Background Endoluminal radiofrequency ablation (RFA) has been promoted as palliative treatment for patients with cholangiocarcinoma (CCA) and pancreatic ductal adenocarcinoma (PDAC) in order to improve biliary drainage and eventually prolong survival. No high level evidence is, however, available on this technique. Design In this randomised controlled study, we compared endoluminal RFA plus stenting with stenting alone (control group) in patients with malignant biliary obstruction; metal stents were primarily placed. Primary outcome was overall survival; secondary outcomes were stent patency, quality of life and adverse events. In a superiority design, survival was assumed to be doubled by RFA as compared with 6.4 months in the control group (n=280). Results A total of 161 patients (male:female 90:71, mean age 71±9 years) were randomised before recruitment was terminated for futility after an interim analysis. Eighty-five patients had CCA (73 hilar, 12 distal) and 76 had pancreatic cancer. There was no difference in survival in both subgroups: for patients with CCA, median survival was 10.5 months (95% CI 6.7 to 18.3) in the RFA group vs 10.6 months (95% CI 9.0 to 24.8), p=0.58)) in the control group. In the subgroup with pancreatic cancer, median survival was 6.4 months (95% CI 4.3 to 9.7) for the RFA vs 7.7 months (95% CI 5.6 to 11.3), p=0.73) for the control group. No benefit was seen in the RFA group with regard to stent patency (at 12 months 40% vs 36% in CCA and 66% vs 65% in PDAC), and quality of life was unchanged by either treatment and comparable between the groups. Adverse events occurred in seven patients in each groups. Conclusion A combination of endoluminal RFA and stenting was not superior to stenting alone in prolonging survival or improving stent patency in patients with malignant biliary obstruction. Trial registration number NCT03166436.

Endoscopic radiofrequency ablation for malignant biliary obstruction

Radiofrequency ablation (RFA) is a mini-invasive loco-regional ablation technique that is increasingly being used as a palliative treatment for pancreatic cancer and cholangiocarcinoma. Ablation-triggered immune system stimulation has been proposed as a mechanism behind the systemic effects of RFA. The aim of our study was to investigate the immune response to endoluminal biliary RFA. Peripheral blood samples were collected from patients with pancreatic cancer and cholangiocarcinoma randomised to receive endoluminal biliary radiofrequency ablation + stent (19 patients) or stent only (21 patients). We observed an early increase in IL-6 levels and a delayed increase in CXCL1, CXCL5, and CXCL11 levels as well as an increase in CD8+ and NK cells. However, these changes were not specific to RFA treatment. Explicitly in response to RFA, we observed a delayed increase in serum CXCL1 levels and an early decrease in the number of anti-inflammatory CD206+ blood monocytes. Our study provides the first evidence of endoluminal biliary RFA-based regulation of the systemic immune response in patients with pancreatic cancer and cholangiocarcinoma. These changes were characterised by a general inflammatory response. RFA-specific activation of the adaptive immune system was not confirmed.

Úvod: Kongenitální extrahepatální portosystémový shunt (CEPS; Abernethyho malformace) může být komplikován rozvojem jaterní encefalopatie, plicní hypertenze nebo hepatocelulárního karcinomu (HCC). Prezentujeme případy dvou pacientů s mnohočetným HCC a současným CEPS. Popis případů: Dívka, 17 let, s mohutným portokaválním shuntem byla odeslaná na naše pracoviště pro progredující mnohočetná ložiska jater charakteru FNH/ adenomů dle MR. Cílená bio­psie jednoho z ložisek prokázala hepatocelulární adenom s rizikovými histologickými znaky, nález byl chirurgicky neřešitelný a pacientka byla indikována k transplantaci jater (LT). V průběhu nekomplikované LT byl zrušen portokavální shunt. V explantátu jater byly přítomny mnohočetné adenomy jater, ně­kte­ré již s transformací do dobře diferencovaného HCC. Pacientka je 2,5 roku po LT s dobrou funkcí štěpu, bez recidivy HCC. Muž, 62 let, s mohutným portosystémovým shuntem mezi vena mesenterica superior a vena cava inferior a anamnézou jedné epizody jaterní encefalopatie byl odeslán na naše pracoviště pro CT nález dvou ložisek jater charakteru HCC v terénu pokročilé fibrózy jater (F3 dle elastografie). MR prokázala celkem šest ložisek jater velikosti do 25 mm charakteru HCC, AFP bylo 496 µg/ l. Nález překračoval indikační kritéria IKEM k LT pro HCC a pacient byl indikován k onkologické terapii. Závěr: Abernethyho malformace je spojena se zvýšeným rizikem rozvoje benigních (adenomy) a maligních tumorů (HCC) jater, pečlivá surveillance pacientů je nezbytná.