10.1245/s10434-006-9156-z
Annals of Surgical Oncology 14:541-547 (2007)
© 2007 Society of Surgical Oncology
Optimal Initial Treatment for Early Hepatocellular Carcinoma in Patients with Preserved Liver Function: Transplantation or Resection?
Ronnie T. P. Poon, MBBS, MS, FRCS (Edin), FACS
Centre for the Study of Liver Disease, Department of Surgery, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China
Correspondence: Address correspondence and reprint requests to: Ronnie T. P. Poon, MBBS, MS, FRCS (Edin), FACS; E-mail: poontp{at}hkucc.hku.hk
 |
ABSTRACT
|
|---|
Partial hepatic resection has been the mainstay of curative treatment for hepatocellular carcinoma (HCC) in cirrhotic patients with preserved liver function. Liver transplantation for HCC was initially developed as a treatment option for patients with unresectable tumors associated with Child B or C cirrhosis. However, in recent years, some authors have advocated liver transplantation even for resectable early HCC associated with Child A cirrhosis. Whether transplantation or liver resection is the optimal initial treatment for early HCC in compensated cirrhosis depends on the survival results and also the availability of liver grafts. Recent studies comparing liver resection and transplantation for early HCC in Child A cirrhotic patients demonstrated similar long-term survival. While liver transplantation is associated with a lower tumor recurrence rate, this benefit is counteracted by long-term complications such as immunosuppression related infections and neoplasms. Patients put on transplantation waiting list run a significant risk of tumor progression and dropout, while liver resection is immediately applicable to all. A premature liver transplantation may expose patients to the side effects of immunosuppression earlier than necessary. With the current shortage of liver grafts, advocating primary liver transplantation for patients with early HCC associated with compensated cirrhosis will increase waiting time of transplantation and further increases the chance of dropout. Resection first and salvage transplantation for recurrent tumors or liver failure has been shown to be a feasible strategy in the majority of patients, and this appears to be the optimal strategy with the best use of organs.
Key Words: Cirrhosis • Hepatocellular carcinoma • Liver resection • Transplantation
|
INTRODUCTION
|
|---|
Hepatocellular carcinoma (HCC) is one of the five most common malignancies in the world, with a particularly high prevalence in Asia but its incidence is rising in Western countries.1 Partial liver resection and liver transplantation are the potentially curative treatments for HCC.2,3 For early HCC associated with severe cirrhosis (Child B and C), liver transplantation is universally accepted to be the best treatment because the poor liver function reserve generally contraindicates hepatic resection.3–5 The most well-established criteria for transplantation for HCC are the Milan criteria: solitary tumor 
5 cm in diameter or two to three tumor nodules with the largest diameter 3 cm, and absence of macroscopic vascular invasion or extrahepatic metastasis.6 For patients with early HCC associated with noncirrhotic liver or Child A cirrhosis, partial hepatectomy used to be the treatment of choice. Recently, some authors advocated primary liver transplantation even for patients with early HCC associated with Child A cirrhosis,7,8 leading to a debate on whether liver resection or transplantation should be the optimal initial treatment for such patients.
|
SURVIVAL RESULTS AFTER RESECTION VERSUS TRANSPLANTATION
|
|---|
The most important outcome measure in comparison of treatments for any cancer is the long-term survival. In this regard, several studies have reported 5-year survival rate of 60–70% after partial hepatectomy for early transplantable HCC,9–12 which seems to be comparable to that reported in studies of transplantation for early HCC.6,13,14 Recently, a few retrospective studies have directly compared liver resection and transplantation for small HCC in Child A cirrhotic patients. Bigourdan et al.7 reported significantly better survival results after liver transplantation than after hepatic resection. However, a closer look at the data of the study revealed that there were significant selection bias in favor of the liver transplantation group, which had smaller tumors, a higher proportion of solitary tumor, lower incidence of vascular invasion and a lower proportion of alcoholic cirrhosis. Shabahang et al.15 reported similar operative mortality and survival results after resection and transplantation for HCC in Child A cirrhotic patients, but hepatic resection was associated with quicker recovery. More recently, Margarit et al.16 reported similar survival results after resection and transplantation in Child A cirrhotic patients, whereas postoperative mortality was higher and hospital stay was longer in the transplantation group.
