Performance of digital single-operator cholangiopancreatoscope for biliopancreatic diseases in real life: results from a prospective multicenter study.

OBJECTIVES: Peroralcholangio-pancreatoscopy (POCP) is used for diagnosis and treatment of biliopancreatic disease when standard endoscopy (ERCP) or pre-operative imaging workup failed. We aimed to evaluate the diagnostic and therapeutic performance of POCP in complex biliary and pancreatic diseases. MATERIALS AND METHODS: Patients with indeterminate biliary or pancreatic duct (PD) strictures, and patients with failure of complex biliary or pancreatic stones removal, were enrolled (six centers). The primary endpoint evaluated malignancy diagnostic performances (accuracy, sensitivity, specificity) and therapeutic performances (biliary or pancreatic stones extraction). Secondary endpoints evaluated: technical success in lesion visualization, ease of maneuvering, image quality and 30-days complications. RESULTS: From November 2016 to March 2018, 66 patients were included: 29/37 women/men, median age (IQR): 73 (64-82). Fifty-three patients had diagnostic POCP and 13 patients therapeutic POCP. One endoscopist with one or two endoscopy nurses performed 94% of the POCP. The 'POCP visual impression' of malignancy showed 92.0% sensitivity, 92.9 % specificity and 92.5 % overall accuracy compared with the final diagnosis. 'POCP-guided samples histological analysis' showed 75.0 % sensitivity and 91.6% specificity. The technical success for lesion visualization was 98.5%. The median VAS scores for insertions in bile and PD were respectively 9.0 (8.1-9.6) and 9.0 (8.8-10.0). Median VAS score for access to the lesion and image quality were respectively 9.0 (7.7-9.6) and 9.0 (7.9-9.7). Only three 30-day minor complications occurred without any major complications. CONCLUSIONS: POCP was an effective, safe and easy-to-use tool in routine clinical practice for the management of complex diagnostic and therapeutic biliary and pancreatic diseases (NCT03190343).

Impact of switching from ranibizumab to aflibercept on the number of intravitreous injection and follow up visit in wet AMD: results of real life ELU study.

AIM: To study if one of the two molecules could lead to a lower number of follow up visits and intra-vitreous injection (IVI) with the same efficacy. METHODS: ELU (or "elected" in French) study is a retrospective study conducted in real life in patients presenting suboptimal response after ranibizumab IVI (phase 1) and secondary switched to aflibercept (phase 2). The number of follow up visits and IVI were compared in both phases. Visual acuity (VA) evolution and "switching" reasons were secondary analyzed. RESULTS: We retrospectively included data of 33 patients (38 eyes) with age-related macular degeneration (AMD; mean age: 77±7.7y). The number of monthly follow up visits [median (Q1; Q3)]: was significantly lower with aflibercept (phase 2), respectively 1.0 (0.81; 1.49) visits in phase 1, versus 0.79 (0.67; 0.86) visits in phase 2. The median number of monthly IVI also significantly decreased in phase 2, respectively 0.67 (0.55; 0.90) IVI in phase 1, versus 0.55 (0.45; 0.67) IVI in phase 2. The mean VA evolution (VA final-VA initial) was similar in both phases, (P>0.05). Whatever the reason for "switching" (loss of efficacy, tachyphylaxis, tolerance problems), there was no incidence on VA evolution over the time. CONCLUSION: Our results show that switching from ranibizumab to aflibercept in "suboptimal" patients significantly reduce the number of follow up visits and IVI, with a comparable efficacy. This decrease in visit number could improve patients' quality of life and reduce surgical risk by reducing the number of injections.

Genomic profile concordance between pancreatic cyst fluid and neoplastic tissue.

BACKGROUND: DNA mutational analysis of pancreatic cystic fluid (CF) is a useful adjunct to the evaluation of pancreatic cysts. KRAS/GNAS or RAF/PTPRD/CTNNB1/RNF43 mutations are highly specific to precancerous or advanced neoplasia. Several studies recently demonstrated the ability of next-generation sequencing (NGS) analysis to detect DNA mutations in pancreatic CF, but few studies have performed a systematic comparative analysis between pancreatic CF and neoplastic surgical tissue (NT). The value of CF-NGS analysis indicators for determining surgical resection necessitates evaluation. AIM: To confirm whether CF genomic profiles are a reliable malignancy predictor by comparing NGS mutational analyses of CF and NT. METHODS: Patients requiring surgery for high-risk pancreatic cysts were included in a multicenter prospective pilot study. DNA from CF (collected by endoscopic ultrasound-guided fine needle aspiration (known as EUS-FNA)) and NT (collected by surgery) were analyzed by NGS. The primary objective was to compare the mutation profiles of paired DNA samples. The secondary objective was to correlate the presence of specific mutations (KRAS/GNAS, RAF/ PTPRD/CTNNB1/RNF43/POLD1/TP53) with a final cancer diagnosis. Sensitivity and specificity were also evaluated. RESULTS: Between December 2016 and October 2017, 20 patients were included in this pilot study. Surgery was delayed for 3 patients. Concordant CF-NT genotypes were found in 15/17 paired DNA, with a higher proportion of mutated alleles in CF than in NT. NGS was possible for all pancreatic CF collected by EUS-FNA. In 2 cases, the presence of a KRAS/GNAS mutation was discordant between CF and NT. No mutations were found in 3 patients with NT or pancreatic cysts with high-grade dysplasia. The sensitivity and specificity of KRAS/GNAS mutations in CF to predict an appropriate indication for surgical resection were 0.78 and 0.62, respectively. The sensitivity and specificity of RAF/PTPRD/CTNNB1 /RNF43/POLD1/TP53 mutations in CF were 0.55 and 1.0, respectively. CONCLUSION: Mutational analyses of CF and NT were highly concordant, confirming the value of NGS analysis of CF in the preoperative malignancy assessment. However, these results need to be confirmed on a larger scale.

