Unraveling molecular advancements in chordoma tumorigenesis and treatment response: a review of scientific discoveries and clinical implications.

Chordomas are tumors thought to originate from notochordal remnants that occur in midline structures from the cloves of the skull base to the sacrum. In adults, the most common location is the sacrum, followed by the clivus and then mobile spine, while in children a clival origin is most common. Most chordomas are slow growing. Clinical presentation of chordomas tend to occur late, with local invasion and large size often complicating surgical intervention. Radiation therapy with protons has been proven to be an effective adjuvant therapy. Unfortunately, few adjuvant systemic treatments have demonstrated significant effectiveness, and chordomas tend to recur despite intensive multimodal care. However, insight into the molecular underpinnings of chordomas may guide novel therapeutic approaches including selection for immune and molecular therapies, individualized prognostication of outcomes, and real-time noninvasive assessment of disease burden and evolution. At the genomic level, elevated levels of brachyury stemming from duplications and mutations resulting in altered transcriptional regulation may introduce druggable targets for new surgical adjuncts. Transcriptome and epigenome profiling have revealed promoter- and enhancer-dependent mechanisms of protein regulation, which may influence therapeutic response and long-term disease history. Continued scientific and clinical advancements may offer further opportunities for treatment of chordomas. Single-cell transcriptome profiling has further provided insight into the heterogeneous molecular pathways contributing to chordoma propagation. New technologies such as spatial transcriptomics and emerging biochemical analytes such as cell-free DNA have further augmented the surgeon-clinician's armamentarium by facilitating detailed characterization of intra- and intertumoral biology while also demonstrating promise for point-of-care tumor quantitation and assessment. Recent and ongoing clinical trials highlight accelerating interest to translate laboratory breakthroughs in chordoma biology and immunology into clinical care. In this review, the authors dissect the landmark studies exploring the molecular pathogenesis of chordoma. Incorporating this into an outline of ongoing clinical trials and discussion of emerging technologies, the authors aimed to summarize recent advancements in understanding chordoma pathogenesis and how neurosurgical care of chordomas may be augmented by improvements in adjunctive treatments.

Use of the Esophageal Sponge in Directing Food Reintroduction in Eosinophilic Esophagitis.

BACKGROUND & AIMS: Dietary therapy is successful in eosinophilic esophagitis (EoE) but requires multiple upper endoscopies. The aim of this study was to determine if food reintroduction in EoE can be directed by minimally-invasive esophageal sponge cytology. METHODS: In this prospective non-blinded trial, 22 responders to 6-food elimination diets underwent sequential food reintroduction guided by esophageal sponge cytology. Foods were reintroduced followed by unsedated esophageal sponge cytology assessment. A food trigger was defined by sponge cytology peak eosinophil count of ≥15 eos/high-powered field (hpf). Symptoms (EoE symptom activity index [EEsAI]), endoscopic score (EoE endoscopic reference score [EREFS]), and biopsy histology (peak eosinophil count) were collected pre-dietary therapy and post-dietary therapy, and then 4 weeks post food reintroduction. RESULTS: The EEsAI and EREFS were similar post-dietary therapy to post-food reintroduction: 12.0 (interquartile range [IQR], 0.0-27.0) vs 16.5 (IQR, 9.0-28.8) (P = .265) and 1.5 (IQR, 0.2-3.0) vs 1.0 (IQR, 0.0-2.0) (P = .185). However, the peak eosinophil count was increased post-food reintroduction compared with post-dietary therapy: 20.0 (IQR, 5.0-51.5) vs 2.0 (IQR, 1.0-4.0) (P < .001), suggesting a failure of identification of all food triggers. The peak eosinophil count was lower post-food reintroduction compared with pre-dietary therapy: 20.0 (IQR, 5.0-51.5) vs 52.0 (IQR, 30.8-76.2) (P = .008). At the post food reintroduction evaluation, sponge cytology and biopsy histology were in agreement in 59% (13/22) of cases using a cutoff of <15 eos/hpf and 68% (15/22) of cases using a cutoff of <6 eos/hpf. CONCLUSIONS: In the first study to evaluate a non-endoscopic technique in the clinical management of EoE, the esophageal sponge was moderately successful at guiding food reintroduction in EoE dietary responders in the outpatient setting. CLINICALTRIALS: gov, Number NCT02599558.

