Esophageal Muscle Research Articles

Long-term regeneration and remodeling of the pig esophagus after circumferential resection using a retrievable synthetic scaffold carrying autologous cells

Treatment of esophageal disease can necessitate resection and reconstruction of the esophagus. Current reconstruction approaches are limited to utilization of an autologous conduit such as stomach, small bowel, or colon. A tissue engineered construct providing an alternative for esophageal replacement in circumferential, full thickness resection would have significant clinical applications. In the current study, we demonstrate that regeneration of esophageal tissue is feasible and reproducible in a large animal model using synthetic polyurethane electro-spun grafts seeded with autologous adipose-derived mesenchymal stem cells (aMSCs) and a disposable bioreactor. The scaffolds were not incorporated into the regrown esophageal tissue and were retrieved endoscopically. Animals underwent adipose tissue biopsy to harvest and expand autologous aMSCs for seeding on electro-spun polyurethane conduits in a bioreactor. Anesthetized pigs underwent full thickness circumferential resection of the mid-lower thoracic esophagus followed by implantation of the cell seeded scaffold. Results from these animals showed gradual structural regrowth of endogenous esophageal tissue, including squamous esophageal mucosa, submucosa, and smooth muscle layers with blood vessel formation. Scaffolds carrying autologous adipose-derived mesenchymal stem cells may provide an alternative to the use of a gastro-intestinal conduit for some patients following resection of the esophagus.

Current Status of Peroral Endoscopic Myotomy.

Peroral endoscopic myotomy (POEM) has been established as an optional treatment for achalasia. POEM is an endoluminal procedure that involves dissection of esophageal muscle fibers followed by submucosal tunneling. Inoue first attempted to use POEM for the treatment of achalasia in humans. Expanded indications of POEM include classic indications such as type I, type II, type III achalasia, failed prior treatments, including Botulinum toxin injection, endoscopic balloon dilation, laparoscopic Heller myotomy, and hypertensive motor disorders such as diffuse esophageal spasm, jackhammer esophagus. Contraindications include prior radiation therapy to the esophagus and prior extensive esophageal mucosal resection/ablation involving the POEM field. Most of the complications are minor and self-limited and can be managed conservatively. As POEM emerged as the main treatment for achalasia, various adaptations to tunnel endoscopic surgery have been attempted. Tunnel endoscopic surgery includes POEM, peroral endoscopic tumor resection, gastric peroral endoscopic pyloromyotomy. POEM has been widely accepted as a treatment for all types of achalasia, even for specific cases such as achalasia with failed prior treatments, and hypertensive motor disorders.

Esophageal diverticula (excluding cricopharyngeal diverticula)

Diverticula of the middle and lower third of the esophagus are commonly associated with esophageal motility disorders. The increase of intraluminal pressure leads to an outpouching of the mucosal and submucosal layers through the esophageal muscle coat. These pouches are also called false diverticula, because they only consist of the mucosal and submucosal esophageal layers. In contrast, the more rarely encountered true diverticula that retain the complete esophageal wall are generally associated with periesophageal granulomatous lymph node disease. Treatment of both true and false diverticula is generally indicated in symptomatic patients; however, even state of the art minimally invasive surgery is accompanied by considerable perioperative morbidity and should only be performed in carefully selected patients. This aim of this article is to summarize the available scientific evidence and to provide the reader with an updated guide to best clinical practice in the treatment of esophageal diverticula.

First molecular characterization of Sarcocystis spp. in cattle in Qena Governorate, Upper Egypt.

Cattle are intermediate hosts for several Sarcocystis species with different definitive hosts. The present study, to our knowledge, is the first to determine the prevalence of Sarcocystis infection and morphologically and molecularly identify Sarcocystis species in cattle in Qena Governorate, Upper Egypt. The samples were collected from the heart and oesophagus muscles of 84 slaughtered cattle (76 males and 8 females) aged between 11months and 3years from slaughterhouses in different localities in Qena Governorate, Upper Egypt. The samples were macroscopically and histologically examined, and the molecular identification of the species was performed using 18S ribosomal subunit DNA through PCR and DNA sequencing. Infection was detected in 72 out of 84 animals (85.7%) and was more prevalent in males (76.2%) than in females (9.5). Using light microscopy, the microscopic sarcocysts were observed to be thin-walled. Sequencing and genotyping revealed one isolate that had 99 and 100% identity, respectively, to Sarcocystis cruzi, while another isolate had 95 and 99% identity to Sarcocystis hjorti. The present study is the first to identify Sarcocystis infection in cattle in Qena Governorate, Upper Egypt both morphologically and molecularly. Sarcocystis cruzi and S. hjorti species were isolated from cattle, which is of veterinary importance and indicates that morphologically similar Sarcocystis species are genetically distinct. Additionally, the results show that Sarcocystis species are not host-specific.

