AQP5 enriches for stem cells and cancer origins in the distal stomach.

LGR5 marks resident adult epithelial stem cells at the gland base in the mouse pyloric stomach1, but the identity of the equivalent human stem cell population remains unknown owing to a lack of surface markers that facilitate its prospective isolation and validation. In mouse models of intestinal cancer, LGR5+ intestinal stem cells are major sources of cancer following hyperactivation of the WNT pathway2. However, the contribution of pyloric LGR5+ stem cells to gastric cancer following dysregulation of the WNT pathway-a frequent event in gastric cancer in humans3-is unknown. Here we use comparative profiling of LGR5+ stem cell populations along the mouse gastrointestinal tract to identify, and then functionally validate, the membrane protein AQP5 as a marker that enriches for mouse and human adult pyloric stem cells. We show that stem cells within the AQP5+ compartment are a source of WNT-driven, invasive gastric cancer in vivo, using newly generated Aqp5-creERT2 mouse models. Additionally, tumour-resident AQP5+ cells can selectively initiate organoid growth in vitro, which indicates that this population contains potential cancer stem cells. In humans, AQP5 is frequently expressed in primary intestinal and diffuse subtypes of gastric cancer (and in metastases of these subtypes), and often displays altered cellular localization compared with healthy tissue. These newly identified markers and mouse models will be an invaluable resource for deciphering the early formation of gastric cancer, and for isolating and characterizing human-stomach stem cells as a prerequisite for harnessing the regenerative-medicine potential of these cells in the clinic.

Neuronal morphology enhances robustness to perturbations of channel densities.

Biological neurons show significant cell-to-cell variability but have the striking ability to maintain their key firing properties in the face of unpredictable perturbations and stochastic noise. Using a population of multi-compartment models consisting of soma, neurites, and axon for the lateral pyloric neuron in the crab stomatogastric ganglion, we explore how rebound bursting is preserved when the 14 channel conductances in each model are all randomly varied. The coupling between the axon and other compartments is critical for the ability of the axon to spike during bursts and consequently determines the set of successful solutions. When the coupling deviates from a biologically realistic range, the neuronal tolerance of conductance variations is lessened. Thus, the gross morphological features of these neurons enhance their robustness to perturbations of channel densities and expand the space of individual variability that can maintain a desired output pattern.

Energy-efficient network activity from disparate circuit parameters.

Neural circuits can produce similar activity patterns from vastly different combinations of channel and synaptic conductances. These conductances are tuned for specific activity patterns but might also reflect additional constraints, such as metabolic cost or robustness to perturbations. How do such constraints influence the range of permissible conductances? Here we investigate how metabolic cost affects the parameters of neural circuits with similar activity in a model of the pyloric network of the crab Cancer borealis. We present a machine learning method that can identify a range of network models that generate activity patterns matching experimental data and find that neural circuits can consume largely different amounts of energy despite similar circuit activity. Furthermore, a reduced but still significant range of circuit parameters gives rise to energy-efficient circuits. We then examine the space of parameters of energy-efficient circuits and identify potential tuning strategies for low metabolic cost. Finally, we investigate the interaction between metabolic cost and temperature robustness. We show that metabolic cost can vary across temperatures but that robustness to temperature changes does not necessarily incur an increased metabolic cost. Our analyses show that despite metabolic efficiency and temperature robustness constraining circuit parameters, neural systems can generate functional, efficient, and robust network activity with widely disparate sets of conductances.

Alterations in network robustness upon simultaneous temperature and pH perturbations.

Nervous systems have evolved to function consistently in the face of the normal environmental fluctuations experienced by animals. The stomatogastric nervous system (STNS) of the crab, Cancer borealis, produces a motor output that has been studied for its remarkable robustness in response to single global perturbations. Changes in environments, however, are often complex and multifactorial. Therefore, we studied the robustness of the pyloric network in the stomatogastric ganglion (STG) in response to simultaneous perturbations of temperature and pH. We compared the effects of elevated temperatures on the pyloric rhythm at control, acid, or base pHs. In each pH recordings were made at 11°C, and then the temperature was increased until the rhythms became disorganized ("crashed"). Pyloric burst frequencies and phase relationships showed minor differences between pH groups until reaching close to the crash temperatures. However, the temperatures at which the rhythms were disrupted were lower in the two extreme pH conditions. This indicates that one environmental stress can make an animal less resilient to a second stressor.NEW & NOTEWORTHY Resilience to environmental fluctuations is important for all animals. It is common that animals encounter multiple stressful events at the same time, the cumulative impacts of which are largely unknown. This study examines the effects of temperature and pH on the nervous system of crabs that live in the fluctuating environments of the Northern Atlantic Ocean. The ranges of tolerance to one perturbation, temperature, are reduced under the influence of a second, pH.

