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肝胰同步手术切除与全身化疗治疗可切除胰腺癌伴肝转移患者的效果比较
DOI: 10.3969/j.issn.1001-5256.2022.03.023
伦理学声明：本研究方案于2021年5月18日经由中国医科大学附属盛京医院伦理委员会审批,批号：2021PS508K。
利益冲突声明：本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突。
作者贡献声明：金添强负责收集数据、资料分析、撰写论文; 戴朝六参与指导撰写文章及修改论文; 徐锋负责拟定写作思路、修改论文及最后定稿。
Clinical effect of simultaneous surgical resection of hepatic and pancreatic lesions versus systemic chemotherapy in treatment of resectable pancreatic cancer with liver metastasis
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摘要:
目的 比较肝胰病灶同步手术切除与全身化疗治疗可切除胰腺癌伴肝转移(PCLM)的效果。 方法 回顾性分析2013年1月—2020年5月中国医科大学附属盛京医院收治的PCLM患者资料。筛选出可切除病例,分为手术组和化疗组。采用倾向性评分匹配(PSM)方法以减少数据偏倚和混杂变量的影响。计量资料两组间比较采用独立样本t检验或Mann-Whitney U检验。计数资料组间比较采用χ2检验。采用Kaplan-Meier法计算患者生存时间,并用log-rank检验进行评估。采用单因素和多因素Cox回归模型分析影响生存的独立危险因素。 结果 筛选出可切除PCLM患者56例,其中手术组33例,化疗组23例,PSM后各组均15例。PSM前后,手术组患者中位总体生存时间(mOS)均显著短于化疗组患者(PSM前：6.6个月vs 10.4个月,χ2=4.476,P=0.034; PSM后：6.4个月vs 10.5个月,χ2=4.309,P=0.038)。多因素Cox分析结果显示,低分化肿瘤(HR=4.945,95%CI：1.980~12.348,P=0.001)和无术后化疗(HR=3.670,95%CI：1.437~9.376,P=0.007)是影响PCLM手术患者预后的独立危险因素。 结论 同步肝胰病灶手术切除相较化疗并未延长可切除PCLM患者的生存时间。低分化肿瘤以及未联合术后化疗者预后较差。 Abstract:Objective To investigate the clinical effect of simultaneous surgical resection of hepatic and pancreatic lesions versus systemic chemotherapy in treatment of resectable pancreatic cancer with liver metastasis (PCLM). Methods A retrospective analysis was performed for related data of the patients with PCLM who were admitted to Shengjing Hospital of China Medical University from January 2013 to May 2020, and the patients with resectable PCLM were screened out and then divided into surgery group and chemotherapy group. The propensity score matching (PSM) method was used to reduce the impact of data bias and confounding factors. The independent samples t-test or the Mann- Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The Kaplan-Meier method was used to calculate survival time, and the log-rank test was used for evaluation. The univariate and multivariate Cox regression models were used to investigate the independent risk factors for survival. Results A total of 56 patients with resectable PCLM were screened out, with 33 patients in the surgery group and 23 patients in the chemotherapy group, and there were 15 patients in each group after PSM. The surgery group had a significantly shorter median overall survival time than the chemotherapy group before PSM (6.6 months vs 10.4 months, χ2=4.476, P=0.034) and after PSM (6.4 months vs 10.5 months, χ2=4.309, P=0.038). The multivariate Cox regression analysis showed that poorly differentiated tumor (hazard ratio [HR]=4.945, 95% confidence interval [CI]: 1.980-12.348, P=0.001) and absence of postoperative chemotherapy (HR=3.670, 95%CI: 1.437-9.376, P=0.007) were independent risk factors for poor prognosis in patients with PCLM. Conclusion Compared with chemotherapy, simultaneous surgical resection of hepatic and pancreatic lesions fails to prolong the overall survival time of patients with resectable PCLM. Patients with poorly differentiated tumor and those without postoperative chemotherapy tend to have poor prognosis. -
图 1 可切除胰腺癌伴肝转移示例
