Effectiveness of beinaglutide in a patient with late dumping syndrome after gastrectomy: A case report.

RATIONALE: Dumping syndrome is a frequent and potentially severe complication after gastric surgery. Beinaglutide, a recombinant human glucagon-like peptide-1 (GLP-1) which shares 100% homology with human GLP-1(7-36), has never been reported in the treatment of dumping syndrome before. PATIENT CONCERNS: The patient had undergone distal gastrectomy for gastric signet ring cell carcinoma 16 months ago. He presented with symptoms of paroxysmal palpitation, sweating, and dizziness for 4 months. DIAGNOSIS: He was diagnosed with late dumping syndrome. INTERVENTIONS AND OUTCOMES: The patient was treated with dietary changes and acarbose for 4 months before admitted to our hospital. The treatment with dietary changes and acarbose did not prevent postprandial hyperinsulinemia and hypoglycemia according to the 75 g oral glucose tolerance test (OGTT) and continuous glucose monitoring (CGM) on admission.Therefore, the patient was treated with beinaglutide 0.1 mg before breakfast and lunch instead of acarbose. After the treatment of beinaglutide for 1 month, OGTT showed a reduction in postprandial hyperinsulinemia compared with before starting treatment, and the time in the range of 3.9 to 10 mmol/L became 100% in CGM. No side effect was observed in this patient during beinaglutide treatment. LESSONS: These findings suggest that beinaglutide may be effective for treating post-gastrectomy late dumping syndrome.

Diagnostic tools for post-gastric bypass hypoglycaemia.

In spite of its evident success, several late complications can occur after gastric bypass surgery. One of these is post-gastric bypass hypoglycaemia. No evidence-based guidelines exist in the literature on how to confirm the presence of this syndrome. This study aims to describe and compare the tests aimed at making a diagnosis of post-gastric bypass hypoglycaemia and to provide a diagnostic approach based upon the available evidence. A search was conducted in PubMed, Cochrane and Embase. A few questionnaires have been developed to measure the severity of symptoms in post-gastric bypass hypoglycaemia but none has been validated. The gold standard for provocation of a hypoglycaemic event is the oral glucose tolerance test or the liquid mixed meal tolerance test. Both show a high prevalence of hypoglycaemia in post-gastric bypass patients with and without hypoglycaemic complaints as well as in healthy volunteers. No uniformly established cut-off values for glucose concentrations are defined in the literature for the diagnosis of post-gastric bypass hypoglycaemia. For establishing an accurate diagnosis of post-gastric bypass hypoglycaemia, a validated questionnaire, in connection with the diagnostic performance of provocation tests, is the most important thing missing. Given these shortcomings, we provide recommendations based upon the current literature.

Octreotide improves early dumping syndrome potentially through incretins: a case report.

Dumping syndrome, or rapid gastric emptying, is a frequent complication after gastric surgery. In this case, the patient was a 47-year-old woman who 10 years previously had undergone distal gastrectomy with Billroth I reconstruction for early-stage gastric cancer. She presented with symptoms of weakness, headache, palpitation, sweating, dizziness and significant fatigue between one and two hours after a meal. Because a 75 g oral glucose tolerance test (75 g-OGTT) induced both acute postprandial tachycardia (within 1 hour) and postprandial hypoglycemia, we diagnosed this patient with early and late dumping syndrome. Dietary measures and acarbose improved symptoms of late dumping syndrome but did not prevent the symptoms of early dumping syndrome such as postprandial tachycardia, weakness, headache, palpitation, and dizziness. We therefore used the somatostatin analogue octreotide, which has been reported as an effective therapy for early dumping syndrome. Octreotide prevented the symptoms of early dumping syndrome, especially postprandial tachycardia, but caused postprandial hyperglycemia. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) were completely suppressed during the 75 g-OGTT following subcutaneous injection of octreotide. No change was observed in vasoactive intestinal polypeptide (VIP), which is the gastrointestinal peptide hormone generally responsible for early dumping syndrome, suggesting possible contribution of incretins in early dumping syndrome of this patient.

Abnormal glucose tolerance testing after gastric bypass.

