Detection and clinical relevance of tumor cells in blood and bone marrow of patients with colorectal cancer.

In colorectal cancer, the predictive value of the currently used staging method is limited. Therefore, many parameters have been studied to improve the prediction of final clinical outcome, including several aspects of the primary tumor that are associated with its aggressiveness and the capacity of the host response. A more direct approach to predict the metastatic potential of a tumor may be the determination of limited disseminated disease at an early stage before it becomes clinically evident. Very sensitive techniques have been developed to detect single or very few tumor cells that have been disseminated into lymph nodes, blood, bone marrow and the peritoneal cavity. This review describes the advantages and disadvantages of the main detection techniques and discusses the current state of clinical relevance of disseminated tumor cells in patients with colorectal cancer

Cancer mortality rates among first and second generation migrants in the Netherlands: convergence toward the rates of the native Dutch population.

This study investigates the difference in cancer mortality rates between migrant groups and the native Dutch population, and determines the extent of convergence of cancer mortality rates according to migrants' generation, age at migration and duration of residence. Data were obtained from the national cause of death and population registries in the period 1995-2000. We used Poisson regression to compare the cancer mortality rates of migrants originating from Turkey, Morocco, Surinam, Netherlands Antilles and Aruba to the rates for the native Dutch. All-cancer mortality among all migrant groups combined was significantly lower when compared to that of the native Dutch population (RR = 0.55, CI: 0.52-0.58). For a large number of cancers, migrants had more than 50% lower risk of death, while elevated risks were found for stomach and liver cancers. Mortality rates for all cancers combined were higher among second generation migrants, among those with younger age at migration, and those with longer duration of residence. This effect was particularly pronounced in lung cancer and colorectal cancer. For most cancers, mortality among second generation migrants remained lower compared to the native Dutch population. Surinamese migrants showed the most consistent pattern of convergence of cancer mortality. The generally low cancer mortality rates among migrants showed some degree of convergence but did not yet reach the levels of the native Dutch population. This convergence implies that current levels of cancer mortality among migrants will gradually increase in future years if no specific preventive measurements are taken. (aut. ref.

Uitgezaaide tumorcellen bij patiënten met dikkedarmkanker.

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Effect of blood sample handling and reverse transcriptase-polymerase chain reaction assay sensitivity on detection of CK20 expression in healthy donor blood.

Item does not contain fulltextData concerning the specificity of cytokeratin 20 (CK20) as a reverse transcriptase-polymerase chain reaction analysis (RT-PCR) marker to detect disseminated tumor cells in blood are conflicting. Underlying causes for these discrepancies need to be determined to clarify the significance of CK20 detection. Because differences in RT-PCR assays and blood sample handling may be important, their influence on CK20 detection was studied. Using a series of healthy donor blood samples spiked with colon tumor cells, the authors compared the sensitivities of two conventional PCRs with different primer sets and a quantitative LightCycler PCR (Roche Diagnostics GmbH, Penzberg, Germany). Additionally, the influence of sample collection and preparation on assay specificity was studied by examining CK20 expression in the mononuclear cell fraction (MNC) of the first and the second aliquot of blood drawn from healthy donors and in the granulocyte cell fraction. At the concentration of one spiked tumor cell/mL blood, the CK20 detection frequency varied from 17% and 67% for the conventional to 78% for the LightCycler PCR. In the unspiked samples, CK20 was detected in 0% and 8% of the conventional and in 11% of the LightCycler PCR tests. Quantitative analysis revealed that CK20 was expressed at a high level in the granulocyte samples. The results demonstrate that differences in assay sensitivity and sample handling influence CK20 detection in blood

Report on the Dutch consensus development meeting for implementation and further development of population screening for colorectal cancer based on FOBT.

Contains fulltext : 47671.pdf (publisher's version ) (Open Access)A consensus development meeting was held to evaluate whether or not in the Netherlands all requirements were fulfilled for implementation of population screening with FOBT for colorectal cancer, or whether consensus was present that fulfilment by additional research or organisational actions could be obtained within 2-3 years. There was consensus that all classical Wilson and Jungner (1968) criteria, and six additional ones added more recently, had already been fulfilled or could be fulfilled within 2-3 years. Consequently, it was concluded that a national population screening for colorectal cancer should be implemented and carried out in the Netherlands in line with current national and European cancer screening programmes. A list of organisational actions to be taken was established. Research that is needed before the actual national launch of the screening within 2-3 years has been defined. Priorities have to be set for research and organisational actions for the coming 2-3 years for the implementation of population screening. In addition, research suggestions have been defined for the next 10-15 years for evaluation and/or improvement of implemented FOBT screening, and for future screening methodology. It was considered essential that infrastructure for future research would be embedded in the screening programme. A project group to arrange this should be formed

Limitations of cytokeratin 20 RT-PCR to detect disseminated tumour cells in blood and bone marrow of patients with colorectal cancer: expression in controls and downregulation in tumour tissue.

