Endobiliary radiofrequency ablation in recurrence and unresectable perihilar cholangiocarcinoma

Endobiliary radiofrequency ablation in recurrence and unresectable perihilar cholangiocarcinoma | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Endobiliary radiofrequency ablation in recurrence and unresectable perihilar cholangiocarcinoma Apiwat Jareanrat, Vasin Thanasukarn, Tharatip Srisuk, Vor Luvira, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5948371/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 07 Jul, 2025 Read the published version in BMC Gastroenterology → Version 1 posted 8 You are reading this latest preprint version Abstract Background: Palliative biliary stenting is the principal treatment for unresectable perihilar cholangiocarcinoma (pCCA) patients who suffer from jaundice. Endobiliary radiofrequency ablation (EBRFA) is the novel treatment in combination with biliary stenting for CCA with the intention to extend the patency and survival of patients which is a lack of knowledge and evident base data for perihilar CCA. This study aims to investigate the safety of EBRFA and efficacy in terms of increasing stent patency and the patient’s survival. Methods: Patients with unresectable perihilar CCA were prospectively randomized into 2 groups including EBRFA with self-expandable metallic stent (SEMS), and SEMS alone. Stent patency time was recorded after stent implantation and until obstructive jaundice occurrence. The median survival time (MST), median stent patency, and adverse event rate were analyzed and compared using Log-rank test. The proportion comparisons of patient characteristics, preoperative testing, procedure detail, and morbidity in two methods were conducted by Chi-squad test. Result: Of a total of 39 patients who were diagnosed pCCA and included in this study, 22 patients were in the EBRFA group and 17 patients in SEMS group. The procedure-related complication rate was not statistically significant different between EBRFA and the SEMS groups. There was no statistically significant difference of stent patency time between EBRFA and SEMS groups (71 vs 78 days, p-value =0.809), as well as The OS of EBRFA group had no statistically significant difference with SEMS group, (94 vs 79 days, HR= 1.31, 95%CI: 0.66-2.58, p-value =0.735). Conclusion: The EBRFA was shown to be safe to use and practical to perform combined with SEMS for treatment unresectable pCCA. Trial registration: TCTR20190704002 Cholangiocarcinoma Klatskin tumor Endobiliary radiofrequency ablation Metallic biliary stent Unresectable treatment palliative treatment Obstructive jaundice Randomized trial Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Background Cholangiocarcinoma (CCA) is the second most common type of liver cancer arising from bile duct epithelial cells involving the intrahepatic (iCCA), perihilar (pCCA), and the distal (dCCA) biliary tree [ 1 ]. The CCA incidence in Thailand, especially in the northeast region, is extremely high compared to most parts of the world. Almost all CCA patients have poor prognosis and short survival outcome due a late CCA diagnosis. Thus, late presentations with locally advanced or metastatic disease contribute to the high mortality in patients. Surgical resection is the only potentially curative treatment in CCA patients who were found to be candidates for surgery, and hence, can prolong the overall survival of patients when compare to unresectable patients [ 2 – 5 ]. Nevertheless, the studies have reported that only 20% of CCA patients are resectable, while 80% was unresectable [ 6 ]. Most of unresectable CCA patients undergo extreme suffering due to several complications, such as obstruction of the bile ducts and jaundice, cholangitis, cirrhosis and malnutrition. These complications lead to reduce quality of life, and subsequently poor survival of unresectable CCA patients [ 5 , 7 ]. Therefore, palliative treatment has an important role to play to improve the outcomes and life quality of patients who are unresectable by surgical treatment or/and patients with recurrence of the disease. Endoscopic biliary stenting (EBS) has been suggested as palliative treatment, because it is associated with a reduction in obstructive rate of bile ducts or jaundice, as well as other symptoms [ 8 ]. Normally, there are two types of material to design endoscopic stents, namely, metal and plastic. The reports revealed that self-expanding metallic stents (SEMS) have an average stent patency time, palliative drainage and obstructive recurrence significantly superior than biliary stents made from plastic material (PS) [ 9 – 11 ]. Even through endoscopic metallic biliary stents are potential tools to reduce bile duct obstruction and prolong outcome of patients, cancer progression by in-/overgrowth biofilm deposition, biliary sludge, or formation of granulation tissue events may cause biliary stasis, subsequently, leading to recurrent biliary obstruction. These progressive causes of obstructive jaundice, subsequently result in significant morbidity and mortality of patients [ 10 , 12 , 13 ]. Therefore, modification of biliary stents is necessary to protect from symptomatic stent occlusion, and, therefore delay biliary obstruction. Radiofrequency ablation (RFA) is applied in the biliary metallic stent placement for the purpose of percutaneous and endoscopic delivery of radiofrequency and heat energy which achieves and leads to coagulation localized tumor necrosis in CCA lesion [ 12 , 14 , 15 ]. RFA has been suggested as having two significant expectations. Firstly, radiofrequency and heat energy from endobiliary radiofrequency ablation (EBRFA) reduces tumor burden, subsequently, delaying tumor growth that is associated with potential extension of stent patency time [ 16 , 17 ]. Secondly, EBRFA may be useful for neoadjuvant therapy in unresectable CCA cases [ 12 , 17 ]. Several studies have repeatedly reported the clinical advantages of EBRFA to extend stent patency when compared with MS, and improved the survival outcome of patients with malignant biliary obstruction, especially in CCA [ 13 , 17 – 22 ]. Thus, the ERFA is an alternative palliative treatment option for unresectable CCA patients. Nevertheless, there is still unclear and robust research in the treatment of unresectable pCCA patients by EBRFA. This study hypothesizes that EBRFA can be safely employed and feasable for unresectable pCCA patients. In addition, EBRFA may provide improvement of the stent patency and survival time extension more than only SEMS. This study thus aims to examine metallic endobiliary stenting methods in prospective, randomized, unresectable pCCA patients, and investigates the safety, efficacy outcomes in term of increasing stent patency, and patient’s survival outcome between patients with EBRFA versus patients with SEMS. Methods Ethic approval and consent to participate The study protocol was performed based on the Declaration of Helsinki and approved by the Human Research Ethics Committee, Khon Kaen University (HE611487). Before the samples were collected, informed and written consent was obtained from all patients. In addition, this study has been registered with Thai Clinical Trials Registry, number TCTR20190704002. Study population and sample size calculation This study included patients diagnosed with cholangiocarcinoma (CCA) who presented with jaundice or recurrent disease and were classified as unresectable cases, receiving treatment at Srinagarind Hospital, Faculty of Medicine, Khon Kaen University between 2021 and 2024, with a total enrollment of 40 patients in this phase II study. The required sample size was determined using STATA (version 13) for the log-rank test, with a significance level of 0.05 and a power of 0.8, estimating that each group would require 36 patients, assuming that the experimental group would have a twofold lower risk of stent occlusion compared to the control group. The sample size calculation was performed using the formula: where: Z α/2 is the critical value of the standard normal distribution at a significance level of 0.05 (typically 1.96 for a two-tailed test). Z β is the critical value corresponding to the statistical power of 0.8 (typically 0.84). p 1 is the estimated probability of stent occlusion in the experimental group. p 2 is the estimated probability of stent occlusion in the control group. Based on this formula, the sample size was calculated considering the hazard ratio, significance level, and statistical power to ensure adequate detection of differences between groups. The patency rate was assessed using a standard method, with an expected stent occlusion rate of 50% at 90 days post-procedure in the experimental group, whereas the control group had an expected occlusion rate of 20% at 90 days post-procedure. An interim analysis was planned once each group had at least 10 patients enrolled. Patient selection and research design The study design was a randomized control trial. Patients with unresectable perihilar cholangiocarcinoma were diagnosed by Computerized Tomography and radiological finding was validated by attending radiologists to confirm diagnosis. Patients with inconclusive radiological finding (differential diagnosed with intrahepatic duct stone or benign biliary stricture) were excluded from this study. Patients with unresectable perihilar cholangiocarcinoma diagnosis had undergone endoscopic retrograde cholangiopancreatography (ERCP) for palliative treatment. Forty-four patients were prospectively randomized into 2 groups using computed generate random assignment order to each group by statisticians from Data Management and Statistical Analysis Center (DAMASAC), Faculty of Public Health, Khon Kaen University. Studied groups were included endobiliary radiofrequency ablation (EBRFA) with metallic biliary stents (MS) (n = 22) and MS alone (n = 22). Forty-four patients were included in this study using the following inclusion and exclusion criteria and the detailed selection process. Inclusion criteria: patients had age range 18–75 years; patients were unresectable or recurrent cholangiocarcinoma diagnosis by pathology or radiographic; patients presented obstructive jaundice or had total bilirubin > 3 mg/dL. Exclusion criteria: patients who had conditions including massive ascites, uncorrectable coagulopathy, presence of main portal vein thrombosis, Child-Pugh Score C cirrhosis, pregnancy, performance status ECOG ≥ 3 (confined to bed / chair > 50% waking hours), presence of other malignancy, life expectancy < 3 months, patients with cardiac pacemakers or other active implants, Comorbidities: congestive heart failure, COPD, Sepsis, uncorrectable thrombocytopenia (less than 100,000 cells/mm 3 ) or uncorrectable coagulopathy (INR > 1.5), prior SEMS placement, patients refused procedure and failure stent placement. Endobiliary radiofrequency ablation procedure steps Endobiliary radiofrequency ablation is a novel new treatment to improve the efficacy of cholangiocarcinoma therapy. This device includes the radio frequency generator and catheter as components. The generation produces radio frequency waves that convert to heat at the catheter's tip. Local ablation of the tumor by thermal action. This treatment consists of local ablation prior to the insertion of a metallic biliary stent in order to delay stent obstruction. It can also be used in cases of biliary metallic stent obstruction caused by tumor. Prior to the procedure, the patient was hospitalized for one day during which time a doctor examined the general appearance and health status of the patient. In addition, blood tests, Coagulograms, chest x-rays, and EKGs were reviewed. The patient had no oral intake after midnight the night before the procedure. During that time, intravenous fluid was administered to maintain body fluid. Antibiotic prophylaxis and NSAID rectal suppository were prepared. Anesthesiologists routinely provided intravenous medication for sedation as a conventional anesthetic technique. The use of general anesthesia is limited to cases with cardiovascular illness, massive ascites that induced respiratory compromise, and severe jaundice. At 30 minutes before the procedure, a prophylactic antibiotic was administered. The patient was placed lying in a prone position, whereupon, the endoscopist initiates the ERCP procedures. A side-viewing duodenoscope was inserted into the duodenum, and the guidewire was advanced through the stricture by a standard sphincterotome, and a cholangiogram was viewed to determine the tumor site (Fig. 1). This was followed by the insertion of an 8-Fr (2.6 mm) bipolar radiofrequency ablation probe with two ring electrodes 8 mm wide stainless steel apart (HabibTM EndoHPB, EMcision Ltd, London, UK) as shown in Fig. 2. This results in an efficient cylindrical ablation over a 25 mm length between the distal and proximal electrodes. It is placed over the 0.035-millimeter guidewire. The tumor was ablated for 90 seconds at 9 Watts. After completing a cycle of ablation, there must be a 60 second interval should be adhered to before beginning the next cycle. The endoscopist relocates the RFA probe to the next obstruction and continues the ablation procedure until the entire tumor region has been treated. The generator uses a RITA 1500X RF generator (Angiodynamics, Latham, NY, USA). Following complete ablation the RFA probe was removed (Fig. 3). Coagulated tumor fragments are eliminated with subsequent balloon sweeps. This is followed by SEMS placement. A self-expanding metallic stent (Niti-S™ Biliary Uncovered Stent, S-Type) of 10 mm in diameter and 80–100 mm in length is placed over the guide wire. For the prevention of post-ERCP pancreatitis, an NSAID