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84例肿瘤相关性急性胰腺炎的发病特征及预后分析
DOI: 10.3969/j.issn.1001-5256.2022.08.027
伦理学声明：本研究方案于2022年2月14日经由郑州大学第一附属医院伦理审查委员会审批，批号：2022-KY-0134。
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：郑琳琳和周琳对研究的思路和设计有关键贡献；何辉、孔笑华、周耘辉参与了研究数据的获取分析解释过程；郑琳琳和刘宁宁参与起草或修改文章关键内容。
Pathogenesis and prognosis of tumor-induced acute pancreatitis: An analysis of 84 cases
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摘要:
目的 通过回顾性分析肿瘤相关性急性胰腺炎(AP)患者的临床资料，评估胆胰及壶腹部肿瘤与AP发病之间的关系，探讨肿瘤相关性AP的临床特点。 方法 收集2013年1月—2021年8月郑州大学第一附属医院收治的AP患者病例资料。分析AP病因构成及肿瘤相关AP的发病率变化；对比分析肿瘤及非肿瘤AP，以及不同肿瘤部位AP的临床特征差异，探讨肿瘤相关AP的发病特点。正态分布的计量资料两组间比较采用t检验，多组间比较采用单因素方差分析，进一步两两比较采用SNK-q检验；非正态分布的计量资料两组间比较采用Mann-Whitney U检验，多组间比较采用Kruskal-Wallis H检验，进一步两两比较采用Wilcoxon秩和检验；计数资料二分类组间采用χ2检验或Fisher’s精确检验法比较，多分类组间比较采用拟合优度检验。应用受试者工作特征曲线(ROC曲线)评估胰腺肿瘤相关AP的鉴别因素；采用logistic多因素回归分析肿瘤相关性AP的独立影响因素。 结果 共入组AP患者8106例，肿瘤相关性AP患者84例，占1.04%。84例肿瘤相关AP患者平均年龄显著大于非肿瘤组(t=6.050, P＜0.001)。初发AP至确诊肿瘤平均时间为7.38个月；轻症急性胰腺炎(MAP)75例(89.2%)，中度重症急性胰腺炎(MSAP)8例(9.5%), 重症急性胰腺炎(SAP)1例(1.2%)。肿瘤来源于胆道下段11例(13.1%)，壶腹部13例(15.5%)，胰腺60例(71.4%)。AP反复发作(RR=8.362, 95%CI: 3.162~22.115)、胰管扩张(RR=10.996, 95%CI: 3.871~31.236)、胆管扩张(RR=7.738, 95%CI: 2.521~23.752) 和白细胞计数(RR=0.766, 95%CI: 0.666~0.881)是肿瘤相关性AP的独立影响因素(P值均＜0.001)。 结论 肿瘤相关AP以中老年男性多发，临床多表现为MAP、易反复，多伴胰胆管扩张，肿瘤标志物CA19-9持续性升高等。具有上述特征且无明显诱因的AP需完善胆胰及壶腹部的影像学精查，并加强随访，避免肿瘤漏诊影响预后。 -
关键词:
- 胰腺炎, 急性坏死性 /
- 病理状态, 体征和症状 /
- 消化系统肿瘤
Abstract:Objective To investigate the association of biliary, pancreatic, and ampullary tumors with the onset of acute pancreatitis (AP) and the clinical features of tumor-induced AP by retrospectively analyzing the clinical data of patients with tumor-induced AP. Methods Related clinical data were collected from the patients with AP who were admitted to The First Affiliated Hospital of Zhengzhou University from January 2013 to August 2021. The etiological composition of AP was analyzed, as well as the change in the incidence rate of tumor-induced AP; the clinical features of AP were compared between tumor-induced and non-tumor-induced AP and between the tumors at different locations to explore the pathogenesis of tumor-induced AP. For normally distributed continuous data, the t-test was used for comparison between two groups; a one-way analysis of variance was used for comparison between multiple groups, and the SNK-q test was used for further comparison between two groups. For non-normally distributed continuous data, the Mann-Whitney U test was used for comparison between two groups; the Kruskal-Wallis H test was used for comparison between multiple groups, and the Wilcoxon rank-sum test was used for further comparison between two groups. The chi-square test or the Fisher's exact test was used for comparison of