Luminal Distension Research Articles

The Effect of Tacrine on Functional Response of the Lower Oesophageal Sphincter Assessed by Endoscopic Luminal Impedance Planimetry in Experimental Pigs

Background/Objectives: Tacrine is a centrally active non-competitive reversible acetylcholinesterase inhibitor. It also exerts antagonising activity against N-methyl-D-aspartate receptors. Tacrine was approved for the treatment of Alzheimer’s disease in 1993, but was withdrawn from clinical use in 2013 because of its hepatotoxicity and gastrointestinal side effects. Nevertheless, tacrine is currently facing a renewed wave of interest primarily due to several new tacrine-incorporated hybrids and derivates. There were two specific aims for this study: firstly, to explain the mechanisms of the adverse action of tacrine, as a distinctive example of a highly effective acetylcholinesterase inhibitor; and secondly to check whether luminal impedance planimetry is feasible for preclinical testing of possible side effects of compounds potentially toxic to the gastrointestinal tract. Methods: Six experimental pigs were used as the animal model in this study. Five major parameters were evaluated: luminal pressure (mmHg), estimated diameter (mm), cross-sectional area (mm2), distensibility (mm2/mmHg), and zone compliance (mm3/mmHg). All measurements were performed before and 360 min after intragastric administration of 200 mg tacrine (at the porcine tacrine Tmax). Results: This study consistently demonstrated an increase in luminal pressure (a directly measured indicator) for the particular balloon filling volumes used, and inversely a reciprocal decrease in the other parameters after tacrine administration. Conclusions: Endoscopic luminal impedance planimetry is a feasible method to evaluate functional response of the lower oesophageal sphincter to tacrine in experimental pigs. Tacrine did not compromise the function of the lower oesophageal sphincter either toward oesophageal spasms or, in contrast, decreased competence of the lower oesophageal sphincter.

B-flow/spatiotemporal image correlation M-mode ultrasound provides novel method to quantify spiral artery remodeling during normal human pregnancy.

During human pregnancy, placental extravillous trophoblasts replace vascular smooth muscle and elastic tissue within the walls of the uterine spiral arteries, thereby remodeling them into distensible low-resistance vessels to promote placental perfusion. The present study determined whether B-flow/spatiotemporal image correlation (STIC) M-mode ultrasonography provides an in-vivo imaging method able to digitally quantify spiral artery luminal distensibility as a physiological index of spiral artery remodeling during the advancing stages of normal human pregnancy. A prospective, longitudinal, observational study was conducted to quantify spiral artery distensibility (i.e. vessel luminal diameter at systole minus diameter at diastole) by B-flow/STIC M-mode ultrasonography during the first, second and third trimesters in 290 women exhibiting a normal pregnancy. Maternal serum levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1), growth factors that modulate important events in spiral artery remodeling, were quantified in a subset of the women in the first, second and third trimesters of pregnancy. Median (interquartile range (IQR)) spiral artery distensibility increased progressively between the first (0.17 (0.14-0.21) cm), second (0.23 (0.18-0.28) cm) and third (0.26 (0.21-0.35) cm) trimesters of pregnancy (P < 0.0001 for all). Median (IQR) spiral artery volume flow increased progressively between the first (2.49 (1.38-4.99) mL/cardiac cycle), second (3.86 (2.06-6.91) mL/cardiac cycle) and third (7.79 (3.83-14.98) mL/cardiac cycle) trimesters (P < 0.001 for all). In accordance with the elevation in spiral artery distensibility, the median (IQR) ratio of serum PlGF/sFlt-1 × 103 levels increased between the first (7.2 (4.5-10.0)), second (22.7 (18.6-42.2)) and third (56.2 (41.9-92.5)) trimesters (P < 0.001 for all). The present study shows that B-flow/STIC M-mode ultrasonography provides an in-vivo imaging technology to quantify digitally the structural and physiological expansion of the walls of the spiral arteries during the cardiac cycle as a consequence of their transformation into compliant vessels during advancing stages of normal human pregnancy. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Is the excretory phase necessary to identify upper tract urothelial neoplasms at CT urography? A 10-year population-based study.

To assess the proportion of upper tract urothelial carcinomas (UTUC) that are evident without the excretory phase at CT urography (CTU), and the proportion of potentially avoidable radiation. UTUCs diagnosed between January 2008-December 2017 were retrospectively identified from a population-based cancer registry. For each patient, US, non-urographic CT, and MRI exams were assessed for a primary mass and secondary imaging findings (hydronephrosis, urinary tract thickening, luminal distention, fat stranding, and lymphadenopathy/metastatic disease). CTUs were assessed for primary and secondary findings, and whether the tumor was evident as a filling defect on excretory phase. The dose-length product (DLP) of potentially avoidable excretory phases was calculated as a fraction of total DLP. 288 patients (mean age, 72±11 years, 165 males) and 545 imaging examinations were included. Of 192 patients imaged with 370 non-urographic CTs, a primary mass was evident in 154 (80.2%), secondary findings were evident in 172 (89.6%), and primary or secondary findings were evident in 179 (93.2%). Of 175 CTUs, primary and secondary findings were evident in 157 (89.7%) and 166 (94.9%) examinations, respectively, and primary or secondary findings were evident in 170/175 (97.1%). 131/175 (74.9%) UTUCs were evident as a filling defect, including the 5/175 (2.9%) UTUCs without primary or secondary findings. Of 144 CTUs with available DLP data, the proportion of potentially avoidable radiation was 103.7/235.8 (44.0%) Gy⋅cm. In our population, almost all UTUCs were evident via primary or secondary imaging findings without requiring the excretory phase. These results support streamlining protocols and pathways.

