title: Doxorubicin-eluting bead vs conventional transcatheter arterial chemoembolization for hepatocellular carcinoma before liver transplantation.
abstract: OBJECTIVE
  To assess the possible effect of two different types of preoperative transcatheter arterial chemoembolization (TACE) on recurrence-free survival after liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) and to analyze the effects of TACE on tumor histology.
  
  
  METHODS
  We retrospectively analyzed the histological features of 130 HCC nodules in 63 native livers removed at transplantation. Patients who received any other type of treatment such as radiofrequency tumor ablation, percutaneous ethanol ablation or who were not treated at all were excluded. All patients in the present study were within the Milan Criteria at the last imaging findings before transplantation. Doxorubicin-eluting bead TACE (DEB-TACE) was performed in 22 patients (38 nodules), and conventional TACE (c-TACE) in 16 (25 nodules). Patients' and tumors' characteristics were retrospectively reviewed. We performed a per-nodule analysis of the explanted livers to establish the mean percentage of necrosis of any nodule treated by TACE (conventional or DEB) and a per-patient analysis to establish the percentage of necrosis in the cumulative tumor area, including 21 nodules not reached by TACE. Inflammatory and fibrotic changes in the tissue surrounding the tumor nodule were analyzed and categorized as poor/absent, moderate and enhanced reaction. Uni- and multivariate analysis of risk factors for HCC-recurrence were performed.
  
  
  RESULTS
  The number and diameter of the nodules, the time spent on the waiting list and the number of treatments were similar in the two groups. A trend towards higher appropriate response rates (necrosis ≥ 90%) was observed in the DEB-TACE group (44.7% vs 32.0%, P = 0.2834). The mean percentage of necrosis in the cumulative tumor area was 58.8% ± 36.6% in the DEB-TACE group and 50.2% ± 38.1% in the c-TACE group (P = 0.4856). Fibrotic and inflammatory reactions surrounding the tumor nodule were markedly more common in the DEB-TACE group (P < 0.0001, for both the parameters). The three-year recurrence-free survival was higher in DEB-TACE-treated patients than in conventionally treated patients (87.4% vs 61.5%, P = 0.0493). Other factors affecting recurrence-free survival included viable tumor beyond Milan Criteria on histopathological examination, the percentage of necrosis on CTA ≤ 50% and a pre-transplant serum α-fetoprotein level greater than 70 ng/mL. On multivariate analysis, the lack of treatment with DEB-TACE, high levels of α-fetoprotein and viable tumor beyond Milan Criteria at histology examination were identified as independent predictors of tumor recurrence.
  
