Dr. John Clarke recently joined the Gastroenterology & Hepatology Division at Stanford University as Director of the Esophageal Program. He previously spent 17 years in Baltimore, including 9 years on the faculty at Johns Hopkins University where he was an Associate Professor and at various times Director of Esophageal Motility, Director of Gastrointestinal Motility, Clinical Director of the Johns Hopkins Center for Neurogastroenterology, and Clinical Director of the Gastroenterology & Hepatology Division at Johns Hopkins Bayview Medical Center.

His career has combined research, education and clinical care. His clinical areas of expertise include achalasia, dysphagia, eosinophilic esophagitis, esophageal dysmotility, gastroesophageal reflux disease, gastroparesis, GI-manifestations of scleroderma and GI dysmotility. While at Johns Hopkins University, he was inducted into The Miller-Coulson Academy for Clinical Excellence, an institutional honor society for master clinicians at the time limited to 50 members across the entire university.

From an education standpoint, he has lectured in over a dozen countries, authored over 25 textbook chapters and serves on the educational affairs committee of the American College of Gastroenterology. He has also won several major teaching awards, including The Johns Hopkins University Alumni Association Award for Excellence in Teaching, given to one faculty member per year in the entire School of Medicine.

His research has focused on optimization and characterization of diagnostic studies to evaluate motility disorders, as well the relationship between therapeutic endoscopic techniques and treatment of motility disorders. He was an investigator on the NIH Gastroparesis Consortium and is also a former recipient of the AGA Don Castell Award.

Clinical Focus

  • Achalasia
  • Amyloidosis
  • Barrett's esophagus
  • Dysphagia
  • Eosinophilic esophagitis
  • Esophageal Dysmotility
  • Esophagus
  • Gastroenterology
  • Gastroesophageal Reflux Disease (GERD)
  • Gastroparesis
  • Motility
  • Scleroderma Bowel Disease

Academic Appointments

Administrative Appointments

  • Director, Esophageal Program, Stanford Medicine (2016 - Present)

Honors & Awards

  • Award for Excellence in Teaching, John Hopkins University Alumni Association (2015)

Boards, Advisory Committees, Professional Organizations

  • Member, Scientific advisory board, Teva (2015 - Present)
  • Member, Scientific advisory board, ProStrakan (2012 - Present)

Professional Education

  • Board Certification: American Board of Internal Medicine, Gastroenterology (2007)
  • Fellowship: Johns Hopkins University Dept of Gastroenterology (2007) MD
  • Board Certification: American Board of Internal Medicine, Internal Medicine (2002)
  • Residency: Johns Hopkins Hospital Internal Medicine Residency (2002) MD
  • Medical Education: Columbia University College of Physicians and Surgeons (1999) NY

Clinical Trials

  • A Trial of IW-3718 for 8 Weeks in Patients With Persistent Gastroesophageal Reflux Disease (GERD) Receiving Proton Pump Inhibitors Recruiting

    The objective of this study is to evaluate the safety and efficacy of IW-3718 administered to patients with GERD who continue to have persistent symptoms, such as heartburn and regurgitation, while receiving once-daily (QD), standard-dose proton pump inhibitors (PPIs).

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  • An Investigation of the EndoStim® Lower Esophageal Sphincter (LES) Stimulation System for the Treatment of Reflux Recruiting

    The purpose of this investigation is to demonstrate the safety and effectiveness of Lower Esophageal Sphincter (LES) Stimulation System in treating gastroesophageal reflux disease (GERD). This investigation is a multicenter, randomized, double-blind, sham-controlled study. After the implant procedure, subjects will be randomized to either the Treatment Group (immediate stimulation) or Control Group (delayed stimulation) for six months followed by an additional open-label phase in which all subjects will receive electrical stimulation. Subjects continue on stimulation treatment in an extended open-label follow-up phase through 5 years post-stimulation.

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  • Novel Endoluminal Clinical TreAtment of Reflux Recruiting

    This is a prospective, multi-center, double-blind, crossover, randomized controlled trial designed to demonstrate the safety and efficacy of Aluvra for the treatment of GERD.

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  • Functional Luminal Imaging Probe (FLIP) Topography Use in Patients With Scleroderma and Trouble Swallowing Not Recruiting

    FLIP topography has been FDA cleared to evaluate a variety of esophageal conditions, but has never been evaluated in patients with scleroderma. The investigators hope to evaluate this technology in patients who have scleroderma and various esophageal symptoms, and compare to non-scleroderma patients.

    Stanford is currently not accepting patients for this trial. For more information, please contact John O Clarke, MD, 650-736-5555.

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All Publications

  • The Stanford Multidisciplinary Swallowing Disorders Center. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Nandwani, M., Dewan, K., Starmer, H., Kamal, A. N., Clarke, J. O. 2021

    View details for DOI 10.1016/j.cgh.2021.04.025

    View details for PubMedID 33887474

  • Development of quality indicators for the diagnosis and management of achalasia. Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society Kamal, A. N., Kathpalia, P., Otaki, F., Bredenoord, A. J., Castell, D. O., Clarke, J. O., Falk, G. W., Fass, R., Prakash Gyawali, C., Kahrilas, P. J., Katz, P. O., Katzka, D. A., Pandolfino, J. E., Penagini, R., Richter, J. E., Roman, S., Savarino, E., Triadafilopoulos, G., Vaezi, M. F., Vela, M. F., Leiman, D. A. 2021: e14118


    BACKGROUND: The management of achalasia has improved due to diagnostic and therapeutic innovations. However, variability in care delivery remains and no established measures defining quality of care for this population exist. We aimed to use formal methodology to establish quality indicators for achalasia patients.METHODS: Quality indicator concepts were identified from the literature, consensus guidelines and clinical experts. Using RAND/University of California, Los Angeles (UCLA) Appropriateness Method, experts in achalasia independently ranked proposed concepts in a two-round modified Delphi process based on 1) importance, 2) scientific acceptability, 3) usability, and 4) feasibility. Highly valid measures required strict agreement (≧ 80% of panelists) in the range of 7-9 for across all four categories.KEY RESULTS: There were 17 experts who rated 26 proposed quality indicator topics. In round one, 2 (8%) quality measures were rated valid. In round two, 19 measures were modified based on panel suggestions, and experts rated 10 (53%) of these measures as valid, resulting in a total of 12 quality indicators. Two measures pertained to patient education and five to diagnosis, including discussing treatment options with risk and benefits and using the most recent version of the Chicago Classification to define achalasia phenotypes, respectively. Other indicators pertained to treatment options, such as the use of botulinum toxin for those not considered surgical candidates and management of reflux following achalasia treatment.CONCLUSIONS & INFERENCES: Using a robust methodology, achalasia quality indicators were identified, which can form the basis for establishing quality gaps and generating fully specified quality measures.

    View details for DOI 10.1111/nmo.14118

    View details for PubMedID 33720448

  • Regional Gastrointestinal Transit and Contractility Patterns Vary in Postural Orthostatic Tachycardia Syndrome (POTS). Digestive diseases and sciences Zhou, W., Zikos, T. A., Clarke, J. O., Nguyen, L. A., Triadafilopoulos, G., Neshatian, L. 2021


    BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) is an autonomic disorder that affects multiple organs, including the gastrointestinal system. These patients often have multiple GI complaints with a severe impact on their quality of life. GI dysmotility patterns in POTS remains poorly understood and difficult to manage.AIMS: The aim of this study was to investigate the diagnostic yield of wireless motility capsule in patients with gastrointestinal symptoms and POTS, with use of a symptomatic control group without POTS as a reference.METHODS: We retrospectively reviewed the charts of patients who had both autonomic testing and wireless motility capsule between 2016 and 2020. The two groups were divided into those with POTS and those without POTS (controls) as diagnosed through autonomic testing. We compared the regional transit times and motility patterns between the two groups using the data collected from wireless motility capsule.RESULTS: A total of 25% of POTS patients had delayed small bowel transit compared to 0% of non-POTS patients (p=0.047). POTS patients exhibited hypo-contractility patterns within the small bowel, including decreased contractions/min (2.95 vs. 4.22, p=0.011) and decreased motility index (101.36 vs. 182.11, p=0.021). In multivariable linear regression analysis, migraine predicted faster small bowel transit (p=0.007) and presence of POTS predicted slower small bowel transit (p=0.044).CONCLUSIONS: Motility abnormalities among POTS patients seem to affect mostly the small bowel and exhibit a general hypo-contractility pattern. Wireless motility capsule can be a helpful tool in patients with POTS and GI symptoms as it can potentially help guide treatment.

    View details for DOI 10.1007/s10620-020-06808-z

    View details for PubMedID 33428036

  • Gastric Mucosal Immune Profiling and Dysregulation in Idiopathic Gastroparesis. Clinical and translational gastroenterology Gottfried-Blackmore, A. n., Namkoong, H. n., Adler, E. n., Martin, B. n., Gubatan, J. n., Fernandez-Becker, N. n., Clarke, J. O., Idoyaga, J. n., Nguyen, L. n., Habtezion, A. n. 2021; 12 (5): e00349


    It is unclear how immune perturbations may influence the pathogenesis of idiopathic gastroparesis, a prevalent functional disorder of the stomach which lacks animal models. Several studies have noted altered immune characteristics in the deep gastric muscle layer associated with gastroparesis, but data are lacking for the mucosal layer, which is endoscopically accessible. We hypothesized that immune dysregulation is present in the gastroduodenal mucosa in idiopathic gastroparesis and that specific immune profiles are associated with gastroparesis clinical parameters.In this cross-sectional prospective case-control study, routine endoscopic biopsies were used for comprehensive immune profiling by flow cytometry, multicytokine array, and gene expression in 3 segments of the stomach and the duodenal bulb. Associations of immune endpoints with clinical parameters of gastroparesis were also explored.The gastric mucosa displayed large regional variation of distinct immune profiles. Furthermore, several-fold increases in innate and adaptive immune cells were found in gastroparesis. Various immune cell types showed positive correlations with duration of disease, proton pump inhibitor dosing, and delayed gastric emptying.This initial observational study showed immune compartmentalization of the human stomach mucosa and significant immune dysregulation at the level of leukocyte infiltration in idiopathic gastroparesis patients that extends to the duodenum. Select immune cells, such as macrophages, may correlate with clinicopathological traits of gastroparesis. This work supports further mucosal studies to advance our understanding of gastroparesis pathophysiology.

    View details for DOI 10.14309/ctg.0000000000000349

    View details for PubMedID 33979305

  • Achalasia: physiology and diagnosis. Annals of the New York Academy of Sciences Rieder, E., Fernandez-Becker, N. Q., Sarosiek, J., Guillaume, A., Azagury, D. E., Clarke, J. O. 2020


    Achalasia is a rare motility disorder with incomplete relaxation of the lower esophageal sphincter and ineffective contractions of the esophageal body. It has been hypothesized that achalasia does not result from only one pathway but rather involves a combination of infectious, autoimmune, and familial etiological components. On the basis of other observations, a novel hypothesis suggests that a muscular form of eosinophilic esophagitis is involved in the pathophysiology of achalasia in some patients. This appears to progressively diminish the myenteric plexus at stage III, gradually destroy it at stage II, and finally eliminate it at stage I, the most advanced and final stage of achalasia. Although high-resolution manometry has identified these three different types of achalasia, another subset of patients with a normal-appearing sphincter relaxation has been proposed. Provocative maneuvers, such as the rapid drinking challenge, have recently been demonstrated to improve diagnosis in certain borderline patients, but have to be studied in more detail. However, whether the different types of achalasia will have a long-term impact on tailored therapies is still a matter of debate. Additionally, novel aspects of the standard timed barium swallow appear to be an important adjunct of diagnosis, as it has been shown to have a diagnostic as well as a predictive value.

    View details for DOI 10.1111/nyas.14510

    View details for PubMedID 33140485

  • Patient Reported Outcomes and Objective Swallowing Assessments in a Multidisciplinary Dysphagia Clinic. The Laryngoscope Dewan, K., Clarke, J. O., Kamal, A. N., Nandwani, M., Starmer, H. M. 2020


    OBJECTIVES/HYPOTHESIS: Dysphagia encompasses a complex compilation of symptoms which often differ from findings of objective swallowing evaluations. The purpose of this investigation was to compare the results of subjective dysphagia measures to objective measures of swallowing in patients evaluated in a multidisciplinary dysphagia clinic.STUDY DESIGN: Prospective cohort study.METHODS: The study cohort included all patients evaluated in the multidisciplinary dysphagia clinic over 24months. Participants were evaluated by a multidisciplinary team including a laryngologist, gastroenterologist, and speech-language pathologist. Evaluation included a videofluoroscopic swallowing study (VFSS), fiberoptic endoscopic evaluation of swallowing (FEES), and transnasal esophagoscopy (TNE). Data collected included diet (FOIS), Eating Assessment Tool (EAT-10) score, Reflux symptom index (RSI) score, and the findings of the VFSS exam.RESULTS: A total of 75 patients were included in the analysis. The average EAT-10 score was 16.3±2.1, RSI was 21.4±0.6, and FOIS score was 6.0±1.33. VFSS revealed impairments in the oral phase in 40% of the cohort, pharyngeal in 59%, and esophageal in 49%. Abnormalities were noted in one phase for 32%, in 2 phases in 32%, and three phases in 18%. Patients with abnormal pharyngeal findings on VFSS had significantly higher EAT-10 scores (P = .04). Patients with abnormal oral findings on VFSS were noted to have significantly lower FOIS scores (P = .03).CONCLUSIONS: Data presented here demonstrate a relationship between patient reported symptoms and objective VFSS findings in a cohort of patients referred for multidisciplinary swallowing assessment suggesting such surveys are helpful screening tools but inadequate to fully characterize swallowing impairment.LEVEL OF EVIDENCE: 3 Laryngoscope, 2020.

    View details for DOI 10.1002/lary.29194

    View details for PubMedID 33103765

  • Type II Achalasia Is Increasing in Prevalence. Digestive diseases and sciences Zhou, M. J., Kamal, A., Freedberg, D. E., Markowitz, D., Clarke, J. O., Jodorkovsky, D. 2020


    BACKGROUND: Three manometric subtypes of achalasia were defined in the Chicago Classification approximately 10years ago: type I (aperistalsis), type II (pan-pressurization), and type III (spastic). Since the widespread use of this classification scheme, the evolving prevalence of these subtypes has not been elucidated. We aim to determine the prevalence of each subtype a decade after the adoption of the Chicago Classification.METHODS: This is a retrospective cohort analysis of patients diagnosed with achalasia on high-resolution manometry (HRM) at two major academic medical centers between 2015 and 2018. Patients were excluded if they had a diagnosis of another esophageal motility disorder, previously treated achalasia, or foregut surgery. Demographic data, manometric subtype, and esophageal dilatation grade on endoscopy were obtained. Prevalence of achalasia subtypes was compared with a published historical control population (2004-2007). Fischer's exact and t tests were used for analysis.RESULTS: Of 147 patients in the contemporary cohort and 99 in the historical control cohort, the prevalence of type I achalasia was 8% versus 21%, type II 63% versus 50%, and type III 29% versus 29%, respectively (p=0.01). The mean age in our population was 58years compared to 57years in the historical control, and the proportion of men 48% versus 47%, respectively (p=0.78). Mean endoscopic dilatation grade in the contemporary cohort was 1.5 for type I patients, 0.9 for type II, and 0.4 for type III, compared with 1.5, 0.6, and 0.4, respectively. Overall mean dilatation grade was 0.8 in our cohort versus 0.7 in the historical control (p=0.58).CONCLUSION: The prevalence of type II achalasia was significantly greater and prevalence of type I significantly less in our patient population compared to our predefined historical control. Other characteristics such as age and sex did not appear to contribute to these differences. Histopathological evidence has suggested that type II achalasia may be an earlier form of type I; thus, the increased prevalence of type II achalasia may be related to earlier detection of the disease. The adoption of HRM, widespread use of the Chicago Classification, and increased disease awareness in the past decade may be contributing to these changes in epidemiology.

    View details for DOI 10.1007/s10620-020-06668-7

    View details for PubMedID 33089487

  • Use of the Functional Lumen Imaging Probe in Clinical Esophagology. The American journal of gastroenterology Savarino, E., di Pietro, M., Bredenoord, A. J., Carlson, D. A., Clarke, J. O., Khan, A., Vela, M. F., Yadlapati, R., Pohl, D., Pandolfino, J. E., Roman, S., Gyawali, C. P. 2020


    The functional lumen imaging probe (FLIP) measures luminal dimensions using impedance planimetry, performed most often during sedated upper endoscopy. Mechanical properties of the esophageal wall and opening dynamics of the esophagogastric junction (EGJ) can be objectively evaluated in esophageal motor disorders, eosinophilic esophagitis, esophageal strictures, during esophageal surgery and in postsurgical symptomatic states. Distensibility index, the ratio of EGJ cross sectional area to intraballoon pressure, is the most useful FLIP metric. Secondary peristalsis from balloon distension can be displayed topographically as repetitive anterograde or retrograde contractile activity in the esophageal body, similar to high-resolution manometry. Real-time interpretation and postprocessing of FLIP metadata can complement the identification of esophageal outflow obstruction and achalasia, especially when findings are inconclusive from alternate esophageal tests in symptomatic patients. FLIP can complement the diagnosis of achalasia when manometry and barium studies are inconclusive or negative in patients with typical symptoms. FLIP can direct adequacy of disruption of the EGJ in achalasia when used during and immediately after myotomy and pneumatic dilation. Lumen diameter measured using FLIP in eosinophilic esophagitis and in complex strictures can potentially guide management. An abbreviated modification of the Grading of Recommendations Assessment, Development, and Evaluation was used to determine the quality of available evidence and recommendations regarding FLIP utilization. FLIP metrics that are diagnostic or suggestive of an abnormal motor pattern and metrics that define normal esophageal physiology were developed by consensus and are described in this review.

    View details for DOI 10.14309/ajg.0000000000000773

    View details for PubMedID 32740073

  • The Role of Symptom Association Analysis in Gastroesophageal Reflux Testing. The American journal of gastroenterology Kamal, A. N., Clarke, J. O., Oors, J. M., Smout, A. J., Bredenoord, A. J. 2020


    Gastroesophageal reflux disease is characterized by the reflux of gastric contents into the esophagus with an estimated worldwide prevalence of 8%-33%. The current paradigm in gastroesophageal reflux disease diagnosis relies on recognition of symptoms and/or the presence of mucosal disease at the time of esophagogastroduodenoscopy. Recognition of symptoms, however, can arise with challenges, particularly when patients complain of less typical symptoms. Since first reported in 1969 by Spencer et al., the application of prolonged intraesophageal pH monitoring to identify pathologic reflux has evolved considerably. Utility of pH monitoring aims to investigate the degree of acid burden and frequency of reflux episode, and the relationship between symptoms and acid reflux events. This relationship is represented by either the Symptom Index, Symptom Sensitivity Index, Symptom Association Probability, or Ghillebert Probability Estimate. This article reviews symptom-association analysis during esophageal reflux testing, covering the literature on current methods of reflux testing, interpretation of symptom association, and practical issues that can arise during symptom analysis.

    View details for DOI 10.14309/ajg.0000000000000754

    View details for PubMedID 32740077

  • Gastric per-oral endoscopic myotomy for severe post-lung transplant gastroparesis: A single-center experience. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Podboy, A. J., Clarke, J. O., Nguyen, L. A., Mooney, J. J., Dhillon, G. S., Hwang, J. H. 2020

    View details for DOI 10.1016/j.healun.2020.06.019

    View details for PubMedID 32711933

  • Mucosal impedance for esophageal disease: evaluating the evidence. Annals of the New York Academy of Sciences Clarke, J. O., Ahuja, N. K., Chan, W. W., Gyawali, C. P., Horsley-Silva, J. L., Kamal, A. N., Vela, M. F., Xiao, Y. 2020


    Impedance has traditionally been employed in esophageal disease as a means to assess bolus flow and reflux episodes. Recent and ongoing research has provided new and novel applications for this technology. Measurement of esophageal mucosal impedance, via either multichannel intraluminal impedance catheters or specially designed endoscopically deployed impedance catheters, provides a marker of mucosal integrity. Mucosal impedance has been shown to segregate gastroesophageal reflux disease (GERD) and eosinophilic esophagitis from non-GERD controls and may play a role in predicting response to reflux intervention. More data are needed with regard to other esophageal subgroups, outcome studies, and functional disease. Our paper reviews the history of impedance in esophageal disease, the means of assessing baseline and mucosal impedance, data with regard to the newly developed mucosal impedance probes, the clinical utility of mucosal impedance in specific clinical conditions, and limitations in our existing knowledge, along with suggestions for future studies.

    View details for DOI 10.1111/nyas.14414

    View details for PubMedID 32588457

  • The role of ambulatory 24-hour esophageal manometry in clinical practice. Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society Kamal, A. N., Clarke, J. O., Oors, J. M., Bredenoord, A. J. 2020: e13861


    High-resolution manometry revolutionized the assessment of esophageal motility disorders and upgraded the classification through the Chicago Classification. A known disadvantage of standard HRM, however, is the inability to record esophageal motility function for an extended time interval; therefore, it represents only a more snapshot view of esophageal motor function. In contrast, ambulatory esophageal manometry measures esophageal motility over a prolonged period and detects motor activity during the entire circadian cycle. Furthermore, ambulatory manometry has the ability to measure temporal correlations between symptoms and motor events. This article aimed to review the clinical implications of ambulatory esophageal manometry for various symptoms, covering literature on the manometry catheter, interpretation of findings, and relevance in clinical practice specific to the evaluation of non-cardiac chest pain, chronic cough, and rumination syndrome.

    View details for DOI 10.1111/nmo.13861

    View details for PubMedID 32391594

  • Marijuana, Ondansetron, and Promethazine Are Perceived as Most Effective Treatments for Gastrointestinal Nausea. Digestive diseases and sciences Zikos, T. A., Nguyen, L., Kamal, A., Fernandez-Becker, N., Regalia, K., Nandwani, M., Sonu, I., Garcia, M., Okafor, P., Neshatian, L., Grewal, D., Garcia, P., Triadafilopoulos, G., Clarke, J. O. 2020


    BACKGROUND: Many anti-nausea treatments are available for chronic gastrointestinal syndromes, but data on efficacy and comparative effectiveness are sparse.AIMS: To conduct a sectional survey study of patients with chronic nausea to assess comparative effectiveness of commonly used anti-nausea treatments.METHODS: Outpatients at a single center presenting for gastroenterology evaluation were asked to rate anti-nausea efficacy on a scale of 0 (no efficacy) to 5 (very effective) of 29 commonly used anti-nausea treatments and provide other information about their symptoms. Additional information was collected from the patients' chart. The primary outcome was to determine which treatments were better or worse than average using a t test. The secondary outcome was to assess differential response by individual patient characteristics using multiple linear regression.RESULTS: One hundred and fifty-three patients completed the survey. The mean efficacy score of all anti-nausea treatments evaluated was 1.73. After adjustment, three treatments had scores statically higher than the mean, including marijuana (2.75, p<0.0001), ondansetron (2.64, p<0.0001), and promethazine (2.46, p<0.0001). Several treatments, including many neuromodulators, complementary and alternative treatments, erythromycin, and diphenhydramine had scores statistically below average. Patients with more severe nausea responded better to marijuana (p=0.036) and diphenhydramine (p<0.001) and less so to metoclopramide (p=0.020). There was otherwise no significant differential response by age, gender, nausea localization, underlying gastrointestinal cause of nausea, and GCSI.CONCLUSIONS: When treating nausea in patients with chronic gastrointestinal syndromes, clinicians may consider trying higher performing treatments first, and forgoing lower performing treatments. Further prospective research is needed, particularly with respect to highly effective treatments.

