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Khan AS, Fowler KJ, Chapman WC. Current surgical treatment strategies for hepatocellular carcinoma in North America. World J Gastroenterol 2014; 20:15007-15017. [PMID: 25386049 PMCID: PMC4223234 DOI: 10.3748/wjg.v20.i41.15007] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2014] [Revised: 06/27/2014] [Accepted: 07/25/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is an aggressive tumor that often occurs in the setting of chronic liver disease. Many patients do not initially manifest any symptoms of HCC and present late when cure with surgical resection or transplantation is no longer possible. For this reason, patients at high risk for developing HCC are subjected to frequent screening processes. The surgical management of HCC is complex and requires an inter-disciplinary approach. Hepatic resection is the treatment of choice for HCC in patients without cirrhosis and is indicated in some patients with early cirrhosis (Child-Pugh A). Liver transplantation has emerged in the past decade as the standard of care for patients with cirrhosis and HCC meeting Milan criteria and in select patients with HCC beyond Milan criteria. Loco-regional therapy with transarterial chemoembolization, transarterial embolization, radiofrequency ablation and other similar local treatments can be used as neo-adjuvant therapy to downstage HCC to within Milan criteria or as a bridge to transplantation in patients on transplant wait list.
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Choi HJ, Kim DG, Na GH, Han JH, Hong TH, You YK. Clinical outcome in patients with hepatocellular carcinoma after living-donor liver transplantation. World J Gastroenterol 2013; 19:4737-4744. [PMID: 23922471 PMCID: PMC3732846 DOI: 10.3748/wjg.v19.i29.4737] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2013] [Revised: 04/12/2013] [Accepted: 06/04/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate risk factors for hepatocellular carcinoma (HCC) recurrence after living donor liver transplantation (LDLT) and efficacy of various criteria.
METHODS: From October 2000 to November 2011, 233 adult patients underwent LDLT for HCC at our institution. After excluding nine postoperative mortality cases, we analyzed retrospectively 224 patients. To identify risk factors for recurrence, we evaluated recurrence, disease-free survival (DFS) rate, survival rate, and various other factors which are based on the characteristics of both the patient and tumor. Additionally, we developed our own criteria based on our data. Next, we compared our selection criteria with various tumor-grading scales, such as the Milan criteria, University of California, San Francisco (UCSF) criteria, TNM stage, Barcelona Clinic Liver Cancer (BCLC) stage and Cancer of the Liver Italian Program (CLIP) scoring system. The median follow up was 68 (6-139) mo.
RESULTS: In 224 patients who received LDLT for HCC, 37 (16.5%) experienced tumor recurrence during the follow-up period. The 5-year DFS and overall survival rates after LDLT in all patients with HCC were 80.9% and 76.4%, respectively. On multivariate analysis, the tumor diameter {5 cm; P < 0.001; exponentiation of the B coefficient [Exp(B)], 11.89; 95%CI: 3.784-37.368} and alpha fetoprotein level [AFP, 100 ng/mL; P = 0.021; Exp(B), 2.892; 95%CI: 1.172-7.132] had significant influences on HCC recurrence after LDLT. Therefore, these two factors were included in our criteria. Based on these data, we set our selection criteria as a tumor diameter ≤ 5 cm and AFP ≤ 100 ng/mL. Within our new criteria (140/214, 65.4%), the 5-year DFS and overall survival rates were 88.6% and 81.8%, respectively. Our criteria (P = 0.001), Milan criteria (P = 0.009), and UCSF criteria (P = 0.001) showed a significant difference in DFS rate. And our criteria (P = 0.006) and UCSF criteria (P = 0.009) showed a significant difference in overall survival rate. But Milan criteria did not show significant difference in overall survival rate (P = 0.137). Among stages 0, A, B and C of BCLC, stage C had a significantly higher recurrence rate (P = 0.001), lower DFS (P = 0.001), and overall survival rate (P = 0.005) compared with the other stages. Using the CLIP scoring system, the group with a score of 4 to 5 showed a high recurrence rate (P = 0.023) and lower DFS (P = 0.011); however, the overall survival rate did not differ from that of the lower scoring group. The TNM system showed a trend of increased recurrence rate, decreased DFS, or survival rate according to T stage, albeit without statistical significance.