Contains fulltext : 173875.pdf (publisher's version ) (Closed access)AIMS: Despite informative staging of patients with colorectal cancer, some patients with localised disease at diagnosis will develop recurrence or metastasis. Attempts to improve staging include sensitive detection of disseminated tumour cells in blood and bone marrow by reverse transcriptase polymerase chain reaction (RT-PCR). The results of this study have been considered in relation to the controversial results in the literature to elucidate the usefulness of cytokeratin 20 (CK20) RT-PCR to detect disseminated tumour cells further. PATIENTS/METHODS: Blood and bone marrow samples from 30 patients with colorectal cancer were studied by CK20 RT-PCR. Specificity was evaluated in 47 blood and 15 bone marrow samples from non-cancer controls. In addition, the expression of CK20 mRNA and protein was studied in normal and tumour colon tissue samples. RESULTS: CK20 expression was detected in nine of 30 and nine of 19 of the blood and bone marrow samples from patients with colorectal cancer, respectively. In non-cancer control blood and bone marrow samples, CK20 expression was detected in 10 of 47 and four of 15, respectively. A difference between patient and control samples may be observed in terms of frequency of positive PCR tests. In tissue samples, CK20 mRNA expression was downregulated in tumour compared with normal colon tissue. CONCLUSIONS: CK20 expression was downregulated in tumour tissue compared with normal colon and a background expression of CK20 was seen in some control blood and bone marrow samples. Despite a lack of standardisation (which hampers comparison of studies), these results, together with other reports in the literature, suggest that CK20 may still be a suitable marker, but that background expression and threshold setting should be studied further

Investigations for a multi-marker RT-PCR to improve sensitivity of disseminated tumor cell detection.

Item does not contain fulltextBACKGROUND: In order to develop a multi-marker RT-PCR, which as such may be more sensitive than a single marker assay for the detection of disseminated tumor cells, we evaluated six RT-PCR markers: cytokeratin 20 (CK20), carcinoembryonic antigen (CEA), guanylyl cyclase C (GCC), epidermal growth factor receptor (EGFR), matrilysin (MMP-7) and HeLa metastatic gene (HLM). MATERIALS AND METHODS: The expression was studied in human colon tumor cell lines, in colon cancer tissues, and in blood and/or bone marrow samples of colorectal cancer patients and control subjects. RESULTS: The cell lines showed a differential expression pattern. The expression of all markers was detected in control blood samples with the lowest frequency for CK20 and EGFR. Semiquantitative analysis, which was performed to study threshold setting, demonstrated that GCC expression was elevated in patient compared to control samples. However, the reproducibility was questionable. CONCLUSION: The results presented in this study suggest an enhanced sensitivity for a combination of RT-PCR markers. Due to limited specificity however, the development of a multi-marker RT-PCR by using conventional PCR does not seem feasible. Future studies should focus on the potential of quantitative RT-PCR

Detection of disseminated tumour cells in blood and bone marrow samples of patients undergoing hepatic resection for metastasis of colorectal cancer.

Contains fulltext : 142620.pdf (publisher's version ) (Closed access)BACKGROUND: In 50-60 per cent of patients who undergo hepatic resection for metastasis of colorectal cancer the first site of tumour recurrence is extrahepatic, indicating the presence of more extensive disease at the time of resection. The aim of this study was to evaluate whether the presence of disseminated tumour cells in blood and bone marrow could predict extrahepatic tumour recurrence. METHODS: Cytokeratin 20 (CK20) reverse transcriptase-polymerase chain reaction was used to study the presence of tumour cells in preoperative peripheral blood and bone marrow samples from 41 patients with liver metastasis scheduled for surgical resection. RESULTS: CK20 expression was detected in six of 41 peripheral blood samples and in eight of 32 bone marrow samples. There was no correlation between CK20-positive samples and subsequent extrahepatic recurrence. Positive blood samples did, however, correlate with high serum carcinoembryonic antigen level and large tumour volume. None of the 14 patients previously treated with chemotherapy had CK20-positive samples, whereas six of 27 blood and eight of 20 bone marrow samples were positive in the chemotherapy-naive group. CONCLUSION: Although the number of patients in this study is limited, the presence of disseminated tumour cells did not predict subsequent extrahepatic recurrence. The results strongly suggest that the presence of circulating tumour cells in peripheral blood may reflect transient shedding of tumour cells related to large tumour volume