肿瘤部位及临床病理特征对不同TNM分期行结直肠癌根治性切除术患者预后的影响研究

背景　近年来越来越多的临床研究证实，晚期结直肠癌的肿瘤部位、临床病理特征影响患者的预后及靶向药物的治疗疗效。但是对于已行结直肠癌根治性切除术的患者，不同肿瘤部位是否对其预后产生不同影响，尚未有明确定论。目的　探讨不同TNM分期行结直肠癌根治性切除术患者预后的影响因素，并重点分析肿瘤部位及临床病理特征对不同TNM分期结直肠癌患者预后的影响。方法　选取2008年1月-2015年3月河北医科大学第四医院收治的符合研究标准的行结直肠癌根治性切除术的结直肠癌患者2 097例。按照发病部位以脾区为界分为左半结直肠癌组（n=1 711）及右半结直肠癌组（n=386）。回顾性收集患者的临床病理特征，包括性别、年龄、病理类型、家族史及术前肠梗阻、TNM分期、T分期、N分期、M分期、脉管瘤栓情况。采用电话、门诊随访、定期复查方式随访患者生存情况，截至2016-01-31。比较左半结直肠癌组与右半结直肠癌组患者临床病理特征；采用Cox比例风险回归分析探究结直肠癌根治性切除术后患者死亡的影响因素；采用Kaplan-Meier法绘制不同肿瘤部位结直肠癌患者的生存曲线，比较不同TNM分期患者总生存期（OS）（其中Ⅱ~Ⅲ期患者细分为结直肠癌根治性切除术后是否接受辅助化疗）；记录并比较随访满5年的左半结直肠癌组与右半结直肠癌组患者生存时间≥5年的发生情况。结果　左半结直肠癌组与右半结直肠癌组患者病理类型、术前肠梗阻、TNM分期、T分期情况比较，差异有统计学意义（P<0.05）。多因素Cox比例风险回归分析结果显示，病理类型、家族史、术前肠梗阻、N分期、M分期是结直肠癌根治性切除术后患者死亡的独立影响因素（P<0.05）。Ⅰ期结直肠癌患者中，左半结直肠癌患者OS优于右半结直肠癌患者（χ2=3.843，P=0.049）。Ⅱ期结直肠癌患者中，左、右半结直肠癌患者OS比较，差异无统计学意义（χ2=0.003，P=0.956）。结直肠癌根治性切除术后未接受辅助化疗的Ⅱ期患者中，左、右半结直肠癌患者OS比较，差异无统计学意义（χ2=0.645，P=0.422）。结直肠癌根治性切除术后接受辅助化疗的Ⅱ期患者中，左、右半结直肠癌患者OS比较，差异无统计学意义（χ2=0.078，P=0.780）。Ⅲ期结直肠癌患者中，左半结直肠癌患者OS优于右半结直肠癌患者（χ2=7.612，P=0.006）。结直肠癌根治性切除术后未接受辅助化疗的Ⅲ期患者中，左、右半结直肠癌患者OS比较，差异无统计学意义（χ2=0.851，P=0.356）。结直肠癌根治性切除术后接受辅助化疗的Ⅲ期患者中，左半结直肠癌患者OS优于右半结直肠癌患者，差异有统计学意义（χ2=7.098，P=0.008）。Ⅳ期结直肠癌患者中，左、右半结直肠癌患者OS比较，差异无统计学意义（χ2=0.504，P=0.478）。2 097例患者中703例患者随访满5年，其中左半结直肠癌组591例（其中直肠癌464例），右半结直肠癌组112例。随访满5年的患者中，左半结直肠癌组患者生存时间≥5年所占比例〔72.9%（431/591）〕高于右半结直肠癌组〔60.7%（68/112）〕（χ2=6.818，P=0.009）。结论　病理类型、家族史、术前肠梗阻、N分期、M分期是结直肠癌根治性切除术后患者预后的独立影响因素。肿瘤部位对不同TNM分期结直肠癌根治性切除术后患者预后的影响不同，其中TNM分期为Ⅰ期的结直肠癌患者中，左半结直肠癌患者OS较右半结直肠癌患者有明显优势；Ⅲ期患者中，左半结直肠癌患者OS优于右半结直肠癌患者。Ⅱ、Ⅳ期患者中，左、右半结直肠癌OS未见明显差异。