The Role of the FODMAP Diet in IBS.

The low FODMAP (fermentable oligosaccharide, disaccharide, monosaccharide, and polyol) diet is a beneficial therapeutic approach for patients with irritable bowel syndrome (IBS). However, how the low FODMAP diet works is still not completely understood. These mechanisms encompass not only traditionally known factors such as luminal distension induced by gas and water but also recent evidence on the role of FOMAPs in the modulation of visceral hypersensitivity, increases in intestinal permeability, the induction of microbiota changes, and the production of short-chain fatty acids (SCFAs), as well as metabolomics and alterations in motility. Although most of the supporting evidence is of low quality, recent trials have confirmed its effectiveness, even though the majority of the evidence pertains only to the restriction phase and its effectiveness in relieving abdominal bloating and pain. This review examines potential pathophysiological mechanisms and provides an overview of the existing evidence on the effectiveness of the low FODMAP diet across various IBS subtypes. Key considerations for its use include the challenges and disadvantages associated with its practical implementation, including the need for professional guidance, variations in individual responses, concerns related to microbiota, nutritional deficiencies, the development of constipation, the necessity of excluding an eating disorder before commencing the diet, and the scarcity of long-term data. Despite its recognized efficacy in symptom management, acknowledging these limitations becomes imperative for a nuanced comprehension of the role of a low FODMAP diet in managing IBS. By investigating its potential mechanisms and evidence across IBS subtypes and addressing emerging modulations alongside limitations, this review aims to serve as a valuable resource for healthcare practitioners, researchers, and patients navigating the intricate landscape of IBS.

P009 IL-17 mediates visceral hypersensitivity by sensitising colonic nociceptors

Abstract Background Comparison of cytokine expression in colitic tissue with respective cytokine receptor expression in pain sensing neurons highlights a likely contribution of IL-17 to the production of abdominal pain during flare. To explore this pro-nociceptive potential of IL-17 in colitis we examined the ability of IL-17 to stimulate sensory neurons and the colonic afferent response to noxious distension. Methods IL-17 mediated sensory neuron activation: changes in the intracellular [Ca2+]i within thoracolumbar (T12-L5 spinal segments) dorsal root ganglia sensory neurons were examined in cells cultured overnight and loaded with Fluo-4-AM (30min) prior to imaging. Responses were measured to IL-17 (10-300 ng/mL) alone and following pre-treatment with either TRPV1 or TRPA1 inhibitors. Afterwards cells were exposed to capsaicin (1 µM) followed by 50 mM KCl, to confirm the presence of nociceptors and neurons respectively by positive response. In a separate set of experiments the effect of IL-17 was also examine on a neuron pure cell culture in which non-neuronal cells were removes by magnet assisted cell sorting. IL-17 mediated colonic nociceptor activation: electrophysiological recordings were made of lumbar splanchnic nerve activity and the response to noxious luminal distension of the isolated colorectum (ex-vivo), perfused with carbogenated Krebs solution, examined following pre-treatment with IL-17 (50 ng/mL) alone or in the presence of respective inhibitors. All experiments were performed using tissue from male C57BL/6J mice euthanaised by rising concentration of CO2followed by exsanguination in accordance with Schedule 1 of the UK Animals Scientific Procedures act (1986). Results Consistent with the ability of IL-17 to stimulate sensory neurons including those classified as nociceptors by their co-sensitivity to capsaicin, pre-treatment with IL-17 also produced a significant sensitisation of the colonic afferent response to luminal distension at noxious distending pressures. The increase in [Ca2+]i produced by IL-17 in sensory neurons was blocked by pre-treament with a TRPV1 antagonist but not a TRPA1 antagonist. Furthermore, the proportion of neurons stimulated by IL-17 was comparable between standard DRG cell cultures and neuron pure cell cultures demonstrating a direct effect of IL-17 on sensory neurons. Finally, IL-17 mediated mechanosensitisation of colonic nociceptors was unaffected by TRPV1 inhibition. Conclusion Our findings demonstrate that IL-17 stimulates capsaicin-sensitive nociceptors and mediates visceral hypersensitivity in colonic nociceptors consistent with a causative role for IL-17 is the generation of abdominal pain in people with colitis.

Utility of Intraprocedural Luminal Diameter and Distensibility Measurements During the Esophageal Peroral Endoscopic Myotomy Procedure.

