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研究生:高秋雅
研究生(外文):KAO, CHIU-YA
論文名稱:膀胱癌病患術後存活預後預測因子分析
論文名稱(外文):An Analysis of Prognostic Factors to Predict Postoperative Survival of Bladder Cancer Patients
指導教授:陳俞成陳俞成引用關係陳珹箖陳珹箖引用關係
指導教授(外文):CHEN, YU-CHENGCHEN, JIN-LIANG
口試委員:林為森陳青浩
口試委員(外文):LIN, WEIR-SENCHEN, CHING-HAO
口試日期:2018-06-15
學位類別:碩士
校院名稱:嘉南藥理大學
系所名稱:醫務管理系
學門:商業及管理學門
學類:醫管學類
論文種類:學術論文
論文出版年:2018
畢業學年度:106
語文別:中文
論文頁數:140
中文關鍵詞:膀胱癌存活時間預後因子
外文關鍵詞:bladder cancersurvival timeprognostic factors
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背景與動機:膀胱癌為台灣地區常見的泌尿道腫瘤,可能因為存在著特殊的致癌因子如尿毒症、烏腳病等,死亡率雖不是很高,發生率卻頗高,所以膀胱癌的診斷及治療已是現代醫學及公共衛生上不可小看的問題。
目的:本研究目的為探討膀胱癌病患術後存活預後及死亡風險的預測因子,以為醫療處置的參考,提升癌症治療之醫療品質。
方法:資料來源為南台灣某醫學中心2010年至2015年之膀胱癌新診斷術後病患共有748人為研究世代。資料分析方法,首先以描述性統計呈現病患人口學特徵、癌症確認、TNM分期、病理檢驗結果與治療方式的分布情形,接著以推論性統計方法,包括卡方檢定、存活分析(Kaplan-Meier方法、Log-rank test),及Cox迴歸模型,探討膀胱癌病人存活預後及死亡風險之預測因子。本研究以Microsoft Excel 2016、SPSS 22.0進行資料整理與分析。
結果:研究樣本中,男性佔68.4%、第一次經尿道膀胱腫瘤切除手術以65歲以上最多(60.4%)、大多數人未抽菸(77.1%)、98.5%病人沒有接受腎移植手術,以及病人80.5%沒有罹患末期腎病變、88.5%術前没罹患上泌尿道上皮癌。Cox向前逐步迴歸模型,進行膀胱癌病患術後存活預後預測因子之相對重要性的分析,結果發現膀胱腫瘤切除年齡、血色素、嗜中性白血球、肌酐酸及癌症期別等,對病人之死亡風險有顯著影響。
結論:本研究主要目的是分析膀胱癌預後因子之探討;在單變量分析整體病患發現罹病年齡、末期腎病變、白血球、血色素、嗜中性白血球、淋巴球、血小板、肌酐酸、腫瘤侵犯程度、淋巴結是否轉移、遠端器官是否轉移、癌症期別、組織病理分級、是否侵犯肌肉層與治療方式等15項是影響膀胱癌病患術後存活預後的獨立預測因子。另外在多變量分析中發現罹病年齡、血色素、嗜中性白血球、肌酐酸及術後癌症期別為最主要的存活預後因子。因此根據本研究結果提出以下具體建議:1.加強國人對膀胱癌早期篩檢的重視,以期早期發現、早期治療,進而降低死亡風險,提升存活率。2.建議納入廣泛使用或常規使用之生化檢驗項目,包括血色素、嗜中性白血球、肌酐酸檢驗等項目,其檢驗結果可協助評估膀胱癌病人,做為臨床決策的重要參考依據。3.膀胱癌病人以手術切除併化療治療之術後存活預後比僅執行手術切除佳,建議臨床醫師完整評估存活預後的預測因子,提供個人化醫療,以提升癌症醫療品質。

