EVIDENCE-BASED GUIDELINES International consensus on the diagnosis and management of dumping syndrome Emidio Scarpellini1, Joris Arts2, George Karamanolis 3, Anna Laurenius 4, Walter Siquini5, Hidekazu Suzuki6, Andrew Ukleja7, Andre Van Beek8, Tim Vanuytsel1, Serhat Bor9, Eugene Ceppa 10, Carlo Di Lorenzo 11, Marloes Emous12, Heinz Hammer13, Per Hellström14, Martine Laville 15, Lars Lundell16, Ad Masclee17, Patrick Ritz18 and Jan Tack1 ✉ Abstract | 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. Dumping syndrome is a frequent complication of can- meal and are primarily the manifestations of hypogly- cer and non- cancer oesophageal and gastric surgery, as caemia, which mainly results from an incretin- driven well as bariatric surgery (also known as metabolic sur- hyperinsulinaemic response after carbohydrate inges- gery). These interventions change gastric anatomy and tion. Hypoglycaemia- related symptoms are attribut- innervation, which can enable a considerable amount able to neuroglycopenia (which is indicated by fatigue, of undigested food to reach the small intestine too rap- weakness, confusion, hunger and syncope) and to vagal idly1–4. Dumping syndrome comprises a constellation and sympathetic activation (indicated by perspiration, of symptoms that can be subdivided into early and late palpitations, tremor and irritability)1,2. The literature has dumping syndrome symptoms, which can occur jointly referred to late dumping syndrome as ‘reactive hypo- or separately1–8. Typically, symptoms of early dumping glycaemia’ or, after bariatric surgery, as ‘postbariatric syndrome occur within the first hour after a meal and hypoglycaemia’. However, on the basis of a common include gastrointestinal symptoms (abdominal pain, pathophysiology of rapid exposure of the small intes- bloating, borborygmi, nausea and diarrhoea) and vaso- tine to nutrients, which is also seen in early dumping motor symptoms (flushing, palpitations, perspiration, syndrome (see subsequent discussion), we refer to this tachycardia, hypotension, fatigue, desire to lie down and, phenomenon as ‘late dumping syndrome’. 1,2 ✉e- mail: jan.tack@ rarely, syncope) . The underlying mechanisms might The prevalence of dumping syndrome depends on med.kuleuven.ac.be involve osmotic effects, peptide hormone release and the type and extent of surgery, and on the criteria used 1 https://doi.org/10.1038/ autonomic neural responses . Symptoms of late dump- to diagnose dumping syndrome. Dumping syndrome s41574-020-0357-5 ing syndrome usually occur between 1 and 3 h after a occurs in approximately 20% of patients undergoing 448 | AUGUST 2020 | VOLUME 16 www.nature.com/nrendo EVIDENCE-BASED GUIDELINES vagotomy with pyloroplasty, in up to 40% of patients Methods after Roux- en- Y gastric bypass (RYGB) or sleeve The process was coordinated by a chair (J.T.) and a gastrectomy and in up to 50% of patients under- co- chair (E.S.), referred to as the chairs. The principal going oesophagectomy5,6,9–11. Furthermore, dumping steps in the process were, first, selection of a Consensus syndrome might also occur after Nissen fundoplica- Group consisting of international experts in dumping tion12,13. According to reports published in the past syndrome management with different clinical and scien- 15 years, bariatric surgery has become the main cause tific backgrounds. Second, draft statements were devel- of postoperative dumping syndrome14,15. Dumping oped by the chairs and were refined by the Consensus syndrome has mainly been reported after RYGB and Group after a preliminary voting round with feedback partial gastrectomy12,13, but might also occur after on the statements. Third, each expert was assigned to restrictive bariatric procedures such as sleeve gastrec- contribute to literature reviews on several topics to sum- tomy, vertical banded gastroplasty and the laparoscopic marize the evidence to support each statement. Fourth, adjustable gastric band, which all reduce the volume two rounds of online voting of the statements (and vot- capacity of the proximal stomach4. The rapid expan- ing discussion) were undertaken until a stable level of sion in the use of bariatric interventions has therefore consensus was reached. Fifth, grading of the strength led to an increasing number of patients with dumping and quality of the evidence and of the strength of the syndrome16. recommendations using grading of recommendations, Symptoms of dumping syndrome are often debili- assessment, development and evaluation (GRADE) tating and emotionally distressing, they are associated criteria was conducted19. Agreement levels were deter- with a substantial reduction in quality of life and might mined as follows: A+, agree strongly; A, agree with lead to considerable weight loss as a result of the patient minor reservation; A−, agree with major reservation; avoiding food intake17. In spite of its effects, guidance D−, disagree with major reservation; D, disagree with is lacking on how to diagnose this condition, which is minor reservation; D+, disagree strongly. probably under- recognized. Moreover, established effi- For the Consensus Group, 18 multidisciplinary cacious treatment options and management guidelines international experts (gastroenterologists, internists, are lacking in the literature. Therefore, we used a Delphi nutritionists, surgeons and endocrinologists) from consensus1,9,10,17,18 process to develop uniform guidance ten countries (Austria, Belgium, France, Greece, Italy, about the definition, diagnosis and management of Japan, Netherlands, Sweden, Turkey and USA) were dumping syndrome. selected based on their participation in clinical trials and publications on dumping syndrome. A literature research was conducted using a number Author addresses of relevant keywords (medical subject headings (MeSH): dumping syndrome, hypoglycaemia and bariatric sur- 1 Translational Research Center for Gastrointestinal Disorders (TARGID), Department of gery). The chairs reviewed the list of publications and Chronic Diseases, Metabolism and Ageing (ChroMetA), Catholic University of Leuven, the relevant ones were stored in PDF format on a central Leuven, Belgium. server to which all Delphi panel members had access. 2Gastroenterology Division, St Lucas Hospital, Bruges, Belgium. 32nd Department of Internal Medicine — Propaedeutic, Hepatogastroenterology Unit, The references cited in this paper are only a selection of Attikon University Hospital, Medical School, Athens University, Athens, Greece. the reviewed articles, chosen to clarify the discussion. 4Department of Gastrosurgical Research and Education, Sahlgrenska Academy, The chairs developed the initial 66 statements that University of Gothenburg, Gothenburg, Sweden. were presented to the Consensus Group, who sub- 5Politechnic University of Marche, “Madonna del Soccorso” General Hospital, sequently revised, expanded and consolidated the San Benedetto del Tronto, Italy. statements, ultimately providing 62 statements for 6Department of Gastroenterology and Hepatology, Tokai University School of Medicine, the Delphi process19. The experts were then allocated Isehara, Japan. to groups of three and each member also functioned as 7 Division of Gastroenterology, Harvard Medical School, Beth Israel Deaconess Medical lead expert for one statement, generating a short sum- Center, Boston, MA, USA. mary of the available evidence for this statement using 8Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands. the papers on the central server as a literature source, 9Division of Gastroenterology, Ege University School of Medicine, Izmir, Turkey. which was further updated as needed. The statements 10Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA. covered the following aspects: definition, pathophysiol- 11Division of Pediatric Gastroenterology, Nationwide Children’s Hospital, Columbus, ogy, diagnosis and treatment. Statements were revised OH, USA. by the chairs based on the feedback from the Consensus 12Department of Bariatric and Metabolic Surgery, Medical Center Leeuwarden, Group before the