Abstract
近20年来，随着计算机断层扫描（computed tomography, CT）技术的提高和肺癌高危人群筛查的普及，越来越多的肺部小结节被发现，然而肺结节的定性诊断仍有很多困难。肺结节是临床上一种常见的现象，恶性结节早期发病比较隐匿，如果不进行早期干预，其病程迅速、恶性程度强、预后差。如果能在早期阶段对病灶进行手术切除，将会明显改善肺癌患者的预后。目前针对肺结节的处理指南层出不穷，但各大指南均未达成统一的共识。本文拟对在国内影响最大的四个指南：美国国家综合癌症网络非小细胞肺癌（non-small cell lung cancer, NSCLC）临床实践指南、美国胸科医师协会肺癌诊疗指南、Fleischner-Society肺结节处理策略指南、肺结节的评估亚洲共识指南所推荐的肺结节诊断和处理策略进行介绍和分析。
Keywords: 肺结节, 共识, 指南
Abstract
In the past 20 years, with the popularization of low-dose computed tomography (CT) screening, detection rate of lung nodules increased significantly. However, there are still many difficulties in making qualitative diagnosis for pulmonary nodules. The Lung nodule is a clinical common lung disease. The early onset for malignant nodules is quite hidden. Without early intervention, the course of disease can develop rapidly. For malignant nodules, the exacerbation can be very severe. Besides, the therapeutic effect can be unsatisfactory. If the lesion resection can be performed in early stage, lung cancer patients' prognosis can be improved significantly. At present, the guidelines of lung nodules' treatment are diverse, but these guidelines still can't reach a consensus until now. This article reviews the literature in National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for Non-Small Cell Lung Cancer (NSCLC), American College of Chest Physicians (ACCP) guidelines for the diagnosis and treatment of pulmonary nodules, Fleischner society lung cancer treatment strategy guide, and clinical practice consensus guidelines for Asia, which are pertaining to lung nodules diagnosis and treatment strategy and try to explain the similarities and differences between them.
Keywords: Lung nodules, Consensus, Guideline
肺结节是一种临床中常见的现象，包括良性结节和恶性结节，恶性肺结节早期发现比较隐匿，如果不早期干预，其病程迅速、恶性度强、预后差。目前对肺结节的定性诊断仍有很多困难，在临床外科切除的肺结节中，30%左右为良性的，所以正确评价肺结节的良恶性，有助选择正确的治疗手段 [ 1 ] 。随着影像学技术的发展以及低剂量计算机断层扫描（low-dose computed tomography, LDCT）的普及，肺结节的检出率明显增高，肺结节的临床处理与决策逐渐成为困扰临床医生的问题之一。2013年美国癌症协会发布的最新报告显示，美国肺癌5年整体存活率为16%，然而，由于早期筛查在美国的开展，早期肺癌5年生存率已达70%-90% [ 2 , 3 ] 。因此，国内外的专家们一直想通过对肺癌的筛查来实现早期诊断及治疗，从而降低死亡率 [ 4 - 9 ] 。目前针对肺结节的处理指南层出不穷，但各大指南均未达成统一的共识。本文对美国国家综合癌症网络（National Comprehensive Cancer Network, NCCN）、Fleischner学会、美国胸科医师协会（American College of Chest Physicians, ACCP）和亚洲共识四大指南进行分析，进一步阐释肺结节诊断和处理策略的异同并对其进行综述。
1. 四大指南肺结节影像学随访策略的区别
影响肺结节的随访策略的主要因素是肺结节的影像学特点以及患者自身的危险因素，影像学因素包括肺结节的大小、形状、密度、数量、肺实质异常以及正电子发射型计算机断层显像（positron emission computed tomography, PET-CT）中的氟脱氧葡萄糖（fluorodeoxy-glucose, FDG）活性，其中最主要的是与之前影像学资料进行比较，评估肺结节的稳定性，影响患者自身的危险因素主要是吸烟史和年龄。四大指南对于肺结节评估筛查的目标人群非常相似，但对于阳性结果的CT随访策略却又有不同之处，且对于筛查风险问题仍存在争议。