CONCLUSION: LDLT is considered the preferred therapeutic option in patients with an AFP level less than 100 ng/mL and a tumor diameter of less than 5 cm.
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Young RS, Aldiwani M, Hakeem AR, Nair A, Guthrie A, Wyatt J, Treanor D, Morris-Stiff G, Jones RL, Prasad KR. Pre-liver transplant biopsy in hepatocellular carcinoma: a potential criterion for exclusion from transplantation? HPB (Oxford) 2013; 15:418-27. [PMID: 23458127 PMCID: PMC3664045 DOI: 10.1111/hpb.12008] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2012] [Accepted: 10/17/2012] [Indexed: 02/07/2023]
Abstract
BACKGROUND In cirrhotic patients with hepatocellular carcinoma (HCC), poor differentiation in pre-liver transplantation (LT) biopsy of the largest tumour is used as a criterion for exclusion from LT in some centres. The potential role of pre-LT biopsy at one centre was explored. METHODS A prospective database of patients undergoing orthotopic LT for radiologically diagnosed HCC at St James's University Hospital, Leeds during 2006-2011 was analysed. RESULTS A total of 60 predominantly male (85.0%) patients with viral hepatitis were identified. There were discrepancies between radiological and histopathological findings with respect to the number of tumours identified (in 27 patients, 45.0%) and their size (in 63 tumours, 64.3%). In four (6.7%) patients, the largest lesion, which would theoretically have been targeted for biopsy, was not the largest in the explant. Nine (31.0%) patients with multifocal HCC had tumours of differing grades. In two (6.9%) patients, the largest tumour was well differentiated, but smaller tumours in the explant were poorly differentiated. In one patient, the largest lesion was benign and smaller invasive tumours were confirmed histologically. CONCLUSIONS The need to optimize selection for LT in HCC remains. In the present series, the largest tumour was not always representative of overall tumour burden or biological aggression and its potential use to exclude patients from LT is questionable.
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Affiliation(s)
- Richard S Young
- Department of Transplant and Hepaticopancreaticobiliary Surgery, St James's University HospitalLeeds, UK
| | - Mohammed Aldiwani
- Department of Transplant and Hepaticopancreaticobiliary Surgery, St James's University HospitalLeeds, UK
| | - Abdul R Hakeem
- Department of Transplant and Hepaticopancreaticobiliary Surgery, St James's University HospitalLeeds, UK
| | - Amit Nair
- Department of Transplant and Hepaticopancreaticobiliary Surgery, St James's University HospitalLeeds, UK
| | - Ashley Guthrie
- Department of Radiology, St James's University HospitalLeeds, UK
| | - Judy Wyatt
- Department of Histology, St James's University HospitalLeeds, UK
| | - Darren Treanor
- Department of Histology, St James's University HospitalLeeds, UK
| | - Gareth Morris-Stiff
- Department of Transplant and Hepaticopancreaticobiliary Surgery, St James's University HospitalLeeds, UK
| | - Rebecca L Jones
- Department of Hepatology, St James's University HospitalLeeds, UK
| | - K Rajendra Prasad
- Department of Transplant and Hepaticopancreaticobiliary Surgery, St James's University HospitalLeeds, UK,Correspondence K. Rajendra Prasad, Department of Transplant and Hepaticopancreaticobiliary Surgery, St James's University Hospital, Beckett Street, Leeds LS9 7TF, UK. Tel: + 44 113 206 5921. Fax: + 44 113 244 8182. E-mail:
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Extended criteria for living donor liver transplantation in patients with advanced hepatocellular carcinoma. Transplant Proc 2012; 44:399-402. [PMID: 22410027 DOI: 10.1016/j.transproceed.2012.01.019] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND The purpose of this study was to evaluate the possibility of expanding the selection criteria in living donor liver transplantation (LDLT) to treat hepatocellular carcinoma (HCC). METHODS From October 2000 to December 2010, we retrospectively analyzed 71 patients who had undergone LDLT beyond the Milan criteria (MC), among the entire cohort of 199 HCC patients. We evaluated the tumor biology as well as overall and disease-free survival (DFS), seeking to identify risk factors for recurrence. The median follow-up was 37 months (range 5-124). RESULTS Among the 71 patients beyond the MC were 18 recurrences and 30 deaths. Their 5-year overall and DFS rates were 52.3% and 67.7%, respectively. On multivariate analysis, tumor diameter, tumor number, and E-S grade significantly influenced overall and DFS. According to our new criteria (size≤7 cm, number≤7), 86% of our patients would be included compared with 64% using MC. Five-year DFS and overall survival rates according to our criteria were comparable with the MC: 86.8% and 72.3% versus 86.8% and 73.4%, respectively. CONCLUSION Our criteria appear to achieve useful cut-off values beyond the MC.
