440例胃肠胰神经内分泌肿瘤的临床病理特征及诊治分析

发布时间：2018-04-25 01:40

本文选题：神经内分泌癌 + 胃肠胰神经内分泌肿瘤　；参考：《郑州大学》2017年硕士论文

【摘要】：神经内分泌肿瘤(NEN),源于神经内分泌细胞和肽能神经元,可以产生多肽激素,并且具有神经内分泌标记物,包括一系列惰性缓慢生长的低度恶性到高转移性等明显恶性的异质性肿瘤,具有广谱的生物学行为[1]。以往被认为是一类比较罕见的疾病。随着内镜、生物标志物等相关诊断技术的发展和普及,近30年来,NEN的发病率以及患病率均呈现显著上升趋势。美国SEER数据库显示,NEN发病率的上升幅度高达500%。其中消化系统为NEN的最常见发病部位,GEP-NENs占NEN比例为65%-75%[2]。虽然近年来我国对GEP-NENs的报道也呈上升趋势,但我国对GEP-NENs尚没有建立覆盖全国的肿瘤登记系统,因此也缺乏同其他数据库可比的信息。2010年,世界卫生组织[3]提出了一个新的NEN分类,及详述其临床,病理,治疗和预后因素。在西方国家,NEN的流行病学,治疗和存活率已经被充分研究[1,2],但亚洲人群中的可比信息有限[4,5]。为了调查中国人群的临床病理特征,转移的危险因素和NEN的预后,本文对我们中心最近5年的该类疾病进行了全面的回顾性分析。目的胃肠胰神经内分泌肿瘤(GEP-NENs)是最常见的神经内分泌肿瘤类型,占超过一半的神经内分泌肿瘤(NEN)。本单中心探讨胃肠胰神经内分泌肿瘤(GEP-NENs)的临床病理特征,筛选转移危险因素,分析诊治及预后。NEN G3被进一步分类为NET G3(具有G3分级的高分化NET)和NEC,并且在本研究中比较NET G3和NEC的预后的差异。方法收集郑州大学第一附属医院2011年1月至2016年3月所有病理诊断为GEP-NENs的临床病历资料,所有病理资料来源于内镜下切除或外科手术。均采用2010年第4版世界卫生组织(WHO)NEN命名及分类标准[3]。收集的信息包括临床特征(性别,年龄,肿瘤部位和症状);诊断方式(内镜和影像学);肿瘤特征(大小,分级,原发性肿瘤的组织病理学,转移);治疗和预后。根据2010年第4版世界卫生组织(WHO)NEN命名及分类标准:根据Ki-67指数,分级为G1,G2和G3≤2%,3?20%,20%。类似地,在10高倍镜视野(HPF)中核分裂象小于2的肿瘤分类为G1,2?20/HPF作为G2,20/HPF作为G3。如果Ki-67指数的分级与有丝分裂率的分级不同,则两者中的较高者被赋予优先权。因此,GEP-NENs被分类为神经内分泌瘤(NET)(G1和G2),神经内分泌癌(NEC)(G3)和混合型腺神经内分泌癌(MANEC)[3,4]。良好分化的G3 NEN(Ki-67阳性指数20%;一般小于60%)被归类为分化良好的NET(NET G3),也称之为高增殖活性NET[8,9]。结果1.一般临床资料440例GEP-NENs患者中男性患者占259(58.9%)例,女性患者占181(41.1%)例,男女比例1.43:1,平均年龄为(54.3±13.5)岁。患者自发病至首次就诊的中位时间为2.0个月(3d-6y)。最常见肿瘤原发部位是胃(24.3%,107/440),其次是直肠(24.1%,106/440),胰腺(20.5%,90/440)。GEP-NENs中大部分肿瘤为非功能性肿瘤(389/440,88.4%),另外51(11.6%)例为功能性肿瘤。主要检查手段有消化内镜,超声内镜,B型超声,CT、MRI、PET-CT,检出率分别为:消化内镜(99.1%)、超声内镜(92.7%)、B型超声(86.7%)、CT(85.4%)、MRI(79.5%)、PET-CT(93.1%)。2.病理学特征GEP-NENs肿瘤的平均直径为2.27cm(0.2?16cm)。GEP-NENs肿瘤130例(29.5%)为G1,G2级肿瘤为120例(27.3%),G3级肿瘤为190例(43.2%)。最常见的神经内分泌肿瘤类型是NET(250,56.8%),其次是NEC(146,33.2%)和MANEC(14,3.2%),其他30例被分类为G3级的高增殖活性G3即NET G3。Syn和CgA的免疫组织化学阳性率分别为为97.7%和48.7%。肿瘤未转移发生在63%(277/440)的患者,局部淋巴结转移发生于12.3%(54/440)的患者。在确诊时90(20.5%)例患者肿瘤发现远处转移。在随访期间,远处转移患者增加至109(24.8%)例。最常见的远处转移部位是肝脏(67/109,61.5%),其次是腹膜(18.3%,20/109),肺(10.1%,11/109)和骨(6.4%,7/109)。3.转移危险因素分析单因素分析显示NEN是否转移与患者的性别、年龄、肿瘤直径、部位、肿瘤功能状态、分级、类型均有关。多变量Logistic回归分析肿瘤转移的独立危险因素,结果显示肿瘤的直径和病理分类是转移的重要的预测因子。4.治疗、随访及预后62.5%患者接受了手术治疗,包括根治性的手术或姑息性的手术,其中50例为经内镜下手术治疗。440例患者中接受化疗的有73例,其中34例为术后辅助化疗。所有肿瘤患者的1年,3年和5年生存率分别为78.7%,60.8%和54.5%。G3级肿瘤患者的1年,3年和5年生存率分别为54.3%,19.4%和7.8%。单变量分析显示,NET G3、无局部或远处转移的患者的生存期优于其他NEN G3。所有NEN G3患者的中位生存期为13.0个月,NET G3中位生存期(中位数34个月)明显高于NEC(中位数11个月)。NEN G3肿瘤的中位生存期在未发生转移肿瘤患者为36个月,局部转移患者为15个月,远处转移患者为6个月。结论1.消化系统神经内分泌肿瘤最常见发病部位是胃、直肠、胰腺。以非功能性肿瘤为主,表现为腹痛、消化道出血、腹泻等非特异性临床症状。功能性肿瘤以胰岛素瘤最为常见。2.消化系统神经内分泌肿瘤转移的危险因素是肿瘤直径、分级。3.肿瘤的预后:分级高者预后较分级低者肿瘤差;NEN G3肿瘤的中位生存期在未发生转移肿瘤患者为36个月,局部转移患者为15个月,远处转移患者为6个月;NET G3中位生存期(中位数34个月)明显高于NEC(中位数11个月)。NET G3、无局部或远处转移的患者的生存期优于其他NEN G3。
[Abstract]:Neuroendocrine tumors (NEN), derived from neuroendocrine cells and peptiderma neurons, can produce polypeptide hormones and have neuroendocrine markers, including a series of evidently malignant heterogenous tumors, such as a series of inert slow growth, low malignancy to high metastasis, and the broad spectrum of biological behavior [1]. has been considered a kind of relatively rare. With the development and popularization of endoscopy, biomarkers and other related diagnostic techniques, the incidence and prevalence of NEN have increased significantly in the last 30 years. The American SEER database shows that the incidence of NEN is up to 500%. and the most common site of NEN is the digestive