Performance of an Artificial Intelligence Model for Recognition and Quantitation of Histologic Features of Eosinophilic Esophagitis on Biopsy Samples.

We have developed an artificial intelligence (AI)-based digital pathology model for the evaluation of histologic features related to eosinophilic esophagitis (EoE). In this study, we evaluated the performance of our AI model in a cohort of pediatric and adult patients for histologic features included in the Eosinophilic Esophagitis Histologic Scoring System (EoEHSS). We collected a total of 203 esophageal biopsy samples from patients with mucosal eosinophilia of any degree (91 adult and 112 pediatric patients) and 10 normal controls from a prospectively maintained database. All cases were assessed by a specialized gastrointestinal (GI) pathologist for features in the EoEHSS at the time of original diagnosis and rescored by a central GI pathologist (R.K.M.). We subsequently analyzed whole-slide image digital slides using a supervised AI model operating in a cloud-based, deep learning AI platform (Aiforia Technologies) for peak eosinophil count (PEC) and several histopathologic features in the EoEHSS. The correlation and interobserver agreement between the AI model and pathologists (Pearson correlation coefficient [rs] = 0.89 and intraclass correlation coefficient [ICC] = 0.87 vs original pathologist; rs = 0.91 and ICC = 0.83 vs central pathologist) were similar to the correlation and interobserver agreement between pathologists for PEC (rs = 0.88 and ICC = 0.91) and broadly similar to those for most other histologic features in the EoEHSS. The AI model also accurately identified PEC of >15 eosinophils/high-power field by the original pathologist (area under the curve [AUC] = 0.98) and central pathologist (AUC = 0.98) and had similar AUCs for the presence of EoE-related endoscopic features to pathologists' assessment. Average eosinophils per epithelial unit area had similar performance compared to AI high-power field-based analysis. Our newly developed AI model can accurately identify, quantify, and score several of the main histopathologic features in the EoE spectrum, with agreement regarding EoEHSS scoring which was similar to that seen among GI pathologists.

Eosinophilic Esophagitis Histologic Scoring System: Correlation with Histologic, Endoscopic, and Symptomatic Disease and Clinical Use.

BACKGROUND: The eosinophilic esophagitis histologic scoring system (EoEHSS) was developed to enhance the diagnostic standard of peak eosinophil count (PEC) in evaluating disease activity in EoE. AIMS: (1) Correlate the EoEHSS and PEC to measures of symptomatic and endoscopic disease activity, (2) Correlate EoEHSS grade and stage subcomponents to clinical, radiology, and endoscopic markers of fibrotic disease, (3) Evaluate EoEHSS remission in asymptomatic patients with PEC < 15 eosinophils per high powered field (eos/hpf). METHODS: Secondary analysis of prospective cohort data of 22 patients with EoE that underwent dietary therapy and endoscopy at 3 time points. Active disease was defined by EoEHSS grade or stage > 0.125, symptomatic disease by EoE symptom activity index > 20, endoscopic disease by endoscopic reference score > 2, and histologic disease by PEC ≥ 15 eos/hpf. EoEHSS remission was defined by esophageal inflammation (EI) grade of 0-1, EI stage of 0, total grade ≤ 3, and total stage ≤ 3. RESULTS: EoEHSS grade and stage did not correlate with symptomatic disease but did with endoscopic and histologic disease. PEC showed similar correlation pattern. Abnormal grade and stage had strong sensitivity (87-100%) but poor specificity (11-36%) to detect symptomatic, endoscopic, and histologic disease activity. Lamina propria fibrosis was evaluated in 36% of biopsies and did not correlate with minimum esophageal diameter. Out of 14 patients who were in complete symptomatic, endoscopic, and histologic remission, 8 met criteria for EoEHSS remission. CONCLUSION: The positive and negative correlations of EoEHSS to specific measures of symptomatic, histologic, and endoscopic activity suggest that it provides complementary information in EoE.

Proton Pump Inhibitor Prescribing and Monitoring Patterns Among Gastroenterology Practitioners.

