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Journal of Gastrointestinal Surgery

, Volume 23, Issue 1, pp 199–209 | Cite as

Current Approaches in the Management of Hepatic Adenomas

  • Diamantis I. Tsilimigras
  • Amir A. Rahnemai-Azar
  • Ioannis Ntanasis-Stathopoulos
  • Maria Gavriatopoulou
  • Demetrios Moris
  • Eleftherios Spartalis
  • Jordan M. Cloyd
  • Sharon M. Weber
  • Timothy M. PawlikEmail author
Review Article

Abstract

Introduction

Hepatic adenomas (HAs) are a benign and relatively rare type of liver neoplasms. We review the diagnosis, evaluation, and potential therapeutic management options for patients with HA.

Methods

A comprehensive review of the English literature was performed utilizing MEDLINE/PubMed and Web of Science databases with end of search date the 30th April of 2018. In PubMed, the terms “hepatocellular,” “hepatic,” “liver,” and “adenoma,” “adenomatosis” were searched in the title and/or abstract.

Results

Recent advances in molecular classification of HA have determined distinct subtypes with specific clinical, pathological, and imaging characteristics. In general, cessation of exogenous hormonal administration or weight loss may lead to HA regression. Surgical resection, either open or laparoscopic, should be considered in patients with symptoms and risk factors for hemorrhage or malignant transformation. These risk factors include tumor diameter greater than 5 cm, β-catenin activated subtype, and/or male gender. The management of acute hemorrhage should primarily aim at achieving hemodynamic stability via angioembolization followed by elective resection, whereas malignant transformation is treated according to oncologic resection principles. Although pregnancy is one of the known risk factors for tumor growth and associated complications, the presence of an HA per se should not be considered a contradiction to pregnancy.

Conclusion

Future genomic-based multicenter studies are required to provide a strong basis for formulating an evidence-based risk-adapted model that guides individualized management strategies for patients with HA.

Keywords

Adenoma Adenomatosis Liver Hepatic HNF-1α β-Catenin JAK-STAT pathway 

Notes

Compliance with Ethical Standards

Conflict of Interest

None declared.

