结直肠癌（CRC）是全世界癌症相关死亡最常见原因之一。早期患者预后良好，但IV期结直肠癌患者5年生存率很低。近年来，随着多款靶向免疫药物获批肠癌治疗，患者的生存期得到显著延长。基于基因检测结果的精准治疗方案，也越来越受到临床医生和患者的青睐。基因检测为肿瘤学医学提供了一种个性化的治疗方法，并可能有助于患者在当前批准的治疗方案已经进展的情况下探索进一步的治疗选择，特别是对于那些保持良好体能状态的患者。
针对基因检测在结直肠癌诊疗中的意义，小编整理了几个问题：1、晚期的结直肠癌患者在治疗上有哪些进展？2、基因检测如何指导晚期结直肠癌的靶向治疗？3、结直肠癌患者检测MSI指标的意义有哪些？4、您在肠癌患者的基因检测上有没有值得分享的经典案例？
本期的【绘真有约·大咖答疑】非常荣幸邀请到了南京医科大学附属苏州医院（苏州市立医院北区）普外科主任——孙春荣教授，针对上述问题做了简要解答。
孙春荣 教授
南京医科大学附属苏州医院（苏州市立医院北区）普外科主任
中国直肠癌保肛联盟常务理事
中国医药教育协会直肠癌保肛专业委员会副主任委员
江苏省研究型医院学会直肠癌保肛专业委员会副主任委员
苏州巿中西结合学会烧伤专业委员会委员
苏州市普外科专业委员会委员
</section></section><section arial="" border-box="" break-word="" center="" flex="" flex-start="" gb="" helvetica="" left="" neue="" powered-by="xiumi.us" rgb="" sans="" sans-serif="" sc="" style="white-space: normal;margin-top: 10px;margin-bottom: 10px;outline: 0px;max-width: 100%;color: rgb(34, 34, 34);font-family: system-ui, -apple-system, BlinkMacSystemFont, " ui="" yahei=""><section style="outline: 0px;max-width: 100%;display: inline-block;vertical-align: top;width: auto;flex: 0 0 auto;border-width: 0px;border-style: none;border-color: rgb(76, 68, 71);overflow: hidden;align-self: flex-start;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section powered-by="xiumi.us" style="outline: 0px;max-width: 100%;text-align: center;transform: translate3d(-10px, 0px, 0px);box-sizing: border-box !important;overflow-wrap: break-word !important;"><section style="padding: 3px 5px 3px 20px;outline: 0px;max-width: 100%;display: inline-block;min-width: 10%;vertical-align: top;transform: matrix(1, 0, -0.2, 1, 0, 0);border-style: solid;border-width: 0px;border-color: rgb(76, 68, 71);background-color: rgb(249, 110, 87);box-sizing: border-box !important;overflow-wrap: break-word !important;"><section powered-by="xiumi.us" style="outline: 0px;max-width: 100%;color: rgb(255, 255, 255);box-sizing: border-box !important;overflow-wrap: break-word !important;"><p style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"><strong style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;">绘真：</strong></p></section></section></section></section><section style="outline: 0px;max-width: 100%;display: inline-block;vertical-align: top;width: auto;flex: 100 100 0%;border-width: 0px;height: auto;box-shadow: rgb(0, 0, 0) 0px 0px 0px;align-self: flex-start;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section powered-by="xiumi.us" style="margin-top: 3px;outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section style="outline: 0px;max-width: 100%;line-height: 1.5;color: rgb(76, 68, 71);text-align: justify;box-sizing: border-box !important;overflow-wrap: break-word !important;"><p style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"><strong style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"/><span style="outline: 0px;max-width: 100%;color: rgb(0, 0, 0);box-sizing: border-box !important;overflow-wrap: break-word !important;"><strong style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"><span style="outline: 0px;max-width: 100%;font-family: 微软雅黑;letter-spacing: 0.3pt;font-size: 15px;box-sizing: border-box !important;overflow-wrap: break-word !important;">晚期的结直肠癌患者在治疗上有哪些进展？</span></strong></span><strong style="outline: 0px;max-width: 100%;color: rgb(0, 0, 0);box-sizing: border-box !important;overflow-wrap: break-word !important;"/></p></section></section></section></section><section arial="" border-box="" break-word="" flex="" flex-start="" gb="" helvetica="" left="" neue="" nowrap="" powered-by="xiumi.us" rgb="" row="" sans="" sans-serif="" sc="" style="white-space: normal;margin-top: 10px;margin-bottom: 10px;outline: 0px;max-width: 100%;color: rgb(34, 34, 34);font-family: system-ui, -apple-system, BlinkMacSystemFont, " ui="" yahei=""><section style="padding: 29px;outline: 0px;max-width: 100%;display: inline-block;width: 677px;vertical-align: top;background-color: rgba(231, 83, 54, 0.07);align-self: flex-start;flex: 0 0 auto;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section powered-by="xiumi.us" style="margin-top: 10px;margin-bottom: 10px;outline: 0px;max-width: 100%;justify-content: flex-start;display: flex;flex-flow: row nowrap;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section style="outline: 0px;max-width: 100%;display: inline-block;width: auto;vertical-align: top;min-width: 10%;flex: 0 0 auto;height: auto;box-shadow: rgb(0, 0, 0) 0px 0px 0px;align-self: