吴文铭, 陈洁, 白春梅, 依荷芭丽·迟, 杜奕奇, 冯仕庭, 霍力, 姜玉新, 李景南, 楼文晖, 罗杰, 邵成浩, 沈琳, 王峰, 王理伟, 王鸥, 王于, 吴焕文, 邢小平, 徐建明, 薛华丹, 薛玲, 杨扬, 虞先濬, 原春辉, 赵宏, 朱雄增, 赵玉沛, 中华医学会外科学分会胰腺外科学组. 中国胰腺神经内分泌肿瘤诊疗指南(2020)[J]. 协和医学杂志, 2021, 12(4): 460-480. DOI: 10.12290/xhyxzz.2021-0481
引用本文: 吴文铭, 陈洁, 白春梅, 依荷芭丽·迟, 杜奕奇, 冯仕庭, 霍力, 姜玉新, 李景南, 楼文晖, 罗杰, 邵成浩, 沈琳, 王峰, 王理伟, 王鸥, 王于, 吴焕文, 邢小平, 徐建明, 薛华丹, 薛玲, 杨扬, 虞先濬, 原春辉, 赵宏, 朱雄增, 赵玉沛, 中华医学会外科学分会胰腺外科学组. 中国胰腺神经内分泌肿瘤诊疗指南(2020)[J]. 协和医学杂志, 2021, 12(4): 460-480. DOI: 10.12290/xhyxzz.2021-0481
WU Wenming, CHEN Jie, BAI Chunmei, YIHEBALI Chi, DU Yiqi, FENG Shiting, HUO Li, JIANG Yuxin, LI Jingnan, LOU Wenhui, LUO Jie, SHAO Chenghao, SHEN Lin, WANG Feng, WANG Liwei, WANG Ou, WANG Yu, WU Huanwen, XING Xiaoping, XU Jianming, XUE Huadan, XUE Ling, YANG Yang, YU Xianjun, YUAN Chunhui, ZHAO Hong, ZHU Xiongzeng, ZHAO Yupei, Chinese Pancreatic Surgery Association, Chinese Society of Surgery, Chinese Medical Association. The Chinese Guidelines for the Diagnosis and Treatment of Pancreatic Neuroendocrine Neoplasms (2020)[J]. Medical Journal of Peking Union Medical College Hospital, 2021, 12(4): 460-480. DOI: 10.12290/xhyxzz.2021-0481
Citation: WU Wenming, CHEN Jie, BAI Chunmei, YIHEBALI Chi, DU Yiqi, FENG Shiting, HUO Li, JIANG Yuxin, LI Jingnan, LOU Wenhui, LUO Jie, SHAO Chenghao, SHEN Lin, WANG Feng, WANG Liwei, WANG Ou, WANG Yu, WU Huanwen, XING Xiaoping, XU Jianming, XUE Huadan, XUE Ling, YANG Yang, YU Xianjun, YUAN Chunhui, ZHAO Hong, ZHU Xiongzeng, ZHAO Yupei, Chinese Pancreatic Surgery Association, Chinese Society of Surgery, Chinese Medical Association. The Chinese Guidelines for the Diagnosis and Treatment of Pancreatic Neuroendocrine Neoplasms (2020)[J]. Medical Journal of Peking Union Medical College Hospital, 2021, 12(4): 460-480. DOI: 10.12290/xhyxzz.2021-0481

中国胰腺神经内分泌肿瘤诊疗指南(2020)

基金项目: 

中国医学科学院医学与健康科技创新工程 2017-I2M-1-001

详细信息
    通讯作者:

    赵玉沛  电话:010-69155810,E-mail: zhao8028@263.net

  • 中图分类号: R58;R735.9;R61

The Chinese Guidelines for the Diagnosis and Treatment of Pancreatic Neuroendocrine Neoplasms (2020)

Funds: 

CAMS Innovation Fund for Medical Sciences 2017-I2M-1-001

More Information
    Corresponding author:

    ZHAO Yupei  Tel: 86-10-69155810, E-mail: zhao8028@263.net

  • 摘要: 胰腺神经内分泌肿瘤具有高度异质性,患者的临床管理存在一定难度。为了应对这一挑战,中华医学会外科学分会胰腺外科学组牵头成立了由肿瘤外科、消化内科、肿瘤内科、内分泌科、影像科、病理科、核医学科等多领域学者组成的专家委员会。该委员会回顾了与胰腺神经内分泌肿瘤诊断和治疗相关的重要问题,并基于循证医学证据提出了相应的诊疗建议,以期进一步改进中国胰腺神经内分泌肿瘤患者的诊疗流程。
    Abstract: Pancreatic neuroendocrine neoplasms (pNENs) are highly heterogeneous, and the management of pNENs patients can be intractable. To address this challenge, an expert committee was established on behalf of the Chinese Pancreatic Surgery Association, Chinese Society of Surgery, Chinese Medical Association, which consisted of surgical oncologists, gastroenterologists, medical oncologists, endocrinologists, radiologists, pathologists, and nuclear medicine specialists. By reviewing the important issues regarding the diagnosis and treatment of pNENs, the committee concluded evidence-based statements and recommendations in this article, in order to further improve the management of pNENs patients in China.
  • X女士78岁,来自中国,是一名退休教师,丧偶,独居,患有多种慢性疾病,包括糖尿病、高血压、缺血性心肌病、慢性肾脏病3期、骨质疏松症和轻度老年痴呆。她的儿子生活在其他城市,很少能来探望她。去年,她注意到自己大便带血,经检查发现患有结肠腺癌,并已转移至肝脏和肺部。儿子知道后坚持让母亲接受化疗,并与妻子共同照顾其起居。

    接受化疗后的一段时间,X女士病情确有缓解,但体质量持续下降,胸片检查结果显示,肺部转移灶仍在扩大。她一天中的大部分时间都在床上度过,不再愿意与邻居及以前的同事聊天,现在连上厕所也需要助行器和他人帮助。1个月前,儿媳购物回来时发现,X女士躺在地板上,已经神志不清。紧急送往医院后,被诊断为肺炎、脓毒性休克、肺水肿和急性肾衰竭,进入ICU后不久,因心脏骤停接受了心肺复苏。心肺复苏后的评估结果显示,X女士多处肋骨骨折、气胸、肾衰竭并出现了缺血性卒中。在儿子的坚持下,X女士接受了气管插管、机械通气、血管活性药物和血液透析治疗,并依靠呼吸机和血液透析维持了两周。在医生提议可以进行胃造瘘手术后,儿子立即要求进行手术,术后继续住在ICU。然而1周后,X女士再次出现心脏骤停,尽管医生全力抢救,30 min后仍因抢救无效而宣布死亡。事后,大多数亲戚都对X女士的儿子表达了称赞,认为他是个孝顺的儿子。

    问题:中国传统死亡文化中将“善终”作为人的最终追求。X女士的经历能否算作善终?如果答案是肯定的,善终究竟是什么意思?对于个体,善终的含义如何确定?什么样的医疗才能使善终成为可能?X女士在生命末期是否得到了最好的关怀?如果没有,什么才是最好的关怀?

    照顾病痛中的亲人以及濒临死亡的人,并不是什么新鲜事,在有文字记载的历史长河中,我们可以看到许多关怀他人痛苦的相关证据。例如,儒家经典《孝经》中提到,孝顺的孩子应该在父母生病时给予他们特别的照顾,并加倍奉养[1]。这种责任源于“孝顺”,它体现了家庭关系的最高价值。大约在同一时期,巴利文典籍《摩诃婆伽》描述了佛陀如何关爱病患:“谁照顾病患,谁就是在照顾我。”[2]这里,照顾他人似乎是一种责任,因为每个人都具有神性或者是神的代表。

    为需要的人提供照护场所同样有着悠久的历史。根据伊斯兰历史学家穆罕默德·伊本·贾里尔·塔巴里的记载,早在公元9世纪,伊斯兰就在贸易和军事路线沿线设立了照顾病患的“临终关怀院”。从公元11世纪开始,基督教十字军也在地中海和朝圣路线沿线建立了临终关怀医院。

    1633年,一个名为“圣文森特·德·保罗慈善之女”的天主教修女协会在法国成立,承担起了在临终关怀医院和家中照顾穷人和病患的工作。然而,当时西方哲学正在经历一场革命,这场革命从根本上改变了照顾病患和临终者的方式及目的。

    17世纪初,法国哲学家勒奈尔·笛卡尔提出,“存在”意味着成为“思考的自我”(ego cogitans)的客体。思考的自我,即思考的主体,对于这个主体而言,世界完全由客体组成,所有客体均可被思考主体测量、研究、操纵和处置。换言之,一切事物都可被认知和掌握。通过阐明自然的力量,即产生、改变和毁灭所有客体并决定其每一次互动的力量,思考主体就能够了解客体。原则上,任何事物都无法抗拒思考主体的阐释和认知。笛卡尔在其1632年出版的《方法论》一书中明确指出了这一点:“……我们可以清楚地认识火、水、空气、星辰、宇宙以及周围一切其他物体的力量和作用,就像熟知什么匠人做什么活一样;我们可以像匠人一样,因势利导将这些知识用于所有适当目的,从而成为大自然的主人和拥有者。”[3-4]

    关于主体认知最适合用于什么目的,笛卡尔认为:“……最重要的是保护健康。健康无疑是人生中最重要的一种幸福,也是其他一切幸福的基础。”即在主体掌握的科学客观领域中,医学是最重要的。虽然所有技术都能够通过保障人类的利益,推动其对幸福的追求,但最大的利益是健康。医学能够通过了解人体及疾病来确保并维护健康这一至高无上的幸福。

    在笛卡尔看来,医学与其他科学一样,只能认知客体。这并不是说医学忽略了主观数据。相反,主观数据通常是关于客体的数据,因此只是客观思考的另一个方面。医学寻求了解正常生理和病理生理知识,进而掌控正常生理和病理生理,通过阐明人体的功能、功能障碍或疾病的原因来认知人体。医学还寻求了解疾病如何发生以及如何恢复和保持健康。笛卡尔认为:“……如果充分认识了各种疾病的原因以及自然界向我们提供的一切药物,我们可以摆脱很多种躯体疾病和精神疾病,甚至可能抵抗衰老、延年益寿。”笛卡尔断言,医学可以驾驭身体,在一定程度上也可以驾驭心灵,从而无限期地保持健康。