References

  1. 1.
    Belghiti J, Cauchy F, Paradis V, Vilgrain V. Diagnosis and management of solid benign liver lesions. Nat Rev Gastroenterol Hepatol. 2014;11(12):737–49.Google Scholar
  2. 2.
    Cristiano A, Dietrich A, Spina JC, Ardiles V, de Santibanes E. Focal nodular hyperplasia and hepatic adenoma: current diagnosis and management. Updates Surg. 2014;66(1):9–21.Google Scholar
  3. 3.
    Agrawal S, Agarwal S, Arnason T, Saini S, Belghiti J. Management of hepatocellular adenoma: recent advances. Clin Gastroenterol Hepatol. 2015;13(7):1221–30.Google Scholar
  4. 4.
    Micchelli ST, Vivekanandan P, Boitnott JK, Pawlik TM, Choti MA, Torbenson M. Malignant transformation of hepatic adenomas. Mod Pathol. 2008;21(4):491–7.Google Scholar
  5. 5.
    Flejou JF, Barge J, Menu Y, Degott C, Bismuth H, Potet F, et al. Liver adenomatosis. An entity distinct from liver adenoma? Gastroenterology. 1985;89(5):1132–8.Google Scholar
  6. 6.
    Ribeiro A, Burgart LJ, Nagorney DM, Gores GJ. Management of liver adenomatosis: results with a conservative surgical approach. Liver Transpl Surg. 1998;4(5):388–98.Google Scholar
  7. 7.
    Grazioli L, Federle MP, Ichikawa T, Balzano E, Nalesnik M, Madariaga J. Liver adenomatosis: clinical, histopathologic, and imaging findings in 15 patients. Radiology. 2000;216(2):395–402.Google Scholar
  8. 8.
    Frulio N, Chiche L, Bioulac-Sage P, Balabaud C. Hepatocellular adenomatosis: what should the term stand for! Clin Res Hepatol Gastroenterol. 2014;38(2):132–6.Google Scholar
  9. 9.
    Rooks JB, Ory HW, Ishak KG, Strauss LT, Greenspan JR, Hill AP, et al. Epidemiology of hepatocellular adenoma. The role of oral contraceptive use. JAMA. 1979;242(7):644–8.Google Scholar
  10. 10.
    Baum JK, Bookstein JJ, Holtz F, Klein EW. Possible association between benign hepatomas and oral contraceptives. Lancet. 1973;2(7835):926–9.Google Scholar
  11. 11.
    Lin H, van den Esschert J, Liu C, van Gulik TM. Systematic review of hepatocellular adenoma in China and other regions. J Gastroenterol Hepatol. 2011;26(1):28–35.Google Scholar
  12. 12.
    Vijay A, Elaffandi A, Khalaf H. Hepatocellular adenoma: An update. World J Hepatol. 2015;7(25):2603–9.Google Scholar
  13. 13.
    Paustian L, Chao MM, Hanenberg H, Schindler D, Neitzel H, Kratz CP, et al. Androgen therapy in Fanconi anemia: a retrospective analysis of 30 years in Germany. Pediatr Hematol Oncol. 2016;33(1):5–12.Google Scholar
  14. 14.
    Velazquez I, Alter BP. Androgens and liver tumors: Fanconi's anemia and non-Fanconi's conditions. Am J Hematol. 2004;77(3):257–67.Google Scholar
  15. 15.
    Noels JE, van Aalten SM, van der Windt DJ, Kok NF, de Man RA, Terkivatan T, et al. Management of hepatocellular adenoma during pregnancy. J Hepatol. 2011;54(3):553–8.Google Scholar
  16. 16.
    van Aalten SM, Broker ME, Busschbach JJ, de Koning HJ, de Man RA, Steegers EA, et al. Pregnancy and liver adenoma management: PALM-study. BMC Gastroenterol. 2012;12:82.Google Scholar
  17. 17.
    Broker MEE, Gaspersz MP, Klompenhouwer AJ, Hansen BE, Terkivatan T, Taimr P, et al. Inflammatory and multiple hepatocellular adenoma are associated with a higher BMI. Eur J Gastroenterol Hepatol. 2017;29(10):1183–8.Google Scholar
  18. 18.
    Bunchorntavakul C, Bahirwani R, Drazek D, Soulen MC, Siegelman ES, Furth EE, et al. Clinical features and natural history of hepatocellular adenomas: the impact of obesity. Aliment Pharmacol Ther. 2011;34(6):664–74.Google Scholar
  19. 19.
    Bioulac-Sage P, Taouji S, Possenti L, Balabaud C. Hepatocellular adenoma subtypes: the impact of overweight and obesity. Liver Int. 2012;32(8):1217–21.Google Scholar
  20. 20.
    Oterdoom LH, Verweij KE, Biermann K, Langeveld M, van Buuren HR. Hepatocellular adenomas and carcinoma in asymptomatic, non-cirrhotic type III glycogen storage disease. J Gastrointestin Liver Dis. 2015;24(4):515–8.Google Scholar
