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Interrater Reliability of Functional Lumen Imaging Probe Panometry and High-Resolution Manometry for the Assessment of Esophageal Motility Disorders

Chen, Joan W; Khan, Abraham; Chokshi, Reena V; Clarke, John O; Fass, Ronnie; Garza, Jose M; Gupta, Milli; Gyawali, C Prakash; Jain, Anand S; Katz, Philip; Konda, Vani; Lazarescu, Adriana; Lynch, Kristle L; Schnoll-Sussman, Felice; Spechler, Stuart J; Vela, Marcelo F; Yadlapati, Rena; Schauer, Jacob M; Kahrilas, Peter J; Pandolfino, John E; Carlson, Dustin A
INTRODUCTION:High-resolution manometry (HRM) and functional lumen imaging probe (FLIP) are primary and/or complementary diagnostic tools for the evaluation of esophageal motility. We aimed to assess the interrater agreement and accuracy of HRM and FLIP interpretations. METHODS:Esophageal motility specialists from multiple institutions completed the interpretation of 40 consecutive HRM and 40 FLIP studies. Interrater agreement was assessed using intraclass correlation coefficient (ICC) for continuous variables and Fleiss' κ statistics for nominal variables. Accuracies of rater interpretation were assessed using the consensus of 3 experienced raters as the reference standard. RESULTS:Fifteen raters completed the HRM and FLIP studies. An excellent interrater agreement was seen in supine median integral relaxation pressure (ICC 0.96, 95% confidence interval 0.95-0.98), and a good agreement was seen with the assessment of esophagogastric junction (EGJ) outflow, peristalsis, and assignment of a Chicago Classification version 4.0 diagnosis using HRM (κ = 0.71, 0.75, and 0.70, respectively). An excellent interrater agreement for EGJ distensibility index and maximum diameter (0.91 [0.90-0.94], 0.92 [0.89-0.95]) was seen, and a moderate-to-good agreement was seen in the assignment of EGJ opening classification, contractile response pattern, and motility classification (κ = 0.68, 0.56, and 0.59, respectively) on FLIP. Rater accuracy for Chicago Classification version 4.0 diagnosis on HRM was 82% (95% confidence interval 78%-84%) and for motility diagnosis on FLIP Panometry was 78% (95% confidence interval 72%-81%). DISCUSSION:Our study demonstrates high levels of interrater agreement and accuracy in the interpretation of HRM and FLIP metrics and moderate-to-high levels for motility classification in FLIP, supporting the use of these approaches for primary or complementary evaluation of esophageal motility disorders.
PMID: 37042784
ISSN: 1572-0241
CID: 5559732

Non-Invasive, MultiOmic and MultiCompartmental Biomarkers of Reflux Disease: A Systematic Review

Farooqi, Muhammad S; Podury, Sanjiti; Crowley, George; Javed, Urooj; Li, Yiwei; Liu, Mengling; Kwon, Sophia; Grunig, Gabriele; Khan, Abraham R; Francois, Fritz; Nolan, Anna
ISSN: 2772-5723
CID: 5422412

Inter- and intra-rater agreement of interpretation of functional lumen imaging probe in healthy subjects

Yadlapati, Rena; Gyawali, C Prakash; Carlson, Dustin A; Pandolfino, John E; Fass, Ronnie; Khan, Abraham; Lin, Haiying; Richter, Joel E; Vela, Marcelo F; Vaezi, Michael; Clarke, John O
BACKGROUND:The functional lumen imaging probe (FLIP) evaluates esophagogastric junction (EGJ) opening and esophageal contractility. Both post hoc and real-time analyses are possible, but reproducibility and reliability of analysis remain undefined. This study assesses inter- and intra-rater agreement of normative FLIP measurements among novice and experienced users. METHODS:Eight motility experts from different institutions independently evaluated de-identified video recordings from 27 asymptomatic healthy subjects using FLIP. Interpretation methods simulating a post-procedure and a live procedure setting were tested. Novice FLIP users (n = 3) received training prior to post-procedure interpretation. Experienced FLIP users (n = 5) interpreted using both methods. Users recorded maximum EGJ and distal esophageal body diameter, distensive pressure, and EGJ distensibility index (EGJ-DI), at balloon fill volumes of 50-, 60-, and 70 ml, as well as repetitive antegrade contractions (RACs). Inter- and intra-rater agreements of diameters, distensive pressure and EGJ-DI were assessed by intra-class correlation coefficient (ICC) and Pearson's correlation coefficient (PCC). Percentage agreement evaluated inter- and intra-rater reliability for RACs. KEY RESULTS/RESULTS:/mmHg, maximum EGJ diameter 18.6 mm, distensive pressure at maximum EGJ diameter 48.1 mmHg, and distal esophageal body diameter 19.5 mm. CONCLUSIONS AND INFERENCES/CONCLUSIONS:Normative FLIP parameters can be reliably extracted from FLIP videos using both real-time and post hoc analyses, with high reliability between experienced and novice users.
PMID: 36480408
ISSN: 1365-2982
CID: 5378762

