可切除胰腺癌术前评分分级体系的建立与应用
DOI: 10.3969/j.issn.1001-5256.2022.10.023
Establishment and application of a preoperative grading system for resectable pancreatic cancer
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摘要:
目的 探讨分析可切除胰腺癌早期复发的危险因素及评分分级体系的建立与应用。 方法 采用回顾性病例对照研究方法,纳入浙江大学医学院附属第二医院肝胆胰外科2015年3月—2021年6月行根治性切除手术的可切除胰腺癌患者303例,其中283例直接手术患者分为早期复发组(术后6个月内)(n=95)和非早期复发组(n=188);术前行新辅助治疗患者20例为新辅助治疗组。观察指标包括患者的一般资料及术前影像资料;患者术前实验室检验资料,血常规、血生化及衍生指标,肿瘤标志物及凝血指标;随访获得无复发生存情况。正态分布的计量资料两组间比较采用t检验;非正态分布的计量资料两组间比较采用Mann-Whitney U检验。计数资料两组间比较采用χ2检验。通过受试者工作特征曲线确定各指标的最佳临界值。采用多因素Logistic回归分析胰腺癌患者早期复发的危险因素。绘制Kaplan-Meier曲线并采用Log-rank检验比较各组患者的无复发生存期。 结果 单因素分析结果显示,与非早期复发组相比,早期复发组患者BMI、甘油三酯较低,CA19-9、CA242、CA125、血浆纤维蛋白原较高(P值均<0.05)。多因素Logistic回归分析结果显示,BMI(OR=1.150,95%CI:1.038~1.273,P=0.007)、血浆纤维蛋白原(OR=2.513,95%CI:1.355~4.663,P=0.003)和CA242(OR=2.482,95%CI:1.067~5.774,P=0.035)是可切除胰腺癌患者早期复发的独立危险因素。将BMI、CA242、血浆纤维蛋白原3项指标纳入评分分级体系,临界值分别为23.00 kg/m2、30.00 U/mL和4.00 g/L。BMI<23.00 kg/m2计为1分,否则计为0分;CA242≥30.0 U/mL计为1分,否则0分;血浆纤维蛋白原≥4.00 g/L计为1分,否则0分,总分为0~3分。对早期复发与非早期复发患者进行评分,结果显示早期复发组评分更高[2(0~3)分vs 1(0~3)分,Z=-5.339,P<0.001]。Kaplan-Meier曲线分析结果显示,不同评分组别的患者无复发生存时间比较差异有统计学意义(χ2=28.116,P<0.001),分值越高预期无复发生存时间越短。将3分定义为高危组,0~2分定义为低危组。高危组早期复发率为84.6%,低危组早期复发率为31.2%。 结论 基于BMI、血浆纤维蛋白原和CA242这3项指标建立的评分系统能够在一定程度上预测患者术后复发情况。 Abstract:Objective To investigate the risk factors for early recurrence of resectable pancreatic cancer and the establishment and application of a grading system. Methods A retrospective case-control study was conducted among 303 patients with resectable pancreatic cancer who underwent radical resection in Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, from March 2015 to June 2021, and according to the presence or absence of early recurrence (within 6 months after surgery), the 283 patients directly operated on were divided into early recurrence group with 95 patients and non-early recurrence group with 188 patients; 20 patients who received neoadjuvant therapy before surgery were enrolled as neoadjuvant therapy group. Observation indicators included general information, preoperative imaging data, preoperative laboratory data, routine blood test/blood biochemistry and derived indicators, tumor markers, and coagulation markers, and follow-up was conducted to observe recurrence-free survival. The t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. A multivariate Logistic regression analysis was used to investigate the risk factors for early recurrence in patients with pancreatic cancer, and the receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value of each indicator. The Kaplan-Meier curve was plotted, and the Log-rank test was used