  21. 21.
    Demo E, Frush D, Gottfried M, Koepke J, Boney A, Bali D, et al. Glycogen storage disease type III-hepatocellular carcinoma a long-term complication? J Hepatol. 2007;46(3):492–8.Google Scholar
  22. 22.
    Sanada Y, Mizuta K, Niki T, Tashiro M, Hirata Y, Okada N, et al. Hepatocellular nodules resulting from congenital extrahepatic portosystemic shunts can differentiate into potentially malignant hepatocellular adenomas. J Hepatobiliary Pancreat Sci. 2015;22(10):746–56.Google Scholar
  23. 23.
    Seyama Y, Sano K, Tang W, Kokudo N, Sakamoto Y, Imamura H, et al. Simultaneous resection of liver cell adenomas and an intrahepatic portosystemic venous shunt with elevation of serum PIVKA-II level. J Gastroenterol. 2006;41(9):909–12.Google Scholar
  24. 24.
    Dhingra S, Fiel MI. Update on the new classification of hepatic adenomas: clinical, molecular, and pathologic characteristics. Arch Pathol Lab Med. 2014;138(8):1090–7.Google Scholar
  25. 25.
    Raft MB, Jorgensen EN, Vainer B. Gene mutations in hepatocellular adenomas. Histopathology. 2015;66(7):910–21.Google Scholar
  26. 26.
    Liau SS, Qureshi MS, Praseedom R, Huguet E. Molecular pathogenesis of hepatic adenomas and its implications for surgical management. J Gastrointest Surg. 2013;17(10):1869–82.Google Scholar
  27. 27.
    Zucman-Rossi J, Jeannot E, Nhieu JT, Scoazec JY, Guettier C, Rebouissou S, et al. Genotype-phenotype correlation in hepatocellular adenoma: new classification and relationship with HCC. Hepatology. 2006;43(3):515–24.Google Scholar
  28. 28.
    Bioulac-Sage P, Rebouissou S, Thomas C, Blanc JF, Saric J, Sa Cunha A, et al. Hepatocellular adenoma subtype classification using molecular markers and immunohistochemistry. Hepatology. 2007;46(3):740–8.Google Scholar
  29. 29.
    Cantu S, Krier J, Hashemi N. Hepatocyte nuclear factor 1alpha mutation-associated MODY-3 and familial liver adenomatosis. J Clin Gastroenterol. 2016;50(2):181–2.Google Scholar
  30. 30.
    Nault JC, Couchy G, Balabaud C, Morcrette G, Caruso S, Blanc JF, et al. Molecular classification of hepatocellular adenoma associates with risk factors, bleeding, and malignant transformation. Gastroenterology. 2017;152(4):880–94 e6.Google Scholar
  31. 31.
    Kohler UA, Bohm F, Rolfs F, Egger M, Hornemann T, Pasparakis M, et al. NF-kappaB/RelA and Nrf2 cooperate to maintain hepatocyte integrity and to prevent development of hepatocellular adenoma. J Hepatol. 2016;64(1):94–102.Google Scholar
  32. 32.
    Liu D, Liu P, Cao L, Zhang Q, Chen Y. Screening the key genes of hepatocellular adenoma via microarray analysis of DNA expression and methylation profiles. Oncol Lett. 2017;14(4):3975–80.Google Scholar
  33. 33.
    Poupon R, Cazals-Hatem D, Arrive L. Fenofibrate-induced massive regression of mutiple inflammatory hepatocellular adenoma. Clin Res Hepatol Gastroenterol. 2016;40(1):e1–3.Google Scholar
  34. 34.
    Khanna M, Ramanathan S, Fasih N, Schieda N, Virmani V, McInnes MD. Current updates on the molecular genetics and magnetic resonance imaging of focal nodular hyperplasia and hepatocellular adenoma. Insights Imaging. 2015;6(3):347–62.Google Scholar
  35. 35.
    De Kock I, Mortele KJ, Smet B, Gillardin P, Pauwels W, De Backer AI. Hepatic adenomatosis: MR imaging features. JBR-BTR. 2014;97(2):105–8.Google Scholar
  36. 36.
    Ronot M, Bahrami S, Calderaro J, Valla DC, Bedossa P, Belghiti J, et al. Hepatocellular adenomas: accuracy of magnetic resonance imaging and liver biopsy in subtype classification. Hepatology. 2011;53(4):1182–91.Google Scholar
  37. 37.
    Roux M, Pigneur F, Baranes L, Calderaro J, Chiaradia M, Decaens T, et al. Differentiating focal nodular hyperplasia from hepatocellular adenoma: is hepatobiliary phase MRI (HBP-MRI) using linear gadolinium chelates always useful? Abdom Radiol (NY). 2017.Google Scholar
  38. 38.