GOALS: The aim was to quantify proton pump inhibitor (PPI) practice habits among gastroenterology (GI) practitioners. BACKGROUND: Reports of side effects have prompted patients and practitioners alike to discontinue PPI use. Emerging evidence-based literature on PPI risks and safety seek to guide practitioners, but the impact of this literature on PPI prescribing patterns has not been evaluated. STUDY: We performed an anonymous online survey of US GI practitioners across 6 academic and community affiliated medical centers. Demographic data including practice type and number of weekly gastroesophageal reflux disease patients seen were obtained. Survey questions evaluated practitioners' monitoring for PPI side effects, dose adjustments, and sources of information about PPI risks. RESULTS: The survey response rate was 60% (256/429). The majority of respondents were male (169, 66%) attending physicians (178, 70%) practicing general GI (63, 25%). There were 92 (36%) respondents who reported testing for PPI side effects at least once a year. Most respondents (143, 56%) reported discontinuing PPIs at least 50% of the time because of patients' concerns about PPI side effects. The majority of respondents reported getting their information regarding PPI safety from published journals (239, 98%) as well as colleagues (222, 91%). CONCLUSIONS: Despite best available evidence suggesting safety of long-term PPI use without routine monitoring, stopping PPIs and monitoring for potential side effects occurs frequently, even within a cohort of mostly academic GI practitioners. Alternative strategies are needed to improve adherence to best practices, especially since gastroenterologists often serve as PPI experts.

Histologic response to steroids in eosinophilic esophagitis is dependent on delivery compound.

Topical steroids are commonly used in treatment of eosinophilic esophagitis (EoE), but currently there is lack of data to clarify most effective regimen. We aimed to study the achievement of histologic remission using the same dose of budesonide in two different delivery formulations. Patients with established EoE treated with pharmacy compounded budesonide capsule or budesonide Rincinol gel (both 3 mg twice daily) were studied retrospectively. Those with pre-treatment and post-treatment histologic assessment were included with main endpoint being histologic remission. 103 patients (62 gel, 41 capsule) were included, with higher rate of histologic remission with gel (84 vs. 59%, P=0.004). A subset of patients in both groups had lack of steroid response (<50% drop in eosinophils) (15% for gel, 32% for capsule). Formulation/delivery vehicle of steroid treatments to esophageal mucosa in EoE appears important for treatment efficacy, with budesonide gel having higher likelihood of histologic remission compared to budesonide capsules in our population. A truly steroid refractory group appears likely in our population. Larger, prospective studies may help clarify best regimen of topical steroids in EoE and may work to identify patients likely to benefit from alternative therapies.

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

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

Effects of Diaphragmatic Breathing on the Pathophysiology and Treatment of Upright Gastroesophageal Reflux: A Randomized Controlled Trial.

INTRODUCTION: Uncontrolled results suggest that diaphragmatic breathing (DB) is effective in gastroesophageal reflux disease (GERD) but the mechanism of action and rigor of proof is lacking. This study aimed to determine the effects of DB on reflux, lower esophageal sphincter (LES), and gastric pressures in patients with upright GERD and controls. METHODS: Adult patients with pH proven upright GERD were studied. During a high-resolution impedance manometry, study patients received a standardized pH neutral refluxogenic meal followed by LES challenge maneuvers (Valsalva and abdominal hollowing) while randomized to DB or sham. After that, patients underwent 48 hours of pH-impedance monitoring, with 50% randomization to postprandial DB during the second day. RESULTS: On examining 23 patients and 10 controls, postprandial gastric pressure was found to be significantly higher in patients compared with that in controls (12 vs 7 mm Hg, P = 0.018). Valsalva maneuver produced reflux in 65.2% of patients compared with 44.4% of controls (P = 0.035). LES increased during the inspiratory portion of DB (42.2 vs 23.1 mm Hg, P < 0.001) in patients and healthy persons. Postprandial DB reduced the number of postprandial reflux events in patients (0.36 vs 2.60, P < 0.001) and healthy subjects (0.00 vs 1.75, P < 0.001) compared with observation. During 48-hour ambulatory study, DB reduced the reflux episodes on day 2 compared with observation on day 1 in both the patient and control groups (P = 0.049). In patients, comparing DB with sham, total acid exposure on day 2 was not different (10.2 ± 7.9 vs 9.4 ± 6.2, P = 0.804). In patients randomized to DB, esophageal acid exposure in a 2-hour window after the standardized meal on day 1 vs day 2 reduced from 11.8% ±6.4 to 5.2% ± 5.1, P = 0.015. DISCUSSION: In patients with upright GERD, DB reduces the number of postprandial reflux events pressure by increasing the difference between LES and gastric pressure. These data further encourage studying DB as therapy for GERD.