was applied to the rectum immediately after the procedure. Cholangitis and pancreatitis are common postoperative complications; serious complications have also been reported, including portal vein thrombosis, haemobilia, hepatic infarction, sepsis, and liver abscess. We graded the complication levels using the Clavien Dindo classification [ 23 ]. We separated the complications into two levels including mild (Clavien Dindo grade I-II) and server complications (Clavien Dindo grade III-V). Percutaneous transhepatic biliary drainage (PTBD) and radiofrequency ablation (RFA) The percutaneous approach was selected for patients with biliary obstructions that could not be addressed by endoscopic stenting due to factors such as anatomical challenges or insufficient duodenal access. This approach was specifically chosen when endoscopic treatment failed, as defined by difficult cannulation, which includes the inability to achieve selective biliary cannulation by standard ERCP techniques within 10 minutes or after up to five cannulation attempts, or failure of access to the major papilla [ 24 ]. Pre-procedure preparation Prior to the procedure, pre-operative imaging is reviewed to assess the anatomy and location of the biliary obstruction. The patient is positioned supine with the right side slightly elevated if targeting the right intrahepatic bile ducts. Local anesthesia is administered to the target area, and sedation is provided to ensure patient comfort. The procedure is performed under sterile conditions to prevent infection. Procedure steps First, a Chiba needle (e.g., 18G) is percutaneously inserted into a dilated intrahepatic bile duct under ultrasound guidance, followed by the injection of a small volume of contrast medium to facilitate visualization of the biliary anatomy via fluoroscopy. Second, a hydrophilic guidewire (e.g., 0.035-inch) is advanced through the needle into the bile duct to establish access. Third, a series of plastic dilators are passed over the guidewire to gradually enlarge the tract, typically up to 7Fr, to accommodate the drainage catheter. Fourth, endobiliary radiofrequency ablation (RFA) is performed using a radiofrequency probe, which is introduced through the percutaneous tract to ablate obstructive tissue within the bile duct, utilizing the same technique as endoscopic RFA. Finally, a drainage catheter (6–8 Fr) with multiple side holes is inserted along the dilated tract and secured at the skin entry site. The catheter is left in place for external drainage to decompress the biliary system, thereby ensuring bile flow and relieving further obstruction. Stent occlusion diagnosis criteria Stent occlusion is defined as the failure of a stent to maintain patency, resulting in blockage or narrowing that impairs bile flow. The diagnosis of stent occlusion is based on both clinical manifestations and laboratory test results. Clinical manifestation, stent occlusion is commonly indicated by the recurrence of obstructive jaundice. Laboratory tests are used to further confirm the diagnosis, with stent occlusion suspected when the total bilirubin level exceeds 3 mg/dL in patients who do not exhibit obstructive jaundice after treatment. Additionally, stent occlusion is diagnosed when total bilirubin levels remain stable or increase over a period of two weeks following treatment in patients who initially did not present with obstructive jaundice. These criteria are critical for identifying stent failure and enabling timely intervention. Outcome Measurement Stent patency is defined as the time interval from the date of operation to the first occurrence of stent occlusion. Stent occlusion is diagnosed based on clinical symptoms (such as the recurrence of obstructive jaundice) and laboratory test results, as outlined in the Stent Occlusion Diagnosis Criteria. These criteria include an increase in total bilirubin greater than 3 mg/dL in patients who do not exhibit obstructive jaundice after treatment, or when total bilirubin levels remain stable or increase over a period of 2 weeks after treatment in patients without initial obstructive jaundice. While, overall survival (OS) is defined as the time from the date of operation to the date of death from any cause. Patients were followed up until death or the last recorded follow-up, whichever occurred first. OS was analyzed using Kaplan-Meier survival curves. Statistical analysis The statistical analyses were performed using SPSS (version 26.0; SPSS, Chicago, Ill, USA). The proportion of patient characteristics, preoperative testing, procedure detail and morbidity were analyzed using the Chi-square test (or Fisher’s exact test as appropriate), whereas continuous variables were analyzed using the student’s t-test for parametric or Mann–Whitney test for nonparametric tests. Patient survival and stent patency time were calculated and compared using the Kaplan-Meier method and a Log-Rank test. Influence survival Factors in pCCA patients (age, gender, bismuth type, tumor morphology, distant metastasis, preoperative testing and MS methods) were further selected to identify independent factors using the Cox regression model. p-value < 0.05 was considered statistically significant. Results Patient characteristics According to inclusion and exclusion criteria (Fig. 4), thirty-nine CCA patients who were diagnose unresectable were randomly separated into SEMS and ERFA groups composing 17/39 cases (44%) and 22/39 cases (56%), respectively. The median age was 62 years. The patient’s gender was 20/39 cases (51.3%) male and 19/39 cases (48.7%) female. Radiological imaging examination showed tumor morphology 3/39 cases (7.7%) such as, intraductal, periductal infiltrating 20/39 cases (51.3%), mass-forming 4/39 cases (10.3%) and combined morphological types 12/39 cases (30.7%). In addition, there was no significant deference of tumor morphology in SEMS and ERFA groups. In this study 30/39 (77%) cases at the time of diagnosis presented with distant metastasis, including 14/30 cases (47%) for SEMS and 16/30 cases (53%) for ERFA. The overall preoperative laboratory characteristics consisted of Hemoglobin (Hb) (11.1 ± 1.8 g/dL), WBC count [9770 cells/mm 3 (range, 7620–12800)], Total bilirubin [16.8 mg/L (range, 6.4–29)], Albumin (3.4 ± 0.6 g/dL), liver enzymes AST [104 U/L (range, 53–168)], ALT [90 U/L (range, 45–131)], [ALP 410 U/L (range, 292–784)]. The proportion of patient’s characteristics and both the endoscopic biliary stent placements was performed. The result showed that there were no statistically significant differences of the patient’s characteristics proportions in both experimental groups namely, in age, gender, Bismuth type, imaging examination, distant metastasis, and preoperative testing (Table 1 ). Table 1 Demographics of patient’s characteristic Characteristic Overall (n = 39) SEMS (n = 17) EBRFA (n = 22) p-value Age ≥ 62 yrs. (range, 41–74) 20 (51.3%) 9 (52.9%) 11 (50.0%) 0.855 Male 19 (48.7%) 9 (53%) 10 (45.5%) 0.643 Bismuth type I 9 (23.1%) 4 (23.5%) 5 (22.7%) 0.762 # III 21 (53.8%) 8 (47.1%) 13 (59.1%) IV 9 (23.1%) 5 (29.4%) 4 (18.2%) Tumor morphology Intraductal (ID) 3 (7.7%) 1 (5.9%) 2 (9.1%) Periductal infiltrating (PI) 20 (51.3%) 11 (64.6%) 9 (40.9%) Mass forming (MF) 4 (10.3%) 2 (11.8%) 2 (9.1%) 0.475 # Combined types 12 (30.7%) 3 (17.7%) 9 (40.9%) Distant metastasis No 9 (23.1%) 3 (17.7%) 6 (27.3%) Yes 30 (76.9%) 14 (82.3%) 16 (72.7%) 0.704 # Pre-procedure lab Hb* (g/dL) 11.1 ± 1.8 11.1 ± 2.4 11.2 ± 1.1 0.905 WBC count $ cells/mm 3 9770 (7620–12800) 11450 (9260–14070) 8590 (7620–10500) 0.785 Total bilirubin $ (mg/dL) 16.8 (6.4–29) 12.9 (7.1–25.1) 18.7 (6.4–30) 0.063 Albumin* (g/dL) 3.24 (0.75) 3.18(0.66) 3.28 (0.83) 0.709 AST $ (U/L) 104 (53–168) 125 (53–170) 81.5 (53–167) 0.499 ALT $ (U/L) 90 (45–131) 67 (45–131) 95.5 (43–131) 0.676 ALP $ (U/L) 410 (292–784) 410 (299–927) 392.5 (292–725) 0.677 Notes: Mean (SD); $ Median (IQR); # Fisher’s exact test. Abbreviation: Hb, hemoglobin. The comparison of procedure details and morbidity between SEMS and EBRFA The route of stent placement composed 34/39 cases (87.2%) for endoscopic and 5/39 cases (12.8%) for percutaneous placement. Stent implements were 2 types, including single 38/39 (97.4%) and double 1/39 (97.4%) stents. Complications included 7/39 cases (17.9%) of pancreatitis by 11.8% for SEMS and 22.7% for EBRFA, and cholangitis (18/25 mild by 29.4% for SEMS and 59.1% for EBRFA and 7/25 severe levels by 23.5% for SEMS and 13.6% for EBRFA). There was no statistically significant difference in the proportion of complications, pancreatitis ( p-value =0.376) and cholangitis ( p-value =0.200), between SEMS and EBRFA. While the median length of patients stayed at hospital was reported as 6 days (range, 2-9 days), there was no significant difference in the length of patients staying at hospital between both groups by 7 (range, 4-11) days for SEMS and 5 (range, 2-7) days for EBRFA (p = 0.237). After 4 weeks, all patients were followed up and total bilirubin reduction evaluated. Overall total bilirubin reduction was 8.2 mg/dL, by 14.7 mg/dL for EBRFA group and 4.1 mg/dL for SEMS group ( p-value =0.197). Postoperative observation, found that patients who survived less than 30-days were 5/39 cases (12.8%) composing 1 case (4.5%) in EBRFA, while 4 cases (23.5%) in SEMS. The comparison of procedure details and morbidity between the two methods showed that there was no significant difference, and stent patency time in this study was 73 days. There was no statistically significant difference of stent patency time between the EBRFA and SEMS (71 vs 78 days, p-value =0.809) (Table 2 and Fig. 5A). Table 2 Procedure detail and morbidity Overall SEMS EBRFA p-value Route of stent placement Endoscopic 34 (87.2%) 14 (82.4%) 20 (90.9%) 0.428 Percutaneous 5 (12.8%) 3 (17.6%) 2 (9.1%) Number of stents 1 38 (97.4%) 17 (100%) 21 (95.5%) 2 1 (2.6%) 0 1 (4.5%) 0.373 Complications Pancreatitis 7 (17.9%) 2 (11.8%) 5 (22.7%) 0.376 Cholangitis ■ mild 18 (47.4%) 5 (29.4%) 13 (59.1%) 0.200 # ■ severe 7 (15.8%) 4 (23.5%) 3 (13.6%) Length of hospital stay (day) $ 6 (2–9) 7 (4–11) 5 (2–7) 0.237 Total bilirubin reduction after 4 weeks (mg/dL) $ 8.2 (2–18) 4.1 (1.8–13) 14.7 (2.2–22.4) 0.197 30-day mortality 5 (12.8%) 4 (23.5%) 1 (4.5%) 0.079 Stent patency time (day) $ 73 (41–137) 78 (29–167) 71 (49–123) 0.809 Notes: $ Median (IQR); # Fisher’s exact test. Survival and Prognosis Analysis The median survival time (MST) of unresectable patients in this study was 94 days. CCA patients who received EBRFA had a trend in survival time to be better than patients who received SEMS (OS = 94 vs 79 days, HR = 1.31, p-value =0.735) (Fig. 5B). The survival time of bismuth type I was 104 days, while bismuth type III and IV were 94 and 41 days, respectively. There were no significant differences of the survival time between the three groups (MST=104 vs 94 and 41 days, HR 1.08 and 1.25, p-value =0.853 and 0.64, respectively). For tumor morphology, ID (MST = 392 days) was used as a reference and compared to PI (MST = 79 days), MF (MST=78 days) and combined types (MST = 73 days). The comparison of the MST in the 4 types of morphology showed no significant difference in survival time. In addition, comparison of distant metastasis status resulted in no markedly different survival time. However, the total bilirubin level (TB) showed that patients with TB < 15 mg/dL had statistically significant better survival than patients with TB ≥15 mg/dL (MST = 201 vs 73 days, HR = 2.76, p-value =0.004) (Table 3). Table 3 Survival analysis of perihilar CCA patients. Variables N MST (Day (95%CI)) Crude HR (95%CI) p-value Overall survival 39 94.0 (66.9- 121.1) SEMS 17 79.0 (26.6–131.4) 1 EBRFA 22 94.0 (58.4–129.6) 1.31 (0.67–2.259) 0.750 Bismuth type I 9 104.0 (86.5-121.5) 1 III 21 94.0 (33.1-154.9) 1.08 (1.07–2.42) 0.875 IV 9 40.0 (23.4–56.6) 1.91 (0.71–5.16) 0.203 Tumor morphology ID 3 392 (126.3-657.7) 1 PI 19 79 (35.2-122.8) 2.19 (0.64–7.52) 0.213 MF 5 78 (12.3-143.7) 2.85 (0.61–13.34) 0.183 Combined 12 73 (61.1–84.9) 3.11 (0.85–11.41 0.087 Distant metastasis No 10 71.0 (1.3-140.7) 1 Yes 29 98.0 (52.3-143.7) 0.69 (0.33–1.44) 0.317 Total Bilirubin level TB < 15 mg/dL 19 201 (71–311) 1 TB ≥ 15 mg/dL 20 73 (37–104) 2.76 (1.37–5.56) 0.004 Abbreviations: ID = intraductal morphology; PI = periductal infiltration morphology; MF = mass-forming morphology; Combined = indicates the presence of more than one morphological type. Discussion Perihilar Cholangiocarcinoma (pCCA) is mostly reported as having the highest incidence when compared to other types of CCA. Patients with pCCA have a poorer survival rate similar to that reported for iCCA and dCCA. Only 20% of patients were diagnosed as respectable patients, but the outcomes, such as 5-year survival and median survival are still not satisfactory, because as several reports have shown more than 50% of surgical patients presented during late stage (III-IV). Moreover, the report by Luvira V et al has shown that approximately 80% were unresectable patients due to presenting in the advanced stage of disease [6, 25, 26]. Therefore, the palliative treatments considered to prolong the survival of patients are chemotherapy and biliary drainage by the endoscopic biliary stent placement to improve quality of patient’s life [6, 27, 28]. Endoscopic biliary stent placement, especially self-expanding metallic stents (SEMS), is the one of palliative treatments in CCA for patients with unresectable status. It has been suggested that they can reduce bile duct obstruction and increase patency rate leading to improved overall survival of CCA patients. SEMS could prolong biliary obstruction and patient’s life expectancy higher than 3 months. Therefore, SEMS