Review article: the impact of bariatric surgery on gastrointestinal motility.

BACKGROUND: Obesity is a major medical problem worldwide. Different treatment modalities have emerged to treat obese patients, but the best long-term results are achieved with bariatric surgery. Currently, the interventions most commonly performed are laparoscopic adjustable gastric banding (LAGB), Roux-en-Y- gastric bypass (RYGB) and sleeve gastrectomy. AIM: To review the gastrointestinal motor complications associated with each of these types of bariatric interventions and the clinical implications of such complications. METHODS: Search of medical database (PubMed) on English-language articles from January 1996 to March 2011. The search terms used were laparoscopic adjustable gastric banding (LAGB), sleeve gastrectomy (LSG), roux-en-Y-gastric bypass (RYGB), using the AND operator with the terms: complications, motility, GERD, reflux, gastric emptying, esophagitis, dysphagia. RESULTS: Of the three bariatric interventions reviewed, LAGB was the most studied. Most studies reported short follow-up, of ≤ 1 year. Oesophageal motor dysfunction is the most common motility complication following the bariatric interventions that were reviewed and is mainly observed after LAGB. Some data suggest that oesophageal motor function testing predicts development of post-operative symptoms and oesophageal dilation. RYGB offers protection from gastro-oesophageal reflux. Sleeve gastrectomy was the least studied and was associated with an acceleration of gastric emptying. CONCLUSIONS: The effects of these interventions on GI motility should be considered when selecting patients for bariatric surgery. There is scant information regarding the overall effect of sleeve gastrectomy on gastro-oesophageal reflux patterns and oesophageal motility.

Efficacy of the glucagon-like peptide-1 agonist exenatide in the treatment of short bowel syndrome.

BACKGROUND: Short bowel syndrome (SBS) is a serious clinical disorder characterized by diarrhea and nutritional deprivation. Glucagon-like peptide-1 (GLP-1) is a key hormone, produced by L-cells in the ileum, that regulates proximal gut transit. When extensive ileal resection occurs, as in SBS, GLP-1 levels may be deficient. In this study, we test whether the use of GLP-1 agonist exenatide can improve the nutritional state and intestinal symptoms of patients with SBS. METHODS: Five consecutive patients with SBS based on ≤90 cm of small bowel and clinical evidence of nutritional deprivation were selected. Baseline SBS symptoms, demographic and laboratory data were obtained. Antroduodenal manometry was performed on each subject. Each patient was then started on exenatide and over the following month, the baseline parameters were repeated. KEY RESULTS: The subjects consisted of four males and one female, aged 46-69 years. At baseline, all had severe diarrhea that ranged from 6 to 15 bowel movements per day, often occurring within minutes of eating. After exenatide, all five patients had immediate improvement in bowel frequency and form; bowel movements were no longer meal-related. Total parenteral nutrition was stopped successfully in three patients. Antroduodenal manometry revealed continuous low amplitude gastric contractions during fasting which completely normalized with exenatide. CONCLUSIONS & INFERENCES: Exenatide is a novel and safe treatment option for SBS. It produced substantial improvement in the bowel habits, nutritional status and quality of life of SBS patients. Successful treatment with exenatide may significantly reduce the need for parenteral nutrition and small bowel transplant.

