Intraductal Radiofrequency Ablation Research Articles

Radiofrequency ablation via catheter and transpapillary access in patients with cholangiocarcinoma (ACTICCA-2 trial) – a multicenter, randomized, controlled, open-label investigator-initiated trial

BackgroundDespite the recent advances in cancer treatment, the therapeutic options for patients with biliary tract cancer are still very limited and the prognosis very poor. More than 50% of newly diagnosed patients with biliary tract cancer are not amenable to curative surgical treatment and thus treated with palliative systemic treatment. Malignant bile duct obstructions in patients with perihilar and/or ductal cholangiocarcinoma (CCA) represents one of the most important challenges in the management of these patients, owning to the risk represented by developing life-threatening cholangitis which, in turn, limits the use of systemic treatment. For this reason, endoscopic stenting and/or bile duct decompression is the mainstay of treatment of these patients. Data on efficacy and safety of adding radiofrequency ablation (RFA) to biliary stenting is not conclusive. The aim of this multicenter, randomized trial is to evaluate the effect of intraductal RFA prior to bile duct stenting in patients with unresectable perihilar or ductal CCA undergoing palliative systemic therapy.Methods/DesignACTICCA-2 is a multicenter, randomized, controlled, open-label, investigator-initiated trial. 120 patients with perihilar or ductal CCA with indication for biliary stenting and systemic therapy will be randomized 1:1 to receive either RFA plus bile duct stenting (interventional arm) or bile duct stenting alone (control arm). Patients will be stratified by trial site and tumor location (perihilar vs. ductal). Both arms receive palliative systemic treatment according to the local standard of care determined by a multidisciplinary tumorboard. The primary endpoint is time to first biliary event, which is determined by an increase of bilirubin to > 5 mg/dl and/or the occurrence of cholangitis leading to premature stent replacement and/or disruption of chemotherapy. Secondary endpoints include overall survival, safety according to NCI CTCAE v5, quality of life assessed by questionnaires (EORTC QLQ-C30 and QLQ-BIL21), clinical event rate at 6 months after RFA and total days of over-night stays in hospital. Follow-up for the primary endpoint will be 6 months, while survival assessment will be continued until end of study (maximum follow-up 30 month). All patients who are randomized and who underwent endoscopic stenting will be used for the primary endpoint analysis which will be conducted using a cause-specific Cox proportional hazards model with a frailty for trial site and fixed effects for the treatment group, tumor location, and stent material.DiscussionACTICCA-2 is a multicenter, randomized, controlled trial to assess efficacy and safety of adding biliary RFA to bile duct stenting in patients with CCA receiving palliative systemic treatment.Trial registrationThe study is registered with ClinicalTrials.gov (NCT06175845) and approved by the local ethics committee in Hamburg, Germany (2024-101232-BO-ff). This manuscript reflects protocol version 1 as of January 9th, 2024.Graphical

Experience in the use of intraductal radiofrequency ablation for adenomas of the major duodenal papilla with intraductal spread

Background. Due to the high risk of malignancy, all adenomas of the major duodenal papilla, regardless of morphological structure, must be removed. Currently, the method of choice for adenomas of the major duodenal papilla is endoscopic surgery, with neoplasms of the major duodenal papilla with intraductal spread (types III and IV according to the endoscopic classification of neoplasms of the major duodenal papilla) representing particular difficulty for endoscopic techniques. The introduction of intraductal radiofrequency ablation into clinical practice provides new opportunities for minimally invasive treatment of patients with adenomas of the major duodenal papilla, including those with extensive spread to the bile and pancreatic ducts. Material and methods. From 2022 to 2024, 14 patients with adenomas of the major duodenal papilla with extension to the common bile and main pancreatic ducts underwent intraductal radiofrequency ablation. The extent of spread of the adenoma to the common bile duct ranged from 10 to 30 mm, to the main pancreatic duct - from 3 to 11 mm. Results. Technical success of intraductal RFA was achieved in all cases. Postoperative complications were noted in 3 cases, in which moderately severe post-manipulation pancreatitis developed. During a follow-up examination after 3-6 months, residual adenomatous growths were detected in 3 patients, which required a repeat session of intraductal RFA. All patients underwent stenting of the main pancreatic duct and the common bile duct was achieved in all cases. Conclusion. Intraductal radiofrequency ablation has opened up the possibility of endoscopic treatment of patients with adenomas of the major duodenal papilla, characterized by extensive spread to the common bile and main pancreatic ducts.