dichotomous categorical data between groups, and the goodness-of-fit test was used for comparison of polytomous categorical data between groups. The receiver operating characteristic (ROC) curve was used to evaluate the differential factors for pancreatic tumor-induced AP, and a multivariate logistic regression analysis was used to investigate the independent predictive factors for tumor-induced AP. Results A total of 8106 patients with AP were enrolled, among whom 84 patients (1.04%) had tumor-induced AP (tumor group). The tumor group had a significantly higher mean age than the non-tumor group (t=6.050, P < 0.001). The mean time from initial onset of AP to tumor diagnosis was 7.38 months. Among the 84 patients with tumor-induced AP, 75 (89.2%) had mild AP (MAP), 8 (9.5%) had moderate severe AP, and 1(1.2%) had severe AP; as for the origin of tumor, 11(13.1%) had tumor originating from the lower biliary tract, 13(15.5%) had tumor originating from the ampulla, and 60(71.4%) had tumor originating from the pancreas. Recurrence of AP (risk ratio [RR]=8.362, 95% confidence interval [CI]: 3.162-22.115, P < 0.001), pancreatic duct dilatation (RR=10.996, 95%CI: 3.871-31.236, P < 0.001), bile duct dilatation (RR=7.738, 95%CI: 2.521-23.752, P < 0.001), and leukocyte count (RR=0.766, 95%CI: 0.666-0.881, P < 0.001) were independent predictive factors for tumor-induced AP. Conclusion Tumor-induced AP is common in middle-aged and elderly men, with the clinical manifestations of MAP, easy recurrence, pancreatic duct dilatation/bile duct dilatation, and a persistent increase in the tumor marker CA19-9. Imaging examination of the biliary, pancreatic, and ampullary regions should be enhanced for AP with the above characteristics and no apparent trigger, and follow-up should be strengthened to avoid the missed diagnosis of tumor and the influence on prognosis. -
表 1 不同部位肿瘤相关性AP临床病理特征比较
Table 1. Comparison of clinicopathological features of tumor induced AP at different sites
临床特征 胰腺(n=60) 壶腹(n=13) 胆道(n=11) 统计值 P值 性别[例(%)] χ2=0.105 0.949 男 39(65.0) 9(69.2) 7(63.6) 女 21(35.0) 4(30.8) 4(36.4) 年龄(岁) 56.35±12.06 54.31±8.71 56.55±11.99 F=0.176 0.839 严重程度[例(%)] χ2=0.330 0.848 轻 54(90.0) 11(84.6) 10(90.9) 中重度 6(10.0) 2(15.4) 1(9.1) 反复发作[例(%)] χ2=0.862 0.650 是 36(60.0) 8(61.5) 5(45.5) 否 24(40.0) 5(38.5) 6(54.5) 胰管扩张[例(%)] χ2=10.373 0.006 是 43(75.4) 5(38.5) 4(36.4) 否 14(24.6) 8(61.5) 7(63.6) 胆管扩张[例(%)] χ2=0.876 0.645 是 34(58.6) 6(46.2) 7(63.6) 否 24(41.4) 7(53.8) 4(36.4) 肿瘤直径(cm) 3.5(2.0~5.0) 1.8(1.5~2.5) 2.0(1.5~2.6) H=11.330 0.003 中性粒细胞百分比(%) 67.0±10.3 60.6±17.1 66.9±11.3 F=1.468 0.237 红细胞比容 0.39±0.04 0.37±0.06 0.36±0.05 F=3.072 0.052 淀粉酶(U/L) 132.0(64.0~236.0) 166.0(72.0~949.0) 370.0(47.5~617.3) H=2.357 0.308 脂肪酶(U/L) 308.0(208.0~919.0) 