淋巴结清扫数目对进展期食管癌TNM分期和预后的影响

Influence of number of removed lymph nodes on the TNM staging and survival in advanced esophageal carcinoma

目的评估食管癌手术淋巴结清扫数目对TNM分期及预后的影响。方法回顾分析1984年至1989年间1098例随访10年以上的进展期食管鳞癌患者的临床资料。应用Kaplan-Meier生存曲线、多变量Cox风险比例模型及单变量Log rank检验,比较手术清扫淋巴结数目<6枚及≥6枚对食管癌TNM分期和预后的影响。结果1098例患者中,378例有淋巴结转移,转移率34.4%。共摘除淋巴结4157枚,其中阳性淋巴结800枚,淋巴结转移度为19.2%。平均每例患者摘除淋巴结3.8枚,其中清扫淋巴结<6枚(A组)825例,≥6枚(B组)273例。Cox回归显示,A组的生存曲线差于B组,且肿瘤侵袭深度、淋巴结转移程度、肿瘤部位及切缘癌残留是影响患者预后的重要因素。A组的淋巴结转移率(30.3%)明显低于B组(46.9%,P<0.001),而A组淋巴结转移度(21.2%)显著高于B组(17.5%,P=0.002)。淋巴结转移状况与手术摘除淋巴结总数呈明显正相关(Phi= 0.151,P<0.001)。分层比较显示,未发现A组淋巴结转移患者的生存状况明显差于B组(P= 0.0034),而两组有1枚或≥2枚淋巴结转移的患者术后生存差异无统计学意义(P=0.919,P= 0.182)。A组中Ⅱa期(T2N0M0,T3N0M0)患者生存状况显著差于B组(P=0.0047),而Ⅱb期和Ⅲ期患者生存差异无统计学意义(P=0.3017,P=0.1078)。结论(1)淋巴结转移数目是影响患者术后生存的重要因素,应在修订TNM分期标准时加以考虑;(2)当手术摘除淋巴结数目<6枚时,可能遗漏已转移的区域淋巴结,影响N分级的准确性,UICC推荐的手术清扫淋巴结数目不低于6枚有其合理性,应予重视。

Objective To evaluate the impact of total number of removed regional lymph nodes （LN） during esophagectomy on TNM staging and long-term survival. Methods Between 1984 and 1989, a total of 1098 patients with advanced squamous cell carcinoma of the thoracic esophagus were surgically treated, and the data were retrospectively analyzed. The survival was analyzed by Kaplan-Meier method. Multivariate and univariate analysis were performed using Cox proportional hazard model and Log-rank test respectively in order to compare the survival difference and the impact of 〈6 or ≥6 removed LN on TNM staging and survival. Results The shortest follow-up time was 10 years with a follow-up rate of 91.4%. Of these 1098 patients, 378 patients were found to have regional LN metastases with a LN metastasis rate of 34.4%. Totally, 4157 LN were removed and tumor spreading into the lymph node was documented in 800 with a lymph node metastasis degree of 19.2%. The mean number of removed LN in each esophgectomy was 3.8. According to the number of total removed LN, patients were divided into group A （ removed LN 〈 6, N = 825） and group B （removed LN≥6, N =273）. The survival of group A was worse than that of group B. The depth of tumor invasion, degree of lymph node metastasis, tumor location, and tumor residual status were the most important prognostic factors. Even though the lymphatic metastasis rate in group A was significantly lower than that in group B （ 30. 3% vs. 46.9% , P 〈 0. 001 ）, the LN metastasis degree was higher in group A than that in group B（21.2% vs. 17.5% , P =0. 002） due to less number of removed LNin group A than in group B. With the stratification analysis according to the nunrber of involved lymph nodes ,for patients without LN spreading, the survival in group A was significantly worse than that in group B （P =0. 003） ,but in the patients with only one or ≥2 positive nodes, the survival was similar （P = 0. 919 and 0.182, respectively）. When stratified patients according to TNM stage, for stage Ha patients （T2NOM0, T3NOM0）, the survival in group A was significantly worse than that in group B （P =0. 006）, while such difference did not exist in patients with stage II b or stage Ⅲ （P = 0. 302 and 0. 108, respectively）. Conclusion A large series of retrospective study on advanced squamous cell carcinoma of the thoracic esophagus demonstrates that the number of metastatic LN is an important prognostic factor, therefore, it should be considered when refining UICC-TNM classification for esophageal cancer. If the total number of LN removed during each esophagectomy is less than 6, the occult positive regional LN might be missed, resulting in an inaccurate N classification and incorrect staging. Removal of ≥6 LN for each esophageal cancer patient during esophagectomy recommended by UICC is rational and should be complied with.