Objective To study the safety and feasibility of endobiliary intraductal radiofrequency ablation (RFA) to reopen occluded self-expandable metal stents in patients with malignant biliary obstruction.Methods 11 patients with malignant biliary obstruction and blocked metal stents were prospectively studied.During ERCP, after biliary cannulation, the blocked metal stents underwent RFA using a bipolar radiofrequency probe which was introduced into the stenotic bile duct via a guide wire.This was followed by a balloon to repeatedly remove debris and then endoscopic nasobiliary drainage.The patients were closely observed and followed up.Results RFA was successfully carried out in all the patients and patencies were achieved when compared with pre-RFA.The median post-RFA luminal diameter of the strictures showed significant improvement: 6 (4 ～ 10) mm versus 2 (0 ～ 5) mm, and the mean post-RFA total bilirubin level decreased sharply : (39.4 ± 8.7) μ mol/L versus (130.1 ± 38.2) μmol/L.Following this intervention, 3 patients developed fever, which were controlled with conservative therapy.There was no mortality, haemorrhage, bile duct perforation or bile leak.Of the 11 patients, 3 were dead and 6 were alive at a median follow-up of 187 (75 ～ 304) days.The median stent patency was 135 (75 ～ 203) days and the median survival was 278 (75 ～ 304) days.Four patients had their stents patent at the time of the last follow-up or death.Seven patients had their stents blocked on 113, 124, 154, 203, 96, 135 and 112 days post-procedure.Condusions Endobiliary intraductal RFA is technically feasible and safe to reopen occluded metal stents in malignant biliary obstruction.This efficacy needs to be confirmed by future randomized studies.

Chemotherapy resistance plays a pivotal role in the prognosis and therapeutic failure of patients with colorectal cancer(CRC).Cisplatin(DDP)-resistant cells exhibit an inherent ability to evade the toxic chemotherapeutic drug effects which are characterized by the activation of slow-cycle programs and DNA repair.Among the elements that lead to DDP resistance,O6-methylguanine(O6-MG)-DNA-meth-yltransferase(MGMT),a DNA-repair enzyme,performs a quintessential role.In this study,we clarify the significant involvement of MGMT in conferring DDP resistance in CRC,elucidating the underlying mechanism of the regulatory actions of MGMT.A notable upregulation of MGMT in DDP-resistant cancer cells was found in our study,and MGMT repression amplifies the sensitivity of these cells to DDP treatment in vitro and in vivo.Conversely,in cancer cells,MGMT overexpression abolishes their sensi-tivity to DDP treatment.Mechanistically,the interaction between MGMT and cyclin dependent kinase 1(CDK1)inducing slow-cycling cells is attainted via the promotion of ubiquitination degradation of CDK1.Meanwhile,to achieve nonhomologous end joining,MGMT interacts with XRCC6 to resist chemotherapy drugs.Our transcriptome data from samples of 88 patients with CRC suggest that MGMT expression is co-related with the Wnt signaling pathway activation,and several Wnt inhibitors can repress drug-resistant cells.In summary,our results point out that MGMT is a potential therapeutic target and predictive marker of chemoresistance in CRC.