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.

Efficacy and safety of lanreotide in postoperative dumping syndrome: A Phase II randomised and placebo-controlled study.

Background: Data on the efficacy and safety of the long-acting somatostatin analogue lanreotide (LAN) for postoperative dumping syndrome are lacking. Objective: We performed a double-blind, randomised and placebo-controlled crossover study of LAN Autogel® 90 mg in postoperative dumping. Methods: Adults with a positive prolonged oral glucose tolerance test or spontaneous hypoglycaemia and total dumping score (DS) ≥ 10 despite dietary measures were treated with three monthly injections of LAN or placebo in a randomised crossover fashion with an eight-week wash-out period. Primary outcome was the effect of LAN on total DS versus placebo. Secondary outcomes were the effect on early and late DS, treatment assessment, quality of life and safety. Results: Of 24 included patients (66.7% female; age 49.1 ± 2.1 years), 12 were randomised to LAN first. Pooled DS after three injections were lower compared to baseline after LAN (median=14 (interquartile range (IQR) 11.5-23) vs. median = 22 (IQR 16-27); p = 0.03) but not placebo (median = 20 (IQR 15-27) vs. median = 23 (IQR 13-29); p = 0.15). Improvement of early (median = 7.5 (IQR 4.5-13) vs. median = 12 (IQR 9-16); p = 0.03) but not late (median = 7 (IQR 6-10.3) vs. median = 9 (IQR 6-13); p = 0.26) DS was seen. Overall treatment assessment correlated with change in DS (r = -0.69, p = 0.004). Symptom improvement was not associated with changes in quality of life. Of the 81 reported adverse events, 44 occurred on LAN compared to 37 on placebo (p > 0.05), with seven serious adverse events on LAN. Conclusions: LAN is effective for treating early postoperative dumping symptoms, although side effects are common and quality of life is not significantly affected.

Pathophysiology, diagnosis and management of postoperative dumping syndrome.

Dumping syndrome is a frequent complication of esophageal, gastric or bariatric surgery. Rapid gastric emptying, with the delivery to the small intestine of a significant proportion of solid food as large particles that are difficult to digest, is a key event in the pathogenesis of this syndrome. This occurrence causes a shift of fluid from the intravascular component to the intestinal lumen, which results in cardiovascular symptoms, release of several gastrointestinal and pancreatic hormones and late postprandial hypoglycemia. Early dumping symptoms comprise both gastrointestinal and vasomotor symptoms. Late dumping symptoms are the result of reactive hypoglycemia. Besides the assessment of clinical alertness and endoscopic or radiological imaging, a modified oral glucose tolerance test might help to establish a diagnosis. The first step in treating dumping syndrome is the introduction of dietary measures. Acarbose can be added to these measures for patients with hypoglycemia, whereas several studies advocate guar gum or pectin to slow gastric emptying. Somatostatin analogs are the most effective medical therapy for dumping syndrome, and a slow-release preparation is the treatment of choice. In patients with treatment-refractory dumping syndrome, surgical reintervention or continuous enteral feeding can be considered, but the outcomes of such approaches are variable.

Incidence of colectomy during long-term follow-up after cyclosporine-induced remission of severe ulcerative colitis.

BACKGROUND & AIMS: Cyclosporine (CSA) has been shown to be effective in steroid-refractory ulcerative colitis (UC) and as an alternative to glucocorticosteroids in patients with severe attacks of UC. Our aim was to investigate the long-term efficacy of CSA. METHODS: We conducted a retrospective cohort study of all patients admitted to our institution with an attack of UC treated with intravenous CSA between November 1992 and October 2004. Patients who responded to intravenous CSA were switched to Neoral for 3 months. Kaplan-Meier curves were used for survival analysis with quantitative variables compared using a 2-tailed Student t test with qualitative variables and differences compared with a chi(2) analysis. RESULTS: A total of 118 (83%) of the 142 patients had an initial response to CSA and avoided colectomy during hospitalization. Of the 118 patients, 41 (35%) [corrected] required a future colectomy. The rate of colectomy in those already on azathioprine compared with those starting azathioprine concurrently with CSA was 59% vs 31%, respectively (P < .05). Also, 88% of patients already on azathioprine and requiring colectomy underwent surgery within the first year of receiving CSA. Life-table analysis shows that although only 33% of patients require colectomy at 1 year, 88% will require colectomy at 7 years. CONCLUSIONS: CSA is an effective short- to medium-term treatment for patients with severe UC but at 7 years, 88% of patients will require a colectomy. Azathioprine-naive patients have better outcomes.

Randomized, double-blind comparison of 4 mg/kg versus 2 mg/kg intravenous cyclosporine in severe ulcerative colitis.

BACKGROUND AND AIMS: Cyclosporine A is highly effective in severe attacks of ulcerative colitis (UC) but is associated with important adverse effects that are mainly dose dependent. Our single center, randomized, double-blind, controlled trial aimed to evaluate the additional clinical benefit of 4 mg/kg over 2 mg/kg IV cyclosporine in the acute treatment of severe UC. METHODS: Primary end point was the proportion of patients with a clinical response. Secondary end points included time to response, colectomy rate, and adverse effects. RESULTS: Seventy-three patients were included. Day-8 response rates were 84.2% (32 of 38, 4 mg/kg) and 85.7% (32 of 35, 2 mg/kg) after a median of 4 days in both groups. Short-term colectomy rates were 13.1% (4 mg/kg) and 8.6% (2 mg/kg). Mean cyclosporine blood levels were 237 +/- 33 in the 2-mg/kg group and 332 +/- 43 ng/mL in the 4-mg/kg group. Active smoking was inversely correlated with clinical response (odds ratio, 0.06), but concomitant azathioprine or steroids were not predictive. A trend toward a higher incidence of hypertension was observed in the 4-mg/kg group (23.7% vs. 8.6%, 2 mg/kg, P < 0.08). CONCLUSIONS: High-dose IV cyclosporine has no additional clinical benefit over low dose in the treatment of severe UC. Although we did not observe differences in adverse effects on the short term, the use of 2 mg/kg IV cyclosporine should provide an improved toxicity profile for medical treatment of severe UC.

Acute and repeated treatment with L-DOPA increase c-jun expression in the 6-hydroxydopamine-lesioned forebrain of rats and common marmosets.

L-DOPA was acutely or repeatedly administered to rats and common marmosets (Callithrix jacchus) with unilateral 6-hydroxydopamine (6-OHDA) denervation of the dopamine inputs to the forebrain. Using in situ hybridization it was found that L-DOPA-treated animals exhibited a pronounced induction in the gene expression of both c-jun and c-fos in striatum and cerebral cortex restricted to the dopamine-depleted hemisphere. In contrast, acute treatment with cocaine induced c-fos mRNA, but not c-jun mRNA, in the striatum of normal animals. These data suggest that dopamine denervation leads to neurochemical adaptations which enables L-DOPA to induce a sustained gene expression of c-jun. Such aberrant gene regulation may underlie the development of L-DOPA-induced movement disorders which are commonly found in patients with Parkinson's disease.