Comparison of arterial wall integration of different flow diverters in rabbits: The CICAFLOW study.

BACKGROUND AND PURPOSE: New coated flow diverters (FDs) claim antithrombotic properties and increased arterial wall integration. The aim of this study is to compare in vivo endothelial coverage of coated and uncoated FD in the context of different antiplatelet regimens. METHODS: Different FDs (Silk Vista - SV, Pipeline with Shield technology - PED shield and Surpass Evolve - SE) were implanted in the aorta of rabbits, all 3 in each animal with 3 different antiplatelet regimens: no antiplatelet therapy, aspirin alone, or aspirin and ticagrelor. Four weeks after FD implantation, angiography, flat-panel CT, and optical coherence tomography (OCT) were performed before harvesting the aorta. Extensive histopathology analyses were performed including environmental scanning electron microscopy (ESEM), multiphoton microscopy (MPM) and histological staining with qualitative and/or quantitative assessment of device coverage. RESULTS: All 23 FDs that were implanted remained patent without hyperplasia. Qualitative stent coverage assessment revealed that there were no statistically significant differences between the FD groups (p = 0.19, p = 0.45, p = 0.40, and p = 0.84 for OCT, ESEM, MPM and histology, respectively). Quantitative neointimal measurement of histological sections also showed similar results in all 3 FD groups (p = 0.70). However, there were significant differences between the 3 groups of antiplatelet regimens (p = 0.07) with a higher rate in the no antiplatelet group (p = 0.05 versus aspirin alone and p = 0.03 versus aspirin and ticagrelor). CONCLUSION: Our study provides evidence that FD integration into the arterial wall is similar with coated (PED shield) and uncoated devices (SV, SE), regardless of the antiplatelet regimen. FD integration with specific surface coverage should be promoted. TRIAL REGISTRATION: APAFIS #2022011215518538.

Intra-arterial in-situ bevacizumab injection effect on angiogenesis. Results on a swine angiogenesis model.

BACKGROUND AND PURPOSE: In this study we tested the effect of antiangiogenics on a swine angiogenesis model that shares some brain AVM histological characteristics. The objective was to determine bevacizumab effects on retia volumes and on vessels' wall. MATERIALS AND METHODS: Fifteen pigs were divided into 3 groups: Five animals served as controls (group A), 5 animals underwent endovascular left external and common carotid artery occlusion (group B) and 5 animals underwent the same procedure and had an intra-arterial in-situ injection of bevacizumab (groupC) 2 months after the occlusion. A DSA associated with 3D-rotational angiography was performed at day 0 and at 3 months in all groups in order to measure rete mirabile volumes. The animals were sacrificed at 3 months and the retia were harvested for pathological and immunohistochemistry examinations. RESULTS: All VEGF-A receptors were blocked at the site of injection and there was a local enhanced endothelial proliferation and apoptosis. The volume of the retia remained unchanged after the bevacizumab injection. Retia vessels presented comparable media thickness, higher endothelial proliferation and apoptosis after the anti-VEGF injection. CONCLUSION: A single in-situ injection of bevacizumab in this swine angiogenesis model showed no change in retia volume and an extensive blockage of VEGF receptors at the site of injection one month later. Rete mirabile vessels presented comparable media thickness, higher endothelial proliferation and apoptosis after the anti-VEGF injection, suggesting that bevacizumab antiangiogenic effect does not fragilize vessel wall. More studies are needed to confirm these preliminary insights of in-situ antiangiogenic effect on vascular malformations.

Analysis of the in vitro and in vivo effects of photodynamic therapy on prostate cancer by using new photosensitizers, protoporphyrin IX-polyamine derivatives.

