内分泌肿瘤在内脏肠道内神经位置的临床特点和相应分析

目的 探讨研究内分泌肿瘤在内脏肠道内神经位置的临床特点,并对其相应特点以及预后情况作出分析.方法 选取于2000年10月~2012年10月间在本院接受手术切除治疗的内脏肠道内神经内分泌肿瘤患者共80例,回顾性分析80例患者的相应病历资料.80例患者中有50例G1级（即神经内分泌瘤1级）患者,15例G2级（即神经内分泌瘤2级）患者,12例G3级（即神经内分泌瘤3级）患者（其中包括4例小细胞癌患者以及6例分化较差的神经内分泌癌患者）,3例MANEC（即混合型的腺-神经内分泌癌）患者.从80例患者体内采取的标本均采用SP法对相关免疫组化标志物进行染色.结果 本次研究的80例患者中男女比例为1.4：1;男性患者的发病年龄为（50.26±9.31）岁,女性患者的发病年龄为（48.56±9.57）岁.发病部位位于直肠的神经内分泌肿瘤患者的最常见的习惯改变是排便与便血（60.0%,39/65）,26例患者临床表现出腹胀腹痛的症状（40%）,其余16例患者并没有显著的临床现象,在某种原因或是常规的体检中发现病情.结论 肠道神经的内分泌肿瘤患者大多数是男性,最常见的内分泌肿瘤发病肠道是直肠,肿瘤多为息肉形状,呈隆起型.而肠道神经内分泌肿瘤患者的预后情况则与肿瘤在组织学上的分类有很大的联系,能够对肠道神经内分泌肿瘤的转移产生较大影响的因素之一是肿瘤的浸润程度.CgA与Syn联合使用能够有效的提高特异性免疫组织的化学标志物的敏感度.     

消化系统神经内分泌肿瘤81例的临床研究

目的通过分析总结消化系统神经内分泌肿瘤（NETs）的临床特征以提高临床医师对该病的认识水平,从而达到能早期诊断,并尽量避免漏诊及误诊的目的。方法回顾分析2011年8月至2012年12月郑州大学附属肿瘤医院及郑州大学第一附属医院住院及门诊经病理确诊的81例患者的临床资料,分析其好发部位,临床表现,治疗措施及预后情况。结果81例消化系统NETs发病部位依次是：胃27例,直肠21例,胰腺10例,阑尾8例,十二指肠7例,结肠5例,食管3例。其临床表现多种多样,无特异性,其症状主要与发病部位明显相关。结论消化系统NETs好发于胃肠道,尤以胃、直肠高发。由于缺乏特异临床表现,在临床工作中应提高对本病的警惕性。当出现与消化器官密切相关的症状时,应及时进行对消化系统NETs诊断有价值的检查,如电子内镜下的黏膜组织活检、CT、彩超及CT、彩超引导下穿刺等。     

结直肠间质瘤22例外科治疗分析

目的探讨结直肠间质瘤的临床特点和手术治疗效果。方法选择我院2001月1月至2009年1月22例,分析其临床表现、肿瘤的部位、大小与病理检查。22例患者均行手术治疗。8例结肠间质瘤患者中6例行所在肠段切除术,其余2例行肿瘤部分切除术 14例直肠间质瘤患者,其中前切除术（Dixon）7例,腹会阴联合切除术（Miles）3例,局部切除术3例,仅作肿瘤切除活检1例。结果本组22例患者,无围手术期死亡。22例患者均完全随访,随访时间平均60个月。在14例直肠间质瘤患者中,8例患者在术后34个月～79个月死亡,其余6例患者无瘤生存。8例结肠间质瘤患者中,3例于术后3个月～16个月死亡,5例无瘤生存。22例患者平均生存时间为（47±6.4）个月。结论对于结直肠间质瘤来说,宜早期诊断及早行手术治疗是治疗结直肠间质瘤的关键。     

直肠神经内分泌肿瘤伴肝转移1例及文献复习

神经内分泌肿瘤,最初被称为类癌,是起源于弥散神经内分泌系统中的神经内分泌细胞的肿瘤,在全部恶性肿瘤中的比例不足1%,多见于消化道。消化道神经内分泌肿瘤是一种低度恶性肿瘤,可发生在消化道任何部位,有文献报道小肠与直肠是消化道神经内分泌肿瘤中最常见的发病部位。由于胃肠道神经内分泌肿瘤在临床发展过程中几乎无症状,所以有三分之二的患者在确诊时已发生远处转移,但5年存活率可超过60%。随着对神经内分泌肿瘤的研究不断深入,检测方法多样,近年来其发病率有很大幅度增加。本文报道1例直肠神经内分泌肿瘤伴肝转移的诊治过程,并对诊断和治疗直肠神经内分泌肿瘤的文献进行复习。     