for comparison of recurrence-free survival time between groups. Results The univariate analysis showed that compared with the non-early recurrence group, the early recurrence group had significantly lower body mass index (BMI) and triglyceride and significantly higher CA19-9, CA242, CA125, and plasma fibrinogen (all P < 0.05). The multivariate logistic regression analysis showed that BMI (odds ratio [OR]=1.150, 95% confidence interval [CI]: 1.038-1.273, P=0.007), plasma fibrinogen (OR=2.513, 95%CI: 1.355-4.663, P=0.003), and CA242 (OR=2.482, 95%CI: 1.067-5.774, P=0.035) were independent risk factors for early recurrence in patients with resectable pancreatic cancer. BMI, CA242, and plasma fibrinogen were included in the grading system, with a cut-off value of 23.00 kg/m2, 30.0 U/mL, and 4.00 g/L, respectively. BMI < 23.00 kg/m2 was counted as 1 point, otherwise it was counted as 0 point; CA242≥30.00 U/mL was counted as 1 point, otherwise it was counted as 0 point; plasma fibrinogen ≥4.00 g/L was counted as 1 point, otherwise it was counted as 0 point; the total score was 0-3 points. The patients in both the early recurrence group and the non-early recurrence group were scored, and the results showed that the early recurrence group had a significantly higher score than the non-early recurrence group [2(0-3) points vs 1(0-3) point, Z=-5.339, P < 0.001]. The Kaplan-Meier curve analysis showed that there was a significant difference in time to recurrence between groups (χ2=28.116, P < 0.001), and the higher the score, the shorter the expected time to recurrence. The patients with 3 points were defined as high-risk group and those with 0-2 points were defined as low-risk group, and the early recurrence rate was 84.6% in the high-risk group and 31.2% in the low-risk group. Conclusion The grading system based on BMI, plasma fibrinogen, and CA242 can reliably predict postoperative recurrence. -
Key words:
- Pancreatic Neoplasms /
- Neoplasm Recurrence, Local /
- Risk Factors
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表 1 患者基线资料
Table 1. Baseline data of patients
指标 早期复发组(n=95) 非早期复发组(n=188) 统计值 P值 男/女(例) 52/43 114/74 χ2=0.906 0.372 年龄(岁) 64.67±9.60 63.31±8.90 t=-1.186 0.236 BMI(kg/m2) 22.04±3.03 23.00±2.99 t=2.522 0.012 糖尿病史[例(%)] 22(23.16) 56(29.79) χ2=1.389 0.262 烟酒史[例(%)] 39(41.05) 92(48.94) χ2=1.578 0.256 肝炎病史[例(%)] 9(9.47) 17(9.04) χ2=0.014 >0.05 术前疼痛[例(%)] 50(52.63) 80(42.55) χ2=2.581 0.130 影像肿瘤直径(mm) 28.50(13.20~102.00) 26.00(3.00~83.00) Z=-1.580 0.114 肿瘤位置[胰头,例(%)] 60(63.16) 99(52.66) χ2=3.186 0.203 肿大淋巴结[例(%)] 44(46.32) 67(35.64) χ2=3.018 0.094 周围血管侵犯1)[例(%)] 39(41.05) 60(31.91) χ2=2.317 0.147 临近器官侵犯2)[例(%)] 11(11.58) 21(11.17) χ2=0.011 >0.05 胰管扩张[例(%)] 74(77.89) 132(70.21) χ2=1.880 0.203 胰腺萎缩[例(%)] 26(27.37) 39(20.74) χ2=1.565 0.233 黄疸[例(%)] 28(29.47) 56(29.79) χ2=0.003 >0.05 术前行胆道引流3)[例(%)] 15(15.79) 33(17.55) χ2=0.139 0.741 注:1),周围血管侵犯均符合可切除胰腺癌标准,包括侵犯门静脉但未超过180°,且静脉轮廓规则;侵犯脾动脉和/或脾静脉;4例胰头癌侵犯胃十二指肠动脉。2),临近器官侵犯主要指十二指肠或胆管下段侵犯。3),术前行胆道引流应用内镜下支架植入术和/或经皮肝穿刺胆道引流术。 表 2 血常规相关指标
