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Clinical and biological characterization of skeletal muscle tissue biopsies of surgical cancer patients.
Journal of Cachexia, Sarcopenia and Muscle ( IF 9.4 ) Pub Date : 2019-07-15 , DOI: 10.1002/jcsm.12466
Ana Anoveros-Barrera 1 , Amritpal S Bhullar 1 , Cynthia Stretch 2 , Nina Esfandiari 3 , Abha R Dunichand-Hoedl 1 , Karen J B Martins 1 , David Bigam 4 , Rachel G Khadaroo 4 , Todd McMullen 4 , Oliver F Bathe 2, 5 , Sambasivarao Damaraju 3, 6 , Richard J Skipworth 7 , Charles T Putman 8 , Vickie E Baracos 3 , Vera C Mazurak 1
Affiliation  

BACKGROUND Researchers increasingly use intraoperative muscle biopsy to investigate mechanisms of skeletal muscle atrophy in patients with cancer. Muscles have been assessed for morphological, cellular, and biochemical features. The aim of this study was to conduct a state-of-the-science review of this literature and, secondly, to evaluate clinical and biological variation in biopsies of rectus abdominis (RA) muscle from a cohort of patients with malignancies. METHODS Literature was searched for reports on muscle biopsies from patients with a cancer diagnosis. Quality of reports and risk of bias were assessed. Data abstracted included patient characteristics and diagnoses, sample size, tissue collection and biobanking procedures, and results. A cohort of cancer patients (n = 190, 88% gastrointestinal malignancies), who underwent open abdominal surgery as part of their clinical care, consented to RA biopsy from the site of incision. Computed tomography (CT) scans were used to quantify total abdominal muscle and RA cross-sectional areas and radiodensity. Biopsies were assessed for muscle fibre area (μm2 ), fibre types, myosin heavy chain isoforms, and expression of genes selected for their involvement in catabolic pathways of muscle. RESULTS Muscle biopsy occurred in 59 studies (total N = 1585 participants). RA was biopsied intraoperatively in 40 studies (67%), followed by quadriceps (26%; percutaneous biopsy) and other muscles (7%). Cancer site and stage, % of male participants, and age were highly variable between studies. Details regarding patient medical history and biopsy procedures were frequently absent. Lack of description of the population(s) sampled and low sample size contributed to low quality and risk of bias. Weight-losing cases were compared with weight stable cancer or healthy controls without considering a measure of muscle mass in 21 out of 44 studies. In the cohort of patients providing biopsy for this study, 78% of patients had preoperative CT scans and a high proportion (64%) met published criteria for sarcopenia. Fibre type distribution in RA was type I (46% ± 13), hybrid type I/IIA (1% ± 1), type IIA (36% ± 10), hybrid type IIA/D (15% ± 14), and type IID (2% ± 5). Sexual dimorphism was prominent in RA CT cross-sectional area, mean fibre cross-sectional area, and in expression of genes associated with muscle growth, apoptosis, and inflammation (P < 0.05). Medical history revealed multiple co-morbid conditions and medications. CONCLUSIONS Continued collaboration between researchers and cancer surgeons enables a more complete understanding of mechanisms of cancer-associated muscle atrophy. Standardization of biobanking practices, tissue manipulation, patient characterization, and classification will enhance the consistency, reliability, and comparability of future studies.

中文翻译:

外科癌症患者骨骼肌组织活检的临床和生物学特征。

背景研究人员越来越多地使用术中肌肉活检来研究癌症患者骨骼肌萎缩的机制。已经评估了肌肉的形态、细胞和生化特征。本研究的目的是对该文献进行科学回顾,其次,评估一组恶性肿瘤患者腹直肌 (RA) 肌肉活检的临床和生物学变异。方法 检索文献,寻找来自癌症诊断患者的肌肉活检报告。评估报告的质量和偏倚风险。提取的数据包括患者特征和诊断、样本量、组织收集和生物样本库程序以及结果。一组癌症患者(n = 190,88% 为胃肠道恶性肿瘤),作为临床护理的一部分接受开腹手术的患者,同意从切口部位进行 RA 活检。计算机断层扫描 (CT) 扫描用于量化总腹部肌肉和 RA 横截面积和放射密度。评估活检的肌肉纤维面积 (μm2)、纤维类型、肌球蛋白重链异构体以及因参与肌肉分解代谢途径而选择的基因的表达。结果 59 项研究(总 N = 1585 名参与者)进行了肌肉活检。在 40 项研究 (67%) 中对 RA 进行了术中活检,其次是股四头肌 (26%;经皮活检) 和其他肌肉 (7%)。癌症部位和分期、男性参与者的百分比和年龄在研究之间差异很大。经常缺少有关患者病史和活检程序的详细信息。缺乏对抽样人群的描述和低样本量导致低质量和偏倚风险。在 44 项研究中的 21 项研究中,将减肥病例与体重稳定的癌症或健康对照组进行了比较,而没有考虑肌肉质量的测量。在为本研究提供活检的患者队列中,78% 的患者进行了术前 CT 扫描,并且很大一部分 (64%) 符合公布的肌肉减少症标准。RA中的纤维类型分布为I型(46%±13)、混合I/IIA型(1%±1)、IIA型(36%±10)、混合IIA/D型(15%±14)和IID (2% ± 5)。RA CT 横截面积、平均纤维横截面积以及与肌肉生长、细胞凋亡和炎症相关的基因表达中性别二态性显着(P < 0.05)。病史揭示了多种合并症和药物治疗。结论 研究人员和癌症外科医生之间的持续合作能够更全面地了解癌症相关肌肉萎缩的机制。生物样本库实践、组织操作、患者表征和分类的标准化将提高未来研究的一致性、可靠性和可比性。
更新日期:2019-11-18
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