BACKGROUND: Symptoms secondary to dumping have been suggested to help patients refrain from simple carbohydrate ingestion after Roux-en-Y gastric bypass (RYGB). During follow-up examinations, we noted many patients with weight regain complaining of fatigue shortly after eating. Thus, we decided to study the glucose tolerance test (GTT) results in a cohort of post-RYGB patients. METHODS: A total of 63 RYGB patients, >6 months postoperatively, were studied with a GTT and measurement of insulin levels. The mean age was 48.5 ± 10.8 years, mean preoperative body mass index was 49.0 ± 6.5 kg/m(2), mean percentage of excess body mass index lost was 64.5% ± 29.0%, mean weight regain at follow-up was 11.6 ± 12.4 lb, and mean follow-up period was 47.9 months. RESULTS: Of the 63 patients, 49 had abnormal GTT results. Of the 63 patients, 6 were diabetic; however, only 1 of these patients had an elevated fasting glucose level. All 6 patients were diabetic preoperatively. Of the 63 patients, 43 had evidence of reactive hypoglycemia at 1-2 hours after the glucose load. Of these patients, 22 had a maximum/minimum glucose ratio >3:1, including 7 with a ratio >4:1. CONCLUSION: The results of the present study have demonstrated that an abnormal GTT result is a common finding after RYGB. Reactive hypoglycemia was found in 43 of 63 patients, with insulin values that do not support nesidioblastosis. It is our hypothesis, that rather than preventing simple carbohydrate ingestion, the induced hypoglycemia that occurs might contribute to weight regain and maladaptive eating in certain post-RYGB patients.

Acarbose improves hypoglycaemia following gastric bypass surgery without increasing glucagon-like peptide 1 levels.

BACKGROUND: Postprandial hypoglycaemia is a severe complication of Roux-en-Y gastric bypass (RYGBP). Acarbose, an α-glucosidase inhibitor (AGI), is employed in its treatment. Several studies have shown that AGIs increase the postprandial levels of glucagon-like peptide 1 (GLP-1). However, an excessive level of GLP-1 is one of the factors involved in the physiopathology of this condition. We analysed the effect of acarbose oral administration in eight RYBGP patients with clinically significant hypoglycaemia or dumping syndrome. METHODS: Glucose, insulin and GLP-1 plasma levels in fasting and after ingestion of a standard meal (Ensure Plus®; 13 g protein, 50 g carbohydrate, 11 g fat) were measured. The test was repeated the following week with the oral administration of 100 mg of acarbose 15 min prior to the meal. RESULTS: Five patients developed asymptomatic hypoglycaemia during the test (glucose level <50 mg/dl) with inappropriately high insulin levels and exaggerated GLP-1 response. Acarbose ingestion avoided hypoglycaemia in all of the patients and increased the lowest plasma glucose level (46.4 ± 4.8 vs. 59.0 ± 2.6 mg/dl, p < 0.01). Acarbose ingestion decreased the area under the curve for serum insulin and GLP-1 levels at 15 min after the meal. CONCLUSIONS: Acarbose avoided postprandial hypoglycaemia following RYGBP by decreasing the hyperinsulinemic response. This was associated with a decrease in early GLP-1 secretion, in contrast to that observed in non-surgical subjects. This finding could be explained by the reduction of glucose load in the jejunum produced by the α-glucosidase inhibition, which is the main stimulus for GLP-1 secretion.

[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

A possible role of GLP-1 in the pathophysiology of early dumping syndrome.

Exaggerated plasma concentrations of GLP-1 precede reactive hypoglycemia after oral glucose in gastrectomy patients, resulting in late dumping syndrome. Recently, we showed that GLP-1 elicits the activation of sympathetic outflow. Because sympathetic activation is thought to be a cause of early dumping, we hypothesized that exaggerated GLP-1 may contribute to the pathophysiology of early dumping syndrome. In 11 patients after gastrectomy and 14 controls, blood pressure, heart rate, and plasma concentrations of norepinephrine, epinephrine, GLP-1, glucagon, insulin, and glucose were measured after oral glucose. In gastrectomy patients, GLP-1, norepinephrine, and heart rate peaked 15 to 30 min after oral glucose. Significant positive correlations were found among GLP-1, norepinephrine, and heart rate at 30 min, and these parameters at 30 min were significantly higher in patients with early dumping syndrome. These results suggest that GLP-1 is involved in the pathophysiology of early dumping syndrome.

Sympathoadrenal activation and the dumping syndrome after gastric surgery.