Switching neuron contributions to second network activity.

Network flexibility is important for adaptable behaviors. This includes neuronal switching, where neurons alter their network participation, including changing from single- to dual-network activity. Understanding the implications of neuronal switching requires determining how a switching neuron interacts with each of its networks. Here, we tested 1) whether "home" and second networks, operating via divergent rhythm generation mechanisms, regulate a switching neuron and 2) if a switching neuron, recruited via modulation of intrinsic properties, contributes to rhythm or pattern generation in a new network. Small, well-characterized feeding-related networks (pyloric, ∼1 Hz; gastric mill, ∼0.1 Hz) and identified modulatory inputs make the isolated crab (Cancer borealis) stomatogastric nervous system (STNS) a useful model to study neuronal switching. In particular, the neuropeptide Gly1-SIFamide switches the lateral posterior gastric (LPG) neuron (2 copies) from pyloric-only to dual-frequency pyloric/gastric mill (fast/slow) activity via modulation of LPG-intrinsic properties. Using current injections to manipulate neuronal activity, we found that gastric mill, but not pyloric, network neurons regulated the intrinsically generated LPG slow bursting. Conversely, selective elimination of LPG from both networks using photoinactivation revealed that LPG regulated gastric mill neuron-firing frequencies but was not necessary for gastric mill rhythm generation or coordination. However, LPG alone was sufficient to produce a distinct pattern of network coordination. Thus, modulated intrinsic properties underlying dual-network participation may constrain which networks can regulate switching neuron activity. Furthermore, recruitment via intrinsic properties may occur in modulatory states where it is important for the switching neuron to actively contribute to network output.NEW & NOTEWORTHY We used small, well-characterized networks to investigate interactions between rhythmic networks and neurons that switch their network participation. For a neuron switching into dual-network activity, only the second network regulated its activity in that network. In addition, the switching neuron was sufficient but not necessary to coordinate second network neurons and regulated their activity levels. Thus, regulation of switching neurons may be selective, and a switching neuron is not necessarily simply a follower in additional networks.

Neuropeptide modulation of bidirectional internetwork synapses.

Oscillatory networks underlying rhythmic motor behaviors, and sensory and complex neural processing, are flexible, even in their neuronal composition. Neuromodulatory inputs enable neurons to switch participation between networks or participate in multiple networks simultaneously. Neuromodulation of internetwork synapses can both recruit and coordinate a switching neuron in a second network. We previously identified an example in which a neuron is recruited into dual-network activity via peptidergic modulation of intrinsic properties. We now ask whether the same neuropeptide also modulates internetwork synapses for internetwork coordination. The crab (Cancer borealis) stomatogastric nervous system contains two well-defined feeding-related networks (pyloric, food filtering, ∼1 Hz; gastric mill, food chewing, ∼0.1 Hz). The projection neuron MCN5 uses the neuropeptide Gly1-SIFamide to recruit the pyloric-only lateral posterior gastric (LPG) neuron into dual pyloric- plus gastric mill-timed bursting via modulation of LPG's intrinsic properties. Descending input is not required for a coordinated rhythm, thus intranetwork synapses between LPG and its second network must underlie coordination among these neurons. However, synapses between LPG and gastric mill neurons have not been documented. Using two-electrode voltage-clamp recordings, we found that graded synaptic currents between LPG and gastric mill neurons (lateral gastric, inferior cardiac, and dorsal gastric) were primarily negligible in saline, but were enhanced by Gly1-SIFamide. Furthermore, LPG and gastric mill neurons entrain each other during Gly1-SIFamide application, indicating bidirectional, functional connectivity. Thus, a neuropeptide mediates neuronal switching through parallel actions, modulating intrinsic properties for recruitment into a second network and as shown here, also modulating bidirectional internetwork synapses for coordination.NEW & NOTEWORTHY Neuromodulation can enable neurons to simultaneously coordinate with separate networks. Both recruitment into, and coordination with, a second network can occur via modulation of internetwork synapses. Alternatively, recruitment can occur via modulation of intrinsic ionic currents. We find that the same neuropeptide previously determined to modulate intrinsic currents also modulates bidirectional internetwork synapses that are typically ineffective. Thus, complementary modulatory peptide actions enable recruitment and coordination of a neuron into a second network.

