Effect of remote ischemic preConditioning on liver injury in patients undergoing liver resection: the ERIC-LIVER trial

OBJECTIVE: Novel hepatoprotective strategies are needed to improve clinical outcomes during liver surgery. There is mixed data on the role of remote ischemic preconditioning (RIPC). We investigated RIPC in partial hepatectomy for primary hepatocellular carcinoma (HCC). METHODS: This was a Phase II, single-center, sham-controlled, randomized controlled trial (RCT). The primary hypothesis was that RIPC would reduce acute liver injury following surgery indicated by serum alanine transferase (ALT) 24 h following hepatectomy in patients with primary HCC, compared to sham. Patients were randomized to receive either four cycles of 5 min/5 min arm cuff inflation/deflation immediately prior to surgery, or sham. Secondary endpoints included clinical, biochemical and pathological outcomes. Liver function measured by Indocyanine Green pulse densitometry was performed in a subset of patients. RESULTS: 24 and 26 patients were randomized to RIPC and control groups respectively. The groups were balanced for baseline characteristics, except the duration of operation was longer in the RIPC group. Median ALT at 24 h was similar between groups (196 IU/L IQR 113.5-419.5 versus 172.5 IU/L IQR 115-298 respectively, p = 0.61). Groups were similar in secondary endpoints. CONCLUSION: This RCT did not demonstrate beneficial effects with RIPC on serum ALT levels 24 h after partial hepatectomy

Dynamic phenotypic heterogeneity and the evolution of multiple RNA subtypes in Hepatocellular Carcinoma: the PLANET study

Intra-tumor heterogeneity (ITH) is a key challenge in cancer treatment, but previous studies have focused mainly on the genomic alterations without exploring phenotypic (transcriptomic and immune) heterogeneity. Using one of the largest prospective surgical cohorts for Hepatocellular Carcinoma (HCC) with multi-region sampling, we sequenced whole genomes and paired transcriptomes from 67 HCC patients (331 samples). We found that while genomic ITH was rather constant across TNM stages, phenotypic ITH had a very different trajectory and quickly diversified in stage II patients. Most strikingly, 30% patients were found to contain more than one transcriptomic subtype within a single tumor. Such phenotypic ITH was found to be much more informative in predicting patient survival than genomic ITH and explains the poor efficacy of single-target systemic therapies in HCC. Taken together, we not only revealed an unprecedentedly dynamic landscape of phenotypic heterogeneity in HCC, but also highlighted the importance of studying phenotypic evolution across cancer types

Affordable and accessible 3D printed models of the liver to support medical education

Three-dimensional (3D) printing (also termed additive manufacturing) has been on the rise across industries and application areas. Advances in materials, printing technologies and affordability have sparked substantial activity in the healthcare and medical education domains, ranging from highly realistic 3D anatomical models for teaching and procedure rehearsal, as well as personalised implants and sophisticated MedTech devices. 3D printing is known for its ability to make people understand complex physical structures and produce difficult to obtain models. Our aim is to explore the use of low-cost SLA and FDM 3D printers to produce realistic anatomical models. Working closely with clinicians from Duke-NUS Medical School and Singapore General Hospital, a use case of the liver was chosen for anatomy teaching and simulation-based skills training, making use of a range of resins and multi-materials.The liver was selected as a good example of a solid organ with internal anatomical detail. In this paper, we will share our progress in 3D-printing liver models from both SLA and FDM printers, as well as the challenges, advantages, and disadvantages of using each of these technologies

Droplet-Based Microfluidics

Droplet-based microfluidics or digital microfluidics is a subclass of microfluidic devices, wherein droplets are generated using active or passive methods. The active method for generation of droplets involves the use of an external factor such as an electric field for droplet generation. Two techniques that fall in this category are dielectrophoresis (DEP) and electrowetting on dielectric (EWOD). In passive methods, the droplet generation depends on the geometry and dimensions of the device. T-junction and flow focusing methods are examples of passive methods used for generation of droplets. In this chapter the methods used for droplet generation, mixing of contents of droplets, and the manipulation of droplets are described in brief. A review of the applications of digital microfluidics with emphasis on the last decade is presented