Effect of Maintenance Therapy for Eosinophilic Esophagitis on Need for Recurrent Dilation.

BACKGROUND: Eosinophilic esophagitis is an inflammatory condition in which eosinophil infiltration leads to esophageal remodeling and stricturing, with dilation therapy often needed. Achieving histologic remission reduces the need for repeat dilation, although little is known about the effects of long-term maintenance therapy. AIMS: To further assess the relationship between short-term histologic remission and maintenance therapy on need for repeat dilation in eosinophilic esophagitis. METHODS: A total of 77 patients with eosinophilic esophagitis (59.7% male; mean age 41.6 years) seen at a single medical center from June 2000 to August 2017 were included. Information on history of dilation and therapy [proton pump inhibitors (PPIs), steroids, elimination diet] was collected. Mean follow-up was 164 weeks. Fifty-one patients achieved histologic remission and 42 of these remained on maintenance therapy (23 PPIs, 14 topical steroids, and 5 dietary therapy). Standard phone interview was completed in cases with lack of follow-up. Only patients who underwent esophageal dilation to ≥ 17 mm were included. RESULTS: A significantly lower proportion of patients on maintenance therapy required repeat dilation (12/42) compared with patients not on maintenance therapy (8/9) (hazard ratio 0.12; p < 0.001). Of patients who received maintenance therapy, 9.1% required re-dilation. The difference in need for repeat dilation in patients who achieved histologic remission on therapy (14/26) versus those who did not (20/51) was not significant (hazard ratio 1.34; p = 0.45). CONCLUSION: In a retrospective analysis of patients with eosinophilic esophagitis, we found that a significantly lower proportion who received maintenance therapy (PPIs, steroids, or dietary exclusions) required repeat dilation.

Proton Pump Inhibitor Therapy in Eosinophilic Esophagitis: Predictors of Nonresponse.

BACKGROUND: Identification of clinical predictors of response to first-line therapies for EoE is needed to guide initial medical management. STUDY DESIGN: A retrospective analysis of patients diagnosed with EoE from 2011 to 2018 was conducted. Clinical and diagnostic variables including demographics, endoscopic, and esophagram findings were compared between PPI responders and PPI nonresponders. All patients underwent a standard 8-week twice-daily PPI trial, with PPI responsiveness defined as < 15 eos/hpf on repeat EGD. Univariate and multivariable analyses were conducted to identify risk factors for nonresponse, and ROC curves were created to identify cutoff values. RESULTS: A total of 223 EoE patients (135 male, median age 39 (29-51)) were identified, with PPI nonresponse (PPI-NR) in 71% of patients. PPI-NR was seen in all 10 patients with failure of scope passage, with an OR of 9.06 by univariate analysis (P = 0.1485). In a multivariable model, age per 10 years (OR 0.71; P = 0.007), BMI per 1 kg/m2 (OR 0.94; P = 0.03), and peripheral eosinophil count per 100 per mm3 (OR 1.37; P = 0.003) were independent risk factors. Dichotomization to maximize sensitivity and specificity identified age ≤ 36 years old, BMI ≤ 25.2 kg/m2, and peripheral eos > 460 per mm3 as predictive thresholds for PPI-NR. The probability of PPI-NR was 72.4-84.5% with 1 risk factor, 87.9-93.8% with 2 risk factors, and 97.2% with all 3 risk factors. CONCLUSIONS: Young age, reduced BMI, elevated peripheral eosinophil count, and likely inability to pass an endoscope predict lack of response to PPIs in patients with EoE.

Postobesity Surgery Esophageal Dysfunction: A Combined Cross-Sectional Prevalence Study and Retrospective Analysis.

