Current advances made in the surgical treatment of hepatocellular carcinoma

Authors

  • Shah Naveed Department of Surgical Oncology, Mahavir Cancer Sansthan, Patna, Bihar
  • Hasina Qari Department of Anesthesia, IGIMS, Patna, Bihar
  • Asma Altaf Department of BDS, GDC, Srinagar, J&K
  • Mah Para Department of BDS, GDC, Srinagar, J&K

Keywords:

Hepatocellular carcinoma, Trans-arterial chemoembolization, Radiofrequency ablation, Liver transplantation, Laparoscopic hepatectomy

Abstract

Hepatocellular carcinoma (HCC) is the fifth most common tumor worldwide. Multiple treatment options are available for HCC like curative resection, liver transplantation, radiofrequency ablation, trans-arterial chemoembolization, radioembolization and systemic targeted agent like sorafenib. The treatment of HCC depends on the tumor stage, patient performance status and liver function reserve and requires a multidisciplinary approach. For localized HCC, surgical resection and orthoptic liver transplantation are the gold standard therapies. In the past few years with significant advances in surgical treatments and locoregional therapies, the short-term survival of HCC has improved. Advances in assessment and treatment, including emerging evidence from laparoscopic hepatectomies and combined treatments with newly developed chemotherapies, may lead to expanded indications for liver resection in HCC. Liver transplantation (LT) is an ideal treatment for chronically injured liver tissue with impaired liver function and risk of multicentric carcinogenesis. The expansion of criteria for LT in HCC patients and combined treatment involving LR and LT are under investigation and discussion. This review presents and discusses recent studies concerning liver resection and transplantation in HCC patients based on our extensive review of relevant literature.

References

El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology. 2012;142:1264-73.

Rahbari NN, Mehrabi A, Mollberg NM, Müller SA, Koch M, Büchler MW, et al. Hepatocellular carcinoma: current management and perspectives for the future. Ann Surg. 2011;253:453-69.

El-Serag HB, Marrero JA, Rudolph L, Reddy KR. Diagnosis and treatment of hepatocellular carcinoma. Gastroenterology. 2008;134:1752-63.

Forner A, Reig ME, de Lope CR, Bruix J. Current strategy for staging and treatment: the BCLC update and future prospects. Semin Liver Dis. 2010;30:61-74.

Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53:1020-2.

European Association for the Study of the Liver, European Organisation for Research and Treatment of Cancer. EASLEORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012;56:908-43.

Torzilli G, Belghiti J, Kokudo N, Takayama T, Capussotti L, Nuzzo G, et al. 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;257:929-37.

Buell JF, Cherqui D, Geller DA, O’Rourke N, Iannitti D, Dagher I, et al. The international position on laparoscopic liver surgery: the Louisville Statement, 2008. Ann Surg. 2009;250:825-30.

Cucchetti A, Vitale A, Del Gaudio M, Ravaioli M, Ercolani G, Cescon M, et al. Harm and benefits of primary liver resection and salvage transplantation for hepatocellular carcinoma. Am J Transplant. 2010;10:619-27.

Yao FY, Ferrell L, Bass NM, Watson JJ, Bacchetti P, Venook A, et al. Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology. 2001;33:1394-403.

Fujiki M, Takada Y, Ogura Y, Oike F, Kaido T, Teramukai S, et al. Significance of des-gamma-carboxy prothrombin in selection criteria for living donor liver transplantation for hepatocellular carcinoma. Am J Transplant. 2009;9:2362-71.

Sarasin FP, Majno PE, Llovet JM, Bruix J, Mentha G, Hadengue A. Living donor liver transplantation for early hepatocellular carcinoma: a life-expectancy and cost-effectiveness perspective. Hepatology. 2001;33:1073-9.

Fuks D, Dokmak S, Paradis V, Diouf M, Durand F, Belghiti J. Benefit of initial resection of hepatocellular carcinoma followed by transplantation in case of recurrence: an intention-to-treat analysis. Hepatology. 2012;55:132-40.

