Oral Ondansetron Offers Effective Antidiarrheal Activity for Carcinoid Syndrome Refractory to Somatostatin Analogs

Kiesewetter, Barbara; Duan, Heying; Lamm, Wolfgang; Haug, Alexander; Riss, Philipp; Selberherr, Andreas; Scheuba, Christian; Raderer, Markus

doi:10.1634/theoncologist.2018-0191

Cited by 12 publications

(10 citation statements)

References 11 publications

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“…Seven articles (5 unique studies) reported a proportion of patients with GEP-NETs and non-CS diarrhoea directly confirmed by clinical tests, including PEI, SIBO, colitis and Campylobacter coli ( C. coli ) infection (Table 2 )[ 6 , 28 , 32 - 35 , 40 ]. BAM was diagnosed in 80% of NET patients who had been to a gastroenterologist service and were tested using the 75-selenium homocholic acid taurine (SeHCAT) scan ( n = 20)[ 33 ].…”

Section: Resultsmentioning

confidence: 99%

“…SIBO, diagnosed by breath tests, was reported in 23.6% to 62% of NET patients who had been tested for the condition[ 32 , 33 ]. Single cases of colitis (20%) and C. coli infection (7.1%) were reported in two studies of patients with CS diarrhoea[ 34 , 36 ].…”

Section: Resultsmentioning

confidence: 99%

“…Initial investigations into the cause of diarrhoea: Fourteen articles recommended or described the use of approaches to facilitate identification of patients who could be experiencing diarrhoea due to a cause other than CS[ 24 , 36 - 38 , 44 , 46 , 49 , 50 , 52 - 57 ]. Representative quotations for each sub-theme are presented in Figure 3 , and full details are available in .…”

Section: Resultsmentioning

confidence: 99%

“…Approaches for confirming the cause of diarrhoea: A total of 19 articles reported on 13 unique tests used to investigate diarrhoea for nine specific causes ( )[ 6 , 32 - 34 , 36 - 38 , 40 , 42 - 44 , 46 , 49 , 50 , 60 - 64 ]. Of these, 12 studies had used a test for diagnosis of a condition in a population of patients with NETs[ 6 , 32 - 34 , 36 - 38 , 40 , 46 , 49 , 50 , 60 ], whereas seven articles only described or recommended a test (Table 2 )[ 42 - 44 , 61 - 64 ].…”

Section: Resultsmentioning

confidence: 99%

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Differential diagnosis of diarrhoea in patients with neuroendocrine tumours: A systematic review

Khan

Walter

Buchanan-Hughes

et al. 2020

WJG

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BACKGROUND Approximately 20% of patients with neuroendocrine tumours (NETs) develop carcinoid syndrome (CS), characterised by flushing and diarrhoea. Somatostatin analogues or telotristat can be used to control symptoms of CS through inhibition of serotonin secretion. Although CS is often the cause of diarrhoea among patients with gastroenteropancreatic NETs (GEP-NETs), other causes to consider include pancreatic enzyme insufficiency (PEI), bile acid malabsorption and small intestinal bacterial overgrowth. If other causes of diarrhoea unrelated to serotonin secretion are mistaken for CS diarrhoea, these treatments may be ineffective against the diarrhoea, risking detrimental effects to patient quality of life. AIM To identify and synthesise qualitative and quantitative evidence relating to the differential diagnosis of diarrhoea in patients with GEP-NETs. METHODS Electronic databases (MEDLINE, Embase and the Cochrane Library) were searched from inception to September 12, 2018 using terms for NETs and diarrhoea. Congresses, systematic literature review bibliographies and included articles were also hand-searched. Any study designs and publication types were eligible for inclusion if relevant data on a cause(s) of diarrhoea in patients with GEP-NETs were reported. Studies were screened by two independent reviewers at abstract and full-text stages. Framework synthesis was adapted to synthesise quantitative and qualitative data. The definition of qualitative data was expanded to include all textual data in any section of relevant publications. RESULTS Forty-seven publications (44 studies) were included, comprising a variety of publication types, including observational studies, reviews, guidelines, case reports, interventional studies, and opinion pieces. Most reported on PEI on/after treatment with somatostatin analogs; 9.5%-84% of patients with GEP-NETs had experienced steatorrhoea or confirmed PEI. Where reported, 14.3%–50.7% of patients received pancreatic enzyme replacement therapy. Other causes of diarrhoea reported in patients with GEP-NETs included bile acid malabsorption (80%), small intestinal bacterial overgrowth (23.6%-62%), colitis (20%) and infection (7.1%). Diagnostic approaches included faecal elastase, breath tests, tauroselcholic (selenium-75) acid (SeHCAT) scan and stool culture, although evidence on the effectiveness or diagnostic accuracy of these approaches was limited. Assessment of patient history or diarrhoea characteristics was also reported as initial approaches for investigation. From the identified evidence, if diarrhoea is assumed to be CS diarrhoea, consequences include uncontrolled diarrhoea, malnutrition, and perceived ineffectiveness of CS treatment. Approaches for facilitating differential diagnosis of diarrhoea include improving patient and clinician awareness of non-CS causes and involvement of a multidisciplinary clinical team, including gastroenterologists. CON...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Differential diagnosis of diarrhoea in patients with neuroendocrine tumours: A systematic review

