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

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. CON...

European Neuroendocrine Tumor Society (ENETS) 2022 Guidance Paper for Carcinoid Syndrome and Carcinoid Heart Disease

“…Also, patients with an established CS, on treatment, can experience deterioration of their symptoms from other causes. 27,28 • Diarrhoea in CS is always secretory, persists with fasting, may occur during the night and is associated with abdominal discomfort and faecal urgency. Sometimes, to prove "secretory" diarrhoea, an estimation of faecal fluid "osmotic gap" is needed, with an "osmotic gap" of A short bowel syndrome, defined as a length of functional small bowel < 200 cm may occur after extensive intestinal resection.…”

“…The most common symptoms in CS (flushing, diarrhoea, their combination) may represent manifestations of other clinical entities. Also, patients with an established CS, on treatment, can experience deterioration of their symptoms from other causes 27,28 Diarrhoea in CS is always secretory, persists with fasting, may occur during the night and is associated with abdominal discomfort and faecal urgency. Sometimes, to prove “secretory” diarrhoea, an estimation of faecal fluid “osmotic gap” is needed, with an “osmotic gap” of < 50 mOsm kg –1 being diagnostic for secretory diarrhoea.…”

An unusual case of chronic diarrhea: a case report

“…This case report describes a nuanced and very insidious clinical presentation of Atypical Carcinoid Syndrome due to a GEP-NEN, characterized by chronic diarrhea as primary symptom. Although several cases of diarrhea due to GEP-NENs are reported in the literature [4], this case underlines how a simple clinical symptom may hide a complex diagnosis. This clinical case highlights the complexity of the diagnostic process and the difficulties in interpreting the examinations for this type of tumor, showing how the negativity of firstlevel examinations did not prevent from performing further investigations, in the presence of a suggestive clinical presentation.…”

Antipsychotic-Related Stigma and the Impact on Treatment Choices: A Systematic Review and Framework Synthesis

“…This method of integrating both quantitative and qualitative data into framework synthesis has previously been used in at least two published literature reviews. 41 , 42 …”

“…This method of integrating both quantitative and qualitative data into framework synthesis has previously been used in at least two published literature reviews. 41,42 To facilitate data extraction and synthesis, a preliminary framework of themes that were expected to be identified was determined through a scoping search of the literature and discussion with clinical experts.…”