Intrabag Pressure Research Articles

Pyloric Functional Lumen Imaging Probe Measurements Are Dependent on Balloon Position.

The functional lumen imaging probe (FLIP) device has been used to assess pyloric dysfunction in patients with gastroparesis. We aim to investigate whether varying FLIP catheter positions affect pyloric FLIP measurements. Patients undergoing endoscopy for chronic unexplained nausea and vomiting (CUNV) or gastroparesis were prospectively enrolled. FLIP balloon was adjusted for 3 positions within the pylorus: (1) proximal position, 75% of FLIP balloon in the duodenum and 25% in the antrum; (2) middle position, 50% in the duodenum and 50% in the antrum; and (3) distal position, 25% in the duodenum and 75% in the antrum. Pylorus cross-sectional area (CSA), intra-bag pressure (P), and distensibility indices (DI) were measured for 30, 40, and 50-mL balloon volumes. Fluoroscopic images were obtained to confirm FLIP balloon geometry. Data was analyzed separately using FLIP Analytic and customized MATLAB software. Twenty-two patients with CUNV (n = 4) and gastroparesis (n = 18) were enrolled. Pressures were significantly higher in the proximal position compared to the middle and distal positions. CSA measurements were significantly higher at the proximal and middle positions for 30-mL and 40-mL volume compared to the distal position values. DI values were significantly lower at the proximal positions for 40-mL and 50-mL distensions when compared to the middle and distal positions. Fluoroscopic images confirmed increased balloon bending when placed mostly in the duodenum. FLIP balloon position within the pylorus directly affects balloon geometry which significantly affects P, CSA, and DI measurements. Standardized pyloric FLIP protocols and balloon design adjustments are needed for the continued application of this technology to the pylorus.

The impact of pneumoperitoneum on esophagogastric junction distensibility during anti-reflux surgery.

We aimed to quantify the contribution of pneumoperitoneum on compliance of the esophagogastric junction (EGJ) during anti-reflux surgery. Compliance of the EGJ is reduced with anti-reflux surgery. EndoFLIP® planimetry can be used to assess dynamic changes of EGJ compliance intraoperatively. It is unclear how pneumoperitoneum impacts intraoperative measurements by EndoFLIP® and the implications thereof on validity of the results. Therefore, determining variability in EndoFLIP® measurements based on pneumoperitoneum is warranted to establish guidelines to interpret clinical outcomes. Primary anti-reflux surgery was performed on 39 consecutive patients with pathologic reflux. Intraoperative EGJ measurements including distensibility index (DI), cross-sectional area (CSA), and intrabag pressure were collected using EndoFLIP® at 0, 10, and 15mmHg of intraperitoneal pressure. Data were acquired pre-procedure, post-hiatal hernia repair, and post-LES augmentation with fundoplications. Patients underwent Nissen (13.2%), Toupet (68.4%), LINX (10.5%), or Hill-fundoplications (7.9%). There was no difference between 0 and 10mmHg of pneumoperitoneum in CSA, pressure, or DI measurements pre-procedure; however, there was a difference between 0 and 15mmHg in pressure (p = 0.016) and DI (p = 0.023) measurements. After LES augmentation, 10mmHg intraperitoneal pressure reduced DI, though the absolute difference is small (2.0 vs. 1.5 mm2/mmHg, p = 0.002). Pneumoperitoneum affected EGJ distensibility at 15mmHg, but not 10mmHg, of insufflation prior to anti-reflux procedures. After anti-reflux surgery, there was a significant variance between 0 and 10mmHg of pneumoperitoneum in pressure and distensibility. The change in pressure appears linear and needs to be considered if procedural modifications are performed based on intraoperative findings and when evaluating clinical outcomes.

The Usefulness of the Measurement of Esophagogastric Junction Distensibility by EndoFLIP in the Diagnosis of Gastroesophageal Reflux Disease.

Background/AimsIncreased esophagogastric junction (EGJ) relaxation is the most important mechanism involved in gastroesophageal reflux disease (GERD). An endoscopic functional luminal imaging probe (EndoFLIPⓇ) is a device used to quantify EGJ distensibility in routine endoscopy. The aim of the current study was to assess the usefulness of EndoFLIPⓇ for the diagnosis of GERD compared to normal controls.MethodsWe analyzed EndoFLIPⓇ data from 204 patients with erosive reflux disease (ERD), 310 patients with nonerosive reflux disease (NERD), and 277 normal subjects. EndoFLIPⓇ uses impedance planimetry to measure 16 cross-sectional areas (CSAs) in conjunction with the corresponding intrabag pressure within a 4.6 cm cylindrical segment of a fluid-filled bag. The EGJ distensibility was assessed using 40 mL volume-controlled distensions.ResultsThe mean distensibility index values were 13.98 mm2/mm Hg in ERD patients, 11.42 mm2/mm Hg in NERD patients, and 9.1 mm2/mm Hg in normal subjects. There were significant differences in EGJ distensibility among the three groups (p<0.001). In addition, the CSAs were significantly higher in the ERD (291.03±160.77 mm2) and NERD groups (285.87±155.47 mm2) than in the control group (249.78±144.76 mm2, p=0.004). We determined the distensibility index cutoff value of EGJ as 10.95 for the diagnosis of GERD by receiver operating characteristic curve analysis.ConclusionsThe EGJ distensibilities of GERD patients were higher than those of normal subjects, regardless of the presence of reflux esophagitis. Thus, the measurement of EGJ distensibility using the EndoFLIPⓇ system could be useful in the diagnosis of GERD.

