Abstract
Background
In perioperative management of hepatic resection for hepatocellular carcinoma, excessive blood loss and blood transfusion greatly influence postoperative complications and prognosis of the patients. We evaluated the influence of blood products use on postoperative recurrence and prognosis of patients with hepatocellular carcinoma.
Methods
The subjects were 66 patients who underwent elective hepatic resection for hepatocellular carcinoma without concomitant microwave or radiofrequency ablation therapy nor other malignancies between January 2001 and June 2006. We retrospectively investigated the influence of the use of blood products including red cell concentration and fresh frozen plasma on recurrence of hepatocellular carcinoma and overall survival.
Results
In multivariate analysis, the dose of blood products transfusion was a significant predictor of disease-free and overall survival. Both disease-free and overall survival rates of those who were given blood products were significantly worse than those who did not receive. On the other hand, in univariate analysis of disease-free and overall survival after hepatic resection and clinical variables, the amount of blood loss was not a significant predictor of recurrence or death.
Conclusion
Transfusion of blood products is associated with increased recurrence rate and worse survival after elective hepatic resection for patients with hepatocellular carcinoma.
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References
Sugioka A, Tsuzuki T, Kanai T. Postresection prognosis of patients with hepatocellular carcinoma. Surgery 1993;113:612–618.
Yamanaka N, Okamoto E, Toyosaka A, Mitunobu M, Fujihara S, Kato T, Fujimoto J, Oriyama T, Furukawa K, Kawamura E. Prognostic factors after hepatectomy for hepatocellular carcinomas. Cancer 1990;65:1104–1110.
Poon RT, Fan ST, Lo CM, Ng IO, Liu CL, Lam CM, Wong J. Improving survival results after resection of hepatocellular carcinoma: a prospective study of 377 patients over 10 years. Ann Surg 2001;234:63–70.
Bismuth H, Chiche L, Castaing D. Surgical treatment of hepatocellular carcinomas in noncirrhotic liver: experience with 68 liver resections. World J Surg 1995;19:35–41.
Fong Y, Sun RL, Jarnagin W, Blumgart LH. An analysis of 412 cases of hepatocellular carcinoma at a Western center. Ann Surg 1999;229:790–800.
Chen MF, Hwang TL, Jeng LB, Jan YY, Wang CS, Chou FF. Hepatic resection in 120 patients with hepatocellular carcinoma. Arch Surg 1989;124:1025–1028.
Nagao T, Inoue S, Yoshimi F, Sodeyama M, Omori Y, Mizuta T, Kawano N, Morioka Y. Postoperative recurrence of hepatocellilar carcinoma. Ann Surg 1990;211:28–33.
Nagasue N, Uchida M, Makino Y, Takemoto Y, Yamanoi A, Hayashi T, Chang YC, Kohno H, Nakamura T, Yukaya H. Incidence and factors associated with intrahepatic recurrence following resection of hepatocellular carcinoma. Gastroenterology 1993;105:488–494.
Belghiti J, Panis Y, Farges O, Benhamou JP, Fekete F. Intrahepatic recurrence after resection of hepatocellular carcinoma complicating cirrhosis. Ann Surg 1991;214:114–117.
Yanaga K, Okudaira S, Kanematsu T, Marsh JW. Hepatic Resection for Hepatocellular Carcinoma. In Carr B, ed. Hepatocellular Cancer: Diagnosis and Treatment. Totowa: Humana Press, 2005, pp 185–198.
Brunson ME, Alexander JW. Mechanisms of transfusion-induced immunosuppression. Transfusion 1990;30:651–658.
Blajchman MA, Bordin JO. Mechanisms of transfusion-associated immunosuppression. Curr Opin Hematol 1994;1:457–461.
Blajchman MA. Immunomodulation and blood transfusion. Am J Ther 2002;9:389–395.
Magee CC, Sayegh MH. Peptide-mediated immunosuppression. Curr Opin Immunol 1997;9:669–675.
Krensky AM, Clayberger C. Structure of HLA molecules and immunosuppressive effects of HLA derived peptides. Int Rev Immunol 1996;13:173–185.
