We investigated whether detection of ctDNA after resection of colorectal cancer identifies the patients with the highest risk of relapse and, furthermore, whether longitudinal ctDNA analysis allows early detection of relapse and informs about response to intervention. In this longitudinal cohort study, we used massively parallel sequencing to identify somatic mutations and used these as ctDNA markers to detect minimal residual disease and to monitor changes in tumor burden during a 3-year follow-up period. A total of 45 patients and 371 plasma samples were included. Longitudinal samples from 27 patients revealed ctDNA postoperatively in all relapsing patients ( = 14), but not in any of the nonrelapsing patients. ctDNA detected relapse with an average lead time of 9.4 months compared with CT imaging. Of 21 patients treated for localized disease, six had ctDNA detected within 3 months after surgery. All six later relapsed compared with four of the remaining patients [HR, 37.7; 95% confidence interval (CI), 4.2-335.5; < 0.001]. The ability of a 3-month ctDNA analysis to predict relapse was confirmed in 23 liver metastasis patients (HR 4.9; 95% CI, 1.5-15.7; = 0.007). Changes in ctDNA levels induced by relapse intervention ( = 19) showed good agreement with changes in tumor volume (κ = 0.41; Spearman = 0.4). Postoperative ctDNA detection provides evidence of residual disease and identifies patients at very high risk of relapse. Longitudinal surveillance enables early detection of relapse and informs about response to intervention. These observations have implications for the postoperative management of colorectal cancer patients. .
The present study, which is the largest ever conducted in this treatment area, supports the hypothesis that PC is an effective treatment modality for critically ill patients with ACC unfit for surgery and results in a low rate of 30-day mortality.
Nearly 50% of patients recur within two years after curatively intended resection of colorectal cancer liver metastasis (CRLM). The optimal surveillance strategy is unknown due to the lack of evidence. Here, we explored the potential for improving postoperative CRLM surveillance by performing serial circulating tumour DNA (ctDNA) assessments parallel to standard-of-care surveillance. Experimental design: 499 prospectively collected serial plasma samples from 96 patients undergoing CRLM resection were analysed using the tumour-agnostic methylation multiplex droplet-digital PCR test 'TriMeth'. Results: Patients with ctDNA postoperatively or post adjuvant chemotherapy experienced a significant lower recurrence-free survival than patients without ctDNA (hazard ratio (HR)
Umbilical cord serum bilirubin concentration as a predictor of subsequent jaundice was studied in 291 newborns. It was possible to define subgroups of infants with significantly higher or lower risks of developing jaundice. If cord bilirubin was below 20 mumol/l, 2.9% became jaundiced as opposed to 85% if cord bilirubin was above 40 mumol/l. Furthermore, 57% of jaundiced infants with cord bilirubin above 40 mumol/l required phototherapy, but only 9% if cord bilirubin was 40 mumol/l or lower (p less than 0.003). Knowledge of infants at risk of developing jaundice allows simple bilirubin reducing methods to be implemented before jaundice is present and could influence a decision regarding early discharge from hospital. Since the ability of plasma to bind bilirubin in cord blood from jaundiced and non-jaundiced infants showed no significant differences, the increased cord bilirubin among infants who later became jaundiced is presumably caused by increased fetal bilirubin production or decreased removal of bilirubin from the fetal circulation.
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