Clinical utility of cricopharyngeal distensibility measurements during endoscopic myotomy for Zenker’s diverticulum

Flexible endoscopic cricopharyngeal myotomy (FECM) allows minimally invasive treatment of patients with Zenker's diverticulum (ZD); however, retreatment rates are substantial. We hypothesized that the functional lumen imaging probe (FLIP) may provide insight into ZD pathophysiology and serve as an intraprocedural guide to adequacy of myotomy. We prospectively evaluated 11 ZD patients undergoing FECM and compared the baseline cricopharyngeal (CP) distensibility with 16 control subjects. Intraprocedural CP distensibility was measured immediately pre- and postmyotomy. The CP distensibility index (CP-DI) was defined as a ratio of the narrowest cross-sectional area (nCSA) and the corresponding intrabag pressure at 40 mL distension. Same-procedure myotomy extension was undertaken in a subgroup if threshold distensibility changes were not met. ZD patients had reduced baseline nCSA and CP-DI compared with control subjects, (169.6 vs 227.5mm2 [P< .001] and 3.8 vs 7.6mm2/mm Hg [P< .001], respectively). After CP myotomy, both nCSA and CP-DI increased significantly by an average of 74.2mm2 (95% confidence interval [CI], 35.1-113.3; P= .002) and 2.2mm2/mm Hg (95% CI, .6-3.8; P= .01), respectively. In the subgroup with no significant change in CP distensibility after initial myotomy (n= 6), myotomy extension resulted in significant increases in both mean nCSA and CP-DI of 66.6mm2 (95% CI, 16.4-116.8; P= .03) and 1.9mm2/mm Hg (95% CI, .4-3.3; P= .015), respectively. There were no adverse events. CP distensibility is reduced in ZD patients and is partially reversible by FECM. An intraprocedural FLIP CP distensibility measurement is safe and sensitive in detecting myotomy-induced changes. These findings support using FLIP to optimize FECM outcome. Further studies are required to derive precise metrics predictive of clinical response.

Is that 'floppy' fundoplication tight enough?

Laparoscopic fundoplication is the treatment of choice for medically refractory gastroesophageal reflux disease (GERD). Surgeons seek to create a competent valve at the gastroesophageal junction (GEJ) but are careful to construct a 'floppy' fundoplication that is not too tight to minimize side effects. The endoscopic functional luminal-imaging probe (EndoFLIP®) uses impedance planimetry to assess the GEJ intraoperatively. We sought to determine if EndoFLIP variables are associated with symptomatic outcomes following fundoplication. We conducted a retrospective review of prospectively maintained data on subjects who underwent primary laparoscopic fundoplication at a single institution between 2014 and 2018. All patients met standard indications for antireflux surgery. Minimum diameter (Dmin), cross-sectional area (CSA), intra-bag pressure, and distensibility index of the GEJ were obtained at 30mL volumes. GERD Health Related Quality of Life (GERD-HRQL) surveys were administered pre- and postoperatively. Patients were excluded if they underwent fundoplication without EndoFLIP assessment or if they did not complete a postop GERD-HRQL survey. Receiver operating characteristic curves were used to determine if EndoFLIP measurements were correlated with symptomatic outcomes. Forty-three patients met inclusion criteria. The change in Dmin and CSA measures during fundoplication were associated with daily or more frequent heartburn at 6 or more months postop. A decrease in Dmin of 0.15mm or less (AUC = 0.718, sensitivity: 71%, specificity: 69%) and a decrease in CSA of 1.5mm2 or less (AUC = 0.728, sensitivity: 71%, specificity: 70%) were associated with severe heartburn. GEJ opening dynamics attained by EndoFLIP appear to be associated with symptomatic outcomes. When the Dmin and CSA do not decrease by a defined threshold, heartburn is more likely to be severe at 6 or more months postoperatively. This suggests that the fundoplication may not be tight enough to prevent persistent or recurrent GERD.

Role of Bitter Taste Receptors in Regulating Gastric Accommodation in Guinea Pigs.