INTRODUCTION: Esophageal dysmotility including features of achalasia may develop because of bariatric surgery. However, the prevalence of these complications is unknown. We sought to define the prevalence of dysphagia and major esophageal motility disorders including achalasia after bariatric surgery through a large retrospective database review. METHODS: Patients with a history of laparoscopic sleeve gastrectomy or Roux-en-Y gastric bypass who underwent a diagnostic high-resolution impedance manometry (HRIM) either before or after bariatric surgery across 3 large tertiary referral sites from June 2012 through February 2019 were identified from a procedural database. HRIM studies were interpreted per the Chicago classification v3.0 by a blinded investigator (K.R.). Demographic/clinical features were collected. In addition, patients who underwent bariatric surgery from January 2014 to April 2015 were contacted and administered a validated symptom assessment survey to gauge the overall prevalence of dysphagia in a postbariatric population. RESULTS: A total of 137 patients were identified, including 97 who underwent HRIM after bariatric surgery (laparoscopic sleeve gastrectomy [n = 39, 40.1%]; Roux-en-Y gastric bypass [n = 58, 59.8%]) at a median of 5.84 years (interquartile range 2.1-12.5) postoperatively and 40 preoperative bariatric surgery candidates with medically complicated obesity. A manometric pattern consistent with achalasia was identified in 7 (7.2%) postsurgical patients compared with none in the preoperative group (P = 0.08). We further identified a separate achalasia-like pattern defined by aperistalsis and increased intragastric pressure (postobesity surgery esophageal dysfunction [POSED]) in 5 (5.2%) postsurgical patients vs none found preoperatively (P = 0.14). Achalasia or POSED was associated with postbariatric surgery (12.4% vs 0%, P = 0.02). Increasing time since surgery was independently associated with the development of achalasia (median 12.5 vs 5.8 years, P = 0.02), POSED (median 15.0 vs 5.8 years, P = 0.02) and major motility disorders (6.6 vs 4.9 years, P = 0.01). Furthermore, among 271 postbariatric surgery patients contacted for symptom assessment via survey, the prevalence of dysphagia was 13.7% at a mean 3.9 years after surgery. DISCUSSION: Postoperative dysphagia is a common long-term complication of bariatric surgery. This is potentially the consequence of a time-dependent association with the development of postoperative esophageal dysmotility, particularly achalasia and POSED. Consequently, esophageal dysmotility may be an important under-recognized complication of bariatric surgery.

Esophageal Hypervigilance and Visceral Anxiety Are Contributors to Symptom Severity Among Patients Evaluated With High-Resolution Esophageal Manometry.

OBJECTIVES: Symptoms are inconsistently associated with esophageal motor findings on high-resolution manometry (HRM). We aimed to evaluate predictors of dysphagia severity, including esophageal hypervigilance and visceral anxiety, among patients evaluated with HRM. METHODS: Adult patients undergoing HRM at 4 academic medical centers (United States and France) were prospectively evaluated. HRM was completed and analyzed per the Chicago Classification v3.0. Validated symptom scores, including the Brief Esophageal Dysphagia Questionnaire and Esophageal Hypervigilance and Anxiety Scale, were completed at the time of HRM. RESULTS: Two hundred thirty-six patients, aged 18-85 (mean 53) years, 65% female, were included. Approximately 59 (25%) patients had a major motor disorder on HRM: 19 achalasia, 24 esophagogastric junction outflow obstruction, 12 absent contractility, and 4 jackhammer. Approximately 177 (75%) patients did not have a major motor disorder: 71 ineffective esophageal motility and 106 normal motility. Having a major motor disorder was a significant predictor of dysphagia severity (Radj = 0.049, P < 0.001), but the Esophageal Hypervigilance and Anxiety Scale score carried a predictive relationship of Brief Esophageal Dysphagia Questionnaire that was 2-fold higher than having a major motor disorder: Radj = 0.118 (P < 0.001). This finding remained when evaluated by the major motor disorder group. HRM metrics were nonsignificant. DISCUSSION: In a prospective, international multicenter study, we found that esophageal hypervigilance and visceral anxiety were the strongest predictors of dysphagia severity among patients evaluated with HRM. Thus, an assessment of esophageal hypervigilance and visceral anxiety is important to incorporate when evaluating symptom severity in clinical practice and research studies.

