Introduction

Minimally invasive irreversible electroporation (IRE) has gained increasing attention for the treatment of endobiliary tumors.^[1-3] However, the clinical application of IRE in hollow organs has been limited due to the lack of suitable electrode designs that can ensure sufficient electrode-tissue contact.^[4] Recently, a novel stent-directed electrode (SDE) made of chemically polished nickel-titanium (Ni-Ti) alloy wires was developed for localized endobiliary IRE.

Aims & Methods

The aim of this study was to investigate feasibility and efficacy of localized IRE using a SDE in both in vitro and in vivo models. Ni-Ti wires were chemically polished to improve surface roughness and electrical conductivity. The SDE was fabricated using the polished wires, and its mechanical properties were characterized. The cytotoxicity and cell viability after IRE treatment were investigated using a colon cancer cell line. The optimal IRE parameter for the in vivo study was determined through triphenyl tetrazolium chloride-stained potato model (field strength: 500 V/cm, pulse width: 100 μs, pulse interval: 2,000 μs, number of pulses: 32). Subsequently, the safety and efficacy of endobiliary IRE using the SDE were evaluated in a porcine common bile duct model.

Results

The chemical polishing process significantly improved the surface roughness, current density, and electrical conductivity of the polished Ni-Ti wires while maintaining their mechanical properties compared with the control wire (p < 0.001). The polished Ni-Ti wire electrode effectively delivered electrical energy to cancer cells, cytotoxicity and cell viability were proportionally decreased according to the electric field strength increased (p < 0.001). IRE-treated potato tissue clearly revealed irreversibly and reversibly electroporated areas containing dead cells in electrical strength-dependent manner. In vivo studies showed that the SDE could be successfully delivered to the target site and achieve uniform and localized ablation of the ductal mucosa without causing severe complications. Histological analyses showed significantly increased apoptosis (p < 0.001), heat shock protein expression (p < 0.01), and inflammatory cell infiltration (p < 0.05) in the IRE-treated tissues compared to the sham control group.

Conclusion

The novel SDE made of chemically polished Ni-Ti wires demonstrated excellent performance for endobiliary IRE in terms of surface characteristics, electrical properties, and ablation efficacy. The in vivo experiments confirmed the safety and efficacy of the stent-directed IRE using the SE for the treatment of endobiliary tumors in a porcine model. These results suggest that this minimally invasive technique may provide a promising treatment option for endobiliary tumors of the gastrointestinal and urinary tracts. Additional preclinical and clinical studies are necessary to assess the long-term safety and efficacy of this technique for various clinical applications.

References

[1] Al-Sakere, B.; André, F.; Bernat, C.; Connault, E.; Opolon, P.; Davalos, R. V.; Rubinsky, B.; Mir, L. M. Tumor Ablation with Irreversible Electroporation. PLoS One 2007, 2, No. e1135.
[2] Silk, M.; Tahour, D.; Srimathveeravalli, G.; Solomon, S. B.; Thornton, R. H. The State of Irreversible Electroporation in interventional Oncology. In Seminars in interventional radiology; Thieme Medical Publishers, 2014; pp. 111−117.
[3] Wagstaff, P. G. K.; Buijs, M.; van den Bos, W.; de Bruin, D. M.; Zondervan, P. J.; de la Rosette, J. J.; Pes, M. P. L. Irreversible Electroporation: State of the Art. OncoTargets Ther. 2016, 2437−2446.
[4] Sánchez-Velázquez, P.; Castellví, Q.; Villanueva, A.; Quesada, R.; Pañella, C.; Cáceres, M.; Dorcaratto, D.; Andaluz, A.; Moll, X.; Trujillo, M.; Burdío, J. M.; Berjano, E.; Grande, L.; Ivorra, A.; Burdío, F. Irreversible Electroporation of the Liver: Is There a Safe Limit to the Ablation Volume? Sci. Rep. 2016, 6, 23781.