Intraductal radiofrequency ablation plus biliary stent versus stent alone for malignant biliary obstruction: a systematic review and meta-analysis.

Background and study aims Recurrent biliary stent occlusion and tumor ingrowth remain a major concern among patients with malignant biliary obstruction (MBO) with significant impact on patient morbidity and survival. Intraductal radiofrequency ablation (RFA) has emerged as a promising treatment that seeks to extend stent patency. This study aimed to evaluate the impact of RFA on overall survival (OS) and stent patency among patients with unresectable MBO. Methods A comprehensive search of electronic databases was performed for randomized controlled trials (RCTs) comparing RFA plus biliary stent (RFA+S) versus biliary stent alone (S-alone). Outcomes assessed included overall survival, stent patency, and adverse events (AEs) with mean difference (MD) calculated from pooled proportions. Subgroup analyses were performed for hilar strictures and cholangiocarcinoma (CCA). Results Six RCTs (n=439 patients) were included and demonstrated improved survival among patients who received RFA+S (MD 85.80 days; 95% confidence interval [CI] 35.02-136.58; I 2 =97%; P <0.0009). The pooled MD for total stent patency was 22.25 days (95% CI 17.38-61.87; I 2 =97%; P =0.27). There was no difference in AEs between RFA+S vs S-alone ( P >0.05). On subgroup analyses, RFA+S was associated with improved stent patency (MD 76.73 days; 95% CI 50.11-103.34; I 2 =67%; P <0.01) and OS (MD 83.14 (95% CI 29.52-136.77; I 2 =97%; P <0.01] for CCA. For hilar strictures, stent patency was improved among patients with RFA+S [MD 83.71 days (95% CI 24.85-142.56; I 2 =84%; P <0.01]. Conclusions RFA+S improved OS in the treatment of MBO when compared with S-alone. Moreover, the RFA therapy prolonged stent patency in hilar strictures and CCA, with similar rates of AEs.

Intraductal radiofrequency ablation for neoplasms of the major duodenal papilla with intraductal spread

To analyze the efficacy of intraductal radiofrequency ablation (RFA) for neoplasms of the major duodenal papilla with intraductal spread. Eleven patients with adenomas of the major duodenal papilla and intraductal spread underwent intraductal RFA between 2022 and 2023. Spread to the common bile duct ranged from 10 to 30 mm, to the main pancreatic duct - from 5 to 11 mm. Technical success was achieved in all cases. Complications after intraductal RFA occurred in 4 cases (post-manipulation pancreatitis - 2 cases, repeated intraductal RFA for residual adenomatous growths - 2 cases). Technical success of stenting of the main pancreatic and common bile ducts was achieved in all cases. Intraductal radiofrequency ablation for neoplasms of the major duodenal papilla with intraductal spread ensured complete destruction of intraductal tumor with adequate clinical effect and no need for highly traumatic surgery.

The first experience of intraductal radiofrequency ablation for a large adenoma of the major duodenal papilla with extended intraductal spread

The first experience of intraductal radiofrequency ablation for a large adenoma of the major duodenal papilla with extended intraductal spread

Feasibility of in vivo swine models using guide wire-assisted intraductal radiofrequency ablation for benign biliary stricture

Several in vivo swine models of benign biliary stenosis (BBS) have been recently reported for preclinical studies of novel endoscopic techniques and devices. The aim of this study was to evaluate the efficacy and feasibility of large animal models of BBS by using intraductal radiofrequency ablation (RFA) assisted by guide wire. Six in vivo swine models were made by using an intraductal RFA for cauterization at 10 W, 80 °C, 90 s in the common bile duct (CBD). Endoscopic retrograde cholangiopancreatography (ERCP) was performed with cholangiography and histologic evaluation was done for the common bile duct. Blood tests were examined before, after, and at the final follow-up. Guide wire assisted RFA electrode produced BBS in all (6/6, 100%) animal models without severe complications. Fluoroscopy findings at 2 weeks after intraductal RFA in every model revealed BBS in the common bile duct. In histologic evaluations, fibrosis and chronic inflammatory changes were noted. After the procedure, ALP, GGT, and CRP were elevated and decreased after an appropriate drain. A swine model of BBS is developed by inducing intraductal thermal injury using intraductal RFA assisted by guide wire. This novel technique for inducing BBS in swine is effective and feasible.

