多点全层穿刺活检对新辅助治疗后直肠癌缓解程度判断指导价值的前瞻性多中心研究

The value of transanal multipoint full-layer puncture biopsy in determining the response degree of rectal cancer following neoadjuvant therapy:a prospective multicenter study

目的探讨经肛直视下多点全层穿刺活检(TMFP)技术判断直肠癌新辅助治疗后肿瘤残留的可行性和准确性。方法采用多中心前瞻性研究方法。前瞻性纳入2020年4月至2022年11月首都医科大学附属北京朝阳医院、首都医科大学附属北京友谊医院、山东大学齐鲁医院、武汉大学中南医院四家医院的78例进展期中低位直肠癌患者的临床和病理学资料,患者在新辅助治疗后实施了TMFP。男性53例,女性25例,年龄[M(IQR)]61(13)岁(范围:35~77岁),肿瘤下缘距肛缘距离5(3)cm(范围:2~10 cm),新辅助治疗后等待时间73(26)d(范围:33~330 d)。采用16 G组织活检针以残留病灶为中心经肛做13点穿刺,标本独立送检,记录穿刺并发症。通过灵敏度、特异度、阴性预测值、阳性预测值和准确性比较TMPF与临床完全缓解(cCR)诊断病理学完全缓解(pCR)的一致性,通过配对χ^(2)检验比较诊断效力。结果TMFP前评估cCR病例27例,接受体内穿刺36例,每例患者穿刺针数13(8)针(4~20针),穿刺标本发现癌残留24例。TMFP判断pCR的灵敏度(100%比60%,χ^(2)=17.500,P<0.01)和准确性(88.5%比74.4%,χ^(2)=5.125,P=0.024)均高于cCR,差异有统计学意义。在cCR判断基础上实施TMFP,将cCR的阳性预测值从77.8%提高到91.3%(χ^(2)=0.834,P=0.361),准确性从74.4%提高到92.6%(χ^(2)=4.026,P=0.045)。体内穿刺判断pCR的准确性为94.4%,体外穿刺为83.3%(χ^(2)=1.382,P=0.240)。随病例数的增多,TMFP的判断准确性逐步提高(χ^(2)=7.112,P=0.029)。结论TMFP技术上可行,可以提高对新辅助治疗后直肠癌pCR判断的灵敏度和准确性,为cCR的判断提供病理学依据,有助于等待观察策略的安全开展。

Objective To verify the feasibility and accuracy of the transanal multipoint full-layer puncture biopsy(TMFP)technique in determining the residual status of cancer foci after neoadjuvant therapy(nCRT)in rectal cancer.Methods Between April 2020 and November 2022,a total of 78 patients from the Beijing Chaoyang Hospital of Capital Medical University,the Beijing Friendship Hospital of Capital Medical University,the Qilu Hospital of Shandong University,the Zhongnan Hospital of Wuhan University with advanced rectal cancer received TMFP after nCRT participated in this prospective multicenter trial.There were 53 males and 25 females,aged(M(IQR))61(13)years(range:35 to 77 years).The tumor distance from the anal verge was 5(3)cm(range:2 to 10 cm).The waiting time between nCRT and TMFP was 73(26)days(range:33 to 330 days).13-point transanal puncture was performed with a 16 G tissue biopsy needle with the residual lesion as the center.The specimens were submitted for independent examination and the complications of the puncture were recorded.The consistency of TMFP and radical operation specimen was compared.The consistency of TMPF with clinical remission rates for the diagnosis of complete pathological remission was compared by sensitivity,specificity,negative predictive value,positive predictive value and accuracy.Statistical analysis between groups was performed using theχ^(2)analysis,and a pairedχ^(2)test was used to compare diagnostic validity.Results Before TMFP,clinical complete response(cCR)was evaluated in 27 cases.Thirty-six cases received in vivo puncture,the number of punctures in each patient was 13(8)(range:4 to 20),24 cases of tumor residue were found in the puncture specimens.The sensitivity to judgment(100%vs.60%,χ^(2)=17.500,P<0.01)and accuracy(88.5%vs.74.4%,χ^(2)=5.125,P=0.024)of TMFP for the pathologic complete response(pCR)were significantly higher than those of cCR.Implement TMFP based on cCR judgment,the accuracy increased from 74.4%to 92.6%(χ^(2)=4.026,P=0.045).The accuracy of the in vivo puncture was 94.4%,which was 83.3%of the in vitro puncture(χ^(2)=1.382,P=0.240).Overall,the accuracy of TMFP improved gradually with an increasing number of cases(χ^(2)=7.112,P=0.029).Conclusion TMFP is safe and feasible,which improves the sensitivity and accuracy of rectal cancer pCR determination after nCRT,provides a pathological basis for cCR determination,and contributes to the safe development of the watch and wait policy.