placement is an alternative tool for palliative treatment in unresectable CCA patients. However, several reports suggested that based on aggressiveness of CCA, the progression of cancer is still a major cause in the recurrence of biliary obstruction by in-/overgrowth biofilm deposition, biliary sludge and/or formation of granulation tissue. These events can lead to significant morbidity and mortality in patients [10, 12, 13]. In 2011, Alan W et al proposed the modification of SEMS placement by applying radiofrequency ablation (RFA) for the purpose of stent patency extension and delayed biliary obstruction. Applying RFA in SEMS has been done in an animal model, and showed improved stent patency and survival outcomes [29]. Therefore, this study showed applying RFA into SEMS in CCA to be safe and potentially feasibile in human subjects, as results showed high technical and functional success rates of more than 90% (Fig. 1). In addition, Endoscopic radiofrequency ablation (EBRFA) has been reported in several studies to improve and extend stent patency and the survival of patients with malignant biliary obstruction in CCA [13, 18-22]. Andrasina T et al investigated endoscopic RFA combined with MS placement (EBRFA) compared to only MS placement (SEMS) in pCCA. Results showed that RFA combined with stent placement significantly extended stent patency time, but there is no significant difference in survival [30]. While, Buerlein R et al showed EBRFA can improve overall survival when compared with SEMS [21]. Overall results have consistently suggested that modification of SEMS by RFA delivery could improve the clinical efficacy, safety and feasibility of endoscopic SEMS implement in CCA. Most of patients in this study did not received chemotherapy, as in several studies where patients not only had EBRFA but also received chemotherapy to suppress tumor growing [16, 17, 20, 30-32]. In our study, the aggressiveness of CCA was still present although RFA is derived in EBRFA group which might be not sufficient to limit the progression of cancer. Our study demonstrated the safety of EBRFA in patients with unresectable disease. Although EBRFA exhibited a higher tendency for pancreatitis and cholangitis compared to SEMS, this difference was not statistically significant, which is consistent with previous studies [20, 32]. However, when comparing the efficacy of EBRFA and SEMS in terms of prolonged stent patency and patient survival, no significant differences were observed. This may be attributed to the limited number of patients enrolled in the study. A key limitation of our study was the inability to recruit the target number of patients as calculated in the methodology. This shortcoming was largely due to disruptions caused by the COVID-19 outbreak during the study period, as well as a high rate of patient refusal to participate in the study. Additionally, several important prognostic factors—such as tumor morphology (ID, PI, MF, combined), Bismuth classification, and the presence of distant metastasis—were not fully controlled during randomization. However, the distributions between groups were not significantly different. The limited sample size also prevented subgroup analyses for each prognostic factor, thereby reducing the power to detect clinically meaningful imbalances (Supplementary Fig. 1). To conclusively evaluate the efficacy of EBRFA, further studies with a larger cohort of patients, ideally from multiple institutions, are needed. These efforts will help provide more robust evidence and validate the findings observed in our study. Despite these limitations our study has provided informative data concerning the safety in the use of EBRFA, its practicality, and feasibility as an alternative tool for palliative CCA treatment. Conclusions This study showed the feasibility and safety of EBRFA which can be used in combination with SEMS for the treatment unresectable pCCA, but there is no significant difference in survival and stent patency time between both currently used methods, EBRFA and SEMS. Abbreviations pCCA Perihilar cholangiocarcinoma EBS Endoscopic biliary stenting SEMS self-expanding metallic stents EBRFA Endobiliary radiofrequency ablation ID Intraductal duct PI Periductal infiltrating MF Mass forming MST Median survival time Declarations Acknowledgements All authors are truly thankful Prof. Narong Khuntikeo at Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand, Cholangiocarcinoma Research Institute (CARI), Khon Kaen University, Khon Kaen, Thailand and Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand for helpful discussions. Assoc. Prof. Dr. Bandit Thinkhamrop at Data Management and Statistical Analysis Center (DAMASAC), Faculty of Public Health, Khon Kaen University, Thailand for suggesting statistical analysis. We are also indebted to all members of CASCAP, particularly the cohort members, and researcher at CARI, Faculty of Medicine, Khon Kaen University for collecting and proofing of CCA patient data. In addition, we also thank Professor Ross H. Andrew for editing the MS via the Publication Clinic KKU, Thailand. Author contributions Conceptualization, A.J., V.T., T.S., V.L., T.T., A.T.; Funding acquisition, A.T.; Sample collection and diagnosis, A.J., V.T., T.S., V.L., T.T., A.A., A.T.; Analysis and interpretation of data, A.J. W.L., P.P., A.T.; Project administration, A.T.; Supervision, A.T.; Validation, A.J., V.T., T.S., V.L., T.T., A.A., W.L., P.P., A.T.; Writing original draft, A.J., P.P.; Writing review and editing, A.J. W.L., P.P., A.T. All authors approved the final version of the manuscript. Funding This work was supported by a grant from Cholangiocarcinoma Screening and Care Program (CASCAP-21), a grant from the National Research Council of Thailand via Cholangiocarcinoma Research Institute (FFTT2-14) and the NSRF under the Basic Research Fund of Khon Kaen University through Cholangiocarcinoma Research Institute allocated to AT. Data availability The datasets created and analyzed in this study are not publicly accessible because of ethical agreements concerning participant privacy. However, data sharing options can be discussed by contacting the corresponding author. Ethics approval and consent to participate The study protocol was performed based on the Declaration of Helsinki and approved by the Human Research Ethics Committee, Khon Kaen University (HE611487). Before the samples were collected, informed and written consent was obtained from all patients. In addition, this study has been registered with Thai Clinical Trials Registry, number TCTR20190704002. Consent for publication Not applicable. Competing interests The authors declare no competing interests References Banales JM, Cardinale V, Carpino G, Marzioni M, Andersen JB, Invernizzi P, Lind GE, Folseraas T, Forbes SJ, Fouassier L, et al. Expert consensus document: Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA). Nat Rev Gastroenterol Hepatol. 2016;13(5):261–80. Rogers JE, Law L, Nguyen VD, Qiao W, Javle MM, Kaseb A, Shroff RT. Second-line systemic treatment for advanced cholangiocarcinoma. J Gastrointest Oncol. 2014;5(6):408–13. Chaiteerakij R, Harmsen WS, Marrero CR, Aboelsoud MM, Ndzengue A, Kaiya J, Therneau TM, Sanchez W, Gores GJ, Roberts LR. A new clinically based staging system for perihilar cholangiocarcinoma. Am J Gastroenterol. 2014;109(12):1881–90. Jarnagin WR, Fong Y, DeMatteo RP, Gonen M, Burke EC, Bodniewicz BJ, Youssef BM, Klimstra D, Blumgart LH. Staging, resectability, and outcome in 225 patients with hilar cholangiocarcinoma. Ann Surg. 2001;234(4):507–17. discussion 517 – 509. Suzuki S, Sakaguchi T, Yokoi Y, Okamoto K, Kurachi K, Tsuchiya Y, Okumura T, Konno H, Baba S, Nakamura S. Clinicopathological prognostic factors and impact of surgical treatment of mass-forming intrahepatic cholangiocarcinoma. World J Surg. 2002;26(6):687–93. Luvira V, Nilprapha K, Bhudhisawasdi V, Pugkhem A, Chamadol N, Kamsa-ard S. Cholangiocarcinoma Patient Outcome in Northeastern Thailand: Single-Center Prospective Study. Asian Pac J Cancer Prev. 2016;17(1):401–6. Kamsa-Ard S, Luvira V, Suwanrungruang K, Kamsa-Ard S, Luvira V, Santong C, Srisuk T, Pugkhem A, Bhudhisawasdi V, Pairojkul C. Cholangiocarcinoma Trends, Incidence, and Relative Survival in Khon Kaen, Thailand From 1989 Through 2013: A Population-Based Cancer Registry Study. J Epidemiol. 2019;29(5):197–204. Monkemuller K, Popa D, Wilcox CM. Endoscopic treatment options for cholangiocarcinomas. Expert Rev Anticancer Ther. 2014;14(4):407–18. Moss AC, Morris E, Leyden J, MacMathuna P. Do the benefits of metal stents justify the costs? A systematic review and meta-analysis of trials comparing endoscopic stents for malignant biliary obstruction. Eur J Gastroenterol Hepatol. 2007;19(12):1119–24. Jang S, Stevens T, Parsi MA, Bhatt A, Kichler A, Vargo JJ. Superiority of Self-Expandable Metallic Stents Over Plastic Stents in Treatment of Malignant Distal Biliary Strictures. Clin Gastroenterol Hepatol. 2022;20(2):e182–95. Xia MX, Pan YL, Cai XB, Wu J, Gao DJ, Ye X, Wang TT, Hu B. Comparison of endoscopic bilateral metal stent drainage with plastic stents in the palliation of unresectable hilar biliary malignant strictures: Large multicenter study. Dig Endosc. 2021;33(1):179–89. Steel AW, Postgate AJ, Khorsandi S, Nicholls J, Jiao L, Vlavianos P, Habib N, Westaby D. Endoscopically applied radiofrequency ablation appears to be safe in the treatment of malignant biliary obstruction. Gastrointest Endosc. 2011;73(1):149–53. Sofi AA, Khan MA, Das A, Sachdev M, Khuder S, Nawras A, Lee W. Radiofrequency ablation combined with biliary stent placement versus stent placement alone for malignant biliary strictures: a systematic review and meta-analysis. Gastrointest Endosc. 2018;87(4):944–e951941. Cho YK, Kim JK, Kim MY, Rhim H, Han JK. Systematic review of randomized trials for hepatocellular carcinoma treated with percutaneous ablation therapies. Hepatology. 2009;49(2):453–9. Mulier S, Ruers T, Jamart J, Michel L, Marchal G, Ni Y. Radiofrequency ablation versus resection for resectable colorectal liver metastases: time for a randomized trial? An update. Dig Surg. 2008;25(6):445–60. Liang H, Peng Z, Cao L, Qian S, Shao Z. Metal Stenting with or without Endobiliary Radiofrequency Ablation for Unresectable Extrahepatic Cholangiocarcinoma. J Cancer Therapy. 2015;06No11:12. Yang J, Wang J, Zhou H, Wang Y, Huang H, Jin H, Lou Q, Shah RJ, Zhang X. Endoscopic radiofrequency ablation plus a novel oral 5-fluorouracil compound versus radiofrequency ablation alone for unresectable extrahepatic cholangiocarcinoma. Gastrointest Endosc. 2020;92(6):1204–e12121201. Dolak W, Schreiber F, Schwaighofer H, Gschwantler M, Plieschnegger W, Ziachehabi A, Mayer A, Kramer L, Kopecky A, Schrutka-Kolbl C, et al. Endoscopic radiofrequency ablation for malignant biliary obstruction: a nationwide retrospective study of 84 consecutive applications. Surg Endosc. 2014;28(3):854–60. Sharaiha RZ, Natov N, Glockenberg KS, Widmer J, Gaidhane M, Kahaleh M. Comparison of metal stenting with radiofrequency ablation versus stenting alone for treating malignant biliary strictures: is there an added benefit? Dig Dis Sci. 2014;59(12):3099–102. Andrasina T, Rohan T, Panek J, Kovalcikova P, Kunovsky L, Ostrizkova L, Valek V. The combination of endoluminal radiofrequency ablation and metal stent implantation for the treatment of malignant biliary stenosis - Randomized study. Eur J Radiol. 2021;142:109830. Buerlein R, Strand DS, Patrie JT, Sauer BG, Shami VM, Scheiman JM, Zaydfudim VM, Bauer TW, Adams RB, Wang AY. 544 ercp-directed biliary ablation prolongs survival in patients with unresectable perihilar cholangiocarcinoma compared to stenting alone. Gastrointest Endosc. 2019;89(6):AB91–2. Cui W, Wang Y, Fan W, Lu M, Zhang Y, Yao W, Li J. Comparison of intraluminal radiofrequency ablation and stents vs. stents alone in the management of malignant biliary obstruction. Int J Hyperth. 2017;33(7):853–61. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205–13. Liao W-C, Angsuwatcharakon P, Isayama H, Dhir V, Devereaux B, Khor CJL, Ponnudurai R, Lakhtakia S, Lee D-K et al. Ratanachu-ek T : International consensus recommendations for difficult biliary access. Gastrointestinal Endoscopy 2017, 85(2):295–304. Aphivatanasiri C, Sa-Ngiamwibool P, Sangkhamanon S, Intarawichian P, Kunprom W, Thanee M, Prajumwongs P, Khuntikeo N, Titapun A, Jareanrat A, et al. Modification of the eighth AJCC/UICC staging system for perihilar cholangiocarcinoma: An alternative pathological staging system from cholangiocarcinoma-prevalent Northeast Thailand. Front Med (Lausanne). 2022;9:893252. Gaspersz MP, Buettner S, van Vugt JLA, Roos E, Coelen RJS, Vugts J, Belt EJ, de Jonge J, Polak WG, Willemssen F, et al. Conditional survival in patients with unresectable perihilar cholangiocarcinoma. HPB (Oxford). 2017;19(11):966–71. Mosconi C, Renzulli M, Giampalma E, Galuppi A, Balacchi C, Brandi G, Ercolani G, Bianchi G, Golfieri R. Unresectable perihilar cholangiocarcinoma: multimodal palliative treatment. Anticancer Res. 2013;33(6):2747–53. Dewald CLA, Becker LS, Meine TC, Maschke SK, Wacker FK, Saborowski A, Vogel A, Hinrichs JB. New perspectives in unresectable cholangiocarcinoma? Evaluation of chemosaturation with percutaneous hepatic perfusion as a palliative treatment option. Clin Exp Metastasis 2022. Khorsandi S. In vivo experiments for the development of a novel bipolar radiofrequency probe (EndoHPB) for the palliation of malignant biliary obstruction. In: EASL Monothematic Conference Liver Cancer: from molecular pathogenesis to new therapies (P97), 2008: 2008 ; 2008. Inoue T, Ibusuki M, Kitano R, Kobayashi Y, Ohashi T, Nakade Y, Sumida Y, Ito K, Yoneda M. Endobiliary radiofrequency ablation combined with bilateral metal stent placement for malignant hilar biliary obstruction. Endoscopy. 