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Su1447 Short Term Non-Invasive Afferent Vagus Nerve Stimulation (nVNS) in Patients With Treatment Refractory Gastroparesis
AGA Abstracts
are computationally intensive and not suitable for real-time pacing applications. Methods: An in-silico ICC network model was developed based on Finite-State Machine theory. This model is composed of 3 states: an initial state that represents the rest potential, a passive state that represents a non-refractory period, and an active state that contains the slow wave potential. Based on this model, a network of ICCs was proposed that consists of 8 superstates representing 8 rings on the stomach arranged along the great curvature from corpus to the antrum. Two, four, and two rings were considered for the pacemaker (P), corpus (C) and antrum (A) regions, respectively. Each ring is composed of 12-30 virtual ICCs, depending on the spatial location of the ring. The sequential activation of the ICCs in each super-state activates the whole ring, which then induces activation of other rings in antegrade sequence. Results: The model simulated normal gastric rhythmicity, and modeled dysrhythmic patterns and frequencies (bradygastria, tachygastria), in real time. When applied with a model input as a mathematical function akin to a single ICC activation i.e., combination of an upstroke and a plateau phase, the model responded with normal antegrade activation at 3 cpm. The propagation velocity matched expected physiological values i.e., 8, 3, and 5.7 mm/s for P, C and A, respectively. Decomposing the same input function into high or low frequency signals (using a Chebyshev filter), the model was able to simulate tachygastric (5 cpm) and bradygastric (2 cpm) conditions. A pacing application was demonstrated, whereby applying external pulse trains at 3 cpm to the 4th ring, in time with dysrhythmic onset, effectively restored bradygastria to a normal frequency. Conclusion: The presented model effectively simulates normal rhythmic and dysrhythmic gastric activities. The model is computationally efficient and can be run in real time; hence, can be used to develop model-driven closedloop pacing applications. Su1446 Randomized Double-Blind Placebo-Controlled Pilot Study of Acupuncture in Idiopathic Gastroparesis Patricia Garcia, Erin Hallinan, Jeffrey Gould, Daniela Jodorkovsky, John O. Clarke, Linda A. Lee Background: Acupuncture has been shown to improve gastric accommodation, visceral hypersensitivity, gastric dysrhythmias and gastric emptying in animal models, making it an attractive target for study in patients with gastroparesis. In humans, clinical trials have shown the effects of acupuncture on post-operative and chemotherapy induced nausea, however, randomized controlled trials of acupuncture in humans with gastroparesis are limited. In addition, clinical trials of acupuncture often use symptom scores as the outcome, whereas effects on human physiology are less frequently assessed. Aim: 1) To perform a randomized controlled trial of acupuncture in idiopathic gastroparesis. 2) To assess physiologic effects of acupuncture on gastric motility. Methods: 18 patients with idiopathic gastroparesis defined by delayed gastric emptying on a 4 hour gastric emptying study were randomized to acupuncture protocols tailored for gastroparesis (GP) or arthralgias (MSK). Patients underwent 2 acupuncture sessions per week for 5 weeks. Gastrointestinal symptoms were assessed with the Patient Assessment of Upper Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM) subscales including gastroparesis cardinal symptom index (GCSI) as the primary outcome; quality of life was assessed with the Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life (PAGI-QOL); motility parameters including gastric emptying time, gastric contractions, gastric motility index, duodenal contractions, and duodenal motility index were assessed via wireless motility capsule (WMC). Symptoms and motility parameters were assessed at enrollment and after completing 5 weeks of acupuncture. Results: Baseline symptom and quality of life scores were similar across groups. Both the MSK and GP acupuncture groups showed significant improvement in GCSI score compared to baseline (overall change -0.6 ± 0.9, p-value 0.02) as well as PAGI-QOL total score (overall change 0.8 ± 0.9, p-value 0.003). There was no difference between MSK and GP acupuncture groups in GCSI change (MSK -0.5 ± 0.9, GP -0.7 ± 1.0, p-value 0.90) or PAGI-QOL score change (MSK 0.8 ± 0.8, GP 0.8 ± 0.9, p-value 0.96). There were no significant overall or between group changes in motility parameters. Conclusions: Both arthralgia and gastroparesis acupuncture lead to significant improvements in GCSI score as well as overall quality of life score. There was no difference between acupuncture groups. There were no significant changes in motility parameters, however, the power to detect differences was low with only 13 patients completing WMC evaluations before and after acupuncture treatment. This pilot study shows the feasibility of performing a larger study to better assess the therapeutic and physiologic effects of acupuncture in gastroparesis.