flex-start;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section powered-by="xiumi.us" style="outline: 0px;max-width: 100%;text-align: center;justify-content: center;display: flex;flex-flow: row nowrap;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section style="padding-right: 10px;padding-left: 10px;outline: 0px;max-width: 100%;display: inline-block;width: auto;vertical-align: top;min-width: 10%;flex: 0 0 auto;height: auto;align-self: flex-start;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section powered-by="xiumi.us" style="outline: 0px;max-width: 100%;color: rgb(97, 97, 97);text-align: justify;box-sizing: border-box !important;overflow-wrap: break-word !important;"><p style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"><strong style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"><span style="outline: 0px;max-width: 100%;color: rgb(0, 0, 0);box-sizing: border-box !important;overflow-wrap: break-word !important;">孙春荣教授：</span></strong></p></section></section></section><section powered-by="xiumi.us" style="outline: 0px;max-width: 100%;justify-content: flex-start;font-size: 0px;display: flex;flex-flow: row nowrap;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section style="outline: 0px;max-width: 100%;display: inline-block;width: 51.3625px;vertical-align: top;flex: 0 0 auto;height: auto;line-height: 0;align-self: flex-start;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section powered-by="xiumi.us" style="margin-top: 0.5em;margin-bottom: 0.5em;outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section style="outline: 0px;max-width: 100%;background-color: rgb(195, 163, 142);height: 2px;box-sizing: border-box !important;overflow-wrap: break-word !important;"><svg style="float:left;line-height:0;width:0;vertical-align:top;" viewbox="0 0 1 1"/></section></section></section></section></section></section><section powered-by="xiumi.us" style="outline: 0px;max-width: 100%;text-align: justify;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section powered-by="xiumi.us" style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section style="outline: 0px;max-width: 100%;line-height: 2em;box-sizing: border-box !important;overflow-wrap: break-word !important;"><span style="outline: 0px;max-width: 100%;font-size: 14px;color: rgb(0, 0, 0);box-sizing: border-box !important;overflow-wrap: break-word !important;">结直肠癌是消化道常见的恶性肿瘤，据统计，在2018年，结直肠癌死亡人数达到了88.1万人，就目前情况来讲，结直肠癌的发病率还有出现上升的一个趋势，结直肠癌患者的诊断和治疗也备受关注。长期以来，手术和化疗是结直肠癌患者主要的一个治疗手段，但由于结直肠癌患者术后预后比较差，容易复发转移，总体来说，患者的疗效不是十分明显。而且化疗的毒副作用和耐药问题也令患者担忧。如今，在化疗用药指导上，</span><span style="outline: 0px;max-width: 100%;font-size: 14px;color: rgb(255, 41, 65);box-sizing: border-box !important;overflow-wrap: break-word !important;"><strong style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;">UGT1A1和DPYD等基因胚系SNP位点的检测</strong></span><span style="outline: 0px;max-width: 100%;font-size: 14px;color: rgb(0, 0, 0);box-sizing: border-box !important;overflow-wrap: break-word !important;">已经走在了前列，而且正式被纳入临床用药指导，以指导伊立替康等化疗药物的使用，在一定程度上也减轻了患者化疗方面的一些痛苦。</span></section><p style="outline: 0px;max-width: 100%;line-height: normal;box-sizing: border-box !important;overflow-wrap: break-word !important;"><br style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"/></p><section style="outline: 0px;max-width: 100%;line-height: 2em;box-sizing: border-box !important;overflow-wrap: break-word !important;"><span style="outline: 0px;max-width: 100%;font-size: 14px;color: rgb(0, 0, 0);box-sizing: border-box !important;overflow-wrap: break-word !important;">近年，随着分子检测技术的发展，以西妥昔单抗和贝伐珠单抗为代表的靶向药物，在延长肠癌患者的生存期､克服化疗耐药等方面，优势比较突出，</span><strong style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"><span style="outline: 0px;max-width: 100%;font-size: 14px;color: rgb(255, 41, 65);box-sizing: border-box !important;overflow-wrap: break-word !important;">靶向治疗使转移性肠癌患者的生存期从既往的6-12个月，延长到目前的30多个月</span></strong><span style="outline: 0px;max-width: 100%;font-size: 14px;color: rgb(0, 0, 0);box-sizing: border-box !important;overflow-wrap: break-word !important;">，而且包括结直肠癌患者的肝转移或肺转移，这些传统上认为是不可治疗的一些情况。除了靶向治疗之外，众多的免疫检查点抑制剂药物的成功上市，表明免疫疗法在肿瘤治疗方面也有很大的潜力。因此，结直肠癌在包括靶向、化疗、免疫等多策略治疗当中展现出了多点开花的局面，为结直肠癌患者的有效生存带来了希望。