Pyloric Research Articles

CNS sites controlling the gastric pyloric sphincter: Neuroanatomical and functional study in the rat.

The pyloric sphincter receives parasympathetic vagal innervation from the dorsal motor nucleus of the vagus (DMV). However, little is known about its higher-order neurons and the nuclei that engage the DMV neurons controlling the pylorus. The purpose of the present study was twofold. First, to identify neuroanatomical connections between higher-order neurons and the DMV. This was carried out by using the transneuronal pseudorabies virus PRV-152 injected into rat pylorus torus and examining the brains of these animals for PRV labeling. Second, to identify the specific sites within the DMV that functionally control the motility and tone of the pyloric sphincter. For these studies, experiments were performed to assess the effect of DMV stimulation on pylorus activity in urethane-anesthetized male rats. A strain gauge force transducer was sutured onto the pyloric tonus to monitor tone and motility. L-glutamate (500pmol/30 nL) was microinjected unilaterally into the rostral and caudal areas of the DMV. Data from the first study indicated that neurons labeled with PRV occurred in the DMV, hindbrain raphe nuclei, midbrain Edinger-Westphal nucleus, ventral tegmental area, lateral habenula, and arcuate nucleus. Data from the second study indicated that microinjected L-glutamate into the rostral DMV results in contraction of the pylorus blocked by intravenously administered atropine and ipsilateral vagotomy. L-glutamate injected into the caudal DMV relaxed the pylorus. This response was abolished by ipsilateral vagotomy but not by intravenously administered atropine or L-NG-nitroarginine methyl ester (L-NAME). These findings identify the anatomical and functional brain neurocircuitry involved in controlling the pyloric sphincter. Our results also show that site-specific stimulation of the DMV can differentially influence the activity of the pyloric sphincter by separate vagal nerve pathways.

ОСОБЕННОСТИ НАРУШЕНИЙ МОТОРНОЙ ФУНКЦИИ ЖЕЛУДКА ПРИ ДИСРЕГЕНЕРАТОРНЫХ ИЗМЕНЕНИЯХ ЕГО СЛИЗИСТОЙ ОБОЛОЧКИ

The study was conducted at the Department and Clinic of Hospital Therapy of the Military Medical Academy. CM. Kirov. The work studied the relationship of motor disorders of the stomach with morphological changes in the gastric mucosa in 90 patients with chronic atrophic gastritis and 93 patients with chronic non-atrophic gastritis aged 20 to 73 years (the average age of patients was 52.7+1.7 years and 48.5+ 3.6 respectively). Motor disorders were characteristic of 87% of patients with chronic atrophic gastritis and 79.6% of patients with chronic non-atrophic gastritis. It was found that in patients with chronic atrophic gastritis significantly more often (p<0.01) than in patients with chronic non-atrophic gastritis, there was an insufficiency of the lower esophageal sphincter. At the same time, insufficiency of the pylorus in comparison with its spasm was significantly more often (p<0.01) detected in chronic atrophic gastritis. Duodenogastric reflux in combination with insufficiency of the lower esophageal sphincter in patients with chronic atrophic gastritis significantly more often (p<0.01) atrophy was observed in the body and antrum of the stomach. When atrophy was localized only in the antrum, pyloric insufficiency was observed significantly more often than spasm (p<0.01). Duodenogastric reflux in combination with insufficiency of lower esophageal sphincter in patients with chronic atrophic gastritis significantly more often (p<0,01) atrophy in the body and antral part of the stomach was observed. Thus, the relationship between insufficiency of the lower esophageal and pyloric sphincters with a diffuse atrophic process has been established.