Redefining the role of lymphocytes in gastroesophageal reflux disease and eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) and reflux esophagitis (RE) overlap clinically and histologically. RE is characterized by epithelial infiltration with small numbers of neutrophils and eosinophils, EoE by a prominent eosinophilic infiltrate. Lymphocytic esophagitis (LE), a new entity characterized by peripapillary lymphocytosis, questions the role lymphocytes play in esophageal inflammation. We test the hypothesis that lymphocyte infiltration in RE differs from EoE. One blinded pathologist read esophageal biopsies from 39 RE and 39 EoE patients. Both groups demonstrated significant numbers of lymphocytes (RE 22.7 +/- 2.2/HPF, EoE 19.8 +/- 1.8/HPF). Eosinophils/HPF in RE and EoE were 2.8 +/- 0.7 and 74.9 +/- 8.2, respectively (P < 0.001). Neutrophils were uncommon in RE (0.26 +/- 0.16/HPF) and EoE (0.09 +/- 0.04; P = 0.07). Eight of the 39 RE specimens had >or=50 lymphocytes in >or=1 HPF. Two were consistent with LE. There was an inverse correlation between numbers of eosinophils and lymphocytes in EoE (R = -0.47; P = 0.002), and no correlation between them in RE (R = 0.18; P = 0.36). The patients with EoE who used antireflux medications had fewer lymphocytes (16.3 +/- 1.3 vs 22.2 +/- 2.3/HPF; P = 0.030) and eosinophils (55.6 +/- 5.2 vs 76.0 +/- 8.7/HPF; P = 0.042) than those who did not. The pathological role of lymphocytes in RE and EoE may be underestimated. Our observation that 5% of the RE specimens meet histopathological criteria for LE potentially blurs the line between these entities. The observation that eosinophil counts are lower in EoE when antireflux meds are used supports the notion that reflux plays a role in the clinical expression of EoE.

The use of gastric electrical signals for algorithm for automatic eating detection in dogs.

Food ingestion increases fundic impedance (FI) and reduces antral slow wave rate (SWR). Our aim was to determine if such changes can be integrated into an algorithm for automatic eating detection (AED). When incorporated in implantable medical devices, AED can time treatment to food intake without need for patient input. Four dogs were implanted with fundic and antral electrodes, connected to an implantable recording device. Changes in FI and SWR induced by fixed meals of different weights were determined, and were used to build an AED algorithm. Its performance was then tested on the same animals given an ad libitum access to food. The effects of gastric balloon distension and nitroglycerin on SWR and FI were also tested. Fixed meals reduced SWR in a weight-dependent manner, R(2) = 0.936, P < 0.05 baseline compared to 50, 100, 200 and 400 g. Meals increased FI above baseline in a weight-dependent manner; R(2) = 0.994, P < 0.05 baseline compared to 200 and 400 g. During ad libitum intake, the AED algorithm detected 86% of all meals > or =15 g. Gastric distension reduced SWR and increased FI. Nitroglycerin reduced SWR. AED, using changes in FI and gastric SWR is feasible. Changes in FI and SWR are induced primarily by the presence of food in the stomach.

Distribution of interstitial cells of Cajal and nitrergic neurons in normal and diabetic human appendix.

The objective of this study was to determine the distribution of enteric nerves and interstitial cells of Cajal (ICC) in the normal human appendix and in type 1 diabetes. Appendixes were collected from patients with type 1 diabetes and from non-diabetic controls. Volumes of nerves and ICC were determined using 3-D reconstruction and neuronal nitric oxide synthase (nNOS) expressing neurons were counted. Enteric ganglia were found in the myenteric plexus region and within the longitudinal muscle. ICC were found throughout the muscle layers. In diabetes, c-Kit positive ICC volumes were significantly reduced as were nNOS expressing neurons. In conclusion, we describe the distribution of ICC and enteric nerves in health and in diabetes. The data also suggest that the human appendix, a readily available source of human tissue, may be useful model for the study of motility disorders.

Circadian patterns of gastric electrical and mechanical activity in dogs.

Gastric motor function assessment, in humans and animals, is typically performed for short recording periods. The aim of this article was to monitor gastric electrical and motor activity in the antrum and fundus simultaneously, for long periods, using a new implantable system. Ten dogs were implanted with fundic and antral electrodes for assessment of impedance and electrical activity. Dogs were studied while in cages, for periods of 22-26 h. From late evening and until feeding on the next day, slow wave (SW) rhythm demonstrated a distinct pattern of intermittent pauses (mean duration = 22.8 +/-4.1 s) that delineated groups of SW's. Phasic increases in fundic tone were seen mostly in association with SW pauses, and were highly correlated with antral contractions, R(2) = 0.652, P < 0.05. The SW rate (events per minute) in the postprandial period, fasting and night time was 4.2 +/- 0.2, 5 +/- 0.2 and 4.7 +/- 0.3, respectively, P < 0.05 postprandial vs other periods. Antral and fundic mechanical activities were highly correlated during fasting, particularly at night. This novel method of prolonged gastric recording provides valuable data on the mechanical and electrical activity of the stomach, not feasible by current methods of recording. During fasting, fundic and antral motor activities are highly correlated and are associated with periodic pauses in electrical activity.

