Horsley‐Silva, Jennifer L.

INTRODUCTION: Epidermal metaplasia is a histological correlate to a white patch on the surface of a mucous membrane that cannot be rubbed off, known as leukoplakia. It is a common finding in oral mucosa, however rare in esophageal mucosa. Etiology of this condition in the esophagus is unclear, thought to be associated with esophageal tobacco and alcohol exposure or possibly an unusual response to chronic acid reflux. In contrast to oral leukoplakia there is a female predominance. Although generally asymptomatic, symptom presentation can include dysphagia. Endoscopic features include slightly elevated whitish surface, which can be translucent or cobblestone-like in appearance. The natural history is unknown though there is concern for an increased risk of squamous cell cancer. Due to paucity of published studies about this condition, we aim to report a case treated with endoscopic submucosal dissection (ESD). CASE DESCRIPTION/METHODS: A 64-year-old Caucasian man with a history of tobacco use and stable weight, presented to Gastroenterology clinic due to an 11-month history of solid food esophageal dysphagia. Physical examination was unremarkable. Upper endoscopy demonstrated white plaques at the gastroesophageal junction (Figure 1A and B). Biopsies obtained from this abnormality showed esophageal epidermoid metaplasia consistent with leukoplakia and mild patchy active chronic inflammation. GMS stain for fungal organisms was negative. An ESD procedure was planned, due to lesion size to ensure complete removal. Chromoscopy with methylene blue was used to mark the borders of the lesion and ESD was accomplished without adverse events (Figure 1C). Histologic examination confirmed hyperplastic squamous esophageal mucosa with marked hyperkeratosis without dysplasia and negative margins. During 2 year follow up, patient reported complete resolution of his dysphagia. DISCUSSION: The management strategy for esophageal leukoplakia is not well defined though reports suggest that endoscopic resection and surveillance are warranted. Here we represent a case where symptoms resolved and the lesion was completely removed by ESD.

INTRODUCTION: Distal esophageal spasm (DES) is a motility disorder characterized by premature contraction of the esophageal body during single swallows. It is thought to be due to impairment of esophageal inhibitory pathways, but studies to support this are limited. Assessment of response to multiple rapid swallows (MRS) during high-resolution esophageal manometry (HRM) enables detection of impaired inhibition during MRS. Healthy subjects respond to MRS by deglutitive inhibition during the MRS sequence. We hypothesize that deglutitive inhibition is impaired in DES patients. Aim: compare response to MRS in DES patients and healthy controls. METHODS: Response to MRS was evaluated in 19 DES patients and 24 asymptomatic healthy controls. Demographic and symptom data were extracted from a prospectively maintained motility database. Patients with history of prior gastroesophageal surgery, endoscopic myotomy (POEM), pneumatic dilation, esophageal botulinum toxin injection within 6 months of HRM, and esophageal stricture were excluded. HRM was performed with a solid state catheter with 36 circumferential pressure sensors 1-cm apart; ten 5-ml liquid swallows were given followed by MRS sequence, analyzed with Manoview software (Medtronic). Esophagogastric junction integrated relaxation pressure (IRP), distal contractile integral (DCI), and distal latency (DL) were calculated, and Chicago Classification v3.0 was applied to diagnose DES (defined by ≥ 2 swallows with DL ≤ 4.5 sec). Response to MRS was evaluated for complete versus impaired inhibition (contractility with DCI > 100 mmHg-sec-cm during MRS), and presence of post MRS contraction augmentation (DCI post MRS greater than single-swallow mean DCI). Chi-Square and Fisher’s exact test were used for statistical analysis. RESULTS: Demographics and symptom data are shown in Table 1. Patients with DES were older and more symptomatic than controls. Impaired inhibition of peristalsis during MRS was significantly more frequent in DES compared to controls (89% vs 0%, P < 0.001, Figure 1). The proportion of subjects with augmentation post MRS was similar for both groups (37% vs 38%, P = 1.00), but mean DCI post MRS was higher in DES than controls (3788 vs 1239, P = 0.013). CONCLUSION: Impaired deglutitive inhibition during MRS is present in the majority of patients with DES, supporting impaired inhibitory pathways in the esophagus as a mechanism of action in this disorder.

