【作者】 陈锦华；

【导师】 蔡琳；

【作者基本信息】 福建医科大学 ， 流行病与卫生统计学， 2013， 硕士

【摘要】 研究目的：分析不同发病年龄、性别、手术方式、肿瘤大小、肿瘤部位、近远端、病理类型、分化程度、脉管浸润、T、N、M、病理分期、淋巴结转移、R0/R1切除、淋巴管癌栓、神经侵犯、血管侵犯、淋巴结活检数、淋巴结活检阳性数和Her-2基因表达情况等对胃癌生存率的影响程度；确定Her-2基因过表达情况及对胃癌生存率的影响程度；确定Her-2基因表达与否对1、3、5年观察生存率和半数生存期的影响；在此基础上确定影响胃癌病人生存率的相关因素。研究方法：通过文献检索收集国内外胃癌Her-2基因相关资料，了解国内外评价胃癌预后指标体系，同时了解我国胃癌生存率现状及发展趋势。以南京军区福州总医院的2004年～2011年7月经病理确诊为胃癌的首发病例为研究对象，并以自编肿瘤病人诊疗与生存状态随访单为调查工具，进行癌症患者的生存期回顾性电话调查，同时结合摘录病历和回访采集患者临床信息，还通过福建省死亡库和公安局人口信息库及回访来核实患者生存状况，最终实际纳入研究对象的胃癌患者为2062例。对随访后获得的数据采用EpiData3.0进行双份录入，数据准确无误，Excel2003进行整理，SPSS13.0和SAS9.1进行统计学处理和绘图；对连续性变量进行描述性统计分析，包括均数、标准差、中位数、最小和最大值；对分类变量计算各类别的频数和百分比；应用SPSS l3.0寿命表方法计算不同发病年龄、性别、手术方式、肿瘤大小、肿瘤部位、近远端、病理类型、分化程度、脉管浸润、T、N、M、病理分期、淋巴结转移、R0/R1切除、淋巴管癌栓、神经侵犯、血管侵犯、淋巴结活检数、淋巴结活检阳性数和Her-2基因表达情况的1、3、5年观察生存率和半数生存期，并应用Log-Rank检验比较了各组生存期的差异，绘制生存曲线；同时以Her-2基因阳性与否为分层变量，采用χ~2检验和χ2趋势检验，对比各指标表达率的差异，并计算上述影响生存期的十二个指标的1、3、5年观察生存率和半数生存期差异，考察Her-2表达与否对这些因素影响生存期的作用，而后进行COX逐步回归分析，确定胃癌的预后因素；设P<0.05有统计学意义。研究结果：1.2062例研究对象有如下特点：以老年人胃癌居多，多实施根治性手术，肿瘤大小在2～10厘米之间，远端切除为主，病理类型主要是管状癌和乳头状癌，主要表现为高中分化，TNM分期主要为Ⅲ期病人，手术绝大部分都能完全切除，大部分病人有脉管浸润、淋巴管癌栓、神经侵犯、血管侵犯和淋巴结转移，好发部位在胃体和贲门，手术切除活检的淋巴结数目大多在11个以上，其中以21个以上最多，活检为阳性的淋巴结数目以1～5个最多。2.单因素分析结果显示：发病年龄、手术方式、肿瘤大小、分化程度、脉管浸润、T、N、M、分期、淋巴结转移、手术切除和淋巴结活检阳性数与胃癌预后有关，发病年龄在60岁及以上、实施姑息性手术、肿瘤大小在10厘米以上、低未分化、有脉管浸润、T为3～4期、N为3期、有远处转移、病理分期为Ⅳ期、有淋巴结转移、手术不完全切除（即病理可见部分切除）和有16个及以上阳性淋巴结都是胃癌预后不良因素；而其余指标与胃癌预后无明显关联。3.好发于胃体、高中分化、无脉管浸润、有远处转移、病理分期Ⅳ期、无神经侵犯、淋巴结活检数和阳性数较少的胃癌患者，其Her-2表达率较高；Her-2表达阳性组中分化程度和脉管浸润两个指标生存率没有差异。4.COX风险比例模型结果显示手术方式、病理类型、脉管浸润、淋巴结活检数、淋巴管癌栓、神经侵犯和Her2基因表达是胃癌的独立预后因素，其中病理类型的RR值最大。研究结论：手术方式、病理类型、脉管浸润、淋巴结活检数、淋巴管癌栓、神经侵犯和Her2基因表达是胃癌的独立预后因素。更多还原