</span></section></section></section></section></section></section><section arial="" border-box="" break-word="" gb="" helvetica="" neue="" normal="" rgb="" sans="" sans-serif="" sc="" style="white-space: normal;margin-bottom: 0px;outline: 0px;max-width: 100%;color: rgb(34, 34, 34);font-family: system-ui, -apple-system, BlinkMacSystemFont, " ui="" yahei=""><br style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"/></section><section arial="" border-box="" break-word="" center="" flex="" flex-start="" gb="" helvetica="" left="" neue="" powered-by="xiumi.us" rgb="" sans="" sans-serif="" sc="" style="white-space: normal;margin-top: 10px;margin-bottom: 10px;outline: 0px;max-width: 100%;color: rgb(34, 34, 34);font-family: system-ui, -apple-system, BlinkMacSystemFont, " ui="" yahei=""><section style="outline: 0px;max-width: 100%;display: inline-block;vertical-align: top;width: auto;flex: 0 0 auto;border-width: 0px;border-style: none;border-color: rgb(76, 68, 71);overflow: hidden;align-self: flex-start;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section powered-by="xiumi.us" style="outline: 0px;max-width: 100%;text-align: center;transform: translate3d(-10px, 0px, 0px);box-sizing: border-box !important;overflow-wrap: break-word !important;"><section style="padding: 3px 5px 3px 20px;outline: 0px;max-width: 100%;display: inline-block;min-width: 10%;vertical-align: top;transform: matrix(1, 0, -0.2, 1, 0, 0);border-style: solid;border-width: 0px;border-color: rgb(76, 68, 71);background-color: rgb(249, 110, 87);box-sizing: border-box !important;overflow-wrap: break-word !important;"><section powered-by="xiumi.us" style="outline: 0px;max-width: 100%;color: rgb(255, 255, 255);box-sizing: border-box !important;overflow-wrap: break-word !important;"><p style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"><strong style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;">绘真：</strong></p></section></section></section></section><section style="outline: 0px;max-width: 100%;display: inline-block;vertical-align: top;width: auto;flex: 100 100 0%;border-width: 0px;height: auto;box-shadow: rgb(0, 0, 0) 0px 0px 0px;align-self: flex-start;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section powered-by="xiumi.us" style="margin-top: 3px;outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section style="outline: 0px;max-width: 100%;line-height: 1.5;color: rgb(76, 68, 71);text-align: justify;box-sizing: border-box !important;overflow-wrap: break-word !important;"><p style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"><strong style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"><span style="outline: 0px;max-width: 100%;font-family: 微软雅黑;letter-spacing: 0.3pt;font-size: 15px;color: rgb(0, 0, 0);box-sizing: border-box !important;overflow-wrap: break-word !important;">基因检测如何指导晚期结直肠癌的靶向治疗？</span></strong></p></section></section></section></section><section arial="" border-box="" break-word="" flex="" flex-start="" gb="" helvetica="" left="" neue="" nowrap="" powered-by="xiumi.us" rgb="" row="" sans="" sans-serif="" sc="" style="white-space: normal;margin-top: 10px;margin-bottom: 10px;outline: 0px;max-width: 100%;color: rgb(34, 34, 34);font-family: system-ui, -apple-system, BlinkMacSystemFont, " ui="" yahei=""><section style="padding: 29px;outline: 0px;max-width: 100%;display: inline-block;width: 677px;vertical-align: top;background-color: rgba(231, 83, 54, 0.07);align-self: flex-start;flex: 0 0 auto;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section powered-by="xiumi.us" style="margin-top: 10px;margin-bottom: 10px;outline: 0px;max-width: 100%;justify-content: flex-start;display: flex;flex-flow: row nowrap;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section style="outline: 0px;max-width: 100%;display: inline-block;width: auto;vertical-align: top;min-width: 10%;flex: 0 0 auto;height: auto;box-shadow: rgb(0, 0, 0) 0px 0px 0px;align-self: flex-start;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section powered-by="xiumi.us" style="outline: 0px;max-width: 100%;text-align: center;justify-content: center;display: flex;flex-flow: row nowrap;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section style="padding-right: 10px;padding-left: 10px;outline: 0px;max-width: 100%;display: inline-block;width: auto;vertical-align: top;min-width: 10%;flex: 0 0 auto;height: auto;align-self: flex-start;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section powered-by="xiumi.us" style="outline: 0px;max-width: 100%;color: rgb(97, 97, 97);text-align: justify;box-sizing: border-box !important;overflow-wrap: break-word !important;"><p style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"><strong style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"><span style="outline: 0px;max-width: 100%;color: rgb(0, 0, 0);box-sizing: border-box !important;overflow-wrap: break-word !important;"><span style="outline: 0px;max-width: 100%;font-size: 15px;box-sizing: border-box !important;overflow-wrap: break-word !important;">孙春荣</span><span style="outline: 0px;max-width: 100%;font-size: 16px;box-sizing: border-box !important;overflow-wrap: break-word !important;">教授：</span></span></strong></p></section></section></section><section powered-by="xiumi.us" style="outline: 0px;max-width: 100%;font-size: 0px;justify-content: flex-start;display: flex;flex-flow: row nowrap;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section style="outline: 0px;max-width: 100%;display: inline-block;width: 51.3625px;vertical-align: top;flex: 0 0 auto;height: auto;line-height: 0;align-self: flex-start;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section powered-by="xiumi.us" style="margin-top: 0.5em;margin-bottom: 0.5em;outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section style="outline: 0px;max-width: 100%;background-color: rgb(195, 163, 142);height: 2px;box-sizing: border-box !important;overflow-wrap: break-word !important;"><svg style="float:left;line-height:0;width:0;vertical-align:top;" viewbox="0 0 1 1"/></section></section></section></section></section></section><section powered-by="xiumi.us" style="outline: 0px;max-width: 100%;font-size: 16px;text-align: justify;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section powered-by="xiumi.us" style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"><p style="outline: 0px;max-width: 100%;line-height: 2em;box-sizing: border-box !important;overflow-wrap: break-word !important;"><span style="outline: 0px;max-width: 100%;font-size: 14px;color: rgb(0, 0, 0);box-sizing: border-box !important;overflow-wrap: break-word !important;">在结直肠癌患者的治疗指南推荐上，</span><strong style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"><span style="outline: 0px;max-width: 100%;font-size: 14px;color: rgb(255, 41, 65);box-sizing: border-box !important;overflow-wrap: break-word !important;">RAS、BRAF和微卫星不稳定（MSI）</span></strong><span style="outline: 0px;max-width: 100%;font-size: 14px;color: rgb(0, 0, 0);box-sizing: border-box !important;overflow-wrap: break-word !important;">是指南中老生常谈的三个指标，在CSCO会议上，</span><strong style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"><span style="outline: 0px;max-width: 100%;font-size: 14px;color: rgb(255, 41, 65);box-sizing: border-box !important;overflow-wrap: break-word !important;">结直肠癌患者的治疗指南推荐所有新诊断的结直肠癌患者常规都进行微卫星不稳定/dMMR检测</span></strong><span style="outline: 0px;max-width: 100%;font-size: 14px;color: rgb(0, 0, 0);box-sizing: border-box !important;overflow-wrap: break-word !important;">。根治术后的患者，我们推荐RAS和BRAF基因检测，检测RAS/BRAF野生型晚期结直肠癌患者，目前，西妥昔单抗、帕尼单抗等抗EGFR靶向治疗已经成为目前临床治疗的一个标准方案。而临床在选择用药方案之前，一定要区分原发灶是位于左侧还是右侧。因为</span><strong style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"><span style="outline: 0px;max-width: 100%;font-size: 14px;color: rgb(255, 41, 65);box-sizing: border-box !important;overflow-wrap: break-word !important;">有充分的证据已经表明，不同部位的结肠癌患者，会影响患者对靶向药物的临床表现、治疗反应和生存结局。</span></strong><span style="outline: 0px;max-width: 100%;font-size: 14px;color: rgb(0, 0, 0);box-sizing: border-box !important;overflow-wrap: break-word !important;">当原发灶位于左半结肠的时候，那么我们往往推荐以西妥昔单抗为基础的单药或联合治疗，而位于右半结肠的，那么这部分患者我们往往推荐是以贝伐珠单抗为基础的单药或联合治疗。</span><strong style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"><span style="outline: 0px;max-width: 100%;font-size: 14px;color: rgb(255, 41, 65);box-sizing: border-box !important;overflow-wrap: break-word !important;">针对于标准治疗失败的一些结直肠癌患者，应增加HER2状态、PIK3CA突变和NTRK融合的检测，以指导进一步的靶向治疗，而且HER2扩增可能是抗EGFR单抗靶向治疗的耐药因素之一。</span></strong><span style="outline: 0px;max-width: 100%;font-size: 14px;color: rgb(0, 0, 0);box-sizing: border-box !important;overflow-wrap: break-word !important;">因此，随着测序平台的逐步完善，合理的检测技术及应用已经成为我们目前临床实践当中一个重要组成部分，可考虑采用多基因NGS检测联合其他平台技术检测结直肠癌相关指标，指导全面治疗。