Stimulation of the autonomic nervous system in colorectal surgery: a study protocol for a randomized controlled trial

BACKGROUND: Postoperative ileus (POI) is a well-known complication of abdominal surgery and is considered to be caused by a local inflammation in the gut. Previously it has been shown that both local and systemic inflammation can be reduced by stimulation of the autonomic nervous system via lipid rich nutrition. Stimulation of the autonomic nervous system releases acetylcholine from efferent vagal nerve endings that binds to nicotinic receptors located on the inflammatory cells leading to a decrease of pro-inflammatory mediators. Besides administration of nutrition there are other ways of stimulating the autonomic nervous system such as gum chewing. METHODS/DESIGN: This prospective, placebo-controlled randomized trial will include 120 patients undergoing colorectal surgery which are randomized for gum chewing preoperatively and in the direct postoperative phase or a placebo. Postoperative ileus will be assessed both clinically by time to first flatus and time to first defecation and by determination of gastric motility using ultrasound to measure dimensions of the antrum. Furthermore the inflammatory response is quantified by analyzing pro-inflammatory mediators. Finally, markers of gut barrier integrity will be measured as well as occurrence of postoperative complications. DISCUSSION: We hypothesize that chewing gum preoperatively and in the direct postoperative phase in patients undergoing colorectal surgery dampens local and systematic inflammation, via activation of the autonomic nervous system. Down-regulation of the inflammatory cascade via stimulation of the vagus nerve will ameleriote POI and enhance postoperative recovery. TRIAL REGISTRATION: NTR286

Nutritional stimulation of cholecystokinin receptors inhibits inflammation via the vagus nerve

The immune system in vertebrates senses exogenous and endogenous danger signals by way of complex cellular and humoral processes, and responds with an inflammatory reaction to combat putative attacks. A strong protective immunity is imperative to prevent invasion of pathogens; however, equivalent responses to commensal flora and dietary components in the intestine have to be avoided. The autonomic nervous system plays an important role in sensing luminal contents in the gut by way of hard-wired connections and chemical messengers, such as cholecystokinin (CCK). Here, we report that ingestion of dietary fat stimulates CCK receptors, and leads to attenuation of the inflammatory response by way of the efferent vagus nerve and nicotinic receptors. Vagotomy and administration of antagonists for CCK and nicotinic receptors significantly blunted the inhibitory effect of high-fat enteral nutrition on hemorrhagic shock-induced tumor necrosis factor-α and interleukin-6 release (P < 0.05). Furthermore, the protective effect of high-fat enteral nutrition on inflammation-induced intestinal permeability was abrogated by vagotomy and administration of antagonists for CCK and nicotinic receptors. These data reveal a novel neuroimmunologic pathway, controlled by nutrition, that may help to explain the intestinal hyporesponsiveness to dietary antigens, and shed new light on the functionality of nutrition

The gut-liver axis

PURPOSE OF REVIEW: The liver adaptively responds to extra-intestinal and intestinal inflammation. In recent years, the role of the autonomic system, intestinal failure and gut microbiota has been investigated in development of hepatic, intestinal and extra-intestinal disease. RECENT The autonomic nervous system can be stimulated via enteral fat leading cholecystokinin release, stimulating receptors in the gut and in the promotes bowel integrity, dampening the inflammatory response to food Consensus exists that intravenously administered long-chain fatty acids liver damage but randomized-controlled trials are lacking. Disruption of enterohepatic circulation of bile salts can give rise to cholestasis and nonalcoholic fatty liver disease, which may progress to fibrosis and Reduced intestinal availability of bile salts reduces stimulation of the farnesoid X receptor. This may induce hepatic bile salt overload and hepatotoxicity through reduced action of intestinal fibroblast growth Evidence is put forward to suggest that the intestinal microbiota is with liver abnormalities. SUMMARY: Enteral lipids reduce inflammation damage during stress or systemic inflammation, whereas parenteral lipid associated with liver damage. Maintaining the enterohepatic circulation salts limits hepatic cholestasis through an farnesoid X receptor pathway. Changes in gut microbiota composition may induce liver disease

Esophageal Cancer After Bariatric Surgery: Increasing Prevalence and Treatment Strategies

Purpose The number of bariatric procedures has increased exponentially over the last 20 years. On the background of ever-increasing incidence of esophageal malignancies, the altered anatomy after bariatric surgery poses challenges in treatment of these cancers. In this study, an epidemiological estimate is presented for the future magnitude of this problem and treatment options are described in a retrospective multicenter cohort.Methods The number of bariatric procedures, esophageal cancer incidence, and mortality rates of the general population were used for epidemiological estimates. A retrospective multicenter cohort was composed; patients were treated in three large oncological centers with a high upper gastrointestinal cancer caseload. Consecutive patients with preceding bariatric surgery who developed esophageal cancer between 2014 and 2019 were included.Results Approximately 3200 out of 6.4 million post bariatric surgery patients are estimated to have developed esophageal cancer between 1998 and 2018 worldwide. In a multicenter cohort, 15 patients with esophageal cancer or Barrett's esophagus and preceding bariatric surgery were identified. The majority of patients had a history of Roux-en-Y gastric bypass (46.7%) and had an adenocarcinoma of the distal esophagus (60%). Seven patients received curative surgical treatment, five of whom are still alive at last follow-up (median follow-up 2 years, no loss to follow-up).Conclusion Based on worldwide data, esophageal cancer development following bariatric surgery has increased over the past decades. Treatment of patients with esophageal cancer after bariatric surgery is challenging and requires a highly individualized approach in which optimal treatment and anatomical limitations are carefully balanced

STATISTICAL METHOD IN GEOPHYSICS PROSPECTING

Let us consider (see figure 1) a very deep horizontal layer of&lt;br /&gt;the earth's crust. The lower line signifies a limit more or less defined.&lt;br /&gt;The simplest possibility which can he supposed is tliat on this limit&lt;br /&gt;the shear components of the stress-tensor (the componente which produce&lt;br /&gt;the angular distortion of an element of the body) are very small&lt;br /&gt;here or even disappear. This can take place either if in the neighbourhood&lt;br /&gt;of the limit the temperature approaches a degree where&lt;br /&gt;the distortion effects disappear and only the pressure components of&lt;br /&gt;the stress-tensor exist, or if the nearest lower consists of a loose body.&lt;br /&gt;But these two examples do not exhaust ali possi bilities. In the first&lt;br /&gt;approximation the limit surface of every two layers lias the supposed&lt;br /&gt;property. Finally, if we wish to reach a higher degree of approximation,&lt;br /&gt;we can always introduce some more complex boundary condition