    View details for DOI 10.1007/s10620-020-06195-5

    View details for PubMedID 32185665

  • Long-term outcomes of per-oral endoscopic myotomy compared to laparoscopic Heller myotomy for achalasia: a single-center experience. Surgical endoscopy Podboy, A. J., Hwang, J. H., Rivas, H., Azagury, D., Hawn, M., Lau, J., Kamal, A., Friedland, S., Triadafilopoulos, G., Zikos, T., Clarke, J. O. 2020


    INTRODUCTION: Many centers have reported excellent short-term efficacy of per-oral endoscopic myotomy (POEM) for the treatment of achalasia. However, long-term data are limited and there are few studies comparing the efficacy of POEM versus Heller Myotomy (HM).AIMS: To compare the long-term clinical efficacy of POEM versus HM.METHODS: Using a retrospective, parallel cohort design, all cases of POEM or HM for achalasia between 2010 and 2015 were assessed. Clinical failure was defined as (a) Eckardt Score>3 for at least 4weeks, (b) achalasia-related hospitalization, or (c) repeat intervention. All index manometries were classified via Chicago Classification v3. Pre-procedural clinical, manometric, radiographic data, and procedural data were reviewed.RESULTS: 98 patients were identified (55 POEM, 43 Heller) with mean follow-up of 3.94years, and 5.44years, respectively. 83.7% of HM patients underwent associated anti-reflux wrap (Toupet or Dor). Baseline clinical, demographic, radiographic, and manometric data were similar between the groups. There was no statistical difference in overall long-term success (POEM 72.7%, HM 65.1% p=0.417, although higher rates of success were seen in Type III Achalasia in POEM vs Heller (53.3% vs 44.4%, p<0.05). Type III Achalasia was the only variable associated with failure on a univariate COX analysis and no covariants were identified on a multivariate Cox regression. There was no statistical difference in GERD symptoms, esophagitis, or major procedural complications.CONCLUSION: POEM and HM have similar long-term (4-year) efficacy with similar adverse event and reflux rates. POEM was associated with greater efficacy in Type III Achalasia.

    View details for DOI 10.1007/s00464-020-07450-6

    View details for PubMedID 32157405

  • Clinical and immunomodulatory effects of transcutaneous vagal nerve stimulation for idiopathic gastroparesis Gottfried-Blackmore, A., Namkoong, H., Adler, E. P., Fernandez-Becker, N., Clarke, J., Habtezion, A., Nguyen, L. WILEY. 2020
  • New Developments in the Diagnosis and Management of Gastroesophageal Reflux. Current treatment options in gastroenterology Jiang, Y., Clarke, J. O. 2020


    PURPOSE OF REVIEW: To examine recent key developments in the pathophysiology, diagnosis, and treatment of gastroesophageal reflux disease (GERD).RECENT FINDINGS: Newer research has suggested cytokine-mediated inflammation may play a role in the physiology of GERD, implying that the underlying mechanism may not be entirely related to chemical damage due to acid. Aided by novel technologies, diagnostic testing is also moving toward elucidating individual mechanisms and better defining specific GERD phenotypes with the goal of providing directed therapy. This is especially important in current times given the increase in coverage of adverse events reportedly linked to long-term proton pump inhibitor use. As patients are looking for potential alternatives, we highlight the key recent updates in pathophysiology and understanding of GERD and current medical and endoscopic/surgical options and explore the exciting treatments in the pipeline.

    View details for DOI 10.1007/s11938-020-00275-1

    View details for PubMedID 32072470

  • Esophagogastric Junction Outflow Obstruction: Current Approach to Diagnosis and Management. Current gastroenterology reports Zikos, T. A., Triadafilopoulos, G., Clarke, J. O. 2020; 22 (2): 9


    PURPOSE OF REVIEW: We summarize the current epidemiology, presentation, diagnostic workup, and treatment of esophagogastric junction outflow obstruction (EGJOO). We also propose a treatment algorithm based upon the literature and our personal clinical experience.RECENT FINDINGS: EGJOO can be caused by functional obstruction (akin to achalasia), mechanical obstruction, medications, or artifact. High-resolution esophageal manometry is currently the gold standard of diagnosis. Recent research on FLIP (functional lumen imaging probe) and timed barium support use as adjunctive testing. The diagnostic yield of cross-sectional imaging is low. Current diagnostic testing and treatment should be targeted to the suspected underlying etiology and clinical presentation of EGJOO. If functional obstruction is present with significant and persistent dysphagia, and either an abnormal FLIP or timed barium swallow, we consider therapy aimed at LES disruption (similar to achalasia). Pharmacologic therapy has a limited role. More research is needed on diagnostic and treatment modalities.

    View details for DOI 10.1007/s11894-020-0743-0

    View details for PubMedID 32020310

  • Changes in high-resolution manometric diagnosis over time: implications for clinical decision-making. Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus Triadafilopoulos, G., Kamal, A., Zikos, T., Nguyen, L., Clarke, J. O. 2020


    Although High resolution esophageal manometry (HRM) is the gold standard to assess esophageal motility, little is known about the stability of the manometric diagnosis over time and its implications for management. To assess the stability and usefulness of repeat HRM in patients presenting with esophageal symptoms over time we performed this retrospective study of patients with esophageal symptoms. Medical records, questionnaires, and HRM tracing were independently reviewed using the Chicago classification. The primary objective was to assess the stability of the manometric diagnosis over time; secondary objective was its change (positive or negative). At least one repeat study was performed in 86 patients (36% women, ages 20-86, with mild to moderate symptoms), while 26 had a third procedure. Mean intervals between studies were 15±1.6months (for baseline v. first study) and 13±0.8months (for second to third study). Of the 27 patients initially with a normal study, 11 changed (five had esophago-gastric junction outflow obstruction [EGJOO], two diffuse esophageal spasm [DES], one jackhammer esophagus [JE], and three ineffective esophageal motility [IEM] [41% change]). Of the 24 patients with initial EGJOO, only nine retained it (65.2% change). Of nine patients with initial DES, four changed (44.4% change). Similarly, different diagnosis was seen in 7 of 24 initial IEM patients (22.7% change). Only one patient had achalasia initially and this remained stable. Additional changes were noted on a third HRM. Fluidity in the HRM diagnosis over time questions its validity at any timepoint and raises doubts about the need for intervention.

    View details for DOI 10.1093/dote/doz094

    View details for PubMedID 31909786

  • Development of a Preliminary Question Prompt List as a Communication Tool for Adults With Gastroesophageal Reflux Disease: A Modified Delphi Study. Journal of clinical gastroenterology Kamal, A. n., Katzka, D. A., Achkar, E. n., Carlson, D. n., Clarke, J. n., Fass, R. n., Gyawali, C. P., Patel, D. n., Penagini, R. n., Rezaie, A. n., Roman, S. n., Savarino, E. n., Shaheen, N. J., Triadafilopoulos, G. n. 2020


    Question prompt lists (QPLs) are structured sets of disease-specific questions intended for patient use, encouraging patients to ask questions to facilitate their consultation with their physician.The aim of this study was to develop a QPL specific to adults with gastroesophageal reflux disease (GERD), created by esophageal experts.The QPL content (78 questions) was derived through a modified Delphi method consisting of 2 rounds. In round 1, 18 esophageal experts provided 5 answers to the prompt "What you wish your patients would ask" and "What questions do patients often not ask, that I wish they would ask?" In round 2, the experts rated each question on a 5-point Likert scale, and responses rated as "essential" or "important," determined by an a priori threshold of ≥4.0, were accepted for the QPL.Twelve esophageal experts participated. Of 143 questions from round 1, 110 (76.9%) were accepted for inclusion in the QPL, meeting a median value of ≥4.0, and, subsequently, it reduced to 78, minimizing redundancy. Median values ranged between 4.0 and 5.0, with the highest agreement median (5.0) for questions asking dosing and timing of proton pump inhibitor therapy, and surveillance in Barrett's. Questions were categorized into the following categories: "What does this illness mean," "lifestyle modifications," "general treatment," "treatment with proton pump inhibitors," "What I should expect for my future," and "Barrett's." The largest number of questions covered lifestyle modifications (21.8%), with the highest agreement median (5.0) for "How helpful are lifestyle modifications in GERD?"A preliminary GERD-specific QPL, the first of its kind, was developed by esophageal experts. Modification after more patient consultation and feedback is planned in subsequent versions to create a GERD-QPL for eventual use in clinical gastroenterology.

    View details for DOI 10.1097/MCG.0000000000001300

    View details for PubMedID 31985713

  • The functional lumen imaging probe in gastrointestinal disorders: the past, present, and future. Annals of the New York Academy of Sciences Clarke, J. O., Ahuja, N. K., Fernandez-Becker, N. Q., Gregersen, H. n., Kamal, A. N., Khan, A. n., Lynch, K. L., Vela, M. F. 2020


    The functional lumen imaging probe (FLIP) is a diagnostic tool that utilizes impedance planimetry to allow the assessment of luminal diameter and distensibility. It has been used primarily in esophageal diseases, in particular, in the assessment of achalasia, esophagogastric junction outflow obstruction, and eosinophilic esophagitis (EoE). The usage and publications have increased over the past decade and it is now an essential tool in the armamentarium of the esophagologist. Indications are emerging outside of the esophagus, in particular with regard to gastroparesis. Our paper will review the history of FLIP, optimal current usage, data for key esophageal disorders (including achalasia, reflux, and EoE), data for nonesophageal disorders, and our sense as to whether FLIP is ready for prime time, as well as gaps in evidence and suggestions for future research.

    View details for DOI 10.1111/nyas.14463

    View details for PubMedID 32814368

  • Diagnosis of gastroesophageal reflux: an update on current and emerging modalities. Annals of the New York Academy of Sciences Ang, D. n., Lee, Y. Y., Clarke, J. O., Lynch, K. n., Guillaume, A. n., Onyimba, F. n., Kamal, A. n., Gyawali, C. P. 2020


    Gastroesophageal reflux disease (GERD) is a common condition characterized by troublesome symptoms or esophageal mucosal lesions attributed to excessive esophageal acid exposure. Various pathophysiological mechanisms account for GERD, including impaired esophageal peristalsis and anatomical or physiological defects at the esophagogastric junction (EGJ). Endoscopy identifies GERD complications and detects potential alternative diagnoses. However, if symptoms persist despite proton pump inhibitor therapy, functional esophageal tests are useful to characterize reflux burden and define the symptom association profile. Ambulatory pH or pH-impedance monitoring measures the 24-h acid exposure time, which remains the most reproducible reflux metric and predicts response to antireflux therapy. Apart from identifying peristaltic dysfunction, esophageal high-resolution manometry defines the morphology and contractile vigor (EGJ-CI) of the EGJ. Novel metrics obtained from pH-impedance monitoring include the postreflux swallow-induced peristaltic wave index and mean nocturnal baseline impedance, which augment the diagnostic value of pH-impedance testing. Mucosal impedance can also be recorded using a probe inserted through a gastroscope, or a novel balloon catheter with arrays of impedance electrodes inserted following sedated endoscopy. The latest developments in functional esophageal tests define the GERD phenotype based on pathogenesis, reflux exposure, structural or motility disorders, and symptom burden, facilitating appropriate treatment.

    View details for DOI 10.1111/nyas.14369

    View details for PubMedID 32428279

  • Gastric antral vascular ectasia in systemic sclerosis: Association with anti-RNA polymerase III and negative anti-nuclear antibodies. Seminars in arthritis and rheumatism Serling-Boyd, N. n., Chung, M. P., Li, S. n., Becker, L. n., Fernandez-Becker, N. n., Clarke, J. n., Fiorentino, D. n., Chung, L. n. 2020; 50 (5): 938–42


    Gastric antral vascular ectasia (GAVE) is a vascular manifestation of systemic sclerosis (SSc) that can lead to iron deficiency anemia or acute gastrointestinal (GI) bleeding. We aimed to identify clinical features associated with GAVE.We performed a cohort study of SSc patients who were seen at Stanford between 2004 and 2018 and had undergone esophagogastroduodenoscopy (EGD). We compared the clinical features of those with and without GAVE, and multivariable logistic regression was performed to identify clinical correlates with GAVE.A total of 225 patients with SSc who underwent EGD were included in this study and 19 (8.4%) had GAVE. Those with GAVE were more likely to have scleroderma renal crisis (SRC) (21% vs 3%; p < 0.01), positive anti-RNA polymerase III antibody (71% vs 19%; p < 0.01), nucleolar pattern of anti-nuclear antibody (ANA) (33% vs 11%; p=0.04), and negative ANA (<1:80 by immunofluorescence) (33% vs 11%; p=0.02). On multivariate analysis with multiple imputation, anti-RNA polymerase III positivity (OR 4.57; 95% CI (1.57 - 13.23), p < 0.01) and ANA negativity (OR 3.75; 95% CI (1.21 - 11.62), p=0.02) remained significantly associated with GAVE.Positive anti-RNA polymerase III antibody and ANA negativity were significantly associated with GAVE. Further studies are necessary to determine whether patients with these autoantibody profiles should undergo screening endoscopies for GAVE.

    View details for DOI 10.1016/j.semarthrit.2020.06.016

    View details for PubMedID 32906028

  • Occam's Razor: An Unusual Shoulder Mass in a Patient with Achalasia. Digestive diseases and sciences Weingarden, A. R., Villescas, V. n., Clarke, J. n., Triadafilopoulos, G. n. 2020

    View details for DOI 10.1007/s10620-020-06558-y

    View details for PubMedID 32833155

  • Autonomic function in gastroparesis and chronic unexplained nausea and vomiting: Relationship with etiology, gastric emptying, and symptom severity. Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society Nguyen, L. n., Wilson, L. A., Miriel, L. n., Pasricha, P. J., Kuo, B. n., Hasler, W. L., McCallum, R. W., Sarosiek, I. n., Koch, K. L., Snape, W. J., Farrugia, G. n., Grover, M. n., Clarke, J. n., Parkman, H. P., Tonascia, J. n., Hamilton, F. n., Abell, T. L. 2020: e13810


    Autonomic dysfunction can be present in patients with idiopathic and diabetic gastroparesis. The role of autonomic dysfunction relating to gastric emptying and upper gastrointestinal symptoms in patients with gastroparesis and chronic unexplained nausea and vomiting (CUNV) remains unclear. The aim of our study is to evaluate autonomic function in patients with gastroparesis and CUNV with respect to etiology, gastric emptying and symptom severity.We studied 242 patients with chronic gastroparetic symptoms recruited at eight centers. All patients had a gastric emptying scintigraphy within 6 months of the study. Symptom severity was assessed using the gastroparesis cardinal symptom index. Autonomic function testing was performed at baseline enrollment using the ANX 3.0 autonomic monitoring system which measures heart rate variability and respiratory activity measurements.Low sympathetic response to challenge (Valsalva or standing) was the most common abnormality seen impacting 89% diabetic and 74% idiopathic patients. Diabetics compared to idiopathics, exhibited greater global hypofunction with sympathetic (OR = 4.7, 95% CI 2.2-10.3; P < .001) and parasympathetic (OR = 7.2, 95% CI 3.4-15.0; P < .001) dysfunction. Patients with delayed gastric emptying were more likely to have paradoxic parasympathetic excessive during sympathetic challenge [(Valsalva or standing) 40% vs. 26%, P = .05]. Patients with more severe symptoms exhibited greater parasympathetic dysfunction compared to those with mild-moderate symptoms: resting sympathovagal balance [LFa/RFa 1.8 (1.0-3.1) vs. 1.2 (0.6-2.3), P = .006)] and standing parasympathetic activity [0.4 (0.1-0.8) vs. 0.6 (0.2-1.7); P = .03].Autonomic dysfunction was common in patients with gastroparesis and CUNV. Parasympathetic dysfunction was associated with delayed gastric emptying and more severe upper gastrointestinal symptoms. Conversely, sympathetic hypofunction was associated with milder symptoms.Gastroparesis and CUNV may be a manifestation of GI autonomic dysfunction or imbalance, such that sympathetic dysfunction occurs early on in the manifestation of chronic upper GI symptoms, while parasympathetic dysfunction results in more severe symptoms and delayed gastric emptying.

    View details for DOI 10.1111/nmo.13810

    View details for PubMedID 32061038

  • How to approach esophagogastric junction outflow obstruction? Annals of the New York Academy of Sciences Patcharatrakul, T. n., Alkaddour, A. n., Pitisuttithum, P. n., Jangsirikul, S. n., Vega, K. J., Clarke, J. O., Gonlachanvit, S. n. 2020


    The diagnosis of esophagogastric junction outflow obstruction (EGJOO) is currently based on high-resolution esophageal manometry and is characterized by impaired EGJ relaxation with preserved esophageal peristalsis. This condition has been defined by the Chicago Classification as a major esophageal motility disorder, although its clinical significance is controversial since heterogeneous and irrelevant presentations have been reported. EGJOO commonly has a benign clinical course, with spontaneous resolution, but it can also be associated with opioid usage, early achalasia, and mechanical obstruction. A careful medical, surgical, and medication history coupled with a careful manometry interpretation focused on the factors that might affect the integrated relaxation pressure are the keys for an accurate diagnosis. The advance of esophageal physiological tests can evaluate the clearance of the esophageal contents across the EGJ. The manometry technique, including testing in an upright position and provocative tests, can also complement those tests and demonstrate the evidence of EGJ obstruction. After making a diagnosis, endoscopy should be an initial step to exclude anatomical causes if it has not yet been done. Imaging studies can identify infiltrative lesions, but the reported diagnostic yield is relatively low. Management of EGJOO depends on the underlying etiology. Functional EGJOO patients with persistent dysphagia associated with the presence of outflow obstruction may require EGJ disruption therapy.

    View details for DOI 10.1111/nyas.14412

    View details for PubMedID 32557701

  • Use of the Functional Lumen Imaging Probe in Clinical Esophagology. The American journal of gastroenterology Savarino, E. n., di Pietro, M. n., Bredenoord, A. J., Carlson, D. A., Clarke, J. O., Khan, A. n., Vela, M. F., Yadlapati, R. n., Pohl, D. n., Pandolfino, J. E., Roman, S. n., Gyawali, C. P. 2020; 115 (11): 1786–96


    The functional lumen imaging probe (FLIP) measures luminal dimensions using impedance planimetry, performed most often during sedated upper endoscopy. Mechanical properties of the esophageal wall and opening dynamics of the esophagogastric junction (EGJ) can be objectively evaluated in esophageal motor disorders, eosinophilic esophagitis, esophageal strictures, during esophageal surgery and in postsurgical symptomatic states. Distensibility index, the ratio of EGJ cross sectional area to intraballoon pressure, is the most useful FLIP metric. Secondary peristalsis from balloon distension can be displayed topographically as repetitive anterograde or retrograde contractile activity in the esophageal body, similar to high-resolution manometry. Real-time interpretation and postprocessing of FLIP metadata can complement the identification of esophageal outflow obstruction and achalasia, especially when findings are inconclusive from alternate esophageal tests in symptomatic patients. FLIP can complement the diagnosis of achalasia when manometry and barium studies are inconclusive or negative in patients with typical symptoms. FLIP can direct adequacy of disruption of the EGJ in achalasia when used during and immediately after myotomy and pneumatic dilation. Lumen diameter measured using FLIP in eosinophilic esophagitis and in complex strictures can potentially guide management. An abbreviated modification of the Grading of Recommendations Assessment, Development, and Evaluation was used to determine the quality of available evidence and recommendations regarding FLIP utilization. FLIP metrics that are diagnostic or suggestive of an abnormal motor pattern and metrics that define normal esophageal physiology were developed by consensus and are described in this review.

    View details for DOI 10.14309/ajg.0000000000000773

    View details for PubMedID 33156096

  • Baseline impedance via manometry and ambulatory reflux testing are not equivalent when utilized in the evaluation of potential extra-esophageal gastroesophageal reflux disease. Journal of thoracic disease Zikos, T. A., Triadafilopoulos, G. n., Kamal, A. n., Podboy, A. n., Sonu, I. S., Regalia, K. A., Nandwani, M. C., Nguyen, L. A., Fernandez-Becker, N. Q., Clarke, J. O. 2020; 12 (10): 5628–38


    Esophageal baseline impedance (BI) shows promise for the diagnosis of gastroesophageal reflux disease (GERD), but means of acquisition and relevance to extra-esophageal manifestations of GERD (EE-GERD) remain unclear. In this study we aim to (I) evaluate concordance between BI as measured by 24-hour pH-impedance (pH-MII) and high-resolution impedance manometry (HRIM), and (II) assess relationship to potential EE-GERD symptoms.In this prospective open cohort study, patients presenting for outpatient HRIM and pH-MII studies were prospectively enrolled. All patients completed the GERD-HRQL, NOSE, and respiratory symptom index questionnaire (RSI), plus questions regarding wheezing and dental procedures. HRIM and pH-MII were evaluated with calculation of BI. Correlations were assessed using either Pearson's correlation or Spearman's rank coefficients.70 HRIM patients were enrolled, 35 of whom underwent pH-MII. There was no correlation between BI measurements as assessed by HRIM and pH-MII proximally, but there was moderate-weak correlation distally (r=0.34 to 0.5). Distal acid exposure time correlated with distal BI only for measurements by pH-MII (rho= -0.5 to -0.65), and not by HRIM. There was no relationship between proximal acid exposure time and proximal BI. There were no correlations when comparing proximal or distal BI measurements, acid exposure times, and impedance events to symptoms.Concordance between BI as measured by HRIM and pH-MII is poor, especially proximally, suggesting that these two methods are not interchangeable. There is no correlation between BI both distally/proximally and symptoms of either GERD/EE-GERD, suggesting that many symptoms are unrelated to acid or that BI is not an adequate marker to assess EE-GERD symptoms.

    View details for DOI 10.21037/jtd-20-1623

    View details for PubMedID 33209395

    View details for PubMedCentralID PMC7656325

  • Esophageal physiology-an overview of esophageal disorders from a pathophysiological point of view. Annals of the New York Academy of Sciences Lottrup, C. n., Khan, A. n., Rangan, V. n., Clarke, J. O. 2020


    The esophagus serves the principal purpose of transporting food from the pharynx into the stomach. A complex interplay between nerves and muscle fibers ensures that swallowing takes place as a finely coordinated event. Esophageal function can be tested by a variety of methods, endoscopy, manometry, and reflux monitoring being some of the most important. Regarding pathophysiology, motor disorders, such as achalasia, often cause dysphagia and/or chest pain. Functional esophageal disorders are a heterogeneous group with hypersensitivity as a dominant pathophysiological factor. Gastroesophageal reflux disease often causes symptoms, such as heartburn and regurgitation, and a spectrum of disease, ranging from minimal mucosal damage visible only in the microscope to esophageal ulcers and strictures in the most severe cases. Eosinophilic esophagitis is an immune-mediated condition that can result in significant dysphagia and associated luminal narrowing. In the following, we will provide an overview of the most common esophageal disorders from a combined pathophysiological and clinical view.

