Gluconeogenesis, liver energy metabolism and weight loss in lung cancer : dynamic studies using stable isotope tracers and 31P magnetic resonance spectroscopy

Weight loss is a major problem in many types of cancer and is associated with reduced quality of life and a poor prognosis. Weight loss can also interfere with potentially curable treatment [41,561. Many uncertainties remain about the mechanisms underlying weight loss in patients with cancer. This thesis describes a series of studies aimed at defining alterations in metabolic processes that are potentially related with weight loss in lung cancer patients. Although in literature the terms 'cachexia' (~ a syndrome of weight loss and rnalnutrition) and 'weight loss' are often used interchangeably, in this thesis weight loss will be preferentially used. In this chapter, current knowledge on weight loss in cancer and its relation with metabolic alterations are reviewed and the aim of this thesis is presented

Weight loss and elevated gluconeogenesis from alanine in lung cancer patients

BACKGROUND: The role of gluconeogenesis from protein in the pathogenesis of weight loss in lung cancer is unclear. OBJECTIVE: Our aim was to study gluconeogenesis from alanine in lung cancer patients and to analyze its relation to the degree of weight loss. DESIGN: In this cross-sectional study, we used primed-constant infusions of [6,6-(2)H(2)]-D-glucose and [3-(13)C]-L-alanine to assess whole-body glucose and alanine turnover and gluconeogenesis from alanine in weight-losing (WL, n = 9) and weight-stable (WS, n = 10) lung cancer patients and healthy control (n = 15) subjects. RESULTS: Energy intake and plasma alanine concentrations did not differ significantly among the subject groups. Mean (+/-SEM) whole-body glucose production was significantly higher in WL than in WS and control subjects (0.74 +/- 0.06 compared with 0.55 +/- 0.04 and 0.51 +/- 0.04 mmol*kg(-)(1)*h(-)(1), respectively, P < 0.01). Alanine turnover was significantly elevated in WL compared with WS and control subjects (0.57 +/- 0.04 compared with 0.42 +/- 0.05 and 0.40 +/- 0.03 mmol*kg(-)(1)*h(-)(1), respectively, P < 0.01). Gluconeogenesis from alanine was significantly higher in WL than in WS and control subjects (0.47 +/- 0.04 compared with 0.31 +/- 0.04 and 0.29 +/- 0.04 mmol*kg(-)(1)*h(-)(1), respectively, P < 0.01). The degree of weight loss was positively correlated with glucose and alanine turnover and with gluconeogenesis from alanine (r = 0.45 for all, P < 0.01). CONCLUSIONS: Aberrant glucose and alanine metabolism occurred in WL lung cancer patients. These changes were related to the degree of weight loss and not to the presence of lung cancer per se

Parametric exploration of the liver by magnetic resonance methods

MRI, as a completely noninvasive technique, can provide quantitative assessment of perfusion, diffusion, viscoelasticity and metabolism, yielding diverse information about liver function. Furthermore, pathological accumulations of iron and lipids can be quantified. Perfusion MRI with various contrast agents is commonly used for the detection and characterization of focal liver disease and the quantification of blood flow parameters. An extended new application is the evaluation of the therapeutic effect of antiangiogenic drugs on liver tumours. Novel, but already widespread, is a histologically validated relaxometry method using five gradient echo sequences for quantifying liver iron content elevation, a measure of inflammation, liver disease and cancer. Because of the high perfusion fraction in the liver, the apparent diffusion coefficients strongly depend on the gradient factors used in diffusion-weighted MRI. While complicating analysis, this offers the opportunity to study perfusion without contrast injection. Another novel method, MR elastography, has already been established as the only technique able to stage fibrosis or diagnose mild disease. Liver fat content is accurately determined with multivoxel MR spectroscopy (MRS) or by faster MRI methods that are, despite their widespread use, prone to systematic error. Focal liver disease characterisation will be of great benefit once multivoxel methods with fat suppression are implemented in proton MRS, in particular on high-field MR systems providing gains in signal-to-noise ratio and spectral resolution

Magnetic resonance spectroscopy to study hepatic metabolism in diffuse liver diseases, diabetes and cancer

This review provides an overview of the current state of the art of magnetic resonance spectroscopy (MRS) in in vivo investigations of diffuse liver disease. So far, MRS of the human liver in vivo has mainly been used as a research tool rather than a clinical tool. The liver is particularly suitable for static and dynamic metabolic studies due to its high metabolic activity. Furthermore, its relatively superficial position allows excellent MRS localization, while its large volume allows detection of signals with relatively low intensity. This review describes the application of MRS to study the metabolic consequences of different conditions including diffuse and chronic liver diseases, congenital diseases, diabetes, and the presence of a distant malignancy on hepatic metabolism. In addition, future prospects of MRS are discussed. It is anticipated that future technical developments such as clinical MRS magnets with higher field strength (3 T) and improved delineation of multi-component signals such as phosphomonoester and phosphodiester using proton decoupling, especially if combined with price reductions for stable isotope tracers, will lead to intensified research into metabolic syndrome, cardiovascular disease, hepato-biliary diseases, as well as non-metastatic liver metabolism in patients with a distant malignant tumor

Adenosine triphosphate infusion increases liver energy status in advanced lung cancer patients: an in vivo 31P magnetic resonance spectroscopy study

