Aligning tumor mutational burden (TMB) quantification across diagnostic platforms: phase II of the Friends of Cancer Research TMB Harmonization Project.

BACKGROUND: Tumor mutational burden (TMB) measurements aid in identifying patients who are likely to benefit from immunotherapy; however, there is empirical variability across panel assays and factors contributing to this variability have not been comprehensively investigated. Identifying sources of variability can help facilitate comparability across different panel assays, which may aid in broader adoption of panel assays and development of clinical applications. MATERIALS AND METHODS: Twenty-nine tumor samples and 10 human-derived cell lines were processed and distributed to 16 laboratories; each used their own bioinformatics pipelines to calculate TMB and compare to whole exome results. Additionally, theoretical positive percent agreement (PPA) and negative percent agreement (NPA) of TMB were estimated. The impact of filtering pathogenic and germline variants on TMB estimates was assessed. Calibration curves specific to each panel assay were developed to facilitate translation of panel TMB values to whole exome sequencing (WES) TMB values. RESULTS: Panel sizes >667 Kb are necessary to maintain adequate PPA and NPA for calling TMB high versus TMB low across the range of cut-offs used in practice. Failure to filter out pathogenic variants when estimating panel TMB resulted in overestimating TMB relative to WES for all assays. Filtering out potential germline variants at >0% population minor allele frequency resulted in the strongest correlation to WES TMB. Application of a calibration approach derived from The Cancer Genome Atlas data, tailored to each panel assay, reduced the spread of panel TMB values around the WES TMB as reflected in lower root mean squared error (RMSE) for 26/29 (90%) of the clinical samples. CONCLUSIONS: Estimation of TMB varies across different panels, with panel size, gene content, and bioinformatics pipelines contributing to empirical variability. Statistical calibration can achieve more consistent results across panels and allows for comparison of TMB values across various panel assays. To promote reproducibility and comparability across assays, a software tool was developed and made publicly available.

Perceptive eating as part of the journey in inflammatory bowel disease: Lessons learned from lived experience.

BACKGROUND: Inflammatory bowel diseases (IBD) include ulcerative colitis (UC) and Crohn's disease (CD), incurable remitting-relapsing conditions that impact more than 3 million people in the United States alone. A diagnosis of IBD can be life-altering; patients must make significant adjustments to manage their symptoms, and this may include dietary changes. While diet may impact IBD symptoms and disease progression, there is currently no one diet recommendation for IBD patients to follow. Few studies explored patient beliefs and practices around their dietary intake. OBJECTIVE: Our objective was to identify patient beliefs, attitudes, and behaviors around diet in management of symptoms and flares in patients with IBD. METHODS: We conducted semi-structured interviews with patients N = 16 patients with UC or Crohn's colitis, recruited from an IBD center in a large metropolitan medical center. All patients were referred by their behavioral health provider. Interviews were transcribed verbatim; two analysts coded the transcripts using NVivo software. This analysis examines the themes derived from the questions about diet. RESULTS: The sample of participants in this study (N = 16) was adult patients of the IBD clinic with either UC or Crohn's disease in the colon. Three main themes emerged from our analysis: evolving attempts at controlling symptoms through diet (subthemes: initial attempts to modify diet to control symptoms, and food avoidance was commonly reported but safe foods were not), beliefs about how food affects IBD (subthemes: liquid nutrition rests the bowels, diet for general health is all that is needed for IBD management, and diet is part of IBD management), and perceptive eating. DISCUSSION: Our findings confirmed those from previous studies that patients with IBD do notice that eating certain foods induces symptoms, and controlling dietary intake is one way that they choose to manage symptoms of IBD. Some patients had beliefs about how food affects their IBD, whether by reducing inflammation, or giving the gut rest. We also noted that patients used perceptive eating in their approach to diet by using a combination of experience and knowledge.

Validation of the oesophageal hypervigilance and anxiety scale for chronic oesophageal disease.