BACKGROUND: Photodynamic therapy, using porphyrins as photosensitizers (PS), has been approved in treatment of several solid tumors. However, commonly used PS induce death but also resistance pathways in cancer cells and an alteration of surrounding normal tissues. Because polyamines (PA) are actively accumulated in cancer cells by the Polyamine Transport System (PTS), they may enable PS to specifically target cancer cells. Here, we investigated whether new protoporphyrin IX-polyamine derivatives were effective PS against prostate cancer and whether PA increased PDT specificity after 630nm irradiation. METHODS: CHO and CHO-MG cells (differing in their PTS activity) were used to assess efficacy of polyamine vectorization. MTT assays were performed on human prostate non-malignant (RWPE-1) and malignant (PC-3, DU 145 and LNCaP) cell lines to test PS phototoxicity. ROS generation, DNA fragmentation and cell signalling were assessed by ELISA/EIA, western-blots and gel shift assays. Finally, PS effects were studied on tumor growth in nude mice. RESULTS: Our PS were more effective on cancer cells compared to non-malignant cells and more effective than PpIX alone. PpIX-PA generated ROS production involved in induction of apoptotic intrinsic pathways. Different pathways involved in apoptosis resistance were studied: PS inhibited Bcl-2, Akt, and NF-κB but activated p38/COX-2/PGE2 pathways which were not implicated in apoptosis resistance in our model. In vivo experiments showed PpIX-PA efficacy was greater than results obtained with PpIX. CONCLUSIONS: All together, our results showed that PpIX-PA exerted its maximum effects without activating resistance pathways and appears to be a good candidate for prostate cancer PDT treatment.

HybridKnife high-pressure glycerol jet injection for endoscopic submucosal dissection increases procedural ease and speed: a randomised study in pigs and a human case series.

BACKGROUND AND AIMS: Good use of the submucosal space is key during endoscopic submucosal dissection (ESD). High-pressure injection of a long-lasting viscous solution using the HybridKnife water-jet system has been demonstrated to be feasible. We compared jet injection of glycerol and normal saline during pig gastric ESD and assessed its feasibility and efficiency during human ESD. MATERIALS AND METHODS: A blinded randomised controlled study of ESD with the HybridKnife injecting either a glycerol mixture or normal saline and a prospective human case series were performed. Twenty gastric pig dissections (10/group) and 38 human ESDs along the gastrointestinal tract were performed. Dissection speed, specimen size, procedure duration, rates of en bloc and R0 resection, and rates of bleeding and perforation were prospectively recorded. An evaluation of operator comfort and perceived safety (dissection score) was performed using a visual analogue scale with zero being the worst score and ten the best. RESULTS: Dissection was significantly more rapid (1.38-fold) with glycerol injection than with normal saline injection (28.94 vs. 20.91 mm(2)/min; p = 0.037). The dissection score was significantly higher in the glycerol group than in the normal saline group (7.3 vs. 4.7; p = 0.0064). No differences were observed in the rates of en bloc resection, bleeding, or perforation. The 38 human cases along the gastrointestinal tract revealed good results (en bloc resection rate = 100 %, R0 resection rate = 90 %) without any complications. CONCLUSION: High-pressure jet injection of glycerol with the HybridKnife for ESD increased the speed and operator comfort of the procedure compared with the use of normal saline, and the procedure was safe and efficient for human ESD. The advantages of using a combination of the HybridKnife system and a viscous glycerol solution will help to spread the use of the ESD technique, particularly in non-Asian countries.

Elaboration of a semi-automated algorithm for brain arteriovenous malformation segmentation: initial results.

