Incidence and risk factors analysis of colorectal adenomatous polyps in recipients after liver transplantation
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摘要:
目的 分析肝移植受者术后结直肠腺瘤性息肉(CAP)的发生情况及危险因素。 方法 选取肝移植受者77例,并选取同期行结肠镜检查的体检者231例,分析结直肠息肉发生情况及病理检查结果。收集肝移植受者的临床资料,并根据CAP的发生情况,将肝移植受者分为CAP组(28例)和非CAP组(49例),分析肝移植术后发生CAP的危险因素。 结果 肝移植受者和体检者结直肠息肉的5年累积发生率分别为43%和34%,CAP的5年累积发生率分别为29%和23%,差异均无统计学意义(均为P > 0.05)。肝移植受者中,除1例因息肉较多未统计外,其余息肉共计65个,部分受者发现多个息肉。5个体积较小者未送病理,有病理结果的共60个,包括炎性息肉25个,CAP 33个(其中8个伴有低级别上皮内瘤变,3个伴有高级别上皮内瘤变),高分化腺癌2个。Cox模型分析提示肝移植受者术后服用环孢素是发生CAP的独立危险因素。 结论 肝移植术后CAP发生风险略有增高,服用环孢素是肝移植受者术后发生CAP的独立危险因素,应重视肝移植受者术后结肠镜检查。 Abstract:Objective To analyze the incidence and risk factors of colorectal adenomatous polyps (CAP) in recipients after liver transplantation. Methods Seventy-seven liver transplant recipients and 231 individuals undergoing colonoscopy during physical examination were recruited in this study. The incidence of CAP and pathological examination results were analyzed. Clinical data of liver transplant recipients were collected. According to the incidence of CAP, liver transplant recipients were divided into the CAP group (n=28) and non-CAP group (n=49). The risk factors of CAP after liver transplantation were identified. Results The 5-year cumulative incidence rates of colorectal polyps in liver transplant recipients and physical examination individuals were 43% and 34%, and 29% and 23% for the 5-year cumulative incidence rates of CAP, with no significant differences (both P > 0.05). Among all liver transplant recipients, 65 polyps were detected. The quantity of polyps in 1 case was excessively high and not counted. Multiple polyps were identified in certain recipients. Five polyps were not prepared for pathological examination due to small size. Pathological examination of 60 polyps demonstrated 25 inflammatory polyps, 33 CAP (8 complicated with low-grade intraepithelial neoplasia and 3 complicated with high-grade intraepithelial neoplasia), and 2 well-differentiated adenocarcinoma. Cox model analysis prompted that use of ciclosporine after liver transplantation was an independent risk factor for CAP in the recipients. Conclusions The risk of CAP is slightly elevated after liver transplantation. Postoperative use of ciclosporine is an independent risk factor for CAP in recipients after liver transplantation. Colonoscopy should be emphasized in the recipients after liver transplantation. -
表 1 肝移植受者术后发生CAP危险因素的单因素分析
Table 1. Univariate analysis of risk factors for postoperative CAP in liver transplant recipients
指标 CAP组(n=28) 非CAP组(n=49) HR(95%CI) P值 移植时年龄(x±s,岁) 55±9 53±9 1.05(1.00~1.10) 0.051 检查时年龄(x±s,岁) 59±9 57±9 1.01(0.97~1.06) 0.620 男性[n(%)] 23(82) 34(69) 1.52(0.58~4.01) 0.398 BMI(x±s,kg/m2) 24±3 25±4 0.94(0.83~1.06) 0.331 吸烟史[n(%)] 11(39) 19(39) 0.67(0.30~1.50) 0.326 饮酒史[n(%)] 12(43) 18(37) 0.77(0.35~1.69) 0.513 高血压[n(%)] 8(29) 15(31) 0.71(0.30~1.70) 0.446 糖尿病[n(%)] 7(25) 12(24) 0.82(0.34~1.99) 0.656 服用阿司匹林[n(%)] 7(25) 18(37) 0.93(0.38~2.25) 0.872 总胆固醇(x±s,mmol/L) 