Barrett's esophagus is the precursor of all esophageal adenocarcinomas
Barrett's esophagus is the precursor of all esophageal adenocarcinomas
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巴雷特食管是所有食管腺癌的先兆
DOI：
10.1101/2020.05.14.096826
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Curtius K
中科院分区：
文献类型：
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作者：
Curtius K
Barrett‘s Eagus(BE)是已知的食管腺癌(EAC)的先兆，但目前的临床资料尚不能确定BE是否是所有EAC的起因，这将为BE的筛查工作提供更多的证据。我们的目标是回答是否所有预期的流行的BE，诊断的和未诊断的，都可以解释美国癌症登记数据中的所有EACS事件。设计我们使用了一个多尺度的EAC计算模型，该模型包括了美国人群个体从正常食道到BE的进化过程。该模型之前已经过校准，以拟合SEER癌症发病率曲线。在这里，我们还使用了年龄和性别特定的美国人口普查数据，以了解高危人数。模型验证的主要结果是给定日历年的预期EAC病例数量。结果该模型估计2010年EAC病例总数为9970例(95%可信区间为9,140-11,980例)，这概括了人口数据中的所有EAC病例。该模型同时预测了45-55岁高危男性中8-9%的BE患病率，以及男性非发育异常BE-to-EAC年进展的0.1-0.2%，与临床研究一致。结论在BE途径之外的美国人群中，没有其他EAC病例可信地出现。对高危患者进行有效的筛查可以捕捉到大多数EAC进展的人群，并在监测期间通过早期发现和根治性切除小(前)癌来降低死亡率。对这一课题已知的情况是什么？Barrett‘s Ereagus(BE)患者发生食管腺癌(EAC)的风险是普通人群的40到50倍，但许多人仍然没有得到诊断。接受监测的BE患者可以通过内窥镜发现早期癌症，这降低了EAC相关的高死亡率。目前，大约90%的EAC患者从未参加过BE监测计划，那些接受监测的BE患者患EAC的年进展率较低，为0.1%-0.3%。新的发现是什么？通过应用一个结合了患者从正常细胞到EAC的进化的模型，我们发现这些数字加起来--美国人口中预期的EAC病例数可以用公布的上述比率来解释。我们集中检查了公布的估计数据，以确定所有EAC可能来自已确定的BE和人群中的隐匿性、未诊断的EAC。在可预见的未来，这可能会对临床实践产生什么影响？基于目前的最佳估计，我们的发现表明，公共卫生没有必要寻找非BE替代途径来治疗EAC。加强对真实BE人群的有效、敏感的筛查和监测将在未来几年降低EAC的死亡率。
ObjectiveBarrett’s esophagus (BE) is a known precursor to esophageal adenocarcinoma (EAC) but current clinical data have not been consolidated to address whether BE is the origin of all incident EAC, which would reinforce evidence for BE screening efforts. We aimed to answer whether all expected prevalent BE, diagnosed and undiagnosed, could account for all incident EACs in the US cancer registry data.DesignWe used a multi-scale computational model of EAC that includes the evolutionary process from normal esophagus through BE in individuals from the US population. The model was previously calibrated to fit SEER cancer incidence curves. Here we also utilized age- and sex-specific US census data for numbers at-risk. The primary outcome for model validation was the expected number of EAC cases for a given calendar year. Secondary outcomes included the comparisons of resulting model-predicted prevalence of BE and BE-to-EAC progression to the observed prevalence and progression rates.ResultsThe model estimated the total number of EAC cases in 2010 was 9,970 (95% CI 9,140 – 11,980), which recapitulates all EAC cases from population data. The model simultaneously predicted 8-9% BE prevalence in high-risk males age 45-55, and 0.1-0.2% non-dysplastic BE-to-EAC annual progression in males, consistent with clinical studies.ConclusionThere are no additional EAC cases that plausibly arise in the US population outside the BE pathway. Effective screening of high-risk patients could capture the majority of population destined for EAC progression and decrease mortality through early detection and curative removal of small (pre)cancers during surveillance.Summary BoxWhat is already known about this subject?Barrett’s esophagus (BE) patients have a 40 to 50-fold higher risk of developing esophageal adenocarcinoma (EAC) than the general population yet many remain undiagnosed.Identified BE patients receiving surveillance can have early cancers discovered endoscopically, which decreases the high overall EAC-associated mortality.Currently around 90% of patients who develop EAC were never part of a BE surveillance program, and those BE patients on surveillance have a low annual progression rate of 0.1 - 0.3% to develop EAC.What are the new findingsBy applying a model that incorporates the evolution from normal cells to BE to EAC in patients, we found that the numbers add up - the expected number of EAC cases in the US population are explained by the published rates of BE described above.We cohesively examined the published estimates to determine that all EAC likely arises from both identified BE and occult, undiagnosed BE in the population.How might it impact on clinical practice in the foreseeable future?Based on current best estimates, our findings suggest there is no public health need to seek cases of a non-BE alternative pathway to EAC.Increasing efforts for effective, sensitive screening and surveillance of the true BE population will decrease EAC mortality in the coming years.