Rabbit Esophagus Research Articles

Detection of MUC1+/MUC2 and MUC5AC- membrane-associated mucins in the intraepithelial surface mucous cells of the developing rabbit esophagus.

Mucins are polydisperse molecules created to perform a variety of functions at the mucosal surface of the adult gastrointestinal tract. Two main groups of mucins could be identified, the membrane associated mucins (MUC1, MUC4, MUC13 and MUC16), those bound to the apical plasma membrane of epithelial cells, and the secreted mucins (MUC2, MUC5AC, MUC5B and MUC6), those secreted from the goblet cells. Little is known about the types and distribution patterns of mucins in prenatal life. We detected mucin secreting cells in the developing rabbit esophagus though these cells are absent in the adult one. In order to identify the content and possible functions of these cells, we investigated the histochemical and immunohistochemical characteristics of their mucins. Starting at 16th day of pregnancy, Periodic acid Schiff (PAS), alcian blue pH (2.5) (AB) and PAS-AB combination, intensely stained the mucous content demonstrating both acidic and neutral mucopolysaccharides. Some blebs could be recognized on the free surface of the esophageal epithelium. Also, the mucous cells and some basal cells strongly immunoreacted with MUC1, but not MUC2, nor MUC5AC antibodies. Collectively, these data suggest that surface mucous cells are modified epithelial cells, not goblet cells, and may originate from the basal layer of the epithelial cells. A possible regulatory role for these MUC1 positive mucins in esophageal epithelial and mesenchymal cell differentiation and late organogenesis is suggested. However, future functional studies are recommended.

Circumferential Esophageal Reconstruction Using a Tissue-engineered Decellularized Tunica Vaginalis Graft in a Rabbit Model

BackgroundPediatric surgeons have faced esophageal reconstruction challenges for decades owing to a variety of congenital and acquired conditions. This work aimed to introduce a reproducible and efficient approach for creating tissue-engineered esophageal tissue using bone marrow mesenchymal stem cells (BMSCs) cultured in preconditioned mediums seeded on a sheep decellularized tunica vaginalis (DTV) scaffold for partial reconstruction of a rabbit's esophagus. MethodsDTV was performed using SDS and Triton X-100 solutions. The decellularized grafts were employed alone (DTV group) or after recellularization with BMSCs cultured for 10 days in preconditioned mediums (RTV group) for reconstructing a 3 cm segmental defect in the cervical esophagus of rabbits (n = 20) after the decellularization process was confirmed. Rabbits were observed for one month, after which they were euthanized, and the reconstructed esophagi were harvested for histological analysis. ResultsSix rabbits in the DTV group and eight rabbits in the RTV group survived until the end of the one-month study period. Despite histological examination demonstrating that both grafts completely repaired the esophageal defect, the RTV graft demonstrated a histological structure similar to that of the normal esophagus. The reconstructed esophagi in the RTV group revealed the arrangement of the different layers of the esophageal wall with the formation of newly formed blood vessels and Schwann-like cells. ConclusionDTV xenograft is a novel scaffold that promotes cell adhesion and differentiation and might be effectively utilized for regenerating esophageal tissue, paving the way for future clinical trials in pediatric patients.

Esophageal Magnetic Anastomosis Device (EMAD) to Simplify and Improve Outcome of Thoracoscopic Repair for Esophageal Atresia with Tracheoesophageal Fistula: A Proof of Concept Study

BackgroundWe designed a new Esophageal Magnetic Anastomosis Device (EMAD) for thoracoscopic repair of esophageal atresia (EA) with tracheoesophageal fistula (TEF) without the need of handheld suturing or additional gastrostomy. MethodsSynthetic EA-TEF model: Spherical and tubular shaped rubber balloons and a term infant sized plastic doll were used. Medical students (n = 10) and surgical trainees (n = 10) were asked to perform thoracoscopic repair of an “EA” with a hand sutured anastomosis (HA) and with the EMAD. Euthanized animal model: The esophagus in 5 piglets (3–4 kg) was dissected and a thoracoscopic esophageal magnetic anastomosis (EMA) was performed. Bursting pressure (BP) and pulling force (PF): HA and EMA were created on ex vivo New Zealand white rabbit (2.5–3 kg) esophagi (n = 25 in each test series). BP and PF were measured and compared against each other. ResultsMedical students were unable to complete HA, but were successful with the EMAD in 11.1 ± 2.78 min. Surgical trainees completed EMA in 4.6 ± 2.06 min vs. HA 30.8 ± 4.29 min (p<0.001). The BP following a HA (14.1 ± 3.32 cmH2O) was close to the physiological intraluminal pressure reported in a neonatal esophagus (around 20 cmH2O), whereas the BP with the EMAD was extremely high (>90 cmH2O) (p<0.001). The PF of an EMA (1.8 ± 0.30 N) was closer to the safety limits of anastomotic tension reported in the literature (i.e. 0.75 N) compared with the HA (3.6 ± 0.43 N) (p<0.0001). ConclusionThe EMAD could simplify, shorten, and potentially improve the outcome of thoracoscopic repair for EA with TEF in the future. A high BS and a relative low PF following EMAD application may lower the risk of postoperative complications such as esophageal leakage and stricture formation.