AGA Abstracts
Su1447 Short Term Non-Invasive Afferent Vagus Nerve Stimulation (nVNS) in Patients With Treatment Refractory Gastroparesis Emma Paulon, Despoina Nastou, Maria F. Jaboli, Owen Epstein Introduction: High frequency, low energy gastric neurostimulation (Enterra®) is indicated for compassionate treatment of patients with refractory gastroparesis. Symptom improvement is reported in 45-60% of patients but not accompanied by improved gastric emptying. It is likely that gastric neurostimulation affects the gut-brain axis influencing autonomic afferents. gammaCore is a non-invasive, afferent selective vagus nerve stimulator(nVNS) used for the treatment of migraine and cluster headache. Methods: 35 consecutive patients with intractable gastroparesis were invited to undergo a course of nVNS whilst being considered for implantable gastric neurostimulation. nVNS delivers a high frequency, low energy stimulus to afferent vagus fibers as they cross the neck adjacent to the carotid arteries. The device is programmed to deliver doses of 120 seconds and patients were trained to deliver 2 doses (240secs) to the left and right vagus nerve respectively. This dosing regimen was self-administered every 8 hours (12 doses/day) for 2 weeks, increasing in week 3 to 3 doses every 8 hours (18 doses/day). Patients were asked to grade their symptoms daily using the 9 item Gastroparesis Cardinal Symptom Index (GCSI) with a 5 point Likert scale. GCSI was completed for 2 weeks prior to commencing treatment, and throughout the treatment period. Symptom change was evaluated in patients who complied with treatment and completed the daily symptom diary. At the end of the treatment period, the mean composite GSCI score at baseline was compared with the composite score of the final week of treatment. Clinically meaningful improvement was defined as a composite GCSI reduction of ≥1. Results:Table 1 indicates patient demographics. 23/35 patients (65.7%) used the gammaCore as instructed and completed the daily diary. At 3 weeks, 8/23 patients (35%) had a ≥1 reduction in the composite GSCI score. Two compliant patients who continued stimulation for more than three weeks experienced a delayed response, giving a total response rate of 43%. In 8 of the responders, improvement was reported within 1 week of commencing treatment. All responders experienced symptom recurrence within a week of stopping treatment. There were no device related adverse events. Conclusions: In this group of patients with treatment refractory gastroparesis, 34% failed to comply with the protocol. In compliant patients, 43% recorded a decrease of ≥1 in their composite GCSI score. As gC stimulates afferent vagus fibers, it is likely that the response is mediated at the level of the gut-brain axis. In refractory gastroparesis, nVNS delivered by gC might offer a new approach to symptom control. The
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AGA Abstracts
dosing and duration of nVNS required to obtain an optimal response deserves further consideration. Table 1
Su1448 Meng Reveals Intestinal Slow Wave Dysrhythmia in Diabetic Gastroparesis Leonard A. Bradshaw, Rachel Moreland, William O. Richards Introduction. Diabetic gastroparesis is defined as delayed gastric emptying not caused by obstruction or structural abnormality. Normal function of the gastric and intestinal mechanical activity is mediated by slow wave electrical activity in the stomach and small bowel. Previous studies using both electrogastrogram and magnetogastrogram have shown gastric slow wave dysrhythmias associated with gastroparesis, but no study has yet examined possible effects of gastroparesis on the intestinal slow wave. Methods. We recorded intestinal slow waves in diabetic patients