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非小细胞肺癌伴纵隔淋巴结转移(N2)的外科治疗策略

Surgical therapeutic strategy for non-small cell lung cancer with mediastinal lymph node metastasis (N2).

作者信息

Ma Qianli, Liu Deruo, Guo Yongqing, Shi Bin, Song Zhiyi, Tian Yanchu

机构信息

Department of Thoracic Surgery, China-Japan Friendship Hospital, Beijing 100029, China.

出版信息

Zhongguo Fei Ai Za Zhi. 2010 Apr;13(4):342-8. doi: 10.3779/j.issn.1009-3419.2010.04.14.

Abstract

BACKGROUND AND OBJECTIVE

Approximately 30% of patients who are diagnosed with non-small cell lung cancer (NSCLC) are classified as N2 on the basis of metastasis to the mediastinal lymph nodes. The effectiveness of surgery for these patients remains controversial. Although surgeries in recent years are proved to be effective to some extent, yet due to many reasons, 5-year survival rate after surgery varies greatly from patient to patient. Thus it is necessary to select patients who have a high probability of being be cured through an operation, who are suitable to receive surgery and the best surgical methods so as to figure out the conditions under which surgical treatment can be chosen and the factors that may influence prognosis.

METHODS

165 out of 173 patients with N2 NSCLC were treated with surgery in our department from January 1999 to May 2003, among whom 130 were male, 43 female and the sex ratio was 3:1, average age 53, ranging from 29 to 79. The database covers the patients' complete medical history including the information of their age, sex, location and size of tumor, date of operation, surgical methods, histologic diagnosis, clinical stage, post-operative TNM stage, neoadjuvant treatment and chemoradiotherapy. The methods of clinical stage verification include chest X-ray, chest CT, PET, mediastinoscopy, bronchoscope (+?), brain CT or MRI, abdominal B ultrasound (or CT), and bone ECT. The pathological classification was based on the international standard for lung cancer (UICC 1997). Survival time was analyzed from the operation date to May 2008 with the aid of SPSS (Statistical Package for the Social Sciences) program. Kaplan-Meier survival analysis, Log-rank test and Cox multiplicity were adopted respectively to obtain patients' survival curve, survival rate and the impact possible factors may have on their survival rate.

RESULTS

The median survival time was 22 months, with 3-year survival rate reaching 28.1% and 5-year survival rate reaching 19.0%. Age, sex, different histological classification and postoperative chemoradiotherapy seem to have no correlation with 5-year survival rate. In all N2 subtypes, 5-year survival rate is remarkably higher for unexpected N2 discovered at thoractomy and proven N2 stage before preoperative work-up and receive a mediastinal down-staging after induction therapy (P < 0.01), reaching 30.4% and 27.3% respectively. 5-year survival rate for single station lymph node metastasis were 27.8%, much higher compared with 9.3% for multiple stations (P < 0.001). Induction therapy which downstages proven N2 in 73.3% patients gains them the opportunity of surgery. The 5-year survival rate were 23.6% and 13.0% for patients who had complete resection and those who had incomplete resection (P < 0.001). Patients who underwent lobectomy (23.2%) have higher survival rate, less incidence rate of complication and mortality rate, compared with pneumonectomy (14.8%) (P < 0.01). T4 patients has a 5-year survival rate as low as 11.1%, much less than T1 (31.5%) and T2 (24.3%) patients (P = 0.01). It is noted through Cox analysis that completeness of resection, number of positive lymph node stations and primary T status have significant correlativity with 5-year survival rate.

CONCLUSION

It is suggested that surgery (lobectomy preferentially) is the best solution for T1 and T2 with primary tumor have not invaded pleura or the distance to carina of trachea no less than 2 cm, unexpected N2 discovered at thoractomy when a complete resection can be applied, and proven N2 discovered during preoperative work-up and is down-staged after induction therapy. Surgical treatment is the best option, lobectomy should be prioritized in operational methods since ise rate of complication and morality are lower than that of pneumonectomy. Patients' survival time will not benefit from surgery if they are with lymph nodes metastasis of multiple stations (Bulky N2 included) and T4 which can be partially removed. Neoadjuvant chemotherapy increases long-term survival rate of those with N2 proven prior to surgery. However, postoperative radiotherapy decreases local recurrence rate but does not contribute to patients' long-term survival rate.

摘要

背景与目的

约30%被诊断为非小细胞肺癌(NSCLC)的患者因纵隔淋巴结转移而被归类为N2期。此类患者手术治疗的有效性仍存在争议。尽管近年来的手术已被证明在一定程度上是有效的,但由于多种原因,术后5年生存率在患者之间差异很大。因此,有必要选择那些通过手术治愈可能性高、适合接受手术及最佳手术方式的患者,以明确可选择手术治疗的条件以及可能影响预后的因素。

方法

1999年1月至2003年5月,我科173例N2期NSCLC患者中有165例接受了手术治疗,其中男性130例,女性43例,男女比例为3:1,平均年龄53岁,年龄范围为29至79岁。数据库涵盖患者完整的病史,包括年龄、性别、肿瘤位置和大小、手术日期、手术方式、组织学诊断、临床分期、术后TNM分期、新辅助治疗及放化疗情况。临床分期验证方法包括胸部X线、胸部CT、PET、纵隔镜检查、支气管镜检查(+?)、脑部CT或MRI、腹部B超(或CT)以及骨ECT。病理分类依据国际肺癌标准(UICC 1997)。借助SPSS(社会科学统计软件包)程序分析从手术日期至2008年5月的生存时间。分别采用Kaplan-Meier生存分析、Log-rank检验和Cox多因素分析来获取患者的生存曲线、生存率以及可能影响生存率的因素。

结果

中位生存时间为22个月,3年生存率达28.1%,5年生存率达19.0%。年龄、性别、不同组织学分类及术后放化疗似乎与5年生存率无相关性。在所有N2亚组中,开胸手术时意外发现的N2以及术前检查确诊为N2期且诱导治疗后纵隔分期降低的患者,其5年生存率显著更高(P<0.01),分别达到30.4%和27.3%。单站淋巴结转移患者的5年生存率为27.8%,远高于多站转移患者的9.3%(P<0.001)。诱导治疗使73.3%确诊为N2期的患者分期降低,从而获得手术机会。完全切除和不完全切除患者的5年生存率分别为23.6%和13.0%(P<0.001)。与全肺切除术(14.8%)相比,接受肺叶切除术的患者生存率更高,并发症发生率和死亡率更低(P<0.01)。T4患者的5年生存率低至11.1%,远低于T1(31.5%)和T2(24.3%)患者(P = 0.01)。通过Cox分析可知,切除完整性、阳性淋巴结站数及原发肿瘤T状态与5年生存率具有显著相关性。

结论

对于T1和T2期、原发肿瘤未侵犯胸膜或距气管隆突不少于2cm、开胸手术时意外发现N2且可完整切除、术前检查确诊为N2且诱导治疗后分期降低的患者,建议手术治疗(优先选择肺叶切除术)。手术治疗是最佳选择,手术方式应优先考虑肺叶切除术,因其并发症发生率和死亡率低于全肺切除术。对于多站淋巴结转移(包括巨大N2)和T4期且仅能部分切除转移灶的患者,手术无法使其生存时间获益。新辅助化疗可提高术前确诊为N2期患者的长期生存率。然而,术后放疗可降低局部复发率,但对患者的长期生存率无贡献。

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