Crowell, Michael D.

INTRODUCTION: Gastric-emptying scintigraphy (GES), routinely used to measure gastric emptying, is an essential tool to diagnose gastroparesis. An accurate diagnosis of gastroparesis relies upon the GES being performed according to a validated protocol. Jointly published protocol guidelines have been available for over a decade; however, the extent to which these guidelines are adhered to is unknown. This study aimed to assess national compliance with established GES protocol guidelines. METHODS: We developed a questionnaire addressing key protocol measures outlined in the published Procedure Guideline for Adult Solid-Meal Gastric Emptying Study 3.0. Survey questions addressed patient information collection (15), patient preparation and procedure protocol (16), meal content and preparation (7), imaging (3), interpretation (4), and reporting (7). Demographic data was also collected. The anonymous questionnaire was distributed electronically to members of the Society of Nuclear Medicine and Medical Imaging (SNMMI) and non-member recipients of the SNMMI daily email newsletter. One response per medical institution was permitted. Data were entered manually and statistically assessed using JMP®, Version 14.0. SAS Institute Inc., Cary, NC. RESULTS: 121 medical institutions (MI) responded; 49 (40.4%) were academic/teaching medical centers. The mean number of annual GES procedures was 199.9 (range, 5 to 2000 GES/year). On average, MI performed 64% (33.5/52) of protocol measures according to guidelines while academic medical centers performed 61% (31.5/52) of protocol measures according to guidelines. Only 59% of MI use the validated meal. 42% of MI reported stopping imaging prior to the validated 4-hour interval. Only 16% of MI test blood glucose levels prior to GES while 71% cancel or reschedule GES if blood glucose levels are above the validated cut-off. 68% of MI ask patients if they take narcotic pain medications; only 49% require that patients stop taking narcotic pain medications at least two days prior to the GES. Only 4.5% of MI perform GES while adhering to 3 critical measures: validated study duration; controlling blood glucose levels; and properly restricting medication use. CONCLUSION: Low compliance with GES protocol guidelines, even among academic medical centers, raises the likely possibility of misdiagnosis and thus improper management of upper gastrointestinal symptoms. These results highlight a need for increased awareness of protocol guidelines.

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.

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.

SummaryBackgroundGastroparesis has a significant negative impact on patients’ quality of life. Only one medication is approved for gastroparesis and it is associated with a significant risk of side effects.AimTo assess the willingness of patients to take risks associated with medications to treat gastroparesis symptoms.MethodsWe developed a questionnaire to assess medication risk‐taking behaviour in patients identified as having documented gastroparesis (consistent symptoms, normal upper endoscopy, delayed gastric emptying). The survey assessed demographics, symptoms, medication use, anxiety, depression and impulsivity. A standard reference gamble evaluated respondents’ willingness to take medication risks.ResultsTwo hundred seven questionnaires were mailed to patients, 103 questionnaires were completed. Seventy‐six percent were female; the mean age was 48 years; average duration of gastroparesis symptoms was 10 years. Self‐reported symptom severity was severe in 52% and moderate in 32%. Gastroparesis patients reported that they would accept a median 13.4% risk of sudden death to cure their symptoms using a hypothetical medication. Self‐reported gastroparesis symptom severity and Gastroparesis Cardinal Symptom Index scores correlated significantly with increased willingness to take risks associated with medications to treat gastroparesis, while anxiety was negatively associated.ConclusionsGastroparesis patients are willing to accept markedly high risks with a hypothetical medication to cure their symptoms. Patients with severe gastroparesis symptoms and higher Gastroparesis Cardinal Symptom Index scores were more willing to take these risks. This study, the first to quantify gastroparesis patients’ willingness to accept medication associated risks, should help clinicians through the complex maze of gastroparesis therapies and their associated risks and benefits.

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.

Abstract Background Patients with postural tachycardia syndrome (POTS) often have gastrointestinal (GI) symptoms. Occasionally, these symptoms can be so severe that nonoral nutrition/hydration support (NONHS), including intravenous fluids (IVFs), enteral nutrition (EN), and parenteral nutrition (PN), becomes necessary. Methods This is a retrospective cohort study of adult patients diagnosed with POTS at the Mayo Clinic Arizona from January 2010 to January 2017 with a minimum of 6 months of follow up. Demographic information, symptomatology, medications, GI testing, autonomic and autoantibody testing, and healthcare utilization data were abstracted from the electronic medical record. Results Three‐hundred thirty‐two patients with POTS were included, of which 32 required NONHS. Patients receiving NONHS were more likely to be female; have lower body mass index; have GI symptoms including nausea, vomiting, diarrhea, and constipation; have abdominal pain; use opiates; have delayed gastric emptying; see more specialists; and be seen in an emergency room or be hospitalized for symptoms. Of these patients, 21 (66%) required IVF, 19 (59%) required EN, and 9 (28%) required PN. Six (19%) patients required all 3 NONHS modalities at some point during their follow‐up period. Conclusions NONHS may be required in a subset of patients with POTS. Those receiving NONHS have more severe symptoms and abnormal GI motility and autonomic testing and exhibit greater healthcare utilization. Management of these patients is complex and challenging and requires a multidisciplinary approach. Further prospective studies are needed to identify optimal management strategies.