直肠癌新辅助治疗及转移相关基因的研究
摘要
目的:探讨超声内镜在直肠癌新辅助治疗后再分期的准确性。评估新辅助治疗在局部进展期直肠癌综合治疗中的意义。研究VEGF和CTHRC1在直肠癌组织中的表达特点及其与转移的相关性。
方法:纳入临床分期T_3/T_4、距肛缘≤12cm、无远处转移的局部进展期直肠癌患者61例,给予术前新辅助治疗,新辅助治疗前、后行超声内镜分期,治疗结束后休息2-4周,按TME操作原则进行根治性切除术,并与手术后病理分期对照。另选择不同临床分期直肠癌患者98例,采用免疫组织化学方法检测直肠癌组织中VEGF和CTHRC1的表达。
结果:61例病人全部完成术前新辅助治疗,超声评估分期后行腹腔镜下直肠癌根治术,其中腹腔镜直肠前切除术(Dixon)59例,腹腔镜经腹会阴联合切除术(Miles)2例。保肛率96.72%。完全缓解率3.28%。肿瘤降期率93.44%。全部病例获得随访,术后肝转移1例。新辅助治疗后EUS对直肠癌T分期的总准确率为59%,对直肠癌N分期准确率为68.9%。VEGF主要分布于肿瘤细胞中,其表达与直肠癌分化程度、临床分期及淋巴结转移密切相关(P＜0.05);CTRHC1表达与直肠癌分化程度、临床分期密切相关(P＜0.05),二者与直肠癌发生的年龄、性别无明显相关。此外,CTRHC1与VEGF的表达量呈正相关(r=0.629,P＜0.001)。
结论:新辅助治疗安全有效,绝大多数病例达到肿瘤降期,提高了手术切除率及保肛率,降低了局部复发率和远处转移率。EUS对新辅助治疗后的直肠癌进行再分期的准确率降低。CTHRC1和VEGF在直肠癌组织中呈高表达,与其分化程度密切相关,在直肠癌侵袭转移中可能起重要作用,二者的表达情况可作为判定直肠癌生物学行为的参考指标。
Objective:To verify the accuracy of endoscopic ultrasonography(EUS) in restaging rectal cancer after neoadjuvant therapy,evaluate the efficacy of neoadjuvant therapy on locally advanced rectal cancer,and study the features of expression and correlation between VEGF and CTHRCl in rectal cancer.
Methods:Sixty-one patients with T_3/T_4 tumors located in less than 12cm from the anal verge,without distant metastases according to clinical staging were adimitted to neoadjuvant therapy.Surgery was performed after 2 to 4 weeks following completion the therapy under the rule of total mesorectal excision for curative resection.EUS staging was used before and after neoadjuvant therapy in all patients,and the results were compared with the pathologic staging.The expression of VEGF and CTHRCl were tested by immunohistochemistry in another 98 patients of rectal cancer.
Results:Sixty-one patients were enrolled in our study.After neoadjuvant therapy,all of them were perfromed curative resection,including Dixon in 59 patients and Miles in 2 patients.The overall sphincter preservation was 96.72%and the complete response rate was 3.28%.The pathologic staging was decreased in 93.44%of the patients after neoadjuvant therapy.Follow-up was taken in all patients.Liver metastases occurred in one patient.After chemoradiation,the total accuracy for T staging by EUS was 59%and the accuracy for N-stage by EUS was 68.9%.VEGF was distributed mainly in the tumor cells,and its expression was correlated with the clinical stages,tumor differentiation and lymph metastasis,statistically(P＜0.05).The expression of CTRHCl was related with the clinical stages and tumor differentiation (P＜0.05),both of them have no correlation with age and gender of patients.Moreover, a positive correlation was showed between VEGF and CTHRCI by correlative analysis(r=0.629,P＜0.001).
Conclusion:Neoadjuvant therapy is highly effective and safe.Down-staging occurred in most of patients.Preoperative radiochemotherapy significantly increased curative respectability and sphincter preservation,with an apparent improvement in local control and overall long-term survival.The accuracy of EUS restaging rectal cancer after neoadjuvant therapy is decreased.There are higher expression of VEGF and CTHRCl in rectal cancer,and both of them may play important roles in invasion and metastasis in rectal cancer.The two biomarkers may be applied to assess the malignancy of rectal cancer.
