Cholangiocarcinoma (CCA) accounts for <2% of all human malignancies and only 10% of hepatobiliary malignancies. The 1-year survival rate for patients with CCA is around 25%. Survival can be improved with grossly complete surgical resection. Unfortunately, CCA often presents (50–90%) with advanced stage (III and IV) and locoregional spread, making this complete resection difficult or impossible. The surgical resection must be extensive, often including partial hepatectomy 1.
Alternatively, some have advocated complete hepatectomy and transplantation 2; however, liver transplantation offers no improvement in survival when compared to hepatic resection, and it taxes an already inadequate donor organ supply.
Table 1 summarises the results for transplantation in patients who have CCA 3,4,5,6,7,8,9,10,11. In series that did not emphasise highly selected early stage disease and neoadjuvant or adjuvant radiation and chemotherapy, the average 1-year, 3-year and 5-year survival rates are 43%, 30% and 10%, respectively 3,4,5,6,7. In the study by Goss and colleagues 8, patients with incidental CCAs treated with transplantation had a 5-year survival rate of 83% (incidental CCAs were lesions <1 cm diameter that were discovered on pathological examination of the explanted liver). However, patients in this same study with known CCA had a 5-year survival of 0% 8. The literature is replete with dismal survival rates after transplantation for CCA. Additionally, there is a high rate of early recurrence (65% at 1 year) among patients receiving transplants for CCA, probably influenced by immunosuppression 12.
Table 1. Survival after liver transplantation for CCA.
| Author | Institution | n | 1-year | 2-year | 3-year | 5-year |
|---|---|---|---|---|---|---|
| Cincinnati registry | 109 | … | 30% | … | 4% | |
| Ringe 3 | Hannover | 30 | 38% | 32% | … | 14% |
| Bismuth 4 | Paul Brousse | 9 | … | … | 33% | … |
| Nashan 5 | Hannover | 10 | 30% | … | 10% | |
| O'Grady 6 | King's College | 26 | 34% | 15% | 8% | 5% |
| Shimoda 7 | UCLA | 25 | 71% | … | 35% | … |
| Goss 8 | UCLA (known) | 4 | 33% | 33% | … | 0% |
| Goss 8 | UCLA (incidental) | 10 | 90% | … | 83% | 83% |
| Iwatsuki 9 | Pittsburgh* | 27 | 60% | 36% | 36% | 36% |
| DeVreede 10 | Mayo* | 11 | 100% | 100% | 100% | 80% |
| Sudan 11 | Nebraska* | 11 | 55% | 45% | 45% | … |
*Neoadjuvant or adjuvant radiation and chemotherapy emphasized.
Highly selected patients found in the study by DeVreede and associates demonstrated an 80% 5-year survival 10. To arrive at this statistic, 10 of the 11 patients transplanted were stage I and II patients who underwent external beam irradiation plus bolus 5-fluorouracil (5-FU), followed by brachytherapy with iridium plus 5-FU infusion, followed by exploratory laparotomy, and finally a continuous 5-FU infusion until transplantation. Furthermore, eight additional patients did not make it through this treatment filter. Sudan, and co-workers using a protocol of intense brachytherapy and 5-FU reached a 3-year survival of 45% and an anticipated 5-year survival of better than 36% in 11 transplanted patients 11. However, five other patients did not make it through this protocol. In all studies in which 5-year survival rates of >30% were demonstrated, the tumours were predominantly of low stage (I and II) and the patients were highly selected through a gruelling neoadjuvant regimen 10,11. Furthermore, an appreciable proportion of patients died from the complications of the therapy. On an intention-to-treat basis, the survival figures are therefore much worse.
If anatomically possible (Bismuth type I, II and III), resection should be applied rather than transplantation. Table 2 shows the results after resection of CCA from several centres. The 1-, 3- and 5-year survival rates were 70%, 35% and 25%, respectively 13,14,15,16,17,18,19,20,21,22,23. Venishi and colleagues reported 5-year survival of 86% after liver resection for patients with stage II CCA 13. These outcomes are better than those for liver transplantation. Furthermore, after liver resection, surgical mortality and morbidity average about 10% and 30%, respectively; while mortality and morbidity after liver transplantation are 16% and 53% 15. Therefore, liver resection offers comparable or better survival and fewer perioperative complications than liver transplantation and does not waste a graft.
Table 2. Survival after resection for cholangiocarcinoma.
| Author | Institution | n | 1-year | 3-year | 5-year |
|---|---|---|---|---|---|
| Uenishi 13 | Osaka (stage I + II) | 10 | 100% | 86% | 86% |
| (stage III + IV) | 43% | 14% | 0% | ||
| Pinson 14 | Lahey Clinic | 25 | 84% | 44% | 35% |
| Baer 15 | Berne University | 20 | 70% | 47% | … |
| Jarnigan 16 | MSKCC | 80 | 80% | 50% | 27% |
| Klempnauer 17 | Hannover | 136 | 80% | 40% | 28% |
| Neuhaus 18 | Berlin | 80 | 67% | … | 22% |
| Lillemoe 19 | Hopkins | 109 | 68% | 30% | 11% |
| Ogura 20 | Mie University | 66 | 60% | 35% | 20% |
| Launois 21 | Hop. Pontchaillou | 36 | 70% | 28% | 13% |
| Bismuth 22 | Paul Brousse | 23 | 87% | 25% | … |
| Madriga 23 | Pittsburgh | 62 | 73% | 40% | 21% |
With an inadequate supply of donor livers for transplantation, it is a misappropriation of these resources to use these grafts generally for a procedure in which only 10% of the recipients are likely to be alive after 5 years. Instead, the grafts can be used for patients with liver diseases in which transplantation yields a 5-year survival rate of around 80%. However, under strict research protocols, it is reasonable to continue transplantation only for the very small subset of anatomically unresectable (Bismuth type IV) patients with stage I and II CCA.
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