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.     

Intraperitoneal therapy for ovarian cancer: analysis of fluid distribution by computerized tomography.

Nineteen patients with ovarian cancer and minimal residual or persistent disease who were treated with cisplatin or carboplatin-based intraperitoneal (IP) regimens had distribution studies of IP contrast and computerized tomography prior to and during treatment. The distribution pattern was assessed retrospectively and scored for the presence of contrast in each of eight regions: the under surface of right and left diaphragms, the right and left paracolic gutters, the lesser omental sac, the intramesenteric region and the true and false pelvis. Assigning a point to each region with adequate distribution, we classified 10 patients to an excellent pattern (greater than or equal to 7 of 8 regions), 6 to a good pattern (5 to less than 7 regions), and 3 to an inadequate distribution pattern (less than 5 regions). Serial studies were performed in 8 patients after more than 4 cycles of IP therapy. In these patients, all of whom were tolerating treatment without progression, the distribution remained virtually unchanged for those with excellent distribution. One of three with good distribution manifested inadequate distribution on repeat study, and one of two with inadequate distribution improved to show a good pattern. In this small study there was no correlation of distribution patterns with plasma CA-125 at onset of IP treatment and prior surgical procedures or placement of the catheter tip. However, three patients with unsatisfactory patterns had procedures consisting of catheter placement only rather than formal reassessment laparotomies for ovarian cancer. Since satisfactory IP distribution may be required for obtaining a therapeutic advantage from IP therapy, methods for its assessment must be developed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Elevated levels of acute phase plasma proteins in major depression.

Levels of acute phase and other plasma proteins were measured in 21 men with major depression, 28 men with alcohol dependence, and 12 men who acted as controls. The depressed men had significantly elevated levels of the acute phase proteins, haptoglobin and alpha-1-antichymotrypsin, and of immunoglobulin G. The elevations in haptoglobin and alpha-1-antichymotrypsin were highly correlated with each other, and were correlated with the severity of depression and negatively correlated with the thyroid stimulating hormone response to thyrotropin. The alcoholic men had elevated haptoglobin levels, but significantly decreased levels of immunoglobulin G. These findings provide further evidence for an inflammatory response during depression.     

FM sonography in diffuse liver disease: prospective assessment and blinded analysis

FM sonography - a signal-processing technique that uses frequency and phase information as well as amplitude data - shows promise in evaluation of patients with diffuse liver disease. In a prospective blinded review of 37 patients with biopsy-proved liver disease and 42 healthy volunteers, FM sonography was clearly superior to traditional amplitude-based (AM) sonography in distinguishing healthy from diseased subjects. Statistically significant differences were seen in accuracy (FM, 98.7%; AM, 84.8%), sensitivity (FM, 97.3%; AM, 70.3%), and negative predictive value (FM, 97.7%; AM, 78.8%). Our data also suggest that current FM sonographic techniques cannot differentiate among histologic findings associated with different hepatic parenchymal abnormalities. It is unclear, therefore, whether FM imaging can reduce the numbers of patients who require biopsy for diagnosis or the frequency of biopsy procedures in patients with known disease.     

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.     

MR imaging of neurocysticercosis

Magnetic resonance (MR) was performed in 50 patients with neurocysticercosis. Comparison was made with other neuroradiological imaging modalities including CT, myelography, CT ventriculography, and CT myelocisternography. Eighteen patients were found to have intraventricular cysts. In several patients, these were multiple and 22 intraventricular cysts were discovered. Although 4 of the 22 ventricular cysts were missed by MR, T1-weighted images can play a significant role in the early detection of intraventricular cysticercosis cysts, showing the cyst wall (9 of 22), a high intensity mural nodule (6 of 22), and increased signal intensity of the cyst fluid (5 of 22). Cisternal cysts (14 cysts in 10 patients) could be identified; they appear similar to intraventricular cysts, but mural nodules are infrequently seen (1 of 14). Twenty-nine patients had 69 parenchymal cysts. An attempt was made to assess the viability of these parenchymal lesions by matching the CT and MR findings with the Escobar pathologic staging system. Neuroimaging findings seemed compatible with early parenchymal lesions in the vesicular stage in 11 instances. Findings in cases with later stage cysts tend to support the concept that a dying larva provokes pronounced inflammatory reaction in the adjacent brain. Computed tomography remains the superior modality for depicting parenchymal calcifications within dead larvae. A case of a spinal cysticercosis cyst demonstrated with MR (in a patient with extensive intracranial cisternal cysts and a fourth ventricular cyst) is described.     

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.     

Blastomycosis: a case study of a dimorphic fungal disease.

A 17-year-old male presented to a local hospital with symptoms of pneumonia and a hacking cough productive of yellow sputum. Direct examination of a bronchial lavage sample revealed organisms morphologically consistent with Blastomyces dermatitidis, which was confirmed by culture. The patient was placed on intravenous antifungal therapy and his condition improved dramatically. OBJECTIVES: to describe the gross and microscopic morphologies of both yeast and mold forms of B. dermatitidis; to identify B. dermatitidis given patient history, and microscopic and colony morphology; to describe the symptoms of primary pulmonary infections caused by B. dermatitidis, and to name additional tissues typically affected by the systemic pathogen.