注：a,增强MRI可见肝脏左叶转移癌2个,较大者直径约1 cm,增强扫描可见环形强化; b,肝左叶转移癌,直径约1.1 cm,增强扫描环形强化; c,胰腺体部可见长T1信号包块,大小约3.6 cm×3.2 cm,增强扫描可见弱强化,邻近脾动脉局部狭窄。
图 2 不可切除胰腺癌伴肝转移示例
注：a,不可切除肝转移病灶,CT扫描可见肝内多发弥漫性低密度转移灶,呈边缘强化; b,不可切除胰腺病灶合并可切除肝脏转移,CT扫描可见胰腺体尾部软组织密度包块,弱强化,包绕腹腔干及分支,肝右叶可见单发低密度转移病灶,直径约2.1 cm,增强扫描环形强化; c,不可切除胰腺癌及肝转移病灶,胰体部肿物包绕腹腔干、肝总动脉及脾动脉,肝内另可见多发弥漫性低密度环形强化转移病灶。
表 1 PSM前后手术组与化疗组患者的一般临床资料比较
指标 匹配前 P值 匹配后 P值 手术组(n=33) 化疗组(n=23) 手术组(n=15) 化疗组(n=15) 年龄(岁) 56.6±8.8 61.6±11.0 0.064 60.7±8.7 59.7±11.9 0.795 男/女(例) 17/16 14/9 0.488 7/8 9/6 0.715 BMI(kg/m2) 22.6±2.4 22.8±2.5 0.781 22.1±1.7 22.5±2.7 0.642 ECOG评分(例) 0.799 0.656 0分 5 5 2 4 1分 18 11 8 7 2分 10 7 5 4 WBC(109/L) 6.7±1.9 6.4±2.2 0.592 6.3±1.6 6.2±2.2 0.904 Hb(g/L) 134.8±18.2 130.5±15.1 0.364 129.7±17.9 130.1±15.0 0.939 PLT(109/L) 209.1±66.0 187.2±63.1 0.218 180.1±48.1 184.4±54.8 0.841 Alb(g/L) 43.7±3.1 42.1±3.2 0.066 42.4±2.8 42.3±2.7 0.928 ALP(U/L) 81.0(65.8~124.3) 100.0(84.0~127.0) 0.564 89.5±50.1 114.4±47.3 0.172 CA19-9(例) 0.177 0.999 ≤300 U/mL 16 7 6 6 ＞300 U/mL 17 16 9 9 CEA(U/mL) 4.9(2.7~10.5) 6.1(3.2~12.6) 0.489 4.4(1.2~13.4) 5.3(3.6~14.4) 0.789 胆汁引流(例) 0.507 0.999 是 2 0 1 0 否 31 23 14 15 原发肿瘤位置(例) 0.389 0.598 胰头 9 4 3 1 胰体尾 24 19 12 14 原发肿瘤大小(cm) 4.8±1.9 4.4±1.3 0.386 4.4±1.7 4.4±1.4 0.963 肝转移瘤数量(例) 0.258 0.976 单发 15 7 6 5 多发 18 16 9 10 肝转移瘤直径(cm) 1.6±1.3 1.5±0.5 0.863 1.7±1.3 1.6±0.5 0.680 注：本研究中手术组患者CA19-9水平的中位数约300 U/mL,因此选用300 U/mL作为分界值。 
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表 2 手术组患者围手术期临床资料及病理结果
指标 手术组(n=33) 平均手术时间(min) 431.6±151.6 住院时长(d) 29.3±13.9 术中失血(mL) 512.1±357.7 术中输血(是/否,例) 19/14 术后出血(是/否,例) 2/31 胰瘘(是/否,例) 11/22 术后感染(是/否,例) 18/15 胃排空延迟(是/否,例) 3/30 二次手术(是/否,例) 2/31 原发灶手术方式(例) 胰十二指肠切除术 11 胰体尾切除术 21 全胰切除术 1 肝转移灶手术方式(例) 楔形切除 27 肝段切除 5 半肝切除 1 肿瘤分化(例) 高/中分化 22 低分化 11 淋巴结转移(是/否,例) 15/18 脉管侵犯(是/否,例) 6/27 神经侵犯(是/否,例) 10/23 胰腺切缘(R0/R1,例) 26/7 肝脏切缘(R0/R1,例) 29/4 术后化疗(是/否,例) 8/25
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表 3 影响PCLM患者预后的单因素及多因素分析结果
因素 单因素分析 多因素分析 HR(95%CI) P值 HR(95%CI) P值 年龄(＞60岁/≤60岁) 0.571(0.309~0.904) 0.028 0.436(0.239~0.796) 0.007 性别(女/男) 1.242(0.739~2.150) 0.413 CA19-9(＞300 U/mL/≤300 U/mL) 1.365(0.824~2.395) 0.235 ALP(＞110 U/L/≤110 U/L) 1.209(0.687~2.218) 0.496 治疗方式(手术/化疗) 1.759(1.063~3.059) 0.034 1.591(0.882~2.868) 0.123 ECOG评分(2/0~1) 1.802(1.094~4.003) 0.031 2.356(1.282~4.328) 0.006 胰腺肿瘤位置(胰头/胰体尾) 1.085(0.593~2.012) 0.788 胰腺肿瘤分级(T3/T1~2) 1.343(0.765~2.541) 0.291 肝转移数目(多发/单发) 1.349(0.804~2.338) 0.262
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表 4 影响手术组患者预后的单因素及多因素分析结果
因素 单因素分析 多因素分析 HR(95%CI) P值 HR(95%CI) P值 年龄＞60岁 1.203(0.536~2.700) 0.536 男性 1.142(0.554~2.353) 0.721 CA19-9＞300 U/mL 1.467(0.721~2.985) 0.291 ALP＞110 U/L 1.876(0.852~4.132) 0.118 1.274(0.225~7.241) 0.784 GGT＞50 U/L 2.617(1.222~5.587) 0.013 1.716(0.747~3.941) 0.203 术中输血 1.260(0.619~2.568) 0.524 胰头癌 1.319(0.598~2.908) 0.493 多发肝转移 1.475(0.719~3.026) 0.289 低分化肿瘤 3.164(1.434~6.980) 0.004 4.945(1.980~12.348) 0.001 淋巴结转移 1.728(0.831~3.591) 0.143 1.188(0.476~2.966) 0.712 脉管侵犯 1.364(0.546~3.401) 0.507 神经侵犯 1.872(0.817~4.087) 0.142 1.460(0.618~3.452) 0.389 胰腺切缘R1 2.076(0.868~4.969) 0.101 1.442(0.457~4.544) 0.637 肝脏切缘R1 1.913(0.644~5.682) 0.243 无术后化疗 2.755(1.148~6.623) 0.023 3.670(1.437~9.376) 0.007
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