Clinical role of ambulatory reflux monitoring in PPI non-responders: Recommendation statements

Yadlapati, Rena; Gawron, Andrew J; Gyawali, C Prakash; Chen, Joan; Clarke, John; Fass, Ronnie; Jain, Anand; Lynch, Kristle; Khan, Abraham; Katz, Philip O; Katzka, David A; Richter, Joel; Schnoll-Sussman, Felice; Spechler, Stuart J; Vaezi, Michael F; Vela, Marcelo; Pandolfino, John E
BACKGROUND:Optimal ambulatory reflux monitoring methodology in symptomatic reflux patients continues to be debated. AIMS/OBJECTIVE:To utilise published literature and expert opinion to develop recommendation statements addressing use of ambulatory reflux monitoring in clinical practice METHODS: The RAND Appropriateness Method (RAM) was utilised among 17 experts with discussion, revision and two rounds of ranking of recommendation statements. Ambulatory reflux monitoring protocol, methodology and thresholds ranked as appropriate by ≥80% of panellists met the criteria for appropriateness. RESULTS:Prolonged (96-h recommended) wireless pH monitoring off proton pump inhibitor (PPI) was identified as the appropriate diagnostic tool to assess the need for acid suppression in patients with unproven gastro-oesophageal reflux disease (GERD) and persisting typical reflux symptoms despite once-daily PPI. Acid exposure time (AET) <4.0% on all days of monitoring with negative reflux-symptom association excludes GERD and does not support ongoing PPI treatment. Conversely, AET >6.0% across ≥2 days is conclusive evidence for GERD and supports treatment for GERD, while AET >10% across ≥2 days identifies severe acid burden that supports escalation of anti-reflux treatment. In previously proven GERD, impedance-pH monitoring on PPI is helpful in defining refractory GERD and mechanisms of continued symptoms; the presence of <40 reflux events, AET <2.0% and a negative reflux-symptom association does not support escalation of anti-reflux treatment. In contrast, AET > 4.0% and positive reflux-symptom association support escalation of anti-reflux treatment, including use of invasive therapeutics. CONCLUSIONS:Statements meeting appropriateness for average clinical care have been identified when utilising reflux monitoring in patients with typical reflux symptoms and PPI non-response.
PMID: 35971888
ISSN: 1365-2036
CID: 5299852

A Low Acid Diet Rarely Normalizes Pathologic Gastroesophageal Reflux Disease [Meeting Abstract]

Skryd, A; Knotts, R; Khan, A
Introduction: Prolonged esophageal 96-hour wireless pH monitoring can reliably diagnose pathologic gastroesophageal reflux disease (GERD), with each study providing ample time to assess dietary influences on esophageal acid exposure time (AET). There is a paucity of literature detailing the influence of acidity in the diet on esophageal AET during ambulatory pH testing. This study aimed to evaluate differences in the quantity of acid reflux during days of high acid and low acid diets during prolonged wireless pH studies.
Method(s): 96 patients who underwent esophageal 96-hour wireless pH monitoring for evaluation of potential GERD were included in the study. The patients were educated on foods of high and low acidity and instructed to consume a primarily high acid diet on one day and a primarily low acid diet on a separate day during the recording period while detailing all consumed meals in a diary. Each food diary was physician confirmed for accuracy. Demographics, BMI, and comorbidities were also assessed. Patients were considered to have pathologic GERD if the average esophageal AET was .6% for the entire pH study and considered normal on an individual day if esophageal AET was , 4%. Statistical relationships between proportions were evaluated by Fisher's exact test and continuous variables were compared using t-tests. Box plots were used to graphically represent the spread of data.
Result(s): Pathologic GERD was found in 30 patients (31.3%) of which the majority (64.7%) recorded their lowest AET on their low acid diet day (Table). Despite this, only 13.3% of patients with pathologic GERD achieved normal acid reflux on their low acid diet day. The highest AET occurred on the high acid diet day for all 30 patients (100%) with pathologic GERD and 36 (54.55%) of the 66 patients without pathologic GERD. In comparison to the high acid diet day, the low acid diet day reduced mean AET from 13% to 6.9% in those with pathologic GERD (Figure) and from 4.2% to 1.8% in patients negative for pathologic GERD. Average body mass index (BMI) was higher in patients with pathologic GERD, while age, sex, and number of the most common reflux symptom did not differ between each group.
Conclusion(s): Acid reflux is reduced overall with a low acid diet in patients with and without pathologic GERD. The majority of patients with pathologic GERD experience their lowest amount of acid reflux during a day of a low acid diet, but only a small minority normalize their acid reflux on that day
ISSN: 1572-0241
CID: 5514972