    在《方法论》和《第一哲学沉思录》中,笛卡尔都将人体描述为一台机器,称之为“人体机器”[5],其由神经、肌肉、静脉、血液、皮肤和其他器官等多个部分组成,这些部件可能像“制作拙劣的时钟”一样失灵,结果就是产生疾病。主体客观化的医学思考模式认为,原则上可以通过明确故障原因和发明治疗方法来排除这些故障。对于某些故障,可以利用药物作为治疗手段。但由于人体机器的复杂性,故障可能产生于一个或多个部件,原则上,医学可以修复或替换任何一个部件。换言之,人体就是由一次性部件和可能被替换的部件组成。

    在科技时代之初,笛卡尔就认为可将器官替换和维持生命的技术作为维持健康的手段,并提出生命可以无限持续,健康也可以无限维持。按照笛卡尔的观点,当医学掌握了足够的人体知识,就能够将人类从“年老体弱”中解放出来,通过治疗疾病、修复或更换故障部件,不断向后延缓死亡时间。掌握了足够的知识和技能后,医学就能战胜死亡本身,与其他任何自然现象一样,死亡也是一个可以阐释和认知的客体。笛卡尔关于掌控死亡的梦想在很大程度上影响了现代西方医学的教育、研究和实践。它将死亡医学化,死亡因而变成了一个主要需要医学干预的技术问题。因此在20世纪50年代之后,西方文化中死亡的地点从家庭转移到了医院[6]

    笛卡尔“战胜死亡”的计划催生了维持生命/延缓死亡的技术,比如心肺复苏、机械通气、血液透析、人工营养等。在美国的短暂历史中,这些维持生命的技术有两个重要共同点:首先,这些技术均在20世纪60年代开始普及,且一旦普及开来,就很难不去使用;其次,早在20世纪70年代中期,人们就开始认识到维持生命的技术不仅能为患者带来明显好处,其也可能是有害的。这些技术既是给我们的伟大恩赐,也会带来不可预见的危险,甚至可能加剧痛苦。从那时起,美国的患者、家属和医生一致认为,有时候最好的选择反而是暂停或撤除维持生命的治疗,法院也找到了允许在某些情况下暂停或撤除维持生命技术的法律依据。例如,医院成立了临床伦理委员会,以帮助患者权衡接受特定维持生命治疗的利弊,开展病例会诊已成为北美地区的标准做法。

    维持生命技术的不利影响通常包括延长或加剧患者的痛苦和衰弱,甚至导致患者出现焦虑、谵妄、抑郁等症状。当患者家属被问及是否使用这些技术时,无论他们作何选择,都可能感到焦虑或内疚,而这些情绪可能会伴随他们一生。对于有机会康复或出院并拥有可接受的生活质量的患者来说,维持生命的技术利大于弊,但许多患者(如X女士)却因病情危重而并无康复的机会。

    回到文章开头的问题:在中国,“善终”意味着什么?现代医学如何实现或推进“善终”?维持生命的技术对于实现“善终”有何作用?是否可能阻碍“善终”的实现?照顾病弱长者的传统责任是否仍有意义?“孝顺”在当今社会的含义与孔子时代的含义是否相同?甚至可以探讨与几十年前的含义是否相同?有创生命维持技术的出现是否应改变“孝顺”的表达方式?或者说改变是否已经发生?掌控生命的技术目标是否在不知不觉中侵蚀或改变了传统文化价值观和意义?维持生命的技术看似是表达孝顺、实现健康和长寿的手段,但技术本身是否已成为目的[7]

    当技术手段成为目的,心肺复苏、机械通气、血液透析等技术本身可能变得至关重要。延缓死亡可能变得比待在家里、感到舒适、和亲人在一起、与亲人告别、与疏远的亲人和解、给予和请求宽恕更为重要,甚至比患者是否有能力做这些事情更为重要。在北美地区,20世纪60年代和70年代的技术思维已经不知道如何不使用维持生命的技术手段,结果对患者造成了很大伤害[4]。如果孝顺不能适应或不符合当前的社会和医疗技术环境,在中国是否也会面临类似的风险?更具体地说,在当代中国,维持生命的有创性治疗如何才能得到最优化利用,实现利益最大化和伤害最小化?对“善终的意义”这一问题的回答可能部分取决于如何回答上述问题。

    与其他医学领域或医疗模式不同,缓和医疗并不是一种固定不变的技能或活动。如果面临严重的疾病、不同的社会经济背景或文化价值观与西方高收入国家存在差异,缓和医疗的需求和实践方式也应有所不同[8-10]

    在我看来,现代缓和医疗的兴起源于对笛卡尔医学模式忽视、制造和再造痛苦的反思。缓和医疗的主要目的是缓解重病患者的痛苦,同时关注维持生命的技术本身可能带来的不必要伤害。缓和医疗并不完全排斥医疗技术的使用,因为缓和医疗关注的是解除痛苦,因此其更强调负责任地使用技术。然而,这并不意味着其主要目的是对适当使用维持生命的治疗或其他医疗技术进行伦理考量,相反,缓和医疗注重倾听患者的痛苦声音并积极响应他们的需求,并以此来决定技术的使用方式。

    缓和医疗会利用医疗技术来缓解患者的痛苦,包括维持生命的必要技术[11],然而缓和医疗并不拘泥于这些技术,甚至可能在必要时放弃使用维持生命的技术,其关注的焦点是缓解患者的痛苦,维持生命的技术并不总是必需的。缓和医疗并非完全由技术所驱动,而是强调技术的使用应当自然、顺应病情。更为重要的是,缓和医疗尊重并接纳死亡的自然过程。这并不意味着忽视临终患者或放弃治疗可能恢复的患者,其目标不仅仅是战胜死亡,而是无目的性地关怀每一位患者,没有预设的目标使缓和医疗能够真正倾听患者的声音。

    在利用最先进的医疗技术快速缓解患者痛苦和其他不适的同时,缓和医疗也关注疾病管理医疗模式所忽视的痛苦。这些痛苦可能来自于身体上的不适,但更多时候来自于患者内心的失落感,比如失去健康、工作、收入、独立生活能力、社交联系以及生活意义,甚至在面对死亡时感到自我价值的丧失。并无任何一种方法可以准确地衡量痛苦,或者完美地应对痛苦,因此不可能制定一个基本的方案来缓解痛苦。真正重要的,是如何关注和应对患者个体化的痛苦,然后制定最适合他们的缓和医疗措施。

    缓和医疗承认自身的局限性和所有技术的局限性,承认死亡是不可避免的,并积极与患者共同寻找最合适的方式,以最自然的方式离世。最重要的是,缓和医疗更关注患者作为“他者”的感受,不仅将患者视为医疗对象,而是让他们在有意义的环境中、在亲密关系网中、在符合其传统文化背景中得到关怀,这种关怀允许“他者”保持他们的独特性。

    近年来,笔者有幸应邀参加了中国关于缓和医疗的讨论,同时倾听了两个紧密相关话题的探讨,即如何翻译“palliative care”这一词汇?如何将西方的缓和医疗实践引入中国?在这两个问题的讨论中,与会者达成了共识,将治疗和缓解严重疾病痛苦的这一学科翻译为“缓和医疗”。医疗保健应以舒适与“和”(harmony)为导向。但是,“和”指的是什么呢?自身的和谐?与他人的和谐?与社会和自然环境的和谐?还是包括以上所有这些含义?无论是何种情况,中文对缓和医疗的重新诠释至少为“善终”的定义提供了部分答案。中国医疗服务提供者和中国医疗体系如何才能让重病患者获得舒适与“和”?孝顺是否意味着年轻人有责任帮助长辈获得舒适与“和”?

    回到文章最初的问题:X女士的经历是否可以被视为“善终”?她的儿子是否尽到了孝顺的责任?他是否可以做得更好,为母亲提供更为人道的临终关怀,让母亲在生命最后的日子里不再受更多的痛苦折磨?比如将母亲接回家,给予她温馨的照料?这样的照护模式能否在全中国得到普及?我们能否认同,尽孝的最佳方式是让母亲在家中获得舒适与和谐,而不是坚持在ICU依赖各种医疗器械尽可能延长和维持她的生命?即使X女士的儿子在感情上能够接受这种观念的转变,他的家人是否会指责甚至排斥他,认为他是不孝之子?开展全国性的讨论和教育能否改变这种态度?