Neural gastrointestinal electrical stimulation enhances colonic motility in a chronic canine model of delayed colonic transit.

Neural gastrointestinal electrical stimulation (NGES) induces sequential contractions and enhances emptying in acute canine gastric and colonic models. This study was set to determine (i) the effect of NGES in a chronic canine model of delayed colonic transit and (ii) possible mechanism of action. Four pairs of electrodes were implanted in the distal colon of nine mongrel dogs. Delayed colonic transit was induced by diphenoxylate/atropine and alosetron. Transit was fluoroscopically determined by the rate of evacuation of radiopaque markers, and was tested twice in each dog, in random order, on and off stimulation. Two stimulation sequences, separated by 1 min, were delivered twice a day via exteriorized electrodes. Colonic manometry during stimulation was performed before and after intravenous (i.v.) injection of 1 mg of atropine. Complete evacuation of all markers was significantly shortened by NGES, from 4 days to 2 days, interquartile range 3-4 days vs 2-3 days, respectively, P = 0.016. NGES induced strong sequential contractions that were significantly diminished by atropine: 190.0 +/- 14.0 mmHg vs 48.7 +/- 19.4 mmHg, respectively (P < 0.001). NGES induces strong sequential colonic contractions and significantly accelerates movement of content in a canine model of delayed colonic transit. The effect is atropine sensitive.

Treatment of gastroparesis: a multidisciplinary clinical review.

This clinical review on the treatment of patients with gastroparesis is a consensus document developed by the American Motility Society Task Force on Gastroparesis. It is a multidisciplinary effort with input from gastroenterologists and other specialists who are involved in the care of patients with gastroparesis. To provide practical guidelines for treatment, this document covers results of published research studies in the literature and areas developed by consensus agreement where clinical research trials remain lacking in the field of gastroparesis.

Adverse effects of laxatives.

Laxatives are among the most commonly used drugs or additives. Most are quite safe when used judiciously, intermittently when possible, and in the absence of contraindications. Bulking agents and nonabsorbable compounds such as lactulose can cause bloating but have very few serious adverse effects except for the allergic reaction to psyllium preparations. Osmotic laxatives containing poorly absorbable ions such as magnesium or phosphate can cause metabolic disturbances, particularly in the presence of renal impairment. However, if taken intermittently, in the absence of conditions such as ileus or bowel obstruction, they have few adverse effects. Polyethylene glycol solutions are emerging as an effective and safe mode of treatment for chronic constipation. Of stimulant laxatives, senna compounds and bisacodyl are the most commonly used. Although there are data to support the neoplastic potential of this class of drugs in in vitro studies, epidemiologic data in humans so far has not established a clear link between these laxatives and colonic neoplasia. The link between stimulant laxatives and structural changes, such as the "cathartic colon" or enteric nerve damage, is not well established either. Danthron compounds should be avoided because of hepatotoxicity.

Loss of interstitial cells of cajal and inhibitory innervation in insulin-dependent diabetes.

BACKGROUND & AIMS: Gastrointestinal complications of long-standing diabetes include nausea, vomiting, abdominal pain, diarrhea, and constipation. The pathophysiology underlying these symptoms is poorly understood. Recent evidence suggests an important role for interstitial cells of Cajal in controlling gastrointestinal motility. The aim of this study was to determine changes in interstitial cells of Cajal and enteric innervation in a patient with insulin-dependent diabetes. METHODS: A full thickness jejunal biopsy was obtained from a 38-year-old insulin-dependent diabetic with evidence for diabetic gastroenteropathy. Immunohistochemistry, confocal microscopy, and 3-dimensional reconstruction techniques were used to quantify changes in the volume of interstitial cells of Cajal and enteric innervation. RESULTS: Interstitial cells of Cajal were markedly decreased throughout the entire thickness of the jejunum. A decrease in neuronal nitric oxide synthase, vasoactive intestinal peptide, PACAP, and tyrosine hydroxylase immunopositive nerve fibers was observed in circular muscle layer while substance P immunoreactivity was increased. CONCLUSIONS: The data suggest that long-standing diabetes is associated with a decrease in interstitial cells of Cajal volume and a decrease in inhibitory innervation, associated with an increase in excitatory innervation. The changes in interstitial cells of Cajal volume and enteric nerves may underlie the pathophysiology of gastrointestinal complications associated with diabetes and suggest future therapeutic targets.

