原发性肝脏神经内分泌肿瘤最新研究

神经内分泌肿瘤(neuroendocrine tumor,NET)在临床上较少见,多发生于支气管肺组织或消化道,发生在肝脏的NET多为胃肠胰神经内分泌肿瘤(gastrointestinal pancreatic neuroendocrine tumor,GEP-NET)转移而来。原发性肝脏神经内分泌肿瘤(primaryhepatic neuroendocrine tumor,PHNET)与转移性肝脏神经内分泌肿瘤(metastatic hepatic neuroendocrine tumor,MHNET)的鉴别缺乏特异性,原发性NET的诊断建立在排除继发性NET病变的基础上。现从分类、临床症状、血清学、影像学检查、鉴别诊断及治疗6个方面作一概述。     

胃肠胰神经内分泌肿瘤的治疗研究进展

胃肠胰神经内分泌肿瘤（GEP-NETs）起源于胃肠胰腺神经内分泌细胞,是一组罕见的、有着不同临床表现的肿瘤。在过去的30a中,GEP—NETs发病率快速增长。为此,美国国家癌症中心已大幅提高GEP—NETs的研究经费,以促进GEP—NETs的基础和临床诊治的研究。我国GEP—NETs发病率也逐年增加,但其治疗效果一直不甚理想。现将近年来GEP—NETs的治疗研究进展情况综述如下。     

胃肠胰腺神经内分泌肿瘤药物治疗进展

胃肠胰腺神经内分泌肿瘤（GEP-NETs）起源于胃肠胰腺神经内分泌细胞（属APUD细胞），分泌多种活性激素，此类肿瘤的临床表现复杂多样，且恶性程度较高，极易误诊、误治。近年来GEP-NETs的治疗。特别是内科治疗取得了较大的进展，主要包括控制症状治疗、化疗、肽受体介导的放射性核素治疗、生物治疗等。本文参考国内外近期文献，就GEP-NETs的药物治疗进展作一概述。     

中国胃肠胰神经内分泌肿瘤临床研究现状分析

背景：神经内分泌肿瘤（NETs）是一组起源于弥散神经内分泌系统的异质性肿瘤,国外流行病学调查显示胃肠胰NETs（GEP-NETs）的患病率在消化道恶性肿瘤中仅次于结直肠癌而居第二位。我国对GEP—NETs的认识和研究相对滞后。目的：汇总我国历年发表的报道GEP-NETs的文献,分析国内GEP-NETs的临床特点和研究现状。方法：以“神经内分泌肿瘤”或“类癌”为检索词检索中国生物医学文献数据库、万方数据、中国知网和维普网,纳入GEP-NETs原始病例相关文献,对GEP—NETs病例的地域分布、临床特征以及诊断、治疗、预后信息进行回顾性分析。结果：共获得有效文献863篇,报道GEP—NETs11671例,报道病例集中分布于华东、华北地区（54．9％）。胰腺NETs报道例数最多（5807例）,其中功能性胰腺NETs占89．6％。5001例（42．8％）患者具有特征性NETs表现。GEP-NETs的误诊率为55．1％（1544／2802）,其定位诊断以常规胃肠镜、B超、CT检查为主。外科手术切除为最主要的治疗方式,治愈率为83．0％（4052／4882）。结论：我国临床医师对GEP-NETs认识不足,误诊率较高,总体发病和预后情况不明。需建立一个全国性的NETs数据库,以了解国内该类疾病的临床和流行病学特点。     

胃肠胰神经内分泌肿瘤诊治进展

在机体经典的内分泌腺体之外，肺、胃肠道等还广泛散在地分布着许多具有内分泌作用的细胞，这些细胞不但本身含有胺，具有摄取胺前体并脱羧的能力，而且与神经细胞有许多共同的形态、生物学和功能特性，故称为神经内分泌细胞。起源于胃肠道和胰腺神经内分泌细胞的肿瘤即胃肠胰神经内分泌细胞肿瘤（GEP-NET）。这是一组罕见的、有着不同临床表现的肿瘤，其发病约占所有消化道肿瘤的2％，在这类肿瘤中最常见的是类癌，其发病率大约为2．5／10万。     

