胃肠道神经内分泌肿瘤的临床病理特征及内镜治疗进展

胃肠道神经内分泌肿瘤（GI-NEN,NEN）近年来受到越来越多的关注。NEN的生物学特性、恶性程度、病理学特征及预后差异很大,多数患者缺乏典型临床表现,有效的治疗方式也颇有争论,而内镜治疗对于局限于黏膜及黏膜下层的NEN越来越体现出它的价值。     

胃肠道神经内分泌肿瘤手术方式选择的对照研究

目的:探讨胃肠道神经内分泌肿瘤(GI-NENs)的内镜表现、诊治方法及预后相关因素。方法:回顾性分析行内镜切除或外科手术诊治的119例GI-NENs患者的临床资料,比较2种治疗方式的疗效和预后。结果:119例GI-NENs患者,病灶分布以直肠最多见(83例,69. 75%),其次为胃(13例,10. 92%)和十二指肠(12例,10. 08%)。病灶直径≤1 cm者54例,1～2 cm者49例,≥2 cm者16例。119例中G1级65例,G2级54例。80例患者采用内镜下治疗,包括73例G1级和7例G2级患者; 39例患者采用外科手术治疗,包括28例G1级和11例G2级患者。2组完全切除率差异无统计学意义(93. 75%vs 94. 87%,P 0. 05),内镜治疗组的住院时间显著短于外科手术组[(11. 26±5. 93) d vs (20. 00±13. 44) d,P 0. 05],且并发症更少、更轻。随访5～77个月,内镜治疗组有1例术后1年局部复发;外科手术组有2例分别出现局部淋巴结及远处转移。结论:内镜切除治疗GI-NENs疗效好、住院时间短、早期和远期并发症少且轻。对于直径2 cm且不伴有局部或远处转移的GI-NENs,内镜切除可作为首选治疗方法。     

内镜诊断胃混合性神经内分泌-非神经内分泌肿瘤1例

报道1例内镜下诊断胃混合性神经内分泌-非神经内分泌肿瘤病例,结合病例的诊疗过程,分析总结其组织学起源、临床特点及内镜诊疗等。     

内镜黏膜下剥离术治疗食管混合性神经内分泌-非神经内分泌肿瘤1例

<正>混合性神经内分泌-非神经内分泌肿瘤(mixedneuroendocrine-non-neuroendocrine neoplasm,MiNEN)是临床上较为罕见的神经内分泌成分和非神经内分泌成分分别至少占病变的30%的肿瘤^[1-2]。其发病率低,多见于中老年男性,临床表现缺乏特异性,确诊需依靠术后病理组织活检联合特异性的免疫组织化学检测^[3]。由于其罕见性,治疗方式的选择上并无明确的指南和规范,对于局限期的肿瘤,主要采取根治性外科手术切除。而进展期肿瘤,主要予以放化疗和其它分子靶向药物治疗^[4]。有文献综述认为,随着内镜技术的发展,神经内分泌肿瘤可在综合评估的基础上,适当的进行内镜下黏膜切除术(EMR)或内镜粘膜下剥离术(ESD)治疗,术后根据病理情况考虑是否追加外科手术及辅助放化疗^[5]。本文报道了1例ESD治疗食管MiNEN病例,为该疾病诊断及治疗提供临床参考。     

内镜下治疗直肠神经内分泌肿瘤的临床效果

目的 比较不同内镜下治疗方式对直肠神经内分泌肿瘤(rectal neuroendocrine tumors, R-NET)的临床疗效。方法 回顾性分析2015年1月至2022年5月于武汉大学人民医院消化内科经内镜下治疗后确诊为R-NET的81例患者的临床资料。结果 81例R-NET患者均在内镜下成功切除病灶,病灶多呈表面光滑隆起型或息肉样病变(95.1%),色泽多为正常或淡黄色(92.6%),大部分位于距肛门5～10 cm处(72.8%)。内镜黏膜下剥离术(endoscopic submucosal dissection, ESD)组61例,其中50例行超声肠镜检查,结果提示,肿瘤起源于黏膜层、黏膜下层43例,固有肌层7例;内镜下黏膜切除术(endoscopic mucosal resection, EMR)组20例,仅2例行EUS检查,其中黏膜层1例,黏膜下层1例;两组在术前EUS检出率差异有统计学意义(P<0.001)。内镜治疗中,EMR较ESD手术时间短、住院时间短、治疗费用低(P均<0.001),而手术并发症发生率差异无统计学意义(P>0.05)。免疫组化结果...     