Реакция эпителия пищевода кролика на острый и хронический стресс

Реакция эпителия пищевода кролика на острый и хронический стресс

COMPARATIVE HISTOCHEMICAL AND HISTOMORPHOMETRICAL STUDY OF ESOPHAGUS STRUCTURES IN SHEEP (Ovis aries) AND RABBITS (Oryctolagus Cuniculus)

Evolution between animals causes many changes so that it can adapt to its environments. Each species has unique features that help them survive and can consume different types of food. Sheep and rabbits are economically important animals and used in many aspects of veterinary medicine.This study aimed to compare the histomorphometric and histochemical features of the esophagus of twenty sheep (n = 10) and rabbit (n = 10) adult males. The samples were collected from slaughterhouse and market Misan and were used for histological studies of two types of stains, hematoxylin and eosin, and special stains (Periodic acid Schiff stains). Histological study showed differences in the type epithelium of mucosa lining the esophagus between sheep and rabbits. The epithelium lining was composed of a keratinized stratified squamous epithelium in sheep while in rabbit was composed of a non-keratinized stratified squamous. In both animals, the submucosa layer does not possess glands. The muscular layer of both was composed of striated muscle in the cervical, thoracic, and abdomen parts of the esophagus. Both animals contained an outer layer of loose connective tissue called the adventitia. All layers in sheep showed more thickness than in rabbits. The histochemical study showed that the reaction to Periodic acid Schiff stain was similar between the animals and in different places. Only stratum corneum cells of the sheep mucosa and squamous cells of the rabbit mucosa demonstrated a strong reaction to this stain. In contrast, the rest of the cells of the mucosa and muscular layers were moderate reactions with Periodic acid Schiff stain in all regions sheep and rabbit esophagus. Submucosa and adventitia showed weakly reaction with Periodic acid Schiff's stain in both animals. In conclusion, this study showed that sheep and rabbits have similarities and differences in the esophagus; that is, the layers of this organ has different thicknesses and respond differently to Periodic acid Schiff stain.

Differentiation of bMSCs on Biocompatible, Biodegradable, and Biomimetic Scaffolds for Largely Defected Tissue Repair.

Biocompatible, biodegradable, and biomimetic scaffolds in combination with stem cells are of great importance for tissue engineering, especially the repairing and regeneration of defected organs. As a case in point, esophageal diseases have become serious clinical problems because of the poor self-repairing ability of the organ. It is crucial to prepare artificial replacements with biological function for serious lesions of the esophagus. However, the pH value, mechanical strength, thickness, and other physical conditions are very different in different organs or different parts of the same organ, which pose high difficulty for successful tissue engineering. In this work, bone marrow mesenchymal stem cells (bMSCs) were isolated from rabbits and transfected with green fluorescent protein (GFP) to follow their capabilities of growth, stemness, and differentiation in ex vivo culture. These bMSCs were seeded on biocompatible, biodegradable, and biomimetic scaffolds to detect the tissue regenerative capability of the esophagus with multilayer hierarchical structure. According to the esophageal bilayer muscle architecture, we designed discontinuous and continuous microchannel patterned scaffolds with medical level polyurethane (PU) as the matrix to guide the inner-circular and outer-longitudinal muscle growth. The gap on the discontinuous walls not only helped cells to communicate with each other but also assisted cells to infiltrate through the gap and grew into the inner circular muscle. The graft of silk fibroin on the scaffold surface using the aminolysis and glutaraldehyde cross-linking method enhanced the substrate's hydrophilicity and biocompatibility. Mucosa-submucosa tissue of rabbit's esophagus was decellularized to obtain the extracellular matrix (ECM) and implanted in situ after recellularizing with bMSCs to repair the partially defected rabbits' esophagus. On the basis of both in vitro and in vivo results, we concluded that esophagus regeneration was promoted by the differentiation of bMSCs on the biocompatible, biodegradable, and biomimetic scaffolds, starting from tissue "niches", to repair the largely defected esophagus, which paves the way for tissue engineering and defected organ treatments.