Taste stimulants play important roles in triggering digestion and absorption of nutrients and in toxin detection, under the control of the gut-brain axis. Bitter compounds regulate gut hormone secretion and gastrointestinal motility through bitter taste receptors (TAS2Rs) located in the taste buds on the tongue and in the enteroendocrine cells. Gastric accommodation (GA) is an important physiologic function. However, the role of TAS2R agonists in regulating GA remains unclear. To clarify whether GA is influenced by bitter stimulants, we examined the effect of TAS2R agonist denatonium benzoate (DB), administered intraorally and intragastrically, by measuring the consequent intrabag pressure in the proximal stomach of guinea pigs. Effects of the Kampo medicine rikkunshito (RKT) and its bitter components liquiritigenin and naringenin on GA were also examined. Intraoral DB (0.2 nmol/ml) administration enhanced GA. Intragastric DB administration (0.1 and 1 nmol/kg) promoted GA, whereas higher DB doses (30 μmol/kg) inhibited it. Similar changes in GA were observed with intragastric (1000 mg/kg) and intraoral (200 mg/ml) RKT administration. Liquiritigenin and naringenin also promoted GA. These findings suggest that GA is affected by the stimulation of TAS2Rs in the oral cavity or gut in guinea pigs.

Novel Intra-Procedural Distensibility Measurement Accurately Predicts Immediate Outcome of Pneumatic Dilatation for Idiopathic Achalasia.

Often 2-3 graduated pneumatic dilatations (PD) are required to treat achalasia as there is no current intra-procedural predictor of clinical response. Distensibility measurements using functional lumen imaging probe (FLIP) may provide an intra-procedural predictor of outcome. Our aim was to determine the optimal criterion for esophagogastric junction (EGJ) distensibility measurements during PD that predicts immediate clinical response. EGJ distensibility was prospectively measured using FLIP immediately pre- and post-PD. The EGJ distensibility index (EGJ-DI) was defined as a ratio of the narrowest cross-sectional area and the corresponding intra-bag pressure at 40 ml distension. Immediate and short-term clinical responses were defined as Eckardt score ≤3 assessed 2 weeks Post-PD and at 3-month follow-up, respectively. In 54 patients, we performed thirty-seven 30 mm; twenty 35 mm and six 40 mm PDs. The short-term response rate to the graded PD was 93% (27/29) in newly diagnosed achalasia; 87% (13/15) and 70% (7/10) in those who had relapsed after previous PD and Heller's Myotomy, respectively. Among those demonstrating an immediate response, EGJ-DI increased by an average of 4.5 mm2/mmHg (95% CI (3.5, 5.5) (P<0.001). Within-subject Δ EGJ-DI was highly predictive of immediate clinical response with AUROC of 0.89 (95% CI [0.80, 0.98], P<0.001). An increment in EGJ-DI of 1.8 mm2/mmHg after a single PD predicts an immediate response with an accuracy of 87%. FLIP-measured Δ EGJ-DI is a novel intra-procedural tool that accurately predicts immediate clinical response to PD in achalasia. This technique may potentially dictate an immediate mechanism to "step-up" dilator size within a single endoscopy session.

Influence of Age and Eosinophilic Esophagitis on Esophageal Distensibility in a Pediatric Cohort.

Sequelae of eosinophilic esophagitis (EoE) include food impaction and esophageal stricture. Duration of inflammation is a predicted risk factor; however, complications remain unpredictable. Studies using the functional lumen imaging probe (FLIP) have demonstrated decreased distensibility of the esophagus in adult patients with EoE. As the impact of inflammation on the developing esophagus is unknown, we investigated esophageal distensibility in a pediatric cohort to determine the effect of age, ongoing inflammation, and fibrotic features on distensibility. We conducted a prospective observational study at two tertiary pediatric institutions. Subjects underwent FLIP evaluation during endoscopy to determine distensibility of the esophagus. During stepwise distension, simultaneous intrabag pressure and 16 channels of cross-sectional areas were measured. The minimal diameter at maximal esophageal distention at an intrabag pressure of 40 mm Hg was identified. Distensibility was compared between EoE and non-EoE subjects and between clinical variables within the EoE cohort. Potential confounding variables were identified. Forty-four non-EoE and 88 EoE subjects aged 3-18 years were evaluated. Age positively correlated with esophageal distensibility in the non-EoE cohort, but this trend was not observed in the EoE population. Subjects with EoE had reduced distensibility even after adjusting for age. Active inflammation (eosinophils >15 eos/high-power field), histological lamina propria fibrosis, and various features of a fibrotic phenotype (stricture, food impaction, circumferential rings on endoscopy) were associated with decreased distensibility within the EoE cohort. FLIP was safe, feasible, and well tolerated. These findings suggest that remodeling occurs in the pediatric EoE population, warranting early diagnosis and initiation of therapy prior to the onset of disease complications.

