原文：Glasgow S C, Gaertner W, Stewart D, et al. The American Society of Colon and Rectal Surgeons, Clinical Practice Guidelines for the Management of Appendiceal Neoplasms[J]. Diseases of the Colon & Rectum, 2019, 62(12): 1425-1438.
翻译：
赵伟杰，福建医科大学2019级硕士研究生
审校：
袁静，中国人民解放军总医院病理科；
陈致奋，福建医科大学附属协和医院结直肠外科
问题陈述
历史上，阑尾肿瘤的年发病率估计为0.12/10万；然而，根据最近的大型数据库研究，年发病率可能高达0.97/10万【1-3】。目前尚不清楚这一增加是否反映了疾病发生的实际变化，或者仅仅是更大的认可度和报告率。尽管阑尾肿瘤很少见，但外科医生应熟悉阑尾病理学的意义，因为在美国每年进行近300,000例阑尾切除术，在这些标本中约有1％至2％会发现肿瘤【4-6】。
按组织病理学分类
描述阑尾肿瘤的术语较为稀有且多样，病理分类若能实现一致性，不仅可以改善报告质量，而且可以进行更精确的管理。一般而言，阑尾肿瘤可广义地描述为上皮性（例如腺瘤或腺癌）或非上皮性（例如神经内分泌肿瘤或淋巴瘤）。由于黏液性肿瘤的生物学行为和肿瘤学结果与非黏液性肿瘤截然不同，因此通常根据是否产生黏蛋白可将上皮性肿瘤进一步细分【4】。世界卫生组织将大多数非浸润性上皮性病变归为低级别阑尾黏液性肿瘤（low-gradeappendiceal mucinousneoplasms，LAMNs）【7】。从组织学上讲，LAMNs的特征是分化良好的腺瘤，可在阑尾外生长，具有恶性生物学行为。LAMNs可以出现无细胞成分或有细胞成分的阑尾外黏液，但这不是诊断所必需的。LAMN相关术语包括以前称为黏液囊肿或黏液性囊腺瘤等病变，这些术语已不再使用。一些作者提出传统LAMNs与浸润性癌之间有一中间分组【8】。这些具有不确定的、潜在恶性的LAMNs可能表现为肉眼穿孔、管壁纤维化、阑尾管壁内黏液夹层或阑尾周围软组织中的无细胞成分的黏液。高级别阑尾黏液性肿瘤（High-grade appendiceal neoplasms，HAMNs）与LAMNs具有一部分相同的组织学特征，但有具更为侵袭性的细胞异型性。HAMNs独特的生物学和临床行为较少在文献中描述【9】。
阑尾腺癌既可以是黏液性也可以是非黏液性。黏液性腺癌的特征是侵袭性腺体内具有高级别细胞异型性，而且细胞外黏液成分＞50%【7】。阑尾腺癌在组织学上类似结直肠癌，常规表达p53、CD44和CDX2。分化差时，常出现印戒细胞，容易发生淋巴结转移，根据TNM分期进行分期。杯状细胞类癌是腺癌的一种特殊类型，其与传统的神经内分泌肿瘤（neuroendocrinetumors，NETs）有一些类似的特征，比如嗜铬蛋白A染色阳性【7】。但是，这种混合性腺神经内分泌癌比传统的NETs更具侵袭性，处理方法需要按照经典的阑尾腺癌治疗模式【10,11】。