Most of the studies that have compared resection and transplantation for early HCC showed that transplantation is associated with a better tumor recurrence-free survival, and this is the main argument in favor of primary liver transplantation for early HCC even in patients with preserved liver function and resectable tumor. The 5-year tumor recurrence-free survival rate after resection of early HCC within the Milan criteria in Child A cirrhotic patients was 40–48%,7,9,12,16 as compared to that of 60–80% after liver transplantation.7,16,17 The lower tumor recurrence rate after transplantation is expected because the cirrhotic liver is an important cause of intrahepatic tumor recurrence after hepatic resection due to multicentric hepatocarcinogenesis.18 However, liver transplantation is associated with other long-term problems such as graft rejection, recurrent viral hepatitis or immunosuppression related complications, which causes long-term mortalities. This explains the similar overall survival after resection and transplantation for HCC observed in most studies comparing the two treatments despite the higher tumor recurrence rate after resection.15,16,19,20 The availability of effective treatments such as re-resection and ablation therapies for recurrent tumors, about 80% of which occurs in the liver remnant, also contributes to the favorable long-term survival after hepatic resection for early HCC despite the high incidence of tumor recurrence.21 Because of the different nature of treatments and associated long-term problems, it is pertinent that overall survival rather than tumor recurrence-free survival be considered the primary outcome in the comparison of the two treatments.
|
ORGAN SHORTAGE—AN UNSOLVED ISSUE FOR LIVER TRANSPLANTATION
|
|---|
Because of the severe shortage of liver grafts worldwide, liver transplantation is not immediately applicable to all patients with HCC. A significant proportion of HCC patients listed for liver transplantation may drop out of the waiting list because of tumor progression. Dropout rates of 15–33% have been reported even in countries where waiting time for deceased donor graft is relatively short.10,22–24 This is the most critical limitation of the approach of primary transplantation for early HCC in patients with Child A cirrhosis, for whom the option of liver resection may be more appealing to the patients because it is immediately applicable.
The high dropout rate of HCC patients put on the waiting list for transplantation has an important implication on comparison of survival results of liver resection and transplantation for HCC. Many studies that compared the survival results of liver resection and transplantation for HCC did not take into account deaths among patients who dropped out of the transplantation waiting list.7,8,15,16,19,20 The importance of intention-to-treat analysis in comparing resection and transplantation for HCC was first raised by Llovet et al.,10 who showed that the results of liver transplantation was adversely affected by increasing waiting time, with 2-year intention-to-treat survival decreasing from 84% for 62 days of waiting time to 54% for 162 days of waiting time. In addition, the authors showed that Child A cirrhotic patients without clinically relevant portal hypertension who had undergone partial resection for HCC survived longer than those who had been placed on the waiting list for transplantation. Since liver resection has been shown to achieve long-term survival comparable to that after liver transplantation even in studies that have not taken into account the adverse impact of dropout on overall survival in patients listed for transplantation,15,16 it is reasonable to speculate that liver resection may have produced better long-term survival in such studies if intention-to-treat analysis has been used to include patients who dropped out of the transplantation waiting list.
The dropout of patients from the waiting list also leads to a selection bias in favor of transplanted patients when compared with resected patients. Patients with biologically aggressive tumors are more likely to progress and drop out from the transplant waiting list, leaving a selected group of patients with biologically less aggressive tumors who are able to wait till a liver graft is available. In contrast, such natural selection does not exist among patients who receive liver resection. Such a selection bias may partly contribute to better survival results observed after transplantation in some studies.7,8,20 In a study comparing 43 cirrhotic patients who underwent liver transplantation and 204 cirrhotic patients who underwent liver resection for HCC within the Milan criteria at Queen Mary Hospital, Hong Kong, China, tumors in the transplanted group were associated with lower incidence of high grade tumors, microscopic venous invasion and microsatellite nodules (Poon et al, unpublished data). When differences in tumor invasiveness were corrected, there was no difference in long-term survival after resection and transplantation.
