I am initially a Pittsburgh, PA native, but have been at Stanford University since 2012 for residency, fellowship, and now as faculty. It is exciting to be affiliated with one of the most dynamic and innovative medical institutions worldwide.

My clinical and research interests focus on functional, motility, and esophageal disorders of the gastrointestinal tract. Outside of this sub-sub specialization, a significant portion of my practice is also devoted to the care of a broad range of “general gastroenterology” concerns.

Functional, motility, esophageal, and general gastroenterology disorders are very common, and can cause significant disability. Some examples include irritable bowel syndrome, functional dyspepsia, gastroparesis, chronic nausea, chronic constipation, achalasia, and gastroesophageal reflux disease.

Despite the common nature of these disorders, many are not well understood, leading to frustration among both patients and clinicians alike. Furthermore, there is an incorrect stigma associated with some of these disorders that “it is all in your head.” On the opposite side of the spectrum, there is sometimes an incorrect assumption that we will be able to pinpoint an exact underlying cause in all cases, but this is not possible with current technology. We aim to bridge this gap using the latest diagnostic testing and treatment paradigms, as well as a healing hand. Additionally, our group is actively engaged in multiple research projects and studies to drive the future of the field.

Though I am early in my career, I am hoping that by the end the field will look nothing like it does today. I am hopeful, and I believe that we can revolutionize the field to better characterize gastrointestinal disorders, and come up with highly effective targeted treatments.

Academic Appointments

Professional Education

  • Board Certification, Gastroenterology and Hepatology, American Board of Internal Medicine (2019)

All Publications

  • 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

  • High Prevalence of Methane Predominant Small Bowel Bacterial Overgrowth and Constipation in Patients With Hypermobile Ehlers-Danlos Syndrome Zhou, W., Zikos, T., Neshatian, L., Nguyen, L. LIPPINCOTT WILLIAMS & WILKINS. 2020: S238
  • 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

  • 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

  • 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

  • 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

  • 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

  • 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
  • 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

  • Arteriovenous malformations respond poorly to argon plasma coagulation in patients with continuous flow left ventricular assist devices. European journal of gastroenterology & hepatology Zikos, T. A., Namdaran, P. n., Banerjee, D. n., Friedland, S. n., Pan, J. Y. 2019; 31 (7): 792–98


    Gastrointestinal bleeding in patients with continuous flow left ventricular assist devices (LVADs) causes significant morbidity. Arteriovenous malformations (AVMs) cause 30-60% of bleeds, yet the efficacy of endoscopic interventions and risk factors for rebleeding have not been studied.The charts of all LVAD patients undergoing endoscopy for gastrointestinal bleeding at Stanford between January 2010 and December 2017 were reviewed. Cox proportional hazard modeling was used to evaluate risk factors for rebleeding, including the type of endoscopic treatment, patient characteristics, and endoscopic findings.Of 54 total LVAD patients presenting with gastrointestinal bleeding, 23 (42.6%) had AVMs documented on endoscopy. Treatment with argon plasma coagulation (APC) alone was associated with a higher risk of rebleeding compared to no treatment [hazard ratio (HR)=4.77, P=0.012], and compared with clip±APC (HR=7.47, P=0.012). The 90-day bleed-free rate was 10.9% with APC, 100% with clipping±APC, and 83.3% with no endoscopic treatment. Additional risk factors for rebleeding included the presence of gastric AVMs (HR=3.64, P=0.024), and presence of hematochezia (HR=5.15, P=0.05). In a multiple Cox regression model, only the presence of gastric AVMs (HR=5.50, P=0.029) and APC use (HR=14.3, P=0.008) remained significant predictors of rebleeding.The use of APC alone for the treatment of AVMs in LVAD patients had a high failure rate. The presence of gastric AVMs was a significant risk factor for rebleeding in LVAD patients. Management decisions should take these factors into account.

