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At 48-weeks, 42% of patients with an initial diagnosis of gastroparesis were reclassified as FD based on gastric-emptying results at this time point; conversely, 37% of patients with FD were reclassified as having gastroparesis
In a subset of patients, full-thickness biopsies of the stomach showed loss of interstitial cells of Cajal and CD206+ macrophages in both groups compared with obese controls.
The 48-week clinical outcomes were similar. Symptom severity remained “on average unchanged despite the change in gastric-emptying status”
My take (borrowed from authors): This study shows that “patients initially classified as one or the other are not distinguishable by clinical features or by follow-up assessment of gastric emptying…both disorders are unified by characteristic pathologic features, best summarized as a macrophage-driven “cajalopathy” of the stomach.”
While the authors state that a GES lacks reliability, the associated editorial argues that a GES may still be useful (J Tan et al. pg 1931. Full text: Gastroparesis: A Dead-end Street After All?) As individuals with delayed GE “fail to benefiit” from neuromodulators, a GES may influence treatment. However, they note that ACG guidelines indicate that a GES is not needed and all patients with dyspepsia symptoms can be treated in a “uniform sequence of proton pump inhibitors, tricyclic antidepressants and prokinetics as third-line therapy.”
Perhaps Socrates was a gastroenterologist. So much of what we think we know, we are finding out is poorly understood. This applies to gallbladder dyskinesia, sphincter of Oddi dysfunction and now gastroparesis.
A recent study (PJ Pasricha et al. Gastroenterol 2015; 149: 1762-74, commentary 1666-68) and commentary show how little we understand about gastroparesis.
The study was a large prospective surgery of 262 adult patients with gastroparesis (either diabetic or idiopathic).
28% had improvement in the gastroparesis cardinal symptom index (GCSI) at 48 weeks. Beyond 48 weeks, there were no significant reductions through week 192.
Favorable characteristics: male gender, age 50 and older, initial infectious prodrome (18% of cohort), antidepressant usage, and 4-hour gastric retention greater than 20%.
Unfavorable characteristics: obesity, smoking, use of pain modulators, moderate to severe abdominal pain, severe reflux, and moderate to severe depression.
The commentary suggests that those with the higher GCSI improved, in part, because of a regression toward the mean bias. Other important commentary:
“More severely delayed gastric emptying was associated with a greater likelihood of improvement”
“There was no differences in outcome between diabetic or idiopathic gastroparesis.”
Gastric emptying tests are not reliable: “Pathophysiologic tests are useful in clinical practice if they are reproducible, explain the symptoms, guide therapeutic choices, and determine response to therapy and long-term prognosis. Despite its popularity, the gastric emptying test scores low on most of these criteria.”
“A metaanalysis found no correlation between the change in gastric emptying rate and the symptom response during prokinetic therapy…A 5-year prospective follow-up study of …functional dyspepsia…found that more than 50% improved…with no relation to the presence of delayed gastric emptying.”
“Using the term gastroparesis also can lead to premature closure in our efforts to understand the pathophysiology of symptoms…can lead to botulinum injections into the pylorus or placement of gastric stimulators (formerly called gastric pacemakers) for gastroparesis, both of which have been shown to be nonefficacious in controlled trials.”
My take: It is unclear “when to consider gastric emptying testing and how to use it in patient management.” For the pediatric population, gastroparesis is more likely to be associated with a prodromal infection which increases the likelihood of recovery.
Virtually everyday, families that I care for are trying to ascertain the link between their GI symptoms and the foods in their diet. Many authoritative recommendations on irritable bowel have concluded that “food allergies (symptoms caused by an immune response) are rarely the culprit in IBS patients. Most IBS patients with food-related symptoms have food sensitivities or intolerances, which are not caused by an immune response.” (From Univ Virginia Irritable Bowel Diet PDF)
Whether the process is a sensitivity or an immune-reaction, many patients are quite sensitive to certain foods and many have had improvement with a low FODMAPs diet.
A much closer look at this problem with confocal laser endomicroscopy (CLE), in a pilot study (Gastroenterol 2014; 147: 1012-20), has shown measurable changes within five minutes of a food challenge that takes place during an endoscopy. In this study, the researchers examined 36 patients with IBS who had suspected food intolerance and 10 control patients with Barrett’s esophagus. Then during an endoscopy, the researchers used provoking solutions of cow’s milk, wheat, yeast, or soy. The subjects had CLE before and after the challenges. To enhance visualization of changes, subjects had fluorescein dye injected intravenously prior to examination of the duodenum.