The high dropout rate of HCC patients waiting for deceased donor liver grafts has led to a recent change in graft allocation policy in the United Network of Organ Sharing in the United States. Based on the model for end-stage liver disease (MELD), candidates with early HCC are given a priority MELD score beyond their degree of hepatic decompensation. This has shortened waiting time and decreased the dropout rate of HCC patients listed for transplantation.25,26 However, dropout remains common despite a higher priority being given to HCC patients because there are simply inadequate grafts for all patients with HCC listed for transplantation.4 Reshuffling of graft allocation cannot solve the problem of graft shortage, and it lengthens the waiting time for other patients requiring liver transplantation. In fact, the number of additional points on the MELD scale awarded to HCC patients in the United States has recently been down-scaled because of a concern about the negative impact of the increased number of liver transplantation for HCC on waiting time for those without tumors.5 The shortage of grafts would become even more critical if primary liver transplantation is offered to all Child A cirrhotic patients with early HCC. Without solving the basic problem of organ shortage, the policy of primary liver transplantation for all early HCC associated with cirrhosis is not a sustainable one.
Some authors have advocated the use of live donor liver transplantation to increase the availability of liver grafts for primary transplantation for early HCC in cirrhotic patients with preserved liver function.8,27 However, live donor liver transplantation cannot completely solve the issue of organ shortage. In our experience, about half of the HCC patients who are initially considered for live donor liver transplantation eventually could not have a live donor for various reasons.28 A more important concern of live donor liver transplantation for patients with otherwise resectable HCC is the potential morbidity and mortality of healthy live donors.29 With the unresolved ethical issues, the role of live donor liver transplantation for HCC remains limited.3,30 Compared with the scenario of live donor liver transplantation for a patient with early HCC and advanced cirrhosis who has no other treatment option, it is more arguable whether it is ethical to risk a healthy donor when there is an alternative option of resection with comparable long-term survival. A further concern of live donor liver transplantation for HCC is whether it may produce similar long-term survival results compared with deceased donor liver transplantation. Kulik et al.31 recently reported that a higher recurrence rate, stage for stage, was found in recipients whose transplants were accelerated by performing a live donor transplantation compared with deceased donor transplantation. Until the ethical issues of live donor liver transplantation is settled and the long-term efficacy of live donor liver transplantation for HCC is clarified, the role of live donor liver transplantation for a Child A cirrhotic patient with resectable early HCC remains uncertain.
|
RESECTION FIRST AND SALVAGE TRANSPLANTATION FOR RECURRENCE OR LIVER FAILURE—A STRATEGY TO OPTIMIZE USE OF GRAFTS
|
|---|
The main argument for primary liver transplantation instead of hepatic resection for early HCC in cirrhotic patients with preserved liver function is the high incidence of recurrence after resection. About 80% of recurrent tumors after hepatic resection for HCC occur in the liver remnant, partly because of the multicentric hepatocarcinogenesis in the cirrhotic liver.18 In patients who develop tumor recurrence, salvage transplantation may still be feasible provided the recurrent tumors are within the Milan Criteria. Hepatic resection as the initial treatment and transplantation as a salvage treatment in case of tumor recurrence or liver failure may be the optimal treatment strategy for cirrhotic patients with early HCC and preserved liver function, with several potential advantages.32 Most importantly, such a strategy reduces the use of liver graft because some patients may survive long-term without tumor recurrence after resection of HCC. Patients who have extrahepatic metastasis after hepatic resection are also spared of liver transplantation. The clinical course of such patients suggests that they have tumors with aggressive biology and may not benefit from liver transplantation anyway. Furthermore, for patients who eventually require a salvage transplantation for intrahepatic recurrent HCC, the delay in liver transplantation and hence the need for long-term immunosuppression till tumor recurrence or deterioration of liver function may be of advantage. Finally, hepatic resection is an immediately applicable and simple treatment option. The option of resection first with transplantation for salvage of recurrence maybe more acceptable for a patient with a resectable early HCC, rather than bearing the risk of tumor progression and dropout after being put on a transplant waiting list.
