Presurgical Transarterial Chemoembolization Does Not Increase Biliary Stricture Incidence in Orthotopic Liver Transplant Patients L. Casadabana, M. Malespinb, A. Cheungc, R.A. McGuffeyb, B.R. Boulayb, A.G. Hallineb, R.D. Brownb, S.J. Cotlerc, H. Jeond, J.T. Buia, and R.C. Gabaa,* a
Division of Interventional Radiology, Department of Radiology, University of Illinois Hospital and Health Sciences System, Chicago, Illinois; bDivision of Digestive Diseases and Nutrition, Department of Medicine, University of Illinois Hospital and Health Sciences System, Chicago, Illinois; cDepartment of Medicine, Section of Hepatology, Loyola University Medical Center, Section of Hepatology, Maywood, Illinois; and dDivision of Transplant Surgery, Department of Surgery, University of Illinois Hospital and Health Sciences System, Chicago, Illinois
ABSTRACT Introduction. The goal of this study was to compare the incidence of biliary strictures in orthotopic liver transplant (OLT) patients treated with previous transarterial chemoembolization (TACE) versus those with no TACE history. Patients and Methods. A single-center retrospective review was performed on 248 patients who underwent OLT from 2006 to 2012. Patient demographic characteristics, history of TACE for treatment of hepatocellular carcinoma, OLT data, and biliary stricture data were obtained. TACE was generally performed in a segmental manner using chemotherapy to ethiodized oil mixture (1:1). Clinically significant biliary strictures resulting in cholestasis or obstructive jaundice were diagnosed by using endoscopic retrograde cholangiopancreatography. Group characteristics were compared by using the Wilcoxon rank sum test, c2 analysis, and Kaplan-Meier statistics with log-rank comparison. Results. Forty-six patients (35 men, 11 women; median age, 58 years) with a history of pre-OLT TACE were compared with 185 patients (111 men, 74 women; median age, 54 years) with no history of TACE. TACE and non-TACE patients had 30% and 31% cumulative incidence of biliary stricture, respectively. The median time to stricture was not reached in either group. There was no statistically significant difference in biliary stricture incidence (P ¼ .928) or time to biliary stricture development (P ¼ .803). Biliary strictures were primarily anastomotic in location in both groups: 79% in TACE patients and 84% in non-TACE patients (P ¼ .233). Conclusions. Selective TACE treatment of hepatocellular carcinoma in pretransplant patients does not increase the rate of posttransplant biliary strictures. These findings corroborate the safety of TACE in the treatment of hepatocellular carcinoma in potential OLT patients as a bridge to transplantation.
B
ILIARY strictures represent a common occurrence after orthotopic liver transplantation (OLT) [1]. Despite advances in surgical and endoscopic techniques, biliary strictures tend to recur [2] and cause significant morbidity, in some cases requiring surgical revision [3] or retransplantation [4]. Patients with liver cirrhosis awaiting OLT are at risk for development of hepatocellular carcinoma (HCC), and transarterial chemoembolization (TACE) is a safe and minimally invasive method for the
treatment of HCC. TACE not only confers survival benefit [5,6] but can also serve as an effective bridge to liver transplantation [7]. However, in targeting the hepatic
*Address correspondence to Ron C. Gaba, MD, Department of Radiology, Section of Interventional Radiology, University of Illinois Hospital and Health Sciences System, 1740 West Taylor Street, MC 931, Chicago, IL 60612. E-mail: [email protected]
ª 2014 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/14/$esee front matter http://dx.doi.org/10.1016/j.transproceed.2014.03.012
Transplantation Proceedings, 46, 1413e1419 (2014)
1413
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arterial system, TACE may result in biliary devascularization [8e10] and theoretically increase the risk for posttransplant stricture formation. The present study was performed to evaluate the risk of TACE-related posttransplant biliary stricture by comparing the incidence of biliary strictures in OLT patients treated with TACE versus those with no TACE history. PATIENTS AND METHODS This study was in compliance with the Health Insurance Portability and Accountability Act, and the institutional review board at our hospital granted approval with waiver of consent for inclusion in the study. All patients provided written informed consent for procedures.