Introduction

Malignant biliary obstruction (MBO) poses significant therapeutic challenges, particularly in patients ineligible for surgery [1]. Endobiliary radiofrequency ablation (RFA) has emerged as a promising palliative therapy, aiming to enhance stent patency and patient survival [2]. However, conventional catheter-based electrodes may encounter limitations, such as incomplete tumor ablation due to insufficient contact with the inner wall of the bile duct [3].

Aims & Methods

This study aimed to validate the feasibility of the stent-based electrode (SBE)-RFA system with polarity-switching and evaluate its efficacy in achieving circumferential ablation lesions in the porcine bile duct. A bipolar SBE consisting of two electrodes fabricated by braiding nitinol wires was designed and characterized along with a custom RFA generator capable of a polarity-switching system. Ex vivo studies using porcine livers were performed to evaluate the ablation ranges under various ablation protocols combining output power and ablation times. Subsequently, an animal study involving nine male Yorkshire pigs was performed, employing selected protocols based on ex vivo findings. The RFA procedure was conducted in the porcine common bile duct (CBD) under fluoroscopic guidance, with pre- and post-procedural assessments including cholangiography, endoscopic examination, and histological analysis.

Results

The SBE with custom RFA generator was demonstrated that temperature feedback and power output were accurate and showed high reproducibility. The SBE was successfully positioned at the correct location during the procedure through fluoroscopy and ultrasound guidance, and complete contact with the bile duct wall was confirmed. The ablation ranges of the porcine liver increased with output power and time, showing proportional growth and an even ablation area between electrodes. Endobiliary RFA in the porcine CBD was technically successful without ductal perforation, resulting in luminal narrowing proportional to output power and ablation time. Mucosal damage, including hemorrhagic erosion and erythema, was observed, intensifying with higher RFA-related parameters. Histological examination revealed increased inflammatory cell infiltration, hemorrhage, and cellular necrosis in correlation with output power and time. Additionally, the ablation area in the porcine CBD was formed in an even circumferential shape, and this also proportionally increased as output power and time increased.

Conclusion

In conclusion, this study demonstrates the technical feasibility and efficacy of endobiliary RFA utilizing a novel bipolar SBE-RFA system with polarity-switching system. This system exhibited controlled and predictable ablation ranges in the porcine CBD, offering potential as a palliative therapeutic option for unresectable MBO. Although further studies in obstructive animal models and long-term efficacy assessments are necessary, these findings suggest that promising prospects form the clinical application of the bipolar SBE-RFA system in managing MBO.

References

[1] Sumiyoshi T, Shima Y, Okabayashi T, Negoro Y, Shimada Y, Iwata J, et al. Chemoradiotherapy for Initially Unresectable Locally Advanced Cholangiocarcinoma. World J Surg. 2018;42(9):2910-8.
[2] Oh D, Chong J, Song TJ, Park DH, Lee SS, Seo DW, et al. The usefulness of endobiliary radiofrequency ablation before metal stent placement in unresectable malignant hilar obstruction. J Gastroenterol Hepatol. 2022;37(11):2083-90.
[3] Inoue T, Yoneda M. Updated evidence on the clinical impact of endoscopic radiofrequency ablation in the treatment of malignant biliary obstruction. Dig Endosc. 2022;34(2):345-58.

Introduction

Endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) is a reliable and minimally invasive method for obtaining tissue samples from organs like the pancreas, adrenal glands, and liver [1]. However, challenges in obtaining sufficient tissue samples persist due to limitations of needles, including design and materials [2]. To overcome these limitations, various FNB needles with different tip design and materials, such as Franseen and fork-tip needles, have been developed [3]. Nevertheless, ongoing enhancement of FNB needles remains crucial for increasing the diagnostic yield and efficacy of EUS-FNB.

