Huang Yu, Cai Yicong, Chen Yingji, Zhu Qianjun, Feng Wei, Jin Longyu, Ma Yuchao
Department of Cardiothoracic Surgery, Third Xiangya Hospital of Central South University, Changsha, China.
Department of Gastrointestinal Surgery, Third Xiangya Hospital of Central South University, Changsha, China.
Front Med (Lausanne). 2024 Jul 18;11:1420462. doi: 10.3389/fmed.2024.1420462. eCollection 2024.
Cholelithiasis or cholecystectomy may contribute to the development of gastroesophageal reflux disease (GERD), Barrett's esophagus (BE), and esophageal adenocarcinoma (EAC) through bile reflux; however, current observational studies yield inconsistent findings. We utilized a novel approach combining meta-analysis and Mendelian randomization (MR) analysis, to assess the association between them.
The literature search was done using PubMed, Web of Science, and Embase databases, up to 3 November 2023. A meta-analysis of observational studies assessing the correlations between cholelithiasis or cholecystectomy, and the risk factors for GERD, BE, and EACwas conducted. In addition, the MR analysis was employed to assess the causative impact of genetic pre-disposition for cholelithiasis or cholecystectomy on these esophageal diseases.
The results of the meta-analysis indicated that cholelithiasis was significantly linked to an elevated risk in the incidence of BE (RR, 1.77; 95% CI, 1.37-2.29; < 0.001) and cholecystectomy was a risk factor for GERD (RR, 1.37; 95%CI, 1.09-1.72; = 0.008). We observed significant genetic associations between cholelithiasis and both GERD (OR, 1.06; 95% CI, 1.02-1.10; < 0.001) and BE (OR, 1.21; 95% CI, 1.11-1.32; < 0.001), and a correlation between cholecystectomy and both GERD (OR, 1.04; 95% CI, 1.02-1.06; < 0.001) and BE (OR, 1.13; 95% CI, 1.06-1.19; < 0.001). After adjusting for common risk factors, such as smoking, alcohol consumption, and BMI in multivariate analysis, the risk of GERD and BE still persisted.
Our study revealed that both cholelithiasis and cholecystectomy elevate the risk of GERD and BE. However, there is no observed increase in the risk of EAC, despite GERD and BE being the primary pathophysiological pathways leading to EAC. Therefore, patients with cholelithiasis and cholecystectomy should be vigilant regarding esophageal symptoms; however, invasive EAC cytology may not be necessary.
胆石症或胆囊切除术可能通过胆汁反流促使胃食管反流病（GERD）、巴雷特食管（BE）和食管腺癌（EAC）的发生；然而，目前的观察性研究结果并不一致。我们采用了一种将荟萃分析和孟德尔随机化（MR）分析相结合的新方法，来评估它们之间的关联。
使用PubMed、Web of Science和Embase数据库进行文献检索，截至2023年11月3日。对评估胆石症或胆囊切除术与GERD、BE和EAC的危险因素之间相关性的观察性研究进行荟萃分析。此外，采用MR分析来评估胆石症或胆囊切除术的遗传易感性对这些食管疾病的因果影响。
荟萃分析结果表明，胆石症与BE发病率升高显著相关（RR，1.77；95%CI，1.37 - 2.29；P < 0.001），胆囊切除术是GERD的一个危险因素（RR，1.37；95%CI，1.09 - 1.72；P = 0.008）。我们观察到胆石症与GERD（OR，1.06；95%CI，1.02 - 1.10；P < 0.001）和BE（OR，1.21；95%CI，1.11 - 1.32；P < 0.001）之间均存在显著的遗传关联，以及胆囊切除术与GERD（OR，1.04；95%CI，1.02 - 1.06；P < 0.001）和BE（OR，1.13；95%CI，1.06 - 1.19；P < 0.001）之间均存在相关性。在多变量分析中对吸烟、饮酒和BMI等常见危险因素进行调整后，GERD和BE的风险仍然存在。
我们的研究表明，胆石症和胆囊切除术均会增加GERD和BE的风险。然而，尽管GERD和BE是导致EAC的主要病理生理途径，但未观察到EAC风险增加。因此，患有胆石症和胆囊切除术的患者应警惕食管症状；然而，可能无需进行侵入性的EAC细胞学检查。
