非小细胞肺癌围手术期免疫治疗相关不良反应管理的临床诊疗建议

背景与目的肺癌围手术期治疗(术前新辅助治疗及术后辅助治疗)作为手术的重要辅助手段,已成为非小细胞肺癌(non-small cell lung cancer,NSCLC)全程管理中越来越重要的环节。近年来,小规模临床研究发现免疫新辅助治疗主要病理缓解率明显提升,甚至达到完全病理缓解,有望成为NSCLC治疗的重要组成部分。然而,免疫新辅助治疗带来疗效和生存获益,同时,其相关严重不良反应(延误手术、丧失手术机会、死亡等)备受关注。本诊疗建议目的是针对免疫检查点抑制剂相关不良反应(immune-related adverse event,irAE)形成适合国内医疗现状的诊疗方案。方法本文由胸外科专家、肿瘤学专家、胸内科专家以及irAE相关科室专家(消化内科、呼吸内科、心血管内科、感染内科、血液内科、内分泌科、风湿免疫科、神经内科、皮肤科和急诊科)共同完成本诊疗意见的制定工作。专家充分参考irAE指南、胸外科公开发表的大型临床研究数据以及国内医生的临床实战经验和公开发表个案,多学科反复讨论,形成针对围手术期免疫治疗相关不良反应的诊疗建议。结果本诊疗意见涵盖irAE相关的预防、评估、检查、治疗和监测全过程,以便全面、有效的指导临床工作。结论围手术期irAE管理是肺癌免疫围手术期治疗的重要组成部分,随着免疫围手术期治疗的不断发展,未来需要更多的研究,以优化围手术irAE的诊疗。

MiR-148b-3p在肺腺癌中的表达及其与患者预后的相关性

背景与目的 MiR-148b-3p是一种重要的微小RNA,已经被报道与多种癌症密切相关,但其在肺腺癌中的作用仍不清楚。本研究的目的是检测miR-148b-3p在肺腺癌中的表达水平,并分析其与临床病理特征及患者预后的相关性。方法收集2011年1月-2012年12月在本科室经手术切除的肺腺癌患者的肿瘤标本123例,利用实时荧光定量PCR方法检测miR-148b-3p的表达量,分析其与患者临床病理特征的相关性。利用多因素Cox比例风险模型分析影响患者总生存的独立预测因子。利用Kaplan-Meier生存分析方法估计miR-148b-3p高表达组和低表达组患者的总生存期,并使用Log-rank检验方法进行显著性检验。结果在123例肺腺癌患者中,有71例高表达miR-148b-3p,52例低表达。miR-148b-3p与肿瘤的分化程度(P=0.001)、肿瘤大小(P=0.007)显著相关,而与年龄、性别、吸烟史、饮酒史、脉管癌栓、胸膜侵犯、淋巴结转移、远处转移和术后治疗不存在统计学显著的相关性。多因素Cox比例风险模型分析显示肿瘤大小(P=0.032)、淋巴结转移(P=0.005)和miR-148b-3p表达量(P=0.047)是影响患者总生存的独立预测因子。Kaplan-Meier生存分析显示miR-148b-3p高表达组患者的总生存显著优于miR-148b-3p低表达组患者(P=0.010)。结论 MiR-148b-3p在肺腺癌中与肿瘤的分化程度、肿瘤大小显著相关,并且是影响患者总生存的独立预测因子。MiR-148b-3p高表达组患者的总生存显著优于低表达组患者。因此,miR-148b-3p可能成为新的肺腺癌治疗靶标或预后生物标志物。

Does an extended mediastinal lymphadenectomy improve outcome after R0 resection in lung cancer?

Objective： This retrospective study was conducted to investigate the impact of more extended mediastinal lymphadenectomy on the outcome of lung cancer patients treated with R0 resection. Methods： During the investigation period, 325 lung cancer cases were enlisted and 278 cases entered the analysis. The patients were divided into Control group （n=116） and Research group （n=162） according to the different extents of mediastinal lymph node clearance at different time periods. Three major parameters were retrospectively assessed to compare the quality of surgical care： extent of lymph node clearance, resection volume, and postoperative recovery process and common complications. Comparison of the outcome between two groups was carried out. Results： Research group showed a significant quality improvement of lymphadenectomy, such as more mediastinal node stations investigated （more than 3 N2 stations investigated： Research group, 90.7% vs. Control group, 55.2%; P=0.001） and more nodes collection （total nodes 26.1±10.0 vs. 19.1±8.3, P=0.000; N2 nodes 15.5±7.2 vs. 9.8±5.6, P=0.000）. However, overall survival （OS） and disease-free survival （DFS） were not significantly different either between two groups （5-year OS： Control group, 56.4±4.6% vs. Research group, 62.6±4.3%; P=0.271） or between subgroups from stage I to IIIa. TNM stage and histology were significant factors associated with OS and DFS in multivariate analysis; extent of mediastinal lymphadenectomy was not associated with OS or DFS. Conclusions： More radical mediastinal lymphadenectomy may not lead to an improved oncological outcome for lung cancer treated with R0 resection.

