Гепатоцеллюлярный рак и трансплантация печени: от хаоса к порядку

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Подходы к  лечению пациентов с  гепатоцеллюлярным раком (ГЦР), развившимся на фоне заболевания печени, быстро меняются. Выбор терапевтического алгоритма осложняется также по причине множества существующих вариантов лечения и участия в процессе большого числа врачей самых разных специальностей. ГЦР независимо от этиологии следует в первую очередь рассматривать как хирургическую болезнь. Возможности хирургии, включая частичную резекцию и  трансплантацию печени, долго недооценивались и даже были сведены к  минимуму вследствие многочисленных исследований, результаты которых привели к  продвижению различных методов местно-регионарного и  системного лечения. Местно-регионарное лечение и хирургические вмешательства следует считать не конкурирующими, а  взаимодополняющими подходами к  лечению. Методы местно-регионарного лечения имеют значение только при невозможности проведения оперативного вмешательства. В контексте трансплантации они играют большую роль как способ уменьшения стадии опухоли, то есть приведения пациентов, которым может быть выполнена трансплантация, в соответствие с требуемыми критериями отбора. В будущем значимость системной терапии и трансплантации печени живого донора в лечении ГЦР, несомненно, будет повышаться.

Об авторах

Я. Лерут

Университетская клиника Св. Луки, Католический университет Лювена

Автор, ответственный за переписку.
Email: jan.lerut@uclouvain.be

Лерут Ян – MD, PhD, профессор.

1200, Брюссель, Авеню Гиппократа, 10

Бельгия

С. Езари

Аквильский университет

Email: fake@neicon.ru

Езари Самуэле – MD, отделение биотехнологических и прикладных клинических наук.

67100, Коппито (Аквила), ул. Джованни Фальконе, 25

Италия

М. Фогенн

Университетская клиника Св. Луки, Католический университет Лювена

Email: fake@neicon.ru

Фогенн Максим – MD, отделение абдоминальной хирургии и трансплантологии им. Т. Старзла.

1200, Брюссель, Авеню Гиппократа, 10

Бельгия

К. Акенин

Университетская клиника Св. Луки, Католический университет Лювена

Email: fake@neicon.ru

Акенин Кевин – MD, отделение абдоминальной хирургии и трансплантологии им. Т. Старзла.

1200, Брюссель, Авеню Гиппократа, 10

Бельгия

К. Лай

Университет «Ла Сапиенца»

Email: fake@neicon.ru

Лай Квирино – MD, PhD, отделение общей хирургии и трансплантации органов.