Macroscopic and Microscopic Studies on Sarcocystis Infection in Buffaloes - Public Health Alert

Sarcocystosis is one of the important zoonotic parasitic diseases and commonly reported in buffaloes, cattle and pigs. Meat and meat products are the main sources of infection in human beings. The present study aimed to record the prevalence of Sarcocystosis in buffaloes during the time of slaughter. Out of 61 buffaloes slaughter for meat purpose, 38 showed the presence of macroscopic sarcocysts in different organs and they were in creamy colour lying parallel in between the muscle bundles. Distribution of the sarcocysts was noticed in the muscles of oesophagus, diaphragm, heart and base of the tongue. Microscopic examination of the stained impression smears collected from the mixed meat which is ready for sale from the 61 buffaloes, 52 were found positive for microscopic bradyzoites. In conclusion, Sarcocystis is more prevalent in buffaloes and diagnosis of the disease can be done by microscopic examination of the stained slide impression smears from the suspected meat along with the macroscopic examination of the muscles.

Comparative Study on Health Knowledge About Biochemical Effect of Chocolate on Human Health Among Females and Males of Hail University

Studies on adverse effects produced by chocolate warn consumers about harmful effects of consumption of large amounts of chocolate but there are more studies about benefits of chocolate. A few studies have documented allergic reactions with chocolate in children. It was found that Chocolate had harmful effect on heart and caused heart burn due to its content which cause relaxation of oesophageal sphincter muscle and permits entrance of stomach acidic contents to the oesophagus. Recently, chocolate products have attracted the attention of many researchers because of their nutritional and medicinal Properties. There are rarely published studies from Saudia Arabia exploring the awareness about benefits of chocolate consumption. So, the present study was conducted with the objectives of evaluating the knowledge about benefits of chocolate consumption among students of Hail University in Saudia Arabia. A survey was planned to evaluate health knowledge about biochemical effect of chocolate consumption on human health among females and males of Hail University in Saudia Arabia through a previously standardized questionnaire for questions related to their dietary habits, preferences, knowledge about benefits of chocolate consumption, its benefits effect on health, types of chocolates and frequency of consumption along with self-reported height and weight. Results of study reported the importance of increasing information about health benefits of chocolate consumption to correct people's thinking that the chocolate is harmful. Also, the current study compared between females and males of Hail University in their knowledge.

Muscular thickness of lower esophageal sphincter and therapeutic outcomes in achalasia: A prospective study using high-frequency endoscopic ultrasound.

Patients with achalasia typically have thicker lower esophageal sphincter muscles, which can affect the distensibility of the esophagogastric junction. We aimed to assess whether these muscular features, measured using high-frequency endoscopic ultrasound, affect treatment outcomes. Consecutive adult patients with suspected achalasia were enrolled prospectively. They underwent a comprehensive diagnostic workup, including endoscopic ultrasound. The thickness of the lower esophageal sphincter, including the internal circular and outer longitudinal muscles, was measured using a 12-MHz ultrasonic miniprobe. Follow-up was performed at 1month and then at 6-month intervals, after treatment. Treatment response was defined as a reduction in Eckardt score to ≤3 or an improvement in the height of the timed barium esophagogram of ≥50%. Of the 29 patients who received pneumatic dilatation, all but one (96.6%) exhibited a good short-term treatment response. At an average follow-up time of 18.5 (12-55.5)months, patients who had a mid-term recurrence after pneumatic dilatation had a significantly thicker outer longitudinal muscle (1.8 [1.5-1.8] vs 0.9 [0.8-1.7]mm, P=0.036), but not internal circular muscle (2.0 [1.9-2.5] vs 2.1 [1.2-2.7]mm, P=0.874) or total lower esophageal sphincter (3.7 [3.5-4.4] vs 3.6 [2.0-4.1] mm, P=0.362). Patients with an outer longitudinal muscle ≥1.3mm thick had a significantly lower mid-term remission rate than others (36.3% vs 100%, P=0.01). Thickening of the outer longitudinal muscle at the lower esophageal sphincter is associated with poor mid-term treatment outcomes for achalasia patients treated with pneumatic dilatation.

