Assessment of a Size-Based Method for Enriching Circulating Tumour Cells in Colorectal Cancer.

Circulating tumour cells (CTC) from solid tumours are a prerequisite for metastasis. Isolating CTCs and understanding their biology is essential for developing new clinical tests and precision oncology. Currently, CellSearch is the only FDA (U.S. Food and Drug Administration)-approved method for CTC enrichment but possesses several drawbacks owing to a reliance on the epithelial cell adhesion molecule (EpCAM) and a resource-intensive nature. Addressing these shortcomings, we optimised an existing size-based method, MetaCell, to enrich CTCs from blood of colorectal cancer (CRC) patients. We evaluated the ability of MetaCell to enrich CTCs by spiking blood with CRC cell lines and assessing the cell recovery rates and WBC depletion via immunostaining and gene expression. We then applied MetaCell to samples from 17 CRC patients and seven controls. Recovery rates were >85% in cell lines, with >95% depletion in WBCs. MetaCell yielded CTCs and CTC clusters in 52.9% and 23.5% of the patients, respectively, without false positives in control patients. CTCs and cluster detection did not correlate with histopathological parameters. Overall, we demonstrated that the MetaCell platform enriched CRC cells with high recovery rates and high purity. Our pilot study also demonstrated the ability of MetaCell to detect CTCs in CRC patients.

Oral ß-blockade in relation to energy expenditure in clinically stable patients with liver cirrhosis: a double-blind randomized cross-over trial.

Elevated resting energy expenditure (REE) is seen in liver cirrhosis and is associated with reduced transplant-free survival. Non-selective ß-blockers reduce REE in acute hypermetabolic conditions. We examined whether non-selective ß-blockers reduce REE in patients with stable liver cirrhosis. Twenty-two stable cirrhotic patients (Child-Pugh grading: 19A, 2B, 1C) were randomized to 3-month treatment with nadolol (titrated to decrease resting pulse rate by 20%) or placebo and after a 1-month washout period crossed to the alternative treatment for a further 3 months. REE was measured by indirect calorimetry and total body protein by neutron activation analysis at the beginning and end of each 3-month period of treatment. A predicted REE was calculated for each patient based on total body protein. A measured to predicted REE ratio >1.22 indicated significantly elevated REE. The primary outcome was REE at the end of 3-month treatment with nadolol compared with placebo. Elevated REE was seen in one patient at study entry. After 3 months on placebo REE was 1506±40 (SEM) kcal/d and on nadolol, 1476±40 kcal/d, a mean reduction of 31±16 kcal/d (P=.076). Total body protein changes were not significant. Nadolol was well tolerated with no increase in the rate of adverse events. In stable cirrhotic patients, nadolol was not associated with reduction in REE. A larger, longer-term study with different eligibility criteria is required to investigate whether this treatment offers benefits additional to its use for prevention of variceal hemorrhage.

Body composition, muscle function, and energy expenditure in patients with liver cirrhosis: a comprehensive study.

BACKGROUND: Data describing the nutritional status of patients with liver cirrhosis of diverse origin, as assessed by direct body-composition methods, are limited. OBJECTIVE: We sought to provide a comprehensive assessment of nutritional status and metabolic activity in patients with liver cirrhosis by using the most accurate direct methods available. DESIGN: Two hundred sixty-eight patients (179 M, 89 F; x +/- SEM age: 50.1 +/- 0.6 y) with liver cirrhosis underwent measurements of total body protein by neutron activation analysis, of total body fat and bone mineral by dual-energy X-ray absorptiometry, of resting energy expenditure by indirect calorimetry, of grip strength by dynamometry, and of respiratory muscle strength by using a pressure transducer. Dietary intakes of energy and protein were assessed and indexed to resting energy expenditure and energy intake, respectively. RESULTS: Significant protein depletion, seen in 51% of patients, was significantly (P<0.0001) more prevalent in men (63%) than in women (28%). This sex difference occurred irrespective of disease severity or origin. The prevalence of protein depletion increased significantly (P<0.0001) with disease severity. Protein depletion was associated with decreased muscle function but not with lower energy and protein intake. Energy intake was significantly (P=0.002) higher in men than in women, whereas protein intakes did not differ significantly (P=0.12). Hypermetabolism, seen in 15% of patients, was not associated with sex, origin or severity of disease, protein depletion, ascites, or presence of tumor. CONCLUSIONS: Poor nutritional status with protein depletion and reduced muscle function was a common finding, particularly in men, and was not related to the presence of hypermetabolism or reduced energy and protein intakes. The greater conservation of protein stores in women than in men warrants further investigation.