阑尾肿瘤可能穿孔或播散到整个腹膜腔【12】。当这种扩散同时产生大量的黏液时，我们便称之为腹膜假黏液瘤(pseudomyxoma peritonei，PMP)。有的学者认为PMP只是一种临床表现而不是一种诊断，黏液在整个腹部的扩散分布才能称之为PMP，黏液仅沉积于阑尾附近则不算PMP【9】。由于PMP在治疗后经常复发，术后10年生存率(OS)为63%，因此PMP应视为恶性疾病【13-14】。PMP的细胞成分可以导致病人的预后有很大的不同【11，13，15，16】。为了减少混乱并提高文献的一致性，最近发表了针对PMP和阑尾肿瘤分类的病理报告共识【14】。共识作者建议根据黏液内的细胞成分将PMP归类如下：无细胞成分、低级别组织学特征、高级别组织学特征以及伴有印戒细胞的PMP（表1）。低级别组包括通常报道的播散性腹膜腺黏液病（disseminated peritonealadenomucinosis），而腹膜黏液癌病（peritoneal mucinous carcinomatosis）被定为高级别组。由于分组是基于组织学，因此临床表现为“大网膜饼”或卵巢受累的病例可能属于低级别或高级别PMP。该分类方法与其他方案一致，有助于确定治疗和预后。
非上皮阑尾肿瘤包括NETs。这类阑尾病变在组织学上与胃肠道其他部位发生的NETs相似【7】。阑尾NETs通常无症状，多在常规阑尾切除术后偶然发现。其分期仍存在争议，可能取决于肿瘤的大小、浸润深度或分化程度。其他少见的非上皮阑尾肿瘤包括胃肠道间质瘤、淋巴瘤和神经增生性病变（本指南中未考虑这些病理类型）。
一般注意事项
1.阑尾肿瘤患者应进行完整的病史和体格检查。等级：基于低质量证据的强烈推荐，1C。
阑尾肿瘤可能在术中或在病理标本中偶然发现。晚期肿瘤会出现疲劳、体重增加、慢性腹痛和易饱等不典型症状。也可表现为阑尾炎、肠梗阻或盆腔肿块等【19,20】。完整的病史和体检是必不可少的。病史应包括既往的手术史，尤其是阑尾切除术史，并应回顾相关的手术记录和病理报告，因为患者可能不知道有意外的肿瘤或黏液的存在。如果诊断不明确，应复核病理切片。体格检查应包括盆腔检查和直肠指检，以评估盆腔肿块及周围组织结构的活动性。黏液性阑尾肿瘤在少数情况下可表现为在腹壁疝、切口疝和腹股沟疝中发现假性黏液样物质【21,22】。
初诊的阑尾炎进行非手术治疗后进行间隔阑尾切除术的决策尽管比较复杂，但外科医生必须考虑到与一般人群相比，该亚组为隐匿性阑尾肿瘤的风险可能更大【23-28】。现代回顾性研究和数据库研究表明，恶性肿瘤的发生率在2.3％至12.0％之间；特别要注意的是，高龄和影像学诊断有疑点是阑尾癌的重要危险因素【23,24,26,27】。阑尾周围脓肿可能是隐匿性肿瘤的更强预测因子。芬兰Peri-Appendicitis Acuta多中心随机对照试验发现，这些患者的肿瘤总发生率为20％【27】。最起码，医生应该告知患者这些风险。
2.应在确诊或疑似阑尾肿瘤患者中进行结肠镜检查。等级：基于低质量证据的强烈推荐，1C
基于人群的研究报告表明，与普通人群相比，阑尾肿瘤患者有更高的同时性结肠病变的风险，13％-42％的原发性上皮阑尾病变的患者中同时存在结直肠肿瘤【5，6，29，30】。荷兰进行了一项基于人群的研究，纳入1995年至2005年期间的1482例阑尾上皮肿瘤患者，意外发现其中193例（13％）患有结肠腺瘤（n =37）或腺癌（n = 156）【5】。该项研究发现，阑尾肿瘤的主要病理类型是黏液性囊腺瘤（32％）、黏液囊肿（31％）和非黏液性腺瘤（26％），所发现的大多数结肠腺癌位于右侧结肠。相比之下，单中心研究表明仅有＜4％的大肠癌患者患有同时性阑尾肿瘤【31，32】。在同一外科医生进行的连续169例结直肠癌切除术（包括63例右结肠切除术）期间行预防性阑尾切除术，阑尾肿瘤意外发现率为4%【32】，尽管阑尾肿瘤在结肠镜检查时很少被诊断出来，但在内镜下，它们可能表现为阑尾开口处有一个内翻的或肿块样的突出物或黏液或息肉样组织【30，33】。