Non-Invasive, MultiOmic and MultiCompartmental Biomarkers of Reflux Disease: A Systematic Review

Farooqi, Muhammad S; Podury, Sanjiti; Crowley, George; Kwon, Sophia; Khan, Abraham R; Francois, Fritz; Nolan, Anna
ISSN: n/a
CID: 5388972

Variability in endoscopic assessment of Nissen fundoplication wrap integrity and hiatus herniation

Song, Erin J; Yadlapati, Rena; Chen, Joan W; Parish, Alice; Whitson, Matthew J; Ravi, Karthik; Patel, Amit; Carlson, Dustin A; Khan, Abraham; Niedzwiecki, Donna; Leiman, David A
BACKGROUND:Upper endoscopy (EGD) is frequently performed in patients with esophageal complaints following anti-reflux surgery such as fundoplication. Endoscopic evaluation of fundoplication wrap integrity can be challenging. Our primary aim in this pilot study was to evaluate the accuracy and confidence of assessing Nissen fundoplication integrity and hiatus herniation among gastroenterology (GI) fellows, subspecialists, and foregut surgeons. METHODS:Five variations of post-Nissen fundoplication anatomy were included in a survey of 20 sets of EGD images that was completed by GI fellows, general GI attendings, esophagologists, and foregut surgeons. Accuracy, diagnostic confidence, and inter-rater agreement across providers were evaluated. RESULTS:There were 31 respondents in the final cohort. Confidence in pre-survey diagnostics significantly differed by provider type (mean confidence out of 5 was 1.8 for GI fellows, 2.7 for general GI attendings, 3.6 for esophagologists, and 3.6 for foregut surgeons, P = 0.01). The mean overall accuracy was 45.9%, which significantly differed by provider type with the lowest rate among GI fellows (37%) and highest among esophagologists (53%; P = 0.01). The accuracy was highest among esophagologists across all wrap integrity variations. Inter-rater agreement was low across wrap integrity variations (Krippendorf's alpha <0.30), indicating low to no agreement between providers. CONCLUSION/CONCLUSIONS:In this multi-center survey study, GI fellows had the lowest accuracy and confidence in assessing EGD images after Nissen fundoplication, whereas esophagologists had the highest. Diagnostic confidence varied considerably and inter-rater agreement was poor. These findings suggest experience may improve confidence, but highlight the need to improve the evaluation of fundoplication wraps.
PMID: 34963133
ISSN: 1442-2050
CID: 5108152