    我认为,找到这些问题的答案对于增进中国人和海外华人的福祉都非常重要。同时,在中国找到的答案也可能为西方文化提供新的视角,帮助其寻找疾病、死亡和医学的真正意义,因为笛卡尔式掌控自然和战胜死亡的模式已经让西方文化在面对死亡时感到迷茫。

    志谢: “中国医学科学院医学与健康科技创新工程(2017-I2M-1-001)”对会议提供支持;北京协和医院基本外科王先泽医师对指南中参考文献的收集、更新、整理和整合工作,以及对指南历次共识会议的组织协调工作。
    作者贡献:赵玉沛院士领导了指南更新项目、组织了指南编辑委员会(编委会)并任命吴文铭教授和陈洁教授全权负责编委会对指南的撰写工作。吴文铭教授和陈洁教授共同起草了指南初稿,并组织编委会其他成员依照指南编写流程对指南初稿进行审校;在吴文铭教授和陈洁教授的主持和参与下,白春梅教授、依荷芭丽·迟教授、杜奕奇教授、冯仕庭教授、霍力教授、姜玉新教授、李景南教授、楼文晖教授、罗杰教授、邵成浩教授、沈琳教授、王峰教授、王理伟教授、王鸥教授、王于教授、吴焕文教授、邢小平教授、徐建明教授、薛华丹教授、薛玲教授、杨扬教授、虞先濬教授、原春辉教授、赵宏教授、朱雄增教授共同参加了三轮指南修订会议,并根据各自专业对指南的相应章节进行了修订;吴文铭教授、陈洁教授、白春梅教授、霍力教授、姜玉新教授、邢小平教授、薛华丹教授、薛玲教授作为各自章节的负责人,参加或委派代表参加了指南定稿会并对指南终稿内容进行确认;吴文铭教授和陈洁教授对指南终稿全文进行了最终审校后,所有作者均通过了指南终稿并形成指南定稿,同时签署了作者贡献声明及版权转让协议。
    利益冲突:
    吴文铭、陈洁对本文同等贡献
  • 表  1   2019年世界卫生组织第5版胃肠胰神经内分泌肿瘤病理学分类和分级标准

    命名 分化程度 分级 核分裂象数a(/2 mm2) Ki-67指数(%)a
    神经内分泌瘤,G1级 高分化 <2 <3
    神经内分泌瘤,G2级 高分化 2~20 3~20
    神经内分泌瘤,G3级b 高分化 >20 >20
    神经内分泌癌,小细胞型 低分化c c >20 >20
    神经内分泌癌,大细胞型 低分化c c >20 >20
    混合性神经内分泌-非神经内分泌肿瘤 高或低分化 多样的d 多样的d 多样的d
    a核分裂象数表示为核分裂象计数/2 mm2(该面积等于40倍放大倍数及每个视野最大径0.5 mm情况下的10个高倍镜视野),计数50个0.2 mm2的视野;Ki-67增殖指数通过计数高染色区域(即热点区)至少500个细胞获得;最终分级采用两种增殖指数所对应分级中的较高者;bG3级神经内分泌瘤的核分裂数和Ki-67指数未设上限,其理由是G3级神经内分泌瘤(尤其G3级胰腺神经内分泌瘤)的Ki-67指数偶可高达70%~80%,故不能仅根据Ki-67指数的高低进行分级,还需结合其形态学分化良好的特点;对难以区分的G3级神经内分泌瘤和神经内分泌癌,需进行TP53、RB1、ATRX和DAXX染色协助鉴别诊断;c神经内分泌癌根据定义为高级别,无需再分级;d在大部分混合性神经内分泌-非神经内分泌肿瘤中,神经内分泌肿瘤和非神经内分泌肿瘤成分均为低分化,且神经内分泌肿瘤成分的增殖指数与其他神经内分泌癌一致,但该类型肿瘤亦允许这两种成分均为高分化,这种情况下,应分别对两种成分进行分级;胰腺的混合性神经内分泌-非神经内分泌肿瘤包括4个亚型:混合性导管癌-神经内分泌癌(小细胞或大细胞)、混合性导管癌-神经内分泌瘤、混合性腺泡细胞癌-神经内分泌癌和混合性腺泡细胞癌-导管癌-神经内分泌癌
    下载: 导出CSV

    表  2   2017年AJCC第8版胰腺神经内分泌肿瘤的TNM分期标准

    分期 特征 分期 特征
    T分期 原发肿瘤a M分期 远处转移
      TX 原发肿瘤无法评价   M0 无远处转移
      T1 局限于胰腺内b,且最大径<2 cm   M1 有远处转移
      T2 局限于胰腺内b,且最大径2~4 cm     M1a 仅存在肝脏转移
      T3 局限于胰腺内b,且最大径>4 cm;或侵犯十二指肠或胆管     M1b 仅存在至少一个肝脏外器官转移(如肺、卵巢、非区域淋巴结、腹膜、骨)
      T4 侵犯邻近器官(如胃、脾、结肠、肾上腺)或大血管壁(腹腔干或肠系膜上动脉)     M1c 同时存在肝脏和肝脏外器官转移
    N分期 区域淋巴结
      NX 区域淋巴结无法评价
      N0 无区域淋巴结转移
      N1 有区域淋巴结转移
    AJCC:美国癌症联合委员会;a若原发肿瘤为多发,则以最大的肿瘤进行T分期;若多发肿瘤数量已知,则记为T(#),如pT3(4)N0M0;若多发肿瘤数量未知或难以计数,则记为T(m),如pT3(m) N0 M0;b“局限于胰腺内”定义为无邻近器官(如胃、脾、结肠、肾上腺)或大血管壁(如腹腔干或肠系膜上动脉)侵犯,肿瘤对胰周脂肪的侵犯不作为分期依据
    下载: 导出CSV

    表  3   2017年AJCC第8版综合分期标准

    分期 T分期 N分期 M分期
    Ⅰ期 T1 N0 M0
    Ⅱ期 T2 N0 M0
    T3 N0 M0
    Ⅲ期 T4 N0 M0
    任何T N1 M0
    Ⅳ期 任何T 任何N M1
    AJCC:同表 2
    下载: 导出CSV

    表  4   pNEN的临床分类与特征[5, 10-11, 15, 20-21]

    类型 年发病率(/106) 分泌激素 常见部位 恶性比率(%) 主要症状
    功能性pNEN
      胰岛素瘤 1~32 胰岛素 胰腺 5~10 低血糖
      胃泌素瘤 0.5~21.5 胃泌素 十二指肠、胰腺 50~60 腹泻、腹痛、反酸
      胰高血糖素瘤 0.01~0.1 胰高血糖素 胰腺 50~80 坏死游走性红斑、贫血、葡萄糖不耐受、体质量下降
      生长抑素瘤 少见 生长抑素 胰腺、十二指肠、空肠 50~60 糖尿病、胆石症、腹泻
      产生ACTH的神经内分泌瘤 少见 ACTH 胰腺 >90 库欣综合征
      血管活性肠肽瘤 0.05~0.2 血管活性肠肽 胰腺 40~80 水样泻、低钾血症
    无功能性pNEN 可能有激素水平的升高但未引起相关临床症状 胰腺 60~90 无特异性症状,常为肿瘤压迫、侵袭、转移引起的相关症状,如消化道梗阻、出血、腹痛、黄疸等
    pNEN:胰腺神经内分泌肿瘤;ACTH:促肾上腺皮质激素
    下载: 导出CSV

    附表 1   本指南使用的指南证据特征分类

    类别 水平 来源 专家共识度
    1A 严谨的Meta分析、大型随机对照临床研究 一致共识
    1B 严谨的Meta分析、大型随机对照临床研究 基本一致共识,但争议小
    2A 稍低 一般质量的Meta分析、小型随机对照研究、设计良好的大型回顾性研究、病例对照研究 一致共识
    2B 稍低 一般质量的Meta分析、小型随机对照研究、设计良好的大型回顾性研究、病例对照研究 基本一致共识,但争议小
    3 非对照的单臂临床研究、病例报告、专家观点 无共识,且争议大
    下载: 导出CSV

    附表 2   本指南使用的指南证据等级分类

    推荐等级 标准
    Ⅰ级推荐 一般情况下,将1A类证据和部分专家共识度高且在中国可及性好的2A类证据作为Ⅰ级推荐。具体来说,Ⅰ级推荐具有如下特征:可及性好的普适性诊治措施(包括适应证明确),肿瘤治疗价值相对稳定,基本为国家医保所收录;Ⅰ级推荐的确定,不因商业医疗保险而改变,主要考虑的因素是患者的明确获益性
    Ⅱ级推荐 一般情况下,将1B类证据和部分专家共识度稍低或在中国可及性不太好的2A类证据作为Ⅱ级推荐。具体来说,Ⅱ级推荐具有如下特征:在国际或国内已有随机对照的多中心研究提供的高级别证据,但是可及性差或者效价比低,已超出平民经济承受能力的药物或治疗措施;对于获益明显但价格昂贵的措施,以肿瘤治疗价值为主要考虑因素,也可以作为Ⅱ级推荐
    Ⅲ级推荐 对于正在探索的诊治手段,虽然缺乏强有力的循证医学证据,但是专家组具有一致共识的,可以作为Ⅲ级推荐供医疗人员参考
    不推荐或反对 对于已有充分证据证明不能使患者获益的,甚至导致患者伤害的药物或者医疗技术,专家组具有一致共识的,应写明“专家不推荐”或者必要时“反对”。可以是任何类别等级的证据
    下载: 导出CSV
  • [1]

    WHO Classification of Tumours. Digestive System Tumours[M]. 5th ed. World Health Organization Press, 2019.

    [2]

    Hallet J, Law CH, Cukier M, et al. Exploring the rising incidence of neuroendocrine tumors: a population-based analysis of epidemiology, metastatic presentation, and outcomes[J]. Cancer, 2015, 121: 589-597. DOI: 10.1002/cncr.29099

    [3]

    Dasari A, Shen C, Halperin D, et al. Trends in the Incidence, Prevalence, and Survival Outcomes in Patients With Neuroendocrine Tumors in the United States[J]. JAMA Oncol, 2017, 3: 1335-1342. DOI: 10.1001/jamaoncol.2017.0589

    [4]

    Fan JH, Zhang YQ, Shi SS, et al. A nation-wide retrospective epidemiological study of gastroenteropancreatic neuroendocrine neoplasms in china[J]. Oncotarget, 2017, 8: 71699-71708. DOI: 10.18632/oncotarget.17599

    [5]

    Ito T, Igarashi H, Nakamura K, et al. Epidemiological trends of pancreatic and gastrointestinal neuroendocrine tumors in Japan: a nationwide survey analysis[J]. J Gastroenterol, 2015, 50: 58-64. DOI: 10.1007/s00535-014-0934-2

    [6]

    Wu W, Jin G, Li H, et al. The current surgical treatment of pancreatic neuroendocrine neoplasms in China: a national wide cross-sectional study[J]. J Pancreatol, 2019, 2: 35-42. DOI: 10.1097/JP9.0000000000000019

    [7]

    Amin MB, Edge, S, Greene F, et al. AJCC Cancer Staging Manual[M]. 8th ed. New York: Springer, 2017.