BACKGROUND: Oesophageal hypervigilance and anxiety can drive symptom experience in chronic oesophageal conditions, including gastro-oesophageal reflux disease, achalasia and functional oesophageal disorders. To date, no validated self-report measure exists to evaluate oesophageal hypervigilance and anxiety. AIMS: This study aims to develop a brief and reliable questionnaire assessing these constructs, the oesophageal hypervigilance and anxiety scale (EHAS). METHODS: Questions for the EHAS were drawn from 4 existing validated measures that assessed hypervigilance and anxiety adapted for the oesophagus. Patients who previously underwent high-resolution manometry testing at a university-based oesophageal motility clinic were retrospectively identified. Patients were included in the analysis if they completed the EHAS as well as questionnaires assessing symptom severity and health-related quality of life at the time of the high-resolution manometry. RESULTS: Nine hundred and eighty-two patients aged 18-85 completed the study. The EHAS demonstrates excellent internal consistency (α = 0.93) and split-half reliability (Guttman = 0.87). Inter-item correlations indicated multicollinearity was not achieved; thus, no items were removed from the original 15-item scale. Principal components factor analysis revealed two subscales measuring symptom-specific anxiety and symptom-specific hypervigilance. Construct validity for total and subscale scores was supported by positive correlations with symptom severity and negative correlations with health-related quality of life. CONCLUSIONS: The EHAS is a 15-item scale assessing oesophageal hypervigilance and symptom-specfic anxiety. The EHAS could be useful in evaluating the role of these constructs in several oesophageal conditions in which hypersensitivity, hypervigilance and anxiety may contribute to symptoms and impact treatment outcomes.

Systematic review: methodological flaws in racial/ethnic reporting for gastroesophageal reflux disease.

Health care disparities affecting the care of multiple disease groups are of growing concern internationally. Research guidelines, governmental institutions, and scientific journals have attempted to minimize disparities through policies regarding the collection and reporting of racial/ethnic data. One area where shortcomings remain is in gastroesophageal reflux disease (GERD). This systematic review, which adheres to the PRISMA statement, focuses on characterizing existing methodological weaknesses in research focusing on studies regarding the assessment, prevalence, treatment, and outcomes of GERD patients. Search terms included GERD and typical symptoms of GERD in ethnic groups or minorities. We reviewed 62 articles. The majority of studies did not report the race/ethnicity of all participants, and among those who did, very few followed accepted guidelines. While there were diverse participants, there was also diversity in the manner in which groups were labeled, making comparisons difficult. There appeared to be a disparity with respect to countries reporting race/ethnicity, with certain countries more likely to report this variable. Samples overwhelmingly consisted of the study country's majority population. The majority of studies justified the use of race/ethnicity as a study variable and investigated conceptually related factors such as socioeconomic status and environment. Yet, many studies wrote as if race/ethnicity reflected biological differences. Despite recommendations, it appears that GERD researchers around the world struggle with the appropriate and standard way to include, collect, report, and discuss race/ethnicity. Recommendations on ways to address these issues are included with the goal of preventing and identifying health care disparities.

Stigma perceptions in patients with eosinophilic gastrointestinal disorders.

This study aims to evaluate the presence of perceived stigma in people diagnosed (self-reported) with an eosinophilic gastrointestinal disorder and examine the relationship to the patient's health-related quality of life and additional psychosocial patient-reported outcomes. One hundred forty-nine patients diagnosed for a minimum of 6 months participated in the study. Eligible participants completed questionnaires to assess perceived stigma, psychological functioning, and health-related quality of life. Perceived stigma was moderately associated with a decrease in total health-related quality of life and perceived treatment efficacy. Additionally, greater perceived stigma was positively correlated with an increase in anxiety, depression, and healthcare utilization. The study demonstrates the influence of perceived stigma on several aspects of health-related quality of life in patients with these illnesses. As such, it is important for health professionals to be aware of stigma in patients diagnosed with an eosinophilic gastrointestinal disorder.

The impact of irritable bowel syndrome on daily functioning: Characterizing and understanding daily consequences of IBS.

BACKGROUND: Despite the well-documented economic and psychosocial burden of irritable bowel syndrome (IBS), few studies have focused on the impact of IBS on daily activities. This study aims to quantitate impairment in daily activities among IBS patients and to evaluate the relationship between impairment, IBS, quality of life, and psychiatric symptoms. METHODS: A total of 179 participants meeting ROME-III criteria for IBS completed an online research survey evaluating the following variables: (i) the impact of IBS on daily activities, (ii) comorbid psychiatric diagnoses, (iii) symptom severity, (iv) quality of life, and (v) symptom-specific cognitive affective factors related to IBS. KEY RESULTS: This sample reported a high degree of impairment due to IBS, with 76% of the sample reporting some degree of IBS-related impairment in at least five different domains of daily life. Rates of impairment were significantly higher for participants who met criteria for anxiety, depression, and/or panic disorder. CONCLUSIONS & INFERENCES: This study contributes to existing literature by demonstrating a high level of daily impairment among patients with IBS, particularly those who meet criteria for anxiety, depression, and panic disorder. These findings support the importance of integrated psychosocial and medical care for IBS patients, and highlight the utility of evaluation and intervention for behavioral avoidance/impairment especially among those who exhibit signs or symptoms of psychiatric diagnoses.