1.1. 对于实性结节影像学随访策略的区别（ 表 1 ）
实性结节影像学随访策略的区别
The difference of the follow up strategy of solid nodules
CT: computed tomography; NCCN: National Comprehensive Cancer Network; ACCP: American College of Chest Physicians; PET: positron emission computed tomography. 2016 NCCN Guidelines No follow-up needed CT at 12 mo, if stable, no further follow-up CT at 6-12 mo, if stable, then repeat CT at 18-24 mo CT at 3, 9, and 24 mo, consider PET or biopsy CT at 12 mo, if stable, no further follow-up CT at 6-12 mo, if stable, repeat CT at 18-24 mo CT at 3-6 mo, if stable, repeat CT at 9-12 mo and 24 mo CT at 3, 9, and 24 mo, consider PET or biopsy 2017 Fleischner Society Guidelines No routine follow-up No routine follow-up CT at 6-12 mo, if stable, then repeat CT at 18-24 mo Consider CT, PET, or tissue sampling at 3 mo Optional CT at 12 mo Optional CT at 12 mo CT at 6-12 mo then CT at 18-24 mo Consider CT, PET or tissue sampling at 3 mo 2013 ACCP Guidelines No follow-up needed CT at 12 mo CT at 6-12 mo, if stable, then repeat CT at 18-24 mo CT at 3, 9, and 24 mo, consider PET or biopsy No follow-up needed CT at 6-12 mo, if stable, repeat CT at 18-24 mo CT at 3-6 mo, if stable, repeat CT at 9-12 mo and 24 mo CT at 3, 9, and 24 mo, consider PET or biopsy 2016 Clinical practice consensus guidelines for Asia Annual CT surveillance CT at 12 mo and then annual CT surveillance CT at 6-12 mo, if stable, then repeat CT at 18-24 mo and then annual CT surveillance CT at 3-6, 9-12, and 18-24 mo, if the nodule sclear growth then surgical biopsy Patient discussion CT at 6-12 mo, if stable, then repeat CT at 18-24 mo and then annual CT surveillance CT at 3, 6, and 12 mo then annual CT surveillance PET scan if hypermetabolic，surgical biopsy, if surgical biopsy is positive, then surgical resection1.1.1. ＜4 mm
NCCN、ACCP、Fleischner协会指南均建议不需要随诊，亚洲共识指南建议每年复查1次CT。
1.1.2. ＞4 mm且＜6 mm
NCCN协会指南建议低危人群1年后复查CT；建议高危人群半年到1年之间、1年半到2年之间复查2次CT [ 10 ] 。ACCP指南处理方案与NCCN大致相同，只是人群分类标准不同，ACCP指南中把人群分为有、无肺癌危险因素，而NCCN和Fleischner协会则根据危险因素的多少，更加详细的分为低风险人群和高风险人群。Fleischner协会指南建议不需常规随访。亚洲共识指南建议低危人群每年复查CT，中、高危人群在NCCN指南基础上每年复查1次CT。
1.1.3. ＞6 mm且＜8 mm
NCCN指南建议低危人群在半年到1年之间、1年半到2年之间复查2次CT，建议高危人群3个月到半年之间、9个月到1年之间、2年复查3次CT。ACCP指南处理方案与NCCN大致相同。Fleischner协会指南建议半年到1年复查CT，之后再考虑1年半到2年之间复查CT。亚洲共识指南建议低危人群半年到1年之间、1年半到2年之间复查2次CT，以后每年复查1次CT；中、高危人群分别在第3个月、半年、1年复查3次CT，以后每年复查1次CT。
1.1.4. ≥8 mm
NCCN和ACCP指南均建议在第3个月、第9个月、2年复查3次CT，可行动态增强CT、PET和（或）活检 [ 11 ] 。Fleischner协会指南建议3个月后复查CT、PET-CT或活检。亚洲共识指南建议低危人群3个月到半年之间、9个月到1年之间、1年半到2年之间复查3次CT，若肺结节较前增大，则建议外科活检；建议中危人群行PET-CT扫描，高度怀疑者可行外科活检，中低度怀疑者建议定期监测；建议高危人群行外科手术活检，若活检结果为阳性，建议手术切除。
1.2. 对于磨玻璃和部分实性结节影像学随访策略的区别（ 表 2 ）
