摘要
胰腺神经内分泌肿瘤(pNEN)是一类罕见且具有高度异质性的胰腺肿瘤,临床表现隐匿,易发生远处转移,其中肝转移最为常见,显著影响患者的预后。尽管近年来对pNEN肝转移的治疗进行了诸多探索,但仍存在诸多争议和空白。随着多学科诊疗模式的发展,pNEN肝转移的治疗策略不断优化,涵盖外科手术、局部治疗(如射频消融、经动脉介入治疗)、全身治疗(如化疗、靶向治疗、免疫治疗、放射性核素治疗、内分泌治疗)等多种手段,且联合治疗已成为重要趋势。对于可手术患者,根治性切除仍是首选,而对于不可手术或耐受性较差的患者,局部治疗与全身治疗的合理联合可改善生存结局。此外,功能性pNEN患者可通过内分泌治疗缓解症状,提高生活质量。多学科协作制定个体化治疗方案,能够显著改善患者预后。本文综述了pNEN肝转移的治疗进展,以期为临床决策提供参考。
胰腺神经内分泌肿瘤(pancreatic neuro-endocrine neoplasm,pNEN)是临床上一种相对少见、具有高度异质性的肿瘤,但随着影像学和生物标志物等诊断技术的发展,pNEN的检出率逐年升
因临床特征不典型,约40%~50%的pNEN患者最初诊断时就已发生远处转移,以肝转移最为多见,远处转移也是影响pNEN患者预后的不良因素之
肝转移并非pNEN患者的手术禁忌证。Yuan
针对NF-pNEN肝转移的患者,肝转移的侵犯类型为Ⅰ型、肝脏储备功能良好、无严重基础疾病、G1/G2级或生物学行为较温和或存在根治性手术可能的G3级NF-pNET患者,根治性手术是最有效的治疗方式,应争取对原发灶和转移灶行根治性切
而针对F-pNEN患者,手术治疗不仅能改善预后,还能减缓其症状,故无论是否肝转移,都应积极手术治
当原发灶及肝转移灶均可行根治性切除时,应尽量行原发灶及转移灶的根治性切除。当无法行根治性切除时,如原发病灶有出血,或造成胆道、消化道梗阻等占位相关症状,切除肿瘤有助于改善患者生活质量,并进一步治疗,可考虑进行原发灶切除。但切除原发灶是否使患者生存获益,仍存在争议。Bertani
肝移植也是pNEN肝转移患者的一种有效治疗手段,但我国肝源紧张,肝移植需求量大,需要严格掌握肝移植的手术适应证,Partelli
对于已经发生肝转移的pNEN患者,单纯的手术治疗效果有限甚至无法手术,因此,通过术前转化治疗降低患者肿瘤分期以达到手术标准,术后辅助治疗改善患者预后,联合多学科制定个体化治疗方案实现患者利益最大化已成为新趋
局部治疗是手术治疗与药物治疗的重要补充手段。对于不能耐受外科手术的肿瘤级别低、肝脏肿瘤负荷小或F-pNEN患者,应积极推荐局部治疗。对于高级别的pNET、NEC及肝脏肿瘤负荷较大的患者,局部治疗也可能改善其预后。
消融治疗是借助超声、CT、MRI的引导,对肿瘤病灶定位,局部采用物理或化学的方法直接杀死肿瘤细胞的治疗方式,主要包括射频消融、微波消融、冷冻消融等。目前在pNEN肝转移主要使用的消融治疗方式是射频消
尽管靶向治疗、免疫治疗及放射治疗等新兴治疗方式在肿瘤治疗运用中成果斐然,传统的化疗仍占据着肿瘤治疗领域相当重要的地位。对于肿瘤分级高、肿瘤负荷较大、疾病进展较快、高Ki-67增值指数的pNEN肝转移患者,化疗可发挥出相当不错的效果。中国抗癌协会神经内分泌肿瘤诊治指南(2022年版
靶向治疗在NEN治疗领域应用较广,但pNEN的靶向治疗药物有限,其中雷帕霉素靶蛋白(mTOR)抑制剂依维莫司和酪氨酸激酶抑制剂舒尼替尼是目前美国食品和药品管理局批准用于pNEN的两种靶向药物。NCCN指南也推荐二者为晚期pNEN的一线治疗靶向用药。依维莫司和舒尼替尼均可用于进展期G1/G2级pNET肝转移患者的治疗。其中,依维莫司还可用于化疗过的进展期G1/G2级pNET肝转移患者,甚至有研究表明依维莫司在G3级pNET中也可发挥一定疗
有研
PPRT通过放射性核
PNEN出现肝转移发病率高、预后较差。近年来,pNEN的治疗方式正在逐步完善。外科手术方式,局部治疗如射频消融治疗、经动脉途径治疗,全身治疗如化学治疗、靶向治疗、免疫治疗、放射性核素治疗、内分泌治疗等多种治疗方式在积极探索中。PPRT是近年研究的热点,出现了越来越多的新型药物。但可以预见的是,多学科诊疗将逐渐成为主要的治疗手段,根据患者的情况及肿瘤的分型分期,联合外科手段、化学治疗、免疫治疗、靶向治疗等多种治疗方式,制定个性化的治疗方案,延长患者生存期和生存质量,将成为未来pNEN的治疗的主要方向。
作者贡献声明
陆绍龙、王小波构思了本文主要框架并进行写作;万叶剑、林杰负责本文的文献收集及部分修改工作;陈洁指导了本文的构思并进行最终修订。所有作者均阅读并批准了最终文稿。
利益冲突
所有作者均声明不存在利益冲突。
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