The effect of body position on esophageal reflexes in cats: a possible mechanism of SIDS?

BackgroundIt has been hypothesized that life threatening events are caused by supra-esophageal reflux (SER) of gastric contents which activates laryngeal chemoreflex-stimulated apnea. Placing infants supine decreases the risk of sudden infant death syndrome (SIDS). The aim of this study was to determine whether body position affects esophageal reflexes that control SER.MethodsWe instrumented the pharyngeal and esophageal muscles of decerebrate cats (N=14) to record EMG or manometry, and investigated the effects of body position on the esophago-upper esophageal sphincter (UES) contractile reflex (EUCR), esophago-UES relaxation reflex (EURR), esophagus-stimulated pharyngeal swallow response (EPSR), secondary peristalsis (SP), and pharyngeal swallow (PS). EPSR, EUCR, and SP were activated by balloon distension, EURR by air pulse, and PS by nasopharyngeal water injection. The esophagus was stimulated in the cervical, proximal thoracic, and distal thoracic regions. The threshold stimulus for activation of EUCR, EURR and PS, and the chance of activation of EPSR and SP were quantified.ResultsWe found that only EPSR was significantly more sensitive in the supine vs prone position regardless of the stimulus or the position of the stimulus in the esophagus.ConclusionWe hypothesize that the EPSR may contribute to the protection of infants from SIDS by placement in the supine position.

Clinical, pathological and epidemiological aspects of outbreaks of bluetongue disease in sheep in the central region of Rio Grande do Sul

ABSTRACT: This article describes the clinical, pathological and epidemiological aspects of 17 outbreaks of bluetongue (BT) disease in sheep occurring between December 2014 and July 2015 in the central region of Rio Grande do Sul state (RS), southern Brazil. Affected farms were visited for clinical examination, necropsy, sample collection and epidemiological investigation. The outbreaks were seasonal and occurred during the summer and autumn. A total of 180 sheep (20.4%) out of 884 in 17 small herds were affected. All ages of Texel and mixed breed sheep were affected. However, lambs (younger than one year) had higher morbidity than adult sheep. The most frequent clinical signs were anorexia, lethargy, loss of body condition, facial swelling mainly involving the lips, and greenish seromucous or mucous nasal discharge. Pulmonary lesions characterized by edema were the most prevalent findings; however, erosive and ulcerative lesions in the upper gastrointestinal tract, as well as cardiac, skeletal muscle and esophageal striated muscle necrosis, and hemorrhage in the pulmonary artery were also frequent. The bluetongue virus (BTV) genome was detected by RT-PCR in blood and tissue samples (spleen and lungs) of 21 animals from 17 outbreaks. The virus involved in the outbreak 3 was subsequently isolated and shown to belong to serotype 17, for the first time reported in Brazil. In summary, our data support the BTV genotype 17 as the etiological agent of the outbreaks and indicate that the central region of RS is an area at risk for BT in sheep, a disease previously not recognized in the region.

Robotic Laparoscopic Enucleation of a Giant Lower Esophageal Leiomyoma: Advantages of the Transabdominal Approach