system, and the proportion of GEP-NENs to NEN is 65%-75%[2].. Although China's reports on GEP-NENs have been rising in recent years, China has not yet established a nationwide tumor registration system for GEP-NENs, and therefore lack of comparable information to other databases,.2010, the WHO [3] proposed a new NEN classification and detailed its clinical, pathological, therapeutic and prognostic factors in the West. At home, the epidemiology, treatment and survival rate of NEN have been fully studied [1,2], but the comparable information in the Asian population is limited [4,5]. to investigate the clinicopathological features of the Chinese population, the risk factors of metastasis, and the prognosis of NEN. This article has conducted a comprehensive retrospective analysis of the disease in our Center for the last 5 years. Endocrine neoplasm (GEP-NENs) is the most common type of neuroendocrine tumor, which accounts for more than half of the neuroendocrine tumor (NEN). The clinicopathological features of the gastrointestinal pancreatic neuroendocrine tumor (GEP-NENs) are discussed in this single center, the risk factors for metastasis are screened, and the diagnosis and treatment and the pre.NEN G3 are further classified as NET G3 (with the high score of G3 grading). NET and NEC, and the differences in the prognosis of NET G3 and NEC were compared in this study. Methods the clinical records of all pathological diagnoses of GEP-NENs from January 2011 to March 2016 of the First Affiliated Hospital of Zhengzhou University were collected. All pathological data were derived from endoscopic resection or surgery. The fourth edition of WHO (WHO) NEN, 2010 2010, was used. The information collected by the naming and classification standard [3]. includes clinical features (sex, age, tumor site and symptoms); diagnostic methods (endoscopy and imaging); tumor characteristics (size, grading, primary tumor histopathology, metastasis); treatment and prognosis. According to the name and classification criteria of the fourth edition of WHO (WHO) 2010: according to the Ki-67 index G1, G2 and G3 < 2%, 3? 20%, 20%. similar, the tumor of the mitosis like less than 2 in the 10 high magnification field of vision (HPF) is classified as G1,2? 20/HPF as G2,20/HPF as G3. if the Ki-67 index classification is different from the mitosis rate, then the higher of the two is given priority. Therefore, GEP-NENs is classified as neuroendocrine tumor (NET). (G1 and G2), neuroendocrine carcinoma (NEC) (G3) and mixed adenocarcinoma (MANEC) [3,4]. well differentiated G3 NEN (Ki-67 positive index 20%; generally less than 60%) classified as well differentiated NET (NET G3), also known as high proliferative activity results 1. general clinical data, 440 cases of male patients accounted for 259 (58.9%) cases, women, women. The sex ratio was 181 (41.1%) cases, the proportion of men and women was 1.43:1, the average age was (54.3 + 13.5) years. The median time of the onset to the first visit was 2 months (3d-6y). The most common primary site of the tumor was the stomach (24.3%, 107/440), the second was the rectum (24.1%, 106/440), and the most of the tumors in the pancreas (20.5%, 90/440) were nonfunctional tumors (389/440,8 8.4%), the other 51 (11.6%) cases were functional tumors. The main methods were digestive endoscopy, endoscopic ultrasonography, B