本文選題：癌前病變 + 風(fēng)險預(yù)測��； 參考：《中國中醫(yī)科學(xué)院》2017年碩士論文

【摘要】：研究背景:胃癌是世界范圍內(nèi)最為常見的惡性腫瘤之一。胃癌在全球范圍內(nèi)的發(fā)病率列居第五,死亡率位居第三。據(jù)世界衛(wèi)生組織/國際癌癥研究中心(IARC)公布的統(tǒng)計(jì)數(shù)據(jù)顯示,2012年全球胃癌新發(fā)病例98.9萬,約50%發(fā)生在東亞地區(qū),尤以中國最多,占全球胃癌發(fā)病的46.8%;2012年全球胃癌的死亡病例為73.7萬,中國死亡病例為35.2萬,占全球胃癌死亡的47.8%。據(jù)統(tǒng)計(jì),2015年我國胃癌發(fā)病率為22.7/10萬,僅次于肺癌,位居第二;胃癌死亡率為17.9/10萬,僅次于肺癌、肝癌,位居第三。胃癌的發(fā)生經(jīng)歷一系列演變過程,由Correa等提出了腸型胃腺癌的演化模式,即:正常胃黏膜—慢性淺表性胃炎—慢性萎縮性胃炎—腸上皮化生—異型增生—腸型胃癌。以胃黏膜萎縮為病變背景的腸上皮化生(Intestinal Meteplasia,IM)及異型增生(Dysplasia,DYS)是目前公認(rèn)的胃癌前病變(precancerous lesions of gastric cancer,PLGC),也是當(dāng)前胃癌防治領(lǐng)域的熱點(diǎn)和難點(diǎn)。重度異型增生有明顯癌變傾向,需積極進(jìn)行內(nèi)鏡下切除治療,中-重度腸化生及輕-中度異型增生者國內(nèi)外一致建議定期進(jìn)行內(nèi)鏡監(jiān)測。電子胃鏡下病理組織活檢屬于介入性操作,其創(chuàng)傷大、費(fèi)用高,在我國現(xiàn)有醫(yī)療條件下作為普查手段進(jìn)行大規(guī)模開展尚有一定困難。血清“ABC”法聯(lián)合G-17檢測助于提高萎縮、胃癌檢出率,并且具有無創(chuàng)、簡便、快速、低廉等優(yōu)點(diǎn),但這些指標(biāo)是否對PLGC的發(fā)生、轉(zhuǎn)歸有預(yù)測意義尚不得而知。目前,國內(nèi)外對PLGC的篩檢工具開發(fā)研究較少,已有的模型建立多局限在環(huán)境因素方面,推廣性欠佳,并且缺少相關(guān)中醫(yī)證候?qū)W內(nèi)容,在臨床實(shí)際運(yùn)用中存在一定局限性。研究目的:1.篩選PLGC相關(guān)的因素及中醫(yī)證候要素,明確PLGC的重要影響因素。2.建立基于Logistic回歸分析的PLGC風(fēng)險預(yù)測模型,為PLGC篩檢提供數(shù)據(jù)模型依據(jù)。3.評估PLGC風(fēng)險預(yù)測模型準(zhǔn)確性,為PLGC高危人群篩檢提供科學(xué)依據(jù)。研究方法:1.根據(jù)慢性萎縮性胃炎、異型增生的診斷標(biāo)準(zhǔn),設(shè)定納入及排除標(biāo)準(zhǔn)。中醫(yī)證型診斷的辯證依據(jù)分為兩個方面:一是共識,即國家、協(xié)會等正式出版發(fā)行的教材、指南及專家意見等;二是兩名從事慢性萎縮性胃炎中醫(yī)診治工作20余年以上的高年資中醫(yī)師的經(jīng)驗(yàn)性證型診斷。于中國中醫(yī)科學(xué)院西苑醫(yī)院脾胃科門診、住院及胃鏡室收集慢性萎縮性胃炎患者,并進(jìn)行篩選。2.通過檢測血清學(xué)相關(guān)指標(biāo)及問卷調(diào)查的方法,采集PLGC臨床資料:包括臨床危險因素(一般信息、生活行為、飲食習(xí)慣、情志因素、家族史、胃鏡及病理表現(xiàn));血清學(xué)指標(biāo):PGI、PGII、HpIgG抗體、G-17及中醫(yī)證候及其要素等;3.比較各因素組間差異,將影響因素納入Logistic單因素及多因素回歸分析,選擇Forward前進(jìn)法,α入=0.05,α出=0.1篩選出PLGC相關(guān)危險因素及中醫(yī)證候要素;4.以極大似然值對自變量進(jìn)行參數(shù)估計(jì),建立基于Logistic回歸的PLGC風(fēng)險預(yù)測模型;5.運(yùn)用Hosmer-Lemeshow擬合優(yōu)度、PesudoR-square、AUC指標(biāo)對PLGC風(fēng)險預(yù)測模型擬合度及準(zhǔn)確性進(jìn)行評價,運(yùn)用ROC曲線分析該模型富集高風(fēng)險人群的能力。研究結(jié)果:1.PLGC相關(guān)因素①生活行為:吸煙在PLGC組與非PLGC組暴露分別為:31%vs24.8%(P0.05);飲酒在PLGC組與非PLGC組暴露分別為:40.5%vs27.7%(P0.05)。②飲食習(xí)慣:喜食蔬菜在PLGC組與非PLGC組暴露分別為:14.0%vs26.3%(P0.05),OR值為0.236(95%CI=0.058-0.952);豆制品在PLGC組與非PLGC組暴露分別為:34.9%vs17.5%,(P0.05);飲濃茶在PLGC組與非PLGC組暴露分別為:16.3%vs4.4%(P0.05),OR值為6.288(95%CI=1.465-26.989);進(jìn)食腌制食品在PLGC組與非PLGC組暴露分別為:37.2%vs16.1%(P0.05),OR值為3.198(95%CI=1.289-7.930)。③Hp感染史:Hp感染史在PLGC組與非PLGC組暴露分別為:7.0%vs16.8%(P0.05);④社會心理因素:焦慮在PLGC組與非PLGC組暴露分別為:41.9%vs19.7%(P0.05),OR值為2.404(95%CI=1.058-5.511);⑤遺傳因素:胃癌家族史在PLGC組與非PLGC組暴露分別為:14.0%vs10.2%(P0.05);消化道腫瘤家族史在PLGC組與非PLGC組暴露分別為:16.3%vs11.7%(P0.05)。⑥合并疾病:胃食管反流病在PLGC組與非PLGC組暴露分別為:39.8%vs23.3%(P0.05);十二指腸潰瘍在PLGC組與非PLGC組暴露分別為:79.3%vs7.3%(P0.05);膽囊切除史在PLGC組與非PLGC組暴露分別為:97.0%vs1.5%(P0.05),OR值為7.351(95%CI=1.824-55.384)。