Predictive value of a clinical imaging model based on multi‑slice helical CT examination in predicting prognosis of advanced gastric adenocarcinoma
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摘要:目的
探讨基于多层螺旋CT(MSCT)检查的临床影像模型对进展期胃腺癌预后的预测价值。
方法采用回顾性队列研究方法。收集2019年1月至2021年1月宁波市鄞州区第二医院收治的88例进展期胃腺癌患者的临床病理资料;男62例,女26例;年龄为(60±15)岁。患者术前均行MSCT检查。正态分布的计量资料以x±s表示;偏态分布的计量资料以M(范围)表示。计数资料以绝对数表示。单因素和多因素分析采用Logstic回归模型。采用受试者工作特征曲线分析预后预测效能,并计算曲线下面积(AUC)、灵敏度及特异度。
结果(1)手术与随访情况。88例患者均行胃癌根治术,术后均经病理学检查确诊为进展期胃腺癌。88例患者术后均获得随访,随访时间为41(36~48)个月,3年总生存率为69.32%。(2)影响进展期胃腺癌根治术后预后的因素分析。多因素分析结果显示:术前癌胚抗原(CEA)和壁外静脉血管侵犯(EMVI)是进展期胃腺癌患者根治术后预后的独立影响因素[比值比=1.10,7.72,95%可信区间(CI)为1.01~3.82,1.42~15.42,P<0.05]。(3)预测模型的构建及评价。术前CEA、EMVI预测进展期胃腺癌患者预后的效能AUC分别为0.90(95%CI为0.82~0.97)、0.80(95%CI为0.71~0.89),灵敏度和特异度分别为85.25%、78.69%和100.00%、81.48%。根据多因素分析结果,联合术前CEA和EMVI建立预测模型,其AUC为0.93(95%CI为0.87~0.98),灵敏度和特异度分别为86.89%和96.30%。
结论术前CEA及EMVI是进展期胃腺癌患者根治术后预后的独立影响因素;联合术前CEA和EMVI建立预测模型,对患者预后的预测效能良好。
Abstract:ObjectiveTo investigate the predictive value of a clinical imaging model based on multi‑slice helical computer tomography (MSCT) examination in predicting prognosis of advanced gastric adenocarcinoma.
MethodsThe retrospective cohort study was conducted. The clinicopatho-logical data of 88 patients with advanced gastric adenocarcinoma who were admitted to the Ningbo Yinzhou No.2 Hospital from January 2019 to January 2021 were collected. There were 62 males and 26 females, aged (60±15)years. All patients underwent preoperative MSCT examination. Measurement data with normal distribution were represented as Mean±SD, and measurement data with skewed distribution were represented as M(range). Count data were expressed as absolute numbers. Univariate and multivariate analyses were conducted using the Logistic regression model. The receiver opera-ting characteristic curve was used to analyze the predictive efficacy of prognosis, and the area under the curve (AUC), sensitivity, and specificity were calculated.
Results(1) Surgical situations and follow‑up. All 88 patients underwent radical gastrectomy for gastric cancer and were diagnosed with advanced gastric adenocarcinoma through postoperative pathological examination. All 88 patients were followed up after surgery for 41(range, 36‒48)months, with a 3‑year overall survival rate of 69.32%. (2) Analysis of factors affecting the prognosis of advanced gastric adenocarcinoma after radical surgery. Results of multivariate analysis showed that preoperative carcinoembryonic antigen (CEA) and extramural venous invasion (EMVI) were independent factors affecting the prognosis of advanced gastric adenocarcinoma after radical surgery (odds ratio=1.10, 7.72, 95% confidence interval as 1.01‒3.82, 1.42‒15.42, P<0.05). (3) Construction and evaluation of predictive model. The AUC of predictive efficacy of prognosis for advanced gastric adenocarcinoma of preoperative CEA and EMVI were 0.90 (95% confidence interval as 0.82‒0.97) and 0.80 (95% confidence interval as 0.71‒0.89), respectively, with sensitivity of 85.25% and 78.69% and specificity of 100.00% and 81.48%, respec-tively. A predictive model was constructed by combining preoperative CEA and EMVI based on the results of multivariate analysis, and the AUC of the predictive model was 0.93 (95% confidence interval as 0.87‒0.98), with sensitivity and specificity of 86.89% and 96.30%.
