双侧同时多原发性非小细胞肺癌外科治疗疗效分析

Survival after surgical treatment of bilateral synchronous multiple primary non-small cell lung cancers

目的探讨双侧同时多原发性非小细胞肺癌患者的临床特点，分析与外科疗效相关的临床预后因素。方法采用改良的Martini—Melamed诊断标准，对2010年1月至2014年12月在中国医学科学院肿瘤医院胸外科手术治疗的96例双侧同时多原发性非小细胞肺癌患者的临床资料进行回顾性分析，双侧病变均行根治性手术切除且有明确的病理诊断与分期。采用Kaplan．Meier法计算无复发生存率和总生存率，Logrank检验比较生存差异，Cox风险比例回归模型进行预后多因素分析。结果96例患者中，有2例患者因术后严重并发症死亡，共94例进行生存分析。94例患者中，分期手术93例，一期手术1例：双原发肺癌患者79例，三原发及以上肺癌患者15例（其中3个癌灶9例，4个癌灶4例，5个癌灶2例）；至少有2个癌灶位于同一肺叶者12例，各个癌灶位于独立的不同肺叶者82例：病理类型均为腺癌者76例，均为鳞癌者12例，腺癌＋鳞癌者5例，腺癌＋腺鳞癌者1例。全组患者的1、3、5年无复发生存率分别为87．4％、70．8％和58．1％，1、3、5年总生存率分别为97．6％、89．0％和82．7％。单因素分析结果显示，最大肿瘤直径、最高胡分期、淋巴结转移情况与患者无复发生存有关（均P〈0．01）；性别、最大肿瘤直径、最高一分期、淋巴结转移情况与患者的总生存有关（均P〈0．05）。Cox多因素回归分析显示，最高胡分期和淋巴结转移情况是影响双侧同时多原发性非小细胞肺癌患者术后无复发生存和总生存的独立因素（均P〈0．05）。结论对双侧多发结节的诊断应仔细谨慎；双侧同时多原发非小细胞肺癌患者根治术后的生存率较高，在充分保证安全和根治原则的基础上能够从分期手术中获益。最高pT分期和淋巴结转移情况是影响双侧多原发非小细胞肺癌患者术后生存的独立因素，应尽量进行充分的手术切除及彻底的淋巴结清扫以准确判断预后。

Objective To explore the clinical characteristics of patients with bilateral synchronous multiple primary non-small eel1 lung cancer （NSCLC） and identify the prognostic indicators associated with survival. Methods From January 2010 to December 2014, clinicopathological data of 96 patients with bilateral synchronous multiple primary NSCLC, who met the modified Martini-Melamed criteria and underwent radical surgical resection, were retrospectively reviewed. Survival was estimated using the Kaplan- Meier method, and the clinical parameters associated with survival were analyzed using a log-rank test. Cox proportional hazards regression models were used to identify the risk factors for this cancer. Results Of the 96 patients, two patients who died of severe postoperative complications were excluded, and 94 patients were analyzed. Of the 94 cases, a two-stage operation was performed in 93 patients, while a single-stage bilateral surgery was performed in only one patient using video-assisted thoracic surgery （VATS）. 79 patients had 2 tumors and the other 15 patients had 3 or more tumors. There were 82 patients with synchronous tumors located in different lobes and 12 patients bad at least two tumors located in the same lobe. Seventy-six patients were found to have multiple lung adenocarcinoma and 12 patients had multiple squamous cell carcinoma （SCCs）. Five patients had adenocarcinoma and SCC, and one patient had adenocarcinoma and adenosquamous carcinoma simultaneously. Univariate analysis showed that the large maximum tumor diameter, highest pT stage and lymph node involvement were associated with an unfavorable DFS （P〈0.01 for all ） , while female gender, small maximum tumor diameter, early highest pT stage and pN0 were associated with a better overall survival （OS）. Multivariate analysis showed that highest pT stage and lymph node metastasis were independent prognostic factors for DFS and OS. Patients with a lower highest pT stage and negative lymph node metastasis had longer DFS and OS （P 〈 0.05 for both）. Conclusions The diagnosis for patients with bilateral synchronous multiple primary NSCLCs should be made very carefully. Two stage surgical treatment is safe, reasonable and effective for patients with bilateral synchronous multiple primary NSCLCs in a relatively early stage. The highest pT stage and pN status are important predictors for long-term survival. Adequate pulmonary tissue resection with complete resection of multiple nodules and systematic lymphadenectomy are suggested.