Yamamoto J, Kosuge T, Takayama T, Shimada K, Yamasaki S, Ozaki H, Yamaguchi N, Mizuno S, Makuuchi M. Perioperative blood transfusion promotes recurrence of hepatocellular carcinoma after hepatectomy. Surgery 1994;115:303–309.
Yanaga K, Kanematsu T, Takenaka K, Matsumata T, Yoshida Y, Sugimachi K. Hepatic resection for hepatocellular carcinoma in elderly patients. Am J Surg 1988;155:238–241.
Nagao T, Inoue S, Goto S, Mizuta T, Omori Y, Kawano N, Morioka Y. Hepatic resection for hepatocellular carcinoma: clinical features and long-term prognosis. Ann Surg 1987;205:22–40.
Asahara T, Katayama K, Itamoto T, Yano M, Hino H, Okamoto Y, Nakahara H, Dohi K, Moriwaki K, Yuge O. Perioperative blood transfusion as a prognostic indicator in patients with hepatocellular carcinoma. World J Surg 1999;23:676–680.
Tralhao JG, Kayal S, Dagher I, Sanhueza M, Vons C, Franco D. Resection of hepatocellular carcinoma: the effect of surgical margin and blood transfusion on long-term survival. Analysis of 209 consecutive patients. Hepatogastroenterology 2007;54:1200–1206.
Sugita S, Sasaki A, Iwaki K, Uchida H, Kai S, Shibata K, Ohta M, Kitano S. Prognosis and postoperative lymphocyte count in patients with hepatocellular carcinoma who received intra-operative allogenic blood transfusion: a retrospective study. Eur J Surg Oncol 2008;34:339–345.
Foster RS, Costanza MC, Foster JC, Wanner MC, Foster CB. Adverse relationship between blood transfusions and survival after colectomy for colon cancer. Cancer 1985;55:1195–1201.
Younes RN, Rogatko A, Brennan MF. The influence of intra-operative hypotension and perioperative blood transfusion on disease-free survival in patients with complete resection of colorectal liver metastases. Ann Surg 1991;214:107–113.
Tartter PI. The association of perioperative blood transfusion with colorectal cancer recurrence. Ann Surg 1992;216:633–638.
Parrott NR, Lennard TW, Taylor RM, Proud G, Shenton BK, Johnston ID. Effect of perioperative blood transfusion on recurrence of colorectal cancer. Br J Surg 1986;73:970–973.
Blumberg N, Agarwal MM, Chuang C. Relation between recurrence of cancer of the colon and blood transfusion. Br Med J 1985;290:1037–1039.
Stephenson KR, Steinberg SM, Hughes KS, Vetto JT, Sugarbaker PH, Chang AE. Perioperative blood transfusions are associated with decreased time to recurrence and decreased survival after resection of colorectal liver metastases. Ann Surg 1988;208:679–687.
Little AG, Wu HS, Ferguson MK, Ho CH, Bowers VD, Segalin A, Staszek VM. Perioperative blood transfusion adversely affects prognosis of patients with stage I non-small-cell lung cancer. Am J Surg 1990;160:630–632.
Tartter PI, Burrows L, Kirschner P. Perioperative blood transfusion adversely affects prognosis after resection of Stage I (subset N0) non-oat cell lung cancer. J Thorac Cardiovasc Surg 1984;88:659–662.
Hyman NH, Foster RS, DeMeules JE, Costanza MC. Blood transfusions and survival after lung cancer resection. Am J Surg 1985;149:502–507.
Moores DW, Piantadosi S, McKneally MF. Effect of perioperative blood transfusion on outcome in patients with surgically resected lung cancer. Ann Thorac Surg 1989;47:346–351.
Crowe JP, Gordon NH, Fry DE, Shuck JM, Hubay CA. Breast cancer survival and perioperative blood transfusion. Surgery 1989;106:836–841.
Nowak MM, Ponsky JL. Blood transfusion and disease-free survival in carcinoma of the breast. J Surg Oncol. 1984;27:124–130.
Kaneda M, Horimi T, Ninomiya M, Nagae M, Mukai K, Takeda I, Shimoyama H, Chohno S, Okabayashi T, Kagawa S. Adverse affect of blood transfusions on survival of patients with gastric cancer. Transfusion 1987;27:375–377.