Ikai I, Arii S, Okazaki M, Okita K, Omata M, Kojiro M, et al. Report of the 17th nationwide follow-up survey of primary liver cancer in Japan. Hepatol Res. 2007;37:676-91.

Bhoori S, Schiavo M, Russo A, Mazzaferro V. First-line treatment for hepatocellular carcinoma: resection or transplantation? Transplant Proc. 2007;39:2271-3.

Beard RE, Hanto DW, Gautam S, Miksad RA. A comparison of surgical outcomes for noncirrhotic and cirrhotic hepatocellular carcinoma patients in a Western institution. Surgery. 2013;154:545-55.

Hoeper MM, Krowka MJ, Strassburg CP. Portopulmonary hypertension and hepatopulmonary syndrome. Lancet. 2004;363:1461-8.

Ziser A, Plevak DJ, Wiesner RH, Rakela J, Offord KP, Brown DL. Morbidity and mortality in cirrhotic patients undergoing anesthesia and surgery. Anesthesiology. 1999;90:42-53.

Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg. 1973;60:646-9.

Mansour A, Watson W, Shayani V, Pickleman J. Abdominal operations in patients with cirrhosis: still a major surgical challenge. Surgery. 1997;122:730-6.

Poon RT, Fan ST, Lo CM, Liu CL, Wong J. Long-term survival and pattern of recurrence after resection of small hepatocellular carcinoma in patients with preserved liver function: implications for a strategy of salvage transplantation. Ann Surg. 2002;235:373-82.

Ishizawa T, Hasegawa K, Aoki T, Takahashi M, Inoue Y, Sano K, et al. Neither multiple tumors nor portal hypertension are surgical contraindications for hepatocellular carcinoma. Gastroenterology. 2008;134:1908-16.

Makuuchi M, Sano K. The surgical approach to HCC: our progress and results in Japan. Liver Transpl. 2004;10:S46-52.

Bruix J, Castells A, Bosch J, Feu F, Fuster J, Garcia-Pagan JC, et al. Surgical resection of hepatocellular carcinoma in cirrhotic patients: prognostic value of preoperative portal pressure. Gastroenterology. 1996;111:1018-22.

Ruzzenente A, Valdegamberi A, Campagnaro T, Conci S, Pachera S, Iacono C, et al. Hepatocellular carcinoma in cirrhotic patients with portal hypertension: is liver resection always contraindicated? World J Gastroenterol. 2011;17:5083-8.

Kawano Y, Sasaki A, Kai S, Endo Y, Iwaki K, Uchida H, et al. Short- and long-term outcomes after hepatic resection for hepatocellular carcinoma with concomitant esophageal varices in patients with cirrhosis. Ann Surg Oncol. 2008;15:1670-6.

Cucchetti A, Ercolani G, Vivarelli M, Cescon M, Ravaioli M, Ramacciato G, et al. Is portal hypertension a contraindication to hepatic resection? Ann Surg. 2009;250:922-8.

Santambrogio R, Kluger MD, Costa M, Belli A, Barabino M, Laurent A, et al. Hepatic resection for hepatocellular carcinoma in patients with Child- Pugh’s A cirrhosis: is clinical evidence of portal hypertension a contraindication? HPB (Oxford). 2013;15:78-84.

Barbier L, Fuks D, Pessaux P, Muscari F, Le Treut YP, Faivre S, et al. Safety of liver resection for hepatocellular carcinoma after sorafenib therapy: a multicenter case-matched study. Ann Surg Oncol. 2013;20:3603-9.

Wong TC, Lo CM. Resection strategies for hepatocellular carcinoma. Semin Liver Dis. 2013;33:273-81.

Cucchetti A, Piscaglia F, Caturelli E, Benvegnù L, Vivarelli M, Ercolani G, et al. Comparison of recurrence of hepatocellular carcinoma after resection in patients with cirrhosis to its occurrence in a surveilled cirrhotic population. Ann Surg Oncol. 2009;16:413-22.

Mazzaferro V, Romito R, Schiavo M, Mariani L, Camerini T, Bhoori S, et al. Prevention of hepatocellular carcinoma recurrence with alpha-interferon after liver resection in HCV cirrhosis. Hepatology. 2006;44:1543-54.