ultrasound, CT, MRI, PET-CT, and the detection rates were: digestive endoscopy (99.1%), endoscopic ultrasonography (92.7%), B type ultrasound (86.7%), CT (85.4%), MRI (79.5%), and PET-CT (93.1%).2. pathological features, the average diameter of GEP-NENs tumor was 2.27cm (0.2 16cm). Ns tumor in 130 cases (29.5%) was G1, grade G2 tumor was 120 cases (27.3%), G3 tumor was 190 (43.2%). The most common neuroendocrine tumor type was NET (250,56.8%), followed by NEC (146,33.2%) and MANEC (14,3.2%), and the other 30 cases were classified as G3 class, and the immunological positive rate was 97.7% and 4, respectively. 8.7%. tumors were not metastases in 63% (277/440) patients. Local lymph node metastasis occurred in 12.3% (54/440) patients. 90 (20.5%) patients found distant metastases at the time of diagnosis. During follow-up, the distant metastasis increased to 109 (24.8%). The most common distant metastasis site was the liver (67/109,61.5%), followed by peritoneum (18.3%, 20/109). A single factor analysis of the risk factors of lung (10.1%, 11/109) and bone (6.4%, 7/109).3. metastasis showed that the metastasis of NEN was related to the sex, age, tumor size, site, tumor function, classification, type of the patient. Independent risk factors of tumor metastasis were analyzed by multivariable Logistic regression. The results showed that the diameter of the tumor and the pathological classification of the tumor were transferred. The important predictor of migration,.4. treatment, follow-up and prognosis of 62.5% patients received surgical treatment, including radical surgery or palliative surgery, of which 50 cases underwent endoscopic surgery for 73 cases of.440 patients receiving chemotherapy, of which 34 were postoperative adjuvant chemotherapy. The 1 years of cancer patients, 3 and 5 year survival rates were 78, respectively. The 1, 3, and 5 year survival rates of patients with.7%, 60.8%, and 54.5%.G3 tumors were 54.3%, 19.4%, and 7.8%. univariate analysis showed that the survival period of NET G3 without local or distant metastasis was 13 months better than that of all other NEN G3 patients with other NEN G3., and NET G3 median survival (median median 34 months) was significantly higher than that of the median NEC (median number). For 11 months) the median survival of.NEN G3 tumor was 36 months without metastatic tumor, 15 months for local metastasis and 6 months for distant metastases. Conclusion the most common sites in the 1. digestive system neuroendocrine tumor are stomach, rectum, and pancreas. Nonfunctional tumors are mainly abdominal pain, gastrointestinal bleeding and diarrhea. Heterosexual clinical symptoms. The most common risk factors for the metastasis of the.2. digestive system with functional tumors were tumor diameter and classification of.3. tumors: the prognosis of higher grade.3. tumors was worse than that of low grade ones; the median survival time of NEN G3 tumor was 36 months in patients with no metastatic tumors and 15 for local metastases. Patients with distant metastasis were 6 months, and the median survival period of NET G3 (median 34 months) was significantly higher than NEC (median 11 months).NET G3, and the survival time of patients with no local or distant metastasis was better than that of other NEN G3.

【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R735

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