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When Should We Propose Liver Transplant After Resection of Hepatocellular Carcinoma? A Comparison of Salvage and De Principe Strategies

  • 2015 SSAT Plenary Presentation
  • Published:
Journal of Gastrointestinal Surgery Aims and scope

Abstract

Introduction

The aim of this study was to compare survival outcomes in patients enlisted for liver transplantation following liver resection for hepatocellular carcinoma before or at recurrence.

Methods

All patients enlisted for liver transplantation following liver resection for hepatocellular carcinoma from 1996 to 2013 were included and compared according to their status at the time of enlistment: before (de principe) or at (salvage) recurrence. Primary end-point was survival since resection.

Results

One hundred and twenty-one patients were enlisted for liver transplantation following liver resection for hepatocellular carcinoma. Ten patients enlisted for cirrhosis decompensation were excluded from the analysis. Sixty-three patients were enlisted de principe, and 48 for a salvage transplantation. Eleven patients dropped-out. According to per-protocol analysis, the mean diameter of the largest tumor was the only different pathological characteristic of initial resection between groups (31.6 mm in the de principe group versus 48.3 in the salvage, p = 0.017). The 5-year overall survival rate was significantly increased in the de principe group compared to salvage (84.6 versus 74.8 %, p = 0.017). In a multivariate analysis, the salvage strategy was the only independent prognostic factor for death (p = 0.040; OR = 2.5 [1.1–5.8]).

Conclusion

De principe enlistment for liver transplantation following liver resection for hepatocellular carcinoma is associated with greater survival.

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Author information

Authors and Affiliations

  1. Hepato-Biliary and Pancreatic Surgery and Liver Transplantation Department, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Paris VII University, Clichy, France

    Ecoline Tribillon, Louise Barbier, Sabine Irtan, Jacques Belghiti & Olivier Soubrane

  2. Digestive, Hepato-Biliary and Pancreatic Surgery Department, Pitié Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, Paris VI University, Paris, France

    Claire Goumard, Fabiano Perdigao-Cotta & Olivier Scatton

  3. Hepatology Department, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Paris VII University, Clichy, France

    François Durand

  4. Pathology Department, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Paris VII University, Clichy, France

    Valérie Paradis

Authors
  1. Ecoline Tribillon
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  2. Louise Barbier
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  3. Claire Goumard
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  4. Sabine Irtan
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  5. Fabiano Perdigao-Cotta
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  6. François Durand
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  7. Valérie Paradis
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  8. Jacques Belghiti
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  9. Olivier Scatton
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  10. Olivier Soubrane
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Corresponding author

Correspondence to Olivier Soubrane.

Additional information

Primary Discussant

Sean P. Cleary, M.D. (Toronto, ON, Canada)

Thank you for that excellent presentation. You and your colleagues at Beaujon and Pitié Salpêtrière are to be congratulated on this excellent work that provides an insight into this truly unique experience in de principe transplantation at your centers. The concept of de principe transplantation is certainly an attractive one given the mixed outcomes of salvage transplantation and the frequency with which patients develop recurrence outside of transplant criteria following resection.

1. In order for us to properly understand this retrospective analysis, I wonder if you could give us some indication as to how patients were for the de principe approach? It would seem from the data that patients in the de principe group had a higher rate of severe fibrosis and non-anatomic resections. Was the decision to list the patient for the de principe approach based on preoperative or postoperative pathologic factors?

2. In your proposed algorithm, you suggest limiting the de principe approach to patients who are within Milan criteria but have negative prognostic factors at the time of resection. Do you feel there is any benefit to de principe transplantation in patients that do not meet that criteria either because of good prognostic features or cancers outside Milan? The latter outside Milan group would be of particular interest given the implications that patients could be downstaged by resection prior to transplantation.

3. Finally, a skeptical view of these results would suggest that the improved outcomes of the de principe group are largely the result of patients who did not have recurrence at the time of transplantation, since the outcome patients who had recurrence in the de principe group appear similar to those treated with salvage transplantation. Furthermore, skeptics might also suggest that patients transplanted de principe without recurrence might not need transplantation. How would you and your group respond to these skeptics?

Closing Discussant

Dr. Tribillon

1. The decision to list the patient for a de principe liver transplantation was based on postoperative pathological factors. This strategy was adopted in both centers following the analysis of their respective series. The prognostic factors that were considered to decide whether the patient would be enlisted de principe or not were as follows: vascular invasion, differentiation, satellite nodules, margins, and underlying cirrhosis. Indeed, this can explain the higher rate of severe fibrosis in the de principe group.

2. It is true that limiting indications for liver transplantation to patients who fulfill Milan criteria is a concern, as these criteria are very restrictive. But, at this time, there is no evidence for us to answer that question. However, our feeling is that regarding patients beyond Milan criteria, primary liver resection, and the use of pathological analysis of the resected specimen, could allow us to identify a sub-group of patients who could benefit from a secondary liver transplantation, as part of a downstaging strategy.

3. I totally understand your point of view. It is not surprising that these patients had better survival outcomes since some of them did not recur at the time of liver transplantation. But, a patient who once had hepatocellular carcinoma, even if it was resected, should not be considered the same as a patient who never had tumoral history. For patients who underwent liver resection for hepatocellular carcinoma, if bad prognostic factors are present at pathological analysis, the recurrence rate can reach 80 %. For these patients, we think it is legitimate to propose liver transplantation before tumor recurrence.

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Tribillon, E., Barbier, L., Goumard, C. et al. When Should We Propose Liver Transplant After Resection of Hepatocellular Carcinoma? A Comparison of Salvage and De Principe Strategies. J Gastrointest Surg 20, 66–76 (2016). https://doi.org/10.1007/s11605-015-3018-6

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  • DOI: https://doi.org/10.1007/s11605-015-3018-6

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