4.2±1.4 4.2±1.4 1.06(0.78~1.43) 0.729 甘油三酯[M(P25,P75), mmol/L] 1.2(0.8,1.7) 1.2(0.9,1.7) 1.08(0.65~1.80) 0.777 高密度脂蛋白胆固醇(x±s,mmol/L) 1.5±0.4 1.4±0.4 1.11(0.68~1.80) 0.684 低密度脂蛋白胆固醇(x±s,mmol/L) 2.5±0.7 2.4±0.9 1.83(0.73~4.56) 0.197 CEA①[M(P25,P75), ng/mL] 2.0(1.5,3.1) 1.5(0.9,2.3) 1.11(0.89~1.38) 0.373 CA19-9②[M(P25,P75), U/mL] 15(10,24) 11(6,14) 1.00(0.99~1.01) 0.727 原发病[n(%)] 乙肝 22(79) 36(73) 0.95(0.38~2.37) 0.919 肝癌 10(36) 24(49) 1.52(0.45~5.15) 0.503 肝硬化 27(96) 45(92) 1.47(0.67~3.22) 0.335 免疫抑制剂[n(%)] 他克莫司 28(100) 49(100) -③ - 环孢素 8(29) 2(4) 10.03(3.58~28.10) 0.000 雷帕霉素 3(11) 11(22) 1.20(0.40~3.59) 0.743 他克莫司血药浓度(x±s,ng/mL) 5.6±1.9 6.1±1.9 1.13(0.93~1.36) 0.217 注:①CEA为癌胚抗原。
②CA19-9为糖类抗原19-9。
③-为无数据。 -
[1] SUNG H, FERLAY J, SIEGEL RL, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249. DOI: 10.3322/caac.21660. [2] RAO W, XIE M, LIU DY, et al. Analysis of de novo malignancies after liver transplantation in China: based on literature published[J/CD]. Chin J Transplant (Electr Edit), 2018, 12(4): 26-30. DOI: 10.3877/cma.j.issn.1674-3903.2018.04.005. [3] 姜晓青, 张群, 解曼, 等. 中国肝移植术后新发消化系统恶性肿瘤文献分析报告[J]. 器官移植, 2020, 11(2): 265-270. DOI: 10.3969/j.issn.1674-7445.2020.02.013.JIANG XQ, ZHANG Q, XIE M, et al. Literature analysis report of de novo malignant tumors of digestive system after liver transplantation in China[J]. Organ Transplant, 2020, 11(2): 265-270. DOI: 10.3969/j.issn.1674-7445.2020.02.013. [4] ZHOU J, HU Z, ZHANG Q, et al. Spectrum of de novo cancers and predictors in liver transplantation: analysis of the scientific registry of transplant recipients database[J]. PLoS One, 2016, 11(5): e0155179. DOI: 10.1371/journal.pone.0155179. [5] ROMPIANESI G, RAVIKUMAR R, JOSE S, et al. Incidence and outcome of colorectal cancer in liver transplant recipients: a national, multicentre analysis on 8115 patients[J]. Liver Int, 2019, 39(2): 353-360. DOI: 10.1111/liv.13947. [6] NORDIN A, ÅBERG F, PUKKALA E, et al. Decreasing incidence of cancer after liver transplantation-a Nordic population-based study over 3 decades[J]. Am J Transplant, 2018, 18(4): 952-963. DOI: 10.1111/ajt.14507. [7] KANG EA, KOH SJ, KIM JW, et al. Prevalence of advanced colorectal neoplasm is higher in liver transplant recipients[J]. Turk J Gastroenterol, 2018, 29(3): 316-324. DOI: 10.5152/tjg.2018.17458. [8] BHAT M, MARA K, DIERKHISING R, et al. Gender, race and disease etiology predict de novo malignancy risk after liver transplantation: insights for future individualized cancer screening guidance[J]. Transplantation, 2019, 103(1): 91-100. DOI: 10.1097/TP.0000000000002113. [9] TIWARI A, SAIGAL S, CHOUDHARY NS, et al. De novo malignancy after living donor liver transplantation: a large volume experience[J]. J Clin Exp Hepatol, 2020, 10(5): 448-452. DOI: 10.1016/j.jceh.2020.02.001. [10] SAGLAM K, SAHIN TT, OGUT Z, et al. De novo malignancies after liver transplantation: experience of a high-volume center[J]. J Gastrointest Cancer, 2021, DOI: 10.1007/s12029-021-00749-0[Epubaheadofprint]. [11] 孟令展, 刘振文, 朱震宇. 