Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Impact Assessment Unit, Department of Health Protection, National Institute for Health and Welfare, Tampere, Finland.
JAMA Oncol. 2018 Nov 1;4(11):1576-1582. doi: 10.1001/jamaoncol.2018.3054.
Gastroesophageal reflux disease (GERD) is associated with a strong and severity-dependent increased risk of esophageal adenocarcinoma. Whether antireflux surgery prevents esophageal adenocarcinoma is a matter of uncertainty.
To examine whether antireflux surgery is associated with reduced risk of esophageal adenocarcinoma and whether the risk is different between surgically and medically treated patients.
DESIGN, SETTING, AND PARTICIPANTS: In this multinational, population-based retrospective cohort study from Denmark, Finland, Iceland, Norway, and Sweden, patients undergoing surgery were followed up for a median of 12.7 years, and a comparison group of patients receiving medication only were followed up for a median of 4.8 years. All patients with a registered diagnosis of GERD (or an associated disorder), including 48 414 individuals undergoing surgery and 894 492 receiving medication only, were included in the study. The study periods varied in the different countries depending on the year of initiation of registration and the date of data retrieval, from January 1, 1964, to December 21, 2014.
Antireflux surgery for GERD.
The risk of esophageal adenocarcinoma over time after surgery was compared with that in a corresponding background population using standardized incidence ratios (SIRs) with 95% CIs and with patients with GERD who received medication using multivariable Cox proportional hazards regression, providing hazard ratios (HRs) with 95% CIs adjusted for confounders.
In this study of 942 906 patients with GERD, 48 414 underwent antireflux surgery (median [interquartile range] age, 66.0 [58.0-73.0] years; 27 161 male [56.1%]) and 894 492 received medication only (median [interquartile range] age, 71.0 [62.0-78.0] years; 434 035 male [48.6%]). Among patients undergoing surgery, 177 developed esophageal adenocarcinoma. Esophageal adenocarcinoma risk decreased in a time-dependent manner after surgery compared with the background population (5 to <10 years after surgery: SIR, 7.63; 95% CI, 5.42-10.43; ≥15 years after surgery: SIR, 1.34; 95% CI, 0.98-1.80). Among patients with more severe and objectively determined GERD, the SIRs were 10.08 (95% CI, 6.98-14.09) at 5 to less than 10 years after surgery and 1.67 (95% CI, 1.15-2.35) at 15 years or more after surgery. The risk of esophageal adenocarcinoma did not change over time in surgical patients compared with patients who received medication only (5 to <10 years after surgery: HR, 2.02; 95% CI, 1.44-2.84; ≥15 years: HR, 1.80; 95% CI, 1.28-2.54). The risk remained stable over time in analyses restricted to severe reflux disease (5 to <10 years after surgery: HR, 1.81; 95% CI, 1.24-2.63; ≥15 years after surgery: HR, 1.69; 95% CI, 1.14-2.51).
Medical and surgical treatment of GERD were associated with a similar reduced esophageal adenocarcinoma risk, with the risk decreasing to the same level as that in the background population over time, supporting the hypothesis that effective treatment of GERD might prevent esophageal adenocarcinoma.
胃食管反流病（GERD）与强烈且与严重程度相关的食管腺癌风险增加有关。抗反流手术是否可预防食管腺癌尚存争议。
研究抗反流手术是否与食管腺癌风险降低相关，以及手术治疗和药物治疗患者的风险是否存在差异。
设计、设置和参与者：本研究为丹麦、芬兰、冰岛、挪威和瑞典开展的一项多国、基于人群的回顾性队列研究，对接受手术的患者进行了中位 12.7 年的随访，对仅接受药物治疗的患者进行了中位 4.8 年的随访。所有患有 GERD（或相关疾病）的患者，包括 48414 例手术患者和 894492 例仅接受药物治疗的患者，均纳入研究。不同国家的研究期间因登记启动年份和数据检索日期而异，从 1964 年 1 月 1 日至 2014 年 12 月 21 日。
用于 GERD 的抗反流手术。
使用标准化发病比（SIR）及其 95%置信区间（CI），与相应背景人群比较手术治疗后一段时间内的食管腺癌风险，使用多变量 Cox 比例风险回归，调整混杂因素后提供风险比（HR）及其 95%CI。
本研究纳入了 942906 例 GERD 患者，其中 48414 例接受了抗反流手术（中位[四分位间距]年龄，66.0[58.0-73.0]岁；27161 例男性[56.1%]），894492 例仅接受了药物治疗（中位[四分位间距]年龄，71.0[62.0-78.0]岁；434035 例男性[48.6%]）。在接受手术的患者中，177 例发生食管腺癌。与背景人群相比，手术后食管腺癌风险呈时间依赖性下降（手术后 5 年至<10 年：SIR，7.63；95%CI，5.42-10.43；手术后≥15 年：SIR，1.34；95%CI，0.98-1.80）。在更严重和客观确定的 GERD 患者中，手术后 5 年至<10 年的 SIR 为 10.08（95%CI，6.98-14.09），手术后 15 年或以上的 SIR 为 1.67（95%CI，1.15-2.35）。与仅接受药物治疗的患者相比，手术患者的食管腺癌风险并未随时间而变化（手术后 5 年至<10 年：HR，2.02；95%CI，1.44-2.84；手术后≥15 年：HR，1.80；95%CI，1.28-2.54）。在仅纳入严重反流疾病的分析中，风险随时间保持稳定（手术后 5 年至<10 年：HR，1.81；95%CI，1.24-2.63；手术后≥15 年：HR，1.69；95%CI，1.14-2.51）。
GERD 的药物和手术治疗与食管腺癌风险降低相关，且随着时间的推移，风险降低至与背景人群相同的水平，支持有效治疗 GERD 可能预防食管腺癌的假说。