INTRODUCTION: We previously showed an association between chronic opioid use and esophageal motor dysfunction characterized by esophagogastric junction outflow obstruction, distal esophageal spasm, achalasia type III, and Jackhammer esophagus. Assessment of response to multiple rapid swallows (MRS) during high-resolution esophageal manometry (HRM) enables detection of impaired inhibition during MRS. Healthy subjects respond to MRS by deglutitive inhibition during MRS followed by an augmented contraction with higher vigor than single swallows. Hypothesis: during MRS, opioids may interfere with deglutitive inhibition and may enhance post MRS contraction. Aim: compare response to MRS in opioid users, non-users and healthy controls. METHODS: Response to MRS was evaluated in 200 patients with esophageal symptoms (100 chronic opioid users on oxycodone, hydrocodone, or tramadol for ≥3 months, 100 not on opioids), and 19 asymptomatic healthy controls that underwent HRM. Patients with prior gastroesophageal surgery, pneumatic dilation, esophageal botulinum toxin injection within 6 months of HRM, esophageal stricture, achalasia type I or II, and scleroderma were excluded. Demographic and symptom data were extracted from a prospectively maintained motility database. Response to MRS was evaluated for complete versus incomplete inhibition (contractility with DCI >100 mmHg-sec-cm during MRS), and presence of post MRS contraction augmentation (DCI post MRS greater than mean DCI for single swallows). Categorical variables were analyzed by chi square. RESULTS: Patients were older than controls (Table 1). HRM indications are shown in Table 2. Incomplete inhibition during MRS was significantly more frequent in chronic opioid users compared to patients not on opioids and healthy controls (26% vs 11% vs 0% P = 0.002; Figure 1). There was a significant difference in the rate of incomplete MRS inhibition for patients on oxycodone, hydrocodone, and tramadol (27% vs 34% vs 22% P = 0.002). The proportion of patients with augmentation post MRS was similar for opioid users, non-opioid users and healthy controls ( P = 0.05). CONCLUSION: Impaired deglutitive inhibition during MRS was significantly more frequent among opioid users compared to non-opioid users and healthy controls. This was more common with stronger opioids (oxycodone and hydrocodone) compared to tramadol. These findings support our hypothesis that opioids interfere with inhibitory signals in the esophagus.

INTRODUCTION: Jackhammer esophagus (JE) is esophageal motility disorder characterized by hypercontractile peristalsis, diagnosed by high resolution manometry (HRM) showing increased contractile vigor distal contractile integral (DCI) >8000 mmHg/s/cm. Hypothesis: hypercontractile peristalsis in JE may be a compensatory mechanism for impaired EGJ relaxation, which even with normal integrated relaxation pressure (IRP), may be expressed as delayed onset of relaxation. We compare time to onset of EGJ relaxation in JE patients with normal IRP, control patients presenting for evaluation of esophageal symptoms with normal HRM, and asymptomatic healthy volunteers. METHODS: We compared time to onset of EGJ relaxation in 44 patients (24 JE, 20 with normal HRM) and 21 asymptomatic healthy volunteers who underwent HRM. Demographic characteristics and validated esophageal questionnaires (GERDQ, BEDQ, Eckardt) collected in all subjects. HRM performed by administering ten 5-ml liquid swallows, Chicago Classification v3.0 used to diagnose JE and normal esophageal motility. Time to onset of EGJ relaxation after swallow initiation was measured in seconds, from time of upper esophageal sphincter opening to EGJ opening. EGJ opening was determined at an isobaric contour of 23 mmHg, based on analysis in the healthy volunteers showing persistent EGJ effacement at this value in 100% of the volunteers. Median times to onset of relaxation for the study groups were compared by Wilcoxon rank sum test. RESULTS: Demographics, questionnaire scores, and HRM metrics in Table 1; patients were older and had higher scores compared to healthy volunteers; HRM metrics were different among the study groups with the exception of DL. Median times to onset of relaxation after swallow initiation shown in Figure 1. There was no difference in median time to onset of relaxation for volunteers compared to patient controls with normal HRM 0.20 s vs 0.90 s, P = 0.149. Median time to onset of relaxation was significantly longer in JE patients compared to volunteers and patient controls 3.30s vs 0.20 s vs 0.90 s, P = 0.001. CONCLUSION: Patients with JE and normal EGJ relaxation by IRP have significantly delayed onset of EGJ relaxation compared to healthy subjects and control patients with normal HRM. Hypercontractile peristalsis in these JE patients could be a compensatory mechanism to overcome outflow obstruction manifested as delayed EGJ relaxation. Therefore, if our findings are confirmed, therapies to address impaired EGJ relaxation could be considered.

