Glass half empty? Lessons learned about gastroparesis

Abstract

Gastroparesis is defined as a combination of chronic dyspeptic symptoms and delayed emptying of a solid test meal. It remains a difficult-to-treat disorder with a significant impact on quality of life. Although gastroparesis is defined by delayed emptying, several important studies did not find a correlation between this biomarker and symptom severity or treatment success. Thus, some of the more recent trials explored strategies that ranged from antiemetics to antidepressants. Although dietary management showed benefit, most of the other interventions were barely superior to placebo or were not superior at all. Placebo responses were often quite high and this complicates the assessment of active agents. While it complicates the design and interpretation of clinical trials, high response rates for active and sham interventions indicate that we can achieve symptom relief in many patients and thus give them some reassurance. If indeed most therapies are only marginally better than placebo, the differences in adverse effects should be weighed more strongly, a point that is especially important in view of the controversy surrounding metoclopramide. Mechanistic studies introduced the network of macrophages as another potentially important player in the development of gastroparesis. Results are too preliminary and are largely based on preclinical data but show up- and downregulation of cellular elements controlling gastric function. Thus, future developments may teach us how they interfere with some of these mechanisms in clinical settings, potentially making gastroparesis a reversible process.

Dietary modifications achieved successful resolution of symptoms of gastroparesis diagnosed by demonstrating gastric food retention after overnight fasting in diabetic dialysis patients: two case reports with literature review

“…Sonographic study in case 2 of the present report actually showed solid gastric content despite the absence of food retention in a previous upper GI endoscopy. Persistent delayed gastric emptying despite relief from the symptoms in the present cases is consistent with the incomplete correlation between symptom improvement and acceleration of gastric emptying [2,11,12,20,21].…”

“…The correlation between gastric emptying and symptom severity is generally poor, as with the correlation between symptom improvement and acceleration of gastric emptying [1,2,11,12,20,21]. Recent studies demonstrated that coexisting anxiety and depression correlate with the perceived severity of gastroparesis symptoms [23,35].…”

“…The proposed mechanisms behind hypersensitivity to gastric distension include genetic factors, inflammation, central and peripheral dysregulation, and emotional factors [38]. Considering these recent findings, impaired gastric emptying remaining the defining endophenotype of gastroparesis is not sufficient to explain the complex symptoms and should not be the sole target of therapeutic interventions [11,12].…”

“…Gastric electrical stimulation has not been approved in Japan. While the definition of gastroparesis focuses on impaired gastric emptying, many pharmacological agents including prokinetics and surgical procedures designed to accelerate gastric emptying have shown disappointing results in randomized controlled studies [11,12]. The limited efficacy of available therapies often leads to frustration of patients and physicians.…”

Role of endoscopic functional luminal imaging probe in predicting the outcome of gastric peroral endoscopic pyloromyotomy (with video)

“…21,22 These findings indicate that GES is a less-reliable tool for assessment of gastroparesis symptoms. On the other hand, although the clinical success rate of G-POEM has not been compared with a placebo-controlled group, studies have shown a high placebo effect rate for other treatment options for gastroparesis, [23][24][25] suggesting that a placebo effect may have been contributing to the high clinical success rate of G-POEM. Sham-controlled studies are needed to objectively study the outcomes of G-POEM.…”