结直肠神经内分泌肿瘤25例临床分析

目的探讨结直肠神经内分泌肿瘤的临床特征、诊治方法及预后。 方法回顾分析湖北省肿瘤医院自2006年1月至2015年1月收治的25例结直肠神经内分泌肿瘤患者的临床资料。 结果肿瘤部位：阑尾3例,升结肠3例,乙状结肠2例,直肠17例。分级情况：NET（G1）11例,NET（G2）3例,NEC（G3）8例,MANEC 3例。免疫组织化学：Syn、CgA、NSE阳性表达率为96%,68%和92%。预后：结直肠神经内分泌肿瘤出现转移部位最多见为肝脏。9例Ⅰ期患者生存时间均长于5年。6例Ⅱ期患者,3年内死亡1例,5年内死亡3例,余1例仍在随访中。8例Ⅲ期患者,1年生存率75%,3年生存率50%,5年生存率25%。2例Ⅳ期患者,1例存活28月,另1例存活37月。 结论结直肠神经内分泌肿瘤缺乏特征性临床表现,主要通过内镜下活组织病理检查明确诊断。结直肠神经内分泌肿瘤治疗方法主要依靠手术治疗,早期预后良好,预后与分期和分级密切相关。     

胃肠胰神经内分泌肿瘤的肿瘤微环境

肿瘤微环境为肿瘤提供了特有的营养代谢环境,使得肿瘤细胞生物学行为受到自身遗传学及其周边微环境的双重调控.胃肠胰神经内分泌肿瘤(gastroenteropancreatic neuroendocrine neoplasms,GEP-NENs)是起源于消化系统神经内分泌细胞的异质性肿瘤,它以分泌生物活性物质为特点.GEP-NENs早期症状不典型,确诊时常已发生转移,对其肿瘤微环境的研究有助于我们进一步认识GEP-NENs的发生发展机制,并能为临床诊断、治疗GEP-NENs提供新的依据.本篇文章综述了肿瘤微环境中不同细胞成分、细胞外基质重塑蛋白、可溶性生长因子以及嗜铬粒蛋白在GEP-NENs进展中的作用.     

87例胃肠胰神经内分泌肿瘤的诊治分析

目的 探讨胃肠胰神经内分泌肿瘤(GEP-NEN)发生部位、临床症状、内镜及影像学表现、病理特点、诊断、治疗及预后。方法收集中山大学附属第一医院2000年1月至2010年6月间收治的87例GEP-NEN患者病历资料,通过对神经内分泌标记物突触素(Syn)和铬粒素A(CgA)的免疫组织化学染色确定肿瘤是否具有神经内分泌性质,按组织学和增殖活性明确肿瘤分级,将GEP-NEN分为神经内分泌瘤（G1和G2级）、神经内分泌癌（G3级）和混合性腺神经内分泌癌(G3级),探讨其临床特点及诊疗情况。结果 36例(41.4 ％)GEP-NEN发生在胰腺,其次为直肠18例(20.7％)、胃9例(10.3％)、十二指肠6例(6.9％)。87例GEP-NEN中65例(74.7％)为非功能性,多以各种消化道症状或肿瘤局部占位为首发症状,无一例出现类癌综合征,内镜及影像学表现主要为肿瘤占位病变。87例GEP-NEN中69例(79.7％)为神经内分泌瘤(NET)、13例(14.9％)为神经内分泌癌(NEC)、5例(5.4％)为混合性腺神经内分泌癌(MANEC);G1、G2和G3级肿瘤分别占64.9％、14.9％和20.2％。22例(47.8％) GEP-NEN患者就诊时肿瘤浸润肌层/浆膜层,18例(20.7％)出现淋巴结转移,18例(20.7％)出现远处转移,大部分转移至肝脏。CgA和Syn免疫组织化学染色阳性率分别为74.2％和88.1％。79例(90.8％)患者进行手术治疗。随访1年、3年和5年生存率分别为76.9％、54.2％和41.7％。结论GEP-NEN可发生于消化系统任何部位,临床表现多样,内镜和影像学检查是重要的诊断手段,确诊主要依赖病理,手术是主要的治疗手段,肿瘤病理分类、分级和远处转移情况等与其预后有关。     