with gastroparesis (N=7) and healthy controls (N=7) using the magnetoenterogram (MENG), which uses a Superconducting QUantum Interference Device (SQUID) to convert magnetic fields associated with intestinal slow waves into voltage signals. Second Order Blind Identification (SOBI) was used to reduce noise and isolate the intestinal slow wave signal from confounding magnetic artifact, and we computed the power spectrum of the intestinal slow wave using a Fast Fourier Transform technique. We analyzed dominant frequency, amplitude and percentage of power distributed (PPD) in brady, normo and tachyarrhythmic frequency ranges. Results. In gastroparesis patients, we found a significant decrease in postprandial dominant intestinal slow wave frequency from 10.2 ± 0.4 cpm to 8.8 ± 0.5 cpm (p<0.05) whereas the dominant frequency for control subjects increased from 9.9 ± 0.5 cpm to 10.8 ± 0.4 cpm (p<0.05). We did not observe significant differences in pre- and postprandial PPDs computed from controls or patients. Conclusions. Diabetic gastroparesis is associated with bradyarrhythmia, but not uncoupling, of the intestinal slow wave. Biomagnetic measurements of the MENG can assess intestinal slow wave activity in healthy and diseased tissue noninvasively.
Su1450 Gastric Mucosal Innervation in Endoscopic Biopsies in Patients With Idiopathic Gastroparesis Is Not Significantly Different Than Normals Ya-Yuan Fu, Sameer Dhalla, Joyce M. Koh, Shazia M. Siddique, Chun-Hao Lee, Carlos R. Mendez, Pankaj J. Pasricha Background & Aims: A major barrier to improving our understanding of motility is disorders is lack of easy access to deeper layers of the gastrointestinal wall where the major elements of the enteric nervous system are located. A recent study has suggested that gastric mucosal nerve density using endoscopic biopsies may be a useful biomarker for diabetic autonomic neuropathy with changes in density and morphology (Neurology. 2010 Sep 14;75(11):97381). We hypothesized that similar changes may be observed in idiopathic gastroparesis (IG). To this end, we developed a method to quantify the complex neuronal networks in the mucosal biopsies obtained during routine endoscopy using high-resolution three-dimensional (3-D) microscopy. Methods: Endoscopic biopsies were obtained from the body and antrum of the stomach of 10 Normal (i.e. no overt gastric motility disorder nor suggestive cardinal symptoms of the same) and 8 IG patients (with documented delayed emptying by standardized 4 hour scintigraphy). Nerves were visualized by staining for PGP9.5, a pan-neuronal marker. Type IV collagen staining was also performed to delineate the boundary between the mucosa and submucosa. Deep-tissue staining, optical-clearing, and 3-D confocal microscopy were combined to acquire two 150-μm-depth image stacks for each sample. 3-D images of nerve fibers were reconstructed and gastric mucosal nerve density quantified by Avizo 7.1. Results: The nerve length density (nerve total length [μm]/tissue total volume [μm3]) in stomach body and antrum of IG patients was similar to that of normal patients (in body, 0.0019 vs. 0.0021, μm/μm3, p=0.597; in antrum, 0.0016 vs. 0.0017, μm/μm3, p=0.628). The nerve volume density (nerve total volume [μm3]/tissue total volume [μm3]) of the IG patients was also not different from controls. We also calculated the average nerve fiber size, which tended to be smaller in IG in antral biopsies (p=0.07). Conclusions: In this pilot sample, the microstructure, nerve length, and nerve volume are not significantly different in IG vs. controls. While more patients are being recruited with both IG and diabetic gastroparesis, it is unlikely that in IG at least, changes in mucosal nerves alone will be a useful biomarker.