2020;52(7):595–9. Alis H, Sengoz C, Gonenc M, Kalayci MU, Kocatas A. Endobiliary radiofrequency ablation for malignant biliary obstruction. Hepatobiliary Pancreat Dis Int. 2013;12(4):423–7. Bokemeyer A, Matern P, Bettenworth D, Cordes F, Nowacki TM, Heinzow H, Kabar I, Schmidt H, Ullerich H, Lenze F. Endoscopic Radiofrequency Ablation Prolongs Survival of Patients with Unresectable Hilar Cholangiocellular Carcinoma - A Case-Control Study. Sci Rep. 2019;9(1):13685. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5948371","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":442543067,"identity":"6c53b04d-181e-43d6-baff-b1f72c52fdbb","order_by":0,"name":"Apiwat Jareanrat","email":"","orcid":"","institution":"Khon Kaen University","correspondingAuthor":false,"prefix":"","firstName":"Apiwat","middleName":"","lastName":"Jareanrat","suffix":""},{"id":442543068,"identity":"98121008-dce7-482e-906f-cef7baa4eccf","order_by":1,"name":"Vasin Thanasukarn","email":"","orcid":"","institution":"Khon Kaen University","correspondingAuthor":false,"prefix":"","firstName":"Vasin","middleName":"","lastName":"Thanasukarn","suffix":""},{"id":442543070,"identity":"9bec59ca-0329-4332-8ef6-09a77756c39b","order_by":2,"name":"Tharatip Srisuk","email":"","orcid":"","institution":"Khon Kaen University","correspondingAuthor":false,"prefix":"","firstName":"Tharatip","middleName":"","lastName":"Srisuk","suffix":""},{"id":442543072,"identity":"5cc12af3-e2ce-40de-a5db-ee299ff08e54","order_by":3,"name":"Vor Luvira","email":"","orcid":"","institution":"Khon Kaen University","correspondingAuthor":false,"prefix":"","firstName":"Vor","middleName":"","lastName":"Luvira","suffix":""},{"id":442543074,"identity":"9f3bf553-d61f-429c-a6f3-9234c47e3601","order_by":4,"name":"Theerawee Tipwaratorn","email":"","orcid":"","institution":"Khon Kaen University","correspondingAuthor":false,"prefix":"","firstName":"Theerawee","middleName":"","lastName":"Tipwaratorn","suffix":""},{"id":442543076,"identity":"30b0b5e1-bfd8-4fc6-915e-4f0c9f7f22f0","order_by":5,"name":"Anucha Ahooja","email":"","orcid":"","institution":"Khon Kaen University","correspondingAuthor":false,"prefix":"","firstName":"Anucha","middleName":"","lastName":"Ahooja","suffix":""},{"id":442543079,"identity":"81ab2096-d389-45b3-ab8a-37a746394b62","order_by":6,"name":"Watcharin Loilome","email":"","orcid":"","institution":"Khon Kaen University","correspondingAuthor":false,"prefix":"","firstName":"Watcharin","middleName":"","lastName":"Loilome","suffix":""},{"id":442543084,"identity":"1b5b349c-10cc-42bc-aa37-9127e2b90c52","order_by":7,"name":"Piya Prajumwongs","email":"","orcid":"","institution":"Cholangiocarcinoma Research Institute, Khon Kaen University","correspondingAuthor":false,"prefix":"","firstName":"Piya","middleName":"","lastName":"Prajumwongs","suffix":""},{"id":442543085,"identity":"e7062447-b1a7-45be-8e0d-086897db0cd6","order_by":8,"name":"Attapol Titapun","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAuklEQVRIiWNgGAWjYNACAxsDCSgzgbBqNmYGhgMGaTAtBsRqYThMghb++f0HP38oOG8sOSOB8cMPhj95BLVIHGNmljhgcNtMWiKBWbKHwaCYsMOOMTOAtNjISSQwSAMdlthASIc80JYfBwzOgbQw/yZKi8ExZjagLQdADmMjzhbDY8lmFmcMko0lex62WfYYGBPWInf44OMbFX/sDGccTz5840eFHGEtSIARqNiABPWjYBSMglEwCnADALBcN1xZp3N7AAAAAElFTkSuQmCC","orcid":"","institution":"Khon Kaen University","correspondingAuthor":true,"prefix":"","firstName":"Attapol","middleName":"","lastName":"Titapun","suffix":""}],"badges":[],"createdAt":"2025-02-03 04:53:25","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5948371/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5948371/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12876-025-04104-6","type":"published","date":"2025-07-07T15:57:52+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":80790770,"identity":"fe504133-ad77-4399-b464-06f7279c68b2","added_by":"auto","created_at":"2025-04-17 06:40:09","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":53639632,"visible":true,"origin":"","legend":"\u003cp\u003eCholangiography demonstrated tumor obstruction of the common hepatic duct, resulting in upstream dilatation of both intrahepatic bile ducts. The endobiliary radio frequency probe ablates tumors.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-5948371/v1/f439861ecaefaecb54f8ca78.png"},{"id":80790773,"identity":"467c9a9c-6283-4990-8110-6dd05e026434","added_by":"auto","created_at":"2025-04-17 06:40:09","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":72815975,"visible":true,"origin":"","legend":"\u003cp\u003eDuodenoscopy revealed two ring electrodes at the tip of the endobiliary radiofrequency probe inserted via the ampulla.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-5948371/v1/3c55ef26b94b7672044dd1dd.png"},{"id":80791201,"identity":"159e9b3c-96f4-4fa9-b82d-ac9e9d284e32","added_by":"auto","created_at":"2025-04-17 06:48:08","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":35519391,"visible":true,"origin":"","legend":"\u003cp\u003eFollowing ablation treatment, a tumor remnant was retrieved while the radiofrequency endobiliary probe was removed.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-5948371/v1/826a567dda110665dda979bd.png"},{"id":80791197,"identity":"edcc8614-352b-46ed-9fc3-c28a984b7093","added_by":"auto","created_at":"2025-04-17 06:48:08","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":5325739,"visible":true,"origin":"","legend":"\u003cp\u003eConsort flow diagram of patient selection process.\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-5948371/v1/b888fe987f49f4cdfc1c3b79.png"},{"id":80791199,"identity":"04d083ef-c80b-4a67-b07d-4698e31cf37f","added_by":"auto","created_at":"2025-04-17 06:48:08","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":4601453,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of the efficacy between SEMS and EBRFA. (A) Stent patency time. (B) Overall survival time.\u003c/p\u003e","description":"","filename":"Figure5.png","url":"https://assets-eu.researchsquare.com/files/rs-5948371/v1/8f2ec111483bcf6c5614e966.png"},{"id":80790745,"identity":"8ecf1f39-5202-49e5-99ae-52933bbbd62a","added_by":"auto","created_at":"2025-04-17 06:40:08","extension":"tif","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":4257646,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFigure1.tif","url":"https://assets-eu.researchsquare.com/files/rs-5948371/v1/66aa46e2bb7d4c41d3cc6c08.tif"}],"financialInterests":"No competing interests reported.","formattedTitle":"Endobiliary radiofrequency ablation in recurrence and unresectable perihilar cholangiocarcinoma","fulltext":[{"header":"Background","content":"\u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eCholangiocarcinoma (CCA) is the second most common type of liver cancer arising from bile duct epithelial cells involving the intrahepatic (iCCA), perihilar (pCCA), and the distal (dCCA) biliary tree [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The CCA incidence in Thailand, especially in the northeast region, is extremely high compared to most parts of the world. Almost all CCA patients have poor prognosis and short survival outcome due a late CCA diagnosis. Thus, late presentations with locally advanced or metastatic disease contribute to the high mortality in patients. Surgical resection is the only potentially curative treatment in CCA patients who were found to be candidates for surgery, and hence, can prolong the overall survival of patients when compare to unresectable patients [\u003cspan additionalcitationids=\"CR3 CR4\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Nevertheless, the studies have reported that only 20% of CCA patients are resectable, while 80% was unresectable [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Most of unresectable CCA patients undergo extreme suffering due to several complications, such as obstruction of the bile ducts and jaundice, cholangitis, cirrhosis and malnutrition. These complications lead to reduce quality of life, and subsequently poor survival of unresectable CCA patients [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Therefore, palliative treatment has an important role to play to improve the outcomes and life quality of patients who are unresectable by surgical treatment or/and patients with recurrence of the disease.\u003c/p\u003e \u003cp\u003eEndoscopic biliary stenting (EBS) has been suggested as palliative treatment, because it is associated with a reduction in obstructive rate of bile ducts or jaundice, as well as other symptoms [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Normally, there are two types of material to design endoscopic stents, namely, metal and plastic. The reports revealed that self-expanding metallic stents (SEMS) have an average stent patency time, palliative drainage and obstructive recurrence significantly superior than biliary stents made from plastic material (PS) [\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Even through endoscopic metallic biliary stents are potential tools to reduce bile duct obstruction and prolong outcome of patients, cancer progression by in-/overgrowth biofilm deposition, biliary sludge, or formation of granulation tissue events may cause biliary stasis, subsequently, leading to recurrent biliary obstruction. These progressive causes of obstructive jaundice, subsequently result in significant morbidity and mortality of patients [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Therefore, modification of biliary stents is necessary to protect from symptomatic stent occlusion, and, therefore delay biliary obstruction.\u003c/p\u003e \u003cp\u003eRadiofrequency ablation (RFA) is applied in the biliary metallic stent placement for the purpose of percutaneous and endoscopic delivery of radiofrequency and heat energy which achieves and leads to coagulation localized tumor necrosis in CCA lesion [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. RFA has been suggested as having two significant expectations. Firstly, radiofrequency and heat energy from endobiliary radiofrequency ablation (EBRFA) reduces tumor burden, subsequently, delaying tumor growth that is associated with potential extension of stent patency time [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Secondly, EBRFA may be useful for neoadjuvant therapy in unresectable CCA cases [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Several studies have repeatedly reported the clinical advantages of EBRFA to extend stent patency when compared with MS, and improved the survival outcome of patients with malignant biliary obstruction, especially in CCA [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan additionalcitationids=\"CR18 CR19 CR20 CR21\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Thus, the ERFA is an alternative palliative treatment option for unresectable CCA patients. Nevertheless, there is still unclear and robust research in the treatment of unresectable pCCA patients by EBRFA.\u003c/p\u003e \u003cp\u003eThis study hypothesizes that EBRFA can be safely employed and feasable for unresectable pCCA patients. In addition, EBRFA may provide improvement of the stent patency and survival time extension more than only SEMS. This study thus aims to examine metallic endobiliary stenting methods in prospective, randomized, unresectable pCCA patients, and investigates the safety, efficacy outcomes in term of increasing stent patency, and patient\u0026rsquo;s survival outcome between patients with EBRFA versus patients with SEMS.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n \u003ch2\u003eEthic approval and consent to participate\u003c/h2\u003e\n \u003cp\u003eThe study protocol was performed based on the Declaration of Helsinki and approved by the Human Research Ethics Committee, Khon Kaen University (HE611487). Before the samples were collected, informed and written consent was obtained from all patients. In addition, this study has been registered with Thai Clinical Trials Registry, number TCTR20190704002.\u003c/p\u003e\n\u003c/div\u003e\n\u003ch3\u003eStudy population and sample size calculation\u003c/h3\u003e\n\u003cp\u003eThis study included patients diagnosed with cholangiocarcinoma (CCA) who presented with jaundice or recurrent disease and were classified as unresectable cases, receiving treatment at Srinagarind Hospital, Faculty of Medicine, Khon Kaen University between 2021 and 2024, with a total enrollment of 40 patients in this phase II study. The required sample size was determined using STATA (version 13) for the log-rank test, with a significance level of 0.05 and a power of 0.8, estimating that each group would require 36 patients, assuming that the experimental group would have a twofold lower risk of stent occlusion compared to the control group. The sample size calculation was performed using the formula:\u003c/p\u003e\n\u003cp\u003e\u003cimg 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\"\u003e\u003c/p\u003e\n\u003cp\u003ewhere:\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003e\n \u003cp\u003eZ\u003csub\u003e\u0026alpha;/2\u003c/sub\u003e is the critical value of the standard normal distribution at a significance level of 0.05 (typically 1.96 for a two-tailed test).\u003c/p\u003e\n \u003c/li\u003e\n \u003cli\u003e\n \u003cp\u003eZ\u003csub\u003e\u0026beta;\u003c/sub\u003e is the critical value corresponding to the statistical power of 0.8 (typically 0.84).\u003c/p\u003e\n \u003c/li\u003e\n \u003cli\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e \u003csub\u003e1\u003c/sub\u003e is the estimated probability of stent occlusion in the experimental group.