[The risk of cancer in the Netherlands]. / De kans op kanker voor Nederlanders.

OBJECTIVE: Calculation of valid and detailed risks of cancer from, and up to, specific ages for inhabitants of the Netherlands. DESIGN: Secondary analyses of cancer incidence and mortality rates. METHOD: Gender and age-specific incidence rates of 56 different types of cancer were obtained from the Netherlands Cancer Registry. Gender and age-specific mortality rates were obtained from Statistics Netherlands. Using survival charts, risks of cancer were calculated from all ages and up to all ages, in steps of 5 years. The US National Cancer Institute's software programme DevCan was used for analyses. RESULTS: One out of every 2.3 newborn males (43.9%) and one out of every 2.6 newborn females (38.1%) in the Netherlands will develop cancer sometime during their life. The risk of developing cancer before the age of 80 is 35.9% for newborn males and 30.2% for newborn females. Women run the greatest risk of developing breast cancer (almost 13%). 50-year-old women have a risk of almost 3% of being diagnosed with breast cancer before the age of 60. Men have the greatest risk of a diagnosis of prostate cancer (almost 10%). The risk for a 50-year-old man of being diagnosed with prostate cancer within the subsequent 10 years however is less than 1%. CONCLUSION: Detailed rates of risks of cancer are useful for policy issues such as decisions to implement screening programmes, for public education, and for patient counselling, as in the field of clinical genetics. The routinely reported risks for newborns developing cancer before the age of 75 lack the necessary detail for such use.

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

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.

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

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.

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.

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

BACKGROUND: 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.

Relevance of disseminated tumour cells in blood and bone marrow of patients with solid epithelial tumours in perspective.

Currently-used systems to predict prognosis in patients with solid epithelial tumours after surgical resection of the tumour do not give any guarantees for the individual patient. In this respect the clinical relevance of the presence of disseminated tumour cells in blood and bone marrow has been frequently studied. Because of growing awareness that information on merely the presence of disseminated tumour cells is not sufficient for prognostic and therapeutic purposes, attention for characterization of disseminated tumour cells has increased. Numerous reviews have already been published on the detection and clinical relevance of disseminated tumour cells. Therefore, this paper will mainly focus on the biological significance of these cells and discusses the (in)efficiency of the metastatic process, the genotypic and phenotypic characteristics of disseminated tumour cells, and their structure of appearance. Despite the fact that information gained on the several individual aspects is substantial, it did not render any solid solutions for individual patient management yet. Hence, a combined approach of several aspects of disseminated tumour cells together with characteristics and behaviour of the primary tumour is needed to substantially improve our knowledge on the role of disseminated tumour cells in the complex process of tumour metastasis.

Reliability of quantitative reverse-transcriptase-PCR-based detection of tumour cells in the blood between different laboratories using a standardised protocol.

Differences in methods of reverse-transcriptase (RT)-polymerase chain reaction (PCR)-based detection of tumour cells in the blood gives rise to conflicting results, and standardisation is urgently needed. This pilot study aimed to assess the variation of RT-PCR-based detection of tumour cells in blood between four different laboratories using a commercially available kit with a standardised protocol. This kit allows comparison of results from different laboratories and facilitates the investigation of the influence of pre-analytical parameters. All laboratories analysed identical sets of blood samples spiked with tumour cells in a concentration range of 1-100 tumour cells/ml. To study at which level variation was introduced, three kinds of sample sets were generated in which (i) tumour cell RNA was spiked in the RNA of mononuclear cells (MNC), (ii) tumour cells were spiked in isolated MNC, and (iii) tumour cells were spiked in blood. Real-time quantitative RT-PCR was used to detect and quantify cytokeratin 20 (CK20) expression, which is indicative for the presence of epithelial tumour cells. All laboratories were able to detect CK20 expression in all spiked-RNA samples with limited variation in expression levels between laboratories. There was a positive correlation between the amount of spiked tumour cell RNA and CK20 expression level. RT-PCR analysis of spiked-MNC samples resulted in more variation in the CK20 expression levels between laboratories, however again all spiked samples were reported to be positive by all of the laboratories. The evaluation of spiked-blood samples gave rise to considerable quantitative and qualitative variation between the laboratories. Our results underline the importance and need for standardisation and extended quality control studies in the field of pre-analytics.

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.

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.