Introduction: Esophageal leiomyomas are the most common benign tumors of esophagus, although rare.1,2 Treatment of esophageal leiomyomas depends on tumor size, location, patient condition, and surgeon experience. For tumors ≤5 cm, transthoracic enucleation is the treatment of choice.3–5 For tumors ≥8–10 cm, termed “giant leiomyomas,” enucleation may still be performed although with an associated higher incidence of both dysphagia after closure of the esophageal muscle defect and reflux if the lower esophageal sphincter is involved.5–8 We present a patient with a giant leiomyoma who underwent robotic laparoscopic enucleation. Case Details: The patient is a 56-year-old female with a body mass index of 32 kg/m2 who presents with 6 months of intermittent chest and epigastric pain and associated dysphagia. Her comorbidities included diabetes, hypertension, and gastroesophageal reflux disease. Esophagogastroduodenoscopy demonstrates external compression of distal esophagus without other intraluminal findings. A subsequent chest computed tomography scan reveals an 8-cm lobular soft tissue mass circumferentially involving the lower esophagus. Endoscopic ultrasound shows a multilobulated hypoechoic mass measuring 8 × 6.2 cm involving 75% of the esophageal circumference. Three distinct lobules were noted as were internal calcifications. Fine-needle aspiration biopsies showed leiomyoma with benign features. Surgical Technique: The patient was positioned supine with both arms extended laterally. The operating table was positioned in steep reverse Trendelenburg and right lateral decubitus. We used four 8 mm robotic trocars, one accessory 11 mm trocar, and a subxyphoid 5 mm skin incision for a Nathanson liver retractor. Upon access to the peritoneum, the gastrohepatic ligament was divided as was the phrenoesophageal membrane. The esophagus was circumferentially dissected from the hiatus. The gastric fundus was mobilized by dividing the short gastric vessels and retrogastric adhesions. The esophagus was enlooped with a Penrose drain to facilitate atraumatic esophageal retraction for further mobilization and mediastinal dissection. The tumor mass was observed and carefully dissected from the esophageal wall and other mediastinal attachments. Once the tumor was fully mobilized from the esophagus, the muscular defect in the esophagus was closed and a contralateral esophageal myotomy was performed. Cruroplasty was performed in a standard manner. Finally, a 270-degree posterior fundoplication was created. The tumor was removed from the abdominal cavity using a nylon-reinforced endobag through a dilated left lateral port site. Results: Our operative time was 132 minutes and the estimated blood loss was 5 mL. The patient was hospitalized overnight and discharged to home on postoperative day 1, on a full liquid diet. She was advanced to a soft diet at 1 week. The patient presented to the outpatient clinic at 2 weeks and 3 months for routine follow-up, and was noted to be doing very well without dysphagia or symptoms of gastroesophageal reflux. Discussion: Our operative technique demonstrates several advantages of the laparoscopic approach for enucleating distal esophageal leiomyomas, even when large. This approach allows direct access to both sides of the esophagus, facilitating the performance of a contralateral myotomy to lower risk of postoperative dysphagia after closure of the esophageal wall muscular defect. Similarly, creation of an antireflux fundoplication is readily performed to minimize risk for postoperative gastroesophageal reflux. In addition, the transabdominal approach for enucleating distal esophageal leiomyoma is more familiar to minimally invasive surgeons and allows a less morbid treatment option to thoracic surgery or esophageal resection. Conclusion: Robotic laparoscopic enucleation of lower esophageal leiomyomas is feasible and safe, even for large tumors. This approach also allows the benefit of concurrent myotomy and antireflux surgery. This technique should be preferred to the usual transthoracic approach when laparoscopic expertise is available. No competing financial interests exist. Runtime of video: 9 mins 20 secs

Esophageal motility disorders: new perspectives from high-resolution manometry and histopathology.

High-resolution manometry (HRM) and peroral endoscopic myotomy (POEM) have contributed significantly to the field of esophageal motility disorders in recent years. The development of HRM has categorized various esophageal motility disorders with a focus on a diverse range of manometric anomalies. Additionally, the Chicago classification criteria is widely used for manometric diagnosis. Moreover, POEM was introduced as a minimally invasive radical therapy for achalasia and shows promise for other spastic esophageal motility disorders as well. POEM has also enabled a transluminal endoscopic approach for determining the histology of the esophageal muscle layer, which is expected to assist in elucidating the etiology of disorders associated with esophageal motility. The purpose of this review is to update the diagnosis, pathology, and treatment of esophageal motility disorders, with a focus on the recent advances in this field.

The signaling of protease-activated receptor-2 activating peptide-induced contraction in cat esophageal smooth muscle cells.

