Upper GI Disorders: Pathophysiology and Current Therapeutic Approaches.

Symptoms referable to the upper digestive tract are associated with abnormalities of upper gastric neuromuscular function including abnormalities of motility, sensation, and absorption. Of the upper digestive tract, the stomach is of particular importance in its role in symptom generation and is highlighted in this chapter. Gastric symptoms can be associated with alterations in the rates of gastric emptying, impaired accommodation, heightened gastric sensation, or alterations in gastric myoelectrical activity and contractility. Treatment of gastric neuromuscular disorders requires an understanding of pathophysiology of the disorders, the appropriate use and interpretation of diagnostic tests, and the knowledge of effective treatment options. This chapter covers the pathophysiology and current treatment approaches to disorders of the upper gastrointestinal tract, focusing on classic disorders of the stomach, particularly gastroparesis and functional dyspepsia.

Dumping Syndrome: A Review of the Current Concepts of Pathophysiology, Diagnosis, and Treatment.

Gastric surgery has long been known to be a cause of dumping syndrome (DS). However, the increasing incidence of gastric bypass surgery, as well as reports of DS unrelated to previous gastric surgeries, has increased the importance of understanding DS in recent years. DS is due to the gastrointestinal response to voluminous and hyperosmolar chyme that is rapidly expelled from the stomach into the small intestine. This response involves neural and hormonal mechanisms. This review encompasses the symptoms, diagnosis, and treatment approaches of DS and also focuses on the current research status of the pathophysiology of DS.

[Dumping syndrome following gastric surgery]. / Dumpingsyndrom etter kirurgi på magesekken.

BACKGROUND: Dumping syndrome is the term used to describe a common set of symptoms following gastric surgery, and is characterised by postprandial discomfort which can entail nutritional problems. The condition was well known when surgery was the usual treatment for peptic ulcer disease. The increasing number of operations for morbid obesity means that the condition is once again of relevance, and health personnel will encounter these patients in different contexts. This article discusses the prevalence, symptomatology and treatment of dumping syndrome. MATERIAL AND METHOD: This review article is based on a selection of articles identified in PubMed and assessed as having particular relevance for elucidating this issue, as well as on the authors' own clinical experience. RESULTS: Early dumping syndrome generally occurs within 15 minutes of ingesting a meal and is attributable to the rapid transit of food into the small intestine. Nausea, abdominal pain, diarrhoea, a sensation of heat, dizziness, reduced blood pressure and palpitations are typical symptoms. Lethargy and sleepiness after meals are common. Late dumping syndrome occurs later and may be attributed to hypoglycaemia with tremors, cold sweats, difficulty in concentrating, and loss of consciousness. Dumping-related symptoms occur in between 20 and 50% of patients following gastric surgery. Early dumping syndrome is more frequent than late dumping syndrome. It is estimated that 10-20% of patients have pronounced symptoms and 1-5% have severe symptoms. The diagnosis is usually made on the basis of typical symptoms. Most patients experience alleviation of the symptoms over time and with changes in diet and eating habits. Further patient evaluation and drug or surgical intervention may be relevant for some individuals. INTERPRETATION: Dumping-related symptoms are common after gastric surgery. The extent of obesity surgery in particular means that health personnel should be familiar with this condition.

[Prevalence of early and late dumping after gastric bypass]. / Prévalence des dumpings précoce et tardif après bypass gastrique.

Gastric bypass surgery is an effective treatment of obesity, bringing a significant weight loss and a major improvement of carbohydrate profile. However, in some patients, a deregulation in carbohydrate metabolism between insulin secretion and sensitivity is observed, whereupon early and late dumping happen. Their prevalence isn't well studied, although it seems that 10 to 20% of patients are affected. We've studied a cohort of 70 patients who undergone gastric bypass surgery at the CHUV. 18 (25.7%) patients have a positive anamnesis for early dumping and 10 (14.3%) for late dumping, being it superior as what is described in the literature.

The role of dumping syndrome in weight loss after gastric bypass surgery.

