Pulsed-field ablation does not induce esophageal and periesophageal injury-A new esophageal safety paradigm in catheter ablation of atrial fibrillation.

INTRODUCTION: Esophageal injury is one of the most serious complications of pulmonary vein isolation (PVI) with thermic energy sources. Better tissue selectivity of primarily non-thermic pulsed field ablation (PFA) may eliminate collateral injury, particularly the risk of atrio-esophageal fistula (AEF). OBJECTIVE: To compare the incidence of any (peri)-esophageal injury following PVI using PFA to thermic energy sources. METHODS: Using endoscopy, endoscopic ultrasound, and electrogastrography before and after PVI, esophageal and periesophageal injury (mucosal lesions, food retention, periesophageal edema, or vagal nerve injury) were assessed following PFA and radiofrequency (RF)- or cryoballoon (CB)-PVI. RESULTS: Between December 2022 and February 2023, 20 patients (67 ± 10 years, 53% male) undergoing PFA (Farapulse, Boston Scientific) for atrial fibrillation (AF) were studied and compared with a previous cohort of 57 patients who underwent thermic PVI (CB: n = 33; RF: n = 24). Following PFA-PVI, none of the patients had mucosal lesions, food retention, or ablation-induced vagal nerve injury; four patients showed periesophageal edema. Following thermic ablation, 33/57 patients (58%) showed esophageal and/or periesophageal injury (CB: 21/33 [64%], RF: 12/24 [50%]), in detail 4/57 mucosal lesions, 18/57 food retention, 17/57 vagal nerve injury, and 20/52 edema. Midterm success rates were similar for all energy sources. CONCLUSION: In contrast to thermic ablation tools, PFA is not associated with relevant esophageal and periesophageal injury, and might, therefore, reduce or eliminate the risk of potentially lethal AEF in interventional treatment of AF. The etiology of ablation-induced periesophageal edema is unknown but has not been shown to be related to lesion progression.

Pulmonary vein isolation-induced vagal nerve injury and gastric motility disorders detected by electrogastrography: The side effects of pulmonary vein isolation in atrial fibrillation (SEPIA) study.

INTRODUCTION: Safety of pulmonary vein isolation (PVI) has been established in clinical studies. However, despite prevention efforts the incidence of damage to (peri)-esophageal tissue has not decreased, and the pathophysiology is incompletely understood. Damage to vagal nerve branches may be involved in lesion progression to atrio-esophageal fistula. Using electrogastrography, we assessed the incidence of periesophageal vagal nerve injury (VNI) following atrial fibrillation ablation and its association with procedural parameters and endoscopic results. METHODS: Patients were studied using electrogastrography, endoscopy, and endoscopic ultrasound before and after cryoballoon (CB) or radiofrequency (RF) PVI. The incidence of ablation-induced neuropathic pattern (indicating VNI) in pre- and postprocedural electrogastrography was assessed and correlated with endoscopic results and ablation data. RESULTS: Between February 2021 und January 2022, 85 patients (67 ± 10 years, 53% male) were included, 33 were treated with CB and 52 with RF (38 with moderate power moderate duration [25-30 W] and 14 with high power short duration [50 W]). Ablation-induced VNI was detected in 27/85 patients independent of the energy form. Patients with VNI more frequently had postprocedural endoscopically detected pathology (8% mucosal esophageal lesions, 36% periesophageal edema, 33% food retention) but there was incomplete overlap. Pre-existing esophagitis increased the likelihood of VNI. Ablation data and esophageal temperature data did not predict VNI. CONCLUSION: PVI-induced VNI is quite common and independent of ablation energy source. VNI is part of (peri)-esophageal damage and only partially overlaps with endoscopic findings. VNI-associated acidic reflux may be involved in the complex pathophysiology of esophageal lesion progression to fistula.

Endoscopic papillectomy for ampullary lesions in patients with familial adenomatous polyposis compared with sporadic lesions: a propensity score-matched cohort.