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Schwartz JJ, Pappas L, Thiesset HF, Vargas G, Sorensen JB, Kim RD, Hutson WR, Boucher K, Box T. Liver transplantation in septuagenarians receiving model for end-stage liver disease exception points for hepatocellular carcinoma: the national experience. Liver Transpl 2012; 18:423-33. [PMID: 22250078 DOI: 10.1002/lt.23385] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Current liver allocation policy in the United States grants liver transplant candidates with stage T2 hepatocellular carcinoma (HCC) a priority Model for End-Stage Liver Disease (MELD) score of 22, regardless of age. Because advanced age may portend an increase in all-cause mortality after transplantation for any diagnosis, the aim of this study was to examine overall posttransplant survival in elderly patients with HCC versus younger cohorts. Based on Organ Procurement and Transplantation Network data, Kaplan-Meier 5-year survival rates were compared. Recipients undergoing primary liver transplantation were stratified into cohorts based on age (<70 or ≥ 70 years) and the receipt of MELD exception points for HCC. Log-rank and Wilcoxon tests were used for statistical comparisons. In 2009, 143 transplants were performed for patients who were 70 years old or older. Forty-two percent of these patients received a MELD exception for HCC. Regardless of the diagnosis, the overall survival rate was significantly attenuated for the septuagenarians versus the younger cohort. After 5 years of follow-up, this disparity exceeded 10% to 15% depending on the populations being compared. The 1-, 2-, 3-, 4-, and 5-year actuarial survival rates were 88.4%, 83.2%, 79.6%, 76.1%, and 72.7%, respectively, for the patients who were younger than 70 years and 81.1%, 73.8%, 67.1%, 61.9%, and 55.2%, respectively, for the patients who were 70 years old or older. Five-year survival was negatively affected for patients with HCC who were younger than 70 years; this disparity was not observed for patients with HCC who were 70 years old or older. In conclusion, although patients who are 70 years old or older compose a small fraction of transplant recipients in the United States, patients in this group undergoing transplantation for HCC form an even smaller subset. Overall, transplantation in this age group yields outcomes inferior to those for younger cohorts. However, unlike patients who are less than 70 years old and receive MELD exception points, overall liver transplant survival is not affected by HCC at an advanced age.
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Affiliation(s)
- Jason J Schwartz
- Section of Transplantation, Department of General Surgery, University of Utah, Salt Lake City, UT 75390, USA.