OBJECTIVES: The purpose of our study was to distinguish the different components of a brain arteriovenous malformation (bAVM) on 3D rotational angiography (3D-RA) using a semi-automated segmentation algorithm. MATERIALS AND METHODS: Data from 3D-RA of 15 patients (8 males, 7 females; 14 supratentorial bAVMs, 1 infratentorial) were used to test the algorithm. Segmentation was performed in two steps: (1) nidus segmentation from propagation (vertical then horizontal) of tagging on the reference slice (i.e., the slice on which the nidus had the biggest surface); (2) contiguity propagation (based on density and variance) from tagging of arteries and veins distant from the nidus. Segmentation quality was evaluated by comparison with six frame/s DSA by two independent reviewers. Analysis of supraselective microcatheterisation was performed to dispel discrepancy. RESULTS: Mean duration for bAVM segmentation was 64 ± 26 min. Quality of segmentation was evaluated as good or fair in 93% of cases. Segmentation had better results than six frame/s DSA for the depiction of a focal ectasia on the main draining vein and for the evaluation of the venous drainage pattern. CONCLUSION: This segmentation algorithm is a promising tool that may help improve the understanding of bAVM angio-architecture, especially the venous drainage. KEY POINTS: • The segmentation algorithm allows for the distinction of the AVM's components • This algorithm helps to see the venous drainage of bAVMs more precisely • This algorithm may help to reduce the treatment-related complication rate.

High-pressure injection of glycerol with HybridKnife for ESD is feasible and increases the ease and speed of the procedure: an in vivo study in pigs and first use in human.

BACKGROUND AND AIMS: The HybridKnife water-jet system (ERBE, Tubingen, Germany) has been shown to increase dissection speed and decreased the risk of perforation during endoscopic submucosal dissection (ESD). Glycerol mixture is a viscous, long-lasting solution preferentially used by Japanese ESD experts. The combination of the HybridKnife system with a glycerol solution has not been evaluated to date. MATERIALS AND METHODS: A prospective non-randomised comparative study of ESD with HybridKnife injecting of either a glycerol mixture or normal saline was performed. Twenty dissections (ten per group) were performed on four anaesthetised domestic mini-pigs. Dissection speed (mm(2)/min), size of the specimen (mm(2)), duration (min), en bloc resection rate, and bleeding and perforation rates were prospectively recorded. An evaluation of operator comfort and perception of safety (dissection score) was performed using a visual analogue scale with 0 being the worst score and 10 the best. RESULTS: High-pressure injection of the glycerol mixture and dissection with the HybridKnife was feasible without complications. Dissection was significantly more rapid (1.67-fold) with glycerol injection than normal saline injection (27.44 vs. 16.44 mm(2)/min; p < 0.001). The dissection score was significantly higher in the glycerol group than in the normal saline group (5.9 vs. 2.9; p < 0.001). No differences were observed in the rates of en bloc resection, bleeding and perforation. Seven first human cases were also easy without need of preliminary incision and technical complication. CONCLUSION: High-pressure jet injection of glycerol with HybridKnife for ESD is feasible and increases the speed and safety of the procedure compared with use of normal saline.

Pelvic magnetic resonance imaging in the ewe: a model for experimental gynecologic research.

AIM: Our goal was to demonstrate the feasibility of pelvic magnetic resonance imaging (MRI) in the ewe. MATERIAL AND METHODS: Two ewes underwent a pelvic 3 Tesla MRI scan, under light anesthesia, with T2-weighted fast spin-echo images and T1-weighted spoiled gradient-echo images. Multiplan T1 weighted images were also obtained after the intravenous injection of a contrast product. One ewe was anestrous and the other one had undergone ovarian stimulation. RESULTS: No incident occurred during the examination. Both the uterus (with two horns) and the ovaries were identified. The intensity of the endometrial, myometrial and ovarian signals was similar to that encountered in women. The uterus and ovaries could be enhanced in both cases. Pelvic vasculature was also studied. In the case of hormonal stimulation, the endometrium was thicker, follicular growth was identified and enhancement seemed greater. CONCLUSION: MRI in the ewe is feasible and could be helpful in experimental gynecologic research, especially in uterus transplantation.

Preclinical in vitro and in vivo results of the new silk vista flow diverter with P8RI coating.