BACKGROUND: Familial adenomatous polyposis (FAP) is a rare inherited syndrome that predisposes the patient to cancer. Treatment of FAP-related ampullary lesions is challenging and the role of endoscopic papillectomy has not been elucidated. We retrospectively analyzed the outcomes of endoscopic papillectomy in matched cohorts of FAP-related and sporadic ampullary lesions (SALs). METHODS: This retrospective multicenter study included 1422 endoscopic papillectomy procedures. Propensity score matching including age, sex, comorbidity, histologic subtype, and size was performed. Main outcomes were complete resection (R0), technical success, complications, and recurrence. RESULTS: Propensity score matching identified 202 patients (101 FAP, 101 SAL) with comparable baseline characteristics. FAP patients were mainly asymptomatic (79.2 % [95 %CI 71.2-87.3] vs. 46.5 % [95 %CI 36.6-56.4]); P < 0.001). The initial R0 rate was significantly lower in FAP patients (63.4 % [95 %CI 53.8-72.9] vs. 83.2 % [95 %CI 75.8-90.6]; P = 0.001). After repeated interventions (mean 1.30 per patient), R0 was comparable (FAP 93.1 % [95 %CI 88.0-98.1] vs. SAL 97.0 % [95 %CI 93.7-100]; P = 0.19). Adverse events occurred in 28.7 %. Pancreatitis and bleeding were the most common adverse events in both groups. Severe adverse events were rare (3.5 %). Overall, 21 FAP patients (20.8 % [95 %CI 12.7-28.8]) and 16 SAL patients (15.8 % [95 %CI 8.6-23.1]; P = 0.36) had recurrence. Recurrences occurred later in FAP patients (25 [95 %CI 18.3-31.7] vs. 2 [95 %CI CI 0.06-3.9] months). CONCLUSIONS: Endoscopic papillectomy was safe and effective in FAP-related ampullary lesions. Criteria for endoscopic resection of ampullary lesions can be extended to FAP patients. FAP patients have a lifetime risk of relapse even after complete resection, and require long-time surveillance.

Reduced mortality for over-the-scope clips (OTSC) versus surgery for refractory peptic ulcer bleeding: a retrospective study.

BACKGROUND: Surgery or transcatheter arterial embolization or are both considered as standard treatment of peptic ulcer bleeding (PUB) refractory to endoscopic hemostasis. Over-The-Scope clips (OTSC) have shown superiority to standard endoscopic treatment but a comparison with surgery has not been performed, yet. PATIENTS AND METHODS: In this retrospective, multicenter study, 103 patients treated with OTSC (n = 66) or surgery (n = 37) for refractory PUB in four tertiary care centers between 2009 and 2019 were analyzed. Primary endpoint was clinical success (successful hemostasis and no rebleeding within seven days). Secondary endpoints were adverse events, length of ICU-stay and in-hospital mortality. Univariable and multivariable regression models were performed to define predictive factors for allocation to surgical therapy and for mortality. RESULTS: Age, comorbidities, anticoagulation therapy, number of pretreatments, ulcer location, and Rockall-Score were similar in both groups. In the surgical group, there were significantly more patients in shock at rebleeding (78.1% vs. 43.9%; p = 0.002), larger ulcers (18.6 ± 7.4 mm vs. 23.0 ± 9.4 mm; p = 0.017) and more FIa bleedings (64.9% vs. 19.7%; p < 0.001) were detected. Clinical success was comparable (74.2% vs. 83.8%; p = 0.329). In the surgical group, length of ICU-stay (16.2 ± 18.0 days vs. 4.7 ± 6.6 days; p < 0.001), severe adverse events (70.3% vs. 4.5%; p < 0.001) and in-hospital mortality (35.1% vs. 9.1%; p = 0.003) were significantly higher. Multivariable analysis defined shock at rebleeding as the main predictor for allocation to surgical therapy (OR 4.063, 95%CI {1.496-11.033}, p = 0.006). Postsurgical adverse events were the main reason for the in-hospital mortality (OR 5.167, 95% CI {1.311-20.363}, p = 0.019). CONCLUSION: In this retrospective study, OTSC compared to surgical treatment showed comparable clinical success but was associated with shorter ICU-stay, less severe adverse events and lower in-hospital mortality.

