I read with great interest the recently published review article “Mechanisms in bariatric surgery: Gut hormones, diabetes resolution, and weight loss” by Holst et al. The study is published in Surgery for Obesity and Related Diseases journal, May 2018 issue. Continue reading “How Does Bariatric Surgery Work? A New Review Article” →

“Gastric pouch emptying of solid food in patients with successful and unsuccessful weight loss after Roux-en-Y gastric bypass surgery” by L.N. Deden et al is a recent publication in SOARD (Surgery for Obesity and Related Disorders). In this interesting article, the authors attempt to elucidate gastric bypass mechanism of action by studying gastric pouch solid food emptying. Altered gastro-intestinal motility is one of the most plausible mechanisms of action of weight loss surgery. Indeed, obesity and type 2 diabetes may be considered gastro-intestinal motility disorders resulting in abnormal post-prandial neuro-hormonal reaction to ingested food.

Several studies in the past have demonstrated that both gastric sleeve surgery and gastric bypass procedure increase gastric emptying and favor food dumping into the intestine stimulating the secretion of gut peptides like GLP-1 and PYY. In this article, the authors demonstrate the opposite; Increased gastric pouch emptying is associated with poor weight loss in a pilot study of 10 patients. The authors compared gastric pouch emptying in 5 gastric bypass patients with successful weight loss to a group of 5 gastric bypass patients with poor weight loss at least 2 years after surgery. they found that the faster emptying rate is mainly due to the first 15 minutes following food ingestion. The authors conclude that if their hypothesis is proven narrowing gastric pouch outlet may lead to decreased food emptying and as a result improved weight loss.

The idea of food retention in the stomach or gastric pouch leading to satiety and consequently weight loss is quite naïve. Gastric pouch outlet narrowing can only result in heartburn and esophageal dysmotility. We have had plenty of experience with this concept in Lap Band patients. We also know that endoscopic gastro-jejunostomy narrowing in the case of gastric bypass does not result in improved and durable weight loss. Accelerated food delivery into the intestines has been established in multiple studies evaluating gastric bypass and sleeve gastrectomy patients. Indeed, I have developed an effective surgery for gastroparesis based on these studies. I doubt that the results published by Deden et al will be reproducible by other investigators. Nonetheless, the authors raise an important question and studying gastro-intestinal motility in weight loss surgery patients will help elucidate some of the mechanisms of action underlying gastric bypass and sleeve gastrectomy.

Gastric emptying is a complex and highly coordinated process that remains poorly understood. Several nutrient stimulated neuro-hormonal signals emanating from the gastro-duodenal control gastric emptying. Since we lack the tools to measure in-vivo gastric emptying James Brasseur, a bio-engineer, at the university of Pennsylvania, developed a computer simulation model of the stomach. Using this model, Brasseur et al were able to numerically calculate intra-gastric fluid motions. In 2006, they published an interesting study, in the journal of Biomechanics, titled “A Stomach Road or Magenstrasse for Gastric Emptying”. In this study, Brasseur demonstrates the existence of early post-prandial rapid emptying. The emptying pattern occurs along the lesser curvature and channels food particles from the fundus into the duodenum before any significant digestion has occurred. The researchers found that gastric fundus contractions in coordination with gastric antrum contractions results in Magenstrasse emptying pattern.

Why does the Magenstrasse exist? The authors of this interesting article explain that a “spot of highly concentrated lipid or glucose in liquid or semi-solid form… rather than waiting patiently in the fundus while the antrum and corpus empties… moves rapidly along the Magenstrasse, bypassing most of the fundus, corpus and antrum, and enters the bowels rapidly in highly concentrated form and leaving behind 77% of gastric content”. This sounds like a Roux-en-Y gastric bypass procedure or sleeve gastrectomy mechanism of action. For Brasseur el al, however, the only potential usage of the Magenstrasse is rapid drug delivery into the intestines. In fact, in 2006, the mechanism of action of bariatric surgery was still unknown. Accelerated gastric emptying and dumping to stimulate neuro-endocrine hormones like GLP-1 were not described at that time.