3.如果在与阑尾无关腹部手术期间遇到严重异常的阑尾，则应进行阑尾切除术。等级：基于低质量证据的强烈推荐，1C。
在腹部或骨盆手术期间，若偶然发现阑尾管腔扩张、浆膜褶皱或不规则或肿块，则有理由进行阑尾切除术。术中应注意避免阑尾穿孔和内容物溢出，必要时并在某些情况下转换为开放手术【34-36】。在一组24例阑尾黏液性肿瘤患者中，均进行了腹腔镜手术，且无术中溢液。在这个系列中，大多数需要部分盲肠切除术（15/24; 62.5％）或回盲部切除术（8/24; 33.3％），而1例患者接受了单纯的阑尾切除术【37】。手术切除范围主要取决于阑尾基底部的累及程度。手术要保证病理切缘阴性。在大多数情况下，当偶然遇到异常阑尾时，阑尾切除术或部分盲肠切除术就足够了。进行腹腔镜手术时，外科医生应考虑使用标本回收袋以防止黏液溢出。
偶然发现的腹腔黏液提示可能存在胃肠道或妇科黏液性肿瘤。在这种情况下，应仔细检查阑尾（女性患者应检查其附件）。多个回顾性研究以及一些单中心研究的数据并不支持对卵巢黏液性肿瘤患者的正常阑尾进行常规行阑尾切除术，因为在这些病例中发现同时性阑尾肿瘤的几率很低【38-40】。
阑尾神经内分泌肿瘤（NETs）
4.阑尾神经内分泌肿瘤患者的术前评估通常应包括病史和体格检查、结肠镜检查、胸部、腹部和骨盆的CT或MRI检查。等级：基于低质量证据的强烈推荐，1C。
阑尾神经内分泌肿瘤的患者的术前评估应包括完整的病史和体格检查，复查并专门记录是否存在类癌综合征相关系统的症状，例如面部潮红、腹泻和呼吸困难等。与阑尾NETs相比，来自小肠或结肠的NETs比阑尾NETs更常见同时性多原发NETs（15％–30％），后者的同时性多发NETs发生率低，在许多研究中均未予以计算【41】。不管同时性多原发NETs的风险如何，术前结肠镜检查都很重要，因为NETs与同时性非类癌肿瘤相关【42】。一项包括身体各个部位NET（包括消化道不同部位）的队列研究报道，全部NET队列中的同时性癌发生率为22.4％【43】。较小型的系列报告了相似的同步恶性肿瘤发病率，结直肠癌占这些同时性病变的25％至50％【44,45】。因为阑尾NETs可转移至肝、肺和肺，而且转移性阑尾NET的管理与非转移性阑尾NET的管理不同，因此患者通常应通过对胸部、腹部和骨盆进行静脉CT增强或MRI的临床分期。
5.并非所有阑尾神经内分泌肿瘤患者都需要NET特异性成像.等级：基于中等质量证据的弱推荐，2B
由于大多数阑尾NETs会表达生长抑素受体，因此可以使用生长抑素受体闪烁显像（SRS）来识别NETs的病灶【46】。此外，由于SRS可以确认强化的病灶是否表达生长抑素受体，因此，该检查可支持生长抑素受体拮抗剂在局部晚期或者晚期的病例中的应用【47】。现代虽有高分辨率的CT和MRI，但对于有潜在转移性疾病的诊断不明确以及患有类癌综合征（例如潮红、腹泻和支气管痉挛）症状的患者，可补充应用SRS以提高确诊率。尽管约有80％或更多的NETs会表达生长抑素受体，提示SRS可用于发现NET的存在【48】，但是目前的数据并不足以支持常规使用SRS进行常规监测。正电子发射断层扫描（PET）-CT扫描是评估阑尾NETs转移性疾病的另一种成像方式。与传统的2-18氟-2-脱氧-D-葡萄糖PET-CT相比，SRS对分化良好的NETs（例如表达生长抑素受体的病例）的检测更为敏感，而2-18氟-2-脱氧-D-葡萄糖PET更易于检测到分化较差的肿瘤【49】。最近，有研究证明（68Ga）dotatate PET-CT用于诊断胃肠道NETs与SRS相当甚至更好【50】。在一项研究中，（68Ga） dotatate PET-CT在65.2％的NET患者生化检查阴性中发现了隐匿性病变，其中40％未出现在SRS上【51】。常规使用（68Ga）dotatate PET-CT成像应与这些检查的高成本相权衡。