Xia Y, Qiu Y, Li J, Shi L, Wang K, Xi T, et al. Adjuvant therapy with capecitabine postpones recurrence of hepatocellular carcinoma after curative resection: a randomized controlled trial. Ann Surg Oncol. 2010;17:3137-44.

Nault JC, De Reyniès A, Villanueva A, Calderaro J, Rebouis-WJG Sou S, Couchy G, et al. A hepatocellular carcinoma 5-gene score associated with survival of patients after liver resection. Gastroenterology. 2013;145:176-87.

Farges O, Malassagne B, Flejou JF, Balzan S, Sauvanet A, Belghiti J. Risk of major liver resection in patients with underlying chronic liver disease: a reappraisal. Ann Surg. 1999;229:210-5.

Belghiti J, Fuks D. Liver resection and transplantation in hepatocellular carcinoma. Liver Cancer. 2012;1:71-82.

Roayaie S, Blume IN, Thung SN, Guido M, Fiel MI, Hiotis S, et al. A system of classifying microvascular invasion to predict outcome after resection in patients with hepatocellular carcinoma. Gastroenterology. 2009;137:850-5.

Belghiti J, Regimbeau JM, Durand F, Kianmanesh AR, Dondero F, Terris B, et al. Resection of hepatocellular carcinoma: a European experience on 328 cases. Hepatogastroenterology. 2002;49:41-6.

Torzilli G, Makuuchi M, Inoue K, Takayama T, Sakamoto Y, Sugawara Y, et al. No-mortality liver resection for hepatocellular carcinoma in cirrhotic and noncirrhotic patients: is there a way? A prospective analysis of our approach. Arch Surg. 1999;134:984-92.

Wakabayashi H, Ishimura K, Izuishi K, Karasawa Y, Maeta H. Evaluation of liver function for hepatic resection for hepatocellular carcinoma in the liver with damaged parenchyma. J Surg Res. 2004;116:248-52.

Fan ST, Lai EC, Lo CM, Ng IO, Wong J. Hospital mortality of major hepatectomy for hepatocellular carcinoma associated with cirrhosis. Arch Surg. 1995;130:198-203.

Lam CM, Fan ST, Lo CM, Wong J. Major hepatectomy for hepatocellular carcinoma in patients with an unsatisfactory indocyanine green clearance test. Br J Surg. 1999;86:1012-7.

Fan ST. Liver functional reserve estimation: state of the art and relevance for local treatments: the Eastern perspective. J Hepatobiliary Pancreat Sci. 2010;17:380-4.

Belli G, Fantini C, Belli A, Limongelli P. Laparoscopic liver resection for hepatocellular carcinoma in cirrhosis: long-term outcomes. Dig Surg. 2011;28:134-40.

Morise Z, Kawabe N, Kawase J, Tomishige H, Nagata H, Ohshima H, et al. Pure laparoscopic hepatectomy for hepatocellular carcinoma with chronic liver disease. World J Hepatol. 2013;5:487-95.

Makuuchi M, Thai BL, Takayasu K, Takayama T, Kosuge T, Gunvén P, et al. Preoperative portal embolization to increase safety of major hepatectomy for hilar bile duct carcinoma: a preliminary report. Surgery. 1990;107:521-7.

Yamakado K, Takeda K, Matsumura K, Nakatsuka A, Hirano T, Kato N, et al. Regeneration of the un-embolized liver parenchyma following portal vein embolization. J Hepatol. 1997;27:871-80.

Ogata S, Belghiti J, Farges O, Varma D, Sibert A, Vilgrain V. Sequential arterial and portal vein embolizations before right hepatectomy in patients with cirrhosis and hepatocellular carcinoma. Br J Surg. 2006;93:1091-8.

Yoo H, Kim JH, Ko GY, Kim KW, Gwon DI, Lee SG, et al. Sequential transcatheter arterial chemoembolization and portal vein embolization versus portal vein embolization only before major hepatectomy for patients with hepatocellular carcinoma. Ann Surg Oncol. 2011;18:1251-7.