INTRODUCTION: High resolution manometry (HRM) is the gold standard to assess esophageal motility. Functional lumen imaging probe topography (FLIP) performed during EGD assesses esophagogastric junction (EGJ) distensibility and esophageal peristalsis. AIM: Evaluate FLIP-HRM agreement and value of FLIP as screening for dysmotility. METHODS: Patients with esophageal symptoms underwent FLIP and HRM. FLIP performed with 16-cm balloon; peristaltic response assessed at 30-40-50-60 ml and classified as repetitive antegrade contractions-RACs, repetitive retrograde contractions-RRCs, diminished/disordered contractility, or absent contractility; median EGJ distensibility index (DI) measured at 60 ml was deemed abnormal (<2 mm 2 /mmHg), indeterminate (2-3 mm 2 /mmHg), normal (> 3 mm 2 /mmHg). Normal FLIP defined by normal EGJ DI and RACs without RRCs. HRM Chicago classification v3.0 diagnosis was dichotomized as normal/minor disorder (normal, ineffective esophageal motility-IEM, or fragmented peristalsis-FP) or abnormal (achalasia, jackhammer esophagus-JE, distal esophageal spasm-DES, EGJ outflow obstruction-EJGOO, absent contractility). FLIP sensitivity/specificity calculated with HRM as gold standard. RESULTS: HRM and FLIP performed a median 18 days apart in 75 patients, 17-92 yo, 65% F. HRM diagnoses: normal/minor disorder 45% (28% normal, 16% IEM, 1% FP), abnormal 55% (17% absent contractility, 16% achalasia, 15 % EGJOO, 4% JE, 3% DES). FLIP diagnoses: 33% normal, 77% abnormal. When FLIP was normal, HRM showed normal/minor disorder in 58% (53% normal, 5% IEM), absent contractility 26%, JE 11%, EGJOO 5% (no achalasia or DES). Normal FLIP had 80% specificity for normal/minor HRM disorder. When FLIP was abnormal, HRM showed achalasia 21%, normal 20%, IEM 19%, EGOO 18%, absent contractility 14%, DES 4%, JE 2%, FP 2%. FLIP had 80% sensitivity for major motility disorder on HRM and was abnormal in 100% patients with achalasia or DES. A normal EGJ DI by itself had a negative predictive value of 90% for normal/minor HRM disorder. CONCLUSION: FLIP topography performed during EGD is promising as a screening tool for esophageal dysmotility, with 80% specificity for normal/minor HRM disorder, and 80% sensitivity for major HRM disorder. Normal FLIP during EGD for evaluation of esophageal symptoms may obviate the need for manometry. Likewise, HRM is clearly indicated in patients with abnormal FLIP, with high likelihood of major motility disorder on HRM in these patients.