In my opinion, dysfunction in the Magenstrasse gastric emptying results in diseases like obesity, type 2 diabetes, gastroparesis and GERD. Weight loss surgery in the form of gastric bypass and sleeve gastrectomy restores the dumping function of the Magenstrasse. The Magenstrasse emptying pattern is crucial to maintaining healthy gut to food interaction. Brasseur el al have found that “The strength of antral motility relative to fundus-induced contractions affects the extent and density of the Magenstrasse”. The coordination of contractile waves between gastric fundus, where food is received, and gastric antrum, where food is ground and mixed, determines the magnitude of the Magenstrasse. Surgical manipulation of the gastric fundus in the form of sleeve gastrectomy seems to restore the Magenstrasse emptying leading to resolution of obesity and diabetes.

Gastric fundus invagination or sleeve gastrotomy brings the gastric fundus in close proximity to the antrum. It would be interesting to apply Brasseur’s mathematical gastric model to study the effect of sleeve gastrotomy on fundic and antral contractions and their effect on the Magenstrasse. I predict that gastric fundus invagination restores the Magenstrasse leading to weight loss, diabetes resolution and possibly curing gastroparesis similar to sleeve gastrectomy.

In 1908, Waldeyer described a longitudinal fold along the lesser curvature of the stomach that he called Magenstrasse. The Magenstrasse is a gastric canal that carries liquid and solid food particles from the cardia, along the lesser curvature and down to the pylorus very quickly. A sample of ingested food is emptied along the Magenstrasse before the stomach is filled. This early gush of food into the duodenum generates several neuro-hormonal signals that prepare the intestines and other organs for the upcoming meal. Glucagon like peptide or GLP-1 is one of those signals and it is probably the most studied intestinal hormone. GLP-1 is secreted by L cells that are mainly located in the distal gut. GLP-1 stimulates post-prandial insulin secretion and inhibits gastric emptying. GLP-1 plays a central role in glucose homeostasis. GLP-1 secretion peaks shortly after a meal is ingested and prior to any significant gastric emptying. It is logical to assume that GLP-1 secretion depends on food delivery into the duodenum via the Magenstrasse pathway. Therefore, loss of the Magenstrasse emptying pathway leads to deficient GLP-1 and other neuro-hormone secretion leading to elevated post-prandial blood and abnormal insulin secretion. Indeed, one of the earliest signs of type 2 diabetes is loss of the post-prandial GLP-1 peak secretion.

Sleeve gastrectomy restores the Magenstrasse pathway of gastric emptying. In fact, during sleeve gastrectomy, most of the stomach is resected preserving the longitudinal fold that was described in 1908 by Waldeyer. Sleeve gastrectomy increases gastric emptying. Gastric sleeve surgery results in post-prandial GLP-1 increase and blood glucose improvement. Currently, there is plenty of evidence in the literature that type 2 diabetes and obesity, like gastroparesis, are gastrointestinal motility disorders. Weight loss surgery in the form of sleeve gastrectomy restores normal gastric emptying patterns, like the Magentrasse, resulting in diabetes resolution and weight loss.

Gastric emptying is a complex process that is a carefully regulated. Neuro-hormonal regulatory mechanisms synchronize the emptying process to achieve optimal nutrient digestion and absorption. Ghrelin is a potent stimulator of gastric contractions and emptying, and GLP-I profoundly inhibits this emptying process. Numerous other signals participate in this process and are yet to be fully elucidated. The sharp rise and fall of these hormones, after food intake, control one of the most important aspects of life: energy metabolism. Unless we understand the interaction between foregut and ingested food, we cannot understand diseases like obesity, type 2 diabetes and gastroparesis, nor can we develop better, safer and less invasive treatment modalities. In my next blog, I will revisit the subject of gastric fundus invagination and its effect on the Magenstrasse pathway of emptying.

