Immune-related adverse events in the gastrointestinal tract: diagnostic utility of upper gastrointestinal biopsies.
Immune-related adverse events in the gastrointestinal tract: diagnostic utility of upper gastrointestinal biopsies.
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DOI：
10.1111/his.13963
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发表时间：
2020-01
期刊：
影响因子：
6.4
通讯作者：
Deshpande V
中科院分区：
文献类型：
--
作者：
Zhang ML;Neyaz A;Patil D;Chen J;Dougan M;Deshpande V
免疫检查点抑制剂（ICI）可改善一系列恶性肿瘤的生存率，但也与一系列胃肠道免疫相关不良事件（GI-irAE）相关。本研究旨在探讨胃和十二指肠活检的诊断价值，并提出鉴别诊断中的注意事项。我们确定了39例接受ICI治疗并随后进行上消化道活检的患者。我们记录了临床资料和内镜检查结果，并回顾了他们的胃、十二指肠和结肠活检。21例（54%）患者单独用抗PD 1/抗PD-L1抗体治疗，17例（44%）患者用抗CTLA-4和抗PD-1抗体联合治疗。32例（82%）患者出现腹泻。胃改变包括腺体周围炎症和肉芽肿，而十二指肠改变包括绒毛钝化、上皮内淋巴细胞增多、肉芽肿和嗜酸性活动。我们识别出四种结肠损伤模式：1）急性自限性结肠炎，2）淋巴细胞性结肠炎，3）胶原性结肠炎，和4）仅细胞凋亡。临床诊断GI-irAE阳性和阴性患者分别为29例（74%）和10例（26%）。胃腺周围炎症（p=0.004）和结肠固有层单核细胞增加（p=0.04）与GI-irAE的临床诊断相关。与ICI损伤相关的组织学改变在上消化道（71%）比结肠活检（65%）更常见。ICI相关GI疾病的形态学谱很广，与一系列感染性和炎性疾病相似。胃腺体周围炎症是GI-irAE的一个较典型的组织学特征。该研究强调了对上、下消化道活检进行全面审查以诊断irAE的重要性。
Immune checkpoint inhibitors (ICI) improve survival across a range of malignancies but are also associated with a spectrum of gastrointestinal immune-related adverse events (GI-irAE). This study aims to explore the diagnostic value of gastric and duodenal biopsies and address considerations in the differential diagnosis. We identified 39 patients who were treated with ICIs and had a subsequent upper GI biopsy. We recorded clinical data and endoscopic findings, and reviewed their gastric, duodenal, and colonic biopsies. 21 (54%) patients were treated with an anti-PD1/anti-PD-L1 antibody alone and 17 (44%) with combination anti-CTLA-4 and anti-PD-1 antibodies. 32 (82%) patients presented with diarrhea. Gastric alterations included peri-gland inflammation and granulomas while the duodenal changes included villous blunting, intraepithelial lymphocytosis, granulomas, and neutrophilic activity. We recognized four patterns of colonic injury: 1) acute self-limiting colitis, 2) lymphocytic colitis, 3) collagenous colitis, and 4) apoptosis only. 29 (74%) and 10 (26%) patients were diagnosed clinically as positive and negative for GI-irAE, respectively. Gastric peri-gland inflammation (p=0.004) and increased colonic lamina propria mononuclear cells (p=0.04) correlated with the clinical diagnosis of GI-irAE. Histologic alterations associated with ICI injury were more often identified in upper GI (71%) than colonic biopsies (65%). The morphologic spectrum of ICI-related GI disease is broad and mimics a range of infectious and inflammatory diseases. Gastric peri-gland inflammation represents one of the more characteristic histologic features of GI-irAE. The study underscores the importance of a comprehensive review of upper and lower GI biopsies for the diagnosis of irAE.
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影响因子：
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