"NR7905"
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Závěrečná zpráva o řešení grantu Interní grantové agentury MZ ČR
Přeruš. str. : il., tab. ; 30 cm
Zhodnocení možnosti monitorování nemocných po resekčních výkonech na játrech pro Tu onemocnění formou dispenzarizace, za využití stanovení hladin metaloproteinaz a jejich tkáň. inhibitorů v séru před a po resekčním či albačním výkonu za pomocí Q-RT-PCR.Sledování hladin metaloproteinaz a jejich tkáňových inhibitorů v séru nemocných a přímo v tumorosním ložišku odebraném z jater, na základě těchto výsledků a celkového klinického stavu stanovení prognozy onemocnění. Porovnání citlivosti metody se stanovením běžných nádorových markerů (karcinom embrionální antigen, alfefetoprotein) v séru; . Assessment of the level of the metalloproteinses (MMPs) and their tissue inhibitors (TIMPs) in tumours and blood of a patient by help of quatitive RT-PCR (Q-RT-PCR) Verifying possibility in using of these results for monitoring of patiens after resections or ablations (RF) in liver in primary or secondary liver tumours .Evaluation of the stage of malignancy and prognosis of the patient in connection with MMPs and TIMPs level in tumour and blood of the patient
- MeSH
- bcr-abl fúzní proteiny MeSH
- nádorové biomarkery analýza MeSH
- nádory jater chirurgie MeSH
- polymerázová řetězová reakce s reverzní transkripcí metody využití MeSH
- prognóza MeSH
- tkáňové inhibitory metaloproteinas analýza MeSH
- Konspekt
- Patologie. Klinická medicína
- NLK Obory
- biologie
- hepatologie
- transplantologie
- onkologie
- NLK Publikační typ
- závěrečné zprávy o řešení grantu IGA MZ ČR
BACKGROUND: Nowadays we know that survival rates do not differ between repeated and single liver resections for colorectal liver metastases (CLM). To be able to determine patients prone to early recurrence, the use of different markers with a better prognostic value than the routinely employed tumor markers is required. AIM OF STUDY: The aim of our study was to assess mRNA expression of MMP-7, MMP-9, TIMP-1, TIMP-2 and CEA in tissue samples from CLM and their relationship to disease-free interval (DFI) and overall survival (OS). PATIENTS AND METHODS: The liver tumor biopsies were obtained from 40 patients suffering from CLM treated with radical surgery. mRNA expression levels of CEA, MMPs and TIMPs and a housekeeping gene (GAPDH) were quantified using RT-PCR. RESULTS: The increased expression of CEA, MMP-9 and TIMP-1 in CLM was associated with a short DFI and a high tendency to early CLM recurrence. Statistical analysis confirmed CEA, MMP-9 and TIMP-1 expression as prognostic factors of survival. CONCLUSION: This study demonstrated the importance of CEA, MMP-9 and TIMP-1 in the prognostication of DFI and OS. Copyright 2007 S. Karger AG, Basel.
- MeSH
- adenokarcinom genetika chirurgie metabolismus mortalita sekundární MeSH
- analýza přežití MeSH
- dospělí MeSH
- financování organizované MeSH
- karcinoembryonální antigen biosyntéza genetika MeSH
- kolorektální nádory genetika metabolismus mortalita MeSH
- lidé středního věku MeSH
- lidé MeSH
- matrixová metaloproteinasa 7 biosyntéza genetika MeSH
- matrixová metaloproteinasa 9 biosyntéza genetika MeSH
- messenger RNA biosyntéza MeSH
- nádorové proteiny biosyntéza genetika MeSH
- nádory jater genetika metabolismus mortalita sekundární MeSH
- přežití bez známek nemoci MeSH
- prognóza MeSH
- RNA nádorová biosyntéza MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- tkáňový inhibitor metaloproteinasy 1 biosyntéza genetika MeSH
- tkáňový inhibitor metaloproteinasy 2 biosyntéza genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
BACKGROUND: Tumor markers are used for the prediction of relapse and in determining the effect of postoperative or post-oncological therapy as a standard component of follow-up. Metastatic processes of the liver and primary malignancies of the liver and gall bladder are very common in the European population. The aim of this study was to demonstrate the behaviour of malignancy in patients who have not undergone surgical therapy and to study serum levels of the monitored tumor markers in relation to the life expectancy of these patients. PATIENTS AND METHODS: The Log-rank test and Wilcoxon test were used for statistical evaluation. Survival was computed using the Kaplan-Meier method. Serum levels of the tumor markers conventionally used in clinical practice in patients with gastrointestinal tumors (CEA, CA19-9, C724) and the markers of the proliferation activity in malignancy (TK, TPA, TPS) were studied. RESULTS: One hundred and nine patients who underwent exploratory laparotomy without any surgical therapy between September 1999 and June 2005 were studied. For patients with a serum level of CEA, CA19-9 and CA72-4 that was higher than the calculated cut-off hazard ratios of early death were respectively 3-, 5- and 9-fold higher than for patients with serum levels of the same tumor markers below the calculated cut-off. Preoperative serum levels of proliferative tumor markers (TK, TPA and TPS) were not statistically significant for the prediction of early death. CONCLUSION: The results of the pilot study suggest the importance of tumor markers for the prediction of the short-term survival rate. These markers could be used to supplement classic clinical, laboratory and radiodiagnostic parameters. It would be very helpful for the planning of palliative oncological therapy for patients with liver malignancies who cannot be treated by surgical therapy.