    View details for DOI 10.1097/MEG.0000000000001427

    View details for PubMedID 31150365

  • 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

  • Thalidomide Use Reduces Risk of Refractory Gastrointestinal Bleeding in Patients with Continuous Flow Left Ventricular Assist Devices. ASAIO journal (American Society for Artificial Internal Organs : 1992) Namdaran, P. n., Zikos, T. A., Pan, J. Y., Banerjee, D. n. 2019


    Gastrointestinal (GI) bleeding is a common complication seen in patients with implanted continuous flow left ventricular assist devices (CF-LVAD), often attributed to arteriovenous malformations (AVMs). Whether thalidomide reduces recurrent GI bleeding risk in CF-LVAD patients has been incompletely evaluated. We conducted a retrospective review of all CF-LVAD patients at our institution with GI bleeding from AVMs who had a trial both off and on thalidomide. The primary endpoint was time to rebleed, while secondary endpoints included overall GI bleeding events, packed red blood cell (PRBC) transfusion requirements, and adverse events related to thalidomide. We report on 24 patients with recurrent AVM-associated GI bleeding who met criteria for and received thalidomide therapy, of which 17 had sufficient follow-up to be ultimately included for final analysis. We found the risk of rebleeding was significantly reduced in those on thalidomide therapy versus off (hazard ratio = 0.23, p = 0.022). The median number of GI bleeds per year was reduced from 4.6 to 0.4 (p = 0.0008) and the PRBC requirement was lower (36.1 vs. 0.9 units per year, p = 0.004) in those on thalidomide therapy. The adverse event rate with thalidomide was 59%, with symptoms resolution in most following dose reduction without increased bleeding. Thalidomide reduced the risk of AVM-associated GI rebleeding, number of bleeding events, and PRBC requirements in CF-LVAD patients. When initiating therapy, potential side effects and overall clinical context should be considered.

    View details for DOI 10.1097/MAT.0000000000001054

    View details for PubMedID 31425265

  • 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

  • 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 Ozeki, K., Zikos, T. A., Clarke, J., Sonu, I. NATURE PUBLISHING GROUP. 2018: S177
  • Blood and Guts: Diarrhea from Colonic Involvement in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. Digestive diseases and sciences Zikos, T. A., Triadafilopoulos, G., Berube, C., Regalia, K. A. 2018

    View details for PubMedID 30155841

  • 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

  • Outcomes of Endoscopic Procedures on Patients With Left-Ventricular Assist Devices: Experiences From a Single-Center Retrospective Case Series Pan, J. Y., Zikos, T., Chang, M. S., Limketkai, B., Banerjee, D., Fernandez-Becker, N. MOSBY-ELSEVIER. 2017: AB207–AB208
  • Efficacy of Video Capsule Endoscopy in the Management of Suspected Small Bowel Bleeding in Patients With Continuous Flow Left Ventricular Assist Devices. Gastroenterology research Zikos, T. A., Pan, J. n., Limketkai, B. n., Banerjee, D. n., Fernandez-Becker, N. n. 2017; 10 (5): 280–87


    Continuous flow left ventricular assist device (CF-LVAD) patients have a high prevalence of gastrointestinal bleeding from the small bowel. Video capsule endoscopy (VCE) is often used for diagnosis in these patients, but efficacy has yet to be determined. In this study, we evaluated the efficacy of VCE in the management of CF-LVAD patients with suspected small bowel bleeding by comparing to a non-VCE CF-LVAD control group.We retrospectively reviewed the charts of all patients with CF-LVADs implanted at Stanford Hospital from January 2010 to October 2015. Patients were included in the study if there was a clinical suspicion of small bowel bleeding and either a negative upper endoscopy or colonoscopy.A total of 26 patients met inclusion criteria for a total of 15 encounters where VCE was done, and 25 where VCE was not done. There were no statistical differences when comparing these groups in terms of medical therapy use (thalidomide or octreotide), enteroscopy use (double-balloon or push), intervention on lesions, or any 30-day outcomes. There was no advantage to VCE with regard to the composite endpoint time to re-bleed or death related to re-bleeding (median 114 vs. 161 days, P = 0.15) after removing patients who did not get a VCE due to death or critical illness.We did not find VCE changed management or outcomes in CF-LVAD patients with suspected small bowel bleeding at our institution when compared to a non-VCE control group. Our experience is small and single center, and larger, multi-center studies could further elucidate the utility of VCE in this patient population.