A PTX/nitinol stent combination with temperature-responsive phase-change 1-hexadecanol for magnetocaloric drug delivery: Magnetocaloric drug release and esophagus tissue penetration

An antitumor drug/esophagus stent combination can palliatively relieve malignant esophageal stricture and exert local chemotherapy to cancer. It is vital for effective treatment of cancer to control drug release and facilitate drug penetration into deep tissue after the combination is placed in the malignant strictured esophagus part. In this study, we firstly designed and prepared a novel antitumor drug/esophagus stent combination: a magnetocaloric nitinol stent coated with a bilayered film that consisted of one ethylene-vinyl acetate copolymer (EVA) layer as drug blocking layer and one EVA layer containing 10% paclitaxel (PTX) and 30% temperature sensitive phase-change fatty alcohol (1-tetradecanol, 1-hexadecanol or 1-octadecanol). The drug release and penetration into rabbit esophagus wall from the combination were investigated. It was found that, under an alternating electromagnetic field at a power of 0.1 kW, the combination was heated to 43 °C, the PTX was faster and more released from the combination, as well as the amount of PTX in esophagus tissue or its deep muscle tissue penetrated from the combination was much higher than that without alternating electromagnetic field. The pathological data showed that the combination was biocompatible and safe after placement in rabbit esophagus even under an alternating electromagnetic field. Overall, the PTX could be magnetocalorically released and effectively penetrated into esophagus wall from the PTX/nitinol stent combination.

Biomechanical and morphological multi-parameter photoacoustic endoscope for identification of early esophageal disease

The combination of phase-sensitive photoacoustic (PA) imaging of tissue viscoelasticity with the esophagus-adaptive PA endoscope (PAE) technique allows the characterization of the biomechanical and morphological changes in the early stage of esophageal disease with high accuracy. In this system, the tissue biomechanics and morphology are obtained by detecting the PA phase and PA amplitude information, respectively. The PAE has a transverse resolution of approximately 37 μm and an outer diameter of 1.2 mm, which is suitable for detecting rabbit esophagus. Here, an in-situ biomechanical and morphological study of normal and diseased rabbit esophagus (tumors of esophagus and reflux esophagitis) was performed. The in-situ findings were highly consistent with those observed by histology. In summary, we demonstrated the potential application of PAE for early clinical detection of esophageal diseases.

The effect of paclitaxel-eluting covered metal stents versus covered metal stents in a rabbit esophageal squamous carcinoma model.

BackgroundThe use of self-expanding metallic stents (SEMSs) is the current treatment of choice for malignant gastrointestinal obstructions. However, these stents can promote only drainage and have no antitumor effect. Some studies have reported that drug-eluting SEMSs may have tumor inhibition potential. The aim of this study was to evaluate the efficiency and safety of paclitaxel-eluting SEMSs (PEMSs) in rabbit esophageal cancer models.Materials and methodsA PEMS was covered with a paclitaxel-incorporated membrane, in which the concentration of paclitaxel was 10% (wt/vol). The rabbit models were created endoscopically. Then, a PEMS or SEMS was endoscopically inserted into the rabbit esophagus. Two weeks after stent placement, the rabbits were sacrificed, and we evaluated the tumor volume, area of the wall defect, area of the tumor under endoscopic ultrasound (EUS) before and after stent placement, status of the proximal esophageal obstruction, tumor metastasis food-intake and weight loss.ResultsA total of 26 rabbits received stent insertion and survived until sacrifice, and migration occurred in 4 cases, 3 in SEMS group and 1 in PEMS group. For the remaining 22 rabbits, at the sacrificed time, the average tumor volume was 7.00±4.30 cm3 in the SEMS group and 0.94±1.51 cm3 in the PEMS group (P<0.05). The area of the esophageal wall defect was 0.70±0.63 cm2 in the SEMS group and 0.17±0.16 cm2 in the PEMS group (P<0.05). The tumor area under EUS was 4.40±1.47 cm2 in the SEMS group and 1.30±1.06 cm2 in the PEMS group (P<0.05). At the time of stent placement, tumor area under EUS was comparable in the two groups. Other indices did not significantly differ between the two groups.ConclusionsSEMS and PEMS are both safe and effective to relieve dysphagia in rabbit esophageal cancer models. A PEMS can serve as an alternative tool for advanced esophageal cancer that may inhibit tumor growth by serving as a drug sustained-release platform. Clinical trials of the stent are warranted in the future.

