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

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(Se HCAT) 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.     

Computed tomography of the brain in the Smith-Lemli-Opitz syndrome

Computed tomographic (CT) scans of the brain in a child with Smith-Lemli-Opitz syndrome revealed enlargement of the ventricular system, hypoplasia of the cerebellum, and abnormal thickening of the gray matter, consistent with pachygyria. These findings have been previously noted in autopsies performed on patients with this disorder. We conclude that CT scanning is a valuable tool in the evaluation of children suspected of having the Smith-Lemli-Opitz syndrome.     

The pH Optima for Papain and Bromelain Treatment of Red Cells

The action of papain and bromelain, prepared over a pH range from 4.6 to 8.6, was evaluated for the ability to render red cells agglutinable by five incomplete antibodies of differing blood group specificities using a two-stage technique. The optimal pH for treatment of red cells by activated papain or bromelain was between 5.4 and 5.8. Above this pH range, a fall in serological sensitivity was apparent which was much more pronounced with papain than with bromelain. The optimal pH for enzyme treatment of red cells can be achieved in two-stage techniques, but not in one-stage techniques due to the buffering effect of serum proteins.     

Mesogonadal shunts for extrahepatic portal vein thrombosis and variceal hemorrhage.

Extrahepatic portal vein thrombosis (EHPVT) may occur in children or adults and usually comes to clinical attention due to complications of portal hypertension such as variceal hemorrhage. A variety of standard surgical techniques exist to manage these patients, but when these fail surgical options are limited. We describe two novel portosystemic shunts that utilize the gonadal vein as an autologous conduit. Four patients were evaluated for EHPVT with variceal bleeding. None of the patients were candidates for a standard splenorenal shunt due to prior surgical procedures. The first patient underwent a left mesogonadal shunt and the remaining 3 patients underwent a right mesogonadal shunt. Postoperative ultrasound or computed tomography (CT) scan confirmed early patency of the shunt in each patient. There have been no further episodes of variceal hemorrhage with follow-up of 3.5 years in the child who underwent the left mesogonadal shunt, and 17, 19, and 20 months in the patients who underwent the right mesogonadal shunt. Three of the 4 shunts remain patent. One shunt thrombosis occurred in a patient homozygous for the Factor V Leiden mutation despite anticoagulation with coumadin. This is the first report of the successful use of the gonadal vein as an in situ conduit for constructing a portosystemic shunt. In conclusion, the right and left mesogonadal shunts may be useful as salvage operations for patients with EHPVT who have failed standard surgical shunt procedures.     

Decreasing incidence of peptic ulcer complications after the introduction of the proton pump inhibitors, a study of the Swedish population from 1974–2002

Background  

Despite a decreasing incidence of peptic ulcer disease, most previous studies report a stabile incidence of ulcer complications. We wanted to investigate the incidence of peptic ulcer complications in Sweden before and after the introduction of the proton pump inhibitors (PPI) in 1988 and compare these data to the sales of non-steroid anti-inflammatory drugs (NSAID) and acetylsalicylic acid (ASA).     

Effects of an exercise intervention for older heart failure patients on caregiver burden and emotional distress.

BACKGROUND: The impact of exercise programmes for heart failure on those close to the patient is largely unknown. We examined the effect of a hospital and home-based exercise intervention on burden, anxiety and depression of informal caregivers. DESIGN: The study was a randomized, controlled trial. Heart failure patients were randomized to a seated 12-week hospital-based exercise programme. Caregiver measures were gathered at baseline, 3 months later and 6 months following baseline. METHODS: Sixty caregivers (mean age 63.4 years, 65% female) of heart failure patients (n = 82, mean age 80.5 years, 44% female) participating in a trial of an exercise intervention were recruited. Caregiver burden, anxiety and depression were assessed. RESULTS: There were no differences in caregiver burden, depression or anxiety between the two groups of caregivers at baseline (caregiver burden, patient control 33.1 versus patient exercise 34.1; anxiety 4.1 versus 5.5; depression 2.8 versus 3.8). At 3 months there were no differences between caregivers in the two groups on outcomes. At 6-month follow-up caregivers of heart failure patients in the exercise group had burden scores that were significantly worse than the control group. There were no differences between the carers of exercise and control groups in anxiety and depression. Levels of anxiety and depression in the entire carer sample were marginally higher than reference values in a healthy non-clinical sample. CONCLUSION: The present exercise interventions for frail older patients did not benefit caregivers and was associated with an increase in caregiver burden. We suggest that future exercise interventions for heart failure patients should actively incorporate informal caregivers into research designs.