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Jarnagin W, Chapman WC, Curley S, D'Angelica M, Rosen C, Dixon E, Nagorney D. Surgical treatment of hepatocellular carcinoma: expert consensus statement. HPB (Oxford) 2010; 12:302-10. [PMID: 20590903 PMCID: PMC2951816 DOI: 10.1111/j.1477-2574.2010.00182.x] [Citation(s) in RCA: 82] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
As the number of effective treatment options has increased, the management of patients with hepatocellular carcinoma has become complex. The most appropriate therapy depends largely on the functional status of the underlying liver. In patients with advanced cirrhosis and tumor extent within the Milan criteria, liver transplantation is clearly the best option, as this therapy treats the cancer along with the underlying hepatic parenchymal disease. As the results of transplantation has become established in patients with limited disease, investigation has increasingly focused on downstaging patients with disease outside of Milan criteria and defining the upper limits of transplantable tumors. In patients with well preserved hepatic function, liver resection is the most appropriate and effective treatment. Hepatic resection is not as constrained by tumor extent and location to the same degree as transplantation and ablative therapies. Some patients who recur after resection may still be eligible for transplantation. Ablative therapies, particularly percutaneous radiofrequency ablation and transarterial chemoembolization have been used primarily to treat patients with low volume irresectable tumors. Whether ablation of small tumors provides long term disease control that is comparable to resection remains unclear.
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Affiliation(s)
- William Jarnagin
- Department of Surgery, Memorial – Sloan Kettering Cancer CenterNew York, NY
| | - William C Chapman
- Section of Transplantation, Barnes – Jewish Hospital, Washington School of MedicineSt. Louis, MO
| | - Steven Curley
- Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer CenterHouston, TX
| | - Michael D'Angelica
- Department of Surgery, Memorial – Sloan Kettering Cancer CenterNew York, NY
| | | | - Elijah Dixon
- Department of Surgery, University of CalgaryCalgary, Canada
| | - David Nagorney
- Department of Gastroenterologic and General Surgery, Mayo ClinicRochester, MN, USA
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Koschny R, Schmidt J, Ganten TM. Beyond Milan criteria--chances and risks of expanding transplantation criteria for HCC patients with liver cirrhosis. Clin Transplant 2010; 23 Suppl 21:49-60. [PMID: 19930317 DOI: 10.1111/j.1399-0012.2009.01110.x] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Orthotopic liver transplantation (OLT) is, apart from resection, one important curative treatment for hepatocellular carcinoma (HCC) in liver cirrhosis, and especially attractive because it eliminates both the tumor and the underlying liver disease. The application of restrictive inclusion criteria for OLT in HCC patients resulted in favorable long-term recurrence-free survival. These criteria, however, exclude a subgroup of patients which, despite advanced tumor size, demonstrate an acceptable outcome. As a consequence, expansion of the strict Milan criteria has been discussed. However, this will also deteriorate the average outcome of OLT in HCC patients. Considering that we run short of donor organs, more sophisticated prediction models for survival after OLT for HCC patients are needed to identify patients who benefit best from OLT. Neoadjuvant treatment that is frequently applied as a bridging technique for patients on the waiting list for OLT could provide useful information on tumor behavior to better predict the risk of post-OLT tumor recurrence. This might also allow expansion of the Milan criteria to patients with good response to downstaging methods without negatively affecting post-OLT survival. Furthermore, alternative scoring systems have been suggested to identify HCC patients that might still benefit from resection instead of OLT, and molecular tools are being explored to provide predictive information on HCC biology. This review discusses the advantages and risks of extended inclusion criteria for OLT and the currently available data on alternative prediction models and bridging methods in HCC patients.