Research progress in anti-reflux reconstructions and mechanism after proximal gastrectomy

The electrophysiological activity of the gastrointestinal tract and the mechanical anti-reflux structure of the gastroesophageal junction are the basis of the anti-reflux function of the stomach. Proximal gastrectomy destroys the mechanical structure and normal electrophysiological channels of the anti-reflux. Therefore, the residual gastric function is disordered. Moreover, gastroesophageal reflux is one of the most serious complications. The emergence of various types of anti-reflux surgery through the mechanism of reconstructing mechanical anti-reflux barrier and establishing buffer zone, and the preservation of, the pacing area and vagus nerve of the stomach, the continuity of the jejunal bowel, the original gastroenteric electrophysiological activity of the gastrointestinal tract, and the physiological function of the pyloric sphincter, are all important measures for gastric conservative operations. There are many types of reconstructive approaches after proximal gastrectomy. The design based on the anti-reflux mechanism and the functional reconstruction of mechanical barrier, and the protection of gastrointestinal electrophysiological activities are important considerations for the selected of reconstructive approaches after proximal gastrectomy. In clinical practice, we should consider the principle of individualization and the safety of radical resection of tumor to select a rational reconstructive approaches after proximal gastrectomy.

Localization of relaxin-like gonad-stimulating peptide expression in starfish reveals the gonoducts as a source for its role as a regulator of spawning.

Oocyte maturation and gamete release (spawning) in starfish are triggered by relaxin-like gonad-stimulating peptide (RGP), a neuropeptide that was first isolated from the radial nerve cords of these animals. Hitherto, it has generally been assumed that the radial nerve cords are the source of RGP that triggers spawning physiologically. To investigate other sources of RGP, here we report the first comprehensive anatomical analysis of its expression, using both in situ hybridization and immunohistochemistry to map RGP precursor transcripts and RGP, respectively, in the starfish Asterias rubens. Cells expressing RGP precursor transcripts were revealed in the ectoneural epithelium of the radial nerve cords and circumoral nerve ring, arm tips, tube feet, cardiac stomach, pyloric stomach, and, most notably, gonoducts. Using specific antibodies to A. rubens RGP, immunostaining was revealed in cells and/or fibers in the ectoneural region of the radial nerve cords and circumoral nerve ring, tube feet, terminal tentacle and other arm tip-associated structures, body wall, peristomial membrane, esophagus, cardiac stomach, pyloric stomach, pyloric caeca, and gonoducts. Our discovery that RGP is expressed in the gonoducts of A. rubens proximal to its gonadotropic site of action in the gonads is important because it provides a new perspective on how RGP may act as a gonadotropin in starfish. Thus, we hypothesize that it is the release of RGP from the gonoducts that triggers gamete maturation and spawning in starfish, while RGP produced in other parts of the body may regulate other physiological/behavioral processes.

Topographical distribution and morphology of SP-IR axons in the antrum, pylorus, and duodenum of mice.

Substance-P (SP) is a commonly used marker of nociceptive afferent axons, and it plays an important role in a variety of physiological functions including the regulation of motility, gut secretion, and vascular flow. Previously, we found that SP-immunoreactive (SP-IR) axons densely innervated the pyloric antrum of the flat-mount of the mouse whole stomach muscular layer. However, the regional distribution and morphology of SP-IR axons in the submucosa and mucosa were not well documented. In this study, the mouse antrum-pylorus-duodenum (APD) were transversely and longitudinally sectioned. A Zeiss M2 imager was used to scan the serial sections of each APD (each section montage consisted of 50-100 all-in-focus maximal projection images). To determine the detailed structures of SP-IR axons and terminals, we used the confocal microscope to scan the regions of interest. We found that 1) SP-IR axons innervated the muscular, submucosal, and mucosal layers. 2) In the muscular layer, SP-IR varicose axons densely innervated the muscles and formed varicose terminals which encircled myenteric neurons. 3) In the submucosa, SP-IR axons innervated blood vessels and submucosal ganglia and formed a network in Brunner's glands. 4) In the mucosa, SP-IR axons innervated the muscularis mucosae. Some SP-IR axons entered the lamina propria. 5) The muscular layer of the antrum and duodenum showed a higher SP-IR axon density than the pyloric sphincter. 6) SP-IR axons were from extrinsic and intrinsic origins. This work provided a comprehensive view of the distribution and morphology of SP-IR axons in the APD at single cell/axon/varicosity scale. This data will be used to create a 3D scaffold of the SP-IR axon innervation of the APD.

