Identification of prognostic inflammatory factors in colorectal liver metastases.

BACKGROUND: The modified Glasgow Prognostic Score (mGPS) has been reported to be an important prognostic indicator in a number of tumor types, including colorectal cancer (CRC). The features of the inflammatory state thought to accompany elevated C-reactive protein (CRP), a key feature of mGPS, were characterized in patients with colorectal liver metastases. Additional inflammatory mediators that contribute to prognosis were explored. METHODS: In sera from 69 patients with colorectal liver metastases, a panel of 42 inflammatory mediators were quantified as a function of CRP levels, and as a function of disease-free survival. Multivariate statistical methods were used to determine association of each mediator with elevated CRP and truncated disease-free survival. RESULTS: Elevated CRP was confirmed to be a strong predictor of survival (HR 4.00, p = 0.001) and recurrence (HR 3.30, p = 0.002). The inflammatory state associated with elevated CRP was comprised of raised IL-1ß, IL-6, IL-12 and IL-15. In addition, elevated IL-8 and PDGF-AB/BB and decreased eotaxin and IP-10 were associated with worse disease-free and overall survival. CONCLUSIONS: Elevated CRP is associated with a proinflammatory state. The inflammatory state is an important prognostic indicator in CRC liver metastases. The individual contributions of tumor biology and the host to this inflammatory response will require further investigation.

Risk of Venous Thromboembolism in Glioblastoma Patients.

Background Patients with cancer are at increased risk of venous thromboembolic events (VTE) with a particularly high prevalence in patients with glioblastoma (GB). We designed this current study to determine the incidence of symptomatic VTE in patients with GB undergoing first-line chemoradiotherapy and to develop a clinical score to help physicians identify those who are at the highest risk of VTE. Methods A retrospective study cohort included patients diagnosed with GBM treated with radical concurrent chemoradiotherapy between 2005 and 2010 in Southern Alberta. Descriptive statistics were used to characterize the patient population. A predictive value for VTE was assessed by comparing logistic models and using the area under the receiver operating characteristic curve. Results Twenty-three out of 115 patients (20%) experienced a symptomatic VTE. This complication was not associated with overall survival at two years (p=0.06, heart rate (HR)=1.61). Hypertension and smoking were associated with VTE (p-values 0.034 and 0.048, respectively). A scoring system with the following variables was developed to predict the likelihood of developing VTE: (1) Karnofsky performance status (KPS) - 70, 1 point; KPS < 70, 2 points; (2) Age - 45 to 60, 1 point; 61 to 70, 2 points; (3) Current smoking, 1 point; (4) Hypertension, 1 point. Patients with >3 points were 5 times more likely to develop a VTE. Conclusions In our population, our simple scoring system allows the identification of patients with GB receiving first-line therapy, who are at the highest risk of VTE. These results require validation in an independent series.

Sarcopenia and myosteatosis are accompanied by distinct biological profiles in patients with pancreatic and periampullary adenocarcinomas.

INTRODUCTION: Pancreatic and periampullary adenocarcinomas are associated with abnormal body composition visible on CT scans, including low muscle mass (sarcopenia) and low muscle radiodensity due to fat infiltration in muscle (myosteatosis). The biological and clinical correlates to these features are poorly understood. METHODS: Clinical characteristics and outcomes were studied in 123 patients who underwent pancreaticoduodenectomy for pancreatic or non-pancreatic periampullary adenocarcinoma and who had available preoperative CT scans. In a subgroup of patients with pancreatic cancer (n = 29), rectus abdominus muscle mRNA expression was determined by cDNA microarray and in another subgroup (n = 29) 1H-NMR spectroscopy and gas chromatography-mass spectrometry were used to characterize the serum metabolome. RESULTS: Muscle mass and radiodensity were not significantly correlated. Distinct groups were identified: sarcopenia (40.7%), myosteatosis (25.2%), both (11.4%). Fat distribution differed in these groups; sarcopenia associated with lower subcutaneous adipose tissue (P<0.0001) and myosteatosis associated with greater visceral adipose tissue (P<0.0001). Sarcopenia, myosteatosis and their combined presence associated with shorter survival, Log Rank P = 0.005, P = 0.06, and P = 0.002, respectively. In muscle, transcriptomic analysis suggested increased inflammation and decreased growth in sarcopenia and disrupted oxidative phosphorylation and lipid accumulation in myosteatosis. In the circulating metabolome, metabolites consistent with muscle catabolism associated with sarcopenia. Metabolites consistent with disordered carbohydrate metabolism were identified in both sarcopenia and myosteatosis. DISCUSSION: Muscle phenotypes differ clinically and biologically. Because these muscle phenotypes are linked to poor survival, it will be imperative to delineate their pathophysiologic mechanisms, including whether they are driven by variable tumor biology or host response.