An Unexpected Pulmonary Complication Following TACE With Low-Dose Doxorubicin-Eluting Beads and Small-Volume Lipiodol for a Small HCC

Abstract

Background: Transarterial chemoembolization (TACE) is a widely accepted palliative intervention for hepatocellular carcinoma (HCC). We report an unexpected pulmonary complication in a patient who underwent low-dose doxyrubicin-eluting bead (DEB)-TACE followed by small-volume lipiodol for a small HCC. Case Presentation: A 62-year-old male with HCV cirrhosis, complicated by a new HCC and portopulmonary hypertension, underwent a DEB-TACE for a 3.9-cm right hepatic lobe HCC without complications resulting in tumor size reduction. He had a second DEB-TACE seven months later for a small recurrent HCC with Doxorubicin (40 mg/5ml)-eluting 100-300 μm LC beads, followed by only 1 ml Lipiodol. The patient developed hypoxemia (SpO2 88%) immediately after the procedure. Chest CTA was negative for PE, but showed multiple bilateral areas of ground-glass opacities. TTE showed mild RV enlargement, worsened pulmonary hypertension with worsened tricuspid regurgitation. Patient was transferred to the ICU on hospital day 3 for worsening respiratory distress, and was treated empirically with broad-spectrum antibiotics initially. Work up for infectious causes of acute hypoxemic respiratory failure was negative. SoluMedrol was initiated on hospital day 7 for post-TACE acute lung injury (ALI). Hypoxemia resolved two days later. The patient subsequently underwent a successful liver transplant. His respiratory function has completely normalized, but he continues to have significant pulmonary hypertension requiring medical therapy. Discussion: Post-TACE pulmonary complications, e.g., ALI, ARDS, are rare events. The injected ethiodized oil or chemotherapeutic agent is thought to migrate to the lung vasculature via arteriovenous (AV) shunts within the hypervascular HCC tumors, causing chemical injury. In rabbits, lipiodol infusion causes severe hypoxemia and lung inflammation. Perfusion of foxhound lungs with doxorubicin causes dose-dependent tissue damage. In humans, doxorubicin is associated with capillary leak syndrome and bronchiolitis obliterans organizing pneumonia. The acute hypoxemic respiratory failure following TACE in our patient may have resulted from pulmonary embolism with doxorubicin-eluting beads and/or lipiodol. The known risk factors for post-TACE pulmonary complications - e.g., large hypervascular HCC, AV shunts, large-volume lipiodol, and trans-inferior phrenic artery embolization - were all absent in our patient, making the post-TACE ALI in our patient an unexpected event.