Associations of Primary Tumor Site and Clinicopathologic Features with TNM-related Survival in Patients with Radical Resection of Colorectal Cancer

Background　An increasing number of studies have confirmed that tumor site and clinicopathological characteristics are associated with the effectiveness of targeted therapy and survival in advanced colorectal cancer patients.But there is no final conclusion on whether tumor site is associated with the survival in those with radical resection.Objective　To investigate the factors（with focus on tumor site and clinicopathological characteristics） associated with TNM-related survival in patients with radical resection of colorectal cancer.Methods　This retrospective study was conducted in 2 097 eligible patients with radical resection of colorectal cancer from Fourth Hospital of Hebei Medical University from January 2008 to March 2015.Clinicopathological characteristics were collected，including gender，age，pathological type，family history of colorectal cancer，preoperative intestinal obstruction，TNM stage，T stage，N stage，M stage，blood vessel invasion and were compared in those with left-sided colorectal cancer（LSCC）（n=1 711） and right-sided colorectal cancer（RSCC）（n=386），namely，by the side that colorectal cancer originates from splenic flexure.Survival status was followed up by telephone，outpatient follow-up and regular review as of January 31，2016.Cox proportional hazards regression analysis was used to investigate the influencing factors of death.Kaplan-Meier method was used to plot the survival curve.The overall survival（OS） was analyzed by TNM stage，specifically involving the influence of adjuvant chemotherapy in those with stage Ⅱ-Ⅲ.Also，the rate of surviving at least 5 years after resection in those with a 5-year follow-up was compared by tumor site.Results　LSCC and RSCC patients showed significant differences in the distribution of pathological type，TNM stage and T stage，and prevalence of preoperative intestinal obstruction（P<0.05）.Multivariate Cox proportional hazards regression analysis showed that pathological type，family history of colorectal cancer，preoperative intestinal obstruction，N stage，and M stage were independently associated with death（P<0.05）.Stage Ⅰ LSCC was associated with longer average OS（χ2=3.843，P=0.049）.Stage ⅡLSCC and RSCC showed no significantly different average OS（χ2=0.003，P=0.956）.The average OS did not vary significantly between stage ⅡLSCC and RSCC with adjuvant chemotherapy（χ2=0.078，P=0.780） or without（χ2=0.645，P=0.422）.Stage Ⅲ LSCC was associated with longer average OS（χ2=7.612，P=0.006）.StageⅢ LSCC and RSCC without adjuvant chemotherapy demonstrated no significantly different average OS（χ2=0.851，P=0.356）.Stage Ⅲ LSCC with adjuvant chemotherapy was associated with longer average OS（χ2=7.098，P=0.008）.StageⅣ LSCC and RSCC showed no significantly different average OS（χ2=0.504，P=0.478）.Altogether，703 patients completed a 5-year follow-up，including 591 with LSCC〔464 with rectal cancer； 431（72.9%） with a survival period of at least 5 years，and 160（27.1%） without〕 and 112 with RSCC〔68（60.7%） with a survival period of at least 5 years，and 44（39.29%） without〕.The rate of LSCC patients surviving at least 5 years was higher than that of RSCC patients（χ2=6.818，P=0.009）.Conclusion　Pathological type，family history of colorectal cancer，preoperative intestinal obstruction，N stage and M stage were independent survival prognostic factors in patients with radical resection of colorectal cancer.TNM-related survival was affected by tumor location.Stage Ⅰ LSCC was associated with longer OS，so was stage Ⅲ LSCC.But the OS of stage Ⅱcolorectal cancer showed no association with tumor site，so did stageⅣcolorectal cancer.