BACKGROUND: Roux-en-Y gastric bypass is the most commonly performed operation for the treatment of morbid obesity in the US. Dumping syndrome is an expected and desired part of the behavior modification caused by gastric bypass surgery; it can deter patients from consuming energy-dense food. In this study we assessed the role dumping has in weight loss and its relationship with the patient's eating behavior. METHODS: Fifty patients who underwent gastric bypass between January 2008 and June 2008 were enrolled. Two questionnaires, the dumping syndrome questionnaire and the Three-Factor Eating Questionnaire (TFEQ), were used to record the patients' responses. The diagnosis of dumping syndrome was based on the Sigstad scoring system, where a score of 7 and above was considered positive. TFEQ evaluated the patients' eating behavior under three scales: cognitive restraint, uncontrolled eating, and emotional eating. The results were analyzed with descriptive and parametric statistics where applicable. RESULTS: The prevalence of dumping syndrome was 42 %, with 66.7 % of the subjects being women. The nondumpers were observed to have a greater mean decrease in body mass index than the dumpers at 1 and 2 years (18.5 and 17.8 vs. 14.4 and 13.7 respectively). There was no definite relationship between the presence of dumping syndrome and the eating behavior of the patient. However, the cognitive restraint scores, greater than 80 %, were associated with an average decrease in BMI of 19 and 20.8 at 1 and 2 years compared with 14.6 and 12.4 in those with scores less than 80 % (p = 0.01 and p = 0.03, respectively). CONCLUSION: The presence of dumping syndrome after gastric bypass does not influence weight loss, though eating behaviors may directly influence it.

Medical and surgical management of esophageal and gastric motor dysfunction.

he occurrence of esophageal and gastric motor dysfunctions happens, when the software of the esophagus and the stomach is injured. This is really a program previously established in the enteric nervous system as a constituent of the newly called neurogastroenterology. The enteric nervous system is composed of small aggregations of nerve cells, enteric ganglia, the neural connections between these ganglia, and nerve fibers that supply effectors tissues, including the muscle of the gut wall. The wide range of enteric neuropathies that includes esophageal achalasia and gastroparesis highlights the importance of the enteric nervous system. A classification of functional gastrointestinal disorders based on symptoms has received attention. However, a classification based solely in symptoms and consensus may lack an integral approach of disease. As an alternative to the Rome classification, an international working team in Bangkok presented a classification of motility disorders as a physiology-based diagnosis. Besides, the Chicago Classification of esophageal motility was developed to facilitate the interpretation of clinical high-resolution esophageal pressure topography studies. This review covers exclusively the medical and surgical management of the esophageal and gastric motor dysfunction using evidence from well-designed studies. Motor control of the esophagus and the stomach, motor esophageal and gastric alterations, treatment failure, side effects of PPIs, overlap of gastrointestinal symptoms, predictors of treatment, burden of GERD medical management, data related to conservative treatment vs. antireflux surgery, and postsurgical esophagus and gastric motor dysfunction are also taken into account.

Safety and efficacy of high-dose acarbose treatment for dumping syndrome.

Dumping syndrome (DS) is a complication of Nissen fundoplication. Dietary strategies can ameliorate symptoms, but this approach is not always foolproof. Limited evidence reports the efficacy of acarbose for children who are unresponsive to feeding manipulations. We report 8 patients with DS aged between 7 and 24 months. In 4 of 8 nutritional strategies failed, and acarbose treatment was started. The initial dose was 25 mg for meals, and increased until postprandial glucose was stable. In 3 of 4 children the final dose was higher than previously reported, without adverse effects. Acarbose is useful to treat DS in cases of failure of dietary strategies.

[Postgastrectomy symptoms following total gastrectomy with or without preservation of the duodenal passage]. / Postgastrectomiás tünetek totális gastrectomia után a duodenalis passage-t megorzo és kizáró rekonstrukciók mellett.

INTRODUCTION: Total gastrectomy leads to decreased quality of life, which is characterized by different symptoms of the postgastrectomy syndrome. Aim of this study was to investigate the correlation of different alimentary symptoms and habits in correlation with the reconstruction type after total gastrectomy. PATIENTS AND METHODS: Between 2005-2009 34 patients after total gastrectomy for gastric cancer were evaluated with questionnaires. Twenty two had a standard Roux-en-Y reconstruction, while 12 Longmire type jejunal interposition. Early dumping syndrome was investigated with the Sigstad score. RESULTS: Most of the investigated parameters were similar in Roux-en-Y and Jejunal Interposition patients. Early dumping syndrome however occurred significantly less frequantly after jejunal interposition. CONCLUSION: Preservation of the duodenal passage after total gastrectomy reduces the prevalence of early dumping.