肝移植术后新发恶性肿瘤危险因素的研究进展[J]. 器官移植, 2020, 11(5): 646-650. DOI: 10.3969/j.issn.1674-7445.2020.05.019.MENG LZ, LIU ZW, ZHU ZY. Research progress on risk factors of de novo malignancy after liver transplantation[J]. Organ Transplant, 2020, 11(5): 646-650. DOI: 10.3969/j.issn.1674-7445.2020.05.019. [12] 国家癌症中心中国结直肠癌筛查与早诊早治指南制定专家组. 中国结直肠癌筛查与早诊早治指南(2020, 北京)[J]. 中华肿瘤杂志, 2021, 43(1): 16-38. DOI: 10.3760/cma.j.cn112152-20210105-00010.National Cancer Center, China, Expert Group of the Development of China Guideline for the Screening, Early Detection and Early Treatment of Colorectal Cancer. China guideline for the screening, early detection and early treatment of colorectal cancer (2020, Beijing)[J]. Chin J Oncol, 2021, 43(1): 16-38. DOI: 10.3760/cma.j.cn112152-20210105-00010. [13] 中华医学会消化病学分会, 中华医学会消化病学分会消化系统肿瘤协作组. 中国结直肠肿瘤综合预防共识意见(2021年, 上海)[J]. 中华消化杂志, 2021, 41(11): 726-759. DOI: 10.3760/cma.j.cn311367-20210809-00431.Chinese Society of Gastroenterology, Cancer Collaboration Group of Chinese Society of Gastroenterology, Chinese Medical Association. Chinese consensus on prevention of colorectal neoplasia (2021, Shanghai)[J]. Chin J Dig, 2021, 41(11): 726-759. DOI: 10.3760/cma.j.cn311367-20210809-00431. [14] 刘东岳, 解曼, 姜英俊, 等. 32例乙肝肝移植受者电子结肠镜筛查结果分析[J]. 中华肝胆外科杂志, 2020, 26(1): 61-62. DOI: 10.3760/cma.j.issn.1007-8118.2020.01.014.LIU DY, XIE M, JIANG YJ, et al. Colonoscopy screening results analysis of 32 cases with liver transplantation for HBV related liver diseases[J]. Chin J Hepatobiliary Surg, 2020, 26(1): 61-62. DOI: 10.3760/cma.j.issn.1007-8118.2020.01.014. [15] LESMANA CRA, PAKASI LS, SUDOYO AW, et al. The clinical significance of colon polyp pathology in nonalcoholic fatty liver disease (NAFLD) and its impact on screening colonoscopy in daily practice[J]. Can J Gastroenterol Hepatol, 2020: 6676294. DOI: 10.1155/2020/6676294. [16] ALBRIGHT JB, BONATTI H, STAUFFER J, et al. Colorectal and anal neoplasms following liver transplantation[J]. Colorectal Dis, 2010, 12(7): 657-666. DOI: 10.1111/j.1463-1318.2009.01840.x. [17] MA AT, THERRIEN A, GIARD JM, et al. Alcoholic liver disease is a strong predictor of colorectal polyps in liver transplant recipients[J]. Endosc Int Open, 2017, 5(9): E918-E923. DOI: 10.1055/s-0043-114660. [18] SPIER BJ, WALKER AJ, CORNETT DD, et al. Screening colonoscopy and detection of neoplasia in asymptomatic, average-risk, solid organ transplant recipients: case-control study[J]. Transpl Int, 2010, 23(12): 1233-1238. DOI: 10.1111/j.1432-2277.2010.01137.x. [19] DANAN G, FAURE S, DUNY Y, et al. 154 prevalence of adenomatous colon polyps after liver transplantation (LT): the level of immunosuppression makes the difference[J]. J Hepatol, 2013, 58: S69. DOI: 10.1016/S0168-8278(13)60156-7. [20] RUDRARAJU M, OSOWO AT, SINGH V, et al. Do patients need more frequent colonoscopic surveillance after liver transplantation?[J]. Transplant Proc, 2008, 40(5): 1522-1524. DOI: 10.1016/j.transproceed.2008.02.070. [21] 中国肝移植注册中心, 国家肝脏移植医疗质量控制中心. 