十二指肠神经内分泌肿瘤1例报道

神经内分泌肿瘤（NETs）是指人体的神经内分泌细胞发生的肿瘤,又称为APUD肿瘤,是一组起源于肽能神经元和神经内分泌细胞的异质性肿瘤,性质上也不完全是恶性。NETs是一种十分罕见的疾病,其在全部恶性肿瘤中比例不足1%,可发生于全身许多器官和组织。多发生于胃、肠、胰腺、支气管和肺等部位。由于该病十分罕见，症状隐匿，临床诊断较困难，预后也各异。胃肠道神经内分泌肿瘤（gastrointestinal neuroendocrine tumors，GE-NETs）是一种极少见的类型特殊的低度恶性肿瘤，可发生在消化道的任何部位，约占消化道所有恶性肿瘤的0．4％-1．8％。而十二指肠神经内分泌肿瘤更是罕见，国内外仅有个案报道。现将本院收治的1例十二指肠神经内分泌肿瘤报道如下。     

13例无功能性阑尾神经内分泌肿瘤临床病理回顾性分析

目的：探讨无功能性阑尾神经内分泌肿瘤的临床病理特点,免疫表型及预后。方法回顾性分析13例无功能性阑尾神经内分泌肿瘤的临床病理资料,对肿瘤进行光镜观察,并做免疫组化。结果无功能性阑尾神经内分泌肿瘤可分为4个临床病理分级,其病理学特点,生物学行为及预后均有不同。本组病例中无功能性阑尾神经内分泌肿瘤G18例,G23例,G3或神经内分泌癌2例,免疫组化检查AE1/AE3阳性3例, Syn阳性11例,CgA阳性10例。随访期内三个级别5年生存率分别为100%,100%,51%。结论无功能性阑尾神经内分泌肿瘤病理分级及临床分期与预后密切相关,对其治疗有指导作用,免疫组化合理应用可提高神经内分泌肿瘤的诊断率,减少临床误诊,避免过度治疗。     

胃癌伴神经内分泌分化和胃混合性腺神经内分泌癌临床病理及预后分析

　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　【摘要】目的 探讨胃癌伴神经内分泌分化和胃混合性腺神经内分泌癌的临床病理及预后。方法 回顾性分析61例胃癌伴神经内分泌分化和34例胃混合性腺神经内分泌癌患者的临床病理资料,对其组织化学及免疫组织化学染色进行观察。结果 胃癌伴神经内分泌分化和胃混合性腺神经内分泌癌患者肿瘤发病部位、远处转移及区域淋巴结转移差异有统计学意义（P<0.05）;SyN 、CgA和CD56三者阳性表达率差异有统计学意义（P<0.05）;区域淋巴结转移和远处转移2个因素与预后相关（P<0.05）;胃混合性腺神经内分泌癌患者术后生存期短于胃癌伴神经内分泌分化患者（P<0.05）。结论 免疫组化染色对胃癌伴神经内分泌分化和胃混合性腺神经内分泌癌的确诊具有重要意义,肿瘤神经内分泌细胞数量的多少对患者预后评估及辅助治疗有指导意义。      

结直肠神经内分泌肿瘤的临床治疗进展

神经内分泌肿瘤(neuroendocrine neoplasms,NENs)是一类异质性较强的肿瘤,多生长在消化道,尤其是胰腺、直肠等部位.随着内镜等相关检测手段的发展,结直肠神经内分泌肿瘤检出率逐年上升.目前该病的致病机制尚不明确,有研究显示NENs的基因分子变异可能是病因之一.虽然手术治疗仍是局限性结直肠神经内分泌肿瘤的首选治疗方式,但抗肿瘤药物对于晚期以及复发的结直肠NENs病人至关重要.本研究着重介绍结直肠NENs手术及辅助治疗等方面最新研究结果,希望给予医务工作者对该病的诊疗新思路.     

