Pathologic response to non-surgical locoregional therapies as potential selection criteria for liver transplantation for hepatocellular carcinoma.

BACKGROUND Preoperative locoregional treatments (PLT) are performed to avoid progression before liver transplantation for hepatocellular carcinoma (HCC). The objective of this study was to analyze the prognostic factors affecting the outcome in patients who received PLT. MATERIAL AND METHODS A retrospective analysis of patients who underwent liver transplantation (LT) was performed. All patients who underwent PLT with confirmed pathological diagnosis of HCC were included. The rate of tumor necrosis (TN) was assessed by microscopic histological examination. RESULTS From January 1997 to December 2010, PLT was performed in 154 patients ROC analysis individuated a TN cut-off value at 40%. Ninety-one patients (59.1%) of the patients presented TN>40%. At multivariate analysis, TN<40% (HR=1.76; p=0.04) and vascular invasion (VI) (HR=2.16; p<0.01) were associated with lower Overall Survival (OS). At multivariate analysis, TN<40% (HR=1.59; p=0.001) and VI (HR=2.51; p=0.001) were significant associated with lower Disease Free Survival (DFS). One, 3 and 5 years OS was 87.9%, 82.0% and 69.1% for patients with TN>40% and 82.5%, 64.2% and 53.2% for those with TN<40% (p=0.02). Tumour size <5 cm (p=0.02); age <55 years (p=0.02); absence of VI (p=0.02) and multiple procedures (p=0.04) were predictive factors for TN>40%. CONCLUSIONS Response to preoperative locoregional treatment can be used as potential selection criteria for LT.

[1]  M. Carpenzano,et al.  Efficacy of selective transarterial chemoembolization in inducing tumor necrosis in small (<5 cm) hepatocellular carcinomas , 2011, Hepatology.

[2]  V. Mazzaferro,et al.  Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. , 1996, The New England journal of medicine.

[3]  G. Otto,et al.  Response to transarterial chemoembolization as a biological selection criterion for liver transplantation in hepatocellular carcinoma , 2006, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[4]  P. Waldenberger,et al.  Chemoembolization followed by liver transplantation for hepatocellular carcinoma impedes tumor progression while on the waiting list and leads to excellent outcome , 2003, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[5]  Wei-Chen Lee,et al.  Significance of Tumor Necrosis for Outcome of Patients with Hepatocellular Carcinoma Receiving Locoregional Therapy Prior to Liver Transplantation , 2011, Annals of Surgical Oncology.

[6]  T. Pfammatter,et al.  Transarterial Chemoembolization as a Bridge to Liver Transplantation for Hepatocellular Carcinoma: An Evidence‐Based Analysis , 2006, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[7]  Myeong-Jin Kim Current limitations and potential breakthroughs for the early diagnosis of hepatocellular carcinoma. , 2011, Gut and liver.

[8]  L. Ellis,et al.  Pathologic response to preoperative chemotherapy: a new outcome end point after resection of hepatic colorectal metastases. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[9]  O. Ciccarelli,et al.  Liver transplantation for hepatocellular cancer: UCL experience in 137 adult cirrhotic patients. Alpha‐foetoprotein level and locoregional treatment as refined selection criteria , 2012, Transplant international : official journal of the European Society for Organ Transplantation.

[10]  Y. Maehara,et al.  Prognostic Significance of Preoperative Imaging in Recipients of Living Donor Liver Transplantation for Hepatocellular Carcinoma , 2011, Transplantation.

[11]  V. Vilgrain Advancement in HCC imaging: diagnosis, staging and treatment efficacy assessments , 2010, Journal of hepato-biliary-pancreatic sciences.

[12]  F. Gheza,et al.  Number and Tumor Size Are Not Sufficient Criteria to Select Patients for Liver Transplantation for Hepatocellular Carcinoma , 2012, Annals of Surgical Oncology.

[13]  P. Berloco,et al.  Predictive factors of recurrence of hepatocellular carcinoma after liver transplantation: a multivariate analysis. , 2009, Transplantation proceedings.