275.4(131.6~1 434.3) 323.7(197.4~1 269.1) H=0.279 0.870 血糖(mmol/L) 6.31(5.17~8.35) 4.64(4.19~6.01) 6.02(5.22~13.17) H=6.403 0.041 血钙(mmol/L) 2.31(2.25~2.36) 2.22(2.13~2.44) 2.25(2.02~2.31) H=6.448 0.040 白蛋白(g/L) 40.34±3.88 41.42±8.92 35.66±4.88 F=4.648 0.012 总胆红素(μmol/L) 15.7(8.9~127.7) 16.9(7.0~53.3) 29.5(7.9~198.7) H=1.294 0.524 直接胆红素(μmol/L) 7.9(3.8~102.4) 6.8(3.6~49.2) 24.6(5.3~181.7) H=1.757 0.415 CEA(ng/mL) 4.13(2.12~8.77) 1.48(0.68~2.39) 2.19(1.22~3.41) H=13.873 0.001 CA125(U/mL) 22.76(13.01~91.22) 38.3(13.18~272.19) 23.51(9.20~62.53) H=0.704 0.703 CA19-9(U/mL) 171.00(53.24~1 693.00) 69.83(6.86~322.25) 93.81(15.22~468.25) H=4.702 0.095 注：胰腺组3例胰管扩张情况不详，2例胆管扩张情况不详。 
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表 2 胰腺不同部位肿瘤特征比较
Table 2. Comparison of tumor features at different parts of pancreas
肿瘤特征 头颈部(n=44) 体尾部(n=16) 统计值 P值 年龄(岁) 58.14±11.32 51.44±13.04 t=1.947 0.056 性别[例(%)] χ2=4.331 0.037 男 32(72.7) 7(43.8) 女 12(27.3) 9(56.3) 胰管扩张[例(%)] χ2=13.257 ＜0.001 是 38(90.5) 6(40) 否 4(9.5) 9(60) 胆管扩张[例(%)] χ2=10.771 0.001 是 32(74.4) 4(26.7) 否 11(25.6) 11(73.3) 病理分类[例(%)] χ2=12.172 0.058 腺癌 39(88.6) 9(56.3) 实性假乳头状肿瘤 0 1(6.3) 小细胞癌 0 1(6.3) 黏液性肿瘤 3(6.8) 3(18.8) 鳞状细胞癌 1(2.3) 0 导管内乳头状瘤 0 1(6.3) 腺泡细胞癌 1(2.3) 1(6.3) 肿瘤直径(cm) 3.5(2.0~4.6) 3.0(2.6~5.8) Z=0.567 0.570 脉管侵犯(例) χ2=1.615 0.346 是 10 4 否 3 4 注：3例胰管扩张、2例胆管扩张及39例脉管侵犯情况不详。
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表 3 肿瘤相关AP与非肿瘤相关AP患者一般资料比较
Table 3. Comparison of general data of patients with tumor induced AP and non-tumor induced AP
临床特征 肿瘤组(n=84) 非肿瘤组(n=360) 统计值 P值 年龄(岁) 56.06±11.5 47.03±15.32 t=6.050 ＜0.001 性别[例(%)] χ2=0.004 0.950 男 55(65.5) 237(65.8) 女 29(34.5) 123(34.2) 长期抽烟[例(%)] χ2=0.805 0.370 否 59(70.2) 270(75) 是 25(29.8) 90(25) 长期饮酒[例(%)] χ2=0.616 0.433 否 71(84.5) 291(80.8) 是 13(15.5) 69(19.2) 糖尿病[例(%)] χ2=0.036 0.849 否 73(86.9) 310(86.1) 是 11(13.1) 50(13.9) 反复发作[例(%)] χ2=80.777 ＜0.001 否 35(41.7) 312(86.7) 是 49(58.3) 48(13.3) 胆管扩张[例(%)] χ2=124.179 ＜0.001 否 33(40.2) 320(92.5) 是 49(59.8) 26(7.5) 胰管扩张[例(%)] χ2=135.040 ＜0.001 否 28(34.6) 316(91.3) 是 53(65.4) 30(8.7) 严重程度[例(%)] χ2=32.277 ＜0.001 MAP 75(89.3) 208(57.8) MSAP 8(9.5) 134(37.2) SAP 1(1.2) 18(5) 白细胞计数(×109/L) 6.1(4.5~7.6) 10.0(7.0~14.3) Z=7.285 ＜0.001 血红蛋白(g/L) 128(118~138) 131(116~148) Z=1.650 0.099 红细胞比容 0.39(0.36~0.42) 0.40(0.35~0.44) Z=1.211 0.226 中性粒细胞百分比(%) 67.8(59.8~73.3) 81.6(69.9~88.3) Z=7.151 ＜0.001 白蛋白(g/L) 39.85(37.05~42.28) 38.10(33.35~41.73) Z=2.866 0.004 碱性磷酸酶(U/L) 118(80~289) 82(64~126) Z=4.750 ＜0.001 直接胆红素(μmol/L) 8.4(3.9~89.4) 7.1(4.4~16.0) Z=1.961 0.050 间接胆红素(μmol/L) 6.2(3.8~13.8) 7.4(4.9~13.3) Z=1.013 0.311 肌酐(μmol/L) 65(55~78) 64(52~80) Z=0.080 0.937 淀粉酶(U/L) 145.0(68.5~312.0) 155.0(75.0~475.0) Z=0.894 0.371 脂肪酶(U/L) 312.5(186.0~949.1) 201.3(80.9~624.5) Z=3.318 0.001 C反应蛋白(mg/L) 4.25(1.73~22.07) 51.10(9.76~159.35) Z=4.889 ＜0.001 血钙(mmol/L) 2.30(2.23~2.35) 2.18(2.06~2.29) Z=5.736 ＜0.001 血糖(mmol/L) 6.17(5.01~7.94) 6.86(5.20~9.32) Z=1.994 0.046 甘油三脂(mmol/L) 1.35(0.83~2.23) 1.75(0.94~4.40) Z=2.653 0.008 注：16例胆管扩张情况不详；17例胰管扩张情况不详。