The strategy of resection first and salvage transplantation for recurrence is based on the premises that most recurrent tumors are still transplantable, and that salvage transplantation can achieve long-term survival results close to that of primary transplantation. A previous study by the author on tumor recurrence after resection of potentially transplantable HCC showed that 80% of recurrent tumors detected by regular postoperative surveillance were still transplantable according to the Milan criteria.11 This finding was corroborated by another study by Cha et al.12 A more recent study of 154 patients with recurrent HCC among a cohort of 252 patients with resection of HCC reported that 52% of recurrent tumors were transplantable.33 However, this study included many patients initially with large HCC >5 cm in diameter, who should not be considered transplantable from the outset. If only patients with resection of small HCC were included in the analysis, the transplantability rate of recurrent tumors might have been higher, as the chance of extrahepatic metastasis or diffuse multifocal intrahepatic recurrence is less in such patients compared with those with large HCC. Nonetheless, the authors of the study supported the strategy of salvage transplantation instead of primary transplantation, and they reported that 33% of patients with resection of HCC had no recurrence and were not in need of liver transplantation after a mean follow-up of 72 months. In contrast, Adam et al.8 advocated primary transplantation because in their experience, salvage transplantation was performed only in 17% of recurrent tumors. However, the reasons for the low salvage transplantation rate were not clear in that study. Recently, Margarit et al.16 reported a potential transplantability rate of 72% for 18 recurrences after resection of single HCC less than 5 cm in diameter in Child A cirrhotic patients but an actual salvage transplantation rate of only 28%. The authors found that advanced age >70 years at the time of recurrence was the main factor for the low salvage transplantation rate. It appears that factors other than the pattern of recurrence, such as advanced age at time of recurrence, lack of access to waiting list and patient’s preference account for the low salvage transplantation rate in some settings.34
One concern of salvage transplantation for recurrent HCC is whether it could produce results similar to primary transplantation in terms of operative mortality and long-term survival. Adam et al.8 reported an operative mortality rate of 28.6% after salvage transplantation in 17 patients, compared with that of 2.1% after primary transplantation in 195 patients. The worse operative outcome after salvage transplantation was attributed to the technical difficulties of transplantation in patients with previous hepatic resection. However, two other groups have reported that the operative mortality and other parameters of operative outcome were similar between salvage transplantation and primary transplantation.16,35 Our group has reported no operative mortality among 16 patients with salvage transplantation after previous resection of HCC at Queen Mary Hospital, Hong Kong, China.36 Regarding long-term survival, Adam et al.8 reported worse 5-year survival after salvage transplantation compared with primary transplantation (41% versus 61%), which was partly attributable to the much higher operative mortality rate in the former group. Others have reported similar long-term survival after salvage transplantation and primary transplantation.16,34,35 The favorable results of salvage transplantation reported in these studies have led to the speculation that the poorer outcome reported by Adam et al. may be related to a different era of liver transplantation (the series started in 1984) or to chance events in a small cohort.34 In studies comparing patients with salvage transplantation and those with primary transplantation, only post-transplant survival was compared, and the survival of patients in the interval between resection and transplantation in the former group has not been taken into account. Should this additional survival be added to the survival after salvage transplantation, it is possible that the strategy of resection and salvage transplantation may achieve better overall survival results than primary transplantation, although this needs to be studied prospectively on an intention-to-treat basis.
