成人胸腺切除对健康的影响

SCI

14 August 2023

Health Consequences of Thymus Removal in Adults

（NEJM; IF:158.5）

Kooshesh KA, Foy BH, Sykes DB, Gustafsson K, Scadden DT. Health Consequences of Thymus Removal in Adults. N Engl J Med 2023;389(5):406-417. (In eng). DOI: 10.1056/NEJMoa2302892.

Correspondence to：dscadden@mgh.harvard.edu

BACKGROUND 背景

The function of the thymus in human adults is unclear, and routine removal of the thymus is performed in a variety of surgical procedures. We hypothesized that the adult thymus is needed to sustain immune competence and overall health.

成人胸腺的功能尚不清楚，胸腺的常规切除在各种外科手术中进行。我们猜测成人的胸腺是维持免疫能力和整体健康所必需的。

METHODS 方法

We evaluated the risk of death, cancer, and autoimmune disease among adult patients who had undergone thymectomy as compared with demographically matched controls who had undergone similar cardiothoracic surgery without thymectomy. T-cell production and plasma cytokine levels were also compared in a subgroup of patients.

我们评估了接受胸腺切除术的成人患者的死亡、癌症和自身免疫病风险，并与接受了类似心胸手术但未接受胸腺切除术的人口匹配对照进行了比较。我们还在一个患者亚组中比较了T细胞生成和血浆细胞因子水平。

RESULTS 结果

After exclusions, 1420 patients who had undergone thymectomy and 6021 controls were included in the study; 1146 of the patients who had undergone thymectomy had a matched control and were included in the primary cohort. At 5 years after surgery, all-cause mortality was higher in the thymectomy group than in the control group (8.1% vs. 2.8%; relative risk, 2.9; 95% confidence interval [CI], 1.7 to 4.8), as was the risk of cancer (7.4% vs. 3.7%; relative risk, 2.0; 95% CI, 1.3 to 3.2). Although the risk of autoimmune disease did not differ substantially between the groups in the overall primary cohort (relative risk, 1.1; 95% CI, 0.8 to 1.4), a difference was found when patients with preoperative infection, cancer, or autoimmune disease were excluded from the analysis (12.3% vs. 7.9%; relative risk, 1.5; 95% CI, 1.02 to 2.2). In an analysis involving all patients with more than 5 years of follow-up (with or without a matched control), all-cause mortality was higher in the thymectomy group than in the general U.S. population (9.0% vs. 5.2%), as was mortality due to cancer (2.3% vs. 1.5%). In the subgroup of patients in whom T-cell production and plasma cytokine levels were measured (22 in the thymectomy group and 19 in the control group; mean follow-up, 14.2 postoperative years), those who had undergone thymectomy had less new production of CD4+ and CD8+ lymphocytes than controls (mean CD4+ signal joint T-cell receptor excision circle [sjTREC] count, 1451 vs. 526 per microgram of DNA [P = 0.009]; mean CD8+ sjTREC count, 1466 vs. 447 per microgram of DNA [P<0.001]) and higher levels of proinflammatory cytokines in the blood.

排除后，1420例胸腺切除术患者和6021例对照纳入研究;1,146例接受胸腺切除术的患者有匹配对照，并被纳入主要队列。术后5年，胸腺切除术组的全因死亡率高于对照组(8.1% VS 2.8%;相对危险度2.9;95%置信区间[CI]1.7 ~ 4.8)，癌症风险也是如此(7.4% VS 3.7%;相对危险度2.0;95% CI, 1.3 ~ 3.2)。尽管在总体主要队列中，自身免疫性疾病的风险无显著组间差异(相对危险度，1.1;95% CI, 0.8 ~ 1.4)，而将术前感染、癌症或自身免疫病患者排除出分析后发现差异(12.3% vs. 7.9%;相对危险度，1.5;95% CI, 1.02 ~ 2.2)。在对随访超过5年(有或无匹配对照)的所有患者进行的一项分析中，胸腺切除术组的全因死亡率(9.0% vs. 5.2%)和癌症死亡率(2.3% vs. 1.5%)均高于美国一般人群。在检测T细胞生成和血浆细胞因子水平的患者亚组中(胸腺切除术组22例，对照组19例;平均随访，术后14.2年)，接受胸腺切除术的患者与对照组相比，新产生的CD4+和CD8+淋巴细胞较少(平均CD4+信号联合T细胞受体删除环[sjTREC]计数，每微克DNA 1,451 VS 526 [P = 0.009];平均CD8+ sjTREC计数，每微克DNA 1,466 VS 447 [P<0.001])，并且血液中促炎细胞因子水平较高。

CONCLUSIONS 结论

In this study, all-cause mortality and the risk of cancer were higher among patients who had undergone thymectomy than among controls. Thymectomy also appeared be associated with an increased risk of autoimmune disease when patients with preoperative infection, cancer, or autoimmune disease were excluded from the analysis.

在这项研究中，接受胸腺切除术的患者的全因死亡率和癌症风险高于对照组。当术前感染、癌症或自身免疫性疾病的患者被排除在分析之外时，胸腺切除术似乎也与自身免疫性疾病的风险增加有关。