00185, Рим, площадь Альдо Моро, 5

Италия

Список литературы

  1. Starzl TE, Demetris AJ. Liver transplantation: a 31-year perspective. In: Current Problems in Surgery. Vol. 27. Chicago: Year Book Medical Publishers; 1990.
  2. Starzl TE. Experience in hepatic transplantation. Philadelphia: W.B. Saunders Co; 1969. 553 p.
  3. Pichlmayr R, Weimann A, Oldhafer KJ, Schlitt HJ, Tusch G, Raab R. Appraisal of transplantation for malignant tumours of the liver with special reference to early stage hepatocellular carcinoma. Eur J Surg Oncol. 1998;24(1): 60–7. doi: 10.1016/S07487983(98)80130-3.
  4. Bismuth H, Chiche L, Adam R, Castaing D, Diamond T, Dennison A. Liver resection versus transplantation for hepatocellular carcinoma in cirrhotic patients. Ann Surg. 1993;218(2): 145–51.
  5. Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F, Montalto F, Ammatuna M, Morabito A, Gennari L. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996;334(11): 693–9. doi: 10.1056/NEJM199603143341104.
  6. Lai Q, Lerut JP. Hepatocellular cancer: how to expand safely inclusion criteria for liver transplantation. Curr Opin Organ Transplant. 2014;19(3): 229–34. doi: 10.1097/MOT.0000000000000085.
  7. Hwang S, Moon DB, Lee SG. Liver transplantation and conventional surgery for advanced hepatocellular carcinoma. Transpl Int. 2010;23(7): 723–7. doi: 10.1111/j.14322277.2010.01103.x.
  8. Yao FY, Ferrell L, Bass NM, Watson JJ, Bacchetti P, Venook A, Ascher NL, Roberts JP. Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology. 2001;33(6): 1394–403. doi: 10.1053/jhep.2001.24563.
  9. Mazzaferro V, Llovet JM, Miceli R, Bhoori S, Schiavo M, Mariani L, Camerini T, Roayaie S, Schwartz ME, Grazi GL, Adam R, Neuhaus P, Salizzoni M, Bruix J, Forner A, De Carlis L, Cillo U, Burroughs AK, Troisi R, Rossi M, Gerunda GE, Lerut J, Belghiti J, Boin I, Gugenheim J, Rochling F, Van Hoek B, Majno P; Metroticket Investigator Study Group. Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol. 2009;10(1): 35–43. doi: 10.1016/S1470-2045(08)70284-5.
  10. Lencioni R, Crocetti L, De Simone P, Filipponi F. Loco-regional interventional treatment of hepatocellular carcinoma: techniques, outcomes, and future prospects. Transpl Int. 2010;23(7): 698–703. doi: 10.1111/j.14322277.2010.01109.x.
  11. Torzilli G, Belghiti J, Kokudo N, Takayama T, Capussotti L, Nuzzo G, Vauthey JN, Choti MA, De Santibanes E, Donadon M, Morenghi E, Makuuchi M. A snapshot of the effective indications and results of surgery for hepatocellular carcinoma in tertiary referral centers: is it adherent to the EASL/AASLD recommendations?: an observational study of the HCC East-West study group. Ann Surg. 2013;257(5): 929–37. doi: 10.1097/SLA.0b013e31828329b8.
  12. Ikai I, Arii S, Okazaki M, Okita K, Omata M, Kojiro M, Takayasu K, Nakanuma Y, Makuuchi M, Matsuyama Y, Monden M, Kudo M. Report of the 17th Nationwide follow-up survey of primary liver cancer in Japan. Hepatol Res. 2007;37(9): 676–91. doi: 10.1111/j.1872034X.2007.00119.x.
  13. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol. 2018;69(1): 182–236. doi: 10.1016/j.jhep.2018.03.019.
  14. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Häussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J; SHARP Investigators Study Group. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359(4): 378–90. doi: 10.1056/NEJMoa0708857.
  15. Longo V, Gnoni A, Casadei Gardini A, Pisconti S, Licchetta A, Scartozzi M, Memeo R, Palmieri VO, Aprile G, Santini D, Nardulli P, Silvestris N, Brunetti O. Immunotherapeutic approaches for hepatocellular carcinoma. Oncotarget. 2017;8(20): 33897–910. doi: 10.18632/oncotarget.15406.