    [8]

    Luo G, Javed A, Strosberg JR, et al. Modified Staging Classification for Pancreatic Neuroendocrine Tumors on the Basis of the American Joint Committee on Cancer and European Neuroendocrine Tumor Society Systems[J]. J Clin Oncol, 2017, 35: 274-280. http://europepmc.org/abstract/MED/27646952

    [9]

    Crona J, Norlén O, Antonodimitrakis P, et al. Multiple and Secondary Hormone Secretion in Patients With Metastatic Pancreatic Neuroendocrine Tumours[J]. J Clin Endocrinol Metab, 2016, 101: 445-452. DOI: 10.1210/jc.2015-2436

    [10]

    Grant CS. Insulinoma[J]. Best Pract Res Clin Gastroenterol, 2005, 19: 783-798. DOI: 10.1016/j.bpg.2005.05.008

    [11]

    Metz DC, Jensen RT. Gastrointestinal neuroendocrine tumors: pancreatic endocrine tumors[J]. Gastroenterology, 2008, 135: 1469-1492. DOI: 10.1053/j.gastro.2008.05.047

    [12]

    Gao H, Wang W, Xu H, et al. Distinct clinicopathological and prognostic features of insulinoma with synchronous distant metastasis[J]. Pancreatology, 2019, 19: 472-477. DOI: 10.1016/j.pan.2019.02.011

    [13]

    Whipple AO, Frantz VK. Adenoma of lslet cells with hyperinsulinism: a review[J]. Ann Surg, 1935, 101: 1299-1335. DOI: 10.1097/00000658-193506000-00001

    [14]

    Alexakis N, Connor S, Ghaneh P, et al. Hereditary pancreatic endocrine tumours[J]. Pancreatology, 2004, 4: 417-435. http://www.karger.com/article/pdf/79616

    [15]

    Jensen RT, Niederle B, Mitry E, et al. Gastrinoma (duodenal and pancreatic)[J]. Neuroendocrinology, 2006, 84: 173-182. DOI: 10.1159/000098009

    [16]

    Gibril F, Schumann M, Pace A, et al. Multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome: a prospective study of 107 cases and comparison with 1009 cases from the literature[J]. Medicine(Baltimore), 2004, 83: 43-83.

    [17]

    Luo G, Liu Z, Guo M, et al. A comprehensive comparison of clinicopathologic and imaging features of incidental/symptomatic non-functioning pancreatic neuroendocrine tumors: A retrospective study of a single center[J]. Pancreatology, 2015, 15: 519-524. DOI: 10.1016/j.pan.2015.08.009

    [18]

    Jensen RT, Berna MJ, Bingham DB, et al. Inherited pancreatic endocrine tumor syndromes: advances in molecular pathogenesis, diagnosis, management, and controversies[J]. Cancer, 2008, 113: 1807-1843. DOI: 10.1002/cncr.23648

    [19]

    Thakker RV. Multiple endocrine neoplasia type 1[J]. Endocrinol Metab Clin North Am, 2000, 29: 541-567. DOI: 10.1016/S0889-8529(05)70150-X

    [20]

    Falconi M, Eriksson B, Kaltsas G, et al. ENETS Cons-ensus Guidelines Update for the Management of Patients with Functional Pancreatic Neuroendocrine Tumors and Non-Functional Pancreatic Neuroendocrine Tumors[J]. Neuroendocrinology, 2016, 103: 153-171. DOI: 10.1159/000443171

    [21]

    Fendrich V, Waldmann J, Bartsch DK, et al. Surgical management of pancreatic endocrine tumors[J]. Nat Rev Clin Oncol, 2009, 6: 419-428. DOI: 10.1038/nrclinonc.2009.82

    [22]

    Yang X, Yang Y, Li Z, et al. Diagnostic value of circulating chromogranin a for neuroendocrine tumors: a systematic review and meta-analysis[J]. PLoS One, 2015, 10: e0124884. DOI: 10.1371/journal.pone.0124884

    [23]

    Han X, Zhang C, Tang M, et al. The value of serum chromogranin A as a predictor of tumor burden, therapeutic response, and nomogram-based survival in well-moderate nonfunctional pancreatic neuroendocrine tumors with liver metastases[J]. Eur J Gastroenterol Hepatol, 2015, 27: 527-535. DOI: 10.1097/MEG.0000000000000332

    [24]

    Panzuto F, Severi C, Cannizzaro R, et al. Utility of combined use of plasma levels of chromogranin A and pancreatic polypeptide in the diagnosis of gastrointestinal and pancreatic endocrine tumors[J]. J Endocrinol Invest, 2004, 27: 6-11. http://www.researchgate.net/publication/8648427_Panzuto_F_Severi_C_Cannizzaro_R_et_al_Utility_of_combined_use_of_plasma_levels_of_chromogranin_A_and_pancreatic_polypeptide_in_the_diagnosis_of_gastrointestinal_and_pancreatic_endocrine_tumors

    [25]

    Baudin E, Bidart JM, Bachelot A, et al. Impact of chromogranin A measurement in the work-up of neuroendocrine tumors[J]. Ann Oncol, 2001, 12 Suppl 2: S79-S82. http://www.tandfonline.com/servlet/linkout?suffix=CIT0003&dbid=8&doi=10.1080%2F2331205X.2018.1484602&key=11762357

    [26]

    Di Giacinto P, Rota F, Rizza L, et al. Chromogranin A: From Laboratory to Clinical Aspects of Patients with Neuroendocrine Tumors[J]. Int J Endocrinol, 2018, 2018: 8126087. http://europepmc.org/articles/PMC6051263/

    [27]

    Cimitan M, Buonadonna A, Cannizzaro R, et al. Somatostatin receptor scintigraphy versus chromogranin A assay in the management of patients with neuroendocrine tumors of different types: clinical role[J]. Ann Oncol, 2003, 14: 1135-1141. DOI: 10.1093/annonc/mdg279

    [28]

    Qiao XW, Qiu L, Chen YJ, et al. Chromogranin A is a reliable serum diagnostic biomarker for pancreatic neuroendocrine tumors but not for insulinomas[J]. BMC Endocr Disord, 2014, 14: 64. DOI: 10.1186/1472-6823-14-64

    [29]

    Korse CM, Taal BG, Vincent A, et al. Choice of tumour markers in patients with neuroendocrine tumours is dependent on the histological grade. A marker study of Chromogranin A, Neuron specific enolase, Progastrin-releasing peptide and cytokeratin fragments[J]. Eur J Cancer, 2012, 48: 662-671. DOI: 10.1016/j.ejca.2011.08.012

    [30]

    Yao JC, Pavel M, Phan AT, et al. Chromogranin A and neuron-specific enolase as prognostic markers in patients with advanced pNET treated with everolimus[J]. J Clin Endocrinol Metab, 2011, 96: 3741-3749. DOI: 10.1210/jc.2011-0666

    [31]

    Chen L, Zhang Y, Lin Y, et al. The role of elevated serum procalcitonin in neuroendocrine neoplasms of digestive system[J]. Clin Biochem, 2017, 50: 982-987. DOI: 10.1016/j.clinbiochem.2017.06.010

    [32]

    Tao M, Yuan C, Xiu D, et al. Analysis of risk factors affecting the prognosis of pancreatic neuroendocrine tumors[J]. Chin Med J (Engl), 2014, 127: 2924-2928. http://www.ncbi.nlm.nih.gov/pubmed/25131229

    [33] Öberg K, Califano A, Strosberg JR, et al. A meta-analysis of the accuracy of a neuroendocrine tumor mRNA genomic biomarker (NETest) in blood[J]. Ann Oncol, 2020, 31: 202-212. https://www.cnki.com.cn/Article/CJFDTOTAL-ZSFX201719005.htm
    [34]

    Cryer PE, Axelrod L, Grossman AB, et al. Evaluation and management of adult hypoglycemic disorders: an Endocrine Society Clinical Practice Guideline[J]. J Clin Endocrinol Metab, 2009, 94: 709-728. DOI: 10.1210/jc.2008-1410

    [35]

    Berna MJ, Hoffmann KM, Serrano J, et al. Serum gastrin in Zollinger-Ellison syndrome: I. Prospective study of fasting serum gastrin in 309 patients from the National Institutes of Health and comparison with 2229 cases from the literature[J]. Medicine (Baltimore), 2006, 85: 295-330. DOI: 10.1097/01.md.0000236956.74128.76

    [36]

    Roy PK, Venzon DJ, Feigenbaum KM, et al. Gastric secretion in Zollinger-Ellison syndrome. Correlation with clinical expression, tumor extent and role in diagnosis--a prospective NIH study of 235 patients and a review of 984 cases in the literature[J]. Medicine (Baltimore), 2001, 80: 189-222. DOI: 10.1097/00005792-200105000-00005

    [37]

    Berna MJ, Hoffmann KM, Long SH, et al. Serum gastrin in Zollinger-Ellison syndrome: Ⅱ. Prospective study of gastrin provocative testing in 293 patients from the National Institutes of Health and comparison with 537 cases from the literature. evaluation of diagnostic criteria, proposal of new criteria, and correlations with clinical and tumoral features[J]. Medicine (Baltimore), 2006, 85: 331-364. DOI: 10.1097/MD.0b013e31802b518c

    [38]

    Corleto VD, Annibale B, Gibril F, et al. Does the widespread use of proton pump inhibitors mask, complicate and/or delay the diagnosis of Zollinger-Ellison syndrome?[J]. Aliment Pharmacol Ther, 2001, 15: 1555-1561. DOI: 10.1046/j.1365-2036.2001.01085.x

    [39]

    Sundin A, Arnold R, Baudin E, et al. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: Radiological, Nuclear Medicine & Hybrid Imaging[J]. Neuroendocrinology, 2017, 105: 212-244. DOI: 10.1159/000471879

    [40]

    Luo Y, Chen J, Huang K, et al. Early evaluation of sunitinib for the treatment of advanced gastroenteropancreatic neuroendocrine neoplasms via CT imaging: RECIST 1.1 or Choi Criteria?[J]. BMC Cancer, 2017, 17: 154. DOI: 10.1186/s12885-017-3150-7

    [41]

    Luo Y, Dong Z, Chen J, et al. Pancreatic neuroendocrine tumours: correlation between MSCT features and pathological classification[J]. Eur Radiol, 2014, 24: 2945-2952. DOI: 10.1007/s00330-014-3317-4

    [42]

