發(fā)布時(shí)間：2018-03-18 15:18

  本文選題：食管癌　切入點(diǎn)：新輔助治療　出處：《河北醫(yī)科大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：目的:研究分析食管鱗狀細(xì)胞癌(Esophageal squamous cell carcinoma,ESCC)的臨床資料與組織病理學(xué)特征,探討影響食管鱗狀細(xì)胞癌患者術(shù)后的生存因素;對(duì)比分析ESCC患者術(shù)前進(jìn)行新輔助治療(NACRT)與術(shù)后組織病理學(xué)證實(shí)淋巴結(jié)轉(zhuǎn)移陽性聯(lián)合輔助化療或放療患者的預(yù)后及相關(guān)影響因素;確定腫瘤干細(xì)胞(CSC)標(biāo)記物CD44與細(xì)胞增殖相關(guān)核抗原(Ki-67)的表達(dá)狀態(tài)在NACRT后進(jìn)行根治性食管切除術(shù)的ESCC患者的化療效能和對(duì)預(yù)后的影響。方法:1回顧性分析2008年1月至2010年12月間河北醫(yī)科大學(xué)第四醫(yī)院收治的組織病理學(xué)診斷為食管鱗狀細(xì)胞癌并隨即進(jìn)行手術(shù)的1782例患者,隨訪成功共1550例,失訪232例,隨訪率為86.9%。記錄觀察食管癌患者的臨床資料和組織病理學(xué)特征,采用統(tǒng)計(jì)學(xué)軟件SPSS 21.00對(duì)所記錄的數(shù)據(jù)進(jìn)行統(tǒng)計(jì)學(xué)分析。2回顧性分析2006-2016年間術(shù)前進(jìn)行新輔助治療的110例患者以及術(shù)前無其他治療、直接進(jìn)行食管根治性切除術(shù)且術(shù)后病理證實(shí)淋巴結(jié)轉(zhuǎn)移后聯(lián)合化/放療的106例患者資料。手術(shù)結(jié)果由以下R分類定義:R0,無殘余腫瘤;R1,微觀殘余腫瘤;R2,宏觀殘余腫瘤。運(yùn)用統(tǒng)計(jì)學(xué)軟件SPSS 21.00,對(duì)所記錄的數(shù)據(jù)進(jìn)行統(tǒng)計(jì)學(xué)分析。3標(biāo)本均經(jīng)10%福爾馬林固定,常規(guī)取材,石蠟包埋制片,進(jìn)行HE染色及免疫組織化學(xué)染色,光鏡觀察。依據(jù)陽性細(xì)胞所占比例以及染色強(qiáng)度分析:染色強(qiáng)度以0分為無色,1分為淡黃色,2分為棕黃色,3分為棕褐色;1~2分為弱陽性,3分為強(qiáng)陽性。陽性細(xì)胞所占比例0分為陰性,l分為陽性細(xì)胞數(shù)20%,2分為陽性細(xì)胞數(shù)在21%~60%,3分為陽性細(xì)胞數(shù)在61%~80%,4分為陽性細(xì)胞數(shù)80%;1~2分為低百分比,3~4分為高百分比。以陽性細(xì)胞數(shù)所占的百分比與染色強(qiáng)度的乘積作為判定標(biāo)準(zhǔn):陰性為0分,低表達(dá)為1~8分,高表達(dá)為9~12分。采用統(tǒng)計(jì)學(xué)軟件SPSS 21.00進(jìn)行分析和處理,Kaplan-Meier法進(jìn)行單因素生存分析,Cox法進(jìn)行多因素生存分析,組間比較使用Log-rank檢驗(yàn),多因素使用Logistic回歸分析法,P0.05為差異具有統(tǒng)計(jì)學(xué)意義。結(jié)果:1本研究1782例ESCC患者,直至隨訪截止日為止,失訪232例,隨訪率為86.9%。生存時(shí)間1~108個(gè)月,中位生存時(shí)間58個(gè)月,平均生存時(shí)間57個(gè)月�；颊叩陌l(fā)病年齡18~81歲,中位年齡60歲,平均年齡59.9歲。生存時(shí)間按照手術(shù)日期到死亡日期計(jì)算,本實(shí)驗(yàn)食管癌患者的1年、3年、5年、7年生存率分別為88.7%、61.9%、48.3%、30.4%。臨床分期Ⅰ期患者236例,1年、3年、5年、7年生存率分別為97.0%、90.3%、82.9%、58.8%。Ⅱ期患者747例,1年、3年、5年、7年生存率分別為92.7%、90.1%、82.7%、33.9%。Ⅲ期患者549例,1年、3年、5年、7年生存率分別為79.8%、39.5%、24.2%、14.5%。腫瘤位上段205例,中段1092例,下段253例;復(fù)發(fā)或淋巴結(jié)轉(zhuǎn)移率38.58%(598/1550),脈管瘤栓陽性率為25.61%(397/1550);組織學(xué)病理分級(jí)G1為121例,G2為1161例,G3為268例;腫瘤浸潤(rùn)深度T1為281例,T2為259例,T3為1010例。Kaplan-Meier單因素分析結(jié)果顯示:性別、腫瘤浸潤(rùn)深度、組織病理學(xué)分型、臨床分期、治療方式、有無脈管瘤栓及神經(jīng)受侵、有無淋巴結(jié)轉(zhuǎn)移與食管癌患者的預(yù)后有關(guān)聯(lián)(P均0.05);發(fā)病年齡、腫瘤部位與食管癌患者的預(yù)后無關(guān)。Cox多因素分析結(jié)果顯示:性別、腫瘤浸潤(rùn)深度、臨床分期、組織病理學(xué)分級(jí)、有無淋巴結(jié)轉(zhuǎn)移是食管癌患者預(yù)后的獨(dú)立影響因素(P均0.05)。