  16. Clavien PA, Lesurtel M, Bossuyt PM, Gores GJ, Langer B, Perrier A; OLT for HCC Consensus Group. Recommendations for liver transplantation for hepatocellular carcinoma: an international consensus conference report. Lancet Oncol. 2012;13(1):e11–22. doi: 10.1016/S14702045(11)70175-9.
  17. Kokudo T, Hasegawa K, Matsuyama Y, Takayama T, Izumi N, Kadoya M, Kudo M, Kubo S, Sakamoto M, Nakashima O, Kumada T, Kokudo N; Liver Cancer Study Group of Japan. Liver resection for hepatocellular carcinoma associated with hepatic vein invasion: A Japanese nationwide survey. Hepatology. 2017;66(2): 510–7. doi: 10.1002/hep.29225.
  18. Yau T, Tang VY, Yao TJ, Fan ST, Lo CM, Poon RT. Development of Hong Kong Liver Cancer staging system with treatment stratification for patients with hepatocellular carcinoma. Gastroenterology. 2014;146(7): 1691–700.e3. doi: 10.1053/j.gastro.2014.02.032.
  19. Takamoto T, Sugawara Y, Hashimoto T, Makuuchi M. Evaluating the current surgical strategies for hepatocellular carcinoma. Expert Rev Gastroenterol Hepatol. 2016;10(3): 341–57. doi: 10.1586/17474124.2016.1116381.
  20. Schnitzbauer AA, Lang SA, Goessmann H, Nadalin S, Baumgart J, Farkas SA, Fichtner-Feigl S, Lorf T, Goralcyk A, Hörbelt R, Kroemer A, Loss M, Rümmele P, Scherer MN, Padberg W, Königsrainer A, Lang H, Obed A, Schlitt HJ. Right portal vein ligation combined with in situ splitting induces rapid left lateral liver lobe hypertrophy enabling 2-staged extended right hepatic resection in small-for-size settings. Ann Surg. 2012;255(3): 405–14. doi: 10.1097/SLA.0b013e31824856f5.
  21. Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet. 2018;391(10127): 1301–14. doi: 10.1016/S0140-6736(18)30010-2.
  22. Sapisochin G, Goldaracena N, Laurence JM, Dib M, Barbas A, Ghanekar A, Cleary SP, Lilly L, Cattral MS, Marquez M, Selzner M, Renner E, Selzner N, McGilvray ID, Greig PD, Grant DR. The extended Toronto criteria for liver transplantation in patients with hepatocellular carcinoma: A prospective validation study. Hepatology. 2016;64(6): 2077–88. doi: 10.1002/hep.28643.
  23. Lai Q, Avolio AW, Graziadei I, Otto G, Rossi M, Tisone G, Goffette P, Vogel W, Pitton MB, Lerut J; European Hepatocellular Cancer Liver Transplant Study Group. Alpha-fetoprotein and modified response evaluation criteria in solid tumors progression after locoregional therapy as predictors of hepatocellular cancer recurrence and death after transplantation. Liver Transpl. 2013;19(10): 1108–18. doi: 10.1002/lt.23706.
  24. Duvoux C, Roudot-Thoraval F, Decaens T, Pessione F, Badran H, Piardi T, Francoz C, Compagnon P, Vanlemmens C, Dumortier J, Dharancy S, Gugenheim J, Bernard PH, Adam R, Radenne S, Muscari F, Conti F, Hardwigsen J, Pageaux GP, Chazouillères O, Salame E, Hilleret MN, Lebray P, Abergel A, Debette-Gratien M, Kluger MD, Mallat A, Azoulay D, Cherqui D; Liver Transplantation French Study Group. Liver transplantation for hepatocellular carcinoma: a model including α-fetoprotein improves the performance of Milan criteria. Gastroenterology. 2012;143(4): 986–94.e3. doi: 10.1053/j.gastro.2012.05.052.
  25. Toso C, Meeberg G, Hernandez-Alejandro R, Dufour JF, Marotta P, Majno P, Kneteman NM. Total tumor volume and alpha-fetoprotein for selection of transplant candidates with hepatocellular carcinoma: A prospective validation. Hepatology. 2015;62(1): 158–65. doi: 10.1002/hep.27787.