</span></p></section></section></section></section></section><p arial="" border-box="" break-word="" gb="" helvetica="" neue="" normal="" rgb="" sans="" sans-serif="" sc="" style="white-space: normal;margin-bottom: 0px;outline: 0px;max-width: 100%;color: rgb(34, 34, 34);font-family: system-ui, -apple-system, BlinkMacSystemFont, " ui="" yahei=""><br style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"/></p><section arial="" border-box="" break-word="" center="" flex="" flex-start="" gb="" helvetica="" left="" neue="" powered-by="xiumi.us" rgb="" sans="" sans-serif="" sc="" style="white-space: normal;margin-top: 10px;margin-bottom: 10px;outline: 0px;max-width: 100%;color: rgb(34, 34, 34);font-family: system-ui, -apple-system, BlinkMacSystemFont, " ui="" yahei=""><section style="outline: 0px;max-width: 100%;display: inline-block;vertical-align: top;width: auto;flex: 0 0 auto;border-width: 0px;border-style: none;border-color: rgb(76, 68, 71);overflow: hidden;align-self: flex-start;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section powered-by="xiumi.us" style="outline: 0px;max-width: 100%;text-align: center;transform: translate3d(-10px, 0px, 0px);box-sizing: border-box !important;overflow-wrap: break-word !important;"><section style="padding: 3px 5px 3px 20px;outline: 0px;max-width: 100%;display: inline-block;min-width: 10%;vertical-align: top;transform: matrix(1, 0, -0.2, 1, 0, 0);border-style: solid;border-width: 0px;border-color: rgb(76, 68, 71);background-color: rgb(249, 110, 87);box-sizing: border-box !important;overflow-wrap: break-word !important;"><section powered-by="xiumi.us" style="outline: 0px;max-width: 100%;color: rgb(255, 255, 255);box-sizing: border-box !important;overflow-wrap: break-word !important;"><p style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"><strong style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;">绘真：</strong></p></section></section></section></section><section style="outline: 0px;max-width: 100%;display: inline-block;vertical-align: top;width: auto;flex: 100 100 0%;border-width: 0px;height: auto;box-shadow: rgb(0, 0, 0) 0px 0px 0px;align-self: flex-start;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section powered-by="xiumi.us" style="margin-top: 3px;outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section style="outline: 0px;max-width: 100%;line-height: 1.5;color: rgb(76, 68, 71);text-align: justify;box-sizing: border-box !important;overflow-wrap: break-word !important;"><p style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"><strong style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"><span style="outline: 0px;max-width: 100%;color: rgb(0, 0, 0);font-family: 微软雅黑;letter-spacing: 0.3pt;font-size: 15px;box-sizing: border-box !important;overflow-wrap: break-word !important;">结直肠癌患者检测MSI指标的意义有哪些？</span></strong></p></section></section></section></section><section arial="" border-box="" break-word="" flex="" flex-start="" gb="" helvetica="" left="" neue="" nowrap="" powered-by="xiumi.us" rgb="" row="" sans="" sans-serif="" sc="" style="white-space: normal;margin-top: 10px;margin-bottom: 10px;outline: 0px;max-width: 100%;color: rgb(34, 34, 34);font-family: system-ui, -apple-system, BlinkMacSystemFont, " ui="" yahei=""><section style="padding: 29px;outline: 0px;max-width: 100%;display: inline-block;width: 677px;vertical-align: top;background-color: rgba(231, 83, 54, 0.07);align-self: flex-start;flex: 0 0 auto;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section powered-by="xiumi.us" style="margin-top: 10px;margin-bottom: 10px;outline: 0px;max-width: 100%;justify-content: flex-start;display: flex;flex-flow: row nowrap;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section style="outline: 0px;max-width: 100%;display: inline-block;width: auto;vertical-align: top;min-width: 10%;flex: 0 0 auto;height: auto;box-shadow: rgb(0, 0, 0) 0px 0px 0px;align-self: flex-start;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section powered-by="xiumi.us" style="outline: 0px;max-width: 100%;text-align: center;justify-content: center;display: flex;flex-flow: row nowrap;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section style="padding-right: 10px;padding-left: 10px;outline: 0px;max-width: 100%;display: inline-block;width: auto;vertical-align: top;min-width: 10%;flex: 0 0 auto;height: auto;align-self: flex-start;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section powered-by="xiumi.us" style="outline: 0px;max-width: 100%;color: rgb(97, 97, 97);text-align: justify;box-sizing: border-box !important;overflow-wrap: break-word !important;"><p style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"><strong