Consistency and effect of body position change on measurement of upper and lower esophageal sphincter geometry using impedance planimetry in a canine model.

The EndoFLIP (Endolumenal Functional Lumen Imaging Probe, Crospon Inc, Galway, Ireland) device uses the technique of impedance planimetry to evaluate dimensions and distensibility of the upper and lower esophageal sphincter. The null hypotheses for this study were that EndoFLIP variables would be stable between anesthestic episodes and would not be affected by body position when evaluating the upper and lower esophageal sphincters in healthy dogs. During each of three consecutive general anesthesia episodes administered to eight healthy adult research colony dogs with a standardized protocol, the EndoFLIP catheter was positioned to measure cross-sectional area, intrabag pressure, upper and lower esophageal sphincter length at two different balloon fill volumes (30 and 40 mL) and two body positions (lateral and dorsal recumbency). From these measured variables, a distensibility index was also calculated. Mixed effect analysis of variance was used to evaluate the fixed marginal and interaction effects of anesthesia episode, body position, and balloon volume on measured and calculated variables. For the upper esophageal sphincter significant interactions were present between anesthetic episode and body position for all variables except intrabag pressure; adjusting for body position significant differences were present between anesthetic episodes for all variables except distensibility index; adjusting for anesthetic episode cross-sectional area, intrabag pressure, upper esophageal sphincter length and distensibility index were all affected by body position. For the lower esophageal sphincter distensibility index was the only variable where a significant interaction between anesthesia episode and body position occurred; cross-sectional area, intrabag pressure, and lower esophageal length were not significantly affected by anesthesia episode when adjusting for body position; distensibility index was the only variable significantly affected by body position. Measurements of the geometry of the lower esophageal sphincter as measured by the EndoFLIP device were consistent under conditions of general anesthesia. Similar measurements taken at the upper esophageal sphincter displayed greater variability between anesthetic episodes and were affected to a greater extent by body position. Body position should be standardized in studies using the EndoFLIP to assess geometric and functional characteristics of the upper and lower esophageal sphincters.

Acotiamide improves stress-induced impaired gastric accommodation.

Gastric accommodation is a reflex reaction related to gastric reservoir function. Psychological stress, such as anxiety, inhibits gastric accommodation in humans. Acotiamide enhances the effect of acetylcholine in the enteric nervous system, enhances gastric contractility, and accelerates delayed gastric emptying. However, the effect of acotiamide on stress-induced impaired gastric accommodation remains unclear. Therefore, we examined the effect of acotiamide on gastric accommodation and stress-induced impaired gastric accommodation using a conscious guinea pig model. A polyethylene bag was inserted through the distal region of the gastric body into the proximal stomach of 5-week-old male Hartley guinea pigs. Gastric accommodation was evaluated by measuring the intrabag pressure in the proximal stomach after oral administration of a liquid meal. In the stress model, animals were subjected to water-avoidance stress. Acotiamide (Z-338) or nizatidine was administered subcutaneously. Fecal output was determined as the number of fecal pellets. Administration of the liquid meal significantly decreased intrabag pressure, indicating induction of gastric accommodation. Acotiamide treatment prolonged liquid meal-induced gastric accommodation and significantly increased the number of fecal pellets compared to controls. Water-avoidance stress significantly inhibited liquid meal-induced gastric accommodation. Pretreatment with acotiamide significantly improved stress-induced impaired gastric accommodation. The number of fecal pellets in the acotiamide group increased significantly compared to controls. Acotiamide, but not nizatidine, significantly decreased gastric emptying. Acotiamide prolongs gastric accommodation and improves stress-induced impaired gastric accommodation, indicating a potential role for acotiamide in the treatment of functional dyspepsia through its effects on gastric accommodation reactions.

Impairment of gastric accommodation induced by water-avoidance stress is mediated by 5-HT2B receptors.

Psychological stress has been shown to impair gastric accommodation (GA), but its mechanism has not been elucidated. This study was conducted to clarify the role of 5-HT2B receptors in a guinea pig model of stress-induced impairment of GA. Gastric accommodation was evaluated by measuring the intrabag pressure in the proximal stomach after administration of a liquid meal. The guinea pigs were subjected to water-avoidance stress. The role of 5-HT2B receptors in impairment of GA was investigated by administering a 5-HT2B receptor agonist (BW723C86) or antagonist (SB215505), the traditional Japanese medicine rikkunshito (RKT), a muscarinic M3 receptor antagonist (1,1-dimethyl-4-diphenylacetoxypiperidium iodide [4-DAMP]), or a nitric oxide synthase inhibitor (Nω -nitro-L-arginine [L-NNA]). In normal animals, liquid meal-induced GA was inhibited by BW723C86, but was not affected by SB215505. The inhibition of GA by BW723C86 was reversed by co-administration of 4-DAMP. Compared to normal animals, GA in stressed animals was significantly inhibited. SB215505 and RKT significantly suppressed stress-induced impairment of GA. After meal administration, the level of cyclic guanosine monophosphate in gastric fundus tissue increased by approximately twofold in normal animals, but did not change in stressed animals. The inhibition of GA by L-NNA was suppressed by SB215505 or RKT. At a dose that did not affect GA in normal animals, BW723C86 exacerbated the impairment of GA in stressed animals. Stress-induced impairment of GA may be mediated by an increased responsiveness of 5-HT2B receptors, and activation of the 5-HT2B receptor signaling pathway may have an inhibitory effect on nitric oxide function.