Su1449 Incidence and Clinical Significance of Delayed Gastric Emptying for Liquids in Gastroparesis and Chronic Unexplained Nausea and Vomiting (CUNV) Pankaj J. Pasricha, Katherine P. Yates, John O. Clarke, Thomas L. Abell, James Tonascia, Linda Nguyen, Gianrico Farrugia, Kenneth L. Koch, William J. Snape, William L. Hasler, Sameer Dhalla, Ellen M. Stein, Linda A. Lee, Jorge Calles, Irene Sarosiek, Richard W. McCallum, Frank A. Hamilton, Henry P. Parkman Background. Gastroparesis has traditionally been defined by emptying of a solid meal. By contrast, the clinical relevance of liquid emptying in patients with gastroparesis has not been well studied. Further, it is not clear whether a liquid emptying test increases the diagnostic yield in patients with otherwise unexplained nausea and vomiting. Methods. We include patients enrolled in the NIDDK Gastroparesis Registry who had undergone both solid and liquid emptying tests, usually in the form of a combined test using Tc-99m labeling for the solid meal and Indium-111 for the liquid (water). Gastric retention of Tc-99m > 60% at 2 hours and/or > 10% at 4 hours was considered evidence of delayed gastric emptying of solids; rapid gastric emptying of solids was defined as < 35% retention of Tc-99m at 1 hour; delayed gastric emptying of liquids in the presence of solids is greater than 50% retention of In-111 at 1 hour. Results. Of a total of 136 patients (33% diabetic, 85%female) analyzed, 86 (63%) had delayed solid emptying, 45 (33%) had normal solid emptying and 5 had rapid emptying. and 45 (33%) had delayed liquid emptying. Of these 45 patients with delayed liquid emptying, 37 (82%) also had delayed solid emptying and seven (15%) had normal solid emptying, with 1 having rapid emptying. Conversely, only 7 of 45 (16%) patients with normal solid emptying had delayed liquid emptying as compared with 37 of 86 patients (43%) with delayed solid emptying (P=0.002). Liquid emptying correlated highly with solid emptying among all patients (Figure). Compared to patients with delayed liquid emptying and delayed solid emptying, all patients with delayed liquid emptying alone were females (100% versus 70%; p=0.17) and were all idiopathic (100% versus 62%); p=0.08). Further, more of them had a history of an acute infectious prodrome (57% versus 19%; P= 0.05). Regardless of the results of solid emptying, patients with delayed liquid emptying had similar overall GCSI scores to other patients; however, retching scores were higher (P= 0.04) and GERD scores tended to be higher (P=0.10). Conclusions. (1) More than 40% of gastroparetic patients with delayed solid emptying also have delayed liquid gastric emptying (2) Patients with delayed liquid emptying alone tend to be idiopathic, female and more likely to have a post-infectious syndrome (3) Patients with delays in both solid and liquid emptying are generally very similar in demographic and clinical attributes as compared with those with only delay in solid emptying (4) A relatively small number of patients with CUNV are found to have delayed liquid emptying on testing (4) In general, there is a strong correlation between liquid and solid emptying across the spectrum. Ongoing research using the Gastroparesis Registry will hopefully establish the utility of liquid gastric emptying.
