Porcine Esophagus Research Articles

Sublingual insulin administration: application of hydroxypropyl beta-cyclodextrin and poloxamer188 as permeation enhancers

The objective of this investigation is to investigate the feasibility of sublingual insulin administration. Insulin solutions formulated with permeation enhancers (HPβCD/poloxamer 188) and their in-vitro and in-vivo performances were evaluated. Thereafter, insulin fast-dissolving film was further developed to have similar properties, upon dissolving the film, of the optimized insulin solution. In-vitro performance was evaluated via effect of HPβCD and/or poloxamer 188 concentration across cellulose acetate membrane and porcine esophagus. In-vivo performance was evaluated via pharmacodynamic and pharmacokinetic profiles of insulin solution administered. Cumulative amounts of insulin permeated at 60 min formulated with HPβCD (5%), poloxamer 188 (0.5%), and their combination were 1.31, 3.23, and 4.99 IU/cm2, respectively, indicating an additive effect of combination of HPβCD and poloxamer 188. Insulin-induced hypoglycemic effect was observed for insulin solutions with combination of HPβCD and poloxamer 188 after sublingual administration to Sprague-Dawley rats. Microscopic evaluation of porcine oesophageal tissue indicates that HPβCD and poloxamer 188 are safe. Furthermore, the cumulative amount permeated across cellulose acetate membrane at 30 min was 1.13 and 1.00 IU/cm2 for insulin solution and fast-dissolving film, respectively, demonstrating to be similar. In conclusion, the use of HPβCD/poloxamer 188 is feasible for the development of sublingual insulin solutions/films.

Evaluation of human keratinocyte sheets transplanted onto porcine excised esophagus after submucosal dissection in an exvivo model.

BackgroundThe utility of endoscopic transplantation of epithelial cell sheets to ulcer sites after endoscopic submucosal dissection (ESD) has been shown to prevent scar stenosis after ESD of early esophageal cancer. Previously, our group reported use of an endoscopic transplantation device fabricated with a 3-dimensional printer. Cell sheets are transplanted to the esophageal wound site with the following procedure: first, a cell sheet harvested from temperature-responsive culture dishes is placed on the device's deflated balloon surface and transported to the wound site with endoscopic forceps; second, by applying pressure from inflating the balloon locally at the wound site, the cell sheet is successfully transferred and adhered to the wound tissue; third, the balloon is deflated, and the device is removed. By repeating the procedure, several cell sheets can be safely transplanted to a wider ESD area. Nonetheless, possible damage to cell sheets using this procedure has not yet been assessed.ObjectiveEffects of endoscopic transplantation balloon inflation on cell viability and damage of normal human epidermal keratinocyte sheets resident on the device's balloon surface were evaluated by histology after sheet placement onto lumenal surfaces in the ex vivo porcine submucosal dissection esophagus model. Endoscopic transplantation of these same cell sheets with conventional methods using a polyvinylidene fluoride (PVDF) cell sheet support membrane, balloon device transfer, and also using a novel modified balloon transfer procedure was also examined. Cell sheet transfer results obtained with these three procedures were compared.MethodNormal human epidermal keratinocyte sheets were fabricated on temperature-responsive culture inserts. By temperature reduction to 20 °C, all cells were harvested as a single contiguous cell sheet. Freshly excised porcine esophagi purchased in a slaughter house were turned inside-out, and the exposed lumenal mucosa and submucosal layers were removed by Cooper scissors. This luminal surface was then utilized as a transplantation bed in ex vivo cell sheet experiments. Cell sheets were adhered to the endoscopic transfer device balloon, expanded by balloon inflation and resulting cell viability was evaluated by trypan blue exclusion test after cell sheet trypsinization and dispersion. Cell sheets were transferred onto the esophagus lumen ex vivo using forceps and the balloon device, and also using a modified balloon transfer method. The obtained results were compared with those without balloon expansion, and evaluated for sheet thickness and lumenal histology. Finally, TUNEL staining was performed to examine cell apoptosis.ResultCell sheets thinned after cell sheet balloon expansion, but no apoptosis was observed after these procedures.ConclusionExpanding keratinocyte cell sheets on a balloon endoscopic transfer device did not damage the cell sheets. This sheet transplantation method using the endoscopic balloon transfer device may be considered as a future standard cell sheet endoscopic transplantation procedure for repairing the esophagus.

