臨床泌尿器科65巻9号

2011年08月発行

綜説

腎移植後の悪性腫瘍

著者： 奥見雅由¹

所属機関： ¹大阪大学大学院医学系研究科器官制御外科学（泌尿器科）

ページ範囲：P.617 - P.625

文献概要

要旨　免疫抑制療法や術後管理の進歩により移植腎生着率は向上したが，腎移植後悪性腫瘍の発生頻度は増加してきている。腎移植後悪性腫瘍は，腎不全・免疫抑制・ウイルス感染などとの関連が多いという特徴を有する。発がん頻度が健常者と比較して高率であり，発生傾向が患者背景や環境の影響を受けることなども知られている。本邦での2009年臨床登録集計報告では，腎移植後患者死因として，感染症に次いで悪性腫瘍が第2位であった。長期成績のさらなる向上を目指すためには，その病態を理解してその診断と治療に臨む必要がある。移植前スクリーニングや移植後定期検診は必須であり，通常の抗悪性腫瘍治療に加え，免疫抑制薬の調節などが行われている。

参考文献

1）高原史郎，湯沢賢治，八木澤隆，他；日本臨床腎移植学会・日本移植学会（編）：腎移植臨床登録集計報告（2010）2009年経過追跡調査結果．移植（0578-7947） 45：608-620，2009

2）Penn I：Post-transplant malignancy：the role of immunosuppression. Drug Saf 23：101-113, 2000

3）Buell JF, Gross TG and Woodle ES：Malignancy after transplantation. Transplantation 80：S254-264, 2005

4）Grulich AE, van Leeuwen MT, Falster MO, et al：Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients：a meta-analysis. Lancet 370：59-67, 2007

5）日本臨床腎移植学会：腎移植臨床登録集計報告（2007）-3―2006年経過追跡調査結果．移植 42：545-557，2007

6）Penn I：Occurrence of cancers in immunosuppressed organ transplant recipients. Clin Transpl 99-109, 1994

7）野島道生，藤澤正人，高原史郎，他：腎移植後の悪性腫瘍とPTLD―アンケートによる症例調査とスクリーニングの状況．今日の移植 21：279-284，2008

malignancies in renal transplant recipients：the past and present. Transpl Int 19：607-620, 2006

9）Kasiske BL, Snyder JJ, Gilbertson DT, et al：Cancer after kidney transplantation in the United States. Am J Transplant 4：905-913, 2004

10）Webster AC, Craig JC, Simpson JM, et al：Identifying high risk groups and quantifying absolute risk of cancer after kidney transplantation：a cohort study of 15,183 recipients. Am J Transplant 7：2140-2151, 2007

11）Dantal J, Hourmant M, Cantarovich D, et al：Effect of long-term immunosuppression in kidney-graft recipients on cancer incidence：randomised comparison of two cyclosporin regimens. Lancet 351：623-628, 1998

12）Imao T, Ichimaru N, Takahara S, et al：Risk factors for malignancy in Japanese renal transplant recipients. Cancer 109：2109-2115, 2007

13）Kauffman HM：Malignancies in organ transplant recipients. J Surg Oncol 94：431-433, 2006

14）Kauffman HM, McBride MA, Cherikh WS, et al：Transplant tumor registry：donors with central nervous system tumors1. Transplantation 73：579-582, 2002

15）Taioli E, Mattucci DA, Palmieri S, et al：A population-based study of cancer incidence in solid organ transplants from donors at various risk of neoplasia. Transplantation 83：13-16, 2007

16）Wong G and Chapman JR：Cancers after renal transplantation. Transplant Rev（Orlando） 22：141-149, 2008

17）Holmes RD and Sokol RJ：Epstein-Barr virus and post-transplant lymphoproliferative disease. Pediatr Transplant 6：456-464, 2002

18）Wigle DA, Chaparro C, Humar A, et al：Epstein-Barr virus serology and posttransplant lymphoproliferative disease in lung transplantation. Transplantation 72：1783-1786, 2001

19）Walker RC, Marshall WF, Strickler JG, et al：Pretransplantation assessment of the risk of lymphoproliferative disorder. Clin Infect Dis 20：1346-1353, 1995

20）Dharnidharka VR and Araya CE：Post-transplant lymphoproliferative disease. Pediatr Nephrol 24：731-736, 2009

21）Abe T, Ichimaru N, Kokado Y, et al：Post-transplant lymphoproliferative disorder following renal transplantation：a single-center experience over 40 years. Int J Urol 17：48-54, 2010