AF Ablation Guided by Spatiotemporal Electrogram Dispersion Without Pulmonary Vein Isolation: A Wholly Patient-Tailored Approach.

BACKGROUND: The use of intracardiac electrograms to guide atrial fibrillation (AF) ablation has yielded conflicting results. OBJECTIVES: The authors evaluated the usefulness of spatiotemporal dispersion, a visually recognizable electric footprint of AF drivers, for the ablation of all forms of AF. METHODS: The authors prospectively enrolled 105 patients admitted for AF ablation. AF was sequentially mapped in both atria with a 20-pole PentaRay catheter. The authors tagged and ablated only regions displaying electrogram dispersion during AF. Results were compared to a validation set in which a conventional ablation approach was used (pulmonary vein isolation/stepwise approach). To establish the mechanism underlying spatiotemporal dispersion of AF electrograms, the authors conducted realistic numerical simulations of AF drivers in a 2-dimensional model and optical mapping of ovine atrial scar-related AF. RESULTS: Ablation at dispersion areas terminated AF in 95% of the 105 patients. After ablation of 17 ± 10% of the left atrial surface and 18 months of follow-up, the atrial arrhythmia recurrence rate was 15% after 1.4 ± 0.5 procedures per patient versus 41% in the validation set after 1.5 ± 0.5 procedures per patient (arrhythmia free-survival: 85% vs. 59%; log-rank p < 0.001). Compared with the validation set, radiofrequency times (49 ± 21 min vs. 85 ± 34.5 min; p = 0.001) and procedure times (168 ± 42 min vs. 230 ± 67 min; p < 0.0001) were shorter. In simulations and optical mapping experiments, virtual PentaRay recordings demonstrated that electrogram dispersion is mostly recorded in the vicinity of a driver. CONCLUSIONS: The clustering of intracardiac electrograms exhibiting spatiotemporal dispersion is indicative of AF drivers. Their ablation allows for a nonextensive and patient-tailored approach to AF ablation. (Substrate Ablation Guided by High Density Mapping in Atrial Fibrillation [SUBSTRATE HD]; NCT02093949).

Electrogram Fractionation-Guided Ablation in the Left Atrium Decreases the Frequency of Activation in the Pulmonary Veins and Leads to Atrial Fibrillation Termination: Pulmonary Vein Modulation Rather Than Isolation.

OBJECTIVES: This study sought to evaluate the impact of a complex fractionated atrial electrogram (CFAE)-guided ablation strategy on atrial fibrillation (AF) dynamics in patients with persistent AF. BACKGROUND: It is still unclear whether complete pulmonary vein isolation (PVI) is required or if the ablation of well-delineated pulmonary vein (PV) subregions could achieve similar outcomes in persistent AF. METHODS: CFAE-guided ablations were performed in 76 patients (65.2 ± 10 years of age) with persistent AF. In 47 patients, we measured mean PVs and left atrial appendage (LAA) cycle length (CL) values (PV-CL and LAA-CL), before ablation and before AF termination. We defined "active" PVs as PV-CL ≤ LAA-CL, "rapid fires" as PV-CL ≤80% of LAA-CL, and "PV-LAA CL gradient" as a significant CL difference between the 2 regions. RESULTS: AF termination (sinus rhythm [SR] or atrial tachycardia [AT] conversion) occurred in 92% and SR conversion in 75%. The radiofrequency time for AF termination and total radiofrequency time were 26 ± 25 min and 61.1 ± 21.6 min, respectively. Thirty of 47 patients had active PV (with 19 PV "rapid fires"). Ablation significantly increased median CL, both at PVs and LAA from 188 ms (interquartile range [IQR]: 161 to 210 ms) to 227.5 ms (IQR: 200 to 256 ms) (p < 0.0001) and from 197 ms (IQR: 168 to 220 ms) to 224 ms (IQR: 193 to 250 ms) (p < 0001), respectively. After ablation, PV-LAA CL gradients were withdrawn and all PV "rapid fires" were extinguished (without PVI). After 17.2 ± 10 months of follow-up and 1.61 ± 0.75 procedures, 86.3% and 73% of the patients were free from AF and from any arrhythmia (AF/AT), respectively. CONCLUSIONS: CFAE-guided ablation leads to a large decrease in PV frequency of activation, preceding AF termination. A PV modulation approach, rather than complete PVI, may be preferable for persistent AF.

