Deep sedation with propofol does not precipitate hepatic encephalopathy during elective upper endoscopy.

Background: The risk of hepatic encephalopathy (HE) precipitated by propofol has not been established.

Objective: To know whether the use of propofol for endoscopy in patients with cirrhosis induces minimal or overt HE.

Design: A cohort study.

Utility of p16 immunohistochemistry for the identification of Lynch syndrome.

Purpose: Immunohistochemistry for mismatch repair proteins has shown utility in the identification of Lynch syndrome, but majority of tumors with loss of MLH1 expression are due to sporadic hypermethylation of the MLH1 promoter. These tumors can also show epigenetic silencing of other genes, such as p16. The aim of our study is to evaluate the utility of p16 immunohistochemistry in the prediction of MLH1 germline mutations.

[New perspectives in predicting response to chemotherapy in colorectal cancer].

In the last few years, major advances have been produced in knowledge of the pathogenesis of colorectal cancer, which have led to the development of new drugs for the treatment of this disease. Likewise, molecular markers have been identified that are useful in prognosis. However, decisions on adjuvant therapy in colorectal cancer continue to be based exclusively on histological stage.

Cytokine association with bacterial DNA in serum of patients with inflammatory bowel disease.

Background: The pathogenesis of inflammatory bowel disease (IBD) involves the interaction between genetic susceptibility, mucosal immunity, and intestinal bacteria. Bacterial translocation is a common event in these patients and plays an important role in the perpetuation of chronic intestinal inflammation. Blood microbiological cultures, however, are frequently negative.

Transgenic expression of VEGF in intestinal epithelium drives mesenchymal cell interactions and epithelial neoplasia.

Background & Aims: Vascular endothelial growth factor (VEGF) is expressed robustly in human colon neoplasia and is a major new "rational" target of therapy for cancers of the colon and other organs. Nonetheless, the mechanism(s) of action of VEGF-targeted therapies and the biologic roles of VEGF in tumorigenesis have not been well defined. We used a transgenic approach to directly test the hypothesis that augmented VEGF expression can drive progression of intestinal neoplasia.

Brain cholinergic impairment in liver failure.

The cholinergic system is involved in specific behavioural responses and cognitive processes. Here, we examined potential alterations in the brain levels of key cholinergic enzymes in cirrhotic patients and animal models with liver failure. An increase (~30%) in the activity of the acetylcholine-hydrolyzing enzyme, acetylcholinesterase (AChE) is observed in the brain cortex from patients deceased from hepatic coma, while the activity of the acetylcholine-synthesizing enzyme, choline acetyltransferase, remains unaffected.

The efficacy of adjuvant chemotherapy with 5-fluorouracil in colorectal cancer depends on the mismatch repair status.

Aims: The aim of this study is to evaluate if mismatch repair (MMR) defective colorectal cancer has a different response to adjuvant 5-fluorouracil (5-FU) chemotherapy in a cohort of patients prospectively followed during 5 years.

Methods: The cohort included 754 surgically treated patients with colorectal cancer. MMR status was diagnosed by MLH1 and MSH2 immunohistochemistry and microsatellite instability analysis.

Role of PET/CT in the evaluation of cervical cancer.

PET imaging utilizes a dedicated camera system with multiple positron detector rings. PET/CT precisely aligns and combines metabolic PET mages with anatomical CT images, and is being increasingly preffered over PET scanning alone. FDG is the most widely used radiotracer in the management of cancer patients, and the prototypical PET/CT protocol used in other cancers can also be applied to the management of cervical carcinoma patients.

Comparison of predictive models, clinical criteria and molecular tumour screening for the identification of patients with Lynch syndrome in a population-based cohort of colorectal cancer patients.

Background: Several models have recently been developed to predict mismatch repair (MMR) gene mutations. Their comparative performance with clinical criteria or universal molecular screening in a population based colorectal cancer (CRC) cohort has not been assessed.

Methods: All 1222 CRC from the EPICOLON cohort underwent tumour MMR testing with immunohistochemistry and microsatellite instability, and those with MMR deficiency (n = 91) underwent MLH1/MSH2 germline testing.

Obesity and fat distribution imply a greater systemic inflammatory response and a worse prognosis in acute pancreatitis.

Background And Aims: Acute pancreatitis (AP) is a systemic inflammatory disease. It is already known that obesity and central fat distribution are related to the severity of AP, but the intimate mechanism of this relationship remains unknown. Obesity and central fat distribution are associated with an inflammatory state that could amplify the systemic inflammatory response (SIR) in AP.

Reelin is overexpressed in the liver and plasma of bile duct ligated rats and its levels and glycosylation are altered in plasma of humans with cirrhosis.

Reelin is an extracellular matrix protein secreted by a variety of cell types in both embryonic and adult tissues, including the liver. However, the physiological significance of Reelin in normal and cirrhotic liver has thus far not been elucidated. We have investigated Reelin levels in the liver and plasma of bile duct ligated (BDL) rats.

ATF5 is a highly abundant liver-enriched transcription factor that cooperates with constitutive androstane receptor in the transactivation of CYP2B6: implications in hepatic stress responses.

Activating transcription factor (ATF) 5 is a member of the ATF/cAMP response element-binding protein family, which has been associated with differentiation, proliferation, and survival in several tissues and cell types. However, its role in the liver has not yet been investigated. We show herein that ATF5 is a highly abundant liver-enriched transcription factor (LETF) whose expression declines in correlation with the level of dedifferentiation in cultured human hepatocytes and cell lines.

Role of K+ and Ca2+ fluxes in the cerebroarterial vasoactive effects of sildenafil.