PAX5表达对神经内分泌肿瘤临床病理特征和预后的影响研究

目的：探讨 PAX5表达与神经内分泌肿瘤临床病理特征和预后的关系。方法收集神经内分泌肿瘤病例的临床资料和石蜡包埋的档案肿瘤组织,用免疫组化染色检测 PAX5的表达,随访研究病例,分析 PAX5表达与神经内分泌肿瘤临床病理特征和预后的关系。结果 PAX5的总阳性表达率为50％;PAX5表达在不同部位的NEN 中有明显差异,以肺 NEN 的阳性表达率最高（68．2％）;PAX5表达在神经内分泌癌（NEC）与神经内分泌瘤（NET）病例之间、早期（Ⅰ期和Ⅱ期）与晚期（Ⅲ期和Ⅳ期）病例之间、淋巴结转移与无转移病例之间差异有统计学意义（P ＜0．05）。在晚期临床分期、NEC 病例和伴有淋巴结转移的 NEN 中 PAX5表达明显增多。生存分析：NENs 的获访率98．2％（55／56）,多因素 Cox-Regression 分析发现肿瘤分级（P ＝0．003）、分期（P ＝0．049）、部位（P＝0．000）、淋巴结转移（P ＝0．014）、PAX5（P ＝0．015）是神经内分泌肿瘤患者预后的独立影响因素。PAX5阳性与阴性表达的 NEN 病例的生存状况差异有统计学意义（P ＜0．05）,阳性表达病例的生存状况较差。结论 PAX5阳性表达对 NENs 的临床病理特征有一定影响,可能是 NEN 不良预后的相关因子。     

血清中性粒细胞胞外诱捕网水平与狼疮性肾炎的相关性 #br#

目的 探讨血清中性粒细胞胞外诱捕网（NETs）水平与狼疮性肾炎（LN）病情以及预后的关系,分析NETs 预测LN预后的价值。方法 选取92例LN患者（LN组）,97例肾功能和尿检正常的SLE患者（SLE组）和83例健康志 愿者（对照组）。根据系统性红斑狼疮疾病活动度评分（SLEDAI）-2000 将 LN 患者分为轻度活动组（评分≤6 分,31 例）,中度活动组（评分7~12分,33例）和重度活动组（评分＞12分,28例）。根据随访期间肾脏相关终点事件发生情 况将LN患者分为预后不良组（25例）和预后良好组（67例）。检测血清NETs水平,分析NETs与脱氧核糖核酸酶1 （DNASE1）、肾功能、SLEDA1-2000评分、肾组织活动性指数（AI）和慢性指数（CI）评分的相关性,多因素Logistic回归 分析影响LN预后的因素,受试者工作特征（ROC）曲线分析NETs预测LN患者预后的价值。结果 LN组血清NETs 水平高于SLE组和对照组,重度活动组血清NETs水平高于中度活动组和轻度活动组,中度活动组血清NETs水平高 于轻度活动组（P＜0.05）。NETs 水平与肾小球滤过率（eGFR）和 DNASE1 呈负相关,与 24 h 尿蛋白定量、SLEDA1- 2000 评分、肾组织 AI 评分和 CI 评分呈正相关（P＜0.05）。高 AI 评分和高 NETs 是 LN 预后不良的危险因素（P＜ 0.05）。NETs预测LN患者预后的曲线下面积（AUC）为0.871,敏感度为80.00%,特异度为86.57%。结论 NETs水平 升高与LN肾损伤程度以及肾脏终点事件发生有关,可作为LN预后评估的指标。     

Neuroendocrine tumors diagnosed at the Antonio Cardarelli hospital (Naples, Italy) between 2006-2009: a single-institution analysis

Neuroendocrine tumors (NETs) are rare, with an incidence of about 5 per 100,000 inhabitants. As no study on NETs has ever been specifically conducted on the population of Campania, we performed a retrospective analysis of all newly diagnosed NETs at the Antonio Cardarelli hospital between 2006-2009. A search of the registry of the Pathology Department of the Antonio Cardarelli hospital was carried out to retrieve available data on all newly diagnosed NET cases. Two hundred and ninety-nine NET tumors were diagnosed at our Institution from January, 2006 to December, 2009. Globally, 121 patients (40% of the population) had a lung NET, while 92 patients (30% of the population) presented a GEP-NET. The most common primary tumor site varied by sex, with female patients being more likely to have a primary NET in the lung, breast or colon, and male patients being more likely to have a primary tumor in the lung. Also, twenty-three cases of breast NETs were identified, and clinical information regarding therapy and response was available for 22 patients. Our study represents a pioneering effort to provide the medical community in Campania with basic information on a large number of patients with different types of NETs. The Antonio Cardarelli hospital could greatly benefit from cooperation with other hospitals in order to become a highly specialized center for NETs in the region and Southern Italy.     

