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

Khan, Mohid S, Walter, Thomas, Buchanan-Hughes, Amy, Worthington, Emma, Keeber, Lucie, Feuilly, Marion and Grande, Enrique 2020. Differential diagnosis of diarrhoea in patients with neuroendocrine tumours: a systematic review. World Journal of Gastroenterology 26 (30) , pp. 4537-4556. 10.3748/wjg.v26.i30.4537

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Abstract

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. CONCLUSION Diarrhoea in GEP-NETs can be multifactorial with misdiagnosis leading to delayed patient recovery and inefficient resource use. This systematic literature review highlights gaps for further research on prevalence of non-CS diarrhoea and suitability of diagnostic approaches, to determine an effective algorithm for differential diagnosis of GEP-NET diarrhoea. Core tip: Patients with gastroenteropancreatic neuroendocrine tumours (GEP-NETs) often experience diarrhoea, which may have multiple synchronous causes. Although this has a considerable impact on patient quality of life, differential diagnosis of diarrhoea in patients with GEP-NETs is a relatively unexplored topic, and there is currently no formal clinical guidance. This systematic literature review provides valuable insight on the prevalence of causes of diarrhoea in patients with GEP-NETs, evidence on how these cause are diagnosed in this patient population specifically, the consequences if the true cause(s) of diarrhoea are not ascertained, and suggestions for improving differential diagnosis of GEP-NET diarrhoea.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Medicine
Publisher:	Baishideng Publishing Group
ISSN:	1007-9327
Date of Acceptance:	23 June 2020
Last Modified:	13 Mar 2025 09:30
URI:	https://orca.cardiff.ac.uk/id/eprint/176557

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