Barrier Effect of a New Topical Agent on Damaged Esophageal Mucosa: Experimental Study on an ex vivo Swine Model.

PurposeAL2106 is a new medical device based on a mixture of chondroitin sulphate in a xyloglucan and glycerol solution made to maximize its bioadhesive capability to the esophageal mucosa. The aim of the present study was twofold to evaluate the AL2106 protective effect on the esophageal mucosa when exposed to an acidic solution mimicking gastric reflux and to assess the resilience of this effect to saline washing.Materials and MethodsA porcine ex vivo model was used and the effects of the new medical device were compared to a sodium alginate suspension (SAS) already present on the market which was assumed as reference. Mucosal damage was induced in 19 porcine esophagi by perfusion with an acidic solution added with pepsin, and Evans blue dye (EBD) tissue uptake was used as an indicator of mucosal permeability. The EBD penetration, expressed as EBD µg/g of dry tissue, was assessed in specimens of untreated damaged mucosa and in specimens treated with AL2106 or SAS. The same evaluation was carried out after washing with normal saline.ResultsBoth topical agents tested significantly reduced the EBD uptake by more than 60% (AL2106 8.4±4.5, SAS 3.6±2.7 vs control 23.2±13.1, p<0.01). The saline washing did not cause any significant reduction in the protective effect of AL2106 (8.6±5.9), while it significantly reduced that of SAS (5.9±4.3, p<0.05).ConclusionThe new AL2106 medical device showed a good barrier effect against a reflux-like damaging solution and preserved this effect after the mucosal washing test, thus suggesting its possible relevance for the treatment of gastroesophageal reflux disease.

Dual Oral Tissue Adhesive Nanofiber Membranes for pH-Responsive Delivery of Antimicrobial Peptides.

Bioadhesive membranes with controllable and reversible underwater adhesion are desirable for several biomedical applications ranging from biosensing, drug/therapeutic delivery, and tissue regeneration. Here, we present dual soft mucosal and hard bone/enamel tissue adhesive nanofiber membranes composed of chitosan and pectin derivatives for pH-controlled delivery of antimicrobial peptides (AMPs) in the oral cavity. Ex vivo testing with porcine esophagus (soft mucosal mimic) indicated a 2-fold increase in the mucoadhesion of chitosan membranes with 0.05 wt % oxidized pectin coating, while the uncoated membranes exhibited 3-4-fold stronger adhesion to hydroxyapatite discs (enamel/hard bone mimic) compared to the coated membranes. The former is attributed to a synergistic interaction of surface nanofiber topography, intermolecular hydrogen bonding, and aldehyde-amine chemistry between surface polar groups and mucosal proteins, while the latter may arise from electrostatic interactions between cationic amines (-NH3+) in chitosan and anionic phosphates (-PO43-) in hydroxyapatite. Further, the dual hard-soft oral tissue adhesive nanofiber membranes loaded with cationic amphipathic AMPs (D-GL13K and IDR-1018) elicited pH-responsive AMP delivery and antimicrobial action comparable to chlorhexidine (CHX) against oral streptococci. Concurrently, the AMP loaded membranes were cytocompatible to both soft epithelial tissue-derived human oral keratinocytes and hard calvarial murine pre-osteoblast cells. We envision these membranes to function as adhesive gingival grafts and guided bone regeneration (GBR) membranes at the hard-soft tissue interface while simultaneously protecting against oral infections.

Perfusion decellularization of porcine esophagus: Study of two processing factors affecting the folded mucosal structure of the esophageal scaffold.