2018年中国肝脏移植医疗质量报告[R/OL]. [2021-12-15]. http://www.cltr.org/pages/index.jsp. [22] SIEGEL RL, MILLER KD, GODING SAUER A, et al. Colorectal cancer statistics, 2020[J]. CA Cancer J Clin, 2020, 70(3): 145-164. DOI: 10.3322/caac.21601. [23] ASHKAR MH, CHEN J, SHY C, et al. Increased risk of advanced colonic adenomas and timing of surveillance colonoscopy following solid organ transplantation[J]. Dig Dis Sci, 2021, DOI: 10.1007/s10620-021-06987-3[Epubaheadofprint]. [24] 中华人民共和国国家卫生健康委员会. 中国结直肠癌诊疗规范(2020版)[J]. 中华消化外科杂志, 2020, 19(6): 563-588. DOI: 10.3760/cma.j.cn115610-20200504-00348.National Health Commission of the People's Republic of China. Chinese protocol of diagnosis and treatment of colorectal cancer (2020 edition)[J]. Chin J Dig Surg, 2020, 19(6): 563-588. DOI: 10.3760/cma.j.cn115610-20200504-00348. [25] JIMÉNEZ-ROMERO C, JUSTO-ALONSO I, CAMBRA-MOLERO F, et al. Incidence, risk factors and outcome of de novo tumors in liver transplant recipients focusing on alcoholic cirrhosis[J]. World J Hepatol, 2015, 7(7): 942-953. DOI: 10.4254/wjh.v7.i7.942. [26] ZHAO Y, LIU Y, ZHOU L, et al. Trends of rapamycin in survival benefits of liver transplantation for hepatocellular carcinoma[J]. World J Gastrointest Surg, 2021, 13(9): 953-966. DOI: 10.4240/wjgs.v13.i9.953. [27] 中国医师协会器官移植医师分会肝移植学组, 中华医学会器官移植学分会肝移植学组. 西罗莫司在肝癌肝移植中应用的中国专家共识(2020版)[J]. 中华消化外科杂志, 2020, 19(6): 589-597. DOI: 10.3760/cma.j.cn115610-20200513-00349.Liver transplantation Group in Branch of Organ Transplant Physicians of Chinese Medical Doctor Association, Liver transplantation Group in Branch of Organ Transplantation of Chinese Medical Association. Chinese expert consensus on application of sirolimus in liver transplantation for hepatocellular carcinoma (2020 edition)[J]. Chin J Dig Surg, 2020, 19(6): 589-597. DOI: 10.3760/cma.j.cn115610-20200513-00349. [28] RADEMACHER S, SEEHOFER D, EURICH D, et al. The 28-year incidence of de novo malignancies after liver transplantation: a single-center analysis of risk factors and mortality in 1616 patients[J]. Liver Transpl, 2017, 23(11): 1404-1414. DOI: 10.1002/lt.24795. [29] BARDOU FN, GUILLAUD O, ERARD-POINSOT D, et al. Tacrolimus exposure after liver transplantation for alcohol-related liver disease: impact on complications[J]. Transpl Immunol, 2019, 56: 101227. DOI: 10.1016/j.trim.2019.101227. [30] TOSO C, MERANI S, BIGAM DL, et al. Sirolimus-based immunosuppression is associated with increased survival after liver transplantation for hepatocellular carcinoma[J]. Hepatology, 2010, 51(4): 1237-1243. DOI: 10.1002/hep.23437. [31] SCHREM H, KUROK M, KALTENBORN A, et al. Incidence and long-term risk of de novo malignancies after liver transplantation with implications for prevention and detection[J]. Liver Transpl, 2013, 19(11): 1252-1261. DOI: 10.1002/lt.23722. [32] WIMMER CD, ANGELE MK, SCHWARZ B, et al. Impact of cyclosporine versus tacrolimus on the incidence of de novo malignancy following liver transplantation: a single center experience with 609 patients[J]. Transpl Int, 2013, 26(10): 999-1006. DOI: 10.1111/tri.12165.