Living donor liver transplantation with two-stage hepatectomy for patients with isolated, irresectable colorectal liver-the LIVER-T(W)O-HEAL study

Falk Rauchfuß, Silvio Nadalin, Alfred Königsrainer, Utz Settmacher, Falk Rauchfuß, Silvio Nadalin, Alfred Königsrainer, Utz Settmacher

Abstract

Background: Colorectal cancer is the third most common malignancy worldwide. The occurrence of liver metastases worsens the prognosis of the patient significantly if the tumor burden is not resectable. Liver transplantation might be an option for otherwise irresectable colorectal liver metastases. In this study, we evaluate the role of two-stage hepatectomy in combination with a left-lateral living donor liver transplantation.

Methods: Patients with irresectable liver metastases having a stable disease or tumor regression after at least 8 weeks of systemic chemotherapy without an extrahepatic tumor burden (except resectable lung metastases) are suitable for study inclusion. A randomization is not planned since the control arm (systemic chemotherapy) is well established and the superiority of the transplantation procedure has to be expected. The surgical treatment consists of two steps: in a first operation, a left hemihepatectomy in the recipient will be performed. At this place, the left lateral liver lobe (segments II and III) of a living donor will be transplanted. To induce a growth of the graft, a portal vein ligation will be performed. Approximately after 2 weeks, the removal of the right hemiliver will be conducted if the control imaging shows a sufficient growth of the graft.

Results: The patient recruitment is ongoing. In total, three patients have been already transplanted with this protocol. Up to now, they are tumor-free and in good clinical health.

Discussion: With the design of the LIVER-T(W)O-HEAL study, it might be possible to offer patients with otherwise irresectable colorectal liver metastases a curative treatment option. The key point of this study will be, most probably, the patient's selection.

Trial registration: Registered at Clinical Trials; NCT03488953 ; registered on April 5, 2018.

Keywords: ALPPS procedure; Colorectal cancer; Hepatectomy; Liver resection; Living donor liver transplantation; Portal vein ligation.

Conflict of interest statement

Ethics approval and consent to participate

The study protocol and the written patient’s information were approved by the ethics committee of the Jena University Hospital (number 5285-10/17) and University Hospital Tübingen (number 204/2016BO1).

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Estimated patient flow in the LIVER-T(W)O-HEAL-study
Fig. 2
Fig. 2
Step 1: Left hemihepatectomy in the recipient. The resection plane might vary according to the localization of the central metastases in each patient
Fig. 3
Fig. 3
Step 1: Auxiliary transplantation of the left lateral lobe of the donor
Fig. 4
Fig. 4
Step 2: Removal of the right hemiliver (probably 2 weeks after step 1)