胃肠胰神经内分泌肿瘤的内镜诊治进展

神经内分泌肿瘤以胃肠胰神经内分泌肿瘤最常见,其在各消化器官中的组织形态学、病理分型、免疫表型、生物学行为等方面各有不同,相关的治疗手段及预后情况亦差别很大。本文通过解读相关指南,对胃肠胰神经内分泌肿瘤的内镜诊治进展作一梳理。     

内镜黏膜下剥离术治疗上消化道神经内分泌肿瘤的临床价值

目的 探讨内镜黏膜下剥离术(ESD)治疗上消化道神经内分泌肿瘤的安全性及其疗效.方法 采用ESD方法对19例上消化道神经内分泌肿瘤进行治疗,术后标本送病理检查,记录不良反应发生情况及疗效,随访肿瘤复发及转移情况.结果 肿瘤直径0.4 ～1.5 cm,平均0.9 cm,均一次性完整剥离切除,ESD手术时间(自黏膜下注射至完整剥离病变)15～ 50 min,平均20 min,无严重出血及穿孔发生.术后18例病理诊断为神经内分泌瘤,其中G1级16例、G2级2例,基底和切缘均未见病变累及;另1例病理显示有浸润性生长倾向,诊断神经内分泌癌(G3级),行外科扩大切除,术后病理未见肿瘤组织残留,无淋巴结转移.平均随访28个月,无一例出现肿瘤复发和转移.结论 ESD治疗上消化道神经内分泌肿瘤具有较好的安全性和疗效,值得在临床上推广应用.     

超声内镜在胰腺神经内分泌肿瘤诊治的新进展

胰腺神经内分泌肿瘤占胰腺原发性肿瘤的1%~2%,呈逐年上升趋势。因其具有独特的生物学表现,超声内镜在其诊疗中具有精准、安全、有效的优势。就胰腺神经内分泌肿瘤的诊疗历程进行了回顾,并展望了未来的研究方向。     

MEN1基因与胃肠道胰腺神经内分泌肿瘤

MEN1基因为多发性内分泌腺肿瘤(MEN1)的易感基因,在调节基因的转录、维持基因的稳定、调控细胞的分裂和增殖方面起重要作用,而MEN1基因失活可能与胃肠道胰腺神经内分泌肿瘤(GEP-NET)发生机制有关。     

放大内镜窄带成像对于胃神经内分泌肿瘤的诊断价值

目的:分析运用白光内镜(WLI)及放大内镜窄带成像(ME-NBI)诊断胃神经内分泌肿瘤(G-NENs)的特点并探讨其临床诊断价值。方法:选择2017年1月-2021年6月西安市人民医院收治的36例G-NENs患者(观察组)及同期收治的40例胃息肉患者(对照组)临床资料,分析观察组临床病理特点及2组病变ME-NBI特点。结果:WLI结合ME-NBI诊断G-NENs敏感性为80.6%,特异性为90.0%,阳性预测值为87.9%,阴性预测值为83.7%,准确度为85.5%,约登指数为0.71。结论:WLI结合ME-NBI有利于观察G-NENs表面特异性的腺体结构改变及上皮下黑棕色迂曲增粗的螺旋状血管,对于鉴别G-NENs及胃息肉有重要意义,能够针对性地对病灶进行靶向活检,避免漏诊及误诊,并对正确治疗方式选择提供帮助。     