Effect of 5-hydroxytryptamine receptor 4 agonist mosapride on human gastric accommodation.

Impaired gastric accommodation is one of the major features of functional dyspepsia. Mosapride citrate is a 5-hydroxytryptamine receptor 4 (5-HT4) agonist, which is shown to improve upper abdominal symptoms. However, effect of mosapride on gastric accommodation was not clear. We tested the hypothesis that mosapride enhances the gastric accommodation in normal individuals. Fourteen male healthy volunteers completed this study. Single administration of mosapride or placebo was performed randomly with more than 1-week interval. Subjects swallowed a triple-lumen polyvinyl tube with a polyethylene bag. The bag was positioned in the proximal stomach and the minimal distending pressure (MDP) was determined. The ramp distension starting from the MDP was then performed and subjects were instructed to score their perception using ordinate scales. Next the intra-bag pressure was set at MDP + 2mmHg and a liquid meal was administered 30min later, and the intra-bag volume was recorded for 60min. We compared the MDP, perception scores, and the intra-bag volume changes by administering placebo and mosapride. Minimal distending pressure was not significantly different in subjects receiving mosapride or placebo. Treatment with mosapride had no effect on intra-bag pressures or volumes inducing first sensation or discomfort. Gastric accommodation, expressed as the difference between pre- and postmeal intra-bag volumes, and the percent change of the intra-bag volumes by the meal was significantly enhanced by mosapride compared with placebo. This is the first study clearly demonstrating that single administration of 5-HT4 agonist can enhance gastric accommodation in humans. (Umin.ac.jp, number UMIN000014063).

The Functional Lumen Imaging Probe Detects Esophageal Contractility Not Observed With Manometry in Patients With Achalasia

The functional lumen imaging probe (FLIP) could improve the characterization of achalasia subtypes by detecting nonocclusive esophageal contractions not observed with standard manometry. We aimed to evaluate esophageal contractions during volumetric distention in patients with achalasia using FLIP topography. Fifty-one treatment-naive patients with achalasia, defined and subclassified by high-resolution esophageal pressure topography, and 10 asymptomatic individuals (controls) were evaluated with the FLIP during endoscopy. During stepwise distension, simultaneous intrabag pressures and 16 channels of cross-sectional areas were measured; data were exported to software that generated FLIP topography plots. Esophageal contractility was identified by noting periods of reduced luminal diameter. Esophageal contractions were characterized further by propagation direction, repetitiveness, and based on whether they were occluding or nonoccluding. Esophageal contractility was detected in all 10 controls: 8 of 10 had repetitive antegrade contractions and 9 of 10 had occluding contractions. Contractility was detected in 27% (4 of 15) of patients with type I achalasia and in 65% (18 of 26, including 9 with occluding contractions) of patients with type II achalasia. Contractility was detected in all 10 patients with type III achalasia; 8 of these patients had a pattern of contractility that was not observed in controls (repetitive retrograde contractions). Esophageal contractility not observed with manometry can be detected in patients with achalasia using FLIP topography. The presence and patterns of contractility detected with FLIP topography may represent variations in pathophysiology, such as mechanisms of panesophageal pressurization in patients with type II achalasia. These findings could have implications for additional subclassification to supplement prediction of the achalasia disease course.

Measurement of Esophagogastric Junction Distensibility May Assist in Selecting Patients for Endoluminal Gastroesophageal Reflux Disease Surgery: Author's Reply.