The 3-D projections of innervation (pan-neuronal marker, PGP9.5, red) from normal stomach antrum biopsy (A) and idiopathic gastroparetic stomach antrum biopsy (B). The slimmer mucosal nerve fibers were observed in idiopathic gastroparesis. Dimensions: 1214.56 (X) × 1214.56 (Y) × 150 (Z) μm. Su1451 Dynamic Antral Scintigraphy Identifies Patterns of Gastric Contractility in Patients With Upper GI Motility Disorders: Comparison to Conventional Gastric Emptying Scintigraphy Data Jesus Diaz, Marvin Friedman, Jaibel Makiyil, Irene Sarosiek, Richard W. McCallum BACKGROUND Gastric emptying scintigraphy (GES) has become the recommended standard for the evaluation of patients with symptoms of an upper GI motility disorder (UGIMD). Dynamic antral scintigraphy (DAS) provides information on antral contractility noninvasively thus yielding additional information to supplement GES. OBJECTIVES Correlate the following parameters to conventional GES results: Frequency, rhythm, coordination, and
S-515
AGA Abstracts
are computationally intensive and not suitable for real-time pacing applications. Methods: An in-silico ICC network model was developed based on Finite-State Machine theory. This model is composed of 3 states: an initial state that represents the rest potential, a passive state that represents a non-refractory period, and an active state that contains the slow wave potential. Based on this model, a network of ICCs was proposed that consists of 8 superstates representing 8 rings on the stomach arranged along the great curvature from corpus to the antrum. Two, four, and two rings were considered for the pacemaker (P), corpus (C) and antrum (A) regions, respectively. Each ring is composed of 12-30 virtual ICCs, depending on the spatial location of the ring. The sequential activation of the ICCs in each super-state activates the whole ring, which then induces activation of other rings in antegrade sequence. Results: The model simulated normal gastric rhythmicity, and modeled dysrhythmic patterns and frequencies (bradygastria, tachygastria), in real time. When applied with a model input as a mathematical function akin to a single ICC activation i.e., combination of an upstroke and a plateau phase, the model responded with normal antegrade activation at 3 cpm. The propagation velocity matched expected physiological values i.e., 8, 3, and 5.7 mm/s for P, C and A, respectively. Decomposing the same input function into high or low frequency signals (using a Chebyshev filter), the model was able to simulate tachygastric (5 cpm) and bradygastric (2 cpm) conditions. A pacing application was demonstrated, whereby applying external pulse trains at 3 cpm to the 4th ring, in time with dysrhythmic onset, effectively restored bradygastria to a normal frequency. Conclusion: The presented model effectively simulates normal rhythmic and dysrhythmic gastric activities. The model is computationally efficient and can be run in real time; hence, can be used to develop model-driven closedloop pacing applications. Su1446 Randomized Double-Blind Placebo-Controlled Pilot Study of Acupuncture in Idiopathic Gastroparesis Patricia Garcia, Erin Hallinan, Jeffrey Gould, Daniela Jodorkovsky, John O. Clarke, Linda A. Lee Background: Acupuncture has been shown to improve gastric accommodation, visceral hypersensitivity, gastric dysrhythmias and gastric emptying in animal models, making it an attractive target for study in patients with gastroparesis. In humans, clinical trials have shown the effects of acupuncture on post-operative and chemotherapy induced nausea, however, randomized controlled trials of acupuncture in humans with gastroparesis are limited. In addition, clinical trials of acupuncture often use symptom scores as the outcome, whereas effects on human physiology are less frequently assessed. Aim: 1) To perform a randomized controlled trial of acupuncture in idiopathic gastroparesis. 2) To assess physiologic effects of acupuncture on gastric motility. Methods: 18 patients with idiopathic gastroparesis defined by delayed gastric emptying on a 4 hour gastric emptying study were randomized to acupuncture protocols tailored for gastroparesis (GP) or arthralgias (MSK). Patients underwent 2 acupuncture sessions per week for 5 weeks. Gastrointestinal symptoms were assessed with the Patient Assessment of Upper Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM) subscales including gastroparesis cardinal symptom index (GCSI) as the primary outcome; quality of life was assessed with the Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life (PAGI-QOL); motility parameters including gastric emptying time, gastric contractions, gastric motility index, duodenal contractions, and duodenal motility index were assessed via wireless motility capsule (WMC). Symptoms and motility parameters were assessed at enrollment and after completing 5 weeks of acupuncture. Results: Baseline symptom and quality of life scores were similar across groups. Both the MSK and GP acupuncture groups showed significant improvement in GCSI score compared to baseline (overall change -0.6 ± 0.9, p-value 0.02) as well as PAGI-QOL total score (overall change 0.8 ± 0.9, p-value 0.003). There was no difference between MSK and GP acupuncture groups in GCSI change (MSK -0.5 ± 0.9, GP -0.7 ± 1.0, p-value 0.90) or PAGI-QOL score change (MSK 0.8 ± 0.8, GP 0.8 ± 0.9, p-value 0.96). There were no significant overall or between group changes in motility parameters. Conclusions: Both arthralgia and gastroparesis acupuncture lead to significant improvements in GCSI score as well as overall quality of life score. There was no difference between acupuncture groups. There were no significant changes in motility parameters, however, the power to detect differences was low with only 13 patients completing WMC evaluations before and after acupuncture treatment. This pilot study shows the feasibility of performing a larger study to better assess the therapeutic and physiologic effects of acupuncture in gastroparesis.