    Dharmana H, Saravana-Bawan S, Girgis S, Low G. Hepatocellular adenoma: imaging review of the various molecular subtypes. Clin Radiol. 2017;72(4):276–85.Google Scholar
  39. 39.
    Laumonier H, Bioulac-Sage P, Laurent C, Zucman-Rossi J, Balabaud C, Trillaud H. Hepatocellular adenomas: magnetic resonance imaging features as a function of molecular pathological classification. Hepatology. 2008;48(3):808–18.Google Scholar
  40. 40.
    Guo Y, Li W, Cai W, Zhang Y, Fang Y, Hong G. Diagnostic value of gadoxetic acid-enhanced mr imaging to distinguish HCA and its subtype from FNH: a systematic review. Int J Med Sci. 2017;14(7):668–74.Google Scholar
  41. 41.
    van den Esschert JW, van Gulik TM, Phoa SS. Imaging modalities for focal nodular hyperplasia and hepatocellular adenoma. Dig Surg. 2010;27(1):46–55.Google Scholar
  42. 42.
    Taimr P, Broker MEE, Dwarkasing RS, Hansen BE, de Knegt RJ, De Man RA, et al. A model-based prediction of the probability of hepatocellular adenoma and focal nodular hyperplasia based on characteristics on contrast-enhanced ultrasound. Ultrasound Med Biol. 2017;43(10):2144–50.Google Scholar
  43. 43.
    Lee SY, Kingham TP, LaGratta MD, Jessurun J, Cherqui D, Jarnagin WR, et al. PET-avid hepatocellular adenomas: incidental findings associated with HNF1-alpha mutated lesions. HPB (Oxford). 2016;18(1):41–8.Google Scholar
  44. 44.
    Sannier A, Cazejust J, Lequoy M, Cervera P, Scatton O, Rosmorduc O, et al. Liver biopsy for diagnosis of presumed benign hepatocellular lesions lacking magnetic resonance imaging diagnostic features of focal nodular hyperplasia. Liver Int. 2016;36(11):1668–76.Google Scholar
  45. 45.
    Bioulac-Sage P, Cubel G, Taouji S, Scoazec JY, Leteurtre E, Paradis V, et al. Immunohistochemical markers on needle biopsies are helpful for the diagnosis of focal nodular hyperplasia and hepatocellular adenoma subtypes. Am J Surg Pathol. 2012;36(11):1691–9.Google Scholar
  46. 46.
    Agostini-Vulaj D, Sharma AK, Findeis-Hosey JJ, McMahon LA, Gonzalez RS. Distinction between inflammatory hepatocellular adenoma and mass effect on liver sampling. Hum Pathol. 2017;61:105–10.Google Scholar
  47. 47.
    Rosales A, Que FG. Spontaneous hepatic hemorrhage: a single institution's 16-year experience. Am Surg. 2016;82(11):1117–20.Google Scholar
  48. 48.
    Srinivasa S, Lee WG, Aldameh A, Koea JB. Spontaneous hepatic haemorrhage: a review of pathogenesis, aetiology and treatment. HPB (Oxford). 2015;17(10):872–80.Google Scholar
  49. 49.
    van Aalten SM, de Man RA, JN IJ, Terkivatan T. Systematic review of haemorrhage and rupture of hepatocellular adenomas. Br J Surg. 2012;99(7):911–6.Google Scholar
  50. 50.
    Bieze M, Phoa SS, Verheij J, van Lienden KP, van Gulik TM. Risk factors for bleeding in hepatocellular adenoma. Br J Surg. 2014;101(7):847–55.Google Scholar
  51. 51.
    Deneve JL, Pawlik TM, Cunningham S, Clary B, Reddy S, Scoggins CR, et al. Liver cell adenoma: a multicenter analysis of risk factors for rupture and malignancy. Ann Surg Oncol. 2009;16(3):640–8.Google Scholar
  52. 52.
    Shao N, Pandey A, Ghasabeh MA, Khoshpouri P, Pandey P, Varzaneh FN, et al. Long-term follow-up of hepatic adenoma and adenomatosis: analysis of size change on imaging with histopathological correlation. Clin Radiol. 2018.Google Scholar
  53. 53.
    Klompenhouwer AJ, de Man RA, Thomeer MG, Ijzermans JN. Management and outcome of hepatocellular adenoma with massive bleeding at presentation. World J Gastroenterol. 2017;23(25):4579–86.Google Scholar
  54. 54.
    Stoot JH, Coelen RJ, De Jong MC, Dejong CH. Malignant transformation of hepatocellular adenomas into hepatocellular carcinomas: a systematic review including more than 1600 adenoma cases. HPB (Oxford). 2010;12(8):509–22.Google Scholar
  55. 55.
    Farges O, Dokmak S. Malignant transformation of liver adenoma: an analysis of the literature. Dig Surg. 2010;27(1):32–8.Google Scholar