Salivary growth factors and cytokines are not deficient in patients with gastroesophageal reflux disease or Barrett's esophagus.

Growth factors, such as epidermal growth factor (EGF), are known to protect upper gut mucosa against irritants and to enhance healing of ulcerative lesions in animal models. A number of salivary growth factors are found in human saliva. The aim of this study was to determine if salivary growth factors and cytokines are deficient in patients with esophagitis or with Barrett's metaplasia. Fifteen healthy subjects, eight patients with esophagitis, and 13 patients with Barrett's metaplasia were included. Salivary concentration of EGF, FGF, IL-1, and IL-6 were measured during esophageal saline and hydrochloric acid perfusion and in the postprandial state. There was no statistically significant difference in the concentration of EGF or cytokines among the three study groups in each experimental condition or among the three experimental conditions in each group. FGF basic could not be detected in saliva. In conclusion, these findings do not support the hypothesis that a deficiency in salivary growth factors or cytokines plays a significant role in the development of mild to moderate reflux esophagitis or Barrett's metaplasia.

A review of diabetic gastropathy.

Diabetes mellitus affects various organs, including the gastrointestinal tract. The stomach is commonly affected, and symptoms related to the upper GI tract are frequently reported. Management of diabetic gastropathy involves dietary modifications, pharmacological agents, and occasionally, alternative feeding methods.

Celiac disease is highly prevalent in lymphocytic colitis.

A high frequency of celiac disease is reported in patients with collagenous colitis. Limited information is available on the frequency of celiac disease in lymphocytic colitis. The aim of our study was to determine the prevalence of celiac disease in microscopic colitis (collagenous and lymphocytic colitis). Patients were identified from a pathology registry of microscopic colitis from 1987 to 1999. Pathology reports and medical records were reviewed for previous small bowel biopsies and/or celiac serology. We identified 113 patients with microscopic colitis, and 46 patients underwent a small bowel biopsy and/or celiac serology. Of these, 27 patients had lymphocytic colitis (63% female; age, 58.6 +/- 16.2 years) and 19 patients had collagenous colitis (79% female; age, 61.8 +/- 13.6 years). Small bowel biopsy alone was performed in 28 of 46 patients, celiac serology alone was performed in 10, and both small bowel biopsy and celiac serology were performed in 8. Celiac disease was identified in 4 patients by small bowel histology; all had lymphocytic colitis (4 of 27 patients, 15%). This frequency of celiac disease is significantly higher than the highest reported U.S. prevalence of celiac disease (4/1,000 individuals; p < 0.01). There is a high frequency of celiac disease in patients with lymphocytic colitis. Given the importance of the early detection of celiac disease, it should be excluded in all patients with lymphocytic colitis, particularly if diarrhea does not respond to conventional treatment.

Small bowel motility: ready for prime time?

The primary function of the small bowel is the absorption of nutrients, and the motor patterns of the healthy bowel are intended to promote that function. The motor patterns of the small bowel are the result of close interaction between the enteric nervous system, extrinsic nerves, regulatory peptides, and the intestinal smooth muscle. The basic electrical rhythm governing intestinal contractions is determined by specialized pacemaker cells called the interstitial cells of Cajal. Diseases affecting any of these components may result in intestinal dysmotility and its associated symptoms. Although transit studies and intestinal manometry are helpful in the diagnosis of dysmotility, our understanding of pathophysiology is hampered by the difficulties involved in obtaining and analyzing intestinal tissue. Treatment of intestinal dysmotility relies on dietary manipulations and nutritional support (enteral or parenteral) because there is no drug therapy that can effectively enhance the propulsive function of the small bowel. Small bowel transplantation remains a life-saving intervention for patients who fail to respond to other therapies.