Granule cell dispersion in two mouse models of temporal lobe epilepsy and reeler mice is associated with changes in dendritic orientation and spine distribution.

Temporal lobe epilepsy is characterized by hippocampal neuronal death in CA1 and hilus. Dentate gyrus granule cells survive but show dispersion of the compact granule cell layer. This is associated with decrease of the glycoprotein Reelin, which regulates neuron migration and dendrite outgrow. Reelin-deficient (reeler) mice show no layering, their granule cells are dispersed throughout the dentate gyrus. We studied granule cell dendritic orientation and distribution of postsynaptic spines in reeler mice and two mouse models of temporal lobe epilepsy, namely the p35 knockout mice, which show Reelin-independent neuronal migration defects, and mice with unilateral intrahippocampal kainate injection. Granule cells were Golgi-stained and analyzed, using a computerized camera lucida system. Granule cells in naive controls exhibited a vertically oriented dendritic arbor with a small bifurcation angle if positioned proximal to the hilus and a wider dendritic bifurcation angle, if positioned distally. P35 knockout- and kainate-injected mice showed a dispersed granule cell layer, granule cells showed basal dendrites with wider bifurcation angles, which lost position-specific differences. Reeler mice lacked dendritic orientation. P35 knockout- and kainate-injected mice showed increased dendritic spine density in the granule cell layer. Molecular layer dendrites showed a reduced spine density in kainate-injected mice only, whereas in p35 knockouts no reduced spine density was seen. Reeler mice showed a homogenous high spine density. We hypothesize that granule cells migrate in temporal lobe epilepsy, develop new dendrites which show a spread of the dendritic tree, create new spines in areas proximal to mossy fiber sprouting, which is present in p35 knockout- and kainate-injected mice and loose spines on distal dendrites if mossy cell death is present, as it was in kainate-injected mice only. These results are in accordance with findings in epilepsy patients.

Calculated parameters of luminal esophageal temperatures predict esophageal injury following conventional and high-power short-duration radiofrequency pulmonary vein isolation.

BACKGROUND: Luminal esophageal temperature (LET) monitoring is not associated with reduced esophageal injury following pulmonary vein isolation (PVI). OBJECTIVE: Detailed analysis of (the temporal and spatial gradients of) LET measurements may better predict the risk for esophageal injury. METHODS: Between January 2020 and December 2021, LET maxima, duration of LET rise above baseline, and area under the LET curve (AUC) were calculated offline and correlated with (endoscopy and endoscopic ultrasound detected) esophageal injury (i.e., mucosal esophageal lesions [ELs], periesophageal edema, and gastric motility disorders) following PVI using moderate-power moderate-duration (MPMD [25-30 W/25-30s]) and high-power short-duration (HPSD [50 W/13s]) radiofrequency (RF) settings. RESULTS: 63 patients (69 ± 9 years old, 32 male, 51 MPMD and 12 HPSD) were studied. The esophageal injury was frequent (40% in both groups), mucosal ELs were more common with MPMD, and edema was frequently observed following HPSD. RF-duration, total RF-energy at the left atrial (LA) posterior wall, and distance between LA and esophagus were not different between patients with/without esophageal injury. In contrast, to LET and LET duration above baseline, AUC was the best predictor and significantly increased in patients with esophageal injury (3422 vs. 2444 K. s). CONCLUSION: For both ablation strategies, AUC of the LET curves best predicted esophageal injury. HPSD is associated with similar rates of esophageal injury when (mostly subclinical) periesophageal alterations (that are of unclear clinical relevance) are included. Whether integration of these calculated LET parameters is useful to prevent esophageal injury remains to be seen.

Proof of Concept of Telemedicine-Assisted Abdominal Ultrasound Examinations to Improve the Quality of Patient Care in Rural Areas.

