Hydroxymethylation profile of cell-free DNA is a biomarker for early colorectal cancer.

Early detection of cancer will improve survival rates. The blood biomarker 5-hydroxymethylcytosine has been shown to discriminate cancer. In a large covariate-controlled study of over two thousand individual blood samples, we created, tested and explored the properties of a 5-hydroxymethylcytosine-based classifier to detect colorectal cancer (CRC). In an independent validation sample set, the classifier discriminated CRC samples from controls with an area under the receiver operating characteristic curve (AUC) of 90% (95% CI [87, 93]). Sensitivity was 55% at 95% specificity. Performance was similar for early stage 1 (AUC 89%; 95% CI [83, 94]) and late stage 4 CRC (AUC 94%; 95% CI [89, 98]). The classifier could detect CRC even when the proportion of tumor DNA in blood was undetectable by other methods. Expanding the classifier to include information about cell-free DNA fragment size and abundance across the genome led to gains in sensitivity (63% at 95% specificity), with similar overall performance (AUC 91%; 95% CI [89, 94]). We confirm that 5-hydroxymethylcytosine can be used to detect CRC, even in early-stage disease. Therefore, the inclusion of 5-hydroxymethylcytosine in multianalyte testing could improve sensitivity for the detection of early-stage cancer.

Assessment of radionuclide arthrography in the evaluation of loosening of knee prostheses.

BACKGROUND: Radionuclide arthrography (RNA) is an established technique in the evaluation of hip prostheses but there is scant literature on its role in knee prostheses and no data specifically related to unicompartmental knee prostheses. We reviewed our experience with radionuclide arthrography in total (TKRs) and unicompartmental (UKRs) knee arthroplasties. METHODS: A retrospective review of 66 consecutive RNA studies that either had direct surgical correlation or arthroscopic assessment in conjunction with at least 12 months of clinical and radiological follow-up. These formed the basis of our case note review. 26 studies had a confirmed diagnosis of prosthetic loosening. RESULTS: By using standardised criteria for diagnosis and an early and late imaging protocol at 30 min and 4 h, RNA had an overall sensitivity of 88% and a specificity of 88% for the diagnosis of prosthetic loosening. The individual sensitivities and specificities were 93% and 86% for TKRs and 82% and 92% for UKRs. The technique was unable to detect femoral component loosening unless a long femoral stem was present, although only 8% of episodes of prosthetic loosening did not involve the tibial component. CONCLUSION: Radionuclide arthrography should be considered as a useful diagnostic test for the evaluation of loosening of the tibial component of knee prostheses but requires early and late imaging and close attention to detail to achieve optimal results.