Aims & Methods

This study aimed to compare the efficacy of newly designed Tricore needles with Franseen needles in a porcine liver model under EUS guidance. A total of four male Yorkshire pigs were randomly divided into two groups: the Franseen group and the Tricore group. Nine EUS-FNB procedures were performed on each pig using three FNB needles. All pigs were euthanized immediately after the final procedure. The maximum resistance force during the puncture and the angle of the FNB needle tip was measured to compare puncture performance of two FNB needles. Visibility under ultrasound, blood contamination, and tissue acquisition time were also evaluated immediately after the EUS-FNB procedure. The sufficiency of the specimen for diagnosis was assessed by measuring the total specimen area, number of fragments, fragment areas, and number of complete portal tracts (CPTs).

Results

Procedural outcomes were successful with no complications observed, yielding specimens with a 100% (36/36) success rate. The Franseen needle (5.97 ± 0.53 N) exhibited significantly higher resistance compared to the Tricore needle (3.83 ± 0.84 N, P < 0.001). The both needle tips were observed considerable bending pre- and post-procedure (P < 0.01); however, the Franseen needle (84.58 ± 39.69°) became more significantly bent than the Tricore needle (32.82 ± 14.17°, P < 0.001). The visibility under ultrasound of the Tricore needle was significantly higher than that of the Franseen group (P < 0.01). While blood contamination was similar between groups (P = 0.926), the Franseen group (59.90 ± 19.15 s) required significantly longer acquisition time than the Tricore group (48.94 ± 9.26 s, P < 0.05). Histological findings revealed significantly larger total specimen area (P < 0.05) and fragment area (P < 0.001) in the Tricore group compared to the Franseen group. Additionally, the Tricore group exhibited significantly higher number of CPTs (P < 0.05).

Conclusion

In conclusion, our study demonstrated that the newly designed Tricore EUS-FNB needle exhibits superior puncture ability and ultrasound visibility, while acquiring liver tissue specimens of greater quantity and quality compared to the commercially available Franseen needle. These findings suggest that the Tricore needle may offer a promising alternative for EUS-FNB procedures. Although further clinical validation is needed to confirm these findings, this novel needle design holds potential for improving the diagnostic yield and efficacy of EUS-FNB in clinical practice.

References

[1] Tanisaka, Y. et al. Comparison of Endoscopic Ultrasound-Guided Fine-Needle Aspiration and Biopsy Device for Lymphadenopathy. Gastroenterol Res Pract 2021, 6640862, doi:10.1155/2021/6640862 (2021).
[2] Song, T. J. et al. The prospective randomized, controlled trial of endoscopic ultrasound-guided fine-needle aspiration using 22G and 19G aspiration needles for solid pancreatic or peripancreatic masses. Am J Gastroenterol 105, 1739-1745, doi:10.1038/ajg.2010.108 (2010).
[3] Mohan, B. P. et al. Comparison of Franseen and fork-tip needles for EUS-guided fine-needle biopsy of solid mass lesions: A systematic review and meta-analysis. Endosc Ultrasound 8, 382-391, doi:10.4103/eus.eus_27_19 (2019).

Introduction

Endo-biliary radiofrequency ablation (RFA) is a novel minimally invasive intervention to treat stent occlusion in malignant biliary strictures1. Advances in oncological therapies have improved survival and tumour ingrowth into uncovered self-expanding metal stents (UcSEMS) is common and strategies to manage this are limited2. We aimed to determine the clinical outcomes of endo-biliary RFA using ELRATM probe (Taewoong) in patients with UcSEMS occlusion.

Aims & Methods

Retrospective data was collected from February 2020 to March 2023 at St Thomas’ Hospital.