⑦血清學(xué)檢查:PLGC者血清PGI、PGII、血清G-17水平在PLGC組水平分別為:55.01 ±35.85ug/L,4.50±2.82 ug/L,4.21±7.69ng/L,在非PLGC組水平分別為:62.40士48.59 ug/L,5.40±5.33 ug/L,4.13±9.77 ng/L(P0.05);HpIgG抗體在PLGC組與非PLGC組暴露分別為:20.9%vs16.1%(P0.05)⑧中醫(yī)證候:癥狀方面:癥狀總積分在PLGC組與非PLGC組分別為:14.19±11.21vs17.97±13.56(P0.05);主要癥狀積分在PLGC組與非PLGC組分別為:10.7±6.11vs11.31±6.21(P0.05);證候要素方面:血瘀在PLGC組與非PLGC組暴露分別為:44.2%vs28.5%(P0.05),OR值為2.420(95CI%=0.998-5.851);濕熱在PLGC組與非PLGC組暴露分別為:41.9%vs27%(P0.05)。2.基于Logistic回歸分析的PLGC危險因素篩選通過運(yùn)用Logistic單因素及多因素回歸分析,最終篩選出腌制、焦慮、膽囊切除史、血瘀、濃茶5個重要危險因素。其中,膽囊切除史與PLGC發(fā)生風(fēng)險關(guān)系最密切,OR值為7.351(95%CI=1.824-55.384);其次是濃茶,OR值為5.351(95%CI=1.824-55.384);腌制、血瘀,OR值分別是3.198(95%CI=1.289-7.930),2.420(95%CI=0.998-5.851);焦慮再次之,OR值為2.404(95%CI=1.058-5.511)。3.基于Logistic回歸分析的PLGC風(fēng)險預(yù)測模型建立ln(p/1-p)=-2.507+2.153X1+1.995X2+1.162X3+0.884X4+0.877X51-P(X1=膽囊切除、X2=濃茶、X3=腌制、X4=血瘀、X5=焦慮)4.PLGC風(fēng)險預(yù)測模型評價模型擬合優(yōu)度:經(jīng) Hosmer-Lemeshow(H-L)檢驗(yàn),χ2值為 3.997,P=0.5500.05,不拒絕關(guān)于模型很好擬合數(shù)據(jù)的假設(shè),即該模型擬合度較好。模型測準(zhǔn)確性:關(guān)于 Pesudo R-square,Cox and Snell 值為 0.209,Nagelkerke值為 0.314;AUC=0.812(95%CI=0.738-0.885),P0.01,表明該模型預(yù)測準(zhǔn)確性尚可。5.PLGC風(fēng)險預(yù)測模型富集高風(fēng)險能力分析根據(jù)模型ROC曲線,靈敏度設(shè)定為100%,對應(yīng)最低1-特異度為66.7%,此條件下,高風(fēng)險人群最低占比為87%,對應(yīng)預(yù)測概率P值為0.00673502。對該高風(fēng)險人群進(jìn)行內(nèi)鏡篩檢,4例高風(fēng)險患者中可發(fā)現(xiàn)1例真正PLGC者需進(jìn)行內(nèi)鏡監(jiān)測,發(fā)現(xiàn)率之比為1.15。研究結(jié)論:1、腌制、膽囊切除、焦慮、濃茶為PLGC者的相關(guān)危險因素。2、血瘀證在PLGC演變過程具有重要意義。3、PLGC風(fēng)險預(yù)測模型為:ln(p/1-p)=-2.507+2.153X1+1.995X2+1.162X3+0.884X4+0.877X5(X1=膽囊切除、X2=濃茶、X3=腌制、X4=血瘀、X5=焦慮)4、PLGC風(fēng)險預(yù)測模型擬合度及預(yù)測準(zhǔn)確性較好,模型進(jìn)一步驗(yàn)證及校準(zhǔn)尚需未來長時間隨訪。
[Abstract]:Background: gastric cancer is one of the most common malignant tumors in the world. The incidence of gastric cancer is fifth in the world and third in the world. According to the statistics published by the WHO / International Center for cancer research (IARC), 989 thousand of the new cases of global gastric cancer in 2012, about 50% are in East Asia, especially in the Middle East. The country is the largest, accounting for 46.8% of global gastric cancer. In 2012, the death cases of global gastric cancer were 737 thousand, the death cases in China were 352 thousand, accounting for 47.8%. according to the global gastric cancer death. In 2015, the incidence of gastric cancer in China was 22.7/10 million, second only to lung cancer, ranked second, the death rate of gastric cancer was 17.9/10 million, second only to lung cancer and liver cancer, the third. Gastric cancer. A series of evolution processes were developed, and the evolution