Through evaluation of the lower esophageal sphincter immediately before and after myotomy using an endoluminal functional lumen imaging probe (EFLIP), our study aimed to determine the clinical response to peroral endoscopic myotomy (POEM) and the incidence of postprocedure reflux. Achalasia is a rare esophageal motility disorder characterized by impaired relaxation of the lower esophageal sphincter (LES) and diminished peristalsis. POEM is a therapeutic option for durable management of achalasia. However, symptomatic acid reflux and esophagitis are well-known adverse effects of the procedure. Electronic medical records of 168 patients who underwent POEM for achalasia at 2 tertiary care referral centers from May 2014 to May 2021 were reviewed. EFLIP was used at a range of catheter fill volumes to assess LES dynamics. Preprocedure and postprocedure Eckardt Symptom Scores were recorded. Significant clinical improvement from POEM was sustained in over 94% of patients after 1 year. EFLIP changed intraprocedural management 5% of the time by means of myotomy extension. In patients with reflux>1 year following POEM, there was no significant difference in post-POEM LES diameter or change in LES diameter compared with those without reflux. However, post-POEM LES distensibility index (DI) was significantly higher in patients with reflux after 1 year compared with those without reflux. POEM is a safe and increasingly effective therapy for patients with symptomatic achalasia. Intraprocedural EFLIP measurements suggest that post-POEM reflux may be correlated more with DI than LES diameter. Yet, more data is needed to substantiate these outcomes.

TOGA Therapeutic Oxygen for Gastrointestinal Atony

Background and aimsIleus, mechanical bowel obstruction and acute colonic pseudo-obstruction [ACPO] are characterized by distension of the intestines with accumulated bowel gas. Current treatments are not completely satisfactory. MethodsBy manipulating the partial pressures of oxygen and nitrogen in the trapped air with a novel 6-hour treatment with 100% oxygen via non-rebreather mask [NRB], the bowel can be successfully decompressed, facilitating resolution of the underlying condition. ResultsA positive clinical response was seen in 7/8 [87.5%] patients after TOGA [therapeutic oxygen for gastrointestinal atony]. Maximal lumen diameter decreased by an average of 1.14 ± 0.87 cm [16%]. ConclusionsIn this first clinical report of TOGA, the provision of 100% oxygen via NRB is a useful therapy. It decreased the diameter of the intestinal lumen and enhanced resolution of ileus, ACPO, and bowel obstruction. This is a low-morbidity, low-cost treatment of gastrointestinal luminal distension. ClinicalTrials.gov Identifier NCT03386136.st

What role does the submucosa play in the pathophysiology and treatment of achalasia? An analysis of impedance planimetry during POEM.

It is thought the therapeutic benefit of per-oral endoscopic myotomy (POEM) in the treatment of esophageal dysmotility disorders is from longitudinal myotomy creation, but it is unknown if the submucosa contributes to the pathophysiology. This study investigates if submucosal tunnel (SMT) dissection alone contributes to POEM's luminal changes as measured by EndoFLIP. A single-center, retrospective review of consecutive POEM cases from June 1, 2011 to September 1, 2022 with intraoperative luminal diameter and distensibility index (DI) data as measured by EndoFLIP. Patients with diagnoses of achalasia or esophagogastric junction outflow obstruction were grouped by those with pre-SMT and post-myotomy measurements (Group 1) and those with a third measurement post-SMT dissection (Group 2). Outcomes and EndoFLIP data were analyzed using descriptive and univariate statistics. There were 66 patients identified, of whom 57 (86.4%) had achalasia, 32 (48.5%) were female, and median pre-POEM Eckardt score was 7 [IQR: 6-9]. There were 42 (64%) patients in Group 1, and 24 (36%) patients in Group 2, with no differences in baseline characteristics. In Group 2, SMT dissection changed luminal diameter by 2.15 [IQR: 1.75-3.28]cm, which comprised 38% of the median 5.6 [IQR: 4.25-6.3]cm diameter of complete POEM change. Similarly, the median post-SMT change in DI of 1 [IQR: 0.5-1.2]units comprised 30% of the median 3.35 [2.4-3.98]units overall change in DI. Post-SMT diameters and DI were both significantly lower than the full POEM. Esophageal diameter and DI are significantly affected by SMT dissection alone, though not equaling the magnitude of diameter or DI changes from full POEM. This suggests that the submucosa does play a role in achalasia, presenting a future target for refining POEM and developing alternative treatment strategies.

Imaging of Small Bowel Tumors and Mimics

AbstractSmall bowel tumors are rare with nonspecific and protean clinical presentation. Early diagnosis of small bowel tumors is desirable as they can be associated with significant morbidity. In malignant small bowel tumors, delayed diagnosis may result in dissemination and metastasis leading to poor clinical outcomes. Imaging evaluation of small bowel can be challenging due to unpredictable luminal distension, peristalsis, and motion. In addition, the lack of distinction between the intraluminal lesions and intraluminal contents can be difficult at times. Computed tomography (CT) and magnetic resonance (MR) enterography are the most common imaging techniques for the evaluation of small bowel tumors. While these techniques may not be able to detect small tumors, they provide comprehensive evaluation of lumen, wall, and extramural structures in tumors more than 2 cm. Acquaintance of imaging appearance of common benign and malignant small bowel tumors may allow improved detection during evaluation of CT and MR enterography studies. In this review, we discuss the imaging appearances, approach, and differential diagnosis of small bowel tumors on cross-sectional imaging studies.

