William Harvey Research Institute, Barts and the London School of Medicine, London, UK.
Universidade de Lisboa, Lisbon Academic Medical Centre and Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal.
Arthritis Rheumatol. 2018 May;70(5):702-710. doi: 10.1002/art.40433. Epub 2018 Apr 2.
To evaluate whether the choice of synovial biopsy technique (arthroscopy, blind needle [BN] biopsy, ultrasound [US]-guided portal and forceps [P&F], or US-guided needle biopsy [NB]) translates to significant variation in synovial tissue quality and quantity, with the aim of informing recommendations for the choice of synovial sampling technique within clinical trials.
In total, 159 procedures from 5 academic rheumatology centers were evaluated. Hematoxylin and eosin-stained, paraffin-embedded synovial tissue sections from patients with inflammatory arthritis were assessed in order to determine the proportion of graded synovial fragments, total area of graded synovial tissue, and synovitis score per procedure. RNA quantity (μg of RNA) and quality (RNA integrity number) per procedure were also assessed in the synovial samples.
In this study, 84 of the 159 procedures performed on large joints at baseline (25 arthroscopic, 35 US-P&F, 11 US-NB, and 13 BN biopsies), 41 of the 159 procedures performed on small joints at baseline (11 US-P&F, 20 US-NB, and 10 BN biopsies), and 34 sequential biopsy procedures were evaluated. Compared to all other techniques evaluated in the small and large joints, fewer small joint BN biopsies and a significantly lower proportion of large joint BN biopsies yielded graded synovial tissue. No significant difference in either the proportion of graded tissue samples or total graded synovial tissue area between the US-NB and arthroscopic large joint procedures was demonstrated. Among the sequential biopsy procedures evaluated (small joint US-NB, large joint arthroscopy, US-P&F biopsy, and BN biopsy), no significant difference in the proportion of graded synovial tissue or total graded synovial tissue area was demonstrated. All procedures yielded RNA of significant quality and quantity for subsequent transcriptomic analysis.
These data support the integration of US-guided methods along with arthroscopic biopsy for clinical trial protocols in which sequential sampling of synovium from the large and small joints is needed for both histologic and molecular analysis. BN biopsy may be considered if graded synovial tissue is not required for subsequent analyses.
评估滑膜活检技术(关节镜、盲针[BN]活检、超声[US]-引导的端口和钳子[P&F]、或 US-引导的针活检[NB])的选择是否会导致滑膜组织质量和数量的显著差异,旨在为临床试验中滑膜取样技术的选择提供建议。
共评估了 5 个学术风湿病中心的 159 例操作。评估了来自炎症性关节炎患者的苏木精和伊红染色、石蜡包埋的滑膜组织切片,以确定分级滑膜碎片的比例、分级滑膜组织的总面积和每个操作的滑膜炎评分。还评估了每个操作的滑膜样本的 RNA 量(μg RNA)和质量(RNA 完整性数)。
在这项研究中,评估了基线时大关节上进行的 84 例操作(25 例关节镜、35 例 US-P&F、11 例 US-NB 和 13 例 BN 活检)、基线时小关节上进行的 41 例操作(11 例 US-P&F、20 例 US-NB 和 10 例 BN 活检)和 34 例连续活检操作。与在大小关节中评估的所有其他技术相比,小关节 BN 活检获得的分级滑膜组织较少,大关节 BN 活检的分级滑膜组织比例显著降低。在 US-NB 和关节镜大关节操作之间,无论是分级组织样本的比例还是总分级滑膜组织面积均无显著差异。在所评估的连续活检操作(小关节 US-NB、大关节关节镜、US-P&F 活检和 BN 活检)中,分级滑膜组织的比例或总分级滑膜组织面积无显著差异。所有操作均产生了用于后续转录组分析的具有显著质量和数量的 RNA。
这些数据支持将 US 引导的方法与关节镜活检结合使用,以纳入临床试验方案,在这些方案中需要对大小关节的滑膜进行连续采样,以进行组织学和分子分析。如果后续分析不需要分级滑膜组织,则可以考虑 BN 活检。