In 22 of 36 patients, the challenges were considered positive. These patients had mucosal changes including increase in intraepithelial lymphocytes, followed by disruption of the villi tips/shedding of cells, then fluorescein leakage into the lumen.
None of the control patients exhibited these changes.
19 of 22 patients with positive challenges had a >50% reduction, after 4-weeks, in symptom score with individualized diet based on inciting antigen.
This provocative study indicates that subtle mucosal changes can occur in a number of IBS patients in a quick and direct response to food challenges. Perhaps when we look closer with technologies like CLE we will find more answers as to why certain foods provoke symptoms in adults and children with IBS.
Over 24 months, 60% had significant improvement regardless of treatment
The second study by Rodriguez et al is titled “Clinical Presentation, Response to Therapy, and Outcome of Gastroparesis in Children.”
Restrospective study with 230 children, mean age 9 years. In adolescents, female gender was more common (77%) whereas in infants (n=36), male gender was more common (61%). Most common causes were postviral in 42%, mitochondrial in 18%, and diabetes in 5%.
Delayed gastric emptying was defined as having solids or liquids emptying <40% of the meal at one hour.
Resolution occurred in 22% at 6 months, 53% at 18 months, and 61% at 36 months. Median time to resolution was 14 months; though among resolvers, 84% did so by 12 months.
Presence of longer duration of symptoms and mitochondrial disorder was associated with lower rates of resolution.
Younger age and response to promotility agents increased likelihood of resolution
Treatment with proton pump inhibitors (PPIs) were used in 79% as first-line agents; only 3% reported resolution of symptoms with PPIs.
Prokinetics: Domperidone (0.1-0.2mg/kg/dose qid to max of 10mg) in 33 patients. Tegaserod in 20 patients. Metoclopropramide in 142 patients. Erythromycin (EES) in 40 patients (3-10 mg/kg/dose qid). Of these agents, metoclopropramide was inferior with an 80% failure rate. In contrast, EES was associated with symptom resolution in 5% and symptom improvement in 46%. Domperidone was associated with symptom resolution in 26% and symptom improvement in 48%.
The third study by Bhardwaj et al highlights “Impaired Gastric Emptying and Small Bowel Transit in Children with Mitochondrial Disorders.”
Prospective study enrolled 26 subjects from mitochondrial clinic. 58 patients were screened but the majority were not eligible; the most common reasons included the following: 14 were receiving enteral feedings, 1 was receiving parenteral nutrition, 6 had no GI symptoms.
Delayed gastric emptying was considered if >50% at 90 minutes of a solid meal was present, at 60 minutes for semisolid, and at 40 minutes for liquid meal. For small bowel transit, delayed transit was considered if radiotracer had not reached cecum within 4 hours. Severely prolonged transit was diagnosed if transit time exceeded 6 hours.
In this cohort, 18 (69%) had delayed gastric emptying and 12 (46%) had prolonged small bowel transit. Common symptoms included abdominal pain and vomiting.
In the small numbers of patients who received prokinetics,there was a poor response. One of three patients with bethanecol and two of five patients with metoclopropramide had normalized GE time; one patient treated with azithromycin continued with abnormal GE time
-Gastroenterol 2011; 140: 101. Clinical features -mostly females, often incr BMI. Defined as severe gastroparesis if >35% at 4hrs, moderate if 20-35%, and mild if <20%.
-Clincal Gastro & Hep 2011; 9: 5. Review of diabetic gastroparesis & mgt.
-Clin Gastro & Hep 2009; 7: 823. Radiation from gastric emptying is ~10mrad, CXR is 12mrad, yearly background is 300mrad.
1 hr 37-90%
2 hr 30-60%
4 hr 0-10%
-Gastroenterol 2009; 136: 1526. Tests of gastric emptying -review.
-Clin Gastro & Hep 2008; 6: 1309. algorithm for nausea & delayed GE. REC;
1. small meals, low fiber/fat
2. prokinetic: reglan, EES, ?domperidone
3. Antiemetics: zofran, prochloroperazine
5. ?Botox injection
6. jejunal feeds