肝癌肝移植未来方向的思考

杨扬; 张英才

doi:10.3969/j.issn.1674-7445.2016.01.001

肝癌肝移植未来方向的思考

doi: 10.3969/j.issn.1674-7445.2016.01.001

杨扬^,,
张英才

510630 广州, 中山大学附属第三医院肝移植中心中山大学器官移植研究所

基金项目:

国家863项目 2012AA02A600

、十二五国家科技重大专项 2012ZX100020100010

国家自然科学基金 81300365

国家自然科学基金 81370575

国家自然科学基金 81570593

广东省自然科学基金研究团队项目 2015A030312013

教育部博士点基金 20120171110082

广州市科技计划健康医疗协同创新重大专项 1581000156

广州市科技计划健康医疗协同创新重大专项 201400000001-3

详细信息

通讯作者:
杨扬, 教授、主任医师, 博士研究生导师。现任中山大学附属第三医院肝脏外科主任, 器官移植中心副主任。兼任中国医师协会器官移植医师分会常委、中华医学会器官移植学分会青年委员会副主任委员、中华医学会外科学分会青年委员会副主任委员、中华医学会外科学分会移植学组委员、广东省医学会医事法学分会副主任委员。兼任《器官移植》杂志常务编委, 《中华肝脏外科手术学电子杂志》副总编辑及编辑部主任, 《中华医学杂志》、《中华肝胆外科杂志》等杂志编委。2001年8月获得外科学(器官移植学)博士学位。2005年在美国Mount Sinai医学院移植中心进修。擅长肝脏、胆道、门静脉高压与胰腺外科疾病的诊断与处理, 主持或参与1 300余例临床肝移植。对肝脏外科、肝移植、移植免疫、干细胞在肝脏疾病的应用等方面有深入的研究, 在肝移植术后并发症的预防和治疗方面有较为丰富的经验。Email:yysysu@163.com

中图分类号: R617;R735.7
计量
- 文章访问数: 94
- HTML全文浏览量: 21
- PDF下载量: 7
- 被引次数: 0
出版历程
- 收稿日期: 2015-12-11
- 网络出版日期: 2021-01-19
- 刊出日期: 2016-01-15

摘要

摘要: 肝细胞癌(肝癌)是全球最常见且致命的恶性肿瘤。肝移植术后肿瘤复发是影响肝癌肝移植开展的主要障碍。探索科学合理的肝癌肝移植适应证标准, 寻找预测肿瘤复发的生物学标志物和肿瘤复发后的治疗方法是肝移植领域未来的研究热点。为提高预测肝癌复发的准确度, 需结合影像学和多个肿瘤生物学标志物建立预测模型。如何准确评估机体免疫状态、平衡免疫抑制和抗肿瘤免疫是预防肝癌肝移植术后肿瘤复发的关键。以自然杀伤细胞为代表的过继免疫细胞治疗为肝移植后预防和治疗肝癌复发提供了的新思路, 是未来重要的研究方向。
- 肝移植 /
- 肝细胞癌 /
- 甲胎蛋白 /
- 维生素K缺乏诱导蛋白原或拮抗剂 /
- 循环肿瘤细胞

HTML全文

参考文献(59)

