The deficit in folate and vitamin B12 triggers liver macrovesicular steatosis and inflammation in rats with dextran sodium sulfate-induced colitis.

The risks of nonalcoholic steatohepatitis (NASH) and deficiency in vitamin B12 and folate (methyl donor deficiency, MDD) are increased in inflammatory bowel disease (IBD). We investigated the influence of MDD on NASH in rats with DSS-induced colitis. Two-month-old male Wistar rats were subjected to MDD diet and/or ingestion of DSS and compared to control animals. We studied steatosis, inflammation, fibrosis, plasma levels of metabolic markers, cytokines and lipopolysaccharide, and inflammatory pathways in liver. MDD triggered a severe macrovesicular steatosis with inflammation in DSS animals that was not observed in animals subjected to DSS or MDD only. The macrovesicular steatosis was closely correlated to folate, vitamin B12, homocysteine plasma level and liver S-adenosyl methionine/S-adenosyl homocysteine (SAM/SAH) ratio. Liver inflammation was evidenced by activation of nuclear factor kappa B (NFκB) pathway and nuclear translocation of NFκB phospho-p65. MDD worsened the increase of interleukin 1-beta (IL-1ß) and abolished the increase of IL10 produced by DSS colitis. It increased monocyte chemoattractant protein 1 (MCP-1). MDD triggers liver macrovesicular steatosis and inflammation through imbalanced expression of IL-1ß vs. IL10 and increase of MCP-1 in DSS colitis. Our results suggest evaluating whether IBD patients with MDD and increase of MCP-1 are at higher risk of NASH.

LRP1 expression in colon cancer predicts clinical outcome.

LRP1 (low-density lipoprotein receptor-related protein 1), a multifunctional endocytic receptor, has recently been identified as a hub within a biomarker network for multi-cancer clinical outcome prediction. As its role in colon cancer has not yet been characterized, we here investigate the relationship between LRP1 and outcome. MATERIALS AND METHODS: LRP1 mRNA expression was determined in colon adenocarcinoma and paired colon mucosa samples, as well as in stromal and tumor cells obtained after laser capture microdissection. Clinical potential was further investigated by immunohistochemistry in a population-based colon cancer series (n = 307). LRP1 methylation, mutation and miR-205 expression were evaluated and compared with LRP1 expression levels. RESULTS: LRP1 mRNA levels were significantly lower in colon adenocarcinoma cells compared with colon mucosa and stromal cells obtained after laser capture microdissection. Low LRP1 immunohistochemical expression in adenocarcinomas was associated with higher age, right-sided tumor, loss of CDX2 expression, Annexin A10 expression, CIMP-H, MSI-H and BRAFV600E mutation. Low LRP1 expression correlated with poor clinical outcome, especially in stage IV patients. While LRP1 expression was downregulated by LRP1 mutation, LRP1 promoter was never methylated. CONCLUSIONS: Loss of LRP1 expression is associated with worse colon cancer outcomes. Mechanistically, LRP1 mutation modulates LRP1 expression.

Prevalence of esophageal squamous papilloma (ESP) and associated cancer in northeastern France.

BACKGROUND AND STUDY AIMS: Esophageal squamous papilloma (ESP) is a rare lesion. The aims of this study were to assess the prevalence of ESP in northeastern France and the risk of associated squamous cell carcinoma (SCC). PATIENTS AND METHODS: The charts of 78 patients who were diagnosed with ESP between January 2005 and February 2013 at three hospitals in northeastern France were reviewed. RESULTS: A total of 55 305 endoscopies were performed and 78 ESP were diagnosed (0.01 %). Patients with ESP included 44 males (56.4 %), 34 females (43.6 %); median age 50, interquartile range (IQR) 19 - 86. Median follow-up was 21 months (IQR 0 - 91 mo) and median time between first and second endoscopy was 7 months (IQR 0.5 - 74 mo). Of the total number of patients, 35 (44.9 %) had a second endoscopy. Main endoscopy indication was dyspepsia (24.4 %). Most ESP were isolated (93.6 %) and located at distal esophagus (27 cm, IQR 16 - 40 cm). Median size was 3 mm (IQR 1 - 20 mm). ESP-associated endoscopic lesions were hiatal hernia in 12 patients and esophagitis in 11 patients. Endoscopic treatment was mainly excisional biopsies (60.3 %). Human papillomavirus (HPV) was not detected in the 6 patients with available data. Low dysplasia was found in 2 ESP. During follow-up endoscopies, 2 SCC were detected in 2 different patients; the first SCC was located at the previous resection site of the ESP and the second had a different location. Prevalence of associated cancer was 1.3 %. CONCLUSION: Prevalence of ESP in northeastern France is similar to that previously reported. Endoscopic findings were also broadly the same as in previous reports. The occurrence of dysplasia and SCC should strongly encourage the endoscopist to totally remove the ESP and to start an endoscopic surveillance, given the potential risk of malignant transformation.