StomachSim: An in-silico simulator of gastric biomechanics with application to pyloroplasty

Aim: We have developed StomachSim, an in-silico simulator that is designed to simulate the biomechanics and fluid mechanics of a wide range of gastric conditions as well as gastric surgical procedures. Here we demonstrate its use in quantifying the effects of motility disorders and pyloroplasty on the hydrolysis and emptying of a liquid meal inside the stomach. Methods: A physiologically realistic model of the stomach, including the antral motility, is synthesized based on in-vivo imaging, and the mixing and gastric emptying are simulated using computational fluid dynamics (CFD). The enzymatic biochemistry for protein hydrolysis is also implemented by incorporating the secretion of a proteolytic enzyme from the proximal stomach walls and the subsequent enzymatic reaction with the protein dissolved in the liquid meal. Using this model, we measured the effect of stomach motility and the diameter of the pyloric orifice on the retropulsive and pyloric jets, the rate of hydrolysis in different regions, and the emptying of gastric contents. Results: This study presents a proof-of-concept for the application of StomachSim in gastric disorders and surgeries. The emptying rate of our model for the healthy case agreed with the in-vivo measurements of similar caloric density liquid meals. A stomach with a 50% lower motility amplitude had a 35% lower net emptying rate and a 41% lower emptying rate of the hydrolyzed protein. Furthermore, the emptying rate showed a non-linear variation with respect to the motility of the stomach. For a simulated pyloroplasty procedure where the pyloric orifice diameter is doubled and the orifice stays open permanently, the emptying rate of the lower motility case doubled over its original value. Conclusion: StomachSim offers a novel and potentially effective modality for examining the effect of gastric conditions and gastric surgical procedures on gastric function. Our simulations show that gastroparesis and pyloroplasty not only affect the emptying rate but also alter the mixing of contents thereby changing the rate of hydrolysis. The model helped quantify the changes in the flow of contents in the antro-duodenal region for varying degrees of gastroparesis and pyloroplasty. The authors acknowledge support from NSF award CBET 2019405 and NIH award 1R21GM139073-01. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

EndoFLIP assessment of pyloric sphincter in children: a single-center experience.

Gastrointestinal complaints are common in children with neurodisabilities, vomiting, retching and poor feed tolerance are frequently reported. Endolumenal functional lumen imaging probe (EndoFLIP) is used to assess compliance and distensibility of the pylorus and can predict response to Botulinum Toxin in adult with gastroparesis. We aimed to review pyloric muscle measurements using EndoFLIP in children with neuromuscular disabilities and significant foregut symptoms and to assess the clinical response to intrapyloric Botulinum Toxin. Retrospective review of clinical notes of all children who underwent pyloric EndoFLIP assessment in Evelina London Children's Hospital from March 2019 to January 2022. EndoFLIP catheter was inserted at the time of endoscopy via existing gastrostomy tract. A total of 335 measurement from 12 children were obtained, mean age 10.7±4.2 years. Measurements (pre and post Botox) were obtained with 20, 30 and 40 mL balloon volume. Diameter (6.5, 6.6), (7.8, 9.4) and (10.1, 11.2), compliance (92.3, 147.9), (89.7, 142.9) and (77, 85.4) mm3/mmHg, distensibility (2.6, 3.8), (2.7, 4.4) and (2.1, 3) mm2/mmHg and balloon pressure was (13.6, 9.6), (20.9, 16.2) and (42.3, 35) mmHg. Eleven children reported clinical symptom improvement after Botulinum Toxin injection. Balloon pressure was positively correlated to diameter (r=0.63, P<0.001). Children with neurodisabilities who present with symptoms suggestive of poor gastric emptying do have a low pyloric distensibility and poor compliance. EndoFLIP via existing gastrostomy tract is quick and easy to perform. Intrapyloric Botulinum Toxin appears to be safe and effective in this cohort of children leading to clinical and measurements improvement.