    View details for DOI 10.1111/nyas.14417

    View details for PubMedID 32648992

  • Non-acid Reflux: When It Matters and Approach to Management. Current gastroenterology reports Zikos, T. A., Clarke, J. O. 2020; 22 (9): 43


    This narrative review focuses on the presentation, contributing factors, diagnosis, and treatment of non-acid reflux. We also propose algorithms for diagnosis and treatment.There is a paucity of recent data regarding non-acid reflux. The recent Porto and Lyon consensus statements do not fully address non-acid reflux or give guidance on classification. However, recent developments in the lung transplantation field, as well as older data in the general population, argue for the importance of non-acid reflux. Extrapolating from the Porto and Lyon consensus, we generally classify pathologic non-acid reflux as impedance events > 80, acid exposure time < 4%, and positive symptom correlation on a standard 24-h pH/impedance test. Other groups not meeting this criteria also deserve consideration depending on the clinical situation. Potential treatments include lifestyle modification, increased acid suppression, alginates, treatment of esophageal hypersensitivity, baclofen, buspirone, prokinetics, and anti-reflux surgery in highly selected individuals. More research is needed to clarify appropriate classification, with subsequent focus on targeted treatments.

    View details for DOI 10.1007/s11894-020-00780-4

    View details for PubMedID 32651702

  • Open-label pilot study: Non-invasive vagal nerve stimulation improves symptoms and gastric emptying in patients with idiopathic gastroparesis. Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society Gottfried-Blackmore, A., Adler, E. P., Fernandez-Becker, N., Clarke, J., Habtezion, A., Nguyen, L. 2019: e13769


    BACKGROUND: Gastroparesis, a chronic motility disorder characterized by delayed gastric emptying, abdominal pain, nausea, and vomiting, remains largely unexplained. Medical therapy is limited, reflecting the complex physiology of gastric sensorimotor function. Vagus nerve stimulation is an attractive therapeutic modality for gastroparesis, but prior methods required invasive surgery. In this open-label pilot study, we aimed to assess the benefit of non-invasive vagal nerve stimulation in patients with mild to moderate idiopathic gastroparesis.METHODS: Patients self-administered the gammaCore vagal nerve stimulator for 4weeks. The gastroparesis cardinal symptom index daily diary (GCSI-dd) was assessed during a two-week run-in period, ≥4weeks of therapy, and 4weeks after therapy was completed. Gastric emptying and autonomic function testing were also performed. The primary endpoint was an absolute reduction in CGSI-dd of 0.75 after nVNS.RESULTS: There was a total improvement in symptom scores (2.56±0.76 to 1.87±1.05; P=.01), with 6/15 (40%) participants meeting our primary endpoint. Therapy was associated with a reduction in gastric emptying (T1/2 155 vs 129minutes; P=.053, CI -0.4 to 45). Therapy did not correct autonomic function abnormalities, but was associated with modulation of reflex parasympathetic activity.CONCLUSIONS: Short-term non-invasive vagal nerve stimulation led to improved cardinal symptoms and accelerated gastric emptying in a subset of patients with idiopathic gastroparesis. Responders had more severe gastric delay at baseline and clinical improvement correlated with duration of therapy, but not with improvements in gastric emptying. Larger randomized sham-controlled trials of greater duration are needed to confirm the results of this pilot study.

    View details for DOI 10.1111/nmo.13769

    View details for PubMedID 31802596

  • Ninety-Six Hour Wireless Esophageal pH Study in Patients with GERD Shows that Restrictive Diet Reduces Esophageal Acid Exposure. Digestive diseases and sciences Triadafilopoulos, G., Korzilius, J. W., Zikos, T., Sonu, I., Fernandez-Becker, N. Q., Nguyen, L., Clarke, J. O. 2019


    BACKGROUND: Prolonged (96h) pH monitoring may explore the effect of diet on pH and symptoms in patients with GERD.AIMS: To assess the usefulness of a 96h esophageal pH study in patients with GER symptoms under different diets (pro- and anti-GER).METHODS: Prospective study of 66 patients with GERD undergoing wireless 96h pH monitoring. Two-day periods, one on liberal (pro-reflux) and another on restricted (anti-reflux) diet assessed esophageal acid exposure and symptoms. The primary end point was normalization of acid exposure time while on restricted diet. Secondary end point was a>50% reduction in symptoms with restricted diet.RESULTS: Normal (pH time<4 of<6%) was found in 34 patients (51.5%) while on the initial 48h (liberal) diet [median % time<4: 3.2 (95% CI, 1.9, 4.0)] and remained normal while on restricted diet [median % time<4: 2.6 (95% CI, 0.8, 3.4)]. Abnormal acid exposure (% pH time<4:>6%) was found in 32 patients (48.5%) while on initial 48h liberal diet [median % time<4: 10.5, (95% CI 8.9, 12.6)], and decreased significantly with restricted diet [median % time<4: 4.5 (95% CI 3.1, 7.3)] (p=0.001), and normalized with anti-GERD diet in 21 patients (65.6%). Only 11/66 patients were candidates for proton pump inhibitor (PPI) use; 34 had either normal pH studies or normalized them with restricted diet (n=21). Symptoms did not improve with restricted diet.CONCLUSIONS: The 96-h esophageal pH study tests for GERD under pro- and anti-GER diets and allows minimization of PPI therapy to only 16.6% of patients.

    View details for DOI 10.1007/s10620-019-05940-9

    View details for PubMedID 31734874

  • Linaclotide for the Treatment of Gastrointestinal Symptoms in Systemic Sclerosis Dein, E., Clarke, J., Wigley, F., McMahan, Z. WILEY. 2019
  • Motility Abnormalities Identified by Wireless Motility Capsule in Postural Orthostatic Tachycardia Syndrome Zikos, T. A., Zhou, W., Clarke, J. O., Nguyen, L. A., Neshatian, L. LIPPINCOTT WILLIAMS & WILKINS. 2019: S279
  • Ineffective esophageal motility: Concepts, future directions, and conclusions from the Stanford 2018 symposium NEUROGASTROENTEROLOGY AND MOTILITY Gyawali, C., Sifrim, D., Carlson, D. A., Hawn, M., Katzka, D. A., Pandolfino, J. E., Penagini, R., Roman, S., Savarino, E., Tatum, R., Vaezi, M., Clarke, J. O., Triadafilopoulos, G. 2019; 31 (9)

    View details for DOI 10.1111/nmo.13584

    View details for Web of Science ID 000481574000003

  • Abdominal Pain in Patients with Gastroparesis: Associations with Gastroparesis Symptoms, Etiology of Gastroparesis, Gastric Emptying, Somatization, and Quality of Life DIGESTIVE DISEASES AND SCIENCES Parkman, H. P., Wilson, L. A., Hasler, W. L., McCallum, R. W., Sarosiek, I., Koch, K. L., Abell, T. L., Schey, R., Kuo, B., Snape, W. J., Nguyen, L., Farrugia, G., Grover, M., Clarke, J., Miriel, L., Tonascia, J., Hamilton, F., Pasricha, P. J. 2019; 64 (8): 2242–55
  • Murky Waters for Diagnosis of Gastroparesis CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Kunkel, D. C., Clarke, J. O. 2019; 17 (9): 1724–25
  • Gastric per-oral endoscopic myotomy: Current status and future directions WORLD JOURNAL OF GASTROENTEROLOGY Podboy, A., Hwang, J., Nguyen, L. A., Garcia, P., Zikos, T. A., Kamal, A., Triadafilopoulos, G., Clarke, J. O. 2019; 25 (21): 2581–90
  • Opioid Use and Potency Are Associated With Clinical Features, Quality of Life, and Use of Resources in Patients With Gastroparesis CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Hasler, W. L., Wilson, L. A., Nguyen, L. A., Snape, W. J., Abell, T. L., Koch, K. L., McCallum, R. W., Pasricha, P. J., Sarosiek, I., Farrugia, G., Grover, M., Lee, L. A., Miriel, L., Tonascia, J., Hamilton, F. A., Parkman, H. P., Pasricha, P., Clarke, J., Kim, Y., Nguyen, L., Ullah, N., Snape, W., DeVole, N., Greene, M., Lee, C., Ponsetto, C., Shetler, K., Parkman, H. P., Kantor, S., Lytes, V., Palit, A., Simmons, K., McCallum, R. W., Hejazi, R., Roeser, K., Sarosiek, I., Vasquez, D., Vega, N., Abell, T., Beatty, K., Hatter, L., Howard, R., Nowotny, L., Tang, S., Amin, O. S., Henry, O., Kedar, A., McNair, V., Pruett, S., Smith, M., Spree, D., Hasler, W., Castle, M., Coleski, R., Wootten, S., Koch, K., Baxter, L., Brown, A., Culler, S., Hooker, J., Stuart, P., Farrugia, G., Grover, M., Bernard, C., Calles-Escandon, J., Serrano, J., Hamilton, F., James, S., Torrance, R., Van Raaphorst, R., Tonascia, J., Belt, P., Hallinan, E., Colvin, R., Donithan, M., Green, M., Isaacson, M., Kim, W., Lee, L., May, P., Miriel, L., Sternberg, A., Van Natta, M., Vaughn, I., Wilson, L., Yates, K., Gastroparesis Clinical Res 2019; 17 (7): 1285-+
  • Under Pressure: Do Volume-Based Measurements Define Rectal Hyposensitivity in Clinical Practice? DIGESTIVE DISEASES AND SCIENCES Kamal, A. N., Garcia, P., Clarke, J. O. 2019; 64 (5): 1062–63
  • Ineffective esophageal motility: Concepts, future directions, and conclusions from the Stanford 2018 symposium. Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society Gyawali, C. P., Sifrim, D., Carlson, D. A., Hawn, M., Katzka, D. A., Pandolfino, J. E., Penagini, R., Roman, S., Savarino, E., Tatum, R., Vaezi, M., Clarke, J. O., Triadafilopoulos, G. 2019: e13584


    BACKGROUND: Ineffective esophageal motility (IEM) is a heterogenous minor motility disorder diagnosed when ≥50% ineffective peristaltic sequences (distal contractile integral <450mm Hgcms) coexist with normal lower esophageal sphincter relaxation (integrated relaxation pressure70% ineffective sequences) is associated with higher esophageal reflux burden, particularly while supine, but milder variants do not progress over time or consistently impact quality of life. Ineffective esophageal motility can be further characterized using provocative maneuvers during HRM, especially multiple rapid swallows, where augmentation of smooth muscle contraction defines contraction reserve. The presence of contraction reserve may predict better prognosis, lesser reflux burden and confidence in a standard fundoplication for surgical management of reflux. Other provocative maneuvers (solid swallows, standardized test meal, rapid drink challenge) are useful to characterize bolus transit in IEM. No effective pharmacotherapy exists, and current managements target symptoms and concurrent reflux. Novel testing modalities (baseline and mucosal impedance, functional lumen imaging probe) show promise in elucidating pathophysiology and stratifying IEM phenotypes. Specific prokinetic agents targeting esophageal smooth muscle need to be developed for precision management.

    View details for PubMedID 30974032

  • Murky Waters for Diagnosis of Gastroparesis. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Kunkel, D. C., Clarke, J. O. 2019

    View details for PubMedID 30978538

  • Under Pressure: Do Volume-Based Measurements Define Rectal Hyposensitivity in Clinical Practice? Digestive diseases and sciences Kamal, A. N., Garcia, P., Clarke, J. O. 2019

    View details for PubMedID 30963367

  • High Prevalence of Slow Transit Constipation in Patients With Gastroparesis JOURNAL OF NEUROGASTROENTEROLOGY AND MOTILITY Zikos, T. A., Kamal, A. N., Neshatian, L., Triadafilopoulos, G., Clarke, J. O., Nandwani, M., Nguyen, L. A. 2019; 25 (2): 267–75

    View details for DOI 10.5056/jnm18206

    View details for Web of Science ID 000464525700012

  • Abdominal Pain in Patients with Gastroparesis: Associations with Gastroparesis Symptoms, Etiology of Gastroparesis, Gastric Emptying, Somatization, and Quality of Life. Digestive diseases and sciences Parkman, H. P., Wilson, L. A., Hasler, W. L., McCallum, R. W., Sarosiek, I., Koch, K. L., Abell, T. L., Schey, R., Kuo, B., Snape, W. J., Nguyen, L., Farrugia, G., Grover, M., Clarke, J., Miriel, L., Tonascia, J., Hamilton, F., Pasricha, P. J. 2019


    Abdominal pain can be an important symptom in some patients with gastroparesis (Gp).AIMS: (1) To describe characteristics of abdominal pain in Gp; (2) describe Gp patients reporting abdominal pain.METHODS: Patients with idiopathic gastroparesis (IG) and diabetic gastroparesis (DG) were studied with gastric emptying scintigraphy, water load test, wireless motility capsule, and questionnaires assessing symptoms [Patient Assessment of Upper GI Symptoms (PAGI-SYM) including Gastroparesis Cardinal Symptom Index (GCSI)], quality of life (PAGI-QOL, SF-36), psychological state [Beck Depression Inventory (BDI), State-Trait Anxiety Index (STAI), PHQ-15 somatization scale].RESULTS: In total, 346 Gp patients included 212 IG and 134 DG. Ninety percentage of Gp patients reported abdominal pain (89% DG and 91% IG). Pain was primarily in upper or central midline abdomen, described as cramping or sickening. Upper abdominal pain was severe or very severe on PAGI-SYM by 116/346 (34%) patients, more often by females than by males, but similarly in IG and DG. Increased upper abdominal pain severity was associated with increased severity of the nine GCSI symptoms, depression on BDI, anxiety on STAI, somatization on PHQ-15, the use of opiate medications, decreased SF-36 physical component, and PAGI-QOL, but not related to severity of delayed gastric emptying or water load ingestion. Using logistic regression, severe/very severe upper abdominal pain associated with increased GCSI scores, opiate medication use, and PHQ-15 somatic symptom scores.CONCLUSIONS: Abdominal pain is common in patients with Gp, both IG and DG. Severe/very severe upper abdominal pain occurred in 34% of Gp patients and associated with other Gp symptoms, somatization, and opiate medication use. Identifier: NCT01696747.

    View details for PubMedID 30852767

  • High Prevalence of Slow Transit Constipation in Patients With Gastroparesis. Journal of neurogastroenterology and motility Zikos, T. A., Kamal, A. N., Neshatian, L., Triadafilopoulos, G., Clarke, J. O., Nandwani, M., Nguyen, L. A. 2019


    Background/Aims: Current evidence suggests the presence of motility or functional abnormalities in one area of the gastrointestinal tract increases the likelihood of abnormalities in others. However, the relationship of gastroparesis to chronic constipation (slow transit constipation and dyssynergic defecation) has been incompletely evaluated.Methods: We retrospectively reviewed the records of all patients with chronic dyspeptic symptoms and constipation who underwent both a solid gastric emptying scintigraphy and a highresolution anorectal manometry at our institution since January 2012. When available, Xray defecography and radiopaque marker colonic transit studies were also reviewed. Based on the gastric emptying results, patients were classified as gastroparesis or dyspepsia with normal gastric emptying (control group). Differences in anorectal and colonic findings were then compared between groups.Results: Two hundred and six patients met the inclusion criteria. Patients with gastroparesis had higher prevalence of slow transit constipation by radiopaque marker study compared to those with normal emptying (64.7% vs 28.1%, P = 0.013). Additionally, patients with gastroparesis had higher rates of rectocele (88.9% vs 60.0%, P = 0.008) and intussusception (44.4% vs 12.0%, P = 0.001) compared to patients with normal emptying. There was no difference in the rate of dyssynergic defecation between those with gastroparesis vs normal emptying (41.1% vs 42.1%, P = 0.880), and no differences in anorectal manometry findings.Conclusions: Patients with gastroparesis had a higher rate of slow transit constipation, but equal rates of dyssynergic defecation compared to patients with normal gastric emptying. These findings argue for investigation of possible delayed colonic transit in patients with gastroparesis and vice versa.

    View details for PubMedID 30870880

  • Reduction in Hospitalizations for Esophageal Reflux in a Decade with Minimal Increases in Other Functional and Motor Disorders. Digestive diseases and sciences Zikos, T. A., Hendler, S. n., Clarke, J. O., Triadafilopoulos, G. n., Nguyen, L. n., Limketkai, B. N. 2019


    Functional and motility disorders (FMDs) are common conditions that cause significant morbidity and economic loss. A comprehensive analysis of these disorders and their impact has not been done in an inpatient setting.We seek to evaluate adult hospitalization trends for FMDs in the USA.The National Inpatient Sample between 2005 and 2014 was analyzed. Poisson regression was used to assess hospitalization trends for FMDs referenced to non-FMD hospitalizations. Linear regression was used to assess cost per hospitalization and length of stay (LOS). All models were adjusted for age, sex, primary insurance, and Charlson comorbidity index.Hospitalizations with FMDs as the primary diagnosis fell by an adjusted 2.46%/year over the study period (p < 0.001). The entirety of this reduction was explained by falling admissions for gastroesophageal reflux (adjusted reduction of 7.04%/year, p < 0.001). The hospitalization rate for all other FMDs (excluding gastroesophageal reflux) minimally increased by 0.75%/year (p = 0.001). Total cost of care for FMD hospitalizations remained relatively stable ($3.17 billion in 2014), while increasing for all other hospitalizations. Mean LOS for FMD hospitalization increased by an adjusted 0.025 days/year, but decreased by 0.038 days/year for all other hospitalizations (p < 0.001).The hospitalization rate for gastroesophageal reflux fell between 2005 and 2014, but remained relatively stable to increase for all other FMDs. These trends may be due to increased proton pump inhibitor use, better patient/provider education, emphasis on outpatient management, and/or coding bias.

    View details for DOI 10.1007/s10620-019-05895-x

    View details for PubMedID 31620929

  • Esophagogastroduodenoscopy and Esophageal Involvement in Patients with Pemphigus Vulgaris. Dysphagia Ozeki, K. A., Zikos, T. A., Clarke, J. O., Sonu, I. n. 2019


    Pemphigus vulgaris (PV) is a rare autoimmune blistering disease involving the skin and mucous membranes. The prevalence of esophageal involvement remains uncertain. The aim of our study was to determine the frequency of esophageal involvement in patients with PV. This is a single-center electronic database retrospective review of patients with a diagnosis of PV. Data abstracted included demographics, disease characteristics (biopsy results, symptoms, areas affected, treatments), and esophagogastroduodenoscopy (EGD) reports. Of the 111 patients that met eligibility criteria, only 22 (19.8%) underwent EGD. Demographic data were similar except those who underwent EGD were more likely to be female (77.3% vs. 51.7%, p = 0.05) and have hypertension (50.0% vs. 24.7%, p = 0.04). Esophageal symptoms were common in both groups; however, those experiencing dysphagia were more likely to undergo EGD (50.0% vs. 20.2%, p = 0.007). Those who underwent EGD had more refractory disease (≥ 3 treatment modalities: 100% vs. 58.4%, p < 0.001), but did not differ in areas affected. Of those who underwent EGD, only 4 (18.2%) had esophageal abnormalities either prior to PV diagnosis (1) or during a disease flare (3). Those having a flare were more likely to experience odynophagia (69.2%) or weight loss (61.5%), p = 0.02 and p = 0.05, respectively. While esophageal symptoms were common in our cohort of PV patients, a minority of patients underwent EGD, and the vast majority of those were unremarkable. This suggests that while esophageal symptoms are common in PV, permanent esophageal injury is more rare.

    View details for DOI 10.1007/s00455-019-10055-4

    View details for PubMedID 31538221

  • Impact of nurse practitioner navigation on access to care for patients with refractory gastroesophageal reflux disease. Journal of the American Association of Nurse Practitioners Nandwani, M. n., Clarke, J. O., Kuriakose, C. n., Stevenson, E. n. 2019


    Gastroesophageal reflux disease (GERD) is a common digestive complaint that can negatively affect patients' quality of life and have serious complications if inadequately treated.Facilitating prompt and efficient access to digestive care is imperative especially given the current burden of gastrointestinal diseases such as GERD.A clinical team conducted a quality improvement study in which a nurse practitioner (NP) navigator performed a preconsultation chart review for patients with refractory GERD referred to an Esophagus Center between August and December 2018.Based on preconsultation chart review, the NP navigator arranged for diagnostic testing and follow-up. Days from consultation to testing completion and establishment of plan were tracked and compared with historic controls. The NP navigator documented time spent for chart review and care coordination.The median number of days from consultation to testing completion for patients who underwent NP navigation and required diagnostic testing (n = 26) was 33.5 as compared with 64.5 for historic controls who required testing but received usual care (n = 28) (p = .005). The median number of days from consultation to establishment of a management plan was 52 for patients who underwent NP navigation as compared with 97 for historic controls who did not (p = .005). The mean amount of time spent by the NP navigator for chart review and care coordination was 17.5 min (n = 30).Incorporation of NP navigators into gastroenterology practices offers a potential solution for timelier patient care delivery.

    View details for DOI 10.1097/JXX.0000000000000296

    View details for PubMedID 31567776

  • Delayed Gastric Emptying Associates With Diabetic Complications in Diabetic Patients With Symptoms of Gastroparesis. The American journal of gastroenterology Parkman, H. P., Wilson, L. A., Farrugia, G. n., Koch, K. L., Hasler, W. L., Nguyen, L. A., Abell, T. L., Snape, W. n., Clarke, J. n., Kuo, B. n., McCallum, R. W., Sarosiek, I. n., Grover, M. n., Miriel, L. n., Tonascia, J. n., Hamilton, F. A., Pasricha, P. J. 2019


    Diabetic gastroparesis (Gp) occurs more often in type 1 diabetes mellitus (T1DM) than in type 2 diabetes mellitus (T2DM). Other diabetic end-organ complications include peripheral neuropathy, nephropathy, and retinopathy (together termed triopathy). This study determines the prevalence of diabetic complications (retinopathy, nephropathy, and peripheral neuropathy) in diabetic patients with symptoms of Gp, assessing the differences between T1DM and T2DM and delayed and normal gastric emptying (GE).Diabetic patients with symptoms of Gp underwent history and physical examination, GE scintigraphy, electrogastrography with water load, autonomic function testing, and questionnaires assessing symptoms and peripheral neuropathy.One hundred thirty-three diabetic patients with symptoms of Gp were studied: 59 with T1DM and 74 with T2DM and 103 with delayed GE and 30 without delayed GE. The presence of retinopathy (37% vs 24%; P = 0.13), nephropathy (19% vs 11%; P = 0.22), and peripheral neuropathy (53% vs 39%; P = 0.16) was not significantly higher in T1DM than in T2DM; however, triopathies (all 3 complications together) were seen in 10% of T1DM and 3% of T2DM (P = 0.04). Diabetic patients with delayed GE had increased prevalence of retinopathy (36% vs 10%; P = 0.006) and number of diabetic complications (1.0 vs 0.5; P = 0.009); however, 39% of diabetic patients with delayed GE did not have any diabetic complications.In diabetic patients with symptoms of Gp, delayed GE was associated with the presence of retinopathy and the total number of diabetic complications. Only 10% of patients with T1DM and 3% of those with T2DM had triopathy of complications, and 39% of diabetic patients with Gp did not have any diabetic complications. Thus, the presence of diabetic complications should raise awareness for Gp in either T1DM or T2DM; however, diabetic Gp frequently occurs without other diabetic complications.

    View details for DOI 10.14309/ajg.0000000000000410

    View details for PubMedID 31658129

  • Gastric per-oral endoscopic myotomy: Current status and future directions. World journal of gastroenterology Podboy, A. n., Hwang, J. H., Nguyen, L. A., Garcia, P. n., Zikos, T. A., Kamal, A. n., Triadafilopoulos, G. n., Clarke, J. O. 2019; 25 (21): 2581–90


    Gastroparesis, or symptomatic delayed gastric emptying in the absence of mechanical obstruction, is a challenging and increasingly identified syndrome. Medical options are limited and the only medication approved by the Food and Drug Administration for treatment of gastroparesis is metoclopramide, although other agents are frequently used off label. With this caveat, first-line treatments for gastroparesis include dietary modifications, antiemetics and promotility agents, although these therapies are limited by suboptimal efficacy and significant medication side effects. Treatment of patients that fail first-line treatments represents a significant therapeutic challenge. Recent advances in endoscopic techniques have led to the development of a promising novel endoscopic therapy for gastroparesis via endoscopic pyloromyotomy, also referred to as gastric per-oral endoscopic myotomy or per-oral endoscopic pyloromyotomy. The aim of this article is to review the technical aspects of the per-oral endoscopic myotomy procedure for the treatment of gastroparesis, provide an overview of the currently published literature, and outline potential next directions for the field.