(1) Background: Unclear sonographic findings without adequate specialist expertise in abdominal ultrasound (AU) may harm patients in rural areas, due to overlooked diagnoses, unnecessary additional imaging (e.g., CT scan), and/or patient transport to referral expert centers. Appropriate telemedical sonography assistance could lead to corresponding savings. (2) Methods: The study was designed as a randomized trial. Selected study centers performed AU with the best local expertise. Patients were selected and monitored according to the indication that they required AU. The study depicted three basic scenarios. Group 1 corresponds to the telemedically assisted cohort, group 2 corresponds to the non-telemedically assisted cohort, and group 3 corresponds to a telemedically supported cohort for teaching purposes. The target case number of all three groups was 400 patients (20 calculated dropouts included). (3) Discussion: This study might help to clarify whether telemedicine-assisted ultrasound by a qualified expert is non-inferior to presence sonography concerning technical success and whether one of the interventions is superior in terms of efficacy and safety in one or more secondary endpoints. Randomization was provided, as every patient who needed an AU was included and then randomized to one of the groups. The third group consisted of a lower number of patients who were selected from group 1 or 2 for teaching purposes in case of rare diseases or findings. (4) Conclusions: The study investigates whether there are benefits of telemedical ultrasound for patients, medical staff, and the health care system.

Outcomes of rescue procedures in the management of locally recurrent ampullary tumors: A Pancreas 2000/EPC study.

BACKGROUND: Ampullary lesions are rare and can be locally treated either with endoscopic papillectomy or transduodenal surgical ampullectomy. Management of local recurrence after a first-line treatment has been poorly studied. METHODS: Patients with a local recurrence of an ampullary lesion initially treated with endoscopic papillectomy or transduodenal surgical ampullectomy were retrospectively included from a multi-institutional database (58 centers) between 2005 and 2018. RESULTS: A total of 103 patients were included, 21 (20.4%) treated with redo endoscopic papillectomy, 14 (13.6%) with transduodenal surgical ampullectomy, and 68 (66%) with pancreaticoduodenectomy. Redo endoscopic papillectomy had low morbidity with 4.8% (n = 1) severe to fatal complications and a R0 rate of 81% (n = 17). Transduodenal surgical ampullectomy and pancreaticoduodenectomy after a first procedure had a higher morbidity with Clavien III and more complications, respectively, 28.6% (n = 4) and 25% (n = 17); R0 resection rates were 85.7% (n = 12) and 92.6% (n = 63), both without statistically significant difference compared to endoscopic papillectomy (P = .1 and 0.2). Pancreaticoduodenectomy had 4.4% (n = 2) mortality. No deaths were registered after transduodenal surgical ampullectomy or endoscopic papillectomy. Recurrences treated with pancreaticoduodenectomy were more likely to be adenocarcinomas (79.4%, n = 54 vs 21.4%, n = 3 for transduodenal surgical ampullectomy and 4.8%, n = 1 for endoscopic papillectomy, P < .0001). Three-year overall survival and disease-free survival were comparable. CONCLUSION: Endoscopy is appropriate for noninvasive recurrences, with resection rate and survival outcomes comparable to surgery. Surgery applies more to invasive recurrences, with transduodenal surgical ampullectomy rather for carcinoma in situ and early cancers and pancreaticoduodenectomy for more advanced tumors.

Incidence and clinical relevance of upper gastrointestinal pathology during preprocedural endoscopy in patients undergoing pulmonary vein isolation.

BACKGROUND: Reflux-induced esophagitis might facilitate ablation-induced esophageal lesions (ELs) following pulmonary vein isolation (PVI), and these may progress to atrio-esophageal fistula (AEF). In contrast, preexisting ELs are not prone to progression but may affect procedure planning. OBJECTIVE: To study the incidence of preexisting esophageal and upper gastrointestinal (UGI) pathology in patients undergoing PVI, and the relation to ablation-induced ELs. METHODS: From 08/2018 to 09/2021, consecutive patients undergoing (radiofrequency [RF] or cryoballoon [CB]) PVI were examined by esophagogastroscopy (EGD) before and following ablation. Postprocedural endoscopic ultrasound (EUS) was added in 2021. RESULTS: 412 patients (median age 67.5 [IQR 61.3-75.0] years, 56.1% male) were studied. Preprocedural EGD showed abnormalities in 226/399 patients, 15% in the lower third of the esophagus. Half (99/226) were relevant for PVI, 13 procedures were postponed, 6 due to pathological EGD results. A third of the patients with new esophageal injury following ablation had preexisting esophagitis which was associated with a trend for a higher incidence of ELs after RF ablation (12.5 vs. 6.9%, p = 0.232), and a six- and two-fold higher rate of food retention after CB-PVI (28.6 vs. 4.5%, p = 0.008) and RF ablation (8.3 vs. 4.4%, p = 0.279), respectively. CONCLUSION: (1) EGD before PVI showed UGI abnormalities in > 50% of patients, one-fourth of these relevant for PVI. (2) Esophageal inflammation was associated with a higher incidence of post-ablation (peri)-esophageal injury. Whether having this information before ablation is able to reduce ELs or AEF remains to be shown.