Enzymatic, skeletal, and histological ontogeny of shi drum (Umbrina cirrosa) larvae under intensive culture conditions

This study was conducted to investigate the structural and ontogenetic development of the skeletal system and digestive tract histologically and enzymatically in larvae of shi drum (U. cirrosa) under intensive rearing conditions until 40days after hatching (DAH). Among digestive enzymes, amylase was detected at 0.89 ± 0.12mUmg protein-1 on the first hatching day. The specific activities of trypsin and lipase were detected simultaneously with mouth opening on 3 DAH with 28.47 ± 3.52 and 2.8 ± 0.32mUmg protein-1, respectively. In addition, pepsin was found for the first time at 0.88 ± 0.21mUmg protein-1 on 15 DAH in association with stomach formation and increased sharply up to 40 DAH. In the structural development of the skeletal system, the development of the caudal fin in larvae was morphologically associated with the flexion of the notochord. It was observed that the shape of the fin and spine, which reached 40 DAH, became similar to the adult shape. Histologically, 3 DAH, the mouth and anus were opened. The formation of the primitive stomach was observed at the end of the seventh day-the pyloric sphincter formed between 13 and 18days. A functional stomach was seen on the 15th DAH. Therefore, U. cirrosa is believed to have critical aquaculture potential that can be cultured under intensive conditions. The developmental profile of skeletal, enzymatic, and histological ontogeny observed in U. cirrosa is similar to that described for other sciaenid species.

Mfge8 is expressed by pericytes in gastric antrum submucosa from patients with obesity.

The main function of the stomach is to digest ingested food. Gastric antrum muscular contractions mix ingested food with digestive enzymes and stomach acid and propel the chyme through the pyloric sphincter at a rate in which the small intestine can process the chyme for optimal nutrient absorption. Mfge8 binding to α8β1 integrins helps regulate gastric emptying by reducing the force of antral smooth muscle contractions. The source of Mfge8 within gastric muscles is unclear. Since Mfge8 is a secreted protein, Mfge8 could be delivered via the circulation, or be locally secreted by cells within the muscle layers. In this study, we identify a source of Mfge8 within human gastric antrum muscles using spatial transcriptomic analysis. We show that Mfge8 is expressed in subpopulations of Mef2c+ perivascular cells within the submucosa layer of the gastric antrum. Mef2c is expressed in subpopulations of NG2+ and PDGFRB+ pericytes. Mfge8 is expressed in NG2+/Mef2c+ pericytes, but not in NG2+/Mef2c-, PDGFRB+/Mef2c-, or PDGFRB+/Mef2c+ pericytes. Mfge8 is absent from CD34+ endothelial cells but is expressed in a small population of perivascular ACTA2+ cells. We also show that α8 integrin is not expressed by interstitial cells of Cajal (ICC), supporting the findings that Mfge8 attenuates gastric antrum smooth muscle contractions by binding to α8β1 integrins on enteric smooth muscle cells. These findings suggest a novel, supplementary mechanism of regulation of gastric antrum motility by cellular regulators of capillary blood flow, in addition to the regulation of gastric antrum motility by the enteric nervous system and the SMC, ICC, and PDGFRα+ cell (SIP) syncytium.

Functional and anatomical gastric regions and their relations to motility control.

The common occurrence of gastric disorders, the accelerating emphasis on the role of the gut-brain axis, and development of realistic, predictive models of gastric function, all place emphasis on increasing understanding of the stomach and its control. However, the ways that regions of the stomach have been described anatomically, physiologically, and histologically do not align well. Mammalian single compartment stomachs can be considered as having four anatomical regions fundus, corpus, antrum, and pyloric sphincter. Functional regions are the proximal stomach, primarily concerned with adjusting gastric volume, the distal stomach, primarily involved in churning and propelling the content, and the pyloric sphincter that regulates passage of chyme into the duodenum. The proximal stomach extends from the dome of the fundus to a circumferential band where propulsive waves commence (slow waves of the pacemaker region), and the distal stomach consists of the pacemaker region and the more distal regions that are traversed by waves of excitation, that travel as far as the pyloric sphincter. Thus, the proximal stomach includes the fundus and different extents of the corpus, whereas the distal stomach consists of the remainder of the corpus and the antrum. The distributions of aglandular regions and of specialized glands, such as oxyntic glands, differ vastly between species and, across species, have little or no relation to anatomical or functional regions. It is hoped that this review helps to clarify nomenclature that defines gastric regions that will provide an improved basis for drawing conclusions for different investigations of the stomach.