Stigmatization toward irritable bowel syndrome and inflammatory bowel disease in an online cohort.

BACKGROUND: Stigma is associated with many negative health outcomes. Research has examined perceived and internalized stigma in individuals with irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), but less has been done to evaluate levels of enacted stigma associated with these conditions. The aim of this study was to evaluate the presence of enacted stigma toward IBS and IBD in the general population compared to an adult-onset asthma (AOA) control group. METHODS: Participants were recruited via social media and a research-dedicated website and completed all measures online. Participants were randomized to one of six clinical vignettes: (i) IBD male, (ii) IBD female, (iii) IBS male, (iv) IBS female, (v) AOA male, or (vi) AOA female. Participants read the assigned vignette and then completed measures of emotional empathy, level of familiarity, and enacted stigma. KEY RESULTS: Participants reported higher levels of enacted stigma toward IBS compared to both IBD and AOA. No differences in stigma were found between IBD and AOA. Higher levels of familiarity were most strongly correlated with reduced IBD-related stigma, with weaker but still significant correlations between level of familiarity and IBS and AOA. Higher levels of emotional empathy were associated with reduced stigma for IBD, IBS, and AOA. CONCLUSIONS & INFERENCES: Individuals with IBS experience greater levels of enacted stigma compared to IBD and AOA. This finding is consistent with previous research that has shown greater levels of perceived and internalized stigma in IBS compared to IBD.

Development and validation of the brief esophageal dysphagia questionnaire.

BACKGROUND: Esophageal dysphagia is common in gastroenterology practice and has multiple etiologies. A complication for some patients with dysphagia is food impaction. A valid and reliable questionnaire to rapidly evaluate esophageal dysphagia and impaction symptoms can aid the gastroenterologist in gathering information to inform treatment approach and further evaluation, including endoscopy. METHODS: 1638 patients participated over two study phases. 744 participants completed the Brief Esophageal Dysphagia Questionnaire (BEDQ) for phase 1; 869 completed the BEDQ, Visceral Sensitivity Index, Gastroesophageal Reflux Disease Questionnaire, and Hospital Anxiety and Depression Scale for phase 2. Demographic and clinical data were obtained via the electronic medical record. The BEDQ was evaluated for internal consistency, split-half reliability, ceiling and floor effects, and construct validity. KEY RESULTS: The BEDQ demonstrated excellent internal consistency, reliability, and construct validity. The symptom frequency and severity scales scored above the standard acceptable cutoffs for reliability while the impaction subscale yielded poor internal consistency and split-half reliability; thus the impaction items were deemed qualifiers only and removed from the total score. No significant ceiling or floor effects were found with the exception of 1 item, and inter-item correlations fell within accepted ranges. Construct validity was supported by moderate yet significant correlations with other measures. The predictive ability of the BEDQ was small but significant. CONCLUSIONS & INFERENCES: The BEDQ represents a rapid, reliable, and valid assessment tool for esophageal dysphagia with food impaction for clinical practice that differentiates between patients with major motor dysfunction and mechanical obstruction.

Feasibility and acceptability of esophageal-directed hypnotherapy for functional heartburn.

Functional heartburn (FH) is a benign but burdensome condition characterized by painful, burning epigastric sensations in the absence of acid reflux or symptom-reflux correlation. Esophageal hypersensitivity and its psychological counterpart, esophageal hypervigilance (EHv) drive symptom experience. Hypnotherapy (HYP) is an established and preferred intervention for refractory symptoms in functional gastrointestinal disorders (FGIDs) and could be applied to FH. The objective of this study was to determine the feasibility, acceptability, and clinical utility of 7 weekly sessions of esophageal-directed HYP (EHYP) on heartburn symptoms, quality of life, and EHv. Similar to other work in FGIDs and regardless of hypnotizability, there were consistent and significant changes in heartburn symptoms, visceral anxiety, and quality of life and a trend for improvement in catastrophizing. We would recommend EHYP in FH patients who are either non-responsive to medications or who would prefer a lifestyle intervention.