  26. Ito T, Takada Y, Ueda M, Haga H, Maetani Y, Oike F, Ogawa K, Sakamoto S, Ogura Y, Egawa H, Tanaka K, Uemoto S. Expansion of selection criteria for patients with hepatocellular carcinoma in living donor liver transplantation. Liver Transpl. 2007;13(12): 1637–44. doi: 10.1002/lt.21281.
  27. Zheng SS, Xu X, Wu J, Chen J, Wang WL, Zhang M, Liang TB, Wu LM. Liver transplantation for hepatocellular carcinoma: Hangzhou experiences. Transplantation. 2008;85(12): 1726–32. doi: 10.1097/TP.0b013e31816b67e4.
  28. Todo S, Furukawa H, Tada M; Japanese Liver Transplantation Study Group. Extending indication: role of living donor liver transplantation for hepatocellular carcinoma. Liver Transpl. 2007;13(11 Suppl 2):S48–54. doi: 10.1002/lt.21334.
  29. Lee JH, Cho Y, Kim HY, Cho EJ, Lee DH, Yu SJ, Lee JW, Yi NJ, Lee KW, Kim SH, Kim JM, Joh JW, Teperman LW, Park JS, Kim YJ, Suh KS, Yoon JH. Serum tumor markers provide refined prognostication in selecting liver transplantation candidate for hepatocellular carcinoma patients beyond the Milan criteria. Ann Surg. 2016;263(5): 842–50. doi: 10.1097/SLA.0000000000001578.
  30. Lai Q, Castro Santa E, Rico Juri JM, Pinheiro RS, Lerut J. Neutrophil and platelet-to-lymphocyte ratio as new predictors of dropout and recurrence after liver transplantation for hepatocellular cancer. Transpl Int. 2014;27(1): 32–41. doi: 10.1111/tri.12191.
  31. Lesurtel M, Müllhaupt B, Pestalozzi BC, Pfammatter T, Clavien PA. Transarterial chemoembolization as a bridge to liver transplantation for hepatocellular carcinoma: an evidence-based analysis. Am J Transplant. 2006;6(11): 2644–50. doi: 10.1111/j.16006143.2006.01509.x.
  32. Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis. 2010;30(1): 52–60. doi: 10.1055/s-0030-1247132.
  33. Vibert E, Azoulay D, Hoti E, Iacopinelli S, Samuel D, Salloum C, Lemoine A, Bismuth H, Castaing D, Adam R. Progression of alphafetoprotein before liver transplantation for hepatocellular carcinoma in cirrhotic patients: a critical factor. Am J Transplant. 2010;10(1): 129–37. doi: 10.1111/j.1600-6143.2009.02750.x.
  34. Manzia TM, Lai Q, Iesari S, Perera MTPR, Komuta M, Carvalheiro A, Shah T, Angelico R, Quaranta C, Nicolini D, Montalti R, Scarpelli M, Palmieri G, Orlacchio A, Vivarelli M, Angelico M, Lerut J, Tisone G. Impact of remnant vital tissue after locoregional treatment and liver transplant in hepatocellular cancer patients, a multicentre cohort study. Transpl Int. 2018;31(9): 988–98. doi: 10.1111/tri.13153.
  35. Merani S, Majno P, Kneteman NM, Berney T, Morel P, Mentha G, Toso C. The impact of waiting list alpha-fetoprotein changes on the outcome of liver transplant for hepatocellular carcinoma. J Hepatol. 2011;55(4): 814–9. doi: 10.1016/j.jhep.2010.12.040.
  36. Hong G, Suh KS, Suh SW, Yoo T, Kim H, Park MS, Choi Y, Paeng JC, Yi NJ, Lee KW. Alpha-fetoprotein and (18)F-FDG positron emission tomography predict tumor recurrence better than Milan criteria in living donor liver transplantation. J Hepatol. 2016;64(4): 852–9. doi: 10.1016/j.jhep.2015.11.033.
  37. Lerut J, Iesari S, Foguenne M, Lai Q. Hepatocellular cancer and recurrence after liver transplantation: what about the impact of immunosuppression? Transl Gastroenterol Hepatol. 2017;2:80. doi: 10.21037/tgh.2017.09.06.
  38. Lerut JP, Pinheiro RS, Lai Q, Stouffs V, Orlando G, Juri JM, Ciccarelli O, Sempoux C, Roggen FM, De Reyck C, Latinne D, Gianello P. Is minimal, [almost] steroid-free immunosuppression a safe approach in adult liver transplantation? Long-term outcome of a prospective, double blind, placebo-controlled, randomized, investigator-driven study. Ann Surg. 2014;260(5): 886–91. doi: 10.1097/SLA.0000000000000969.