Percutaneous transhepatic or endoscopic ultrasound-guided biliary drainage in malignant distal bile duct obstruction using a self-expanding metal stent: Study protocol for a prospective European multicenter trial (PUMa trial).

BACKGROUND: Endoscopic ultrasound-guided biliary drainage (EUS-BD) was associated with better clinical success and a lower rate of adverse events (AEs) than fluoroscopy-guided percutaneous transhepatic biliary drainage (PTBD) in recent single center studies with mainly retrospective design and small case numbers (< 50). The aim of this prospective European multicenter study is to compare both drainage procedures using ultrasound-guidance and primary metal stent implantation in patients with malignant distal bile duct obstruction (PUMa Trial). METHODS: The study is designed as a non-randomized, controlled, parallel group, non-inferiority trial. Each of the 16 study centers performs the procedure with the best local expertise (PTBD or EUS-BD). In PTBD, bile duct access is performed by ultrasound guidance. EUS-BD is performed as an endoscopic ultrasound (EUS)-guided hepaticogastrostomy (EUS-HGS), EUS-guided choledochoduodenostomy (EUS-CDS) or EUS-guided antegrade stenting (EUS-AGS). Insertion of a metal stent is intended in both procedures in the first session. Primary end point is technical success. Secondary end points are clinical success, duration pf procedure, AEs graded by severity, length of hospital stay, re-intervention rate and survival within 6 months. The target case number is 212 patients (12 calculated dropouts included). DISCUSSION: This study might help to clarify whether PTBD is non-inferior to EUS-BD concerning technical success, and whether one of both interventions is superior in terms of efficacy and safety in one or more secondary endpoints. Randomization is not provided as both procedures are rarely used after failed endoscopic biliary drainage and study centers usually prefer one of both procedures that they can perform best. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03546049 (22.05.2018).

Temperature monitoring and temperature-driven irrigated radiofrequency energy titration do not prevent thermally induced esophageal lesions in pulmonary vein isolation: A randomized study controlled by esophagoscopy before and after catheter ablation.

BACKGROUND: Endoscopically detected esophageal lesions (EDELs) are common following pulmonary vein isolation (PVI) and may progress to atrioesophageal fistula (AEF). OBJECTIVE: The purpose of this study was to study (1) the benefit of luminal esophageal temperature (LET) monitoring and (2) the impact of esophagogastroduodenoscopy (EGD) in detecting EDEL and defining pre-existing lesions. The primary endpoint was the number of ablation-induced lesions. METHODS: Patients with atrial fibrillation were randomized to PVI with LET monitoring (LET[+]) or without LET monitoring (LET[-]). All patients underwent EGD before and after PVI. Ablation power at the left atrial (LA) posterior wall was limited to 25 W in all patients and was titrated to a minimum of 10 W guided by esophageal temperature in the LET[+] group. RESULTS: Eighty-six patients (age 67 ± 10 years; 57% male) were included (44 LET[+], 42 LET[-]). PVI was achieved in all, and additional linear LA lesions were done in 50%. Eight patients developed EDEL (6 LET[+], 2 LET[-]; P = NS). Whereas LET <41°C did not differentiate with regard to EDEL formation, temperature overshooting ≥42°C was associated with a higher risk for new EDEL. Two-thirds of patients showed incidental findings (esophagitis, gastric ulcer) on preprocedural EGD; 8 esophageal lesions were pre-existing. Four patients in the LET[+] group developed epistaxis following insertion of the probe. CONCLUSION: Monitoring of LET does not prevent ablation-induced esophageal lesions. Patients without temperature surveillance were not at higher risk, but temperatures ≥42°C were associated with increased likelihood of mucosal lesions.