\u003c/p\u003e\n \u003c/li\u003e\n \u003cli\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e \u003csub\u003e2\u003c/sub\u003e is the estimated probability of stent occlusion in the control group.\u003c/p\u003e\n \u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eBased on this formula, the sample size was calculated considering the hazard ratio, significance level, and statistical power to ensure adequate detection of differences between groups. The patency rate was assessed using a standard method, with an expected stent occlusion rate of 50% at 90 days post-procedure in the experimental group, whereas the control group had an expected occlusion rate of 20% at 90 days post-procedure. An interim analysis was planned once each group had at least 10 patients enrolled.\u003c/p\u003e\n\u003ch3\u003ePatient selection and research design\u003c/h3\u003e\n\u003cp\u003eThe study design was a randomized control trial. Patients with unresectable perihilar cholangiocarcinoma were diagnosed by Computerized Tomography and radiological finding was validated by attending radiologists to confirm diagnosis. Patients with inconclusive radiological finding (differential diagnosed with intrahepatic duct stone or benign biliary stricture) were excluded from this study. Patients with unresectable perihilar cholangiocarcinoma diagnosis had undergone endoscopic retrograde cholangiopancreatography (ERCP) for palliative treatment. Forty-four patients were prospectively randomized into 2 groups using computed generate random assignment order to each group by statisticians from Data Management and Statistical Analysis Center (DAMASAC), Faculty of Public Health, Khon Kaen University. Studied groups were included endobiliary radiofrequency ablation (EBRFA) with metallic biliary stents (MS) (n\u0026thinsp;=\u0026thinsp;22) and MS alone (n\u0026thinsp;=\u0026thinsp;22). Forty-four patients were included in this study using the following inclusion and exclusion criteria and the detailed selection process.\u003c/p\u003e\n\u003cp\u003eInclusion criteria: patients had age range 18\u0026ndash;75 years; patients were unresectable or recurrent cholangiocarcinoma diagnosis by pathology or radiographic; patients presented obstructive jaundice or had total bilirubin\u0026thinsp;\u0026gt;\u0026thinsp;3 mg/dL.\u003c/p\u003e\n\u003cp\u003eExclusion criteria: patients who had conditions including massive ascites, uncorrectable coagulopathy, presence of main portal vein thrombosis, Child-Pugh Score C cirrhosis, pregnancy, performance status ECOG\u0026thinsp;\u0026ge;\u0026thinsp;3 (confined to bed / chair\u0026thinsp;\u0026gt;\u0026thinsp;50% waking hours), presence of other malignancy, life expectancy\u0026thinsp;\u0026lt;\u0026thinsp;3 months, patients with cardiac pacemakers or other active implants, Comorbidities: congestive heart failure, COPD, Sepsis, uncorrectable thrombocytopenia (less than 100,000 cells/mm\u003csup\u003e3\u003c/sup\u003e) or uncorrectable coagulopathy (INR\u0026thinsp;\u0026gt;\u0026thinsp;1.5), prior SEMS placement, patients refused procedure and failure stent placement.\u003c/p\u003e\n\u003ch3\u003eEndobiliary radiofrequency ablation procedure steps\u003c/h3\u003e\n\u003cp\u003eEndobiliary radiofrequency ablation is a novel new treatment to improve the efficacy of cholangiocarcinoma therapy. This device includes the radio frequency generator and catheter as components. The generation produces radio frequency waves that convert to heat at the catheter\u0026apos;s tip. Local ablation of the tumor by thermal action. This treatment consists of local ablation prior to the insertion of a metallic biliary stent in order to delay stent obstruction. It can also be used in cases of biliary metallic stent obstruction caused by tumor. Prior to the procedure, the patient was hospitalized for one day during which time a doctor examined the general appearance and health status of the patient. In addition, blood tests, Coagulograms, chest x-rays, and EKGs were reviewed. The patient had no oral intake after midnight the night before the procedure. During that time, intravenous fluid was administered to maintain body fluid. Antibiotic prophylaxis and NSAID rectal suppository were prepared. Anesthesiologists routinely provided intravenous medication for sedation as a conventional anesthetic technique. The use of general anesthesia is limited to cases with cardiovascular illness, massive ascites that induced respiratory compromise, and severe jaundice. At 30 minutes before the procedure, a prophylactic antibiotic was administered. The patient was placed lying in a prone position, whereupon, the endoscopist initiates the ERCP procedures. A side-viewing duodenoscope was inserted into the duodenum, and the guidewire was advanced through the stricture by a standard sphincterotome, and a cholangiogram was viewed to determine the tumor site (Fig.\u0026nbsp;1). This was followed by the insertion of an 8-Fr (2.6 mm) bipolar radiofrequency ablation probe with two ring electrodes 8 mm wide stainless steel apart (HabibTM EndoHPB, EMcision Ltd, London, UK) as shown in Fig.\u0026nbsp;2. This results in an efficient cylindrical ablation over a 25 mm length between the distal and proximal electrodes. It is placed over the 0.035-millimeter guidewire. The tumor was ablated for 90 seconds at 9 Watts. After completing a cycle of ablation, there must be a 60 second interval should be adhered to before beginning the next cycle. The endoscopist relocates the RFA probe to the next obstruction and continues the ablation procedure until the entire tumor region has been treated. The generator uses a RITA 1500X RF generator (Angiodynamics, Latham, NY, USA). Following complete ablation the RFA probe was removed (Fig.\u0026nbsp;3). Coagulated tumor fragments are eliminated with subsequent balloon sweeps. This is followed by SEMS placement. A self-expanding metallic stent (Niti-S\u0026trade; Biliary Uncovered Stent, S-Type) of 10 mm in diameter and 80\u0026ndash;100 mm in length is placed over the guide wire. For the prevention of post-ERCP pancreatitis, an NSAID was applied to the rectum immediately after the procedure. Cholangitis and pancreatitis are common postoperative complications; serious complications have also been reported, including portal vein thrombosis, haemobilia, hepatic infarction, sepsis, and liver abscess. We graded the complication levels using the Clavien Dindo classification [\u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e]. We separated the complications into two levels including mild (Clavien Dindo grade I-II) and server complications (Clavien Dindo grade III-V).\u003c/p\u003e\n\u003ch3\u003ePercutaneous transhepatic biliary drainage (PTBD) and radiofrequency ablation (RFA)\u003c/h3\u003e\n\u003cp\u003eThe percutaneous approach was selected for patients with biliary obstructions that could not be addressed by endoscopic stenting due to factors such as anatomical challenges or insufficient duodenal access. This approach was specifically chosen when endoscopic treatment failed, as defined by difficult cannulation, which includes the inability to achieve selective biliary cannulation by standard ERCP techniques within 10 minutes or after up to five cannulation attempts, or failure of access to the major papilla [\u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n \u003ch2\u003ePre-procedure preparation\u003c/h2\u003e\n \u003cp\u003ePrior to the procedure, pre-operative imaging is reviewed to assess the anatomy and location of the biliary obstruction. The patient is positioned supine with the right side slightly elevated if targeting the right intrahepatic bile ducts. Local anesthesia is administered to the target area, and sedation is provided to ensure patient comfort. The procedure is performed under sterile conditions to prevent infection.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\n \u003ch2\u003eProcedure steps\u003c/h2\u003e\n \u003cp\u003eFirst, a Chiba needle (e.g., 18G) is percutaneously inserted into a dilated intrahepatic bile duct under ultrasound guidance, followed by the injection of a small volume of contrast medium to facilitate visualization of the biliary anatomy via fluoroscopy. Second, a hydrophilic guidewire (e.g., 0.035-inch) is advanced through the needle into the bile duct to establish access. Third, a series of plastic dilators are passed over the guidewire to gradually enlarge the tract, typically up to 7Fr, to accommodate the drainage catheter. Fourth, endobiliary radiofrequency ablation (RFA) is performed using a radiofrequency probe, which is introduced through the percutaneous tract to ablate obstructive tissue within the bile duct, utilizing the same technique as endoscopic RFA. Finally, a drainage catheter (6\u0026ndash;8 Fr) with multiple side holes is inserted along the dilated tract and secured at the skin entry site. The catheter is left in place for external drainage to decompress the biliary system, thereby ensuring bile flow and relieving further obstruction.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\n \u003ch2\u003eStent occlusion diagnosis criteria\u003c/h2\u003e\n \u003cp\u003eStent occlusion is defined as the failure of a stent to maintain patency, resulting in blockage or narrowing that impairs bile flow. The diagnosis of stent occlusion is based on both clinical manifestations and laboratory test results. Clinical manifestation, stent occlusion is commonly indicated by the recurrence of obstructive jaundice. Laboratory tests are used to further confirm the diagnosis, with stent occlusion suspected when the total bilirubin level exceeds 3 mg/dL in patients who do not exhibit obstructive jaundice after treatment. Additionally, stent occlusion is diagnosed when total bilirubin levels remain stable or increase over a period of two weeks following treatment in patients who initially did not present with obstructive jaundice. These criteria are critical for identifying stent failure and enabling timely intervention.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\n \u003ch2\u003eOutcome Measurement\u003c/h2\u003e\n \u003cp\u003eStent patency is defined as the time interval from the date of operation to the first occurrence of stent occlusion. Stent occlusion is diagnosed based on clinical symptoms (such as the recurrence of obstructive jaundice) and laboratory test results, as outlined in the Stent Occlusion Diagnosis Criteria. These criteria include an increase in total bilirubin greater than 3 mg/dL in patients who do not exhibit obstructive jaundice after treatment, or when total bilirubin levels remain stable or increase over a period of 2 weeks after treatment in patients without initial obstructive jaundice. While, overall survival (OS) is defined as the time from the date of operation to the date of death from any cause. Patients were followed up until death or the last recorded follow-up, whichever occurred first. OS was analyzed using Kaplan-Meier survival curves.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\n \u003ch2\u003eStatistical analysis\u003c/h2\u003e\n \u003cp\u003eThe statistical analyses were performed using SPSS (version 26.0; SPSS, Chicago, Ill, USA). The proportion of patient characteristics, preoperative testing, procedure detail and morbidity were analyzed using the Chi-square test (or Fisher\u0026rsquo;s exact test as appropriate), whereas continuous variables were analyzed using the student\u0026rsquo;s t-test for parametric or Mann\u0026ndash;Whitney test for nonparametric tests. Patient survival and stent patency time were calculated and compared using the Kaplan-Meier method and a Log-Rank test. Influence survival Factors in pCCA patients (age, gender, bismuth type, tumor morphology, distant metastasis, preoperative testing and MS methods) were further selected to identify independent factors using the Cox regression model. \u003cem\u003ep-value\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec17\" class=\"Section2\"\u003e\n \u003ch2\u003ePatient characteristics\u003c/h2\u003e\n \u003cp\u003eAccording to inclusion and exclusion criteria (Fig.\u0026nbsp;4), thirty-nine CCA patients who were diagnose unresectable were randomly separated into SEMS and ERFA groups composing 17/39 cases (44%) and 22/39 cases (56%), respectively. The median age was 62 years. The patient\u0026rsquo;s gender was 20/39 cases (51.3%) male and 19/39 cases (48.7%) female. Radiological imaging examination showed tumor morphology 3/39 cases (7.7%) such as, intraductal, periductal infiltrating 20/39 cases (51.3%), mass-forming 4/39 cases (10.3%) and combined morphological types 12/39 cases (30.7%). In addition, there was no significant deference of tumor morphology in SEMS and ERFA groups. In this study 30/39 (77%) cases at the time of diagnosis presented with distant metastasis, including 14/30 cases (47%) for SEMS and 16/30 cases (53%) for ERFA. The overall preoperative laboratory characteristics consisted of Hemoglobin (Hb) (11.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8 g/dL), WBC count [9770 cells/mm\u003csup\u003e3\u003c/sup\u003e(range, 7620\u0026ndash;12800)], Total bilirubin [16.8 mg/L (range, 6.4\u0026ndash;29)], Albumin (3.