本文選題：神經(jīng)內(nèi)分泌癌 + 胃腸胰神經(jīng)內(nèi)分泌腫瘤��； 參考：《鄭州大學(xué)》2017年碩士論文

【摘要】：神經(jīng)內(nèi)分泌腫瘤(NEN),源于神經(jīng)內(nèi)分泌細(xì)胞和肽能神經(jīng)元,可以產(chǎn)生多肽激素,并且具有神經(jīng)內(nèi)分泌標(biāo)記物,包括一系列惰性緩慢生長(zhǎng)的低度惡性到高轉(zhuǎn)移性等明顯惡性的異質(zhì)性腫瘤,具有廣譜的生物學(xué)行為[1]。以往被認(rèn)為是一類比較罕見的疾病。隨著內(nèi)鏡、生物標(biāo)志物等相關(guān)診斷技術(shù)的發(fā)展和普及,近30年來,NEN的發(fā)病率以及患病率均呈現(xiàn)顯著上升趨勢(shì)。美國(guó)SEER數(shù)據(jù)庫(kù)顯示,NEN發(fā)病率的上升幅度高達(dá)500%。其中消化系統(tǒng)為NEN的最常見發(fā)病部位,GEP-NENs占NEN比例為65%-75%[2]。雖然近年來我國(guó)對(duì)GEP-NENs的報(bào)道也呈上升趨勢(shì),但我國(guó)對(duì)GEP-NENs尚沒有建立覆蓋全國(guó)的腫瘤登記系統(tǒng),因此也缺乏同其他數(shù)據(jù)庫(kù)可比的信息。2010年,世界衛(wèi)生組織[3]提出了一個(gè)新的NEN分類,及詳述其臨床,病理,治療和預(yù)后因素。在西方國(guó)家,NEN的流行病學(xué),治療和存活率已經(jīng)被充分研究[1,2],但亞洲人群中的可比信息有限[4,5]。為了調(diào)查中國(guó)人群的臨床病理特征,轉(zhuǎn)移的危險(xiǎn)因素和NEN的預(yù)后,本文對(duì)我們中心最近5年的該類疾病進(jìn)行了全面的回顧性分析。目的胃腸胰神經(jīng)內(nèi)分泌腫瘤(GEP-NENs)是最常見的神經(jīng)內(nèi)分泌腫瘤類型,占超過一半的神經(jīng)內(nèi)分泌腫瘤(NEN)。本單中心探討胃腸胰神經(jīng)內(nèi)分泌腫瘤(GEP-NENs)的臨床病理特征,篩選轉(zhuǎn)移危險(xiǎn)因素,分析診治及預(yù)后。NEN G3被進(jìn)一步分類為NET G3(具有G3分級(jí)的高分化NET)和NEC,并且在本研究中比較NET G3和NEC的預(yù)后的差異。方法收集鄭州大學(xué)第一附屬醫(yī)院2011年1月至2016年3月所有病理診斷為GEP-NENs的臨床病歷資料,所有病理資料來源于內(nèi)鏡下切除或外科手術(shù)。均采用2010年第4版世界衛(wèi)生組織(WHO)NEN命名及分類標(biāo)準(zhǔn)[3]。收集的信息包括臨床特征(性別,年齡,腫瘤部位和癥狀);診斷方式(內(nèi)鏡和影像學(xué));腫瘤特征(大小,分級(jí),原發(fā)性腫瘤的組織病理學(xué),轉(zhuǎn)移);治療和預(yù)后。根據(jù)2010年第4版世界衛(wèi)生組織(WHO)NEN命名及分類標(biāo)準(zhǔn):根據(jù)Ki-67指數(shù),分級(jí)為G1,G2和G3≤2%,3?20%,20%。類似地,在10高倍鏡視野(HPF)中核分裂象小于2的腫瘤分類為G1,2?20/HPF作為G2,20/HPF作為G3。如果Ki-67指數(shù)的分級(jí)與有絲分裂率的分級(jí)不同,則兩者中的較高者被賦予優(yōu)先權(quán)。因此,GEP-NENs被分類為神經(jīng)內(nèi)分泌瘤(NET)(G1和G2),神經(jīng)內(nèi)分泌癌(NEC)(G3)和混合型腺神經(jīng)內(nèi)分泌癌(MANEC)[3,4]。良好分化的G3 NEN(Ki-67陽性指數(shù)20%;一般小于60%)被歸類為分化良好的NET(NET G3),也稱之為高增殖活性NET[8,9]。結(jié)果1.一般臨床資料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,平均年齡為(54.3±13.5)歲�；颊咦园l(fā)病至首次就診的中位時(shí)間為2.0個(gè)月(3d-6y)。最常見腫瘤原發(fā)部位是胃(24.3%,107/440),其次是直腸(24.1%,106/440),胰腺(20.5%,90/440)。GEP-NENs中大部分腫瘤為非功能性腫瘤(389/440,88.4%),另外51(11.6%)例為功能性腫瘤。