Double bare metal stent deployment combined with intraductal radiofrequency ablation for malignant distal biliary obstruction: a prospective pilot study

Although uncovered self-expandable metal stents (SEMSs) possess certain advantages such as averting cystic duct obstruction and stent migration, they are susceptible to ingrowth occlusion. The combination of the double bare stent (DBS) and endobiliary radiofrequency ablation (RFA) may reduce ingrowth. Hence, this study aimed to examine the utility of this method for the treatment of unresectable malignant distal biliary obstruction (MDBO). This prospective, single-center, pilot study enrolled 51 patients who met the eligibility criteria between February 2020 and January 2022. The study outcomes included technical success, clinical success, recurrent biliary obstruction (RBO), and other adverse events (AE) besides RBO associated with DBS placement with RFA for MDBO. The technical success rate was 98.0% (50/51). Clinical success was achieved in all patients in whom technical success was achieved. The rates of early and late AEs were 5.9% (3/51) and 8.0% (4/50), respectively. The incidence rate of RBO was 38.0% (19/50). Sludge occlusion, ingrowth occlusion, and overgrowth occlusion occurred in 26.0% (13/50), 8.0% (4/50), and 2.0% (1/50) of patients, respectively (the main cause of RBO was undeterminable in 1 patient). The median time to RBO was 241 days. DBS with RFA showed good technical feasibility, good long-term outcomes, acceptable AE rates, and most importantly, a low ingrowth occlusion rate when employed for the treatment of MDBO.

Radiofrequency ablation for pancreatobiliary disease: an updated review.

Endoscopic radiofrequency ablation (RFA) has emerged as a minimally invasive treatment option in cases of malignant biliary obstruction, pancreatic cancer, and other pancreatic cystic neoplasms. Intraductal biliary RFA is safe, effective, and confers a survival advantage over stenting alone, where it should be used an adjunct to biliary stenting. Endoscopic ultrasound-guided RFA can also provide pancreatic cyst resolution in patients who are not ideal operative candidates. The aim of this review is to describe the endoscopic applications and associated outcomes of RFA.

Long-term Outcomes of Endoscopic Intraductal Radiofrequency Ablation for Ampullary Adenoma with Intraductal Extension after Endoscopic Snare Papillectomy.

There are limitations in treating ampullary adenomas with intraductal extension using conventional endoscopic modalities. Endoscopic intraductal radiofrequency ablation (ID-RFA) may be useful for treating intraductal (common bile duct [CBD] and/or pancreatic duct [PD]) extensions of ampullary adenomas, but long-term data are lacking. We thus evaluated the long-term outcomes of endoscopic ID-RFA for managing ampullary adenomas with intraductal extension. Prospectively collected endoscopic ID-RFA database at Asan Medical Center was reviewed to identify consecutive patients with ampullary adenoma who underwent ID-RFA for intraductal extension between January 2018 and August 2021. Technical success, short-term and long-term clinical success, and adverse events were evaluated. A total of 29 patients (14 CBD, 1 PD, and 14 CBD and PD) were analyzed. All patients had undergone endoscopic snare papillectomy prior to ID-RFA. A median of one session of ID-RFA (range, 1 to 3) for residual or relapsed intraductal extension of ampullary adenoma were successfully performed (technical success=100%). Both biliary and pancreatic stenting were routinely performed after ID-RFA to prevent ductal stricture. After a median follow-up of 776 days (interquartile range, 470 to 984 days), the short-term and long-term clinical success rates were 93% and 76%, respectively. Seven patients experienced procedural adverse events and three patients developed ductal strictures. Endoscopic ID-RFA showed good long-term outcomes in treating residual or relapsed ampullary adenomas with intraductal extension. Repeated ID-RFA may be considered as an option for managing recurrence. Further studies are needed to standardize the procedure.