6.应对局部或转移性阑尾NETs患者进行生化检查，为今后的监测和疾病监测进行基线测量。等级：基于中等质量证据的弱推荐，2B。
阑尾NETs通常不具有生化活性，除非肝转移性疾病的负担很大。阑尾NETs产生的最常见代谢物包括嗜铬粒蛋白A和5-羟基吲哚乙酸，前者可用血清评估，后者可用24小时尿液收集【52,53】。重要的是，这些标志物对于诊断是否有NET或指导治疗NET是不可靠的【54,55】。
7.阑尾NETs手术切除的范围取决于肿瘤的大小和组织学特征。等级：基于低质量证据的强烈推荐，1C
对于局限于阑尾的无转移性NETs，治疗方式一般是根据原发肿瘤的大小而定。直径<1cm且无不利特征的病变可通过阑尾切除术进行治疗，术中注意切除整个阑尾系膜。这些患者的长期无病生存率为100％。＞2cm的肿瘤最好采用正规的右半结肠切除术，因为据报道淋巴结转移的风险可能高达40%【56,59-61】。肿瘤大小在1到2cm之间的阑尾NETs在大多数研究中都有中等风险发生淋巴结转移。然而，最大的临床研究发现小于2cm的原发性肿瘤中无淋巴结转移，一些作者建议在此阈值以下的所有病变均单独进行阑尾切除术【63,64】。除大小外，组织学特征也影响手术决策，组织学的不良因素包括阑尾系膜浸润>3mm、高级别肿瘤[包括核分裂像(>2个/每高倍镜视野)、Ki-67指数(>3%)和淋巴管/血管侵犯]等等。在中小尺寸的阑尾NETs中是否进行右半结肠切除术的应根据具体情况进行，要考虑组织学特征、患者是否有合并症以及患者的选择等【60】。虽然阑尾NETs的位置大部分在阑尾的顶端，但对于阑尾底部的肿瘤患者或切缘阳性的肿瘤患者可能需要扩大切除范围以获得阴性的切缘【63】。
8.阑尾NETs治愈性切除术后的监测应包括体格检查、系列生化检查以及胸部、腹部和骨盆的CT或MRI成像。等级：基于低质量证据的弱推荐，2C。
对于已行根治性手术切除阑尾NETs的患者，建议对有可能需要进一步治疗的患者进行疾病复发的监测。监测内容包括临床症状、生化指标和影像学复查等。尽管由于NETs的稀有性和惰性，监测评估的间隔时间和监测持续时间尚无标准，但监测检查之间的间隔通常为6到12个月，具体取决于NET的组织学分级，通常建议根治性切除术后的监测时间延长至10年【66,67】。血清嗜铬粒蛋白A水平和尿液5-羟吲哚乙酸水平可能与治疗效果和复发相关，但由于这些生物标志物的非特异性，需要结合影像学检查综合判断【68】。目前尚无足够数据支持常规使用SRS或其他NET特异性成像方式进行常规监测，尽管它们可能有助于确认CT或MRI上发现的复发性疾病以及评估生长抑素受体表达用于潜在的治疗【69,70】。
阑尾黏液性肿瘤与腺癌
9.在阑尾上皮肿瘤的诊断中，通常应对肿瘤标志物进行评估，并在切除后进行常规随访。等级：基于低质量证据的弱推荐，2C