Dumping symptoms suggest concomitant sympathoadrenal activation. To evaluate the relation between dumping symptoms and postprandial plasma catecholamine changes, standardized dumping-provocation tests with use of oral glucose were performed for 16 gastric surgery patients with dumping, for 14 gastric surgery patients without dumping, and for 14 healthy control patients. Early dumping symptoms were present for all patients with dumping, and late symptoms developed in three patients with dumping after glucose ingestion. Patients without dumping and healthy control patients had slight complaints or no complaints. Systolic and diastolic blood pressure remained unaffected for the three groups. Positive breath-hydrogen tests, heart rate increments, and reactive plasma glucose decrements were present for patients with dumping and for patients without dumping, but not for control patients. Plasma noradrenaline and adrenaline increased for patients with dumping and for patients without dumping, but not for control patients. The noradrenaline increment was higher for patients with dumping (98%) than for patients without dumping (78%; p <0.05). The noradrenaline increment was related to the dumping score and to the heart rate increment for the first hour after glucose ingestion, whereas the adrenaline increment was related to the plasma glucose decrement for the third hour. Therefore, dumping symptoms clearly are accompanied by postprandial sympathoadrenal activation, but sympathoadrenal activation cannot account completely for development of dumping symptoms.

Long-term results of octreotide-therapy in severe dumping syndrome.

OBJECTIVE: Little is known about the long-term results of octreotide therapy in dumping syndrome. We report the results of an open study including 20 patients with severe dumping symptoms after gastric surgery treated with octreotide between 1987 and 1997 at the Leiden University Medical Centre. DESIGN: Patient selection was based on (1) the results of a dumping provocation test and (2) symptoms that were refractory to other therapeutic measures. At regular intervals the presence of dumping symptoms was evaluated together with measurement of body weight and faecal fat excretion. RESULTS: Mean follow-up was 37 +/- 9 months (range 1-107 months). Doses of octreotide ranged from 25 to 200 microg/day. Initial relief of symptoms was achieved in all subjects, but after three months of therapy symptom relief persisted in 80% of patients. Mean body weight increased by 2.4 +/- 1.2 kg despite a significant increase in faecal fat excretion from 10 +/- 2 g/24 h to 24 +/- 3 g/24 h. Reasons for discontinuation of therapy were diminished efficacy in the longer term in 4 patients and side-effects in 7 patients. Biliary complications were encountered in 3 patients. CONCLUSIONS: Self-administration of octreotide proves an effective symptomatic treatment of severe dumping, even on the long-term. Its use is frequently limited by the occurrence of side-effects.

Vasoactive substances in early dumping syndrome: effects of dumping provocation with and without octreotide.

In patients after gastric surgery, early dumping symptoms can be provoked by oral glucose challenge. Octreotide effectively prevents the occurrence of dumping symptoms. We have studied plasma renin activity (PRA), aldosterone and atrial natriuretic peptide (ANP) concentrations in nine patients with early dumping, 10 surgical control subjects and nine healthy control subjects after an oral glucose challenge preceded by either placebo or 25 micrograms of octreotide subcutaneously (s.c.). In the dumping group, basal PRA was significantly (P < 0.01) higher (3.9 +/- 0.6 micrograms L-1 h-1) than in either surgical or healthy control subjects (1.1 +/- 0.3 micrograms L-1 h-1 and 1.1 +/- 0.2 micrograms L-1 h-1 respectively) and showed a significant rise after glucose ingestion to 5.4 +/- 0.9 micrograms L-1 h-1 that did not occur in control subjects. Aldosterone concentration showed a concomitant rise. In dumping patients, plasma ANP decreased after glucose ingestion from 31 +/- 6 ngL-1 to 21 +/- 5 ngL-1 (P < 0.05). This decrease did not occur in control subjects. Early dumping is associated with an activation of the renin-aldosterone axis and a decrease in plasma ANP, reflecting a hypovolaemic state. Octreotide prevents the occurrence of these changes.

The successful application of jejunal interposition for severe dumping syndrome: report of a case.