    View details for PubMedID 29118868

    View details for PubMedCentralID PMC5667693

  • Eculizumab Induces Sustained Remission in a Patient With Refractory Primary Catastrophic Antiphospholipid Syndrome. Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases Zikos, T. A., Sokolove, J., Ahuja, N., Berube, C. 2015; 21 (6): 311-313


    Catastrophic antiphospholipid syndrome (CAPS) is fatal in approximately 44% of patients in whom the diagnosis is made, thus demonstrating the inadequacy of current medical therapy. In this report, we discuss a 47-year-old man with a known history of primary antiphospholipid syndrome, who presented with CAPS after undergoing cholecystectomy and a treatment-refractory early relapse after development of colitis. Given the potential therapeutic efficacy of complement inhibition in antiphospholipid syndrome, the patient was administered eculizumab, a terminal complement inhibitor. Progressive clinical improvement and laboratory improvement were observed upon initiation of eculizumab. He has remained in remission for over 16 months of follow-up while on eculizumab. In conclusion, this case represents successful use of eculizumab for the treatment of primary CAPS.

    View details for DOI 10.1097/RHU.0000000000000290

    View details for PubMedID 26267719

  • Cyst Fluid Glucose is Rapidly Feasible and Accurate in Diagnosing Mucinous Pancreatic Cysts. American journal of gastroenterology Zikos, T., Pham, K., Bowen, R., Chen, A. M., Banerjee, S., Friedland, S., Dua, M. M., Norton, J. A., Poultsides, G. A., Visser, B. C., Park, W. G. 2015; 110 (6): 909-914


    Better diagnostic tools are needed to differentiate pancreatic cyst subtypes. A previous metabolomic study showed cyst fluid glucose as a potential marker to differentiate mucinous from non-mucinous pancreatic cysts. This study seeks to validate these earlier findings using a standard laboratory glucose assay, a glucometer, and a glucose reagent strip.Using an IRB-approved prospectively collected bio-repository, 65 pancreatic cyst fluid samples (42 mucinous and 23 non-mucinous) with histological correlation were analyzed.Median laboratory glucose, glucometer glucose, and percent reagent strip positive were lower in mucinous vs. non-mucinous cysts (P<0.0001 for all comparisons). Laboratory glucose<50 mg/dl had a sensitivity of 95% and a specificity of 57% (LR+ 2.19, LR- 0.08). Glucometer glucose<50 mg/dl had a sensitivity of 88% and a specificity of 78% (LR+ 4.05, LR- 0.15). Reagent strip glucose had a sensitivity of 81% and a specificity of 74% (LR+ 3.10, LR- 0.26). CEA had a sensitivity of 77% and a specificity of 83% (LR+ 4.67, LR- 0.27). The combination of having either a glucometer glucose<50 mg/dl or a CEA level>192 had a sensitivity of 100% but a low specificity of 33% (LR+ 1.50, LR- 0.00).Glucose, whether measured by a laboratory assay, a glucometer, or a reagent strip, is significantly lower in mucinous cysts compared with non-mucinous pancreatic cysts.

    View details for DOI 10.1038/ajg.2015.148

    View details for PubMedID 25986360

  • Evaluation and Management of Pancreatic Cystic Lesions Journal of Clinical Outcomes Management Zikos, T., Park, W. G. 2015; 22 (12): 566-576
  • Rapid Point-of-Care Measurement of Cyst Fluid Glucose Is Feasible and Accurate in Predicting Mucinous Pancreatic Cysts Zikos, T., Pham, K., Chen, A., Banerjee, S., Friedland, S., Dua, M., Norton, J., Poultsides, G., Visser, B., Park, W. NATURE PUBLISHING GROUP. 2014: S86
  • Lung T-cell subset composition at the time of surgical resection is a prognostic indicator in non-small cell lung cancer CANCER IMMUNOLOGY IMMUNOTHERAPY Zikos, T. A., Donnenberg, A. D., Landreneau, R. J., Luketich, J. D., Donnenberg, V. S. 2011; 60 (6): 819-827