S1833 Single Operator Cholangioscopy in a Patient With Pancreaticoduodenectomy

Introduction: Cholangioscopy in patients with surgically altered anatomy can be technically challenging. In most patients with pancreaticoduodenectomy undergoing single operator cholangioscopy, the most common approach is through a percutaneous biliary drain placed by interventional radiology. We present a case in which a modified therapeutic upper endoscope (1T scope) was used for single operator cholangioscopy in a patient with pancreaticoduodenectomy. Case Description/Methods: A 64-year-old female with Gardner syndrome requiring colectomy and classic pancreaticoduodenectomy for an ampullary adenoma 10 years prior presented for surveillance endoscopy. She previously underwent endoscopic mucosal resection and intraductal radiofrequency ablation (RFA) of adenomatous tissue at the hepaticojejunal (HJ) anastomosis. She subsequently developed a stricture at the HJ anastomosis needing sequential dilations. A 1T scope was used and advanced to the HJ anastomosis. After balloon dilation of the HJ anastomotic stricture, cholangioscopy was performed and revealed abnormal biliary mucosa (Figure) approximately 2 cm below the hilum raising concern for intraductal extension of adenomatous tissue. Cholangioscopy directed biopsies were obtained and pathology revealed tubular adenoma without high-grade dysplasia. Intraductal RFA is planned in the future. Discussion: ERCP in patients with pancreaticoduodenectomy can be challenging. Different endoscopes have been used to overcome some challenges of ERCP in altered anatomy, each offering certain advantages and limitations. Commonly used endoscopes for ERCP in patients with pancreaticoduodenectomy include the adult and pediatric colonoscopes and single balloon enteroscope. These endoscopes do not allow for performing single operator cholangioscopy due to the length of the scope or the width of the accessory channel. Our report highlights that the 1T endoscope allows for performing single operator cholangioscopy in patients with prior pancreaticoduodenectomy when the HJ anastomosis can be reached.Figure 1.: Intraductal extension of adenomatous tissue seen on cholangioscopy.

Single-operator cholangioscopy in a patient with prior pancreaticoduodenectomy.

A 64-year-old woman with a history of Gardner syndrome requiring classic pancreaticoduodenectomy for an ampullary adenoma 10 years prior presents for follow-up of adenomatous tissue at the hepaticojejunal anastomosis ([Fig. 1]) with an intraductal extension of adenomatous tissue ([Fig. 2]). She previously underwent endoscopic mucosal resection (EMR) of the adenomatous tissue and intraductal radiofrequency ablation (RFA) ([Fig. 3]). After EMR and RFA, the patient developed a stricture at the hepaticojejunal anastomosis. Subsequently, stricture dilations at the anastomosis were performed. The decision was made to perform cholangioscopy to evaluate for intraductal extension of adenomatous tissue ([Video 1]). A modified therapeutic upper endoscope (1T; GIF-1TH190 Olympus, Center Valley, Pennsylvania, United States) was used and advanced to the anastomosis. Cholangioscopy showed intraductal extension of adenomatous tissue. Cholangioscopy-directed biopsies were obtained. Pathology revealed tubular adenoma without high grade dysplasia. Repeat intraductal RFA is planned.

Intraductal Radiofrequency Ablation as a Palliative Treatment for Advanced Malignant Hilar Biliary Obstruction

Malignant hilar biliary obstruction (MHBO) frequently accompanies cholestasis and cholangitis, and requires biliary stent placement. To prevent stent occlusion and prolong survival, local ablation therapy can be considered adjunctive to stent placement. Intraductal radiofrequency ablation (ID-RFA) is a recently developed local therapy for malignant biliary obstruction that can be easily performed employing endoscopic retrograde cholangiography. The use of ID-RFA to treat MHBO (as distinct from distal biliary obstruction) was suggested to be associated with severe adverse events. However, recent comparative studies have shown that ID-RFA is feasible and safe, and acceptably efficacious, in patients with advanced MHBO; newer temperature-controlled ID-RFA devices may enhance safety further. Regularly repeated ID-RFA with stent exchange affords better survival than stenting alone. However, the optimal ID-RFA strategy for MHBO remains inconclusive given the lack of data. Further large-scale clinical trials are needed.