Fong Y, Karpeh M, Mayer K, Brennan MF. Association of perioperative transfusions with poor outcome in resection of gastric adenocarcinoma. Am J Surg 1994;167:256–260.
Shiba H, Ishii Y, Ishida Y, Wakiyama S, Sakamoto T, Ito R, Gocho T, Uwagawa T, Hirohara S, Kita Y, Misawa T, Yanaga K. Assessment of blood products use as predictors of pulmonary complications and surgical site infection after hepatectomy for hepatocellular carcinoma. J Hepatobiliary Pancreat Surg 2009;16:69–74.
Vamvakas EC, Carven JH. Exposure to allogeneic plasma and risk of postoperative pneumonia and/or infection in coronary artery bypass graft surgery. Transfusion 2002;42:107–113.
Matsumata T, Ikeda Y, Hayashi H, Kamakura T, Taketomi A, Sugimachi K. The association between transfusion and cancer-free survival after curative resection for hepatocellular carcinoma. Cancer 1993;72:1866–1871.
Kwon AH, Matsui Y, Kamiyama Y. Perioperative blood transfusion in hepatocellular carcinomas: influence of immunologic profile and recurrence free survival. Cancer 2001;91:771–778.
Yamamoto J, Kosuge T, Saiura A, Sakamoto Y, Shimada K, Sano T, Takayama T, Sugawara Y, Yamaguchi T, Kokudo N, Makuuchi M. Effectiveness of hepatic resection for early-stage hepatocellular carcinoma in cirrhotic patients: subgroup analysis according to Milan criteria. Jpn J Clin Oncol 2007;37:287–295.
Zhou L, Rui JA, Wang SB, Chen SG, Qu Q, Chi TY, Wei X, Han K, Zhang N, Zhao HT. Outcomes and prognostic factors of cirrhotic patients with hepatocellular carcinoma after radical major hepatectomy. World J Surg 2007;31:1782–1787.
Miyagawa S, Makuuchi M, Kawasaki S, Kakazu T. Criteria for safe hepatic resection. Am J Surg 1995;169:589–594.
Bureau of Medicinal Safety, Ministry of Health and Welfare. Guidelines for administering blood preparations. Medical and Pharmaceutical Notification No. 715, June 10, 1999
Ueno S, Tanabe G, Nuruki K, Hamanoue M, Komorizono Y, Oketani M, Hokotate H, Inoue H, Baba Y, Imamura Y, Aikou T. Prognostic performance of the new classification of primary liver cancer of Japan (4th edition) for patients with hepatocellular carcinoma: a validation analysis. Hepatol Res 2002;24:395–403.
Weiden PL, Bean MA, Schultz P. Perioperative blood transfusion does not increase the risk of colorectal cancer recurrence. Cancer 1987;60:870–874.
Keller SM, Groshen S, Martini N, Kaiser LR. Blood transfusion and lung cancer recurrence. Cancer 1988;62:606–610.
Foster RS, Foster JC, Costanza MC. Blood transfusions and survival after surgery for breast cancer. Arch Surg 1984;119:1138–1140.
Voogt PJ, van de Velde CJ, Brand A, Hermans J, Stijnen T, Bloem R, Leer JW, Zwaveling A, van Rood JJ. Perioperative blood transfusion and cancer prognosis: different effects of blood transfusion on prognosis of colon and breast cancer patients. Cancer 1987;59:836–843.
Eickhoff JH, Andersen J, Laybourn C. Perioperative blood transfusion does not promote recurrence and death after mastectomy for breast cancer. The Danish Breast Cancer Cooperative Group. Br J Surg 1991;78:1358–1361.
van de Watering LM, Brand A, Houbiers JG, Klein Kranenbarg WM, Hermans J, van de Velde C. Cancer Recurrence and Blood Transfusion Study Group. Perioperative blood transfusions, with or without allogeneic leucocytes, relate to survival, not to cancer recurrence. Br J Surg 2001;88:267–272.
Fan ST, Ng IO, Poon RT, Lo CM, Liu CL, Wong J. Hepatectomy for hepatocellular carcinoma: the surgeon's role in long-term survival. Arch Surg 1999;134:1124–1130.
de Boer MT, Molenaar IQ, Porte RJ. Impact of blood loss on outcome after liver resection. Dig Surg 2007;24:259–264.