Physiological characterization of gastric emptying using high-resolution antropyloroduodenal manometry.

Delayed gastric emptying (GE) has been associated with antral and pyloric dysmotility. We aimed to characterize differences in the antral, duodenal, and pyloric motility profiles associated with delayed GE, using high-resolution antropyloroduodenal manometry (HR-ADM). Patients referred for HR-ADM for dyspeptic symptoms performed a concurrent GE breath test (NCT01519180 and NCT04918329). HR-ADM involved 36 sensors 1 cm apart, placed across the pylorus. Interdigestive and postprandial periods were identified. Antral, pyloric, and duodenal motor profiles were analyzed recording the frequency, amplitude, and propagative nature of contractions for each period. Plots of patients with normal and delayed GE were compared. Sixty patients underwent both HR-ADM and GE tests. Twenty-five and 35 patients had delayed and normal GE, respectively. Antral and duodenal motor profiles were not different between the two groups during the interdigestive period. During the postprandial period, a lower frequency of antral contractions was associated with delayed GE (2.22 vs. 1.39 contractions/min; P = 0.002), but no difference in mean contraction amplitude was observed. The pyloric region was identified in all the patients and pylorospasms, defined as 3 min of repeated isolated pyloric contractions, were more frequent in patients with delayed GE (32.0% vs. 5.7%; P = 0.02) during the postprandial period. No difference in duodenal contraction profiles was observed. Manometric profile alterations were observed in 72% of the patients with delayed GE, with 56% having a low frequency of antral contractions. Using HR-ADM, patients with delayed GE displayed different postprandial antropyloric motility as compared with patients with normal GE.NEW & NOTEWORTHY High-resolution antropyloroduodenal manometry (HR-ADM) allows precise characterization of antral, pyloric, and duodenal motility, although its association with gastric emptying (GE) has been poorly investigated. Concurrent HR-ADM with GE measurement showed a lower frequency of antral postprandial contractions and an increased frequency of postprandial pylorospasms in patients with delayed GE. HR-ADM could, therefore, be useful in the future to better select patients for treatments targeting the pylorus.

Gastric peroral endoscopic myotomy versus botulinum toxin injection for the treatment of refractory gastroparesis: results of a double-blind randomized controlled study.

INTRODUCTION: Gastric peroral endoscopic myotomy (G-POEM) is a promising technique for treating refractory gastroparesis. We present the first double-blind randomized study comparing the clinical efficacy of G-POEM versus pyloric botulinum toxin injection (BTI). METHODS: This randomized study, conducted in two expert centers, enrolled patients with refractory gastroparesis, medically managed for >6 months and confirmed by gastric emptying scintigraphy (GES), into two groups, G-POEM versus BTI, with follow-up of 1 year. The primary end point was the 3-month clinical efficacy, defined as a >1-point decrease in the mean Gastroparesis Cardinal Symptom Index (GCSI) score. Secondary end points were: 1-year efficacy, GES evolution, adverse events, and quality of life. RESULTS: 40 patients (22 women; mean age 48.1 [SD 17.4]), with mean symptom duration of 5.8 (SD 5.7) years, were randomized. Etiologies included idiopathic (n=18), diabetes (n=11), postoperative (n=6), and mixed (n=4). G-POEM showed a higher 3-month clinical success than BTI (65% vs. 40%, respectively; P=0.10), along with non-significantly higher 1-year clinical success (60% vs. 40%, respectively) on intention-to-treat analysis. The GCSI decreased in both groups at 3 months and 1 year. Only three minor adverse events occurred in the G-POEM group. The GES improvement rate was 72% in the G-POEM group versus 50% in the BTI group (non-significant). CONCLUSION: G-POEM seems to have a higher clinically relevant success rate than BTI, but this was not statistically demonstrated. This study confirms the interest in treatments targeting the pylorus, either mechanically or chemically, for managing refractory gastroparesis.

Equal short-term outcomes of intracorporeal mechanical gastrogastrostomy in laparoscopic pylorus-preserving gastrectomy for cT1N0 gastric cancer in the middle stomach compared with the extracorporeal hand-sewing method.