Stercoral colitis: CT imaging findings and clinical risk factors.

To describe and update stercoral colitis clinical risk factors, relative frequency, location, and CT imaging features correlated with surgical and pathological results. CT reports over a 5-year period (05/2017-05/2022) at a single medical center were searched. Main inclusion criteria were luminal distention with formed stool, wall thickening, and surrounding inflammation. Positive cases were graded as mild (early or developing stercoral colitis) versus moderate-to-severe based on CT findings. Medical records were reviewed for risk factors and outcome data in moderate-to-severe cases. P-values were tabulated for comparison. 545 total cases (71 (60, 82) years, 278 males) were identified on CT, including 452 mild (82.9%) and 93 moderate-to-severe cases (17%, 67 (55, 79) years, 48 females). Twenty cases showed evidence of perforation (3.7% total cohort, 22% moderate-to-severe cohort). Diagnosis as an incidental finding was frequent (46.0% of mild cases). Most cases involved the rectum (97.6% of mild cohort and 69% of moderate-to-severe cohort). The sigmoid was involved in 31% of moderate-to-severe cases, but 95% of the perforated subcohort (19/20, 13/20 without rectal involvement). Among the moderate-to-severe cohort, perforation was associated with slightly increased wall thickness (6.4 vs. 5.7 mm, p = 0.03), opioid use (50 vs. 23%, p = 0.04), and disease-specific mortality (11 vs. 0%, p =0.04). Perforation was less associated with major neurocognitive disorders (20 vs. 60%, p = 0.003), institutionalized status (5 vs. 38%, p = 0.005), and a prescribed bowel regimen (30 vs. 63%, p = 0.01). Stercoral colitis may be under-reported. Perforation tends to favor sigmoid involvement and a less traditional patient cohort.

MR enterography in small bowel diseases, adding multipoint Dixon sequence, is it worth?

BackgroundMR enterography (MRE) has been increased in the last decade as a modality of choice in diagnosis and evaluation of small bowel diseases in both children and adults. Lacking ionizing radiation, non-invasiveness, excellent soft tissue resolution, adequate luminal distension of small bowel loops are the advantages of this technique. Acquisition of images was used to be: T2WI, steady-state free precession, and T1WI, fat-suppressed gadolinium contrast-enhanced sequences. Multipoint Dixon sequence was added recently to the routine MR enterography protocol. The current study aimed to evaluate the added value of multipoint Dixon sequence as a valuable modification of MR enterography protocol for better assessment of small bowel lesions as activity of Crohn’s disease, small bowel polyps, fibrotic strictures, with modification of MRE protocol in the future with less time consumption and better radiological evaluation.MethodsThe current research was a prospective cross-sectional study. Data were collected prospectively after getting ethical approval from the ethical committee of the faculty of medicine, in our university.Study populationThe sample size was 69 adult patients with suspected small bowel lesions, within the period from January 2022 to 30th December 2022. Written informed consent was obtained from all studied cases before the study, who were enrolled in this study. This number was calculated by using MedCalc 19 program by setting alpha error significance of 0.05%, 95% confidence level, and 80% power sample.ResultsThis study enrolled 69 patients with recurrent abdominal pain and/or bleeding in stool. The patients’ age ranged from 18 to 50 years, with a mean of 32.6 ± 8.8. There is slightly higher female prevalence. The most common positive imaging findings in the studied patients were mucosal thickening in terms of submucosal fat deposition (36.23% of the MRE examination and 39.13% of the MRE with added Dixon sequence). Adding Dixon sequence yielded significantly higher AUC (97.2% vs. 90.5%, p = 0.047), higher sensitivity (100% vs. 92.16%), specificity (94.4% vs. 88.89%), accuracy (98.55% vs. 91.3%), positive predictive value (98.08% vs. 95.92%), and negative predictive value (100% vs. 80%).ConclusionsMRE is an excellent imaging modality in the assessment of small bowel diseases without the use of ionizing radiation. Developing MR-based sequences as multi-point Dixon sequence have the potential to improve the ability of MRE to image the subtle changes as Crohn’s accompanying early inflammatory changes and fibrosis, as well as small intestinal polyps. Familiarity with MR enterography is essential for radiologists and gastroenterologists who participate in the clinical management of small intestinal diseases.

Endoscopic severity of gastric sleeve stenosis can be quantified using impedance planimetry.