The concept of salvage transplantation previously advocated by our group applies to patients who have developed recurrence or liver failure and hence requires transplantation as a rescue.11 Some authors have proposed immediate salvage transplantation when adverse tumor pathological features such as microvascular invasion and microsatellite nodules are found, since these features are predictive of early tumor recurrence.35,37 However, this may not be an optimal strategy because patients with these adverse tumor features are also at high risk of recurrence after liver transplantation and are considered less favorable candidates or even contraindications for transplantation. If donor shortage is a major problem, it may be more reasonable to wait and observe whether extrahepatic metastasis will appear before considering salvage transplantation. Margarit et al.16 have recently reported a higher incidence of extra-hepatic recurrence after resection or transplantation for tumors with unfavorable histological criteria and suggested that if known in advance from the resected specimens, the presence of microvascular invasion could be a contraindication for liver transplantation rather than an indication for immediate transplantation. However, this issue requires more data to clarify. In the author’s opinion, immediate salvage transplantation for patients with unfavorable tumor histological features seems unreasonable if optimal graft usage is the main purpose of salvage transplantation instead of primary transplantation.
|
ROLE OF INTERVENTIONAL BRIDGE THERAPIES PRIOR TO TRANSPLANTATION
|
|---|
To reduce the chance of dropout due to tumor progression, interventional therapies such as transarterial chemoembolization (TACE), percutaneous ethanol injection (PEI) and radiofrequency ablation (RFA) are commonly used to control tumors while the patient is put on the waiting list for a graft. Interventional bridging therapies are less invasive than resection. However, tumor control is less radical with interventional therapies than with resection. TACE is the most commonly used bridge therapy prior to liver transplantation, yet there is an ongoing debate whether TACE is able to reduce the dropout rate of patients in the waiting list for liver transplantation or to prolong patient survival.23,38,39 In most patients, TACE can only produce partial tumor necrosis,38–40 and there is a concern that partial necrosis in the tumor nodule may enhance tumor recurrence after liver transplantation.
Ablation therapies such as PEI or RFA can achieve a higher rate of complete tumor necrosis than TACE. In particular, RFA has been shown to achieve a complete tumor necrosis rate of greater than 90%, and it has been shown to be superior to PEI in prospective randomized trials.41,42 However, some studies have shown incomplete tumor necrosis in a significant proportion of liver explants of patients treated with RFA prior to transplantation.43,44 Whether RFA can produce tumor control comparable to that achieved with resection remains uncertain. Furthermore, there is a concern of the risk of needle track seeding after percutaneous RFA. Llovet et al.45 reported a rate of 12.5% of tumor seeding in the needle track, although the risk has been reported to be less than 1% in more recent studies.46,47 The role of interventional bridge therapies prior to liver transplantation has not been fully established yet. For a patient with preserved liver function and a respectable early HCC, resection remains the best choice for tumor control prior to transplantation, and there is a potential for cure without the need of transplantation in a proportion of patients after liver resection.
|
CONCLUSIONS
|
|---|
Based on the results of recent studies, operative mortality and long-term survival after liver resection are similar to those after liver transplantation for early HCC in patients with preserved liver function. Liver transplantation provides the best cure with removal of the cirrhotic liver and hence reduced risk of tumor recurrence from multicentric hepatocarcinogenesis, but this benefit is counteracted by long-term problems specifically associated with transplantation, such as immunosuppression, graft rejection and recurrent viral hepatitis. A premature liver transplantation will expose patients to the side effects of immunosuppressive agents earlier than necessary. Furthermore, patients with early HCC in Child A cirrhosis runs the risk of tumor progression and dropout if put on a transplantation waiting list, whereas liver resection is an immediately applicable option for all patients. This is a major drawback of primary transplantation when it comes to individual consideration for the patients. With the current severe shortage of grafts, to advocate liver transplantation as an initial treatment for all patients with early HCC associated with Child A cirrhosis may not be an optimal use of organs for the community. Such a policy will certainly increase the waiting time for deceased donor liver transplantation and decrease the chance of obtaining a liver graft for other patients with advanced cirrhosis who have no alternative treatment options. The use of live donor liver transplantation, with a potential risk of mortality in a healthy donor, for a condition that is still treatable by resection may not be ethically acceptable. For patients with early HCC associated with Child A cirrhosis, liver resection should remain the initial treatment of choice, and liver transplantation should be reserved as an option for salvage in case of tumor recurrence or liver failure.
