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.     

Choristomas of the seventh and eighth cranial nerves.

Choristomas, masses of normal tissues in aberrant locations, contain smooth muscle fibers and fibrous tissues. We describe the MR imaging features of two choristomas located in the internal auditory canals and arising from the facial and vestibulocochlear nerves. Both lesions enhanced with contrast material. In one case, enhancement was seen in the geniculate ganglion and greater superficial petrosal nerve. In the other, a medial component enhanced less than the lateral component did.     

Effects of halothane on calcium release from sarcoplasmic reticulum of rabbit psoas and semitendinosus skinned muscle fibers

Calcium release from sarcoplasmic reticulum was investigated using skinned fibers isolated from rabbit semitendinosus and psoas muscles, representative of slow and fast fibers, respectively. In both types of fibers, halothane at the concentration of 0.03% (v/v) enhanced the Ca2(+)-induced calcium release. In the absence of cytoplasmic free Ca2+, halothane induced calcium release in a dose-dependent manner, with a similar sensitivity for both semitendinosus and psoas fibers. These results are discussed in connection with muscular diseases such as malignant hyperthermia in which the crisis is triggered during anesthesia by halothane.     

Cephalometric measurements in snorers, non-snorers, and patients with sleep apnoea.

Cephalometry is often used to assess patients with sleep apnoea but whether these measurements differ from those in non-apnoeic snorers and how they are influenced by age is not clear. Cephalometric radiographs of patients with sleep apnoea were compared with those of snorers without sleep apnoea and those of non-snorers. Fifty two snorers with suspected sleep apnoea had a conventional sleep study and were divided into two groups: those with an apnoea-hypopnoea index greater than 10/h (n = 40, sleep apnoea group) and those whose apnoea-hypopnoea index was 10/h or less (n = 12, snorer group). The cephalometric measurements in these patients were compared with those of 34 non-snoring control subjects. Controls were subdivided into two groups: control group 1 included 17 subjects similar in age to the sleep apnoea and snorer groups (mean (SD) age 50.0 (10.9), 50.7 (9.4), and 50.6 (9.7) years); control group 2 included 15 young men (25.4 (2.6) years). The distance from the mandibular plane to the hyoid bone (MP-H) and the length of the soft palate were greater in the patients with sleep apnoea (28.7 (7.8) and 43.6 (5.0) mm) than in the snorers (23.7 (4.2) and 40.3 (4.9 mm). The MP-H was similar in snorers and age matched control subjects, but was significantly greater in the older than in the younger control subjects (22.1 (6.1) vs 17.0 (6.8]. The soft palate was longer in subjects who snored (both sleep apnoea patients and snorers) than in control subjects. The MP-H distance significantly correlated with age for all subjects (snorers and controls) and for the control subjects alone. This study shows that non-apnoeic snorers have cephalometric abnormalities that differ from those of patients with sleep apnoea and that cephalometric values are influenced by the subject's age.     

Effect of silymarin and its polyphenolic fraction on cholesterol absorption in rats.

This study evaluated the influence of silymarin (SM) and polyphenolic fraction (PF) of silymarin on cholesterol absorption in rats fed on high cholesterol diet (HCD). HCD induced a remarkable increase in hepatic, plasma, VLDL and LDL cholesterol, a decrease in HDL cholesterol and an elevation in triacylglycerol (TAG) levels in plasma, VLDL and in the liver. SM and PF were administered as dietary supplements (1.0%) in HCD for 18 days. Intestinal cholesterol absorption was measured by dual-isotope plasma ratio method, which calculates percent of cholesterol absorption from the ratio of two labelled cholesterol doses, one given intragastrically (14C) and one intravenously (3H). Silymarin and PF significantly reduced cholesterol absorption in rats fed on HCD and caused significant decreases in plasma and VLDL cholesterol and content of cholesterol and TAG in the liver. The level of HDL cholesterol was significantly increased after silymarin, but not after administration of PF. The levels of TAG in plasma and VLDL were not affected by either silymarin or PF. These results suggest that the inhibition of cholesterol absorption caused by silymarin and its polyphenolic fraction could be a mechanism contributing to the positive changes in plasma cholesterol lipoprotein profile and in lipid content in liver.     

A Brief Mental Health Outcomes Measure: Translation and Validation of the Czech Version of the Schwartz Outcomes Scale-10

The Schwartz Outcomes Scale-10 (SOS-10) is a 10-item scale developed to measure the effectiveness of psychiatric treatments. Using standard methodology, we translated the scale into Czech and examined the psychometric properties of the Czech version. 207 in-patients admitted to Prague Psychiatric Center were included in the study. All patients completed the SOS at admission and discharge. The SOS-10 scale was also administered to 170 persons from the general population. Reliability, validity and sensitivity to treatment change of the Czech SOS-10 were analyzed. The Cronbach’s α coefficient was 0.92. The item-total correlation coefficients varied from 0.56 to 0.82. The SOS-10 correlated well with condition-specific measures including depression (BDI) and anxiety (BAI) and a global self-rated symptom severity scale (CGI). The SOS-10 also had significant correlations with the Health, Basic needs, Relationship, and Leisure time domains of the Czech version of the Subjective Quality of Life Analysis (SQUALA-CZ). The scale discriminated well between patients and controls, with patients scoring significantly lower on all SOS items. The patient sample’s admission and discharge scores were significantly different, indicating that the scale is sensitive to treatment changes. We concluded that the Czech SOS-10 is valid with reliability and factor structure similar to the American language version.     

Une évaluation des besoins en transplantation d'organes au Québec.

OBJECTIVES: To evaluate the demand for organs for transplantation and to recommend a reorganization of transplantation services in Quebec. DESIGN: Retrospective study. SETTING: Province of Quebec, 1988 to 1992. PATIENTS: All patients on waiting lists for organ transplantation and patients who received transplants registered in national data banks. MAIN OUTCOME MEASURES: The actual annual demand for organ transplantation and the rate of transplantations performed. RESULTS: The rates of heart transplantation were lower than the actual annual demand, which resulted in many patients dying while awaiting transplantation. The actual annual demand for heart transplantation decreased during the last 5 years from 10.9 per million people in 1987 to 6.7 in 1992. The rates of heart transplantation in Quebec were higher than the Canadian average. The actual demand for lung transplantation was only 2.9 per million people on average in 1992. Demand for liver transplantation increased annually, reaching 8.6 per million in 1992. The rate of transplantation increased likewise but remained insufficient. The demand for kidney transplantation reached 27.2 per million people in 1992, and the transplantation rate was 17.8. CONCLUSIONS: Taking into account the actual demand for and supply of organ transplantation, to insure high-quality service and to control costs associated with organ transplantation, we recommend that the present system in Quebec be reorganized so that transplantations are performed in 12 centres: 7 for kidney transplantation, 2 for hearts, 2 for livers and 1 for lungs.