磨玻璃和部分实性结节影像学随访策略的区别
The difference of the follow-up strategies between the ground-glass nodules and part solid nodules
No follow-up needed CT at 3 mo, and annual CT for at least 3 years CT at 3 mo, and annual CT for at least 3 years CT at 3 mo, and annual CT for at least 3 years Biopsy or surgical resection Biopsy or surgical resection Biopsy or surgical resection 2017 Fleischner Society Guidelines No follow-up needed No follow-up needed CT at 6-12 mo to confirm persistence, then CT every 2 years until 5 years No follow-up needed No follow-up needed CT at 3-6 mo to confirm persistence, if unchanged and solid component remains 6 mm, annual CT should be performed for 5 years CT at 3-6 mo to confirm persistence, if unchanged and solid component remains 6 mm, annual CT should be performed for 5 years 2013 ACCP Guidelines No follow-up needed Annual CT for at least 3 years Annual CT for at least 3 years CT at 3, 12, 24 mo, and then annual CT for at 1-3 years CT at 3, 12, 24 mo, and then annual CT for at 1-3 years CT at 3, 12, 24 mo, and then annual CT for at 1-3 years CT at 3 mo to confirm, persistencIf persistent, biopsy surgical resection if a nodule ＞15 mm at first CT scan，then biopsy, PET or surgical resection 2016 Clinical practice consensus guidelines for Asia Discuss role of continued surveillance with patient Annual CT surveillance for at least 3 years, consider ongoing annual CT surveillance after discussion with patient Annual CT surveillance for at least 3 years, consider ongoing annual CT surveillance after discussion with patient CT at 3, 12, 24 mo, and then annual CT surveillance CT at 3, 12, 24 mo, and then annual CT surveillance CT at 3, 12, 24 mo, and then annual CT surveillance CT at 3 mo, and consider antimicrobial therapy (nonsurgical or surgical biopsy consider PET scanning for staging before biopsy)1.2.1. ＜5 mm孤立性纯磨玻璃结节
NCCN、Fleischner协会和ACCP指南均建议不需要随诊 [ 12 , 13 ] ，亚洲共识指南建议每年复查1次CT。
1.2.2. ≥5 mm孤立性纯磨玻璃结节
NCCN指南建议3个月、1年、2年、3年共复查4次CT。ACCP指南与NCCN指南大致相同，但强调3个月内不需要复查CT。亚洲共识指南建议每年复查1次CT，亚洲共识指南与Fleischner协会指南的区别在于亚洲共识要求连续3年复查CT后，如果结节无明显变化，仍需继续年度复查CT，而Fleischner协会则建议3个月-6个月复查CT，确定病灶是否还存在，如果病灶不变或者实性成分维持在＜6 mm，需每年复查CT，满5年。
1.2.3. 孤立部分实性结节
NCCN指南建议结节稳定或实性成分＜5 mm时，3个月、1年、2年、3年复查4次CT；结节稳定或实性成分≥5 mm时，活检或手术切除 [ 14 ] 。ACCP指南建议结节≤8 mm时，3个月、1年、2年复查3次CT，然后进行1年-3年的年度随访。建议结节 ＞8 mm时，3个月复查1次CT，如果结节持续存在，需考虑PET、非手术活检或手术切除。如果结节发现时即 ＞15 mm，直接进行PET，非手术活检或手术切除 [ 15 ] 。Fleischner协会指南建议结节 ＞6 mm时，3个月-6个月复查CT，确定病灶是否还存在，如果病灶不变或者实性成分维持在＜6 mm，需每年复查CT，满5年；结节≤6 mm时，无需常规随访。亚洲共识指南建议结节≤8 mm时，3个月、1年、2年复查3次CT，然后每年复查1次CT；建议结节 ＞8 mm时，3个月复查1次CT，可行抗炎治疗、手术或非手术方式活检，活检前可先行PET-CT检测。