Cajal Cell Counts are Important Predictors of Outcomes in Drug Refractory Gastroparesis Patients With Neurostimulation.

BACKGROUND AND AIMS: Cajal cells serve as the pacemaker cells of the gastrointestinal tract and regulates peristalsis. On the baisis of that fact, it has been hypothesized that a decrease in Cajal cells can lead to gastroparesis and other motility issues. Treatment with medications has a limited efficacy and most resort to gastric electrical stimulation (GES) devices for symptomatic relief. We believe that the number of Cajal cells present is directly proportional to symptomatic relief with GES. MATERIALS AND METHODS: Twenty-three (white female) subjects were recruited from the gastric motility clinic University of Mississipi for this study with the criteria of drug refractory gastropersis. Symptoms were measured using Likert scale and gastric emptying times were measured pre-GES and post-GES. Serosal electrogram measurements were recorded during surgical placement of permanent electrical stimulator under various modes. Cajal cell count scoring via immunohistochemistry were performed during the implantaion of the GES. RESULTS: The data were grouped in 2 categories based on the Cajal cells that is ≥2.00 and <2.00. Subjects with higher Cajal cells reported a statiscially improvement in gastroperesis symptoms. Significant differences were also noted in the first hour gastric emptying study. The mean group difference is 17.5 (95% confidence interval, 1.41-33.58; P=0.035). Serosal amplitude differences were noted being significantly higher in the group with ≥2 cajal cells. CONCLUSIONS: Electrograms obtained after GES demonstrates immediate improvement in gastric electrical activity and gastroparesis symptoms in patients with relatively higher Cajal cell counts when compared with patients with extensive loss of Cajal cells.

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 electrical stimulation for abdominal pain in patients with symptoms of gastroparesis.

Abdominal pain physiology may be better understood studying electrophysiology, histology, and symptom scores in patients with the symptoms of gastroparesis (Gp) treated with gastric electrical stimulation (GES). Ninety-five Gp patients' symptoms were recorded at baseline and during temporary and permanent GES. Gastric-emptying times and cutaneous, mucosal, and serosal electrogastrograms were obtained. S100-stained, full-thickness gastric biopsies were compared with autopsy controls. Sixty-eight patients reported severe pain at baseline. Severe pain patients' mean pain scores decreased with temporary GES from 3.62 to 1.29 (P < 0.001) and nonsevere pain from 1.26 to 0.67 (P = 0.01). With permanent GES, severe mean pain scores fell to 2.30 (P < 0.001); nonsevere pain changed to 1.60 (P = 0.221). Mean follow-up was 275 days. Mean cutaneous, mucosal, and serosal frequencies and frequency-to-amplitude ratios were markedly higher than literature controls. For patients with Gp overall and subdivided by etiology and severity of pain, S-100 neuronal fibers were significantly reduced in both muscularis propria layers. GES improved severe pain associated with symptoms of Gp. This severe pain is associated with abnormal electrogastrographic activity and loss of S100 neuronal fibers in the stomach's inner and outer muscularis propria and, therefore, could be the result of gastric neuropathy.

Long-term effects of gastric stimulation on gastric electrical physiology.

INTRODUCTION: This study evaluates the modeling of gastric electrophysiology tracings during long-term gastric electrical stimulation for gastroparesis. We hypothesized that serosal electrogastrogram may change over time representing gastric remodeling from gastric stimulation. PATIENTS: Sixty-five patients with gastroparesis underwent placement of gastric stimulator for refractory symptoms. Mean age at initial stimulator placement was 44 years (range, 8-76), current mean age was 49, and the majority of the subjects were female (n = 51, 78 %). Only a minority had diabetes-induced gastroparesis (n = 16, 25 %); the remainder were either idiopathic or postsurgical. METHODS: At the time of stimulator placement, electrogastrogram was performed after the gastric leads were placed but before stimulation was begun. Patients underwent continuous stimulation until pacer batteries depleted. At the time of replacement, before the new pacemaker was attached, electrogastrogram was again performed. RESULTS: After a mean of 3.9 years of stimulation therapy, the mean of baseline frequency before stimulation therapy was 5.06 cycles/min and declined to 3.66 after replacement (p = 0.0000002). The mean amplitude was 0.33 mV before stimulation therapy and decreased to 0.31 mV (p = 0.73). The frequency/amplitude ratio was 38.4 before stimulation therapy and decreased to 21.9 (p = 0.001). CONCLUSION: Long-term gastric electrical stimulation causes improvement in basal unstimulated gastric frequency to near normal.