BACKGROUND: Intracorporeal mechanical gastrogastrostomy (IMG) techniques have recently been developed and their short-term safety was presented in their initial evaluation. However, whether they are comparable to extracorporeal hand-sewing gastrogastrostomy (EHG) remains unclear. The aim of the study is to establish the safety of IMG in totally laparoscopic pylorus-preserving gastrectomy (TLPPG) compared to EHG in laparoscopy-assisted pylorus-preserving gastrectomy (LAPPG). METHODS: We retrospectively analyzed the short-term outcomes of patients with middle-third early gastric cancer who underwent LAPPG or TLPPG between 2005 and 2022. The primary objective of this study was to evaluate the non-inferiority of IMG to EHG in terms of safety, with the primary endpoint being the risk difference in anastomosis-related complications (ARCs). The sample size required to achieve a statistical power of 80% for the non-inferiority test was 971 with a one-sided alpha level of 5% and non-inferiority of 5%. RESULTS: The analysis included a total of 1,021 patients who underwent LAPPG or TLPPG during the study period. Among them, 488 patients underwent EHG, while 533 underwent IMG. The incidences of ARCs were 11.3% and 11.4% in EHG and IMG, respectively. The observed difference in incidence was 0.0017 (90% confidence interval - 0.0313 to 0.0345), which statistically demonstrated the non-inferiority of IMG to EHG in the incidence of ARCs. Among other complications, the incidence of wound infection in IMG was lower than that in EHG. CONCLUSION: IMG is safe regarding ARCs compared with EHG. These results will encourage surgeons to introduce IMG for patients with early middle gastric cancer.

The impact of high-frequency transducers on the sonographic measurements of the pyloric muscle thickness in infants.

BACKGROUND: Ultrasound is the modality of choice for the diagnosis of hypertrophic pyloric stenosis (HPS). The evolution of high-frequency transducers in ultrasound has led to inconsistent ways of measuring the pylorus. OBJECTIVE: To standardize the measurements and evaluate the appearance of the normal and hypertrophied pylorus with high-frequency transducers. MATERIALS AND METHODS: We retrospectively analyzed abdominal ultrasounds of infants with suspected HPS from January 2019-December 2020. We classified the layers of the pylorus while assessing the stratified appearance. Two pediatric radiologists measured the muscle thickness of the pylorus independently by two methods for interrater agreement. Measurement (a) includes the muscularis propria and muscularis mucosa. Measurement (b) includes only the muscularis propria. We also evaluated the echogenicity of the muscularis propria. The interrater agreement, mean, range of the muscle thickness, and the diagnostic accuracy of the two sets of measurements were calculated. RESULTS: We included 300 infants (114 F:186 M), 59 with HPS and 241 normal cases. There was a strong agreement between the readers assessed in the first 100 cases, and ICC was 0.99 (95% CI, 0.98-0.99). Measurement (a), median thickness is 2.4 mm in normal cases and 4.8 mm in HPS. Measurement (b), median thickness is 1.4 mm in normal cases and 4.0 mm in HPS. Measurement (a) has an accuracy of 89.7% (95% CI, 85.7-92.8%) with 98.3% sensitivity and 87.6% specificity. Measurement (b) has an accuracy of 98.0% (95% CI, 95.7-99.3%) with 89.8% sensitivity and 100.0% specificity. The pylorus stratification is preserved in all normal cases and 31/59 (52.5%) cases of HPS. There was complete/partial loss of stratification in 28/59 (47.5%) cases of HPS. In all HPS cases, the muscularis propria was echogenic. CONCLUSION: Measuring the muscularis propria solely has a better diagnostic accuracy, decreasing the overlap of negative and positive cases. The loss of pyloric wall stratification and echogenic muscularis propria is only seen in HPS.

Procedures for a Transpyloric Feeding Tube Inserted Into Newborns and Infants: A Systematic Review.