[1]	Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma[J]. Lancet, 2012, 379(9822):1245-1255. doi: 10.1016/S0140-6736(11)61347-0
[2]	Malek NP, Schmidt S, Huber P, et al. The diagnosis and treatment of hepatocellular carcinoma[J]. Dtsch Arztebl Int, 2014, 111(7):101-106. http://med.wanfangdata.com.cn/Paper/Detail/PeriodicalPaper_PM24622679
[3]	Byam J, Renz J, Millis JM. Liver transplantation for hepatocellular carcinoma[J]. Hepatobiliary Surg Nutr, 2013, 2(1):22-30.
[4]	王征, 周俭.肝癌肝移植术后的综合治疗[J].中华肝脏病杂志, 2013, 21(5):324-325. Wang Z, Zhou J. Combined modality therapy for recurrent hepatocellular carcinoma following liver transplantation[J]. Chin J Hepatol, 2013, 21(5):324-325.
[5]	Mazzaferro V, Regalia E, Doci R, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis[J]. N Engl J Med, 1996, 334(11):693-699. doi: 10.1056/NEJM199603143341104
[6]	Yao FY, Ferrell L, Bass NM, et al. Liver transplantation for hepatocellular carcinoma:expansion of the tumor size limits does not adversely impact survival[J]. Hepatology, 2001, 33(6):1394-1403. doi: 10.1053/jhep.2001.24563
[7]	Herrero JI, Sangro B, Pardo F, et al. Liver transplantation in patients with hepatocellular carcinoma across Milan criteria[J]. Liver Transpl, 2008, 14(3):272-278. doi: 10.1002/(ISSN)1527-6473
[8]	Mazzaferro V, Llovet JM, Miceli R, et al. Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria:a retrospective, exploratory analysis[J]. Lancet Oncol, 2009, 10(1):35-43. doi: 10.1016/S1470-2045(08)70284-5
[9]	Toso C, Asthana S, Bigam DL, et al. Reassessing selection criteria prior to liver transplantation for hepatocellular carcinoma utilizing the Scientific Registry of Transplant Recipients database[J]. Hepatology, 2009, 49(3):832-838. doi: 10.1002/hep.22693
[10]	Zheng SS, Xu X, Wu J, et al. Liver transplantation for hepatocellular carcinoma:Hangzhou experiences[J]. Transplantation, 2008, 85(12):1726-1732. doi: 10.1097/TP.0b013e31816b67e4
[11]	Merani S, Majno P, Kneteman NM, et al. The impact of waiting list alpha-fetoprotein changes on the outcome of liver transplant for hepatocellular carcinoma[J]. J Hepatol, 2011, 55(4):814-819. doi: 10.1016/j.jhep.2010.12.040
[12]	Vibert E, Azoulay D, Hoti E, et al. Progression of alphafetoprotein before liver transplantation for hepatocellular carcinoma in cirrhotic patients:a critical factor[J]. Am J Transplant, 2010, 10(1):129-137. doi: 10.1111/j.1600-6143.2009.02750.x
[13]	Chon YE, Choi GH, Lee MH, et al. Combined measurement of preoperative α-fetoprotein and des-γ-carboxy prothrombin predicts recurrence after curative resection in patients with hepatitis-B-related hepatocellular carcinoma[J]. Int J Cancer, 2012, 131(10):2332-2341. doi: 10.1002/ijc.v131.10
[14]	Ito T, Takada Y, Ueda M, et al. Expansion of selection criteria for patients with hepatocellular carcinoma in living donor liver transplantation[J]. Liver Transpl, 2007, 13(12):1637-1644. doi: 10.1002/(ISSN)1527-6473
[15]	Balkwill F, Mantovani A. Inflammation and cancer:back to Virchow?[J]. Lancet, 2001, 357(9255):539-545. doi: 10.1016/S0140-6736(00)04046-0
[16]	Coussens LM, Werb Z. Inflammation and cancer[J]. Nature, 2002, 420(6917):860-867. doi: 10.1038/nature01322
[17]	Mantovani A, Allavena P, Sica A, et al. Cancer-related inflammation[J]. Nature, 2008, 454(7203):436-444. doi: 10.1038/nature07205
[18]	An HJ, Jang JW, Bae SH, et al. Serum C-reactive protein is a useful biomarker for predicting outcomes after liver transplantation in patients with hepatocellular carcinoma[J]. Liver Transpl, 2012, 18(12):1406-1414. doi: 10.1002/lt.v18.12
[19]	Bertuzzo VR, Cescon M, Ravaioli M, et al. Analysis of factors affecting recurrence of hepatocellular carcinoma after liver transplantation with a special focus on inflammation markers[J]. Transplantation, 2011, 91(11):1279-1285. doi: 10.1097/TP.0b013e3182187cf0
[20]	Sharaiha RZ, Halazun KJ, Mirza F, et al. Elevated preoperative neutrophil:lymphocyte ratio as a predictor of postoperative disease recurrence in esophageal cancer[J]. Ann Surg Oncol, 2011, 18(12):3362-3369. doi: 10.1245/s10434-011-1754-8
[21]	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