Background and motivation: Bladder cancer is a common urinary tract cancer in Taiwan. There are special carcinogenic factors such as kidney dialysis, black foot disease, etc. although the mortality rate of bladder cancer is not very high. The incidence rate of bladder cancer is high, so the diagnosis and treatment can not be ignored on modern medicine and public health issues.
Objectives: The purpose of this study was to investigate the prognosis factors of postoperative survival and the risk factors of death in bladder cancer patients. The results could be a reference for medical treatment and improving the medical quality of cancer treatment.
Methods: The source of data is a total of 748 postoperative patients with newly diagnosed bladder cancer from 2010 to 2015 at a medical center in the south Taiwan. The descriptive statistics were used to present patient demographic characteristics, cancer confirmation, TNM stage, pathological test results, and the distribution of treatment methods. The inferential statistical methods include the Chi-square test, the Kaplan-Meier method, the Log-rank test, and the Cox regression model to investigate the predictors of survival prognosis of bladder cancer and the risk factors of death. This study uses Microsoft Excel 2016 and SPSS 22.0 to organize and analyze data.
Results: In the study sample, we got men accounted for 68.4%. The first transurethral resection of the bladder tumors was at most those were above 65 years old (60.4%). The most people were not smoking (77.1%), 98.5% of patients not received kidney transplants, and 80.5 %, 88.5% of patients not having end-stage renal disease, upper urinary tract urothelial carcinoma. The Cox forward stepwise regression model was used for analysis of the relative importance of the prognostic predictors of postoperative survival in patients with bladder cancer. The age of bladder tumor resection, hemoglobin, neutrophils, creatinine acid, and cancer stage, etc. were the significant risk factors of the mortality rate of patient.
Conclusions: This study was to investigate the prognostic factors of bladder cancer. In univariate analysis found the overall morbidity in patients age, end stage renal disease, white blood cells, hemoglobin, neutrophil (seg), lymphocyte, platelets, creatinine, the degree of tumor invasion, lymph node metastasis, whether distant organs metastasis, cancer of stage, histological grade, whether the muscle layer is invaded and treatment modalities such as 15 independent are predictors factors of survival time in patients with bladder cancer prognosis. Also found that the age of morbidity in the multivariate analysis, hemoglobin, neutrophil (seg), creatinine and postoperative cancer of the other as the most important survival time prognostic factors. Based on the results of this study, the following specific recommendations are made: 1.To strengthen the attention to early screening for bladder cancer, with early detection and early treatment, thereby the reducing the risk of death and improving survival are possible. 2. The routine use of biochemical test items, including hemoglobin, neutrophil (Seg), creatinine testing, may assist in the evaluation of bladder cancer, and be an important reference for clinical decision making. 3. The prognosis of surgical resection and chemotherapy for bladder cancer patients is better than that of only surgical resection. Clinicians should evaluate the predictors of survival prognosis and provide personalized medicine to improve the medical quality of cancer treatment.

目錄
中文摘要 I
ABSTRACT III
誌謝 V
目錄 VI
表目錄 IX
圖目錄 XI
第一章 緒論 1
第一節 研究背景與動機 1
第二節 研究目的 3
第二章 文獻探討 5
第一節 膀胱癌的簡介 5
第二節 膀胱癌的診斷 21
第三節 膀胱癌的治療及追蹤準則 27
第四節 膀胱癌的預後因子及相關實證研究 33
第三章 研究方法 51
第一節 研究設計 51
第二節 研究對象與資料來源 56
第三節 研究變項操作型定義 58
第四節 資料分析方法 63
第四章 資料分析 64
第一節 描述性及推論性分析結果 64
第二節 存活分析結果 73
第三節 COX迴歸分析結果 95
第五章 結果討論 103
第一節 膀胱癌之存活預後及存活預後預測因子 103
第二節 膀胱癌之死亡風險預測 107
第六章 結論與建議 109
第一節 結論 109
第二節 建議 111
第三節 研究限制與未來研究建議 113
參考文獻 114
中文文獻 114
英文文獻 115
附錄 139
附錄一 臨床試驗同意證明書 139
附錄二 臨床試驗計畫結案報告 140