The Role of Kunjal Kriya in Upper Respiratory Tract Disorders w.s.r. to Bronchial Asthma

Bronchial Asthma is one of the distressing ailments of the present time and is notable for its episodic and chronic course which influences the entire human race &amp; it is a sickness of the human respiratory framework where the aviation routes get restricted. This limiting causes side effects, for example, wheezing, windedness, chest snugness, and hacking, which answer bronchodilators. Kunjal Kriya is the most straightforward technique among all types of Dhouti. The cleaning up of the whole track beginning from the mouth to the stomach related way toward the start of the small digestion tracts, that is mouth, and throat. Asthmatics might notice huge globs of mucus in the ousted water; the solid reflex from the pyloric valve will release bodily fluid discharges from the bronchial cylinders. Kunjal Kriya is suggested as a protected technique during an assault, as the strong activity of the vagus nerve delivers fit in the respiratory framework. Every day Kunjal Kriya is suggested for asthmatics under the arrangement of prepared instructors. In this review study, the author focused to rule out the mode of action of Kunjal Kriya in Upper Respiratory Tract Infections w.s.r. to Bronchial Asthma.

Ultrasound of Hypertrophic Pylorian Stenosis: About A Case and Literature Review

Hypertrophic pyloric stenosis is an obstruction of the lumen of the pylorus by muscular hypertrophy of the pyloric sphincter, more common in boys. We report the case of a male newborn at 13 weeks of life, born at term with a birth weight estimated at 2900 grams without any particular history. Clinically he had an increased frequency of sputum and postprandial jet vomiting, dehydration and weight loss. Abdominal ultrasound found a lengthening of the pyloric canal measuring 22 mm in length associated with a thickening of the muscularis of the pyloric region measuring 4 mm forming a "pyloric olive" 13 mm in diameter. There was also significant gastric stasis upstream of the hypertrophic stenosis. The examination was carried out at the reference health center of commune III in the district of Bamako. The objective of this work was to provide our experience on the ultrasound semiology of hypertrophic pyloric stenosis with a review of the literature.

Histology of the Hindgut of Solitary Locusta (Orthoptera: Acrididae )

Hindgut of Solitary has been into its three regions: ileum, colon, and rectum, and each region was studied morphologically, histologically and functionally. Ileal structure has been investigated throughout its length from pyloric valve ( the border between the midgut and the hindgut) to its end ,which marks the border between the ileum and the colon. The 6 layers apical wall of circular muscles were fully described with the longitudinal muscles. The 12 inner ileal epithelial folds consist of columnar cells with microvilli, which suggest that the ileum is involved with nutrition absorption. The 12 ileal folds are close to the inner wall of the proximal circular muscles, but in another locust are projecting inward the lumen centre. But in both structures the subintimal space is clear. The 12 ileal folds become reduced to the smallest in size and less in count. Their reduction continues to the lowest size till they become traces at the end of the ileum. The colon structure shows that the diameter becomes small and the tissue between the layer circular muscles and the 4 thick folds of the colon. The area between the circulat muscles and the inner columnar cells is full of thick longitudinal muscles. The rectal structure shows the 6 large rectal papillae and small rectal pads which grow to replace the rectal papillae. Rectal papillae are involved with mineral and water re-absorption. At the middle rectal area structure shows 6 areas occupied by rectal pads and 6 reduced between rectal areas, which have columnar epithelial cells. Their function is to facilitate the faeces evacuation by their contraction and expanding as they do as articulation. Rectal pads show different type of cells such principal cells, basic cells and junctional cells. Also intrapapillar lumen, tracheae, and also the circular and longitudinal muscles are very clear .