style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"><span style="outline: 0px;max-width: 100%;color: rgb(0, 0, 0);box-sizing: border-box !important;overflow-wrap: break-word !important;">孙春荣教授：</span></strong></p></section></section></section><section powered-by="xiumi.us" style="outline: 0px;max-width: 100%;justify-content: flex-start;font-size: 0px;display: flex;flex-flow: row nowrap;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section style="outline: 0px;max-width: 100%;display: inline-block;width: 51.3625px;vertical-align: top;flex: 0 0 auto;height: auto;line-height: 0;align-self: flex-start;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section powered-by="xiumi.us" style="margin-top: 0.5em;margin-bottom: 0.5em;outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section style="outline: 0px;max-width: 100%;background-color: rgb(195, 163, 142);height: 2px;box-sizing: border-box !important;overflow-wrap: break-word !important;"><svg style="float:left;line-height:0;width:0;vertical-align:top;" viewbox="0 0 1 1"/></section></section></section></section></section></section><section powered-by="xiumi.us" style="outline: 0px;max-width: 100%;text-align: justify;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section style="outline: 0px;max-width: 100%;line-height: 2em;box-sizing: border-box !important;overflow-wrap: break-word !important;"><span style="outline: 0px;max-width: 100%;font-size: 14px;color: rgb(0, 0, 0);box-sizing: border-box !important;overflow-wrap: break-word !important;">MSI是一个微卫星指标，它主要是指细胞基因当中少数几个以核苷酸为单位串联重复的DNA序列，又称为短串联重复。因此，国内外结直肠癌患者诊疗指南当中均推荐微卫星不稳定MSI的检测用于所有结直肠癌患者，它的临床意义：第一、</span><strong style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"><span style="outline: 0px;max-width: 100%;font-size: 14px;color: rgb(255, 41, 65);box-sizing: border-box !important;overflow-wrap: break-word !important;">微卫星不稳定（MSI）是Ⅱ期结直肠癌患者的预后指标。</span></strong><span style="outline: 0px;max-width: 100%;font-size: 14px;color: rgb(0, 0, 0);box-sizing: border-box !important;overflow-wrap: break-word !important;">目前已有大量的证据表明，相比于微卫星稳定性者，MSI-H（</span><span style="outline: 0px;max-width: 100%;font-size: 14px;color: rgb(136, 136, 136);box-sizing: border-box !important;overflow-wrap: break-word !important;">微卫星高度不稳定</span><span style="outline: 0px;max-width: 100%;font-size: 14px;color: rgb(0, 0, 0);box-sizing: border-box !important;overflow-wrap: break-word !important;">）表型的结直肠癌患者通常为低级别腺癌，具有较长的生存期，是结直肠癌患者预后良好的指标。第二、</span><strong style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"><span style="outline: 0px;max-width: 100%;font-size: 14px;color: rgb(255, 41, 65);box-sizing: border-box !important;overflow-wrap: break-word !important;">指导患者术后辅助治疗。</span></strong><span style="outline: 0px;max-width: 100%;font-size: 14px;color: rgb(0, 0, 0);box-sizing: border-box !important;overflow-wrap: break-word !important;">对于具有MSI-H表型的Ⅱ期结直肠癌患者，术后给予氟尿嘧啶的辅助治疗，非但不能获益，反而可能导致过度治疗。因此，具有MSI-H状态的Ⅱ期结直肠癌患者，指南不建议使用氟尿嘧啶单药术后辅助治疗。第三，</span><strong style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"><span style="outline: 0px;max-width: 100%;font-size: 14px;color: rgb(255, 41, 65);box-sizing: border-box !important;overflow-wrap: break-word !important;">指导晚期患者免疫治疗。</span></strong><span style="outline: 0px;max-width: 100%;font-size: 14px;color: rgb(0, 0, 0);box-sizing: border-box !important;overflow-wrap: break-word !important;">在KEYNOTE-177临床试验显示，MSI-H的晚期结直肠癌使用免疫检查点抑制剂的中位无进展生存期是化疗组的两倍以上。国内外监管机构也陆续批准帕博利珠单抗、纳武利尤单抗、恩沃利单抗等多款免疫药物用于治疗MSI-H的实体肿瘤。第四，</span><strong style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"><span style="outline: 0px;max-width: 100%;font-size: 14px;color: rgb(255, 41, 65);box-sizing: border-box !important;overflow-wrap: break-word !important;">可以初步筛选林奇综合征患者。</span></strong><span style="outline: 0px;max-width: 100%;font-size: 14px;color: rgb(0, 0, 0);box-sizing: border-box !important;overflow-wrap: break-word !important;">林奇综合征是一种常染色体显性遗传性肿瘤综合征，携带者结直肠癌的发病年龄早于普通人群，MSI-H患者可初步确定为林奇综合征患者，携带者也应该进一步筛查错配修复基因的胚系变异。总的来说，微卫星不稳定检测对于结直肠癌患者的预后判断、指导治疗、遗传的筛选，具有十分重要的指导意义。而根据既往CSCO的指南，2021年CSCO指南就首次将MSI的检测指标指导治疗单独列出来，在2022年CSCO又进一步进行了一个更新，指导该指标的免疫药物也进行了获批。所以在指南当中，它也强调了MSI检测在结直肠癌患者中的重要性！