, these factors have been underestimated. The prognostic parameters of ER, PR and MIB1 were statistically significant. While no prognostic importance was confirmed for c-erbB-2 positivity; this factor cannot be evaluated in premenopausal females separately from the other prognostic factors due to the predictive value in relation to the adjuvant therapy (patients with HER+, ER+, PR-).

Thymidine kinase is involved in nucleic acid synthesis and is, therefore, considered to be an important proliferation tumor marker. For this reason, we monitored this marker in the course of colorectal cancer chemotherapy.We examined thymidine kinase (TK) levels in 30 patients with colorectal cancer who underwent adjuvant or palliative chemotherapy (CHT schemes). The condition for being included in the study was a minimum of 3 cycles of chemotherapy. TK was always assessed with radio-receptor analysis, before and after every chemotherapy cycle, together with other tumor markers.From the monitored tumor markers, only TK changed typically in the course of chemotherapy. In adjuvant chemotherapy, it was mostly low at the beginning of the cycle and its values usually increased considerably at the end. On the other hand, in palliative chemotherapy the dynamics of TK varied mainly depending on the effect of the therapy. Other tumor markers showed nonstandard behavior and minimal correlation with TK changes.Thymidine kinase seems to be a suitable parameter for monitoring the effect of adjuvant and palliative chemotherapy in colorectal cancer.