Clinical Setting, Study Design, and Patient Cohort In this retrospective study, 248 adult patients who underwent primary OLT between January 2006 and December 2012 at a single tertiary care, academic university-affiliated hospital in a large metropolitan area were identified for potential investigation. Inclusion criteria included deceased or living-donor OLT and at least 30 days of posttransplant survival. Patients who did not achieve at least 30-day survival after OLT (n ¼ 14 [6%]) or who underwent repeat liver transplantation within 30 days (n ¼ 3 [1%]) were excluded from analysis (1 patient who died on the day of his second OLT, which occurred within 30 days of initial transplant, is represented in both exclusion groups). Ten patients underwent 2 liver transplantations; in cases of repeat liver transplantation beyond 30 days (n ¼ 7), only the first liver transplant was included in the analysis. A total of 232 patients were thus included in the final study cohort, of whom 46 (20%) had undergone underwent TACE before liver transplantation, and 186 (80%) who had not. Chart review was performed to identify patient demographic parameters as well as liver disease and tumor information. Model for End-Stage Liver Disease (MELD) scores were recorded at time of transplant, with use of exception points in patients with HCC. For HCC patients, tumor diagnosis was established by using results of percutaneous biopsy or noninvasively based on the presence of a hepatic mass >2 cm in diameter with characteristic cross-sectional imaging findings in the setting of liver cirrhosis and tumor marker elevation (alpha-fetoprotein, 400 ng/dL) [11,12]. Surgical unresectability was determined by consensus at a multidisciplinary tumor board meeting. Inclusion criteria for TACE included HCC with therapeutic intent as a bridge or downstage to OLT, ability to undergo angiography and selective visceral catheterization, ability to lay supine postprocedure, and ability to provide informed consent. Relative contraindications to TACE therapy included total bilirubin level >3.0 mg/dL, serum creatinine level >2.0 mg/dL, international normalized ratio >1.5, platelet count
Division of Interventional Radiology, Department of Radiology, University of Illinois Hospital and Health Sciences System, Chicago, Illinois; bDivision of Digestive Diseases and Nutrition, Department of Medicine, University of Illinois Hospital and Health Sciences System, Chicago, Illinois; cDepartment of Medicine, Section of Hepatology, Loyola University Medical Center, Section of Hepatology, Maywood, Illinois; and dDivision of Transplant Surgery, Department of Surgery, University of Illinois Hospital and Health Sciences System, Chicago, Illinois
ABSTRACT Introduction. The goal of this study was to compare the incidence of biliary strictures in orthotopic liver transplant (OLT) patients treated with previous transarterial chemoembolization (TACE) versus those with no TACE history. Patients and Methods. A single-center retrospective review was performed on 248 patients who underwent OLT from 2006 to 2012. Patient demographic characteristics, history of TACE for treatment of hepatocellular carcinoma, OLT data, and biliary stricture data were obtained. TACE was generally performed in a segmental manner using chemotherapy to ethiodized oil mixture (1:1). Clinically significant biliary strictures resulting in cholestasis or obstructive jaundice were diagnosed by using endoscopic retrograde cholangiopancreatography. Group characteristics were compared by using the Wilcoxon rank sum test, c2 analysis, and Kaplan-Meier statistics with log-rank comparison. Results. Forty-six patients (35 men, 11 women; median age, 58 years) with a history of pre-OLT TACE were compared with 185 patients (111 men, 74 women; median age, 54 years) with no history of TACE. TACE and non-TACE patients had 30% and 31% cumulative incidence of biliary stricture, respectively. The median time to stricture was not reached in either group. There was no statistically significant difference in biliary stricture incidence (P ¼ .928) or time to biliary stricture development (P ¼ .803). Biliary strictures were primarily anastomotic in location in both groups: 79% in TACE patients and 84% in non-TACE patients (P ¼ .233). Conclusions. Selective TACE treatment of hepatocellular carcinoma in pretransplant patients does not increase the rate of posttransplant biliary strictures. These findings corroborate the safety of TACE in the treatment of hepatocellular carcinoma in potential OLT patients as a bridge to transplantation.