patterns of intestinal gastric adenocarcinoma were proposed by Correa, such as normal gastric mucosa - chronic superficial gastritis - chronic atrophic gastritis - intestinal metaplasia - dysplasia - intestinal type of gastric cancer. Intestinal metaplasia (Intestinal Meteplasia, IM) and dysplasia (Dysp) with gastric mucosal atrophy as the background (Dysp Lasia, DYS) is currently recognized as the precancerous lesions of gastric cancer, PLGC. It is also a hot and difficult point in the field of prevention and control of gastric cancer. Severe dysplasia has a tendency of obvious canceration and needs to be actively treated by endoscopic resection. The moderate to severe intestinal metaplasia and mild to moderate dysplasia are consistently recommended at home and abroad. Pathological tissue biopsy under electronic gastroscopy belongs to interventional operation, which has great trauma and high cost. It is difficult to carry out large-scale development as a census method under the existing medical conditions in our country. The serum "ABC" method combined with G-17 detection helps to improve the atrophy, the detection rate of gastric cancer, and has the advantages of noninvasive, simple, rapid and low. It is not known whether these indicators have a predictive significance for the occurrence and outcome of PLGC. At present, there are few studies on the development of PLGC screening tools at home and abroad. The existing models are mostly limited to environmental factors, poor popularization, and lack of relevant TCM syndromes, and there are some limitations in the practical application of the hospital. The purpose of this study is 1. Screening PLGC related factors and TCM syndrome factors, and defining the important influence factors of PLGC,.2. set up the PLGC risk prediction model based on Logistic regression analysis, providing data model for PLGC screening based on.3. evaluation of the accuracy of PLGC risk prediction model, providing a scientific basis for screening PLGC high-risk population. Research methods: 1. according to chronic atrophy The diagnostic criteria of gastritis and dysplasia are set up and excluded. The dialectical basis of TCM syndrome diagnosis is divided into two aspects: one is the common understanding, that is, the textbook, guide and expert opinion of the state, the association and so on; two is the two senior Chinese medicine teacher who has been engaged in the diagnosis and treatment of chronic atrophic gastritis for more than 20 years. The patients with chronic atrophic gastritis were collected in the outpatient of the spleen and stomach department of Xiyuan Hospital of Chinese Academy of Chinese medicine, China