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Affiliation(s)
- Ronald Koschny
- Department of Internal Medicine, University of Heidelberg, Heidelberg, Germany
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D'Amico F, Schwartz M, Vitale A, Tabrizian P, Roayaie S, Thung S, Guido M, del Rio Martin J, Schiano T, Cillo U. Predicting recurrence after liver transplantation in patients with hepatocellular carcinoma exceeding the up-to-seven criteria. Liver Transpl 2009; 15:1278-87. [PMID: 19790142 DOI: 10.1002/lt.21842] [Citation(s) in RCA: 99] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The up-to-seven (Up-to-7) criteria [with 7 being the sum of the size and number of tumors for any given hepatocellular carcinoma (HCC)] have been recently proposed to identify potential candidates for liver transplantation (LT) among patients exceeding the Milan criteria. The aim of this study was to compare the ability of the available pathologic staging systems (the Milan, University of California San Francisco, and Up-to-7 criteria) to predict recurrence. A study population of 479 HCC transplanted patients was identified from prospectively collected databases at Mount Sinai Medical Center (New York, NY) and the University of Padua (Padua, Italy). The best pathologic staging system was identified with log rank, proportion separation index (PSEP), and Cox analyses. Pathologic tumor characteristics (tumor number, tumor size, sum of diameters, macroscopic and microscopic vascular invasion, and grading) were then tested by univariate and multivariate Cox analyses in the prognostic subgroups within and beyond the calculated criteria. The Up-to-7 criteria performed as the best pathologic staging system, the calculated 1-, 3-, and 5-year recurrence probabilities being 4%, 8%, and 14% within the criteria (n = 355) and 22%, 45%, 51% beyond the criteria (n = 124; P < 0.0001) and the calculated PSEP being 0.27 (95% confidence interval = 0.23-0.31). In multivariate analysis, only biological variables (vascular invasion and tumor grade) significantly predicted recurrence beyond the Up-to-7 criteria. A 3-stage pathologic staging system with a potential to be applied in the preoperative setting was thus created: within the Up-to-7 criteria (recurrence rate = 8%), beyond the Up-to-7 criteria without macrovascular invasion and poorly differentiated grade (recurrence rate = 24%), and beyond the Up-to-7 criteria with macrovascular invasion and/or poorly differentiated grade (recurrence rate = 45%). In conclusion, HCC patients within the pathologic Up-to-7 criteria were associated with a low risk of recurrence after LT. Beyond these criteria, however, a significant proportion of patients with a good HCC biological profile had an acceptable risk of recurrence.
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Affiliation(s)
- Francesco D'Amico
- Hepatobiliary Surgery and Liver Transplant Unit, Department of General Surgery and Organ Transplantation, University of Padua, Padua, Italy.
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Schwartz M, D'Amico F, Vitale A, Emre S, Cillo U. Liver transplantation for hepatocellular carcinoma: Are the Milan criteria still valid? Eur J Surg Oncol 2008; 34:256-62. [DOI: 10.1016/j.ejso.2007.07.208] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2007] [Accepted: 07/20/2007] [Indexed: 02/08/2023] Open
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Bozorgzadeh A, Orloff M, Abt P, Tsoulfas G, Younan D, Kashyap R, Jain A, Mantry P, Maliakkal B, Khorana A, Schwartz S. Survival outcomes in liver transplantation for hepatocellular carcinoma, comparing impact of hepatitis C versus other etiology of cirrhosis. Liver Transpl 2007; 13:807-813. [PMID: 17539001 DOI: 10.1002/lt.21054] [Citation(s) in RCA: 60] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
The incidence of hepatocellular carcinoma (HCC) is on the rise worldwide as the most common primary hepatic malignancy. In the US approximately one half of all HCC is related to Hepatitis C virus (HCV) infection. The relationship between the primary disease and HCC recurrence after liver transplantation is unknown. We hypothesized that the primary hepatic disease underlying the development of cirrhosis and HCC would be associated with the risk of recurrent HCC after transplantation. A retrospective review was conducted of all primary liver transplants performed at the University of Rochester Medical Center from May 1995 through June 2004. The pathology reports from the native livers of 727 recipients were examined for the presence of HCC. There were 71 liver transplant recipients with histopathological evidence of HCC. These patients were divided in two groups on the basis of HCV status. Group 1 consisted of 37 patients that were both HCV and HCC positive, and Group 2 consisted of 34 patients that were HCC positive but HCV negative. Patient characteristics were analyzed, as well as number of tumors, tumor size, presence of vascular invasion, lobe involvement, recipient demographics, donor factors, pretransplantation HCC therapy, rejection episodes, and documented HCC recurrence and treatment. There were no statistically significant differences between the 2 groups, with the exception of recipient age and the presence of hepatitis B coinfection. The tumor characteristics of both groups were similar in numbers of tumors, Milan criteria status, vascular invasion, incidental HCC differentiation, and largest tumor size. The HCV positive population had a far lower patient survival rate with patient survival in Group 1 at 1, 3, and 5 years being 81.1%, 57.4%, and 49.3% respectively, compared with 94.1%, 82.8%, and 76.4% in Group 2 (p = 0.049). Tumor-free survival in Group 1 at 1, 3, and 5 years was 70.3%, 43%, and 36.8% respectively, vs. 88.1%, 73%, and 60.8% in Group 2. In a subgroup analysis, tumor-free survival was further examined by stratifying the patients on the basis of Milan criteria. Group 1 patients outside of Milan criteria had a statistically lower tumor-free survival. By contrast, there was no statistical difference in tumor-free survival in Group 2 patients stratified according to Milan criteria. Cox regression analysis identified HCV and vascular invasion as significant independent predictors of tumor-free survival. Our results suggest that Milan selection criteria may be too limiting and lose their predictive power when applied to patients without HCV infection.