Received for publication March 7, 2006.
Accepted for publication April 5, 2006.
|
REFERENCES
|
|---|
- El-Serag HB. Epidemiology of hepatocellular carcinoma. Clin Liver Dis 2001; 5:87–107,vi.[CrossRef][Medline]
- Poon RT, Fan ST, Lo CM, et al. Improving survival results after resection of hepatocellular carcinoma: a prospective study of 377 patients over 10 years. Ann Surg 2001; 234:63–70.[CrossRef][Medline]
- Llovet JM, Schwartz M, Mazzaferro V. Resection and liver transplantation for hepatocellular carcinoma. Semin Liver Dis 2005; 25:181–200.[CrossRef][Medline]
- Schwartz M. Liver transplantation for hepatocellular carcinoma. Gastroenterology 2004; 127(5 Suppl 1):S268–76.[CrossRef][Medline]
- Kurtovic J, Riordan SM, Williams R. Liver transplantation for hepatocellular carcinoma. Best Pract Res Clin Gastroenterol 2005; 19:147–60.[CrossRef][Medline]
- Mazzaferro V, Regalia E, Doci R, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 1996; 334:693–9.[Abstract/Free Full Text]
- Bigourdan JM, Jaeck D, Meyer N, et al. Small hepatocellular carcinoma in Child A cirrhotic patients: hepatic resection versus transplantation. Liver Transpl 2003; 9:513–20.[CrossRef][Medline]
- Adam R, Azoulay D, Castaing D, et al. Liver resection as a bridge to transplantation for hepatocellular carcinoma on cirrhosis: a reasonable strategy? Ann Surg 2003; 238:508–18.[Medline]
- Poon RT, Fan ST, Lo CM, et al. Long-term prognosis after resection of hepatocellular carcinoma associated with hepatitis B-related cirrhosis. J Clin Oncol 2000; 18:1094–101.[Abstract/Free Full Text]
- Llovet JM, Fuster J, Bruix J. Intention-to-treat analysis of surgical treatment for early hepatocellular carcinoma: resection versus transplantation. Hepatology 1999; 30:1434–40.[CrossRef][Medline]
- Poon RT, Fan ST, Lo CM, et al. Long-term survival and pattern of recurrence after resection of small hepatocellular carcinoma in patients with preserved liver function: implications for a strategy of salvage transplantation. Ann Surg 2002; 235:373–82.[CrossRef][Medline]
- Cha CH, Ruo L, Fong Y, et al. Resection of hepatocellular carcinoma in patients otherwise eligible for transplantation. Ann Surg 2003; 238:315–21.[Medline]
- Benckert C, Jonas S, Thelen A, et al. Liver transplantation for hepatocellular carcinoma in cirrhosis: prognostic parameters. Transpl Proc 2005; 37:1693–4.[CrossRef][Medline]
- Ravaioli M, Ercolani G, Cescon M, et al. Liver transplantation for hepatocellular carcinoma: further considerations on selection criteria. Liver Transpl 2004; 10:1195–202.[CrossRef][Medline]
- Shabahang M, Franceschi D, Yamashiki N, et al. Comparison of hepatic resection and hepatic transplantation in the treatment of hepatocellular carcinoma among cirrhotic patients. Ann Surg Oncol 2002; 9:881–6.[Abstract/Free Full Text]
- Margarit C, Escartin A, Castells L, Vargas V, Allende E, Bilbao I. Resection for hepatocellular carcinoma is a good option in Child–Turcotte–Pugh class A patients with cirrhosis who are eligible for liver transplantation. Liver Transpl 2005; 11:1242–51.[CrossRef][Medline]
- Bechstein WO, Guckelberger O, Kling N, et al. Recurrence-free survival after liver transplantation for small hepatocellular carcinoma. Transpl Int 1998; 11(Suppl 1):S189–92.[Medline]