22）Caillard S, Dharnidharka V, Agodoa L, et al：Posttransplant lymphoproliferative disorders after renal transplantation in the United States in era of modern immunosuppression. Transplantation 80：1233-1243, 2005

23）EBPG Expert Group on Renal Transplantation：European best practice guidelines for renal transplantation. Section Ⅳ：Long-term management of the transplant recipient. Ⅳ.6.1. Cancer risk after renal transplantation. Post-transplant lymphoproliferative disease（PTLD）：prevention and treatment. Nephrol Dial Transplant 17（Suppl 4）：31-33, 35-36, 2002

24）EBPG Expert Group on Renal Transplantation：European best practice guidelines for renal transplantation. Section Ⅳ：Long-term management of the transplant recipient. Ⅳ.6.2. Cancer risk after renal transplantation. Skin cancers：prevention and treatment. Nephrol Dial Transplant 17（Suppl 4）：31-36, 2002

25）EBPG Expert Group on Renal Transplantation：European best practice guidelines for renal transplantation. Section Ⅳ：Long-term management of the transplant recipient. Ⅳ.6.3. Cancer risk after renal transplantation. Solid organ cancers：prevention and treatment. Nephrol Dial Transplant 17（Suppl 4）：32, 34-36, 2002

26）Kasiske BL, Vazquez MA, Harmon WE, et al：Recommendations for the outpatient surveillance of renal transplant recipients. American Society of Transplantation. J Am Soc Nephrol 11（Suppl 15）：S1-S86, 2000

27）Penn I：Evaluation of transplant candidates with pre-existing malignancies. Ann Transplant 2：14-17, 1997

28）Woodle ES, Gupta M, Buell JF, et al：Prostate cancer prior to solid organ transplantation：the Israel Penn International Transplant Tumor Registry experience. Transplant Proc 37：958-959, 2005

29）Hojo M, Morimoto T, Maluccio M, et al：Cyclosporine induces cancer progression by a cell-autonomous mechanism. Nature 397：530-534, 1999

30）Maluccio M, Sharma V, Lagman M, et al：Tacrolimus enhances transforming growth factor-beta1 expression and promotes tumor progression. Transplantation 76：597-602, 2003

31）Webster AC, Woodroffe RC, Taylor RS, et al：Tacrolimus versus ciclosporin as primary immunosuppression for kidney transplant recipients：meta-analysis and meta-regression of randomised trial data. BMJ 331：810, 2005

32）Sorensen HT, Mellemkjaer L, Nielsen GL, et al：Skin cancers and non-hodgkin lymphoma among users of systemic glucocorticoids：a population-based cohort study. J Natl Cancer Inst 96：709-711, 2004

33）Karagas MR, Cushing GL Jr, Greenberg ER, et al：Non-melanoma skin cancers and glucocorticoid therapy. Br J Cancer 85：683-686, 2001

34）Muirhead R and Ritchie DM：Partial regression of Merkel cell carcinoma in response to withdrawal of azathioprine in an immunosuppression-induced case of metastatic Merkel cell carcinoma. Clin Oncol（R Coll Radiol） 19：96, 2007

35）Rawoot A, Little F and Heckmann JM：Risk of malignancy in myasthenia gravis patients exposed to azathioprine therapy for a median period of 3 years. S Afr Med J 96：1249-1251, 2006

36）Chen SC, Cummings OW, Hartley MP, et al：Hepatocellular carcinoma occurring in a patient with Crohn's disease treated with both azathioprine and infliximab. Dig Dis Sci 51：952-955, 2006

37）Cherikh WS, Kauffman HM, McBride MA, et al：Association of the type of induction immunosuppression with posttransplant lymphoproliferative disorder, graft survival, and patient survival after primary kidney transplantation. Transplantation 76：1289-1293, 2003

38）Yu J, Lemas V, Page T, et al：Induction of erythroid differentiation in K562 cells by inhibitors of inosine monophosphate dehydrogenase. Cancer Res 49：5555-5560, 1989

39）Vegso G, Sebestyen A, Paku S, et al：Antiproliferative and apoptotic effects of mycophenolic acid in human B-cell non-Hodgkin lymphomas. Leuk Res 31：1003-1008, 2007

40）Engl T, Makarevic J, Relja B, et al：Mycophenolate mofetil modulates adhesion receptors of the beta1 integrin family on tumor cells：impact on tumor recurrence and malignancy. BMC Cancer 5：4, 2005

41）Opelz G and Dohler B：Lymphomas after solid organ transplantation：a collaborative transplant study report. Am J Transplant 4：222-230, 2004

