American Journal of Transplantation 2008; 8: 1085–1086Blackwell Munksgaard

C© 2008 The AuthorsJournal compilation C© 2008 The American Society of

Transplantation and the American Society of Transplant Surgeons

doi: 10.1111/j.1600-6143.2008.02193.xEditorial

Salvage Transplantation: Does SavingLivers Save Lives?

J.F. Botha∗ and B.D. Campos

Department of Surgery, University of Nebraska MedicalCenter, Nebraska Medical Center, Omaha, NE∗Corresponding author: Jean F. Botha, jbotha@unmc.edu

Received 27 December 2007, revised and accepted forpublication 28 January 2008

Liver transplantation remains the most effective treatmentfor patients with both hepatocellular carcinoma that arewithin Milan criteria (HCC) and cirrhosis, including thosewith well-compensated cirrhosis. Numerous studies overthe past decade have documented patient survival ratesgreater than 75% at 4 years with HCC recurrence ratesof less than 10%, which compares favorably with all otherforms of treatment including liver resection (1). As a resultliver transplantation is often considered to be the treatmentof choice for many patients. Limited availability of donorlivers has resulted in prolonged waiting times with the po-tential for tumor progression and subsequent ‘drop out’from the waiting list. For many patients, in the absence ofHCC, progressive liver disease with decompensation maybe years away. For these reasons many programs haveproposed liver resection as the primary treatment for pa-tients followed by salvage transplantation in the event ofHCC recurrence or liver failure.

A surgical plan of liver resection followed with salvageliver transplantation may have some distinct advantages.Firstly, there is immediate access to an effective and rel-atively safe form of therapy. Secondly, transplantation canbe delayed until the time of recurrence or development ofdecompensation. Thirdly, is the ability to avoid transplanta-tion in patients that are at risk of developing metastasis andin whom transplantation would not provide a survival ad-vantage. Lastly, patients could delay exposure to the risksof transplantation and immunosuppression. Furthermore,some patients will survive long term after resection with-out recurrence or decompensation, thus reducing the loadon the donor pool. In this issue of the journal, Del Gau-dio and colleagues from the University of Bologna presenttheir experience with the strategy of liver resection fol-lowed by transplantation (2). They demonstrated that suchan approach is surgically feasible and can be carried out

with low morbidity and mortality. What is less certain iswhether such a strategy provides patients with the besttreatment.

The strategy of salvage transplantation for HCC recurrenceafter liver resection is based on the premise that most pa-tients will still be transplantable at the time of HCC recur-rence. Del Gaudio et al. compared the outcome of 159patients with HCC treated with primary liver transplanta-tion to a group of 86 patients who were eligible for ei-ther transplantation or resection but were treated withliver resection. Forty-seven patients (54.6%) in the liverresection group developed HCC recurrence in the rem-nant liver within 5 years. They did not report the rate ofrecurrence in the patients that underwent primary livertransplantation. In this study we find that more than halfof the resection patients that developed recurrent HCCwithin the liver were no longer transplant candidates. Sev-enteen (36%) patients had tumors outside of Milan cri-teria and a further seven patients were over 65 yearsold and beyond this program’s cutoff age for transplan-tation. Only 10 patients with HCC recurrence were ableto undergo salvage transplantation, a salvage transplantrate of only 21.2%. One could suggest that closer follow-up may have detected the recurrent tumors before theywere outside Milan guidelines. The 65-year age limit isprobably not one that is applicable to many US programs.On the other hand, waitlist times in the United Statesfor patients with HCC requiring transplantation are lessthan 6 months, a fact that favors transplantation overresection.

Salvage transplant rates have been reported from othergroups in a range of 16.2% and 25% respectively (3–5).Poon et al. reported a HCC recurrence rate of 51% in pa-tients treated primarily with liver resection. In their theoret-ical analysis of this sub-group of patients they found that79% would have met criteria for transplantation at the timeof recurrence. These results have not been translated intoreality (6). Others have not been able to duplicate theseresults and in all the other studies, including the one byDel Gaudio, on average only one out of five patients whounderwent liver resection benefited from a salvage trans-plant. This was mainly as a result of recurrence outsideof Milan criteria, outside of age cutoffs, as well as deathon the waiting list. This low salvage rate may represent alost opportunity for a number of patients who, had they

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Botha and Campos

received a primary transplant may have had better long-term survival. For these patients the potential for cure hasbeen lost.

Therefore, if we are going to propose resection to thepatient with HCC and cirrhosis we are potentially treat-ing the patient with an option that gives this patient agreater chance of recurrence and a questionable overallsurvival when compared to primary liver transplantation.Still there is no question that a certain number of indi-viduals will receive effective and durable results with re-section while others avoid a liver transplant that wouldnot have conferred a survival advantage. The key stillrests in trying to identify these people in a prospectivemanner. It is hoped that the clinical application of newmolecular markers of HCC will allow us to reliably iden-tify these patients and better guide our current forms oftreatment. The answers still elude us and in the upcom-ing decade of rising HCC incidence, limited organ sup-ply and high mortality and dropout rates of cirrhotic pa-tients awaiting transplantation, more work still needs tobe done. The answer becomes, to some extent, an ethicaldilemma.

References

1. Mazzaferro V, Regalia E, Doci R et al. Liver transplantation for thetreatment of small hepatocellular carcinomas in patients with cir-rhosis. N Engl J Med 1996; 334: 693–699.

2. Del Gaudio M, Ercolani G, Ravaioli M et al. Liver transplantation forrecurrent hepatocellular carcinoma on cirrhosis after liver resection:University of Bologna experience. Reference not yet in press in AJT:Manuscript Number: AJT-O-07–00063.R2

3. Margarit C, Escartin A, Castells L, Vargas V, Allende, Bilbao I. Resec-tion of hepatocellular carcinoma is a good option in Child-Turcotte-Pugh class a patients with cirrhosis who are eligible for transplan-tation. Liver Transpl 2005; 11: 1177–1180.

4. Llovet JM, Fuster J, Bruix J. Intention to treat analysis of surgi-cal treatment of early hepatocellular carcinoma: Resection versustransplantation. Hepatology 1999; 30: 1434–1440.

5. Belghiti J, Cortes A, Abdalla EK et al. Resection prior to liver trans-plantation for hepatocellular carcinoma. Ann Surg 2003; 238: 885–893.

6. Poon RT, Fan ST, Lo CM et al. Long-term survival and pattern ofrecurrence after resection of small hepatocellular carcinoma in pa-tients with preserved liver function: Implications for a strategy ofsalvage transplantation. Ann Surg 2002; 235: 373–382.

1086 American Journal of Transplantation 2008; 8: 1085–1086