Silicone-covered biodegradable magnesium-stent insertion in the esophagus: a comparison with plastic stents.

Background:We determined the feasibility of, and tissue response to silicone-covered biodegradable magnesium- and plastic-stent insertion into the esophagus in rabbits.Methods:The mechanical compression–recovery characteristics and degradation behaviors of the magnesium stent were investigated in vitro. A total of 45 rabbits were randomly divided into a magnesium- (n = 15) and a plastic- (n = 15) stent group, and underwent stent insertion into the lower third of the esophagus under fluoroscopic guidance; a control group (n = 15) did not undergo the intervention. Esophagography was performed at 1, 2, and 4 weeks. Five rabbits in each group were euthanized at each time point for histological examination.Results:Silicone-covered magnesium stents showed similar radial force to plastic stents (p > 0.05). The magnesium stents degraded rapidly in an acidic solution, but 90.2% ± 3.1% of the residual mass was maintained after a 2-week degradation in a solution with a pH of 4.0. All stent insertions were well tolerated. Magnesium stents migrated in six rabbits (one at 1 week, one at 2 weeks and four at 4 weeks), and plastic stents migrated in three rabbits (one at 2 weeks and two at 4 weeks; p > 0.05). Esophageal wall remodeling (thinner epithelial and smooth muscle layers) was similar in both stented groups (p > 0.05), and the esophagus wall was found to be significantly thinner in the stented groups than in the control group (p < 0.05). Esophageal injury and collagen deposition following stent insertion were similar and did not differ from the control group (p > 0.05).Conclusions:Esophageal silicone-covered magnesium stents provided reliable support for at least 2 weeks, with acceptable migration rates and without causing severe injury or tissue reaction compared with plastic stents.

Evaluación de tres diferentes posiciones de los puertos de entrada para la funduplicatura de Nissen laparoscópica en conejos

Introduction: Paediatric laparoscopic surgery provides new challenges for surgeons; therefore there is a need for adequate training before performing procedures directly on patients. Several different models were designed for training, including both virtual simulators and live animals. However, training with animal models is the most appropriate method for surgical instruction, as it reproduces similar surgical conditions. The objective of this study was to establish the best localization of surgical ports for Nissen fundoplication in rabbit cadavers for both experimental and teaching purposes. Method: The research was conducted using six New Zealand white rabbit cadavers. The location of the trocars was established by two veterinary and one paediatric with experience in laparoscopy surgery. The model was evaluated by four paediatric surgeons. A 5 mm trocar was used, and a laparoscope of 5 mm and 30° attached to a microcamera was inserted. The abdomen was insufflated (to a pressure of 6-8 mm Hg). The placement of secondary trocars was conducted with direct visualization. Diverse factors were considered to establish the location of the trocars such the anatomy of the rabbit stomach and esophagus, laparoscopic Nissen fundoplication performed in rabbits with conventional laparoscopic instruments, and the length of paediatric laparoscopic instruments. Three approaches were repeated in order to locate a satisfactory view of the surgical area. Every position of the ports received a score: one point was scored when the instrumentation was crossed, one point when the organs were too far away to manipulate, and one point when the organs were too close to manipulate. The position was considered ideal when a zero value was obtained. Fleiss Kappa coefficient for 4 raters was used to estimate the level of concordance between observers. Results: It was possible to obtain a value of zero in the latter approach. The position of the trocars was established in the following way: the telescope port positioned at midline 1.6 cm caudal to the umbilical scar (2.0 cm with insufflation), and with the secondary ports placed slightly lateral to the third mammary glands. To establish the exact location of these trocars a point was established at 1.5 cm caudal to the telescope trocar. After forming an angle of 90°, 3.3 cm were measured on each side. These last measures were taken with the abdomen insufflated. Discussion or Conclusion: In this research was established the appropriate positions of the working ports, without causing fatigue of the operator’s wrist joint and with adequate space for comfortable movement. In addition, this would also reduce the use of live rabbits for the establishment of the ports in future research, accepting the concept of the three Rs for animal experimentation. With these models was obtained an excellent view of the surgical field without interference between the instruments and telescope.