Novel targets for the treatment and palliation of gastrointestinal neuroendocrine tumors

Gastrointestinal (GI) neuroendocrine tumors (NETs), for example, carcinoids, are rare neoplasms characterized by the production of bioactive markers, such as 5-HT and chromogranin A. With the exception of surgery, there are limited curative and palliative treatments available for this type of tumor. Therefore, there is a great need to develop new pharmacological strategies to reduce tumor burden and control symptoms in patients with metastatic carcinoid tumors and the carcinoid syndrome. In this review, several pathways thought to be involved in GI NET carcinogenesis are discussed, and novel approaches that are currently in development to target these pathways are highlighted.     

Successful treatment of gallbladder neuroendocrine carcinoma with combined chemo-radiotherapy: a case report and literature review

Neuroendocrine tumors (NETs) occur in the bronchopulmonary system. Extrapulmonary NETs are rare and are considered to ac count for 2.5 - 5% of all NETs, with more than 60% of these tumors occurring along the gastro intestinal tract, including primary NET of the gall bladder. Pri mary NETs of the gall bladder have been classified as carcinoid, neuroendocrine carcinoma or heterogeneous carcinoma. Currently, the main treatment of neuroendocrine car ci noma re mains surgery. The role of radiotherapy and chemotherapy is undefined be cause of the paucity of data. In advanced cases, chemotherapy has been prescribed with such effective agents as cisplatin, carboplatin, etoposide and paclitaxel. Here we re port a case of a 64-year-old Taiwanese male patient with neuroendocrine carcinoma of the gall bladder who received combined chemoradiotherapy (CCRT) with cisplatin, 5- fluorouracil and leucovorin (PFL) from June 2009 un til now, and whose disease is stable. CCRT with PFL may be a possible reg i men for high-grade neuroendocrine carcinoma of the gall bladder.     

The molecular pathogenesis and management of bronchial carcinoids

INTRODUCTION: In terms of well-differentiated neuroendocrine tumors (NETs), the lung is the second most common site of occurrence, after the gastro-entero-pancreatic axis, and comprises ～ 25% of all NETs which may occur in various parts of the body. Pulmonary NETs are classified into four groups including typical carcinoid tumors, atypical carcinoid tumors, small cell lung carcinoma and large cell neuroendocrine carcinomas. Among pulmonary NETs, typical and atypical carcinoid tumors of the lung are generally indolent, but do have a (albeit low) potential to metastasize. AREAS COVERED: The molecular biology and novel molecular pathways and drug targets in bronchial carcinoids are reviewed in this paper. A full data search is performed through PubMed over the years 2000 - 2010 with key words 'neuroendocrine tumors of the lung, bronchial carcinoid, lung carcinoid, foregut carcinoid, pulmonary carcinoid, pulmonary NETs, lung NETs, molecular biology, autoradiography, nuclear medicine, treatment'; all relevant publications are included, together with selected publications prior to that date. EXPERT OPINION: Although lying at the benign end of the spectrum of pulmonary NETs, bronchial carcinoids can metastasize, and the pathogenesis of these tumors is poorly understood. Several intracellular signaling pathways are under investigation to define new targets for the successful treatment of these tumors. In terms of treatment, further research should additionally focus on the already known but promising drug options.     

The molecular pathogenesis and management of bronchial carcinoids

Introduction: In terms of well-differentiated neuroendocrine tumors (NETs), the lung is the second most common site of occurrence, after the gastro-entero-pancreatic axis, and comprises ～ 25% of all NETs which may occur in various parts of the body. Pulmonary NETs are classified into four groups including typical carcinoid tumors, atypical carcinoid tumors, small cell lung carcinoma and large cell neuroendocrine carcinomas. Among pulmonary NETs, typical and atypical carcinoid tumors of the lung are generally indolent, but do have a (albeit low) potential to metastasize.

Areas covered: The molecular biology and novel molecular pathways and drug targets in bronchial carcinoids are reviewed in this paper. A full data search is performed through PubMed over the years 2000 – 2010 with key words ‘neuroendocrine tumors of the lung, bronchial carcinoid, lung carcinoid, foregut carcinoid, pulmonary carcinoid, pulmonary NETs, lung NETs, molecular biology, autoradiography, nuclear medicine, treatment’; all relevant publications are included, together with selected publications prior to that date.

