Ravi, Karthik

INTRODUCTION: Histologic response rates to steroids for eosinophilic esophagitis (EoE) vary from < 50% to >90% in controlled trials. We have used varied steroid preparations and higher doses than typically used and aimed to study if steroid dose and delivery vehicle might explain the wide variation in response. METHODS: A database of patients with EoE created in our esophageal clinic was reviewed and patients treated with at least an 8 week course of topical steroid therapy and undergoing pre and post-steroid histologic evaluation were included. Histologic remission was defined as eosinophil count < 15/hpf. Symptomatic remission was defined as complete resolution of symptoms and eating an unlimited diet. Endoscopy reports were reviewed. RESULTS: 94 patients were included, 45 on 3 mg budesonide-Rincinol gel twice daily (HBRG), 29 on 3 mg budesonide capsules BID (BC), and 20 on lower doses of BRG (1.5 mg daily to 2 mg BID) (LBRG). 88.5% had dysphagia at time of steroid initiation. Mean eosinophil count before steroids was 58.6/hpf. 38.3% had esophageal dilation just prior to steroids. Average EFERS prior to steroid treatment was 1.8. There were not significant differences between the groups in terms of demographics, initial eosinophil counts, symptoms, visual EoE assessment (EREFS) or dilation rates. Histologic remission rate for HBRG was 82.2% vs 55.1% for all others combined ( P < 0.001), 51.7% for BC ( P = 0.005 vs 3 mg BRG BID), and 60.0% for LBRG ( P = 0.06 vs 3 mg BRG BID). Symptomatic remission was similar between groups, as was change in EREFS and change in eosinophil counts. Non-responders to HBRG had mean decrease in eosinophil count of only 0.3/hpf (vs 53.2/hpf for responders, P < 0.003) and mean change in EREFS of +1.6 (vs −1.1 for responders, P < 0.001). 62.5% of non-responders to HBRG actually had increase in eosinophil count after steroids. Response rate to HBRG at < 5 eos/hpf was 77.8% overall and 94.6% in those achieving remission. CONCLUSION: A higher remission rate achieved with a more viscous steroid preparation compared to other formulations suggests the importance of both dose and esophageal delivery in treatment of EoE. Further, with adequate mucosal delivery and dosing of topical steroids, steroid refractory EoE appears to be uncommon. On the other hand, these results suggest the existence of a small truly steroid refractory group of EoE patients with negligible histologic, symptomatic and endoscopic response to high dose steroids that warrant further investigation.

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.

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.

AbstractBackgroundThe most recent Chicago Classification expanded the criteria for diagnosis of jackhammer esophagus (JHE) to include the distal contractile integral (DCI) of the lower esophageal sphincter (LES). The clinical impact of the manometric inclusion of LES hypercontractility remains unclear. We aimed to analyze the clinical features and long‐term outcomes of measured LES‐dependent (LD‐JHE) and LES‐independent (LI‐JHE) jackhammer esophagus.MethodsPatients meeting diagnostic criteria for JHE were identified at two academic medical centers. High‐resolution esophageal manometry data were re‐analyzed with inclusion and exclusion of the LES DCI. LD‐JHE was defined by falling outside JHE diagnostic criteria with exclusion of the LES. A telephone survey was conducted for follow‐up utilizing the impact dysphagia (IDQ‐10) questionnaire.Key ResultsEighty‐one patients met study inclusion criteria, with 12 (14.8%) classified as LD‐JHE. LD‐JHE patients had a significantly lower mean DCI and fewer swallows with DCI >8000 mm Hg‐s‐cm. Basal LES pressure was higher in patients with dysphagia to solids than those with dysphagia to solids and liquids. Clinical and manometric parameters were otherwise similar between groups. Sixty‐six patients had clinical or phone follow‐up at a median of 46.6 months. Forty‐one patients (62.1%) received therapies directed at JHE. There was no difference in symptom improvement for treated vs untreated patients or for JHE subtype.Conclusions and InferencesOur findings suggest that LD‐JHE and LI‐JHE are clinically indistinguishable and thus support existing diagnostic criteria. Furthermore, our long‐term follow‐up data suggest that JHE, irrespective of LES involvement, may improve without treatment. Further study is needed to clarify which patients merit therapeutic intervention.