[14]  F. Roudot-thoraval,et al.  Impact of pretransplantation transarterial chemoembolization on survival and recurrence after liver transplantation for hepatocellular carcinoma , 2005, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[15]  L. Wong,et al.  Pre‐transplant treatment of hepatocellular carcinoma: assessment of tumor necrosis in explanted livers , 2004, Clinical transplantation.

[16]  L. Mariani,et al.  Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. , 2009, The Lancet. Oncology.

[17]  H. Edmondson,et al.  Primary carcinoma of the liver. A study of 100 cases among 48,900 necropsies , 1954, Cancer.

[18]  Charles M. Miller,et al.  Long-Term Results With Multimodal Adjuvant Therapy and Liver Transplantation for the Treatment of Hepatocellular Carcinomas Larger Than 5 Centimeters , 2002, Annals of surgery.

[19]  T. Piardi,et al.  Liver Transplantation Exceeding UCSF Criteria: Case Report of a Late Recurrence Treated by Surgery and Review of the Literature , 2009, European Surgical Research.

[20]  E. Hatano,et al.  Results of hepatic resection for hepatocellular carcinoma invading major portal and/or hepatic veins. , 2003, Surgical oncology clinics of North America.

[21]  P Neuhaus,et al.  Vascular invasion and histopathologic grading determine outcome after liver transplantation for hepatocellular carcinoma in cirrhosis , 2001, Hepatology.

[22]  G. Grazi,et al.  Surgical treatment of hepatocellular carcinoma on cirrhosis: a Western experience. , 1998, Hepato-gastroenterology.

[23]  Y. Tajima,et al.  Actual therapeutic efficacy of pre-transplant treatment on hepatocellular carcinoma and its impact on survival after salvage living donor liver transplantation , 2009, Journal of Gastroenterology.

[24]  A. Venook,et al.  Liver transplantation for hepatocellular carcinoma: Expansion of the tumor size limits does not adversely impact survival , 2001, Hepatology.

[25]  Chih-Yung Yu,et al.  Locoregional Therapy-Induced Tumor Necrosis as a Predictor of Recurrence after Liver Transplant in Patients with Hepatocellular Carcinoma , 2011, Annals of Surgical Oncology.

[26]  Ryutaro Hirose,et al.  Excellent outcome following down‐staging of hepatocellular carcinoma prior to liver transplantation: An intention‐to‐treat analysis , 2008, Hepatology.

[27]  W. Chapman,et al.  Pre-liver transplantation locoregional adjuvant therapy for hepatocellular carcinoma as a strategy to improve longterm survival. , 2006, Journal of the American College of Surgeons.

[28]  Carmine Tinelli,et al.  Predictors of Long-Term Survival After Liver Transplantation for Hepatocellular Carcinoma , 2005, The American Journal of Gastroenterology.

[29]  L. Forzenigo,et al.  The diagnostic and economic impact of contrast imaging techniques in the diagnosis of small hepatocellular carcinoma in cirrhosis , 2009, Gut.

[30]  T. Kawai,et al.  Donor difficulties in Japan and Asian countries. , 1995, Transplantation Proceedings.

[31]  M Galanski,et al.  Arterial chemoembolization before liver transplantation in patients with hepatocellular carcinoma: marked tumor necrosis, but no survival benefit? , 1998, Journal of hepatology.

[32]  L Pagliaro,et al.  Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. , 2001, Journal of hepatology.

[33]  J. Belghiti,et al.  Intrahepatic Recurrence After Resection of Hepatocellular Carcinoma Complicating Cirrhosis , 1991, Annals of surgery.

[34]  T. Davern,et al.  A prospective study on downstaging of hepatocellular carcinoma prior to liver transplantation , 2005, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[35]  D. Jaeck,et al.  Four hundred and twenty‐three consecutive adults piggy‐back liver transplantations with the three suprahepatic veins: Was the portal systemic shunt required? , 2010, Journal of gastroenterology and hepatology.

[36]  G Malandain,et al.  An automatic virtual patient reconstruction from CT-scans for hepatic surgical planning. , 2000, Studies in health technology and informatics.

[37]  E. Furth,et al.  Lack of benefit of pre‐transplant locoregional hepatic therapy for hepatocellular cancer in the current MELD era , 2006, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.