Yana Nikitina

Immunomodulation for treatment of drug and device refractory gastroparesis.

Objective Patients with generalized autoimmune dysautonomia may also present with gastroparesis. Immune dysfunction in such patients can be evaluated using antibodies to glutamic acid decarboxylase (GAD) and full thickness biopsy of stomach. In this study, we utilize immunotherapy for treatment of drug and Gastric Electrical Stimulation (GES) resistant gastroparetic patients with evidence of neuroinflammation on full thickness gastric biopsy and had positive GAD65 autoantibodies. Material and methods We conducted a retrospective chart review of 11 female patients with drug and device resistant gastroparesis. Patients were treated for a total of 8–12 weeks with either intravenous immunoglobulin (IVIg), or combined mycophenolate mofetil (MM) and methylprednisolone, or only MM. Patients were excluded if they had previous side effects from steroid therapy, low scores on dual-energy X-ray absorptiometry (DEXA) scan results, immune-compromised conditions with infections like tuberculosis and zoster. Symptoms of nausea, vomiting, abdominal pain, early satiety/anorexia, bloating and total symptom score (TSS) as reported by the patients were recorded before and after the treatment at a follow up visit 2 to 16 weeks after initiation of therapy. Results Maximum symptom improvement was seen in patients treated with IVIg (67%). 6 patients (55%) had improvement in vomiting, whereas 5 patients (45%) had improvements in nausea, abdominal pain and bloating. Conclusions Immunomodulatory therapy shows positive outcomes in improving vomiting symptom in some gastroparetic patients who have coexisting positive autoimmune profiles. This preliminary data suggests the need for further investigations in immunotherapy targeted to patients with gastroparetic symptoms refractory to approved drug and device therapies.

Analysis of Adipose Tissue Lipid Using Mass Spectrometry

Mass spectrometry technology has enabled significant advances in detailing the alterations of the lipidome in response to pathological conditions or experimental manipulations. Lipids comprise a wide range of compounds with functions that include structural, intracellular signaling, trafficking, and storage. Characterization of lipid species has evolved significantly over recent years due to the progress made in the area of mass spectrometry. This chapter details the methods used for the analysis of lipids tailored to the intrinsic characteristics of adipose tissue. Particular attention is given to the analysis of triglycerides, diacylglycerols, and phospholipid.

Gastric Dysmotility and Low Serum Vitamin D Levels in Patients with Gastroparesis

Nutritional abnormalities are common in patients with gastroparesis (Gp), a disorder that may affect gastric motility and may delay emptying. The aim of this work was to identify relationships between serum nutrition markers including 25-OH vitamin D and gastric motility measures in Gp patients. We enrolled 59 consecutive gastric motility clinic patients (48 females, 11 males; mean age 44 years; 42 idiopathic; 17 diabetes mellitus) with Gp symptoms. The 25-OH vitamin D levels, for most patients slightly above the lower limit of normal (96.98 nmol/l ± 60.99), were lowest in diabetic range (DM) (75.68 nmol/l ± 34.22) vs. idiopathic (ID) (105.03 nmol/l ± 67.08) gastroparesis patients. First hour GET: one unit increase in 25-OH vitamin D level was associated 0.11% improvement (95% CI -0.22, 0.01 p=0.056) in gastric motility in all patients; this association, although marked in ID Gp patients, (-0.13, CI -0.25, -0.01 p=0.034), was not seen in DM Gp, (0.2, CI -0.45, 0.87, p=0.525). Fourth hour GET: Every unit increase of 25-OH vitamin D was associated with significant improvement in all patients, ( 0.11% CI -0.23, 0.01, p=0.053), and some weak improvement in ID group, (0.11% -0.24, 0.01, p=0.076) and absent in patients with DM (0.03, CI -0.66, 0.72, p=0.932). It is concluded that 25-OH vitamin D levels may influence gastric emptying. Underlying mechanisms for this observation might include the impact of 25-OH vitamin D on the health of the enteric nervous system. 25-OH vitamin D contributions to enteric nerve functions should be explored, particularly where autonomic nervous system comorbidities exist.