Effect of a paclitaxel-eluting metallic stent on rabbit esophagus.

The use of self-expanding metallic stents (SEMS) is the current treatment of choice for malignant gastrointestinal obstructions. A paclitaxel-eluting metallic SEMS (PEMS) may have an antitumor effect on esophageal tissue. PEMS with 10% paclitaxel or conventional SEMS were inserted into the lower esophagus of rabbits. Following the insertion of the stents for 1, 2, 4 and 6 weeks, the rabbits were sacrificed and the status of the stent insertion was examined, as well as any macroscopic or microscopic mucosal changes in the esophageal tissue. All the rabbits survived until death without any complications. No migration following stent insertion occurred. The number of cases with proximal obstruction increased in a time-dependent manner, and no significant difference was observed between the two groups. Gross histological examination showed similar tissue reaction to the stents at 1, 2 and 4 weeks, and inflammatory cell infiltrating was higher in the SEMS group at 1 and 2 weeks. However, inflammatory cell infiltration was markedly higher in the PEMS group at 4 and 6 weeks. Food-intake and weight were similar in the two groups. The results of the present study demonstrated that PEMS may serve as a safe alternative treatment strategy for esophageal obstruction. Furthermore, PEMS may inhibit the tumor growth of the esophageal wall through inflammatory infiltration and targeted drug delivery. A tumor model will be required in the future for evaluating the prognosis of patients with advanced esophageal carcinoma.

Macrophage-Targeted Indocyanine Green-Neomannosyl Human Serum Albumin for Intraoperative Sentinel Lymph Node Mapping in Porcine Esophagus

The sentinel lymph node (SLN) concept has been proposed to avoid unnecessary invasive LN dissection in surgery for esophageal cancer. This study evaluated a new macrophage-targeting fluorescent agent, indocyanine green-neomannosyl human serum albumin (ICG:MSA), for SLN mapping using a custom-made intraoperative color and fluorescence-merged imaging system (ICFIS) in porcine esophagus. The LN targeting ability of ICG:MSA, indocyanine green-human serum albumin (ICG:HSA), and ICG was examined invitro using the U937 differentiated monocyte cell line and invivo in a mouse footpad model using fluorescence imaging. SLN identification in rabbit esophagus was then performed using ICG:MSA, ICG:HSA, and ICG. Finally, intraoperative SLN detection was conducted in porcine esophagus after esophagoscopic injection of ICG:MSA. The fluorescence signal of U937 cells treated by ICG:MSA was significantly higher than that of ICG or ICG:HSA (ICG: 1.0 ± 0.37; ICG:HSA: 3.4 ± 0.28, ICG:MSA: 6.8 ± 1.61; ICG to ICG:HSA, p= 0.03; ICG:HSA to ICG:MSA, p= 0.04; ICG to ICG:MSA, p= 0.0009). ICG:MSA was retained in popliteal LNs as long as 3 h, while ICG rapidly diffused through the entire mouse lymphatic system within 5 min. Esophageal SLN was detected within 15 min after injection of either ICG or ICG:MSA, but ICG:MSA provided more distinguishable images of LNss than ICG in rabbit esophagus. The SLN was also successfully detected in all porcine esophagus; the mean number of SLNs identified per esophagus was 1.6 ± 0.55. ICG:MSA has more specific macrophage-targeting properties, which could overcome the limitation of the low SLN retention of ICG, and could provide more precise real-time SLN detection during esophageal cancer surgery.

Three-dimensional photoacoustic endoscopic imaging of the rabbit esophagus.