- Poon RT, Fan ST, Wong J. Risk factors, prevention and management of postoperative recurrence after resection of hepatocellular carcinoma. Ann Surg 2000; 232:10–24.[CrossRef][Medline]
- Otto G, Heuschen U, Hofmann WJ, et al. Survival and recurrence after liver transplantation versus liver resection for hepatocellular carcinoma: a retrospective analysis. Ann Surg 1998; 227:424–32.[CrossRef][Medline]
- Figueras J, Jaurrieta E, Valls C, et al. Resection or transplantation for hepatocellular carcinoma in cirrhotic patients: outcomes based on indicated treatment strategy. J Am Coll Surg 2000; 190:580–7.[CrossRef][Medline]
- Poon RT, Fan ST, Lo CM, Liu CL, Wong J. Intrahepatic recurrence after hepatectomy for hepatocellular carcinoma: long-term results of management and prognostic factors. Ann Surg 1999; 229:216–22.[CrossRef][Medline]
- Yao F, Bass NM, Nikolai B, et al. Liver transplantation for hepatocellular carcinoma: analysis of survival according to the intention-to-treat principle and dropout from the waiting list. Liver Transpl 2002; 8:873–83.[CrossRef][Medline]
- Maddala YK, Stadheim L, Andrews JC, et al. Drop-out rates of patients with hepatocellular cancer listed for liver transplantation: outcome with chemoembolization. Liver Transpl 2004; 10:449–55.[CrossRef][Medline]
- Pierie JP, Muzikansky A, Tanabe KK, Ott MJ. The outcome of surgical resection versus assignment to the liver transplant waiting list for hepatocellular carcinoma. Ann Surg Oncol 2005; 12:552–60.[Abstract/Free Full Text]
- Sharma P, Balan V, Hernandez JL, et al. Liver transplantation for hepatocellular carcinoma: the MELD impact. Liver Transpl 2004; 10:36–41.[CrossRef][Medline]
- Yao FY, Bass NM, Ascher NL, Roberts JP. Liver transplantation for hepatocellular carcinoma: lessons from the first year under the model of end-stage liver disease (MELD) organ allocation policy. Liver Transpl 2004; 10:621–30.[CrossRef][Medline]
- Gondolesi G, Munoz L, Matsumoto C, et al. Hepatocellular carcinoma: a prime indication for living donor liver transplantation. J Gastrointest Surg 2002; 6:102–7.[CrossRef][Medline]
- Lo CM, Fan ST, Liu CL, et al. The role and limitation of living donor liver transplantation for hepatocellular carcinoma. Liver Transpl 2004; 10:440–7.[CrossRef][Medline]
- Brown RS Jr, Russo MW, Lai M, et al. A survey of liver transplantation from living adult donors in the United States. N Engl J Med 2003; 348:818–25.[Abstract/Free Full Text]
- Sutcliffe R, Maguire D, Portmann B, Rela M, Heaton N. Selection of patients with hepatocellular carcinoma for liver transplantation. Br J Surg 2005; 93:11–8.[CrossRef]
- Kulik L, Abecassis M. Living donor liver transplantation for hepatocellular carcinoma. Gastroenterology 2004; 127(5 Suppl 1):S277–82.[CrossRef][Medline]
- Poon RT, Fan ST. Resection prior to liver transplantation for hepatocellular carcinoma: a strategy of optimizing the role of resection and transplantation in cirrhotic patients with preserved liver function. Liver Transpl 2004; 10:813–5.[CrossRef][Medline]
- Hu RH, Ho MC, Wu YM, Yu SC, Lee PH. Feasibility of salvage liver transplantation for patients with recurrent hepatocellular carcinoma. Clin Transpl 2005; 19:175–80.[CrossRef]
