Liver transplantation and neuroendocrine tumors: lessons from a single centre experience and from the literature review

Abstract

Summary Neuroendocrine tumor (NET) metastases represent at this moment the only accepted indication of liver transplantation (LT) for liver secondaries. Between 1984–2007, nine (1.1%) of 824 adult LTs were performed because of NET. There were five well differentiated functioning NETs (four carcinoids and one gastrinoma), three well differentiated non functioning NETs and one poorly differentiated NET. Indications for LT were an invalidating unresectable tumor (4×), and/or a diffuse tumor localization (3×) and/or a refractory hormonal syndrome (5×). Median post‐LT patient survival is 60.9 months (range 4.8–119). One‐, 3‐ and 5‐year actuarial survival rates are 88%, 77% and 33%; 1, 3 and 5 years disease free survival rates are 67%, 33% and 11%. Due to a more rigorous selection procedure, results improved since 2000; three out of five patients are alive disease‐free at 78, 84 and 96 months. Review of these series together with a review of the literature reveals that results of LT for this oncological condition can be improved using better selection criteria, adapted immunosuppression and neo‐ and adjuvant surgical as well as medical tretament. LT should be considered earlier in the therapeutic algorithm of selected NET patients as it is the only therapy that can offer a cure.

Neuroendocrine tumor disease: an evolving landscape

“…In contrast to liver secondaries of adenocarcinomas, nonresectable neuroendocrine LM are an indication for LT under consideration of strict evaluation process (Lerut et al 2007, Bonaccorsi-Riani et al 2010, Gedaly et al 2011. While nonresectable extrahepatic tumor manifestation, Ki-67% O15%, and severe carcinoid heart disease are generally accepted as exclusion criteria for LT, patient age (!50 vs O50 years), the dynamics of the hepatic tumor growth (stable disease vs rapid tumor progress), the extent of hepatic involvement, and timing of transplantation (first-line treatment vs an ultima ratio approach after unsuccessful previous treatment) remain controversial (Olausson et al 2002, Rosenau et al 2002, Le Treut et al 2008.…”

GEP–NETS UPDATE: A review on surgery of gastro-entero-pancreatic neuroendocrine tumors

“…The review of the European Liver Transplant Registry (ELTR) data reveals that the transplant experience in NET patients is limited and ill defined (80). Moreover, all usable information about the value of LT in the treatment of NETs comes from small, single-center series and from two multicentric retrospective studies (81,82).…”

Pancreatic neuroendocrine tumor accompanied with multiple liver metastases

“…Effective and beneficial treatment options for P-NET patients with liver metastases should be carefully considered. From the viewpoint of surgical option, surgical indications for primary tumor [1,[4][5][6]16] and hepatic surgery, including LT for liver metastases [1,10,20,[24][25][26][27][28] have already been stated. However, it seems to be not easy to decide optimal timing of surgery for primary tumor and liver metastases.…”

“…In the last decade, selection criteria based on clinical presentation have been integrated with a proper histopathologic classification and diagnostic techniques [21] . In particular, Ki67 expression has been considered as a prognostic factor of risk of recurrence [21,[24][25][26][27][28] . A Ki67 proliferation index of < 10% is a characteristic of welldifferentiated tumor, which we have adopted as a cutoff value to consider GEP-NET patients for LT candidates [21,24] .…”

“…A Ki67 proliferation index of < 10% is a characteristic of welldifferentiated tumor, which we have adopted as a cutoff value to consider GEP-NET patients for LT candidates [21,24] . Current studies suggest a growing consensus concerning LT for liver metastases of P-NET as follows [20,[24][25][26][27][28] : (1) liver metastases of symptomatic or asymptomatic P-NET are unresectable; (2) disease is confined to the liver, and extrahepatic metastases are ruled out; (3) LT is indicated for well-differentiated P-NET categorized as GEP-NET G1/G2. Poorly differentiated P-NET categorized as GEP-NET G3 is considered as a contraindication for LT. Ki67 index < 10% is recommended; and (4) LT should not be associated with major extrahepatic resection.…”