血清肿瘤标志物CEA、CA19-9和CA125常用于阑尾黏液性肿瘤的诊断、定期监测以评估疾病的缓解或进展【71】。虽然它们对疾病复发的个别可预测性还没有很好的特异性，但大多数高容量医疗机构通常在可行的情况下于基线、化疗期间和术后等时间节点将肿瘤标志物等与影像学结合起来综合判断。在阑尾黏液腺癌中，基线的正常CA-125与实现完全细胞减灭术的可能性相关【72】。基线CA19-9升高也被描述为无进展生存期（PFS）较差的独立预测因素，对于细胞减灭术（CRS）和腹腔内温热化疗（HIPEC）（CRS+HIPEC详见本公众号译文：“结直肠癌腹膜转移的细胞减灭术加腹腔热灌注化疗的进展：单中心的8年经验”）治疗后的疾病复发有诊断价值【72，73】。有研究表明CEA在完全细胞减灭术后可恢复正常，而CA19-9和CA-125可保持升高【74】。Taflampasetal【75】等发现术前肿瘤标记物正常的已治疗患者中存在更长的疾病特异性生存期，他们认为肿瘤标记物的升高可能有助于指导围手术期个体化全身化疗。然而，影像学监测对发现腹膜疾病复发似乎比单独检测肿瘤标志物更敏感【76】。
关于使用其他标记来区分LAMNs和HAMNs，许多人提出了分子表达谱分析，包括环氧合酶2表达和KRAS、TP53及SMAD4等基因突变，但没有确凿证据表明它们对诊断或治疗的存在影响【77-81】。尽管一些结论可能是从结直肠癌中推断出来的，但阑尾腺癌的罕见性限制了对特定基因缺陷的影响做出结论的能力。
10.在诊断阑尾上皮肿瘤时应进行CT或MRI横断面成像，并在切除术后常规随访。等级：基于低质量证据的强力推荐，1C
胸部、腹部和骨盆的CT是用于评估原发性肿瘤和转移性肿瘤最常用的影像学检查方法。附加的PET扫描未能提高分期能力或者显著性改变治疗方案【82】。MRI能检测腔外黏液蛋白，其联合应用弥散加权成像及钆造影剂延迟增强序列在腹膜转移性疾病的诊断上优于CT【83】。在小型非对照研究中，证明MRI可在术前对腹膜癌指数（PCI）进行预测，并且通常用于CRS和HIPEC后的术后监测【76，83】。不幸的是，准确的术前诊断极具挑战性，因为由于不典型的临床表现和不同阑尾肿瘤有类似的影像学表现。尽管有人提出使用2010年世界卫生组织病理学分类作为报告阑尾肿瘤患者影像学报告的框架，但目前尚未常规应用这样结构化成像报告系统【84】。
尽管没有针对阑尾切除术后阑尾肿瘤的正式监测指南，但是局限性低级别阑尾肿瘤若仅接受阑尾切除术，术后很少发生PMP；因此，术后延长随访并在那期间频繁影像学检查获益很小【6，85，86】。术后必须根据肿瘤和病人的特点进行个体化监测。对于完整切除的LAMN的一种监测方案是术后两年内每6个月进行一次MRI检查及肿瘤标志物检测，因为大多数早期复发都发生在该时间范围内【85】。高级别肿瘤患者或因肿瘤局部进展期、穿孔、手术边缘可疑阳性而行行右半结肠切除术的患者，或有淋巴或腹膜转移的患者，术后前2年内应每4至6个月进行一次CT或MRI检查，≥5年后每年进行一次。对于存在无细胞成分的黏液或低级别腹膜转移患者，应在术后2个月(基线)进行腹部和骨盆CT或MRI检查，然后每年进行一次，复查持续时间≥5年【86,87】。对于患有高级别腹膜转移的患者，在术后头6年要进行额外的胸部影像检查，并在每6个月进行更频繁的监视可能有助于更早发现复发性疾病【88】。尽管腹膜复发可能发生在术后10年以上，某些特定医疗机构的监测方案可能延长至15年，但没有明确证据支持长期监测【89】。
11.腹膜细胞学检查对阑尾肿瘤患者的治疗影响很小，不推荐作为常规做法。等级：基于低质量证据的弱推荐，2C
