11C-Acetate and 18F-FDG PET/CT for Clinical Staging and Selection of Patients with Hepatocellular Carcinoma for Liver Transplantation on the Basis of Milan Criteria: Surgeon’s Perspective

The success of liver transplantation (LT) for hepatocellular carcinoma (HCC) is enhanced by careful patient selection on the basis of the Milan criteria. The criteria are traditionally assessed by contrast CT, which is known to be affected by structural or architectural changes in cirrhotic livers. We aimed to compare dual-tracer (11C-acetate and 18F-FDG) PET/CT with contrast CT for patient selection on the basis of the Milan criteria. Methods: Patients who had HCC and had undergone both preoperative dual-tracer PET/CT and contrast CT within a 1-mo interval were retrospectively studied. They then underwent either LT (n = 22) or partial hepatectomy (PH) (n = 21; HCC of ≤ 8 cm). Imaging data were compared with data from postoperative pathologic analysis for accuracy in assessment of parameters specified by the Milan criteria (tumor size and extent, vascular invasion, and metastasis), TNM staging, and patient selection for LT. Results: Dual-tracer PET/CT performed equally well in both LT and PH groups for HCC detection (94.1% vs. 95.8%) and TNM staging (90.9% vs. 90.5%). Contrast CT performed reasonably well in the LT group but not in the PH group for HCC detection (67.6% vs. 37.5%) and TNM staging (54.5% vs. 28.6%). In the LT group, the sensitivity and specificity of contrast CT for patient selection on the basis of the Milan criteria were 43.8% and 66.7%, respectively (comparable to values in the literature); the sensitivity and specificity of dual-tracer PET/CT were 93.8% and 100%, respectively (both Ps < 0.05). From the surgeon’s perspective, we tended to perform transplantation for patients with higher diagnostic certainty (stricter CT criteria) because of a shortage of donor grafts. Patients who were not transplant candidates usually underwent up-front hepatectomy without the benefit of reassessment contrast CT, resulting in lower accuracies for the PH group. The overall sensitivity (96.8%) and specificity (91.7%) of dual-tracer PET/CT for patient selection for LT were significantly higher than those of contrast CT (41.9% and 33.0%, respectively) (both Ps < 0.05). Sources of error for contrast CT were related to cirrhosis or previous treatment and included difficulty in differentiating cirrhotic nodules from HCC (39%) and estimation of tumor size (14%). Overstaging of vascular invasion (4.6%) and extrahepatic metastases (4.6%) was infrequent. The rate of false-negative results of dual-tracer PET/CT was 4.7%. Conclusion: Dual-tracer PET/CT was significantly less affected by cirrhotic changes than contrast CT for HCC staging and patient selection for LT on the basis of the Milan criteria. The inclusion of dual-tracer PET/CT in pretransplant workup may warrant serious consideration.

[1]  D. Lu,et al.  CT and MRI improve detection of hepatocellular carcinoma, compared with ultrasound alone, in patients with cirrhosis. , 2011, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[2]  Josep Fuster,et al.  The Barcelona approach: Diagnosis, staging, and treatment of hepatocellular carcinoma , 2004, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[3]  Sirong Chen,et al.  PET/CT characteristics of isolated bone metastases in hepatocellular carcinoma. , 2011, Radiology.

[4]  Jeong Min Lee,et al.  Diagnostic Accuracy of Multi-/Single-Detector Row CT and Contrast-Enhanced MRI in the Detection of Hepatocellular Carcinomas Meeting the Milan Criteria before Liver Transplantation , 2008, Intervirology.

[5]  Sirong Chen,et al.  Dual-Tracer PET/CT Imaging in Evaluation of Metastatic Hepatocellular Carcinoma , 2007, Journal of Nuclear Medicine.

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

[7]  K. Hwang,et al.  Evaluation of patients with hepatocellular carcinomas using [(11)C]acetate and [(18)F]FDG PET/CT: A preliminary study. , 2009, Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine.

[8]  M. Abecassis,et al.  AHPBA/AJCC consensus conference on staging of hepatocellular carcinoma: consensus statement. , 2003, HPB : the official journal of the International Hepato Pancreato Biliary Association.