Academy of science of traditional Chinese medicine (Xiyuan Hospital), and selected.2. to collect PLGC clinical data by screening the related indexes of serology and questionnaire survey, including clinical risk factors (general information, life behavior, dietary habits and emotional factors, Family history, gastroscopy and pathological manifestations); serological indexes: PGI, PGII, HpIgG antibody, G-17 and TCM syndrome and its factors, etc.; 3. compare the differences among the factors in various factors, take the influencing factors into Logistic single factor and multiple factor regression analysis, select Forward forward method, alpha into =0.05, and alpha out =0.1 to screen out PLGC related risk factors and TCM syndrome factors; 4. The maximum likelihood value is used to estimate the parameters of the independent variables, and the PLGC risk prediction model based on Logistic regression is established. 5. the fitting degree and accuracy of the PLGC risk prediction model are evaluated by using Hosmer-Lemeshow goodness of fit, PesudoR-square, AUC index, and the ability of the model type to enrich the high risk population by using the ROC curve. The result of the study: 1.PLGC Related factors: life behavior: smoking in group PLGC and non PLGC group were 31%vs24.8% (P0.05); drinking in group PLGC and non PLGC group were respectively 40.5%vs27.7% (P0.05). The exposure of non PLGC group was 34.9%vs17.5%, (P0.05), and the exposure of drinking thick tea in group PLGC and non PLGC group was 16.3%vs4.4% (P0.05), OR value was 6.288 (95%CI=1.465-26.989), and the food pickled food in PLGC group and non PLGC group were respectively: 37.2%vs16.1% (37.2%vs16.1%) and 3.198. The exposure of non PLGC group was 7.0%vs16.8% (P0.05); (4) social psychological factors: anxiety in group PLGC and non PLGC group were respectively: 41.9%vs19.7% (P0.05) and OR value 2.404 (95%CI=1.058-5.511); 5. The exposure of the group was 16.3%vs11.7% (P0.05). 6. The exposure to gastroesophageal reflux disease in group PLGC and non PLGC group was 39.8%vs23.3% (P0.05), and the exposure of duodenal ulcer in PLGC group and non PLGC group was 79.3%vs7.3% (P0.05), and the history of cholecystectomy in PLGC group and non PLGC group was 7.351. I=1.824-55.384). Serological examination: the level of serum PGI, PGII and serum G-17 in the group of PLGC were 55.01 + 35.85ug/L, 4.50 + 2.82 ug/L, 4.21 + 7.69ng/L respectively, in the non PLGC group, 62.40 and 48.59 ug/L, 5.40 + 5.33 ug/L, 4.13 + 9.77, respectively. 