Kaizen: Perpetual improvement in biliary ablation – From technical validation to clinical translation

The evolution of minimally invasive endoscopic techniques has established endoscopic papillectomy (EP) as a primary treatment for ampullary adenomas, with support from international guidelines.^{1, 2} Despite its widespread adoption and proven efficacy, EP faces a critical challenge: the management of residual lesions that extend into the biliary or pancreatic ducts. These intraductal extensions present a unique therapeutic dilemma, as conventional ablative techniques like argon plasma coagulation and additional endoscopic resection often prove inadequate.³ While intraductal radiofrequency ablation (ID-RFA) has emerged as a promising solution, having demonstrated success in biliary malignancy, its application in post-EP scenarios requires technical validation. The optimization of device settings, particularly with newer-generation radiofrequency (RF) generator, represents a knowledge gap that impacts both treatment efficacy and safety.

RFA has evolved from its established applications in Barrett's esophagus and hepatocellular carcinoma to become an increasingly refined tool for biliary interventions. The technology's core strength lies in its precise delivery of thermal energy through bipolar electrode arrays, achieving controlled coagulative necrosis in confined anatomical spaces. Modern RFA systems pair sophisticated generators with specialized catheters, enabling precise control of both voltage and power – critical parameters that determine treatment efficacy and safety in the biliary tract.

The study by Yamamoto et al., published in this issue of Digestive Endoscopy, provides crucial insights into the technical optimization of ID-RFA through a comprehensive three-tier investigation.⁴ Their methodical approach commenced with in-vitro validation using porcine liver models, which revealed a critical technical principle: achieving the desired ablation effect requires sufficient voltage to enable the generator to reach its set power output. This initial phase allowed precise measurement of ablation patterns and tissue effects under controlled conditions. Building on these findings, they progressed to in-vivo experiments in live porcine models, where they could evaluate the real-time tissue response and assess healing patterns over time. Through systematic comparison with the conventional VIO300D generator (Erbe, Tübingen, Germany), they established optimal parameters for the newer VIO3 system (bipolar 3.0, 125 Vp, 30 W, 30 s) (Erbe, Tübingen, Germany) to achieve effective ablation patterns. Their findings translated successfully to clinical practice, with their preliminary five-patient experience demonstrating complete ablation without recurrence over a median 24-month follow-up period. A key advantage of the VIO3 system is its ability to display real-time power output during the procedure, providing better visualization of the automatic power reduction that occurs when tissue resistance increases.

In Japan, the VIO3 generator became available as a high-end model ~5 years ago and has gradually replaced the VIO300D, particularly in high-volume centers and teaching institutions. As a result, its adoption has expanded widely across various clinical settings. Although multiple electrosurgical generators are used for tumor ablation, the specific feedback mechanisms and energy delivery characteristics of each system result in nuanced differences in ID-RFA settings. The experimental validation conducted for these two generators offers valuable insights that may be extrapolated to optimize ID-RFA protocols for other electrosurgical platforms.

The clinical impact and optimal parameters for ID-RFA continue to be refined through ongoing research. A multicenter prospective study of 20 patients using VIO300D (10 W, 30 s) reported a 30% recurrence rate at 12 months after a single ID-RFA session.⁵ Another retrospective analysis of 14 patients achieved a 92% treatment success rate using settings of 7–10 W for 60–140 s.⁶ A recent systematic review and meta-analysis encompassing seven studies with 124 patients demonstrated a clinical success rate of 75.7%, although biliary strictures and recurrence were observed in 22.2% and 24.3% of cases, respectively.⁷ These varying outcomes underscore the critical importance of optimizing ID-RFA techniques and settings.

While the study achieved excellent therapeutic outcomes, the establishment of appropriate follow-up protocols after ID-RFA is crucial. While routine surveillance typically relies on standard duodenoscopy or cross-sectional imaging, the potential for buried tumor formation beneath fibrotic or newly epithelialized tissue poses a significant diagnostic challenge. In this context, endoscopic ultrasound (EUS) and EUS-guided core needle biopsy may serve as valuable tools for comprehensive follow-up evaluation.

In addition to follow-up strategies, the balance between efficacy and safety in ID-RFA is paramount. Excessive ablation risks complications such as postoperative biliary or pancreatic duct strictures, while insufficient ablation may result in incomplete treatment and recurrence. The ability to monitor real-time tissue changes during RFA, as demonstrated in this study, represents a significant advancement toward achieving consistent and effective outcomes. Furthermore, experimental validation has highlighted the importance of understanding device-specific parameters to improve performance.