    Luo Y, Chen X, Chen J, et al. Preoperative Prediction of Pancreatic Neuroendocrine Neoplasms Grading Based on Enhanced Computed Tomography Imaging: Validation of Deep Learning with a Convolutional Neural Network[J]. Neuroendocrinology, 2020, 110: 338-350. DOI: 10.1159/000503291

    [43]

    Liu Y, Chen W, Cui W, et al. Quantitative Pretreatment CT Parameters as Predictors of Tumor Response of Neuroendocrine Tumor Liver Metastasis to Transcatheter Arterial Bland Embolization[J]. Neuroendocrinology, 2020, 110: 697-704. DOI: 10.1159/000504257

    [44]

    Liang W, Yang P, Huang R, et al. A Combined Nomo-gram Model to Preoperatively Predict Histologic Grade in Pancreatic Neuroendocrine Tumors[J]. Clin Cancer Res, 2019, 25: 584-594. DOI: 10.1158/1078-0432.CCR-18-1305

    [45]

    Zhu L, Wu WM, Xue HD, et al. Sporadic insulinomas on volume perfusion CT: dynamic enhancement patterns and timing of optimal tumour-parenchyma contrast[J]. Eur Radiol, 2017, 27: 3491-3498. DOI: 10.1007/s00330-016-4709-4

    [46]

    Zhu L, Xue HD, Sun H, et al. Isoattenuating insulinomas at biphasic contrast-enhanced CT: frequency, clinicopathologic features and perfusion characteristics[J]. Eur Radiol, 2016, 26: 3697-3705. DOI: 10.1007/s00330-016-4216-7

    [47]

    Zhu L, Xue HD, Sun H, et al. Insulinoma detection with MDCT: is there a role for whole-pancreas perfusion?[J]. AJR Am J Roentgenol, 2017, 208: 306-314. DOI: 10.2214/AJR.16.16351

    [48]

    Li J, Chen XY, Xu K, et al. Detection of insulinoma: one-stop pancreatic perfusion CT with calculated mean temporal images can replace the combination of bi-phasic plus perfusion scan[J]. Eur Radiol, 2020, 30: 4164-4174. DOI: 10.1007/s00330-020-06657-4

    [49]

    d'Assignies G, Assignies G, Couvelard A, et al. Pancreatic endocrine tumors: tumor blood flow assessed with perfusion CT reflects angiogenesis and correlates with prognostic factors[J]. Radiology, 2009, 250: 407-416. DOI: 10.1148/radiol.2501080291

    [50]

    Zhu L, Xue H, Sun Z, et al. Prospective comparison of biphasic contrast-enhanced CT, volume perfusion CT, and 3 Tesla MRI with diffusion-weighted imaging for insulinoma detection[J]. J Magn Reson Imaging, 2017, 46: 1648-1655. DOI: 10.1002/jmri.25709

    [51]

    He M, Xu J, Sun Z, et al. Prospective Comparison of Reduced Field-of-View (rFOV) and Full FOV (fFOV) Diffusion-Weighted Imaging (DWI) in the Assessment of Insulinoma: Image Quality and Lesion Detection[J]. Acad Radiol, 2020, 27: 1572-1579. DOI: 10.1016/j.acra.2019.11.019

    [52]

    Pamuklar E, Semelka RC. MR imaging of the pancreas[J]. Magn Reson Imaging Clin N Am, 2005, 13: 313-330. DOI: 10.1016/j.mric.2005.03.012

    [53]

    Sun H, Zhou J, Liu K, et al. Pancreatic neuroendocrine tumors: MR imaging features preoperatively predict lymph node metastasis[J]. Abdom Radiol (NY), 2019, 44: 1000-1009. DOI: 10.1007/s00261-018-1863-y

    [54]

    Tirumani SH, Jagannathan JP, Braschi-Amirfarzan M, et al. Value of hepatocellular phase imaging after intravenous gadoxetate disodium for assessing hepatic metastases from gastroenteropancreatic neuroendocrine tumors: comparison with other MRI pulse sequences and with extracellular agent[J]. Abdom Radiol (NY), 2018, 43: 2329-2339. DOI: 10.1007/s00261-018-1496-1

    [55]

    Chiti A, Fanti S, Savelli G, et al. Comparison of somatostatin receptor imaging, computed tomography and ultrasound in the clinical management of neuroendocrine gastro-entero-pancreatic tumours[J]. Eur J Nucl Med, 1998, 25: 1396-1403. DOI: 10.1007/s002590050314

    [56]

    Dietrich CF, Jenssen C. Modern ultrasound imaging of pancreatic tumors[J]. Ultrasonography, 2020, 39: 105-113. DOI: 10.14366/usg.19039

    [57]

    Wu W, Chen MH, Yin SS, et al. The role of contrast-enhanced sonography of focal liver lesions before percutaneous biopsy[J]. AJR Am J Roentgenol, 2006, 187: 752-761. DOI: 10.2214/AJR.05.0535

    [58]

    Liu Y, Shi S, Hua J, et al. Differentiation of solid-pseudopapillary tumors of the pancreas from pancreatic neuroendocrine tumors by using endoscopic ultrasound[J]. Clin Res Hepatol Gastroenterol, 2020, 44: 947-953. DOI: 10.1016/j.clinre.2020.02.002

    [59]

    Di Leo M, Poliani L, Rahal D, et al. Pancreatic Neuroendocrine Tumours: The Role of Endoscopic Ultrasound Biopsy in Diagnosis and Grading Based on the WHO 2017 Classification[J]. Dig Dis, 2019, 37: 325-333. DOI: 10.1159/000499172

    [60]

    Choi JH, Park DH, Kim MH, et al. Outcomes after endoscopic ultrasound-guided ethanol-lipiodol ablation of small pancreatic neuroendocrine tumors[J]. Dig Endosc, 2018, 30: 652-658. DOI: 10.1111/den.13058

    [61]

    He G, Wang J, Chen B, et al. Feasibility of endoscopic submucosal dissection for upper gastrointestinal submucosal tumors treatment and value of endoscopic ultrasonography in pre-operation assess and post-operation follow-up: a prospective study of 224 cases in a single medical center[J]. Surg Endosc, 2016, 30: 4206-4213. DOI: 10.1007/s00464-015-4729-1

    [62]

    Li W, An L, Liu R, et al. Laparoscopic ultrasound enhances diagnosis and localization of insulinoma in pancreatic head and neck for laparoscopic surgery with satisfactory postsurgical outcomes[J]. Ultrasound Med Biol, 2011, 37: 1017-1023. DOI: 10.1016/j.ultrasmedbio.2011.04.003

    [63]

    Ruf J, Heuck F, Schiefer J, et al. Impact of Multiphase 68Ga-DOTATOC-PET/CT on therapy management in patients with neuroendocrine tumors[J]. Neuroendocrinology, 2010, 91: 101-109. DOI: 10.1159/000265561

    [64]

    Luo Y, Pan Q, Yao S, et al. Glucagon-Like Peptide-1 Receptor PET/CT with 68Ga-NOTA-Exendin-4 for Detecting Localized Insulinoma: A Prospective Cohort Study[J]. J Nucl Med, 2016, 57: 715-720. DOI: 10.2967/jnumed.115.167445

    [65]

    Binderup T, Knigge U, Loft A, et al. Functional imaging of neuroendocrine tumors: a head-to-head comparison of somatostatin receptor scintigraphy, 123I-MIBG scintigraphy, and 18F-FDG PET[J]. J Nucl Med, 2010, 51: 704-712. DOI: 10.2967/jnumed.109.069765

    [66]

    Rinzivillo M, Partelli S, Prosperi D, et al. Clinical usefulness of (18)F-fluorodeoxyglucose positron emission tomography in the diagnostic algorithm of advanced entero-pancreatic neuroendocrine neoplasms[J]. Oncologist, 2018, 23: 186-192. DOI: 10.1634/theoncologist.2017-0278

    [67]

    Grillo F, Albertelli M, Brisigotti MP, et al. Grade incre-ases in gastroenteropancreatic neuroendocrine tumor metas-tases compared to the primary tumor[J]. Neuroendocrinology, 2016, 103: 452-459. DOI: 10.1159/000439434

    [68]

    Botling J, Lamarca A, Bajic D, et al. Longitudinal increase in Ki67 and high-grade transformation in pancreatic neuroendocrine tumours(PNETs)[J]. Ann Oncol, 2019, 30: v564-v573. http://www.researchgate.net/publication/336195649_1386PDLongitudinal_increase_in_Ki67_and_high-grade_transformation_in_pancreatic_neuroendocrine_tumours_PNETs

    [69]

    Rindi G, Bordi C, La Rosa S, et al. Gastroenteropan-creatic (neuro)endocrine neoplasms: the histology report[J]. Dig Liver Dis, 2011, 43 Suppl 4: S356-S360. DOI: 10.1016/S1590-8658(11)60591-4

    [70]

    Schmitt AM, Riniker F, Anlauf M, et al. Islet 1 (Isl1) expression is a reliable marker for pancreatic endocrine tumors and their metastases[J]. Am J Surg Pathol, 2008, 32: 420-425. DOI: 10.1097/PAS.0b013e318158a397

    [71]

    Sangoi AR, Ohgami RS, Pai RK, et al. PAX8 expression reliably distinguishes pancreatic well-differentiated neuroendocrine tumors from ileal and pulmonary well-differentiated neuroendocrine tumors and pancreatic acinar cell carcinoma[J]. Mod Pathol, 2011, 24: 412-424. DOI: 10.1038/modpathol.2010.176

    [72]

    Al-Hawary MM, Francis IR, Chari ST, et al. Pancreatic ductal adenocarcinoma radiology reporting template: consensus statement of the society of abdominal radiology and the american pancreatic association[J]. Gastroenterology, 2014, 146: 291-304. e1. DOI: 10.1053/j.gastro.2013.11.004

    [73]

    Goode PN, Farndon JR, Anderson J, et al. Diazoxide in the management of patients with insulinoma[J]. World J Surg, 1986, 10: 586-592. DOI: 10.1007/BF01655532

    [74]