Gastric sleeve stenosis (GSS) is an adverse event following sleeve gastrectomy for which objective tools are needed for diagnosis and treatment. Endoscopic treatment with serial pneumatic balloon dilation may relieve symptoms and prevent the need for conversion to Roux-en-Y gastric bypass. Endoluminal functional impedance planimetry (EndoFLIP) is an endoscopic tool that measures luminal diameter and distensibility indices (DI) and could be used to characterize severity of GSS. This was a retrospective analysis of a prospective database of patients referred for symptoms suggestive of GSS. Severity was determined at each endoscopy by a bariatric endoscopist blinded to EndoFLIP measurements. Successive pneumatic balloon dilations were performed until symptoms resolved; failure was defined as referral for conversion. EndoFLIP measurements of stenosis diameter and DI were obtained pre- and post-dilation. Primary outcomes were pre- and post-dilation luminal diameter and DI of GSS. Secondary outcomes were endoscopic severity of GSS, patient characteristics, and need for surgical revision. 26 patients were included; 23 (85%) were female. Mean age was 45.3 (± 9.9) years. Mean number of dilations was 2.4 (± 1.3) and 10 (38%) patients were referred for conversion. Mild, moderate, and severe GSS was found in 10 (38%), 6 (23%), and 10 (38%) patients, respectively. Moderate and severe GSS underwent more dilations (2.5 ± 1.0 and 3.2 ± 1.6) than mild GSS (1.8 ± 0.8) and were more likely to be referred for conversion. Both pre- and post-dilation diameters were significantly larger in mild versus moderate or severe GSS. Additionally, pre- and post-dilation DI at 30ml were significantly higher for mild compared to moderate and severe GSS. EndoFLIP measurements correlate well with endoscopic assessment of GSS. While more data are needed to determine ideal balloon size and threshold measurements, our results suggest EndoFLIP may help expedite diagnosis and treatment of GSS.

Intestinal distension orchestrates neuronal activity in the enteric nervous system of adult mice.

The enteric nervous system (ENS) regulates the motor, secretory and defensive functions of the gastrointestinal tract. Enteric neurons integrate mechanical and chemical inputs from the gut lumen to generate complex motor outputs. How intact enteric neural circuits respond to changes in the gut lumen is not well understood. We recorded intracellular calcium in live-cell confocal recordings in neurons from intact segments of mouse intestine in order to investigate neuronal response to luminal mechanical and chemical stimuli. Wnt1-, ChAT- and Calb1-GCaMP6mice were used to record neurons from the jejunum and colon. We measured neuronal calcium response to KCl (75mM), veratridine (10μM), 1,1-dimethyl-4-phenylpiperazinium (DMPP; 100μM) or luminal nutrients (Ensure®), in the presence or absence of intraluminal distension. In the jejunum and colon, distension generated by the presence of luminal content (chyme and faecal pellets, respectively) renders the underlying enteric circuit unresponsive to depolarizing stimuli. In the distal colon, high levels of distension inhibit neuronal response to KCl, while intermediate levels of distension reorganize Ca2+ response in circumferentially propagating slow waves. Mechanosensitive channel inhibition suppresses distension-induced Ca2+ elevations, and calcium-activated potassium channel inhibition restores neuronal response to KCl, but not DMPP in the distended colon. In the jejunum, distension prevents a previously unknown tetrodotoxin-resistant neuronal response to luminal nutrient stimulation. Our results demonstrate that intestinal distension regulates the excitability of ENS circuits via mechanosensitive channels. Physiological levels of distension locally silence or synchronize neurons, dynamically regulating the excitability of enteric neural circuits based on the content of the intestinal lumen. KEY POINTS: How the enteric nervous system of the gastrointestinal tract responds to luminal distension remains to be fully elucidated. Here it is shown that intestinal distension modifies intracellular calcium levels in the underlying enteric neuronal network, locally and reversibly silencing neurons in the distended regions. In the distal colon, luminal distension is integrated by specific mechanosensitive channels and coordinates the dynamics of neuronal activation within the enteric network. In the jejunum, distension suppresses the neuronal calcium responses induced by luminal nutrients. Physiological levels of distension dynamically regulate the excitability of enteric neuronal circuits.

Use of Irrigation Device for Duct Dilatation during Sialendoscopy

Continuous irrigation of the duct with isotonic saline is one of the fundamental stages of a successful sialendoscopic procedure. It allows for an adequate luminal distension for the removal of debris and mucous plugs and for the conservative treatment of strictures. This procedure, which commonly involves the use of a medical syringe, can be laborious, and it is often necessary to interrupt irrigation during surgery due to the high resistance to saline. Academic university hospital. We propose the use of an irrigation device which consists of a high-pressure syringe barrel, an ergonomic piston handle, and a gauge used to monitor the inflation and deflation of balloon catheters. The system allows for a simple and safe dilation, ensuring good visualization of the salivary duct lumen during sialendoscopy. The irrigation system described can be widely used to perform a diagnostic or interventional sialendoscopy more effectively than with a typical manual irrigation procedure.

Esophageal wall compliance/stiffness during peristalsis in patients with functional dysphagia and high-amplitude esophageal contractions.