[Postgastrectomy syndromes in therapeutic practice ].

AIM: To specify policy of nutritive support late after radical gastric resection. MATERIAL AND METHODS: Patients with postgastroresectional dystrophy were examined using standard techniques and estimation of intestinal electric activity (registration of body surface biopotentials on Conan-M myngograph). RESULTS: Frequency-amplitude parameters of the intestine serve the basis for choice of mixtures for enteral correction. Nutritive support provided for on demand pharmaconutrients--microbiotic correctors. CONCLUSION: Myography gives additional information for decisions on the policy of nutritive support.

Clinical features and gastric myoelectrical activity in patients with idiopathic and post-surgical rapid gastric emptying who present with unexplained chronic nausea.

BACKGROUND: The cause of chronic nausea can be difficult to diagnose. Idiopathic rapid gastric emptying (iRGE) can cause nausea, but limited literature exists on clinical and pathophysiological features. In contrast, dumping syndrome or post-surgical rapid gastric emptying (psRGE) is well-known and may present with early phase vasomotor symptoms, diarrhea, and late phase reactive hypoglycemia. Our aim is to compare clinical and gastric motility characteristics in patients with iRGE and psRGE and unexplained chronic nausea. METHODS: A retrospective study was conducted on patients with unexplained chronic nausea and RGE (<30% retention of a standard isotope-labeled solid meal at 1-h). Gastric myoelectrical activity (GMA) was recorded during water load satiety tests (WLST) using validated electrogastrogram (EGG) recording methods. KEY RESULTS: Thirty iRGE and sixteen psRGE patients with unexplained chronic nausea were identified; average 1-hour meal retention was 18.6% and 16.2%, respectively. Nausea, bloating, early satiety, and bowel function were similar in the two groups; fewer iRGE patients had abdominal pain and none had vasomotor symptoms. Normal 3 cpm GMA was recorded in 44% of iRGE vs 29% of psRGE, tachygastria in 13% vs 43%, bradygastria in 25% vs 14%, and mixed in 19% vs 14% (p values >0.05). Abnormal WLST volume (<300 ml) was found in 69% of iRGE and 43% of psRGE (p = 0.36). CONCLUSIONS & INFERENCES: (a) iRGE and psRGE patients may present with unexplained chronic nausea rather than classic vasomotor symptoms and diarrhea. (b) iRGE and psRGE patients had similar gastric dysrhythmias and accommodation dysfunction, which may contribute to RGE.

Prevalence and intensity of dumping symptoms and their association with health-related quality of life following surgery for oesophageal cancer.

BACKGROUND & AIMS: This study aimed to investigate the prevalence and intensity of symptoms of dumping syndrome (early and late) experienced by oesophageal cancer survivors one year after surgery and their association with health related quality of life (HRQL). METHODS: A prospective cohort study of patients who underwent surgery for oesophageal cancer in Sweden from January 2013 to April 2018, included at one year after surgery with follow-up at 1.5 years. Common symptoms of dumping syndrome were the exposure, classified as early and late onset, further divided into 'moderate' or 'severe' based on symptom intensity, and no dumping symptoms (reference group). The primary outcome was mean summary score of HRQL, and secondary outcomes were global quality of life, physical, role, emotional, cognitive and social function measured using the EORTC QLQ-C30 1.5 years after surgery. An ANCOVA model, adjusted for potential confounders was used to study the association between dumping symptoms and HRQL, presented as mean score differences (MD) with 95% confidence intervals (CI). RESULTS: Among 188 patients, moderate early dumping symptoms was experienced by 45% and severe early dumping by 9%. Moderate late dumping symptoms was reported by 13%, whereas 5% reported severe late dumping symptoms. Severe early dumping symptoms was associated with worse HRQL in 4 out of 7 aspects with worse global quality of life (MD -16, 95% CI: -27 to -4) and social function (MD -17, 95% CI: -32 to -3), which showed clinically large differences compared to having no such symptoms. Patients with moderate late dumping symptoms reported poorer HRQL in 6 out of 7 aspects compared to those with no dumping symptoms. Cognitive function (MD -27, 95% CI: -47 to -7) and emotional function (MD -24, 95% CI: -47 to -2) were significantly declined (clinically large relevance) in those with severe late dumping symptoms. CONCLUSIONS: Patients who have undergone curative treatment for oesophageal cancer experience reduced HRQL from early and late dumping symptoms at one year after surgery that indicate clear implications for clinical routine. Medical support and additional dietary counselling are required as potential ways to alleviate dumping symptoms on clinical repercussions.