【Abstract】 Objective: To analyze the influence on the survival rate of gastric cancerof different age, gender, surgery types, tumor size, tumor location, proximalor distal ends, pathology type, differentiation levels, lymphatic/vascularinvasion, T stage, N stage, M stage, pathology stage, lymph node metastasis,R0/R1ablation, lymphaticum invasion, nerve invasion, vessel invasion,lymphaden biopsy number, lymphaden biopsy positive number and Her-2geneexpression. To clarify Her-2gene over-expression and its influence on survivalrate of gastric cancer, and the influence of Her-2gene expression on observedsurvival rate in1-year,3-year,5-year and median survival time. Then todetermine the prognostic correlative factors of survival rate of gastric cancerpatients.Method: To collect the correlative data of Her-2gene in gastric cancer fromhome and abroad through literature search. To understand the prognostic indexsystem of gastric cancer, current research situation and developing trend ofsurvival rate of gastric cancer. This article studys the incidence cases ofgastric cancer which were determined by pathology method from January2004toJuly2011in Fuzhou General Hospital of Nanjing Military Command. Use follow-upsurvey list of treatments and survival conditions for patients as surveymanagement, and make telephone investigation of survival status, then combineclinical history and return visit to collect clinical data of patients. Verifysurvival situation of patients through death data library of Fujian Provinceand population information library of Public Security. At last,2062gastriccancer patients were selected as research targets.All data were input by using a double entry method with EPI data3.0softwareand analyzed statistically and plotted by Excel2003, SPSS13.0and SAS9.1.Continuous variables were displayed by descriptive statistics, including mean, standard deviation, median, minimum and maximum value. Classified variables werecalculated by frequence and percentage. Observed survival rate in1-year,3-year,5-year and median survival time of age, gender, surgery types, tumor size, tumorlocation, proximal or distal ends, pathology type, differentiation levels,lymphatic/vascular invasion, T stage, N stage, M stage, pathology stage, lymphnode metastasis, R0/R1ablation, lymphaticum invasion, nerve invasion, vesselinvasion, lymphaden biopsy number, lymphaden biopsy positive number and Her-2gene expression were analyzed by life table method in SPSS13.0. Different groupsof survival curve were compared and plotted by Log-Rank test. Differenced inrate of Her-2gene expression, observed survival rate in1-year,3-year,5-yearand median survival time of12indexes between Her-2gene expression negativeand positive was contrasted by Chi-square test and Chi-square trend test. Thereaction of survival time influenced by these factors was inspected. Thenprognosis factors of gastric cancer were found by Cox stepwise regressionanalysis. P＜0.05was set as statistical significance.Result:1．2062gastric cancer cases have these following features: aged peoplewere the most. Radical surgery was mostly executed. Cancer size is between2～10cm, and cancer was mainly treated by distal end excision. Pathology types weretubular carcinoma and papillary carcinoma. The most were well and moderatelydifferentiated. Pathology stage is Ⅲ period. Most of the surgery couldcompletely remove the cancer. Lymphatic/vascular invasion, lymphaticum cancerembolus, nerve invasion, vessel invasion and lymph node metastasis were foundin most patients. Body of stomach and cardia were predilection sites. Numbersof biopsy lymph nodes removed by surgery was over11. Among those, numbers oflymph nodes which was over21are the most. Biopsy positive lymph nodes between1～5were the most.2．The result of univariate analysis showed that: gastric cancer prognosisis related to age of onset, surgery types, tumor size, differentiation levels,lymphatic/vascular invasion, T stage, N stage, M stage, pathology stage, lymph node metastasis, R0/R1ablation and lymphaden biopsy positive number. Age ofonset over60, palliative operation, cancer size over10cm, poor ornon-differentiation, vessel infiltration, T in Ⅲ or Ⅳperiod, N in Ⅲ period,distant metastasis, Ⅳ period of pathology, lymph node metastasis, R1ablationand above16biopsy positive lymph nodes are risk factors of gastric cancer.The rest factors have no relation to gastric cancer prognosis.3．Gastric cancer patients, who have the following features of predilectionsite in body of stomach, well and moderately differentiated, no vesselinfiltration, distant metastasis and Ⅳ period of pathology, no nerve invasion,low numbers of biopsy lymph nodes, low numbers of biopsy positive lymph nodesand have a high expression of Her-2gene. The survival rate between two indexesincluding differentiation levels and vessel infiltration has no difference inpositive group.4．Results of Cox ’s proportional hazard model shows that surgery type,pathology type, vessel infiltration, number of lymphaden biopsy, lymphaticuminvasion, nerve invasion and Her-2gene expression are dependent factors ofgastric cancer prognosis. The RR (risk ratio) value of pathology type is maximum.Conclusion:Surgery type, pathology type, vessel infiltration, number of lymphadenbiopsy, lymphaticum invasion, nerve invasion and Her-2gene expression areindependent factors of gastric cancer prognosis.更多还原