</span></section></section></section></section><p arial="" border-box="" break-word="" gb="" helvetica="" neue="" normal="" rgb="" sans="" sans-serif="" sc="" style="white-space: normal;margin-bottom: 0px;outline: 0px;max-width: 100%;color: rgb(34, 34, 34);font-family: system-ui, -apple-system, BlinkMacSystemFont, " ui="" yahei=""><br style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"/></p><section arial="" border-box="" break-word="" center="" flex="" flex-start="" gb="" helvetica="" left="" neue="" powered-by="xiumi.us" rgb="" sans="" sans-serif="" sc="" style="white-space: normal;margin-top: 10px;margin-bottom: 10px;outline: 0px;max-width: 100%;color: rgb(34, 34, 34);font-family: system-ui, -apple-system, BlinkMacSystemFont, " ui="" yahei=""><section style="outline: 0px;max-width: 100%;display: inline-block;vertical-align: top;width: auto;flex: 0 0 auto;border-width: 0px;border-style: none;border-color: rgb(76, 68, 71);overflow: hidden;align-self: flex-start;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section powered-by="xiumi.us" style="outline: 0px;max-width: 100%;text-align: center;transform: translate3d(-10px, 0px, 0px);box-sizing: border-box !important;overflow-wrap: break-word !important;"><section style="padding: 3px 5px 3px 20px;outline: 0px;max-width: 100%;display: inline-block;min-width: 10%;vertical-align: top;transform: matrix(1, 0, -0.2, 1, 0, 0);border-style: solid;border-width: 0px;border-color: rgb(76, 68, 71);background-color: rgb(249, 110, 87);box-sizing: border-box !important;overflow-wrap: break-word !important;"><section powered-by="xiumi.us" style="outline: 0px;max-width: 100%;color: rgb(255, 255, 255);box-sizing: border-box !important;overflow-wrap: break-word !important;"><p style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"><strong style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;">绘真：</strong></p></section></section></section></section><section style="outline: 0px;max-width: 100%;display: inline-block;vertical-align: top;width: auto;flex: 100 100 0%;border-width: 0px;height: auto;box-shadow: rgb(0, 0, 0) 0px 0px 0px;align-self: flex-start;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section powered-by="xiumi.us" style="margin-top: 3px;outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section style="outline: 0px;max-width: 100%;line-height: 1.5;color: rgb(76, 68, 71);text-align: justify;box-sizing: border-box !important;overflow-wrap: break-word !important;"><p style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"><span style="outline: 0px;max-width: 100%;color: rgb(0, 0, 0);box-sizing: border-box !important;overflow-wrap: break-word !important;"><strong style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"><span style="outline: 0px;max-width: 100%;font-family: 微软雅黑;letter-spacing: 0.3pt;background-image: initial;background-position: initial;background-size: initial;background-repeat: initial;background-attachment: initial;background-origin: initial;background-clip: initial;font-size: 15px;box-sizing: border-box !important;overflow-wrap: break-word !important;">您在肠癌患者的基因检测上有没有值得分享的经典案例？</span></strong></span><strong style="outline: 0px;max-width: 100%;letter-spacing: 0.544px;color: rgb(0, 0, 0);box-sizing: border-box !important;overflow-wrap: break-word !important;"/><strong style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"/></p></section></section></section></section><section arial="" border-box="" break-word="" flex="" flex-start="" gb="" helvetica="" left="" neue="" nowrap="" powered-by="xiumi.us" rgb="" row="" sans="" sans-serif="" sc="" style="white-space: normal;margin-top: 10px;margin-bottom: 10px;outline: 0px;max-width: 100%;color: rgb(34, 34, 34);font-family: system-ui, -apple-system, BlinkMacSystemFont, " ui="" yahei=""><section style="padding: 29px;outline: 0px;max-width: 100%;display: inline-block;width: 677px;vertical-align: top;background-color: rgba(231, 83, 54, 0.07);align-self: flex-start;flex: 0 0 auto;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section powered-by="xiumi.us" style="margin-top: 10px;margin-bottom: 10px;outline: 0px;max-width: 100%;justify-content: flex-start;display: flex;flex-flow: row nowrap;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section style="outline: 0px;max-width: 100%;display: inline-block;width: auto;vertical-align: top;min-width: 10%;flex: 0 0 auto;height: auto;box-shadow: rgb(0, 0, 0) 0px 0px 0px;align-self: flex-start;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section powered-by="xiumi.us" style="outline: 0px;max-width: 100%;text-align: center;justify-content: center;display: flex;flex-flow: row