Acellular scaffolds from decellularized donor organs are showing promising clinical results in tissue and organ repair and regeneration. A successful decellularization process is determined by (a) its capability to decellularize complete organs of large animals, (b) retention of the extracellular matrix (ECM) structures and morphologies, and (c) minimal loss of ECM proteins. In this study, porcine esophagi were perfused in full thickness with 0.25% w/v sodium dodecyl sulfate at perfusion rates 0.1-0.2 ml/min for up to 5 days. Decellularized tissues were characterized for their residual DNA, histological staining for their matrix structures, immunohistochemical staining for collagen type IV and laminin, and scanning electron microscopy for structural integrity. Our results showed that full thickness esophageal tissues treated using the horizontal perfusion setup were decellularized with good structural and biochemical integrity in the ECM. Residual DNA content in decellularized tissues was found to be 36 ± 12 ng/mg of tissues (n = 6) which was significantly lower than that of native tissues (p = .00022). Our study showed that the organ must be decellularized in full thickness and perfusion pressure must be controlled to minimize radial expansion. These factors were found to be critical in preserving the folded mucosa in the decellularized tissues.

The Lubricating Function of Mucin at the Gastroscope Device-Esophagus Interface

The mucous layer on the surface of human digestive tract is a dynamically balanced protective system, mainly containing mucin, enzymes, bicarbonate, epidermal growth factor and other protective factors. It has been found that mucins can protect epithelial cells from infection, dehydration, and physical, mechanical or chemical damage. There are a variety of disturbances that affect or destroy the function of the mucous layer, including mucus dysfunction and diseases of digestive tract. In this paper, the mechanical function of mucin on the surface of esophagus was studied using the UMT Tribometer with the porcine esophagus as the experiment sample. Trypsin was used to control the mucin content on the surface of esophagus. Results showed that the trypsin can affect the function of the mucin on the surface of esophagus. The friction coefficient and the relevant energy dissipation of trypsin-treated and non-trypsin-treated samples were significantly different. Due to the reduction of mucin on the esophageal surface by trypsin treatment, the friction coefficient and energy dissipation of the esophageal surface were significantly higher than that of the samples without trypsin treatment. During the friction test, the esophagus surface was severely damaged at both macro and micro scales after trypsin treatment, which indicated that the mucin can play a lubrication role at the gastroscope device-esophagus interface. The results can provide reference for clinical endoscopic examination and medical advice for clinical practice.

Magnetic Resonance Guided Navigation of Untethered Microgrippers.

Microsurgical tools offer a path to less invasive clinical procedures with improved access, reduced trauma, and better recovery outcomes. There are a variety of rigid and flexible endoscopic devices that have significantly advanced diagnostics and microsurgery. However, they rely on wires or tethers for guidance and operation of small end-effector tools. While untethered physiologically responsive microgrippers have been previously shown to excise tissue from deep gastrointestinal locations in animal models, there are challenges associated with guiding them along paths and moving them to specific locations. In this communication, the magnetic dipole moment of untethered thermally responsive grippers is optimized for efficient coupling to external magnetic resonance (MR) fields. Gripper encapsulation in a millimeter sized wax pellet reduces the friction with the surrounding tissue and MR Navigation (MRN) of a 700µm sized microgripper is realized within narrow channels in tissue phantoms and in an ex vivo porcine esophagus. The results show convincing proof-of-concept evidence that it is possible to sequentially image, move, and guide a submillimeter functional microsurgical tool in tissue conduits using a commercial preclinical MR system, and when combined with prior demonstrations of physiologically responsive in vivo biopsy are an important step towards the clinical translation of untethered microtools.

A Continuous Suture Anastomosis Outperforms a Simple Interrupted Suture Anastomosis in Esophageal Elongation.