[9]  T. Roskams,et al.  Focal lesions in cirrhotic explant livers: Pathological evaluation and accuracy of pretransplantation imaging examinations , 2002, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[10]  Carmen Ayuso,et al.  MRI angiography is superior to helical CT for detection of HCC prior to liver transplantation: An explant correlation , 2003, Hepatology.

[11]  J W Marsh,et al.  Pretransplantation surveillance for possible hepatocellular carcinoma in patients with cirrhosis: epidemiology and CT-based tumor detection rate in 430 cases with surgical pathologic correlation. , 2000, Radiology.

[12]  D. Harnois The diagnostic and economic impact of contrast imaging techniques in the diagnosis of small hepatocellular carcinoma in cirrhosis , 2010 .

[13]  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.

[14]  S. Fan,et al.  Liver transplantation for hepatocellular carcinoma: the Hong Kong experience , 2010, Journal of hepato-biliary-pancreatic sciences.

[15]  P. Tam,et al.  Ten-year experience with liver transplantation at Queen Mary Hospital: retrospective study. , 2002, Hong Kong medical journal = Xianggang yi xue za zhi.

[16]  O. Dirsch,et al.  Liver Transplantation for Hepatocellular Carcinoma in Cirrhosis: Is Clinical Tumor Classification before Transplantation Realistic? , 2005, Transplantation.

[17]  Chi-Lai Ho,et al.  11C-acetate PET imaging in hepatocellular carcinoma and other liver masses. , 2003, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[18]  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.

[19]  Sandro Sironi,et al.  Role of MDCT in the diagnosis of hepatocellular carcinoma in patients with cirrhosis undergoing orthotopic liver transplantation. , 2007, AJR. American journal of roentgenology.

[20]  Double-contrast MRI (DC-MRI) in the study of the cirrhotic liver: utility of administering Gd-DTPA as a complement to examinations in which SPIO liver uptake and distribution alterations (SPIO-LUDA) are present and in the identification and characterisation of focal lesions , 2006, La radiologia medica.

[21]  D. Lu,et al.  Liver Transplantation Criteria For Hepatocellular Carcinoma Should Be Expanded: A 22-Year Experience With 467 Patients at UCLA , 2007, Annals of surgery.

[22]  J. Bruix,et al.  Diagnosis of hepatic nodules 20 mm or smaller in cirrhosis: Prospective validation of the noninvasive diagnostic criteria for hepatocellular carcinoma , 2007, Hepatology.

[23]  U. Schmiedl,et al.  Significance of hyperattenuating and contrast-enhancing hepatic nodules detected in the cirrhotic liver during arterial phase helical CT in pre–liver transplant patients: radiologic–histopathologic correlation of explanted livers , 2003, Abdominal Imaging.

[24]  Jae Young Lee,et al.  Diagnostic Performance of Multidetector Row Computed Tomography, Superparamagnetic Iron Oxide-Enhanced Magnetic Resonance Imaging, and Dual-Contrast Magnetic Resonance Imaging in Predicting the Appropriateness of a Transplant Recipient Based on Milan Criteria: Correlation With Histopathological Find , 2009, Investigative radiology.

[25]  Günter Tusch,et al.  Surgical treatment of hepatocellular carcinoma: Experience with liver resection and transplantation in 198 patients , 1991, World Journal of Surgery.

[26]  S. Fan,et al.  Locoregional Therapies for Hepatocellular Carcinoma: A Critical Review From the Surgeon’s Perspective , 2002, Annals of surgery.

[27]  T. Davern,et al.  Liver transplantation for hepatocellular carcinoma: Analysis of survival according to the intention‐to‐treat principle and dropout from the waiting list , 2002, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[28]  Hyun Woo Kwon,et al.  Prediction of Tumor Recurrence by 18F-FDG PET in Liver Transplantation for Hepatocellular Carcinoma , 2009, Journal of Nuclear Medicine.

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

[30]  B. Taouli,et al.  Diagnostic imaging of hepatocellular carcinoma in patients with cirrhosis before liver transplantation , 2006, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.