Majority of symptoms in esophageal reflux PPI non-responders are not related to reflux.

BACKGROUND: Genesis of persistent gastro-esophageal reflux symptoms despite proton pump inhibitor (PPI) therapy is not fully understood. We aimed at determining reflux patterns on 24-h pH-impedance monitoring performed on PPI and correlating impedance patterns and symptom occurrence in PPI non-responders. METHODS: Seventy-eight PPI non-responder patients underwent 24-h pH-impedance monitoring on PPI. Reflux impedance characterization included gastric and supragastric belches and proximal extent of reflux. Symptoms were considered associated with reflux if occurring within 5 min after a reflux event. Patients were classified into three groups: persistent acid reflux (acid esophageal exposure [AET] >5% of time), reflux sensitivity (AET <5%, symptom index [SI] ≥50%), and functional symptoms (AET <5%, SI <50%). Dominant impedance pattern was determined for each patient. KEY RESULTS: Seven patients (9%) had persistent acid reflux, 28 (36%) reflux sensitivity, and 43 (55%) functional symptoms. A total of 4296 reflux events were identified (median per patient 45 [range 4-221]). Although liquid reflux was the most common pattern in all groups, patients with reflux sensitivity and functional symptoms had much more variability in their pattern profile with a large proportion being associated with gastric and supragastric belching. Only 417 reflux events (9.7%) were associated with symptoms. Reflux with a supragastric component and proximal extent were more likely to be associated with symptoms. CONCLUSIONS & INFERENCES: The impedance reflux profile in PPI non-responders was heterogeneous and the majority of reflux events were not associated with symptoms. Thus, the treatment of PPI non-responders should focus on mechanisms beyond reflux, such as visceral hypersensitivity and hypervigilance.

Patients with refractory reflux symptoms: What do they have and how should they be managed?

With the widespread use of proton pump inhibitors (PPIs), the frontier of treating reflux disease has shifted from refractory esophagitis to PPI-refractory symptoms. However, symptoms are inherently less specific than mucosal disease and, as noted by Herregods et al. in their contribution appearing in this issue of Neurogastroenterology and Motility, patients with refractory gastroesophageal reflux disease (GERD) symptoms often do not have GERD. This review discusses potential etiologies for PPI-refractory symptoms. Three major concepts are explored: subendoscopic esophagitis, weakly acidic reflux events, and alternative explanations for persistent symptoms. With respect to subendoscopic esophagitis and unsuppressed reflux, ample evidence exists that these are present in PPI-refractory patients. The problem is that these findings are also often present in substantial numbers of individuals with a satisfactory response to PPI therapy. Hence, the emphasis shifts to determinants of symptom perception. The major conclusion of the review is that psychogenic factors such as hyperalgesia, allodynia, hypervigilance, and heightened anxiety are the most plausible explanations as the dominant determinants of PPI-refractory symptoms.

Gender differences in irritable bowel syndrome: the interpersonal connection.

BACKGROUND: While irritable bowel syndrome (IBS) affects women more than men, the reasons are unclear. Research on the female preponderance of IBS has focused on gender differences in sex-linked biological processes; much less attention has been paid to the role of psychosocial factors. Interpersonal difficulties may be one source of stress that may significantly impact on women with IBS. Because of the importance that women attach to relationships, we suspected they would be more reactive to interpersonal stress. METHODS: A total of 283 (M age = 41 years, F = 80%), Rome III-diagnosed IBS patients completed a test battery that included the IBS Symptom Severity Scale, McGill Pain Questionnaire, Inventory of Interpersonal Problems (IIP), interpersonal support evaluation list (social support), Negative Interactions Scale, Brief Symptom Inventory (distress), Beck Depression Inventory, Anxiety Sensitivity Inventory, and IBS-Quality of Life as part of baseline assessment of an NIH trial. KEY RESULTS: Males scored higher on two IIP scales reflecting a hostile-dominant interpersonal pattern, and reported less social support. The quality of relationship problems (more interpersonal difficulties, lower support) correlated with IBS symptom severity as measured mainly by gastroenterologists. CONCLUSIONS & INFERENCES: Male, not female, IBS patients reported more interpersonal difficulties. Male patients-a population for whom little is known-are characterized by hostile-dominant interpersonal problems. This finding has clinical importance, given that relationship problems may influence MDs' estimation of IBS symptom severity and undermine the physician-patient relationship.