Silver Nanofunctionalized Stent after Radiofrequency Ablation Suppresses Tissue Hyperplasia and Bacterial Growth.

Intraductal radiofrequency (RF) ablation combined with placement of a self-expandable metal stent (SEMS) for malignant biliary obstruction has risks such as stent- and heat-induced biliary sludge and restenosis. Here, we investigated the efficacy of a silver nanoparticles (AgNPs)-coated SEMS to inhibit tissue hyperplasia and bacterial growth caused by RF ablation with stent placement in the rabbit bile duct. The release behavior and antibacterial effects of AgNPs-coated SEMSs were evaluated. Then, SEMSs were successfully placed in all rabbits immediately after RF ablation. Ag ions were rapidly released at the beginning and then showed a gradual release behavior. The AgNPs-coated SEMS significantly inhibited bacterial activity compared to the uncoated SEMS (p < 0.05). Cholangiography and histological examination confirmed that the level of tissue hyperplasia was significantly lower in the AgNPs group than in the control group (all p < 0.05). Immunohistochemistry analyses revealed that TUNEL-, HSP 70-, and α-SMA-positive areas were significantly lower in the AgNPs group than in the control group (all p < 0.05). Intraductal RF ablation combined with nanofunctionalized stent placement represents a promising new approach for suppressing thermal damage as well as stent-induced tissue hyperplasia and bacterial growth.

Intraductal radiofrequency ablation therapy for eradication of intraductal residual lesions after endoscopic papillectomy for ampullary adenoma

Yamamoto et al. report a case of intraductal residual lesions after endoscopic papillectomy successfully treated with endoscopic radiofrequency ablation therapy. This report provides readers with images and videos of precise intraductal radiofrequency ablation therapy methods for safe and effective eradication of intraductal residual lesions.

The Efficacy and Safety of Endoscopic Papillectomy Combined With Endobiliary Radiofrequency Ablation for Ampullary Neoplasms With Intraductal Biliary Extension

Background and aimsEndoscopic papillectomy is the preferred approach for management of ampullary adenomas. Endobiliary radiofrequency ablation (RFA) is an ablative therapy that has been used to treat malignant biliary strictures. The aim of this study was to evaluate the safety and efficacy of endoscopic papillectomy combined with endobiliary RFA for ampullary neoplasms with intraductal biliary extension. MethodsThis international multicenter retrospective study included patients with histologically proven ampullary neoplasms with intraductal biliary extension treated with endobiliary RFA. Descriptive statistics were used to characterize patient characteristics, endoscopic features, and recurrence. ResultsIn all, 8 patients (mean age: 75.9 ± 4.9 years; 5 males) were included in this study. EUS was performed in all cases prepapillectomy and the mean size of the lesion was 29.7 (SD 12.6) mm with a mean intraductal extension length of 14.4 (SD 4.2) mm. Histology consisted of adenocarcinoma in 5 patients (67.5%) and high-grade dysplasia in 3 patients (37.5%). A range of 1-3 RFA sessions was performed with biliary stent placement. For surveillance after completion of therapy, patients received a mean of 4.1 (SD 1.64) ERCPs with intraductal biopsy over a mean follow-up period of 28.5 (SD 10.4) months. Recurrence occurred in 2 (25%) patients at 14 and 20 months (both with adenocarcinoma initially), respectively (incidence rate of 15.8%/year). ConclusionEndoscopic papillectomy combined with intraductal RFA may be an effective and safe treatment for ampullary neoplasms with intraductal extension, particularly for patients who are poor surgical candidates. Given the risk of recurrence, indefinite surveillance is recommended.

Efficacy and safety of temperature-controlled intraductal radiofrequency ablation in advanced malignant hilar biliary obstruction: A pilot multicenter randomized comparative trial.