Endoscopic Intrapyloric Botulinum Toxin Injection with Pyloric Balloon Dilation for Symptoms of Delayed Gastric Emptying after Distal Esophagectomy for Esophageal Cancer: A 10-Year Experience.

Patients with esophageal cancer undergoing esophagectomy have an improved survival over time, however adverse events associated with the use of a gastric conduit are increasingly being reported. Delayed gastric emptying (DGE) is an esophagectomy-related complication which can decreased quality of life by causing debilitating gastrointestinal symptoms and malnutrition. The aim of our study was to evaluate the effect of endoscopic intrapyloric botulinum (BT) injection in combination with pyloric balloon dilation in patients with DGE following distal esophagectomy at our tertiary cancer center. Patients with a prior history of distal esophagectomy who had also undergone endoscopic BT injection with pyloric balloon dilation by a single endoscopist between 2007 and 2017 were included in the study. One hundred units of BT were injected endoscopically into the pylorus in four quadrants using an injection needle. Following BT injection, a standard through-the-scope balloon was passed to the pylorus and inflated to a maximum diameter of 12−20 mm. For patients who underwent repeat procedures, the symptomatic outcomes were assessed and documented by the endoscopist; for the other patients, the electronic medical records were reviewed. A total of 21 patients undergoing 44 endoscopic intrapyloric botox injections combined with balloon dilatations were identified. The patients underwent the procedures at a median of 22 months (range, 1−108 months) after esophagectomy. The procedures were performed only once in 43% of the patients; 43% patients underwent the procedure twice, while 14% had it multiple times (>2). Overall, intrapyloric BT injection coupled with balloon dilation was a safe procedure, without any major immediate or delayed (1 month) procedure-related adverse events. Eighteen patients (85%) reported a significant overall improvement in symptoms from the initial presentation. One patient (5%) showed no improvement, whereas in two (10%) patients responses were not available. In our particular cohort of patients, the interventions of endoscopic intrapyloric BT injection with pyloric balloon dilation proved to be very beneficial, leading to significant symptomatic improvement. The balloon dilation after BT injection might have resulted in better diffusion of the BT into the pyloric sphincter complex, possibly increasing its therapeutic effects. Further prospective studies are needed to validate these results.

Ultrasonographic Imaging of the Fetal Pyloric Sphincter.

In this study, we hypothesized that the pyloric sphincter can be directly visualized by ultrasonography in the prenatal period. This study was designed as a cross-section. Single, healthy pregnancies between 18 and 22 weeks of gestation who applied to the Perinatology outpatient clinic for second-level ultrasonography were included in the study. In addition to the demographic characteristics of the participants, fetal pyloric mucosa, fetal pyloric sphincter length, and fetal pyloric sphincter thickness were measured by ultrasonography. Intrarater variability was calculated. A total of 93 eligible patients were evaluated in the study. The mean age of the participants was 27.25 ± 6.23, and the gestational age was 21.18 ± 0.98. Pylorus imaging and measurements were possible in all fetuses that were in the optimal position. Mean pyloric sphincter length (mm) was 5.32 ± 0.93, pyloric sphincter thickness (mm) was 2.13 ± 0.44, and sphincter muscle thickness (mm) was 1.05 ± 0.24. The pyloric sphincter can be easily visualized on a second-trimester ultrasound scan when the appropriate technique is used. This may make an additional contribution to the diagnosis of fetal gastrointestinal tract pathologies.