胰腺神经内分泌肿瘤

胰腺神经内分泌肿瘤（PNET）临床少见，表现为功能性和无功能性，来源于胰岛细胞，又称为胰岛细胞瘤（ICTs）。PNET是胰腺肿瘤很重要的一种类型，约占临床诊断胰腺肿瘤的2％-4％，包括单发、多发，良性、恶性等多种类型，其中10％～20％伴有多发内分泌肿瘤（MEN）。     

胃肠混合性腺神经内分泌癌的回顾性病例分析

背景：近年来,胃肠腺神经内分泌肿瘤发病率不断上升,为推动疾病的防治,我国制定了中国胃肠胰神经内分泌肿瘤病理学诊断共识。目的：探讨胃肠混合性腺神经内分泌癌（MANEC）的临床病理特点。方法：选取2002年4月-2009年1月天津大港油田总医院确诊的胃肠腺癌患者100例,对患者肿瘤组织标本进行免疫组化染色,检测突触素（Syn）、嗜铬粒素A（CgA）、癌胚抗原（CEA）、细胞角蛋白8/18（CK8/18）、Ki-67的表达。分析MANEC患者的临床资料,包括性别、年龄、临床症状、病理特征以及预后。结果：100例胃肠腺癌患者中,MANEC 6例,发生率为6%。MANEC临床表现以腹痛、腹胀、便血常见。MANEC发生于胃小弯2例、回盲部1例、升结肠1例、直肠2例。镜下可见MANEC由腺癌和神经内分泌癌两种成分构成。6例患者均接受手术治疗,5例在短时间内复发和（或）腹腔转移。结论：MANEC形态学上与低分化腺癌不易区别,确诊主要依赖于组织学证据和免疫组化标记,预后较普通腺癌差。     

血浆嗜铬粒蛋白A对多种神经内分泌肿瘤的诊断价值

目的 探讨血浆嗜铬粒蛋白A(CgA)对神经内分泌肿瘤的诊断价值,同时评价血浆CgA对胃肠胰腺内分泌肿瘤的诊断效力,初步探讨血浆CgA对胃肠胰腺内分泌肿瘤预后的监测作用.方法 应用酶联免疫试剂盒检测56例胃肠胰腺内分泌肿瘤、52例嗜铬细胞瘤和7例小细胞肺癌的血浆CgA浓度,同时以52例健康体检者作为对照,计算血浆CgA诊...     

Management of pancreatic neuroendocrine tumors

Neuroendocrine tumors are a heterogeneous group of rare tumors originating from neuroendocrine cells with secretory characteristics, and are primarily located in gastric, duodenal, pancreatic, and small and large bowel mucosa. Due to their extremely variable biologic and clinical behaviour, diagnosis is often delayed after a prolonged workup. Many advances have been made in recent years in the diagnosis, characterization, and treatment of neuroendocrine tumors. This review focuses on pancreatic neuroendocrine tumors, discussing the relatively new, multidisciplinary approach to their management. A Pubmed search was performed, limited to papers published within the last five years, using the key words NETs, pancreatic NETs, pancreatic tumors, diagnosis, imaging, nuclear imaging, endoscopy, endoscopic ultrasound, and biochemical markers.     

Plasma chromogranin A in patients with sporadic gastro-entero-pancreatic neuroendocrine tumors or multiple endocrine neoplasia type 1