内镜超声在胃肠神经内分泌瘤诊治中的应用价值

【摘要】目的探讨EUS在胃肠神经内分泌瘤（GI—NEN）诊治中的应用价值。方法回顾性总结44例行内镜检查并经组织病理及免疫组化确诊的GI—NEN患者的临床资料、EUS下特点及EUS指导下的内镜治疗情况和术后随访结果。结果44例共发现47处病灶（其中有2例为多发）,其中4l处病理证实为神经内分泌瘤,6处病理证实为神经内分泌癌。EUS诊断41处神经内分泌瘤中18处起源于黏膜层、23处起源于黏膜下层,与病理结果符合率为100．O％,均为低回声团块,内部回声均匀,边界较清楚。41处神经内分泌瘤均行EUS指导下的内镜切除术,其中17处行EMR或ESD切除、24处行高频电切除,术后患者均恢复良好,分别于术后3—6个月、12个月复查胃肠镜和（或）EUS,显示创面愈合良好,病变切除处胃肠壁各层次清晰,原病灶边缘取组织活检均证实无残留及复发。结论EUS可准确判断GI—NEN病灶的起源、大小、边界、回声等,为最佳治疗方式的选择提供重要信息,在GI—NEN的诊治中有较高的应用价值。     

Current updates and future directions in diagnosis and management of gastroenteropancreatic neuroendocrine neoplasms

Gastroenteropancreatic neuroendocrine neoplasms are a heterogenous group of rare neoplasms that are increasingly being discovered, often incidentally, throughout the gastrointestinal tract with varying degrees of activity and malignant potential. Confusing nomenclature has added to the complexity of managing these lesions. The term carcinoid tumor and embryonic classification have been replaced with gastroenteropancreatic neuroendocrine neoplasm, which includes gastrointestinal neuroendocrine and pancreatic neuroendocrine neoplasms. A comprehensive multidisciplinary approach is important for clinicians to diagnose, stage and manage these lesions. While histological diagnosis is the gold standard, recent advancements in endoscopy, conventional imaging, functional imaging, and serum biomarkers complement histology for tailoring specific treatment options. In light of developing technology, our review sets out to characterize diagnostic and therapeutic advancements for managing gastroenteropancreatic neuroendocrine tumors, including innovations in radiolabeled peptide imaging, circulating biomarkers, and endoscopic treatment approaches adapted to different locations throughout the gastrointestinal system.     

New insights in diagnosis and treatment of gastroenteropancreatic neuroendocrine neoplasms

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare epithelial neoplasms derived from pluripotent endocrine cells along the gastrointestinal tract and pancreas. GEP-NENs are classified into well-differentiated neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas. Despite overlapping morphological features, GEP-NENs vary in molecular biology, epigenetic, clinical behavior, treatment response, and prognosis features and remain an unmet clinical challenge. In this review, we introduce recent updates on the histopathologic classification, including the tumor grading and staging system, molecular genetics, and systemic evaluation of the diagnosis and treatment of GEP-NENs at different anatomic sites, together with some insights into the diagnosis of challenging and unusual cases. We also discuss the application of novel therapeutic approaches for GEP-NENs, including peptide receptor radionuclide therapy, targeted therapy, and immunotherapy with immune checkpoint inhibitors. These findings will help improve patient care with precise diagnosis and individualized treatment of patients with GEP-NENs.     

Update on surgical treatment of pancreatic neuroendocrine neoplasms

Pancreatic neuroendocrine neoplasms (PNENs) are rare and account for only 2%-4% of all pancreatic neoplasms. All PNENs are potential (neurendocrine tumors PNETs) or overt (neuroendocrine carcinomas PNECs) malignant, but a subset of PNETs is low-risk. Even in case of low-risk PNETs surgical resection is frequently required to treat hormone-related symptoms and to obtain an appropriate pathological diagnosis. Low-risk PNETs in the body and the tail are ideal for minimally-invasive approaches which should be tailored to the individual patient. Generally, surgeons must aim for parenchyma sparing in these cases. In high-risk and malignant PNENs, indications for tumor resection are much wider than for pancreatic adenocarcinoma, in many cases due to the relatively benign tumor biology. Thus, patients with locally advanced and metastatic PNETs may benefit from extensive resection. In experienced hands, even multi-organ resections are accomplished with acceptable perioperative morbidity and mortality rates and are associated with excellent long term survival. However, poorly differentiated neoplasms with high proliferation rates are associated with a dismal prognosis and may frequently only be treated with chemotherapy. The evidence on surgical treatment of PNENs stems from reviews of mostly single-center series and some analyses of nation-wide tumor registries. No randomized trial has been performed to compare surgical and non-surgical therapies in potentially resectable PNEN. Though such a trial would principally be desirable, ethical considerations and the heterogeneity of PNENs preclude realization of such a study. In the current review, we summarize recent advances in the surgical treatment of PNENs.     