對(duì)于淋巴結(jié)轉(zhuǎn)移的單因素分析結(jié)果:臨床分期、組織病理學(xué)分級(jí)、腫瘤浸潤(rùn)深度、有無脈管瘤栓及神經(jīng)受侵與食管癌患者淋巴結(jié)轉(zhuǎn)移有關(guān)聯(lián)(P均0.05)。采用Logistic進(jìn)行多因素分析顯示:組織病理學(xué)分級(jí)、腫瘤浸潤(rùn)深度、有無脈管瘤栓是食管癌患者淋巴結(jié)轉(zhuǎn)移預(yù)后的獨(dú)立影響因素(P均0.05)。2在NACRT組和術(shù)前未經(jīng)治療組之間觀察到生存率(NACRT組的1年、3年、5年生存率分別為97.4%、60.7%、40.4%;術(shù)前未治療組的1年、3年、5年生存率分別為98.8%、80.3%、55.1%)差異有統(tǒng)計(jì)學(xué)意義(P0.01)。對(duì)于NACRT組和術(shù)前未治療組術(shù)后治療效果均為R0的患者,生存差異不明顯(NACRT組的5年的生存率為54.3%;術(shù)前未治療組的5年的生存率為51.3%,P=0.087)。3 NACRT組CD44和Ki-67的表達(dá)與臨床病理指標(biāo)的相關(guān)性CD44和Ki-67陽性細(xì)胞在新輔助治療聯(lián)合手術(shù)切除后標(biāo)本中可以廣泛觀察到。在一些具有良好化療效應(yīng)的情況下,NACRT之后在ESCC的切除標(biāo)本的壞死和纖維化區(qū)域中觀察到CD44陽性細(xì)胞簇。然而,在具有差的化療效應(yīng)的情況下,CD44陽性細(xì)胞分布呈彌漫片狀分布。在NACRT后切除標(biāo)本中具有CD44強(qiáng)陽性表達(dá)的ESCC患者顯示比CD44弱陽性表達(dá)的患者的預(yù)后更差(P0.05)。我們還分析了CD44和Ki-67的組合表達(dá)對(duì)ESCC的結(jié)果的影響,并發(fā)現(xiàn)具有CD44、Ki-67均高表達(dá)的ESCC患者顯示比具有CD44或Ki-67低表達(dá)的患者預(yù)后更差。結(jié)論:1性別、腫瘤浸潤(rùn)深度、組織病理學(xué)分級(jí)、臨床分期、治療方式、有無脈管瘤栓及神經(jīng)受侵、淋巴結(jié)轉(zhuǎn)移與ESCC患者的預(yù)后有關(guān)聯(lián);且性別、腫瘤浸潤(rùn)深度、臨床分期、組織病理學(xué)分級(jí)、有無淋巴結(jié)轉(zhuǎn)移是食管癌患者預(yù)后的獨(dú)立影響因素。2臨床分期、組織病理學(xué)分級(jí)、腫瘤浸潤(rùn)深度、有無脈管瘤栓及神經(jīng)受侵與食管鱗癌患者淋巴結(jié)轉(zhuǎn)移有關(guān)聯(lián);且組織病理學(xué)分級(jí)、腫瘤浸潤(rùn)深度、有無脈管瘤栓是食管鱗癌患者淋巴結(jié)轉(zhuǎn)移預(yù)后的獨(dú)立影響因素。3 NACRT組比術(shù)前未治療組的生存預(yù)后差,且差異有顯著統(tǒng)計(jì)學(xué)意義(P0.01)。4生存分析顯示,NACRT術(shù)后CD44和Ki-67的高表達(dá)與食管癌患者低的生存率顯著相關(guān)(P0.05)。5 CD44高表達(dá)且Ki-67高表達(dá)的ESCC患者顯示出比具有CD44或Ki-67低表達(dá)的患者預(yù)后更差,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。
[Abstract]:Objective: To study the esophageal squamous cell carcinoma (Esophageal squamous cell carcinoma, ESCC) of the clinical data and pathology, to explore the factors affecting survival of patients with esophageal squamous cell carcinoma after neoadjuvant therapy; comparative analysis of ESCC patients before surgery (NACRT) and postoperative histopathologic examination confirmed lymph node metastasis and related factors positive prognostic combined with adjuvant chemotherapy or radiotherapy were determined; tumor stem cell marker CD44 (CSC) and cell proliferation associated nuclear antigen (Ki-67) expression in NACRT after ESCC in patients with chemotherapy efficacy of radical resection of the esophagus and the influence on the prognosis. Methods: 1 retrospective diagnosis of esophageal squamous cell and then