Introduction: Gastric electrical stimulation (GES) is a surgically implanted treatment option for drug refractory gastroparesis syndromes. Evidence supporting use of GES and the pathophysiology of gastroparesis syndromes is not widely known. We conducted a descriptive review to elucidate the pathophysiology of gastroparesis syndromes, with particular focus on gastrointestinal neuromodulation and the known mechanisms of action of GES. Methods: A descriptive review of PubMed, Web of Science and Cochrane Library was conducted using the keywords gastric electrical stimulation, gastroparesis, nausea, vomiting, neuromodulation, gastroparesis syndromes, central nervous system, gastric pacing and electrical stimulation. Results: 1040 potentially relevant articles were identified, of which 34 were included. These studies explored various central and peripheral effects of GES, as well as its effect on quality of life, hospital stay, mortality and health-related costs. Conclusion: Although evidence supporting gastrointestinal (GI) electrical stimulation and GI neuromodulation use is not widely known, GES does seem to offer significant improvement in symptom control, quality of life and other effects to many patients. GES exerts its effects through multiple central and peripheral mechanisms and has potential to modify the natural history of disease. Future work on gastroparetic syndromes and their treatment might be better focused in terms of pathophysiologic mechanisms. Improving outcomes with specific neuromodulation therapies, like GES, may offer improvements in health for many patients with refractory upper gastrointestinal symptoms.

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INTRODUCTION: The widespread use of Angiotensin converting enzyme inhibitors (ACEi), especially lisinopril, and their association with colorectal cancer (CRC) has been studied with mixed results. Data suggest angiotensin II inhibition may decrease CRC risk. Contrasting studies suggest a role for kinins in pro-angiogenic effects with their accumulation blunting the effects of angiotensin II inhibition. Since ACEi’s affect both angiotensin II and bradykinin levels, we studied the effect of lisinopril on the risk of developing pre-cancerous (PC) colon polyps. METHODS: Data were collected on 3,541 patients admitted to the Louisville Veterans Affairs Medical Center, and 2,312 were excluded based on specific criteria, including pro-inflammatory states postulated to increase polyposis (e.g., IBD history and pre-existing malignancies). Of the 1,229 patients who were included, 393 (32%) used lisinopril; median age was 61; 88% of patients were male; and 24% were African American. Retrospective chart review of the patients’ active medications at the time of initial colonoscopy was done. Lisinopril use was further stratified by duration of usage. A Poisson Regression Model was employed for analysis with upper and lower bounds, and rate ratios (RR) with corresponding P-values calculated. Statistical significance was set at P < 0.05. Age, sex, race, smoking history, and NSAID use were controlled for. RESULTS: Our study indicates that long-term lisinopril use may be associated with increased PC colon polyp rates. Long-term (>10 years) lisinopril use was associated with a 35% increase in PC colon polyp risk (n = 46, RR = 1.35, P = 0.049). Short-term (<5 years) lisinopril use was associated with a 4%, statistically insignificant, increase in PC polyp risk (n = 273, RR = 1.04, P = 0.64). The total exposure (defined here as dose multiplied by years of use) of lisinopril did not show any difference in risk. CONCLUSION: The mechanisms of ACEi effects are complex and relate to their specific pharmacological properties. It needs to be determined whether or not the accumulation of kinins generated by ACEi’s attenuates their overall anti-angiogenesis effect. Our study indicates that long-term use of lisinopril, irrespective of dose, may increase PC colon polyp risk. This suggests that long-term usage changes the dynamics of the pro- and anti-neoplastic effects of ACEi’s. Larger studies are needed to determine the dose-duration relationship between ACEi and PC colon polyps, given their widespread use.