Endoscopic Treatment of Upper Tract Urothelial Carcinoma: Challenging the Definition of the Maximal Lesion Size for Safe Ablation

Introduction: With advances in endoscopic treatment of upper tract urothelial carcinoma (UTUC) lesions, the recommended upper limit of lesion size amenable to laser ablation was set to 2 cm. However, this limit is based on expert opinion only, and debate still exists regarding this definition. Objective: To determine the maximal size of the tissue, for which total endoscopic ablation with laser energy is achievable, from a laser performance perspective. Materials and Methods: Simulating endoscopic surgery conditions, renal tissue blocks from pork kidneys in growing size from 1 cm3 to 3 cm3 were totally ablated with Ho:YAG laser (1 J, 10 Hz). The time to ablation was recorded for each tissue mass. Following the ablation, each sample was inspected microscopically by an expert pathologist to determine the extent to which the tissue was destroyed. Results: Time to ablation ranged from 16.4 min for a 1 cm3 mass, to 69.7 min for a 3 cm3 mass. Histologic evaluation after laser ablation showed that ablation was achieved in all tissue masses, and no “unaffected” tissue was present, even for lesions with a size of 3 cm3. Conclusions: This study showed that laser ablation can be achieved for tumor lesions up to a size of 3 cm3. The results of this study can contribute to the debate regarding the limits of endoscopic management of UTUC lesions and strengthen the recommended upper limit of 2 cm3 for endoscopic treatment of tumor lesions.

Duodenal mucosal resurfacing with GLP-1 receptor agonism increases postprandial unconjugated bile acid in patients with insulin-dependent type 2 diabetes

Introduction: Duodenal Mucosal Resurfacing (DMR) is a new endoscopic ablation technique aimed at improving glycemia and metabolic control in patients with type 2 diabetes mellitus (T2DM). DMR appears to improve insulin resistance, which is the root cause of T2DM, but its mechanism of action is largely unknown. Bile acids function as intestinal signalling molecules in glucose and energy metabolism via the activation of farnesoid X receptor and secondary signalling (e.g. via fibroblast growth factor 19[FGF19]), and are linked to metabolic health. Methods: We investigated the effect of DMR and GLP-1 on postprandial bile acid responses in 16 patients with insulin-dependent T2DM, using mixed meal tests performed at baseline and six months after the DMR procedure. Results: The combination treatment allowed discontinuation of insulin treatment in 11/16 (69%) of patients while improving glycaemic and metabolic health. We found increased postprandial unconjugated bile acid responses (all p<0.05), an overall increased secondary bile acid response (p=0.036) and a higher 12α-hydroxylated:non12α-hydroxylated ratio (p<0.001). Total bile acid concentrations were unaffected by the intervention. Postprandial FGF19 and 7-alpha-hydroxy-4-cholesten-3-one (C4) concentrations decreased post-intervention (both p<0.01). Conclusion and discussion: Our study demonstrates that DMR with GLP-1 modulates the postprandial bile acid response. The alterations in postprandial bile acid responses may be the result of changes in the microbiome, ileal bile acid uptake and improved insulin sensitivity. Controlled studies are needed to elucidate the mechanism linking the combination treatment to metabolic health and bile acids.

Preliminary Results of Endoscopic Radiofrequency Treatment of the Sacroiliac Joint Syndrome

Background and Study The sacroiliac joint (SIJ) may be the primary source of pain in 15 to 25% of patients with axial low back pain. Furthermore, 75% of patients who have had fusion surgery develop SIJ pain within 10 years. Treatment options include SIJ blocks, radiofrequency (RF) denervation, and fusion. The RF techniques range from ablation of the nerves supplying the joint, creating lesions to the joint itself, or a combination of both techniques. However, different clinical studies could only identify a limited or, in some cases, no effect in decreasing of pain intensity and duration of the effect. Methods In this retrospective study, we selected 23 patients with SIJ pain, with a duration of more than 12 months and a 50% pain reduction on the Numeric Rating Scale (NRS) after diagnostic block. All patients received endoscopic ablation of the medial branch L5/S1 and the lateral branches, exiting the sacral foramina on S1/S2 and S2/S3 on both sides while using only one incision on each side. Telephone interviews were conducted with all patients. The outcome was determined with Odom's criteria, percent reduction NRS, subjective assessment of the patient, and duration of the effect. Results According to Odom's criteria, 79% of the patients showed acceptable to excellent results and confirmed that denervation helped them to manage their daily lives better. The average pain reduction in the responder group was 57% with an average duration of 13.4 months. Conclusion In this retrospective study, we could demonstrate the practicability and effectiveness of endoscopic SIJ denervation in the treatment of SIJ pain using only one incision for three levels on each side. Further studies should investigate if this procedure is more effective than percutaneous RF.