BACKGROUND: Flow diverting stents (FDS) have transformed the treatment of intracranial aneurysms; however, their metallic structure associated with their intra-luminal positioning hamper angiographic and clinical outcomes. Therefore, there is a need to develop FDS with optimized surfaces that reduce thrombogenicity while promoting the healing process and endothelialization. METHODS: P8RI, a peptide mimicking the CD31 protein, was previously developed and grafted onto Silk Vista (SV) FDS. P8RI-SV and bare-SV were used in vitro in a blood loop model to test their hemocompatibility using human whole blood and in vivo using the rabbit elastase model for optical coherence tomography (OCT) comparisons of neointimal formation at day 5 and day 28. RESULTS: After blood loop incubation, P8RI-SV showed significant reduction in fibrin binding (p=0.004) and platelet adhesion (p=0.041) compared with bare-SV. Similarly, derivative markers measured in blood, thromboxane B2 (platelet activation) and Thrombin-Antithrombin III complexes (coagulation activation), were also significantly reduced in the P8RI-SV group (both p=0.002). In vivo, complete or near-complete occlusion was reached in all aneurysms (n=6) at day 28. Excellent rate of stent-coverage ratio was obtained at day 5 (89.3% (79.1%-98.7%)) comparable to the observation at day 28 (91.8% (79.1%-100%); p=0.44). These rates were significantly higher compared with bare-SV at day 5 (77.8% (58.3%-86.8%); p<0.001) and at day 28 (67.7% (52.6%-88.9%); p<0.0001). CONCLUSION: In vitro results confirm enhanced hemocompatibility with a significant anti-thrombotic effect of the P8RI-SV. In vivo results provide evidence of rapid neo-intimal growth reaching near-complete tissue healing as early as day 5 in a rabbit model.

WEB shape modifications: angiography-histopathology correlations in rabbits.

BACKGROUND: WEB Shape Modification (WSM) over time is frequent after aneurysm treatment. In this study, we explored the relationship between histopathological changes and angiographic evolution over time in experimental aneurysms in rabbits treated with the Woven EndoBridge (WEB) procedure. METHODS: Quantitative WSM was assessed using flat-panel computed tomography (FPCT) during follow-up by calculating height and width ratio (HR, WR), defined as the ratio between either measurement at an index time point and the measurement immediately after WEB implantation. The index time point varied from 1 day to 6 months. HR and WR were evaluated with angiographic and histopathological assessments of aneurysm healing. RESULTS: Final HR of devices varied from 0.30 to 1.02 and final WR varied from 0.62 to 1.59. Altogether, at least 5% of HR and WR variations were observed in 37/40 (92.5%) and 28/40 (70%) WEB devices, respectively, at the time of final assessment. There was no significant correlation between complete or incomplete occlusion groups and HR or WR (p=0.15 and p=0.43). Histopathological analysis revealed a significant association between WR and aneurysm healing and fibrosis 1 month following aneurysm treatment (both p<0.05). CONCLUSION: Using longitudinal FPCT assessment, we observed that WSM affects both the height and width of the WEB device. No significant association was found between WSM and aneurysm occlusion status. Although presumably a multifactorial phenomenon, the histopathological analysis highlighted a significant association between width variations, aneurysm healing and fibrosis in the first month following aneurysm treatment.

Bioactive refinement for endosaccular treatment of intracranial aneurysms.

Endovascular treatment is the first-line therapy for most intracranial aneurysms; however, recanalisation remains a major limitation. Developments in bioengineering and material science have led to a novel generation of coil technologies for aneurysm embolisation that address clinical challenges of aneurysm recurrence. This review presents an overview of modified surface coil technologies and summarises the state of the art regarding their efficacy and limitations based on experimental and clinical results. We also present potential perspectives to develop biologically optimised devices.

Integron Digestive Carriage in Human and Cattle: A "One Health" Cultivation-Independent Approach.

