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2026年8月13日星期四
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胸外文献周报

2026.07.27 – 08.02
本周收录 41 篇
肺癌 27 篇
临床研究

本周16项临床研究（编号[1]至[16]）覆盖肺癌风险预测、筛查、诊断、治疗、预后及临终关怀全链条。在风险与预防方面，[1]基于9,464名煤矿工人的横断面分析结合孟德尔随机化发现累积夜班暴露与肺功能降低相关，PER1表达降低部分介导该关联，且提示昼夜节律紊乱可能通过NF-κB炎症通路影响肺癌风险；[12]利用全国性健康保险数据库的14,927例COPD合并2型糖尿病患者队列，显示SGLT2抑制剂相较磺脲类药物与新发肺癌风险降低相关，为这一高危人群的肺癌预防提供了人群层面证据。筛查与早期发现方面，[6]报道了一项利用电子病历（EHR）提醒纠正吸烟史记录以改善肺癌筛查的随机对照质量改进研究，提示系统级干预可优化筛查对象识别；[8]基于MISCAN-Lung微模拟模型评估1080种CT筛查策略，整合NELSON证据后显示基于PLCOm2012风险招募较包年标准更高效且总体具有成本效益；[10]通过混合方法研究（40名访谈加全国调查）阐释了美国临床医师在肺结节评估与管理中的实践影响因素与优化障碍；[13]则对肺癌筛查中病灶内工具的使用提出警示，认为其可能偏离预期目标。在证据解读上，[3]指出早期NSCLC汇总证据存在局限，解读间接比较或荟萃分析时需分辨所比较的究竟是治疗本身还是患者人群。诊断方面，[14]报告了NEBULA随机对照试验，在200例患者中比较电磁导航支气管镜联合径向腔内超声与单独电磁导航对周围型肺部病变的诊断价值，以最终病理或6个月CT为参考并采用意向性分析，具体诊断率未在摘要中报告。治疗与耐药方面，[4]针对HBsAg阳性肺癌患者一线化疗联合免疫治疗的真实世界队列，评估客观缓解率、无进展生存期、总生存期及免疫相关肝脏不良事件，并分析基线抗-HBs水平对HBsAg阴性/抗-HBc阳性患者预后的影响；[5]采用匹配调整间接比较，在未接受TKI治疗的ROS1+ NSCLC中对比taletrectinib与克唑替尼、恩曲替尼，显示新一代TKI的相对获益需在缺乏头对头试验背景下谨慎解读；[9]来自捷克全国8个中心的前瞻性多中心队列显示，按CheckMate 816方案接受新辅助nivolumab联合化疗的可切除PD-L1≥1% NSCLC患者中87.5%成功接受根治性切除，微创尝试率46.4%，中转开胸率11.5%，支持该方案在真实世界全国推广中的可行性；[7]通过一例KRASG12C/STK11/KEAP1突变肺腺癌患者的连续ctDNA监测，显示adagrasib治疗中ctDNA水平先降至3.2拷贝/mL后于第6个月升至315.2拷贝/mL，并出现多种新KRAS突变，提示ctDNA可提前捕获多克隆耐药；[2]在荷兰7家医院365例转移性NSCLC患者的多中心回顾队列中发现37%在死亡前6周接受全身抗癌治疗，提示需进一步优化临终治疗决策。在预后与支持方面，[11]通过对产品特性摘要与EORTC QLQ-C30/LC29的结构化映射，发现现有生活质量问卷可能未充分捕获NSCLC治疗相关的常见症状性不良事件；[16]检测手术切除肺腺癌和鳞癌中BACH1表达并结合无病生存分析与体外顺铂敏感性实验，提示BACH1可能作为预后标志和耐药靶点；[15]利用Optimum Patient Care Research Database进行匹配病例对照和队列分析，比较不同间质性肺病亚型（IPF、过敏性肺炎及结缔组织病相关ILD）的肺癌患病率和发病率，采用竞争风险模型，明确了纤维化性ILD亚型间肺癌风险的差异。综上，本周临床证据在筛查策略、围术期治疗和真实世界安全性方面提供了增量信息，但多项研究的具体效应量未在摘要中完整报告。

AI/ML

3项人工智能与机器学习研究[17-19]分别从预后预测、无创筛查分诊和真实世界数据挖掘三个方向探索了AI在肺癌中的应用。[17]汇总了IMpower130/131/132/150/110五项临床试验中超过2,300例转移性NSCLC患者的血清样本，检测包括CA125、CEA、Cyfra21-1、NSE、SCC和ProGRP在内的六种循环肿瘤抗原（ctA）及CRP，构建联合模型在atezolizumab±bevacizumab±化疗的一线治疗背景下展现出了额外的预后价值，该策略相比循环肿瘤DNA具有检测时间和成本优势。[18]开展了一项大规模前瞻性多中心诊断准确性研究，纳入5,214例伴影像学肺部异常的症状性患者，利用质子转移反应飞行时间质谱分析呼出气挥发性有机物，并结合临床因素的机器学习模型进行肺癌分诊，发现队列（4,669例）与地理独立外部验证队列（545例）中验证了模型的效能，提示呼气组学可作为CT阳性结节的低成本、无创分诊工具以减少不必要的有创操作。[19]验证了基于自然语言处理的文本挖掘工具CTcue在早期可切除NSCLC患者常规电子健康记录数据自动提取中的准确性，研究覆盖2018至2021年荷兰莱顿大学医学中心接受肺切除术的全部I-III期NSCLC患者，以人工图表回顾为金标准比较加权F1、准确率、精确率与召回率，并使用Bland-Altman法评估连续变量的一致性，证明NLP工具可提高真实世界数据研究的可重复性和可扩展性。综合来看[17-19]，AI工具正从辅助科研的数据提取扩展到面向临床决策的预测与分诊，但其泛化性仍须在更大规模外部队列和前瞻性场景中持续验证。

