Evaluation of health economic impact of initial diagnostic modality selection for colorectal cancer liver metastases in suspected patients in China, Japan and the USA.

AIMS: To compare cost offsets and contributing factors (false-negative rates and confirmatory imaging requirements, potentially leading to longer waiting times for diagnosis) as well as long-term cost effectiveness associated with the diagnostic and treatment pathways for colorectal cancer liver metastases (CRCLM) in the US, Japan, and China according to initial imaging modality used. Gadoxetate disodium (ethoxylbenzyl-diethylenetriaminepentaacetic acid)-enhanced magnetic resonance imaging (EOB-MRI) was compared to multidetector computed tomography (MDCT), extracellular contrast media enhanced-MRI (ECCM-MRI) (the US and China only) and contrast-enhanced ultrasound (CEUS). MATERIALS AND METHODS: Decision tree models were developed to simulate the clinical pathway, from first diagnostic test to initial treatment decision, based on local clinical guidelines and validated by experts. Input data were derived from the literature (up to 31st December 2020) as well as from interviews with local experts. A Markov model extension was built to evaluate the number of false-negative patients and associated costs, over a lifetime horizon. RESULTS: The decision-tree models showed that, increasing proportionate use of initial EOB-MRI resulted in a cost-offset per patient (excluding false-negative patients) in all countries (USD 201 for the US, JPY 6,284 for Japan and CNY 446 for China) driven by reductions in follow-on diagnostic procedures and unnecessary treatment. The use of EOB-MRI was also associated with a shorter average waiting time to a final diagnosis and treatment decision compared to MDCT, ECCM-MRI and CEUS. The Markov model showed that with an increase in EOB-MRI use, there are fewer false-negative diagnoses over a lifetime horizon. In all three countries, the incremental cost-effectivenes ratio (ICER) was below standard willingness-to-pay thresholds. CONCLUSION: The findings of these models demonstrate that use of EOB-MRI early in the diagnostic pathway for CRCLM results in short-term cost savings, as well as being cost effective in the long term.

Ultrafilter co-culture, a new method for estimating the molecular mass of bioactive substances, indicates a small molecule neurotrophic substance is released from cultured cerebellar granule neurons of the BALB/c mouse.

Cultured rat cerebellar granule neurons (CGNs), which require a depolarizing agent in the medium for long-term survival, are widely used for the analysis of mechanisms underlying the activity-dependent survival of neurons. It was recently found that this is not the case for BALB/c mouse CGNs, which survive without a depolarizing agent. Co-culture experiments indicated that the mouse cells release a neurotrophic substance. However, the substance is apparently short-living in the medium, making its molecular identification difficult. Here a novel co-culture method was devised for estimating the relative molecular masses of biologically active substances, using a commercially available dialysis membrane filter unit to separate substance-donor from substance-recipient cells. By this simultaneous fractionation/bioassay, the molecular mass of the assumed neurotrophic substance was estimated to be <3 kDa. Neurotrophic substances previously reported to be effective in rat CGNs, including neurotrophins, pituitary adenylate cyclase-activating polypeptide, parathyroid hormone-related polypeptide, glutamic acid, gamma-aminobutyric acid, and D-serine, were excluded as candidate molecules. Estrogen, however, remained a candidate. It should be stressed that the requirements for the activity-dependent survival of CGNs are species-dependent. Care should be taken in the analysis of activity-dependent neuronal survival using transgenic animals.