AGA Abstracts
Su1447 Short Term Non-Invasive Afferent Vagus Nerve Stimulation (nVNS) in Patients With Treatment Refractory Gastroparesis Emma Paulon, Despoina Nastou, Maria F. Jaboli, Owen Epstein Introduction: High frequency, low energy gastric neurostimulation (Enterra®) is indicated for compassionate treatment of patients with refractory gastroparesis. Symptom improvement is reported in 45-60% of patients but not accompanied by improved gastric emptying. It is likely that gastric neurostimulation affects the gut-brain axis influencing autonomic afferents. gammaCore is a non-invasive, afferent selective vagus nerve stimulator(nVNS) used for the treatment of migraine and cluster headache. Methods: 35 consecutive patients with intractable gastroparesis were invited to undergo a course of nVNS whilst being considered for implantable gastric neurostimulation. nVNS delivers a high frequency, low energy stimulus to afferent vagus fibers as they cross the neck adjacent to the carotid arteries. The device is programmed to deliver doses of 120 seconds and patients were trained to deliver 2 doses (240secs) to the left and right vagus nerve respectively. This dosing regimen was self-administered every 8 hours (12 doses/day) for 2 weeks, increasing in week 3 to 3 doses every 8 hours (18 doses/day). Patients were asked to grade their symptoms daily using the 9 item Gastroparesis Cardinal Symptom Index (GCSI) with a 5 point Likert scale. GCSI was completed for 2 weeks prior to commencing treatment, and throughout the treatment period. Symptom change was evaluated in patients who complied with treatment and completed the daily symptom diary. At the end of the treatment period, the mean composite GSCI score at baseline was compared with the composite score of the final week of treatment. Clinically meaningful improvement was defined as a composite GCSI reduction of ≥1. Results:Table 1 indicates patient demographics. 23/35 patients (65.7%) used the gammaCore as instructed and completed the daily diary. At 3 weeks, 8/23 patients (35%) had a ≥1 reduction in the composite GSCI score. Two compliant patients who continued stimulation for more than three weeks experienced a delayed response, giving a total response rate of 43%. In 8 of the responders, improvement was reported within 1 week of commencing treatment. All responders experienced symptom recurrence within a week of stopping treatment. There were no device related adverse events. Conclusions: In this group of patients with treatment refractory gastroparesis, 34% failed to comply with the protocol. In compliant patients, 43% recorded a decrease of ≥1 in their composite GCSI score. As gC stimulates afferent vagus fibers, it is likely that the response is mediated at the level of the gut-brain axis. In refractory gastroparesis, nVNS delivered by gC might offer a new approach to symptom control. The
S-514
AGA Abstracts
dosing and duration of nVNS required to obtain an optimal response deserves further consideration. Table 1
Su1448 Meng Reveals Intestinal Slow Wave Dysrhythmia in Diabetic Gastroparesis Leonard A. Bradshaw, Rachel Moreland, William O. Richards Introduction. Diabetic gastroparesis is defined as delayed gastric emptying not caused by obstruction or structural abnormality. Normal function of the gastric and intestinal mechanical activity is mediated by slow wave electrical activity in the stomach and small bowel. Previous studies using both electrogastrogram and magnetogastrogram have shown gastric slow wave dysrhythmias associated with gastroparesis, but no study has yet examined possible effects of gastroparesis on the intestinal slow wave. Methods. We recorded intestinal slow waves in diabetic patients with gastroparesis (N=7) and healthy controls (N=7) using the magnetoenterogram (MENG), which uses a Superconducting QUantum Interference Device (SQUID) to convert magnetic fields associated with intestinal slow waves into voltage signals. Second Order Blind Identification (SOBI) was used to reduce noise and isolate the intestinal slow wave signal from confounding magnetic artifact, and we computed the power spectrum of the intestinal slow wave using a Fast Fourier Transform technique. We analyzed dominant frequency, amplitude and percentage of power distributed (PPD) in brady, normo and tachyarrhythmic frequency ranges. Results. In gastroparesis patients, we found a significant decrease in postprandial dominant intestinal slow wave frequency from 10.2 ± 0.4 cpm to 8.8 ± 0.5 cpm (p<0.05) whereas the dominant frequency for control subjects increased from 9.9 ± 0.5 cpm to 10.8 ± 0.4 cpm (p<0.05). We did not observe significant differences in pre- and postprandial PPDs computed from controls or patients. Conclusions. Diabetic gastroparesis is associated with bradyarrhythmia, but not uncoupling, of the intestinal slow wave. Biomagnetic measurements of the MENG can assess intestinal slow wave activity in healthy and diseased tissue noninvasively.
Su1450 Gastric Mucosal Innervation in Endoscopic Biopsies in Patients With Idiopathic Gastroparesis Is Not Significantly Different Than Normals Ya-Yuan Fu, Sameer Dhalla, Joyce M. Koh, Shazia M. Siddique, Chun-Hao Lee, Carlos R. Mendez, Pankaj J. Pasricha Background & Aims: A major barrier to improving our understanding of motility is disorders is lack of easy access to deeper layers of the gastrointestinal wall where the major elements of the enteric nervous system are located. A recent study has suggested that gastric mucosal nerve density using endoscopic biopsies may be a useful biomarker for diabetic autonomic neuropathy with changes in density and morphology (Neurology. 2010 Sep 14;75(11):97381). We hypothesized that similar changes may be observed in idiopathic gastroparesis (IG). To this end, we developed a method to quantify the complex neuronal networks in the mucosal biopsies obtained during routine endoscopy using high-resolution three-dimensional (3-D) microscopy. Methods: Endoscopic biopsies were obtained from the body and antrum of the stomach of 10 Normal (i.e. no overt gastric motility disorder nor suggestive cardinal symptoms of the same) and 8 IG patients (with documented delayed emptying by standardized 4 hour scintigraphy). Nerves were visualized by staining for PGP9.5, a pan-neuronal marker. Type IV collagen staining was also performed to delineate the boundary between the mucosa and submucosa. Deep-tissue staining, optical-clearing, and 3-D confocal microscopy were combined to acquire two 150-μm-depth image stacks for each sample. 3-D images of nerve fibers were reconstructed and gastric mucosal nerve density quantified by Avizo 7.1. Results: The nerve length density (nerve total length [μm]/tissue total volume [μm3]) in stomach body and antrum of IG patients was similar to that of normal patients (in body, 0.0019 vs. 0.0021, μm/μm3, p=0.597; in antrum, 0.0016 vs. 0.0017, μm/μm3, p=0.628). The nerve volume density (nerve total volume [μm3]/tissue total volume [μm3]) of the IG patients was also not different from controls. We also calculated the average nerve fiber size, which tended to be smaller in IG in antral biopsies (p=0.07). Conclusions: In this pilot sample, the microstructure, nerve length, and nerve volume are not significantly different in IG vs. controls. While more patients are being recruited with both IG and diabetic gastroparesis, it is unlikely that in IG at least, changes in mucosal nerves alone will be a useful biomarker.
