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慢性开放乳突腔分泌物的组织病理学和炎症特征:一项随机临床试验的二次分析。

Histopathological and Inflammatory Features of Chronically Discharging Open Mastoid Cavities: Secondary Analysis of a Randomized Clinical Trial.

机构信息

Department of Otorhinolaryngology-Head and Neck Surgery, Maastricht University Medical Center+, Maastricht, the Netherlands.

Internal Medicine, Clinical and Experimental Immunology, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center+, Maastricht, the Netherlands.

出版信息

JAMA Otolaryngol Head Neck Surg. 2018 Mar 1;144(3):211-217. doi: 10.1001/jamaoto.2017.2801.

Abstract

IMPORTANCE

Many patients with an open radical mastoid cavity experience therapy-resistant otorrhea. Little is known about the underlying histopathological substrate of unstable cavities and the correlation with treatment failure.

OBJECTIVE

To study the histopathological and inflammatory features of chronically discharging open radical mastoid cavities and the influence of different treatments.

DESIGN, SETTING, AND PARTICIPANTS: This secondary analysis of a randomized clinical trial was a histopathology study of tissue samples of a cohort of 30 patients with a chronically discharging open mastoid cavity. Samples were taken from the cavities, which were treated with either honey gel or conventional eardrops in a tertiary center between 2012 and 2013. Tissue staining was performed in May 2014; final computer analysis/correlation studies were performed in June 2016.

MAIN OUTCOMES AND MEASURES

Differences of epithelial tissue coverage, infiltration of T cells (CD3, CD4, CD8) and macrophage (CD68, isoenzyme nitric oxide synthase, arginase 1) (sub-)populations, infection status, and the correlation with clinical presentation.

RESULTS

There were 30 patients (24 [80%] male; mean [SD] age, 59 [14] years). Cavities were covered with either stratified squamous (keratinized) epithelium (n = 10), respiratory columnar epithelium (n = 9), or granulation tissue (n = 10). The presence of respiratory epithelium was associated with lower treatment success (posttreatment VAS improvement of 3.1 [95% CI, 0.5 to 5.8] for discomfort and 3.6 [95% CI, 0.2 to 6.9] for otorrhea in the group with granulation tissue coverage vs 4.9 [95% CI, 0.2 to 9.6] and 5.8 [95% CI, -0.1 to 11.6] in the group with squamous [keratinized] epithelium coverage and 1.4 [95% CI, -1.2 to 4.1] and 2.5 [95% CI, -1.3 to 6.2] in the group with respiratory columnar epithelium coverage). In all 3 tissue types of cavity-covering tissues, T-cell infiltrates consisted of helper T cells and cytotoxic T cells, together with a lower number of macrophages. The immunopositivity for isoenzyme nitric oxide synthase and arginase 1 was high and not restricted to a macrophage subpopulation, but seen in various cell types. Inflammatory infiltrations varied strongly in all 3 tissue modalities.

CONCLUSIONS AND RELEVANCE

Discharging open mastoid cavities can be classified histologically into 3 different types, based on their coverage: squamous epithelium, respiratory epithelium, or granulation tissue. Treatment is less successful in cavities covered with respiratory epithelium, possibly explained by the status of bacterial infection and local immunological differences.

摘要

重要性

许多患有开放性根治性乳突腔的患者经历了治疗抵抗性耳漏。对于不稳定腔的潜在组织病理学基础以及与治疗失败的相关性知之甚少。

目的

研究慢性排液性开放性根治性乳突腔的组织病理学和炎症特征,以及不同治疗方法的影响。

设计、地点和参与者:这是一项随机临床试验的二次分析,是对 2012 年至 2013 年在一家三级中心接受慢性排液性开放性乳突腔治疗的 30 例患者队列的组织样本进行的组织病理学研究。在组织样本取自乳突腔后,分别用蜂蜜凝胶或常规滴耳液进行治疗。组织染色于 2014 年 5 月进行;最终的计算机分析/相关性研究于 2016 年 6 月进行。

主要结果和措施

上皮组织覆盖、T 细胞(CD3、CD4、CD8)和巨噬细胞(CD68、诱导型一氧化氮合酶、精氨酸酶 1)(亚)群浸润、感染状态以及与临床表现的相关性差异。

结果

共有 30 名患者(24 名[80%]为男性;平均[标准差]年龄 59[14]岁)。乳突腔被复层鳞状(角化)上皮(n=10)、呼吸柱状上皮(n=9)或肉芽组织(n=10)覆盖。存在呼吸上皮与治疗成功率较低相关(治疗后疼痛视觉模拟评分(VAS)改善:肉芽组织覆盖组为 3.1[95%置信区间(CI),0.5 至 5.8],耳漏为 3.6[95%CI,0.2 至 6.9];鳞状[角化]上皮覆盖组为 4.9[95%CI,0.2 至 9.6]和 5.8[95%CI,-0.1 至 11.6];呼吸柱状上皮覆盖组为 1.4[95%CI,-1.2 至 4.1]和 2.5[95%CI,-1.3 至 6.2])。在所有 3 种组织类型的腔覆盖组织中,T 细胞浸润由辅助性 T 细胞和细胞毒性 T 细胞组成,同时巨噬细胞数量较少。诱导型一氧化氮合酶和精氨酸酶 1 的免疫阳性率较高,不仅局限于巨噬细胞亚群,而且可见于各种细胞类型。在所有 3 种组织学模式中,炎症浸润差异很大。

结论和相关性

根据其覆盖物,排出的开放性乳突腔可分为 3 种不同类型:鳞状上皮、呼吸上皮或肉芽组织。用呼吸上皮覆盖的腔治疗效果较差,这可能与细菌感染状态和局部免疫差异有关。

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