Table 2. Blood routine related indexes
指标 早期复发组(n=95) 非早期复发组(n=188) 统计值 P值 白细胞(×109/L) 5.90(3.10~11.70) 5.40(2.20~10.50) Z=-1.512 0.131 血红蛋白(g/L) 126.85±16.54 128.49±15.28 t=0.830 0.407 红细胞(×1012/L) 4.14±0.52 4.20±0.53 t=0.778 0.437 血小板计数(×109/L) 207.68±69.40 196.18±66.01 t=-1.361 0.175 中性粒细胞计数(×109/L) 3.98±1.59 3.71±1.28 t=-1.546 0.123 中性粒细胞百分比 64.06±9.19 63.58±9.23 t=-0.412 0.680 淋巴细胞计数(×109/L) 1.45±0.47 1.45±0.54 t=-0.028 0.978 中性粒细胞/淋巴细胞比值 2.56(1.05~20.80) 2.49(0.69~9.30) Z=-0.456 0.648 单核细胞计数(×109/L) 0.40(0.20~1.80) 0.39(0.13~1.08) Z=-0.876 0.381 嗜酸性粒细胞计数(×109/L) 0.12(0.02~0.66) 0.10(0~1.38) Z=-1.832 0.067 嗜碱性粒细胞计数(×109/L) 0.03(0~0.10) 0.02(0~0.08) Z=-1.091 0.275 血小板/淋巴细胞比值 154.15±62.20 149.99±64.94 t=-0.516 0.607 表 3 生化指标比较
Table 3. Comparison of biochemical indexes
指标 早期复发组(n=95) 非早期复发组(n=188) 统计值 P值 PNI 46.82±5.21 47.38±5.62 t=0.805 0.421 GPS评分1)(0/1/2,例) 39/12/8 79/34/10 χ2=2.051 0.359 CRP/白蛋白比值 0.18(0~2.00) 0.13(0~4.27) Z=-1.102 0.271 总蛋白(g/L) 67.07±6.29 68.14±7.11 t=1.238 0.217 白蛋白(g/L) 39.56±4.05 40.13±4.46 t=1.037 0.301 谷草转氨酶(U/L) 24.0(13.0~588.0) 24.5(9.0~480.0) Z=-0.412 0.681 谷丙转氨酶(U/L) 23.0(5.0~846.0) 25.0(7.0~828.0) Z=-0.799 0.425 脂肪酶(U/L) 61.5(3.0~3 138.0) 51.0(8.0~923.0) Z=-0.757 0.449 淀粉酶(U/L) 78.0(16.0~1 053.0) 69.0(26.0~572.0) Z=-0.286 0.775 葡萄糖(mmol/L) 5.85(3.35~17.28) 6.20(3.62~18.57) Z=-0.713 0.476 糖化白蛋白(%) 16.40(8.40~47.60) 16.70(10.60~45.60) Z=-0.202 0.840 糖化白蛋白1(g/L) 6.00(3.60~36.90) 5.70(3.10~12.70) Z=-1.018 0.309 糖化白蛋白2(g/L) 39.34±7.26 39.12±6.12 t=-0.185 0.854 尿素氮(mmol/L) 4.60(1.84~9.65) 4.63(2.64~13.67) Z=-1.064 0.287 肌酐(μmol/L) 56.00(32.00~126.00) 59.00(13.00~160.00) Z=-1.716 0.086 总胆固醇(mmol/L) 4.98(2.14~14.46) 4.69(1.97~16.69) Z=-1.016 0.310 甘油三酯(mmol/L) 1.16(0.42~4.34) 1.40(0.46~7.36) Z=-2.501 0.012 CRP(mg/L) 7.50(0.10~76.40) 5.10(0.10~141.40) Z=-1.082 0.279 碱性磷酸酶(U/L) 106.0(53.0~1 220.0) 103.0(53.0~1 558.0) Z=-0.273 0.785 γ-谷氨酰转肽酶(U/L) 32.0(10.0~2 230.0) 38.0(9.0~2 634.0) Z=-0.406 0.684 α-L-岩藻糖苷酶(U/L) 27.00(12.00~75.00) 27.00(9.00~93.00) Z=-0.282 0.778 注:1),部分患者观察指标数据缺失。 表 4 肿瘤标志物及凝血指标
Table 4. Coagulation and tumor markers