    Ito T, Igarashi H, Uehara H, et al. Pharmacotherapy of Zollinger-Ellison syndrome[J]. Expert Opin Pharmacother, 2013, 14: 307-321. DOI: 10.1517/14656566.2013.767332

    [75]

    Oberg KE, Reubi JC, Kwekkeboom DJ, et al. Role of somatostatins in gastroenteropancreatic neuroendocrine tumor development and therapy[J]. Gastroenterology, 2010, 139: 742-753, 753. e1. DOI: 10.1053/j.gastro.2010.07.002

    [76]

    Eldor R, Glaser B, Fraenkel M, et al. Glucagonoma and the glucagonoma syndrome - cumulative experience with an elusive endocrine tumour[J]. Clin Endocrinol (Oxf), 2011, 74: 593-598. DOI: 10.1111/j.1365-2265.2011.03967.x

    [77]

    Graham GW, Unger BP, Coursin DB. Perioperative management of selected endocrine disorders[J]. Int Anesthesiol Clin, 2000, 38: 31-67. DOI: 10.1097/00004311-200010000-00004

    [78]

    Chua TC, Yang TX, Gill AJ, et al. Systematic Review and Meta-Analysis of Enucleation Versus Standardized Resection for Small Pancreatic Lesions[J]. Ann Surg Oncol, 2016, 23: 592-599. http://europepmc.org/abstract/MED/26307231

    [79]

    Tian F, Hong XF, Wu WM, et al. Propensity score-matched analysis of robotic versus open surgical enucleation for small pancreatic neuroendocrine tumours[J]. Br J Surg, 2016, 103: 1358-1364. DOI: 10.1002/bjs.10220

    [80]

    Partelli S, Cirocchi R, Crippa S, et al. Systematic review of active surveillance versus surgical management of asymptomatic small non-functioning pancreatic neuroendocrine neoplasms[J]. Br J Surg, 2017, 104: 34-41. DOI: 10.1002/bjs.10451

    [81]

    Lee LC, Grant CS, Salomao DR, et al. Small, nonfunctioning, asymptomatic pancreatic neuroendocrine tumors (PNETs): role for nonoperative management[J]. Surgery, 2012, 152: 965-974. DOI: 10.1016/j.surg.2012.08.038

    [82]

    Lombardi M, De Lio N, Funel N, et al. Prognostic factors for pancreatic neuroendocrine neoplasms (pNET) and the risk of small non-functioning pNET[J]. J Endocrinol Invest, 2015, 38: 605-613. DOI: 10.1007/s40618-014-0219-x

    [83]

    Liu Y, Ye S, Zhu Y, et al. Impact of tumour size on metastasis and survival in patients with pancreatic neuroen-docrine tumours (PNETs): A population based study[J]. J Cancer, 2019, 10: 6349-6357. DOI: 10.7150/jca.27779

    [84]

    Mao WL, Han X, Lyu Y, et al. Propensity score-matched analysis of clinical outcome after enucleation versus regular pancreatectomy in patients with small non-functional pancreatic neuroendocrine tumors[J]. Pancreatology, 2020, 20: 169-176. DOI: 10.1016/j.pan.2019.12.007

    [85]

    Mao R, Zhao H, Li K, et al. Outcomes of Lymph Node Dissection for Non-metastatic Pancreatic Neuroendocrine Tumors: A Propensity Score-Weighted Analysis of the National Cancer Database[J]. Ann Surg Oncol, 2019, 26: 2722-2729. DOI: 10.1245/s10434-019-07506-5

    [86]

    Sallinen V, Haglund C, Seppänen H. Outcomes of resected nonfunctional pancreatic neuroendocrine tumors: Do size and symptoms matter?[J]. Surgery, 2015, 158: 1556-1563. DOI: 10.1016/j.surg.2015.04.035

    [87]

    Kuo EJ, Salem RR. Population-level analysis of pancreatic neuroendocrine tumors 2 cm or less in size[J]. Ann Surg Oncol, 2013, 20: 2815-2821. DOI: 10.1245/s10434-013-3005-7

    [88]

    Curran T, Pockaj BA, Gray RJ, et al. Importance of lymph node involvement in pancreatic neuroendocrine tumors: impact on survival and implications for surgical resection[J]. J Gastrointest Surg, 2015, 19: 152-160; discussion 160. DOI: 10.1007/s11605-014-2624-z

    [89]

    Hashim YM, Trinkaus KM, Linehan DC, et al. Regional lymphadenectomy is indicated in the surgical treatment of pancreatic neuroendocrine tumors (PNETs)[J]. Ann Surg, 2014, 259: 197-203. DOI: 10.1097/SLA.0000000000000348

    [90]

    Yang M, Zeng L, Zhang Y, et al. Surgical treatment and clinical outcome of nonfunctional pancreatic neuroendocrine tumors: a 14-year experience from one single center[J]. Medicine (Baltimore), 2014, 93: e94. DOI: 10.1097/MD.0000000000000094

    [91]

    Wu L, Sahara K, Tsilimigras DI, et al. Therapeutic index of lymphadenectomy among patients with pancreatic neuroendocrine tumors: A multi-institutional analysis[J]. J Surg Oncol, 2019, 120: 1080-1086. DOI: 10.1002/jso.25689

    [92]

    Luo G, Jin K, Cheng H, et al. Revised nodal stage for pancreatic neuroendocrine tumors[J]. Pancreatology, 2017, 17: 599-604. DOI: 10.1016/j.pan.2017.06.003

    [93]

    Sahara K, Tsilimigras DI, Mehta R, et al. Trends in the Number of Lymph Nodes Evaluated Among Patients with Pancreatic Neuroendocrine Tumors in the United States: A Multi-Institutional and National Database Analysis[J]. Ann Surg Oncol, 2020, 27: 1203-1212. DOI: 10.1245/s10434-019-08120-1

    [94]

    Zhang XF, Lopez-Aguiar AG, Poultsides G, et al. Minimally invasive versus open distal pancreatectomy for pancreatic neuroendocrine tumors: An analysis from the U.S. neuroendocrine tumor study group[J]. J Surg Oncol, 2019, 120: 231-240. http://www.ncbi.nlm.nih.gov/pubmed/31001868

    [95]

    Chen L, Chen J. Perspective of neo-adjuvant/conversion and adjuvant therapy for pancreatic neuroendocrine tumors[J]. J Pancreatol, 2019, 2: 91-99. DOI: 10.1097/JP9.0000000000000023

    [96]

    Solorzano CC, Lee JE, Pisters PW, et al. Nonfunctioning islet cell carcinoma of the pancreas: survival results in a contemporary series of 163 patients[J]. Surgery, 2001, 130: 1078-1085. DOI: 10.1067/msy.2001.118367

    [97]

    Sarmiento JM, Heywood G, Rubin J, et al. Surgical treatment of neuroendocrine metastases to the liver: a plea for resection to increase survival[J]. J Am Coll Surg, 2003, 197: 29-37. DOI: 10.1016/S1072-7515(03)00230-8

    [98]

    Kleine M, Schrem H, Vondran FW, et al. Extended surgery for advanced pancreatic endocrine tumours[J]. Br J Surg, 2012, 99: 88-94.

    [99]

    Lin C, Dai H, Hong X, et al. The prognostic impact of primary tumor resection in pancreatic neuroendocrine tumors with synchronous multifocal liver metastases[J]. Pancreatology, 2018, 18: 608-614. DOI: 10.1016/j.pan.2018.04.014

    [100]

    Schurr PG, Strate T, Rese K, et al. Aggressive surgery improves long-term survival in neuroendocrine pancreatic tumors: an institutional experience[J]. Ann Surg, 2007, 245: 273-281. DOI: 10.1097/01.sla.0000232556.24258.68

    [101]

    Frilling A, Li J, Malamutmann E, et al. Treatment of liver metastases from neuroendocrine tumours in relation to the extent of hepatic disease[J]. Br J Surg, 2009, 96: 175-184. DOI: 10.1002/bjs.6468

    [102]

    Jin K, Xu J, Chen J, et al. Surgical management for non-functional pancreatic neuroendocrine neoplasms with synchronous liver metastasis: A consensus from the Chinese Study Group for Neuroendocrine Tumors (CSNET)[J]. Int J Oncol, 2016, 49: 1991-2000. DOI: 10.3892/ijo.2016.3711

    [103]

    De Jong MC, Farnell MB, Sclabas G, et al. Liver-directed therapy for hepatic metastases in patients undergoing pancreaticoduodenectomy: a dual-center analysis[J]. Ann Surg, 2010, 252: 142-148. DOI: 10.1097/SLA.0b013e3181dbb7a7

    [104]

    Bertani E, Fazio N, Botteri E, et al. Resection of the primary pancreatic neuroendocrine tumor in patients with unresectable liver metastases: possible indications for a multimodal approach[J]. Surgery, 2014, 155: 607-614. DOI: 10.1016/j.surg.2013.12.024

    [105]

    Oberg K, Kvols L, Caplin M, et al. Consensus report on the use of somatostatin analogs for the management of neuroendocrine tumors of the gastroenteropancreatic system[J]. Ann Oncol, 2004, 15: 966-973. DOI: 10.1093/annonc/mdh216

    [106]

    Han X, Lou W. Concomitant pancreatic neuroendocrine tumors in hereditary tumor syndromes: who, when and how to operate?[J]. J Pancreatol, 2019, 2: 48-53. DOI: 10.1097/JP9.0000000000000016

    [107]

    Yates CJ, Newey PJ, Thakker RV. Challenges and controversies in management of pancreatic neuroendocrine tumours in patients with MEN1[J]. Lancet Diabetes Endocrinol, 2015, 3: 895-905. DOI: 10.1016/S2213-8587(15)00043-1

    [108]

    Nell S, Verkooijen HM, Pieterman C, et al. Management of MEN1 Related Nonfunctioning Pancreatic NETs: A Shifting Paradigm: Results From the DutchMEN1 Study Group[J]. Ann Surg, 2018, 267: 1155-1160. DOI: 10.1097/SLA.0000000000002183

    [109]