We report herein the case of a 76-year-old man with intractable dumping syndrome which had manifested itself 3 years after he underwent a gastric resection and Billroth I reconstruction for a gastric ulcer. Despite aggressive medical therapy by the time of admission, he had suffered from disabling dumping symptoms for 9 years. In an attempt to relieve these symptoms, a 15-cm segment of the jejunum was placed isoperistaltically between the lesser curvature of the remnant stomach and the duodenum, and a selective vagotomy was performed. The dumping symptoms that he had experienced preoperatively completely disappeared after the revisory surgery. Postoperatively, an upper gastrointestinal series demonstrated a larger gastric pouch and slower gastric passage into the small intestine than what was seen preoperatively, while gastric emptying studies using the acetaminophen method also showed normal patterns in both the early and late postoperative phases. Thus, we consider that this surgical procedure is a simple and effective way to inhibit rapid gastric emptying and to slow intestinal transit in the treatment of dumping syndrome.

[The release of vasoactive intestinal peptide in patients with dumping syndrome and its clinical significance].

Plasma vasoactive intestinal peptide (VIP), blood glucose concentration and hematocrit (HCT) were measured in 15 patients after Billroth-II subtotal gastrectomy (B-II SG) and 8 healthy controls before and after oral glucose ingestion. In B-II SG group the rate of rise of VIP concentration was in positive correlation to the rate of rise of HCT (r = 0.501 P < 0.05) and to that of blood glucose (r = 0.715 P < 0.01). Also, the elevation rate of HCT blood glucose and VIP concentration was significant higher in B-II SG group than in controls (P < 0.05). It was found that the elevation rate of VIP concentration was much higher in patients with dumping syndrome after B-II SG than those without (P < 0.05). The results suggest that VIP may play a role in the pathogenesis of dumping syndrome.

Simultaneous measurement of intestinal blood flow and plasma levels of vasoactive substances in a case of early dumping syndrome. Case report.

Increase in intestinal blood flow was observed in a patient with postprandial hypotension. Simultaneous measurement of hemodynamic parameters and plasma levels of gut hormones revealed that the release of various vasoactive substances and resulting vasodilation of abdominal organs were responsible for the vasomotor changes of early dumping syndrome.

Octreotide acetate induces fasting small bowel motility in patients with dumping syndrome.

The long acting somatostatin analogue octreotide acetate has been effective in the treatment of early dumping syndrome. We hypothesized that this may be related to its effects on inhibiting gastric emptying and delaying intestinal transit. To study the effect of octreotide acetate on intestinal motility in patients we carried out a randomized, double-blinded study using a subcutaneous injection of either octreotide acetate (100 micrograms) or placebo given 20 min prior to ingestion of a high carbohydrate "dumping" meal in six patients with known severe dumping syndrome. Prior to each study a multilumen polyethylene tube was inserted into the efferent limb to study small intestinal contractions using low compliance pneumo-hydraulic water-perfused manometry. Octreotide acetate prevented dumping symptoms in all six patients and induced the appearance of migrating myoelectric complexes (MMC) characteristic of interdigestive motility. After ingestion of the dumping meal the postprandial "fed" motility pattern lasted for 141 +/- 9 min while after octreotide acetate the fed motility lasted for 29 +/- 5 min (P less than 0.03). The vigor of the fed motility pattern as measured by the motility index (MI = loge (sum of amplitudes X No. of contractions + 1] was lower after octreotide acetate than after placebo (15.1 +/- 0.1 vs 13.4 +/- 0.2, P less than 0.03). The induction of fasting MMC motility pattern and reduction in the duration and vigor of fed motility may explain the symptomatic relief these patients obtained with octreotide acetate. It is not known whether the induction of the MMC is a direct effect of octreotide acetate or secondary to the concomitant inhibition of peptide release (neurotensin, insulin, glucagon, pancreatic polypeptide) that has been demonstrated in earlier studies.

Long acting somatostatin analogue in dumping syndrome.