指标 早期复发组(n=95) 非早期复发组(n=188) 统计值 P值 CA19-9(U/mL) 426.90(2.00~12 000.00) 197.70(2.00~12 000.00) Z=-3.433 <0.001 CA242(U/mL) 40.90(1.00~530.00) 19.50(0.50~1 000.00) Z=-3.804 <0.001 CA125(U/mL) 17.65(4.20~114.20) 14.40(2.10~893.90) Z=-2.383 0.017 CEA(ng/mL) 3.40(0.70~125.90) 3.25(0.80~258.50) Z=-0.198 0.843 AFP(ng/mL) 2.50(0.90~8.30) 2.70(0.70~90.90) Z=-1.740 0.082 凝血酶原时间(s) 13.1(11.5~18.5) 13.0(11.0~32.6) Z=-0.613 0.540 D-二聚体(μg/L) 480(180~7140) 440(40~11 340) Z=-0.524 0.600 血浆纤维蛋白原(g/L) 3.76(2.16~7.94) 3.52(2.16~7.33) Z=-2.266 0.023 国际标准化比值 1.01(0.85~1.55) 0.99(0.82~3.33) Z=-0.580 0.562 FPR 21.09±8.54 20.76±7.82 t=-0.321 0.748 表 5 术后病理指标与辅助治疗
Table 5. Post-operative clinicopathologic characteristics and adjuvant therapy
指标 早期复发组(n=95) 非早期复发组(n=188) 统计值 P值 肿瘤直径(cm) 3.17±1.22 3.06±1.25 t=-0.741 0.459 T分期(1/2/3/4,例) 21/54/16/1 56/98/29/1 χ2=2.223 0.695 N分期(0/1/2,例) 42/42/8 120/37/23 χ2=18.880 <0.001 R0切除[例(%)] 90(94.7) 176(93.6) χ2=0.140 0.797 神经侵犯[例(%)] 78(82.1) 158(84.0) χ2=0.171 0.736 脉管侵犯[例(%)] 37(38.9) 67(35.6) χ2=0.297 0.603 肿瘤分化情况(0/1/2/3/4,例) 12/32/44/4/3 9/39/100/19/20 χ2=17.581 0.004 术后辅助治疗[例(%)] 62(65.3) 143(76.1) χ2=3.687 0.067 注:T分期、N分期、肿瘤分化情况中部分患者观察指标数据缺失。肿瘤分化情况,0/1/2/3/4依次为低分化/中低分化/中分化/中高分化/高分化。 表 6 多因素Logistic回归分析
Table 6. Multivariate Logistic regression analysis
项目 B值 SE Wald P值 OR 95%CI 截距 -4.506 1.230 13.414 0.000 BMI 0.139 0.052 7.191 0.007 1.150 1.038~1.273 甘油三酯 0.243 0.160 2.305 0.129 1.275 0.932~1.746 淋巴结肿大 0.309 0.289 1.139 0.286 1.362 0.772~2.402 CA19-9 0.400 0.418 0.914 0.339 1.492 0.657~3.386 CA242 0.909 0.431 4.450 0.035 2.482 1.067~5.774 CA125 0.479 0.294 2.655 0.103 1.614 0.907~2.870 血浆纤维蛋白原 0.922 0.315 8.540 0.003 2.513 1.355~4.663 -
[1] SIEGEL RL, MILLER KD, FUCHS HE, et al. Cancer statistics, 2021[J]. CA Cancer J Clin, 2021, 71(1): 7-33. DOI: 10.3322/caac.21654. [2] CHEN X, YI B, LIU Z, et al. Global, regional and national burden of pancreatic cancer, 1990 to 2017: Results from the Global Burden of Disease Study 2017[J]. Pancreatology, 2020, 20(3): 462-469. DOI: 10.1016/j.pan.2020.02.011. [3] ZHANG QH, NI QX, Coordination Group of The Committee on Pancreatic Cancer. Clinical analysis of 2340 cases of pancreatic cancer[J]. Natl Med J China, 2004, 84(3): 214-218. DOI: 10.3760/j:issn:0376-2491.2004.03.010.张群华, 倪泉兴, 中国抗癌协会胰腺癌专业委员会. 胰腺癌2340例临床病例分析[J]. 中华医学杂志, 2004, 84(3): 214-218. DOI: 10.3760/j:issn:0376-2491.2004.03.010. [4] GROOT VP, DAAMEN LA, HAGENDOORN J, et al. Current strategies for detection and treatment of recurrence of pancreatic ductal adenocarcinoma after resection: A nationwide survey[J]. Pancreas, 2017, 46(9): e73-e75. DOI: 10.1097/MPA.0000000000000899. [5] NEOPTOLEMOS JP, PALMER DH, GHANEH P, et al. Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial[J]. Lancet, 2017, 389(10073): 1011-1024. DOI: 10.1016/S0140-6736(16)32409-6. [6] CONROY T, HAMMEL P, HEBBAR M, et al. FOLFIRINOX or gemcitabine as adjuvant therapy for pancreatic cancer[J]. N Engl J Med, 2018, 379(25): 2395-2406. DOI: 10.1056/NEJMoa1809775. [7] GROOT VP, GEMENETZIS G, BLAIR AB, et al. Defining and predicting early recurrence in 957 patients with resected pancreatic ductal adenocarcinoma[J]. Ann Surg, 2019, 269(6): 1154-1162. DOI: 10.1097/SLA.0000000000002734. [8] TEMPERO MA, MALAFA MP, AL-HAWARY M, et al. Pancreatic adenocarcinoma, Version 2.2021, NCCN Clinical Practice Guidelines in oncology[J]. J Natl Compr Canc Netw, 2021, 19(4): 439-457. DOI: 10.6004/jnccn.2021.0017. [9] Chinese Pancreatic Surgery Association, Chinese Society of Surgery, Chinese Medical Association. Guidelines for the diagnosis and treatment of pancreatic cancer in China (2021)[J]. Chin J Pract Surg, 2021, 41(7): 725-738. DOI: 10.19538/j.cjps.issn1005-2208.2021.07.02.中华医学会外科学分会胰腺外科学组. 中国胰腺癌诊治指南(2021)[J]. 中国实用外科杂志, 2021, 41(7): 725-738. DOI: 10.19538/j.cjps.issn1005-2208.2021.07.02. [10] SUR YK, KIM YC, KIM JK, et al. Comparison of ultrasound-guided core needle biopsy and endoscopic ultrasound-guided fine-needle aspiration for solid pancreatic lesions[J]. J Ultrasound Med, 2015, 34(12): 2163-2169. DOI: 10.7863/ultra.14.11030. [11] SOHN TA, YEO CJ, CAMERON JL, et al. Resected adenocarcinoma of the pancreas-616 patients: results, outcomes, and prognostic indicators[J]. J Gastrointest Surg, 2000, 4(6): 567-579. DOI: 10.1016/s1091-255x(00)80105-5. [12] WAGNER M, REDAELLI C, LIETZ M, et al. Curative resection is the single most important factor determining outcome in patients with pancreatic adenocarcinoma[J]. Br J Surg, 2004, 91(5): 586-594. DOI: 10.1002/bjs.4484. [13] HAENO H, GONEN M, DAVIS MB, et al. Computational modeling of pancreatic cancer reveals kinetics of metastasis suggesting optimum treatment strategies[J]. Cell, 2012, 148(1-2): 362-375. DOI: 10.1016/j.cell.2011.11.060. [14] ZHENG MH, SHAO CH. Evaluation of neoadjuvant chemotherapy for pancreatic cancer and timing of surgery[J/CD]. Chin J Hepat Surg: Electronic Edition, 2020, 9(5): 418-420. DOI: 10.3877/cma.j.issn.2095-3232.2020.05.005.郑明辉, 邵成浩. 胰腺癌新辅助化疗疗效评估及手术时机[J/CD]. 中华肝脏外科手术学电子杂志, 2020, 9(5): 418-420. DOI: 10.3877/cma.j.issn.2095-3232.2020.05.005. [15] YANG YM, ZHAO XD. Evaluation of neoadjuvant therapy for pancreatic cancer: is it the best choice?[J]. Chin J Dig Surg, 2020, 19(1): 41-45. DOI: 10.3760/cma.j.issn.1673-9752.2020.01.006.杨尹默, 赵旭东. 肯定还是否定: 胰腺癌新辅助治疗[J]. 