BACKGROUND: Enteral feeding by a transpyloric tube in critically ill infants is indicated when there is a failure in gastric feeding. However, there is a wide variability regarding the insertion technique. PURPOSE: To perform a systematic review of the methods for inserting a transpyloric feeding tube in newborns and infants. DATA SOURCES: Nine databases, without date or language restrictions, accessed in September 2021. STUDY SELECTION: A systematic review of experimental and nonexperimental studies, according to the "Patient/problem; Intervention; Comparison; Outcome" strategy and the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" guidelines. The clinical question was about the measurement and insertion techniques, as well as the success rates of properly placing a transpyloric tube in newborns and infants. DATA EXTRACTION: Two authors (N.M.Q. and J.F.S.) analyzed 6 observational descriptive prospective studies, all of them published in peer-reviewed indexed medical journals and one in the official journal of the National Association of Neonatal Nurses. RESULTS: The success rate varied between 70% and 100%. There was an important variability in the type of tube, measurement method, and insertion techniques. It was found that the most common strategies to achieve proper positioning were glabella-calcaneal measurements, gastric air insufflation, and right lateral decubitus. IMPLICATIONS FOR PRACTICE: A transpyloric catheter insertion protocol needs to be established in each neonatal unit, according to the literature findings. IMPLICATIONS FOR RESEARCH: Randomized controlled studies that evaluate the gastric air insufflation technique and other adjuvant measures could elucidate the knowledge gap concerning the correct positioning of transpyloric tubing in newborns and infants.

Effectiveness of two-dimensional shear-wave sonoelastography in the diagnosis and follow-up of infantile hypertrophic pyloric stenosis.

INTRODUCTION: We sought to determine the effectiveness and utility of two-dimensional shear-wave sonoelastography (2D-SW-SE) in the diagnosis and postoperative follow-up of infantile hypertrophic pyloric stenosis (IHPS). MATERIALS AND METHODS: Twenty-three infants were included in the study, 13 in the IHPS group and 10 in the control group (CG). Preoperative B-mode ultrasonography measurements (longitudinal length and single-wall thickness of the pylorus) and 2D-SW-SE measurements (pylorus tissue stiffness and shear-wave propagation speed) were compared between the groups. The infants with IHPS then underwent Ramstedt pyloromyotomy and were invited for follow-ups on the tenth day and the first, third, and sixth months postoperatively. Measurements taken at the follow-ups were compared with the preoperative values. RESULTS: No differences were found between the groups regarding age, gender, body weight, or week of birth. The pyloric lengths in the IHPS group were longer than in the CG (p < 0.001), and the single-wall thicknesses were thicker (p < 0.001). The pylorus in the IHPS group was four times stiffer than in the CG (27.4 kPa versus 7.66 kPa), and the shear-wave propagation speed in the tissue was higher (1.34 m/s versus 2.69 m/s; p < 0.001). Both values decreased over time in the IHPS group and were normal by the third postoperative month. CONCLUSIONS: 2D-SW-SE can be used as an assistive imaging tool alongside B-mode ultrasound for diagnosing IHPS. It can also be used to identify inadequate surgery by detecting whether the pyloric tissue has softened at follow-up.

Hyperechogenicity of the pyloroduodenal junction in small dogs: Population prevalence in 175 dogs and histological correlation in 14 specimens.

At the pyloroduodenal junction (PDJ), an increase in wall echogenicity is frequently observed. A prospective study was performed to assess the PDJ sonographically in 175 adults and small dogs (>1 year old, <11.4 kg (25 lb)) over 12 months to evaluate the prevalence of this finding. Additionally, changes in echogenicity were correlated with histology in 14 postmortem specimens. A scoring system of echogenicity change centered on the mucosa and submucosa of the PDJ was implemented; 0: no change, 1: mild, 2: moderate to marked. Other included parameters were age, sex, breed, gastric distention, gastric contents, and reported vomiting at the time of presentation. Hyperechogenicity of the PDJ was highly prevalent (scores 1 and 2: 85.7%). No statistical association between hyperechogenicity of the PDJ and age, sex, gastric distention, gastric contents, or vomiting was identified. Hyperechogenicity of the PDJ is thought to represent an anatomical transition zone, and based on histology, hyperechogenicity of the PDJ may represent a variation in distribution and amount of fibrous connective tissue, glandular number, and glandular dilation within the submucosa and mucosa.

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 α8ß1 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 α8ß1 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.

Motor neurons within a network use cell-type specific feedback mechanisms to constrain relationships among ion channel mRNAs.