Microanatomy of the digestive tract and accessory organs of the Japanese flathead (Inegocia japonica Cuvier, 1829) (Scorpaeniformes, Platycephalidae)

AbstractThe Japanese flathead, Inegocia japonica Cuvier, 1829 is a commercially important fish in small‐scale coastal fisheries in Thailand; however, an explanation of its digestive biology is missing. This study describes the digestive tract and accessory organs of I. japonica, using morphological and histological methods. The fish (10 individual fish, 24.5 ± 0.98 cm in total length) were obtained from Libong Island, Thailand. Integrated morphological and histological data showed that the digestive tract was composed of oesophagus, stomach, pyloric caeca and intestine, with accessory organs. All digestive tracts consisted of four layers, including mucosa, submucosa, muscularis and serosa. Two stomach regions were identified (cardiac and pyloric stomachs). Several clusters of gastric glands were identified in the cardiac stomach. Each gland was a unicellular structure. The apical surface of this gland contained the vacuolar cell. The intestine was lined with a simple columnar structure with goblet cells that was similar to pyloric caecum. Goblet cells were rare in the anterior intestine, in contrast to the posterior intestine where goblet cells were abundant. The numerous of hepatocyte was mostly observed in the liver, whereas an exocrine acinar cell of pancreas was also identified. The results of our observations provided the first information of the digestive tract of I. japonica and can be applied to advanced study, such as physiology and histopathology.

S1566 Evaluation of the Pharmacokinetics of PGN-OB1 Following Oral Administration of an Oral Biotherapeutics Delivery System (OBDS) in Yucatan Swine

Introduction: Biologics/peptides/nucleic acids are highly effective drugs; however, oral delivery of these therapeutics has proved to be difficult due to the harsh conditions of the upper gastrointestinal tract (GIT) and the poor absorption rate in the small intestinal mucosa. We aimed to develop an oral biotherapeutic delivery system (OBDS) that protects these biomolecules from degradation in the upper GIT and increases oral bioavailability via needless injection in the submucosal space of the small intestine. We describe the development of models to assess the functional capability of the OBDS capsule. A Yucatan minipig model was chosen to better represent the pharmacokinetic properties of submucosal injection in humans and evaluate the injection efficiency of OBDS in vivo. Methods: Due to prolonged and variable gastric residence times in the swine model, the semi-autonomous OBDS capsules containing a variant of adalimumab (PGN-001), PGN-OB1, were administrated by intraduodenal endoscopic placement (ID) and released into the proximal small intestines of the female Yucatan swine. Blood samples post-ID dosing were collected to evaluate the injection efficiency of the OBDS compared with the IV control group. Results: All OBDS capsules were successfully advanced through the pyloric sphincter via endoscopic placement, without early deployment, and released in the proximal duodenum to naturally transit and deploy in vivo. Out of 13 animals dosed, 8 animals showed detectable drug levels (Figure), and an oral bioavailability average of 22% or 25% (range from 7-55%) excluding an animal showing a late deployment at 72hr post-dose. The variability in the swine model is believed to be due to physiologic variability that may not directly translate to humans including variability in small intestinal transit time, and more frequent and larger, gas and fluid pockets in the swine. Conclusion: Here we have provided proof-of-concept of a semi-autonomous OBDS device that can achieve as high as 55% bioavailability of a variant of adalimumab that is a magnitude higher than current oral protein or peptide delivery technology in the market and at levels much closer to the subcutaneous route of administration estimated in human trials. The OBDS capsules could potentially provide a better alternative for the non-invasive route of administration with better patient compliance.Figure 1.: Plasma concentration of PGN-001 treated with ID and IV over time