尽管腹膜细胞学检查阳性在胰腺、胃或卵巢的恶性肿瘤患者中有不同程度的用途，但在阑尾肿瘤患者中效果未知【90-92】。通过对腹膜转移的结直肠癌研究的外推可能会获得一些借鉴。有研究发现接受治疗的结直肠癌患者中有23.5％发生了腹膜细胞学阳性，并且与OS相关（19月vs腹膜细胞学阴性的44月 p = 0.01）【93】。Yonemura等人【94】还表明，205例接受完全CRS和HIPEC的结直肠癌患者中，阳性细胞学检查与较差的PFS独立相关。这两项研究均未对阑尾恶性肿瘤患者进行亚组分析，也未评估其在决定实施HIPEC中的作用。在阑尾肿瘤患者中，没有证据支持腹膜细胞学的常规评估，因为其对治疗和预后的影响尚不清楚。
12.切缘阴性、无穿孔或腹膜受累迹象的LAMNs患者可仅行阑尾切除术。建议等级：基于中等质量的证据的强烈建议，1B
在现代观察研究中，对于穿孔或腹膜受累的LAMN的病例，进行阑尾系膜切除在内的阑尾切除术后的肿瘤学结果显示其复发率非常低，与这些肿瘤惰性的行为相一致【95-97】。合适的初始外科治疗是至关重要的，因为医源性阑尾破裂可将病情从局限性转变为播散性；因此，如果腹腔镜下不能安全切除未破裂的LAMN，建议改用开放手术。有限的公开数据表明，对于未穿孔的LAMN行阑尾切除术后，镜下切缘阳性不能预测疾病的复发，因此该指标不能作为正式的右半结肠切除术的指征【98】。Guaglio等人【85】前瞻性纳入41例LAMN患者，分别行阑尾切除术(31例)和右半结肠切除术(5例)，并进行密切的影像学和生化指标监测。研究中有阑尾破裂21例(51%)。在58个月的中位随访中，5年无复发生存率为95％，只有2例患者在阑尾切除术后18和22个月出现腹膜复发。
罕见的情况下，原发阑尾黏液性肿瘤包含高级别细胞异型性，但缺乏与腺癌相关的浸润性病变，这些肿瘤最好被归类为HAMNs【14】。尽管仅行阑尾切除术通常足以治疗HAMNs，但应注意排除相关浸润性腺癌的存在，包括对整个手术标本进行全面的组织学评估。
附图注：根治性阑尾切除术。Sugarbaker建议对可能存在阑尾恶性肿瘤的患者在行阑尾切除术时应行根治性阑尾切除术（如上图所示），同时他也建议切除1-2枚靠近阑尾的回结肠动脉淋巴结。如果术后病理显示阑尾切端阴性、所切除的腹膜病理阴性且区域淋巴结阴性，则可能无需进一步行扩大手术[Sugarbaker P H. Management of Appendiceal Malignancy[J]. Journal of the American College of Surgeons, 2019, 229(5): 517-519.]。
13. 阑尾非转移性腺癌患者应行右半结肠切除术。但如果存在腹膜转移的情况下，结肠切除术可能不会转换为生存获益。等级：基于低质量证据的强烈推荐，1C。
阑尾腺癌的区域淋巴结转移率为20%-67%，非黏液性(肠)亚型的淋巴结阳性率较高【99-103】。由于存在这种巨大风险，局限于阑尾的腺癌应进行右半结肠切除术，因为区域淋巴结的正规清扫可实现更完整的分期并可能具有治疗益处【102】。阑尾杯状细胞类癌的肿瘤组织学特征是神经内分泌肿瘤和腺癌的混合，建议对其进行正规结肠切除术【104】。阑尾杯状细胞类癌患者的自然病史与高级别阑尾肿瘤极为相似，应采取类似的治疗方法【103，105-107】。