ConclusionsCEA and EMVI are independent factors affecting the prognosis of advanced gastric adenocarcinoma after radical surgery. The predictive model constructed by combining preoperative CEA and EMVI has good predictive efficacy for patient prognosis.
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胃癌是常见的消化道肿瘤,其发病率和病死率均较高,且缺乏典型的临床表现,发现时多为中晚期,预后较差[1‑9]。多层螺旋CT(multi‑slice helical CT,MSCT)检查可通过分析病灶密度值、外观及强化程度,提供可靠临床信息,对肿瘤诊断、术前分期及预后评估均有突出价值[10⁃12]。已有研究结果显示:包括多种血清肿瘤标志物在内的临床特征在胃癌诊断及预后评估中均具有研究价值,但其因无法全面表征肿瘤特点而存在局限性[13⁃17]。因此,联合肿瘤影像学及临床特征有望提高疾病诊断率。本研究回顾性分析2019年1月至2021年1月我院收治的88例进展期胃腺癌患者的临床病理资料,探讨基于MSCT检查的临床影像模型对进展期胃腺癌预后的预测价值。
资料与方法
一、一般资料
采用回顾性队列研究方法。收集88例进展期胃腺癌患者的临床病理资料;男62例,女26例;年龄为(60±15)岁。患者术前均行MSCT检查,检查后2周内均行胃癌D2根治术;术后均接受标准辅助化疗4个周期(奥沙利铂联合卡培他滨)。本研究通过宁波市鄞州区第二医院医学伦理委员会审批,批号为鄞二伦审2024研批012号。患者及家属均签署知情同意书。
二、纳入标准和排除标准
纳入标准:(1)术后经组织病理学确诊为进展期胃腺癌,病理学分期为Ⅱ~Ⅲ期(pT1N2~3M0期、T2N1~3M0期、T3~4NanyM0期)。(2)术前未接受系统性肿瘤治疗。(3)MSCT检查图像清晰。(4)临床资料完整。
排除标准:(1)合并心、肝、肾等重要脏器功能障碍。(2)存在增强CT检查的禁忌证。
三、检查方法
(一)扫描参数和图像重建
检查设备采用美国GE公司Opiima CT660 64排CT机及对应GE扫描后图像处理工作站。患者检查前空腹时间>12 h,检查时饮用温水800~1 000 mL。扫描参数:管电压为120 kV,自动管电流,层间距及层厚度均为5 mm,螺距为0.984∶1,球管转速为0.8 s/r,矩阵为512×512,自膈顶部开始扫描整个胃部。行仰卧位平扫及动脉期、静脉期动态增强扫描检查。对比剂采用碘帕醇370 mgI/mL高压注射器经肘静脉快速注入,注入速度为3.5 mL/s,注射剂量为1.5 mL/kg,设定注射对比剂后35 s为动脉期,55 s为静脉期。完善检查后将相关原始数据上传至工作站进行分析,对图像进行冠状位和矢状位重建,重建图像层厚度及层间距均为1.25 mm。
(二)影像学特征的描述及定义
(1)病灶浸润深度分为浆膜侵犯与无浆膜侵犯。(2)肿瘤长径分为>5 cm与≤5 cm[18]。(3)淋巴结转移:参照UICC/AJCC第8版中关于TNM分期的标准进行N分期,分为N0~1期及N2~3期[19]。(4)根据病灶的纵向范围是否超过胃食管连接处与幽门管连线1/2分为局限型与非局限型[20]。(5)病灶部位:将胃小弯和胃大弯三等分,按照各自三等分点的连线将全胃分为上、中、下部,记作A、B、C,超过2个部位或肿瘤侵犯全胃部记作D。(6)Borrmann分型:Ⅰ型(肿块型)为病灶呈结节状突向胃腔内部,病灶边缘清晰。Ⅱ型(局部溃疡型)为病灶呈溃疡状,边缘较为清晰。Ⅲ型(溃疡浸润型)为病灶呈溃疡状并向周边浸润,边缘不清晰。Ⅳ型(弥漫浸润型)为癌组织向胃壁弥漫性浸润扩散,造成整个胃壁变硬,即皮革胃[21]。(7)参照文献[22]评估壁外静脉血管侵犯(extramural venous invasion,EMVI)。(8)病灶的强化程度:在最大肿瘤间3个层面上,勾画出3个圆形或类圆形感兴趣区域(region of interest,ROI),保证ROI边缘无明显坏死区域及所有患者的ROI面积相等。测量ROI平扫及双期增强扫描MSCT值,计算病灶的强化程度=双期增强下最大CT值/平扫CT值,强化值>30 HU为高度强化,10~30 HU为中度强化,<10 HU为轻度强化[23]。见图1。