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Affiliation(s)
- Adel Bozorgzadeh
- Department of Surgery, University of Rochester Medical Center, Rochester, NY, USA.
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Vauthey JN, Ribero D, Abdalla EK, Jonas S, Bharat A, Schumacher G, Lerut J, Chapman WC, Hemming AW, Neuhaus P. Outcomes of Liver Transplantation in 490 Patients with Hepatocellular Carcinoma: Validation of a Uniform Staging after Surgical Treatment. J Am Coll Surg 2007; 204:1016-27; discussion 1027-8. [PMID: 17481532 DOI: 10.1016/j.jamcollsurg.2006.12.043] [Citation(s) in RCA: 69] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2006] [Accepted: 12/15/2006] [Indexed: 01/09/2023]
Abstract
BACKGROUND The aim of this study was to compare the ability of staging systems (American Joint Committee on Cancer/Union Internationale contre le Cancer [AJCC/UICC], Japanese TNM, Pittsburgh, United Network for Organ Sharing [UNOS], Cancer of the Liver Italian Program [CLIP], Japan Integrated Staging [JIS], and Barcelona Clinic Liver Cancer [BCLC]) to predict survival after liver transplantation for hepatocellular carcinoma. STUDY DESIGN Four hundred ninety consecutive patients who underwent liver transplantation for hepatocellular carcinoma at 4 centers (1985 to 2005) were identified using a registry (US, Belgium, Germany). End points were overall (OS) and recurrence-free survival (RFS). Survival by stage was compared with the log-rank test. Sequential stage-wise discrimination of each system was evaluated using Cox regression. RESULTS Three- and 5-year overall survival rates were 71% and 64%, respectively; recurrence-free survival rates were 67% and 61%, respectively. Median followup among 327 living and 308 recurrence-free patients was 40 months. In only three systems--AJCC/UICC, Japanese TNM, and Pittsburgh--were overall and recurrence-free survivals longer for patients with low stage versus more advanced stage. For overall and recurrence-free survivals, sequential stages were different only for AJCC/UICC. In the Japanese TNM system, stages II and I were similar; for Pittsburgh, grades 3 and 2 were similar. For the United Network for Organ Sharing system, stages II and I and stages IVA1 and III were similar. All stages were similar for the Cancer of the Liver Italian Program. For the Japan Integrated Staging, scores 2 and 1 and scores 4 and 3 were similar. In the Barcelona Clinic Liver Cancer, stage D patients had significantly better survival than patients at stage C. CONCLUSIONS The AJCC/UICC staging system provides the best stratification of prognosis for patients undergoing liver transplantation for hepatocellular carcinoma. This confirms previous analyses in patients treated with hepatic resection. The AJCC/UICC staging system should be considered for uniform prediction of outcomes after surgery for hepatocellular carcinoma.