基础研究

6项基础研究[20-25]从遗传易感、翻译调控、凋亡机制、免疫微环境和代谢重编程等层面揭示了肺癌发生发展的新机制。[20]利用UK Biobank（2,272例肺癌病例/185,510例对照）和RUSH队列（824例病例）及gnomAD对照，采用基于基因的负荷检验在123个ClinGen遗传性癌症基因中筛查罕见种系变异，发现10个基因的罕见变异与肺癌风险显著关联，扩展了肺癌的胚系易感基因谱。[21]在肺腺癌中发现HERC4通过不依赖E3连接酶活性的方式与去泛素化酶USP16协同，阻止40S核糖体蛋白RPS15的K48连接泛素化，从而稳定RPS15并增强翻译相关蛋白向核糖体的招募，促进肿瘤细胞增殖，敲低HERC4或USP16可逆转该过程，提示该轴是潜在治疗靶点。[22]在多种人NSCLC细胞系中系统使用BH3模拟物靶向BCL-2、BCL-XL或MCL-1，发现单独抑制仅产生微弱且异质的凋亡反应，但双靶向BCL-XL与MCL-1可快速诱导凋亡，揭示了NSCLC中可利用的协同抗凋亡网络，尤其对p53突变型肿瘤可能具有重要意义。[23]针对小细胞肺癌开发了人源化抗SEZ6单克隆抗体，通过PET成像和α粒子放射性免疫治疗实现肿瘤检测与治疗，患者组织免疫组化显示SEZ6强表达且与分期无关，细胞实验证实高受体密度介导快速内吞，为SCLC提供了诊疗一体化策略。[24]在新辅助PD-1阻断治疗的NSCLC手术标本中，发现肿瘤内三级淋巴结构富含CD138+浆细胞，从这些浆细胞克隆的抗体可识别肿瘤细胞表面的瓜氨酸化蛋白，其中候选抗体PC-1的单链可变区构建的CAR-T细胞在体内特异性靶向肿瘤和促肿瘤髓系细胞且无脱靶活性，支持体液免疫在检查点阻断疗效中的角色。[25]揭示了RNA结合蛋白ZC3H18在肺癌中通过拷贝数增加而过表达，其相分离可结合LDHA启动子激活转录，促进乳酸生成，乳酸再通过组蛋白H3K18乳酸化和ZC3H18 K186位乳酸化形成正反馈环路，在患者来源异种移植模型中验证了该环路对肺癌生长的驱动作用。这些研究[20-25]共同拓展了肺癌的分子调控网络，并为靶向翻译、凋亡、免疫和代谢的联合治疗策略提供了实验依据。

综述Meta

2篇综述与Meta分析[26-27]聚焦肺癌诊疗中的社会属性和性别差异。[26]采用历史研究方法梳理了胸外科医生在肺癌诊疗中的角色演变，指出随着技术干预手段的积累，外科医生已从单一的技术专家转变为多学科团队与共情式沟通的协调者；肺癌特有的社会身份——包括吸烟污名化、诊断-手术路径的多样化——使外科协作决策变得格外复杂，文章在此基础上建议将共享决策作为胸外科医生核心胜任力加以培训。[27]则从性别维度出发，强调肺癌在不同性别中表现出显著差异，涉及流行病学特征、组织学类型、驱动基因谱及治疗结局，提示应将性别作为生物学变量纳入研究设计和临床管理。两篇综述[26-27]从历史和社会决定因素出发，共同提醒肺癌管理不能只关注分子靶点，还需将患者的社会身份、性别差异与决策偏好整合进个体化治疗框架。