AbstractBackgroundThe mechanism by which obesity leads to damage independent of reflux is unclear. We aimed to determine the influence of obesity on mean nocturnal baseline impedance (MNBI), a functional measure of the epithelial barrier, in the presence and absence of acid reflux, using ambulatory pH impedance measurements.MethodsTwenty‐four‐hour pH impedance studies performed off medications in Caucasian men with a normal endoscopic examination were assessed for level of acid exposure and MNBI. Four patient groups were studied: Group 1, Not obese and normal acid exposure; Group 2, Obese and normal acid exposure; Group 3, Not obese and increased acid exposure; and Group 4, Obese with increased acid exposure.ResultsOne hundred patients were studied (25 in each group). Mean esophageal mucosal impedance (MI) was substantially lower in obese patients without reflux (Group 2) and non‐obese patients with reflux (Group 3) compared to normal controls (non‐obese, no reflux, Group 1). MI was progressively lower in the distal (vs the proximal) esophagus in GER patients, compared to those without GER. This difference persisted in the presence or absence of obesity. In contrast, in obese patients, the mean MI was significantly lower throughout the esophagus when compared to the non‐obese patients and also persisted in the presence and absence of accompanying reflux. Obesity and reflux were both independently negatively correlated with MI.ConclusionObesity is associated with abnormal esophageal MNBI. In contrast to gastro‐esophageal reflux, this decrease is pan‐esophageal. These data may support a systemic mechanism by which obesity alters the esophageal barrier function.

Introduction. Idiopathic subglottic stenosis represents a spectrum of subglottic disease without a clear underlying cause. Prior studies have implicated a pathogenic role of gastroesophageal reflux disease in idiopathic subglottic stenosis. The aim of this study was to examine the presence and pattern of gastroesophageal reflux in a large cohort of patients with idiopathic subglottic stenosis at a tertiary referral center. Methods. We performed a retrospective review of patients with idiopathic subglottic stenosis from January 2010 to December 2016 who had undergone combined pH impedance testing. Patients with prior gastric or esophageal surgery were excluded. Data obtained included esophageal acid exposure times, number of reflux events, patient position during reflux events (defined as upright, supine, or mixed), body mass index, and the presence of proton pump inhibitor therapy. Results. 159 patients with the idiopathic subglottic stenosis were identified, of whom 41 had undergone esophageal pH impedance testing. 40 (97.6%) were women, with a mean age of 54.8 (range 31–79) years and BMI of 31.0 (range 17–55). Overall, 19 (46.3%) patients were found to reflux as confirmed by abnormal esophageal acid exposure or abnormal number of reflux events. 15 of the 19 patients with reflux had predominantly upright gastroesophageal reflux disease, whereas 2 had supine and 2 mixed reflux. Discussion. In patients with idiopathic subglottic stenosis who underwent evaluation by combined pH impedance, close to half were found to have gastroesophageal reflux disease. The majority of gastroesophageal reflux occurred while the patients were in the upright position.

AbstractBackgroundAlthough major manometric abnormalities, the significance of esophagogastric junction outflow obstruction (EGJOO) and hypercontractile esophagus (HE) is poorly understood. We sought to determine long term outcomes for EGJOO and HE.MethodsHigh‐resolution impedance manometry (HRIM) studies conducted from 5/30/2012 to 8/1/2014 consistent with EGJOO and HE and normal studies from 5/30/12 to 11/1/12 were identified. Standardized follow up was conducted with a phone survey utilizing the impact dysphagia questionnaire (IDQ‐10).Key Results56 EGJOO, 40 HE patients and 33 controls were identified. Structural evaluation with EGD and esophagram did not differ among groups. Use of opiates in EGJOO (P<.05) and of anticholinergics in EGJOO and HE patients was more prevalent than in controls (P<.005). Dysphagia was more common in EGJOO (P<.05) and chest pain more common in HE (P<.005) at presentation. While HE patients were more likely to be symptomatic (P<.05), the majority of EGJOO and HE patients overall were asymptomatic at a mean 2.8 years follow up without medical or procedural intervention in the majority (72.5%). Symptom persistence at follow up was predicted by maximum distal contractile integral (DCI) and IRP in both EGJOO and HE (P<.05).Conclusions & InferencesThe majority of patients with EGJOO and HE appear to have a benign clinical course similar to controls in the absence of specific treatment. However, the combination of abnormal IRP and DCI in both HE and EGJOO appears to discriminate an important subset of patients who may benefit from treatment. Further refinement of manometric criteria may therefore provide more useful clinical definitions of EGJOO and HE.

