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Background: The presence of circulating tumor cells (CTC) has been reported in patients with advanced colorectal cancer. Monitoring CTC (also known as a liquid-biopsy) has recently become the center of interest for low-invasive monitoring of cancer progression and predictive biomarkers testing. Along with high-cost technology and a complex methodology, a straightforward method based on magnetic beads enrichment followed by RT-PCR is set to allow for routine CTC analysis in colorectal cancer patients., Objectives: The main purpose of this study was to evaluate the possibility of CTC detection in routine monitoring of patients starting before and continuing after surgery., Material and Methods: The investigated group consisted of 30 patients mainly in advanced stages of colorectal cancer. In all patients, CTC detection was performed prior to surgery, in a subset of 14 patients additional sampling was done during and after surgery. In all cases, peripheral blood was processed using AdnaTest ColonCancer kit, which relies on enriching CTCs using EpCAM-functionalized magnetic beads and subsequently identifying tumorspecific CEA, EGFR and GA733-2 mRNA transcripts., Results: Out of all the tested samples, CTC were found in one patient suffering from advanced disease with lung and liver metastases. There, however, the positive finding was confirmed in 3 consecutive samples acquired before, during and shortly after palliative R2 resection., Conclusions: The presence of CTC may be used to observe post-operative disease development. Due to the overall low CTC detection, further technology development may be necessary before its universal applicability to manage colorectal cancer patients.

Purpose: DNA repair capacity (DRC) is a determinant not only of cancer development but also of individual response to therapy. Previously, altered base and nucleotide excision repair (BER and NER) have been described in lymphocytes of patients with sporadic colorectal cancer. We, for the first time, evaluate both excision repair capacities in human colon biopsies to study their participation in colorectal tumorigenesis., Experimental Design: Seventy pairs of tumor and adjacent healthy tissues were analyzed for BER- and NER-specific DRC by a comet repair assay. Tissue pairs were further compared for expression levels of a panel of 25 BER and NER genes complemented by their promoter methylation status., Results: We observed a moderate increase of NER-DRC (P = 0.019), but not of BER-DRC in tumors. There was a strong correlation between both tissues for all investigated parameters (P < 0.001). However, 4 NER (CSB, CCNH, XPA, XPD) and 4 BER (NEIL1, APEX1, OGG1, PARP1) genes showed a 1.08- to 1.28-fold change difference in expression in tumors (P < 0.05). Individual gene expression levels did not correlate with overall DRC, and we did not detect any aberrant methylation of the investigated genes., Conclusions: Our complex analysis showed that tumor cells are not deficient in BER and NER, but rather follow patterns characteristic for each individual and are comparable with adjacent tissue. Alteration of excision repair pathways is not a pronounced event in colorectal carcinogenesis. This study shows the feasibility of DRC evaluation in human solid tissues, representing a complex marker of multigene DNA repair processes., (©2012 AACR.)

Reduced DNA repair capacity and DNA damage accumulation may lead to cancer development. Regulation of and coordination between genes involved in DNA repair pathways is fundamental for maintaining genome stability, and post-transcriptional gene regulation by microRNAs (miRNAs) may therefore be of particular relevance. In this context, the presence of single nucleotide polymorphisms (SNPs) within the 3'untranslated regions of target DNA repair genes could alter the binding with specific miRNAs, modulating gene expression and ultimately affecting cancer susceptibility. In this study, we investigated the role of genetic variations in miRNA-binding sites of nucleotide excision repair (NER) genes in association with colorectal cancer (CRC) risk. From 28 NER genes, we screened among SNPs residing in their 3'untranslated regions and simultaneously located in miRNA-binding sites, with an in silico approach. Through the calculation of different binding free energy according to both alleles of identified SNPs, and with global binding free energies median providing a threshold, we selected nine NER gene variants. We tested those SNPs in 1098 colorectal cancer cases and 1469 healthy controls from the Czech Republic. Rs7356 in RPA2 and rs4596 in GTF2H1 were associated with colorectal cancer risk. After stratification for tumor location, the association of both SNPs was significant only for rectal cancer (rs7356: OR 1.52, 95% CI 1.02-2.26, P = 0.04 and rs4596: OR 0.69, 95% CI 0.50-0.94, P = 0.02; results not adjusted for multiple testing). Variation in miRNA target binding sites in the 3'untranslated region of NER genes may be important for modulating colorectal cancer risk, with a different relevance according to tumor location.