Protease-activated receptors (PARs) are a family of G protein-coupled receptors with a unique activation mechanism involving proteolytic cleavage of the extracellular N-terminal domain of the receptor. PAR2 has a contractile effect on esophageal smooth muscle. We investigate the signaling pathways of the PAR2-activating peptide (PAR2-AP) induced contraction in cat esophageal smooth muscle cells. The length of freshly isolated smooth muscle cells and permeabilized cells from feline esophagus were measured by scanning micrometry, and by confirming molecular basis via western blot analysis. The responses to PAR2-AP were initial and sustained contractions, depending on time. The maximum contraction of the initial phase occurred at 60s. The PAR2-AP-induced contraction was mediated by Gαi1, Gαi3, and Gαq protein activation, leading to phospholipase-c (PLC) and myosin light chain kinase (MLCK) activation. 20kDa myosin light chain (MLC20) was phosphorylated by PAR2-AP. Rho kinase-2 (ROCK-2), an activator of 17kDa C-kinase potentiated Protein phosphatase-1 Inhibitor (CPI-17), was increased by PAR2 receptor activation. In conclusion, PAR2-AP produced an initial contraction mediated by Gαi1, Gαi3, and Gαq protein activation, resulting in PLC and MLCK activation. The sustained contraction by PAR2-AP was mediated by the Rho/Rho kinase-dependent pathway.

Distinct projection targets define subpopulations of mouse brainstem vagal neurons that express the autism‐associated MET receptor tyrosine kinase

AbstractDetailed anatomical tracing and mapping of the viscerotopic organization of the vagal motor nuclei has provided insight into autonomic function in health and disease. To further define specific cellular identities, we paired information based on visceral connectivity with a cell‐type specific marker of a subpopulation of neurons in the dorsal motor nucleus of the vagus (DMV) and nucleus ambiguus (nAmb) that express the autism‐associated MET receptor tyrosine kinase. As gastrointestinal disturbances are common in children with autism spectrum disorder (ASD), we sought to define the relationship between MET‐expressing (MET+) neurons in the DMV and nAmb, and the gastrointestinal tract. Using wholemount tissue staining and clearing, or retrograde tracing in a METEGFP transgenic mouse, we identify three novel subpopulations of EGFP+ vagal brainstem neurons: (a) EGFP+ neurons in the nAmb projecting to the esophagus or laryngeal muscles, (b) EGFP+ neurons in the medial DMV projecting to the stomach, and (b) EGFP+ neurons in the lateral DMV projecting to the cecum and/or proximal colon. Expression of the MET ligand, hepatocyte growth factor (HGF), by tissues innervated by vagal motor neurons during fetal development reveal potential sites of HGF‐MET interaction. Furthermore, similar cellular expression patterns of MET in the brainstem of both the mouse and nonhuman primate suggests that MET expression at these sites is evolutionarily conserved. Together, the data suggest that MET+ neurons in the brainstem vagal motor nuclei are anatomically positioned to regulate distinct portions of the gastrointestinal tract, with implications for the pathophysiology of gastrointestinal comorbidities of ASD.

Serotonin Receptors Mediate Contractile Activity of Rat’s Esophagus in-vivo

Serotonin (5-hydroxytryptamine, 5-HT) is a regulatory and biologically active neurotransmitter and a hormone in the CNS and many organs, including the esophagus. It is known that serotonin as well as acetylcholine stimulates contractile activity of the esophageal muscles. However, role of different serotonin receptors in the 5-HT contractile activity of the esophagus is insufficiently known.

Distinct projection targets define subpopulations of mouse brainstem vagal neurons that express the autism-associated MET receptor tyrosine kinase.

Detailed anatomical tracing and mapping of the viscerotopic organization of the vagal motor nuclei has provided insight into autonomic function in health and disease. To further define specific cellular identities, we paired information based on visceral connectivity with a cell-type specific marker of a subpopulation of neurons in the dorsal motor nucleus of the vagus (DMV) and nucleus ambiguus (nAmb) that express the autism-associated MET receptor tyrosine kinase. As gastrointestinal disturbances are common in children with autism spectrum disorder (ASD), we sought to define the relationship between MET-expressing (MET+) neurons in the DMV and nAmb, and the gastrointestinal tract. Using wholemount tissue staining and clearing, or retrograde tracing in a METEGFP transgenic mouse, we identify three novel subpopulations of EGFP+ vagal brainstem neurons: (a) EGFP+ neurons in the nAmb projecting to the esophagus or laryngeal muscles, (b) EGFP+ neurons in the medial DMV projecting to the stomach, and (b) EGFP+ neurons in the lateral DMV projecting to the cecum and/or proximal colon. Expression of the MET ligand, hepatocyte growth factor (HGF), by tissues innervated by vagal motor neurons during fetal development reveal potential sites of HGF-MET interaction. Furthermore, similar cellular expression patterns of MET in the brainstem of both the mouse and nonhuman primate suggests that MET expression at these sites is evolutionarily conserved. Together, the data suggest that MET+ neurons in the brainstem vagal motor nuclei are anatomically positioned to regulate distinct portions of the gastrointestinal tract, with implications for the pathophysiology of gastrointestinal comorbidities of ASD.

