Percutaneous electrochemotherapy in the treatment of portal vein tumor thrombosis at hepatic hilum in patients with hepatocellular carcinoma in cirrhosis: A feasibility study

Abstract

Aim: To treated with electrochemotherapy (ECT) a prospective case series of patients with liver cirrhosis and Vp3-Vp4- portal vein tumor thrombus (PVTT) from hepatocellular carcinoma (HCC), in order to evaluate the feasibility, safety and efficacy of this new non thermal ablative technique in those patients.

Methods: Six patients (5 males and 1 female), aged 61-85 years (mean age, 70 years), four in Child-Pugh A and two in Child-Pugh B class, entered our study series. All patients were studied with three-phase computed tomography (CT), contrast enhanced ultrasound (CEUS) and ultrasound-guided percutaneous biopsy of the thrombus before ECT. All patients underwent ECT treatment (Cliniporator Vitae^®, IGEA SpA, Carpi, Modena, Italy) of Vp3-Vp4 PVTT in a single session. At the end of the procedure a post-treatment biopsy of the thrombus was performed. Scheduled follow-up in all patients entailed: CEUS within 24 h after treatment; triphasic contrast-enhanced CT and CEUS at 3 mo after treatment and every six months thereafter.

Results: Post-treatment CEUS showed complete absence of enhancement of the treated thrombus in all cases. Post-treatment biopsy showed apoptosis and necrosis of tumor cells in all cases. The follow-up ranged from 9 to 20 mo (median, 14 mo). In 2 patients, the follow-up CT and CEUS demonstrated complete patency of the treated portal vein. Other 3 patients showed a persistent avascular non-tumoral shrinked thrombus at CEUS and CT during follow-up. No local recurrence was observed at follow-up CT and CEUS in 5/6 patients. One patient was lost to follow-up because of death from gastrointestinal hemorrage 5 wk after ECT.

Conclusion: In patients with cirrhosis, ECT seems effective and safe for curative treatment of Vp3-Vp4 PVTT from HCC.

Keywords: Electrochemotherapy; Hepatocellular carcinoma; Portal vein tumor thrombosis.

Figure 1

Selection of eligible patients to electrochemotherapy among a consecutive series of 42 patients with VP3-VP4 portal vein tumor thrombosis. ECT: Electrochemotherapy; PVTT: Portal vein tumor thrombosis; HCC: Hepatocellular carcinoma.

Figure 2

Illustrative sketch of the mechanism with which electrochemotherapy operates: After insertion of the electrodes in the tissue, a bleomycin bolus is administered intravenously. Eight minutes after injection, bleomycin diffuses in the tumor tissue. At this point the electric pulses are started in order to alter permeability of cells’ membranes. The electroporation process greatly increases the bleomycin intracellular entrance. Therefore by self repair of the membranes, pores reseal and the bleomycin is entrapped in the cells.

Figure 3

Insertion of six electrodes for electrochemotherapy treatment of right portal vein. A: Illustrative sketch showing schematically the position of electrodes around the external margin of the Tumor thrombosis; B: Up to six electrode-needles are inserted percutaneously; C: The position of electrodes can be monitored with US during the procedure.

Figure 4

All patients underwent pre- and post-treatment biopsy of the portal vein tumor thrombus. A: ultrasound scan demonstrate the correct positioning of the needle tip (arrow) in the thrombus; B: Intraoperative pre-treatment biopsy of the thrombus was adequate and showed viable cells from hepatocellular carcinoma in 5/6 cases; C: High magnification of biopsy specimen showed severe involutive changes of tumor cells with cellular apoptosis (arrows) and areas of necrosis (arrowheads) in all six cases. Low magnification in the same specimen, beside the altered tumor thrombus, showed absence of damage from the procedure to portal vein wall (arrows); D: Portal endothelium shows normal appearance with regular wall layers.

Figure 5

M.D.S. 64 years hepatitis C virus related cirrhosis. A: On september 2014 computed tomography (CT) showed complete malignant thrombosis of right portal vein (arrows); B: Pretreatment contrast enhanced ultrasound showed diffuse enhancement of the thrombus (arrows) consistent with malignant thrombosis; The patient underwent electrochemotherapy with insertion of 6 electrode-needles and i.v. Bleomicin bolus; C: Three months monthly color-Doppler ultrasound control showed complete patency of the right portal vein; D: Persistent patency of right portal vein (arrows) and absence of local recurrence was confirmed at 3, 9, 15 mo follow-up CT control.