TO THE EDITOR: We thank the author for his interest in our manuscript.1,2 During the transoral incisionless fundoplication (TIF) procedure, a retractor is anchored at the esophagogastric junction (EGJ) after which tension is applied to advance the EGJ caudally.3,4 Therefore, we agree that lengthening of the EGJ is a substantial mode of action of the TIF procedure. In addition, transmural placement of polypropylene fasteners creates an endoluminal fundoplication through permanent serosa-to-serosa or serosa-to-muscularis fusion with tightening of the distal esophagus, which decreases EGJ diameter and distensibility. 5,6 Therefore, we believe that EGJ distensibility can be an important parameter for evaluation of endoluminal gastroesophageal reflux disease (GERD) surgery like the TIF procedure, although we agree that the immediate decrease in EGJ distensibility after the TIF procedure might be the consequence of postoperative edema.7 It is important to note that consensus is lacking with regard to analysis of parameters obtained from EndoFLIP measurements. According to the most widely accepted approach, EGJ distensibility is assessed based on the narrowest cross sectional area and corresponding intra-bag pressure. Standardized methods to evaluate the change in EGJ length with the EndoFLIP technique are still to be defined. Therefore, we anticipate that development of more extensive biomechanical measures will result in more accurate interpretation of EndoFLIP data. In the present study, we used the EndoFLIP technique in the preoperative diagnostic work-up to predict postoperative outcome. Recent studies highlight that the EndoFLIP technique could be used as an intra-operative quality tool during either anti-reflux or achalasia surgery.8,9 Teitelbaum et al10 described that the EndoFLIP technique is able to guide laparoscopic Heller myotomy and peroral esophageal myotomy to obtain an ideal postoperative EGJ distensibility with regard to both postoperative achalasia and reflux symptoms. In addition, Perretta et al8 provided observational data about the change in EGJ distensibility and diameter during different stages of laparoscopic Nissen fundoplication. In the future, the EndoFLIP method could potentially be used during laparoscopic fundoplication to prevent creation of a hypercompetent valve with associated postoperative symptoms (eg, dysphagia or gas bloating).8 It therefore appears that the EndoFLIP technique has considerable potential as an intra-operative tool. On the other hand, currently available methodologies limit its role with regards to the assessment of EGJ distensibility in the preoperative diagnostic work-up or in post-procedure evaluation of patients undergoing endoluminal GERD surgery like TIF. Additional research is necessary to define the role of the EndoFLIP technique for both the preoperative work-up and tool for intraoperative calibration.

The effect of incremental distal gastric myotomy lengths on EGJ distensibility during POEM for achalasia.

During peroral esophageal myotomy (POEM) for the treatment of achalasia, the optimal distal gastric myotomy length is unknown. In this study, we used a functional lumen imaging probe (FLIP) to intraoperatively measure the effect of variable distal myotomy lengths on esophagogastric junction (EGJ) distensibility. EGJ distensibility index (DI) (minimum cross-sectional area divided by intrabag pressure) was measured with FLIP after each operative step. Each patient's myotomy was performed in four increments from proximal to distal: (1) an esophageal myotomy (from 6 cm proximal to the EGJ to 1 cm proximal to it), (2) a myotomy ablating the lower esophageal sphincter (LES) complex (from 1 cm proximal to the EGJ to 1 cm distal to it), (3) an initial gastric extension (from 1 cm distal to the EGJ to 2 cm distal), and (4) a final gastric extension (from 2 cm distal to the EGJ to 3 cm distal). Measurements were taken in 16 achalasia patients during POEM. POEM resulted in an overall increase in DI (pre 1.2 vs. post 7.2 mm(2)/mmHg, p < .001). Initial creation of the submucosal tunnel resulted in a threefold increase in DI (1.2 vs. 3.6 mm(2)/mmHg, p < .001). When the myotomy was then performed in a stepwise fashion from proximal to distal, the initial esophageal myotomy component had no effect on DI. Subsequent myotomy extension across the LES complex resulted in an increase in DI, as did the initial gastric myotomy extension (to 2 cm distal to the EGJ). The final gastric myotomy extension (to 3 cm distal) had no further effect. During POEM, creation of the submucosal tunnel prior to myotomy resulted in a marked improvement in EGJ physiology. Myotomy extension across the LES complex and to 2 cm onto the gastric wall resulted in the normalization of EGJ distensibility, whereas subsequent extension to 3 cm distal to the EGJ did not increase compliance further.

Utilizing functional lumen imaging probe topography to evaluate esophageal contractility during volumetric distention: a pilot study.

The functional lumen imaging probe (FLIP) measures luminal cross-sectional area and pressure during volumetric distension. By applying novel customized software to produce FLIP topography plots, organized esophageal contractility can be visualized and analyzed. We aimed to describe the stimulus thresholds and contractile characteristics for distension-induced esophageal body contractility using FLIP topography in normal controls. Ten healthy controls were evaluated during endoscopy with FLIP. During stepwise bag distension, simultaneous intra-bag pressure and luminal diameter measurements were obtained and exported to a MatLab program to generate FLIP topography plots. The distension volume, intra-bag pressure, and maximum esophageal body diameters were measured for the onset and cessation of repetitive antegrade contractions (RACs). Contraction duration, interval, magnitude, and velocity were measured at 8 and 3-cm proximal to the esophagogastric junction. Eight of ten subjects demonstrated RACs at a median onset volume of 29 mL (IQR: 25-38.8), median intra-bag pressure of 10.7 mmHg (IQR: 8.6-15.9), and median maximum esophageal body diameter of 18.5 mm (IQR: 17.5-19.6). Cessation of RACs occurred prior to completion of the distension protocol in three of the eight subjects exhibiting RACs. Values of the RAC-associated contractile metrics were also generated to characterize these events. Distension-induced esophageal contractions can be assessed utilizing FLIP topography. RACs are a common finding in asymptomatic controls in response to volume distention and have similar characteristics to secondary peristalsis and repetitive rapid swallows.