References

    1. Allemani C, Matsuda T, Di Carlo V, Harewood R, Matz M, Niksic M, Bonaventure A, Valkov M, Johnson CJ, Esteve J, et al. Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet. 2018;391(10125):1023–1075. doi: 10.1016/S0140-6736(17)33326-3.
    1. Mohammad WM, Balaa FK. Surgical management of colorectal liver metastases. Clin Colon Rectal Surg. 2009;22(4):225–232. doi: 10.1055/s-0029-1242462.
    1. Wasan HS, Gibbs P, Sharma NK, Taieb J, Heinemann V, Ricke J, Peeters M, Findlay M, Weaver A, Mills J, et al. First-line selective internal radiotherapy plus chemotherapy versus chemotherapy alone in patients with liver metastases from colorectal cancer (FOXFIRE, SIRFLOX, and FOXFIRE-Global): a combined analysis of three multicentre, randomised, phase 3 trials. Lancet Oncol. 2017;18(9):1159–1171. doi: 10.1016/S1470-2045(17)30457-6.
    1. Foss A, Lerut JP. Liver transplantation for metastatic liver malignancies. Curr Opin Organ Transplant. 2014;19(3):235–244.
    1. Leporrier J, Maurel J, Chiche L, Bara S, Segol P, Launoy G. A population-based study of the incidence, management and prognosis of hepatic metastases from colorectal cancer. Br J Surg. 2006;93(4):465–474. doi: 10.1002/bjs.5278.
    1. Schnitzbauer AA, Lang SA, Goessmann H, Nadalin S, Baumgart J, Farkas SA, Fichtner-Feigl S, Lorf T, Goralcyk A, Horbelt R, et al. Right portal vein ligation combined with in situ splitting induces rapid left lateral liver lobe hypertrophy enabling 2-staged extended right hepatic resection in small-for-size settings. Ann Surg. 2012;255(3):405–414. doi: 10.1097/SLA.0b013e31824856f5.
    1. Sasaki K, Margonis GA, Andreatos N, Kim Y, Wilson A, Gani F, Amini N, Pawlik TM. Combined resection and RFA in colorectal liver metastases: stratification of long-term outcomes. J Surg Res. 2016;206(1):182–189. doi: 10.1016/j.jss.2016.06.098.
    1. Huang SY, Aloia TA. Portal vein embolization: state-of-the-art technique and options to improve liver hypertrophy. Visc Med. 2017;33(6):419–425. doi: 10.1159/000480034.
    1. Tzeng CW, Aloia TA. Colorectal liver metastases. J Gastrointest Surg. 2013;17(1):195–201. doi: 10.1007/s11605-012-2022-3.
    1. Muhlbacher F, Huk I, Steininger R, Gnant M, Gotzinger P, Wamser P, Banhegyi C, Piza F. Is orthotopic liver transplantation a feasible treatment for secondary cancer of the liver? Transplant Proc. 1991;23(1 Pt 2):1567–1568.
    1. Gorgen A, Muaddi H, Zhang W, McGilvray I, Gallinger S, Sapisochin G. The new era of transplant oncology: liver transplantation for nonresectable colorectal cancer liver metastases. Can J Gastroenterol Hepatol. 2018;2018:9531925. doi: 10.1155/2018/9531925.
    1. Moris D, Tsilimigras DI, Chakedis J, Beal EW, Felekouras E, Vernadakis S, Schizas D, Fung JJ, Pawlik TM. Liver transplantation for unresectable colorectal liver metastases: a systematic review. J Surg Oncol. 2017;116(3):288–297. doi: 10.1002/jso.24671.
    1. Quante AS, Ming C, Rottmann M, Engel J, Boeck S, Heinemann V, Westphalen CB, Strauch K. Projections of cancer incidence and cancer-related deaths in Germany by 2020 and 2030. Cancer Med. 2016;5(9):2649–2656. doi: 10.1002/cam4.767.
    1. Statistical Report 2017 [].
    1. Line PD, Hagness M, Berstad AE, Foss A, Dueland S. A novel concept for partial liver transplantation in nonresectable colorectal liver metastases: the RAPID concept. Ann Surg. 2015;262(1):e5–e9. doi: 10.1097/SLA.0000000000001165.
    1. Konigsrainer A, Templin S, Capobianco I, Konigsrainer I, Bitzer M, Zender L, Sipos B, Kanz L, Wagner S, Nadalin S. Paradigm shift in the management of irresectable colorectal liver metastases: living donor auxiliary partial orthotopic liver transplantation in combination with two-stage hepatectomy (LD-RAPID). Ann Surg. 2018. [Epub ahead of print].
    1. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205–213. doi: 10.1097/.
    1. Nadalin S, Malago M, Radtke A, Erim Y, Saner F, Valentin-Gamazo C, Schroder T, Schaffer R, Sotiropoulos GC, Li J, et al. Current trends in live liver donation. Transpl Int. 2007;20(4):312–330. doi: 10.1111/j.1432-2277.2006.00424.x.
    1. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1) Eur J Cancer. 2009;45(2):228–247. doi: 10.1016/j.ejca.2008.10.026.
    1. Nadalin S, Capobianco I, Konigsrainer I, Harder B, Konigsrainer A: [Living liver donor: indications and technical aspects]. Chirurg 2015, 86(6):609–621; quiz 622.
    1. Troisi RI, Berardi G, Tomassini F, Sainz-Barriga M. Graft inflow modulation in adult-to-adult living donor liver transplantation: a systematic review. Transplant Rev (Orlando) 2017;31(2):127–135. doi: 10.1016/j.trre.2016.11.002.
    1. Gray R. A class of K-sample tests for comparing the cumulative incidence of a competing risk. Ann Stat. 1988;16:1140–1154. doi: 10.1214/aos/1176350951.
    1. Schaefer B, Zoller H, Schneeberger S. Con: liver transplantation for expanded criteria malignant diseases. Liver Transpl. 2018;24(1):104–111. doi: 10.1002/lt.24975.
    1. Mazzaferro V, Battiston C, Sposito C. Pro (With Caution): extended oncologic indications in liver transplantation. Liver Transpl. 2018;24(1):98–103. doi: 10.1002/lt.24963.
    1. Dueland S, Guren TK, Hagness M, Glimelius B, Line PD, Pfeiffer P, Foss A, Tveit KM. Chemotherapy or liver transplantation for nonresectable liver metastases from colorectal cancer? Ann Surg. 2015;261(5):956–960. doi: 10.1097/SLA.0000000000000786.
    1. Grut H, Solberg S, Seierstad T, Revheim ME, Egge TS, Larsen SG, Line PD, Dueland S. Growth rates of pulmonary metastases after liver transplantation for unresectable colorectal liver metastases. Br J Surg. 2018;105(3):295–301. doi: 10.1002/bjs.10651.

Source: PubMed

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

3
Abonnieren