In a single-institution study reported in The New England Journal of Medicine, Kooshesh et al found that adults who had undergone thymectomy may be at an increased risk of death; cancer; and, in certain cases, autoimmune disease.
As stated by the investigators: “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.”
Study Details
The study included 1,420 patients who had undergone thymectomy and 6,021 controls who had undergone similar cardiothoracic surgeries without thymectomy at Massachusetts General Hospital between January 1993 and March 2020. Patients who died within 90 days after thymectomy or had nonlaparoscopic cardiac surgery within 5 years after the procedure were excluded from analysis. A total of 1,146 patients who had undergone thymectomy and had a demographically matched control were included in the primary cohort.
Key Findings
At 5 years after surgery, patients in the thymectomy group had a significantly greater risk of all-cause mortality (8.1% vs 2.8%; relative risk [RR] = 2.9, 95% confidence interval [CI] = 1.7–4.8) and risk of cancer (7.4% vs 3.7%; RR = 2.0, 95% CI = 1.3–3.2) compared with matched controls. Overall, there was no difference between the thymectomy and control groups in terms of the risk for autoimmune disease (RR = 1.1, 95% CI = 0.8–1.4); an analysis excluding patients with a preoperative infection, cancer, or autoimmune disease showed an increased risk in the thymectomy group (12.3% vs 7.9%; RR = 1.5, 95% CI = 1.02–2.2).
An analysis involving all patients who underwent thymectomy (with or without matched controls) with more than 5 years of follow-up showed greater all-cause mortality (9.0% vs 5.2%) and death from cancer (2.3% vs 1.5%) in the thymectomy group vs the general U.S. population.
Among 22 patients in the thymectomy group and 19 in the matched control group who underwent analysis of T-cell production and plasma cytokine levels (mean follow-up of 14.2 postoperative years), those in the thymectomy group showed reduced new production of CD4-positive and CD8-positive lymphocytes—indicated by mean CD4-positive signal joint T-cell receptor excision circle (TREC) count of 526 vs 1,451/µg DNA (P = .009) and mean CD8-positive signal joint TREC count of 477 vs 1,466/µg DNA (P < .001)—as well as higher levels of proinflammatory cytokines.
The investigators concluded: “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.”
David T. Scadden, MD, of the Center for Regenerative Medicine, Massachusetts General Hospital, is the corresponding author of The New England Journal of Medicine article.
Disclosure: The study was supported by the Tracey and Craig A. Huff Harvard Stem Cell Institute Research Support Fund and others. For full disclosures of the study authors, visit nejm.org.