Tu1141 Esophageal Body Response to Volumetric Distension in Patients With Achalasia: A Study Utilizing the Functional Lumen Imaging Probe

Background: Achalasia subtypes are differentiated by esophageal body pressurization patterns identified with esophageal pressure topography (EPT). The functional lumen imaging probe (FLIP), which measures cross-sectional area (CSA) as a function of pressure during volume distension, may enhance characterization of achalasia subtypes by detection of non-occlusive esophageal contractions not appreciated with standard manometric assessment. Our aim was to evaluate the esophageal body response to volumetric distention in achalasia patients using a new analysis paradigm, FLIP topography. Methods: Treatment-naive patients with achalasia defined and sub-classified by EPT were evaluated with the FLIP (Crospon, Inc, Gallway, Ireland) during endoscopy. The FLIP consisted of an infinitely compliant cylindrical bag with 17 ring impedance-planimetry electrodes spaced 1 cm apart and a solid-state transducer for simultaneous measurements of 16 channels of CSA and intra-bag pressure. The distal end of the FLIP was positioned across the esophagogastric junction to allow three intragastric channels. Stepwise bag distension from 5 to 60 mL was conducted and CSA and intrabag pressure data was exported to MATLABTM (The Math Works, Natick, MA). A customized MATLAB program generated FLIP topography plots (Figure) of CSA by axial position over time. Esophageal reactivity was identified by noting periods of reduced CSA as a surrogate for contractions. The intrabag pressure and distension volume at the onset of esophageal body contraction was measured and compared between achalasia subtypes using non-parametric tests. Results: 19 patients (ages 19-72; 6 female) with achalasia (2 type I, 11 type II, and 6 type III) were studied. Esophageal reactivity was observed in 0/2 type I, 6/11 (55%) type II, and 6/6 type III patients. Of patients that exhibited reactivity, numerically, but not statistically significantly, higher pressures at reactivity onset were seen in type II [median (IQR): 18.8mmHg (8.8-32.4)] than type III [10.2 (10-13.2), p =0.42] achalasia patients. The distension volumes at the onset of reactivity between subtypes were similar [type II: 27.5mL (25-30); type III: 27.5 (21.25-30); p =0.74]. Retrograde contractions were observed in 4/6 type II patients and 5/6 type III patients demonstrating reactivity. Conclusions: Assessment with FLIP topography detected variable reactivity to esophageal body distension between achalasia subtypes and among patients with type II achalasia. In approximately half of our studied type II achalasia patients, FLIP topography demonstrated some degree of preserved esophageal body contractility. Subclassification by esophageal body reactivity may help predict symptom development and/or response to treatment.

Tu1971 Circular & Longitudinal Muscles Slide Against Each Other in Opposite Directions During Peristalsis & Transient Lower Esophageal Sphincter Relaxation

planimetry data from each subject were exported to MATLABTM (The Math Works, Natick, MA). A customized MATLAB program generated a plot (Figure) that included distension volume (bottom panel), 16 channels of diameter changes (middle panel) and intrabag pressure (top panel) over whole study period. The start of reactivity defined by nonpropagating or intermittent contractions and the onset of continuous secondary peristalsis were identified by noting periods of reduced diameter as a surrogate for contraction. The pressure and volume at the onset of these events were measured and compared using nonparametric tests. Results: All healthy subjects had evidence of reactivity and 8 of 10 had secondary peristaltic contractions either lasting to the maximal distension volume (60 ml in 6 subjects) or stopping earlier (35-45 ml in 2 subjects). Thirteen EoE patients had reactivity, but only 7 had secondary peristaltic contractions, few than healthy controls but not reaching statistical significance (see Table). The threshold intrabag pressure values associated with onset of reactivity and onset of secondary peristaltic contractions were significantly higher in the EoE group compared with healthy controls (see Table). The intrabag volumes at onset of reactivity and onset of continuous contractions were also significantly higher in the EoE group (see Table). Conclusions: Patients with EoE require higher intra-esophageal pressures to generate esophageal reactivity and secondary peristalsis when compared with healthy controls. Of the EoE patients who develop reactivity with balloon distention, significantly fewer went on to develop evidence of secondary peristalsis than healthy controls.Whether this difference is associated with known clinical complications of EoE such as food impaction or GERD requires further study.

