Department of Agricultural, Food and Nutritional Science, Faculty of Agricultural, Life and Environmental Sciences, University of Alberta, Edmonton, AB, Canada.
Department of Oncology, University of Calgary, Calgary, AB, Canada.
J Cachexia Sarcopenia Muscle. 2019 Dec;10(6):1356-1377. doi: 10.1002/jcsm.12466. Epub 2019 Jul 15.
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.
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 (μm ), fibre types, myosin heavy chain isoforms, and expression of genes selected for their involvement in catabolic pathways of muscle.
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.
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.
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。肌肉的形态、细胞和生化特征已经得到评估。本研究的目的是对这一文献进行综述，并评估来自癌症患者队列的腹直肌（RA）活检的临床和生物学变异性。
检索了关于癌症患者肌肉活检的报告。评估了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、组织采集和生物样本库程序以及结果。作为临床护理的一部分，接受开放式腹部手术的癌症患者队列（n = 190，88%为胃肠道恶性肿瘤）同意从切口部位进行 RA 活检。使用计算机断层扫描（CT）扫描来量化腹部肌肉和 RA 横截面积和放射密度。对肌肉纤维面积（μm）、纤维类型、肌球蛋白重链同工型以及选择参与肌肉分解代谢途径的基因表达进行评估。
在 59 项研究中进行了肌肉活检（总 N = 1585 名参与者）。40 项研究（67%）在术中进行 RA 活检，26%（经皮活检）和其他肌肉（7%）。研究之间癌症部位和分期、男性参与者的百分比和年龄差异很大。关于患者病史和活检程序的详细信息经常缺失。缺乏对采样人群的描述和样本量小导致了低质量和偏倚风险。在 44 项研究中有 21 项将体重减轻的病例与体重稳定的癌症或健康对照进行比较，而没有考虑肌肉量的测量。在为本研究提供活检的患者队列中，78%的患者有术前 CT 扫描，高比例（64%）符合发表的肌少症标准。RA 中的纤维类型分布为 I 型（46%±13）、I/IIA 混合型（1%±1）、IIA 型（36%±10）、IIA/D 混合型（15%±14）和 IID 型（2%±5）。RA 的 CT 横截面积、平均纤维横截面积以及与肌肉生长、凋亡和炎症相关的基因表达存在明显的性别二态性（P < 0.05）。病史揭示了多种合并症和药物治疗。
研究人员与癌症外科医生的持续合作使我们更全面地了解癌症相关肌肉萎缩的机制。生物样本库实践、组织处理、患者特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。