Recent studies that utilized distension/contraction plots to study peristalsis reveal poor distension of the esophagus in patients with functional dysphagia and high-amplitude contractions [high-amplitude esophageal contractions (HAECs)] even though the contraction phase of peristalsis is normal in these patients. Our goal was to determine biomechanical properties of the esophageal wall and bolus flow characteristics in patients with functional dysphagia and HAEC during primary peristalsis. Studies were performed on 30 healthy subjects, 30 patients with functional dysphagia, and 25 patients with HAEC. Subjects swallowed 10 mL, 0.5 N saline bolus in the Trendelenburg position to study primary peristalsis. A custom-built software (Dplots) determined peak distension from the impedance measurements, pressure at peak distension, wall tension (pressure × radius), wall distensibility [cross-sectional area (CSA)/pressure], and bolus flow (cm3/s) in four segments of esophagus (between upper and lower esophageal sphincter). Luminal CSA of distal esophagus was smaller, and average bolus flow rate was faster in patients with functional dysphagia and HAEC. Esophageal wall distensibility, a measure of esophageal wall compliance was lower and wall tension was higher in the distal esophagus of both patient groups compared with normal subjects. Ultrasound imaging confirmed poor distension of the esophagus. A trend toward greater wall thickness at the peak of distension was found in patients with functional dysphagia compared with normal subjects. A stiffer or noncompliant esophageal wall is the reason for poor distension of the esophagus during primary peristalsis in patients with functional dysphagia and HAEC.NEW & NOTEWORTHY We studied healthy asymptomatic subject, patients with functional dysphagia (FD), and patients with high-amplitude esophageal contractions (HAEC). Our data show that in patients with HAEC and functional dysphagia, luminal distension is smaller (low luminal CSA at peak distension), intraluminal pressure is higher, and liquid bolus travels faster through the esophagus as compared with normal subjects. We conclude that patients with functional dysphagia and HAEC have a stiffer distal esophageal wall during bolus transport related to primary peristalsis.

S507 Esophageal Function Assessment Using Endoscopic Functional Luminal Imaging Probe (ENDOFLIP) in Patients With Different Obesity Classes

Introduction: Patients with obesity have been found to have a higher prevalence of esophageal motor disorders compared to the general population, with abnormal lower esophageal sphincter (LES) function and altered peristalsis on manometry. Patients with class 3 obesity can experience minimal symptoms despite abnormal manometry suggesting abnormal visceral sensation. Endoscopic functional luminal imaging probe (EndoFLIP) assesses luminal distensibility and peristalsis during endoscopy. This study aims to evaluate esophageal characteristics using EndoFLIP in patients with obesity and esophageal symptoms and determine clinical differences between obesity classes. Methods: We conducted retrospective chart review of patients with obesity and esophageal symptoms who had undergone EndoFLIP testing at a single tertiary care center between 2020-2022. Data was collected on patient demographics, symptoms, medical history, and EndoFLIP measurements. Statistical analysis was performed using Fisher exact testing. Results: 33 patients with a BMI ≥30 were included (81% women, mean age 50.2 years, mean BMI 39.4). 9 (27%) had class 3 obesity, 9 (27%) class 2 obesity and 15 (45%) class 1 obesity. Most common symptoms were dysphagia (72%), heartburn (48%), reflux (48%), and regurgitation (42%). On EndoFLIP, 8 (24%) had reduced esophagogastric junction distensibility index (EGJ-DI), of which 2 (13%) were classified as obesity class 1, 4 (44%) obesity class 2 and 2 (22%) obesity class 3 (Table). 17 (52%) had normal repetitive antegrade contractions (RACs), 7 (21%) diminished/disordered contractile response (DDCRs) and 9 (27%) absent contractility. Abnormal contractility patterns were seen in 7 (47%) obesity class 1, 4 (44%) obesity class 2 and 5 (56%) obesity class 3. There were no significant differences between obesity classes with regards to medication use, co-morbidities, symptoms, endoscopy and EndoFLIP findings. Conclusion: In this cohort, symptomatic patients in different obesity classes did not have significantly different LES function or peristalsis on EndoFLIP. EGJ distensibility was reduced in a quarter of the study population and seen more frequently in patients with class 2 obesity. Nearly half of the patients had abnormal peristalsis with DDCRs and absent contractility, with similar representation between obesity classes. Prospective controlled studies with EndoFLIP comparing symptomatic and asymptomatic patients in different obesity classes are needed to validate these findings. Table 1. - Comparison of patient characteristics and EndoFLIP findings by obesity class Class 1 Obesity BMI 30-35 (N=15) Class 2 Obesity BMI 35-40 (N=9) Class 3 Obesity BMI >40 (N=9) p-value MEDICATIONS N (%) PPI 8 (53) 6(67) 5 (56) 0.67 H2 blocker 5 (33) 1 (11) 2 (22) Opiods 2 (13) 0 2 (22) Benzodiazepines 0 1 (11) 0 SYMPTOMS N (%) Reflux 6 (40) 6 (67) 4 (44) 0.57 Dysphagia 12 (80) 7 (78) 5 (56) Heartburn 7 (47) 4 (44) 5 (56) Regurgitation 3 (20) 4 (44) 7 (78) Belching/Nausea 2 (13) 1 (11) 1 (11) Epigastric abdominal pain 4 (27) 2 (22) 2 (22) Vomiting 1 (7) 2 (22) 1 (11) EGD FINDINGS N (%) Esophagitis 4 (27) 2 (22) 3 (33) 0.78 Gastritis 8 (53) 4 (44) 5 (56) Fluid in esophagus 1 (7) 2 (22) 3 (33) ENDOFLIP FINDINGS EGJ-distensibility index N (%) [mean] Normal 13 (87) [5.4] 5 (56) [4.65] 7 (78) [4.98] 0.26 Reduced 2 (13) [2.27] 4 (44) [0.91] 2 (22) [2.82] Contractility pattern N (%) RACs 8 (53) 5 (56) 4 (44) 1 DDCRs 3 (20) 2 (22) 2 (22) Absent contractility 4 (27) 2 (22) 3 (33) BMI = Body Mass Index; PPI = Proton pump inhibitor; H2 blocker = histamine 2 blocker (eg. famotidine); EGD = Esophagogastroduodenoscopy; EGJ = Esophagogastric Junction; RACs = Repetitive Antegrade Contractions; DDCRs = Diminished or Disordered Contractile Responses