Expert opinion: Although lying at the benign end of the spectrum of pulmonary NETs, bronchial carcinoids can metastasize, and the pathogenesis of these tumors is poorly understood. Several intracellular signaling pathways are under investigation to define new targets for the successful treatment of these tumors. In terms of treatment, further research should additionally focus on the already known but promising drug options.     

Review article: future therapies for management of metastatic gastroenteropancreatic neuroendocrine tumours

Background  Gastroenteropancreatic neuroendocrine tumours (GEP NETs) are relatively uncommon tumours that occur anywhere within the gastrointestinal tract. The prevalence of GEP NETs is estimated to be 35 per 100 000 population. Patients often present with metastatic disease and consequently, palliative treatments form the mainstay of therapy.
Aim  To review the current and novel therapeutic options for management of GEP NETs.
Methods  Searches for all studies related to GEP NETs, NETs and carcinoid tumours in Medline and abstracts from international meetings.
Results  Somatostatin analogues remain the first line therapy for management of symptoms of GEP NETs and may have anti-proliferative action. New somatostatin analogues with different somatostatin receptor affinity have been developed. Radionuclide peptide receptor therapy is established in patients with positive somatostatin scintigraphy. A number of new agents and targeted therapies are currently being evaluated in a phase I and II studies and these include angiogenic inhibitors, mammalian target of rapamycin inhibitors and immune therapies.
Conclusions  A number of nonsurgical therapies are available for management of gastroenteropancreatic neuroendocrine tumours. It is hoped, the development of some of these promising novel therapies will expand the therapeutic armamentarium.     

Therapy innovation for the treatment of pancreatic neuroendocrine tumors

INTRODUCTION: Traditional therapeutic approaches for patients with advanced neuroendocrine tumors (NETs) have included treatment with somatostatin analogs, hepatic-directed therapies, interferon and cytotoxic chemotherapy. Current knowledge about biological behavior of pancreatic neuroendocrine tumors (pNETs) has increased in the last decade, and some studies have been conducted to translate in the clinical setting. Among several molecular agents investigated in patients with progressive pNETs, everolimus and sunitinib have been studied in large Phase III trials. Both have produced significant benefit, with improvement in progression-free survival. These results were published last year by NEJM and were updated at the ASCO Annual Meeting in June 2011. AREAS COVERED: This review focuses on the potential molecular targets in pancreatic NETs in the light of recent advances. Furthermore, it summarizes the available data for targeted agents from Phase II and III trials open to patients with this tumor. EXPERT OPINION: These new agents are likely to play an increasingly important role in the future management of advanced pNETs. Their use in earlier phases of the disease could improve clinical outcome, avoiding side effects of the more toxic chemotherapy. The challenge in medical treatment of pNET is to define the patients who can benefit from this innovative therapy; future research should be directed to find predictive markers for response to the targeted agent.     

Novel fluoropyrimidine-based chemotherapy for advanced well-differentiated neuroendocrine tumors: a clinical update

Introduction: Patients with advanced well-differentiated neuroendocrine tumors (NETs) who have bulky and/or symptomatic and/or rapidly progressive disease require chemotherapy treatment.

Areas covered: This review summarizes the accumulating evidence for treatment with fluorouracil-based chemotherapy in well-differentiated NETs. The main clinical studies, toxicity and predictors of fluorouracil- based chemotherapy regimens in well-differentiated NETs are discussed, along with the current issues, future research directions and therapeutic prospects.

Expert opinion: Somatostatin analogs may control symptoms of hormone excess and tumor growth in patients with well-differentiated metastatic NETs, and biological therapies may improve progression-free survival for these patients. However, chemotherapy leads to higher objective response rates and symptom control by reducing tumor bulk. The low response rate and significant toxicities of conventional chemotherapy regimens limit their widespread use. Fortunately, some novel fluoropyrimidine-based treatment including fluorouracil, capecitabine, or S-1 based chemotherapy with or without antiangiogenic agents have been investigated in recent years. These treatments showed significant efficacy and less toxicity in pancreatic and non-pancreatic metastatic well-differentiated NETs. Additionally, non-pancreatic well-differentiated NETs have also achieved similar tumor response or survival comparable to pancreatic NETs. Moreover, some predictors of response to these treatment regimens have been evaluated.