Baseline Impedance Measured During High-resolution Esophageal Impedance Manometry in Patients With Rumination Syndrome is as Abnormal as in Patients With GERD.

GOALS AND BACKGROUND: Baseline impedance measured during high-resolution impedance manometry (HRIM) can distinguish patients with gastroesophageal reflux disease (GERD) from controls, presumably due to differences in esophageal acid exposure. The characteristics of regurgitation and reflux in rumination syndrome and GERD are very different, and thus we investigated whether baseline esophageal impedance would differ in these 2 patient groups compared with controls. STUDY: We compared 20 patients with rumination syndrome with 20 patients who had GERD and 40 controls. Baseline impedance was measured over 15 seconds during the landmark period of HRIM in all 18 impedance sensors on a HRIM catheter. RESULTS: The mean distal baseline impedance measured in ohms during HRIM was 1336 Ω [95% confidence interval (CI)=799, 1873) in patients with GERD, 1536 Ω in rumination syndrome (95% CI=1012, 2061), and 3379 Ω in controls (95% CI=2999, 3759) (P<0.0001). Proximal impedance was significantly lower in the GERD and rumination groups compared with controls; rumination syndrome (2026; 95% CI=1493, 2559 Ω), GERD (2572; 95% CI=2027, 3118 Ω), and controls (3412; 95% CI=3026, 3798 Ω) (P<0.001). CONCLUSIONS: Baseline impedance measured during HRIM in patients with rumination syndrome is significantly lower than controls and appears similar to patients with GERD both in the proximal and distal esophagus. These findings suggest that the postprandial regurgitation in rumination syndrome alters both the distal and proximal esophageal mucosal barrier.

Correction to: Targeting and Therapeutic Monitoring of H3K27M-Mutant Glioma.

The original version of this review article unfortunately contained a mistake in the author group section.

Targeting and Therapeutic Monitoring of H3K27M-Mutant Glioma.

PURPOSE OF REVIEW: H3K27M is a frequent histone mutation within diffuse midline gliomas and is associated with a dismal prognosis, so much so that the 2016 CNS WHO classification system created a specific category of "Diffuse Midline Glioma, H3K27M-mutant". Here we outline the latest pre-clinical data and ongoing current clinical trials that target H3K27M, as well as explore diagnosis and treatment monitoring by serial liquid biopsy. RECENT FINDINGS: Multiple epigenetic compounds have demonstrated efficacy and on-target effects in pre-clinical models. The imipridone ONC201 and the IDO1 inhibitor indoximod have demonstrated early clinical activity against H3K27M-mutant gliomas. Liquid biopsy of cerebrospinal fluid has shown promise for clinical use in H3K27M-mutant tumors for diagnosis and monitoring treatment response. While H3K27M has elicited a widespread platform of pre-clinical therapies with promise, much progress still needs to be made to improve outcomes for diffuse midline glioma patients. We present current treatment and monitoring techniques as well as novel approaches in identifying and targeting H3K27M-mutant gliomas.

Erosive Esophagitis Portends a Benign Clinical Course in the Majority of Patients.

INTRODUCTION: Indefinite proton pump inhibitor (PPI) therapy and endoscopic evaluation for Barrett's esophagus is recommended for erosive esophagitis (EE). However, the clinical course of EE remains undefined. METHODS: Adults with EE on esophagogastroduodenoscopy (EGD) were identified at Mayo Clinic Rochester between January 2003 and September 2005. Patients with repeat EGD performed after index endoscopy were included. Patients with a history of upper gastrointestinal surgery, esophageal cancer, achalasia, or Barrett's on initial EGD were excluded. RESULTS: Of 219 patients identified, 98 had LA grade A, 72 LA grade B, and 49 LA grade C esophagitis. Persistent EE was found in 27% on repeat endoscopy. No patients progressed to more severe grades of esophagitis. While discontinuation of PPI was associated with persistent esophagitis, long-term healing of esophagitis occurred in the majority of patients despite discontinuation of PPI. Grade A or B esophagitis and the absence of hiatal hernia were also independent predictors of esophagitis healing on multivariate analysis. The rate of Barrett's esophagus was similar among patients with LA grade A/B and C esophagitis on initial EGD (5% vs. 14%, p = 0.6). CONCLUSION: The majority of patients with EE demonstrated healing at follow-up endoscopy regardless of continued PPI use. A small proportion developed Barrett's esophagus, including those with LA grade A and B esophagitis, highlighting a potential role for repeat endoscopy in all grades of EE. A more conservative long-term PPI strategy may be reasonable in patients with LA grade A or B esophagitis in the absence of hiatal hernia.

