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低位直肠癌做术前新辅助放化疗的必要性和专家利弊分析
第一节 摘录肠癌专家对术前新辅助放化疗的权威论述
与结肠癌相比．直肠癌，尤其是中低位直肠癌在解剖和治疗学上有许多不同之处。首先大多数中低位直肠癌患者面临着是进行传统的经腹会阴联合切除，还是进行保留括约肌的保肛手术的问题；其次，虽然近年来随着手术技术的不断改进．尤其是在直肠全系膜切除技术得到推广以后，患者的保肛率、长期生存率得到明显的提高；但是术后局部复发仍然是直肠癌手术失败的重要原因之一，尤其是直肠癌侵犯深达全层以上、淋巴结有转移或周边切缘肿瘤阳性的患者盆腔或局部复发的机会仍然比较高，即使采用TME技术，仍然可达5-40％。另外．由于直肠位于狭小的盆腔内．尤其是男性患者．如果肿瘤体积较大、比较固定手术操作常常比较困难因此如何通过辅助治疗，提高肿瘤的切除率，降低局部复发率，提高长期生存率成为临床研究的重点之一。
1．术后放疗的缺点
直肠癌术后放疗已被很多外科医生采用，两组70年代开始的随机实验显示，对TNMⅡ、Ⅲ级的直肠癌患者行手术切除，术后追加盆腔放疗虽然总体生存率没提高，但盆腔复发率明显降低n1。然而与术前放疗相比，术后放疗有许多缺点：
1.1 局部组织结构被手术破坏，残余肿瘤组织被疤痕组织包裹处于乏氧状态肿瘤组织对放疗的敏感性降低。
1.2 术后坠入盆腔放疗区内的小肠常常由于手术粘连而比较固定，不能自由移动，容易在固定的部位接受大剂量的放射线，诱发放射性小肠炎；
1.3 术后重建的直肠位于放射区内，放疗后肠管的功能情况受损，常常出现排便次数增多，控便能力下降等情况。
2．术前放疗的优点
有鉴于此，人们开始尝试术前放疗，研究显示与术后放疗相比，术前放疗具有更加明显的优点。
2.1 术前放疗时肿瘤对放疔的敏感性更高，疗效更加确切；
2.2 术前进行放疗后，经过一定的时间肿瘤的体积可以明显缩小，许多由于肿瘤较大，原本无法根治性切除的局部比较晚期的患者，经过术前放疗后肿瘤变得可以切除或根治性切除率得到明显的提高。
2.3 与没有进行放疗的肿瘤相比，经过术前放疗的肿瘤组织在很大的程度上出现坏死、纤维化等改变。肿瘤细胞的活性降低，在手术切除的分离过程中，由于肿瘤挤压引起的肿瘤细胞脱落减少；即使有肿瘤细胞脱落。其在靶器官生存的机会也较未行术前放疗肿瘤的机会降低，因此术后出现远处转移和局部复发的机会减少。
2.4 通过术前放疗，肿瘤的侵犯深度较放疗前明显变浅，部分肿瘤甚至在形态学上完全消失；肿瘤周围的转移淋巴结的数量明显变少，具有明显的降级作用m。
3．术前放疗病人的选择
对于哪些患者应当进行术前放疗有不同的观点，少数医生认为所有的中低位直肠癌均应当先行术前放疗再进行手术，但多数主张应选择那些真正可能从术前放疗中受益的患者进行放疗M。毕竟术前放疗具有一定的并发症，而且患者将等待比较长的时间才能手术，期间是否会延误潜在的转移病变的治疗难以确定。而对于单纯通过手术即可以取得比较良好的治疗效果的患者，附加的术前放疗难以使治疗效果得到更大的提升。因此高位直肠癌或者原发肿瘤体积较小、侵犯深度为Tl-T2，不伴有淋巴结转移的直肠癌一般不主张进行术前放疗。另外，如果患者全身其它部位，如肝脏、肺等部位已经明确有转移，术后影响患者的生存的主要因素将是远处转移，一般认为应当先将原发病灶切除，再进行综合治疗。
但对于以下情况一般认为应当先行术前放疗再行手术：
3.1 肿瘤体积较大的中低位直肠癌；
3.2 直肠指诊肿瘤固定或者影像学检查提示肿瘤侵犯周围脏器，如膀胱、精囊腺、阴道壁或骶前组织等；
3.3 腔内超声或其它影像学检查提示为T3、T4期肿瘤；
3.4 术前影像学检查提示可能伴有直肠系膜或盆腔淋巴结转移的直肠癌；5．直肠癌侵犯肛管或组织学分化差的直肠癌。
4．术前放疗的不足