图 1 进展期胃腺癌患者术前多层螺旋CT检查结果 1A:平扫示胃窦部病灶向腔内突出(←),周围脂肪间隙稍模糊;1B:增强检查示胃窦部病灶向腔内突出(←),病灶明显强化;1C:胃小弯侧见肿大淋巴结(←);1D:冠状位示胃窦部病灶向腔内突出(←)Figure 1. Results of preoperative multi⁃slice helical computer tomography (CT) imaging for patients of advanced gastric adenocarcinoma 1A: Results of CT plain scan show the lesion in the gastric antrum protruding into the cavity (←), and the surrounding fat space is slightly blurred; 1B: Results of CT enhanced scan show the lesion in the gastric antrum protruding into the cavity (←), and the lesion is significantly enhanced; 1C: Enlarged lymph nodes are seen in the lesser curvature of the stomach (←); 1D: Results of coronal CT scan show the lesion in the gastric antrum protruding into the cavity (←)对于上述MSCT影像学特征的判读由2名高年资放射科主治医师(>5年腹部影像诊断经验)予以评估,存在分歧时由第3名放射科副主任职称以上医师(>10年腹部影像诊断经验)参与讨论后予以评估。
四、随访
采用门诊或电话方式进行随访,了解患者生存情况。随访时间截至2024年1月。
五、观察指标
(1)手术与随访情况。(2)影响进展期胃腺癌根治术后预后的因素分析。(3)预测模型的构建及评价。
六、统计学分析
应用SPSS 22.0统计软件进行分析。正态分布的计量资料以x±s表示;偏态分布的计量资料以M(范围)表示。计数资料以绝对数表示。单因素和多因素分析采用Logstic回归模型。采用受试者工作特征曲线(receiver operator curve,ROC)分析预后预测效能,并计算曲线下面积(area under curve,AUC)、灵敏度及特异度。P<0.05为差异有统计学意义。
结果
一、手术与随访情况
88例患者均行胃癌根治术,术后均经病理学检查确诊为进展期胃腺癌(图2)。88例患者术后均获得随访,随访时间为41(36~48)个月,3年总生存率为69.32%。见图3。
二、影响进展期胃腺癌根治术后预后的因素分析
单因素分析结果显示:年龄、术前CEA、术前CA19‑9、浆膜侵犯、淋巴结转移、EMVI、肿瘤强化程度是影响进展期胃腺癌患者根治术后预后的相关因素(P<0.05);而性别、饮酒史、吸烟史、BMI、肿瘤分化程度、肿瘤长径、病灶局限性、病灶部位、Borrmann分型不是影响进展期胃腺癌患者根治术后预后的相关因素(P>0.05)。见表1。
表 1 影响88例进展期胃腺癌患者根治术后预后的单因素分析Table 1. Univariate analysis of prognosis of 88 patients with advanced gastric adenocarcinoma after radical resection临床及影像学特征 b值 标准误 Wald值 比值比(95%可信区间) P值 年龄 0.02 0.01 0.57 1.02(0.60~1.45) 0.045 性别(男比女) 0.07 0.17 0.20 0.93(0.56~1.32) 0.991 饮酒史(否比是) -0.04 0.15 0.05 0.97(0.43~1.31) 0.787 吸烟史(否比是) -2.44 0.64 2.21 0.08(0.01~2.18) 0.141 体质量指数 1.37 0.64 0.70 3.94(0.16~11.64) 0.431 肿瘤分化程度(高中分化比低分化) 0.55 0.17 13.06 1.74(0.64~4.25) 0.064 术前癌胚抗原 -0.91 0.30 18.01 0.40(0.17~1.99) <0.001 术前CA19‑9 0.67 0.17 14.62 1.96(0.32~3.43) 