S3554 Pylorus-Directed Therapy for Gastroparesis Using EsoFLIP

Introduction: Gastroparesis is a complex disease with limited pharmacologic treatment options. Pyloric dysfunction is increasingly recognized as playing an important role in the pathophysiology of the disease which has led to increasing interest in pylorus-directed therapy. The novel endoscopic functional lumen imaging probe (EndoFLIP) and the EsoFLIP catheter allows for dynamic measurement and directed intervention. Case Description/Methods: A 34-year-old man with a past medical history of diabetes mellitus and gastroparesis was admitted after presenting with significant epigastric pain, nausea and vomiting. His initial glucose was 451 mg/dL. The patient was initially treated with an insulin drip, intravenous fluids, and antiemetics including alternating ondansetron, promethazine, and metoclopramide. Despite improvement in the patient's hyperglycemia, the symptoms of nausea and vomiting persisted. The patient underwent esophagogastroduodenoscopy (EGD) with therapeutic intent. The initial endoscopic exam ruled out any mucosal lesions or mechanical obstruction. The EsoFLIP catheter was placed side-by-side the endoscope and under direct visualization was advanced past the pylorus. Proper balloon placement was verified by an hourglass shape of the balloon displayed on the monitor. Measurements were obtained of the cross-sectional area of the pylorus at various balloon volumes starting at 30 ml. The balloon is inflated stepwise at 5 ml intervals and measurements were obtained. The initial pylorus diameter was measured to be 13.7 mm. Care was taken to directly visualize the mucosa during the procedure. The pylorus was dilated up to a diameter of 25 mm. Mucosal rents (tears) were seen after the balloon was deflated. The patient tolerated the procedure well without any immediate complication. His symptoms resolved and he was able to tolerate a regular diet. Discussion: Endoscopic functional lumen imaging probe uses impedance planimetry to calculate pyloric distensibility. Therapeutic dilation using the EsoFLIP system allows real-time and dynamic visualization of the pyloric sphincter with measurements of diameter, cross-sectional area and intra-balloon pressure. This case highlights the therapeutic protentional of EsoFLIP pylorus dilation for refractory gastroparesis. Here we follow a previously described step wise protocol for using the EsoFLIP with the goal of achieving a target pylorus diameter of 25 mm. This protocol has been shown to lead to improvements in symptoms and FLIP metrics as demonstrated in our case.

S1589 Effects of Surgical Pyloroplasty on Pyloric EndoFLIP Measurements and Gastric Emptying in Patients With Refractory Gastroparesis and Identification of Pyloric Sphincter Smooth Muscle Pathology

S1589 Effects of Surgical Pyloroplasty on Pyloric EndoFLIP Measurements and Gastric Emptying in Patients With Refractory Gastroparesis and Identification of Pyloric Sphincter Smooth Muscle Pathology

223. INTRAOPERATIVE PYLOROPLASTY DURING OESOPHAGECTOMY: A 12 YEAR TERTIARY CENTRE EXPERIENCE

Abstract Delayed gastric emptying (DGE) is a known complication following oesophagectomy with gastric conduit reconstruction. Pyloroplasty is often performed to mitigate the consequences of DGE. It remains contentious whether performing a pyloroplasty has a significant role in reducing DGE. We discuss our twelve-year experience at a single centre routinely performing Heineke-Mikulicz pyloroplasty for all oesophagectomies. This retrospective study employed an electronic database containing information on all patients who underwent elective Ivor Lewis oesophagectomies from April 2009 to December 2021 in a tertiary upper gastrointestinal cancer centre. Across six surgeons in the centre, a standardised pyloroplasty technique was performed. DGE was defined as patients who had high nasogastric output (&amp;gt; 1.5 litres per day) after ten post-operative days or required endoscopic pyloric balloon dilatation within one year following oesophagectomy. 578 patients underwent Ivor Lewis oesophagectomy during the study period. The mean age was sixty years and the male to female ratio was 1.8:1. The median length of stay was 13 days (3–148). DGE was seen in 9.9% (n = 57) patients. Of these patients, 39.7% (n = 29) cases required oesophageal dilatation within 12 months after their oesophagectomy. 50.8% (n = 21) required in-patient endoscopic dilatation, 14.0% (n = 8) required out-patient endoscopic dilatation. From those who developed DGE, the 30- and 90-day mortality was nil. There were 1.2% (n = 7) leaks specifically from the pyloroplasty which were all managed conservatively. The rate of delayed gastric emptying is reported to be approximately 15% (Zhang &amp; Zhang, 2018). Our study demonstrates that performing a pyloroplasty reduces this risk to 9.9% and is worthwhile as the complication rate from pyloroplasty is low. Although there are various methods employed in overcoming pyloric sphincter denervation following oesophagectomy (pyloroplasty, pyloromyotomy, digital or instrumental pyloric stretching or intra-operative balloon dilatation), the most effective method of reducing DGE warrants a randomised control trial.