支气管覆膜支架封堵治疗右肺中下叶切除术后支气管残端瘘经验1例

背景与目的支气管胸膜瘘是临床上较为严重且罕见的术后并发症之一,尤其是肺叶/全肺切除术后支气管残端瘘,处理起来较为棘手。常见治疗方案包括内科保守治疗联合外科手术,但由于瘘口迁延不愈导致胸腔持续与外界相通,患者容易合并严重的胸腔感染及呼吸衰竭等合并症,以至于身体状况无法耐受二次手术。而内镜下治疗,为该合并症的治疗提供了新的思路。方法回顾性分析了北京大学肿瘤医院胸外二科2016年6月收治的1例右肺鳞癌患者的诊断、治疗过程,并文献复习。结果患者男性,65岁,因"咳嗽伴痰中带血3月余"入院,胸部计算机断层扫描提示右肺下叶软组织密度肿块影,气管镜提示右肺中叶及下叶基底段开口可见肿物,活检病理证实为鳞癌。诊断考虑:右肺中下叶鳞癌(c T2aN2,IIIa期)。患者接受了吉西他滨+顺铂方案新辅助化疗2个周期,评效为疾病稳定(stable disease,SD)。末次化疗结束4周之后,患者接受了胸腔镜辅助右肺中下叶切除、纵隔淋巴结清扫术。术后第5天患者出现急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)再次气管插管转入重症加强护理病房(intensive care unit,ICU),并给予激素冲击治疗。术后第7天患者出现右肺中间干支气管残端瘘,但由于合并ARDS,患者身体情况无法耐受二次手术。遂于体外人工膜肺(extracorporeal membrane oxygenation,ECMO)支持下,经硬质支气管镜在中间干支气管残端置入一枚定制的覆膜、可膨胀金属铰链支架,并成功封堵。由于患者的ARDS未见好转,出现不可逆的肺间质纤维化,经过系统的抗感染治疗之后,患者成功接受了双肺移植手术。结论内镜下放置覆膜支架是一种简单、安全、有效的支气管残端瘘闭合术。当患者的临床情况不适合立即手术时,内镜下支架植入可作为一种优选的治疗方法,为后续治疗创造机会。

Adjuvant chemotherapy may improve outcome of patients with non-small-cell lung cancer with metastasis of intrapulmonary lymph nodes after systematic dissection of N1 nodes

Objective: Survival benefit of adjuvant chemotherapy(AC) of patients with intrapulmonary lymph node(IPLN)metastasis(level 12-14) needs investigation.We evaluated the impact of AC on patients whose metastatic nodes were limited to intrapulmonary levels after systematic dissection of N1 nodes.Methods: First,155 consective cases of lung cancer confirmed as pathologic N1 were collected and evaluated.Patients received systematic dissection of N2 and N1 nodes.For patients with IPLN metastasis,survival outcomes were compared between those receiving AC and those not receiving AC.Results: In this group,112 cases(72.3%) had IPLN metastasis and 55 cases(35.5%) had N1 involvement limited to level 13-14 without further disease spread to higher levels.Patients with IPLN involvement had a better prognosis than that of patients with hilar-interlobar involvement.For the intrapulmonary N1 group(level 12-14-positive,level 10-11-negative or unknown,n=112),no survival benefit was found between the AC group and nonAC group [5-year overall survival(OS): 54.6±1.6 vs.50.4±2.4 months,P=0.177].However,76 of 112 cases for whom harvesting of level-10 and level-11 nodes was done did not show cancer involvement in pathology reports(level 12-14-positive,level 10-11 both negative),oncologic outcome was better for patients receiving AC than those not receiving AC in this subgroup(5-year OS: 57.3±1.5 vs.47.1±3.2 months,P=0.002).Conclusions: Oncologic outcome may be improved by AC for patients with involvement of N1 nodes limited to intrapulmonary levels after complete examination of N1 nodes.