We recently observed inhibition of weight loss in patients with advanced nonsmall-cell lung cancer after intravenous infusion of ATP. Because liver ATP levels were found to be decreased in lung cancer patients with weight loss, the present 31P magnetic resonance spectroscopy (MRS) study was aimed at investigating whether ATP infusion restores liver energy status in these patients. Nine patients with advanced nonsmall-cell lung cancer (stage IIIB/IV) were studied 1 week before (baseline) and at 22 to 24 hours of continuous ATP infusion (37-75 microg/kg/min). Localized hepatic 31P MR spectra (repetition time 15 seconds), obtained in the overnight-fasted state, were analyzed for ATP and P(i) content. Ten healthy subjects (without ATP infusion) served as control. Liver ATP levels in lung cancer patients increased from 8.8 +/- 0.7% (relative to total MR-detectable phosphate; mean +/- SE) at baseline to 12.2 +/- 0.9% during ATP infusion (P or = 5% weight loss (baseline: 7.9 +/- 0.7%, during ATP infusion: 12.8 +/- 1.0%, P < 0.01). In conclusion, ATP infusion restores hepatic energy levels in patients with advanced lung cancer, especially in weight-losing patients. These changes may contribute to the previously reported beneficial effects of ATP infusion on the nutritional status of lung cancer patients

Decreased energy and phosphorylation status in the liver of lung cancer patients with eight loss

Background/Aims: Altered energy status has been reported in the liver of tumour-bearing animals, but data on energy status in humans are scarce. Therefore, bioenergetics in tumour-free liver of lung cancer patients were monitored using P-31 magnetic resonance spectroscopy (MRS) with infusion of L-alanine as a gluconeogenic challenge. Methods: Twenty-one overnight-fasted lung cancer patients without liver metastases, with (CaWL) or without weight loss (CaWS), and 12 healthy control subjects (C) were studied. Hepatic energy status was monitored before and during an i.v. L-alanine infusion of 1.4-2.8 mmol/kg + 2.8 mmol . kg(-1). h(-1) for 90 min by P-31 MR spectroscopy. Results: Baseline levels of ATP in WL lung cancer patients, expressed relative to total MR-detectable phosphate, were reduced (CaWL, 9.5+/-0.9% vs. CaWS, 12.6+/-0.8% and C, 12.4+/-0.8%;

Hepatic sugar phosphate levels reflect gluconeogenesis in lung cancer: simultaneous turnover measurements and 31P magnetic resonance spectroscopy in vivo

Stable-isotope tracers were used to assess whether levels of phosphomonoesters (PME) and phosphodiesters (PDE) in the livers of lung cancer patients, as observed by P-31 magnetic resonance (MR) spectroscopy, reflect elevated whole-body glucose turnover and gluconeogenesis from alanine. Patients with advanced non-small-cell lung cancer without liver metastases (n = 24;weight loss 0-24%) and healthy control subjects (n = 13) were stud led after an overnight fast. P-31 MR spectra of the liver in vivo were obtained, and glucose turnover and gluconeogenesis from alanine were determined simultaneously using primed-constant infusions of [6,6-H-2(2)]glucose and [3-C-13]alanine. Liver PME concentrations were 6% higher in lung cancer patients compared with controls (not significant); PME levels in patients with greater than or equal to 5% weight loss were significantly higher than in patients with <5% weight loss (P <0.01). PDE levels did not differ between the groups. In lung cancer patients, whole-body glucose production was 19% higher (not significant) and gluconeogenesis from alanine was 42% higher (P <0.05) compared with healthy subjects; turnover rates in lung cancer patients with greater than or equal to 5% weight loss were significantly elevated compared with both patients with <5% weight loss and healthy subjects (P <0.05). PME levels were significantly correlated with glucose turnover and gluconeogenesis from alanine in lung cancer patients (r = 0.48 and r = 0.48 respectively; P <0.05). In conclusion, elevated PME levels in lung cancer patients appear to reflect increased glucose flux and gluconeogenesis from alanine. These results are consistent with the hypothesis that elevated PME levels are due to contributions from gluconeogenic intermediates

Observing cultural competence of healthcare professionals: A systematic review of observational assessment instruments

Contains fulltext : 232480.pdf (Publisher’s version ) (Open Access)OBJECTIVE: Observational instruments are preferred for assessment of cultural competence. The aim of the current study is to identify observational instruments to assess cultural competence in healthcare providers and dieticians specifically and assess their psychometric properties. METHODS: A systematic review was conducted in Cinahl, Cochrane, EMBASE, PsycInfo, Pubmed, and Web of Science using search terms related to cultural competency and measurement properties. Methodological quality of the selected studies of observational cultural competence instruments in dieticians, other healthcare professionals and psychological counsellors and the measurement properties of instruments were assessed using the COSMIN checklist. RESULTS: From 11,913 articles, six articles on five instruments were selected. Instruments were targeted at health professionals and counsellors only, and designed for face-to-face communication (n = 4) or verbal responses to videotaped simulated interactions (n = 1). The instruments' content varied largely, with main focus on attitude, and little on knowledge and skills. The measurement properties were suboptimal. CONCLUSION: No observational instrument are available to evaluate cultural competence of dieticians. Studies on psychometric properties of instruments targeted at other health professionals lack methodological rigour. PRACTICE IMPLICATIONS: Future work should focus on developing an instrument that encompasses both 'general' cultural competences necessary for all healthcare professionals and dietetic specific competences