在腹膜转移的情况下，不建议常规行右半结肠切除术以清扫临床上正常的淋巴结。在接受CRS和HIPEC的患者中，几个单中心和回顾性研究未能证明右结肠切除术相对于单纯阑尾切除术有生存获益【100，102，108，109】。Turaga等【102】使用美国的SEER数据库对基于人群的数据进行了研究，在对年龄、性别、T分期、转移性疾病和组织学分级进行调整后，发现右半结肠切除术并不能提高生存率。有趣的是，在无腹膜转移的淋巴结阳性患者中未见到行结肠切除术的生存获益，这表明淋巴结阳性只是反映了一种更具侵略性的生物学特性，该生物学特性不受手术切除方式的影响。尽管有这些对扩大手术的保留意见，但应注意，有时必须进行右半结肠切除术才能完全消除源自阑尾的腹膜转移病灶。
14.CRS适用于腹膜受累的部分阑尾肿瘤患者。等级：基于中等质量证据的强烈推荐，1B。
阑尾肿瘤患者伴腹膜转移的，手术切除仍是基准疗法。 CRS的目标是清楚肉眼可见病灶；当实现这一目标时，CRS通常与腹腔内化疗（例如HIPEC）联合使用（请参阅后续推荐）。通常，CRS需要进行选择性的腹膜切除术（尤其是在膈肌处和骨盆内的腹膜）、切除小肠和结肠表面浸润性病灶、大网膜切除术以及其他受累器官的切除（如脾切除术）【110-112】。CRS±HIPEC的个体化治疗决策应该由一个多学科的团队来进行，最好是在有经验的中心进行【109，113】。正确的病例选择对于治疗腹膜受累的患者是至关重要的【114】。横断面成像有助于确定手术的可切除性和指导选择适合行细胞减灭术的病例【115，116】。如果其他技术（例如CT引导的活检）不可行，诊断性腹腔镜探查还可用于评估完全细胞减灭术的可能性或获取组织标本。腹膜受累可以用Sugarbaker's腹膜癌变指数(Peritoneal Carcinomatosis Index，PCI)或腹膜表面疾病严重程度评分来量化【117-119】。PCI是术中根据肿瘤大小确定的，其位于腹部的13个区域，评分范围从0到39。腹膜表面疾病严重程度评分包括临床症状、PCI和肿瘤组织学，最高评分为22分；>10分IV期。尽管这些评分系统可用于客观地测量疾病，但其评分系统可能与行完全细胞减灭术的阑尾肿瘤的术后存活率不相关【110】。然而，在胆道或输尿管梗阻、多发性肠梗阻或广泛的小肠受累患者中，成功施行细胞减灭术的可能性较小。几乎所有临床和病理因素分析中，细胞减灭满意度（CC）始终是一个独立的预后指标【13、15、110、114、120-126】。
腹膜转移的妇女经常会出现卵巢受累。卵巢转移瘤可能迅速生长，并且通常对全身化疗有耐药性。Mehta等【127】回顾性评价了258例存在单侧或双侧卵巢的女性结直肠和阑尾肿瘤患者，这些病例均接受了CRS和HIPEC治疗。258例患者中有141例(55%)卵巢肿瘤存在受累。在40名一侧肉眼可见卵巢转移病人中，18例对侧卵巢存在镜下转移(45%，18/40)。141例卵巢肉眼观察正常的患者中，24例(17%，24/141)为镜下卵巢受累。鉴于此患者人群中出现隐匿性卵巢转移的风险，应大力考虑双侧输卵管卵巢切除术，并应在术前进行适当咨询【128】。
在LAMN病例中，存在无细胞成分的黏液有限性腹膜浸润的患者的治疗仍存在争议，特别是当其局限于右下腹时【6，86，129】。在这些病例中，阑尾切除联合阑尾周围腹膜的腹膜切除术可实现较低的腹膜复发率，腹膜复发率在3%到7%之间。反之，有细胞成分的黏液病灶的LAMN与后续的腹膜受累的风险较高（33％–78％）；这些患者应考虑进行HIPEC【130，131】。
15.对于选择性阑尾上皮肿瘤的患者中，与单独使用CRS相比，腹腔内化疗可能为减少腹膜疾病复发提供额外获益。等级：基于中等质量证据的强烈推荐，1B
