Role of Intraductal RFA: A Novel Tool in the Palliative Care of Perihilar Cholangiocarcinoma

Abstract

<b><i>Background:</i></b> Patients with irresectable perihilar cholangiocarcinoma (PHC) have a limited prognosis with median survival times still less than 1 year. In addition to the current standard first-line systemic chemotherapy (gemcitabine and a platinum derivate), endoscopic treatment aims to ensure adequate drainage of the biliary system by placing biliary plastic or metal stents. Local ablative procedures like intraluminal biliary brachytherapy (ILBT) or photodynamic therapy (PDT) are used to improve local tumor control and to optimize the stent patency. <b><i>Summary:</i></b> Intraductal radiofrequency ablation (RFA) is another promising tool in the therapeutic armamentarium for the endoscopic management and tumor ablation of extrahepatic cholangiocarcinoma (eCCA). By applying thermal energy to the tissue through high-frequency alternating current, RFA induces coagulative necrosis and causes local destruction of the tumor. It is established as a first line percutaneous treatment of solid liver tumors, and since 2011 an endoscopic catheter is available that allows intraductal RFA in the biliary or pancreatic ducts. While the first pilot studies primarily evaluated this new method in patients with distal eCCA, there is now evidence accumulating also for PHC. Two retrospective and two prospective studies demonstrated a significantly improved overall survival and a longer stent patency with intraductal RFA, which overall had a favorable safety profile and was not associated with a significant increase in adverse events. However, prospective studies comparing the efficacy and safety of intraductal RFA, PDT, and/or ILBT are lacking. <b><i>Key Messages:</i></b> Recent studies suggest that intraductal RFA is an effective and well-tolerated additional treatment option with regard to stent patency but also overall survival. Since RFA has fewer systemic side effects and requires less logistical effort when compared to ILBT and PDT, intraductal RFA should be considered as another safe and feasible adjuvant method for the palliative care of patients with advanced PHC. Since comparative studies are lacking, the choice of the local ablative method remains in each case an individual decision.

Endoscopic palliation of malignant biliary obstruction

“…PDT utilizes a photosensitizing agent (which is activated by laser light) to ablate tumor tissue via apoptosis, necrosis, and an immunomodulatory effect[ 105 ]. The porphyrin phototoxic substance is given intravenously 3-4 d prior to the procedure to allow for preferential accumulation in the malignant tissue-during this period patients are advised to stay in a darkened room to avoid an accidental inflammatory reaction in normal tissue if exposed to light[ 106 , 107 ]. Next a guidewire and catheter position the fiberoptic probe in the bile duct where laser light at certain wavelengths (typically 630 nm) trigger the photosensitizing agent for 750 sec to generate free oxygen radicals that destroy the tumor bed and/or stricture[ 106 , 108 , 109 ].…”

Palliative endoskopische Therapie bei Klatskin-Tumoren

“…Die Radiofrequenzablation ist als Erstlinientherapie für die perkutane Ablation von soliden Lebertumoren etabliert. Seit 2011 ist ein endoskopischer Applikator verfügbar, der die intraduktale Applikation in den Gallengängen erlaubt 12 .…”

“…RFA induziert die direkte Koagulationsnekrose durch Applikation von thermischer Energie im Tumorgewebe. Zudem stimuliert sie eine tumorspezifische Immunreaktion, ähnlich zu PDT 12 , 91 .…”

Palliative endoskopische Therapie bei Klatskin-Tumoren

“…Zusätzlich zur traditionellen, perkutanen transhepatischen Cholangiodrainage (PTCD) können der Ductus hepatocholedochus (DHC) oder die intrahepatischen Gallengänge endosonografisch transgastral oder transduodenal eingestellt und abgeleitet werden. Intraduktale ablative Verfahren, wie die photodynamische Therapie (PDT), die Radiofrequenzablation (RFA) und die Brachytherapie, können in Kombination mit ableitenden Verfahren zur lokalen Kontrolle des Tumorwachstums und Verbesserung der Stentoffenheitsrate eingesetzt werden [12].…”