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Affiliation(s)
- Jean-Nicolas Vauthey
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
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12
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Cillo U, Vitale A, Grigoletto F, Gringeri E, D'Amico F, Valmasoni M, Brolese A, Zanus G, Srsen N, Carraro A, Burra P, Farinati F, Angeli P, D'Amico DF. Intention-to-treat analysis of liver transplantation in selected, aggressively treated HCC patients exceeding the Milan criteria. Am J Transplant 2007; 7:972-81. [PMID: 17391137 DOI: 10.1111/j.1600-6143.2006.01719.x] [Citation(s) in RCA: 97] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
This prospective study analyzed the dropout probability and intention-to-treat survival rates of patients with hepatocellular carcinoma (HCC) selected and treated according to our policy before liver transplantation (LT), with particular attention to those exceeding the Milan criteria. Exclusion criteria for LT were macroscopic vascular invasion, metastases, and poorly differentiated disease at percutaneous biopsy. A specific multi-modal adjuvant algorithm was used to treat HCC before LT. A total of 100 HCC patients were listed for LT: 40 exceeded the Milan criteria in terms of nodule size and number (MILAN OUT) either at listing or in list, while 60 patients continued to meet the criteria (MILAN IN). The Milan criteria did not prove to be a significant predictor of dropout probability or survival rates using Cox's analysis. Cumulative dropout probability at 6 and 12 months was 0% and 4% for MILAN OUT, and 6% and 11% for MILAN IN. The intention-to-treat survival rates at 1 and 3 years were 95% and 85% in MILAN OUT, and 84% and 69% in MILAN IN. None of the 68 transplanted patients had recurrent HCC after a median 16-month follow-up (0-69 months). In conclusion, LT may be effective for selected, aggressively-treated HCC patients exceeding the Milan criteria.
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Affiliation(s)
- U Cillo
- Unità di Chirurgia Epatobiliare e Trapianto Epatico, Dipartimento di Chirurgia Generale e Trapianti d'Organo, Azienda Ospedaliera di Padova, Italy
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Bharat A, Brown DB, Crippin JS, Gould JE, Lowell JA, Shenoy S, Desai NM, Chapman WC. Pre-liver transplantation locoregional adjuvant therapy for hepatocellular carcinoma as a strategy to improve longterm survival. J Am Coll Surg 2006; 203:411-20. [PMID: 17000383 DOI: 10.1016/j.jamcollsurg.2006.06.016] [Citation(s) in RCA: 83] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2006] [Revised: 06/15/2006] [Accepted: 06/19/2006] [Indexed: 02/07/2023]
Abstract
BACKGROUND Preorthotopic liver transplantation locoregional therapy (LRT) for hepatocellular carcinoma (HCC) reduces drop-out rates in patients awaiting orthotopic liver transplantation (OLT). In this study, we investigated the efficacy of LRT as a strategy to improve longterm survival after transplantation. STUDY DESIGN A retrospective analysis of prospectively collected data identified 100 patients with HCC who underwent OLT between 1985 and 2005. Of these, 46 received LRT in the form of transarterial chemoembolization, radiofrequency ablation, percutaneous ethanol injection, or a combination of these. RESULTS The 1-, 3-, and 5-year survivals, regardless of LRT, were 81.3%, 66.1%, and 61.3%, respectively. Demographic data and waiting time for OLT were similar between LRT and untreated groups. Pre-OLT radiologic stage was comparable (LRT: 2.11 +/- 0.74 versus Untreated: 2.39 +/- 0.94; p = 0.16). At the time of transplantation, the LRT group had notable tumor downstaging (1.50 +/- 1.34 versus 2.49 +/- 1.17; p = 0.008). The LRT group had better 5-year survival (82.4% versus 51.8%; p = 0.01), but this improvement was observed in patients with HCC stages II, III, and IV (77.6% versus 37.4%; p = 0.016). Sixteen LRT patients, and none untreated, revealed complete tumor necrosis with no viable tumor cells on explant pathology (pT0). These patients did not experience any longterm recurrence, in contrast to those with similar pre-OLT tumors. CONCLUSIONS OLT is a viable treatment option for primary HCC. LRT substantially downstages the primary tumor and improves longterm survival in patients with advanced disease. Complete tumor necrosis with LRT is associated with excellent longterm recurrence-free survival.