Tu2101 Gastric Myenteric Plexus Changes and Autonomic Dysfunction in Patients With Chronic Migraine and Gastroparesis

groups according to Rome III classification; postprandial distress syndrome (PDS, n = 67) and epigastric pain syndrome (EPS, n = 36). Since irritable bowel syndrome (IBS) tends to overlap with FD, the patients with IBS symptoms were not excluded. Questionnaire including FD, GERD and IBS symptoms was used. Fasting blood sample for acylated ghrelin, leptin and serotoin levels by ELISA method and two body specimens for evaluating the relative amount of mRNA expression of ghrelin and leptin were compared. Results: Compared to the control (14.4%), the FD group (28.4%) had more patients with IBS symptom (P = 0.016). Plasma acylated ghrelin level of FD was significantly lower than that of control (P = 0.036), while there was no significant difference in leptin and serotonin levels between control and FD (P = 0.123 and P = 0.442, respectively). In addition, when we subclassified FD to PDS and EPS, plasma acylated ghrelin level of PDS was significantly lower than EPS and control (P = 0.013, P = 0.003). On the other hand, plasma leptin in EPS was higher than that of control (P = 0.038). However, no significant difference was shown in quantity of mRNA expression of ghrelin and leptin (P = 0.538 and P = 0.796, respectively). Conclusion: Our results suggest that acylated ghrelin might play an important role in development of PDS and leptin may be related with the pathophysiology of EPS via posttranslational modification.

Su1563 Evaluation and Treatment of Gastric Stimulator Failure

Introduction: Some patients who undergo gastric electrical stimulation (GES) for gastroparesis (GP) develop recurrent symptoms i.e.: vomiting, nausea, early satiety, bloating, and abdominal pain despite an initial good result, replete with a functioning stimulator and unbroken leads. This study evaluates treatment for these patients, which includes temporary stimulation at a new gastric location and if symptoms are relieved this is followed by implantation of new leads and stimulator. We expect symptom scores to significantly decrease in the control group; we hypothesize that the symptom scores will also show a significant decrease in the replacement group. Patients: 15 patients with recurrent symptoms after placement of GES have undergone surgical insertions of a new gastric electrical stimulation (GES) system. Of the 15 replacement surgeries, 10 (67%) were female, 5 were male (33%) (mean age of all: 45), and 3 (20%) had diabetes-induced gastroparesis; the remainder (80%) were either idiopathic, post-surgical, or sarcoidosis-induced. Of 87 patients without recurrent symptoms after placement of GES who have not needed a replacement, 15 were selected as the control arm, matched by the three variables of investigator-derived independent outcome score (IDIOMS), baseline symptom scores before initial GES implantation, and etiology of disease (i.e. diabetic or idiopathic). Methods: Each patient met specific indications to receive GES replacement surgery. All patients had a preoperative diagnosis of either diabetic or idiopathic, drug-refractory, or post-surgical gastroparesis, and disordered gastric emptying with significant weight change. Patients with failed GES were evaluated over a 1-2 week period with insertion of a temporary endoscopic gastric stimulator. Patients with a positive response to temporary stimulation undergo GES replacement surgery. Common gastroparesis symptoms were evaluated before and after gastric pacemaker replacement using the Likert score system 0-4. These symptoms include vomiting, nausea, epigastric pain, early satiety and bloating. Results: See Tables 1 and 2. Total score of symptoms improved for 12 out of the 15 (80%) patients that underwent the GES replacement surgery. The frequency, amplitude, freq/ amplitude ratio (FAR), and gastric emptying times (GET) are displayed to reinforce physiological similarity between the two groups. Conclusion: Trial gastric mucosal electrical stimulation followed by implantation of new leads and stimulator successfully salvages the majority of patients whose gastric electrical stimulator is no longer relieving symptoms. Table 1 Comparison of Mean Pre-Op and Mean Post-Op Symptom Scores