Objectives: Dissemination of antimicrobial resistance (AMR) is a global issue that requires the adoption of a "One-Health" approach promoting integration of human and animal health. Besides culture-dependent techniques frequently used for AMR surveillance, cultivation-independent methods can give additional insights into the diversity and reservoir of AMR genetic determinants. Integrons are molecular markers that can provide overall and reliable estimation of AMR dissemination. In this study, considering the "One-Health" approach, we have analyzed the integron digestive carriage from stools of humans and cattle living in a same area and exposed to different antibiotic selection pressures. Methods: Three collections of human [general population (GP) and intensive care unit patients (ICUs)] and bovine (BOV) stool samples were analyzed. The three main classes of integrons were detected using a multiplex qPCR both from total DNA extracted from stools, and from Gram-negative bacteria obtained by culture after an enrichment step. Results: With the cultivation-independent approach, integron carriage was 43.8, 52.7, and 65.6% for GP, ICU, and BOV respectively, percentages being at least twofold higher to those obtained with the cultivation-dependent approach. Class 1 integrons were the most prevalent; class 2 integrons seemed more associated to cattle than to humans; no class 3 integron was detected. The integron carriage was not significantly different between GP and ICU populations according to the antibiotic consumption, whatever the approach. Conclusion: The cultivation-independent approach constitutes a complementary exploratory method to investigate the integron digestive carriage of humans and bovines, notably within subjects under antibiotic treatment. The high frequency of carriage of integrons in the gut is of clinical significance, integrons being able to easily acquire and exchange resistant genes under antibiotic selective pressure and so leading to the dissemination of resistant bacteria.

Development of an angiogenesis animal model featuring brain arteriovenous malformation histological characteristics.

BACKGROUND: Angiogenesis has a key role in the formation and evolution of brain arteriovenous malformations (AVMs). Numerous models have been developed aiming to recreate configuration of brain AVMs. OBJECTIVE: To develop an animal model sharing the same pathological characteristics as human brain AVMs. MATERIALS AND METHODS: Ten pigs were divided into two groups. Five animals underwent endovascular left common carotid artery (CCA) and external carotid artery (ECA) occlusion and five animals served as controls. DSA, associated with 3D-rotational angiography, was performed at day 0 and at 3 months in both groups. The volume of the retia was calculated. Vascular endothelial growth factor (VEGF)-A serum levels were measured in both groups at the same time intervals. Finally, the animals were sacrificed at 3 months and the retia were harvested for pathological and immunohistochemistry examinations. RESULTS: At 3 months, a significantly higher rete volume was seen in group A than in group B (2.92±0.33 mL vs 1.87±0.69 mL, respectively; p=0.016). There was a trend for increased VEGF-A levels in group A at 3 months. In the occlusion group, histological findings showed significant reduction of media thickness and disrupted internal elastic lamina; immunohistochemistry findings showed strong reactivity for VEGF receptors and interleukin 6. CONCLUSIONS: Unilateral endovascular occlusion of the CCA-ECA results in angiogenesis triggering of the rete mirabile with both significant augmentation of the rete volume and histological evidence of pro-angiogenic stimulation.

Uterus tolerance to extended cold ischemic storage after auto-transplantation in ewes.

OBJECTIVE: To assess how the uterus tolerates extended cold ischemic storage before auto-transplantation in ewes. STUDY DESIGN: Fourteen uterine auto-transplantations were performed in ewes from November 2014 to June 2015 at the Analysis and Research Laboratory of Limoges, France. The animals were divided into 2 groups: 7 after 3h of cold ischemia timeand 7 after 24h. Transplant was assessed ≥8days after transplantation. Histology and apoptosis analyses (TUNEL method and indirect immunohistochemistry of cleaved Caspase 3) were performed before uterus retrieval (control), after 90min following reperfusion and ≥8days after transplantation. RESULTS: Twelve uterine auto-transplantations were successfully performed. The histological analysis at 90min following reperfusion revealed a moderate inflammation of the endometrium and serosa in the 3-h group and severe inflammation in the 24-h group, but no significant apoptotic signal was found in either group. Seven ewes were alive at ≥8days after transplantation: the macroscopic and histological analyses revealed two viable uteri in the 3-h group and three in the 24-h group. In each group one uterus was necrotic. CONCLUSION: These first results in ewes suggest that the uterus is an organ with a good tolerance to extended cold ischemic storage before transplantation.