Long-gap esophageal atresia represents a distinct entity among the esophageal atresia spectrum. In many patients, achieving a reasonable anastomosis depends on some millimeters of tissue. We aimed to determine what effect the suturing technique would have on esophageal ex vivo elongation as it may determine the strength of a primary anastomosis. In an analysis of porcine esophagi from animals for slaughter (100-120 days old with a weight of 100-120 kg), we determined esophageal length gain of simple continuous and simple interrupted suture anastomoses subjected to linear traction until linear breaking strength was reached. Statistical power of 80% was ensured based on an a priori power analysis using five specimens per group in a separate exploratory experiment. The simple continuous suture anastomosis in 15 porcine esophagi ( = 4.47 cm, 95% confidence interval: 4.08-4.74 cm) outperformed the simple interrupted suture anastomosis in another 15 esophagi ( = 3.03 cm, 95% confidence interval: 2.59-3.43 cm) in length gain (Δ = 1.44 cm, 95% confidence interval: 0.87-2.01 cm, p < 0.0001). Simple continuous anastomoses achieved higher length gain compared with simple interrupted suture anastomoses. This effect warrants an experimental assessment in vivo to assess its potential merits for clinical applicability.

Lubiprostone protects esophageal mucosa from acid injury in porcine esophagus.

Esophageal injury from acid exposure related to gastroesophageal reflux disease is a common problem and a risk factor for development of Barrett's esophagus and esophageal adenocarcinoma. Our previous work highlights the benefits of using porcine esophagus to study human esophageal disease because of the similarities between porcine and human esophagus. In particular, esophageal submucosal glands (ESMGs) are present in human esophagus and proximal porcine esophagus but not in rodent esophagus. Although CFTR is expressed in the ducts of ESMGs, very little is known about CFTR and alternate anion channels, including ClC-2, in the setting of acid-related esophageal injury. After finding evidence of CFTR and ClC-2 in the basal layers of the squamous epithelium, and in the ducts of the ESMGs, we developed an ex vivo porcine model of esophageal acid injury. In this model, esophageal tissue was placed in Ussing chambers to determine the effect of pretreatment with the ClC-2 agonist lubiprostone on tissue damage related to acid exposure. Pretreatment with lubiprostone significantly reduced the level of acid injury and significantly augmented the recovery of the injured tissue (P < 0.05). Evaluation of the interepithelial tight junctions showed well-defined membrane localization of occludin in lubiprostone-treated injured tissues. Pretreatment of tissues with the Na+-K+-2Cl- cotransporter inhibitor bumetanide blocked lubiprostone-induced increases in short-circuit current and inhibited the reparative effect of lubiprostone. Furthermore, inhibition of ClC-2 with ZnCl2 blocked the effects of lubiprostone. We conclude that ClC-2 contributes to esophageal protection from acid exposure, potentially offering a new therapeutic target.NEW & NOTEWORTHY This research is the first to describe the presence of anion channels ClC-2 and CFTR localized to the basal epithelia of porcine esophageal mucosa and the esophageal submucosal glands. In the setting of ex vivo acid exposure, the ClC-2 agonist lubiprostone reduced acid-related injury and enhanced recovery of the epithelial barrier. This work may ultimately provide an alternate mechanism for treating gastroesophageal reflux disease.

A clinical-grade acellular matrix for esophageal replacement.

In pathologies of the esophagus such as esophageal atresia, cancers, and caustic injuries, methods for full thickness esophageal replacement require the sacrifice of healthy intra-abdominal organs such as the stomach and the colon and are associated with high morbidity, mortality, and poor functional results. To overcome these problems, tissue engineering methods are developed to create a substitute with scaffolds and cells. The aim of this study was to develop a simple and safe decellularization process in order to obtain a clinical grade esophageal extracellular matrix. Following the decontamination step, porcine esophagi were decellularized in a bioreactor with sodium dodecyl sulfate and ethylenediaminetetraacetic acid for 3days and were rinsed with deionized water. DNA was eliminated by a 3-hr DNase treatment. To remove any residual detergent, the matrix was then incubated with an absorbing resin. The resulting porcine esophageal matrix was characterized by the assessment of the efficiency of the decellularization process (DNA quantification), evaluation of sterility and absence of cytotoxicity, and its composition and biomechanical properties, as well as the possibility to be reseeded with mesenchymal stem cells. Complete decellularization with the preservation of the general structure, composition, and biomechanical properties of the native esophageal matrix was obtained. Sterility was maintained throughout the process, and the matrix showed no cytotoxicity. The resulting matrix met clinical grade criteria and was successfully reseeded with mesenchymal stem cells..