  39. Lee SG. A complete treatment of adult living donor liver transplantation: a review of surgical technique and current challenges to expand indication of patients. Am J Transplant. 2015;15(1): 17–38. doi: 10.1111/ajt.12907.
  40. Friemel J, Rechsteiner M, Frick L, Böhm F, Struckmann K, Egger M, Moch H, Heikenwalder M, Weber A. Intratumor heterogeneity in hepatocellular carcinoma. Clin Cancer Res. 2015;21(8): 1951–61. doi: 10.1158/1078-0432.CCR-14-0122.
  41. Liebman HA, Furie BC, Tong MJ, Blanchard RA, Lo KJ, Lee SD, Coleman MS, Furie B. Des-gamma-carboxy (abnormal) prothrombin as a serum marker of primary hepatocellular carcinoma. N Engl J Med. 1984;310(22): 1427–31. doi: 10.1056/NEJM198405313102204.
  42. Nakao A, Virji A, Iwaki Y, Carr B, Iwatsuki S, Starzl E. Abnormal prothrombin (DES-gamma-carboxy prothrombin) in hepatocellular carcinoma. Hepatogastroenterology. 1991;38(5): 450–3.
  43. Lai Q, Nicolini D, Inostroza Nunez M, Iesari S, Goffette P, Agostini A, Giovagnoni A, Vivarelli M, Lerut J. A novel prognostic index in patients with hepatocellular cancer waiting for liver transplantation: Time-Radiological-response-Alpha-fetoprotein-INflammation (TRAIN) Score. Ann Surg. 2016;264(5): 787–96. doi: 10.1097/SLA.0000000000001881.
  44. Vitale A, Morales RR, Zanus G, Farinati F, Burra P, Angeli P, Frigo AC, Del Poggio P, Rapaccini G, Di Nolfo MA, Benvegnù L, Zoli M, Borzio F, Giannini EG, Caturelli E, Chiaramonte M, Trevisani F, Cillo U; Italian Liver Cancer group. Barcelona Clinic Liver Cancer staging and transplant survival benefit for patients with hepatocellular carcinoma: a multicentre, cohort study. Lancet Oncol. 2011;12(7): 654–62. doi: 10.1016/S1470-2045(11)70144-9.
  45. Cillo U, Burra P, Mazzaferro V, Belli L, Pinna AD, Spada M, Nanni Costa A, Toniutto P; I-BELT (Italian Board of Experts in the Field of Liver Transplantation). A multistep, consensus-based approach to organ allocation in liver transplantation: toward a "blended principle model". Am J Transplant. 2015;15(10): 2552–61. doi: 10.1111/ajt.13408.
  46. Lai Q, Vitale A, Iesari S, Finkenstedt A, Mennini G, Spoletini G, Hoppe-Lotichius M, Vennarecci G, Manzia TM, Nicolini D, Avolio AW, Frigo AC, Graziadei I, Rossi M, Tsochatzis E, Otto G, Ettorre GM, Tisone G, Vivarelli M, Agnes S, Cillo U, Lerut J; European Hepatocellular Cancer Liver Transplant Study Group. Intention-to-treat survival benefit of liver transplantation in patients with hepatocellular cancer. Hepatology. 2017;66(6): 1910–9. doi: 10.1002/hep.29342.
  47. Yang JD, Kim WR, Park KW, Chaiteerakij R, Kim B, Sanderson SO, Larson JJ, Pedersen RA, Therneau TM, Gores GJ, Roberts LR, Park JW. Model to estimate survival in ambulatory patients with hepatocellular carcinoma. Hepatology. 2012;56(2): 614–21. doi: 10.1002/hep.25680.
  48. Vitale A, Volk ML, De Feo TM, Burra P, Frigo AC, Ramirez Morales R, De Carlis L, Belli L, Colledan M, Fagiuoli S, Rossi G, Andorno E, Baccarani U, Regalia E, Vivarelli M, Donataccio M, Cillo U; Liver Transplantation North Italy Transplant program (NITp) working group. A method for establishing allocation equity among patients with and without hepatocellular carcinoma on a common liver transplant waiting list. J Hepatol. 2014;60(2): 290–7. doi: 10.1016/j.jhep.2013.10.010.
  49. Berry K, Ioannou GN. Comparison of liver transplant-related survival benefit in patients with versus without hepatocellular carcinoma in the United States. Gastroenterology. 2015;149(3): 669–80. doi: 10.1053/j.gastro.2015.05.025.

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