Abstract Background Baseline impedance measured with ambulatory impedance pH monitoring ( MII ‐pH) and a mucosal impedance catheter detects gastroesophageal reflux disease ( GERD ). However, these tools are limited by cost or patient tolerance. We investigated whether baseline impedance measured during high‐resolution impedance manometry ( HRIM ) distinguishes GERD patients from controls. Methods Consecutive patients with clinical HRIM and MII ‐pH testing were identified. Gastroesophageal reflux disease was defined by esophageal pH <4 for ≥5% of both the supine and total study time, whereas controls had an esophageal pH <4 for ≤3% of the study performed off PPI . Baseline impedance was measured over 15 seconds during the landmark period of HRIM and over three 10 minute intervals during the overnight period of MII ‐pH. Key Results Among 29 GERD patients and 26 controls, GERD patients had a mean esophageal acid exposure time of 22.7% compared to 1.2% in controls ( P <.0001). Mean baseline impedance during HRIM was lower in GERD (1061 Ω) than controls (2814 Ω) ( P <.0001). Baseline mucosal impedance measured during HRIM and MII ‐pH correlated ( r =0.59, P <.0001). High‐resolution esophageal manometry baseline impedance had high diagnostic accuracy for GERD , with an area under the curve ( AUC ) of 0.931 on receiver operating characteristics ( ROC ) analysis. A HRIM baseline impedance threshold of 1582 Ω had a sensitivity of 86.2% and specificity of 88.5% for GERD , with a positive predictive value of 89.3% and negative predictive value of 85.2%. Conclusions & Inferences Baseline impedance measured during HRIM can reliably discriminate GERD patients with at least moderate esophageal acid exposure from controls. This diagnostic tool may represent an accurate, cost‐effective, and less invasive test for GERD .

Abstract Background Acetylcholinesterase inhibitors ( ACI s), e.g., neostigmine, are known to increase upper and lower gastrointestinal ( GI ) motility and are used to treat acute colonic pseudoobstruction. However, their effects on gastroduodenal motility in humans are poorly understood. Our hypotheses were that, in patients with suspected GI motility disorders, neostigmine increases gastric and small intestinal motor activity, and these effects are greater in patients with cardiovagal neuropathy, reflecting denervation sensitivity. Methods In this open label study, the effects of neostigmine (1 mg intravenously) on gastroduodenal motor activity recorded with manometry were assessed in 28 patients with a suspected GI motility disorder. Cardiovagal function was assessed with the heart rate response to deep breathing and GI transit by scintigraphy. Key Results The final diagnoses were gastroparesis (6 patients), gastroparesis with intestinal neuropathy (3 patients), intestinal neuropathy or pseudoobstruction (5 patients), functional dyspepsia (6 patients), chronic abdominal pain (3 patients), mechanical small intestinal obstruction (3 patients), and pelvic floor dysfunction (2 patients). Neostigmine increased both antral and intestinal phasic pressure activity ( p < 0.001). Neostigmine increased antral and intestinal pressure activity in 81% and 50% of patients with reduced postprandial antral and intestinal contractile responses to meal, respectively. The antroduodenal pressure response to neostigmine was not higher in patients with cardiovagal dysfunction. Conclusions & Inferences Neostigmine increased antral and intestinal motor activity in patients with hypomotility, including intestinal dysmotility. These responses to neostigmine were not greater in patients with cardiovagal dysfunction. The use of longer‐acting ACI s for treating antroduodenal dysmotility warrant further study.