Role of terminal and anastomotic circulation in the patency of arteries jailed by flow-diverting stents: from hemodynamic changes to ostia surface modifications.

OBJECTIVE The outcome for jailing arterial branches that emerge near intracranial aneurysms during flow-diverting stent (FDS) deployment remains controversial. In this animal study, the authors aimed to elucidate the role of collateral supply with regard to the hemodynamic changes and neointimal modifications that occur from jailing arteries with FDSs. To serve this purpose, the authors sought to quantify 1) the hemodynamic changes that occur at the jailed arterial branches immediately after stent placement and 2) the ostia surface values at 3 months after stenting; both parameters were investigated in the presence or absence of collateral arterial flow. METHODS After an a priori power analysis, 2 groups (Group A and Group B) were created according to an animal flow model for terminal and anastomotic arterial circulation; each group contained 7 Large White swine. Group A animals possessed an anastomotic-type arterial configuration to supply the territory of the right ascending pharyngeal artery (APhA), while Group B animals possessed a terminal-type arterial configuration to supply the right APhA territory. Subsequently, all animals underwent FDS placement, thereby jailing the right APhAs. Mean flow rates and velocities inside the jailed branches were quantified using time-resolved 3D phase-contrast MR angiography before and after stenting. Three months after stent placement, the jailed ostia surface values were quantified on scanning electron micrographs. The data were analyzed using descriptive statistics and group comparisons with parametric and nonparametric tests. RESULTS The endovascular procedures were feasible, and there were no findings of in situ thrombus formation on postprocedural optical coherence tomography or ischemia on postprocedural diffusion-weighted imaging. In Group A, the mean flow rate values at the jailed right APhAs were reduced immediately following stent placement as compared with values obtained before stent placement (p = 0.02, power: 0.8). In contrast, the mean poststenting flow rates for Group B remained similar to those obtained before stent placement. Three months after stent placement, the mean ostia surface values were significantly higher for Group B (527,911 ± 306,229 µm2) than for Group A (89,329 ± 59,762 µm2; p < 0.01, power: 1.00), even though the initial dimensions of the jailed ostia were similar between groups. A statistically significant correlation was found between groups (A or B), mean flow rates after stent placement, and ostia surface values at 3 months. CONCLUSIONS When an important collateral supply was present, the jailing of side arteries with flow diverters resulted in an immediate and significant reduction in the flow rate inside these arteries as compared with the prestenting values. In contrast, when competitive flow was absent, jailing did not result in significant flow rate reductions inside the jailed arteries. Ostium surface values at 3 months after stent placement were significantly higher in the terminal group of jailed arteries (Group B) than in the anastomotic group (Group A) and strongly correlated with poststenting reductions in the velocity value.

Role of terminal and anastomotic circulation in the patency of arteries jailed by flow-diverting stents: animal flow model evaluation and preliminary results.