Evolution in lesion index durability using the new third generation laser balloon catheter for pulmonary vein isolation – does the mechanical innovation mean also clinical innovation?

Background The new second- and third-generation endoscopic ablation systems (EAS 2 and EAS 3) have been launched in recent years. We aimed to assess the index lesion durability as well as gap localization using the multigenerational novel technologies in patients with recurrent atrial fibrillation (AF). Methods Consecutive patients who underwent the second ablation for recurrent AF following the initial pulmonary vein isolation (PVI) with EAS 2 or EAS 3 were investigated. The persistent durability of PVI and gap localization at the second procedure were analyzed using spiral mapping catheter and three-dimensional mapping system. Results A total of 34 patients (EAS3: N=13, 50 PVs, EAS2: N=21, 82 PVs) were enrolled. Repeat procedure was performed mean 11.9±9.3 months after the initial procedure. Persistent durable isolation of all four PVs was recorded in 6 (46.2%) patients in EAS3 and 4 (19.1%) patients in EAS2 (P=0.130). Ninety-one out of 132 (68.9%) PVs were persistently isolated with a higher rate in EAS3 (EAS3: 82.0% vs. EAS2: 61.0%, P=0.0113). A total of 45 gaps were recorded in 41 PVs, of which right superior PV (RSPV) was the predominantly common reconnected vein (15 gaps in 14 PVs) irrespective of generation difference (EAS 3: 4 gaps in 3 PVs and EAS 2: 12 gaps in 11 PVs). Anterior-segment of RSPV was the most common gap distribution (EAS 3: 2 gaps and EAS 2: 6 gaps). Logistic multivariate regression analysis revealed high-dose (≥8.5W) only ablation as an independent predictor of durable PVI (adjusted OR: 3.70, 95% CI [1.408 - 10.003], P=0.008) Conclusion The multigenerational technical innovation resulted in a higher index lesion durability in EAS3 guided PVI in patients with recurrent AF. The specific gap patterns frequent at RSPV, especially at the anterior-superior segment, and the feasibility of high-dose ablation were confirmed in successor EASs. FUNDunding Acknowledgement Type of funding sources: None.

Real use of a novel automatic motorized laser balloon for the ablation of atrial fibrillation

Background Electric isolation of the pulmonary veins (PVs) can successfully treat patients with atrial fibrillation (AF). Isolation of pulmonary veins can be achieved by several methods: radiofrequency, cryoballoon or laser balloon ablation (LBA). The main procedural challenge with either method is to achieve a continuous circumferential lesion at the left atrium-PVs junction, with the persistence of functional gaps. Purpose A novel endoscopic ablation system equipped with a precise motor control system (MCS) has been evaluated. The balloon is used with an endoscope to directly visualize and ablate tissue at the left atrial-PVs junction with laser energy. This system enables uninterrupted, high-speed, circumferential lesion creation under direct control of the physician. The MCS is intended to reduce procedure time and to ensure continuity of ablation lesions. The feasibility of the motorized ablation in terms of extent of applicability along each PV-left atrium junction and time of use of the manual point-by-point mode has been investigated. Methods 27 consecutive patients (male 70.3%, age 61.2±8.7 years) with paroxysmal or persistent AF who underwent LBA were enrolled in our institution. Exclusion criteria were any contraindication for the procedure including the presence of intracavitary thrombosis and contraindications to general anesthesia or deep sedation. After transseptal puncture, the balloon-based endoscopic ablation system was advanced to each PV ostium, and laser energy were projected onto the target. Results A total of 110 PVs were treated with LBA; in 9 patients there was a redundant right intermediate pulmonary vein; in 4 patients there was a right common ostium and in 2 a left common ostium. MCS was used for 82 PVs (74.5%): in particular, MCS was used continuously between 180° and 325° degrees (50 to 90% of PV circumference) for 35 PVs (31.8%) and between 326° and 359° degrees (91 to 99% of PV circumference) for 25 veins (22.7%). In 13 PVs (12%) MCS was used for the entire circumference. During 8508 (19.6%) seconds out of a total of 43.368 seconds, laser energy delivery occurred in the rapid mode by MCS. No clinical complications, either local or systemic (stroke or TIA, pericardial effusion, pericardial tamponade, pulmonary vein stenosis, esophageal injury, temporary or permanent phrenic nerve palsy), were observed neither during the use of MSC nor during the use of manual point-by-point mode. Of note, a pinhole rupture of the balloon occurred in 3 cases of our series, during the use of MCS, without harm to the patient and requiring only replacement of the LBA. Conclusions In our case series, laser balloon ablation with the help of motor control system appears safe and feasible in most cases for large portions of pulmonary vein circumference, providing considerable time sparing (74.5% of total ablation extent in 19.6% of total ablation time). FUNDunding Acknowledgement Type of funding sources: None.