42）Sehgal SN, Baker H and Vezina C：Rapamycin（AY-22,989）, a new antifungal antibiotic. Ⅱ. Fermentation, isolation and characterization. J Antibiot（Tokyo） 28：727-732, 1975

. Transplantation 64：36-42, 1997

44）Dennis PB, Fumagalli S and Thomas G：Target of rapamycin（TOR）：balancing the opposing forces of protein synthesis and degradation. Curr Opin Genet Dev 9：49-54, 1999

45）Nashan B：Review of the proliferation inhibitor everolimus. Expert Opin Investig Drugs 11：1845-1857, 2002

46）Nepomuceno RR, Balatoni CE, Natkunam Y, et al：Rapamycin inhibits the interleukin 10 signal transduction pathway and the growth of Epstein Barr virus B-cell lymphomas. Cancer Res 63：4472-4480, 2003

47）Garcia VD, Bonamigo-Filho JS, Neumann J, et al：Rituximab and rapamycin for posttransplant lymphoproliferative disease treatment：report of three cases. Transplant Proc 34：2993-2995, 2002

48）Majewski M, Korecka M, Joergensen J, et al：Immunosuppressive TOR kinase inhibitor everolimus（RAD）suppresses growth of cells derived from posttransplant lymphoproliferative disorder at allograft-protecting doses. Transplantation 75：1710-1717, 2003

49）Al-Akash SI, Al Makadma AS and Al Omari MG：Rapid response to rituximab in a pediatric liver transplant recipient with post-transplant lymphoproliferative disease and maintenance with sirolimus monotherapy. Pediatr Transplant 9：249-253, 2005

50）Stallone G, Schena A, Infante B, et al：Sirolimus for Kaposi's sarcoma in renal-transplant recipients. N Engl J Med 352：1317-1323, 2005

51）Schena FP, Pascoe MD, Alberu J, et al：Conversion from calcineurin inhibitors to sirolimus maintenance therapy in renal allograft recipients：24-month efficacy and safety results from the CONVERT trial. Transplantation 87：233-242, 2009

renal transplant patients. Am J Transplant 5：2521-2530, 2005

renal transplant recipients：a 3-year randomized, multicenter, phase Ⅲ study. Transplantation 80：244-252, 2005

54）Orentas RJ, Schauer DW Jr, Ellis FW, et al：Monitoring and modulation of Epstein-Barr virus loads in pediatric transplant patients. Pediatr Transplant 7：305-314, 2003

55）Rowe DT, Webber S, Schauer EM, et al：Epstein-Barr virus load monitoring：its role in the prevention and management of post-transplant lymphoproliferative disease. Transpl Infect Dis 3：79-87, 2001

56）Funch DP, Walker AM, Schneider G, et al：Ganciclovir and acyclovir reduce the risk of post-transplant lymphoproliferative disorder in renal transplant recipients. Am J Transplant 5：2894-2900, 2005

57）Green M, Michaels MG, Katz BZ, et al：CMV-IVIG for prevention of Epstein Barr virus disease and posttransplant lymphoproliferative disease in pediatric liver transplant recipients. Am J Transplant 6：1906-1912, 2006

58）Penn I：The role of immunosuppression in lymphoma formation. Springer Semin Immunopathol 20：343-355, 1998

59）Choquet S, Oertel S, LeBlond V, et al：Rituximab in the management of post-transplantation lymphoproliferative disorder after solid organ transplantation：proceed with caution. Ann Hematol 86：599-607, 2007

60）Wong G, Chapman JR and Craig JC：Cancer screening in renal transplant recipients：what is the evidence? Clin J Am Soc Nephrol 3（Suppl 2）：S87-S100, 2008

61）Kanaan N and Goffin E：Multiple bilateral fibroadenomas of the breasts requiring mastectomy in a renal transplant patient. Clin Nephrol 61：151-154, 2004

62）LeBrun CJ, Diehl LF, Abbott KC, et al：Life expectancy benefits of cancer screening in the end-stage renal disease population. Am J Kidney Dis 35：237-243, 2000

63）日本泌尿器学会（編）：腎癌診療ガイドライン2007年版．金原出版，東京，2008

64）Kiberd BA, Keough-Ryan T and Clase CM：Screening for prostate, breast and colorectal cancer in renal transplant recipients. Am J Transplant 3：619-625, 2003

65）Wong G, Howard K, Craig JC, et al：Cost-effectiveness of colorectal cancer screening in renal transplant recipients. Transplantation 85：532-541, 2008