INTRODUCTION: Inpatient status has been shown to be a predictor of poor bowel preparation for colonoscopy since these patients are usually older, less mobile, have more medical comorbidities, and often require emergent evaluation. Our aim was to compare the efficacy of bowel preparation volume size in hospitalized patients undergoing inpatient colonoscopy. METHODS: This prospective, single blinded (endoscopist), randomized controlled trial was IRB approved and conducted as a pilot study at a Tertiary Referral Medical Center between September 2013 and March 2019. Hospitalized patients aged 18 years or older undergoing inpatient colonoscopy were assigned randomly to receive a high-volume solution (GoLYTELY®, medium-volume solution (MoviPrep®) or a low-volume Prepopik® solution. Adverse effects including unpleasant taste, nausea, and vomiting were scored through a questionnaire using a five-point scale ranging from 0 (no symptoms) to 4 (severe symptoms). Boston Bowel Prep Score (BBPS) was used to evaluate colon cleanliness. Descriptive statistics are presented as mean values ± standard deviation (SD), and P -values were calculated using Chi-Square and Kruskal-Wallis tests. RESULTS: Twenty-five colonoscopies were performed in 25 subjects. Mean age was 66.6 years (16.34) and 68% were male (Table 1). Indications for colonoscopy varied and are shown in Table 1. Total BBPS scores were higher in patients who received Prepopik®, 7.4 (1.62), than GoLYTELY® 6.6 (2.19) or MoviPrep® 6.9 (1.55), P = 0.66 (Figure 1). There was no difference in BBPS in right, transverse, or left colon scores. Regarding tolerance to preparation, 100% of the Prepopik® group reported completing the bowel preparation compared to 77.8% of the GoLYTELY® group and 66.4% of the MoviPrep® group ( P = 0.24). The Prepopik® group reported fewer side effects than GoLYTELY®/MoviPrep® groups (Table 2). CONCLUSION: In this pilot study, a low-volume colon preparation demonstrated at least equivalent quality of bowel preparation measured by BBPS in comparison with traditional higher volume regimens, with less adverse effects, and better compliance for cleansing completion. This study suggests small volume purgative may lead to better patient compliance and therefore, better bowel preparation in the inpatient setting. The lack of statistical significance is likely due to a type II error. Further more robust studies are required to confirm these findings.

OBJECTIVE: Data regarding opioid effects on esophageal function are limited. We previously demonstrated an association between chronic opioid use and esophageal motor dysfunction characterized by esophagogastric junction outflow obstruction, distal esophageal spasm, achalasia type III, and possibly Jackhammer esophagus. Our aim was to characterize the influence of different opioids and doses on esophageal dysfunction. METHODS: Retrospective review of 225 patients prescribed oxycodone, hydrocodone, or tramadol for >3 months, who completed high-resolution manometry from 2012 to 2017. Demographic and manometric data were extracted from a prospectively maintained motility database. Frequency of opioid-induced esophageal dysfunction (OIED, defined as distal esophageal spasm, esophagogastric junction outflow obstruction, achalasia type III, or Jackhammer esophagus on high-resolution manometry, was compared among different opioids. The total 24-hour opioid doses for oxycodone, hydrocodone, and tramadol were converted to a morphine equivalent for dose effect analysis. RESULTS: OIED was present in 24% (55 of 225) of opioid users. OIED was significantly more prevalent with oxycodone or hydrocodone use compared with tramadol (31% vs 28% vs 12%, P = 0.0162), and for oxycodone alone vs oxycodone with acetaminophen (43% vs 21%, P = 0.0482). There was no difference in OIED for patients taking hydrocodone alone vs hydrocodone with acetaminophen. Patients with OIED were taking a higher median 24-hour opioid dose than those without OIED (45 vs 30 mg, P = 0.058). DISCUSSION: OIED is more prevalent in patients taking oxycodone or hydrocodone compared with tramadol. There is greater likelihood of OIED developing with higher doses. Reducing the opioid dose or changing to tramadol may reduce OIED in opioid users.

Background/Aims. The aim of this study was to evaluate the association of fluid balance with outcomes in patients hospitalized with acute pancreatitis (AP).Methods. This was a retrospective study of patients hospitalized between May 2008 and June 2016 with AP and a clinical order for strict recording of intake and output. Data collected included various types of fluid intake and output at 24 and 48 hours after admission. The primary outcome was length of stay (LOS). Analysis was performed using single-variable and multivariable negative binomial regression models.Results. Of 1256 patients hospitalized for AP during the study period, only 71 patients (5.6%) had a clinical order for strict recording of intake and output. Increased urine output was associated with a decreased LOS at 24 and 48 hours in univariable analysis. An increasingly positive fluid balance (total intake minus urine output) at 24 hours was associated with a longer LOS in multivariable analysis.Conclusions. Few patients hospitalized for AP had a documented order for strict monitoring of fluid intake and output, despite the importance of monitoring fluid balance in these patients. Our study suggests an association between urine output and fluid balance with LOS in AP.