Active or passive pulmonary vein in atrial fibrillation: is pulmonary vein isolation always essential?

BACKGROUND: The role of pulmonary veins (PVs) in persistent atrial fibrillation (AF) perpetuation appears less important than in paroxysmal AF. Electrogram-based substrate ablation is not widely performed as a stand-alone strategy. OBJECTIVE: To evaluate PV activity in AF perpetuation and efficacy of our patient-tailored ablation strategy (electrogram-based substrate ablation with or without pulmonary vein isolation [PVI]). METHODS: One hundred twenty-one patients with paroxysmal (n = 19; 15.7%), persistent (n = 77; 63.6%), or long-standing persistent (n = 25; 20.7%) AF underwent electrogram-based substrate ablation with AF termination end point: sinus rhythm or atrial tachycardia conversion. Before ablation, we classified PVs as "passive" if silent PV or if PV cycle length is greater than left atrial appendage cycle length. No PVI was performed in such cases. RESULTS: Passive PVs were observed in 52 of 121 patients (paroxysmal AF = 0%, persistent AF = 40%, and long-standing persistent AF = 76%; P < .0001]). Substrate ablation terminated AF in 95.6% (sinus rhythm conversion in 80.2%). Compared with patients with active PVs, patients with passive PVs had longer AF sustained duration (19.1 ± 29.7 months vs 4.9 ± 11.1 months; P < .0001), larger left atrial diameter (46.9 ± 7.3 mm vs 41.9 ± 6.0 mm; P = .0014), lower left ventricular ejection fraction (45.4% ± 13.5% vs 55.1% ± 9.4%; P < .0001), and more often structural heart disease (57% vs 33%; P = .02). After a follow-up of 20.39 ± 11.23 months (1.6 procedures per patient), 82% were arrhythmia free with this strategy. CONCLUSIONS: PV activity during AF decreases with AF chronicity, left atrial dilatation, and left ventricular ejection fraction. Our patient-tailored ablation strategy without systematic PVI provides good results.

Automated Detection of Complex Fractionated Atrial Electrograms In Substrate-Based Atrial Fibrillation Ablation: Better Discrimination with a New Setting of CARTO® Algorithm.

Background and purpose: Up until recently complex fractionated atrial electrogram (CFAE) ablation has been considered as time consuming and its achievement as challenging, especially for non experimented operators. Moreover, results of substrate ablation based on CFAE detection in atrial fibrillation (AF) are very disparate, mainly because of the operator's subjective electrogram visual analysis and the difficult distinction between CFAEs really involved in AF perpetuation from other CFAE. Automatic detection provided by 3D mapping system (CARTO® algorithm) can be helpful but is not selective enough, drawing too wide CFAE areas. We sought to demonstrate a better selectivity of a new CFAE algorithm setting in order to better discriminate CFAEs really involved in AF perpetuation from other CFAE. Methods and subjects: A population of 32 patients (60.4±12.7 years) with paroxysmal (n=3) AF (PAF), persistent (n=16) AF (PeAF) or long-standing persistent (n=13) AF (LSPeAF), and AF history =56±65 months, underwent CFAE ablation based on visual analysis. Before ablation, left atrium CFAE mapping was performed on CARTO® shortest complex interval (SCI) algorithm and reanalyzed after ablation with the two different settings: nominal (SCI 60-120ms/0.05-0.15mV) vs. customized setting (SCI 30-40ms/0,04-0.15mV). CFAE areas automatically detected by both settings (CFAE-CARTO® areas) were respectively measured. The decision to ablate CFAE was only based upon the operator's electrogram visual analysis taken as reference because of high AF termination rate (93.7%) due to operator's CFAE selection experience. These ablation points drawn reference-CFAE areas involved in AF perpetuation (ablation point=60mm2) allowing to compare the selectivity of the two previous automatic maps. Results: With the customized CARTO® SCI setting, we observed a significant reduction of CFAE areas detected by CARTO® (CFAE-CARTO® areas) and of the ablated CFAE surface inside non-CFAE CARTO® areas, (30.6±20.5cm2 vs. 68.8±24.5cm2, p<0.0001, and 1.86±1.82% vs. 3±3%, p=0.003). Furthermore the proportion of ablated areas/detected CFAE-CARTO® areas were higher with customized setting (38.2±19.6% vs. 20.4±17.5%, p=0.008). Conclusions: This new customized CFAE algorithm setting is significantly more selective than the nominal one and allows an automated detection of CFAE really involved in AF perpetuation truer to an efficient experienced operator's electrogram visual analysis.