Non-functioning parathyroid carcinoma: a case report

BackgroundNon-functioning parathyroid carcinoma is a rare disease that is difficult to distinguish from other diseases based on the lack of hyperparathyroidism. This is a report of non-functioning parathyroid carcinoma diagnosed by reverse transcription polymerase chain reaction (RT-PCR) targeting parathyroid hormone (PTH) messenger RNA.Case PresentationThe patient is a 67-year-old male who visited our hospital for the chief complaint of hoarseness. A 5-cm mass was observed in the right lobe of the thyroid gland, and poorly differentiated thyroid carcinoma was suspected according to the fine-needle biopsy results. The laboratory data for thyroid functions, thyroglobulin, anti-thyroglobulin antibodies, calcium, phosphorus, and intact-PTH were all within the normal range. Right recurrent nerve paralysis was observed preoperatively. The patient was diagnosed with poorly differentiated thyroid carcinoma, and total thyroidectomy and central node dissection with partial resection of the right recurrent nerve and esophageal muscle were performed. The pathological findings revealed atypical cells containing clear cells in solid and alveolar structures with broad fibrosis. Mitosis, focal coagulative necrosis, and vascular and capsular invasions were observed. A slightly positive PTH immunohistochemical stain was noted, whereas the RT-PCR results were positive. We finally diagnosed this tumor as non-functioning PTC. No distant metastasis occurred, and the patient is still alive.ConclusionsThis is a report of a patient with non-functioning parathyroid carcinoma, which is clinically very rare. We diagnosed this tumor as non-functioning parathyroid carcinoma using RT-PCR for PTH mRNA.

Characterization and mechanisms of the supragastric belch in the cat.

A response in which a belch occurs without gastric involvement, i.e., the supragastric belch (SGB), has been characterized in humans. The aims of this study were to determine whether animals have an SGB and, if so, to determine its mechanisms. Studies were conducted in decerebrate cats (n = 30) with electromyographic electrodes on hyoid, pharyngeal, esophageal, and diaphragm muscles. The effects of distending different regions of the esophagus in different manners using a balloon were quantified to determine the most appropriate stimulus for activating the cat SGB. The effects of esophageal perfusion of lidocaine (n = 3), vagus nerve transection (n = 3), or esophageal acidification (n = 5) on activation of the SGB were determined. Rapid large distensions of the thoracic esophagus best activated responses similar to the human SGB, i.e., rapid inhalation followed by a belch. The rapid inhalation was associated with activation of hiatal fibers and the belch with activation of dome fibers of the diaphragm. The rapid inhalation response was independent of the belch response. Lidocaine perfusion of the esophagus blocked the belch response without blocking the rapid inhalation, HCl perfusion sensitized the esophagus to activation of both the rapid inhalation and the belch response, and vagotomy blocked both responses. We conclude that the cat has an SGB that is composed of two independent reflex responses, i.e., rapid inhalation and belch, that are mediated by the vagus nerves and tension/mucosal receptors of the esophagus and sensitized by esophageal acid exposure. We hypothesize that the SGB is a learned voluntarily activated reflex response.NEW & NOTEWORTHY Rapid strong distension of the thoracic esophagus activates rapid inhalation followed by a belch, which is the sequence of responses that compose the human supragastric belch (SGB). The rapid inhalation and belch phases of the cat SGB are activated by hiatal and dome fibers of the diaphragm, respectively, and are mediated by the vagus nerves and tension/mucosal receptors of the esophagus and sensitized by esophageal acid exposure. There are many similarities between the cat and human SGB.