阑尾肿瘤患者在全部肉眼可见腹腔病变完全切除后，看要接受腹腔内化疗。最常见的情况是，CRS与HIPEC同时进行。一项针对结直肠癌和阑尾癌的癌变的大型随机对照试验表明，与单独使用全身化疗相比，CRS/HIPEC的生存期增加了一倍（中位OS为22.3-vs.12.6月），此后，学界对于CRS和HIPEC用于治疗阑尾肿瘤的兴趣大大增加【120】。额外的长期随访显示，对于实现完全的细胞减灭的患者，其中位OS为48个月，5年生存率为45%【132】。多项大型回顾性和前瞻性II期研究（包括低级别和高级别腹膜转移患者）均显示，在接受CRS+HIPEC治疗的患者与进行减瘤手术或姑息性全身化疗相比，长期生存率提高、肿瘤复发率降低、疾病进展时间更长、重复进行手术干预的频率更低【13、15、124、133-141】。Chua等人在2012年进行一项观察性研究【13】，研究纳入2298例患者，报告了转移性阑尾黏液性肿瘤CRS后行HIPEC伴有较高的PFS（HR = 0.65； p = 0.03），但多因素分析无OS差异【142】。中位OS为16.3年，PFS中位数为8.2年。丝裂霉素或铂类化疗药物是HIPEC最常用的药物。
除HIPEC外，其他腹腔化疗方法还包括术后早期腹腔化疗(EPIC)或其他术后延期的方法【16，126，143-149】。通常，在各种方法中获得相似的结果，并且几乎没有逐一进行对比。挪威的一项回顾性研究对93例完全细胞减灭术后的EPIC和HIPEC进行了比较，结果显示两者之间10年OS和DFS没有差异【16】。一项正在进行的HIPEC与EPIC的随机对照试验可能可以回答关于哪种治疗效果更好【142】。
16.全身化疗可提高转移性HAMNs患者的生存率。对于腹膜转移的低级别病变，全身化疗的益处尚存质疑。等级：强烈推荐基于低质量的证据，1C
全身化疗和最佳化疗方案的意义在转移性阑尾恶性肿瘤中的作用仍有待进一步研究。虽然缺乏一级证据，对于有高级别腹膜转移或淋巴结转移的患者，通常推荐采用5-氟尿嘧啶为基础的全身化疗(类似于结直肠腺癌)。lackham等【150】报道，接受CRS+HIPEC的高级别PMP患者，围手术期全身化疗改善了PFS，特别是在未达到最优细胞减灭术目的的患者以及印戒细胞组织学检查的患者中。全身化疗对低级别PMP患者中无益处。Bijelic等【151】报道，在接受术前全身化疗后行CRS加HIPEC的高级别PMP患者中，有30％肿瘤部分或完全缓解。与无治疗反应的患者相比，这组患者的OS明显延长(中位生存期未达到vs无反应组中位时间为29.5mo；p=0.03)。通过免疫组织化学检测环氧合酶2的表达和KRAS突变状态，并采用靶向治疗和术前非细胞毒性药物对生存期均无明显影响【78】。相反，全身化疗联合贝伐单抗对于不可切除的高级别阑尾腺癌可以提高OS和PFS，目前有一项前瞻性II期临床试验正在评估5-氟尿嘧啶的辅助化疗与贝伐单抗的疗效（clinicaltrials.govNCT02420509）【152】。尽管围手术期全身化疗的时机已显示出与其他恶性肿瘤相矛盾的结果，但术前化疗有若干潜在优势，包括：评估疾病对化疗的反应和患者耐受性的能力、前期实施全身化疗对大多数患者多意味着术后也要化疗，而且还可以使得影像学上暂时未能发现的病灶得以显现，以避免不必要的CRS【153】。
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