Irreversible Electroporation Treatment With Intraoperative Biliary Stenting for Unresectable Perihilar Cholangiocarcinoma: A Pilot Study

Abstract

Background: Treating perihilar cholangiocarcinoma (PHCC) is particularly difficult due to the fact that it is usually in an advanced stage at the time of diagnosis. Irreversible electroporation treatment (IRE) involves the local administration of a high-voltage electric current to target lesions without causing damage to surrounding structures. This study investigated the safety and efficacy of using IRE in conjunction with intraoperative biliary stent placement in cases of unresectable PHCC.

Methods: This study enrolled 17 patients with unresectable Bismuth type III/IV PHCC who underwent IRE in conjunction with intraoperative biliary stent placement (laparotomic) in two medical centers in Asia between June 2015 and July 2018. Analysis focused on the perioperative clinical course, the efficacy of biliary decompression, and outcomes (survival).

Results: Mean total serum bilirubin levels (mg/dL) on postoperative day (POD) 7, POD30, and POD90 were significantly lower than before IRE (respectively 3.46 vs 4.54, p=0.007; 1.21 vs 4.54, p<0.001; 1.99 vs 4.54, p<0.001). Mean serum carbohydrate antigen 19-9 (CA19-9, U/ml) levels were significantly higher on POD3 than before the operation (518.8 vs 372.4, p=0.001) and significantly lower on POD30 and POD90 (respectively 113.7 vs 372.4, p<0.001; 63.9 vs 372.4, p<0.001). No cases of Clavien-Dindo grade III/IV adverse events or mortality occurred within 90 days post-op. The median progression-free survival was 21.5 months, and the median overall survival was 27.9 months. All individuals who survived for at least one year did so without the need to carry percutaneous biliary drainage (PTBD) tubes.

Conclusions: It appears that IRE treatment in conjunction with intraoperative biliary stent placement is a safe and effective approach to treating unresectable PHCC. The decompression of biliary obstruction without the need for PTBD tubes is also expected to improve the quality of life of patients.

Keywords: Jaundice cholangitis; biliary stent; irreversible electroporation; perihilar cholangiocarcinoma (PHCCA); unresectable abdominal neoplasms.

Figure 1

Four electrodes placed parallel to the hepatoduodenal ligament to embrace the tumor (yellow target in left image) in a caudal to cranial direction for the treatment of unresectable Bismuth type IIIA perihilar cholangiocarcinoma.

Figure 2

Endoscopic retrograde biliary drainage (ERBD) stents were replaced by expandable fully-covered metallic stents via endoscopic retrograde cholangiography (ERC) at three months after operation. (A) ERBD stent in situ. (B) ERBD stent removed by endoscopic snare. (C) ERC after insertion of metallic stents into extrahepatic bile duct.

Figure 3

(A) Total serum total bilirubin levels on postoperative day (POD) 7, POD30, and POD90 were significantly lower than prior to irreversible electroporation treatment (IRE). (B) Serum carbohydrate antigen CA19-9 levels were higher on POD3 and lower on POD30 and POD90, compared to before IRE.

Figure 4

(A) Arrow indicates enhanced Bismuth type IIIA perihilar cholangiocarcinoma (PHCC) with percutaneous biliary drainage (PTBD) tube in computed tomography (CT) scan. (B) No evidence of enhanced tumor (arrow) with patent biliary tract was observed in CT scan at one month after irreversible electroporation treatment (IRE).

Figure 5

(A) Kaplan-Meier progression-free survival (PFS) curve showed median PFS was 21.5 months. (B) Kaplan-Meier overall survival curve (OS) curve showed median OS was 27.9 months.