Role of a health psychologist in the management of functional esophageal complaints.

Upper gastrointestinal complaints are common among patients in a gastrointestinal clinic. Outside of typical gastroesophageal reflux disease symptoms that are treated with medication, the symptom presentations of esophageal patients, particularly those with functional conditions, are often difficult to treat and account for high health-care utilization. This manuscript describes the role of a health psychologist in the treatment of esophageal disorders using behavioral medicine interventions. Observations over the course of a 1-year period indicate that the sample presents with a relatively low level of psychological distress but reports negative effects of their symptoms on health-related quality of life. Five case examples of commonly treated disorders (globus, non-cardiac chest pain, functional dysphagia, rumination syndrome, supragastric belching) are described to highlight how behavioral treatment can improve patients' symptoms, decrease health-care utilization, and improve overall quality of life in a timely and relatively simple manner. Successful treatment outcomes are associated with a collaborative working alliance between patient, health psychologist, and gastroenterologist. Results indicate the benefit of referring appropriate esophageal patients to a health psychologist with specialization in gastroenterology.

The potential role of behavioral therapies in the management of centrally mediated abdominal pain.

BACKGROUND: Chronic abdominal pain carries a substantial health care burden but little is known about best practices for it management across ambulatory, hospital, and emergency room settings. This is especially true when abdominal pain presents in the absence of peripheral triggers like tissue injury (e.g. appendicitis) or altered bowel movements (e.g. IBS). Unfortunately, once central sensitization has occurred, pain can present without any stimulation or with minimal peripheral stimulation (feeling of clothing on the area) to the abdominal region. Several studies have proven the superior efficacy of behavioral interventions on many centrally mediated pain conditions including headaches and musculoskeletal problems. However, behavioral treatment of centrally mediated abdominal pain is less investigated due to the complexity of the patients involved and the poor understanding of the factors which either initiate or maintain persistent GI pain. PURPOSE: We examine the evidence for a range of psychological and behavioral interventions in the context of centrally mediated abdominal pain. In addition to a strong rationale for a behavioral approach tied to the fear avoidance model of pain, we describe the structure, therapeutic targets, current evidence and relevance for each class of behavioral interventions.

The accuracy of patient-reported measures for GI symptoms: a comparison of real time and retrospective reports.

BACKGROUND: Obtaining accurate information about gastrointestinal (GI) symptoms is critical to achieving the goals of clinical research and practice. The accuracy of patient data is especially important for functional GI disorders (e.g., IBS) whose symptoms lack a biomarker and index illness severity and treatment response. Retrospective patient-reported data are vulnerable to forgetting and various cognitive biases whose impact has not been systematically studied in patients with GI disorders. The aim of this study was to document the accuracy of patient-reported GI symptoms over a reporting period (1 week) most representative of the time frame used in research and clinical care. METHODS: Subjects were 273 Rome III-diagnosed IBS patients (mean age = 39 years, 89% F) who completed end of day GI symptom ratings for 7 days using an electronic diary. On Day 8, Subjects recalled the frequency and/or intensity of IBS symptoms over the past 7 days. Reports were then compared against a validation criterion based on aggregated end of day ratings. KEY RESULTS: At the group level, subjects recalled most accurately abdominal pain and urgency intensity at their worst, urgency days, and stool frequency. When data were analyzed at the individual level, a subgroup of subjects had difficulty recalling accurately symptoms that showed convergence between recall and real time reports at the group level. CONCLUSIONS & INFERENCES: Although many patients' recollection for specific GI symptoms (e.g., worst pain, stool frequency) is reasonably accurate, a non-trivial number of other symptoms (e.g., typical pain) are vulnerable to distortion from recall biases that can reduce sensitivity of detecting treatment effects in clinical and research settings.

Moving beyond perceptions: internalized stigma in the irritable bowel syndrome.