OBJECTIVE The authors describe herein the creation of an animal model capable of producing quantifiable data regarding blood flow rate and velocity modifications in terminal and anastomotic types of cerebrofacial circulation. They also present the preliminary results of a translational study aimed at investigating the role of terminal and anastomotic types of circulation in arterial branches jailed by flow-diverting stents as factors contributing to arterial patency or occlusion. METHODS Two Large White swine were used to validate a terminal-type arterial model at the level of the right ascending pharyngeal artery (APhA), created exclusively by endovascular means. Subsequently 4 Large White swine, allocated to 2 groups corresponding to the presence (Group B) or absence (Group A) of terminal-type flow modification, underwent placement of flow-diverting stents. Blood flow rates and velocities were quantified using a dedicated time-resolved 3D phase-contrast MRA sequence before and after stenting. Three months after stent placement, the stented arteries were evaluated with digital subtraction angiography (DSA) and scanning electron microscopy (SEM). Patent (circulating) ostia quantification was performed on the SEM images. RESULTS Terminal-type flow modification was feasible; an increase of 75.8% in mean blood velocities was observed in the right APhAs. The mean blood flow rate for Group A was 0.31 ± 0.19 ml/sec (95% CI -1.39 to 2.01) before stenting and 0.21 ± 0.07 ml/sec (95% CI -0.45 to 0.87) after stenting. The mean blood flow rate for Group B was 0.87 ± 0.32 ml/sec (95% CI -1.98 to 3.73) before stenting and 0.76 ± 0.13 ml/sec (95% CI -0.41 to 1.93) after stenting. Mean flow rates after stenting showed a statistically significant difference between Groups A and B (Welch test). Mean and maximal blood velocities were reduced in Group A cases and did not decrease in Group B cases. Control DSA and SEM findings showed near occlusion of the jailed APhAs in both cases of anastomotic circulation (mean patent ostium surface 32,776 µm2) and patency in both cases of terminal-type circulation (mean patent ostium surface 422,334 µm2). CONCLUSIONS Terminal-type arterial modification in swine APhAs is feasible. Sufficient data were acquired to perform an a priori analysis for further research. Flow diversion at the level of the APhA ostium resulted in significant stenosis in cases of anastomotic circulation, while sufficient patency was observed in terminal-type circulation.

Jailed Artery Ostia Modifications After Flow-Diverting Stent Deployment at Arterial Bifurcations: A Scanning Electron Microscopy Translational Study.

BACKGROUND: Even though flow-diverting stents are being increasingly used to treat intracranial aneurysms, the fate of jailed side branches remains controversial, with recent clinical data contradicting finding of earlier animal studies that reported patency. OBJECTIVE: To quantify the surface area of the ostia after 3 months of jailing by flow-diverting stents as a more accurate means of patency evaluation. METHODS: Ten large white swine were stented by flow-diverting stents placed at common carotid-ascending pharyngeal arterial bifurcation sites. A dual antiplatelet regimen was initiated 72 hours before stenting and maintained during follow-up. Optical coherence tomography was used to search for per-procedural thrombus formation. Selective control digital subtraction angiography was performed 12 weeks post-stenting. Subsequently, the stented arterial segments were harvested en bloc and observed under scanning electron microscopy, photographed, and quantified. RESULTS: The absence of per-procedural thrombus formation was confirmed. All ostia were patent at 12 weeks (or 3 months) post stenting, with no angiographic or scanning electron microscopy-evident thrombus formation. The mean initial ostium surface was 2 048 617 ± 731 625 µm. At 3 months, the mean nonendothelialized ostium surface was 229 218 ± 140 172 µm, and mean endothelialized ostium surface was 1 819 399 ± 672 632 µm. A statistically significant difference (reduction) was observed between the initial and 12-week ostium surfaces (P < .001), with an significant statistical power (1.000). CONCLUSION: Jailed side branches remained patent after stenting, but the surface quantifications showed significant endothelial coverage, with a significant reduction of patent ostium surfaces at 12 weeks post-stenting. ABBREVIATIONS: APhA, ascending pharyngeal arteryCI, confidence interval3DRA, 3-dimensional rotational angiographyDSA, digital subtraction angiographyFDS, flow-diverting stentOCT, optical coherence tomographyOS, ostium surfaceSEM, scanning electron microscopy.

Peroral endoscopic pyloromyotomy accelerates gastric emptying in healthy pigs: proof of concept.

