Department of Surgery, Division of Surgical Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
J Am Coll Surg. 2013 Jan;216(1):123-34. doi: 10.1016/j.jamcollsurg.2012.08.027. Epub 2012 Oct 11.
Neuroendocrine tumors (NETs) are rare neoplasms arising from cells of the neuroendocrine system in a multitude of anatomic locations, and representing a wide range of histologies. Compared with other malignancies from the same organ (eg, pancreatic NET vs pancreatic ductal adenocarcinoma), NETs are often indolent in both biology and disease progression. However, metastasis will develop in almost 40% of patients with NETs during the course of their disease, most commonly to the liver. In contrast to other malignancies, in a proportion of patients with neuroendocrine liver metastasis (NELM) disabling clinical symptoms can develop secondary to the production of specific biogenic amines and polypeptide hormones. Therefore, treatment of patients with NELM is focused on optimizing quality of life through reduction of such hormone-related symptoms, and improving survival in patients with disease amenable to liver-directed therapy, including hepatic resection, thermal ablation, and intra-arterial therapy (IAT). To date, hepatic resection remains the only potentially curative option for patients with NELM, with 5-year survival after hepatectomy ranging from 60% to 80% in recent series. Until recent reports of the use of somatostatin analogues in neuroendocrine tumors of mid-gut origin, and sunitinib and everolimus in patients with advanced pancreatic NETs (PNETs), there has been little success in the use of systemic therapy to treat patients with advanced NELM, with historic responses ranging from 15% to 20%. As these systemic agents are not curative, there is still considerable interest in the use of liver-directed therapy to increase patient survival and address hormonally related symptoms. In addition to surgery, IAT has emerged as an alternative liver-directed approach to treat patients with NELM. We review the management of patients with NELM with an emphasis on clarifying the relative roles of surgery, IAT, as well as emerging systemic therapeutic agents. To accomplish this, we performed an extensive literature search in PubMed using medical subject headings (ie, neuroendocrine, carcinoid, liver metastasis, hepatic metastases, hepatectomy, liver resection, transplantation, intra-arterial therapy, radiation therapy, chemotherapy) to identify relevant articles for inclusion.
神经内分泌肿瘤（NET）是起源于神经内分泌系统细胞的罕见肿瘤，发生于许多解剖部位，并具有广泛的组织学特征。与同一器官的其他恶性肿瘤（例如，胰腺 NET 与胰腺导管腺癌）相比，NET 在生物学和疾病进展方面通常较为惰性。然而，在疾病过程中，几乎 40%的 NET 患者会发生转移，最常见的转移部位是肝脏。与其他恶性肿瘤不同，在一部分神经内分泌肝脏转移（NELM）患者中，由于特定生物胺和多肽激素的产生，可能会出现导致失能的临床症状。因此，NELM 患者的治疗重点是通过减轻与激素相关的症状来提高生活质量，并改善对肝定向治疗有反应的患者的生存，包括肝切除术、热消融和肝内动脉治疗（IAT）。迄今为止，肝切除术仍然是 NELM 患者唯一可能治愈的选择，在最近的系列研究中，肝切除术后 5 年生存率为 60%至 80%。直到最近有报告称使用生长抑素类似物治疗起源于中肠的神经内分泌肿瘤，以及舒尼替尼和依维莫司治疗晚期胰腺神经内分泌肿瘤（PNET），在使用全身治疗治疗晚期 NELM 患者方面几乎没有取得成功，历史缓解率为 15%至 20%。由于这些全身药物无法治愈，因此人们仍然对使用肝定向治疗来增加患者生存并解决与激素相关的症状非常感兴趣。除了手术，IAT 已成为治疗 NELM 患者的另一种肝定向方法。我们重点讨论了 NELM 患者的管理，以阐明手术、IAT 以及新兴的全身治疗药物的相对作用。为了实现这一目标，我们在 PubMed 中使用医学主题词（即神经内分泌、类癌、肝转移、肝转移、肝切除术、肝切除术、肝移植、肝内动脉治疗、放射治疗、化疗）进行了广泛的文献检索，以确定相关文章。