与采用术后放疗可以根据患者的病理分期、病理类型、手术情况以及患者术后局部复发的可能性决定是否追加放射治疗相比，术前放疗最大的缺点是病人的选择具有一定的盲目性。直肠癌，做为一种腺癌其整体对单纯放射治疗不如鳞癌、恶性淋巴瘤等敏感，对放疗有明显效果、部分效果和效果不明显的患者各占约三分之一左右161，后者从术前放疗中受益较少。因此。许多研究试图找到有关直肠癌放疗敏感性的生物学标志物，更好的对患者进行选择，包括／>53和t21等仍，但在临床上尚难以得到广泛的应用。目前 ，主要还是依据肿瘤的临床特征，包括肿瘤的大小、活动度，肿瘤分化程度以及影像学检查提示的肿瘤分期等进行选择，而这些临床指标缺乏与肿瘤放疗敏感性的关系M。
5．直肠癌放射治疗的种类：
直肠癌术前放疗的方法有腔内放疗和体外放疗两种。前者于70年代初首次应用于直肠癌治疗，Papillon创建了单独放疗和联合保留括约肌手术的技术。与体外放疗相比，腔内放疗的优点在于大剂量的照射集中于肿瘤部位，但同时具有比较大的局限性，临床应用的比较少，仅限于局部治疗的直肠癌患者，包括远端接近括约肌的肿瘤、瘤径小于3era、无淋巴结转移、存在息肉状病灶及高分化癌的患者¨q。体外放疗是目前最常用的方式，许多研究显示可以使肿瘤的体积明缩小、病理学降级、术后局部复发率降低H。但是具体采用的方法缺乏统一模式，包括每次给予多少剂量；给予的总的剂量多少；是否同时结合化疗；与哪种化疗方案相结合以及放疗结束后多长时间进行手术等等。
对于术前体外放疗，目前最常用的方案有两种。一种是短疗程、每次大剂量方案。一组包括1399例患者的前展性分组研究，术前放疗组7天内分5次给予35Gy，放疗结束后l周内进行手术，结果显示与单纯手术组相比，术前放疗组患者术后2年的局部复发率明显下降，但同时术后并发症的发生率也有所上升。而另外一组瑞典的相关研究采用显示的方案，但总剂量由35Gy改为25Gy，结果显示术后2年的局部复发率与单纯手术组相比下降65％。5年生存率则分别为58％和48％112l。
上述方法虽然在降低术后局部复发率方面效果明显，但是由于放疗后间隔时间较短，肿瘤细胞尚未明显坏死和缩小，对于提高手术切除率帮助不大。因此目前在临床上采用更多的是长疗程、每次小剂量的方法。一般每天给予2Gy，每周连续5天，休息2天，总剂量30-50Gy。英国一组研究采用总剂量40Gy，分20次，4个星期，每次2Gy，结果显示术后局部复发率术前放疗组较单纯手术组明显降低，但5年生存率没有明显改变㈣。MRC的一组临床研究显示分次小剂量放疗后淋巴结的数量减少约30％，而行单次放疗的患者没有变化041。
对于放疗后多长时问进行手术更为合适，意见尚不统一。研究显示，放疗后4—6周肿瘤组织的坏死和纤维化即比较明显．并有一定的缩小。但是效果完全显现要8周左右时间，此时部分肿瘤甚至在组织学上完全消失。对于这部分患者是否
还需要进行根治性手术，目前尚有争议。
Habr-Gama报道直肠癌进行放化疗后即使局部肿瘤在组织学上完全消失也有一定的局部复发率，其发生远处转移的可能性手术组与非手术组相似，建议密切随访。
6．放疗于化疗相结合
为了更好的提高治疗的效果，近年来许多作者采用术前放疗和化疗相结合的方法对中晚期直肠癌进行治疗，取得比单纯术前放疗更明显的疗效。Wheeler采用每次2GY，总剂量45-50GY进行术前放疗，并结合5-Fu化疗．结果46％的术前放化疗患者的肿瘤缩小l度，14％的患者放疗后肿瘤完全消失。术后平均随访39个月(24．83个月)，总的生存率为67％．与肿瘤的降级有明显的联系．术后局部复发率为5．8％，其中肿瘤缩小1度的患者的局部复发率明显降低。在9例肿瘤完全消失的患者中，8例随访平均4】个月(24-70个月)均无复发，无瘤生存。
比较术前放疗加化疗与单纯术前放疗的效果，两者的肿瘤降级的比例分别为62％和42％。保肛率前者为39％，而后者仅为13％。差别非常显著。
7．术前放疗的副作用：