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6 g/dL), liver enzymes AST [104 U/L (range, 53\u0026ndash;168)], ALT [90 U/L (range, 45\u0026ndash;131)], [ALP 410 U/L (range, 292\u0026ndash;784)]. The proportion of patient\u0026rsquo;s characteristics and both the endoscopic biliary stent placements was performed. The result showed that there were no statistically significant differences of the patient\u0026rsquo;s characteristics proportions in both experimental groups namely, in age, gender, Bismuth type, imaging examination, distant metastasis, and preoperative testing (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec18\" class=\"Section2\"\u003e\n \u003ch2\u003e\u0026nbsp;\u003c/h2\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eDemographics of patient\u0026rsquo;s characteristic\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCharacteristic\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOverall\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;39)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSEMS\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;17)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eEBRFA\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;22)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003ep-value\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge\u0026thinsp;\u0026ge;\u0026thinsp;62 yrs. (range, 41\u0026ndash;74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20 (51.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9 (52.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11 (50.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.855\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19 (48.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9 (53%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10 (45.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.643\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBismuth type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9 (23.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (23.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (22.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" align=\"left\"\u003e\n \u003cp\u003e0.762\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21 (53.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 (47.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13 (59.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9 (23.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (29.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (18.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTumor morphology\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIntraductal (ID)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (7.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (5.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (9.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePeriductal infiltrating (PI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20 (51.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11 (64.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9 (40.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMass forming (MF)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (10.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (11.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (9.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.475\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCombined types\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12 (30.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (17.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9 (40.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDistant metastasis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9 (23.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (17.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (27.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30 (76.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14 (82.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16 (72.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.704\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePre-procedure lab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHb* (g/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.905\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWBC count\u003csup\u003e$\u003c/sup\u003e cells/mm\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9770\u003c/p\u003e\n \u003cp\u003e(7620\u0026ndash;12800)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11450\u003c/p\u003e\n \u003cp\u003e(9260\u0026ndash;14070)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8590\u003c/p\u003e\n \u003cp\u003e(7620\u0026ndash;10500)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.785\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTotal bilirubin\u003csup\u003e$\u003c/sup\u003e (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16.8 (6.4\u0026ndash;29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12.9 (7.1\u0026ndash;25.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18.7 (6.4\u0026ndash;30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.063\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAlbumin* (g/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.24 (0.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.18(0.66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.28 (0.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.709\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAST\u003csup\u003e$\u003c/sup\u003e (U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e104 (53\u0026ndash;168)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e125 (53\u0026ndash;170)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e81.5 (53\u0026ndash;167)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.499\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eALT\u003csup\u003e$\u003c/sup\u003e (U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e90 (45\u0026ndash;131)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e67 (45\u0026ndash;131)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e95.5 (43\u0026ndash;131)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.676\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eALP\u003csup\u003e$\u003c/sup\u003e (U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e410 (292\u0026ndash;784)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e410 (299\u0026ndash;927)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e392.5 (292\u0026ndash;725)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.677\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eNotes:\u003c/strong\u003e Mean (SD); \u003csup\u003e$\u003c/sup\u003eMedian (IQR); \u003csup\u003e#\u003c/sup\u003eFisher\u0026rsquo;s exact test.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eAbbreviation:\u003c/strong\u003e Hb, hemoglobin.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eThe comparison of procedure details and morbidity between SEMS and EBRFA\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eThe route of stent placement composed 34/39 cases (87.2%) for endoscopic and 5/39 cases (12.8%) for percutaneous placement. Stent implements were 2 types, including single 38/39 (97.4%) and double 1/39 (97.4%) stents. Complications included 7/39 cases (17.9%) of pancreatitis by 11.8% for SEMS and 22.7% for EBRFA, and cholangitis (18/25 mild by 29.4% for SEMS and 59.1% for EBRFA and 7/25 severe levels by 23.5% for SEMS and 13.6% for EBRFA). There was no statistically significant difference in the proportion of complications, pancreatitis (\u003cem\u003ep-value\u003c/em\u003e=0.376) and cholangitis (\u003cem\u003ep-value\u003c/em\u003e=0.200), between SEMS and EBRFA. While the median length of patients stayed at hospital was reported as 6 days (range, 2-9 days), there was no significant difference in the length of patients staying at hospital between both groups by 7 (range, 4-11) days for SEMS and 5 (range, 2-7) days for EBRFA (p = 0.237). After 4 weeks, all patients were followed up and total bilirubin reduction evaluated. Overall total bilirubin reduction was 8.2 mg/dL, by 14.7 mg/dL for EBRFA group and 4.1 mg/dL for SEMS group (\u003cem\u003ep-value\u003c/em\u003e=0.197). Postoperative observation, found that patients who survived less than 30-days were 5/39 cases (12.8%) composing 1 case (4.5%) in EBRFA, while 4 cases (23.5%) in SEMS. The comparison of procedure details and morbidity between the two methods showed that there was no significant difference, and stent patency time in this study was 73 days. There was no statistically significant difference of stent patency time between the EBRFA and SEMS (71 vs 78 days, \u003cem\u003ep-value\u003c/em\u003e=0.809) (Table 2 and Fig. 5A).\u003c/p\u003e\n \u003c/div\u003e\n \u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eProcedure detail and morbidity\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOverall\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSEMS\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eEBRFA\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003ep-value\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRoute of stent placement\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEndoscopic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34 (87.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14 (82.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20 (90.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003e0.428\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePercutaneous\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (12.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (17.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (9.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNumber of stents\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38 (97.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21 (95.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (2.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (4.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.373\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eComplications\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePancreatitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7 (17.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (11.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (22.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.376\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCholangitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e■ mild\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18 (47.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (29.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13 (59.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" align=\"char\"\u003e\n \u003cp\u003e0.200\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e■ severe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7 (15.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (23.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (13.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLength of hospital stay (day) \u003csup\u003e$\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (2\u0026ndash;9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7 (4\u0026ndash;11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (2\u0026ndash;7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.237\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTotal bilirubin reduction\u003c/p\u003e\n \u003cp\u003eafter 4 weeks (mg/dL) \u003csup\u003e$\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.2 (2\u0026ndash;18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.1 (1.8\u0026ndash;13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14.7 (2.2\u0026ndash;22.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.197\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30-day mortality\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (12.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (23.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (4.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.079\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eStent patency time (day)\u003csup\u003e$\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e73 (41\u0026ndash;137)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e78 (29\u0026ndash;167)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e71 (49\u0026ndash;123)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.809\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003cstrong\u003eNotes:\u003c/strong\u003e \u003csup\u003e$\u003c/sup\u003eMedian (IQR); \u003csup\u003e#\u003c/sup\u003eFisher\u0026rsquo;s exact test.\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSurvival and Prognosis Analysis\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eThe median survival time (MST) of unresectable patients in this study was 94 days. CCA patients who received EBRFA had a trend in survival time to be better than patients who received SEMS (OS = 94 vs 79 days, HR = 1.31, \u003cem\u003ep-value\u003c/em\u003e=0.735) (Fig. 5B). The survival time of bismuth type I was 104 days, while bismuth type III and IV were 94 and 41 days, respectively. There were no significant differences of the survival time between the three groups (MST=104 vs 94 and 41 days, HR 1.08 and 1.25, \u003cem\u003ep-value\u003c/em\u003e=0.853 and 0.64, respectively). For tumor morphology, ID (MST = 392 days) was used as a reference and compared to PI (MST = 79 days), MF (MST=78 days) and combined types (MST = 73 days). The comparison of the MST in the 4 types of morphology showed no significant difference in survival time. In addition, comparison of distant metastasis status resulted in no markedly different survival time. However, the total bilirubin level (TB) showed that patients with TB \u0026lt; 15 mg/dL had statistically significant better survival than patients with TB \u0026ge;15 mg/dL (MST = 201 vs 73 days, HR = 2.76, \u003cem\u003ep-value\u003c/em\u003e=0.004) (Table 3).