新辅助放化疗联合手术治疗中低位直肠癌淋巴结检出数目对预后的影响

Effects of the number of harvested lymph nodes in neoadjuvant chemoradiotherapy combined with surgery on prognosis of middle-low rectal cancer

  • 摘要: 目的:探讨新辅助放化疗(nCRT)联合手术治疗中低位直肠癌淋巴结检出数目对预后的影响。
    方法:采用回顾性病例对照研究方法。收集2009年1月至2013年12月福建医科大学附属协和医院收治的373例行nCRT联合手术治疗中低位直肠癌患者的临床病理资料;男241例,女132例;年龄为(55±11)岁,年龄范围为26~81岁。观察指标:(1)治疗情况。(2)随访和生存情况。(3)淋巴结检出数目影响因素分析。(4)不同淋巴结数目作为分组截点的预后分析。(5)分层分析。采用电话、门诊复查的方式进行随访,了解患者术后生存情况。术后2年内每3个月随访1次,术后第3年每6个月随访1次。随访终点为肿瘤复发、转移或患者死亡。随访时间截至2016年3月。正态分布的计量资料以Mean±SD表示,组间比较采用独立样本t检验。偏态分布的计量资料以M(范围)表示,组间比较采用Kruskal-Wallis H检验。计数资料以绝对数表示。采用多元线性回归进行单因素和多因素分析。采用Kaplan-Meier法计算生存率,采用Log-rank检验进行生存情况分析。
    结果:(1)治疗情况:373例患者均完成nCRT联合手术治疗,其中联合行保留括约肌直肠切除术329例,联合行腹会阴联合直肠切除术44例。373例患者淋巴结检出数目为(12±6)枚,其中淋巴结检出数目<12枚185例,淋巴结检出数目≥12枚188例。(2)随访和生存情况:373例患者均获得术后随访,随访时间为5~77个月,中位随访时间为43个月。随访期间,373例患者术后1、3、5年总体无病生存率分别为90.4%、76.3%、67.5%。(3)淋巴结检出数目影响因素分析。单因素分析结果显示:肿瘤距肛缘距离、肿瘤直径、肿瘤病理学N分期、直肠癌消退分级是影响患者淋巴结检出数目的相关因素(t=3.156,2.992, x2=8.183,10.839,P<0.05)。多因素分析结果显示:肿瘤距肛缘距离、直肠癌消退分级、肿瘤病理学N分期是影响患者淋巴结检出数目的独立因素(t=3.308,2.690,2.584,95%可信区间为0.808~3.180,0.446~2.873,0.332~2.448,P<0.05)。(4)不同淋巴结数目作为分组截点的预后分析:以 6枚(<6枚组、≥6枚组),7枚(<7枚组、≥7枚组),8枚(<8枚组、≥8枚组),9枚(<9枚组、≥9枚组), 10枚(<10枚组、≥10枚组),11枚(<11枚组、≥11枚组),12枚(<12枚组、≥12枚组),13枚(<13枚组、≥13枚组),14枚(<14枚组、≥14枚组),15枚(<15枚组、≥15枚组),16枚(<16枚组、≥16枚组)淋巴结作为分组截点,各截点两组患者3年无病生存率、累计局部复发率、累计远处转移率比较,差异均无统计学意义(P>0.05)。(5)分层分析:45例直肠癌消退分级Ⅱ~Ⅲ级、淋巴结阴性(N0期)患者以7枚(<7枚组、≥7枚组),8枚(<8枚组、≥8枚组),9枚(<9枚组、≥9枚组),10枚(<10枚组、≥10枚组)淋巴结作为分组截点,各截点两组患者3年无病生存率比较,差异均有统计学意义(x2=3.946,5.346,6.375,4.297,P<0.05)。
    结论:12枚淋巴结不是影响nCRT联合手术治疗中低位直肠癌患者预后的独立因素。对于nCRT联合手术治疗中低位直肠癌消退分级Ⅱ~Ⅲ级、淋巴结阴性(N0期)患者,术后检出7~10枚淋巴结是评价其预后的重要因素。

     