- MeSH
- antigen CA-19-9 krev MeSH
- financování organizované MeSH
- Kaplanův-Meierův odhad MeSH
- karcinoembryonální antigen krev MeSH
- laparotomie MeSH
- lidé MeSH
- míra přežití MeSH
- nádorové biomarkery analýza MeSH
- nádory jater krev mortalita patologie MeSH
- peptidy krev MeSH
- pilotní projekty MeSH
- prognóza MeSH
- thymidinkináza krev MeSH
- tkáňový polypeptidový antigen krev MeSH
- Check Tag
- lidé MeSH
BACKGROUND: 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. PATIENTS AND METHODS: 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). RESULTS: 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. CONCLUSION: 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.
BACKGROUND: The authors present a statistical analysis of the dynamics of tumour markers and compare these with single serum levels in patients before and after liver surgery for colorectal liver metastases (CLM). PATIENTS AND METHODS: The serum levels of tumor markers conventionally used in clinical practice (CA19-9, CEA, CA72-4) and markers informing of the proliferation activity of malignancy (TKI TPA, TPS) were statistically analysed. The authors studied 144 patients who underwent liver surgery for colorectal liver metastases between September 1999 and June 2005. Serum levels of tumor markers before surgery (maximally two weeks before the operation), after surgery (maximally one month after the operation - usually on the day of dismission), six months (+/- one month) and twelve months after the surgery (+/- one month) were determined. The Log Rank test and the Wilcoxon test were used for statistical evaluation. The survival rate and disease-free intervals (DFI) were computed using the Kaplan-Meier method. RESULTS: The statistical analysis of tumour marker dynamic after liver surgery (speed and power of recurrence) supported the dynamics of CA 19-9 and CEA as excellent prognostic factors of early recurrence of CLM in contrast to proliferative tumor markers. CONCLUSION: The results of the study suggest the importance of tumour markers for the prediction of a short survival rate or DFI. This approach would be very helpful for the planning of palliative oncological treatment for patients with liver malignancies that cannot be treated by surgical therapy. Current patients with a high tendency of recurrence of CLM after liver surgery should be followed up more thoroughly to increase the possibility of successful reoperation.
V období 11/1999 – 6/2003 bylo na Chirurgické klinice Fakultní nemocnice Plzeň operováno 78 nemocných pro metastatický proces kolorektálního carcinomu v játrech. V multifaktoriální analýze byly hodnoceny následující klinické parametry: věk, pohlaví, lokalizace primárního tumoru, Dukesova klasifikace, grading, staging a histologický nález u primárního karcinomu, postižení resekční linie maligními buňkami, chemoterapie či radioterapie po operaci kolorekta, typ jaterní resekce, komplikace po jaterní operaci, radikální nebo paliativní jaterní výkon, lateralita metastatického procesu, počet metastáz, krevní převody během jaterní operace, opakovaný jaterní výkon a objem metastáz. Pro zhodnocení celkového přežití a bezpříznakového přežití (DFI) byla použita Kaplanova-Meierové metoda. Zhodnocení statistické významnosti sledovaných parametrů bylo provedeno Log-rank testem a Wilcoxonovým testem. Medián DFI pro všechny pacienty byl 16 měsíců (rozpětí 0–55 měsíců). Medián DFI pacientů, kteří podstoupili radikální výkon byl 18 měsíců. Medián celkového přežití pro všechny pacienty byl 30 měsíců (1–57). Medián celkového přežití u radikálně operovaných pacientů byl 32 měsíců, zatímco u pacientů s paliativním výkonem byl jen 29 měsíců. Čtyřleté přežití po operaci jater u všech pacientů bylo 37 %. Jako statisticky významné prognostické faktory, které měly vztah k DFI byly prokázány: bilateralita metastatického procesu, resekční linie nepostižená metastatickým procesem, radikální operace versus RFA, unilateralita metastatického procesu. Multifaktoriální analýzou byla prokázána statistická významnost následujících prognostických faktorů vzhledem k celkovému přežití: grading kolorektálního karcinomu a věk pacientů. Predikce časné recidivy nám umožňuje vhodnou volbu vlastní chirurgické léčby, eventuálně její doplnění léčbou onkologickou. Důkladnější dispenzarizace u těchto nemocných vede k včasnému záchytu recidivy, kterou můžeme ještě chirurgicky ošetřit.
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.