Truant S, Oberlin O, Sergent G, Lebuffe G, Gambiez L, Ernst O, et al. Remnant liver volume to body weight ratio & gt; or = 0.5%: a new cut-off to estimate postoperative risks after extended resection in noncirrhotic liver. J Am Coll Surg. 2007;204:22-33.

Chun YS, Ribero D, Abdalla EK, Madoff DC, Mortenson MM, Wei SH, et al. Comparison of two methods of future liver remnant volume measurement. J Gastrointest Surg. 2008;12:123-8.

Farges O, Belghiti J, Kianmanesh R, Regimbeau JM, Santoro R, Vilgrain V, et al. Portal vein embolization before right hepatectomy: prospective clinical trial. Ann Surg. 2003;237:208-17.

Imamura H, Matsuyama Y, Miyagawa Y, Ishida K, Shimada R, Miyagawa S, et al. Prognostic significance of anatomical resection and des-gamma-carboxy prothrombin in patients with hepatocellular carcinoma. Br J Surg. 1999;86:1032-8.

Wakai T, Shirai Y, Sakata J, Kaneko K, Cruz PV, Akazawa K, et al. Anatomic resection independently improves long-term survival in patients with T1-T2 hepatocellular carcinoma. Ann Surg Oncol. 2007;14:1356-65.

Ueno S, Kubo F, Sakoda M, Hiwatashi K, Tateno T, Mataki Y, et al. Efficacy of anatomic resection vs nonanatomic resection for small nodular hepatocellular carcinoma based on gross classification. J Hepatobiliary Pancreat Surg. 2008;15:493-500.

Shi M, Guo RP, Lin XJ, Zhang YQ, Chen MS, Zhang CQ, et al. Partial hepatectomy with wide versus narrow resection margin for solitary hepatocellular carcinoma: a prospective randomized trial. Ann Surg. 2007;245:36-43.

Arii S, Tanaka S, Mitsunori Y, Nakamura N, Kudo A, Noguchi N, et al. Surgical strategies for hepatocellular carcinoma with special reference to anatomical hepatic resection and intraoperative contrast-enhanced ultrasonography. Oncology. 2010;78(Suppl 1):125-30.

Poon RT, Fan ST, Ng IO, Lo CM, Liu CL, Wong J. Different risk factors and prognosis for early and late intrahepatic recurrence after resection of hepatocellular carcinoma. Cancer. 2000;89:500-7.

Radtke A, Sotiropoulos GC, Molmenti EP, Schroeder T, Peitgen HO, Frilling A, et al. Computer-assisted surgery planning for complex liver resections: when is it helpful? A single-center experience over an 8-year period. Ann Surg. 2010;252:876-83.

Kaneko H, Tsuchiya M, Otsuka Y, Yajima S, Minagawa T, Watanabe M, et al. Laparoscopic hepatectomy for hepatocellular carcinoma in cirrhotic patients. J Hepatobiliary Pancreat Surg. 2009;16:433-8.

Mirnezami R, Mirnezami AH, Chandrakumaran K, Abu Hilal M, Pearce NW, Primrose JN, et al. Short- and long-term outcomes after laparoscopic and open hepatic resection: systematic review and meta-analysis. HPB (Oxford). 2011;13:295-308.

Tsuchiya M, Otsuka Y, Tamura A, Nitta H, Sasaki A, Wakabayashi G, et al. Status of endoscopic liver surgery in Japan: a questionnaire survey conducted by the Japanese Endoscopic Liver Surgery Study Group. J Hepatobiliary Pancreat Surg. 2009;16:405-9.

Tranchart H, Di Giuro G, Lainas P, Roudie J, Agostini H, Franco D, et al. Laparoscopic resection for hepatocellular carcinoma: a matched-pair comparative study. Surg Endosc. 2010;24:1170-6.

Vigano L, Laurent A, Tayar C, Tomatis M, Ponti A, Cherqui D. The learning curve in laparoscopic liver resection: improved feasibility and reproducibility. Ann Surg. 2009;250:772-82.