We report photoacoustic and ultrasonic endoscopic images of two intact rabbit esophagi. To investigate the esophageal lumen structure and microvasculature, we performed in vivo and ex vivo imaging studies using a 3.8-mm diameter photoacoustic endoscope and correlated the images with histology. Several interesting anatomic structures were newly found in both the in vivo and ex vivo images, which demonstrates the potential clinical utility of this endoscopic imaging modality. In the ex vivo imaging experiment, we acquired high-resolution motion-artifact-free three-dimensional photoacoustic images of the vasculatures distributed in the walls of the esophagi and extending to the neighboring mediastinal regions. Blood vessels with apparent diameters as small as 190 μm were resolved. Moreover, by taking advantage of the dual-mode high-resolution photoacoustic and ultrasound endoscopy, we could better identify and characterize the anatomic structures of the esophageal lumen, such as the mucosal and submucosal layers in the esophageal wall, and an esophageal branch of the thoracic aorta. In this paper, we present the first photoacoustic images showing the vasculature of a vertebrate esophagus and discuss the potential clinical applications and future development of photoacoustic endoscopy.

Tracheoplasty with cartilage-engineered esophagus environments

PurposeOur objective was to investigate the feasibility of engineering cartilage on the esophagus layer and outside the esophagus. Moreover, we investigated the feasibility of tracheoplasty with cartilage engineered on the esophagus in rabbits. MethodsChondrocytes were isolated from auricular cartilages. 1. Engineered cartilage formation by histological findings on/into the esophageal layer was compared with that of injectable scaffold and preformed scaffold with chondrocytes. 2. Chondrocytes adhered to gelatin+vicryl mesh™ and b-FGF, were implanted on the outer esophageal surface. Four weeks after seeding, we found that cartilage was implanted in the midposterior portion of the cervical trachea (n=5), and it was retrieved 8weeks after seeding. Results1. A gelatin sponge incorporating β-TCP with vicryl mesh™ showed the best performance for fabricating engineered cartilage on the outer side of the esophagus. 2. Two of 5 rabbits died due to obstructed esophagus. Cartilage engineered outside the esophagus by a composite scaffold as the main material in the gelatin sponge, maintained the airway structure for up to 1month after implantation. Tracheal epithelial regeneration occurred in the internal lumen of this engineered cartilage. ConclusionTracheoplasty with cartilage engineered outside the esophagus may be useful for reconstructing airways.

Comparison of Endoscopic Submuscosal Implantation vs. Surgical Intramuscular Implantation of VX2 Fragments for Establishing a Rabbit Esophageal Tumor Model for Mimicking Human Esophageal Squamous Carcinoma

PurposeThis study was undertaken to establish a rabbit esophageal tumor model for mimicking human esophageal squamous carcinoma (ESC) by endoscopic and surgical implantation of VX2 tumors.MethodsFragments of a VX2 tumour were endoscopically implanted in the submucosal layer of the thoracic esophagus of 32 New Zealand white rabbits, while 34 animals received surgical implantation into the muscular layer. Then, the animals were studied endoscopically and pathologically. The safety and efficiency of the two methods and the pathological features of the animal models were analyzed.ResultsBoth the endoscopic and the surgical method had a relatively high success rate of tumor implantation [93.7% (30/32) vs. 97.1% (33/34)] and tumor growth [86.7% (26/30) vs. 81.8% (27/33)], and the variation in the results was not statistically significant (P>0.05). Compared with those produced by the surgical method, the models produced by the endoscopic method had a higher rate of severe esophageal stricture [61.5% (16/26) vs. 29.6% (8/27)] and of intra-luminal tumor growth [73.1% (19/26) vs. 37.0% (10/27)], and had a lower rate of tumor invasion of adjacent organs [53.8% (14/26) vs. 81.5% (22/27)]; all of these results were statistically significant (P<0.05). However, the difference in the survival time and the rates of tumor regional/distant metastasis [38.5% (10/26) vs. 51.8% (14/27)] between the two methods were not statistically significant (P>0.05).ConclusionThe endoscopic and surgical methods are both safe and effective for establishment of VX2 tumors in the rabbit esophagus. The models produced by the two methods have different pathologic features mimicking that of human ESC. We recommend the models for studies on surgical procedures and minimally invasive treatments.

Poly-ε-caprolactone mesh as a scaffold forin vivotissue engineering in rabbit esophagus

Repair of long-gap esophageal atresia is associated with a high degree of complications. Tissue engineering on a scaffold of a bioresorbable material could be a solution. The aim of the present study was to investigate the in vivo tissue engineering of smooth muscle cells and epithelium on a poly-ε-caprolactone mesh in rabbit esophagus. Twenty female rabbits had a window of 0.6 × 1 cm cut in the abdominal part of the esophagus. The defect was covered with a poly-ε-caprolactone mesh. The rabbits were killed on postoperative day 28-30, and mesh with surrounding esophagus was removed for histological examination. Fifteen rabbits survived the trial period. Six had no complications and had the mesh in situ. They all had ingrowth of epithelial and smooth muscle cells and an almost completely degraded mesh. Nine rabbits developed pseudo-diverticula. It proved possible to engineer both epithelial and smooth muscle cells on the poly-ε-caprolactone mesh in spite of a fast mesh degradation. The latter may be the explanation to the development of pseudo-diverticula; this is a problem that needs attention in future experimental trials.