Su1449 Incidence and Clinical Significance of Delayed Gastric Emptying for Liquids in Gastroparesis and Chronic Unexplained Nausea and Vomiting (CUNV) Pankaj J. Pasricha, Katherine P. Yates, John O. Clarke, Thomas L. Abell, James Tonascia, Linda Nguyen, Gianrico Farrugia, Kenneth L. Koch, William J. Snape, William L. Hasler, Sameer Dhalla, Ellen M. Stein, Linda A. Lee, Jorge Calles, Irene Sarosiek, Richard W. McCallum, Frank A. Hamilton, Henry P. Parkman Background. Gastroparesis has traditionally been defined by emptying of a solid meal. By contrast, the clinical relevance of liquid emptying in patients with gastroparesis has not been well studied. Further, it is not clear whether a liquid emptying test increases the diagnostic yield in patients with otherwise unexplained nausea and vomiting. Methods. We include patients enrolled in the NIDDK Gastroparesis Registry who had undergone both solid and liquid emptying tests, usually in the form of a combined test using Tc-99m labeling for the solid meal and Indium-111 for the liquid (water). Gastric retention of Tc-99m > 60% at 2 hours and/or > 10% at 4 hours was considered evidence of delayed gastric emptying of solids; rapid gastric emptying of solids was defined as < 35% retention of Tc-99m at 1 hour; delayed gastric emptying of liquids in the presence of solids is greater than 50% retention of In-111 at 1 hour. Results. Of a total of 136 patients (33% diabetic, 85%female) analyzed, 86 (63%) had delayed solid emptying, 45 (33%) had normal solid emptying and 5 had rapid emptying. and 45 (33%) had delayed liquid emptying. Of these 45 patients with delayed liquid emptying, 37 (82%) also had delayed solid emptying and seven (15%) had normal solid emptying, with 1 having rapid emptying. Conversely, only 7 of 45 (16%) patients with normal solid emptying had delayed liquid emptying as compared with 37 of 86 patients (43%) with delayed solid emptying (P=0.002). Liquid emptying correlated highly with solid emptying among all patients (Figure). Compared to patients with delayed liquid emptying and delayed solid emptying, all patients with delayed liquid emptying alone were females (100% versus 70%; p=0.17) and were all idiopathic (100% versus 62%); p=0.08). Further, more of them had a history of an acute infectious prodrome (57% versus 19%; P= 0.05). Regardless of the results of solid emptying, patients with delayed liquid emptying had similar overall GCSI scores to other patients; however, retching scores were higher (P= 0.04) and GERD scores tended to be higher (P=0.10). Conclusions. (1) More than 40% of gastroparetic patients with delayed solid emptying also have delayed liquid gastric emptying (2) Patients with delayed liquid emptying alone tend to be idiopathic, female and more likely to have a post-infectious syndrome (3) Patients with delays in both solid and liquid emptying are generally very similar in demographic and clinical attributes as compared with those with only delay in solid emptying (4) A relatively small number of patients with CUNV are found to have delayed liquid emptying on testing (4) In general, there is a strong correlation between liquid and solid emptying across the spectrum. Ongoing research using the Gastroparesis Registry will hopefully establish the utility of liquid gastric emptying.
The 3-D projections of innervation (pan-neuronal marker, PGP9.5, red) from normal stomach antrum biopsy (A) and idiopathic gastroparetic stomach antrum biopsy (B). The slimmer mucosal nerve fibers were observed in idiopathic gastroparesis. Dimensions: 1214.56 (X) × 1214.56 (Y) × 150 (Z) μm. Su1451 Dynamic Antral Scintigraphy Identifies Patterns of Gastric Contractility in Patients With Upper GI Motility Disorders: Comparison to Conventional Gastric Emptying Scintigraphy Data Jesus Diaz, Marvin Friedman, Jaibel Makiyil, Irene Sarosiek, Richard W. McCallum BACKGROUND Gastric emptying scintigraphy (GES) has become the recommended standard for the evaluation of patients with symptoms of an upper GI motility disorder (UGIMD). Dynamic antral scintigraphy (DAS) provides information on antral contractility noninvasively thus yielding additional information to supplement GES. OBJECTIVES Correlate the following parameters to conventional GES results: Frequency, rhythm, coordination, and
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AGA Abstracts