[22]	Lee YY, Choi CH, Kim HJ, et al. Pretreatment neutrophil:lymphocyte ratio as a prognostic factor in cervical carcinoma[J]. Anticancer Res, 2012, 32(4):1555-1561.
[23]	Mallappa S, Sinha A, Gupta S, et al. Preoperative neutrophil to lymphocyte ratio >5 is a prognostic factor for recurrent colorectal cancer[J]. Colorectal Dis, 2013, 15(3):323-328. doi: 10.1111/codi.2013.15.issue-3
[24]	He W, Yin C, Guo G, et al. Initial neutrophil lymphocyte ratio is superior to platelet lymphocyte ratio as an adverse prognostic and predictive factor in metastatic colorectal cancer[J]. Med Oncol, 2013, 30(1):439. doi: 10.1007/s12032-012-0439-x
[25]	Pichler M, Hutterer GC, Stoeckigt C, et al. Validation of the pre-treatment neutrophil-lymphocyte ratio as a prognostic factor in a large European cohort of renal cell carcinoma patients[J]. Br J Cancer, 2013, 108(4):901-907. doi: 10.1038/bjc.2013.28
[26]	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
[27]	Dalpiaz O, Ehrlich GC, Mannweiler S, et al. Validation of pretreatment neutrophil-lymphocyte ratio as a prognostic factor in a European cohort of patients with upper tract urothelial carcinoma[J]. BJU Int, 2014, 114(3):334-339.
[28]	Cananzi FC, Dalgleish A, Mudan S. Surgical management of intraabdominal metastases from melanoma:role of the neutrophil to lymphocyte ratio as a potential prognostic factor[J]. World J Surg, 2014, 38(6):1542-1550. doi: 10.1007/s00268-013-2418-6
[29]	Mcnamara MG, Templeton AJ, Maganti M, et al. Neutrophil/lymphocyte ratio as a prognostic factor in biliary tract cancer[J]. Eur J Cancer, 2014, 50(9):1581-1589. doi: 10.1016/j.ejca.2014.02.015
[30]	Halazun KJ, Hardy MA, Rana AA, et al. Negative impact of neutrophil-lymphocyte ratio on outcome after liver transplantation for hepatocellular carcinoma[J]. Ann Surg, 2009, 250(1):141-151. doi: 10.1097/SLA.0b013e3181a77e59
[31]	Wang GY, Yang Y, Li H, et al. A scoring model based on neutrophil to lymphocyte ratio predicts recurrence of HBV-associated hepatocellular carcinoma after liver transplantation[J]. PLoS One, 2011, 6(9):e25295. doi: 10.1371/journal.pone.0025295
[32]	Limaye AR, Clark V, Soldevila-Pico C, et al. Neutrophil-lymphocyte ratio predicts overall and recurrence-free survival after liver transplantation for hepatocellular carcinoma[J]. Hepatol Res, 2013, 43(7):757-764. doi: 10.1111/hepr.2013.43.issue-7
[33]	Motomura T, Shirabe K, Mano Y, et al. Neutrophil-lymphocyte ratio reflects hepatocellular carcinoma recurrence after liver transplantation via inflammatory microenvironment[J]. J Hepatol, 2013, 58(1):58-64. doi: 10.1016/j.jhep.2012.08.017
[34]	Yoshizumi T, Ikegami T, Yoshiya S, et al. Impact of tumor size, number of tumors and neutrophil-to-lymphocyte ratio in liver transplantation for recurrent hepatocellular carcinoma[J]. Hepatol Res, 2013, 43(7):709-716. doi: 10.1111/hepr.2013.43.issue-7
[35]	Sun YF, Xu Y, Yang XR, et al. Circulating stem cell-like epithelial cell adhesion molecule-positive tumor cells indicate poor prognosis of hepatocellular carcinoma after curative resection[J]. Hepatology, 2013, 57(4):1458-1468. doi: 10.1002/hep.26151
[36]	Davis E, Wiesner R, Valdecasas J, et al. Treatment of recurrent hepatocellular carcinoma after liver transplantation[J]. Liver Transpl, 2011, 17(Suppl 2):S162-S166.
[37]	Kornberg A, Küpper B, Tannapfel A, et al. Long-term survival after recurrent hepatocellular carcinoma in liver transplant patients:clinical patterns and outcome variables[J]. Eur J Surg Oncol, 2010, 36(3):275-280. doi: 10.1016/j.ejso.2009.10.001
[38]	Kim HR, Cheon SH, Rha SY, et al. Treatment of recurrent hepatocellular carcinoma after liver transplantation[J]. Asia Pac J Clin Oncol, 2011, 7(3):258-269. doi: 10.1111/ajco.2011.7.issue-3
[39]	Roh YN, David Kwon CH, Song S, et al. The prognosis and treatment outcomes of patients with recurrent hepatocellular carcinoma after liver transplantation[J]. Clin Transplant, 2014, 28(1):141-148. doi: 10.1111/ctr.12286
[40]	Sposito C, Mariani L, Germini A, et al. Comparative efficacy of sorafenib versus best supportive care in recurrent hepatocellular carcinoma after liver transplantation:a case-control study[J]. J Hepatol, 2013, 59(1):59-66. doi: 10.1016/j.jhep.2013.02.026