Using high resolution manometry impedance to diagnose upper esophageal sphincter and pharyngeal motor disorders.

Oro-pharyngeal pathophysiology, including upper esophageal sphincter (UES) and pharyngeal disorders, can be assessed by pharyngeal high-resolution manometry impedance (P-HRM-I). We aimed to establish methodology to diagnose disorders utilizing P-HRM-I, hypothesizing that the objective measures could be used to diagnose disordered deglutition evidenced by greater aspiration scores. Patients (n=509, 18-91 years) were compared to controls (n=120, 20-94 years). Variables measuring UES relaxation, UES opening extent, intrabolus pressure, and pharyngeal contractile strength were derived for 10ml liquid swallows. Three associated pharyngeal pressurization patterns, which may be indicative of obstructed flow, were characterized: pan-pressurization (Type 1), distal compartmentalized pressurization (Type 2), and transient pressurization (Type 3). Deglutitive aspiration was determined from video fluoroscopy. UES relaxation pressure was best able to differentiate patients from controls (T 6.528, p < 0.0001). Patients with abnormal relaxation pressure (>8 mmHg) more frequently exhibited pharyngeal pressurization patterns and had adjunct evidence of reduced luminal distensibility (high intrabolus pressure and/or reduced UES opening). Utilizing this information, a diagnostic scheme was devised identifying 138 patients with UES disorder. A further 96 patients without evidence of UES disorder had abnormally weak pharyngeal pressures, confirming propulsive disorder. Amongst a sub-sample of 320 patients undergoing video fluoroscopy, those with pharyngeal pressurizations and adjunct evidence of reduced UES relaxation and/or distensibility had higher aspiration scores (Chi-square 60.169, p < 0.0001). P-HRM-I can provide evidence for UES disorder based on pharyngeal pressurization patterns and abnormal findings for UES relaxation pressure, UES opening, and intrabolus pressure. Measuring pharyngeal contractility requires further optimization.

Comparison of adenoma detection in different colorectal segments between deep-sedated and unsedated colonoscopy

To investigate if deep-sedated colonoscopy affects adenoma detection in certain colorectal segment. Review of colonoscopy reports, electronic images and medical records of individuals underwent screening colonoscopy with or without propofol sedation between October 2020 and March 2021 from seven hospitals in China. A total of 4500 individuals were analyzed. There was no significant difference in ADR between deep-sedated colonoscopy and unsedated colonoscopy [45.4% vs. 46.3%, P > 0.05]. The APP of deep-sedated colonoscopy was lower than unsedated colonoscopy (1.76 ± 0.81 vs. 2.00 ± 1.30, P < 0.05). Both average number of adenomas and luminal distention score of splenic flexure and descending colon were lower in deep-sedated colonoscopy (P < 0.05), and average number of adenomas was positively correlated with an improved distension score in splenic flexure and descending colon (splenic flexure r = 0.031, P < 0.05; descending colon r = 0.312, P < 0.05). Linear regression model showed deep-sedated colonoscopy significantly affected luminal distention of splenic flexure and descending colon as well as average number of adenomas detected in splenic flexure (P < 0.05). Deep-sedated colonoscopy decreased adenoma detection in splenic flexure and the luminal distention of splenic flexure and descending colon compared with unsedated colonoscopy.