Correlation between the length of the pyloric cuff and postoperative evaluation after pylorus-preserving gastrectomy.

BACKGROUND: Recent years have seen the preserved pyloric cuff being lengthened in pylorus-preserving gastrectomy for early gastric cancer. We performed clinical assessment of the symptoms after pylorus-preserving gastrectomy in patients treated at the National Cancer Center Hospital in Japan during the past 9 years. METHODS: Four hundred and fifty-six patients who had undergone pylorus-preserving gastrectomy and been followed up for at least 3 years were studied. We classified the patients into two groups according to the length of the pyloric cuff (group A, within 3.0 cm; group B, more than 3.0 cm). Medical records were reviewed for further histological and follow-up data. A questionnaire regarding dumping syndrome and gastric stasis was also completed by the patients. RESULTS: Our results showed no statistically significant differences in symptoms, such as dumping syndrome or emptying disturbances, between the two groups. CONCLUSION: Our study revealed that the differences in several functions and symptom scales were not pronounced between the two groups. Regardless of the length of the pyloric cuff, pylorus-preserving gastrectomy can be utilized for the treatment of early gastric cancer even if the tumor is located proximal to the middle body.

Dumping syndrome: establishing criteria for diagnosis and identifying new etiologies.

AIMS: To investigate the current incidence and identify the current etiologies of rapid gastric emptying (dumping syndrome) in patients with a spectrum of gastrointestinal symptoms, including nausea, vomiting, abdominal pain, or diarrhea. METHODS: The results for a 4-h radionuclide gastric emptying test (GET) using a standardized scintigraphic technique were reviewed in 545 patients to see which patients met criteria for rapid gastric emptying, defined as >50% emptying of isotope-labeled solid meal at 1 h. RESULTS: Forty-eight of 545 (8.8%) patients (28 females, mean age 46 +/- 2 years, range 32-58 years) had rapid GET. Seventeen of 59 (35%) met Rome III diagnostic criteria for cyclic vomiting syndrome (CVS). Twelve of these 59 (25%) patients were regarded as non-ulcer dyspepsia and six (13%) had dyspepsia in the setting of diabetes mellitus. Five (10.5%) were post-fundoplication surgery, where an accidental vagotomy was confirmed by sham meal challenge; previous gastric bypass surgery for obesity had been performed in three (6%) patients. Five (10.5%) patients with unexplained abdominal pain and diarrhea had the working diagnosis of irritable bowel syndrome. CONCLUSIONS: Rapid gastric emptying can be identified in a sizeable subset (9%) of patients with unexplained nausea, vomiting, abdominal pain, and diarrhea when criteria are applied to the standardized scintigraphic gastric emptying meal.

[Modifications of the glucose curves and gastric voiding of children with Dumping syndrome after laparoscopic Nissen surgery]. / Modificaciones de las curvas de glucemia y vaciamiento gástrico de los niños con síndrome de dumping tras cirugía de nissen laparoscópico.