    View details for DOI 10.3748/wjg.v25.i21.2581

    View details for PubMedID 31210711

    View details for PubMedCentralID PMC6558440

  • Helping Patients with Gastroparesis. The Medical clinics of North America Onyimba, F. U., Clarke, J. O. 2019; 103 (1): 71–87


    Gastroparesis is an increasing concern and options remain limited. Diagnosis hinges on recognition of delayed gastric emptying in the absence of mechanical obstruction. Nontransit studies evaluating gastric motility serve a complementary role and may help guide therapy. Treatment consists of a combination of lifestyle and dietary medication, medications (antiemetics, prokinetics, neuromodulators, and accommodation-enhancers), alternative and complementary therapy, endoscopic therapy (pyloric-directed therapy, temporary stimulation, jejunostomy, or venting gastrostomy) and surgical therapy (pyloroplasty, gastric electrical stimulation, gastrectomy). Treatment can be tailored to the individual needs and symptoms of the affected patient.

    View details for PubMedID 30466677

  • Esophagogastroduodenoscopy and Esophageal Involvement in Patients With Pemphigus Vulgaris Ozeki, K., Zikos, T. A., Clarke, J., Sonu, I. NATURE PUBLISHING GROUP. 2018: S177
  • Incorporating Advanced Practice Providers into Gastroenterology Practice. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Nandwani, M. C., Clarke, J. O. 2018

    View details for PubMedID 30218703

  • Gastrointestinal Involvement in Systemic Sclerosis An Update JCR-JOURNAL OF CLINICAL RHEUMATOLOGY Miller, J. B., Gandhi, N., Clarke, J., McMahan, Z. 2018; 24 (6): 328–37

    View details for PubMedID 29095721

    View details for PubMedCentralID PMC6110377

  • Identification of Risk Factors for Gastric Antral Vascular Ectasia (GAVE) Among Systemic Sclerosis Patients Serling-Boyd, N., Li, S., Fiorentino, D., Becker, L., Fernandez-Becker, N., Clarke, J., Chung, L. WILEY. 2018
  • Multi-Organ RNA-Sequencing of Patients with Systemic Sclerosis (SSc) Finds That Intrinsic Subsets Are Conserved across Organ Systems Mehta, B. K., Franks, J., Wang, Y., Cai, G., Toledo, D. M., Wood, T. A., Archambault, K. A., Kosarek, N., Kolstad, K. D., Stark, M., Valenzuela, A., Fiorentino, D., Fernandez-Becker, N., Becker, L., Nguyen, L., Clarke, J., Boin, F., Wolters, P., Chung, L., Whitfield, M. L. WILEY. 2018
  • Use of Esophageal pH Monitoring to Minimize Proton-Pump Inhibitor Utilization in Patients with Gastroesophageal Reflux Symptoms. Digestive diseases and sciences Triadafilopoulos, G., Zikos, T., Regalia, K., Sonu, I., Fernandez-Becker, N. Q., Nguyen, L., Nandwani, M. C., Clarke, J. O. 2018


    BACKGROUND: Due to concerns about long-term PPI use in patients with acid reflux, we aimed at minimizing PPI use, either by avoiding initiating therapy, downscaling to other therapies, or introducing endoscopic or surgical options.AIMS: To examine the role of esophageal ambulatory pHmetry in minimizing PPI use in patients with heartburn and acid regurgitation.METHODS: Retrospective cohort analysis of patients with reflux symptoms, who underwent endoscopy, manometry, and ambulatory pHmetry to define the need for PPI. Patients were classified as: (1) never users; (2) partial responders to PPI; (3) users with complete response to PPI. Patients were then managed as: (1) PPI non-users; (2) PPI-initiated, and (3) PPI-continued.RESULTS: Of 286 patients with heartburn and regurgitation, 103 (36%) were found to have normal and 183 (64%) abnormal esophageal acid exposure (AET). In the normal AET group, 44/103 had not been treated and were not initiated on PPI. Of the 59 who had previously received PPI, 52 stopped and 7 continued PPI. Hence, PPI were avoided in 96/103 patients (93%). In the abnormal AET group, 61/183 had not been treated and 38 were initiated on PPI and 23 on other therapies. In the 122 patients previously treated with PPI, 24 were not treated with PPI, but with H2RAs, prokinetics, endoscopic, or surgical therapy. Hence, PPI therapy was avoided in 47/183 patients (26%).CONCLUSIONS: In patients with GER symptoms, esophageal pHmetry may avert PPI use in 50%. In the era of caution regarding PPIs, early testing may provide assurance and justification.

    View details for PubMedID 29959725

  • A Positive Correlation Between Gastric and Esophageal Dysmotility Suggests Common Causality. Digestive diseases and sciences Zikos, T. A., Clarke, J. O., Triadafilopoulos, G., Regalia, K. A., Sonu, I. S., Fernandez-Becker, N. Q., Nandwani, M. C., Nguyen, L. A. 2018


    BACKGROUND: Gastric and esophageal dysmotility syndromes are some of the most common motility diagnoses, but little is known about their interrelationship.AIMS: The aim of our study was to determine if a correlation exists between gastric and esophageal dysmotility syndromes.METHODS: We reviewed the records of all patients who underwent both solid gastric emptying scintigraphy (GES) and high-resolution esophageal manometry (HRM) withina 2 year period, with both done between August 2012 and August 2017. All GESs were classified as either rapid, normal, or delayed. All HRMs were classified according to the Chicago Classification 3.0. Correlations were assessed using Fisher's exact test and multiple logistic regression.RESULTS: In total, 482 patients met inclusion criteria. Of patients with a normal, delayed, and rapid GES, 53.1, 64.5, and 77.3% had an abnormal HRM, respectively (p<0.05 vs. normal GES). Likewise, patients with an abnormal HRM were more likely to have an abnormal GES (54.9 vs. 41.8%, p=0.005). Multiple logistic regression showed abnormal GES [odds ratio (OR) 2.14], age (OR 1.013), scleroderma (OR 6.29), and dysphagia (OR 2.63) were independent predictors of an abnormal HRM. Likewise, an abnormal HRM (OR 2.11), diabetes (OR 1.85), heart or lung transplantation (OR 2.61), and autonomic dysfunction (OR 2.37) were independent predictors of an abnormal GES.CONCLUSIONS: The correlation between an abnormal GES and HRM argues for common pathogenic mechanisms of these motility disorders, and possibly common future treatment options. Clinicians should have a high index of suspicion for another motility disorder if one is present.

    View details for PubMedID 29946871

  • REFRACTORY GASTROPARESIS: GASTRIC PERORAL ENDOSCOPIC MYOTOMY (G-POEM) VS. INTRAPYLORIC BOTULINUM TOXIN INJECTION Parsa, N., Yang, J., Gutierrez, O., Moran, R., Sanaei, O., Fayad, L., Dbouk, M., Paiji, C., Kumbhari, V., Mullin, G., Stein, E. M., Abdi, T., Garcia, P., Kalloo, A. N., Canto, M. I., Clarke, J. O., Khashab, M. A. MOSBY-ELSEVIER. 2018: AB241–AB242
  • Advances in the diagnosis and classification of gastric and intestinal motility disorders NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY Keller, J., Bassotti, G., Clarke, J., Dinning, P., Fox, M., Grover, M., Hellstrom, P. M., Ke, M., Layer, P., Malagelada, C., Parkman, H. P., Scott, S., Tack, J., Simren, M., Tornblom, H., Camilleri, M., Int Working Grp Disorders Gastroin 2018; 15 (5): 291–308


    Disturbances of gastric, intestinal and colonic motor and sensory functions affect a large proportion of the population worldwide, impair quality of life and cause considerable health-care costs. Assessment of gastrointestinal motility in these patients can serve to establish diagnosis and to guide therapy. Major advances in diagnostic techniques during the past 5-10 years have led to this update about indications for and selection and performance of currently available tests. As symptoms have poor concordance with gastrointestinal motor dysfunction, clinical motility testing is indicated in patients in whom there is no evidence of causative mucosal or structural diseases such as inflammatory or malignant disease. Transit tests using radiopaque markers, scintigraphy, breath tests and wireless motility capsules are noninvasive. Other tests of gastrointestinal contractility or sensation usually require intubation, typically represent second-line investigations limited to patients with severe symptoms and are performed at only specialized centres. This Consensus Statement details recommended tests as well as useful clinical alternatives for investigation of gastric, small bowel and colonic motility. The article provides recommendations on how to classify gastrointestinal motor disorders on the basis of test results and describes how test results guide treatment decisions.

    View details for PubMedID 29622808

  • Baclofen and gastroesophageal reflux disease: seeing the forest through the trees. Clinical and translational gastroenterology Clarke, J. O., Fernandez-Becker, N. Q., Regalia, K. A., Triadafilopoulos, G. 2018; 9 (3): 137


    Baclofen has been shown to decrease reflux events and increase lower esophageal sphincter pressure, yet has never established a clear role in the treatment of gastroesophageal reflux disease (GERD). Lei and colleagues have shown in a recent elegant study that baclofen reduces the frequency and initiation of secondary peristalsis and heightens esophageal sensitivity to capsaicin-mediated stimulation. These findings may help explain both the benefit of baclofen in conditions such as rumination and supragastric belching, as well as the apparent lack of benefit of baclofen and other GABAB agonists in long-term treatment of GERD.

    View details for PubMedID 29599487

  • The Effect of Race in Patients with Achalasia Diagnosed With High-Resolution Esophageal Manometry AMERICAN JOURNAL OF THE MEDICAL SCIENCES Chedid, V., Rosenblatt, E., Gandhi, K., Dhalla, S., Nandwani, M. C., Stein, E. M., Clarke, J. O. 2018; 355 (2): 126–31


    The advent of the Chicago Classification for esophageal motility disorders allowed for clinically reproducible subgrouping of patients with achalasia based on manometric phenotype. However, there are limited data with regards to racial variation using high-resolution esophageal manometry (HREM). The aim of our study was to evaluate the racial differences in patients with achalasia diagnosed with HREM using the Chicago Classification. We evaluated the clinical presentation, treatment decisions and outcomes between blacks and non-blacks with achalasia to identify potential racial disparities.We performed a retrospective review of consecutive patients referred for HREM at a single tertiary referral center from June 2008 through October 2012. All patients diagnosed with achalasia on HREM according to the Chicago Classification were included. Demographic, clinical and manometric data were abstracted. All studies interpreted before the Chicago Classification was in widespread use were reanalyzed. Race was defined as black or non-black. Patients who had missing data were excluded. Proportions were compared using chi-squared analysis and means were compared using the Student's t-test.A total of 1,268 patients underwent HREM during the study period, and 105 (8.3%) were manometrically diagnosed with achalasia (53% female, mean age: 53.8 ± 17.0 years) and also met the aforementioned inclusion and exclusion criteria. A higher percentage of women presented with achalasia in blacks as compared to whites or other races (P < 0.001). Non-blacks were more likely to present with reflux than blacks (P = 0.01), while blacks were more likely to be treated on the inpatient service than non-blacks (P < 0.001). There were no other significant differences noted in clinical presentation, treatment decisions and treatment outcomes among blacks and non-blacks.Our study highlights possible racial differences between blacks and non-blacks, including a higher proportion of black women diagnosed with achalasia and most blacks presenting with dysphagia. There is possibly a meaningful interaction of race and sex in the development of achalasia that might represent genetic differences in its pathophysiology. Further prospective studies are required to identify such differences.

    View details for PubMedID 29406039

  • Nonerosive reflux disease: clinical concepts. Annals of the New York Academy of Sciences Gyawali, C. P., Azagury, D. E., Chan, W. W., Chandramohan, S. M., Clarke, J. O., de Bortoli, N. n., Figueredo, E. n., Fox, M. n., Jodorkovsky, D. n., Lazarescu, A. n., Malfertheiner, P. n., Martinek, J. n., Murayama, K. M., Penagini, R. n., Savarino, E. n., Shetler, K. P., Stein, E. n., Tatum, R. P., Wu, J. n. 2018


    Esophageal symptoms can arise from gastroesophageal reflux disease (GERD) as well as other mucosal and motor processes, structural disease, and functional esophageal syndromes. GERD is the most common esophageal disorder, but diagnosis may not be straightforward when symptoms persist despite empiric acid suppressive therapy and when mucosal erosions are not seen on endoscopy (as for nonerosive reflux disease, NERD). Esophageal physiological tests (ambulatory pH or pH-impedance monitoring and manometry) can be of value in defining abnormal reflux burden and reflux-symptom association. NERD diagnosed on the basis of abnormal reflux burden on ambulatory reflux monitoring is associated with similar symptom response from antireflux therapy for erosive esophagitis. Acid suppression is the mainstay of therapy, and antireflux surgery has a definitive role in the management of persisting symptoms attributed to NERD, especially when the esophagogastric junction is compromised. Adjunctive approaches and complementary therapy may be of additional value in management. In this review, we describe the evaluation, diagnosis, differential diagnosis, and management of NERD.

    View details for PubMedID 29761528

  • Clinical and manometric characteristics of patients with oesophagogastric outflow obstruction: towards a new classification. BMJ open gastroenterology Triadafilopoulos, G., Clarke, J. O. 2018; 5 (1): e000210


    Background: The Chicago Classification (CC) defines oesophagogastric junction outflow obstruction (EGJOO) as the presence of an elevated integrated residual pressure (IRP) together with preserved oesophageal body peristalsis but its clinical significance is evolving.Aims: To describe the clinical and manometric characteristics in patients with EGJOO and propose a new classification.Methods: In this retrospective cohort study, patients with functional oesophageal symptoms underwent clinical and endoscopic assessment and oesophageal high-resolution manometry (HRM). The CC V.3 was used to define and redefine abnormalities.Results: Of 478 HRM studies performed, EGJOO, defined as median IRP >15mm Hg, was diagnosed in 116 patients; 17 underwent a follow-up HRM. Forty-four patients had otherwise normal oesophageal motility, with the only finding being EGJOO; 14 had achalasia, 19 had EGJOO plus ineffective oesophageal motility (IEM), 28 had EGJOO plus diffuse oesophageal spasm (DES) (n=25) or jackhammer oesophagus (n=3), and 11 had EGJOO plus IEM and DES. Patients with EGJOO+IEM had lower distal contractile integral (DCI) while those with EGJOO+DES had higher DCI. All groups exhibited high percentages of incomplete bolus clearance. On repeat studies, EGJOO preceded or followed another HRM diagnosis and remained permanent in 2/17 patients. Only one patient transitioned to achalasia.Conclusions: The new classification further defines EGJOO by considering abnormalities in the body of the oesophagus that could contribute to symptoms or require therapy. Most patients with EGJOO have a coexisting motility disorder and do not have isolated EGJOO. There is a fluidity of the HRM diagnosis that needs to be considered prior to therapy.

    View details for PubMedID 30073090

  • Aprepitant Has Mixed Effects on Nausea and Reduces Other Symptoms in Patients With Gastroparesis and Related Disorders GASTROENTEROLOGY Pasricha, P. J., Yates, K. P., Sarosiek, I., McCallum, R. W., Abell, T. L., Koch, K. L., Nguyen, L. B., Snape, W. J., Hasler, W. L., Clarke, J. O., Dhalla, S., Stein, E. M., Lee, L. A., Miriel, L. A., Van Natta, M. L., Grover, M., Farrugia, G., Tonascia, J., Hamilton, F. A., Parkman, H. P., NIDDK Gastroparesis Clinical Res 2018; 154 (1): 65-+


    There are few effective treatments for nausea and other symptoms in patients with gastroparesis and related syndromes. We performed a randomized trial of the ability of the neurokinin-1 receptor antagonist aprepitant to reduce symptoms in patients with chronic nausea and vomiting caused by gastroparesis or gastroparesis-like syndrome.We conducted a 4-week multicenter, double-masked trial of 126 patients with at least moderate symptoms of chronic nausea and vomiting of presumed gastric origin for a minimum of 6 months. Patients were randomly assigned to groups given oral aprepitant (125 mg/day, n = 63) or placebo (n = 63). The primary outcome from the intention-to-treat analysis was reduction in nausea, defined as a decrease of 25 mm or more, or absolute level below 25 mm, on a daily patient-reported 0-to-100 visual analog scale (VAS) of nausea severity. We calculated relative risks of nausea improvement using stratified Cochran-Mental-Haenszel analysis.Aprepitant did not reduce symptoms of nausea, based on the primary outcome measure (46% reduction in the VAS score in the aprepitant group vs 40% reduction in the placebo group; relative risk, 1.2; 95% CI, 0.8-1.7) (P = .43). However, patients in the aprepitant group had significant changes in secondary outcomes such as reduction in symptom severity (measured by the 0-5 Gastroparesis Clinical Symptom Index) for nausea (1.8 vs 1.0; P = .005), vomiting (1.6 vs 0.5; P = .001), and overall symptoms (1.3 vs 0.7; P = .001). Adverse events, predominantly mild or moderate in severity grade, were more common in aprepitant (22 of 63 patients, 35% vs 11 of 63, 17% in the placebo group) (P = .04).In a randomized trial of patients with chronic nausea and vomiting caused by gastroparesis or gastroparesis-like syndrome, aprepitant did not reduce the severity of nausea when reduction in VAS score was used as the primary outcome. However, aprepitant had varying effects on secondary outcomes of symptom improvement. These findings support the need to identify appropriate patient outcomes for trials of therapies for gastroparesis, including potential additional trials for aprepitant. no: NCT01149369.

    View details for PubMedID 29111115

  • Indications and interpretation of esophageal function testing. Annals of the New York Academy of Sciences Gyawali, C. P., de Bortoli, N. n., Clarke, J. n., Marinelli, C. n., Tolone, S. n., Roman, S. n., Savarino, E. n. 2018


    Esophageal symptoms are common, and can arise from mucosal, motor, functional, and neoplastic processes, among others. Judicious use of diagnostic testing can help define the etiology of symptoms and can direct management. Endoscopy, esophageal high-resolution manometry (HRM), ambulatory pH or pH-impedance manometry, and barium radiography are commonly used for esophageal function testing; functional lumen imaging probe is an emerging option. Recent consensus guidelines have provided direction in using test findings toward defining mechanisms of esophageal symptoms. The Chicago Classification describes hierarchical steps in diagnosing esophageal motility disorders. The Lyon Consensus characterizes conclusive evidence on esophageal testing for a diagnosis of gastroesophageal reflux disease (GERD), and establishes a motor classification of GERD. Taking these recent advances into consideration, our discussion focuses primarily on the indications, technique, equipment, and interpretation of esophageal HRM and ambulatory reflux monitoring in the evaluation of esophageal symptoms, and describes indications for alternative esophageal tests.

    View details for PubMedID 29754440

  • Relating gastric scintigraphy and symptoms to motility capsule transit and pressure findings in suspected gastroparesis. Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society Hasler, W. L., May, K. P., Wilson, L. A., Van Natta, M. n., Parkman, H. P., Pasricha, P. J., Koch, K. L., Abell, T. L., McCallum, R. W., Nguyen, L. A., Snape, W. J., Sarosiek, I. n., Clarke, J. O., Farrugia, G. n., Calles-Escandon, J. n., Grover, M. n., Tonascia, J. n., Lee, L. A., Miriel, L. n., Hamilton, F. A. 2018; 30 (2)


    Wireless motility capsule (WMC) findings are incompletely defined in suspected gastroparesis. We aimed to characterize regional WMC transit and contractility in relation to scintigraphy, etiology, and symptoms in patients undergoing gastric emptying testing.A total of 209 patients with gastroparesis symptoms at NIDDK Gastroparesis Consortium centers underwent gastric scintigraphy and WMCs on separate days to measure regional transit and contractility. Validated questionnaires quantified symptoms.Solid scintigraphy and liquid scintigraphy were delayed in 68.8% and 34.8% of patients; WMC gastric emptying times (GET) were delayed in 40.3% and showed 52.8% agreement with scintigraphy; 15.5% and 33.5% had delayed small bowel (SBTT) and colon transit (CTT) times. Transit was delayed in ≥2 regions in 23.3%. Rapid transit was rarely observed. Diabetics had slower GET but more rapid SBTT versus idiopathics (P ≤ .02). GET delays related to greater scintigraphic retention, slower SBTT, and fewer gastric contractions (P ≤ .04). Overall gastroparesis symptoms and nausea/vomiting, early satiety/fullness, bloating/distention, and upper abdominal pain subscores showed no relation to WMC transit. Upper and lower abdominal pain scores (P ≤ .03) were greater with increased colon contractions. Constipation correlated with slower CTT and higher colon contractions (P = .03). Diarrhea scores were higher with delayed SBTT and CTT (P ≤ .04).Wireless motility capsules define gastric emptying delays similar but not identical to scintigraphy that are more severe in diabetics and relate to reduced gastric contractility. Extragastric transit delays occur in >40% with suspected gastroparesis. Gastroparesis symptoms show little association with WMC profiles, although lower symptoms relate to small bowel or colon abnormalities.

    View details for PubMedID 28872760

  • Pyridostigmine for the treatment of gastrointestinal symptoms in systemic sclerosis. Seminars in arthritis and rheumatism Ahuja, N. K., Mische, L. n., Clarke, J. O., Wigley, F. M., McMahan, Z. H. 2018


    Symptoms of gastrointestinal dysmotility are common among patients with systemic sclerosis (SSc), and the management of severe cases is often limited by a relative lack of effective interventions. The objective of this case series was to review our experience with pyridostigmine as a treatment for patients with SSc and symptomatic gastrointestinal disease.This study evaluated rates of symptom improvement, side effects, medication adherence, and dose ranges for SSc patients prescribed pyridostigmine for refractory gastrointestinal symptoms over a 10-year period at a quaternary referral center. Patients were defined as responders if they remained on pyridostigmine for at least 4 weeks and clinical benefit was documented by the recorded response of the patient or by the treating physician RESULTS: Of 31 patients treated with pyridostigmine for at least 4 weeks, 51.6% reported symptomatic improvement. Constipation was the most commonly improved symptom based on prevalence prior to therapy (noted by 6/20 patients suffering with constipation). Fifteen of 31 patients reported adverse effects, most commonly diarrhea. Throughout the duration of follow-up (median 126 days, range: 28-506 days), pyridostigmine was continued by 81.3% of patients who reported symptomatic benefit and 58.1% of patients overall.Pyridostigmine holds promise for the treatment of various gastrointestinal symptoms in SSc patients, particularly in patients with refractory constipation. Though side effects may limit its use, most patients who experienced benefit chose to continue therapy.