[41]	Pfeiffenberger J, Koschny R, Hoffmann K, et al. Sorafenib treatment is save and may affect survival of recurrent hepatocellular carcinoma after liver transplantation[J]. Langenbecks Arch Surg, 2013, 398(8):1123-1128. doi: 10.1007/s00423-013-1114-1
[42]	Couzin-Frankel J. Immune therapy steps up the attack[J]. Science, 2010, 330(6003):440-443. doi: 10.1126/science.330.6003.440
[43]	Mellman I, Coukos G, Dranoff G. Cancer immunotherapy comes of age[J]. Nature, 2011, 480(7378):480-489. doi: 10.1038/nature10673
[44]	Topalian SL, Weiner GJ, Pardoll DM. Cancer immunotherapy comes of age[J]. J Clin Oncol, 2011, 29(36):4828-4836. doi: 10.1200/JCO.2011.38.0899
[45]	Couzin-Frankel J. Breakthrough of the year 2013. cancer immunotherapy[J]. Science, 2013, 342(6165):1432-1433. doi: 10.1126/science.342.6165.1432
[46]	Lizée G, Overwijk WW, Radvanyi L, et al. Harnessing the power of the immune system to target cancer[J]. Annu Rev Med, 2013, 64:71-90. doi: 10.1146/annurev-med-112311-083918
[47]	Takayama T, Sekine T, Makuuchi M, et al. Adoptive immunotherapy to lower postsurgical recurrence rates of hepatocellular carcinoma:a randomised trial[J]. Lancet, 2000, 356(9232):802-807. doi: 10.1016/S0140-6736(00)02654-4
[48]	Cui J, Wang N, Zhao H, et al. Combination of radiofrequency ablation and sequential cellular immunotherapy improves progression-freesurvival for patients with hepatocellular carcinoma[J]. Int J Cancer, 2014, 134(2):342-351. doi: 10.1002/ijc.28372
[49]	Huang ZM, Li W, Li S, et al. Cytokine-induced killer cells in combination with transcatheter arterial chemoembolization and radiofrequency ablation for hepatocellular carcinoma patients[J]. J Immunother, 2013, 36(5):287-293. doi: 10.1097/CJI.0b013e3182948452
[50]	陈规划, 陈文捷, 张琪.过继免疫细胞治疗预防肝癌肝移植术后复发的新思路探究[J].器官移植, 2014, 5(3):131-136. http://www.organtranspl.com/browse/detail/qkid/29/id/452.html Chen GH, Chen WJ, Zhang Q. Adoptive immune cell therapy, a potential strategy to reduce hepatocellular carcinoma recurrence after liver transplantation[J]. Organ Transplant, 2014, 5(3):131-136. http://www.organtranspl.com/browse/detail/qkid/29/id/452.html
[51]	El Ansary M, Mogawer S, Elhamid SA, et al. Immunotherapy by autologous dendritic cell vaccine in patients with advanced HCC[J]. J Cancer Res Clin Oncol, 2013, 139(1):39-48. doi: 10.1007/s00432-012-1298-8
[52]	吕晓霞, 陈帼玲, 王学群, 等.自体CIK细胞治疗21例中晚期恶性实体瘤的肿瘤标志物变化观察[J/CD].中华细胞与干细胞杂志(电子版), 2014, 4(3):15-24. Lyu XX, Chen GL, Wang XQ, et al. Self-derived cytokine-induced killer cells for patients with aduanced malignant solid tumor[J/CD]. Chin J Cell Stem Cell(Electr Edit), 2014, 4(3):15-24.
[53]	Ma Y, Xu YC, Tang L, et al. Cytokine-induced killer (CIK) cell therapy for patients with hepatocellular carcinoma:efficacy and safety[J]. Exp Hematol Oncol, 2012, 1(1):11. doi: 10.1186/2162-3619-1-11
[54]	Ruggeri L, Capanni M, Urbani E, et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants[J]. Science, 2002, 295(5562):2097-2100. doi: 10.1126/science.1068440
[55]	Ohira M, Ishiyama K, Tanaka Y, et al. Adoptive immunotherapy with liver allograft-derived lymphocytes induces anti-HCV activity after liver transplantation in humans and humanized mice[J]. J Clin Invest, 2009, 119(11):3226-3235.
[56]	Mehta BA, Schmidt-Wolf IG, Weissman IL, et al. Two pathways of exocytosis of cytoplasmic granule contents and target cell killing by cytokine-induced CD3⁺ CD56⁺ killer cells[J]. Blood, 1995, 86(9):3493-3499.
[57]	Nishida S, Levi DM, Tzakis AG. Liver natural killer cell inoculum for liver transplantation with hepatocellular carcinoma[J]. Curr Opin Organ Transplant, 2013, 18(6):690-694.
[58]	Kayashima H, Toshima T, Okano S, et al. Intratumoral neoadjuvant immunotherapy using IL-12 and dendritic cells is an effective strategy to control recurrence of murine hepatocellular carcinoma in immunosuppressed mice[J]. J Immunol, 2010, 185(1):698-708. doi: 10.4049/jimmunol.0900187
[59]	Ohira M, Nishida S, Tryphonopoulos P, et al. Clinical-scale isolation of interleukin-2-stimulated liver natural killer cells for treatment of liver transplantation with hepatocellular carcinoma[J]. Cell Transplant, 2012, 21(7):1397-1406. doi: 10.3727/096368911X627589