Results

28 endo-biliary RFA’s were performed in 12 patients for occluded UcSEMS over this period, delivered by 3 operators. Demographics are shown in table 1. Excluding two recent cases, 60% required multiple RFA interventions. The median number of RFA’s was 2, with one patient requiring 9 sessions. One patient was excluded as there was significant parenchymal disease in addition to UcSEMS occlusion and despite RFA, there was progression in liver metastasis. For patients with bilirubin monitoring post RFA, 11 (100%) procedures resulted in a reduction in bilirubin between 1-4 weeks. The average reduction in bilirubin was 61.4% (6/11 patients) at week 1 and 77.4% (9/11 patients) at week 2-4. Excluding 2 recent cases, survival was 90 % at 30 days post procedure, and 70% at 90 days. Survival was 100% at 90 days for cholangiocarcinoma. The patient requiring 9 sessions (not on chemotherapy), survived for 18 months with significantly improved quality of life. There were no recorded complications. Technical difficulties were encountered in 2 cases due to impedance in bilobar stents with a Y configuration due to contact of the probe with metal at the hilum.
Table 1: Demographics
M:F 7:5
Mean age 71
Performance status 0-2
Malignancy Cholangiocarcinoma=5, Pancreatic cancer=4, gall bladder=1, Hepatocellular carcinoma=1,metastatic breast cancer=1

Conclusion

Endo-biliary RFA had good technical and clinical success with measurable reduction in bilirubin in patients with UcSEMS occlusion without any complications in our cohort. It is difficult to say if survival is purely due to biliary drainage or if there is an anti-tumour effect with RFA, especially given the 100% survival at 3 months in patients with cholangiocarcinoma. Additional data from randomised controlled trials is required to assess the role of RFA in malignant strictures.

References

Management of malignant biliary obstruction. Gut 64, A216–A217 (2015).
2. Steel, A. W. et al. Endoscopically applied radiofrequency ablation appears to be safe in the treatment of malignant biliary obstruction. (2011) doi:10.1016/j.gie.2010.09.031.

Disclosure

Nothing to disclose

Introduction

Malignant biliary obstruction/MBO/is generally managed by biliary stenting however major following problem is stent patency. Recent studies show the advantages of endoscopic retrograde cholangiopancreatography-guided intraductal radiofrequency ablation/ ERCP ID-RFA/ as adjunctive therapeutic modality.

Aims & Methods

Aims: To evaluate the efficacy and safety of ID-RFA in terms of stent patency,symptom–free survival and adverse events/AE/.Primary endpoints–evaluating the period of stent patency and survival;secondary endpoints-assessing AE.
Methods: We performed retrospective analysis of a prospective database including all consecutive patients who underwent ID-RFA for the period July 2021 – December 2022.17 procedures in 16 patients who were unresectable or poor surgical candidates were performed followed by stenting in the study period.

Results

Endobiliary RFA/EB-RFA /catheter (ELRA, STARmed, Taewoong Medical) and RF generator system (VIVA combo, STARmed) were used in 15 of the procedures. In two cases ID-RFA was performed with Habib EndoHPB catheter/Boston Scientific.After passing a guidewire the catheter was positioned at the targeted lesion, followed by 120 s of ablation (target temperature 80°C, 7–10 W,temperature control mode)–in two to three sessions,unilaterally or bilaterally depending on the type and lenght of the stenosis verified by the proceding cholangiogram. The mean period of stent patency defined as time between the date of the procedure and the last follow up of the patient without signs of stent occlusion was 144,36 ± 89.3 days. In this period all of the patients were symptom–free with good quality of life and without any signs of cholangitis.The indications were:10 patients with CCA,two patients/n=2-12.5%/ with intraductal extension of papillary adenoma-both poor surgical candidates -one with HGD;one with HGD with intramucosal carcinoma who underwent endoscopic snare papillectomy /ESP/ followed by endoscopic ID-RFA and placement of stents,2 patients with gallbladder cancer,2 patients with bile duct occlusion due to metastasis.In 9 of the patients with CCA /90% of patients with CCA ;56,25 % of the total number/chemotherapy with Cisplatina/Gemcitabine followed with no interruption of the courses during the period of treatment; one refused chemotherapy.In three of the patients/18.75%/ we performed ID RFA in order to prolong stent patency in occluded by tumor ingrowth metal stents.The rate of the AE was 18.75%/n=3/ - 1 patient with self-limited bleeding;1 patient with postprocedural cholangitis and 1 patient with liver abcess – managed percutaneously.There were no deaths or ICU admissions. We experienced two stent occlusions – in one in patient with papillary adenoma with HGD–on day 169– managed with second session of ID- RFA followed by metal stent placement - asymptomatic up to the last follow up,the second with tumor ingrowth from endobiliary metastasis in previously placed metal stent -the patency after RFA was 116 days – managed with metal stent in stent placement