Background: While efficient surgical treatment is the key to prolonged survival of patients with colorectal cancer, post-surgical follow-up is important for the early detection of relapsing disease or of disease progression. Current dispensarization, typically based on imaging CT, PET, MR, is frequently supported by the observation of tumour markers (CEA, CA19-9). Due to their limited sensitivity and selectivity, better tools for monitoring of the disease are desirable. Tumour cell-free DNA (cfDNA) has been recently demonstrated as a new promising molecular marker for observation and early detection of disease progression., Patients and Methods: We present results of post-surgical monitoring tumour cfDNA in the cases of seven patients suffering from advanced forms of CRC. We applied a mutation-based approach in which the total cfDNA was screened for a specific somatic mutation present in the primary tumour. We screened a panel of the most frequent somatic mutations covering the genes APC, KRAS, TP53, PIK3CA and BRAF. All patients were tested positive for tumour cfDNA prior to surgery. cfDNA was then evaluated within a week after surgery and subsequently in monthly intervals., Results: We present typical cases of colorectal cancer patients who underwent surgical treatment at different levels of radicality with or without adjuvant chemo/biotherapy. The tumour cfDNA status was found to be always closely correlated with the actual clinical status of the patient., Conclusion: The cfDNA appears to be a viable tool for the monitoring of the clinical progression of CRC in patients with cfDNA positivity prior to surgery.

Interindividual differences in DNA repair capacity (DRC) represent an important source of variability in genome integrity and thus influence health risk. In the last decade, DRC measurement has attracted attention as a potential biomarker in cancer prediction. Aim of the present exploratory study was to characterize the variability in DNA damage and DRC on 100 healthy individuals and to identify biological, lifestyle, or genetic factors modulating these parameters. The ultimate goal was to obtain reference data from cancer-free population, which may constitute background for further investigations on cancer patients. The endogenous DNA damage was measured as a level of DNA single-strand breaks and DRC, specific for nucleotide excision repair (NER), was evaluated using modified comet assay, following the challenge of peripheral blood mononuclear cells with benzo[a]pyrene diolepoxide. Additionally, genetic polymorphisms in NER genes (XPA, XPC, XPD, and XPG) were assessed. We have observed a substantial interindividual variability for both examined parameters. DNA damage was significantly affected by gender and alcohol consumption (P = 0.003 and P = 0.012, respectively), whereas DRC was associated with family history of cancer (P = 0.012). The stratification according to common variants in NER genes showed that DNA damage was significantly modulated by the presence of the variant T allele of XPC Ala499Val polymorphism (P = 0.01), while DRC was modulated by the presence of the A allele of XPA G23A polymorphism (P = 0.048). Our results indicate the range of endogenous DNA single-strand breaks and capacity of NER in healthy volunteers as well as the role of potentially relevant confounders. Environ. Mol. Mutagen. 2011. © 2011 Wiley-Liss, Inc., (Copyright © 2011 Wiley-Liss, Inc.)

Celiac axis stenosis can lead to a fatal hepatic ischemia after pancreaticoduodenectomy unless a simultaneous revascularisation of the celiac circulation is performed. In the present study are reported three cases of celiac axis stenosis, all of which had histologically confirmed periampullary cancer. Case 1: a 50-year-old male with a history of myocardial infarction and liver steatosis; visceral arteriography prior to the surgery demonstrated a celiac axis stenosis. Whipple operation was performed. After removing the specimen, no signs of liver ischemia were found (liver was cholestatic) and pulsation of the hepatic artery was strong. The patient died on the second postoperative day after an abrupt irreversible cardiac arrest. Autopsy proved acute severe hepatic ischemia. Case 2: a 64-year-old female. Preoperative visceral angiography showed significant celiac axis stenosis. As a first step of surgery the root of the celiac trunk was exposed, a fibrotic ring around it was divided. Standard D1 pylorus preserving pancreaticoduodenectomy was performed. Case 3: a 58-year-old female without preoperative angiography, indicated for surgery. After an occlusion test of the gastroduodenal artery the liver became ischemic. Division of the fibrotic ring around celiac axis was performed together with a standard D1 pylorus preserving pancreaticoduodenectomy. No postoperative complications were reported in both case 2 and 3.

The precise preoperative staging of colorectal cancer is fundamental for surgical strategy, incomplete staging means incomplete treatment and poor outcome. Large-scale clinical evaluations of predictive markers are currently in progress, including determination of their ability to predict response of patients to therapy for advanced disease and for adjuvant treatment. Lack of specificity and sensitivity preclude the use of all existing serum markers for the early detection of colorectal carcinoma. The aim of the study was to investigate the clinical significance of serum tumor markers and biological activity markers -- oncofetal tumormarker CEA, mucin tumormarkers CA19-9, CA242, proliferative tumor markers Thymidine kinase, soluble cytoceratines fragments TPS, TPA, adhesive molecules ICAM - 1, VCAM -1, IGF-1, and adipocytokinins Adiponectin, Leptin in patients with colorectal cancer before primary operation. The study included 142 patients between the ages of 35 - 89 years. Operated between November 2003 to March 2006. We have confirmed that CA19-9 is besides CEA an important marker in colorectal cancer. Comparing CA19-9 and CA242 in preoperative staging, CA242 is more specific. Statistical significant difference between early and metastatic stage of colorectal cancer was not confirmed in markers: ICAM-1, VCAM, adiponectin, leptin. Statistical significant difference between early and metastatic stage of colorectal cancer was confirmed in markers: CEA, CA19-9, CA242, TPS, TPA, TK, IGF-1. None of the used markers was able to distinguish stage II and III, in other words to identify patients with infiltration of lymph nodes. This fact is very important in our aspirations to find which marker from periferal blood could help to poit out patients in risk of lymphatic infiltration and to indicate these patients for adjuvant therapy. Combination of CEA and either CA19-9 or CA242 can be recommended for preoperative investigation. CA 242 in this study seems to have slightly better results in preoperative staging.