B
ILIARY strictures represent a common occurrence after orthotopic liver transplantation (OLT) [1]. Despite advances in surgical and endoscopic techniques, biliary strictures tend to recur [2] and cause significant morbidity, in some cases requiring surgical revision [3] or retransplantation [4]. Patients with liver cirrhosis awaiting OLT are at risk for development of hepatocellular carcinoma (HCC), and transarterial chemoembolization (TACE) is a safe and minimally invasive method for the
treatment of HCC. TACE not only confers survival benefit [5,6] but can also serve as an effective bridge to liver transplantation [7]. However, in targeting the hepatic
*Address correspondence to Ron C. Gaba, MD, Department of Radiology, Section of Interventional Radiology, University of Illinois Hospital and Health Sciences System, 1740 West Taylor Street, MC 931, Chicago, IL 60612. E-mail: [email protected]
ª 2014 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/14/$esee front matter http://dx.doi.org/10.1016/j.transproceed.2014.03.012
Transplantation Proceedings, 46, 1413e1419 (2014)
1413
1414
arterial system, TACE may result in biliary devascularization [8e10] and theoretically increase the risk for posttransplant stricture formation. The present study was performed to evaluate the risk of TACE-related posttransplant biliary stricture by comparing the incidence of biliary strictures in OLT patients treated with TACE versus those with no TACE history. PATIENTS AND METHODS This study was in compliance with the Health Insurance Portability and Accountability Act, and the institutional review board at our hospital granted approval with waiver of consent for inclusion in the study. All patients provided written informed consent for procedures.
Clinical Setting, Study Design, and Patient Cohort In this retrospective study, 248 adult patients who underwent primary OLT between January 2006 and December 2012 at a single tertiary care, academic university-affiliated hospital in a large metropolitan area were identified for potential investigation. Inclusion criteria included deceased or living-donor OLT and at least 30 days of posttransplant survival. Patients who did not achieve at least 30-day survival after OLT (n ¼ 14 [6%]) or who underwent repeat liver transplantation within 30 days (n ¼ 3 [1%]) were excluded from analysis (1 patient who died on the day of his second OLT, which occurred within 30 days of initial transplant, is represented in both exclusion groups). Ten patients underwent 2 liver transplantations; in cases of repeat liver transplantation beyond 30 days (n ¼ 7), only the first liver transplant was included in the analysis. A total of 232 patients were thus included in the final study cohort, of whom 46 (20%) had undergone underwent TACE before liver transplantation, and 186 (80%) who had not. Chart review was performed to identify patient demographic parameters as well as liver disease and tumor information. Model for End-Stage Liver Disease (MELD) scores were recorded at time of transplant, with use of exception points in patients with HCC. For HCC patients, tumor diagnosis was established by using results of percutaneous biopsy or noninvasively based on the presence of a hepatic mass >2 cm in diameter with characteristic cross-sectional imaging findings in the setting of liver cirrhosis and tumor marker elevation (alpha-fetoprotein, 400 ng/dL) [11,12]. Surgical unresectability was determined by consensus at a multidisciplinary tumor board meeting. Inclusion criteria for TACE included HCC with therapeutic intent as a bridge or downstage to OLT, ability to undergo angiography and selective visceral catheterization, ability to lay supine postprocedure, and ability to provide informed consent. Relative contraindications to TACE therapy included total bilirubin level >3.0 mg/dL, serum creatinine level >2.0 mg/dL, international normalized ratio >1.5, platelet count