Belghiti J, Hiramatsu K, Benoist S, Massault P, Sauvanet A, Farges O. Seven hundred forty-seven hepatectomies in the 1990s: an update to evaluate the actual risk of liver resection. J Am Coll Surg. 2000;191:38-46.

Lai EC, Fan ST, Lo CM, Chu KM, Liu CL, Wong J. Hepatic resection for hepatocellular carcinoma. An audit of 343 patients. Ann Surg. 1995;221:291-8.

Morise Z, Sugioka A, Kawabe N, Umemoto S, Nagata H, Ohshima H, et al. Pure laparoscopic hepatectomy for hepatocellular carcinoma patients with severe liver cirrhosis. Asian J Endosc Surg. 2011;4:143-6.

Cha CH, Ruo L, Fong Y, Jarnagin WR, Shia J, Blumgart LH, et al. Resection of hepatocellular carcinoma in patients otherwise eligible for transplantation. Ann Surg. 2003;238:315-23.

Imamura H, Matsuyama Y, Tanaka E, Ohkubo T, Hasegawa K, Miyagawa S, et al. Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy. J Hepatol. 2003;38:200-7.

Hoshida Y, Villanueva A, Kobayashi M, Peix J, Chiang DY, Camargo A, et al. Gene expression in fixed tissues and outcome in hepatocellular carcinoma. N Engl J Med. 2008;359:1995-2004.

Zhou WP, Lai EC, Li AJ, Fu SY, Zhou JP, Pan ZY, et al. A prospective, randomized, controlled trial of preoperative transarterial chemoembolization for resectable large hepatocellular carcinoma. Ann Surg. 2009;249:195-202.

Lau WY, Leung TW, Ho SK, Chan M, Machin D, Lau J, et al. Adjuvant intra-arterial iodine-131-labelled lipiodol for resectable hepatocellular carcinoma: a prospective randomised trial. Lancet. 1999;353:797-801.

Takayama T, Sekine T, Makuuchi M, Yamasaki S, Kosuge T, Yamamoto J, et al. Adoptive immunotherapy to lower postsurgical recurrence rates of hepatocellular carcinoma: a randomised trial. Lancet. 2000;356:802-7.

Muto Y, Moriwaki H, Ninomiya M, Adachi S, Saito A, Takasaki KT, et al. Prevention of second primary tumors by an acyclic retinoid, polyprenoic acid, in patients with hepatocellular carcinoma. Hepatoma Prevention Study Group. N Engl J Med. 1996;334:1561-7.

Vincent T. DeVita Jr, Theodore S. Lawrence, Steven A. Rosenberg. Liver transplantation. In: Vincent T. DeVita Jr, Theodore S. Lawrence, Steven A. Rosenberg, eds. DeVita, Hellman, and Rosenberg’s Cancer. 10th ed. Philadelphia: Lippincott Williams and Wilkins; 2014: 699-701.

Bruix J, Sherman M; American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53:1020-2.

Clavien PA, Lesurtel M, Bossuyt PM, Gores GJ, Langer B, Perrier A. Recommendations for liver transplantation for hepatocellular carcinoma: an international consensus conference report. Lancet Oncol. 2012;13:e11-22.

Germani G, Gurusamy K, Garcovich M, Toso C, Fede G, Hemming A, et al. Which matters most: number of tumors, size of the largest tumor, or total tumor volume? Liver Transpl. 2011;17(Suppl 2):S58-66.

Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996;334:693-9.

Mazzaferro V, Bhoori S, Sposito C, Bongini M, Langer M, Miceli R, et al. Milan criteria in liver transplantation for hepatocellular carcinoma: an evidence-based analysis of 15 years of experience. Liver Transpl. 2011;17(Suppl 2):S44-57.

Yao FY, Ferrell L, Bass NM, Bacchetti P, Ascher NL, Roberts JP. Liver transplantation for hepatocellular carcinoma: comparison of the proposed UCSF criteria with the Milan criteria and the Pittsburgh modified TNM criteria. Liver Transpl. 2002;8:765-74.