\u003c/p\u003e\n \u003c/div\u003e\n \u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eSurvival analysis of perihilar CCA patients.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003cth style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/th\u003e\n \u003cth style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/th\u003e\n \u003cth style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eMST (Day (95%CI))\u003c/p\u003e\n \u003c/th\u003e\n \u003cth style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eCrude HR (95%CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003ep-value\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eOverall survival\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e94.0 (66.9- 121.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eSEMS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e79.0 (26.6\u0026ndash;131.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eEBRFA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e94.0 (58.4\u0026ndash;129.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e1.31 (0.67\u0026ndash;2.259)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.750\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eBismuth type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e104.0 (86.5-121.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eIII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e94.0 (33.1-154.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e1.08 (1.07\u0026ndash;2.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.875\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eIV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e40.0 (23.4\u0026ndash;56.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e1.91 (0.71\u0026ndash;5.16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.203\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eTumor morphology\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eID\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e392 (126.3-657.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003ePI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e79 (35.2-122.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e2.19 (0.64\u0026ndash;7.52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.213\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eMF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e78 (12.3-143.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e2.85 (0.61\u0026ndash;13.34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.183\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eCombined\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e73 (61.1\u0026ndash;84.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e3.11 (0.85\u0026ndash;11.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.087\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eDistant metastasis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e71.0 (1.3-140.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e98.0 (52.3-143.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e0.69 (0.33\u0026ndash;1.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.317\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eTotal Bilirubin level\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eTB\u0026thinsp;\u0026lt;\u0026thinsp;15 mg/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e201 (71\u0026ndash;311)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eTB\u0026thinsp;\u0026ge;\u0026thinsp;15 mg/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e73 (37\u0026ndash;104)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e2.76 (1.37\u0026ndash;5.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr style=\"height: 26px;\"\u003e\n \u003ctd style=\"height: 26px;\" colspan=\"5\"\u003eAbbreviations: ID\u0026thinsp;=\u0026thinsp;intraductal morphology; PI\u0026thinsp;=\u0026thinsp;periductal infiltration morphology; MF\u0026thinsp;=\u0026thinsp;mass-forming morphology; Combined\u0026thinsp;=\u0026thinsp;indicates the presence of more than one morphological type.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003ePerihilar Cholangiocarcinoma (pCCA) is mostly reported as having the highest incidence when compared to other types of CCA. Patients with pCCA have a poorer survival rate similar to that reported for iCCA and dCCA. Only 20% of patients were diagnosed as respectable patients, but the outcomes, such as 5-year survival and median survival are still not satisfactory, because as several reports have shown more than 50% of surgical patients presented during late stage (III-IV). Moreover, the report by Luvira V et al has shown that approximately 80% were unresectable patients due to presenting in the advanced stage of disease [6, 25, 26]. Therefore, the palliative treatments considered to prolong the survival of patients are chemotherapy and biliary drainage by the endoscopic biliary stent placement to improve quality of patient\u0026rsquo;s life [6, 27, 28].\u003c/p\u003e\n\u003cp\u003eEndoscopic biliary stent placement, especially self-expanding metallic stents (SEMS), is the one of palliative treatments in CCA for patients with unresectable status. It has been suggested that they can reduce bile duct obstruction and increase patency rate leading to improved overall survival of CCA patients. SEMS could prolong biliary obstruction and patient\u0026rsquo;s life expectancy higher than 3 months. Therefore, SEMS placement is an alternative tool for palliative treatment in unresectable CCA patients. However, several reports suggested that based on aggressiveness of CCA, the progression of cancer is still a major cause in the recurrence of biliary obstruction by in-/overgrowth biofilm deposition, biliary sludge and/or formation of granulation tissue. These events can lead to significant morbidity and mortality in patients [10, 12, 13]. In 2011, Alan W et al proposed the modification of SEMS placement by applying radiofrequency ablation (RFA) for the purpose of stent patency extension and delayed biliary obstruction. Applying RFA in SEMS has been done in an animal model, and showed improved stent patency and survival outcomes [29]. Therefore, this study showed applying RFA into SEMS in CCA to be safe and potentially feasibile in human subjects, as results showed high technical and functional success rates of more than 90% (Fig. 1). In addition, Endoscopic radiofrequency ablation (EBRFA) has been reported in several studies to improve and extend stent patency and the survival of patients with malignant biliary obstruction in CCA [13, 18-22]. Andrasina T et al investigated endoscopic RFA combined with MS placement (EBRFA) compared to only MS placement (SEMS) in pCCA. Results showed that RFA combined with stent placement significantly extended stent patency time, but there is no significant difference in survival [30]. While, Buerlein R et al showed EBRFA can improve overall survival when compared with SEMS [21]. Overall results have consistently suggested that modification of SEMS by RFA delivery could improve the clinical efficacy, safety and feasibility of endoscopic SEMS implement in CCA.\u003c/p\u003e\n\u003cp\u003eMost of patients in this study did not received chemotherapy, as in several studies where patients not only had EBRFA but also received chemotherapy to suppress tumor growing [16, 17, 20, 30-32]. In our study, the aggressiveness of CCA was still present although RFA is derived in EBRFA group which might be not sufficient to limit the progression of cancer.\u003c/p\u003e\n\u003cp\u003eOur study demonstrated the safety of EBRFA in patients with unresectable disease. Although EBRFA exhibited a higher tendency for pancreatitis and cholangitis compared to SEMS, this difference was not statistically significant, which is consistent with previous studies [20, 32]. However, when comparing the efficacy of EBRFA and SEMS in terms of prolonged stent patency and patient survival, no significant differences were observed. This may be attributed to the limited number of patients enrolled in the study. A key limitation of our study was the inability to recruit the target number of patients as calculated in the methodology. This shortcoming was largely due to disruptions caused by the COVID-19 outbreak during the study period, as well as a high rate of patient refusal to participate in the study. Additionally, several important prognostic factors\u0026mdash;such as tumor morphology (ID, PI, MF, combined), Bismuth classification, and the presence of distant metastasis\u0026mdash;were not fully controlled during randomization. However, the distributions between groups were not significantly different. The limited sample size also prevented subgroup analyses for each prognostic factor, thereby reducing the power to detect clinically meaningful imbalances (Supplementary Fig. 1). To conclusively evaluate the efficacy of EBRFA, further studies with a larger cohort of patients, ideally from multiple institutions, are needed. These efforts will help provide more robust evidence and validate the findings observed in our study.\u003c/p\u003e\n\u003cp\u003eDespite these limitations our study has provided informative data concerning the safety in the use of EBRFA, its practicality, and feasibility as an alternative tool for palliative CCA treatment.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis study showed the feasibility and safety of EBRFA which can be used in combination with SEMS for the treatment unresectable pCCA, but there is no significant difference in survival and stent patency time between both currently used methods, EBRFA and SEMS.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003epCCA\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Perihilar cholangiocarcinoma\u003c/p\u003e\n\u003cp\u003eEBS\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Endoscopic biliary stenting\u003c/p\u003e\n\u003cp\u003eSEMS\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;self-expanding metallic stents\u003c/p\u003e\n\u003cp\u003eEBRFA\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Endobiliary radiofrequency ablation\u003c/p\u003e\n\u003cp\u003eID\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Intraductal duct\u0026nbsp; \u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePI\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Periductal infiltrating\u003c/p\u003e\n\u003cp\u003eMF\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Mass forming\u003c/p\u003e\n\u003cp\u003eMST \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Median survival time\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors are truly thankful Prof. Narong Khuntikeo at Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand, Cholangiocarcinoma Research Institute (CARI), Khon Kaen University, Khon Kaen, Thailand and Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand for helpful discussions. Assoc. Prof. Dr. Bandit Thinkhamrop at Data Management and Statistical Analysis Center (DAMASAC), Faculty of Public Health, Khon Kaen University, Thailand for suggesting statistical analysis. We are also indebted to all members of CASCAP, particularly the cohort members, and researcher at CARI, Faculty of Medicine, Khon Kaen University for collecting and proofing of CCA patient data. In addition, we also thank Professor Ross H. Andrew for editing the MS via the Publication Clinic KKU, Thailand.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceptualization, A.J., V.T., T.S., V.L., T.T., A.T.; Funding acquisition, A.T.; Sample collection and diagnosis, A.J., V.T., T.S., V.L., T.T., A.A., A.T.; Analysis and interpretation of data, A.J. W.L., P.P., A.T.; Project administration, A.T.; Supervision, A.T.; Validation, A.J., V.T., T.S., V.L., T.T., A.A., W.L., P.P., A.T.; Writing original draft, A.J., P.P.; Writing review and editing, A.J. W.L., P.P., A.T. All authors approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by a grant from Cholangiocarcinoma Screening and Care Program (CASCAP-21), a grant from the National Research Council of Thailand via Cholangiocarcinoma Research Institute (FFTT2-14) and the NSRF under the Basic Research Fund of Khon Kaen University through Cholangiocarcinoma Research Institute allocated to AT.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets created and analyzed in this study are not publicly accessible because of ethical agreements concerning participant privacy. However, data sharing options can be discussed by contacting the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study protocol was performed based on the Declaration of Helsinki and approved by the Human Research Ethics Committee, Khon Kaen University (HE611487). Before the samples were collected, informed and written consent was obtained from all patients. In addition, this study has been registered with Thai Clinical Trials Registry, number TCTR20190704002.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;Not applicable.\u003cbr\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;The authors declare no competing interests\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBanales JM, Cardinale V, Carpino G, Marzioni M, Andersen JB, Invernizzi P, Lind GE, Folseraas T, Forbes SJ, Fouassier L, et al. Expert consensus document: Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA). Nat Rev Gastroenterol Hepatol. 2016;13(5):261\u0026ndash;80.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRogers JE, Law L, Nguyen VD, Qiao W, Javle MM, Kaseb A, Shroff RT. Second-line systemic treatment for advanced cholangiocarcinoma. J Gastrointest Oncol. 2014;5(6):408\u0026ndash;13.