Full-thickness oesophageal regeneration in pig using a polyurethane mucosal cell seeded graft

Malignant oesophageal pathology typically requires resection of a portion of oesophagus. The aim of this study was to investigate attachment and growth of swine oesophageal mucosal cells on electrospun synthetic nanofibre matrices of varying chemistries and to determine whether a mucosal-seeded graft, in a swine animal model, could induce regeneration. Swine mucosal oesophageal cells were isolated and seeded them onto five different matrix materials. Matrix samples were cultured for up to 14days, after which matrices were analysed for cell attachment. Attachment varied for each of the matrix materials tested, with the most rigid showing the lowest levels of attachment. Importantly, sections of these matrices illustrated that multiple layers of mucosal cells formed, mimicking endogenous oesophageal structure. A tdTomato reporter line (mucosaltdt cells) was created to enable cell tracking. As polyurethane matrix was found optimal through in vitro testing, a graft was prepared using mucosaltdt cells, along with an unseeded control, and implanted into swine for determination of oesophageal regeneration. Mucosal seeded polyurethane grafts initiated full thickness regeneration of the oesophagus, including epithelial, submucosal, and skeletal muscle layers which were highly vascularized. Interestingly, an unseeded graft showed similar regeneration, indicating that the role of cells in the process of oesophageal regeneration is still unclear. The electrospun polyurethane matrix does appear suitable for multilayered cellular attachment and growth of oesophageal mucosal cells, and implantation of polyurethane grafts initiated full thickness regeneration of the oesophagus, indicating potential for oesophageal reconstruction in humans. Copyright © 2016 John Wiley & Sons, Ltd.

Osr1 functions downstream of Hedgehog pathway to regulate foregut development

During early fetal development, paracrine Hedgehog (HH) ligands secreted from the foregut epithelium activate Gli transcription factors in the surrounding mesenchyme to coordinate formation of the respiratory system, digestive track and the cardiovascular network. Although disruptions to this process can lead to devastating congenital defects, the underlying mechanisms and downstream targets, are poorly understood. We show that the zinc finger transcription factor Osr1 is a novel HH target as Osr1 expression in the foregut mesenchyme depends on HH signaling and the effector of HH pathway Gli3 binds to a conserved genomic loci near Osr1 promoter region. Molecular analysis of mouse germline Osr1 mutants reveals multiple functions of Osr1 during foregut development. Osr1 mutants exhibit fewer lung progenitors in the ventral foregut. Osr is then required for the proper branching of the primary lung buds, with mutants exhibiting miss-located lung lobes. Finally, Osr1 is essential for proper mesenchymal differentiation including pulmonary arteries, esophageal and tracheal smooth muscle as well as tracheal cartilage rings. Tissue specific conditional knockouts in combination with lineage tracing indicate that Osr1 is required cell autonomously in the foregut mesenchyme. We conclude that Osr1 is a novel downstream target of HH pathway, required for lung specification, branching morphogenesis and foregut mesenchymal differentiation.

Esophagogastric junction in systemic sclerosis: A study with the functional lumen imaging probe.

Fibrosis and atrophy of esophageal smooth muscle cells cause gastro-esophageal reflux and dysphagia in most patients with systemic sclerosis (SSc). Recent studies indicate that distensibility of the esophagogastric junction (EGJ), assessed with the Functional Lumen Imaging Probe (FLIP) may be a more sensitive and accurate measure of sphincter function than manometry. We aim to describe and compare distension parameters of the EGJ in a well-characterized group of patients with SSc. Twelve patients with SSc reporting reflux or dysphagia (11 women, median age 53 [range 35-72], duration of disease: 1-20years) were investigated using distensibility testing of the EGJ. Patients were compared with 11 healthy volunteers (HV) (10 women, median age 53 [range 40-68]). The pressure and minimum diameter along the EGJ during ramp distension were used for distensibility analysis. Patients with SSc had significantly lower EGJ yield pressure (median: 4.0mmHg [Inter Quartile Range (IQR): 2.8-7.7]) than HV (median: 6.2mmHg [IQR: 9.4-26]) (P=.007). Likewise, the pressure-strain elastic modulus was lower in SSc patients (median 1.73 kPa [IQR: 1.16-2.15]) than in HV (median 2.41 kPa [IQR: 1.85-2.67]) (P=.03), indicating the reduced resistance to distension in SSc patient. Patients with SSc and symptoms of reflux and dysphagia have significantly reduced resistance to distension of the EGJ.