    Abstract: Objective:To investigate the effects of the number of harvested lymph nodes in neoadjuvant chemoradiotherapy (nCRT) combined with surgery on prognosis of middlelow rectal cancer.
    Methods:The retrospective casecontrol study was conducted. The clinicopathological data of 373 patients with middlelow rectal cancer who underwent nCRT combined with surgery in the Fujian Medical University Union Hospital from January 2009 to December 2013 were collected. There were 241 males and 132 females, aged from 26 to 81 years, with the age of (55±11)years. Observation indicators: (1) treatment situations; (2) follow-up and survival; (3) influencing factors for the number of harvested lymph nodes; (4) prognostic analysis of the different number of harvested lymph nodes as cutoff for grouping; (5) stratified analysis. Follow-up using telephone interview and outpatient examination was performed to detect postoperative survival of patients once every three months within postoperative 2 years and once every 6 months during the postoperative third year up to March 2016. The endpoint of follow-up was tumor recurrence, retastasis or death. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was done using the independent sample t test. Measurement data with skewed distribution were represented as M (range), and comparison between groups was done using the KruskalWallis H test. Count data was described as absolute numbers. Univariate and multivariate analyses were done by the multiple linear regression model. Survival rate was calculated by the Kaplan-Meier method, and Logrank test was used for survival analysis.
    Results:(1) Treatment situations: 373 patients underwent nCRT combined with surgery, including 329 combined with sphinctersparing rectal resection and 44 combined with abdominoperineal rectal resection. The number of harvested lymph nodes was 12 ± 6 in 373 patients. There were 185 patients with the number of harvested lymph nodes <12 and 188 with the number of harvested lymph nodes ≥12. (2) Follow-up and survival: 373 patients were followed up for 5-77 months, with a median follow-up time of 43 months. During the follow-up, the 1, 3, 5year diseasefree survival rates were respectively 90.4%, 76.3%, and 67.5% in the 373 patients. (3) Influencing factors for the number of harvested lymph nodes: univariate analysis showed that distance between the tumor and anal verge, tumor diameter, tumor pathological N staging, and regression grade of rectal cancer were associated factors for the number of harvested lymph nodes (t=3.156, 2.992, x2=8.183, 10.839, P<0.05). Multivariate analysis showed that distance between the tumor and anal verge, regression grade of rectal cancer, and tumor pathological N staging were independent factors for the number of harvested lymph nodes (t=3.308, 2.690, 2.584, 95% confidence interval: 0.808-3.180, 0.446-2.873, 0.332-2.448, P<0.05). (4) Prognostic analysis of the different number of harvested lymph nodes as cutoff for grouping: with the number of harvested lymph nodes of 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, and 16 as cutoff for grouping, there was no significant difference in the 3year diseasefree survival rate, cumulative local recurrence rate, and cumulative distant metastasis rate between <6 group and ≥6 group, between <7 group and ≥7 group, between<8 group and ≥8 group, between <9 group and ≥9 group, between <10 group and ≥10 group, between <11 group and ≥11 group, between <12 group and ≥12 group, between <13 group and ≥13 group, between <14 group and ≥14 group, between <15 group and ≥15 group, between <16 group and ≥16 group, respectively (P>0.05). (5) Stratified analysis: with the number of harvested lymph nodes of 7, 8, 9, and 10 as cutoff for grouping in 45 of 373 patients with Ⅱ-Ⅲ regression grade of rectal cancer and negative lymph nodes (N0 staging), there was no significant difference in the 3year diseasefree survival rate between <7 group and ≥7 group, between <8 group and ≥8 group, between <9 group and ≥9 group, between<10 group and ≥10 group, respetively (x2=3.946, 5.346, 6.375, 4.297, P<0.05).
    Conclusions:The number of lymph nodes as 12 is not the independent factor for prognosis of patients with middlelow rectal cancer after nCRT combined with surgery. The number of harvested lymph nodes as 7 to 10 is the important factor for evaluating the prognosis of middlelow rectal cancer patients with Ⅱ-Ⅲ regression grade of rectal cancer and negative lymph nodes after nCRT combined with surgery.

     

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