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChaiteerakij R, Harmsen WS, Marrero CR, Aboelsoud MM, Ndzengue A, Kaiya J, Therneau TM, Sanchez W, Gores GJ, Roberts LR. A new clinically based staging system for perihilar cholangiocarcinoma. Am J Gastroenterol. 2014;109(12):1881\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJarnagin WR, Fong Y, DeMatteo RP, Gonen M, Burke EC, Bodniewicz BJ, Youssef BM, Klimstra D, Blumgart LH. Staging, resectability, and outcome in 225 patients with hilar cholangiocarcinoma. Ann Surg. 2001;234(4):507\u0026ndash;17. discussion 517\u0026thinsp;\u0026ndash;\u0026thinsp;509.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSuzuki S, Sakaguchi T, Yokoi Y, Okamoto K, Kurachi K, Tsuchiya Y, Okumura T, Konno H, Baba S, Nakamura S. Clinicopathological prognostic factors and impact of surgical treatment of mass-forming intrahepatic cholangiocarcinoma. World J Surg. 2002;26(6):687\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLuvira V, Nilprapha K, Bhudhisawasdi V, Pugkhem A, Chamadol N, Kamsa-ard S. Cholangiocarcinoma Patient Outcome in Northeastern Thailand: Single-Center Prospective Study. Asian Pac J Cancer Prev. 2016;17(1):401\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKamsa-Ard S, Luvira V, Suwanrungruang K, Kamsa-Ard S, Luvira V, Santong C, Srisuk T, Pugkhem A, Bhudhisawasdi V, Pairojkul C. Cholangiocarcinoma Trends, Incidence, and Relative Survival in Khon Kaen, Thailand From 1989 Through 2013: A Population-Based Cancer Registry Study. J Epidemiol. 2019;29(5):197\u0026ndash;204.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMonkemuller K, Popa D, Wilcox CM. Endoscopic treatment options for cholangiocarcinomas. Expert Rev Anticancer Ther. 2014;14(4):407\u0026ndash;18.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMoss AC, Morris E, Leyden J, MacMathuna P. Do the benefits of metal stents justify the costs? A systematic review and meta-analysis of trials comparing endoscopic stents for malignant biliary obstruction. Eur J Gastroenterol Hepatol. 2007;19(12):1119\u0026ndash;24.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJang S, Stevens T, Parsi MA, Bhatt A, Kichler A, Vargo JJ. Superiority of Self-Expandable Metallic Stents Over Plastic Stents in Treatment of Malignant Distal Biliary Strictures. Clin Gastroenterol Hepatol. 2022;20(2):e182\u0026ndash;95.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXia MX, Pan YL, Cai XB, Wu J, Gao DJ, Ye X, Wang TT, Hu B. Comparison of endoscopic bilateral metal stent drainage with plastic stents in the palliation of unresectable hilar biliary malignant strictures: Large multicenter study. Dig Endosc. 2021;33(1):179\u0026ndash;89.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSteel AW, Postgate AJ, Khorsandi S, Nicholls J, Jiao L, Vlavianos P, Habib N, Westaby D. Endoscopically applied radiofrequency ablation appears to be safe in the treatment of malignant biliary obstruction. Gastrointest Endosc. 2011;73(1):149\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSofi AA, Khan MA, Das A, Sachdev M, Khuder S, Nawras A, Lee W. Radiofrequency ablation combined with biliary stent placement versus stent placement alone for malignant biliary strictures: a systematic review and meta-analysis. Gastrointest Endosc. 2018;87(4):944\u0026ndash;e951941.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCho YK, Kim JK, Kim MY, Rhim H, Han JK. Systematic review of randomized trials for hepatocellular carcinoma treated with percutaneous ablation therapies. Hepatology. 2009;49(2):453\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMulier S, Ruers T, Jamart J, Michel L, Marchal G, Ni Y. Radiofrequency ablation versus resection for resectable colorectal liver metastases: time for a randomized trial? An update. Dig Surg. 2008;25(6):445\u0026ndash;60.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiang H, Peng Z, Cao L, Qian S, Shao Z. Metal Stenting with or without Endobiliary Radiofrequency Ablation for Unresectable Extrahepatic Cholangiocarcinoma. J Cancer Therapy. 2015;06No11:12.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYang J, Wang J, Zhou H, Wang Y, Huang H, Jin H, Lou Q, Shah RJ, Zhang X. Endoscopic radiofrequency ablation plus a novel oral 5-fluorouracil compound versus radiofrequency ablation alone for unresectable extrahepatic cholangiocarcinoma. Gastrointest Endosc. 2020;92(6):1204\u0026ndash;e12121201.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDolak W, Schreiber F, Schwaighofer H, Gschwantler M, Plieschnegger W, Ziachehabi A, Mayer A, Kramer L, Kopecky A, Schrutka-Kolbl C, et al. Endoscopic radiofrequency ablation for malignant biliary obstruction: a nationwide retrospective study of 84 consecutive applications. Surg Endosc. 2014;28(3):854\u0026ndash;60.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSharaiha RZ, Natov N, Glockenberg KS, Widmer J, Gaidhane M, Kahaleh M. Comparison of metal stenting with radiofrequency ablation versus stenting alone for treating malignant biliary strictures: is there an added benefit? Dig Dis Sci. 2014;59(12):3099\u0026ndash;102.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAndrasina T, Rohan T, Panek J, Kovalcikova P, Kunovsky L, Ostrizkova L, Valek V. The combination of endoluminal radiofrequency ablation and metal stent implantation for the treatment of malignant biliary stenosis - Randomized study. Eur J Radiol. 2021;142:109830.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBuerlein R, Strand DS, Patrie JT, Sauer BG, Shami VM, Scheiman JM, Zaydfudim VM, Bauer TW, Adams RB, Wang AY. 544 ercp-directed biliary ablation prolongs survival in patients with unresectable perihilar cholangiocarcinoma compared to stenting alone. Gastrointest Endosc. 2019;89(6):AB91\u0026ndash;2.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCui W, Wang Y, Fan W, Lu M, Zhang Y, Yao W, Li J. Comparison of intraluminal radiofrequency ablation and stents vs. stents alone in the management of malignant biliary obstruction. Int J Hyperth. 2017;33(7):853\u0026ndash;61.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205\u0026ndash;13.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiao W-C, Angsuwatcharakon P, Isayama H, Dhir V, Devereaux B, Khor CJL, Ponnudurai R, Lakhtakia S, Lee D-K et al. Ratanachu-ek T : International consensus recommendations for difficult biliary access. \u003cem\u003eGastrointestinal Endoscopy\u003c/em\u003e 2017, 85(2):295\u0026ndash;304.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAphivatanasiri C, Sa-Ngiamwibool P, Sangkhamanon S, Intarawichian P, Kunprom W, Thanee M, Prajumwongs P, Khuntikeo N, Titapun A, Jareanrat A, et al. Modification of the eighth AJCC/UICC staging system for perihilar cholangiocarcinoma: An alternative pathological staging system from cholangiocarcinoma-prevalent Northeast Thailand. Front Med (Lausanne). 2022;9:893252.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGaspersz MP, Buettner S, van Vugt JLA, Roos E, Coelen RJS, Vugts J, Belt EJ, de Jonge J, Polak WG, Willemssen F, et al. Conditional survival in patients with unresectable perihilar cholangiocarcinoma. HPB (Oxford). 2017;19(11):966\u0026ndash;71.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMosconi C, Renzulli M, Giampalma E, Galuppi A, Balacchi C, Brandi G, Ercolani G, Bianchi G, Golfieri R. Unresectable perihilar cholangiocarcinoma: multimodal palliative treatment. Anticancer Res. 2013;33(6):2747\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDewald CLA, Becker LS, Meine TC, Maschke SK, Wacker FK, Saborowski A, Vogel A, Hinrichs JB. New perspectives in unresectable cholangiocarcinoma? Evaluation of chemosaturation with percutaneous hepatic perfusion as a palliative treatment option. Clin Exp Metastasis 2022.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKhorsandi S. In vivo experiments for the development of a novel bipolar radiofrequency probe (EndoHPB) for the palliation of malignant biliary obstruction. In: \u003cem\u003eEASL Monothematic Conference Liver Cancer: from molecular pathogenesis to new therapies (P97), 2008: 2008\u003c/em\u003e; 2008.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eInoue T, Ibusuki M, Kitano R, Kobayashi Y, Ohashi T, Nakade Y, Sumida Y, Ito K, Yoneda M. Endobiliary radiofrequency ablation combined with bilateral metal stent placement for malignant hilar biliary obstruction. Endoscopy. 2020;52(7):595\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlis H, Sengoz C, Gonenc M, Kalayci MU, Kocatas A. Endobiliary radiofrequency ablation for malignant biliary obstruction. Hepatobiliary Pancreat Dis Int. 2013;12(4):423\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBokemeyer A, Matern P, Bettenworth D, Cordes F, Nowacki TM, Heinzow H, Kabar I, Schmidt H, Ullerich H, Lenze F. Endoscopic Radiofrequency Ablation Prolongs Survival of Patients with Unresectable Hilar Cholangiocellular Carcinoma - A Case-Control Study. Sci Rep. 2019;9(1):13685.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":false,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-gastroenterology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmge","sideBox":"Learn more about [BMC Gastroenterology](http://bmcgastroenterol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmge/default.aspx","title":"BMC Gastroenterology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Cholangiocarcinoma, Klatskin tumor, Endobiliary radiofrequency ablation, Metallic biliary stent, Unresectable treatment, palliative treatment, Obstructive jaundice, Randomized trial","lastPublishedDoi":"10.21203/rs.3.rs-5948371/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5948371/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Palliative biliary stenting is the principal treatment for unresectable perihilar cholangiocarcinoma (pCCA) patients who suffer from jaundice. Endobiliary radiofrequency ablation (EBRFA) is the novel treatment in combination with biliary stenting for CCA with the intention to extend the patency and survival of patients which is a lack of knowledge and evident base data for perihilar CCA. This study aims to investigate the safety of EBRFA and efficacy in terms of increasing stent patency and the patient’s survival.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e Patients with unresectable perihilar CCA were prospectively randomized into 2 groups including EBRFA with self-expandable metallic stent (SEMS), and SEMS alone. Stent patency time was recorded after stent implantation and until obstructive jaundice occurrence. The median survival time (MST), median stent patency, and adverse event rate were analyzed and compared using Log-rank test. The proportion comparisons of patient characteristics, preoperative testing, procedure detail, and morbidity in two methods were conducted by Chi-squad test.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResult:\u003c/strong\u003e Of a total of 39 patients who were diagnosed pCCA and included in this study, 22 patients were in the EBRFA group and 17 patients in SEMS group. The procedure-related complication rate was not statistically significant different between EBRFA and the SEMS groups. There was no statistically significant difference of stent patency time between EBRFA and SEMS groups (71 vs 78 days, \u003cem\u003ep-value\u003c/em\u003e=0.809), as well as The OS of EBRFA group had no statistically significant difference with SEMS group, (94 vs 79 days, HR= 1.31, 95%CI: 0.66-2.58, \u003cem\u003ep-value\u003c/em\u003e=0.735).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e The EBRFA was shown to be safe to use and practical to perform combined with SEMS for treatment unresectable pCCA.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial registration:\u003c/strong\u003e \u003cstrong\u003eTCTR20190704002\u003c/strong\u003e\u003c/p\u003e","manuscriptTitle":"Endobiliary radiofrequency ablation in recurrence and unresectable perihilar cholangiocarcinoma","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-17 06:40:03","doi":"10.21203/rs.3.rs-5948371/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-04-25T15:09:24+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-23T11:44:23+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-16T23:12:11+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"72597458458642669902830167567030831160","date":"2025-04-16T23:04:32+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"77399753498067941479019589666512451095","date":"2025-04-15T04:50:05+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-04-14T07:23:57+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-14T01:17:03+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Gastroenterology","date":"2025-04-11T05:22:39+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-gastroenterology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmge","sideBox":"Learn more about [BMC Gastroenterology](http://bmcgastroenterol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmge/default.aspx","title":"BMC Gastroenterology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5ddc09c5-4d23-4afc-85e8-47485584ebdf","owner":[],"postedDate":"April 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-07-14T16:06:43+00:00","versionOfRecord":{"articleIdentity":"rs-5948371","link":"https://doi.org/10.1186/s12876-025-04104-6","journal":{"identity":"bmc-gastroenterology","isVorOnly":false,"title":"BMC Gastroenterology"},"publishedOn":"2025-07-07 15:57:52","publishedOnDateReadable":"July 7th, 2025"},"versionCreatedAt":"2025-04-17 06:40:03","video":"","vorDoi":"10.1186/s12876-025-04104-6","vorDoiUrl":"https://doi.org/10.1186/s12876-025-04104-6","workflowStages":[]},"version":"v1","identity":"rs-5948371","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5948371","identity":"rs-5948371","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}