Non-thermal Resection Device for Ablation of Barrett’s Esophagus – a Feasibility and Safety Study

Background and study aims Several techniques exist for the eradication of Barrett’s esophagus (BE); however, all have limitations regarding successful conversion to squamous epithelium and a complication profile. We aimed to assess the feasibility and safety of a new non-thermal device, the EndoRotor, for the eradication of BE as a first-line ablation technique. Patients and methods Patients with BE were prospectively included in 2 tertiary referral centers in The Netherlands. Inclusion criteria: BE-length 2-5cm, with low-grade dysplasia, high-grade dysplasia or residual BE after endoscopic resection (ER) of a lesion containing early neoplasia. Exclusion criteria: previous ER >50% circumference, or previous ablation therapy. Follow-up endoscopy was performed after 3 months. Outcomes were the percentage of endoscopically visible BE surface regression and complications. Results Thirty patients (25 male, age 66 years [IQR: 59–73], median BE C0M3) were included. Eighteen patients underwent ER prior to ablation. Median percentage BE ablated was 100% (IQR: 94-100). Median visual BE surface regression at three-months follow-up was 80% (IQR: 68–95). Multiple residual Barrett’s islands were commonly seen. Six patients(20%) had a treatment-related complication requiring intervention, including one perforation(3%), one postprocedural hemorrhage(3%), and four strictures(13%). Post-procedural pain was reported in 18 patients(60%). Conclusions For the endoscopic ablation of BE, the EndoRotor procedure was found to be technically demanding with a longer procedure time compared to established ablation techniques and a high complication rate. Based on these results, we do not recommend the EndoRotor as a first-line ablation technique for the eradication of BE.

Single-Sweep Pulmonary Vein Isolation using the new third-generation laser balloon -- Evolution in ablation style using endoscopic ablation system

Background: The endoscopic ablation system (EAS) is an established ablation device for pulmonary vein isolation (PVI) in patients with atrial fibrillation (AF). The novel X3 EAS is now equipped with a contiguous circumferential ablation mode (RAPID mode). Aim: To determine the feasibility of single-sweep ablation using X3. Methods: Consecutive patients who underwent AF ablation using X3 were enrolled. We assessed the acute procedural data focusing on “Single-sweep PVI” defined as PVI with a single energy application using RAPID mode to complete the circular lesion set, and on “first-pass isolation” defined as successful visually guided PVI after initial circular lesion set. Results: One-hundred AF patients (56% male, age 68±10 years, 66% paroxysmal AF) were analyzed. A total of 379 of 383 PVs (99%) were isolated with X3. Single-sweep isolation and first-pass-isolation were achieved in 214 PVs (56%) and in 362 PVs (95%), respectively. Single-sweep isolation rates varied across PVs with higher rates at the superior PVs (61.2% vs. inferior PVs:49.5%, P=0.0239) and at PVs with maximal ostial diameter <24mm (57.6% vs. >24mm: 36.8%, P=0.0151). The mean total procedure and fluoroscopy times were 43.0±10 and 4.0±2 mins, respectively. In none of the patients an acute thromboembolic event (stroke or transient ischemic attack) or a pericardial effusion/tamponade occurred. A single transient phrenic nerve palsy was observed. Conclusion: The new X3 EAS allows for single-sweep PVI in 56% of PVs. The new RAPID ablation mode leads to an improved rate of first-pass isolation associated with very short procedure times without compromising safety.

Single sweep pulmonary vein isolation using the endoscopic ablation system. Dream or reality?

Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): CardioFocus Background The endoscopic ablation system (EAS) is an established ablation device for pulmonary vein isolation (PVI) in patients with paroxysmal and persistent atrial fibrillation (AF). In randomized studies, however, point-by-point laser ablation resulted in longer procedure times. The novel X3 EAS is now equipped with a motor driven laser generator that sweeps the diode laser beam around the individual PV ostium at a pre-defined speed (2.25°/sec) thus allowing for contiguous circumferential ablation (RAPID mode). Purpose To determine the feasibility of single sweep ablation using the new X3 EAS. Methods Consecutive AF patients were enrolled. After single transseptal puncture selective PV angiographies were performed. A 3D enabled circular mapping catheter was used to record PV potentials and to create a 3D map of the left atrium. Then, the transseptal sheath was exchanged for the 12F EAS delivery sheath. The EAS was inflated to obtain optimal circumferential contact to the PV ostium. Before ablation, the laser generator was retracted to ensure optimal contact behind the catheter shaft (blind spot). Ideally, RAPID mode ablation was employed at 13-15W. In case of esophageal heating &gt;39°C or suboptimal tissue exposure point-by-point ablation (5.5-12W for 20-30 secs) was used instead. During ablation at the septal PVs phrenic nerve pacing was performed via a diagnostic catheter in the superior vena cava. Single sweep ablation was defined as one single RAPID energy application per PV to complete the singular, circular lesion set. PV conduction was re-assessed after all PVs had been treated. In case of residual PV conduction, gap mapping followed by EAS guided ablation was performed. If EAS failed to achieve complete PVI, touch up ablation was allowed at the discretion of the operator. Hemostasis was achieved by means of a figure of 8 suture. Procedure time was defined as initial groin puncture to groin closure. Follow-up included office visits at 3, 6 and 12 months including 72 h Holter monitoring. Results One-hundred AF patients (56% male, mean age 6810 years, 66% PAF) with normal LV ejection fraction (mean 60 ± 10%) and normal LA size (41 ± 6mm) underwent X3 EAS ablation. Of 382 PVs 378 (99%) were isolated with the X3 EAS. In 214 PVs (56%) single sweep isolation was achieved. First pass isolation and RAPID mode only PVI was achieved in 362 (95%) and 357 (94%), respectively. Single sweep isolation rates varied across PVs from 46% at LIPV to 64% at RSPV. The mean total procedure and fluoroscopy times were 43 ± 10 and 4 ± 2 mins, respectively. Safety data and the complete follow-up will be reported. Conclusion The new X3 EAS equipped with a motor driven laser generator allows for single sweep PVI in 56% of PVs. Almost all PVs (94%) may be isolated with RAPID mode only leading to a very high first pass isolation rate. Altogether, this leads to substantially faster procedure times compared to the predecessor EAS.

Real use of a novel automatic motorized laser balloon for the ablation of atrial fibrillation

Funding Acknowledgements Type of funding sources: None. Background Electric isolation of the pulmonary veins (PVs) can successfully treat patients with atrial fibrillation (AF). Isolation of pulmonary veins can be achieved by several methods: radiofrequency, cryoballoon or laser balloon ablation (LBA). The main procedural challenge with either method is to achieve a continuous circumferential lesion at the left atrium-PVs junction, with the persistence of functional gaps. Purpose A novel endoscopic ablation system equipped with a precise motor control system (MCS) has been evaluated. The balloon is used with an endoscope to directly visualize and ablate tissue at the left atrial-PVs junction with laser energy. This system enables uninterrupted, high-speed, circumferential lesion creation under direct control of the physician. The MCS is intended to reduce procedure time and to ensure continuity of ablation lesions. The feasibility of the motorized ablation in terms of extent of applicability along each PV-left atrium junction and time of use of the manual point-by-point mode has been investigated. Methods sixteen consecutive patients (male 68.7%, age 60.9 ± 7.8 years) with paroxysmal or persistent AF who underwent LBA were enrolled in our institution. Exclusion criteria were any contraindication for the procedure including the presence of intracavitary thrombosis and contraindications to general anesthesia or deep sedation. After transseptal puncture, the balloon-based endoscopic ablation system was advanced to each PV ostium, and laser energy were projected onto the target. Results A total of 62 PVs were treated with LBA; in 3 patients there was a redundant right intermediate pulmonary vein; in 4 patients there was a right common ostium and in one a left common ostium. MCS was used for 41 PVs (66.1%): in particular, MCS was used continuously between 180° and 325° degrees (50 to 90% of PV circumference) for 22 PVs (35.5%) and between 326° and 359° degrees (91 to 99% of PV circumference) for 16 veins (25.8%). In 3 PVs (4.8%) MCS was used for the entire circumference. During 5.659 (23.6%) seconds out of a total of 23.986 seconds, laser energy delivery occurred in the rapid mode by MCS. No clinical complications, either local or systemic (stroke or TIA, pericardial effusion, pericardial tamponade, pulmonary vein stenosis, esophageal injury, temporary or permanent phrenic nerve palsy), were observed neither during the use of MSC nor during the use of manual point-by-point mode. Of note, a pinhole rupture of the balloon occurred in the first 2 cases of our series, during the use of MCS, without harm to the patient and requiring only replacement of the LBA. Conclusions In our case series, laser balloon ablation with the help of motor control system appears safe and feasible in most cases for large portions of pulmonary vein circumference, providing considerable time sparing (66.1% of total ablation extent in 23.6% of total ablation time).