Purpose: The conventional diagnostic techniques used to assess recurrence of colorectal cancer (CRCR) often yield unspecific findings. Integrated FDG-PET/CT seems to offer promise for the differential diagnosis of benign and malignant lesions. The aim of this study was to compare the value of FDG-PET and PET/CT in the detection of CRCR subsequent to colonic resection or rectal amputation., Methods: The population for this retrospective study comprised 84 patients with suspected CRCR. The sensitivity, specificity and accuracy of PET and PET/CT were calculated for (a) intra-abdominal extrahepatic recurrences, (b) extra-abdominal and/or hepatic recurrences and (c) all recurrences, and tumour marker levels were analysed., Results: The sensitivity, specificity and overall accuracy of PET in detecting intra-abdominal extrahepatic CRCR were 82%, 88% and 86%, respectively, compared with 88%, 94% and 92%, respectively, for PET/CT. The corresponding figures for detection of extra-abdominal and/or hepatic CRCR were 74%, 88% and 85% for PET and 95%, 100% and 99% for PET/CT. Considering the entire population, the sensitivity, specificity and overall accuracy of PET were 80%, 69% and 75%, respectively, compared with 89%, 92% and 90%, respectively, for PET/CT. FDG-PET/CT examination correctly detected 40 out of a total of 45 patients with CRCR. Two of five patients with falsely negative FDG-PET/CT findings had local microscopic recurrences and one had miliary liver metastases. Of 39 patients without CRCR, three showed false positive FDG-PET/CT results. Two of these cases were due to increased accumulation in inflammatory foci in the bowel wall, while one was due to haemorrhaging into the adrenal gland., Conclusion: FDG-PET/CT appears to be a very promising method for distinguishing a viable tumour from fibrous changes, thereby avoiding unnecessary laparotomy.

Background: A retrospective review is presented of a single institution's experience with multivisceral resections for locally-advanced colorectal cancer., Materials and Methods: Twenty-eight patients, who had undergone RO multiorgan resection, were identified from the database of a total of 1150 patients operated on for colorectal carcinoma in the years 1995-2005 at a single center. There were twelve total pelvic exenterations and 16 patients had undergone en bloc primary tumor resection with adherent organs, such as the spleen, diaphragm, pancreas, stomach, kidney, etc. The patients were followed-up according to a standard protocol., Results: The post-operative mortality was 7%, the average follow-up 21.6 months and the 5-year survival 45%., Conclusion: Our results confirmed that, in the case of invasion of colorectal cancer to the adjacent intra-abdominal organs or structures, multiorgan resection 'offers the only chance of potentially-curative treatment.

A 54-year-old woman was operated for obstructive ileus in 1996. Obstruction was caused by a tumor of the descending colon invading the abdominal wall. Urgent left colectomy with lymphadenectomy was performed. Microscopically six lymphatic nodes were positive. The patient was postoperatively treated with adjuvant chemotherapy. Fifteen months later the patient underwent a resection of central hepatic segments (Couinaud's segment 4,5,8) for metachronous metastasis. At present the patient has no signs of recurrence, she has returned back to her normal life. Despite several unfavorable prognostic factors--obstruction, abdominal wall infiltration, number of positive nodes, short time between primary tumor resection and diagnosis of liver metastasis and centrally located metastasis with satellite lesions, the patient has been surviving for 6 years now.

Unlabelled: 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., Materials and Methods: 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., Results: 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., Conclusion: Thymidine kinase seems to be a suitable parameter for monitoring the effect of adjuvant and palliative chemotherapy in colorectal cancer.

The analysis of the first admission to hospitals showed that nearly 90% of patients with manifestations of brain stroke were referred to neurological departments. The indices of incidence calculated on the basis of first admissions were usually low, which was due to young age of the studied population. A comparison of the incidence indices standardized or age in the Nowa Huta values were nearly identical. The pattern of diagnoses resembled that reported by other authors. The most frequently observed form of brain stroke was infarction, diagnosed in over 50% of cases.

The probability of survival after a first stroke is as a rule small because less than half patients survive one year. The greater probability of survival observed in the group of males depends probably on a younger age of the patients at the time of disease onset. The probability of surviving the first day, first month and first year is lowest in cerebral haemorrhage. The prognosis is best in subarachnoid haemorrhage and cerebral infarction. The youngest patients were in the group of subarachnoid haemorrhage (45 years mean age) and in the group of cerebral haemorrhage (55 years), in the other groups of stroke the mean age was about 70 years. Coexistence of hypertension and atheromatosis decreased most the probability of one-year survival.