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表 4 肿瘤相关AP的多因素logistic回归分析
Table 4. Multivariate Logistic regression analysis of tumor induced AP
影响因素 回归系数 SE Wald值 P值 RR 95%CI 常数 -0.909 0.573 2.521 0.112 0.403 - 反复发作 2.124 0.496 18.318 ＜0.001 8.362 3.162~22.115 胰管扩张 2.398 0.533 20.259 ＜0.001 10.996 3.871~31.236 胆管扩张 2.046 0.572 12.788 ＜0.001 7.738 2.521~23.752 白细胞计数 0.267 0.071 14.013 ＜0.001 0.766 0.666~0.881 注：RR，危险比；95%CI，95%可信区间。
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[1] XIAO AY, TAN ML, WU LM, et al. Global incidence and mortality of pancreatic diseases: a systematic review, meta-analysis, and meta-regression of population-based cohort studies[J]. Lancet Gastroenterol Hepatol, 2016, 1(1): 45-55. DOI: 10.1016/S2468-1253(16)30004-8. [2] BOXHOORN L, VOERMANS RP, BOUWENSE SA, et al. Acute pancreatitis[J]. Lancet, 2020, 396(10252): 726-734. DOI: 10.1016/S0140-6736(20)31310-6. [3] PU W, LUO G, CHEN T, et al. A 5-year retrospective cohort study: epidemiology, etiology, severity, and outcomes of acute pancreatitis[J]. Pancreas, 2020, 49(9): 1161-1167. DOI: 10.1097/MPA.0000000000001637. [4] MCGUIGAN A, KELLY P, TURKINGTON RC, et al. Pancreatic cancer: A review of clinical diagnosis, epidemiology, treatment and outcomes[J]. World J Gastroenterol, 2018, 24(43): 4846-4861. DOI: 10.3748/wjg.v24.i43.4846. [5] Chinese Pancreatic Surgery Association, Chinese Society of Surgery, Chinese Medical. Association. Guidelines for diagnosis and treatment of acute pancreatitis in China (2021)[J]. Chin J Dig Surg, 2021, 20(7): 730-739. DOI: 10.3760/cma.j.cn115610-20210622-00297.中华医学会外科学分会胰腺外科学组. 中国急性胰腺炎诊治指南(2021)[J]. 中华消化外科杂志, 2021, 20(7): 730-739. DOI: 10.3760/cma.j.cn115610-20210622-00297. [6] BANKS PA, BOLLEN TL, DERVENIS C, et al. Classification of acute pancreatitis-2012: revision of the Atlanta classification and definitions by international consensus[J]. Gut, 2013, 62(1): 102-111. DOI: 10.1136/gutjnl-2012-302779. [7] CHEN YH, XIE SM, ZHANG H, et al. Clinical impact of preoperative acute pancreatitis in patients who undergo pancreaticoduodenectomy for periampullary tumors[J]. World J Gastroenterol, 2015, 21(22): 6937-6943. DOI: 10.3748/wjg.v21.i22.6937. [8] GUDA NM, TRIKUDANATHAN G, FREEMAN ML. Idiopathic recurrent acute pancreatitis[J]. Lancet Gastroenterol Hepatol, 2018, 3(10): 720-728. DOI: 10.1016/S2468-1253(18)30211-5. [9] NICCOLINI DG, GRAHAM JH, BANKS PA. Tumor-induced acute pancreatitis[J]. Gastroenterology, 1976, 71(1): 142-145. [10] KEANE MG, HORSFALL L, RAIT G, et al. A case-control study comparing the incidence of early symptoms in pancreatic and biliary tract cancer[J]. BMJ Open, 2014, 4(11): e005720. DOI: 10.1136/bmjopen-2014-005720. [11] WANG H, KANG ZL, PENG XH, et al. Misdiagnosed analysis of severe acute pancreatitis[J]. Clin Misdiagn Misther, 2021, 34(12): 12-15. DOI: 10.3969/j.issn.1002-3429.2021.12.003.