    View details for PubMedID 29397195

  • Multi-Organ RNA-Sequencing of Patients with Systemic Sclerosis (SSc) Finds That Intrinsic Subsets Are Conserved across Organ Systems Mehta, B. K., Franks, J., Cai, G., Toledo, D., Wood, T. A., Archambault, K. A., Kosarek, N., Kolstad, K., Stark, M., Valenzuela, A., Fiorentino, D., Fernandez-Becker, N., Becker, L., Nguyen, L., Clarke, J., Boin, F., Wolters, P., Chung, L., Whitfield, M. L. WILEY. 2017
  • Esophageal distensibility measurement: impact on clinical management and procedure length. Diseases of the esophagus Ahuja, N. K., Agnihotri, A., Lynch, K. L., Hoo-Fatt, D., Onyimba, F., McKnight, M., Okeke, F. C., Garcia, P., Dhalla, S., Stein, E., Pasricha, P. J., Clarke, J. O. 2017; 30 (8): 1-8


    Luminal distensibility measurement has demonstrated relevance to various disease processes, though its effects on clinical decision-making have been less well understood. This study aims to characterize the clinical impact of impedance planimetry measurement as well as the learning curve associated with its use in the esophagus. A single provider performed distensibility measurement in conjunction with upper endoscopy for a variety of clinical indications with the functional lumen imaging probe (FLIP) over a period of 21 months. Procedural data were prospectively collected and, along with medical records, retrospectively reviewed. Seventy-three procedures (70 patients) underwent esophageal distensibility measurement over the timeline of this study. The most common procedural indications were known or suspected achalasia (32.9%), dysphagia with connective tissue disease (13.7%), eosinophilic esophagitis (12.3%), and dysphagia with prior fundoplication (9.6%). FLIP results independently led to a change in management in 29 (39.7%) cases and supported a change in management in an additional 15 (20.5%) cases. The most common change in management was a new or amended therapeutic procedure (79.5%). Procedural time added by distensibility measurement was greater among earlier cases than among later cases. The median time added overall was 5 minutes and 46 seconds. Procedural time added varied significantly by procedural indication, but changes in management did not. Distensibility measurement added meaningful diagnostic information that impacted therapeutic decision-making in the majority of cases in which it was performed. Procedural time added by this modality is typically modest and decreases with experience.

    View details for DOI 10.1093/dote/dox038

    View details for PubMedID 28575249

  • What is the clinical significance of esophagogastric junction outflow obstruction? evaluation of 60 patients at a tertiary referral center. Neurogastroenterology and motility Okeke, F. C., Raja, S., Lynch, K. L., Dhalla, S., Nandwani, M., Stein, E. M., Chander Roland, B., Khashab, M. A., Saxena, P., Kumbhari, V., Ahuja, N. K., Clarke, J. O. 2017; 29 (6)


    Esophagogastric junction (EGJ) outflow obstruction (EGJOO) is characterized by impaired EGJ relaxation with intact or weak peristalsis. Our aims were to evaluate: (i) prevalence, (ii) yield of fluoroscopy, endoscopy, and endoscopic ultrasound (EUS), (iii) outcomes, and (iv) whether this data differed based on quantitative EGJ relaxation.Studies that met criteria for EGJOO were identified. Demographics, encounters, endoscopy, radiology, treatment decisions, and outcomes were extracted.Sixty studies were identified. Dysphagia was the most common symptom. Forty patients underwent barium esophagram (BE): normal (11), hiatal hernia (20), spasm/dysmotility (17), EGJ narrowing (10), compression (2), Schatzki's ring (5), malrotation (1), gastric volvulus (1), mass (1). Esophagogastroduodenoscopy (EGD) was performed in 41 patients: normal (19), hiatal hernia (13), Schatzki's ring (6), esophagitis (3), esophageal candidiasis (3), mass (1). EUS was performed in 20 patients and was frequently normal. Twenty-two patients underwent intervention. While transient improvement was noted in the majority, persistent improvement was seen in only one of nine patients (dilatation), four of six patients (botulinum toxin), and three patients who underwent per-oral endoscopic myotomy. No patients treated with medical therapy alone had improvement in dysphagia. There was no difference in symptoms or outcomes based on quantitative EGJ relaxation.The manometric criterion EGJOO defines a heterogeneous clinical group. While BE, EGD, and EUS all provide complementary information, a significant percentage of these studies will be normal. For patients with dysphagia, outcome may depend on EGJ disruption. There were no differences in symptoms our outcomes based on quantitative EGJ relaxation.

    View details for DOI 10.1111/nmo.13061

    View details for PubMedID 28393437

  • Early satiety and postprandial fullness in gastroparesis correlate with gastroparesis severity, gastric emptying, and water load testing NEUROGASTROENTEROLOGY AND MOTILITY Parkman, H. P., Hallinan, E. K., Hasler, W. L., Farrugia, G., Koch, K. L., Nguyen, L., Snape, W. J., Abell, T. L., McCallum, R. W., Sarosiek, I., Pasricha, P. J., Clarke, J., Miriel, L., Tonascia, J., HAMILTON, F. 2017; 29 (4)

    View details for DOI 10.1111/nmo.12981

    View details for Web of Science ID 000398086800008

  • The Changing Impact of Gastroesophageal Reflux Disease in Clinical Practice: An Updated Study ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY Akst, L. M., Haque, O. J., Clarke, J. O., Hillel, A. T., Best, S. R., Altman, K. W. 2017; 126 (3): 229-235
  • Three-Dimensional Anorectal Manometry Enhances Diagnostic Gain by Detecting Sphincter Defects and Puborectalis Pressure. Digestive diseases and sciences Raja, S., Okeke, F. C., Stein, E. M., Dhalla, S., Nandwani, M., Lynch, K. L., Gyawali, C. P., Clarke, J. O. 2017


    Constipation and fecal incontinence (FI) are common and are often evaluated with anorectal manometry. Three-dimensional high-resolution anorectal manometry (HRAM) is a promising technology; however, implementation has been limited by lack of metrics and unclear clinical utility.To investigate the diagnostic utility of 3D HRAM compared to 2D HRAM.Three-dimensional HRAM studies performed from April 2012 to October 2013 were identified and re-interpreted by two blinded investigators examining 3D function. Disagreements were resolved by a third investigator. Puborectalis (PR) visualization, focal defects, and dyssynergy were reported. Differences between groups were analyzed with Fisher's exact test. Discordance was analyzed with McNemar Chi-square test.Two hundred and twenty-one 3D HRAM studies were identified. Mean age and BMI were 52.2 ± 17.4 and 27.1 ± 7.5 years (81% female, 74% white). Most common indications for 3D HRAM were constipation (65%) and FI (28%). PR function was visualized in 81% (rest), 97% (squeeze), and 73% (strain). PR was visualized less often at rest in FI than constipation (68 vs. 85%, p = 0.007). Defects were identified twice as often in FI than constipation (19 vs. 10%, p = 0.113). Twenty-nine defects (86% anterior) were visualized on 3D HRAM. Inter-reader agreement was moderate for PR function (κ = 0.471), but fair for focal defects (κ = 0.304).PR function and focal defects can be visualized on 3D-HRAM with added diagnostic benefit compared to 2D. Fair inter-reader agreement for focal defects highlights the need for quantitative metrics.

    View details for DOI 10.1007/s10620-017-4466-5

    View details for PubMedID 28194667

  • The Role of Impedance Planimetry in the Evaluation of Esophageal Disorders. Current gastroenterology reports Ahuja, N. K., Clarke, J. O. 2017; 19 (2): 7-?


    Impedance planimetry measures tissue wall distensibility as a function of pressure and cross-sectional area. Recent interest in this technique's relevance to the gastrointestinal tract has been accelerated by the availability of the functional lumen imaging probe, a catheter-based system that dynamically quantitates these biomechanical properties. Herein, we review the device's particular utility in the setting of esophageal pathology, including processes affecting the esophageal body as well as the upper and lower esophageal sphincters.An expanding suite of disease-specific indications for impedance planimetry includes achalasia, gastroesophageal reflux disease, and eosinophilic esophagitis. The technique has also demonstrated a role in the intraoperative guidance of therapy and in the definition of hitherto unrecognized patterns of esophageal dysmotility. Device-specific technology remains in active evolution, which, in conjunction with progressively larger datasets, sets the stage for broader clinical applicability in the near future.

    View details for DOI 10.1007/s11894-017-0544-2

    View details for PubMedID 28220362

  • Pyloric Therapies for Gastroparesis. Current treatment options in gastroenterology Ahuja, N. K., Clarke, J. O. 2017


    Gastroparesis is a syndrome that can be difficult to treat effectively and likely represents the common clinical presentation of multiple underlying mechanisms. One of these presumed mechanisms involves pyloric dysfunction, tied perhaps to spasm or fibrosis, manifesting as functional gastric outlet obstruction. Various diagnostic modalities have been used to better characterize this hypothesized abnormality, including most recently antroduodenal manometry and impedance planimetry. A variety of therapeutic interventions specific to the pylorus have also been proposed in the last several years, including intrapyloric injections of botulinum toxin, transpyloric stenting, surgical pyloroplasty, and endoscopic pyloromyotomy. The clinical application of these maneuvers has been mostly empiric thus far, but efforts are ongoing to identify the subset of patients whose physiology best positions them to benefit from such therapy. Early results for many of these interventions have been promising and will serve as the basis for larger and more systematic research frameworks moving forward.

    View details for DOI 10.1007/s11938-017-0124-4

    View details for PubMedID 28124202

  • Patients with symptoms of delayed gastric emptying have a high prevalence of oesophageal dysmotility, irrespective of scintigraphic evidence of gastroparesis. BMJ open gastroenterology Triadafilopoulos, G. n., Nguyen, L. n., Clarke, J. O. 2017; 4 (1): e000169


    Patients with symptoms suggestive of gastroparesis exhibit several symptoms, such as epigastric pain, postprandial fullness, bloating and regurgitation. It is uncertain if such symptoms reflect underlying oesophageal motor disorder.To examine whether patients with epigastric pain and postprandial distress syndrome suggestive of functional dyspepsia and/or gastroparesis also have concomitant oesophageal motility abnormalities and, if so, whether there are any associations between these disturbances.In this retrospective cohort study, consecutive patients with functional gastrointestinal symptoms suggestive of gastric neuromuscular dysfunction (gastroparesis or functional dyspepsia) underwent clinical assessment, gastric scintigraphy, oesophageal high-resolution manometry and ambulatory pH monitoring using standard protocols.We studied 61 patients with various functional upper gastrointestinal symptoms who underwent gastric scintigraphy, oesophageal high-resolution manometry and ambulatory pH monitoring. Forty-four patients exhibited gastroparesis by gastric scintigraphy. Oesophageal motility disorders were found in 68% and 42% of patients with or without scintigraphic evidence of gastroparesis respectively, suggesting of overlapping gastric and oesophageal neuromuscular disorder. Forty-three per cent of patients with gastroparesis had abnormal oesophageal acid exposure with mean % pH <4.0 of 7.5 in contrast to 38% of those symptomatic controls with normal gastric emptying, with mean %pH <4.0 of 5.4 (NS). Symptoms of epigastric pain, heartburn/regurgitation, bloating, nausea, vomiting, dysphagia, belching and weight loss could not distinguish patients with or without gastroparesis, although weight loss was significantly more prevalent and severe (p<0.002) in patients with gastroparesis. There was no relationship between oesophageal symptoms and motor or pH abnormalities in either groups.Irrespective of gastric emptying delay by scintigraphy, patients with symptoms suggestive of gastric neuromuscular dysfunction have a high prevalence of oesophageal motor disorder and pathological oesophageal acid exposure that may contribute to their symptoms and may require therapy. High-resolution oesophageal manometry and pH monitoring are non-invasive and potentially useful in the assessment and management of these patients.

    View details for PubMedID 29177065

  • Intraoperative measurement of esophagogastric junction cross-sectional area by impedance planimetry correlates with clinical outcomes of peroral endoscopic myotomy for achalasia: a multicenter study SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES Ngamruengphong, S., von Rahden, B. H., Filser, J., Tyberg, A., Desai, A., Sharaiha, R. Z., Lambroza, A., Kumbhari, V., El Zein, M., Abdelgelil, A., Besharati, S., Clarke, J. O., Stein, E. M., Kalloo, A. N., Kahaleh, M., Khashab, M. A. 2016; 30 (7): 2886-2894


    Peroral endoscopic myotomy (POEM) has been introduced as an endoscopic alternative to surgical myotomy. The endoluminal functional lumen imaging probe (endoFLIP) evaluates esophagogastric junction (EGJ) distensibility based on cross-sectional area and pressure in response to volume distension. The aim of this study was to evaluate whether there is a correlation between endoFLIP measurements during POEM and postoperative clinical outcomes in terms of symptom relief and development of post-procedure reflux.We conducted a retrospective review of achalasia patients who underwent POEM and intraoperative endoFLIP at three tertiary centers. Patients were divided into two groups based on clinical response measured by Eckardt score (ES): good response (ES < 3) or poor response (ES ≥ 3). Post-procedure reflux was defined as the presence of esophagitis and/or abnormal pH study. EGJ diameter, cross-sectional area, and distensibility measured by endoFLIP were compared.Of the 63 treated patients, 50 had good and 13 had poor clinical response. The intraoperative final EGJ cross-sectional area was significantly higher in the good-response group versus poor-response group; median (interquartile range): 89.0 (78.5-106.7) versus 72.4 (48.8-80.0) mm(2) [p = 0.01]. The final EGJ cross-sectional area was also significantly higher in patients who had reflux esophagitis after POEM: 99.5 (91.2-103.7) versus 79.3 (57.1-94.2) mm(2) [p = 0.02].Intraoperative EGJ cross-sectional area during POEM for achalasia correlated with clinical response and post-procedure reflux. Impedance planimetry is a potentially important tool to guide the extent and adequacy of myotomy during POEM.

    View details for DOI 10.1007/s00464-015-4574-2

    View details for Web of Science ID 000378791200033

    View details for PubMedID 26487227

  • Nausea and vomiting in gastroparesis: similarities and differences in idiopathic and diabetic gastroparesis. Neurogastroenterology and motility Parkman, H. P., Hallinan, E. K., Hasler, W. L., Farrugia, G., Koch, K. L., Calles, J., Snape, W. J., Abell, T. L., Sarosiek, I., McCallum, R. W., Nguyen, L., Pasricha, P. J., Clarke, J., Miriel, L., Lee, L., Tonascia, J., HAMILTON, F. 2016


    Nausea and vomiting are classic symptoms of gastroparesis. It remains unclear if characteristics of nausea and vomiting are similar in different etiologies of gastroparesis. The aims of this article were as follows: to describe characteristics of nausea and vomiting in patients with gastroparesis and to determine if there are differences in nausea and vomiting in diabetic (DG) and idiopathic gastroparesis (IG).Gastroparetic patients enrolling in the NIDDK Gastroparesis Registry underwent assessment with history and questionnaires assessing symptoms, quality of life, and a questionnaire characterizing nausea and vomiting.Of 159 gastroparesis patients (107 IG, 52 DG), 96% experienced nausea, whereas 65% experienced vomiting. Nausea was predominant symptom in 28% and vomiting was predominant in 4%. Nausea was severe or very severe in 41%. PAGI-SYM nausea/vomiting subscore was greater with increased vomiting severity, but not nausea severity in DG than IG. Nausea was related to meals in 71%; lasting most of the day in 41%. Increasing nausea severity was related to decreased quality of life. Nausea often preceded vomiting in 82% of patients and vomiting often relieved nausea in 30%. Vomiting was more common in DG (81%) compared to IG (57%; p = 0.004). Diabetic patients more often had vomiting in the morning before eating, during the night, and when not eating.Nausea is present in essentially all patients with gastroparesis irrespective of cause and associated with decreased quality of life. In contrast, vomiting was more prevalent, more severe, and occurred more often in DG than IG. Thus, characteristics of vomiting differ in IG vs DG.

    View details for DOI 10.1111/nmo.12893

    View details for PubMedID 27350152

  • Learning curve for peroral endoscopic myotomy ENDOSCOPY INTERNATIONAL OPEN El Zein, M., Kumbhari, V., Ngamruengphong, S., Carson, K. A., Stein, E., Tieu, A., Chaveze, Y., Ismail, A., Dhalla, S., Clarke, J., Kalloo, A., Canto, M., Khashab, M. A. 2016; 4 (5): E577–E582


    Although peroral endoscopic myotomy (POEM) is being performed more frequently, the learning curve for gastroenterologists performing the procedure has not been well studied. The aims of this study were to define the learning curve for POEM and determine which preoperative and intraoperative factors predict the time that will be taken to complete the procedure and its different steps.Consecutive patients who underwent POEM performed by a single expert gastroenterologist for the treatment of achalasia or spastic esophageal disorders were included. The POEM procedure was divided into four steps: mucosal entry, submucosal tunneling, myotomy, and closure. Nonlinear regression was used to determine the POEM learning plateau and calculate the learning rate.A total of 60 consecutive patients underwent POEM in an endoscopy suite. The median length of procedure (LOP) was 88 minutes (range 36 - 210), and the mean (± standard deviation [SD]) LOP per centimeter of myotomy was 9 ± 5 minutes. The total operative time decreased significantly as experience increased (P < 0.001), with a "learning plateau" at 102 minutes and a "learning rate" of 13 cases. The mucosal entry, tunneling, and closure times decreased significantly with experience (P < 0.001). The myotomy time showed no significant decrease with experience (P = 0.35). When the mean (± SD) total procedure times for the learning phase and the corresponding comparator groups were compared, a statistically significant difference was observed between procedures 11 - 15 and procedures 16 - 20 (15.5 ± 2.4 min/cm and 10.1 ± 2.7 min/cm, P = 0.01) but not thereafter. A higher case number was significantly associated with a decreased LOP (P < 0.001).In this single-center retrospective study, the minimum threshold number of cases required for an expert interventional endoscopist performing POEM to reach a plateau approached 13.

    View details for DOI 10.1055/s-0042-104113

    View details for Web of Science ID 000376516100015

    View details for PubMedID 27227118

    View details for PubMedCentralID PMC4874807

  • Gender is a determinative factor in the initial clinical presentation of eosinophilic esophagitis DISEASES OF THE ESOPHAGUS Lynch, K. L., Dhalla, S., Chedid, V., Ravich, W. J., Stein, E. M., Montgomery, E. A., Bochner, B. S., Clarke, J. O. 2016; 29 (2): 174-178


    Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disease resulting in symptoms of esophageal dysmotility. Abnormalities include dysphagia, food impaction and reflux. Although men appear to comprise a majority of the EoE population, few studies have directly assessed gender-associated clinical differences. The aim of this study is to identify the effect of gender on the initial clinical presentation of adult-onset EoE patients. We reviewed our electronic medical record database from January 2008 to December 2011 for adults diagnosed with EoE per the 2011 updated consensus guidelines. Patient demographics, presenting symptoms, endoscopy findings and complications were recorded. Proportions were compared using chi-squared analysis, and means were compared using the Student's t-test. A total of 162 patients met the inclusion criteria and 71 (44%) were women. Women were more likely to report chest pain (P = 0.03) and heartburn (P = 0.06), whereas men more commonly reported dysphagia (P = 0.04) and a history of food impaction (P = 0.05). Endoscopic findings were similar between groups. No patients suffered esophageal perforations. These data suggest that men report more fibrostenotic symptoms and women report more inflammatory symptoms at the time of diagnosis. There was no difference in endoscopic findings between genders. This is one of the only reviews comparing differences in clinical presentation, endoscopic findings and complications between gender for EoE. The current recommended guidelines state that any patient with symptoms of esophageal dysfunction should be biopsied for EoE. Our findings support biopsying patients with typical and atypical symptoms of dysmotility including heartburn and chest pain.

    View details for DOI 10.1111/dote.12307

    View details for Web of Science ID 000371535800009

    View details for PubMedID 25626069

  • Clinical and pH study characteristics in reflux patients with and without ineffective oesophageal motility (IEM). BMJ open gastroenterology Triadafilopoulos, G., Tandon, A., Shetler, K. P., Clarke, J. 2016; 3 (1)


    The aetiology and clinical impact of ineffective oesophageal motility (IEM) remain poorly understood, but the condition is thought to worsen supine gastro-oesophageal acid reflux (GERD).In this retrospective cohort analysis of symptomatic patients with abnormal oesophageal acid exposure, we sought to determine any clinical or functional characteristics that would distinguish those with normal peristalsis from those with IEM, defined using the Chicago classification. We hypothesised that the impaired oesophageal clearance in IEM would be contributing to more severe degrees of pathological acid exposure, as well as clinical and endoscopic GERD severity.Consecutive symptomatic patients with GERD underwent clinical, endoscopic and functional evaluation that included high-resolution impedance manometry (HRIM) and ambulatory pH monitoring performed 'off' acid suppressive therapy.Of the 114 patients with abnormal oesophageal acid exposure, 71 had normal oesophageal motility by HRIM and 43 were diagnosed with IEM (38% prevalence). Age, gender and symptom duration were similar between the two groups. Both groups had similar magnitude and frequency of symptoms, making a distinction clinically impossible. Endoscopically, the two groups had similar rates of erosive disease, hiatal hernia and Barrett's oesophagus. Ambulatory pH, proton pump inhibitor (PPI) dosage and PPI response rates were also similar. Nevertheless, patients with IEM had significantly more impairment of oesophageal clearance (mean 56.9±6.4) than those with normal motility (mean 32.4±5.0) (p<0.003).Symptomatic patients with IEM exhibit significant impairment of oesophageal clearance but are otherwise clinically indistinguishable from those with normal oesophageal motility and have a similar prevalence of erosive disease and pathological acid exposure.

    View details for DOI 10.1136/bmjgast-2016-000126

    View details for PubMedID 28074151

    View details for PubMedCentralID PMC5174815

  • Comprehensive analysis of efficacy and safety of peroral endoscopic myotomy performed by a gastroenterologist in the endoscopy unit: a single-center experience GASTROINTESTINAL ENDOSCOPY Khashab, M. A., El Zein, M., Kumbhari, V., Besharati, S., Ngamruengphong, S., Messallam, A., Abdelgalil, A., Saxena, P., Tieu, A. H., Raja, S., Stein, E., Dhalla, S., Garcia, P., Singh, V. K., Pasricha, P. J., Kalloo, A. N., Clarke, J. O. 2016; 83 (1): 117-125


    The safety and efficacy of peroral endoscopic myotomy (POEM) when performed by gastroenterologists in the endoscopy unit are currently unknown. The aims of this study were to assess (1) the safety and efficacy of POEM in which all procedures were performed by 1 gastroenterologist in the endoscopy unit, and (2) the predictors of adverse events and nonresponse.All consecutive patients who underwent POEM at 1 tertiary center were included. Clinical response was defined by a decrease in the Eckardt score to 3 or lower. Adverse events were graded according to the American Society for Gastrointestinal Endoscopy lexicon's severity grading system.A total of 60 consecutive patients underwent POEM in the endoscopy suite with a mean procedure length of 99 minutes. The mean length of submucosal tunnel was 14 cm and the mean myotomy length was 11 cm. The median length of hospital stay was 1 day. Among 52 patients with a mean follow-up period of 118 days (range 30-750), clinical response was observed in 48 patients (92.3%). There was a significant decrease in Eckardt score after POEM (8 vs 1.19, P < .0001). The mean lower esophageal sphincter pressure decreased significantly after POEM (29 mm Hg vs 11 mm Hg, P < .0001). A total of 10 adverse events occurred in 10 patients (16.7%): 7 rated as mild, 3 as moderate, and none as severe. Procedure length was the only predictor of adverse events (P = .01). pH impedance testing was completed in 25 patients, and 22 (88%) had abnormal acid exposure, but positive symptom correlation was present in only 6 patients. All patients with symptomatic reflux were successfully treated with proton pump inhibitors.POEM can be effectively and safely performed by experienced gastroenterologists at a tertiary care endoscopy unit. Adverse events are infrequent, and most can be managed intraprocedurally. Post-POEM reflux is frequent but can be successfully managed medically.