食管癌 10 篇
临床研究

本周9项临床研究[28-36]覆盖食管癌及其癌前病变的多个环节。[28]为单臂初步研究，纳入23例Barrett食管患者，每日两次摄入含干酪乳杆菌代田株的发酵乳饮品共4周，结果显示化生柱状上皮中革兰氏阳性厚壁菌门显著增加（p<0.01），变形菌门由74%降至52%、厚壁菌门由20%升至31%，微生物多样性显著增加（p=9.98×10⁻⁷），提示益生菌干预可调节食管微生物组，但未报告临床结局。[30]为单中心回顾性分析，评估Barrett食管合并食管裂孔疝患者中CYP2C19表型分布，以指导质子泵抑制剂剂量调整，但结果未报告。[29]探索内镜组织学验证新辅助化疗免疫治疗后临床完全缓解的价值，具体设计、样本量与结果未报告。[31]为多中心欧洲队列研究，纳入2018—2023年接受新辅助化疗或放化疗后食管切除术的食管腺癌患者，运用RA-CUSUM与自举重采样确定与总生存期和无病生存期改善相关的淋巴结清扫数量阈值，具体最佳数值尚未报告。[33]为中国8家中心的多中心回顾性队列，纳入非病理完全缓解的食管鳞癌患者，比较新辅助放化疗与新辅助免疫化疗的预后，采用倾向性评分匹配，但具体效应量未报告。[34]为回顾性单中心队列，106例经胸食管切除+颈部重建患者术后第14天内镜检查，16例（15%）发生吻合口狭窄，多因素分析显示溃疡形成和食管水肿是独立危险因素（均P=0.03），提示早期内镜可预测狭窄风险。[36]为多中心回顾性研究，纳入263例cT2N0胸段食管鳞癌，比较新辅助化疗+手术与直接手术，结果显示临床分期准确性低（仅15.3%为pT2N0），48.3%直接手术患者存在隐匿性淋巴结转移，支持对cT2N0患者进行新辅助治疗。[32]报道光动力治疗后局部复发食管癌行补救性内镜黏膜下剥离术（连续冲洗法）的经验，但具体结果未报告。[35]为多中心前瞻性队列，纳入158例胃癌和食管癌术后患者，124例（78.5%）术后18个月仍在工作，高龄（≥65岁）及病理分期≥III期与延迟或未能返工相关。

综述Meta

本周1项系统综述与个体患者数据荟萃分析[37]比较了食管及食管胃结合部腺癌新辅助化疗（nCT）与新辅助放化疗（nCRT）后达到病理完全缓解（pCR）患者的长期结局。作者系统检索至2025年11月的PubMed、Embase等数据库，最终纳入6项研究共1454例pCR患者（nCT组374例，nCRT组1080例）。IPD荟萃分析显示，nCT组1年总生存率优于nCRT组（95.4% vs 87.8%），3年和5年总生存率亦均呈现nCT组优势（具体数值未完整报告），提示尽管nCT的pCR率较低，但一旦达到pCR，其长期生存可能优于nCRT。该结果对多模式治疗策略的选择具有潜在意义，但需注意为回顾性数据，且不同研究的异质性与分期差异可能影响结论强度。

纵隔肿瘤 1 篇
临床研究

本周仅 1 项临床研究[38]，为一项基于日本全国性数据库的回顾性分析，纳入 2018–2022 年间诊断的 III 期胸腺瘤（556 例）、III 期胸腺癌（312 例）、IV 期胸腺瘤（431 例）及 IV 期胸腺癌（976 例），系统描述了晚期胸腺上皮肿瘤的真实世界治疗实践。结果显示，完全切除后术后放疗在 III 期胸腺癌中的应用频率显著高于胸腺瘤（34.1% vs 10.7%），提示组织学类型显著影响辅助治疗决策；同时研究还评估了围手术期化疗、放疗以及新一代全身治疗的使用比例和具体化疗方案，但摘要未报告生存终点或效应量。该研究为晚期胸腺瘤和胸腺癌的治疗模式提供了大样本的真实世界证据，弥补了此类罕见肿瘤临床证据有限的短板，但其回顾性设计及缺乏结局比较限制了因果推断。未来需基于该队列进一步分析生存差异及治疗策略的优化，以指导个体化决策。

气胸·外伤·胸壁 3 篇
临床研究

本周3项临床研究[39-41]分别关注Nuss手术镇痛、漏斗胸年龄分层结局和肋骨骨折固定术中血胸处理，均为回顾性队列研究。[39]纳入82例≤21岁Nuss手术患者，比较标准单点冷冻消融与双点冷冻消融（额外处理肋间神经侧支）的术后镇痛效果，主要终点包括疼痛评分、阿片类药物用量（吗啡当量）及住院时间，具体结果未报告。[40]纳入526例按手术年龄分四组（3-6岁、7-10岁、11-14岁、≥15岁）的漏斗胸患者，拔棒后随访≥2年，结果显示术前Haller指数随年龄增长而降低（P<0.001），年龄较大组手术时间延长、出血量增多、支撑棒使用增多且非致命性并发症发生率升高（均P<0.001），总体不完全矫治率为6.3%（33/526），但该率随年龄的变化趋势未完整报告。[41]基于胸壁损伤学会国际数据库，纳入276例接受肋骨骨折手术固定（SSRF）合并血胸的患者，比较术中盲法血胸清除（IOPI）与直视下胸腔镜辅助（VATS）的预后，主要终点为术后胸管留置天数，次要终点包括肺炎、死亡率、ICU及住院时间等，结果未报告。三项研究均呈回顾性设计，样本量从数十至数百例不等，分别从手术细节和患者分层角度提供了临床证据，但需前瞻性或随机对照研究进一步验证。

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