THE FUTURE OF TRANSPLANTATION IN HPB ONCOLOGY

Alvaro Alcaraz MD*

*Liver and Pancreas Transplant Program. HPB Surgery department.

Hospital Privado Universitario de Córdoba. Instituto Universitario de Ciencias Biomedicas de Cordoba

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Perihiliar and Intrahepatic Cholangiocarcinoma

Hepatoblastoma

Colorectal Cancer Liver Metastases

Neuroendocrine Liver Metastases

What is Transplant Oncology?

Hepatocellular Carcinoma

Glimps into the Future

What is Transplant Oncology?“Concept encompassing multiple disciplines of transplantation medicine

and oncology designed to push the envelope of the treatment and research of hepatobiliary cancers.”

Four E´s of Transplant Oncology

T. Hibi and G. Sapisochin, What is transplant oncology? Surgery, https://doi.org/10.1016/j.surg.2018.10.024

Hepatocellular Carcinoma

Mazzaferro V , Regalia E , Doci R , Andreola S , Pulvirenti A , Bozzetti F , et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med . 1996;334:693–699 .

Aucejo F, Kim R. Can Milan criteria be expanded effectively for liver transplantation in patients with HCC? Transl Gastrointest Cancer 2015;4(4):313-315. doi: 10.3978/j.issn.2224-4778.2015.07.08Xu X, Lu D, Ling Q, Wei X, Wu J, Zhou L, et al. Liver transplantation for hepatocellular carcinoma beyond the Milan criteria. Gut. 2016 Jun;65(6):1035-41. doi: 10.1136/gutjnl-2014-308513.

1. New drugs for HCV diminishes the incidence and allows expanding criteriawithout harming others in the waiting list.

2. Adult to adult LDLT for HCC beyong Milan

3. Biological Markers (AFP) helps better prediction of OS and recurrence

4. Molecular and genetic analyses and investigations into the relationship of tumor biology and recurrence

Neuroendocrine Liver Metastases

Mazzaferro V , Pulvirenti A , Coppa J . Neuroendocrine tumors metastatic to the liver: How to select patients for liver transplantation? J Hepatol. 2007;47:460–466 .Mazzaferro V , Sposito C , Coppa J , Miceli R , Bhoori S , Bongini M , et al. The Long-term benefit of liver transplantation for hepatic metastases from neuroen- docrine tumors. Am J Transplant . 2016;16:2892–2902 .

Perihiliar Cholangiocarcinoma

De Vreede I , Steers JL , Burch PA , Rosen CB, et al. Prolonged disease-free survival after orthotopic liver transplanta- tion plus adjuvant chemoirradiation for cholangiocarcinoma. Liver Transpl . 20 0 0;6:309–316 .Rea DJ , Heimbach JK , Rosen CB , Haddock MG , Alberts SR , Kremers WK , et al. Liver transplantation with neoadjuvant chemoradiation is more effective than resection for hilar cholangiocarcinoma. Ann Surg . 2005;242:451–458 dis- cussion 8–61 .

Perihiliar Cholangiocarcinoma

Intrahepatic Cholangiocarcinoma

Sapisochin G , Facciuto M , Rubbia-Brandt L , Marti J , Mehta N , Yao FY , et al. Liver transplantation for "very early" intrahepatic cholangiocarcinoma: Interna- tional retrospective study supporting a prospective assessment. Hepatology . 2016;64:1178–1188 .

January 2000 and December 2013, 25.016 LT were performed at the 17 institutions. Pathological examonation.

Lunsford K, Javle M, Heyne K, Rachna T. Excellent Outcomes for Liver Transplantation for Locally Advanced Intrahepatic Cholangiocarcinoma Comparable to Locally Advanced Hilar Cholangiocarcinoma: a Single Center Experience

Hepatoblastoma

Lim et al, Hepatoblastoma- the evolution of biology, surgery and transplantation. Children 2019, 6, 1; doi:10.3390/children6010001

Ruiz Figueroa et al. Monosegmental ALPPS: a long-term survival alternative to liver transplant in PRETEXT IV hepatoblastoma. Journal of Surgical Case Reports, 2019;5, 1–4

1. Few studies have identified a clear mechanistic pathway of this tumor

2. Current 5-year event-free survival (EFS) rates for patients with lower risk HB approach 80% [5] but may be significantly worse (30–40%) for relapsed or higher risk HB

3. Determination of histological subtype is becoming increasingly important as it can change the treatment algorithm

4. HB treatment has evolved from a singular treatment plan to a risk-stratified management strategy.

Colorectal Liver Metastases

MorisD,TsilimigrasDI,ChakedisJ,etal.Livertransplantationforunresectable colorectal liver metastases: a systematic review. J Surg Oncol 2017; 116:288 – 297. T. Hibi and G. Sapisochin, What is transplant oncology? Surgery, https://doi.org/10.1016/j.surg.2018.10.024

• Abandoned, given the dismal prognoses in the early 1990s

• SECA I study: 60% survival at 5 years. High recurrence rate.

• Toso et al. on behalf of the ‘Compagnons Hepato-biliaires,’ multiinstitutional retrospective cohort study: similar results.

• Organ shortage and ethical issues

Colorectal Liver Metastases

Line PD , Hagness M , Berstad AE , Foss A , Dueland S . A novel concept for par- tial liver transplantation in nonresectable colorectal liver metastases: The RAPID concept. Ann Surg . 2015;262:e5–e9 .T. Hibi and G. Sapisochin, What is transplant oncology? Surgery, https://doi.org/10.1016/j.surg.2018.10.024

• RAPID concept (Resection And Partial Liver Segment 2/3 Transplantation With Delayed Total Hepatectomy)->ALPPS with living donor LT of segments 2 and 3, followed by total hepatectomy.

• SECA II study (NCT01479608) includes a phase 3 trial, comparing deceased donor LT with liver resection

• TRANSMET study: Liver Transplantation in Patients With Un-resectable Colorectal Liver Metastases Treated by Chemotherapy .

Glimps into the Future• New Chemotherapy and ¨Push the limits¨ resections

Glimps into the Future

Glimps into the Future

Glimps into the Future

Glimps into the Future• Evolution of multidisciplinary cancer care by integrating LT.

• Autotransplantation with ex vivo “back table”.

• Ante situm resection of the liver, combined

with hypothermic perfusion .

• Extended Criteria.

• Multiorgan transplant.

• RAPID concept.

• TRANSMET and SECA II study.

• Exploration of biomechanism of disease through genomic studies

Is there an impossible outcome?

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