0.032 浆膜侵犯(否比是) 0.52 0.19 7.17 1.67(0.58~4.65) 0.028 肿瘤长径(>5 cm比≤5 cm) 0.21 0.19 0.86 1.23(0.76~5.32) 0.484 淋巴结转移(否比是) 0.67 0.25 0.86 1.96(0.27~7.97) 0.037 病灶局限性(非局限性比局限性) 1.97 0.65 3.52 7.72(1.15~23.43) 0.661 病灶部位 0.856 A - - - - - B -0.92 0.21 18.02 0.40(0.11~2.43) 0.197 C -0.75 0.30 12.86 0.47(0.13~8.75) 0.213 D -0.41 0.17 6.01 0.67(0.22~9.75) 0.182 Borrmann分型 Ⅰ型 - - - - - Ⅱ型 0.20 0.53 0.88 1.22(0.53~11.32) 0.422 Ⅲ型 0.67 0.21 14.53 1.96(0.42~23.21) 0.323 Ⅳ型 -0.81 0.64 1.98 0.45(0.12~8.43) 0.753 壁外静脉血管侵犯(否比是) 2.93 0.34 1.05 11.04(10.28~23.52) <0.001 肿瘤强化程度(高度强化比中低度强化) -0.68 0.54 1.37 0.51(0.28~3.52) 0.049 注: “-”为此项无多因素分析结果显示:术前CEA和EMVI是进展期胃腺癌患者根治术后预后的独立影响因素(P<0.05)。见表2。
表 2 影响88例进展期胃腺癌患者根治术后预后的多因素分析Table 2. Multivariate analysis of prognosis of 88 patients with advanced gastric adenocarcinoma after radical resection临床及影像学特征 b值 标准误 Wald值 比值比(95%可信区间) P值 术前癌胚抗原 -0.96 0.02 23.34 1.10(1.01~3.82) <0.001 壁外静脉血管侵犯 1.97 1.05 3.52 7.72(1.42~15.42) 0.004 三、预测模型的构建及评价
术前CEA、EMVI预测进展期胃腺癌患者预后的效能AUC分别为0.90(95%CI为0.82~0.97)、0.80(0.71~0.89),灵敏度和特异度分别为85.25%、78.69%和100.00%、81.48%。根据多因素分析结果,联合术前CEA和EMVI建立预测模型,其AUC为0.93(95%CI为0.87~0.98),灵敏度和特异度分别为86.89%和96.30%。见图4。
图 4 术前CEA联合EMVI预测88例进展期胃腺癌患者根治术后预后的受试者工作特征曲线注:CEA为癌胚抗原,EMVI为壁外静脉血管侵犯Figure 4. The receiver operating characteristic curve of pre⁃operative carcinoembryonic antigen combined with extramural venous invasion in predicting prognosis of 88 patients with advanced gastric adenocarcinoma after radical resection讨论
随着胃癌学科及临床规范化管理模式的发展,对可切除胃癌患者的术前准确评估有更高要求[24⁃25]。病灶评估目前仍依赖于病理学检查,但患者的病理学检查结果只能在术后获得,影响术前判断[26]。术前CT检查有助于患者预后评估。早期Park等[27]的研究结果显示:术前CT检查可直接用于进展期胃癌患者的危险分层和辅助治疗方案的制订。UICC与AJCC联合制订的以CT检查为基础的TNM分期是当前胃癌国际通用的分期系统[28]。对胃癌患者良好的临床评估需要精准判断肿瘤位置、大小及侵犯程度,但胃同时毗邻多个脏器,常规CT检查显影的图像有限[29]。MSCT检查可对患者腹腔内部进行多角度观察,具有清晰、方便、快捷等优势[30]。
