Transarterial Embolization of Liver Cancer in a Transgenic Pig Model

Fuad Nurili, Sebastien Monette, Adam O. Michel, Achiude Bendet, Olca Basturk, Gokce Askan, Christopher Cheleuitte-Nieves, Hooman Yarmohammadi, Aaron W.P. Maxwell, Etay Ziv, Kyle M. Schachtschneider, Ron C. Gaba, Lawrence B. Schook, Stephen B. Solomon, F. Edward Boas

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: To develop and characterize a porcine model of liver cancer that could be used to test new locoregional therapies. Materials and Methods: Liver tumors were induced in 18 Oncopigs (transgenic pigs with Cre-inducible TP53R167H and KRASG12D mutations) by using an adenoviral vector encoding the Cre-recombinase gene. The resulting 60 tumors were characterized on multiphase contrast-enhanced CT, angiography, perfusion, micro-CT, and necropsy. Transarterial embolization was performed using 40–120 μm (4 pigs) or 100–300 μm (4 pigs) Embosphere microspheres. Response to embolization was evaluated on imaging. Complications were determined based on daily clinical evaluation, laboratory results, imaging, and necropsy. Results: Liver tumors developed at 60/70 (86%) inoculated sites. Mean tumor size was 2.1 cm (range, 0.3–4 cm) at 1 week. Microscopically, all animals developed poorly differentiated to undifferentiated carcinomas accompanied by a major inflammatory component, which resembled undifferentiated carcinomas of the human pancreatobiliary tract. Cytokeratin and vimentin expression confirmed epithelioid and mesenchymal differentiation, respectively. Lymph node, lung, and peritoneal metastases were seen in some cases. On multiphase CT, all tumors had a hypovascular center, and 17/60 (28%) had a hypervascular rim. After transarterial embolization, noncontrast CT showed retained contrast medium in the tumors. Follow-up contrast-enhanced scan showed reduced size of tumors after embolization using either 40–120 μm or 100–300 μm Embosphere microspheres, while untreated tumors showed continued growth. Conclusions: Liver tumors can be induced in a transgenic pig and can be successfully treated using bland embolization.

Original languageEnglish (US)
Pages (from-to)510-517.e3
JournalJournal of Vascular and Interventional Radiology
Volume32
Issue number4
DOIs
StatePublished - Apr 2021

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

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