Recently, activity has been proposed as a primary feedback mechanism used by continuously bursting neurons to coordinate ion channel mRNA relationships that underlie stable output. However, some neuron types only have intermittent periods of activity and so may require alternative mechanisms that induce and constrain the appropriate ion channel profile in different states of activity. To address this, we used the pyloric dilator (PD; constitutively active) and the lateral gastric (LG; periodically active) neurons of the stomatogastric ganglion (STG) of the crustacean Cancer borealis. We experimentally stimulated descending inputs to the STG to cause release of neuromodulators known to elicit the active state of LG neurons and quantified the mRNA abundances and pairwise relationships of 11 voltage-gated ion channels in active and silent LG neurons. The same stimulus does not significantly alter PD activity. Activation of LG upregulated ion channel mRNAs and lead to a greater number of positively correlated pairwise channel mRNA relationships. Conversely, this stimulus did not induce major changes in ion channel mRNA abundances and relationships of PD cells, suggesting their ongoing activity is sufficient to maintain channel mRNA relationships even under changing modulatory conditions. In addition, we found that ion channel mRNA correlations induced by the active state of LG are influenced by a combination of activity- and neuromodulator-dependent feedback mechanisms. Interestingly, some of these same correlations are maintained by distinct mechanisms in PD, suggesting that these motor networks use distinct feedback mechanisms to coordinate the same mRNA relationships across neuron types.NEW & NOTEWORTHY Neurons use various feedback mechanisms to adjust and maintain their output. Here, we demonstrate that different neurons within the same network can use distinct signaling mechanisms to regulate the same ion channel mRNA relationships.

Gastroparesis.

Gastroparesis is characterized by symptoms suggestive of, and objective evidence of, delayed gastric emptying in the absence of mechanical obstruction. This review addresses the normal emptying of solids and liquids from the stomach and details the myogenic and neuromuscular control mechanisms, including the specialized function of the pyloric sphincter, that result in normal emptying, based predominantly on animal research. A clear understanding of fundamental mechanisms is necessary to comprehend derangements leading to gastroparesis, and additional research on human gastric muscles is needed. The section on pathophysiology of gastroparesis considers neuromuscular diseases that affect nonsphincteric gastric muscle, disorders of the extrinsic neural control, and pyloric dysfunction that lead to gastroparesis. The potential cellular basis for gastroparesis is attributed to the effects of oxidative stress and inflammation, with increased pro-inflammatory and decreased resident macrophages, as observed in full-thickness biopsies from patients with gastroparesis. Predominant diagnostic tests involving measurements of gastric emptying, the use of a functional luminal imaging probe, and high-resolution antral duodenal manometry in characterizing the abnormal motor functions at the gastroduodenal junction are discussed. Management is based on supporting nutrition; dietary interventions, including the physical reduction in particle size of solid foods; pharmacological agents, including prokinetics and anti-emetics; and interventions such as gastric electrical stimulation and pyloromyotomy. These are discussed briefly, and comment is added on the potential for individualized treatments in the future, based on optimal gastric emptying measurement and objective documentation of the underlying pathophysiology causing the gastroparesis.

Gastric Peroral Endoscopic Pyloromyotomy for Infants With Congenital Hypertrophic Pyloric Stenosis.

INTRODUCTION: Congenital hypertrophic pyloric stenosis (CHPS), the most common infantile disease requiring surgical intervention, is routinely treated with open or laparoscopic pyloromyotomy. Recently, gastric peroral endoscopic pyloromyotomy (G-POEM) has been used for adult gastroparesis. We aimed to evaluate the efficacy and safety of G-POEM in treating infantile CHPS. METHODS: We reviewed data from 21 G-POEM-treated patients at 3 tertiary children's endoscopic centers in China between January 2019 and December 2020. Clinical characteristics, procedure-related parameters, perioperative management, and follow-up outcomes were summarized. RESULTS: G-POEM was performed successfully in all patients. The median operative duration was 49 (14-150) minutes. The submucosal tunnels were successfully established along the greater curvature of the stomach in 19 cases, and 2 cases were switched to the lesser curvature because of difficulty. No perioperative major adverse events occurred. Minor adverse events included inconsequential mucosal injury in 5 cases and unsatisfactory closure of the mucosal incision in 1 case. Upper gastrointestinal contrast radiography in all patients showed smooth passage of the contrast agent through the pylorus on postoperative day 3. The growth curves of the patients reached normal levels 3 months after the procedure. No recurrent clinical symptoms occurred in any patient during the median follow-up period of 25.5 (14-36) months. DISCUSSION: G-POEM is feasible, safe, and effective for infants with CHPS, with satisfactory clinical responses over a short-term follow-up. Further multicenter studies should be performed to compare the long-term outcomes of this minimally invasive technique with open or laparoscopic pyloromyotomy.