Over-the-scope clip versus transcatheter arterial embolization for refractory peptic ulcer bleeding-A propensity score matched analysis.

BACKGROUND: Transcatheter arterial embolization (TAE) or surgery are standard treatment of peptic ulcer bleeding (PUB) refractory to endoscopic hemostasis. Over-the-scope clips (OTSC) have shown superiority to standard endoscopic treatment. OBJECTIVE: To compare OTSC treatment to TAE in refractory peptic ulcer bleeding. PATIENTS AND METHODS: In this retrospective, multicenter study, 128 patients treated with OTSC (n = 66) or TAE (n = 62) for refractory PUB between 2009 and 2019 in four academic centers were analyzed. Primary endpoint was clinical success (hemostasis + no rebleeding within 7 days). Secondary endpoints were adverse events, length of ICU stay, and mortality. Propensity score matching was performed to adjust for differences in baseline characteristics. RESULTS: Patients characteristics were similar in both groups but ulcers in the TAE group were larger, more often located in the duodenal bulb (85.5% vs. 65.2%; p = 0.014), and that the proportion of Forrest Ia bleedings was higher (38.7% vs. 19.7%; p = 0.018). Clinical success was comparable in both groups (74.2% vs. 59.7%; p = 0.092). Stay on the intensive care unit (ICU) was significantly longer in the TAE group (mean 8.0 vs. 4.7 days; p = 0.002). Serious adverse events after re-therapy (12.9% vs. 1.5%; p = 0.042) and in-hospital mortality were significantly higher in the TAE group (9.1 vs. 22.6%, OR 2.92 [95% CI 1.04-8.16]; p = 0.05). After propensity score matching, the differences found regarding ICU stay (4.9± 5.9 and 9.2 ± 11.2; p = 0.009) and in-hospital mortality (5% vs. 22.5%; OR 5.52 [95% CI: 1.11-27.43]; p = 0.048) stayed significant. CONCLUSIONS: OTSC treatment for refractory PUB was superior to TAE in terms of ICU stay and in-hospital mortality.

Vascular pattern and diagnostic accuracy of contrast-enhanced ultrasound (CEUS) in spleen alterations.

BACKGROUND: Contrast-enhanced ultrasound (CEUS) has been used as an additional imaging technique in order to clarify rare focal splenic lesions (FSL). CEUS is a safe and cost-effective modality for assessment of perfusion. OBJECTIVE: To validate contrast enhancement pattern and evaluate the diagnostic accuracy of CEUS in unclear FSL. METHODS: CEUS examinations of the spleen in 50 patients between 2012 and 2018 were included in the study. Examinations were performed using B-mode, colour-coded Doppler ultrasound (CCDS) and CEUS after injection of sulphur hexafluoride microbubbles and interpreted in consensus by two experienced radiologists. Reference standard was defined as histopathological report and clinical course (treatment response, long term follow up). RESULTS: All patients were successfully examined by CEUS without an adverse reaction. CEUS presented the correct differentiation of benign and malignant alterations in 49/50 (98%). Lesion washout was found in all malignant but also 16.7% of all benign lesions. Matched to the histopathological report and clinical follow up, CEUS represented a sensitivity of 100% (95% -CI, 57-100), a specificity of 98% (95% -CI, 88-100), a positive predictive value (PPV) of 83% (95% -CI, 44-97) and a negative predictive value (NPV) of 100% (95% -CI, 92-100). CONCLUSION: CEUS may provide additional information by visualization of dynamic contrast enhancement pattern to differentiate benign and malignant lesions. Nevertheless, established criteria for malignancy (early enhancement or washout) in FSL should be considered with caution since they are also found in benign lesions.