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ObjectivesTo examine the distribution of birth weight in children with nonalcoholic fatty liver disease (NAFLD) compared with the general US population, and to investigate the relationship between birth weight and severity of NAFLD.Study designA multicenter, cross-sectional study of children with biopsy-proven NAFLD enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network Database. Birth weight was categorized as low birth weight (LBW), normal birth weight (NBW), or high birth weight (HBW) and compared with the birth weight distribution in the general US population. The severity of liver histology was assessed by birth weight category.ResultsChildren with NAFLD (n = 538) had overrepresentation of both LBW and HBW compared with the general US population (LBW, 9.3%; NBW, 75.8%; HBW, 14.9% vs LBW, 6.1%; NBW, 83.5%; HBW 10.5%; P

Background & aimsSex and sex hormones can affect responses of patients with nonalcoholic fatty liver disease (NAFLD) to metabolic stress and development of hepatocyte injury and inflammation.MethodsWe collected data from 3 large U.S. studies of patients with NAFLD (between October 2004 and June 2013) to assess the association between histologic severity and sex, menopause status, synthetic hormone use, and menstrual abnormalities in 1112 patients with a histologic diagnosis of NAFLD. We performed logistic or ordinal logistic regression models, adjusting for covariates relevant to an increase of hepatic metabolic stress.ResultsPremenopausal women were at an increased risk of lobular inflammation, hepatocyte ballooning, and Mallory-Denk bodies than men and also at an increased risk of lobular inflammation and Mallory-Denk bodies than postmenopausal women (P < .01). Use of oral contraceptives was associated with an increased risk of lobular inflammation and Mallory-Denk bodies in premenopausal women, whereas hormone replacement therapy was associated with an increased risk of lobular inflammation in postmenopausal women (P < .05).ConclusionsBeing a premenopausal woman or a female user of synthetic hormones is associated with increased histologic severity of hepatocyte injury and inflammation among patients with NAFLD at given levels of hepatic metabolic stress.

Serum Cytokines Correlate with Pretreatment Body Mass Index-Adjusted Body Weight Loss Grading and Cancer Progression in Patients with Stage III Esophageal Squamous Cell Carcinoma Undergoing Neoadjuvant Chemoradiotherapy Followed by Surgery. Circulating cytokines have been linked to the development of esophageal squamous cell carcinoma (ESCC) and its associated malnutrition process. Nonetheless, given the varied disease stages and treatment modalities in previous studies, the clinical relevance of their findings is limited. We retrospectively studied 52 patients with stage III ESCC who underwent neoadjuvant chemoradiotherapy and curative-intent surgery. We investigated the association of clinicopathological features, pretreatment laboratory data, and pretreatment inflammatory status, as indicated by the levels of albumin, C-reactive protein, and 10 circulating cytokines, namely tumor necrosis factor-alpha (TNF-α), interferon-gamma, interleukin-1-beta (IL-1β), IL-4, IL-6, IL-8, IL-12, IL-13, IL-17A, and IL-23, with malnutrition, as shown by body mass index-adjusted body weight loss (BMI-BWL) grading, cancer progression. Half the patients showed severe malnutrition and high BMI-BWL grades (3 and 4). Multivariate analysis revealed an independent association between the levels of three cytokines (TNF-α, ≤ 5.8 pg/ml; IL-1β, > 0.4 pg/ml; IL-6, ≤ 12.4 pg/ml) and high BMI-BWL grades and between IL-4 levels > 22.5 pg/ml and cancer progression. All 10 cytokines were closely correlated with each other. In conclusion, TNF-α, IL-1β, and IL-6 were independent markers of malnutrition status and IL-4 was a prognostic factor for cancer progression in this patient population. [ABSTRACT FROM AUTHOR]

Systemic inflammation plays a pivotal role in colorectal cancer (CRC) development. Two hallmarks reflect the severity of inflammation—circulating cytokines and nutrition-inflammation biomarkers (NIBs); however, their interplay has not been fully investigated. In total, 128 CRC patients were included. Ten circulating cytokines (TNF-α, TGF-β, IFN-γ, IL-1β, IL-4, IL-6, IL-10, IL-12, IL-13, and IL-23) and NIBs were analyzed. The relationship between cytokines, NIBs, clinicopathological variables, and overall survival (OS) was assessed using univariate and multivariate analyses. Three NIBs (CRP-to-albumin ratio [CAR]), neutrophil-to-lymphocyte ratio [NLR]), and prognostic nutritional index [PNI]) were associated with OS in univariate analysis; however, CAR was better for OS prediction in multivariate analysis (P = 0.015). None of the serum cytokines analyzed showed a significant association with OS. High CAR (≥0.25) and high IL-10 (≥76.6 pg/mL), high NLR (≥8.2) and high IL-23 (≥51.2 pg/mL), and high PNI (≥42.4) and high IL-1β (≥14.3 pg/mL) values were correlated. CAR, NLR, and PNI were not correlated with each other, whereas circulating cytokines were closely interrelated. High CAR was an independent predictor of poor OS in patients with CRC. Different NIBs have unique cytokine profiles, but show no correlation with each other. There is a close association among the circulating cytokines. [ABSTRACT FROM AUTHOR]

