Endocrine Abstracts

Background: Liver transplantation is now recognized by ENETS as a valid indication for liver-metastatic gastro-entero-pancreatic (GEP) neuroendocrine tumors (NETs). Since 2021, the UK initiated a pilot program for selected patients — specifically, primary amenable to complete resection, low-grade, well-differentiated GEP-NETs, with 6-months stability and <50%-liver-involvement.^1-3

Case-summary: A 34-year-old woman, ECOG-PS-0, non-smoker, non-alcoholic, without significant medical or familial history, presented in March 2013 with transient severe right hypochondriac pain. Suspected of biliary colic, further evaluation was prompted by involuntary weight-loss, fatigue, and mild iron-deficiency anemia. By June 2013, imaging and duodenal-directed biopsy revealed a non-functional, well-differentiated ampullary NET with bilobar liver metastases, showing avid-uptake on Octreoscan. MEN-1 genetic testing was negative. She underwent Whipple’s pancreaticoduodenectomy with synchronous left lateral hepatic segmentectomy. Histopathology confirmed pT4N1M1 ampullary NET, Ki-67-index 3%, involving 4/10 lymph-nodes and liver metastases. She commenced monthly Sandostatin-LAR® 20mg, well-tolerated. The plan included imaging-surveillance and potential liver-directed therapy for residual metastases. Recovery was uneventful aside from a superficial infection, with occasional nausea and mild exocrine insufficiency managed using dietary adjustments, Creon, and proton pump inhibitors. By March 2015 imaging revealed stable disease, but rising chromogranin-A and 5-HIAA levels prompted Lutetium-177 peptide receptor radionuclide therapy (PRRT) initiation. Four well-tolerated cycles completed from May 2015 to June 2016 — achieving maximum response by January 2017. Stable under Sandostatin-LAR® until October 2020, but subtle liver-metastases progression required dose increase to 30mg. Liver surgery and focal treatments were considered but deemed unfeasible due to extensive disease. Following liver-disease progression in April 2021, she started Everolimus 10mg daily — tolerating well despite mild skin rash and pruritus managed with low-dose topical steroids. After 24 cycles, given persistent liver-only disease with limited options, she successfully underwent liver transplantation (piggyback hepatic veins; Roux-en-Y hepaticojejunostomy) in October 2023. Histology confirmed multifocal well-differentiated NET, Ki67-index 7.7%, clear margins. Rapid recovery to PS-ECOG-0, reporting only intermittent mild intention tremors related to tacrolimus immunosuppression. By August 2024, follow-up MRI and Ga-68-DOTATATE-PET scans showed no recurrence, maintaining stable graft and kidney function.

Conclusion: This case highlights the importance of multidisciplinarity, opportune referral, and the life-saving potential of transplantation in selected patients with unresectable liver-metastatic NET.