方法:纳入临床分期T_3/T_4、距肛缘≤12cm、无远处转移的局部进展期直肠癌患者61例,给予术前新辅助治疗,新辅助治疗前、后行超声内镜分期,治疗结束后休息2-4周,按TME操作原则进行根治性切除术,并与手术后病理分期对照。另选择不同临床分期直肠癌患者98例,采用免疫组织化学方法检测直肠癌组织中VEGF和CTHRC1的表达。
结果:61例病人全部完成术前新辅助治疗,超声评估分期后行腹腔镜下直肠癌根治术,其中腹腔镜直肠前切除术(Dixon)59例,腹腔镜经腹会阴联合切除术(Miles)2例。保肛率96.72%。完全缓解率3.28%。肿瘤降期率93.44%。全部病例获得随访,术后肝转移1例。新辅助治疗后EUS对直肠癌T分期的总准确率为59%,对直肠癌N分期准确率为68.9%。VEGF主要分布于肿瘤细胞中,其表达与直肠癌分化程度、临床分期及淋巴结转移密切相关(P＜0.05);CTRHC1表达与直肠癌分化程度、临床分期密切相关(P＜0.05),二者与直肠癌发生的年龄、性别无明显相关。此外,CTRHC1与VEGF的表达量呈正相关(r=0.629,P＜0.001)。
结论:新辅助治疗安全有效,绝大多数病例达到肿瘤降期,提高了手术切除率及保肛率,降低了局部复发率和远处转移率。EUS对新辅助治疗后的直肠癌进行再分期的准确率降低。CTHRC1和VEGF在直肠癌组织中呈高表达,与其分化程度密切相关,在直肠癌侵袭转移中可能起重要作用,二者的表达情况可作为判定直肠癌生物学行为的参考指标。
Objective:To verify the accuracy of endoscopic ultrasonography(EUS) in restaging rectal cancer after neoadjuvant therapy,evaluate the efficacy of neoadjuvant therapy on locally advanced rectal cancer,and study the features of expression and correlation between VEGF and CTHRCl in rectal cancer.
Methods:Sixty-one patients with T_3/T_4 tumors located in less than 12cm from the anal verge,without distant metastases according to clinical staging were adimitted to neoadjuvant therapy.Surgery was performed after 2 to 4 weeks following completion the therapy under the rule of total mesorectal excision for curative resection.EUS staging was used before and after neoadjuvant therapy in all patients,and the results were compared with the pathologic staging.The expression of VEGF and CTHRCl were tested by immunohistochemistry in another 98 patients of rectal cancer.
Results:Sixty-one patients were enrolled in our study.After neoadjuvant therapy,all of them were perfromed curative resection,including Dixon in 59 patients and Miles in 2 patients.The overall sphincter preservation was 96.72%and the complete response rate was 3.28%.The pathologic staging was decreased in 93.44%of the patients after neoadjuvant therapy.Follow-up was taken in all patients.Liver metastases occurred in one patient.After chemoradiation,the total accuracy for T staging by EUS was 59%and the accuracy for N-stage by EUS was 68.9%.VEGF was distributed mainly in the tumor cells,and its expression was correlated with the clinical stages,tumor differentiation and lymph metastasis,statistically(P＜0.05).The expression of CTRHCl was related with the clinical stages and tumor differentiation (P＜0.05),both of them have no correlation with age and gender of patients.Moreover, a positive correlation was showed between VEGF and CTHRCI by correlative analysis(r=0.629,P＜0.001).
Conclusion:Neoadjuvant therapy is highly effective and safe.Down-staging occurred in most of patients.Preoperative radiochemotherapy significantly increased curative respectability and sphincter preservation,with an apparent improvement in local control and overall long-term survival.The accuracy of EUS restaging rectal cancer after neoadjuvant therapy is decreased.There are higher expression of VEGF and CTHRCl in rectal cancer,and both of them may play important roles in invasion and metastasis in rectal cancer.The two biomarkers may be applied to assess the malignancy of rectal cancer.
引文
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