Gastroparesis: Concepts, Controversies, and Challenges

Abstract

Patients with gastroparesis often present a challenge to the treating physician. Postprandial symptoms with nausea and vomiting may not only lead to nutritional and metabolic consequences, but also cause significant disruptions to social activities that often center around food. While the definition of gastroparesis focuses on impaired gastric emptying, treatment options that affect gastric function are limited and often disappointing. The female predominance, the mostly idiopathic nature of the illness with a common history of abuse, and coexisting anxiety or depression show parallels with other functional disorders of the gastrointestinal tract. These parallels provided the rationale for some initial studies investigating alternative therapies that target the brain rather than the stomach. This emerging shift in medical therapy comes at a time when clinical studies suggest that gastric electrical stimulation may exert its effects by modulating visceral sensory processing rather than altering gastric motility. Physiologic and detailed anatomic investigations also support a more complex picture with different disease mechanisms, ranging from impaired accommodation to apparent visceral hypersensitivity or decreased interstitial cells of Cajal to inflammatory infiltration of myenteric ganglia. Delayed gastric emptying remains the endophenotype defining gastroparesis. However, our treatment options go beyond prokinetics and may allow us to improve the quality of life of affected individuals.

Bioengineered Human Pyloric Sphincters Using Autologous Smooth Muscle and Neural Progenitor Cells

“…Color images available online at www.liebertpub.com/tea Treatments for gastroparesis are rarely curative and primarily help manage the condition. [1][2][3][4] Alternative treatments for gastroparesis have produced mixed results. 3,4 Regenerative medicine approaches may provide long-term treatments for these diseases through the development of functional engineered pyloric sphincters that possess the appropriate smooth muscle and neural components to modulate relaxation of sphincter tone.…”

“…[1][2][3][4] Alternative treatments for gastroparesis have produced mixed results. 3,4 Regenerative medicine approaches may provide long-term treatments for these diseases through the development of functional engineered pyloric sphincters that possess the appropriate smooth muscle and neural components to modulate relaxation of sphincter tone. Evidence of the postnatal development of enteric nervous system indicates that SMCs in the gut mesenchyme release factors that stimulate NPC differentiation.…”

“…[1][2][3] Consequently, newer therapies are being developed and tested, however, these alternative treatments for delayed gastric emptying are producing mixed results. 1,4 One promising approach is targeting the function of the pyloric sphincter. Administration of botulinum toxin into the pyloric sphincter leads to significant improvements in gastric emptying, but these effects are only transient and long-term trials show no improvement compared to placebo.…”

The Framework of a Mathematical Model of the Autonomic Nervous System and Physiological Systems: Using the Neuroregulation of Blood Glucose as an Example

“…In recognition of these phenomena a number of tests [101][102][103][104][105][106] have been developed which attempt to quantify the level of autonomic dysfunction e.g. Stress-testing, Valsalva test, Tilt table test, etc; however these tests are experiential.…”

“…the quality and quantity of sleep, regulation of blood pressure and blood glucose, feelings of appetite and satedness, the function of the intestines and subsequently the quality of excrement, the frequency of urination, the smooth function of the lungs, regulation of acidity, menstrual cycle, etc. The development of pathological manifestations to cellular and molecular biochemistry is the consequence of this instability.In recognition of these phenomena a number of tests [101][102][103][104][105][106] have been developed which attempt to quantify the level of autonomic dysfunction e.g. Stress-testing, Valsalva test, Tilt table test, etc; however these tests are experiential.…”