  
  CONCLUSIONS
  DEB-TACE can effectively promote tumor necrosis and improves recurrence-free survival after LT in HCC.
authors.affiliation: Daniele Nicolini, Federico Mocchegiani, Andrea Vecchi, Roberto Montalti, Marco Vivarelli, Division of Hepatobiliary and Transplant Surgery, Department of Gastroenterology and Transplantation, Polytechnic University of Marche, 60129 Ancona, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Nicolini
authors.forename: Gianluca
authors.initials: G
authors.lastname: Svegliati-Baroni
authors.forename: Roberto
authors.initials: R
authors.lastname: Candelari
authors.forename: Cinzia
authors.initials: C
authors.lastname: Mincarelli
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mandolesi
authors.forename: Italo
authors.initials: I
authors.lastname: Bearzi
authors.forename: Federico
authors.initials: F
authors.lastname: Mocchegiani
authors.forename: Andrea
authors.initials: A
authors.lastname: Vecchi
authors.forename: Roberto
authors.initials: R
authors.lastname: Montalti
authors.forename: Antonio
authors.initials: A
authors.lastname: Benedetti
authors.forename: Andrea
authors.initials: A
authors.lastname: Risaliti
authors.forename: Marco
authors.initials: M
authors.lastname: Vivarelli
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000401:mortality / Q000628:therapy*; D016461:Chemoembolization, Therapeutic; D004317:Doxorubicin / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008113:Liver Neoplasms / Q000401:mortality / Q000628:therapy*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology; D011300:Preoperative Care; D012189:Retrospective Studies
chemical_list: D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin
keywords: Doxorubicin-eluting bead; Hepatocellular carcinoma; Liver transplantation; Locoregional therapies; Recurrence-free survival; Transcatheter arterial chemoembolization; Tumor histology
references.citation: Am J Transplant. 2010 Apr;10(4 Pt 2):1003-19
references.pmid: 20420649
references.citation: Liver Int. 2011 Sep;31(8):1081-9
references.pmid: 22008644
references.citation: Am J Transplant. 2009 May;9(5):1158-68
references.pmid: 19344435
references.citation: Pathol Res Pract. 2012 Jan 15;208(1):15-21
references.pmid: 22088254
references.citation: Gastroenterology. 2004 Nov;127(5 Suppl 1):S35-50
references.pmid: 15508101
references.citation: Hepatology. 2008 Sep;48(3):819-27
references.pmid: 18688876
references.citation: World J Gastroenterol. 2011 Nov 21;17(43):4741-6
references.pmid: 22147974
references.citation: J Vasc Interv Radiol. 2011 Nov;22(11):1545-52
references.pmid: 21849247
references.citation: Ann Surg. 2004 Feb;239(2):150-9
references.pmid: 14745321
references.citation: Liver Transpl. 2003 Jul;9(7):684-92
references.pmid: 12827553
references.citation: N Engl J Med. 1996 Mar 14;334(11):693-9
references.pmid: 8594428
references.citation: Liver Transpl. 2005 Jul;11(7):767-775
references.pmid: 15973710
references.citation: Radiology. 2010 Apr;255(1):289-300
references.pmid: 20308465
references.citation: Liver Transpl. 2006 Aug;12(8):1260-7
references.pmid: 16826556
references.citation: Clin Cancer Res. 2004 Mar 1;10(5):1789-95
references.pmid: 15014033
references.citation: Liver Transpl. 2007 Feb;13(2):272-9
references.pmid: 17256758
references.citation: J Hepatol. 1998 Dec;29(6):953-9
references.pmid: 9875642
references.citation: Dig Liver Dis. 2010 Jul;42 Suppl 3:S206-14
references.pmid: 20547305
references.citation: Cancer. 1954 May;7(3):462-503
references.pmid: 13160935
references.citation: J Gastrointest Surg. 2002 Mar-Apr;6(2):224-32; discussion 232
references.pmid: 11992808
references.citation: Ann Surg. 1997 Dec;226(6):688-701; discussion 701-3
references.pmid: 9409568
references.citation: J Vasc Interv Radiol. 2006 Aug;17(8):1335-43
references.pmid: 16923981
references.citation: Radiology. 1982 Apr;143(1):29-36
references.pmid: 7063747
references.citation: Eur Radiol. 2010 Jun;20(6):1456-67
references.pmid: 20033179
references.citation: Cancer. 2009 Feb 1;115(3):616-23
references.pmid: 19117042
references.citation: Hepatology. 2011 May;53(5):1580-9
references.pmid: 21351114
references.citation: Cardiovasc Intervent Radiol. 2010 Jun;33(3):541-51
references.pmid: 19937027
references.citation: Clin Transplant. 2004 Jun;18(3):227-34
references.pmid: 15142041
references.citation: Liver Transpl. 2003 Jun;9(6):557-63
references.pmid: 12783395
references.citation: Ann Surg. 2002 Apr;235(4):533-9
references.pmid: 11923610
references.citation: J Hepatol. 2007 Mar;46(3):474-81
references.pmid: 17239480
references.citation: J Natl Cancer Inst. 2008 May 21;100(10):698-711
references.pmid: 18477802
references.citation: J Surg Oncol. 2010 May 1;101(6):476-80
references.pmid: 20213741
references.citation: Cardiovasc Intervent Radiol. 2010 Feb;33(1):41-52
references.pmid: 19908093
references.citation: Transplantation. 2005 Feb 27;79(4):483-7
references.pmid: 15729176
references.citation: Semin Oncol. 1997 Apr;24(2 Suppl 6):S6-38-S6-45
references.pmid: 9151915
references.citation: J Vasc Interv Radiol. 2010 Mar;21(3):327-32
references.pmid: 20097098
references.citation: J Hepatol. 2001 Sep;35(3):421-30
references.pmid: 11592607
references.citation: Ann Surg. 2008 Oct;248(4):617-25
references.pmid: 18936575
references.citation: Dig Surg. 2004;21(2):152-9; discussion 159-60
references.pmid: 15166485