Systematic Review and Meta-Analysis of Epidural Analgesia Versus Different Analgesic Regimes Following Oesophagogastric Resection.

INTRODUCTION: Effective analgesia following open oesophagogastric (OG) resection is considered a key determinant of recovery. This review aimed to compare epidural to alternative analgesic techniques in patients undergoing major open resection for OG cancer. METHODS: A systematic review and meta-analysis was conducted of randomized controlled trials comparing epidural with alternative analgesic methods in open OG surgery. Primary outcome was the overall post-operative morbidity rate. Secondary outcomes included pulmonary complication rates, length of stay (LOS) and pain scores at 24 h. RESULTS: Six trials which comprised of 249 patients were identified (3 following gastrectomy and 3 following oesophagectomy). Following gastrectomy, secondary outcomes including pulmonary complications and dynamic pain scores at 24 h were improved in the epidural groups. No difference was observed in overall morbidity rates or LOS. Following oesophagectomy, overall morbidity rates were not reported at all. LOS was not shortened, and rest pain was not significantly different in the epidural group, but dynamic pain scores were reported to be improved. CONCLUSION: Few trials of analgesic regimen have been performed following open OG resection. In those trials that have been performed, epidural analgesia has not been shown to reduce overall morbidity. Epidural is associated with reduced pulmonary complications after gastrectomy, but no benefit has been shown after oesophagectomy. Whilst widespread investigation of minimally invasive OG techniques currently takes place, it is clear that the most effective patient pathway following open OG surgery, particularly oesophagectomy, is still not proven. Further trials are required.

New genetic signatures associated with cancer cachexia as defined by low skeletal muscle index and weight loss.

BACKGROUND: Cachexia affects the majority with advanced cancer. Based on current demographic and clinical factors, it is not possible to predict who will develop cachexia or not. Such variation may, in part, be due to genotype. It has recently been proposed to extend the diagnostic criteria for cachexia to include a direct measure of low skeletal muscle index (LSMI) in addition to weight loss (WL). We aimed to explore our panel of candidate single nucleotide polymorphism (SNPs) for association with WL +/- computerized tomography-defined LSMI. We also explored whether the transcription in muscle of identified genes was altered according to such cachexia phenotype METHODS: A retrospective cohort study design was used. Analysis explored associations of candidate SNPs with WL (n = 1276) and WL + LSMI (n = 943). Human muscle transcriptome (n = 134) was analysed using an Agilent platform. RESULTS: Single nucleotide polymorphisms in the following genes showed association with WL alone: GCKR, LEPR, SELP, ACVR2B, TLR4, FOXO3, IGF1, CPN1, APOE, FOXO1, and GHRL. SNPs in LEPR, ACVR2B, TNF, and ACE were associated with concurrent WL + LSMI. There was concordance between muscle-specific expression for ACVR2B, FOXO1 and 3, LEPR, GCKR, and TLR4 genes and LSMI and/or WL (P < 0.05). CONCLUSIONS: The rs1799964 in the TNF gene and rs4291 in the ACE gene are new associations when the definition of cachexia is based on a combination of WL and LSMI. These findings focus attention on pro-inflammatory cytokines and the renin-angiotensin system as biomarkers/mediators of muscle wasting in cachexia.

P-selectin genotype is associated with the development of cancer cachexia.

The variable predisposition to cachexia may, in part, be due to the interaction of host genotype. We analyzed 129 single nucleotide polymorphisms (SNPs) in 80 genes for association with cachexia based on degree of weight loss (>5, >10, >15%) as well as weight loss in the presence of systemic inflammation (C-reactive protein, > 10 mg/l). 775 cancer patients were studied with a validation association study performed on an independently recruited cohort (n = 101) of cancer patients. The C allele (minor allele frequency 10.7%) of the rs6136 (SELP) SNP was found to be associated with weight loss >10% both in the discovery study (odds ratio (OR) 0.52; 95% confidence intervals (CI), 0.29-0.93; p = 0.026) and the validation study (OR 0.09, 95% CI 0.01-0.98, p = 0.035). In separate studies, induction of muscle atrophy gene expression was investigated using qPCR following either tumour-induced cachexia in rats or intra-peritoneal injection of lipopolysaccharide in mice. P-selectin was found to be significantly upregulated in muscle in both models. Identification of P-selectin as relevant in both animal models and in cachectic cancer patients supports this as a risk factor/potential mediator in cachexia.