I read with great interest this new study published by O’Grady el al in Obesity Surgery journal and titled “Patterns of Abnormal Gastric Pacemaking After Sleeve Gastrectomy Defined by Laparoscopic High-Resolution Electrical Mapping”. The authors attempt to study gastric electric activity following resection of the greater curvature in gastric sleeve surgery patients. Gastric pacemaker cells also known as the cells of Cajal are in higher concentration along the greater curvature. The cells of Cajal are also distributed throughout the gastrointestinal tract including the esophagus, small intestine, colon and pancreas. There are different types of cells of Cajal and each type plays a different role. Some generate intrinsic electrical rhythmicity in smooth muscle cells and others have mechano-receptor properties. They play a role in coordinating gastro-intestinal motility and their absence or dysfunction is associated with gastrointestinal disorders like irritable bowel syndrome, gastroparesis, achalasia, and hypertrophic pyloric stenosis. Gastrointestinal motility is a complex and highly regulated process that remains poorly understood. Gastrointestinal motility is crucial to life and several diseases like obesity, type 2 diabetes and gastroparesis are associated with gastrointestinal dymotility. Several studies have demonstrated that gastric emptying is accelerated following sleeve gastrectomy. We have taken this finding and applied to several gastroparesis patients. By performing a modified sleeve gastrectomy that preserves the gastric antrum and resects the gastric fundus, we demonstrated an increase in gastric emptying. The underlying mechanisms of such observations are not understood. However, it appears that by resecting the pacemaker cells of Cajal along the greater curvature gastric emptying increases. There is strong agreement in the literature that the cells of Cajal generate gastric slow wave depolarizations. Gastric slow waves can be measured using electric mapping.

In this article, O’Grady attempts to evaluate the effect of gastric sleeve surgery on gastric slow-wave pacemaking using laparoscopic high-resolution electric mapping. Mapping was performed on 8 patients before and after gastric sleeve resection. Slow wave activity parameters included propagation pattern, frequency, velocity, and amplitude. The authors show that the wave velocity significantly increased following gastric sleeve surgery whereas the frequency and amplitude remained unchanged. 50% of the patients developed a distal unifocal ectopic pacemaker with retrograde propagation. The remaining 50% showed no electrical activity. The significance of these findings is unknown. Do patients with bioelectrical quiescence following sleeve gastrectomy loose less weight than those with accelerated retrograde slow wave propagation? Is accelerated retrograde slow wave propagation associated with increased incidence of postoperative GERD? What happened to gastric slow wave propagation one year after surgery and is weight regain following sleeve gastrectomy associated with changes in gastric bioelectric activity?

Understanding gastrointestinal motility and its underlying bioelectrical activity is crucial to elucidating the pathophysiology of many diseases like obesity, type 2 diabetes and gastroparesis. These healthcare issues affect millions of people worldwide. New noninvasive, accurate and sensitive testing modalities need to be developed to evaluate gastrointestinal bioelectric activity in health and disease.

Surgical manipulation of the gastric fundus by resection, plication, invagination or bypass results in physiologic changes. These changes have immediate and significant therapeutic effect leading to improvement and sometimes cure of chronic progressive diseases like obesity, GERD, gastroparesis and type 2 diabetes. Indeed, the most effective and most reliable treatment for morbid obesity and type 2 diabetes is gastric fundus resection in the form of sleeve gastrectomy, or gastric fundus bypass in the form of Roux-en-Y gastric bypass surgery. Similarly, the best treatment for acid reflux disease is a 360 or 270-degree fundoplication. As for gastroparesis, I have had great success performing a longitudinal gastrectomy that preserves the gastric antrum and resects most of the gastric fundus to promote gastric emptying.