The placement of temporary pancreatic and/or biliary stents offers a promising approach to managing complications associated with ID-RFA. Following adequate ablation, biliary wall expansion using fully-covered self-expanding metal stents (FCSEMS) could potentially prevent bleeding and perforation, while potentially reducing the risk of late-stage complications such as strictures. Moreover, in the management of papillary adenocarcinoma after ID-RFA, the use of drug-eluting FCSEMS, which has shown promising results for cholangiocarcinoma, may improve treatment outcomes.⁸ Future clinical development of such supportive techniques would be valuable for improving the safety and efficacy of ID-RFA.

Technical refinement of RFA devices warrants further consideration. The bile duct's complex anatomical course through the duodenal papilla, transitioning into the larger duodenal lumen, presents unique challenges. A critical technical limitation arises from the acute angle between the duodenoscope elevator exit and the biliary orifice, where the RFA probe's rigidity can impede successful cannulation if it lacks adequate flexibility at the elevator interface. Moreover, excessive elevator use required to navigate this angle risks damaging the probe itself, potentially compromising treatment delivery or necessitating device replacement. Resection of tumors within the duodenal lumen is often necessary to ensure adequate RFA access. Additionally, irregular surfaces of papillary lesions can impede proper probe–tissue contact. Development of devices capable of uniform ablation across varying duct angles, diameters, and surface topographies is essential. For instance, the success of balloon-type probes in Barrett's esophagus RFA suggests that similar adaptations – using softer, thinner, and more flexible balloon-based designs – could enhance contact and efficacy in biliopancreatic applications while better accommodating the challenging anatomy of the papillary region.⁹

Biliary ablation following EP is particularly valuable for managing refractory residual lesions, especially those with deeper bile duct invasion, where conventional modalities such as snare resection, biopsy forceps, or argon plasma coagulation (APC) may prove insufficient. Although ID-RFA has begun to be utilized in clinical practice, its application remains limited, and further experience is necessary to optimize its role. As global adoption of this technique expands, the findings of this study provide practical guidance on the appropriate ablation methodology, potentially enhancing both the safety and efficacy of ablative therapy for papillary lesions. Currently, most studies on RFA have focused on its use for treating residual or recurrent lesions after primary therapy. However, an important consideration for future practice is the potential for incorporating RFA as an adjunct to EP or endoscopic submucosal dissection of the papilla (ESDIP) in a single session. If RFA can be safely and efficiently performed concomitantly with resection during the index treatment, it may significantly improve the likelihood of achieving complete eradication of neoplastic tissue. Such an approach may significantly advance the treatment of ampullary tumors, offering a more definitive and streamlined therapeutic strategy.

As we advance RFA technology validation and clinical implementation, several emerging ablative techniques merit exploration. Irreversible electroporation (IRE), a nonthermal ablation method, minimizes collateral thermal injury to critical structures, making it particularly suitable for treating locally advanced malignancies with vascular involvement.¹⁰ Microwave ablation, well-established in hepatocellular carcinoma treatment, offers another promising approach, potentially providing more uniform heating patterns and shorter ablation times than conventional RFA. Cryoablation, which achieves tissue destruction through freeze–thaw cycles and has proven effective in bronchoscopic applications, could open new possibilities in pancreatobiliary endoscopy, especially given its ability to create precise ablation margins visible in real-time imaging. The integration of these technologies into the therapeutic armamentarium for biliopancreatic diseases will require careful validation studies similar to those presented in this article, focusing not only on technical parameters but also on safety profiles in this anatomically challenging region.

The present study establishes a robust foundation for the clinical application of ID-RFA in managing post-EP residual lesions. Through systematic validation of a novel RF generator and meticulous documentation of tissue response patterns, the authors have provided critical technical guidance for therapeutic endoscopy. As endoscopic ablative therapies continue to evolve, this work underscores the importance of rigorous technical validation coupled with careful attention to clinical outcomes. In this spirit, we are reminded of the Japanese philosophy of Kaizen – a principle of continuous, incremental improvement that permeates high-performance disciplines. Applying Kaizen to the development of biliary ablation strategies encourages us to pursue refinement not through revolutionary leaps, but through meticulous iteration, thoughtful design, and constant evaluation. The future of minimally invasive tissue ablation in biliopancreatic diseases looks promising, and its success – as with all endoscopic innovation – will depend on embracing the spirit of Kaizen: balancing technological optimization with clinical safety, and advancing through steady, purposeful progress that endures.

Eisuke Iwasaki is associate editor of Digestive Endoscopy.

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