Cachexia is a devastating muscle-wasting syndrome that occurs in patients who have chronic diseases. It is most commonly observed in individuals with advanced cancer, presenting in 80% of these patients, and it is one of the primary causes of morbidity and mortality associated with cancer. Additionally, although many people with cachexia show hypermetabolism, the causative role of metabolism in muscle atrophy has been unclear. To understand the molecular basis of cachexia-associated muscle atrophy, it is necessary to develop accurate models of the condition. By using transcriptomics and cytokine profiling of human muscle stem cell-based models and human cancer-induced cachexia models in mice, we found that cachectic cancer cells secreted many inflammatory factors that rapidly led to high levels of fatty acid metabolism and to the activation of a p38 stress-response signature in skeletal muscles, before manifestation of cachectic muscle atrophy occurred. Metabolomics profiling revealed that factors secreted by cachectic cancer cells rapidly induce excessive fatty acid oxidation in human myotubes, which leads to oxidative stress, p38 activation and impaired muscle growth. Pharmacological blockade of fatty acid oxidation not only rescued human myotubes, but also improved muscle mass and body weight in cancer cachexia models in vivo. Therefore, fatty acid-induced oxidative stress could be targeted to prevent cancer-induced cachexia.

Intratumor heterogeneity (ITH) contributes to cancer progression and chemoresistance. We sought to comprehensively describe ITH of somatic mutations, copy number, and transcriptomic alterations involving clinically and biologically relevant gene pathways in colorectal cancer (CRC). We performed multiregion, high‐depth (384× on average) sequencing of 799 cancer‐associated genes in 24 spatially separated primary tumor and nonmalignant tissues from four treatment‐naïve CRC patients. We then used ultra‐deep sequencing (17 075× on average) to accurately verify the presence or absence of identified somatic mutations in each sector. We also digitally measured gene expression and copy number alterations using NanoString assays. We identified the subclonal point mutations and determined the mutational timing and phylogenetic relationships among spatially separated sectors of each tumor. Truncal mutations, those shared by all sectors in the tumor, affected the well‐described driver genes such as APC, TP53, and KRAS. With sequencing at 17 075×, we found that mutations first detected at a sequencing depth of 384× were in fact more widely shared among sectors than originally assessed. Interestingly, ultra‐deep sequencing also revealed some mutations that were present in all spatially dispersed sectors, but at subclonal levels. Ultra‐high‐depth validation sequencing, copy number analysis, and gene expression profiling provided a comprehensive and accurate genomic landscape of spatial heterogeneity in CRC. Ultra‐deep sequencing allowed more sensitive detection of somatic mutations and a more accurate assessment of ITH. By detecting the subclonal mutations with ultra‐deep sequencing, we traced the genomic histories of each tumor and the relative timing of mutational events. We found evidence of early mixing, in which the subclonal ancestral mutations intermixed across the sectors before the acquisition of subsequent nontruncal mutations. Our findings also indicate that different CRC patients display markedly variable ITH, suggesting that each patient's tumor possesses a unique genomic history and spatial organization.

Aims To evaluate preliminary effects of a newly developed STOMA psychosocial intervention programme that was delivered via a multi‐modal and multi‐dimensional approach on the improvement of outcomes of colorectal cancer patients with stoma. Background With a distorted body image and the loss of an essential body function, stoma patients face difficulties in everyday life in terms of physical, psychological, and social aspects. Few studies have explored effects of psychosocial interventions on improving stoma‐related health outcomes. Design This was a two‐group pre‐test‐post‐test pilot randomized controlled trial. Methods Fifty‐three participants were recruited from July 2015–November 2016 in a tertiary public hospital in Singapore. They were randomized into either intervention group (N = 29) or control group (N = 24). Stoma care self‐efficacy, acceptance of stoma, stoma proficiency, length of hospital stay, anxiety and depression and quality of life were measured. IBM SPSS 24.0 was used to analyse the data. Results There was an improvement in acceptance of stoma in the intervention group (p < 0.05). Significant effects on stoma care self‐efficacy, stoma proficiency, length of hospital stay, anxiety and depression level and quality of life were not shown. Conclusion This study developed a feasible and applicable psychosocial intervention programme and generated preliminary evidence in the positive outcomes of colorectal cancer patients with stoma. Future studies can explore technology‐based interventions to provide a more sustainable support for patients with stoma.

TGN 0.2 per cent ointment improved wound healing rates, but did not reduce pain in this study.

This study will develop a psychosocial intervention programme, which may improve patients' stoma-related outcomes. The findings will provide direction to health professionals about education and the type of support that could be offered to patients concerning stoma care in the hospital setting, which will eventually improve their quality of life.