nowrap;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section style="padding-right: 10px;padding-left: 10px;outline: 0px;max-width: 100%;display: inline-block;width: auto;vertical-align: top;min-width: 10%;flex: 0 0 auto;height: auto;align-self: flex-start;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section powered-by="xiumi.us" style="outline: 0px;max-width: 100%;color: rgb(97, 97, 97);text-align: justify;box-sizing: border-box !important;overflow-wrap: break-word !important;"><p style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"><strong style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"><span style="outline: 0px;max-width: 100%;color: rgb(0, 0, 0);box-sizing: border-box !important;overflow-wrap: break-word !important;">孙春荣教授：</span></strong></p></section></section></section><section powered-by="xiumi.us" style="outline: 0px;max-width: 100%;justify-content: flex-start;font-size: 0px;display: flex;flex-flow: row nowrap;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section style="outline: 0px;max-width: 100%;display: inline-block;width: 51.3625px;vertical-align: top;flex: 0 0 auto;height: auto;line-height: 0;align-self: flex-start;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section powered-by="xiumi.us" style="margin-top: 0.5em;margin-bottom: 0.5em;outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section style="outline: 0px;max-width: 100%;background-color: rgb(195, 163, 142);height: 2px;box-sizing: border-box !important;overflow-wrap: break-word !important;"><svg style="float:left;line-height:0;width:0;vertical-align:top;" viewbox="0 0 1 1"/></section></section></section></section></section></section><section powered-by="xiumi.us" style="outline: 0px;max-width: 100%;text-align: justify;box-sizing: border-box !important;overflow-wrap: break-word !important;"><section style="outline: 0px;max-width: 100%;line-height: 2em;box-sizing: border-box !important;overflow-wrap: break-word !important;"><span style="outline: 0px;max-width: 100%;font-size: 14px;color: rgb(0, 0, 0);box-sizing: border-box !important;overflow-wrap: break-word !important;">目前，结直肠癌患者的治疗药物还是比较丰富的，而</span><strong style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"><span style="outline: 0px;max-width: 100%;font-size: 14px;color: rgb(255, 41, 65);box-sizing: border-box !important;overflow-wrap: break-word !important;">NGS技术的广泛应用也能为患者一次性明确多个治疗指标的状态，为患者提供多角度的治疗指导。</span></strong><span style="outline: 0px;max-width: 100%;font-size: 14px;color: rgb(0, 0, 0);box-sizing: border-box !important;overflow-wrap: break-word !important;">面对多个指标的检测结果，也需要我们临床上权衡利弊，精准决策。那么最近，我们正巧，有一位晚期的肠癌患者检出了，<strong style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;">dMMR、NTRK1融合和RAS/BRAF阴性</strong>的结果。据报道，在结直肠癌中，NTRK基因融合仅有0.35%的发生率，而且绝大多数患者都跟我们这位患者一样，为dMMR/MSI-H型，指南也推荐该类患者应该积极检测NTRK融合变异。而在治疗上，这类患者由于检出的这几个指标结果均能指导用药，那么用药选择和顺序问题也值得深思。</span></section><p style="outline: 0px;max-width: 100%;line-height: normal;box-sizing: border-box !important;overflow-wrap: break-word !important;"><br style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;"/></p><section style="outline: 0px;max-width: 100%;line-height: 2em;box-sizing: border-box !important;overflow-wrap: break-word !important;"><span style="outline: 0px;max-width: 100%;font-size: 14px;color: rgb(0, 0, 0);box-sizing: border-box !important;overflow-wrap: break-word !important;">恰巧，国外最近有一篇报道，报道了一个跟我们相似的一个病例，案例中检测的MSI-H和NTRK融合的肠癌患者，先是经过4个周期的帕博利珠单抗序贯2个周期的双免疫治疗，但是这个患者仅4个月肿瘤就发生了进展，疗效不明显。后来这个患者接受了拉罗替尼治疗，疗效获益明显。2个月以后，患者接受了手术，疾病得到了缓解，而且生存获益时间长达了26个月，最后文章中也提到了这类患者一线使用拉罗替尼治疗的可行性。前段时间，</span><span style="outline: 0px;max-width: 100%;font-size: 14px;color: rgb(255, 41, 65);box-sizing: border-box !important;overflow-wrap: break-word !important;"><strong style="outline: 0px;max-width: 100%;box-sizing: border-box !important;overflow-wrap: break-word !important;">拉罗替尼在NTRK融合阳性实体瘤患者中获批，这也为我们对后续治疗大大增强了信心</strong></span><span style="outline: 0px;max-width: 100%;font-size: 14px;color: rgb(0, 0, 0);box-sizing: border-box !important;overflow-wrap: break-word !important;">。当然，对于该患者的具体治疗，我们还需要组织MDT讨论，在分子指导的基础上，结合患者的实际情况，集思广益，以实现患者后续治疗的最佳获益。</span></section></section></section></section><p arial="" border-box="" break-word="" center="" gb="" helvetica="" neue="" sans="" sans-serif="" sc="" style="color: rgb(0, 0, 0);white-space: normal;margin-bottom: 0px;outline: 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