表目錄
表2- 1 膀胱癌潛在危險因素 20
表2- 2 膀胱癌TNM分期 44
表2- 3 美國癌症聯合委員會第八屆膀胱癌分期系統AJCC 45
表3- 1 變項及操作型定義 61
表3- 2 變項及操作型定義(續) 62
表4- 1 膀胱癌病人之人口學特性分佈(N=748) 67
表4- 2 膀胱癌病人之生存死亡數之分析-按人口學特性(N=748) 68
表4- 3 膀胱癌病人之生化檢驗結果分布(N=748) 69
表4- 4 膀胱癌病人之生存死亡數之分析-按生化檢驗結果(N=748) 70
表4- 5 TNM分期、病理檢驗及治療方式結果分析(N=748) 71
表4- 6 TNM分期、病理檢驗及治療方式結果生存死亡數之分析(N=748) 72
表4- 7 膀胱癌病人1年、3年,及5年之存活分布-按人口學特性 79
表4- 8 膀胱癌病人1年、3年,及5年之存活分布-按生化檢驗結果(N=748) 86
表4- 9 膀胱癌病人1年、3年,及5年之存活分布-按TNM分期及治療方式 94
表4- 10 COX迴歸模型之人口學特性單變量分析(N=748) 97
表4- 11 COX迴歸模型之生化檢驗單變量分析(N=748) 98
表4- 12 COX迴歸模型單變量TNM分期、病理檢驗及治療方式分析結果(N=748) 99
表4- 13 COX向前逐步迴歸模型多變量分析(N=748) 102
表6- 1 存活預後因子假設結果 110

圖目錄
圖1- 1 泌尿解剖圖 3
圖2-1 台灣男女性95年-103年膀胱癌發生率 6
圖2-2 1973年至2004年期間WHO乳頭狀尿路上皮腫瘤分級系統 8
圖2- 3 移行細胞癌膀胱癌的T期(TNM分期) 10
圖2- 4 苯胺的化學結構 14
圖2- 5 非肌層浸潤性膀胱癌治療方式(依據歐洲泌尿學協會) 28
圖2- 6 肌肉浸潤性膀胱癌的治療方式(依據歐洲泌尿學協會) 31
圖3- 1 研究架構 53
圖3- 2 研究流程 55
圖3- 3 資料處理流程圖 57
圖4- 1 不同性別之存活時間的KAPLAN-MEIER 73
圖4- 2 不同年齡之存活時間的KAPLAN-MEIER 74
圖4- 3 是否抽煙者之存活時間的KAPLAN-MEIER 75
圖4- 4 是否接受過腎移植者之存活時間的KAPLAN-MEIER 76
圖4- 5 是否罹患末期腎病變者之存活時間的KAPLAN-MEIER 77
圖4- 6 是否罹病前罹患泌尿道上皮癌之存活時間的KAPLAN-MEIER 78
圖4- 7 術前生化檢驗白血球是否正常值之存活時間的KAPLAN-MEIER 80
圖4- 8 術前生化檢驗血色素是否正常值之存活時間的KAPLAN-MEIER 81
圖4- 9 術前生化檢驗嗜中性白血球是否正常值之存活時間的KAPLAN-MEIER 82
圖4- 10 術前生化檢驗淋巴球是否正常值之存活時間的KAPLAN-MEIER 83
圖4- 11 術前生化檢驗血小板是否正常值之存活時間的KAPLAN-MEIER 84
圖4- 12 術前生化檢驗肌酐酸是否正常值之存活時間的KAPLAN-MEIER 85
圖4- 13 不同T分期之腫瘤相關存活時間的KAPLAN-MEIER 87
圖4- 14 不同N分期之腫瘤相關存活時間的KAPLAN-MEIER 88
圖4- 15 是否遠端器官移轉M之腫瘤相關存活時間的KAPLAN-MEIER 89
圖4- 16 不同癌症期別之腫瘤相關存活時間的KAPLAN-MEIER 90
圖4- 17 不同病理分級之腫瘤相關存活時間的KAPLAN-MEIER 91
圖4- 18 是否侵犯到肌肉層之腫瘤相關存活時間的KAPLAN-MEIER 92
圖4- 19 是否接受化療治療之相關存活時間的KAPLAN-MEIER 93







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