本研究结果显示:浆膜侵犯、淋巴结转移、EMVI、肿瘤强化程度均是影响进展期胃腺癌患者预后的相关因素,其中EMVI为影像学特征中的独立预后因素。浆膜层是阻挡胃癌细胞向远处扩散的最后一道屏障,浆膜侵犯即意味着肿瘤细胞更容易突破浆膜形成腹膜转移及远处播散[31]。淋巴结转移是胃癌最重要的转移方式,大量的研究结果显示:胃癌患者术前淋巴结转移数目越多,根治术后的生存时间越短,进展期胃癌的淋巴结转移状态是制订个体化胃癌临床管理方式的必要条件[32]。EMVI指肿瘤直接侵犯胃肠道固有肌层外的静脉血管,是病灶发展及侵犯周围器官的指标之一。胃癌患者中的EMVI发生率为20%~30%,与影像学TNM分期系统比较,EMVI也是预测胃癌及结直肠癌局部复发及远处转移的独立危险因素之一[33]。CT动态增强检查是观察肿瘤血管的常见标准,病灶高度强化的患者意味着肿瘤内部血管丰富,肿瘤本身具有较大进展潜能,实体瘤的高度强化多与肿瘤浸润、侵袭、转移等密切相关。
本研究结果显示:影像学特征中肿瘤长径、病灶局限性、病灶部位、Borrmann分型并非影响胃腺癌患者预后的相关因素。肿瘤长径>7 cm是进展期胃癌患者术后发生腹膜转移的重要危险因素之一[34]。但考虑到胃活动度大,基于CT检查图像测量肿瘤长径欠精准,临床实践中难以避免人工测量造成误差。此外,病灶部位及局限性程度也是对实体肿瘤观察的直接标准,肿瘤长径越大,患者行R0切除的可能性越小,手术难度越大,术后复发风险越高。从流行病学角度而言,以胃体部胃癌患者的生存率最高,贲门及广泛型最低,胃窦部居中[35]。Borrmann分型Ⅳ型患者的预后较差,最为常见的Borrmann分型Ⅲ型的预后与多种因素有关,当前对此种类型的生存率尚无统一定论[36]。
本研究结果显示:年龄、术前CEA、术前CA19‑9是影响进展期胃腺癌患者预后的相关因素,其中术前CEA为独立预后因素。部分高龄患者术后营养吸收欠佳,对术后辅助化疗耐受性差,这些都可能是导致年龄越大预后越差的原因。而肿瘤标志物是一种常见的评估肿瘤发生、发展的指标,CEA及CA19‑9在胃癌、结直肠癌的消化道肿瘤中应用广泛,但特异性欠佳,未来仍需进一步探索。临床实践中,单纯的肿瘤标志物升高并不能准确提示患者肿瘤发生,如影像学特征同时支持肿瘤表现,二者联合可提高术前诊断效能。本研究联合术前CEA及EMVI两个独立预后因素,发现诊断效能AUC值升高至0.93。
综上,术前CEA及EMVI是进展期胃腺癌患者根治术后预后的独立影响因素;联合术前CEA和EMVI建立预测模型,对患者预后的预测效能良好。
陈义林:酝酿设计试验,实施研究,采集数据,起草文章,统计分析;夏文评:分析、解释数据,对文章的知识性内容作批评性审阅;王华:收集、分析、解释数据;刘橼:采集数据;王志炎、董永权:分析、解释数据;分析、解释数据;陈俊波:对文章的知识性内容作批评性审阅;陈小言:统计指导,英文摘要撰写所有作者均声明不存在利益冲突陈义林, 夏文评, 王华, 等. 基于多层螺旋CT检查的临床影像模型对进展期胃腺癌预后的预测价值[J]. 中华消化外科杂志, 2024, 23(9): 1220-1226. DOI: 10.3760/cma.j.cn115610-20240612-00289.http://journal.yiigle.com/LinkIn.do?linkin_type=cma&DOI=10.3760/cma.j.cn115610-20240612-24289
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图 1 进展期胃腺癌患者术前多层螺旋CT检查结果 1A:平扫示胃窦部病灶向腔内突出(←),周围脂肪间隙稍模糊;1B:增强检查示胃窦部病灶向腔内突出(←),病灶明显强化;1C:胃小弯侧见肿大淋巴结(←);1D:冠状位示胃窦部病灶向腔内突出(←)
Figure 1. Results of preoperative multi⁃slice helical computer tomography (CT) imaging for patients of advanced gastric adenocarcinoma 1A: Results of CT plain scan show the lesion in the gastric antrum protruding into the cavity (←), and the surrounding fat space is slightly blurred; 1B: Results of CT enhanced scan show the lesion in the gastric antrum protruding into the cavity (←), and the lesion is significantly enhanced; 1C: Enlarged lymph nodes are seen in the lesser curvature of the stomach (←); 1D: Results of coronal CT scan show the lesion in the gastric antrum protruding into the cavity (←)
