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Summary Very few patients with liver metastases from colorectal cancer can be cured. We have investigated whether a treatment to slow the growth of liver metastases, hepatic-artery infusion of floxuridine, improves palliation in this setting. In a randomised study of 100 patients, we compared quality of life and survival in patients who received hepatic-artery infusion of floxuridine and in those who received conventional symptom palliation. 95% of control patient survival time was spent with normal quality-of-life scores, which suggests that the aim of treatment should be to prolong normal-quality survival rather than merely to sustain quality of life. There was a significant prolongation (p=0·03) in overall survival in floxuridine-treated patients compared with controls (median 405 vs 226 days). There were similar significant prolongations in normal-quality (ie, normal symptom scores) survival for physical symptoms (p=0·04), anxiety (p=0·04), and depression (p=0·04). This survival benefit was associated with significant reductions in metastasis size on computed tomography (p=0·001) and in serum carcinoembryonic antigen concentration (p=0·006) in floxuridine-treated patients. There was no evidence of treatment-related hepatotoxicity as assessed by serum aspartate aminotransferase and bilirubin measurements. This is the first demonstration that survival can be prolonged with normal quality of life in patients with colorectal liver metastases. We conclude that hepatic-artery floxuridine infusion can be recommended for suitable patients.

The aim of this study was to determine whether flow cytometry (FACS) could detect spiked or circulating colorectal cancer cells. A flow cytometric assay was developed and its sensitivity compared with the reverse transcription polymerase-chain reaction (RT-PCR), using carcinoembryonic antigen (CEA) and cytokeratin (CK) 20 mRNA as target markers. Sensitivity limits for RT-PCR and flow cytometry (FACS) were established using spiked blood, and pre-operative blood samples from 20 colorectal cancer patients and 16 healthy no-cancer controls were analysed for circulating tumour cells (CTC) using both methods. Blood samples for FACS analysis were immuno-magnetically enriched using ferrofluid particles. CTC were defined as positive for pan-cytokeratin and negative for CD45 pan-leucocyte antigen (CK+/CD45- events). There was a significant (P < 0.0001) correlation between the number of spiked cancer cells and their recovery using FACS. The lowest detectable concentration was 20 spiked cancer cells in 14 ml blood for both RT-PCR and FACS. A positive FACS result significantly (P < 0.05) concurred with a positive RT-PCR result in spiked blood. The number of CK+/CD45- events detected in the blood of colorectal cancer patients was not significantly greater (P = 0.07) than in blood taken from 'no cancer' controls and furthermore there was no concordance (P = 1) between RT-PCR and FACS positivity in cancer patients' blood. FACS detection of tumour cells was feasible in vitro, and correlated with RT-PCR. However, its sensitivity in vivo was poor and did not correlate with RT-PCR detection of CTC. Uncertainties about antigen expression on normal circulating cells and about CTC phenotype need to be resolved, before FACS can be developed for detection of tumour cells within the circulation.

We assessed whether circulating cell positivity using RT-PCR for carcinoembryonic antigen (CEA) cDNA was affected by venesection via a needle compared with a pre-aspirated venous cannula, and by increased PCR cycles. Systemic blood was sampled by needle and pre-aspirated cannula in 101 healthy individuals with no cancer history. After erythrocyte removal, samples were subjected to RT-PCR using specific primers for CEA, with 29 or 35 RT-PCR cycles. There was a significant difference between the number of subjects whose samples were negative when collected via needle venesection and positive when collected via pre-aspirated cannula, compared with positive by needle venesection and negative by pre-aspirated cannula for both 29 (P = 0.016) and 35 (P = 0.0111) RT-PCR cycles. Venesection technique (P = 0.01) and number of cycles (P = 0.003) were significant predictors of a positive result. Positive results in healthy subjects were reduced to less than 3% when an aspirated cannula was used for venesection and >29 PCR cycles were avoided.