    View details for DOI 10.1016/j.gie.2015.06.013

    View details for Web of Science ID 000369230900017

    View details for PubMedID 26212369

  • Outcomes and Factors Associated With Reduced Symptoms in Patients With Gastroparesis GASTROENTEROLOGY Pasricha, P. J., Yates, K. P., Nguyen, L., Clarke, J., Abell, T. L., Farrugia, G., Hasler, W. L., Koch, K. L., Snape, W. J., McCallum, R. W., Sarosiek, I., Tonascia, J., Miriel, L. A., Lee, L., Hamilton, F., Parkman, H. P. 2015; 149 (7): 1762-?


    Gastroparesis is a chronic clinical syndrome characterized by delayed gastric emptying. However, little is known about patient outcomes or factors associated with reduction of symptoms.We studied adult patients with gastroparesis (of diabetic or idiopathic type) enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium Gastroparesis Registry, seen every 16 weeks and treated according to the standard of care with prescribed medications or other therapies at 7 tertiary care centers. Characteristics associated with reduced symptoms, based on a decrease of 1 or more in the gastroparesis cardinal symptom index (GCSI) score after 48 weeks of care, were determined from logistic regression models. Data were collected from patients for up to 4 years (median, 2.1 y).Of 262 patients, 28% had reductions in GCSI scores of 1 or more at 48 weeks. However, there were no significant reductions in GCSI score from weeks 48 through 192. Factors independently associated with reduced symptoms at 48 weeks included male sex, age 50 years and older, initial infectious prodrome, antidepressant use, and 4-hour gastric retention greater than 20%. Factors associated with no reduction in symptoms included overweight or obesity, a history of smoking, use of pain modulators, moderate to severe abdominal pain, a severe gastroesophageal reflex, and moderate to severe depression.Over a median follow-up period of 2.1 years, 28% of patients treated for gastroparesis at centers of expertise had reductions in GCSI scores of 1 or greater, regardless of diabetes. These findings indicate the chronic nature of gastroparesis. We identified factors associated with reduced symptoms that might be used to guide treatment. no: NCT00398801.

    View details for DOI 10.1053/j.gastro.2015.08.008

    View details for PubMedID 26299414

  • Refractory gastroparesis can be successfully managed with endoscopic transpyloric stent placement and fixation (with video) GASTROINTESTINAL ENDOSCOPY Khashab, M. A., Besharati, S., Ngamruengphong, S., Kumbhari, V., El Zein, M., Stein, E. M., Tieu, A., Mullin, G. E., Dhalla, S., Nandwani, M. C., Singh, V., Canto, M. I., Kalloo, A. N., Clarke, J. O. 2015; 82 (6): 1106-1109


    Medical treatment options for gastroparesis are limited. Data from studies of botulinum toxin and surgical pyloroplasty suggest that disruption of the pylorus can result in symptomatic improvement in some patients with refractory gastroparetic symptoms. The aim of this study was to determine the clinical response to transpyloric stent (TPS) placement in patients with gastroparetic symptoms refractory to standard therapy.Patients with gastroparesis refractory to medical treatment were referred for TPS placement for salvage therapy. Self-reported symptom improvement, stent migration rate, and pre- and post-stent gastric-emptying study results were collected.A total of 30 patients with refractory gastroparesis underwent 48 TPS procedures. Of these, 25 of 48 (52.1%) were performed in patients admitted to the hospital with intractable gastroparetic symptoms. Successful stent placement in the desired location across the pylorus (technical success) was achieved during 47 procedures (98%). Most (n = 24) stents were anchored to the gastric wall by using endoscopic suturing with a mean number of sutures of 2 (range 1-3) per procedure. Clinical response was observed in 75% of patients, and all inpatients were successfully discharged. Clinical success in patients with the predominant symptoms of nausea and vomiting was higher than in those patients with a predominant symptom of pain (79% vs 21%, P = .12). A repeat gastric-emptying study was performed in 16 patients, and the mean 4-hour gastric emptying normalized in 6 patients and significantly improved in 5 patients. Stent migration was least common (48%) when stents were sutured.TPS placement is a feasible novel endoscopic treatment modality for gastroparesis and improves both symptoms and gastric emptying in patients who are refractory to medical treatment, especially those with nausea and vomiting. TPS placement may be considered as salvage therapy for inpatients with intractable symptoms or potentially as a method to select patients who may respond to more permanent therapies directed at the pylorus.

    View details for DOI 10.1016/j.gie.2015.06.051

    View details for Web of Science ID 000365585000021

    View details for PubMedID 26253017

  • Small Intestinal Transit Time Is Delayed in Small Intestinal Bacterial Overgrowth JOURNAL OF CLINICAL GASTROENTEROLOGY Roland, B. C., Ciarleglio, M. M., Clarke, J. O., Semler, J. R., Tomakin, E., Mullin, G. E., Pasricha, P. J. 2015; 49 (7): 571-576


    Altered small intestinal motility is thought to contribute to the development of small intestinal bacterial overgrowth (SIBO). The clinical manifestations of SIBO and consequent malabsorption are wide ranging and include abdominal pain, bloating, diarrhea, weight loss, and nutritional deficiencies. However, due to the nonspecific nature of symptoms, the diagnosis may often be overlooked. To date, few studies have illustrated a direct relationship between impaired small intestinal motility and SIBO. In addition, further study has been limited by the technical challenges and lack of widespread availability of antroduodenal manometry. The development of a wireless motility capsule (WMC) (SmartPill) that evaluates pressure, pH, and temperature throughout the GI tract offers the potential to identify patients with small bowel transit delays who may be at risk for bacterial overgrowth.The primary aims of this study were to: (1) characterize the relationship of prolonged small bowel transit time (SBTT) in patients undergoing WMC with SIBO as based on a positive lactulose breath testing (LBT); and (2) to assess the relationship of prolonged gastric, colonic, and whole gut transit times (WGTT) and additional motility parameters with SIBO (positive LBT). We also sought to evaluate the relationship of small bowel motility parameters (SB motility index, contractions per minute, and SB peak amplitudes) with LBT results.We performed a retrospective study of consecutive patients who were referred for wireless motility testing at a single, tertiary care institution from April 2009 to December 2012. Of the 72 total patients identified, 34 underwent both WMC and LBT. Gastric, small bowel, colonic, WGTT, and SB motility parameters were measured and correlated with LBT results. Statistical methods utilized for data analysis include ANOVA, 2-sample t tests, nonparametric Kruskal Wallis test, Wilcoxon rank-sum test, and the Fisher exact test.Of the 37 patients who underwent both WMC and LBT, 24 (65%) were LBT positive. The mean SBTT among those who were LBT positive was 6.6 hours as compared with 4.2 hours in those who were LBT negative (P=0.04). Among patients who were LBT positive, 47.6% had prolonged SBTT (≥6 h), whereas only 7.7% of those who were LBT negative had a delay in their SBTT (P=0.01). In addition, patients who were LBT positive were more likely to have prolongation of both colonic and WGTT versus those who were LBT negative (CTT: positive LBT=64.4 h vs. negative LBT=35.5 h, P=0.02; WGTT: positive LBT=70.5 h vs. negative LBT=44.1 h, P=0.02). However, there were no statistical differences observed between the groups for gastric emptying times or other small intestinal motility parameters (SB motility index, contractions per minute, and peak amplitudes) between the 2 groups.Patients with underlying SIBO have significant delays in SBTT as compared with those without. The association between prolonged SBTT and positive LBT may be useful in identifying those patients with SIBO diagnosed by LBT and potentially target therapeutic options for those refractory to standard therapy. Interestingly, patients with positive LBT did not necessarily have a generalized gastrointestinal motility (similar GETs among groups), suggesting that small bowel transit specifically predisposes to the development of SIBO. Future, prospective studies are needed to further characterize intestinal dysmotility and other contributing pathophysiological mechanisms in SIBO and to investigate the potential benefits of prokinetics in this challenging patient population.

    View details for DOI 10.1097/MCG.0000000000000257

    View details for Web of Science ID 000358209900006

    View details for PubMedID 25319735

  • Learning Curve for PerOral Endoscopic Myotomy Deciphered: a Comprehensive Analysis Using Two Different Methodologies 46th Annual Digestive Diseases Week (DDW) / Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) / Annual Meeting of the American-Society-for-Gastrointestinal-Endoscopy (ASGE) El Zein, M. H., Kumbhari, V., Saxena, P., Kamal, A., Ngamruengphong, S., Besharati, S., Abdelgelil, A., Stein, E. M., Tieu, A. H., Raja, S., Garcia, P., Dhalla, S., Clarke, J. O., Khashab, M. MOSBY-ELSEVIER. 2015: AB167–AB167
  • Comprehensive Radionuclide Esophagogastrointestinal Transit Study: Methodology, Reference Values, and Initial Clinical Experience JOURNAL OF NUCLEAR MEDICINE Antoniou, A. J., Raja, S., El-Khouli, R., Mena, E., Lodge, M. A., Wahl, R. L., Clarke, J. O., Pasricha, P., Ziessman, H. A. 2015; 56 (5): 721-727


    A radionuclide methodology and reference values have been developed for a single gastrointestinal transit study including esophageal transit, liquid and solid gastric emptying, and small- and large-bowel transit, using (111)In-diethylenetriaminepentaacetic acid (DTPA) with the standardized (99m)Tc-labeled solid meal.Eighteen healthy subjects and 18 patients were investigated. The esophageal transit study was performed with 3.7 MBq (0.1 mCi) of (111)In-DTPA in 15 mL of water. A liquid-only 30-min gastric-emptying study followed, with ingestion of 3.7 MBq (0.1 mCi) of (111)In-DTPA in 300 mL of water. Then, a simultaneous solid-liquid emptying study was acquired after ingestion of a solid (99m)Tc-sulfur colloid-labeled meal and 7.4 MBq (0.2 mCi) of (111)In-DTPA in 120 mL of water. Images were acquired intermittently for 4 h. Additional (111)In images were acquired at 5 and 6 h to measure small-bowel transit, and at 24, 48, and 72 h for large-bowel transit.Reference values were determined for esophageal transit (transit time, percentage emptying at 10 s), liquid-only gastric emptying (emptying half-time), liquid and solid emptying in a dual-phase solid-liquid study (emptying half-time and percentage emptying at 1, 2, 3, and 4 h), small-bowel transit index (percentage transit to ileocecal valve at 6 h), and colonic transit (geometric center and percentage colonic emptying) at 24, 48, and 72 h. Results from the first 18 patients found abnormal transit in 72% (13/18); clinical management changed in 61% (11/18).We have developed a radionuclide methodology and derived reference values for a comprehensive gastrointestinal transit study using (111)In-DTPA with the standardized (99m)Tc-labeled solid meal. Our initial clinical experience suggests clinical value.

    View details for DOI 10.2967/jnumed.114.152074

    View details for Web of Science ID 000353831000018

    View details for PubMedID 25766893

  • Upper Esophageal Sphincter Abnormalities Frequent Finding on High-resolution Esophageal Manometry and Associated With Poorer Treatment Response in Achalasia JOURNAL OF CLINICAL GASTROENTEROLOGY Chavez, Y. H., Ciarleglio, M. M., Clarke, J. O., Nandwani, M., Stein, E., Roland, B. C. 2015; 49 (1): 17-23


    Abnormalities of the upper esophageal sphincter (UES) on high-resolution esophageal manometry (HREM) have been observed in both symptomatic and asymptomatic individuals and are often interpreted as incidental findings of unclear clinical significance.Our primary aims were: (1) to assess the frequency of UES abnormalities in consecutive patients referred for HREM studies; and (2) to characterize the demographics, clinical symptoms, and manometric profiles associated with UES abnormalities as compared with those with normal UES function.We performed a retrospective study of 200 consecutive patients referred for HREM. Patients were divided into those with normal and abnormal UES function, including impaired relaxation (residual pressure >12 mm Hg), hypertensive (>104 mm Hg), and hypotensive (<34 mm Hg) resting pressure. Clinical and manometric profiles were compared.A total of 32.5% of patients had UES abnormalities, the majority of which were hypertensive (55.4%). Patients with achalasia were significantly more likely to have UES abnormalities as compared with normal UES function (57.2% vs. 42.9%, P=0.04), with the most frequent abnormality being a hypertensive UES (50%). In addition, patients with impaired lower esophageal sphincter (LES) relaxation (esophagogastric junction outflow obstruction or achalasia) were more likely to have an UES abnormality present as compared with those with normal LES relaxation (53.1% vs. 28.6%, P=0.01). When we assessed for treatment response among patients with achalasia, we found that subjects with evidence of UES dysfunction had significantly worse treatment outcomes as compared with those without UES abnormalities present (20% improved vs. 100%, P=0.015). This remained true even after adjusting for type of treatment received (surgical myotomy, per-oral endoscopic mytotomy, botulinum toxin injection, pneumatic dilatation, medical therapy, P=0.67) and achalasia subtype (P=1.00).UES abnormalities are a frequent finding on HREM studies, especially in patients with impaired LES relaxation, including both achalasia and esophagogastric junction outflow obstruction. Interestingly, the most common UES abnormality associated with achalasia was a hypertensive resting UES, despite the fact that achalasia is thought to spare striated muscle. Among patients with achalasia, we found a significant association between the lack of treatment response and the presence of UES dysfunction. The routine evaluation of UES function in patients referred for manometry may enhance our understanding of esophageal motility disorders and may yield important prognostic information, particularly in subjects with achalasia. Future prospective studies are needed to further delineate the underlying mechanism between UES dysfunction with achalasia and other esophageal motility disorders to predict treatment response and guide therapeutic treatment modalities.

    View details for Web of Science ID 000346149800006

    View details for PubMedID 24859712

  • High-resolution anorectal manometry and dynamic pelvic magnetic resonance imaging are complementary technologies JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY Jodorkovsky, D., Macura, K. J., Gearhart, S. L., Dunbar, K. B., Stein, E. M., Clarke, J. O. 2015; 30 (1): 71-74


    Dynamic pelvic magnetic resonance imaging (DP-MRI) offers a comprehensive evaluation of pelvic organ structure in addition to functional information regarding evacuation. Opportunity to apply this technology can be limited due to regional lack of availability. Ideally, clues from standard anorectal testing could predict abnormalities on DP-MRI, leading to its efficient use. The aim of this study is to determine whether high-resolution anorectal manometry (HR-ARM) correlates with findings on DP-MRI.This is a retrospective study of HR-ARM performed on patients with constipation who also underwent DP-MRI. Studies were reviewed for significant findings including posterior pelvic organ prolapse, rectocele > 3 cm, rectal intussusception, and anorectal angle. Statistical analysis was performed using Pearson's correlation coefficient, Student's t-test, and Fisher's exact test.Twenty-three patients undergoing HR-ARM (age range 25-78) also underwent DP-MRI. All were female; 76% were Caucasian. Twenty had significant structural findings: small pelvic prolapse (n = 2), moderate pelvic prolapse (n = 10), large pelvic prolapse (n = 9), rectocele (n = 8), or rectal intussusception (n = 3). Only intrarectal pressure on HR-ARM weakly correlated with size of rectocele (r = 0.46; P = 0.03) and degree of pelvic organ prolapse (r = 0.48; P = 0.02). The remainder of the HR-ARM parameters did not significantly correlate with DP-MRI findings. Patients with dyssynergy were not more likely to have rectoceles > 3 cm (44.4% versus 35.7%; P = 0.5) or large prolapses (44.4% versus 50%, P = 1.0), compared with those without dyssynergy, on HR-ARM.We were unable to find a correlation between HR-ARM findings and structural pelvic defects on DP-MRI. Therefore, these two technologies provide complementary information in the evaluation of defecatory dysfunction.

    View details for DOI 10.1111/jgh.12697

    View details for Web of Science ID 000346783900014

    View details for PubMedID 25088015

  • Multichannel Intraluminal Impedance-pH Testing Is Clinically Useful in the Management of Patients with Gastroesophageal Reflux Symptoms DIGESTIVE DISEASES AND SCIENCES Jodorkovsky, D., Price, J. C., Kim, B., Dhalla, S., Stein, E. M., Clarke, J. O. 2014; 59 (8): 1817-1822


    Multichannel intraluminal impedance-pH testing (MII-pH) allows for the detection of acid and non-acid reflux, thus, increasing yield over pH testing. Limited data exist on how physicians use test results in practice.The aim of our study was to evaluate the influence of MII-pH testing on patient care.We reviewed records of patients with symptoms of gastroesophageal reflux disease who underwent MII-pH testing. Management decisions evaluated included changes in prescribed medications and surgical consultation for anti-reflux surgery. Statistical analysis was performed using Pearson Chi square test, and multivariable logistic regression.MII-pH testing resulted in a medication change in 41% of patients, surgical consultation in 19.7%, and anti-reflux surgery in 11.1%. In patients who were not on proton pump inhibitor (PPI) therapy, MII-pH results were most useful in the decision to start a PPI. On PPI therapy, results were more often used to decide whether to increase (32.3%) or switch the PPI (23.5%) in patients with continued acid reflux. Results were most useful to stop the PPI in normal studies (11.1%). More patients with non-acid reflux (14.3%) and normal results (19.7%) were started on a neuromodulator compared to other diagnoses. The MII-pH result was most useful in the decision to start baclofen or bethanecol when the patient was found to have non-acid reflux (25%). Patients with an abnormal MII-pH or abnormal MII alone were more likely to be referred to surgery (OR 19.5, p < 0.001; OR 19.77, p < 0.001).MII-pH testing impacted medical or surgical management in over half the patients tested.

    View details for DOI 10.1007/s10620-014-3080-z

    View details for Web of Science ID 000340051200088

    View details for PubMedID 24563276

  • Low Ileocecal Valve Pressure Is Significantly Associated with Small Intestinal Bacterial Overgrowth (SIBO) DIGESTIVE DISEASES AND SCIENCES Roland, B. C., Ciarleglio, M. M., Clarke, J. O., Semler, J. R., Tomakin, E., Mullin, G. E., Pasricha, P. J. 2014; 59 (6): 1269-1277


    Small intestinal bacterial overgrowth (SIBO) is a significant and increasingly recognized syndrome. While the development may be multifactorial, impairment of the ileocecal valve (ICV), small bowel motility, and gastric acid secretion have been hypothesized to be risk factors. ICV dysfunction remains largely unexplored using standard technology. The wireless motility capsule (WMC) that evaluates pressure, pH, and temperature throughout the GI tract provides the ability to assess these parameters.The primary aims of this study were to assess the relationship of ICV pressures, small bowel transit time (SBTT) and intestinal pH with lactulose hydrogen breath testing (LBT) results in subjects with suspected SIBO.We retrospectively studied consecutive patients referred to our institution for WMC and LBT from 2010-2012. Ileocecal junction pressures (IJP), as a surrogate for ICV pressures, were defined as the highest pressure over a 4-min window prior to the characteristic ileocecal pH drop. SBTT and pH were calculated and compared with LBT results.Twenty-three patients underwent both WMC and LBT, with positive results observed in 15 (65.2%). IJP were significantly higher in LBT(-) negative vs. LBT(+) (79.9 vs. 45.1, p < 0.01). SBTT was significantly longer in LBT(+) versus LBT(-) (5.82 vs. 3.81 h, p = 0.05). Among LBT(+) subjects, gastric pH was significantly higher versus LBT(-) subjects (2.76 vs. 1.63, p = 0.01). There was poor correlation between IJP and other parameters (SBTT, small bowel pH, and gastric pH).Low IJP is significantly associated with SIBO. While this is physiologically plausible, to our knowledge, this is the first study to make this connection. Prolonged SBTT and higher pH are also independently associated with SIBO. Our findings add value of the WMC test as a diagnostic tool in patients with functional gastrointestinal complaints and suggest re-focus of attention on the ileocecal valve as a prominent player in intestinal disorders.

    View details for DOI 10.1007/s10620-014-3166-7

    View details for Web of Science ID 000336386000029

    View details for PubMedID 24795035

  • Herbal therapy is equivalent to rifaximin for the treatment of small intestinal bacterial overgrowth. Global advances in health and medicine Chedid, V., Dhalla, S., Clarke, J. O., Roland, B. C., Dunbar, K. B., Koh, J., Justino, E., Tomakin, E., Mullin, G. E. 2014; 3 (3): 16-24


    Patients with small intestine bacterial overgrowth (SIBO) have chronic intestinal and extraintestinal symptomatology which adversely affects their quality of life. Present treatment of SIBO is limited to oral antibiotics with variable success. A growing number of patients are interested in using complementary and alternative therapies for their gastrointestinal health. The objective was to determine the remission rate of SIBO using either the antibiotic rifaximin or herbals in a tertiary care referral gastroenterology practice.One hundred and four patients who tested positive for newly diagnosed SIBO by lactulose breath testing (LBT) were offered either rifaximin 1200 mg daily vs herbal therapy for 4 weeks with repeat LBT post-treatment.Three hundred ninety-six patients underwent LBT for suspected SIBO, of which 251 (63.4%) were positive 165 underwent treatment and 104 had a follow-up LBT. Of the 37 patients who received herbal therapy, 17 (46%) had a negative follow-up LBT compared to 23/67 (34%) of rifaximin users (P=.24). The odds ratio of having a negative LBT after taking herbal therapy as compared to rifaximin was 1.85 (CI=0.77-4.41, P=.17) once adjusted for age, gender, SIBO risk factors and IBS status. Fourteen of the 44 (31.8%) rifaximin non-responders were offered herbal rescue therapy, with 8 of the 14 (57.1%) having a negative LBT after completing the rescue herbal therapy, while 10 non-responders were offered triple antibiotics with 6 responding (60%, P=.89). Adverse effects were reported among the rifaximin treated arm including 1 case of anaphylaxis, 2 cases of hives, 2 cases of diarrhea and 1 case of Clostridium difficile. Only one case of diarrhea was reported in the herbal therapy arm, which did not reach statistical significance (P=.22).SIBO is widely prevalent in a tertiary referral gastroenterology practice. Herbal therapies are at least as effective as rifaximin for resolution of SIBO by LBT. Herbals also appear to be as effective as triple antibiotic therapy for SIBO rescue therapy for rifaximin non-responders. Further, prospective studies are needed to validate these findings and explore additional alternative therapies in patients with refractory SIBO.

    View details for DOI 10.7453/gahmj.2014.019

    View details for PubMedID 24891990

    View details for PubMedCentralID PMC4030608

  • Jet injection of dyed saline facilitates efficient peroral endoscopic myotomy ENDOSCOPY Khashab, M. A., Messallam, A. A., Saxena, P., Kumbhari, V., Ricourt, E., Aguila, G., Roland, B. C., Stein, E., Nandwani, M., Inoue, H., Clarke, J. O. 2014; 46 (4): 298-301


    Peroral endoscopic myotomy (POEM) is technically challenging and time consuming. Repeated injection of dyed saline during tunneling is performed to enhance the demarcation between the submucosal layer and the muscularis propria. This process requires exchanging the knife for a catheter to spray dyed saline and is time consuming. This study aimed to describe a new method of injecting dyed saline through an integrated water jet channel during POEM.POEM was performed using a triangular tip knife. Repeated jet injection of saline mixed with indigo carmine was performed whenever the submucosal dissection plane became unclear.The study cohort consisted of nine patients (8 achalasia, 1 Jackhammer esophagus). All procedures were technically feasible and successful without any complications and resulted in the patients' Eckhardt's scores returning to normal. The mean submucosal tunnel length was 13.3 cm and the mean myotomy length was 9.9 cm. The mean procedure time was 127 minutes.The modified POEM technique with use of jet injection of dyed saline is simple and may render POEM easier and more efficient than the standard dissection method.