图 4 术前CEA联合EMVI预测88例进展期胃腺癌患者根治术后预后的受试者工作特征曲线
注:CEA为癌胚抗原,EMVI为壁外静脉血管侵犯
Figure 4. The receiver operating characteristic curve of pre⁃operative carcinoembryonic antigen combined with extramural venous invasion in predicting prognosis of 88 patients with advanced gastric adenocarcinoma after radical resection
表 1 影响88例进展期胃腺癌患者根治术后预后的单因素分析
Table 1 Univariate analysis of prognosis of 88 patients with advanced gastric adenocarcinoma after radical resection
临床及影像学特征 b值 标准误 Wald值 比值比(95%可信区间) P值 年龄 0.02 0.01 0.57 1.02(0.60~1.45) 0.045 性别(男比女) 0.07 0.17 0.20 0.93(0.56~1.32) 0.991 饮酒史(否比是) -0.04 0.15 0.05 0.97(0.43~1.31) 0.787 吸烟史(否比是) -2.44 0.64 2.21 0.08(0.01~2.18) 0.141 体质量指数 1.37 0.64 0.70 3.94(0.16~11.64) 0.431 肿瘤分化程度(高中分化比低分化) 0.55 0.17 13.06 1.74(0.64~4.25) 0.064 术前癌胚抗原 -0.91 0.30 18.01 0.40(0.17~1.99) <0.001 术前CA19‑9 0.67 0.17 14.62 1.96(0.32~3.43) 0.032 浆膜侵犯(否比是) 0.52 0.19 7.17 1.67(0.58~4.65) 0.028 肿瘤长径(>5 cm比≤5 cm) 0.21 0.19 0.86 1.23(0.76~5.32) 0.484 淋巴结转移(否比是) 0.67 0.25 0.86 1.96(0.27~7.97) 0.037 病灶局限性(非局限性比局限性) 1.97 0.65 3.52 7.72(1.15~23.43) 0.661 病灶部位 0.856 A - - - - - B -0.92 0.21 18.02 0.40(0.11~2.43) 0.197 C -0.75 0.30 12.86 0.47(0.13~8.75) 0.213 D -0.41 0.17 6.01 0.67(0.22~9.75) 0.182 Borrmann分型 Ⅰ型 - - - - - Ⅱ型 0.20 0.53 0.88 1.22(0.53~11.32) 0.422 Ⅲ型 0.67 0.21 14.53 1.96(0.42~23.21) 0.323 Ⅳ型 -0.81 0.64 1.98 0.45(0.12~8.43) 0.753 壁外静脉血管侵犯(否比是) 2.93 0.34 1.05 11.04(10.28~23.52) <0.001 肿瘤强化程度(高度强化比中低度强化) -0.68 0.54 1.37 0.51(0.28~3.52) 0.049 注: “-”为此项无表 2 影响88例进展期胃腺癌患者根治术后预后的多因素分析
Table 2 Multivariate analysis of prognosis of 88 patients with advanced gastric adenocarcinoma after radical resection
临床及影像学特征 b值 标准误 Wald值 比值比(95%可信区间) P值 术前癌胚抗原 -0.96 0.02 23.34 1.10(1.01~3.82) <0.001 壁外静脉血管侵犯 1.97 1.05 3.52 7.72(1.42~15.42) 0.004 -
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