Local hyperthermia for esophageal cancer in a rabbit tumor model: Magnetic stent hyperthermia versus magnetic fluid hyperthermia

Magnetic-mediated hyperthermia (MMH) is a promising local thermotherapy approach for cancer treatment. The present study investigated the feasibility and effectiveness of MMH in esophageal cancer using a rabbit tumor model. The therapeutic effect of two hyperthermia approaches, magnetic stent hyperthermia (MSH), in which heat is induced by the clinical stent that is placed inside the esophagus, and magnetic fluid hyperthermia (MFH), where magnetic nanoparticles are applied as the agent, was systematically evaluated. A rabbit esophageal tumor model was established by injecting VX2 carcinoma cells into the esophageal submucosa. The esophageal stent was deployed perorally into the tumor segment of the esophagus. For the MFH, magnetic nanoparticles (MNPs) were administered to the rabbits by intratumoral injection. The rabbits were exposed under a benchtop applicator using an alternative magnetic field (AMF) with 300 kHz frequency for the hyperthermia treatment. The results demonstrated that esophageal stents and MNPs had ideal inductive heating properties upon exposure under an AMF of 300 kHz. MSH, using a thermal dose of 46°C with a 10-min treatment time, demonstrated antitumor effects on the rabbit esophageal cancer. However, the rabbit esophageal wall is not heat-resistant. Therefore, a higher temperature or longer treatment time may lead to necrosis of the rabbit esophagus. MFH has a significant antitumor effect by confining the heat within the tumor site without damaging the adjacent normal tissues. The present study indicates that the two hyperthermia procedures have therapeutic effects on esophageal cancer, and that MFH may be more specific than MSH in terms of temperature control during the treatment.

Comparative study of direct and indirect immunofluorescence and of bullous pemphigoid 180 and 230 enzyme-linked immunosorbent assays for diagnosis of bullous pemphigoid

Direct immunofluorescence (DIF), indirect immunofluorescence (IIF), and enzyme-linked immunosorbent assay (ELISA) are used for the laboratory diagnosis of bullous pemphigoid (BP). The diagnostic value of DIF and IIF on rabbit and monkey esophagus or human salt-split skin and commercial ELISAs was assessed. This was a single-center retrospective study where 313 patients with BP were compared with 488 control subjects. DIF was the most sensitive test (90.8%) whereas sensitivities for IIF on rabbit esophagus, IIF on monkey esophagus, IIF on salt-split skin, BP180 ELISA, and BP230 ELISA were 76.0%, 73.2%, 73.3%, 72.0%, and 59.0%, respectively. The sensitivity of the serologic tests was 88.8% altogether. The specificities for DIF, IIF on rabbit esophagus, IIF on monkey esophagus, IIF on salt-split skin, BP180 ELISA, and BP230 ELISA were 98%, 96.5%, 97.1%, 100%, 94.1%, and 99.2%, respectively. The retrospective nature of study was a limitation. Correlation of diagnostic data with clinical manifestations or disease course was not possible. In suspected BP, both serologic tests and DIF have to be performed because of a sensitivity issue. Although the ELISAs had a relatively low sensitivity, the serologic tests altogether almost reached the level of sensitivity of DIF. The specificities of all assays were excellent.

Structurally-motivated characterization of the passive pseudo-elastic response of esophagus and its layers

This paper reports on the implementation of microstructurally-motivated models for material characterization of the passive esophagus and its layers. The principal findings afforded herewith were that the comprehensive model with two- and four-fiber family terms for elastin and collagen fitted more accurately the inflation/extension data of healthy rabbit esophagus than traditional phenomenological models. An analysis of material constant behavior was also performed from which concise, specific models were derived, neither missing essential collagen and elastin structures in mucosa, submucosa, and muscle layers nor being over-parameterized, while providing equally-accurate fits with all the advantages of computational economy and material constant interpretability.