主要檢查手段有消化內(nèi)鏡,超聲內(nèi)鏡,B型超聲,CT、MRI、PET-CT,檢出率分別為:消化內(nèi)鏡(99.1%)、超聲內(nèi)鏡(92.7%)、B型超聲(86.7%)、CT(85.4%)、MRI(79.5%)、PET-CT(93.1%)。2.病理學(xué)特征GEP-NENs腫瘤的平均直徑為2.27cm(0.2?16cm)。GEP-NENs腫瘤130例(29.5%)為G1,G2級(jí)腫瘤為120例(27.3%),G3級(jí)腫瘤為190例(43.2%)。最常見的神經(jīng)內(nèi)分泌腫瘤類型是NET(250,56.8%),其次是NEC(146,33.2%)和MANEC(14,3.2%),其他30例被分類為G3級(jí)的高增殖活性G3即NET G3。Syn和CgA的免疫組織化學(xué)陽性率分別為為97.7%和48.7%。腫瘤未轉(zhuǎn)移發(fā)生在63%(277/440)的患者,局部淋巴結(jié)轉(zhuǎn)移發(fā)生于12.3%(54/440)的患者。在確診時(shí)90(20.5%)例患者腫瘤發(fā)現(xiàn)遠(yuǎn)處轉(zhuǎn)移。在隨訪期間,遠(yuǎn)處轉(zhuǎn)移患者增加至109(24.8%)例。最常見的遠(yuǎn)處轉(zhuǎn)移部位是肝臟(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.轉(zhuǎn)移危險(xiǎn)因素分析單因素分析顯示NEN是否轉(zhuǎn)移與患者的性別、年齡、腫瘤直徑、部位、腫瘤功能狀態(tài)、分級(jí)、類型均有關(guān)。多變量Logistic回歸分析腫瘤轉(zhuǎn)移的獨(dú)立危險(xiǎn)因素,結(jié)果顯示腫瘤的直徑和病理分類是轉(zhuǎn)移的重要的預(yù)測(cè)因子。4.治療、隨訪及預(yù)后62.5%患者接受了手術(shù)治療,包括根治性的手術(shù)或姑息性的手術(shù),其中50例為經(jīng)內(nèi)鏡下手術(shù)治療。440例患者中接受化療的有73例,其中34例為術(shù)后輔助化療。所有腫瘤患者的1年,3年和5年生存率分別為78.7%,60.8%和54.5%。G3級(jí)腫瘤患者的1年,3年和5年生存率分別為54.3%,19.4%和7.8%。單變量分析顯示,NET G3、無局部或遠(yuǎn)處轉(zhuǎn)移的患者的生存期優(yōu)于其他NEN G3。所有NEN G3患者的中位生存期為13.0個(gè)月,NET G3中位生存期(中位數(shù)34個(gè)月)明顯高于NEC(中位數(shù)11個(gè)月)。NEN G3腫瘤的中位生存期在未發(fā)生轉(zhuǎn)移腫瘤患者為36個(gè)月,局部轉(zhuǎn)移患者為15個(gè)月,遠(yuǎn)處轉(zhuǎn)移患者為6個(gè)月。結(jié)論1.消化系統(tǒng)神經(jīng)內(nèi)分泌腫瘤最常見發(fā)病部位是胃、直腸、胰腺。以非功能性腫瘤為主,表現(xiàn)為腹痛、消化道出血、腹瀉等非特異性臨床癥狀。功能性腫瘤以胰島素瘤最為常見。2.消化系統(tǒng)神經(jīng)內(nèi)分泌腫瘤轉(zhuǎn)移的危險(xiǎn)因素是腫瘤直徑、分級(jí)。3.腫瘤的預(yù)后:分級(jí)高者預(yù)后較分級(jí)低者腫瘤差;NEN G3腫瘤的中位生存期在未發(fā)生轉(zhuǎn)移腫瘤患者為36個(gè)月,局部轉(zhuǎn)移患者為15個(gè)月,遠(yuǎn)處轉(zhuǎn)移患者為6個(gè)月;NET G3中位生存期(中位數(shù)34個(gè)月)明顯高于NEC(中位數(shù)11個(gè)月)。NET G3、無局部或遠(yuǎn)處轉(zhuǎn)移的患者的生存期優(yōu)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.

【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R735

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10 喬新偉;陳原稼;邱玲;陳杰;向紅丁;魯重美;;胰腺神經(jīng)內(nèi)分泌腫瘤病人手術(shù)前后以及術(shù)后復(fù)發(fā)時(shí)血清鉻粒素A的變化[A];2012中國(guó)消化系疾病學(xué)術(shù)大會(huì)論文匯編[C];2012年

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7 李e，

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