Diabetic gastropathy: a practical approach to a vexing problem.

The clinical presentation of diabetic gastropathy varies, and a diagnosis usually must be confirmed with tests that evaluate the structure and function of the upper gut. Although glucose control, dietary changes, and drug therapy are the current mainstays of treatment, they may not be effective. Gastric pacing, a new technique that stimulates gastric motility, may give physicians another management tool.

Colonic motor function in humans is not affected by gender.

Functional abdominal pain, including the irritable bowel syndrome, is more common in females. Our aim was to determine if differences in motility or biomechanical properties of the colon could account for this gender difference. In 18 healthy subjects (nine males), a catheter assembly incorporating a balloon and perfused side holes, connected to a barostat, was positioned in the left colon. The system was used to determine compliance, sensation in response to phasic balloon distension, and changes in motor activity and tone in response to a meal. There was no significant difference in any of these variables between males and females. We conclude that there is no gender difference in colonic motor function or sensation to balloon distension. The increased prevalence of irritable bowel syndrome in females may be related to psychosocial factors rather than differences in colonic motor function.

Fecal incontinence: a practical approach to evaluation and treatment.

Fecal incontinence is a common problem and can have a major impact on the quality of life of those affected. Various disease processes affecting stool consistency, rectal sensitivity, or the anal sphincters can cause fecal incontinence. Obstetric trauma is now known to be a major cause of sphincter dysfunction. The evaluation of the patient with incontinence helps to determine the choice of therapy-medical or surgical. The two most important tests are anorectal manometry, which provides information on sphincter pressures, and rectal sensation, and anal endosonography, which is currently the test of choice for defining the anatomy of the anal sphincters. The choice of therapy depends on the etiology of incontinence, the anatomy of the sphincters, and also on the effect of incontinence on the quality of life of the patient. Control of diarrhea, regardless of the cause, should be attempted first. Biofeedback therapy is effective in the majority of patients and is particularly attractive because it is safe and well tolerated. Surgery is offered when medical therapy is unsuccessful or when the etiology is thought to respond best to surgery, such as in postobstetric trauma. Sphincter repair, for treatment of selective sphincter defects, is the best surgical option. Neoanal sphincters and implanted artificial sphincters are far less attractive because of technical difficulties and low success rate.

Intestinal motility in small bowel diverticulosis: a case report and review of the literature.

Small bowel diverticulosis is a rare disease that is usually associated with recurrent pseudo-obstruction, bacterial overgrowth, and malabsorption. The more severe complications include hemorrhage and perforation. There is evidence to suggest that this entity is a result of small bowel motor dysfunction. For this reason, it has been associated with disorders in which a myopathic or neuropathic process is involved, such as scleroderma. The majority of patients with jejunal diverticulosis do not require surgery and can be managed medically. We report a case of jejunal diverticulosis in a 63-year-old gentleman who presented with symptoms of pseudo-obstruction. Ambulatory duodenojejunal manometry revealed several abnormalities suggestive of small bowel motor dysfunction. Enteroclysis, however, did not find evidence of mechanical obstruction, and the patient had marked improvement with cisapride and antibiotics.

Saliva and esophageal protection.

There has been much interest in recent years in the potential protective role of saliva in the esophagus. Variables such as salivary volume and neutralizing capacity have been studied both during basal conditions and in response to esophageal acid exposure, in healthy subjects and in patients with esophagitis. In addition to its known neutralizing capacity, saliva also contains growth factors. These polypeptides (of which epidermal growth factor has been studied most) have cytoprotective and healing properties in various segments of the gastrointestinal tract. Therefore, a deficiency in one or more of these growth factors might be a contributing factor in the development of gastroesophageal reflux disease (GERD) or its complication, such as Barrett's metaplasia. However, human studies have produced contradictory results regarding salivary growth factor deficiency in such patients. Current methods of investigation make it difficult to assess the importance of saliva in GERD. This may be due in part to the multifactorial nature of the disease and the difficulty in long-term, selective manipulation of salivary function in humans. Given the present data in the literature, it is therefore unknown if saliva plays an important role in esophageal protection.