Esophageal Lichen Planus Is Associated With a Significant Increase in Risk of Squamous Cell Carcinoma.

Esophageal lichen planus (ELP) is a chronic inflammatory process characterized by apoptotic activity of cytotoxic CD8+ T cells on basal keratinocytes as well as regulatory and helper T cells.1-3 Due to chronic inflammation, malignant transformation may be a concern and has been documented in case reports.4,5 We describe the occurrence of esophageal cancer in ELP patients from a large tertiary patient population.

Measurement of Observed Eating Behaviors in Patients With Active and Inactive Eosinophilic Esophagitis.

Subjective measures of eating difficulties in eosinophilic esophagitis (EoE) such as the presence of dysphagia, food modifications, and prolonged eating times are well documented. Although it is assumed that these measures reflect adaptive measures for eating with EoE, this is not well studied. The aim of this study was to directly observe and measure eating behaviors in patients with EoE and assess the degree of correlation to subjective assessment and validated EoE scoring systems.

Model to Select On-Therapy vs Off-Therapy Tests for Patients With Refractory Esophageal or Extraesophageal Symptoms.

BACKGROUND & AIMS: It is not clear whether we should test for reflux in patients with refractory heartburn or extraesophageal reflux (EER) symptoms, such as cough, hoarseness, or asthma. Guidelines recommend testing patients by pH monitoring when they are on or off acid-suppressive therapies based on pretest probability of reflux, determined by expert consensus. However, it is not clear what constitutes a low or high pretest probability of reflux in these patients. We aimed to develop a model that clinicians can use at bedside to estimate pretest probability of abnormal reflux. METHODS: We performed a prospective study of 471 adult patients with refractory heartburn (n = 214) or suspected EER symptoms (n = 257) who underwent endoscopy with wireless pH monitoring while they were off acid-suppressive treatment and assigned them to groups based on symptoms at presentation (discovery cohort). Using data from the discovery cohort, we performed proportional odds ordinal logistic regression to select factors (easy to obtain demographic criteria and clinical symptoms such as heartburn, regurgitation, asthma, cough, and hoarseness) associated with esophageal exposure to acid. We validated our findings in a cohort of 118 patients with the same features from 2 separate tertiary care centers (62% women; median age 59 years; 62% with cough as presenting symptom). RESULTS: Abnormal pH (>5.5% of time spent at pH <4) was found in 56% of patients with heartburn and 63% of patients with EER (P = .15). Within EER groups, abnormal pH was detected in a significantly larger proportion (80%) of patients with asthma compared with patients with cough (60%) or hoarseness (51%; P < .01). Factors significantly associated with abnormal pH in patients with heartburn were presence of hiatal hernia and body mass index >25 kg/m2. In patients with EER, the risk of reflux was independently associated with the presence of concomitant heartburn (odds ratio [OR] 2.0; 95% confidence interval [CI] 1.3-3.1), body mass index >25 kg/m2 (OR 2.1; 95% CI 1.5-3.1), asthma (OR 2.0; 95% CI 1.2-3.5), and presence of hiatal hernia (OR 1.9; 95% CI 1.2-3.1). When we used these factors to create a scoring system, we found that a score of ≤2 excluded patients with moderate to severe reflux, with a negative predictive value of 80% in the discovery cohort and a negative predictive value of 85% in the validation cohort. CONCLUSION: We developed a clinical model to estimate pretest probability of abnormal pH in patients who were failed by proton pump inhibitor therapy. This system can help guide clinicians at bedside in determining the most appropriate diagnostic test in this challenging group of patients.

Opioid-Induced Esophageal Dysfunction: Differential Effects of Type and Dose.

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.