Leung JY, Zhu AX, Gordon FD, Pratt DS, Mithoefer A, Garrigan K, et al. Liver transplantation outcomes for early-stage hepatocellular carcinoma: results of a multicenter study. Liver Transpl. 2004;10:1343-54.

Patel SS, Arrington AK, McKenzie S, Mailey B, Ding M, Lee W, et al. Milan criteria and UCSF criteria: a preliminary comparative study of liver transplantation outcomes in the United States. Int J Hepatol. 2012;2012:253517.

Decaens T, Roudot-Thoraval F, Hadni-Bresson S, Meyer C, Gugenheim J, Durand F, et al. Impact of UCSF criteria according to pre- and post-OLT tumor features: analysis of 479 patients listed for HCC with a short waiting time. Liver Transpl. 2006;12:1761-9.

Duffy JP, Vardanian A, Benjamin E, Watson M, Farmer DG, Ghobrial RM, et al. Liver transplantation criteria for hepatocellular carcinoma should be expanded: a 22-year experience with 467 patients at UCLA. Ann Surg. 2007;246:502-11.

Strong RW. Whither living donor liver transplantation? Liver Transpl Surg. 1999;5:536-8.

Llovet JM, Fuster J, Bruix J. Intention-to-treat analysis of surgical treatment for early hepatocellular carcinoma: resection versus transplantation. Hepatology. 1999;30:1434-440.

Yao FY, Bass NM, Nikolai B, Davern TJ, Kerlan R, Wu V, et al. Liver transplantation for hepatocellular carcinoma: analysis of survival according to the intention-to-treat principle and dropout from the waiting list. Liver Transpl. 2002;8:873-83.

Toso C, Dupuis-Lozeron E, Majno P, Berney T, Kneteman NM, Perneger T, et al. A model for dropout assessment of candidates with or without hepatocellular carcinoma on a common liver transplant waiting list. Hepatology. 2012;56:149-56.

Vitale A, Morales RR, Zanus G, Farinati F, Burra P, Angeli P, et al. Barcelona clinic liver cancer staging and transplant survival benefit for patients with hepatocellular carcinoma: a multicentre, cohort study. Lancet Oncol. 2011;12:654-62.

Avolio AW, Cillo U, Salizzoni M, De Carlis L, Colledan M, Gerunda GE, et al. Balancing donor and recipient risk factors in liver transplantation: the value of D-MELD with particular reference to HCV recipients. Am J Transplant. 2011;11:2724-36.

Vitale A, D’Amico F, Frigo AC, Grigoletto F, Brolese A, Zanus G, et al. Response to therapy as a criterion for awarding priority to patients with hepatocellular carcinoma awaiting liver transplantation. Ann Surg Oncol. 2010;17:2290-302.

Roayaie K, Feng S. Allocation policy for hepatocellular carcinoma in the MELD era: room for improvement? Liver Transpl. 2007;13:S36-43.

Freeman RB, Edwards EB, Harper AM. Waiting list removal rates among patients with chronic and malignant liver diseases. Am J Transplant. 2006;6:1416-21.

Pompili M, Mirante VG, Rondinara G, Fassati LR, Piscaglia F, Agnes S, et al. Percutaneous ablation procedures in cirrhotic patients with hepatocellular carcinoma submitted to liver transplantation: Assessment of efficacy at explant analysis and of safety for tumor recurrence. Liver Transpl. 2005;11:1117-26.

Pompili M, Francica G, Ponziani FR, Iezzi R, Avolio AW. Bridging and down staging treatments for hepatocellular carcinoma in patients on the waiting list for liver transplantation. World J Gastroenterol. 2013;19:7515-30.

Belghiti J, Cortes A, Abdalla EK, Régimbeau JM, Prakash K, Durand F, et al. Resection prior to liver transplantation for hepatocellular carcinoma. Ann Surg. 2003;238:885-93.

Majno PE, Sarasin FP, Mentha G, Hadengue A. Primary liver resection and salvage transplantation or primary liver transplantation in patients with single, small hepatocellular carcinoma and preserved liver function: an outcome-oriented decision analysis. Hepatology. 2000;31:899-906.

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2016-12-13

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