Thiolated hydroxypropyl-β-cyclodextrin as mucoadhesive excipient for oral delivery of budesonide in liquid paediatric formulation.

Budesonide (BUD) is a low water soluble (S0 = 5.028·10-5 M) corticosteroid used as preferred therapy for the treatment of Eosinophilic Esophagitis (EoE), a chronic allergic-immune condition with an increased incidence in the paediatric population. Currently there are no commercial medicines indicated for EoE, and, therefore, in the hospital pharmacy the BUD is extemporaneously formulated as viscous oral suspension at the initial dose of 1-2 mg per day for children, highlighting the need of a mucoadhesive drug delivery system (MDDS) that adheres to the site of action and prolongs the therapeutic activity of the administered drug. Considering the ability of hydroxypropyl-β-cyclodextrin (HP-β-CD, 100 mM) to increase the water solubility of BUD (SHP-β-CD = 4.3·10-3 M; K1:1 = 861.11 M-1), a mucoadhesive thiolated HP-β-CD (HP-β-CD-SH) was synthesized and characterized by mass spectroscopy, 1H- and 13C NMR techniques. Phase-solubility studies demonstrated the capability of HP-β-CD-SH (100 mM) to form a reversible water soluble inclusion complex with BUD (SHP-β-CD-SH = 10.9·10-3 M; K1:1 = 2013.52 M-1), which increases its permanence on the target site as proved by mucoadhesive studies on porcine oesophagus mucosa. HP-β-CD-SH might be a useful MDDS for the pharmacist to prepare BUD oral liquid formulations at the recommended doses, with pH values below 5, which guarantee the chemical stability of the new mucoadhesive excipient.

Usefulness of 3-Dimensional Flexible Endoscopy in Esophageal Endoscopic Submucosal Dissection in an Ex Vivo Animal Model.

Background and Aims Three-dimensional (3D) rigid endoscopy has been clinically introduced in surgical fields to enable safer and more accurate procedures. To explore the feasibility of 3D flexible endoscopy, we conducted a study comparing 2-dimensional (2D) and 3D visions for the performance of esophageal endoscopic submucosal dissection (ESD). Methods Six endoscopists (3 experts and 3 trainees) performed ESD of target lesions in isolated porcine esophagus using a prototype 3D flexible endoscope under 2D or 3D vision. Study endpoints were procedure time, speed of mucosal incision and submucosal dissection, number of technical adverse events (perforation, muscle layer damage, and sample damage), and degree of sense of security, fatigue, and eye strain. Results Procedure time and speed of mucosal incision/submucosal dissection were equivalent for 2D and 3D visions in both experts and trainees. The number of technical adverse events using 2D vision (mean [standard deviation], 3.5 [4.09]) tended to be higher than that using 3D vision in trainees (1.33 [2.80]; P = .06). In experts, 2D and 3D visions were equivalent. The degree of sense of security using 3D vision (3.67 [0.82]) was significantly higher than that using 2D vision (2.67 [0.52]) in trainees (P = .04), but was equivalent in experts. The degree of eye strain using 3D vision (3.00 [0.00]) was significantly higher than that using 2D vision (2.17 [0.41]) in trainees, but was equivalent in experts. Conclusions 3D vision improves the sense of security during ESD and may reduce technical errors, especially in trainees, indicating the feasibility of a clinical trial of ESD under 3D vision.

Polarization-sensitive optical coherence elastography.