Various malnutrition and inflammation criteria were associated with prognosis of esophageal squamous cell carcinoma (ESCC) patients. Nonetheless, the interplay of clinicopathological features, malnutrition, and inflammation criteria with overall survival in ESCC patients remains unclear. We retrospectively reviewed medical records of 205 patients diagnosed with ESCC between 2007 and 2012, and evaluated the status of participant malnutrition and inflammation, including body mass index < 18.5 kg/m2, body weight loss > 5.0%, serum albumin level < 3.5 g/dl, neutrophil-to-lymphocyte ratio > 3.5, platelet-to-lymphocyte ratio > 20, prognostic nutrition index < 40, blood total lymphocyte count < 1600 cells/mm3, and grades of body mass index-adjusted body weight loss (combined BMI-BWL). We assessed the association of clinicopathological features, nutritional status, and inflammation condition with overall survival using univariate and multivariate Cox regression analyses. The mean overall survival of ESCC patients was 28.8 mo,. The multivariate logistic regression model after adjustment for clinicopathological variables, malnutrition status, inflammation condition, and co-morbid status found that tumor stage and grades of combined BMI-BML served as equally important prognostic factors for overall survival. Advanced tumor stage and high grades of combined BMI-BWL were independent prognostic factors for overall survival in ESCC patients. [ABSTRACT FROM AUTHOR]

Background and Objectives: To examine the relationship between malnutrition criteria, serum glutamine and arginine concentrations, and clinicopathological features in Taiwan colorectal cancer patients.Methods and Study Design: Three malnutrition criteria (body weight loss>5% over past 6 months, body mass index (BMI)<18.5 kg/m2, and hypoalbuminemia) and serum levels of glutamine and arginine were measured in 164 colorectal patients. Malnutrition status and serum glutamine and arginine concentrations were tested for their association with each other, as well as with the clinicopathological variables.Results: Of the 164 patients, 38 (23.5%) had body weight loss, 19 (11.9%) had low BMI, and 57 (35.8%) had hypoalbuminemia. The univariate analysis showed hypoalbuminemia was correlated with advanced tumour stage, lower concentrations of glutamine, higher C-reactive protein level, and progression-free survival rate. Univariate analysis also showed glutamine levels were lower in advanced tumour stage, but arginine levels were not associated with any clinicopathologic variables. Neither the nutrition criteria used in this study nor glutamine and arginine levels were correlated with hospital stay or progression-free survival rate in multivariate analysis.Conclusions: Different nutrition assessment criteria produced different malnutrition rates in colorectal cancer patients; however, pre-treatment malnourished status and low serum glutamine and arginine concentrations were not correlated with hospital stay and progressionfree survival rate. [ABSTRACT FROM AUTHOR]

The correlations of pretreatment serum concentrations of proinflammatory cytokines such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNFα) with the clinicopathologic features and progression of colorectal cancer (CRC) were investigated. The pretreatment serum levels of IL-1β, IL-6, and TNFα were measured in 164 CRC patients before treatment. The relationships between changes in proinflammatory cytokine and C-reactive protein (CRP) levels and both clinicopathologic variables and disease progression were examined by univariate and multivariate analysis. Advanced tumor stage was associated with a poorer histologic differentiation, higher CRP level, lower albumin level, and inferior progression-free survival rate (PFSR). Furthermore, high levels of CRP (>5 mg/L) were associated with proinflammatory cytokine intensity, defined according to the number of proinflammatory cytokines with levels above the median level (IL-1β ≥10 pg/mL; IL-6 ≥ 10 pg/mL; and TNFα ≥55 pg/mL). Under different inflammation states, proinflammatory cytokine intensity, in addition to tumor stage, independently predicted PFSR in patients with CRP <5 mg/L, whereas tumor stage was the only independent predictor of PFSR in patients with CRP ≥5 mg/L. Proinflammatory cytokine intensity and the CRP level are clinically relevant for CRC progression. Measurement of IL-1β, IL-6, and TNFα serum levels may help identify early cancer progression among patients with CRP <5 mg/L in routine practice., (© 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)