Khan

Walter

Buchanan-Hughes

et al. 2020

WJG

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“…e aforementioned meta-analysis shows 64-74% of symptom improvement based on 4 small-phase II studies [61]. Two small studies with 11 and 14 NEN patients with carcinoid syndrome report a good effect of ondansetron in reducing diarrhoea [70,71].…”

Section: Treatment Updatesmentioning

confidence: 99%

Update on Pathophysiology, Treatment, and Complications of Carcinoid Syndrome

Clement

Ramage

Srirajaskanthan

2020

Journal of Oncology

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Carcinoid syndrome (CS) develops in patients with hormone-producing neuroendocrine neoplasms (NENs) when hormones reach a significant level in the systemic circulation. The classical symptoms of carcinoid syndrome are flushing, diarrhoea, abdominal pain, and wheezing. Neuroendocrine neoplasms can produce multiple hormones: 5-hydroxytryptamine (serotonin) is the most well-known one, but histamine, catecholamines, and brady/tachykinins are also released. Serotonin overproduction can lead to symptoms and also stimulates fibrosis formation which can result in development of carcinoid syndrome-associated complications such as carcinoid heart disease (CaHD) and mesenteric fibrosis. Transforming growth factor beta (TGF-β) is one of the main factors in developing fibrosis, but platelet-derived growth factor (PDGF), basic fibroblast growth factor (FGF2), and connective tissue growth factor (CTGF or CCN2) are also related to fibrosis development. Treatment of CS focuses on reducing serotonin levels with somatostatin analogues (SSA’s). Telotristat ethyl and peptide receptor radionuclide therapy (PRRT) have recently become available for patients with symptoms despite being established on SSA’s. Screening for CaHD is advised, and early intervention prolongs survival. Mesenteric fibrosis is often present and associated with poorer survival, but the role for prophylactic surgery of this is unclear. Depression, anxiety, and cognitive impairment are frequently present symptoms in patients with CS but not always part of their care plan. The role of antidepressants, mainly SSRIs, is debatable, but recent retrospective studies show evidence for safe use in patients with CS. Carcinoid crisis is a life-threatening complication of CS which can appear spontaneously but mostly described during surgery, anaesthesia, chemotherapy, PRRT, and radiological procedures and may be prevented by octreotide administration.

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Pulmonary Carcinoid

Patel

Verma

2022

Medical Radiology

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Oral Ondansetron Offers Effective Antidiarrheal Activity for Carcinoid Syndrome Refractory to Somatostatin Analogs

Cited by 12 publications

References 11 publications

Differential diagnosis of diarrhoea in patients with neuroendocrine tumours: A systematic review

Differential diagnosis of diarrhoea in patients with neuroendocrine tumours: A systematic review

Update on Pathophysiology, Treatment, and Complications of Carcinoid Syndrome

Pulmonary Carcinoid

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