  56. 56.
    Bossen L, Gronbaek H, Lykke Eriksen P, Jepsen P. Men with biopsy-confirmed hepatocellular adenoma have a high risk of progression to hepatocellular carcinoma: a nationwide population-based study. Liver Int. 2017;37(7):1042–6.Google Scholar
  57. 57.
    Sempoux C, Bisig B, Couchy G, Balabaud C, Zucman-Rossi J, Bioulac-Sage P. Malignant transformation of a beta-catenin inflammatory adenoma due to an S45 beta-catenin-activating mutation present 12 years before. Hum Pathol. 2017;62:122–5.Google Scholar
  58. 58.
    Page AJ, Cosgrove DC, Philosophe B, Pawlik TM. Hepatocellular carcinoma: diagnosis, management, and prognosis. Surg Oncol Clin N Am. 2014;23(2):289–311.Google Scholar
  59. 59.
    Blanc JF, Frulio N, Chiche L, Sempoux C, Annet L, Hubert C, et al. Hepatocellular adenoma management: call for shared guidelines and multidisciplinary approach. Clin Res Hepatol Gastroenterol. 2015;39(2):180–7.Google Scholar
  60. 60.
    van Aalten SM, Terkivatan T, de Man RA, van der Windt DJ, Kok NF, Dwarkasing R, et al. Diagnosis and treatment of hepatocellular adenoma in the Netherlands: similarities and differences. Dig Surg. 2010;27(1):61–7.Google Scholar
  61. 61.
    van Aalten SM, Witjes CD, de Man RA, Ijzermans JN, Terkivatan T. Can a decision-making model be justified in the management of hepatocellular adenoma? Liver Int. 2012;32(1):28–37.Google Scholar
  62. 62.
    Sinclair M, Schelleman A, Sandhu D, Angus PW. Regression of hepatocellular adenomas and systemic inflammatory syndrome after cessation of estrogen therapy. Hepatology. 2017;66(3):989–91.Google Scholar
  63. 63.
    Dokmak S, Belghiti J. Will weight loss become a future treatment of hepatocellular adenoma in obese patients? Liver Int. 2015;35(10):2228–32.Google Scholar
  64. 64.
    Khaoudy I, Rebibo L, Regimbeau JM. Is bariatric surgery a potential new treatment for large inflammatory hepatocellular adenomas in obese patients? Surg Obes Relat Dis. 2018;14(4):535–8.Google Scholar
  65. 65.
    Beegle RD, Brown LM, Weinstein DA. Regression of hepatocellular adenomas with strict dietary therapy in patients with glycogen storage disease type I. JIMD Rep. 2015;18:23–32.Google Scholar
  66. 66.
    van der Windt DJ, Kok NF, Hussain SM, Zondervan PE, Alwayn IP, de Man RA, et al. Case-orientated approach to the management of hepatocellular adenoma. Br J Surg. 2006;93(12):1495–502.Google Scholar
  67. 67.
    Yamaguchi T, Kokudo T, Zingg T, Halkic N. The management of hepatocellular adenoma in obese patients: issues to consider. Liver Int. 2016;36(1):152.Google Scholar
  68. 68.
    Wilson CH, Manas DM, French JJ. Laparoscopic liver resection for hepatic adenoma in pregnancy. J Clin Gastroenterol. 2011;45(9):828–33.Google Scholar
  69. 69.
    van Rosmalen BV, Coelen RJS, Bieze M, van Delden OM, Verheij J, Dejong CHC, et al. Systematic review of transarterial embolization for hepatocellular adenomas. Br J Surg. 2017;104(7):823–35.Google Scholar
  70. 70.
    Zhao C, Pei SL, Cucchetti A, Tong TJ, Ma YL, Zhong JH, et al. Systematic review: benefits and harms of transarterial embolisation for treating hepatocellular adenoma. Aliment Pharmacol Ther. 2017.Google Scholar
  71. 71.
    Mironov O, Jaberi A, Beecroft R, Kachura JR. Retrospective single-arm cohort study of patients with hepatocellular adenomas treated with percutaneous thermal ablation. Cardiovasc Intervent Radiol. 2018;41(6):935–41.Google Scholar
  72. 72.
    Scheffer HJ, Melenhorst MC, van Tilborg AA, Nielsen K, van Nieuwkerk KM, de Vries RA, et al. Percutaneous irreversible electroporation of a large centrally located hepatocellular adenoma in a woman with a pregnancy wish. Cardiovasc Intervent Radiol. 2015;38(4):1031–5.Google Scholar
  73. 73.
    Smolock AR, Cristescu MM, Potretzke TA, Ziemlewicz TJ, Lubner MG, Hinshaw JL, et al. Microwave ablation for the treatment of hepatic adenomas. J Vasc Interv Radiol. 2016;27(2):244–9.Google Scholar