An Unusual Cause of Obstructive Jaundice

Question: A 45-year-old man presented with painless obstructive jaundice for 1 month. His past medical history was unremarkable. Significant laboratory results included total bilirubin of 73.4 μmol/L (normal 5.1-20 μmol/L), direct bilirubin of 46.5 μmol/L (normal <6.1 μmol/L), alanine transaminase of 168.3 U/L (normal 9-50 U/L), alkaline phosphatase of 438 U/L (normal 50-135 U/L) and gamma-glutamyl transferase of 1321.6 U/L (normal 10-60 U/L). Abdominal ultrasonography showed a gallstone in the common hepatic duct with intrahepatic ductal dilation, and the gallbladder was atrophic. Contrast-enhanced computed tomographic (CT) scan in a dual-energy mode showed luminal distension of gallbladder neck (Figure A, white arrow), with hepatic hilar stenosis (Figure A, blue arrow) and bilateral intrahepatic ductal dilation. Coronal virtual monoenergetic image reconstruction at 40 keV clearly showed an intraluminal lesion with hypodensity in gallbladder neck (Figure B, red arrow). The spectral Hounsfield unit curve showed the decreased attenuation values of the lesion as the energy level decreased (Figure C). What is the most likely diagnosis? Look on page 197 for the answer and see the Gastroenterology website (www.gastrojournal.org) for more information on submitting to Gastro Curbside Consult. Dual-energy CT suggested that the lesion was a cholesterol gallstone. Magnetic resonance cholangiopancreatography (MRCP) was then performed and confirmed a stone (Figure D, white arrow) in the gallbladder neck, with external compression of the common hepatic duct and dilation of the intrahepatic biliary duct, highly suggestive of Mirizzi syndrome (MS). In addition, a long cystic duct running parallel to the common bile duct with low insertion was found. Subsequent cholecystectomy confirmed a 1.7-cm cholesterol gallstone in the neck of the gallbladder causing hepatic hilar stricture, which was consistent with MS. The patient had an unremarkable recovery. MS, as a rare complication of gallstone disease, refers to impaction of a gallstone in the gallbladder neck or cystic duct causing obstruction of the extrahepatic bile duct.1Abou-Saif A. Al-Kawas F. Complications of gallstone disease: Mirizzi syndrome, cholecystocholedochal fistula, and gallstone ileus.Am J Gastroenterol. 2002; 97: 249-254Crossref PubMed Google Scholar MS can be tricky and may mimic cholangiocarcinoma, especially when gallstones are radiolucent on conventional CT.2Chen Y. Chang C. Liu K. Mirizzi syndrome due to a large radiolucent gallstone.Am J Gastroenterol. 2016; 111: 599Crossref PubMed Scopus (2) Google Scholar With the ability to differentiate materials on the basis of their differential attenuation at 2 different energy levels, dual-energy CT can help to identify the composition of internal body constituents, such as gallstones. Previous studies have reported that dual-energy CT can increase the conspicuity of isoattenuating gallstones.3Soesbe T.C. Lewis M.A. Xi Y. et al.A technique to identify isoattenuating gallstones with dual-layer spectral CT: an ex vivo phantom study.Radiology. 2019; 292: 400-406Crossref PubMed Scopus (15) Google Scholar In this case, dual-energy CT was first used to diagnose MS, clearly showing the gallstone in the gallbladder neck as the cause of the hepatic hilar obstruction, and to provide a diagnostic clue to confirm MS. This technique can potentially reduce the need for further imaging, such as MRCP, leading to a reduction in imaging cost and time to diagnosis for selected patients.

Distension contraction plots of pharyngeal/esophageal peristalsis: next frontier in the assessment of esophageal motor function.

Esophageal peristalsis consists of initial inhibition (relaxation) followed by excitation (contraction), both of which move sequentially in the aboral direction. Initial inhibition results in receptive relaxation and bolus-induced luminal distension, which allows propulsion by the contraction with minimal resistance to flow. Similar to the contraction wave, luminal distension has unique waveform characteristics in normal subjects; both are modulated by bolus volume, bolus viscosity, and posture, suggesting a possible cause-and-effect relationship between the two. Distension contraction plots in patients with dysphagia with normal bolus clearance [high-amplitude esophageal contractions (HAECs), esophagogastric junction outflow obstruction (EGJOO), and functional dysphagia (FD)] reveal two major findings: 1) unlike normal subjects, there is luminal occlusion distal to bolus during peristalsis in certain patients, i.e., with type 3 achalasia and nonobstructive dysphagia; and 2) bolus travels through a narrow lumen esophagus during peristalsis in patients with HAECs, EGJOO, and FD. Aforementioned findings indicate a relative dynamic obstruction to the bolus flow during peristalsis and reduced distensibility of esophageal wall in the bolus segment of the esophagus. We speculate that a normal or supernormal contraction wave pushing bolus against resistance is the mechanism of dysphagia sensation in significant number of patients. Representations of distension and contraction, combined with objective measures of flow timing and distensibility are complementary to the current scheme of classifying esophageal motility disorders based solely on the characteristics of contraction phase of peristalsis. Better understanding of the distensibility of the bolus-containing segment of the esophagus during peristalsis will lead to the development of novel medical and surgical therapies in the treatment of dysphagia in significant number of patients.