BACKGROUND: Internalized stigma (IS) is an important construct in the chronic illness literature with implications for several patient reported outcomes. To date, no study exists evaluating IS in patients with the irritable bowel syndrome (IBS). METHODS: Two hundred and forty three online and clinical participants completed the following questionnaires: the IS scale for mental illness (ISMI; modified for IBS), perceived stigma scale for IBS, NIH-PROMIS Anxiety and Depression Scales, IBS quality of life scale, and the Perceived Health Competence Scale. Demographical and clinical data were also collected. KEY RESULTS: The modified ISMI was reliable and valid in this population. Participants reported both perceived and IS. Alienation was most reported, followed by social withdrawal and discrimination experiences. IS predicted 25-40% of the variance in psychological functioning, quality of life, healthcare utilization, and health competence when controlling for stigma perception and disease variables. IBS patients perceived more stigma from personal relations than healthcare providers. Hispanic participants reported more perceived stigma, indicating there may be cultural differences in IBS-related stigma experience. Symptom severity, disruptiveness, and treatment choices are also implicated in stigma perception and internalization. CONCLUSIONS & INFERENCES: Patients with IBS report both perceived and IS with alienation most reported. However, IS significantly predicts several patient outcomes when controlling for PS. Cultural and illness traits may influence how stigma is perceived and internalized. Future research is warranted.

Gut-directed hypnotherapy significantly augments clinical remission in quiescent ulcerative colitis.

BACKGROUND: Psychotherapy is not routinely recommended for in ulcerative colitis (UC). Gut-directed hypnotherapy (HYP) has been linked to improved function in the gastrointestinal tract and may operate through immune-mediated pathways in chronic diseases. AIMS: To determine the feasibility and acceptability of HYP and estimate the impact of HYP on clinical remission status over a 1-year period in patients with an historical flare rate of 1.3 times per year. METHODS: A total of 54 patients were randomised at a single site to seven sessions of gut-directed HYP (n = 26) or attention control (CON; n = 29) and followed for 1 year. The primary outcome was the proportion of participants in each condition that had remained clinically asymptomatic (clinical remission) through 52 weeks post treatment. RESULTS: One-way analysis of variance comparing HYP and CON subjects on number of days to clinical relapse favoured the HYP condition [F = 4.8 (1, 48), P = 0.03] by 78 days. Chi-squared analysis comparing the groups on proportion maintaining remission at 1 year was also significant [χ²(1) = 3.9, P = 0.04], with 68% of HYP and 40% of CON patients maintaining remission for 1 year. There were no significant differences between groups over time in quality of life, medication adherence, perceived stress or psychological factors. CONCLUSION: This is the first prospective study that has demonstrated a significant effect of a psychological intervention on prolonging clinical remission in patients with quiescent ulcerative colitis (Clinical Trial # NCT00798642).

Diagnostic yield of a novel jumbo biopsy "unroofing" technique for tissue acquisition of gastric submucosal masses.

BACKGROUND AND STUDY AIMS: Adequate tissue acquisition for the diagnosis of gastric submucosal masses (GSMs) has been challen ging for gastroenterologists. The use of standard biopsy forceps generally recovers non-diagnostic overlying mucosa. Endoscopic ultrasound (EUS) with fine-needle aspiration (FNA) provides a significant improvement, but is often still inadequate for diagnosis. The aim of the current study was to assess the efficacy of a novel jumbo biopsy unroofing technique (JUT) for tissue acquisition in GSM. PATIENTS AND METHODS: This prospective study recruited patients who were referred for EUS for the evaluation of GSM between 2006 and 2009. All patients underwent EUS with FNA when feasible followed by JUT. The primary outcome was diagnostic yield of JUT. RESULTS: A total of 93 patients were enrolled, 72 of whom were included in the investigation; 16 patients were excluded with no evidence of a submucosal mass or extrinsic compression, and five patients were further excluded by pathology confirming mucosal lesions. Of the 72 jumbo biopsies 66 (92%) provided diagnostic tissue without significant complications and 42 (58%) had lesions amenable to FNA. Although 34 of the 42 lesions were deemed adequate at the time of on-site cytological evaluation, only 28 (67%) provided sufficient tissue for final diagnosis. More importantly, only 37/72 (52%) of all patients had lesions that required any further intervention. CONCLUSIONS: Utilization of JUT is safe and effective for diagnosis of GSM. The data suggest that the jumbo biopsy unroofing technique should be considered as an initial diagnostic strategy for GSMs found during upper endoscopy.