The effect of long acting somatostatin analogue, SMS 201-995, on postprandial dumping syndrome was studied in eight patients with Billroth II gastric resection. Each patient was subjected to two oral glucose challenges with 75 g glucose. One challenge was premedicated with 50 micrograms SMS 201-995 subcutaneously 15 min before the oral intake of glucose, the other with placebo. With placebo all patients experienced the subjective symptoms of the early dumping syndrome with significant (P less than 0.001) increases (mean (s.d.)) in pulse rate (from 66 (8) to 102 (10) beats/min), in packed cell volume (from 0.36 (0.05) to 0.43 (0.1) l/l) and in the plasma levels of vasoactive intestinal polypeptide (from 3.0 (0.5) to 10.2 (1.8) pmol/l). During the somatostatin study the subjective symptoms and the changes in the various parameters were not detected. In the control study seven patients showed postprandial hypoglycemia. In these patients significant elevations (P less than 0.001) in the insulin level (from 10 (0.9) to 40 (9.1) microE/ml) and gastric inhibitory peptide (GIP) concentration (from 100 (13) to 220 (41) ng/l) were seen, compared with the initial values. During the application of SMS 201-995 hypoglycaemia did not develop and plasma insulin and GIP concentrations remained unchanged. These results indicate that the long acting somatostatin analogue alleviates the symptoms of early and late postprandial dumping syndromes.

[The relations between the morphology of the postresection gastric stump after a gastroduodenal ulcer and the dumping syndrome]. / Relatii între morfologia bontului gastric post rezectie dupa ulcerul gastroduodenal si sindromul "dumping".

Of a group of 272 patients subjected to gastric resection for gastric-duodenal ulcer, the "dumping" syndrome was found in 46 (17%). The most frequent (39.7%) was in the Reichel-Polya anastomosis type and the less frequent (9%) in pyloroplasties. The test of induced hyperglycemia by ingesting 15 g/kg body glucose did not show differences in the values of the maximum glycemia in the patients with the "dumping" syndrome versus the other group. The surface of the anastomosis opening and the length of the gastric stump were appreciated with a central imaging endoscope. The surface of the anastomosis opening was found larger in those with a "dumping" syndrome and Reichel-Polya's resection, although the differences are not statistically significant; likewise, there seems to be a less length of the gastric stump and a higher weight difference in those with the "dumping" syndrome. The lack of pyloric sphincter seems to be very important in producing the "dumping" syndrome due to the fact that the alimentary bolus is not fractionated and its sequential evacuation in duodenum and jejunum does not take place.

[Diagnosis and therapy of dumping syndrome following Nissen fundoplication with reference to pathogenetic aspects]. / Diagnose und Therapie des Dumping-Syndroms nach Nissen-Fundoplikation unter Berücksichtigung pathogenetischer Gesichtspunkte.

Between 1982 and 1987 27 Nissen's fundoplications were carried out in our institution. Postoperatively 7 infants showed a typical dumping syndrome. The symptoms were irritability, pallor, sweating, tachycardia, lethargy, diarrhoea and vomiting. In all cases an absolute refusal of feeding was observed. The diagnosis was confirmed by a typical early postprandial hyperglycaemia with hyperinsulinaemia leading to a reactive hypoglycaemia. Additionally, we were able to demonstrate an increased HbA1c as an expression of recurrent hyperglycaemias in 3 infants. In 6 infants the dumping syndrome was of short duration and the symptoms disappeared after application of a so-called dumping diet. In this diet the easily resorbable carbohydrates are replaced by uncooked starch. But in one case we were forced to use continuous enteral nutrition because of persistence of the symptoms 1 year after the Nissen fundoplication. Complete refusal of feeding is an early symptom of the dumping syndrome. If this symptom is observed after a Nissen's fundoplication, a dumping syndrome must be excluded.

Dumping syndrome in children. Diagnosis and effect of glucomannan on glucose tolerance and absorption.

Dumping syndrome is rarely seen in children. We studied ten children with symptoms following various types of gastric surgery. All had abnormal blood glucose and breath hydrogen responses after oral glucose challenge, indicating reduction of both glucose tolerance and glucose absorption, as compared to controls. Glucose tolerance was best expressed as the difference between peak and subsequent lowest blood glucose level, the upper limit of normal (mean + 3 SD) being 5.9 mmol/l. In eight children with persisting symptoms we tested the effects of glucomannan, a highly hygroscopic tasteless fibre, on glucose tolerance and glucose absorption. Glucomannan significantly improved glucose tolerance, but did have no overall effect on glucose absorption. Four children tested glucomannan added to the main meals. Breath hydrogen excretion, as established with the daytime breath hydrogen profile, decreased significantly in two, but complaints increased in three children. Glucomannan does not appear to be suitable for the treatment of dumping syndrome in children as the side effects seem to overrule the beneficial effects.