王辉, 康志龙, 彭新华, 等. 重症急性胰腺炎误诊原因分析[J]. 临床误诊误治, 2021, 34(12): 12-15. DOI: 10.3969/j.issn.1002-3429.2021.12.003. [12] SINGHI AD, KOAY EJ, CHARI ST, et al. Early detection of pancreatic cancer: opportunities and challenges[J]. Gastroenterology, 2019, 156(7): 2024-2040. DOI: 10.1053/j.gastro.2019.01.259. [13] MUJICA VR, BARKIN JS, GO VL. Acute pancreatitis secondary to pancreatic carcinoma. Study Group Participants[J]. Pancreas, 2000, 21(4): 329-332. DOI: 10.1097/00006676-200011000-00001. [14] BARTELL N, BITTNER K, VETTER MS, et al. Role of endoscopic ultrasound in detecting pancreatic cancer missed on cross-sectional imaging in patients presenting with pancreatitis: a retrospective review[J]. Dig Dis Sci, 2019, 64(12): 3623-3629. DOI: 10.1007/s10620-019-05807-z. [15] XIONG Y, ZHAO Y, HAN X, et al. Clinical characteristics and outcome of tumor-associated acute pancreatitis: a single-center cohort study[J]. Ann Transl Med, 2021, 9(8): 639. DOI: 10.21037/atm-20-7196. [16] SADR-AZODI O, OSKARSSON V, DISCACCIATI A, et al. Pancreatic cancer following acute pancreatitis: a population-based matched cohort study[J]. Am J Gastroenterol, 2018, 113(11): 1711-1719. DOI: 10.1038/s41395-018-0255-9. [17] MATOS JM, SCHMIDT CM, TURRINI O, et al. Pancreatic acinar cell carcinoma: a multi-institutional study[J]. J Gastrointest Surg, 2009, 13(8): 1495-1502. DOI: 10.1007/s11605-009-0938-z. [18] CHO JH, CHOI JS, HWANG ET, et al. Usefulness of scheduled follow-up CT in discharged patients with acute pancreatitis[J]. Pancreatology, 2015, 15(6): 642-646. DOI: 10.1016/j.pan.2015.09.004. [19] LU XZ, HUANG SM, WEI JS. Clinical causes and imaging features of pancreatic duct dilatation[J]. Chin J Pancreatol, 2021, 21(4): 300-303. DOI: 10.3760/cma.j.cn115667-20201126-00192.卢孝治, 黄诗朦, 卫积书. 胰管扩张的临床原因及影像学特征[J]. 中华胰腺病杂志, 2021, 21(4): 300-303. DOI: 10.3760/cma.j.cn115667-20201126-00192. [20] SMITH I, MONKEMULLER K, WILCOX CM. Incidentally identified common bile duct dilatation: a systematic review of evaluation, causes, and outcome[J]. J Clin Gastroenterol, 2015, 49(10): 810-815. DOI: 10.1097/MCG.0000000000000394. [21] FENG Q, LI C, ZHANG S, et al. Recurrence and survival after surgery for pancreatic cancer with or without acute pancreatitis[J]. World J Gastroenterol, 2019, 25(39): 6006-6015. DOI: 10.3748/wjg.v25.i39.6006. -
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