Reflux Esophagitis After Laparoscopic Pylorus-Preserving Gastrectomy for Gastric Cancer.

BACKGROUND: Laparoscopic pylorus-preserving gastrectomy (LPPG) is performed for cT1N0 gastric cancer as a function-preserving surgery, but reflux esophagitis can develop as a mid- to long-term complication postoperatively. We aimed to clarify the incidence rate of this complication and the factors correlated with it. METHODS: Patients with gastric cancer who underwent LPPG between 2005 and 2017 were analyzed. Postoperative reflux esophagitis was evaluated with esophagogastroduodenoscopy; patients were diagnosed as having reflux esophagitis with erosive esophagitis using the modified Los Angeles classification. The incidence rate of postoperative reflux esophagitis was estimated; factors correlated with postoperative reflux esophagitis were analyzed using the logistic regression model. RESULTS: During the study period, 813 patients underwent LPPG for gastric cancer, and 127 (15.6%) of them developed grade B or more severe postoperative reflux esophagitis. The factors correlated with postoperative reflux esophagitis were male sex (odds ratio, 2.68; 95% confidence interval, 1.77-4.05; P < 0.001), preoperative grade A reflux esophagitis (odds ratio, 3.05; 95% confidence interval, 1.28-7.27; P = 0.012), body mass index of ≥ 23 kg/m2 at 1 year postoperatively (odds ratio, 2.18; 95% confidence interval, 1.34-3.53; P = 0.002), postoperative hiatal hernia (odds ratio, 4.35; 95% confidence interval, 2.35-8.04; P < 0.001), and long-term stasis (odds ratio, 1.58; 95% confidence interval, 1.01-2.47; P = 0.044). CONCLUSIONS: Careful attention should be paid in performing LPPG and in postoperative management after LPPG for gastric cancer patients with those risk factors.

Gastroparesis: time for a paradigm change.

PURPOSE OF REVIEW: Gastroparesis (GP) is a syndrome defined by symptoms and delayed gastric emptying in the absence of mechanical obstruction. Typical symptoms include nausea, vomiting, abdominal pain, and early satiety. Only one medication is currently FDA-approved for the treatment of GP. This review highlights recent research findings pertaining to GP and provides evidence to support a change in the current GP diagnostic and treatment paradigm. RECENT FINDINGS: An analysis of GP trials over the past four decades demonstrates the power of placebo and the need to perform longer studies with clearly defined patient populations. Two studies highlight the need to evaluate patients with suspected GP carefully and to perform gastric emptying studies properly. The misdiagnosis of GP symptoms is reviewed, preceded by a discussion of whether GP should be considered a disorder of gut-brain interaction. Finally, new data on therapies that target the pylorus are highlighted. SUMMARY: Gastroparesis is frequently over-diagnosed and incorrectly diagnosed. Performing a proper gastric emptying study which adheres to standard protocol, and accurately interpreting the results in the context of the individual patient, are critical to making an accurate diagnosis of GP. The treatment paradigm needs to shift from simply aiming to accelerate gastric emptying to treating global symptoms of a chronic syndrome that may represent gut-brain dysfunction in many patients.

A Contemporary Review of Surgical Approach and Outcomes in Pediatric Hypertrophic Pyloric Stenosis.

INTRODUCTION: In order to define optimal resources and outcome standards for infant pyloromyotomy, we sought to perform a contemporary analysis of surgical approach (laparoscopic versus open) and outcomes. METHODS: The National Surgical Quality Improvement Project Pediatrics Participant Use File (NSQIP PUF) was queried from 2016 to 2020. Utilization of laparoscopy was trended over time. Complication rates and length of stay were compared by operative approach. RESULTS: 9752 pyloromyotomies were included in the analysis. The utilization of laparoscopy steadily increased over the study time period (66% to 79%) and was associated with a shorter operative time. On multivariate regression, the utilization of laparoscopy was associated with a lower risk of overall complications, length of stay, and superficial surgical site infections. Overall complication rates were lower than previously reported (2.02%). The most common complication was superficial infection (1.2%). CONCLUSIONS: In facilities reporting to pediatric National Quality Improvement Project, utilization of laparoscopy has steadily increased, and complication rates are lower than previously reported. Complication rates and length of stay were lower with the laparoscopic approach in this contemporary cohort. These results offer benchmarks for quality improvement initiatives. The laparoscopic approach should be standard in facilities performing this procedure.