Polarization-sensitive optical coherence elastography (PS-OCE) is developed for improved tissue discrimination. It integrates Jones matrix-based PS-optical coherence tomography (PS-OCT) with compression OCE. The method simultaneously measures the OCT intensity, attenuation coefficient, birefringence, and microstructural deformation (MSD) induced by tissue compression. Ex vivo porcine aorta and esophagus tissues were investigated by PS-OCE and histological imaging. The tissue properties measured by PS-OCE are shown as cross-sectional images and a three-dimensional (3-D) depth-trajectory plot. In this trajectory plot, the average attenuation coefficient, birefringence, and MSD were computed at each depth, and the trajectory in the depth direction was plotted in a 3-D feature space of these three properties. The tissue boundaries in a histological image corresponded with the depth-trajectory inflection points. Histogram analysis and t-distributed stochastic neighbour embedding (t-SNE) visualization of the three tissue properties indicated that the PS-OCE measurements provide sufficient information to discriminate porcine esophagus tissues.

Use of the extracellular matrix from the porcine esophagus as a graft for bladder enlargement

Some patients with diseases that involve increased bladder pressure or low-capacity bladders may need bladder enlargement surgery. In current techniques for bladder enlargement, autologous tissue such as small intestine or colon tissue is used to perform cystoplasties, which is far from ideal for these patients. In search of biomaterials with appropriate regeneration and safety profiles, tissue engineering has resulted in preclinical studies with acellular matrices in animal models that have yielded positive preliminary results with respect to the urothelial cell and smooth muscle repopulation; these studies have primarily been performed with matrices originating from the bladder or intestinal submucosa. The aim of the study was to assess an extracellular matrix device derived from the porcine esophagus for augmentation cystoplasty in an animal model. Seven male Wistar rats weighing 357-390g were subjected to augmentation cystoplasty with a circular segment of the acellular matrix from the porcine esophagus. Daily postoperative follow-up was performed with evaluation of changes in body weight, behavior, and wound status. During follow-up, there were no complications associated with the process. Three specimens were sacrificed at day30, and three, at day 60. Necropsy was performed, with a description of the macroscopic findings and a morphological study. Epithelialization was observed, with different stages of mucosal development in all specimens analyzed. Repopulation of smooth muscle cells, mixed inflammatory infiltrate, and vascular neoformation were identified in the matrices. The urothelium and fibers of the smooth muscle were observed inside the implanted matrix. Additional investigations in larger animal models that allow urodynamic evaluation of the bladder with the matrix implanted are needed. However, to compare the results of this study model with those reported in the literature, a matrix derived from an organ different from the bladder was used because it could prevent the use of an intestinal segment in augmentation cystoplasty. The acellular porcine esophagus matrix offers positive results regarding the repopulation of the urothelium and smooth muscle when used in augmentation cystoplasty in a murine model.

Evaluation of the extent of damage to the esophageal wall caused by press-through package ingestion

Press-through package (PTP) is the most common accidentally ingested foreign body in Japan. Accidental ingestion of PTP can result in esophageal damage. An approach for evaluating the risk of esophageal injury has not been established. Therefore, we used porcine esophageal tissue and silicone sheets to establish a method for assessing the risk of esophageal damage on accidental PTP ingestion. We pathologically evaluated porcine lower esophageal tissue using a scratch tester. Using porcine esophageal tissue, scratch tests were performed with 4 test objects and pathological damage was compared. It was assumed that each object was accidentally ingested. The objects were polyvinylidene chloride (PVDC)-coated polyvinyl chloride (PVC) PTP, soft PThPa, round PTP, and a disposable scalpel. The porcine esophagus was replaced with a silicon sheet, and an automatic friction machine was used for quantitative evaluation. The silicon sheet was scratched using HHS 2000 with 750-g load at 50 mm/min. We investigated the frictional force exerted on the surface for each of the objects. The degree of damage (depth) was the highest for the disposable scalpel, followed by PVDC-coated PVC PTP, while the degree of damage (depth) was the lowest for soft PThPa and round PTP. The mean frictional forces on the silicon sheet were 524.0 gf with PVDC-coated PTP, 323.5 gf with soft PThPa, 288.7 gf with round PTP, and 922.7 gf with the disposable scalpel. We developed approaches to qualitatively and quantitatively evaluate the risk of esophageal damage after accidental PTP ingestion. Our findings indicate that the risk of gastrointestinal damage after accidental PTP ingestion is low with soft PTP and round PTP.