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Affiliation(s)
- Ankit Bharat
- Department of Surgery, Section of Abdominal Transplantation, Washington University School of Medicine, 660 S, Euclid Avenue, St Louis, MO 63110, USA
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Shah SA, Tan JCC, McGilvray ID, Cattral MS, Cleary SP, Levy GA, Greig PD, Grant DR. Accuracy of staging as a predictor for recurrence after liver transplantation for hepatocellular carcinoma. Transplantation 2006; 81:1633-9. [PMID: 16794527 DOI: 10.1097/01.tp.0000226069.66819.7e] [Citation(s) in RCA: 109] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Tumor number, size, and macrovascular invasion (MacroVI) are the most widely used predictors of survival after liver transplantation (LT) for hepatocellular carcinoma (HCC). We analyzed all patients undergoing LT for HCC at our center to establish the accuracy of preoperative clinical staging and to determine which patients have a higher probability of being understaged. METHODS In all, 118 patients with confirmed HCC after LT from April 1991 to October 2004 at our institution were reviewed. All patients were monitored with serial imaging every 3 months to ensure their eligibility for LT within Milan criteria. Understaging in the 118 patients was defined as evidence on explant pathology that Milan criteria (TNM stage pT1 or pT2) had been exceeded. RESULTS Five-year DFS was 78% with a recurrence rate of 15% after a median follow-up after LT of 30 months. On explant pathology, 43% (51/118) of patients exceeded Milan criteria and had a worse DFS (1 year, 95% vs. 87%; 3 year, 87% vs. 64%; P=0.03) compared to those who met LT criteria. Understaging was more likely in patients with imaging characteristics of > or = 2 tumor nodules (P=0.005) and tumor growth > 0.25 cm/month (P=0.02) and pathologic findings of vascular invasion (P=0.001) and bilobar tumors (P=0.002). CONCLUSIONS Preoperative imaging every 3 months while on the waiting list frequently understages HCC as assessed by explant pathology. Recurrence after LT often occurred in patients that were understaged. Improving the accuracy of clinical staging and inclusion parameters will ensure proper organ allocation and acceptable outcomes after LT.
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Affiliation(s)
- Shimul A Shah
- Department of Surgery, Multi-Organ Transplantation Program, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Canada
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Karp SJ, Ku Y, Johnson S, Khwaja K, Curry M, Hanto D. Surgical and non-surgical approaches to hepatocellular cancer. Curr Opin Organ Transplant 2006. [DOI: 10.1097/01.mot.0000227837.06582.94] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Chu F, Morris DL. Single centre experience of liver resection for hepatocellular carcinoma in patients outside transplant criteria. Eur J Surg Oncol 2006; 32:568-72. [PMID: 16616451 DOI: 10.1016/j.ejso.2006.02.005] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2005] [Accepted: 02/08/2006] [Indexed: 01/17/2023] Open
Abstract
INTRODUCTION To report analysis of our results of liver resection for HCC outside the transplant criteria with preserved liver function. METHODS Between January 1990 and March 2005, 279 patients with HCC were seen at our institution and entered into a prospective database. There were 51 patients who did not fulfill the transplant criteria and underwent partial hepatectomy. Survival was determined by Kaplan-Meier analysis. RESULTS The median tumour size was 10.0 cm with a range of 3-20 cm. Twenty-nine patients had solitary tumours and 21 patients had two or more liver tumours, with four patients whose tumours were less than 5 cm in maximal diameter. Ten patients had bilobar disease. The 30-day mortality was 8%. The 1-, 3- and 5-year overall survival was 63, 40 and 33%, respectively, and the median survival was 16.6 months. Fifteen potential variables were analysed as potential predictors of adverse outcome. Multivariate analysis showed Child-Pugh classification, presence of cirrhosis, rupture on presentation and tumour histology to be independent prognostic factors on survival. CONCLUSION Partial hepatectomy in patients with advanced HCC who are ineligible for transplantation can be performed safely and can achieve a 5-year survival of 33%.
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Affiliation(s)
- F Chu
- UNSW Department of Surgery, St George Hospital, Sydney, NSW, Australia
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