    Triponez F, Sadowski SM, Pattou F, et al. Long-term Follow-up of MEN1 Patients Who Do Not Have Initial Surgery for Small ≤2 cm Nonfunctioning Pancreatic Neuroendocrine Tumors, an AFCE and GTE Study: Association Franco-phone de Chirurgie Endocrinienne & Groupe d'Etude des Tumeurs Endocrines[J]. Ann Surg, 2018, 268: 158-164. DOI: 10.1097/SLA.0000000000002191

    [110]

    Kim H, Song KB, Hwang DW, et al. Time-trend and recurrence analysis of pancreatic neuroendocrine tumors[J]. Endocr Connect, 2019, 8: 1052-1060. DOI: 10.1530/EC-19-0282

    [111]

    Chouliaras K, Newman NA, Shukla M, et al. Analysis of recurrence after the resection of pancreatic neuroendocrine tumors[J]. J Surg Oncol, 2018, 118: 416-421. DOI: 10.1002/jso.25146

    [112]

    Gao H, Liu L, Wang W, et al. Novel recurrence risk stratification of resected pancreatic neuroendocrine tumor[J]. Cancer Lett, 2018, 412: 188-193. DOI: 10.1016/j.canlet.2017.10.036

    [113]

    Dong DH, Zhang XF, Lopez-Aguiar AG, et al. Resection of pancreatic neuroendocrine tumors: defining patterns and time course of recurrence[J]. HPB (Oxford), 2020, 22: 215-223. DOI: 10.1016/j.hpb.2019.05.020

    [114]

    Marchegiani G, Landoni L, Andrianello S, et al. Patterns of Recurrence after Resection for Pancreatic Neuroendocrine Tumors: Who, When, and Where?[J]. Neuroendocrinology, 2019, 108: 161-171. DOI: 10.1159/000495774

    [115]

    Ausania F, Senra Del Rio P, Gomez-Bravo MA, et al. Can we predict recurrence in WHO G1-G2 pancreatic neuroendocrine neoplasms? Results from a multi-institutional Spanish study[J]. Pancreatology, 2019, 19: 367-371. DOI: 10.1016/j.pan.2019.01.007

    [116]

    Dong DH, Zhang XF, Poultsides G, et al. Impact of tumor size and nodal status on recurrence of nonfunctional pancreatic neuroendocrine tumors ≤2 cm after curative resection: A multi-institutional study of 392 cases[J]. J Surg Oncol, 2019, 120: 1071-1079. DOI: 10.1002/jso.25716

    [117]

    Zhou B, Duan J, Yan S, et al. Prognostic factors of long-term outcome in surgically resectable pancreatic neuroendocrine tumors: A 12-year experience from a single center[J]. Oncol Lett, 2017, 13: 1157-1164. DOI: 10.3892/ol.2017.5561

    [118]

    Sorbye H, Welin S, Langer SW, et al. Predictive and prognostic factors for treatment and survival in 305 patients with advanced gastrointestinal neuroendocrine carcinoma (WHO G3): the NORDIC NEC study[J]. Ann Oncol, 2013, 24: 152-160. DOI: 10.1093/annonc/mds276

    [119]

    Lu Y, Zhao Z, Wang J, et al. Safety and efficacy of combining capecitabine and temozolomide (CAPTEM) to treat advanced neuroendocrine neoplasms: A meta-analysis[J]. Medicine (Baltimore), 2018, 97: e12784. DOI: 10.1097/MD.0000000000012784

    [120]

    Barrett JR, Rendell V, Pokrzywa C, et al. Adjuvant therapy following resection of gastroenteropancreatic neuroendocrine tumors provides no recurrence or survival benefit[J]. J Surg Oncol, 2020, 121: 1067-1073. DOI: 10.1002/jso.25896

    [121]

    Gao S, Shi X, Ma H, et al. The effect of using long-acting octreotide as adjuvant therapy for patients with grade 2 pancreatic neuroendocrine tumors after radical resection[J]. J Pancreatol, 2020, 3: 167-172. DOI: 10.1097/JP9.0000000000000058

    [122]

    Kvols LK, Moertel CG, O'Connell MJ, et al. Treatment of the malignant carcinoid syndrome. Evaluation of a long-acting somatostatin analogue[J]. N Engl J Med, 1986, 315: 663-666. DOI: 10.1056/NEJM198609113151102

    [123]

    Ruszniewski P, Ish-Shalom S, Wymenga M, et al. Rapid and sustained relief from the symptoms of carcinoid syndrome: results from an open 6-month study of the 28-day prolonged-release formulation of lanreotide[J]. Neuroendocrinology, 2004, 80: 244-251. DOI: 10.1159/000082875

    [124]

    Rinke A, Krug S. Neuroendocrine tumours-Medical therapy: Biological[J]. Best Pract Res Clin Endocrinol Metab, 2016, 30: 79-91. DOI: 10.1016/j.beem.2015.09.004

    [125]

    Caplin ME, Pavel M, Ćwikła JB, et al. Lanreotide in metastatic enteropancreatic neuroendocrine tumors[J]. N Engl J Med, 2014, 371: 224-233. DOI: 10.1056/NEJMoa1316158

    [126]

    Rinke A, Müller HH, Schade-Brittinger C, et al. Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group[J]. J Clin Oncol, 2009, 27: 4656-4663. DOI: 10.1200/JCO.2009.22.8510

    [127]

    Oberg K. Interferon in the management of neuroendocrine GEP-tumors: a review[J]. Digestion, 2000, 62 Suppl 1: 92-97. http://www.karger.com/Article/Abstract/51862

    [128]

    Pavel ME, Baum U, Hahn EG, et al. Efficacy and tolerability of pegylated IFN-alpha in patients with neuroendocrine gastroenteropancreatic carcinomas[J]. J Interferon Cytokine Res, 2006, 26: 8-13. DOI: 10.1089/jir.2006.26.8

    [129]

    de Mestier L, Walter T, Brixi H, et al. Comparison of Temozolomide-Capecitabine to 5-Fluorouracile-Dacarbazine in 247 Patients with Advanced Digestive Neuroendocrine Tumors Using Propensity Score Analyses[J]. Neuroendocrinology, 2019, 108: 343-353. DOI: 10.1159/000498887

    [130]

    Cives M, Ghayouri M, Morse B, et al. Analysis of potential response predictors to capecitabine/temozolomide in metastatic pancreatic neuroendocrine tumors[J]. Endocr Relat Cancer, 2016, 23: 759-767. DOI: 10.1530/ERC-16-0147

    [131]

    Kouvaraki MA, Ajani JA, Hoff P, et al. Fluorouracil, doxorubicin, and streptozocin in the treatment of patients with locally advanced and metastatic pancreatic endocrine carcinomas[J]. J Clin Oncol, 2004, 22: 4762-4771. DOI: 10.1200/JCO.2004.04.024

    [132]

    Kunz PL, Catalano PJ, Nimeiri H, et al. A randomized study of temozolomide or temozolomide and capecitabine in patients with advanced pancreatic neuroendocrine tumors: a trial of the ECOG-ACRIN Cancer Research Group(E2211)[J]. J Clin Oncol, 2018, 36: 4004. DOI: 10.1200/JCO.2018.36.15_suppl.4004

    [133]

    Wang W, Zhang Y, Peng Y, et al. A Ki-67 index to predict treatment response to the capecitabine temozolomide(CAPTEM) regimen in neuroendocrine neoplasms: a retrospective multicenter study[J]. Neuroendocrinology, 2020. doi: 10.1159/000510159[Epub ahead of print].

    [134]

    Mitry E, Baudin E, Ducreux M, et al. Treatment of poorly differentiated neuroendocrine tumours with etoposide and cisplatin[J]. Br J Cancer, 1999, 81: 1351-1355. DOI: 10.1038/sj.bjc.6690325

    [135]

    Iwasa S, Morizane C, Okusaka T, et al. Cisplatin and etoposide as first-line chemotherapy for poorly differentiated neuroendocrine carcinoma of the hepatobiliary tract and pancreas[J]. Jpn J Clin Oncol, 2010, 40: 313-318. DOI: 10.1093/jjco/hyp173

    [136]

    Lu ZH, Li J, Lu M, et al. Feasibility and efficacy of combined cisplatin plus irinotecan chemotherapy for gastroenteropancreatic neuroendocrine carcinomas[J]. Med Oncol, 2013, 30: 664. DOI: 10.1007/s12032-013-0664-y

    [137]

    Nakano K, Takahashi S, Yuasa T, et al. Feasibility and efficacy of combined cisplatin and irinotecan chemotherapy for poorly differentiated neuroendocrine carcinomas[J]. Jpn J Clin Oncol, 2012, 42: 697-703. DOI: 10.1093/jjco/hys085

    [138]

    Bajetta E, Catena L, Procopio G, et al. Are capecitabine and oxaliplatin (XELOX) suitable treatments for progressing low-grade and high-grade neuroendocrine tumours?[J]. Cancer Chemother Pharmacol, 2007, 59: 637-642. DOI: 10.1007/s00280-006-0306-6

    [139]

    Hadoux J, Malka D, Planchard D, et al. Post-first-line FOLFOX chemotherapy for grade 3 neuroendocrine carcinoma [J]. Endocr Relat Cancer, 2015, 22: 289-298. DOI: 10.1530/ERC-15-0075

    [140]

    Hentic O, Hammel P, Couvelard A, et al. FOLFIRI regimen: an effective second-line chemotherapy after failure of etoposide-platinum combination in patients with neuroendocrine carcinomas grade 3[J]. Endocr Relat Cancer, 2012, 19: 751-757. DOI: 10.1530/ERC-12-0002

    [141]

    Chan JA, Stuart K, Earle CC, et al. Prospective study of bevacizumab plus temozolomide in patients with advanced neuroendocrine tumors[J]. J Clin Oncol, 2012, 30: 2963-2968. DOI: 10.1200/JCO.2011.40.3147

    [142]

    Yao JC, Shah MH, Ito T, et al. Everolimus for advanced pancreatic neuroendocrine tumors[J]. N Engl J Med, 2011, 364: 514-523. DOI: 10.1056/NEJMoa1009290

    [143]