INTRODUCTION: Gastroparesis, or delayed gastric emptying, can be diagnosed with gastric emptying scintigraphy. Manometric studies of patients with gastroparesis show increased pyloric tone (pylorospasm). Among the recent endoscopic therapies for pylorospasm is peroral endoscopic pylorotomy (POP). In this study, we explored the effect of POP on gastric emptying in healthy pigs. MATERIAL AND METHODS: Four mini-pigs underwent POP following general anaesthesia. The mucosal entrance was situated 5 cm above the pylorus. POP was performed through a submucosal tunnel dissection. The duration of gastric emptying was assessed by scintigraphy before and after the procedure. The pigs were then euthanised for necropsy and pathologic assessment of the pylorus. RESULTS: The mean duration of the procedure was 55 (±â€Š4 SD) min. All surgeries were performed in their entirety with 100 % feasibility. There were no cases of bleeding. The one case of perforation had no clinical significance. The duration of gastric emptying was 2.22-fold shorter after POP compared with before POP (T½ post-POP = 84.5 [±â€Š35.7 SD] min vs. T½ pre-POP = 188.4 [±â€Š87.3 SD] min; P = 0.029). In agreement with the endoscopic observations, sectioning of the pyloric muscle in each pig was histologically complete. CONCLUSION: The efficacy of the procedure provides indirect proof of the involvement of the pyloric ring in delayed gastric emptying and suggests new therapies for patients with gastroparesis. Our protocol combining gastric emptying scintigraphy and POP validated the use of anaesthetised mini-pigs as a learning and training model for POP or other endoscopic/surgical procedures related to gastric emptying.

A local structured training program with live pigs allows performing ESD along the gastrointestinal tract with results close to those of Japanese experts.

BACKGROUND AND AIMS: The high specific skill needed by ESD limit its widespread use in Europe and animal training is recommended in Europe to improve the results of ESD that are far from Japanese at present. We create a local training program using live pigs as models, along with our human cases, to provide continuous exposure to the technique. METHODS: Between February 2013 and December 2015, two young operators performed 55 pig gastric ESDs in parallel with 62 human cases for large superficial cancerous lesions. The number and training dates of pig cases were adapted to those of the human cases to achieve continuous exposure to ESD cases. RESULTS: The en bloc, R0, and curative resection rates were 100%, 85.5% (53/62), and 77.5% (48/62), respectively with no recurrence observed during the one year follow up. There was no statistically significant difference in terms of the R0 or curative resection rates among ESDs performed during 2013-2015 (R0: 80% vs. 86.6% vs. 86.4%; Curative: 80% vs. 86.6% vs. 73%). CONCLUSION: A local structured training program using live pig models was used to train endoscopists for ESD in humans with high safety and efficiency, similar to results published by Japanese experts.

Plasma kinetics and efficacy of oral megazol treatment in Trypanosoma brucei brucei-infected sheep.

Experimentally infected sheep have been previously developed as an animal model of trypanosomosis. We used this model to test the efficacy of megazol on eleven Trypanosoma brucei brucei-infected sheep. When parasites were found in blood on day 11 post-infection, megazol was orally administered at a single dose of 40 or 80mg/kg. After a transient aparasitaemic period, all animals except two relapsed starting at day 2 post-treatment, which were considerated as cured on day 150 post-treatment and showed no relapse after a follow-up period of 270 days. In order to understand the high failure of megazol treatment to cure animals, a kinetic study was carried out. Plasma concentrations of megazol determined, by reverse-phase high-performance liquid chromatography at 8h post-treatment in these animals, were lowered, suggesting slow megazol absorption, except in cured animals. However, megazol plasma profiles in uninfected sheep after a single oral dose of megazol showed a fast megazol lowered absorption associated with a short plasma half-life of drug. Inter-individual variation of megazol pharmacokinetic properties was also observed. These findings suggested that the high failure rates of megazol treatment were related to poor drug availability after oral administration in sheep. In conclusion, megazol could cure sheep with T. b. brucei infection but oral administration was not an effective route.