the operation of cancer from January 2008 to December 2010 between the fourth hospital of Hebei Medical University from pathology in 1782 patients were successfully followed up, a total of 1550 cases, 232 cases were lost, with the Visit rate of 86.9%. was observed and recorded the clinical data and pathological features of esophageal cancer patients, using statistical software SPSS 21 of the recorded data were statistically analyzed with.2 in 2006-2016 years were analyzed retrospectively. Preoperative neoadjuvant therapy in 110 patients before surgery and no other treatment, direct esophageal radical resection and operation after the pathology of lymph node metastasis after radiotherapy / combined with the clinical data of 106 patients with surgical results. By the following R classification: R0, R1, no residual tumor; microscopic residual tumor; R2, residual tumor. The use of statistical software SPSS 21 for statistical analysis of.3 specimens were fixed in 10% formalin and conventional materials of the recorded data, cut paraffin section, HE staining and immunohistochemical staining, light microscope. According to the analysis of the proportion of positive cells and staining intensity accounted for by 0 points: colorless staining intensity, The 1 is divided into yellow, 2 yellow brown, 3 brown; 1~2 was weakly positive, 3 positive cells were strong positive. The proportion of 0 is negative, l positive cells are divided into 20%, 2 points for the number of positive cells in the 21%~60%, 3 points for the number of positive cells in 61%~80% 4, divided into 80% positive cells; 1~2 divided into low percentage, 3~4 is divided into a high percentage. The product percentage and staining intensity to the number of positive cells accounted for as criteria: negative 0 points, low expression of 1~8, high expression of 9~12. Using SPSS 21 statistical software for analysis and processing Kaplan-Meier method, univariate survival analysis, Cox method for multivariate survival analysis, comparison between groups using Log-rank test, multivariate Logistic regression analysis, P0.05 was a statistically significant difference. The results of this study: 1 of 1782 patients with ESCC, until the end of the follow-up date, 232 patients lost to follow-up rate was 86.9 %.鐢熷瓨鏃墮棿1~108涓湀,涓綅鐢熷瓨鏃墮棿58涓湀,騫沖潎鐢熷瓨鏃墮棿57涓湀.鎮(zhèn)ｈ，

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