OBJECTIVE: As circulating chromogranin A (CgA) has been claimed to be the best general neuroendocrine marker so far available, we evaluated the usefulness of CgA determination in the clinical assessment of patients with sporadic gastro-entero-pancreatic neuroendocrine tumors (GEP NETs) or multiple endocrine neoplasia type 1 (MEN 1). DESIGN AND METHODS: Plasma CgA levels were measured using a commercial enzyme-linked immunosorbent assay in 61 patients with sporadic GEP NET and in 25 with MEN 1 including 16 with GEP NET. Controls were 50 healthy volunteers, 46 patients with pituitary adenoma and 35 patients with primary hyperparathyroidism. RESULTS: The cutoff value for CgA established in our healthy subjects (as mean+2 s.d.) was 20 U/l. CgA levels were above the normal range in 71/77 patients with sporadic or MEN 1-related GEP NETs (92%), in four out of nine MEN 1 patients without GEP NETs (44%), and only in 22/81 control patients with pituitary or parathyroid disease (27%). Furthermore, CgA levels of over 100 U/l occurred in 36/77 patients with GEP NETs (47%) and only in one patient with a non-functioning pituitary adenoma. In the patients with GEP NETs, both tumor burden and secretory activity affected CgA levels, and successful surgical resection was associated with markedly decreased CgA values. CONCLUSIONS: Plasma CgA was confirmed to be a reliable marker for GEP NETs. Moreover, in MEN 1 patients the finding of very high CgA levels strongly suggests the presence of a GEP NET, as both primary hyperparathyroidism and pituitary adenomas rarely cause marked CgA increases.     

Neuroendocrine tumors of the gastro-entero-pancreatic system

Gastro-entero-pancreatic （GEP） neuroendocrine tumors （NETs） are rare neoplasms, although their prevalence has increased substantially over the past three decades. Moreover, there has been an increased clinical recognition and characterization of these neoplasms. They show extremely variable biological behavior and clinical course. Most NETs have endocrine function and secrete peptides and neuroamines that cause distinct clinical syndromes, including carcinoid syndrome; however, many are clinically silent until late presentation with mass effects. Investigation and management should be individualized for each patient, taking into account the likely natural history of the tumor and general health of the patient. Management strategies include surgery for cure or palliation, and a variety of other cytoreductive techniques, and medical treatment including chemotherapy, and biotherapy to control symptoms due to hormone release and tumor growth, with somatostatin analogues （SSAs） and alphainterferon. New biological agents and somatostatintagged radionuclides are under investigation. Advances in the therapy and development of centers of excellence which coordinate multicenter studies, are needed to improve diagnosis, treatment and therefore survival of patients with GEP NETs.     

Therapy of metastatic pancreatic neuroendocrine tumors (pNETs): recent insights and advances

Neuroendocrine tumors (NETs) [carcinoids, pancreatic neuroendocrine tumors (pNETs)] are becoming an increasing clinical problem because not only are they increasing in frequency, but they can frequently present with advanced disease that requires diagnostic and treatment approaches different from those used in the neoplasms that most physicians are used to seeing and treating. In the past few years there have been numerous advances in all aspects of NETs including: an understanding of their unique pathogenesis; specific classification systems developed which have prognostic value; novel methods of tumor localization developed; and novel treatment approaches described. In patients with advanced metastatic disease these include the use of newer chemotherapeutic approaches, an increased understanding of the role of surgery and cytoreductive methods, the development of methods for targeted delivery of cytotoxic agents, and the development of targeted medical therapies (everolimus, sunitinib) based on an increased understanding of the disease biology. Although pNETs and gastrointestinal NETs share many features, recent studies show they differ in pathogenesis and in many aspects of diagnosis and treatment, including their responsiveness to different therapies. Because of limited space, this review will be limited to the advances made in the management and treatment of patients with advanced metastatic pNETs over the past 5?years.     

Clinical features of pancreatic neuroendocrine tumors

Pancreatic neuroendocrine tumors (PNETs), also known as islet cell tumors, are rare neoplasms that arise in the endocrine tissues of the pancreas. Most of pancreatic NETs (50–75%) are nonfunctioning (not associated with a hormonal clinical syndrome); however, in up to one third they can secrete a variety of peptide hormones, including insulin, gastrin, glucagon, vasoactive intestinal peptide, somatostatin etc., resulting in rare but unique clinical syndromes. In this article, the clinical features of the different types of PNETs will be reviewed. Other aspects of the management of these tumors (surgery, treatment of advanced disease, tumor localization) are not dealt with here, as they are covered by other papers in this volume.     