中华消化外科杂志, 2020, 19(1): 41-45. DOI: 10.3760/cma.j.issn.1673-9752.2020.01.006. [16] KURAHARA H, MAEMURA K, MATAKI Y, et al. A Therapeutic strategy for resectable pancreatic cancer based on risk factors of early recurrence[J]. Pancreas, 2018, 47(6): 753-758. DOI: 10.1097/MPA.0000000000001066. [17] IMAMURA M, NAGAYAMA M, KYUNO D, et al. Perioperative predictors of early recurrence for resectable and borderline-resectable pancreatic cancer[J]. Cancers (Basel), 2021, 13(10): 2285. DOI: 10.3390/cancers13102285. [18] HANK T, HINZ U, REINER T, et al. A pretreatment prognostic score to stratify survival in pancreatic cancer[J]. Ann Surg, 2021. DOI: 10.1097/SLA.0000000000004845. [Online ahead of print] [19] KIM DW, LEE SS, KIM SO, et al. Estimating recurrence after upfront surgery in patients with resectable pancreatic ductal adenocarcinoma by using pancreatic CT: Development and validation of a risk score[J]. Radiology, 2020, 296(3): 541-551. DOI: 10.1148/radiol.2020200281. [20] OKABAYASHI T, SHIMA Y, SUMIYOSHI T, et al. A novel physiobiological parameter-based grading system for resectable pancreatic cancer[J]. Ann Surg Oncol, 2018, 25(7): 1889-1895. DOI: 10.1245/s10434-018-6485-7. [21] HOSHIMOTO S, HISHINUMA S, SHIRAKAWA H, et al. Validation and clinical usefulness of pre- and postoperative systemic inflammatory parameters as prognostic markers in patients with potentially resectable pancreatic cancer[J]. Pancreatology, 2020, 20(2): 239-246. DOI: 10.1016/j.pan.2019.12.004. [22] YAMADA S, FUJII T, YABUSAKI N, et al. Clinical implication of infammation-based prognostic score in pancreatic cancer: Glasgow prognostic score is the most reliable parameter[J]. Medicine (Baltimore), 2016, 95(18): e3582. DOI: 10.1097/MD.0000000000003582. [23] LIU Z, JIN K, GUO M, et al. Prognostic value of the CRP/Alb ratio, a novel inflammation-based score in pancreatic cancer[J]. Ann Surg Oncol, 2017, 24(2): 561-568. DOI: 10.1245/s10434-016-5579-3. [24] KANDA M, FUJII T, KODERA Y, et al. Nutritional predictors of postoperative outcome in pancreatic cancer[J]. Br J Surg, 2011, 98(2): 268-274. DOI: 10.1002/bjs.7305. [25] STOTZ M, GERGER A, EISNER F, et al. Increased neutrophil-lymphocyte ratio is a poor prognostic factor in patients with primary operable and inoperable pancreatic cancer[J]. Br J Cancer, 2013, 109(2): 416-421. DOI: 10.1038/bjc.2013.332. [26] BHATTI I, PEACOCK O, LLOYD G, et al. Preoperative hematologic markers as independent predictors of prognosis in resected pancreatic ductal adenocarcinoma: neutrophil-lymphocyte versus platelet-lymphocyte ratio[J]. Am J Surg, 2010, 200(2): 197-203. DOI: 10.1016/j.amjsurg.2009.08.041. [27] CHENG Y, LI LX, ZENG WB. Prediction of combination detection of serum CEA, CA19-9 and CA50 levels for surgical resectability of pancreatic cancer[J]. Clin Misdiagn Misther, 2020, 33(1): 84-87. DOI: 10.3969/j.issn.1002-3429.2020.01.020.