    View details for DOI 10.1055/s-0033-1359024

    View details for Web of Science ID 000337153500005

    View details for PubMedID 24338241

  • Domperidone for delayed gastric emptying in lung transplant recipients with and without gastroesophageal reflux PROGRESS IN TRANSPLANTATION Lidor, A. O., Ensor, C. R., Sheer, A. J., Orens, J. B., Clarke, J. O., McDyer, J. F. 2014; 24 (1): 27-32


    Evidence demonstrates a link between gastroesophageal reflux disease and chronic allograft dysfunction in lung transplant recipients. Delayed gastric emptying plays an important role in the occurrence of gastroesophageal reflux disease, with limited therapeutic options available for treatment. This retrospective observational study reports the use of domperidone in the management of delayed gastric emptying in lung transplant recipients. All patients who underwent lung transplant at our institution from 2007 to 2011 were reviewed and patients who were treated with domperidone were identified. Clinical symptoms and results of gastric emptying studies before and after initiation of domperidone were documented. QTc intervals were compared from before to after domperidone treatment at 3 months and at 1 year. Weight and dose-normalized calcineurin inhibitor troughs were evaluated before and 2 weeks after domperidone treatment was started. Of 82 patients, 24% (n = 20) had documented delayed gastric emptying and 35% (n = 29) had documented gastroesophageal reflux disease. Twelve of the 20 patients with delayed gastric emptying started treatment with domperidone. All patients responded symptomatically and 6 patients with gastric emptying studies before and after domperidone had documented improvement. No adverse effects were observed in any patients treated with domperidone. Results indicate that domperidone can be used safely and may improve symptoms related to delayed gastric emptying in lung transplant recipients.

    View details for DOI 10.7182/pit2014823

    View details for Web of Science ID 000344983800007

    View details for PubMedID 24598562

  • Peroral endoscopic myotomy as a platform for the treatment of spastic esophageal disorders refractory to medical therapy (with video) GASTROINTESTINAL ENDOSCOPY Khashab, M. A., Saxena, P., Kumbhari, V., Nandwani, M., Roland, B. C., Stein, E., Clarke, J. O., Stavropoulos, S., Inoue, H., Pasricha, P. J. 2014; 79 (1): 136-139

    View details for DOI 10.1016/j.gie.2013.08.021

    View details for Web of Science ID 000328736700023

    View details for PubMedID 24342590

  • Through-the-scope transpyloric stent placement improves symptoms and gastric emptying in patients with gastroparesis ENDOSCOPY Clarke, J. O., Sharaiha, R. Z., Valeshabad, A. K., Lee, L. A., Kalloo, A. N., Khashab, M. A. 2013; 45: E189-E190
  • Upper Esophageal Sphincter Abnormalities Are Strongly Predictive of Treatment Response in Patients with Achalasia Mathews, S., Chavez, Y., Ciarleglio, M., Clarke, J., Stein, E., Roland, B. NATURE PUBLISHING GROUP. 2013: S1–S2
  • Biofeedback Therapy for Defecatory Dysfunction "Real Life" Experience JOURNAL OF CLINICAL GASTROENTEROLOGY Jodorkovsky, D., Dunbar, K. B., Gearhart, S. L., Stein, E. M., Clarke, J. O. 2013; 47 (3): 252-255


    Biofeedback therapy (BF) is a well-established treatment modality for patients with dyssynergic defecation and fecal incontinence (FI). Randomized controlled trials from highly specialized tertiary care centers report response rates of 70% to 80% for dyssynergic defecation and 55% to 75% for FI. Whether this therapy is as successful outside of clinical trials or specialized biofeedback referral centers remains unclear.Our primary aim was to determine what percentage of patients referred for BF actually complete therapy and identify barriers to treatment. Our secondary aim was to determine the clinical response rate in a heterogeneous population of patients undergoing BF at our institution and a variety of regional locations.We retrospectively reviewed patients who underwent high resolution anorectal manometry between 2007 and 2010 for symptoms of defecatory dysfunction. BF was recommended at the time of manometry analysis based on findings of dyssynergy, impaired or heightened rectal sensation, or poor augmentation of sphincter on squeeze maneuvers. Clinical response was recorded after a course of BF (≥ 5 sessions).Two hundred three patients (78% female, 72% white; median age 52) underwent anorectal manometry for symptoms of constipation (130), FI (54), combination (12), and rectal pain (7). BF was recommended in 119 cases (58.6%): constipation (80), FI (27), combination (9), and rectal pain (3). Only 39 out of 80 (48%) patients with constipation ultimately underwent BF. Of the 27 FI cases, only 12 (44%) patients underwent BF. Barriers to BF included lack of insurance coverage, distance to local treatment facilities, and acute medical issues taking precedence. Of those who underwent at least 5 BF sessions, subjective short-term response rates based on patient opinion were 17/28 (60%) in the constipation group and 8/10 (80%) in the FI group. Age, sex, and race had no effect on whether the patients attended biofeedback or whether they responded to treatment. The location of BF also did not predict response to therapy.In a heterogeneous patient population, less than half of patients recommended for BF ultimately underwent therapy. Despite this, the response rates in this small population undergoing BF in the "real world" are only slightly less than published randomized control trials. Prospective studies are warranted to further elucidate and eliminate barriers to BF, especially given that "real world" BF response rates may be comparable with those seen in clinical trials.

    View details for DOI 10.1097/MCG.0b013e318266f43a

    View details for Web of Science ID 000314863800013

    View details for PubMedID 23328298

  • The Relationship Between Depressive Symptoms and Voice Handicap Index Scores in Laryngopharyngeal Reflux LARYNGOSCOPE Elam, J. C., Ishman, S. L., Dunbar, K. B., Clarke, J. O., Gourin, C. G. 2010; 120 (9): 1900-1903


    To determine if a relationship exists between depression and Voice Handicap Index (VHI) scores in patients with laryngopharyngeal reflux (LPR) disease.Retrospective analysis of prospectively collected data.One hundred nineteen patients were prospectively evaluated with the VHI questionnaire and the Beck Depression Inventory Fast Screen (BDI-FS) survey. Patients with a pre-existing diagnosis of depression were excluded.Complete data was available for 36 patients with LPR and 53 controls. No significant differences existed between groups with respect to age, race, or gender. Mild depressive symptoms were identified in 9% of controls and 3% of LPR patients by BDI-FS screening (P = .4); no patients had moderate or severe depression symptoms. Compared to controls, patients with LPR had significantly higher mean scores for total VHI (16.2 vs. 6.6, P = .002), functional VHI (5.8 vs. 2.4, P = .02), and physical VHI (6.9 vs. 2.5, P = .008) domains. Mean scores for the VHI emotional domain (3.5 vs. 1.7, P = .2) and BDI-FS (0.2 vs. 0.8, P = .3) did not differ between patients with LPR and controls. For all participants, a positive correlation was found between BDI-FS score and VHI emotional domain score (r = 0.3, P = .008).Patients with LPR report poorer VHI functional and physical scores compared to controls; however, LPR symptoms do not result in significantly worse VHI emotional domain scores or depressive symptoms. There is a correlation between VHI emotional domain scores and BDI-FS scores. These data suggest that LPR patients with poor VHI emotional domain scores might benefit from screening for depressive symptoms.

    View details for DOI 10.1002/lary.21012

    View details for Web of Science ID 000281430600030

    View details for PubMedID 20717946

  • The Added Diagnostic Value of Liquid Gastric Emptying Compared with Solid Emptying Alone JOURNAL OF NUCLEAR MEDICINE Ziessman, H. A., Chander, A., Clarke, J. O., Ramos, A., Wahl, R. L. 2009; 50 (5): 726–31


    The medical literature states that solid gastric-emptying studies are more sensitive for the detection of gastroparesis than are liquid studies; thus, liquid studies are rarely required. However, we have seen patients with normal solid but delayed liquid emptying. The purpose of this investigation was to determine whether a study of clear liquid gastric emptying has added value for the diagnosis of gastroparesis over a study of solid emptying alone.A total of 101 patients underwent both solid and liquid gastric-emptying studies, acquired sequentially on the same day. A 30-min (1-min frames) liquid study (300 mL of water with 7.4 MBq [0.2 mCi] of (111)In-diethylenetriaminepentaacetic acid) was followed by a standardized 4-h solid-meal study (a (99m)Tc-sulfur colloid-labeled egg-substitute sandwich meal). Emptying was quantified as a best-fit exponential emptying rate (T1/2) for liquids and percentage emptying at 4 h for solid emptying. Thirty healthy volunteers underwent a study of clear liquid emptying to establish normal values. The results of the liquid and solid studies were compared. (111)In liquid downscatter into the subsequent (99m)Tc solid meal results was analyzed.The upper range of normal for clear liquid emptying (T1/2) for healthy volunteers was 22 min (mean +/- 3 SDs) and 19 min (mean +/- 2 SDs). Of 101 patients, delayed emptying was found in 36% of liquid and 16% of solid studies. Of all patients with normal solid emptying, 32% had delayed liquid emptying. (111)In downscatter into the (99m)Tc window was not generally significant.For the detection of gastroparesis, a 30-min study of clear liquid gastric-emptying has considerable added diagnostic value over a study of solid emptying alone.

    View details for DOI 10.2967/jnumed.108.059790

    View details for Web of Science ID 000272487900010

    View details for PubMedID 19372480

  • Endoscopic retrograde cholangiopancreatography, but not esophagogastroduodenoscopy or colonoscopy, significantly increases portal venous pressure: direct portal pressure measurements through endoscopic ultrasound-guided cannulation ENDOSCOPY Buscaglia, J. M., Shin, E. J., Clarke, J. O., Giday, S. A., Ko, C. W., Thuluvath, P. J., Magno, P., Dray, X., Kantsevoy, S. V. 2008; 40 (8): 670-674


    Changes in portal pressure during endoscopy have not been previously evaluated. The aims of this study were to assess the effect of esophagogastroduodenoscopy (EGD), colonoscopy, and endoscopic retrograde cholangiopancreatography (ERCP) on portal vein, inferior vena cava (IVC), and systemic pressures.Five acute experiments were performed on 50-kg pigs utilizing endoscopic ultrasound (EUS)-guided catheterization of the portal vein and IVC. Systemic, intra-abdominal, IVC, and portal vein pressures were monitored during colonoscopy, EGD, and ERCP with endoscopic sphincterotomy. After endoscopy the animals were sacrificed for necropsy. The main outcome measure was pressure change during each type of endoscopic procedure.There were no significant changes in heart rate or systemic pressure during all endoscopic procedures. Intra-abdominal pressure increased during colonoscopy ( P = 0.02) and ERCP ( P = 0.007). However, mean portal venous pressure was significantly elevated only after the injection of contrast into the common bile duct, reaching its peak value at the time of biliary sphincterotomy (39.0 +/- 15.2 mm Hg vs. 13.4 +/- 3.6 mm Hg at baseline, P = 0.006). Mean peak IVC pressure was also elevated during ERCP, but it did not reach statistical significance (24.0 +/- 10.7 mm Hg vs. 12.6 +/- 4.1 mm Hg at baseline, P = 0.06).EGD and colonoscopy did not cause significant changes in portal vein, IVC, or systemic pressures. ERCP with biliary sphincterotomy increased portal pressure with only limited effect on IVC and systemic pressures. These new data indicate a possible connection between ERCP with sphincterotomy and portal pressure, and may be clinically important for patients with liver disease and other causes of portal hypertension who undergo this procedure.

    View details for DOI 10.1055/s-2008-1077341

    View details for Web of Science ID 000258361600008

    View details for PubMedID 18561105

  • How good is capsule endoscopy for detection of periampullary lesions? Results of a tertiary-referral center GASTROINTESTINAL ENDOSCOPY Clarke, J. O., Giday, S. A., Magno, P., Shin, E. J., Buscaglia, J. M., Jagannath, S. B., Mullin, G. E. 2008; 68 (2): 267-272


    Ampullary adenomas are increasingly being recognized, particularly in patients with familial adenomatous polyposis. A capsule endoscopy (CE) is routinely recommended for surveillance of small-intestinal polyposis. Performance characteristics of CE for the detection of periampullary lesions are unclear.To evaluate the ability of CE to detect the major duodenal papilla.A total of 146 consecutive CE studies were reviewed by 2 CE gastroenterologists at 5 frames per second. Primary outcome was visualization of the major duodenal papilla. Discrepancies were reviewed by 5 CE gastroenterologists.A tertiary-referral center.The ability of CE to detect the duodenal papilla.Among 146 consecutive CE studies, 21 were excluded: capsule retention (3), patient age <18 years (6), duplicate study (8), and prior surgery disrupting duodenal anatomy (4). Of the remaining 125 studies, indications were the following: obscure GI bleeding (45.6%), iron deficiency anemia (19.2%), abdominal pain (17.6%), diarrhea (10.4%), and Crohn's disease (4.8%). In total, 13 major duodenal papillae were visualized. The median time of detection was 31 seconds after the first duodenal image. This translates to a CE sensitivity of 10.4% for detection of the major papilla.Papilla position was not verified by an EGD.CE has limited sensitivity to visualize the major papilla and lesions in the periampullary small intestine. Nondiagnostic CE studies must not be relied upon as proof that small-bowel lesions do not exist. Consideration should be given for an enteroscopy or side-viewing duodenoscopy in cases where significant clinical concern exists for unrecognized periampullary lesions. The current recommendations about surveillance for small-bowel polyposis should be revised.

    View details for DOI 10.1016/j.gie.2007.11.055

    View details for Web of Science ID 000258368200011

    View details for PubMedID 18378233

  • EUS-guided submucosal implantation of a radiopaque marker: a simple and effective procedure to facilitate subsequent surgical and radiation therapy GASTROINTESTINAL ENDOSCOPY Magno, P., Giday, S. A., Gabrielson, K. L., Shin, E., Clarke, J. O., Ko, C., Buscaglia, J. M., Jagannath, S. B., Canto, M. I., Kantsevoy, S. V. 2008; 67 (7): 1147–52


    Endosonography (EUS) is widely used for locoregional staging of malignant GI tumors. Delineation of a tumor's margins with a long-lasting fluoroscopically visible material will facilitate subsequent surgical and radiation therapy.To assess the feasibility of EUS-guided submucosal implantation of a radiopaque marker in a porcine model.Survival experiments on four 50-kg pigs.A linear array echoendoscope was introduced into the esophagus and advanced to the stomach. With a 19-gauge FNA needle, a submucosal bleb was created by injecting 3 mL of normal saline solution into the gastric and esophageal wall followed by injection of 1 mL of tantalum suspension under fluoroscopic observation. Fluoroscopy was repeated after 1, 2, and 4 weeks followed by euthanasia and necropsy.Long-term depositions of the marker in the injection sites.Submucosal injections of tantalum were easily performed through the 19-gauge FNA needle, resulting in good fluoroscopic opacification of injected material. Follow-up fluoroscopy in 1, 2, and 4 weeks demonstrated stable deposition of the tantalum at the sites of injection. There were no complications during and after the tantalum implantation. Histologic examination of the injection sites demonstrated submucosal tantalum depositions without signs of infection, inflammation, tissue damage, or necrosis.Animal experiments with 4 weeks' follow-up.EUS-guided implantation of tantalum as a radiopaque marker into the submucosal layer of the GI tract in a porcine model is technically feasible and safe. Long-lasting fluoroscopically visible tantalum markings could facilitate subsequent surgical and radiation therapy.

    View details for DOI 10.1016/j.gie.2008.02.053

    View details for Web of Science ID 000256516100025

    View details for PubMedID 18513556

  • Severity of post-ERCP pancreatitis directly proportional to the invasiveness of endoscopic intervention: a pilot study in a canine model ENDOSCOPY Buscaglia, J. M., Simons, B. W., Prosser, B. J., Ruben, D. S., Giday, S. A., Magno, P., Clarke, J. O., Shin, E. J., Kalloo, A. N., Kantsevoy, S. V., Gabrielson, K. L., Jagannath, S. B. 2008; 40 (6): 506–12


    Pancreatitis complicates 1% - 22% of endoscopic retrograde cholangiopancreatography procedures. The study aims were to develop a reproducible animal model of post-ERCP pancreatitis (PEP), and investigate the impact of endoscopic technique on severity of PEP.ERCP was carried out in six male hound dogs. Pancreatitis was induced by one of three escalating methods: 1) pancreatic acinarization with 20 - 30 mL of contrast; 2) acinarization + ductal balloon occlusion + sphincterotomy; 3) acinarization + intraductal synthetic bile injection + ductal balloon occlusion + sphincterotomy. Dogs 5 and 6 received a pancreatic stent. Necropsy was performed on postoperative day 5. All pancreatic specimens were graded by two blinded pathologists according to a validated scoring system. All dogs were compared with three control dogs.Dogs 1 - 4 developed clinical pancreatitis and hyperamylasemia (11 736 vs. 722 U/L, P = 0.02). Total injury scores were significantly elevated compared with controls (6.85 vs. 1.06, P = 0.004). There was significant increase in acinar cell necrosis (0.86 vs. 0.06, P = < 0.001), and all other categories (except fibrosis) demonstrated elevated injury scores . Dogs 5 and 6 developed clinical pancreatitis without significant hyperamylasemia; total injury scores were elevated compared with controls (4.83 vs. 1.06, P = 0.01), but lower than in Dogs 1 - 4 (4.83 vs. 6.85, P = 0.25). There was escalating severity of pancreatic injury from Dogs 1 to 4 correlating with the method of endoscopic injury used.Severity of PEP is directly proportional to invasiveness of endoscopic intervention. Pancreatic acinarization, even without balloon occlusion and sphincterotomy, can be used as a reliable animal model for future studies investigating therapy and prevention of disease.

    View details for DOI 10.1055/s-2007-995653

    View details for Web of Science ID 000257075300009

    View details for PubMedID 18478511

  • Performance characteristics of the suspected blood indicator feature in capsule endoscopy according to indication for study CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Buscaglia, J. M., Giday, S. A., Kantsevoy, S. V., Clarke, J. O., Magno, P., Yong, E., Mullin, G. E. 2008; 6 (3): 298–301


    The suspected blood indicator (SBI) feature of wireless capsule endoscopy (WCE) was developed for rapid screening of intestinal lesions with bleeding potential. Our aim was to assess the accuracy and performance characteristics of the SBI according to the indications for study in a large cohort of patients.We reviewed collected data on all WCE studies performed at Johns Hopkins Hospital from January 2006 to June 2007. Study indications were as follows: anemia of unknown origin (n = 53), obscure gastrointestinal bleeding (n = 112), suspected Crohn's disease (n = 122), and other (n = 4). Concordant and discordant findings between gastroenterologists' readings and SBI were recorded for each patient.A total of 221 lesions with bleeding potential was detected. The overall sensitivity, specificity, positive predictive value, and negative predictive value for the SBI were 56.4%, 33.5%, 24.0%, and 67.3%, respectively. For actively bleeding lesions, the SBI sensitivity and positive predictive value were only 58.3% and 70%, respectively. The sensitivity was highest (64%) in patients undergoing WCE for suspected Crohn's disease, with a negative predictive value of 80.4%. The sensitivity was only 58.3% and 41.3%, respectively, in studies performed for obscure gastrointestinal bleeding and anemia.Performance characteristics of the currently available SBI feature in WCE are suboptimal and insufficient to screen for lesions with bleeding potential. Even in patients with active intestinal bleeding, the sensitivity of SBI was less than 60%, which is lower than previously reported. However, in patients with suspected Crohn's disease, the high sensitivity and negative predictive value of SBI may make it a useful tool for the detection of large areas of abnormal mucosa.

    View details for DOI 10.1016/j.cgh.2007.12.029

    View details for Web of Science ID 000253961100009

    View details for PubMedID 18255353

  • EUS-guided portal vein catheterization: a promising novel approach for portal angiography and portal vein pressure measurements GASTROINTESTINAL ENDOSCOPY Giday, S. A., Clarke, J. O., Buscaglia, J. M., Shin, E. J., Ko, C., Magno, P., Kantsevoy, S. V. 2008; 67 (2): 338–42


    Portal vein (PV) pressure measurements can provide valuable information for the management of patients with liver disease and portal hypertension.To evaluate the feasibility and the safety of EUS-guided PV catheterization and pressure measurements in a porcine model.Acute and survival experiments on five 50-kg pigs.Intrahepatic PV was punctured under EUS guidance by using a 19-gauge FNA needle. A 0.035-inch guidewire was advanced through the needle into the PV. The needle was withdrawn. A 5.5F ERCP catheter was advanced over the guidewire into the PV and then connected to a pressure monitor. Continuous PV measurements were obtained for an hour. Afterward, the catheter was removed, and the animals were observed for 30 minutes. Three animals were then immediately euthanized for a necropsy. The other two animals were observed for two weeks and then were euthanized.The ability to perform EUS-guided PV catheterization and pressure measurement without complications.PV catheterization, angiography, and pressure measurements were performed without any problems or complications. There were no changes in vital signs and hemodynamic parameters during PV catheterizations, angiography, pressure measurements, and catheter removal. Survival experiments did not demonstrate any change in animal condition, behavior, or eating habits after the procedure. A necropsy in all animals revealed no active bleeding, and no damage to the liver, other intra-abdominal organs, or blood vessels.No validation of measured PV pressure was made.EUS-guided PV catheterization is feasible, safe, and can be used for portal angiography and pressure measurements.

    View details for DOI 10.1016/j.gie.2007.08.037

    View details for Web of Science ID 000253368100027

    View details for PubMedID 18226699

  • Enhanced diagnostic yield with prolonged small bowel transit time during capsule endoscopy. International journal of medical sciences Buscaglia, J. M., Kapoor, S., Clarke, J. O., Bucobo, J. C., Giday, S. A., Magno, P., Yong, E., Mullin, G. E. 2008; 5 (6): 303-308


    The effect of small bowel transit time (SBTT) on diagnostic yield during capsule endoscopy (CE) has not been previously evaluated. Our study aim was to assess the effect of SBTT on the likelihood of detecting intestinal pathology during CE.We reviewed collected data on CE studies performed at Johns Hopkins Hospital from January 2006 to June 2007. In patients investigated for anemia or obscure bleeding, the following lesions were considered relevant: ulcers, erosions, AVMs, red spots, varices, vascular ectasias, and presence of blood. In patients with diarrhea or abdominal pain, ulcers, erosions, and blood were considered relevant. Age, gender, study indication, hospital status, and quality of bowel preparation were identified as candidate risk factors affecting SBTT. Univariate logistic and linear regression analyses were performed to study the effect of SBTT on diagnostic yield.Total of 212 CE studies were analyzed; most were in outpatients (n=175, 82.9%) and with excellent bowel preparation (n=177, 83.5%). Mean SBTT was 237.0 min (3.9 hrs). Age, gender, bowel prep, hospital status, and study indication did not significantly affect SBTT. However, increased SBTT was independently associated with increased diagnostic yield; OR=1.7 in SBTT=2-4 hr (p=0.41), OR=1.8 in SBTT=4-6 hrs (p=0.30), OR=9.6 in SBTT=6-8 hrs (p=0.05).Prolonged SBTT during CE (>6 hr) is associated with an increased diagnostic yield. This may be due to a positive effect on image quality during a "slower" study. The use of promotility agents may adversely affect the ability of CE to detect significant intestinal pathology.