    Kulke MH, Ruszniewski P, Van Cutsem E, et al. A randomized, open-label, phase 2 study of everolimus in combination with pasireotide LAR or everolimus alone in adv-anced, well-differentiated, progressive pancreatic neuroendocrine tumors: COOPERATE-2 trial[J]. Ann Oncol, 2017, 28: 1309-1315. DOI: 10.1093/annonc/mdx078

    [144]

    Panzuto F, Rinzivillo M, Fazio N, et al. Real-world study of everolimus in advanced progressive neuroendocrine tumors[J]. Oncologist, 2014, 19: 966-974. DOI: 10.1634/theoncologist.2014-0037

    [145]

    Raymond E, Dahan L, Raoul JL, et al. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors[J]. N Engl J Med, 2011, 364: 501-513. DOI: 10.1056/NEJMoa1003825

    [146]

    Wang Y, Jin K, Tan H, et al. Sunitinib is effective and tolerable in Chinese patients with advanced pancreatic neuroendocrine tumors: a multicenter retrospective study in China[J]. Cancer Chemother Pharmacol, 2017, 80: 507-516. DOI: 10.1007/s00280-017-3367-9

    [147]

    Xu J, Shen L, Bai C, et al. Surufatinib in advanced pancreatic neuroendocrine tumours (SANET-p): a randomised, double-blind, placebo-controlled, phase 3 study[J]. Lancet Oncol, 2020, 21: 1489-1499. DOI: 10.1016/S1470-2045(20)30493-9

    [148]

    Capdevila J, Fazio N, Lopez CL, et al. Final results of the TALENT trial(GETNE1509): a prospective multicohort phase Ⅱ study of lenvatinib in patients(pts) with G1/G2 advanced pancreatic(panNETs) and gastrointestinal(giNETs) neuroendocrine tumors(NETs)[J]. J Clin Oncol, 2019, 37: 4106. DOI: 10.1200/JCO.2019.37.15_suppl.4106

    [149]

    Strosberg J, El-Haddad G, Wolin E, et al. Phase 3 Trial of (177)Lu-Dotatate for Midgut Neuroendocrine Tumors[J]. N Engl J Med, 2017, 376: 125-135. DOI: 10.1056/NEJMoa1607427

    [150]

    Villard L, Romer A, Marincek N, et al. Cohort study of somatostatin-based radiopeptide therapy with [(90)Y-DOTA]-TOC versus[(90)Y-DOTA]-TOC plus [(177)Lu-DOTA]-TOC in neuroendocrine cancers[J]. J Clin Oncol, 2012, 30: 1100-1106. DOI: 10.1200/JCO.2011.37.2151

    [151]

    McStay MK, Maudgil D, Williams M, et al. Large-volume liver metastases from neuroendocrine tumors: hepatic intraarterial 90Y-DOTA-lanreotide as effective palliative therapy[J]. Radiology, 2005, 237: 718-726. DOI: 10.1148/radiol.2372041203

    [152]

    Claringbold PG, Brayshaw PA, Price RA, et al. Phase Ⅱ study of radiopeptide 177Lu-octreotate and capecitabine therapy of progressive disseminated neuroendocrine tumours[J]. Eur J Nucl Med Mol Imaging, 2011, 38: 302-311. DOI: 10.1007/s00259-010-1631-x

    [153]

    Kashyap R, Hofman MS, Michael M, et al. Favourable outcomes of (177)Lu-octreotate peptide receptor chemoradionuclide therapy in patients with FDG-avid neuroendocrine tumours[J]. Eur J Nucl Med Mol Imaging, 2015, 42: 176-185. DOI: 10.1007/s00259-014-2906-4

    [154]

    Vezzosi D, Bennet A, Rochaix P, et al. Octreotide in insulinoma patients: efficacy on hypoglycemia, relationships with Octreoscan scintigraphy and immunostaining with anti-sst2A and anti-sst5 antibodies[J]. Eur J Endocrinol, 2005, 152: 757-767. DOI: 10.1530/eje.1.01901

    [155]

    Healy ML, Dawson SJ, Murray RM, et al. Severe hypoglycaemia after long-acting octreotide in a patient with an unrecognized malignant insulinoma[J]. Intern Med J, 2007, 37: 406-409. DOI: 10.1111/j.1445-5994.2007.01371.x

    [156]

    Kulke MH, Bergsland EK, Yao JC. Glycemic control in patients with insulinoma treated with everolimus[J]. N Engl J Med, 2009, 360: 195-197. DOI: 10.1056/NEJMc0806740656566.7.2.169

    [157]

    Nieto JM, Pisegna JR. The role of proton pump inhibitors in the treatment of Zollinger-Ellison syndrome[J]. Expert Opin Pharmacother, 2006, 7: 169-175. DOI: 10.1517/14656566.7.2.169

    [158]

    Ito T, Jensen RT. Association of long-term proton pump inhibitor therapy with bone fractures and effects on absorption of calcium, vitamin B12, iron, and magnesium[J]. Curr Gastroenterol Rep, 2010, 12: 448-457. DOI: 10.1007/s11894-010-0141-0

    [159]

    Lamberts SW, van der Lely AJ, de Herder WW, et al. Octreotide[J]. N Engl J Med, 1996, 334: 246-254. DOI: 10.1056/NEJM199601253340408

    [160]

    Delaunoit T, Neczyporenko F, Rubin J, et al. Medical management of pancreatic neuroendocrine tumors[J]. Am J Gastroenterol, 2008, 103: 475-483; quiz 484. DOI: 10.1111/j.1572-0241.2007.01643.x

    [161]

    Daniel E, Aylwin S, Mustafa O, et al. Effectiveness of Metyrapone in Treating Cushing's Syndrome: A Retrospective Multicenter Study in 195 Patients[J]. J Clin Endocrinol Metab, 2015, 100: 4146-4154. DOI: 10.1210/jc.2015-2616

    [162]

    Yuen KC, Williams G, Kushner H, et al. Association between mifepristone dose, efficacy, and tolerability in patients with cushing syndrome[J]. Endocr Pract, 2015, 21: 1087-1092. DOI: 10.4158/EP15760.OR

    [163]

    Wang YH, Lin Y, Xue L, et al. Relationship between clinical characteristics and survival of gastroenteropancreatic neuroendocrine neoplasms: a single-institution analysis (1995-2012) in South China[J]. BMC Endocr Disord, 2012, 12: 30. DOI: 10.1186/1472-6823-12-30

    [164]

    Farley HA, Pommier RF. Treatment of Neuroendocrine Liver Metastases[J]. Surg Oncol Clin N Am, 2016, 25: 217-225. DOI: 10.1016/j.soc.2015.08.010

    [165]

    Du S, Ni J, Weng L, et al. Aggressive Locoregional Treatment Improves the Outcome of Liver Metastases from Grade 3 Gastroenteropancreatic Neuroendocrine Tumors[J]. Medicine (Baltimore), 2015, 94: e1429. DOI: 10.1097/MD.0000000000001429

    [166]

    Kitano M, Davidson GW, Shirley LA, et al. Transarterial Chemoembolization for Metastatic Neuroendocrine Tumors With Massive Hepatic Tumor Burden: Is the Benefit Worth the Risk?[J]. Ann Surg Oncol, 2016, 23: 4008-4015. DOI: 10.1245/s10434-016-5333-x

    [167]

    Engelman ES, Leon-Ferre R, Naraev BG, et al. Compar-ison of transarterial liver-directed therapies for low-grade metastatic neuroendocrine tumors in a single institution[J]. Pancreas, 2014, 43: 219-225. DOI: 10.1097/MPA.0000000000000030

    [168]

    Vogl TJ, Naguib NN, Zangos S, et al. Liver metastases of neuroendocrine carcinomas: interventional treatment via transarterial embolization, chemoembolization and thermal ablation[J]. Eur J Radiol, 2009, 72: 517-528. DOI: 10.1016/j.ejrad.2008.08.008

    [169]

    Kose E, Kahramangil B, Aydin H, et al. Outcomes of laparoscopic tumor ablation for neuroendocrine liver metastases: a 20-year experience[J]. Surg Endosc, 2020, 34: 249-256. DOI: 10.1007/s00464-019-06759-1

    [170]

    Mohan H, Nicholson P, Winter DC, et al. Radiofre-quency ablation for neuroendocrine liver metastases: a systematic review[J]. J Vasc Interv Radiol, 2015, 26: 935-942. e1. DOI: 10.1016/j.jvir.2014.12.009

    [171]

    Rossi RE, Burroughs AK, Caplin ME. Liver transplanta-tion for unresectable neuroendocrine tumor liver metastases[J]. Ann Surg Oncol, 2014, 21: 2398-2405. DOI: 10.1245/s10434-014-3523-y

    [172]

    Mazzaferro V, Pulvirenti A, Coppa J. Neuroendocrine tumors metastatic to the liver: how to select patients for liver transplantation?[J]. J Hepatol, 2007, 47: 460-466. DOI: 10.1016/j.jhep.2007.07.004

    [173]

    Howlader N, Noone AM, Krapcho M, et al. SEER Cancer Statistics Review, 1975—2016[EB/OL]. https://seer.cancer.gov/archive/csr/1975_2016/.

    [174]

    Feng T, Lv W, Yuan M, et al. Surgical resection of the primary tumor leads to prolonged survival in metastatic pancreatic neuroendocrine carcinoma[J]. World J Surg Oncol, 2019, 17: 54. DOI: 10.1186/s12957-019-1597-5

    [175]

    Mehrabi A, Fischer L, Hafezi M, et al. A systematic review of localization, surgical treatment options, and outcome of insulinoma[J]. Pancreas, 2014, 43: 675-686. DOI: 10.1097/MPA.0000000000000110

表(6)
计量
  • 文章访问数:  3899
  • HTML全文浏览量:  613
  • PDF下载量:  1485
  • 被引次数: 0
出版历程
  • 收稿日期:  2021-06-17
  • 录用日期:  2021-06-17
  • 网络出版日期:  2021-06-20
  • 刊出日期:  2021-07-29

目录

/

返回文章
返回
x 关闭 永久关闭