Endoscopic diagnosis of gastrointestinal graft-versus-host disease

AIM：To evaluate the diagnostic value of endoscopy in patients with gastrointestinal graft-versus-host disease （GI GVHD）. METHODS：We identified 8 patients with GI GVHD following allogeneic hematopoietic stem cell trans-plantation （HSCT）. GVHD was defined histologically as the presence of gland apoptosis, not explained by other inflammatory or infectious etiologies. RESULTS：The symptoms of GI GVHD included anorexia, nausea, vomiting, watery diarrhea, abdominal pain, GI bleeding, etc. Upper endoscopic appearance varied from subtle mucosal edema, hyperemia, erythema to obvious erosion. Colonoscopic examination showed diffuse edema, hyperemia, patchy erosion, scattered ulcer, sloughing and active bleeding. Histological changes in GI GVHD included apoptosis of crypt epithelial cells, dropout of crypts, and lymphocytic infiltration in epithelium and lamina propria. The involvement of stomach and rectocolon varied from diffuse to focal. CONCLUSION：Endoscopy may play a significant role in early diagnosis of GI GVHD patients following allogeneic HSCT, and histologic examination of gastrointestinal biopsies is needed to confirm the final diagnosis.     

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。     

胃肠神经内分泌肿瘤和胰腺神经内分泌肿瘤的区别

胃肠胰神经内分泌肿瘤（GEP-NETs）主要来源于胃肠胰系统的神经内分泌细胞,这一细胞系统和肿瘤是以表达细胞类型特异的肽激素和普通标记物（突触囊泡蛋白、铬粒素A）为特征。其特点为：临床上少见;肿瘤通常较小（〈1 cm）;生长速度较慢（数月或数年）,呈阶段性表达,可能数年无症状;通常在出现症状前即有转移,转移部位多为肝脏和骨,而此时肿瘤的体积通常〉2cm。因此这类肿瘤经常被误诊,诊断过程较复杂,不单单依靠临床,往往需要高端的实验室和扫描手段支持。而GEP-NETs中胃肠神经内分泌肿瘤（NET）和胰腺NET,两者在临床表现、诊断和治疗方面也有不同,需要临床医生重视和加以区分。     

Advances in medical treatment for pancreatic neuroendocrine neoplasms

Pancreatic neuroendocrine neoplasms (PanNENs) are rare neoplasms with strong heterogeneity that have experienced an increasing incidence rate in recent years. For patients with locally advanced or distant metastatic PanNENs, systemic treatment options vary due to the different differentiations, grades and stages. The available options for systemic therapy include somatostatin analogs, mole-cularly targeted agents, cytotoxic chemotherapeutic agents, immune checkpoint inhibitors, and peptide receptor radionuclide therapy. In addition, the development of novel molecularly targeted agents is currently in progress. The sequence of selection between different chemotherapy regimens has been of great interest, and resistance to chemotherapeutic agents is the major limitation in their clinical application. Novel agents and high-level clinical evidence continue to emerge in the field of antiangiogenic agents. Peptide receptor radionuclide therapy is increasingly employed for the treatment of advanced neuroendocrine tumors, and greater therapeutic efficacy may be achieved by emerging radio-labeled peptides. Since immune checkpoint inhibitor monotherapies for PanNENs appear to have limited antitumor activity, dual immune checkpoint inhibitor therapies or combinations of antiangiogenic therapies and immune checkpoint inhibitors have been applied in the clinic to improve clinical efficacy. Combining the use of a variety of agents with different mechanisms of action provides new possibilities for clinical treatments. In the future, the study of systemic therapies will continue to focus on the screening of the optimal benefit population and the selection of the best treatment sequence strategy with the aim of truly achieving individualized precise treatment of PanNENs.