程勇, 李领侠, 曾文斌. 血清CEA、CA19-9、CA50联合检测对胰腺癌手术可切除性的预测价值研究[J]. 临床误诊误治, 2020, 33(1): 84-87. DOI: 10.3969/j.issn.1002-3429.2020.01.020. [28] LUO G, LIU C, GUO M, et al. Potential biomarkers in lewis negative patients with pancreatic cancer[J]. Ann Surg, 2017, 265(4): 800-805. DOI: 10.1097/SLA.0000000000001741. [29] LIU L, XU H, WANG W, et al. A preoperative serum signature of CEA+/CA125+/CA19-9≥1000 U/mL indicates poor outcome to pancreatectomy for pancreatic cancer[J]. Int J Cancer, 2015, 136(9): 2216-2227. DOI: 10.1002/ijc.29242. [30] VYAS SJ, PURI YS, JOHN BJ, et al. Radiological tumor density and lymph node size correlate with survival in resectable adenocarcinoma of the pancreatic head: A retrospective cohort study[J]. J Cancer Res Ther, 2016, 12(1): 417-421. DOI: 10.4103/0973-1482.171358. [31] STRIJKER M, van der SIJDE F, SUKER M, et al. Preoperative serum ADAM12 levels as a stromal marker for overall survival and benefit of adjuvant therapy in patients with resected pancreatic and periampullary cancer[J]. HPB (Oxford), 2021, 23(12): 1886-1896. DOI: 10.1016/j.hpb.2021.05.001. [32] Early Diagnosis and Treatment Group, the Oncology Committee of Chinese Medical Association. Expert consensus of Oncology Committee of Chinese Medical Association in early diagnosis and treatment of pancreatic cancer[J]. J Clin Hepatol, 2020, 36(12): 2675-2680. DOI: 10.3969/j.issn.1001-5256.2020.12.008.中华医学会肿瘤学分会早诊早治学组. 中华医学会肿瘤学分会胰腺癌早诊早治专家共识[J]. 临床肝胆病杂志, 2020, 36(12): 2675-2680. DOI: 10.3969/j.issn.1001-5256.2020.12.008. [33] HISADA Y, MACKMAN N. Cancer-associated pathways and biomarkers of venous thrombosis[J]. Blood, 2017, 130(13): 1499-1506. DOI: 10.1182/blood-2017-03-743211. [34] SGOUROS J, MARAVEYAS A. Excess premature (3-month) mortality in advanced pancreatic cancer could be related to fatal vascular thromboembolic events. A hypothesis based on a systematic review of phase III chemotherapy studies in advanced pancreatic cancer[J]. Acta Oncol, 2008, 47(3): 337-346. DOI: 10.1080/02841860701687267. [35] CAO J, FU Z, GAO L, et al. Evaluation of serum D-dimer, fibrinogen, and CA19-9 for postoperative monitoring and survival prediction in resectable pancreatic carcinoma[J]. World J Surg Oncol, 2017, 15(1): 48. DOI: 10.1186/s12957-017-1104-9. [36] ARAKAWA Y, MIYAZAKI K, YOSHIKAWA M, et al. Value of the fibrinogen-platelet ratio in patients with resectable pancreatic cancer[J]. J Med Invest, 2021, 68(3.4): 342-346. DOI: 10.2152/jmi.68.342. [37] DREYER SB, PINESE M, JAMIESON NB, et al. Precision oncology in surgery: Patient selection for operable pancreatic cancer[J]. Ann Surg, 2020, 272(2): 366-376. DOI: 10.1097/SLA.0000000000003143.