    View details for PubMedID 18974857

    View details for PubMedCentralID PMC2574018

  • Classifying esophageal motility by pressure topography characteristics: A study of 400 patients and 75 controls AMERICAN JOURNAL OF GASTROENTEROLOGY Pandolfino, J. E., Ghosh, S. K., Rice, J., Clarke, J. O., Kwiatek, M. A., Kahrilas, P. J. 2008; 103 (1): 27–37


    This study aimed to devise a scheme for the systematic analysis of esophageal high-resolution manometry (HRM) studies displayed using topographic plotting.A total of 400 patients and 75 control subjects were studied with a 36-channel HRM assembly. Studies were analyzed in a stepwise fashion for: (a) the adequacy of deglutitive esophagogastric junction (EGJ) relaxation, (b) the presence and propagation characteristics of distal esophageal persitalsis, and (c) an integral of the magnitude and span of the distal esophageal contraction.Two strengths of pressure topography plots compared to conventional manometric recordings were: (a) the ability to delineate the spatial limits, vigor, and integrity of individual contractile segments along the esophagus, and (b) the ability to distinguish between loci of compartmentalized intraesophageal pressurization and rapidly propagated contractions. Making these distinctions objectified the identification of distal esophageal spasm (DES), vigorous achalasia, functional obstruction, and nutcracker esophagus subtypes. Applying these distinctions made the diagnosis of spastic disorders quite rare: (a) DES in 1.5% patients, (b) vigorous achalasia in 1.5%, and (c) a newly defined entity, spastic nutcracker, in 1.5%.We developed a systematic approach to analyzing esophageal motility using HRM and pressure topography plots. The resultant scheme is consistent with conventional classifications with the caveats that: (a) hypercontractile conditions are more specifically defined, (b) distinctions are made between rapidly propagated contractions and compartmentalized esophageal pressurization, and (c) there is no "nonspecific esophageal motor disorder" classification. We expect that pressure topography analysis, with its well-defined functional implications, will prove valuable in the clinical management of esophageal motility disorders.

    View details for DOI 10.1111/j.1572-0241.2007.01532.x

    View details for Web of Science ID 000252108400006

    View details for PubMedID 17900331

  • Preliminary pneumoperitoneum facilitates transgastric access into the peritoneal cavity for natural orifice transluminal endoscopic surgery: A pilot study in a live porcine model ENDOSCOPY Ko, C., Shin, E. J., Buscaglia, J. M., Clarke, J. O., Magno, P., Giday, S. A., Chung, S. S., Cotton, P. B., Gostout, C. J., Hawes, R. H., Pasricha, P. J., Kalloo, A. N., Kantsevoy, S. V. 2007; 39 (10): 849-853


    Safe entrance into the peritoneal cavity through the gastric wall is paramount for the successful clinical introduction of natural orifice transluminal endoscopic surgery (NOTES). The aim of the study was to develop alternative safe transgastric access to the peritoneal cavity.We performed 11 survival experiments on 50-kg pigs. In sterile conditions, the abdominal wall was punctured with a Veress needle. The peritoneal cavity was insufflated with 2 L carbon dioxide (CO (2)). A sterile endoscope was introduced into the stomach through a sterile overtube; the gastric wall was punctured with a needle-knife; after balloon dilation of the puncture site, the endoscope was advanced into the peritoneal cavity. Peritoneoscopy with biopsies from abdominal wall, liver and omentum, was performed. The endoscope was withdrawn into the stomach. The animals were kept alive for 2 weeks and repeat endoscopy was followed by necropsy.The pneumoperitoneum, easily created with the Veress needle, lifted the abdominal wall and made a CO (2)-filled space between the stomach and adjacent organs, facilitating gastric wall puncture and advancement of the endoscope into the peritoneal cavity. There were no hemodynamic changes or immediate or delayed complications related to pneumoperitoneum, transgastric access, or intraperitoneal manipulations. Follow-up endoscopy and necropsy revealed no problems or complications inside the stomach or peritoneal cavity.Creation of a preliminary pneumoperitoneum with a Veress needle facilitates gastric wall puncture and entrance into the peritoneal cavity without injury to adjacent organs, and can improve the safety of NOTES.

    View details for DOI 10.1055/s-2007-966844

    View details for Web of Science ID 000250719700001

    View details for PubMedID 17968798

  • Impaired deglutitive EGJ relaxation in clinical esophageal manometry: a quantitative analysis of 400 patients and 75 controls AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY Ghosh, S. K., Pandolfino, J. E., Rice, J., Clarke, J. O., Kwiatek, M., Kahrilas, P. J. 2007; 293 (4): G878–G885


    Assessing deglutitive esophagogastric junction (EGJ) relaxation is an essential focus of clinical manometry. Our aim was to apply automated algorithmic analyses to high-resolution manometry (HRM) studies to ascertain the optimal method for discriminating normal from abnormal deglutitive EGJ relaxation. All 473 subjects (73 controls) were studied with a 36-channel solid-state HRM assembly during water swallows. Patients were classified as: 1) achalasia, 2) postfundoplication, 3) nonachalasia with normal deglutitive EGJ relaxation, or 4) functional obstruction (preserved peristalsis with incomplete EGJ relaxation). Automated computer programs assessed the adequacy of EGJ relaxation by using progressively complex analysis routines to compensate for esophageal shortening, crural diaphragm contraction, and catheter movement, all potential confounders. The single-sensor method of assessing EGJ relaxation had a sensitivity of only 52% for detecting achalasia. Of the automated HRM analysis paradigms tested, the 4-s integrated relaxation pressure using a cutoff of 15 mmHg performed optimally with 98% sensitivity and 96% specificity in the detection of achalasia. We also identified a heterogeneous group of 26 patients with functional EGJ obstruction attributed to variant achalasia and other diverse pathology. Although further clinical experience will ultimately judge, it is our expectation that applying rigorous methodology such as described herein to the analysis of HRM studies will improve the consistency in the interpretation of clinical manometry and prove useful in guiding clinical management.

    View details for DOI 10.1152/ajpgi.00252.2007

    View details for Web of Science ID 000249995200027

    View details for PubMedID 17690172

  • Comparative study of endoscopic clips: duration of attachment at the site of clip application GASTROINTESTINAL ENDOSCOPY Shin, E., Ko, C., Magno, P., Giday, S. A., Clarke, J. O., Buscaglia, J. M., Scdrakyan, G., Jagannath, S. B., Kalloo, A. N., Kantsevoy, S. V. 2007; 66 (4): 757–61


    Several designs of endoscopic clips are now commercially available, and the indications for endoclip application are rapidly expanding. However, very limited data have been published to aid in choosing between the different types of endoclips.To compare the duration of clip attachment between all commercially available endoclips.Long-term experiments on 50-kg pigs under general anesthesia.Upper endoscope was inserted into the stomach. One clip of each type (Resolution clip, TriClip, and HX-5L clip) was placed along the same gastric fold at a distance of 0.5 to 1 cm from each other. The animals were recovered. In pig nos. 1 and 2, repeat endoscopy was performed after 2 and 4 weeks. In pig nos. 3 to 5, endoscopy was repeated after 1, 2, and 5 weeks.Duration of clip retention at the site of application.In all animals, only the Resolution endoclip remained attached to the site of application for the entire duration of the study (4-5 weeks). No TriClips or HX-5L clips were attached at the 4- to 5-week follow-up endoscopies. Most of the TriClips (67%) detached within the first week after application. Most of the HX-5L clips (80%) dislodged within the first 2 weeks of follow-up.The study was performed in a porcine model with a small number of animals.The Resolution clip has the longest duration of retention at the site of application (more than 4-5 weeks) and should be preferred when long-term attachment of endoclips is necessary.

    View details for DOI 10.1016/j.gie.2007.03.1049

    View details for Web of Science ID 000250166200020

    View details for PubMedID 17905019

  • EUS-guided portal vein carbon dioxide angiography: a pilot study in a porcine model GASTROINTESTINAL ENDOSCOPY Giday, S. A., Ko, C., Clarke, J. O., Shin, E., Magno, P., Jagannath, S. B., Buscaglia, J. M., Kantsevoy, S. V. 2007; 66 (4): 814–19


    Direct portal vein (PV) angiography can provide valuable clinical information but is not performed due to the high risk of complications.To assess the feasibility of EUS-guided PV angiography with a small-caliber FNA needle by using carbon dioxide (CO(2)) as a contrast agent in a porcine model.Acute experiments with 50-kg pigs under general anesthesia.Under linear array EUS guidance, the intrahepatic PV branch was punctured with a 25-gauge FNA needle. Portal venography was performed with iodinated contrast (Hypaque) and then with medical grade CO(2). After portography, the needle was removed from the PV and the animals were observed for 30 minutes, then euthanized for necropsy.Ability to visualize portal anatomy.Six animal experiments were performed without complications. EUS-guided PV puncture with 25-gauge FNA needle was technically straightforward. Injection of ionic iodinated contrast through the 25-gauge FNA needle was arduous (mean [+/-SD] pressure 76.7 +/- 5.2 pounds per square inch [psi]), resulting in short (6.02 +/- 1.15 seconds) and poor opacification of the PV (visualization score 1.33 +/- 0.52). CO(2) injection through a 25-gauge needle was simple and easy (pressure 20.8 +/- 2.0 psi), producing prolonged (19.83 +/- 1.68 seconds) opacification of the entire portal system (visualization score 4.33 +/- 0.52). There was a statistically significant difference in all compared parameters (P < .0001) favoring injection of CO(2) over viscous iodinated contrast during portal angiography through a 25-gauge FNA needle. Postmortem examination revealed no active bleeding and no damage to the liver, other intra-abdominal organs, or blood vessels.Acute animal experiments.EUS-guided portal venography with CO(2) using a small (25 gauge) FNA needle appears feasible, technically simple, and safe.

    View details for DOI 10.1016/j.gie.2007.05.056

    View details for Web of Science ID 000250166200029

    View details for PubMedID 17905028

  • EUS-guided angiography: a novel approach to diagnostic and therapeutic interventions in the vascular system GASTROINTESTINAL ENDOSCOPY Magno, P., Ko, C., Buscaglia, J. M., Giday, S. A., Jagannath, S. B., Clarke, J. O., Shin, E. J., Kantsevoy, S. V. 2007; 66 (3): 587-591


    Indications for diagnostic and therapeutic procedures under EUS guidance continue to expand.To assess the feasibility and safety of EUS-guided angiography in a live porcine model.Five acute experiments under general anesthesia.A linear echoendoscope was advanced into the stomach. Thoracic and abdominal aorta, celiac axis, superior mesenteric and splenic artery, splenic, portal, and hepatic veins were injected with contrast by using FNA needles under fluoroscopy. The animals were then killed for postmortem examination.Ability to achieve angiography without complications.All vessels were identified and punctured without technical difficulties. Injections of the large-caliber vessels resulted in a blush of contrast, whereas selective injection of the smaller vessels (splenic artery, hepatic veins) demonstrated clear vascular opacification. Injection of contrast was technically easiest with the 19-gauge FNA needle and most difficult with the 25-gauge needle. There were no changes in vital signs and hemodynamic parameters during vascular injection of any vessel. At necropsy, the 25-gauge FNA needle did not cause any visible vascular injury or bleeding. The 22-gauge needle left a visible puncture mark without active bleeding. In 1 of 5 pigs, the 19-gauge needle caused a localized vascular hematoma around large-caliber vessels and 150 mL of intra-abdominal blood.Technical challenges remain to achieve an adequate flow rate of contrast for prolonged visualization of large vessels.EUS-guided angiography is technically easy and safe and has potential for a wide array of diagnostic and therapeutic vascular interventions.

    View details for DOI 10.1016/j.gie.2007.01.011

    View details for Web of Science ID 000249503700026

    View details for PubMedID 17725951

  • EUS-guided implantation of radiopaque marker into mediastinal and celiac lymph nodes is safe and effective GASTROINTESTINAL ENDOSCOPY Magno, P., Giday, S. A., Gabrielson, K. L., Shin, E. J., Buscaglia, J. M., Clarke, J. O., Ko, C., Jagannath, S. B., Canto, M. I., Sedrakyan, G., Kantsevoy, S. V. 2007; 66 (2): 387-392


    EUS is the preferred modality for local staging of esophageal cancer. The presence of a long-lasting fluoroscopically visible marker of malignant lymph nodes would facilitate subsequent radiation and surgical therapy.To assess the feasibility of EUS-guided implantation of a radiopaque marker (tantalum) into mediastinal and celiac lymph nodes in a porcine model.Survival experiments on six 50-kg pigs.A linear-array echoendoscope was advanced into the esophagus and the stomach. Mediastinal and celiac lymph nodes were identified and injected with 1 mL tantalum suspension by using 19- and 22-gauge FNA needles under fluoroscopy. The pigs were recovered. Fluoroscopy was repeated after 1, 2, and 4 weeks, then a postmortem examination was performed.Long-term opacification of lymph nodes.It was not possible to inject tantalum through the 22-gauge FNA needle because of its rapid precipitation inside the needle, which caused needle occlusion. Intranodal injection with the 19-gauge FNA needle was easily accomplished and resulted in excellent fluoroscopic opacification of injected lymph nodes. Repeat fluoroscopy at 1, 2, and 4 weeks demonstrated stable tantalum deposition at the injection site. There were no complications. Histologic examination of harvested lymph nodes revealed intranodal tantalum depositions without signs of infection, inflammation, tissue damage, or necrosis.EUS-guided implantation of tantalum as a radiopaque marker into mediastinal and celiac lymph nodes in a porcine model is technically feasible, safe, and results in long-lasting intranodal depositions to facilitate subsequent surgical and radiotherapeutic interventions.

    View details for DOI 10.1016/j.gie.2006.12.063

    View details for Web of Science ID 000248678700032

    View details for PubMedID 17643719

  • The utility of contrast-enhanced endoscopic ultrasound in monitoring ethanol-induced pancreatic tissue ablation: a pilot study in a porcine model ENDOSCOPY Giday, S. A., Magno, P., Gabrielson, K. L., Buscaglia, J. M., Canto, M. I., Ko, C. W., Clarke, J. O., Kalloo, A. N., Jagannath, S. B., Shin, E. J., Kantsevoy, S. V. 2007; 39 (6): 525–29


    Pancreatic ablation is gaining popularity for the treatment of focal pancreatic lesions. The aim of our study was to evaluate local effects of intrapancreatic alcohol injection and the utility of contrast-enhanced endoscopic ultrasound (EUS) for its monitoring in a porcine model.We performed four survival experiments on 50-kg pigs. Under linear EUS guidance, 0.5 mL of 50% ethanol plus purified carbon particle solution (GI Spot) was injected into the pancreatic body to create a focal area of pancreatic necrosis. The animals survived for 24-48 hours (pigs # 1, # 2, and # 3) and 7 days (pig # 4). EUS was then repeated with and without perflutren lipid microspheres (Definity) administration through the peripheral vein. Standard and microsphere-enhanced images of the pancreas were compared. Afterwards the animals were euthanized for necropsy.Alcohol injection caused focal pancreatic necrosis, which was barely seen by standard EUS as a subtle hypoechoic lesion 1 cm in diameter. Color and power Doppler EUS of this region did not reveal any blood flow. After intravenous injection of microspheres, color Doppler EUS revealed marked contrast enhancement of normal pancreatic parenchyma with a clearly delineated avascular alcohol-treated area, which on postmortem examination corresponded to the discrete necrotic area marked with carbon particles.EUS-guided alcohol injection consistently causes focal areas of pancreatic necrosis. Contrast-enhanced EUS with microspheres improves visualization of altered pancreatic vascular perfusion and can be used to facilitate detection of small pancreatic lesions and its follow-up post-ablation.

    View details for DOI 10.1055/s-2007-966391

    View details for Web of Science ID 000247624500009

    View details for PubMedID 17554648

  • High-resolution manometry of the EGJ: An analysis of crural diaphragm function in GERD AMERICAN JOURNAL OF GASTROENTEROLOGY Pandolfino, J. E., Kim, H., Ghosh, S. K., Clarke, J. O., Zhang, Q., Kahrilas, P. J. 2007; 102 (5): 1056–63


    High-resolution manometry (HRM) provides a spatially enhanced, dynamic representation of the esophagogastric junction (EGJ) high-pressure zone making it possible to isolate the crural diaphragm (CD) contraction from expiratory lower esophageal sphincter (LES) pressure. This study compared CD function of subjects with and without gastroesophageal reflux disease (GERD).A total of 75 asymptomatic controls and 156 GERD patients (EGD or pH monitoring positive) underwent HRM. The EGJ axial pressure profile was analyzed over five respiratory cycles to quantify the position and contractile vigor of the CD relative to the LES. Correlations between EGJ HRM attributes and GERD status were examined.GERD patients had significantly greater CD-LES separation compared with either controls or EGD-/pH- patients. GERD patients also had significantly less inspiratory augmentation of EGJ pressure (EGD-/pH+, 11.5 +/- 1.9 mmHg; EGD+, 10.0 +/- 1.2 mmHg) compared with controls (16.9 +/- 1 mmHg) or EGD-/pH- patients (16.7 +/- 0.2 mmHg). Using a logistic regression model that simultaneously examined expiratory LES pressure, LES-CD separation, and inspiratory EGJ augmentation while controlling for age and BMI, only inspiratory augmentation had a significant independent association with GERD.HRM characterization of EGJ morphology correlates with the objective demonstration of GERD. Although both LES pressure and LES-CD separation are associated with GERD, the strongest association and the only independent predictor of GERD as a categorical outcome in a logistic regression analysis was impaired CD function as indicated by reduced inspiratory augmentation of EGJ pressure.

    View details for DOI 10.1111/j.1572-0241.2007.01138.x

    View details for Web of Science ID 000246186700022

    View details for PubMedID 17319930

  • An endoscopically implantable device stimulates the lower esophageal sphincter on demand by remote control: a study using a canine model ENDOSCOPY Clarke, J. O., Jagannath, S. B., Kalloo, A. N., Long, V. R., Beitler, D. M., Kantsevoy, S. V. 2007; 39 (1): 72-76


    Implantable microstimulators (IMS) have been used in a variety of medical conditions. Selective stimulation to increase lower esophageal sphincter (LES) pressure may be useful in the control of gastroesophageal reflux disease. We evaluated on-demand stimulation of the LES with an endoscopically implanted microstimulator.We performed acute experiments in three 30-kg dogs. After LES manometry, a 3.3 mm x 28 mm microstimulator (the Bion) was implanted into the LES. Manometry was repeated with and without IMS stimulation to record the changes in LES pressure. Stimulation amplitude was varied from 3 mA to 10 mA, with a fixed frequency of 20 Hz and a pulse width of 200 microsec.The mean LES pressures prior to IMS implantation in the three dogs were 13.0 mm Hg, 5.0 mm Hg, and 14.9 mm Hg. The mean pressures were not significantly changed by IMS placement. There were no documented changes in LES pressure when the amplitude of stimulation was less than 8 mA. After stimulation of the IMS at a setting of 10 mA in dogs 1 and 2 and at 8mA in dog 3, however, the resultant LES pressures were 62.1 mm Hg, 35.1 mm Hg, and 26.8 mm Hg respectively, more than three times higher than post-implantation baseline levels (P < 0.02).The LES pressure can be increased using an on-demand microstimulator. The implantation procedure is minimally invasive, represents a novel therapeutic approach to gastroesophageal reflux disease, and may have therapeutic potential for other gastrointestinal motility disorders.

    View details for DOI 10.1055/s-2006-945102

    View details for Web of Science ID 000244178100014

    View details for PubMedID 17252464

  • Is blood the ideal submucosal cushioning agent? A comparative study in a porcine model ENDOSCOPY Giday, S. A., Magno, P., Buscaglia, J. M., Canto, M. I., Ko, C., Shin, E. J., Xia, L., Wroblewski, L. M., Clarke, J. O., Kalloo, A. N., Jagannath, S. B., Kantsevoy, S. V. 2006; 38 (12): 1230-1234


    Creation of a submucosal cushion before endoscopic mucosal resection (EMR) significantly reduces perforation risk. We evaluated six solutions as cushioning agents in live pigs.5 ml of normal saline, normal saline plus epinephrine, albumin 12.5 %, albumin 25 %, hydroxypropyl methylcellulose, and the pig's own whole blood were endoscopically injected into the porcine esophageal submucosa. Blood was obtained from a peripheral vein immediately before injection. Injections were made every 4 cm from the gastroesophageal junction. The time from completion of the injection to disappearance of the cushion was recorded. Endoscopy was repeated at 48 hours post injection. Two EMRs were performed after blood injection. Statistical analysis employed one-way analysis of variance followed by pairwise T test comparisons using the Bonferroni correction.Five animal experiments were completed. The mean time to dissipation of the submucosal cushion was shortest for saline plus epinephrine sites (2.87 minutes, SD 2.21) followed by the saline (4.8 minutes, SD 1.56), albumin 12.5 % (5.68 minutes, SD 3.48), albumin 25 % (7.83 minutes, SD 2.02), hydroxypropyl methylcellulose (9.77 minutes, SD 1.55), and blood sites (38.6 minutes, SD 6.07). Injection of blood resulted in significantly longer mucosal elevation than any other solution ( P < 0.0007). Blood from the cushion did not hamper visualization and facilitated EMR.Blood produces the most durable cushion compared with standard agents, also having the advantages of being readily available and without cost. Albumin 25 % provides as durable a cushion as hydroxypropyl methylcellulose.

    View details for DOI 10.1055/s-2006-944971

    View details for Web of Science ID 000243101300006

    View details for PubMedID 17163324

  • D-1- and D-2-like dopamine receptors are co-localized on the presynaptic varicosities of striatal and nucleus accumbens neurons in vitro NEUROSCIENCE Wong, A. C., Shetreat, M. E., Clarke, J. O., Rayport, S. 1999; 89 (1): 221-233


    The neuromodulatory actions of dopamine in the striatum and nucleus accumbens are likely to depend on the distribution of dopamine receptors on individual postsynaptic cells. To address this, we have visualized D1- and D2-like receptors on living medium-spiny GABAergic neurons in cultures from the striatum and nucleus accumbens using receptor antagonist fluoroprobes. We labeled D1-like receptors with rhodamine-SCH23390, D2-like receptors with rhodamine-N-(p-aminophenethyl)spiperone and synaptic sites with K+-stimulated uptake of the activity-dependent endocytic tracer FM-143. The fluoroprobes were applied in sequence to assess co-localization. We found that D1- or D2-like receptors were present on about two-thirds of the cells, and co-localized on 22+/-3% (mean +/- S.E.M.) of striatal and 38+/-6% of nucleus accumbens cells. On either D1 or D2 labeled cells, postsynaptic labeling continuously outlined the cell body membrane and extended to proximal dendrites, but not axons. About two-thirds of synaptic varicosities showed D1 or D2 labeling. D1- and D2-like receptors were co-localized on 21+/-4% of striatal and 27+/-3% of nucleus accumbens varicosities. Presynaptic labeling was typically more intense than postsynaptic labeling. The distribution of presynaptic dopamine receptors contrasted with that of postsynaptic GABA(A) receptors, which were clustered in longer patches on neighboring postsynaptic membranes. The extensive presence of D1- and D2-like receptors on presynaptic varicosities of medium-spiny neurons suggests that the receptors are likely to play an important and interacting role in the presynaptic modulation of inhibitory synaptic transmission in the striatum and nucleus accumbens. The significant overlap in labeling suggests that D1-D2 interactions, which occur at the level of individual postsynaptic cells, the circuit level and the systems level, may also be mediated at the presynaptic level. Finally, the ability to visualize dopamine, as well as GABA(A), receptors on the individual synapses of living neurons now makes possible physiological studies of individual mesolimbic system synapses with known receptor expression.

    View details for Web of Science ID 000078087000020

    View details for PubMedID 10051231