0.05) symptom: symptom: the total symptom score was 14.19 + 11.21vs17.97 + 13.56 (P0.05) in group PLGC and non PLGC group, and the main symptom integral was 10.7 + 6.11vs11.31 + 6.21 (P0.05) in PLGC group and non PLGC group, and syndrome factor: the blood stasis in PLGC group and non PLGC group were respectively 44.2%vs28.5% (P0.05) and 2.420 I%=0.998-5.851); heat and heat in group PLGC and non PLGC group exposure, respectively: 41.9%vs27% (P0.05).2. based on Logistic regression analysis of PLGC risk factors screening through the use of Logistic single factor and multiple factor regression analysis, and finally screened out the salting, anxiety, cholecystectomy history, blood stasis, thick tea 5 important risk factors. Among them, the history of cholecystectomy and PLGC hair. The most closely related risk relationship, OR value of 7.351 (95%CI=1.824-55.384), followed by thick tea, OR value of 5.351 (95%CI=1.824-55.384), pickled and blood stasis, OR value was 3.198 (95%CI=1.289-7.930), 2.420 (95%CI=0.998-5.851), OR value was 2.404 (95%CI=1.058-5.511).3. based on Logistic regression analysis of the PLGC risk prediction model. /1-p) =-2.507+2.153X1+1.995X2+1.162X3+0.884X4+0.877X51-P (X1= cholecystectomy, X2= thick tea, X3= pickled, X4= blood stasis, X5= anxiety) 4.PLGC risk prediction model evaluation model goodness of fit: through Hosmer-Lemeshow (H-L) test, the chi 2 value is 3.997, P=0.5500.05, do not reject the model is very good fitting data hypothesis, that is, the model fitting degree is better. Accuracy of model measurement: on Pesudo R-square, Cox and Snell value is 0.209, Nagelkerke value is 0.314; AUC=0.812 (95%CI=0.738-0.885), P0.01, indicating that the prediction accuracy of the model still can enrich the high risk capability analysis of the.5.PLGC risk prediction model based on the model ROC curve, the sensitivity is set to 100%, corresponding to the minimum 1- specificity of 66.7%, this The lowest percentage of the high risk population was 87%, and the corresponding predictive probability P was 0.00673502. for the high risk population. In 4 patients with high risk, 1 cases of real PLGC were found to be endoscopically monitored. The ratio of the rate of discovery was 1.15.: 1, pickled, cholecystectomy, anxiety, and thick tea as PLGC related risk factors.2, blood stasis. The PLGC evolution process has important significance.3. The PLGC risk prediction model is: ln (p/1-p) =-2.507+2.153X1+1.995X2+1.162X3+0.884X4+0.877X5 (X1= cholecystectomy, X2= thick tea, X3= pickling, X4= blood stasis, X5= anxiety), the PLGC risk prediction model is better and the prediction accuracy is better, the further verification and calibration of the model still needs long follow-up in the future.
【學(xué)位授予單位】：中國中醫(yī)科學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R273

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