We aimed to evaluate the efficacy and safety of temperature-controlled intraductal radiofrequency ablation (ID-RFA) for advanced malignant hilar biliary obstruction (MHBO). Patients were randomly assigned to RFA group (ID-RFA and bilateral plastic stent [PS]) or non-RFA group (bilateral PS) at a 1:1 ratio. Exchange to self-expanding metal stent (SEMS) was performed after 3months or when premature PS occlusion occurred. Total event-free stent patency, overall survival (OS), and adverse events (AEs) were analyzed. A total of 30 patients from three hospitals were enrolled. Stent patency and OS did not differ between the two groups (178days vs 122days, P=.154; 230days vs 144days, P=.643; respectively). In patients with each stricture length ≥11mm on both sides, stent patency was longer in the RFA group than in the non-RFA group (175days vs 121days, P=.028). More patients received elective exchange to SEMS without PS occlusion in the RFA group than in the non-RFA group (69.2% vs 23.1%, P=.018). AE rates did not differ between the two groups. Temperature-controlled ID-RFA for advanced MHBO was safe and feasible. It could prevent premature PS occlusion within 3months.

Gastrointestinal: Pancreatic duct perforation following endoscopic intraductal radiofrequency ablation for pancreatic duct stricture.

Gastrointestinal: Pancreatic duct perforation following endoscopic intraductal radiofrequency ablation for pancreatic duct stricture.

Recent Updates on Endoscopic Retrograde Cholangiography-guided Intraductal Radiofrequency Ablation for Malignant Biliary Stricture

Malignant biliary strictures are caused by pancreatobiliary cancer and other metastatic malignancies. Most of them are unresectable at diagnosis with a dismal prognosis. Various new ablation methods have been introduced. Of them, ERCP-guided intraductal radiofrequency ablation (ID-RFA) appears to be the most promising minimally invasive endoscopic treatment by delivering a high-frequency alternating current to the target tissue, leading to coagulative necrosis. Thus far, many studies have provided evidence that ERCP-guided ID-RFA is a safe, feasible, and effective treatment modality for stent patency and overall survival. Compared to other ablation treatments, ERCP-guided ID-RFA has several advantages, including ease of delivery, controlled application of thermal energy, low cost, and fewer systemic side effects with an acceptable safety profile. Therefore, ERCP-guided ID-RFA can be considered an adjunctive treatment for the palliation of unresectable malignant biliary strictures. On the other hand, the decision of local ablation treatment should be individualized by multidisciplinary team support due to the lack of comparative studies.

A review of the recent advances in endoscopic retrograde cholangiography-guided intraductal radiofrequency ablation for malignant biliary strictures

A review of the recent advances in endoscopic retrograde cholangiography-guided intraductal radiofrequency ablation for malignant biliary strictures

Radiofrequency ablation for intraductal extension of ampullary adenomatous lesions: proposal for a standardized protocol.

Background and study aims Intraductal extension of ampullary adenoma represents a challenging endoscopic issue. Intraductal radiofrequency ablation (RFA) has been recently suggested, but evidence and standardization of this technique are still lacking. This study aimed to provide a long-term evaluation of clinical efficacy and safety of intraductal RFA ablation with a standardized algorithm of treatment. Patients and methods Data were prospectively collected from consecutive patients with intraductal extension of adenomatous ampullary lesions from January 2016 to November 2018. Endpoints of the study were clinical success evaluated on histology results at the last follow-up, technical success, and adverse events assessment. Results Nine patients with intraductal (biliary ± pancreatic) extension of ampullary adenomas were treated with RFA during the study period. Histology on the papillectomy specimen confirmed intraductal involvement with low-grade dysplasia (LGD) in five cases (56 %), high-grade dysplasia (HGD) in three (33 %), and HGD with intramucosal adenocarcinoma in one patient (11 %). Additional argon plasma coagulation to ablate the adenoma on the duodenal mucosa was applied in five patients (56 %). Technical success was 100 %. One patient (11 %) with failed pancreatic stenting, developing acute pancreatitis after RFA, recovered with medical therapy. After a median follow-up of 21 months (IQR 20–31), six patients (67 %) achieved clinical success being free of recurrence, whereas one was diagnosed with persistence of adenocarcinoma, one with recurrent HGD, and one with recurrent LGD. Conclusions In our experience, intraductal RFA achieved acceptable results after a 2-year follow-up. Further studies are required to confirm our results and to select those patients most likely to respond.