Balloon catheter-based radiofrequency ablation monitoring in porcine esophagus using optical coherence tomography.

We present a microscopic image guidance platform for radiofrequency ablation (RFA) using a clinical balloon-catheter-based optical coherence tomography (OCT) system, currently used in the surveillance of Barrett's esophagus patients. Our integrated thermal therapy delivery and monitoring platform consists of a flexible, customized bipolar RFA electrode array designed for use with a clinical balloon OCT catheter and a processing algorithm to accurately map the thermal coagulation process. Non-uniform rotation distortion was corrected using a feature tracking-based technique, which enables robust, frame-to-frame analysis of the temporal fluctuation of the complex OCT signal. With proper noise calibration, precise delineation of the thermal therapy zone was demonstrated using cumulative complex differential variance in porcine esophagus ex vivo with the integrated OCT-RFA system, as validated by nitroblue tetrazolium chloride (NBTC) histology. The ability to directly and accurately visualize the thermal coagulation process at high resolution is critical to the precise delivery of thermal energy to a wide range of epithelial lesions.

Miniaturized High-Resolution Integrated 360° Electronic Radial Ultrasound Endoscope for Digestive Tract Imaging.

To improve the accuracy and operating flexibility of digestive diagnostic applications in situ, this paper demonstrates the design, fabrication, and evaluation of a miniaturized high-resolution integrated 360° electronic radial ultrasound endoscope. To improve the uniformity between elements of the radial array transducer, an optimal fabrication procedure based on a flexible matching layer was developed. The radial ultrasound endoscope has a 128.3° 5-million-pixel camera module integrated with an approximately 8-MHz 128-element radial ultrasonic array in a package with an outer diameter of 9.5 mm. The results showed that the array has a center frequency of 8.2 MHz, a -6-dB fractional bandwidth of 83.4%, and a two-way insertion loss of 39.62 dB at the center frequency. Annulus and wire phantoms can be distinctly imaged with the radial array. Printed eight-point font can be distinctly imaged with both a large view and a 3-18-mm depth of field in lumen short-range optical imaging. A porcine esophagus can be distinctly imaged in vitro with the integrated endoscope. The results indicate that the fabrication method based on a flexible matching layer can achieve high uniformity between elements of a radial array transducer. In addition, the proposed ultrasound endoscope demonstrates a good image resolution.

Esophageal Biomechanics Revisited: A Tale of Tenacity, Anastomoses, and Suture Bite Lengths in Swine

Anastomotic tension has repeatedly been associated with anastomotic leakages after esophagectomy for cancer or esophageal atresia repair. We therefore aimed to determine which anastomotic technique would come as close as possible to the native esophagus in sustaining traction forces. Constant traction for several minutes at esophageal remnants and large suture bites are also considered relevant in long-gap esophageal atresia repair. Porcine esophagi were subjected to linear traction using a motorized horizontal test stand. We compared breaking strengths of native esophagi to simple continuous, simple interrupted, stapled, and barbed suture anastomoses. We also investigated the effects of suture bite length and phases of constant traction on breaking strengths and powered all experiments to at least 80% using exploratory investigations (n= 5 per group). Continuous suture anastomoses had a breaking strength comparable to native esophagi (Δ=-5.25 Newton, 95% confidence interval:-10.69 to 0.19 Newton, p= 0.058) and outperformed all other investigated anastomoses (Δ ≥14.01 Newton, p ≤ 0.02). Breaking strength correlated with suture bite length (R= 0.905) and predicted breaking strength for the simple stitch (adjusted R2= 0.812, p < 0.0001), but not for anastomoses. Phases of incrementally increasing constant traction resulted in higher breaking strengths (Δ= 13.36 Newton, 95% confidence interval: 9.93 to 16.79 Newton, p< 0.0001) and higher length gain (Δ= 1.06 cm, 95% confidence interval: 0.65 to 1.48 cm, p < 0.0001) compared with controls. Only simple continuous anastomoses achieved the linear breaking strength of native tissue. Our study provides important insights in tolerance to traction forces, but its results have to be corroborated in living animals as anastomotic leakages are multifactorial processes.