Oral and gastric microbiome in relation to gastric intestinal metaplasia

Wu, Fen; Yang, Liying; Hao, Yuhan; Zhou, Boyan; Hu, Jiyuan; Yang, Yaohua; Bedi, Sukhleen; Sanichar, Navin Ganesh; Cheng, Charley; Perez-Perez, Guillermo; Tseng, Wenche; Tseng, Wenzhi; Tseng, Mengkao; Francois, Fritz; Khan, Abraham R; Li, Yihong; Blaser, Martin J; Shu, Xiao-Ou; Long, Jirong; Li, Huilin; Pei, Zhiheng; Chen, Yu
Evidence suggests that Helicobacter pylori plays a role in gastric cancer (GC) initiation. However, epidemiologic studies on the specific role of other bacteria in the development of GC are lacking. We conducted a case-control study of 89 cases with gastric intestinal metaplasia (IM) and 89 matched controls who underwent upper gastrointestinal endoscopy at three sites affiliated with NYU Langone Health. We performed shotgun metagenomic sequencing using oral wash samples from 89 case-control pairs and antral mucosal brushing samples from 55 case-control pairs. We examined the associations of relative abundances of bacterial taxa and functional pathways with IM using conditional logistic regression with and without elastic-net penalty. Compared with controls, oral species Peptostreptococcus stomatis, Johnsonella ignava, Neisseria elongata and Neisseria flavescens were enriched in cases (odds ratios [ORs] = 1.29-1.50, P = .004-.01) while Lactobacillus gasseri, Streptococcus mutans, S parasanguinis and S sanguinis were under-represented (ORs = 0.66-0.76, P = .006-.042) in cases. Species J ignava and Filifactor alocis in the gastric microbiota were enriched (ORs = 3.27 and 1.43, P = .005 and .035, respectively), while S mutans, S parasanguinis and S sanguinis were under-represented (ORs = 0.61-0.75, P = .024-.046), in cases compared with controls. The lipopolysaccharide and ubiquinol biosynthesis pathways were more abundant in IM, while the sugar degradation pathways were under-represented in IM. The findings suggest potential roles of certain oral and gastric microbiota, which are correlated with regulation of pathways associated with inflammation, in the development of gastric precancerous lesions.
PMID: 34664721
ISSN: 1097-0215
CID: 5043202

Classifying Esophageal Motility by FLIP Panometry: A Study of 722 Subjects With Manometry

Carlson, Dustin A; Gyawali, C Prakash; Khan, Abraham; Yadlapati, Rena; Chen, Joan; Chokshi, Reena V; Clarke, John O; Garza, Jose M; Jain, Anand S; Katz, Philip; Konda, Vani; Lynch, Kristle; Schnoll-Sussman, Felice H; Spechler, Stuart J; Vela, Marcelo F; Prescott, Jacqueline E; Baumann, Alexandra J; Donnan, Erica N; Kou, Wenjun; Kahrilas, Peter J; Pandolfino, John E
INTRODUCTION/BACKGROUND:Functional luminal imaging probe (FLIP) panometry can evaluate esophageal motility in response to sustained esophageal distension at the time of sedated endoscopy. This study aimed to describe a classification of esophageal motility using FLIP panometry and evaluate it against high-resolution manometry (HRM) and Chicago Classification v4.0 (CCv4.0). METHODS:Five hundred thirty-nine adult patients who completed FLIP and HRM with a conclusive CCv4.0 diagnosis were included in the primary analysis. Thirty-five asymptomatic volunteers ("controls") and 148 patients with an inconclusive CCv4.0 diagnosis or systemic sclerosis were also described. Esophagogastric junction (EGJ) opening and the contractile response (CR) to distension (i.e., secondary peristalsis) were evaluated with a 16-cm FLIP during sedated endoscopy and analyzed using a customized software program. HRM was classified according to CCv4.0. RESULTS:In the primary analysis, 156 patients (29%) had normal motility on FLIP panometry, defined by normal EGJ opening and a normal or borderline CR; 95% of these patients had normal motility or ineffective esophageal motility on HRM. Two hundred two patients (37%) had obstruction with weak CR, defined as reduced EGJ opening and absent CR or impaired/disordered CR, on FLIP panometry; 92% of these patients had a disorder of EGJ outflow per CCv4.0. DISCUSSION/CONCLUSIONS:Classifying esophageal motility in response to sustained distension with FLIP panometry parallels the swallow-associated motility evaluation provided with HRM and CCv4.0. Thus, FLIP panometry serves as a well-tolerated method that can complement, or in some cases be an alternative to HRM, for evaluating esophageal motility disorders.
PMID: 34668487
ISSN: 1572-0241
CID: 5043282

Functional Chest Pain and Esophageal Hypersensitivity: A Clinical Approach

Bhardwaj, Richa; Knotts, Rita; Khan, Abraham
Functional chest pain, functional heartburn, and reflux hypersensitivity are 3 functional esophageal disorders defined by the Rome IV criteria. Specific criteria, combining symptoms and the results of objective testing, allow for an accurate diagnosis of these conditions. Management may include medications targeted at optimizing acid suppression or neuromodulation, as well as a host of complementary or alternative treatment options. Psychological and behavioral interventions, such as cognitive behavioral therapy and hypnotherapy, have displayed substantial benefits in the treatment of functional chest pain and functional heartburn. Acid suppression and focused neuromodulation are key evidence-based treatment options for reflux hypersensitivity.
PMID: 34717874
ISSN: 1558-1942
CID: 5037692