The aim of this study was to assess the role of K(+) and Ca(2+) fluxes in the cerebroarterial vasoactive effects of the phosphodiesterase-5 inhibitor sildenafil. We used isolated rabbit basilar arteries to assess the effects of extracellular K(+) raising on sildenafil-induced vasodilatation, and studied the pharmacological interaction of sildenafil with selective modulators of membrane K(+) and Ca(2+) channels. Expression of Kv1 subunits of K(+) channels was assessed at messenger and protein levels.

A prospective, multicenter, population-based study of BRAF mutational analysis for Lynch syndrome screening.

Background & Aims: Mismatch repair (MMR) deficiencies are the hallmark of tumors arising in Lynch syndrome, however, in approximately 15% of sporadic colorectal cancers (CRC) these deficiencies most often are associated with somatic methylation of the MMR gene MLH1. Recently, an oncogenic mutation in the BRAF gene has been involved in sporadic CRC showing MMR deficiencies as a result of MLH1 promoter methylation. The aim of this study was to evaluate the contribution of BRAF V600E mutation analysis in the identification of MSH2/MLH1 gene mutation carriers in newly diagnosed CRC patients.

Validation and extension of the PREMM1,2 model in a population-based cohort of colorectal cancer patients.

Background & Aims: Early recognition of patients at risk for Lynch syndrome is critical but often difficult. Recently, a predictive algorithm-the PREMM(1,2) model-has been developed to quantify the risk of carrying a germline mutation in the mismatch repair (MMR) genes MLH1 and MSH2. However, the model's performance in an unselected, population-based colorectal cancer population as well as its performance in combination with tumor MMR testing are unknown.

Detection of metachronous neoplasms in colorectal cancer patients: identification of risk factors.

Purpose: Patients with colorectal cancer have a high risk of developing metachronous neoplasms. Identification of predictive factors associated with such conditions would allow individualized follow-up strategies in these patients. This study was designed to identify individual and familial factors associated with the development of metachronous colorectal neoplasms in patients with colorectal cancer.

Association of the ARLTS1 Cys148Arg variant with sporadic and familial colorectal cancer.

ARLTS1 was recently identified in chromosome 13q14 as a tumor suppressor gene of the ADP-ribosylation factor family with pro-apoptotic characteristics. Additionally, one of its genetic variants (W149X) was hypothesized to be a polymorphism associated with familial cancer. We performed a large case-control association study within the EPICOLON project aimed at evaluating the sporadic and familial colorectal cancer (CRC) risk associated with ARLTS1 genetic variants.

Low adherence to colonoscopy in the screening of first-degree relatives of patients with colorectal cancer.

Background: Colonoscopy is one of the methods of choice for screening relatives of patients with colorectal cancer.

Objective: To evaluate the rate of adherence to colonoscopy in first-degree relatives of patients with colorectal cancer and describe the lesions found.

Methods: A prospective, cross-sectional, multicentre, nationwide study was conducted.

Value of the critical flicker frequency in patients with minimal hepatic encephalopathy.

Unlabelled: Minimal hepatic encephalopathy (MHE) is mainly diagnosed using psychometric tests such as the psychometric hepatic encephalopathy score (PHES). Despite the clinical and social relevance of MHE, psychometric testing is not widespread in routine clinical care. We assessed the usefulness of the critical flicker frequency (CFF), for the diagnosis of MHE and for the prediction of the development of overt episodes of HE.

Identification of MYH mutation carriers in colorectal cancer: a multicenter, case-control, population-based study.

Background & Aims: Whereas it has conclusively been demonstrated that biallelic MutY human homolog (MYH) mutations confer a significant risk for colorectal cancer (CRC), the influence of monoallelic mutations remains controversial. Characterization of MYH-associated CRC is critical to identify individuals who might benefit from preventive strategies. This prospective, multicenter, case-control, population-based study was aimed at (1) establishing the CRC risk associated with specific germline MYH mutations and (2) devising a set of clinical criteria to identify MYH carriers among newly diagnosed CRC.

Transcriptional regulation and expression of CYP3A4 in hepatocytes.

CYP3A4 is the most abundantly expressed drug-metabolizing P450 enzyme in human liver and contributes to the metabolism of a large number of drugs in use today. CYP3A4 is constitutively expressed in adult hepatocytes but it can also be transcriptionally induced by a variety of structurally diverse xenochemicals. CYP3A4 strongly contributes to the important variability in the therapeutic and toxic effects of drugs owing to the major role it plays in xenobiotic metabolism and the large intra- and inter-individual variability to which it is subjected.

Performance of different microsatellite marker panels for detection of mismatch repair-deficient colorectal tumors.

Background: Colorectal tumors caused by failure of the DNA mismatch repair system commonly show microsatellite instability. Our goals were to compare the performance of two panels of markers (a panel previously recommended by the National Cancer Institute [NCI] and a pentaplex of mononucleotide repeats) and to devise the simplest diagnostic strategy for identification of patients with colorectal cancer characterized by defects in mismatch repair.

Methods: We recruited 1058 patients who were newly diagnosed with colorectal cancer.

Transcription factors involved in the expression of SLC28 genes in human liver parenchymal cells.

Human nucleoside transporters are encoded by SLC28 (hCNTs) and SLC29 (hENTs) genes. These proteins mediate the uptake of anticancer and some antiviral drugs and are also suitable candidates to facilitate nucleoside-derived drug uptake into hepatocytes for detoxification. Despite the putative relevance of these genes in liver physiology, the human SLC28 and SLC29 expression pattern is not known and suitable cell models are not available.