    NSCLC arises in the complex environment of chronic inflammation. Depending on lung immune polarization, infiltrating immune cells may either promote or suppress tumor growth. Despite the importance of the immune microenvironment, current staging techniques for NSCLC do not take into consideration the immune milieu in which the neoplasms arise. T-cell subset content was compared between paired tumor-bearing and contralateral lungs, patient and control peripheral blood. The relationship between T-cell subset distribution and survival were evaluated. CD4 and CD8+ T cells were subsetted by CD45RA/CD27 and analyzed for expression of activation, adhesion, and homing markers. Strikingly, T-cell content was indistinguishable between lungs. Compared with peripheral blood, naïve CD4 and CD8 T cells were rare in BAL. CD4+ BAL T cells showed increased CD95 (higher apoptotic potential) and CD103 expression (epithelial adhesion), but decreased CD38 (activation) and CCR7 expression (lymph node homing). CD8+ BAL T cells showed increased CD103 expression and decreased CD28 expression (co-stimulation). Differences in CD28, CD95, and CCR7 expression were more pronounced within memory cells, while differences in CD4+ CD103 expression were more prominent in effector/memory cells. Of these populations, the absence of lung CD4 T cells with an effector-like phenotype (CD45RA+/CD27-) emerged as a predictor of favorable outcome. Patients with a low proportion (≤0.44%) had 90% 5-year survival (n = 10, median survival 2,343 days), compared with 0% (n = 9, median survival 516 days) of patients with a higher proportion. Further study is required to confirm this association prospectively and define the function of this subpopulation.

    View details for DOI 10.1007/s00262-011-0996-4

    View details for Web of Science ID 000290802200006

    View details for PubMedID 21373990

  • The Impact of Scoliosis Among Patients with Giant Paraesophageal Hernia JOURNAL OF GASTROINTESTINAL SURGERY Schuchert, M. J., Adusumilli, P. S., Cook, C. C., Colovos, C., Kilic, A., Nason, K. S., Landreneau, J. P., Zikos, T., Jack, R., Luketich, J. D., Landreneau, R. J. 2011; 15 (1): 23-28


    Kyphoscoliosis is seen in approximately 1.4-15% of the octogenarian population of the US. We hypothesized that patients with kyphoscoliosis are affected with a reduced intra-abdominal volume and progressive laxity of the diaphragmatic hiatal sling musculature leading to an increased risk of hiatal hernia formation and progression over time.We retrospectively reviewed the clinical history and roentgenographic data of 320 paraesophageal hernia patients from 2003 to 2007. The prevalence of kyphoscoliosis among this patient cohort and the outcomes of surgical management were compared to paraesophageal hernia patients without kyphoscoliosis.Ninety-three of the 320 patients (29.1%) were found to have significant K/S (mean age 74; 83% female). Laparoscopic repair of paraesophageal hernia with fundoplication was performed in 91% of these patients. There was one death (1.1%; aspiration pneumonia) and 17.2% major postoperative morbidity. Mean length of hospital stay was 8 days (median = 4; range 2-71). Prolonged stays were related mainly to marginal pulmonary status. Kyphoscoliosis was associated with increased peri-operative pulmonary morbidity (16.1%) compared to patients without kyphoscoliosis (7.0%, p = 0.02).Kyphoscoliosis may contribute to the development and progression of paraesophageal hernias. Surgeons approaching paraesophageal hernia repair should be aware of the increased pulmonary morbidity and the postoperative care required in managing these patients.

    View details for DOI 10.1007/s11605-010-1307-7

    View details for Web of Science ID 000286396600003

    View details for PubMedID 20824386