Fujimoto J, Okamoto E, Yamanaka N, Tanaka T, Tanaka W. Adverse effect of perioperative blood transfusions on survival after hepatic resection for hepatocellular carcinoma. Hepatogastroenterology 1997;44:1390–1396.
Hsu HC, Wu TT, Wu MZ, Wu CY, Chiou TJ, Sheu JC, Lee CS, Chen DS. Evolution of expression of hepatitis B surface and core antigens (HBsAg, HBcAg) in resected primary and recurrent hepatocellular carcinoma in HBsAg carriers in Taiwan: correlation with local host immune response. Cancer 1988;62:915–921.
Yamasaki H, Okamoto E, Komatsu T, Manabe Y, Shinka S. Relationship between general or specific immunoreactivity and prognosis in postoperative patients with hepatocellular carcinoma. Cancer Immunol Immunother 1990;31:107–114.
Ayers RC, Robertson DA, Dewbury KC, Millward-Sadler GH, Smith CL. Spontaneous regression of hepatocellular carcinoma. Gut 1990;31:722–724.
Suzuki M, Okazaki N, Yoshino M, Yoshida T. Spontaneous regression of a hepatocellular carcinoma: a case report. Hepatogastroenterology 1989;36:160–163.
Sato Y, Fujiwara K, Nakagawa S, Kanishima S, Ohta Y, Oka Y, Hayashi S, Oka H. A case of spontaneous regression of hepatocellular carcinoma with bone metastasis. Cancer 1985;56:667–671.
Ohta H, Sakamoto Y, Ojima H, Yamada Y, Hibi T, Takahashi Y, Sano T, Shimada K, Kosuge T. Spontaneous regression of hepatocellular carcinoma with complete necrosis: case report. Abdom Imaging 2005;30:734–737.
Ashkenazi A, Dixit VM. Death receptors: signaling and modulation. Science 1998;281:1305–1308.
Pitti RM, Marsters SA, Lawrence DA, Roy M, Kischkel FC, Dowd P, Huang A, Donahue CJ, Sherwood SW, Baldwin DT, Godowski PJ, Wood WI, Gurney AL, Hillan KJ, Cohen RL, Goddard AD, Botstein D, Ashkenazi A. Genomic amplification of a decoy receptor for Fas ligand in lung and colon cancer. Nature 1998;396:699–703.
Ghio M, Contini P, Mazzei C, Brenci S, Barberis G, Filaci G, Indiveri F, Puppo F. Soluble HLA class I, HLA class II, and Fas ligand in blood components: a possible key to explain the immnomodulatory effects of allogeneic blood transfusions. Blood 1999;93:1770–1777.
Puppo F, Contini P, Ghio M, Brenci S, Scudeletti M, Filaci G, Ferrone S, Indiveri F. Soluble human MHC class I molecules induce soluble Fas ligand secretion and trigger apoptosis in activated CD8(+) Fas (CD95)(+) T lymphocytes. Int Immunol 2000;12:195–203.
Puppo F, Ghio M, Contini P, Mazzei C, Indiveri F. Fas, Fas ligand, and transfusion immunomodulation. Transfusion 2001;41:416–418.
Minagawa M, Makuuchi M, Takayama T, Kokudo N. Selection criteria for repeated hepatectomy in patients with recurrent hepatocellular carcinoma. Ann Surg 2003;238:703–710.
Torzilli G, Makuuchi M, Inoue K, Takayama T, Sakamoto Y, Sugawara Y, Kubota K, Zucchi A. 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;134:984–992.
Fan ST, Lo CM, Liu CL, Lam CM, Yuen WK, Yeung C, Wong J. Hepatectomy for hepatocellular carcinoma: toward zero hospital deaths. Ann Surg 1999;229:322–330.
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Shiba, H., Ishida, Y., Wakiyama, S. et al. Negative Impact of Blood Transfusion on Recurrence and Prognosis of Hepatocellular Carcinoma After Hepatic Resection. J Gastrointest Surg 13, 1636–1642 (2009). https://doi.org/10.1007/s11605-009-0963-y
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DOI: https://doi.org/10.1007/s11605-009-0963-y