Regional variation in distal esophagus distensibility assessed using the functional luminal imaging probe (FLIP)

This study aimed to evaluate the spatial variation in esophageal distensibility in normal subjects using a novel multichannel functional luminal imaging probe (FLIP). Ten healthy subjects (four men, age 21-49years) were evaluated during endoscopy with a high-resolution impedance planimetry probe (FLIP) positioned through the esophagogastric junction (EGJ) and distal 10cm of the esophageal body. Stepwise bag distensions using 5-mL increments from 0 to 60mL were conducted, and simultaneous measurements of cross-sectional area (CSA) and the associated intrabag pressure from each subject were analyzed using a customized MATLAB™ program. The distensibility along the esophagus was determined and compared between the EGJ and interval locations at 2-5cm and 6-10cm above the EGJ. The pressure-CSA relationship was nearly linear among sites at lower pressures (0 to 7.5mmHg) and reached a distension plateau at pressures ranging from 8 to 24mmHg. The location of greatest distensibility was 4cm above the EGJ. Although the CSAs of individual recording loci were not significantly different, there was a significant difference between the mean CSAs when comparing the region 2 to 5cm proximal to EGJ with that 6 to 10cm proximal to the EGJ. There were significant regional differences in distensibility along the distal esophagus with lower values in the proximal part compared with more distal part. The greatest distensibility was noted to occur at about 4cm above the EGJ in close proximity to the location of the contractile deceleration point and phrenic ampulla.

Su2058 Chronic Homotypic Stress May Affect GI Functions Through Upregulation of Oxytocin Within PVN-DVC Neurocircuits

Background and Aims: Gastric accommodation is a reflex reaction related to gastric reservoir function by which the gastric fundus is relaxed when food enters the stomach. Gastric fundus relaxation induced by accommodation is mediated by nitric oxide (NO), produced by NO neurons. Depletion of NO thus inhibits gastric accommodation. Serotonin (5-HT) 2B receptors exist at the gastric fundus and 5-HT2B receptor activation induces contraction of smoothmuscle. However, the relationship between 5-HT2B receptor and gastric accommodation has not been elucidated. This study investigated the involvement of 5-HT2B receptors and the relationship to NO in gastric accommodation using a conscious guinea pig model. Methods: A polyethylene bag was inserted through the distal part of the gastric body and placed in the proximal stomach of 5-week-old male Hartley guinea pigs. Measurement of gastric accommodation was performed as follows: air (6 mL) was injected into the polyethylene bag at a rate of 2 mL/min, and intrabag pressure at baseline was recorded for 1 min. Immediately after oral administration of a liquid meal (4 mL, 1.7 kcal), air (6 mL) was again injected into the bag, and intrabag pressure was recorded 6 times, for 1 min each time at intervals of 5 min. NG-nitro-L-arginine (L-NNA) (a NO synthase inhibitor; 1-10 mg/kg) or BW723C86 (a 5-HT2B receptor agonist; 5 mg/kg) were administered orally 60 or 20 min before the liquid meal. SB215505 (a 5-HT2B receptor antagonist; 6 mg/kg), rikkunshito (traditional Japanese medicine; 250-1,000 mg/kg), or isoliquiritigenin (component of rikkunshito with 5-HT2B receptor antagonism; 0.125-4 mg/kg) were administered orally 30 min before the liquid meal. Results: Intrabag pressure was significantly decreased 5-25 min after liquid meal administration compared to baseline levels. SB215505 (6 mg/kg) did not affect liquid meal-induced decreases in intrabag pressure. Conversely, BW723C86 (5 mg/kg) significantly inhibited liquid meal-induced decreases in intrabag pressure. The effect of BW723C86 was abolished by co-administration of SB215505 (6 mg/kg). L-NNA dosedependently inhibited liquid meal-induced decreases in intrabag pressure and completely blocked the decrease at a dose of 10 mg/kg (-1.91 ± 0.83 vs. 0.05 ± 1.01 mmHg; p , 0.01). SB215505 (6 mg/kg), rikkunshito (1000 mg/kg), and isoliquiritigenin (4 mg/kg) significantly ameliorated L-NNA (10 mg/kg)-induced inhibition of decreases in intrabag pressure (0.03 ± 1.01 vs. -1.77 ± 0.62 mmHg, p , 0.01; -0.16 ± 0.46 vs. -1.79 ± 0.74 mmHg, p , 0.001; -0.38 ± 0.76 vs. -1.82 ± 0.58 mmHg, p , 0.01). Conclusions: The activation of 5-HT2B receptor inhibits gastric accommodation and may be regulated in part by NO neurons.