INTRODUCTION: There has been an important evolution of surgical treatment in recent years due to the progressive generalization of laparoscopic surgery. All of the available techniques can be done laparoscopically with similar results to those of open surgery. In 1978, Villet et al. described the Dumping syndrome (DS) as a frequent complication of Nissen fundoplication. DS is a group of signs and symptoms that appear shortly after surgery, including abdominal pain, paleness, sweating, diarrhea, nausea, even weight loss. These symptoms can be differentiated into early dumping that occurs between 30 to 60 minutes after eating and late dumping that occurs 92-240 minutes after the postprandial period. MATERIAL AND METHODS: A total of 8 patients (3 boys and 5 girls) have been studied. Their ages ranged from 3 to 12 years (mean 9 years), and they were diagnosed of dumping syndrome after performing the laparoscopic Nissen-Rossetti. All underwent a gastric voiding study by scintigraphy after administration of a volume of milk adjusted to their weight labeled with 99Tc-DTPA and oral glucose overload test with 1.75 g/kg of glucose, determining the baseline glycemia and every 30 minutes post-intake, at 0, 30 and 90 minutes. Insulin was also measured to obtain the glucose/insulin ratio. This study was conducted for all patient diagnosed of dumping syndrome before and after laparoscopic Nissen-Rossetti surgery. RESULTS: The following results were obtained: Glucose Curve: 1. Maximum glycemia. PreNissen. The mean of the maximum glycemia values before surgery was 133.9+/-32.11 mg/dl. Post-Nissen. Mean maximum glycemias after surgery was 208.5 +/- 45.07 mg/dl with a range of 147-276 mg/dl. These differences of maximum glycemia were clearly significant with a p <0.002. Minimum glycemia. The mean value of the minimum glycemias after the surgery, compared with the previous value, did not show significant differences: 62.6+/- 11.51 mg/dl versus 71.8 +/- 28.04 mg/dl. Glucose/insulin ratio. The hyperinsulinism values after the intervention studied by means of the glucose/insulin ratio were abnormal in 70.5% (defined as ratio under 3). The mean value was also characteristic of hyperinsulinism (2.3 +/- 1.62). The mean value of the coefficient prior to the surgery was 4.6 with a deviation of 3.04, the differences not being statistically significant with a p= 0.097. Measurement of gastric voiding: The T1/2 (decay) value in post-Nissen patients was significantly lower than in pre-Nissen patients. The postsurgical mean and standard deviation was 29.74 +/- 7.92 min, while in the presurgical group, the mean and standard deviation was 73.75 +/- 28.34 min with p< 0.011; statistically significant. CONCLUSIONS: From the values obtained, we can state that a significant increase in maximum glycemia has been found in all children after surgery who were diagnosed of dumping syndrome and a significant decrease in the mean time of gastric voiding and therefore an increase in the acceleration of gastric voiding after the performance of the Nissen regarding the previous values. The dumping syndrome is a frequent side effect that we must keep in mind in patients who have been previously operated for anti-reflex surgery, the symptoms being greater in most of the transitory cases. Furthermore, it is important to keep in mind because it has an easy treatment that reverts the symptoms in a short time

Alcohol and gastric motility: pathophysiological and therapeutic implications.

Alcohol has been associated with alterations in gastric motility. The literature identifies that various factors play a role in alcohol's effect on gastric emptying including differences in alcohol concentration, osmolarity, caloric content, amino acids as well as different processing techniques (fermentation vs distillation). Additionally, chronic alcohol consumption has been shown to alter the myenteric nitrergic system resulting in impaired gastrointestinal motor function, and it also has an inhibitory effect on the release of several neurotransmitters that play a key role in gastrointestinal motility, including acetylcholine. Whether social or limited intake of alcohol could have a therapeutic role has not been apparent. Serendipitously, we have identified a therapeutic role for alcohol with a meal in the entity of dumping syndrome (DS) where there is postprandial rapid emptying of voluminous and hyperosmolar gastric contents into the small bowel. In the clinical setting of DS attributed to impaired vagal nerve function, there was normalization of gastric emptying and resolution of accompanying symptoms when drinking a glass of wine before and during meals. We propose that alcohol's anticholinergic effect was augmented in the setting of vagal nerve denervation resulting in slowing of gastric emptying and in alleviation of symptoms of early DS. This review article provides an in-depth analysis of the published literature on alcohol and gastric motility focusing on the accumulated knowledge that may have clinical application and relevance.

International consensus on the diagnosis and management of dumping syndrome.