  74. 74.
    van Rosmalen BV, Bieze M, Besselink MG, Tanis P, Verheij J, Phoa SS, et al. Long-term outcomes of resection in patients with symptomatic benign liver tumours. HPB (Oxford). 2016;18(11):908–14.Google Scholar
  75. 75.
    Newhook TE, LaPar DJ, Lindberg JM, Bauer TW, Adams RB, Zaydfudim VM. Morbidity and mortality of hepatectomy for benign liver tumors. Am J Surg. 2016;211(1):102–8.Google Scholar
  76. 76.
    Hoffmann K, Unsinn M, Hinz U, Weiss KH, Waldburger N, Longerich T, et al. Outcome after a liver resection of benign lesions. HPB (Oxford). 2015;17(11):994–1000.Google Scholar
  77. 77.
    Hau HM, Kloss A, Wiltberger G, Jahn N, Krenzien F, Benzing C, et al. The challenge of liver resection in benign solid liver tumors in modern times—in which cases should surgery be done? Z Gastroenterol. 2017;55(7):639–52.Google Scholar
  78. 78.
    Laurent A, Dokmak S, Nault JC, Pruvot FR, Fabre JM, Letoublon C, et al. European experience of 573 liver resections for hepatocellular adenoma: a cross-sectional study by the AFC-HCA-2013 study group. HPB (Oxford). 2016;18(9):748–55.Google Scholar
  79. 79.
    Addeo P, Cesaretti M, Fuchshuber P, Langella S, Simone G, Oussoultzoglou E, et al. Outcomes of liver resection for haemorrhagic hepatocellular adenoma. Int J Surg. 2016;27:34–8.Google Scholar
  80. 80.
    Bieze M, Busch OR, Tanis PJ, Verheij J, Phoa SS, Gouma DJ, et al. Outcomes of liver resection in hepatocellular adenoma and focal nodular hyperplasia. HPB (Oxford). 2014;16(2):140–9.Google Scholar
  81. 81.
    Klompenhouwer AJ, Broker MEE, Thomeer MGJ, Gaspersz MP, de Man RA, JNM IJ. Retrospective study on timing of resection of hepatocellular adenoma. Br J Surg. 2017;104(12):1695–703.Google Scholar
  82. 82.
    Landi F, De’ Angelis N, Scatton O, Vidal X, Ayav A, Muscari F, et al. Short-term outcomes of laparoscopic vs. open liver resection for hepatocellular adenoma: a multicenter propensity score adjustment analysis by the AFC-HCA-2013 study group. Surg Endosc. 2017;31(10):4136–44.Google Scholar
  83. 83.
    Sundar Alagusundaramoorthy S, Vilchez V, Zanni A, Sourianarayanane A, Maynard E, Shah M, et al. Role of transplantation in the treatment of benign solid tumors of the liver: a review of the United Network of Organ Sharing data set. JAMA Surg. 2015;150(4):337–42.Google Scholar
  84. 84.
    Chiche L, David A, Adam R, Oliverius MM, Klempnauer J, Vibert E, et al. Liver transplantation for adenomatosis: European experience. Liver Transpl. 2016;22(4):516–26.Google Scholar
  85. 85.
    Thapar M, Grapp O, Fisher C. Management of hepatic adenomatosis. Curr Gastroenterol Rep. 2015;17(3):12.Google Scholar

Copyright information

© The Society for Surgery of the Alimentary Tract 2018

Authors and Affiliations

  • Diamantis I. Tsilimigras
    • 1
  • Amir A. Rahnemai-Azar
    • 2
  • Ioannis Ntanasis-Stathopoulos
    • 3
  • Maria Gavriatopoulou
    • 3
  • Demetrios Moris
    • 4
  • Eleftherios Spartalis
    • 1
  • Jordan M. Cloyd
    • 4
  • Sharon M. Weber
    • 2
  • Timothy M. Pawlik
    • 4
    • 5
    Email author return OK on get
  1. 1.Laboratory of Experimental Surgery and Surgical Research, School of MedicineNational and Kapodistrian University of AthensAthensGreece
  2. 2.Department of Surgery, Division of Surgical OncologyUniversity of Wisconsin HospitalMadisonUSA
  3. 3.Department of Clinical Therapeutics, School of MedicineNational and Kapodistrian University of Athens, Alexandra General HospitalAthensGreece
  4. 4.Department of Surgery, Division of Surgical OncologyThe Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research InstituteColumbusUSA
  5. 5.Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, Oncology, Health Services Management and PolicyThe Ohio State University, Wexner Medical CenterColumbusUSA

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