Circulating miR-203 derived from metastatic tissues promotes myopenia in colorectal cancer patients

Sarcopenia frequently occurs in metastatic cancer patients. Emerging evidence has revealed that various secretory products from metastatic tumours can influence host organs and promote sarcopenia in patients with malignancies. Furthermore, the biological functions of microRNAs in cell-to-cell communication by incorporating into neighbouring or distal cells, which have been gradually elucidated in various diseases, including sarcopenia, have been elucidated. We evaluated psoas muscle mass index (PMI) and intramuscular adipose tissue content (IMAC) using pre-operative computed tomography imaging in 183 colorectal cancer (CRC) patients. miR-203 expression levels in CRC tissues and pre-operative serum were evaluated using quantitative polymerase chain reaction. Functional analysis of miR-203 overexpression was investigated in human skeletal muscle cells (SkMCs), and cells were analysed for proliferation and apoptosis. Expressions of several putative miR-203 target genes (CASP3, CASP10, BIRC5, BMI1, BIRC2, and BIRC3) in SKMCs were validated. A total of 183 patients (108 men and 75 women) were included. The median age of enrolled patients at diagnosis was 68.0 years (range 35-89 years). High IMAC status significantly correlated with female gender (P = 0.004) and older age (P = 0.0003); however, no other clinicopathological factors correlated with IMAC status in CRC patients. In contrast, decreased PMI significantly correlated with female gender (P = 0.006) and all well-established disease development factors, including advanced T stage (P = 0.035), presence of venous invasion (P = 0.034), lymphovascular invasion (P = 0.012), lymph node (P = 0.001), distant metastasis (P = 0.002), and advanced Union for International Cancer Control tumour-node-metastasis stage classification (P = 0.0004). Although both high IMAC status and low PMI status significantly correlated with poor overall survival (IMAC: P = 0.0002; PMI: P < 0.0001; log-rank test) and disease-free survival (IMAC: P = 0.0003; PMI: P = 0.0002; log-rank test), multivariate Cox's regression analysis revealed that low PMI was an independent prognostic factor for both overall survival (hazard ratio: 4.69, 95% confidence interval (CI): 2.19-10, P = 0.0001) and disease-free survival (hazard ratio: 2.33, 95% CI: 1.14-4.77, P = 0.021) in CRC patients. Serum miR-203 expression negatively correlated with pre-operative PMI level (P = 0.0001, ρ = -0.25), and multivariate logistic regression analysis revealed that elevated serum miR-203 was an independent risk factor for myopenia (low PMI) in CRC patients (odds ratio: 5.16, 95% CI: 1.8-14.8, P = 0.002). Overexpression of miR-203 inhibited cell proliferation and induced apoptosis via down-regulation of BIRC5 (survivin) expression in human SkMC line. Assessment of serum miR-203 expression could be used for risk assessment of myopenia, and miR-203 might be a novel therapeutic target for inhibition of myopenia in CRC

Block of the Ganglion Impar for Treatment of a Patieat with Non-malignant Chronic Perineal Pain

A 62 year-old woman with chronic perineal pain was successfully managed by chemical neurolysis. When she was referred to us, other practitioners had already investigated her. However, the cause of pain was not identified and the pain was refractory to conventional analgesic treatment. She underwent caudal block with 0.25% bupivacaine 5 ml six times to avoid placebo response of the block prior to therapeutic neurolysis. Then, block of the ganglion impar with phenol water under fluoroscopy was performed. Six months later, she still has no pain

Differences In Duration and Magnitude of Vasodilative Effect by Sympathetic Block with Ropivacaine 0.2 % and Mepivacaine 0.5 % in Dogs

To clarify differences in the duration and magnitude of vasodilative effect induced by sympathetic block with ropivacaine and mepivacaine. We measured mean arterial pressure (MAP), heart rate (HR), and right and left brachial artery blood flow (BABF) before and after stellate ganglion block (SGB) used as sympathetic block in twelve dogs. The experimental protocol was designed as follows : (1) left SGB using 0.2% ropivacaine 1.0 mL (n=6) and left SGB using 0.5 % mepivacaine 1 mL (n=6). MAP and HR did not change significantly through-out the study in either group. Left SGB with ropivacaine increased left BABF significantly from 5 min through 80 min after SGB (baseline, 100% ; peak at 10 min after SGB, 257±39% ; P<0.01). Left SGB with mepivacaine increased left BABF significantly from 5 min through 50 min after SGB (baseline, 100% ; peak at 10 min after SGB, 183±31% ; P<0.01). The values of left BABF after SGB with ropivacaine were significantly higher than those of SGB with mepivacaine from 5 min through 80 min after the block. Right BABF after left SGB decreased in both groups. Sympathetic block with 0.2% ropivacaine induces significant increases in both duration and magnitude of action in the peripheral blood flow compared with that of 0.5% mepivacaine

Close relationship between immunological/inflammatory markers and myopenia and myosteatosis in patients With colorectal cancer: A Propensity score matching analysis

The systemic inflammatory response (SIR) via host-tumor interactions has been termed the seventh hallmark of cancer, and several studies demonstrated that SIR might be a pivotal mediator for progression of cancer cachexia. The objective of this study was to clarify the correlation between sarcopenia and SIR in patients with colorectal cancer (CRC). A total of 308 patients with CRC were enrolled in this study. Preoperative psoas muscle mass index and intramuscular adipose tissue content were evaluated using preoperative computed tomographic images, and the correlation between body composition status and several SIR markers, including C-reactive protein (CRP), serum albumin level, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and systemic immune-inflammation index (SII) was assessed using statistical methods. Whereas preoperative myosteatosis was not correlated with clinicopathological factors except for aging and the presence of lymphovascular invasion, preoperative myopenia was significantly associated with well-established clinicopathological factors. Furthermore, the presence of myopenia was significantly correlated with elevated CRP, SII, and neutrophil-platelet score, and decreased lymphocyte-monocyte ratio, prognostic nutrition index, and serum albumin level. Logistic regression analysis revealed that an elevated CRP concentration was an independent risk factor for the presence of preoperative myopenia (odds ratio [OR] 2.49, 95% CI: 1.31-4.72; P = .005). Furthermore, these findings were validated using propensity score matching analysis (OR 2.35, 95% CI: 1.17-4.75; P = .017). Quantification of preoperative CRP could identify patients at high risk for development of myopenia who will likely require individualized treatment plans, including postoperative nutrition intervention, rehabilitation, and oncological follow-up in patients with CRC. [Abstract copyright: © 2018 American Society for Parenteral and Enteral Nutrition.