Dumping syndrome is a common but underdiagnosed complication of gastric and oesophageal surgery. We initiated a Delphi consensus process with international multidisciplinary experts. We defined the scope, proposed statements and searched electronic databases to survey the literature. Eighteen experts participated in the literature summary and voting process evaluating 62 statements. We evaluated the quality of evidence using grading of recommendations assessment, development and evaluation (GRADE) criteria. Consensus (defined as >80% agreement) was reached for 33 of 62 statements, including the definition and symptom profile of dumping syndrome and its effect on quality of life. The panel agreed on the pathophysiological relevance of rapid passage of nutrients to the small bowel, on the role of decreased gastric volume capacity and release of glucagon-like peptide 1. Symptom recognition is crucial, and the modified oral glucose tolerance test, but not gastric emptying testing, is useful for diagnosis. An increase in haematocrit >3% or in pulse rate >10 bpm 30 min after the start of the glucose intake are diagnostic of early dumping syndrome, and a nadir hypoglycaemia level <50 mg/dl is diagnostic of late dumping syndrome. Dietary adjustment is the agreed first treatment step; acarbose is effective for late dumping syndrome symptoms and somatostatin analogues are preferred for patients who do not respond to diet adjustments and acarbose.

The mechanisms of weight loss after bariatric surgery.

Studies of lifestyle advice and dietary intervention show that although moderate, clinically significant weight loss is achievable and results in concomitant improvements in comorbidities, it is invariably transient and recidivism is almost universal. Pharmacotherapeutic options do show promise but are currently inadequate to address many obesity-associated comorbidities. Bariatric surgery consistently results in considerable improvement in weight, alongside a remarkable amelioration in comorbid conditions. Here we describe the physiology of energy balance and the putative mechanisms of change in weight set point following bariatric surgical procedures such as Roux-en-Y gastric bypass and adjustable gastric banding.

Prevalence and pathophysiology of early dumping in patients after primary Roux-en-Y gastric bypass during a mixed-meal tolerance test.

BACKGROUND: Early dumping is a poorly defined and incompletely understood complication after Roux-en-Y gastric (RYGB). OBJECTIVE: We performed a mixed-meal tolerance test in patients after RYGB to address the prevalence of early dumping and to gain further insight into its pathophysiology. SETTING: The study was conducted in a regional hospital in the northern part of the Netherlands. METHODS: From a random sample of patients who underwent primary RYGB between 2008 and 2011, 46 patients completed the mixed-meal tolerance test. The dumping severity score for early dumping was assessed every 30 minutes. A sum score at 30 or 60 minutes of ≥5 and an incremental score of ≥3 points were defined as indicating a high suspicion of early dumping. Blood samples were collected at baseline, every 10 minutes during the first half hour, and at 60 minutes after the start. RESULTS: The prevalence of a high suspicion of early dumping was 26%. No differences were seen for absolute hematocrit value, inactive glucagon-like peptide-1, and vasoactive intestinal peptide between patients with or without early dumping. Patients at high suspicion of early dumping had higher levels of active glucagon-like peptide-1 and peptide YY. CONCLUSION: The prevalence of complaints at high suspicion of early dumping in a random population of patients after RYGB is 26% in response to a mixed-meal tolerance test. Postprandial increases in both glucagon-like peptide-1 and peptide YY are associated with symptoms of early dumping, suggesting gut L-cell overactivity in this syndrome.

Post-prandial hypoglycemia after bariatric surgery: pharmacological treatment with verapamil and acarbose.

Postprandial hypoglycemia is a common complication of bariatric surgery. It is usually caused by late dumping syndrome, but a few other causes have already been described, including insulinoma and noninsulinoma pancreatogenous hypoglycemic syndrome (NIPHS). Considering that NIPHS is a recently described syndrome and is also very rare, therapeutic approaches are still not consensual. We report the case of a 26-year-old woman who was submitted to bariatric surgery and presented episodic postprandial hypoglycemic episodes after 16 months. Fasting C-peptide, insulin, and glucose were normal. Because of the possibility of NIPHS, clinical treatment was initiated with verapamil and acarbose, leading to a significant reduction of hypoglycemic episodes and also their severity. Surgery is the most common approach to NIPHS. However, in cases of mild or moderate symptoms, it is important to consider the possibility of pharmacological treatment. This approach may result, at least for some time, in an amelioration of symptoms without the need of an aggressive procedure.