Gastroenteropancreatic neuroendocrine tumors: Role of surgery

Natural history of gastroenteropancreatic (GEP) Neuroendocrine tumors (NETs) is better and better known so indications of surgery are presently selective. Surgical resection, but also endoscopic resection and observation, can be proposed for gastric NETs according to presentation, size and grade. For small bowel NETs, resection is frequently needed but should obtain the best compromise between radicality and postoperative functional disorders. Appendiceal NETs are frequently diagnosed by appendectomy for appendicitis, but some patients at high risk for lymph node metastasis and recurrence should be reoperated for radical resection. Rectal NETs are often diagnosed incidentally; the smallest (< 1 cm) can be resected endoscopically but the most aggressive need a oncological proctectomy. Pancreatic NETs represent a wide spectrum, ranging from fully benign tumors to very aggressive ones. Insulinomas are mostly benign, responsible for incapacitating symptoms despite medical treatment, and should ideally be treated by parenchyma sparing resection, mainly enucleation. Conversely, symptoms of gastrinomas are efficiently treated medically but their resection needs an oncological approach. Nonfunctioning PNETs are more and more frequently and incidentally discovered. According to their size, presentation and patient's characteristics, they need a resection (oncological or parenchyma-sparing) or a close observation.     

Small bowel neuroendocrine tumors: From pathophysiology to clinical approach

Neuroendocrine tumors(NETs), defined as epithelial tumors with predominant neuroendocrine differentiation, are among the most frequent types of small bowel neoplasm. They represent a rare, slow-growing neoplasm with some characteristics common to all forms and others attributable to the organ of origin. The diagnosis of this subgroup of neoplasia is not usually straight-forward for several reasons. Being a rare form of neoplasm they are frequently not readily considered in the differential diagnosis. Also, clinical manifestations are nonspecific lending the clinician no clue that points directly to this entity. However, the annual incidence of NETs has risen in the last years to 40 to 50 cases per million probably not due to a real increase in incidence but rather due to better diagnostic tools that have become progressively available. Being a rare malignancy, investigation regarding its pathophysiology and efforts toward better understanding and classification of these tumors has been limited until recently. Clinical societies dedicated to this matter are emerging(NANETS, ENETS and UKINETS) and several guidelines were published in an effort to standardize the nomenclature, grading and staging systems as well as diagnosis and management of NETs. Also, some investigation on the genetic behavior of small bowel NETs has been recently released, shedding some light on the pathophysiology of these tumors, and pointing some new directions on the possible treating options. In this review we focus on the current status of the overall knowledge about small bowel NETs, focusing on recent breakthroughs and its potential application on clinical practice.     

Pancreatic neuroendocrine tumors

Pancreatic neuroendocrine tumors (pancreatic NETs) are rare, low- to intermediate-grade neoplasms thought to arise from the pancreatic islets. Recent advances in pathology and our understanding of the biological behavior of this group of tumors has resulted in changes in their nomenclature and how we treat them. This review puts into perspective our current understanding of pancreatic NETs in terms of their incidence, pathology, and management.     

Pancreatic neuroendocrine tumors

Pancreatic neuroendocrine tumors (PNETs) are rare neoplasms representing <5% of all pancreatic malignancies with an estimated incidence of 1-1.5 cases/100,000. PNETs are broadly classified as either functional or nonfunctional. Functional PNETs include insulinomas, gastrinomas, vasoactive intestinal peptideomas, glucagonomas, and somatostatinomas. The clinical manifestations associated with these tumors are the result of excessive hormonal secretion and action. The functional nature of these tumors makes pancreatic hormone testing critical not only for initial diagnosis but also for follow-up, because they are important tumor markers. Nonfunctional PNETs typically remain clinically silent until a substantial mass effect occurs. Although the majority of PNETs occur sporadically, it is important to recognize that these tumors may be associated with a variety of familial syndromes and in many cases genetic testing of PNET patients is warranted. This article familiarizes the reader with the clinical presentation and the biochemical, radiologic, and genetic testing indicated for diagnosis and follow-up of patients with PNET.