- Majno P, Mentha G, Mazzaferro V. Resection, transplantation, either, or both? Other pieces of the puzzle. Liver Transpl 2005; 11:1177–80.[CrossRef][Medline]
- Belghiti J, Cortes A, Abdalla EK, et al. Resection prior to liver transplantation for hepatocellular carcinoma. Ann Surg 2003; 238:885–93.[CrossRef][Medline]
- Poon RT, Fan ST. Is primary resection and salvage transplantation for hepatocellular carcinoma a reasonable strategy? Ann Surg 2004; 240:925–8.[CrossRef][Medline]
- Sala M, Fuster J, Llovet JM, et al. High pathological risk of recurrence after surgical resection for hepatocellular carcinoma. An indication for salvage transplantation. Liver Transpl 2004; 10:1294–300.[CrossRef][Medline]
- Graziadei IW, Sandmueller H, Waldenberger P, et al. Chemoembolization followed by liver transplantation for hepatocellular carcinoma impedes tumor progression while on waiting list and leads to excellent outcome. Liver Transpl 2003; 9:557–63.[CrossRef][Medline]
- Decaens T, Roudot-Thoraval F, Bresson-Hadni S, et al. Impact of pretransplantation transarterial chemoembolization on survival and recurrence after liver transplantation for hepatocellular carcinoma. Liver Transpl 2005; 11:767–75.[CrossRef][Medline]
- Ravaioli M, Grazi GL, Ercolani G, et al. Partial necrosis on hepatocellular carcinoma nodules facilitates tumor recurrence after liver transplantation. Transplantation 2004; 78:1780–6.[CrossRef][Medline]
- Lin SM, Lin CJ, Lin CC, Hsu CW, Chen YC. Radiofrequency ablation improves prognosis compared with ethanol injection for hepatocellular carcinoma < or =4 cm. Gastroenterology 2004; 127:1714–23.[CrossRef][Medline]
- Shiina S, Teratani T, Obi S, et al. A randomized controlled trial of radiofrequency ablation with ethanol injection for small hepatocellular carcinoma. Gastroenterology 2005; 129:122–30.[CrossRef][Medline]
- Fontana RJ, Hamidullah H, Nghiem H, et al. Percutaneous radiofrequency thermal ablation of hepatocellular carcinoma: a safe and effective bridge to liver transplantation. Liver Transpl 2002; 8:1165–74.[CrossRef][Medline]
- Wong LL, Tanaka K, Lau L, Komura S. Pre-transplant treatment of hepatocellular carcinoma: assessment of tumor necrosis in explanted livers. Clin Transpl 2004; 18:227–34.[CrossRef]
- Llovet JM, Vilana R, Bru C, et al. Increased risk of tumor seeding after percutaneous radiofrequency ablation for single hepatocellular carcinoma. Hepatology 2001; 33:1124–9.[CrossRef][Medline]
- De Baere T, Risse O, Kuoch V, et al. Adverse events during radiofrequency treatment of 582 hepatic tumors. AJR Am J Roentgenol 2003; 181:695–700.[Abstract/Free Full Text]
- Poon RT, Ng KK, Lam CM, et al. Radiofrequency ablation for subcapsular hepatocellular carcinoma. Ann Surg Oncol 2004; 11:281–9.[Abstract/Free Full Text]
This article has been cited by other articles:
|
|
|
|
 
C. E. Woodall, C. R. Scoggins, J. Loehle, K. V. Ravindra, K. M. McMasters, and R. C. G. Martin
Hepatic Imaging Characteristics Predict Overall Survival in Hepatocellular Carcinoma
Ann. Surg. Oncol.,
October 1, 2007;
14(10):
2824 - 2830.
[Abstract]
[Full Text]
[PDF]
|
|
|
TOP
ABSTRACT
INTRODUCTION
