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.     

Classic complication of uterine revision after a late abortion: uterine synechia. Current review based on two cases]

The authors use two personal cases to review the etiological circumstances, pathology and clinical and paraclinical manifestations, stressing in particular the current value of diagnostic and therapeutic hysteroscopy. Advice is given concerning prevention and treatment.     

Per operative localization of a carcinoid tumour of the breast using indium-111 pentetreotide and a nuclear surgical probe

A 69-year-old woman presented with a single enlarged lymph node in the left axilla. Clinical examination and other investigations, including various imaging methods, failed to reveal the primary tumour. However, indium-111 pentetreotide scan revealed a site of uptake in the anterior region of the left thorax. Peroperative imaging with t¹¹¹In-pentetreotide confirmed the tumour uptake and use of a nuclear surgical probe allowed precise localization of the tumour, which was completely resected.     

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.     

Central serous chorioretinopathy and risk for obstructive sleep apnea

Patients with obstructive sleep apnea (OSA), in comparison to controls, have increased levels of circulating epinephrine and norepinephrine, both of which are risk factors for the development of central serous chorioretinopathy (CSCR). The aim of this pilot study was to investigate the frequency of symptoms that suggest OSA in CSCR patients and normal controls. The Berlin Questionnaire, a validated research tool to assess risk for OSA, was administered to 29 patients who met the criteria for active, acute, non-steroid-induced CSCR and 29 controls matched for age and sex. In this retrospective case-controlled study, the main outcome measure was increased risk for OSA. The mean age of the patients was 47.8 years (range 29–72) and the mean age of controls was 47.3 years (range 25–70). Seventy-six percent (22) of both groups were men. Survey scores showed 58.6% (17) of patients with CSCR to be at an increased risk for OSA compared to 31.0% (nine) of controls. A conditional logistic regression analysis showed that the CSCR group had a higher proportion with an increased risk for OSA compared to the control group (odds ratio=3.67; 95% CI: 1.02, 13.14; P = 0.046). Patients with CSCR may be more likely than other adults to have OSA, and screening for this sleep disorder should be considered in this population. Further research is warranted to determine whether sleep apnea may contribute to the development of CSCR, and to assess whether treatment of sleep apnea might offer a new therapeutic option for some patients with CSCR.     

Evaluation of the polymorphisms associated with tandem repeats for Pseudomonas aeruginosa strain typing

We report on the development of a scheme for the typing of Pseudomonas aeruginosa, multiple-locus variable number of tandem repeat (VNTR) analysis (MLVA). We first evaluated the polymorphisms of 201 tandem repeat loci selected from more than 3,000 such sequences present in strain PAO1 with a test collection of 12 genotypically distinct clinical strains. Seven VNTR loci which can be easily scored with the technology used here were identified and used to genotype a collection of 89 clinical isolates that had previously been classified into 46 ribotypes, including 2 widespread ribotypes. Seventy-one different MLVA genotypes could be distinguished. With only two exceptions, strains with identical ribotypes were grouped together upon cluster analysis of the MLVA data. The 27 isolates with the most frequent ribotype were divided into 14 MLVA types, and the 18 isolates with the second most frequent ribotype were divided into 15 MLVA types. Analysis of a subset of 17 strains belonging to the major ribotype by pulsed-field gel electrophoresis with the enzyme SpeI distinguished seven types, identical to the number of MLVA types in this subset. Our data show that MLVA typing of P. aeruginosa based on the first set of loci has a high discriminatory power. Because MLVA is highly reproducible and easily portable among laboratories, it represents a very promising tool for the molecular surveillance of P. aeruginosa. A free, online strain identification service based on the genotyping data produced herein has been developed.     

Stimulation of capillary tube polymorph migration: an indirect glucocorticoid effect on microtubular function.

Polymorph migration stimulator (PMS) is a peptide factor produced by an in vitro reaction between glucocorticoids and human mononuclear phagocytes. This study was undertaken to determine the significance of the stimulatory effect of PMS on the capillary tube migration of human polymorphs. Colchicine, vinblastine and Nocodazole, all of which inhibit microtubular assembly, are shown to stimulate migration. Conversely, deuterium oxide which stabilizes microtubules inhibits migration. Increased intracellular cyclic AMP is associated with microtubular inhibition and isoprenaline, theophylline and dibutyryl cyclic AMP are also found to stimulate capillary tube migration. These results suggest that PMS acts by inhibiting the assembly of polymorph microtubules, an effect which may be mediated by cyclic AMP in the same manner as other peptide hormones.     

Genetic variants of homocysteine metabolizing enzymes and the risk of coronary artery disease

It is unresolved whether elevated homocysteine in coronary artery disease (CAD) is the cause of arteriosclerosis or its consequence. In contrast, genetic variants of enzymes that metabolize homocysteine cannot be altered by arteriosclerosis. Consequently, their association with CAD would permit to imply causality. We modeled by regression analysis the effect of 11 variants in the methionine cycle upon CAD manifestation in 591 controls and 278 CAD patients. Among the examined variants only the carriership for the c.844ins68 in the cystathionine beta-synthase (CBS) gene was associated with a significantly lowered risk of CAD (OR=0.56; 95% CI=0.35-0.90 in the univariable, and OR=0.41, 95% CI=0.19-0.89 for obese people in the multivariable analysis, respectively). Healthy carriers of the c.844ins68 variant exhibited, compared to the wild type controls, significantly higher postload ratios of blood S-adenosylmethionine to S-adenosylhomocysteine (61.4 vs. 54.9, p=0.001) and of plasma total cysteine to homocysteine (8.6 vs. 7.3, p=0.004). The changes in these metabolites are compatible with an improved methylation status and with enhanced activity of homocysteine transsulfuration. In conclusion, the coincidence of clinical and biochemical effects of a common c.844ins68 CBS variant supports the hypothesis that compounds relating to homocysteine metabolism may play role in the development and/or progression of CAD.