术前放疗的副作用包括两个方面：主要是对手术以及术后肠道功能恢复的影响。与未行术前放疗的患者相比。行短疗程放疗的患者手术时肿瘤以及肿瘤周围组织尚处于炎性期，充血水肿比较明显，术中出血的机会相对增高。而进行长疗程放疗的患者，此时组织已经进入纤维化期，肿瘤与周围结构的粘着比较紧密，分离时难度相应增加，但出血较少。另外．放疗患者尽管受放射线损伤的组织大部分已经被连同肿瘤一起切除，但剩余部分的愈合能力与没有进行放疗的患者相比较差，术后吻合口的愈合能力降低，吻合口漏的发生率上升。在进行腹会阴联合切除的患者，术后会阴部切口裂开的发生率术前放疗组为非放疗组的两倍。
与单纯手术的患者相比，术前放疗组患者术后排便次数有所增加，控便功能降低，但比行术后放疗的患者要好。另外，单纯行放射治疗患者的控便功能好于放化疗相结合的患者。
总之，大量临床研究结果显示中低位直肠癌，尤其是肿瘤体积较大的局部比较晚期的中低位直肠癌，如果采用术前放疗或术前放化疗相结合，虽然术后手术并发症的发生率有一定的升高，肠道功能会受到一定的影响，但肿瘤根治性切除率可以得到明显的提高，术后局部复发率明显下降：应当做为一种常规进行采用。
第二节 怎么理解医生要做术前新辅助放化疗和怎么样配合医生做好新辅助放化疗。
医生说需要做术前新辅助的患者，一般都是低位直肠癌或者肿瘤周边怀疑被侵犯、或证实被侵犯的患者，这种病情一般是先做4次化疗，和做完24次左右的长程放疗，再评估手术时机，而医生说术前要做完8次化疗（奥沙利铂＋卡倍他滨片）的一般都是核磁发现切缘阳性，也就是现在就手术有手术切除不了的被侵犯病灶，要做足放化疗之后，等切缘以外不可以切除的病灶消失之后再做手术，这类病情的患者不要跟跟医生讨价还价少做化疗，或者担心是不是化疗多做了，群里经常有患者或家属，对医生的术前新辅助放化疗疗程不太理解，我经常通过研究患者发群里的核磁或ct报告内容，跟群友解释清楚医生要这么做的原因和依据，和给患者、家属科普要怎么配合医生治疗的事情！
术前新辅助主要是缩小肿瘤和解除粘连、缩小肿大的淋巴结、杀灭术区的癌细胞。做术前放化疗的患者，大多数术后发现肿大的淋巴结找不到癌细胞了，就是因为术前放疗的效果，也是能够证明术前放疗对肿大淋巴结有效的证明。
第三节 做术前新辅助放化疗再手术的患者，要注意时时会发生的沟通协调问题
而在不专业医院做术前放化疗之后再手术的患者，术后拿着术后病理跟肿瘤内科医生做术后化疗方案的时候，一定要跟医生讲清楚自己接受了术前放化疗，目前的术后病理分期和治疗前的综合病情程度，比现在的术后病理要严重，这个术后病理是治疗一半的术后病理；因为群里经验上经常看到很多粗心或水平低的放化疗医生容易犯的错误，术前接受过新辅助放化疗的患者，其手术后做的术后病理病情其实是治疗了一半的病情现状，医生不考虑治疗一半的因素，而按照病理科写的术后病理去做放化疗方案，就把病情估计轻了一半了！术后病理几乎是一切后续治疗的根本依据和病情判断的重要参考，这种做过术前放化疗的患者，做放化疗方案是必须要参考术前分期、术前核磁报告分期、结合术后病理做综合判断制定放化疗方案才行的；要避免粗心的化疗科医生拿着治疗一半才手术的术后病理去判断病情，而做出不用化疗的决定，或化疗方案过轻的决定。
术前放化疗本身就是给外科医生手术创造条件的，术前新辅助治疗和术后的化疗强度和次数，肿瘤外科手术医生的参考意见很重要，通常术前化疗4次就要找外科医生评估是否能够手术，尽量将4次化疗疗程留在术后做化疗，不要因为手术医生和化疗医生的沟通、协调的问题，患者和家属的误解，而把化疗疗程在术前全部做完了，导致术后没有化疗疗程可做；一般要做完8次化疗再手术的通常都是有周边侵犯切缘阳性或有远端转移灶，才会在2次、4次、6次的阶段评估之后不能够手术，才会术前就做完化疗疗程，一般3b-3c左右的低位直肠癌患者，新辅助一般是做4次左右，低位直肠癌的新辅助放疗疗程一般会在术前做完，恢复期结束就手术，而恢复期似乎各个专业医院和专家医生、各个患者的时间都不太一样，患者和家属要自己学会这些知识，才有跟手术医生和化疗医生沟通的基础，完全理解医生的治疗意图和依据，患者和家属心中有数，术前术后放化疗的穿插疗程才能比较顺利的进行！
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