The oldest surgery performed on the gastric fundus to alter a pathophysiologic process was the Nissen fundoplication. Dr Nissen came across his procedure by serendipity more than 50 years ago. It is thought that wrapping the gastric fundus around the lower esophagus, reinforces the lower esophageal sphincter leading to acid reflux control. However, we know now that acid reflux disease is a multifactorial problem and the exact mechanism of Nissen fundoplication is not well understood. Rather than increasing the resting lower esophageal sphincter pressure, Nissen fundoplication alters gastric motility and emptying patterns favoring cephalad movement of gastric content away from the gastro-esophageal junction. A short and floppy fundoplication that avoids constricting the lower esophageal sphincter is currently the accepted surgical standard. The purpose of fundoplication surgery is to reconfigure the gastric fundus anatomy and wall compliance rather than reinforce the lower esophageal sphincter. Similarly, gastric fundus resection in sleeve gastrectomy results in increased gastric emptying and altered gastro-intestinal neuro-hormonal signaling. Such physiologic changes are more important than mechanical restriction to achieve significant and durable weight loss as well as type 2 diabetes remission. Few years ago, I published a case report about a type 2 diabetes patient with severe and medically refractory gastroparesis. The patient had been constantly vomiting and had lost significant amount of weight. He was TPN dependent to meet his calorie needs and replace his electrolytes. His stomach and duodenum were dilated. I performed a longitudinal gastrectomy that preserved the antrum. Due to his malnutrition, I elected to preserve some of the gastric fundus and body. I also performed a side to side duodeno-jejunostomy to decompress the dilated duodenum. Patient’s gastroparesis related symptoms immediately resolved and tolerated liquid diet on day one after surgery. His diet was rapidly advanced to regular food and 4 years following surgery the patient remains asymptomatic. Interestingly, the patient type 2 diabetes of 15 years resolved and his blood sugar normalized as he was regaining all his lost weight. The case clearly illustrated the relationship between gastric fundus surgery and gastric emptying and their effect on type 2 diabetes remission.

Gastric fundus anatomy and physiology plays a crucial role in the pathophysiology of many diseases that have reached an epidemic level in our society. Gastric fundus surgery alters gastro-intestinal motility patterns leading to improvement and most often remission of obesity, GERD, type 2 diabetes and gastroparesis.

Reference:
Laparoscopic longitudinal gastrectomy and duodenojejunostomy for treatment of diabetic gastroparesis. Surg Obes Relat Dis. 2012 Nov-Dec;8(6):811-3.
Darido E, Farrell TM.

A prospective study titled “The effect of sleeve gastrectomy on GLP-1 secretion and gastric emptying” has recently been published in SOARD (Surgery for Obesity and Related Disorders) journal. Sista el al demonstrate that gastric sleeve surgery results in significant increase in both gastric emptying rate and post-prandial GLP-1 secretion, 3 months after surgery for both solids and liquids.

The authors attribute the increased gastric emptying following sleeve gastrectomy to altered stomach functional anatomy and gastric fundus accommodation reflex. Furthermore, they show a strong linear correlation between percentage gastric retention rate and post-prandial GLP-1 blood levels. The authors conclude that accelerated gastric emptying following gastric sleeve surgery increases GLP-1 secretion by distal intestinal L cells most likely by increasing undigested nutrient transit across the small intestine. Chronic exposure to a high nutrient flux into the intestine enhances intestinal nutrient sensing leading to increased GLP-1 secretion.

Indeed, the central mechanism of action of metabolic and weight loss surgery is altering the interaction between ingested food and gastro-intestinal tract. Altered interaction results in the secretion of several neuro-endocrine signals like GLP-1 that results in weight loss, improved blood glucose levels, insulin secretion and insulin resistance…

Unfortunately, research in this field remains weak. Most bariatric related research and publications are still focused on the outdated concept of mechanical restriction. New procedures like gastric balloon and gastric plication (endoscopic or laparoscopic) are developed and offered as effective weight loss solutions.

Gastrointestinal motility research is vital in elucidating the mechanism of action of bariatric surgery. Gastroparesis, GERD, type 2 diabetes and obesity are different kinds of gastro-intestinal motility disorders. Unraveling the mechanisms of gastro-intestinal motility in health and disease will yield great solutions to these disorders that have reached epidemic levels.

Glucagon-like peptide-1, GLP-1, is the most studied gut hormone. It promotes weight loss, increases satiety and stimulates insulin secretion while blocking glucagon release. Gastric bypass surgery and gastric sleeve procedure result in significant post-prandial increase in GLP-1. Continue reading “The GLP-1 Debate” →

Appetite control is a major factor when it comes to successful weight loss. Hunger is a powerful built in survival drive controlled by the brain. It is difficult if not impossible to subdue your hunger using will power. Many neuro-hormonal signals contribute to a delicate hunger-satiety balance. Among these hormones are ghrelin and leptin, both secreted by the gastric fundus. Continue reading “Gastric Leptin and The Feeling of Fullness after Metabolic Surgery?” →