Conclusion

ID-RFA is a promising new tool which provides improved outcomes in patients with MBO both in stent patency and symptom free survival.It has many advantages – easy delivery of controlled temperature application and good safety profile.Therefore ID-RFA can be proposed as adjunctive treatment in patients with MBO although more randomized studies are needed.

Clinical Case Summary

The syndrome of buried lumen-apposing metal stents (LAMS) occurs in 4.7% of cases and is caused by a foreign body reaction characterised by tissue overgrowth embedded in the stent. This complication often requires surgery or "stent-in-stent" endoscopic procedures (1). Stent in a stent safely and effectively recanalises LAMS placed as esophagogastric anastomosis (2), gallbladder drainage (3), and endoscopic ultrasound (EUS)-directed transgastric ERCP (EDGE) (4). We report the first EUS-directed transenteric ERCP (EDEE) case using this approach. In 2023 a patient with Roux-en-Y hepaticojejunostomy (HJ) substenosis and recurrent cholangitis was admitted to our institution. The first attempt to perform an EUS-guided gastrojejunostomy (GJ) as part of EDEE failed; EUS -Hepaticogastrostomy (HGS) was conducted. One month later, a Hot-Axios LAMS (15mm x 15mm) EUS-GJ was placed, and prior 15 mm balloon dilatation, the second part of the EDEE operation was conducted, accessing the surgical HJ with a paediatric colonoscope and placing a Nagi stent (16mm x 20mm) towards the substenosis. The LAMS completely buried itself during the 6-month Nagi removal follow-up, making it impossible to determine its gastric mucosal location. We placed a fully covered self-expandable metal stent (10mm x 8cm) on the HGS for antegrade Nagi stent extraction. Recurrent HJ substenosis and bile duct stones induced cholangitis in 2024. EUS-guided identification and cannulation of the buried LAMS involved passing a 19-G fine needle biopsy needle through the LAMS, advancing a Jagwire deep into the jejunum, and bridging it with a second Hot-Axios LAMS (15mm x 15mm) using a non-cautery enhanced (cold LAMS-in-LAMS) technique.A frontal scope was used to remove bile duct stones before the latest 15 mm balloon was expanded, and a third 15 mm x 10 mm LAMS was placed across the substenotic HJ. EUS-guided management of buried LAMS was safe and effective, with normal liver function tests and clinical outcomes.

References

1) Nayar, M., Leeds, J. S., UK & Ireland LAMS Colloborative, & Oppong, K. (2022). Lumen-apposing metal stents for drainage of pancreatic fluid collections: does timing of removal matter?. Gut, 71(5), 850–853. https://doi.org/10.1136/gutjnl-2021-325812
2) Bazaga Pérez de Rozas, S., Chahal, P., Sánchez-Ocaña, R., García-Alonso, F. J., Carbajo, A. Y., de la Serna-Higuera, C., & Manuel, P. M. (2019). Buried lumen-apposing metal stent (LAMS) in esophagogastric anastomosis: the LAMS-in-LAMS rescue treatment. Endoscopy, 51(6), 600–601. https://doi.org/10.1055/a-0861-99074)
3) Ligresti, D., Cipolletta, F., Amata, M., Cimavilla, M., Traina, M., & Tarantino, I. (2018). Buried lumen-apposing metal stent (LAMS) following endoscopic ultrasound-guided gallbladder drainage: the LAMS-in-LAMS rescue treatment. Endoscopy, 50(8), 822–823. https://doi.org/10.1055/a-0624-2050
4) Honan, B. M., Mulki, R., & Sánchez-Luna, S. A. (2024). Bridging the Buried GATE: LAMS-in-LAMS Rescue Technique for Endoscopic Ultrasound-Directed Transgastric ERCP. ACG case reports journal, 11(9), e01497. https://doi.org/10.14309/crj.0000000000001497