Technical Aspects in Esophageal Lengthening: An Investigation of Traction Procedures and Suturing Techniques in Swine.

Traction procedures are useful to preserve the child's own esophagus in long-gap forms of esophageal atresia. To date, it remains unclear what suture size or position of the traction sutures is optimal to account for differences in anatomy and to reduce the risk of traction sutures being torn out of the esophageal tissue. Explanted porcine esophagi (from swine aged 100-120 days and weighing 100-120 kg) were divided at the carinal level. Traction sutures were either placed circumferentially or only in the dorsal wall and the breaking strength-circumferential disruption of the muscular layer-was measured. Suture size (USP 4-0 vs. 5-0) was also evaluated in a similar way. Neither traction suture position did not influence breaking strengths between circumferentially placed traction sutures or those exclusively placed in the dorsal esophageal wall (Δ = 0.47 N, 95% confidence interval: -2.83 to 3.76 N, p = 0.771, n = 11 per group) nor differing suture sizes of USP 4-0 and USP 5-0 (Δ = 1.46 N, 95% confidence interval: -3.2 to 0.28 N, p = 0.0946, n = 9 per group) affected breaking strengths. Suture size and suture positioning do not affect mechanical stability in Foker's procedure and therefore can be adapted as needed according to patient's anatomy and size.

3D-printed flexible polymer stents for potential applications in inoperable esophageal malignancies

Palliation therapy for dysphagia using esophageal stents is the current treatment of choice for those patients with inoperable esophageal malignancies. However, the metallic and plastic stents currently used in the clinical setting may cause complications, such as tumor ingrowth and stent migration into the stomach. To effectively reduce/overcome these complications, we designed a tubular, flexible polymer stent with spirals. The parameters of the spirals were computationally optimized by using a finite element analysis. The designed polymer stents with optimized spirals were then printed by a 3D printing technique. 3D-printed tubular polymer stents without spirals served as controls. The self-expansion and anti-migration properties of the printed stent were characterized in an ex vivo normal porcine esophagus. The biodegradability test of the stent was performed in a neutral buffer and acidic gastric buffer. The cytotoxicity of the new stent was examined through the viability test of human esophagus epithelial cells. Results showed the self-expansion force of the 3D-printed polymer stent with spirals was higher than the stent without spirals. The anti-migration force of the 3D-printed stent with spirals was significantly higher than that of the stent without spirals. Furthermore, the stent with spirals significantly decreased the migration distance compared to the non-spiral 3D-printed polymer stent. Degradation study showed that the polymer materials started to degrade after six weeks and the compressive strength of the stent was not significantly decreased with time. In vitro cell viability results further indicated that the polymer stent does not have any cytotoxicity. Together, these results showed that the 3D-printed stent with spirals has potential applications in the treatment of inoperable esophageal malignancies. Statement of significanceIn this study, we developed a new 3D-printed flexible tubular polymeric stent with spirals. The mechanical properties of the 3D-printed polymer stent are modulated by changing the ratios of PLA to TPU. The stent is flexible enough to be compressed in a clinically available stent delivery system, and can self-expand after it is released. The self-expansion force of the stent with spirals is higher than that of non-spiral stents. The spirals on the outside of the stent significantly increased the anti-migration force compared to non-spiral stents in an ex vivo normal pig esophagus. Together, the 3D-printed stent with spirals will bring promising potential in the treatment of inoperable esophagus malignancies or benign strictures.