Introduction

Endobiliary radiofrequency ablation (eRFA) is expected to prolong stent patency in malignant biliary obstruction. However, data on eRFA combined with uncovered self-expanding metal stents (uSEMS) in perihilar cholangiocarcinoma (pCCA) are scarce.(1,2)

Aims & Methods

Aim of this prospective single-centre pilot study was to evaluate whether eRFA prior to uSEMS placement is feasible in patients with inoperable pCCA. This study included 10 patients with inoperable pCCA undergoing eRFA prior to endoscopic placement of uSEMS. Endobiliary RFA was performed using a temperature controlled RFA electrode at 7 watt, 90 sec, 75°C. All patients were followed up until death or the end of the study (after at least 12 months follow up). Primary endpoints were technical success, clinical success and adverse events (AEs). Secondary endpoints were time to recurrent biliary obstruction, stent patency at 6 months, and overall survival.

Results

Baseline characteristics are presented in the table. All patients underwent previous successful drainage with plastic stents and/or percutaneous in-/external drainage catheters. In 7 patients the procedure was scheduled electively, where in 3 patients there was an increase in cholestasis and/or fever in the days before the intervention.
The procedure was technically and clinically successful in all patients. One patient was admitted due to self-limiting bleeding after the intervention preceded by sphincterotomy. No other procedure related serious AEs occurred <30 days. Seven patients experienced transient abdominal discomfort after the procedure, sufficiently treated with oral analgesics. The median score on a Numeric Rating Scale (NRS) was 2 (IQR 0.25-3.75) after 1 day and the median duration of pain was 1 day (IQR 0-2.5) after the procedure.
During follow-up 7 patients experienced recurrent biliary obstruction caused by tumor ingrowth (n=6) or sludge (n=1) after a median of 6 months (range 1-8). Of the 3 patients with a patent stent at end of follow-up, two patients deceased after 2 and 6 months follow-up, the other patient still had a patent stent at the end of follow-up. Stent patency rate at 6 months follow-up was 67% (6/9). Four patients died after a median of 16 months (range 4-24) since diagnosis, not related to stent dysfunction.

Table. Baseline characteristics of 10 patients with pCCA undergoing eRFA and uSEMS placement

Conclusion

This pilot study confirms the safety and feasibility of eRFA in patients with pCCA. Risk of adverse events seems low and abdominal pain after the procedure mild. Randomised controlled trials are warranted to assess the efficacy of eRFA for pCCA.

References

1. Sofi AA, Khan MA, Das A, Sachdev M, Khuder S, Nawras A, et al. 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):944-51.e1.
2. de Jong DM, Fritzsche JA, Audhoe AS, Yi SSL, Bruno MJ, Voermans RP, et al. Comparison of Intraductal RFA Plus Stent versus Stent-Only Treatment for Unresectable Perihilar Cholangiocarcinoma-A Systematic Review and Meta-Analysis. Cancers (Basel). 2022;14(9).

Disclosure

Jeska A. Fritzsche, Mattheus C.B. Wielenga, Otto M. van Delden and Joris I. Erdmann have no conflicts of interest or financial ties to disclose.
Heinz-Josef Klümpen performed in advisory board for Janssen, Astra-Zeneca, and IPSEN. Received Speaker’s fee from CCO and MedTalks. Roy L.J. van Wanrooij performed as a consultant for Boston Scientific. Paul Fockens performed as a consultant for Olympus and Cook Endoscopy.
Cyriel Y. Ponsioen reports research grants from Gilead and Perspectum, performed as a consultant for Pliant, Takeda and Shire, and received speaker’s fees from Tillotts.
Rogier P. Voermans reports research grants from Boston Scientific and Prion Medical, performed as a consultant for Boston Scientific, and received speaker’s fee from Mylan and Zambon.
All outside the submitted work.