Importance of Bile Composition for Diagnosis of Biliary Obstructions

Determination of the cause of a biliary obstruction is often inconclusive from serum analysis alone without further clinical tests. To this end, serum markers as well as the composition of bile of 74 patients with biliary obstructions were determined to improve the diagnoses. The samples were collected from the patients during an endoscopic retrograde cholangiopancreatography (ERCP). The concentration of eight bile salts, specifically sodium cholate, sodium glycocholate, sodium taurocholate, sodium glycodeoxycholate, sodium chenodeoxycholate, sodium glycochenodeoxycholate, sodium taurodeoxycholate, and sodium taurochenodeoxycholate as well as bile cholesterol were determined by HPLC-MS. Serum alanine aminotransferase (ALT), aspartate transaminase (AST), and bilirubin were measured before the ERCP. The aim was to determine a diagnostic factor and gain insights into the influence of serum bilirubin as well as bile salts on diseases. Ratios of conjugated/unconjugated, primary/secondary, and taurine/glycine conjugated bile salts were determined to facilitate the comparison to literature data. Receiver operating characteristic (ROC) curves were determined, and the cut-off values were calculated by determining the point closest to (0,1). It was found that serum bilirubin was a good indicator of the type of biliary obstruction; it was able to differentiate between benign obstructions such as choledocholithiasis (at the concentration of >11 µmol/L) and malignant changes such as pancreatic neoplasms or cholangiocarcinoma (at the concentration of >59 µmol/L). In addition, it was shown that conjugated/unconjugated bile salts confirm the presence of an obstruction. With lower levels of conjugated/unconjugated bile salts the possibility for inflammation and, thus, neoplasms increase.

Targeting Farnesoid X receptor (FXR) for developing novel therapeutics against cancer

Cancer is one of the lethal diseases that arise due to the molecular alterations in the cell. One of those alterations associated with cancer corresponds to differential expression of Farnesoid X receptor (FXR), a nuclear receptor regulating bile, cholesterol homeostasis, lipid, and glucose metabolism. FXR is known to regulate several diseases, including cancer and cardiovascular diseases, the two highly reported causes of mortality globally. Recent studies have shown the association of FXR overexpression with cancer development and progression in different types of cancers of breast, lung, pancreas, and oesophagus. It has also been associated with tissue-specific and cell-specific roles in various cancers. It has been shown to modulate several cell-signalling pathways such as EGFR/ERK, NF-κB, p38/MAPK, PI3K/AKT, Wnt/β-catenin, and JAK/STAT along with their targets such as caspases, MMPs, cyclins; tumour suppressor proteins like p53, C/EBPβ, and p-Rb; various cytokines; EMT markers; and many more. Therefore, FXR has high potential as novel biomarkers for the diagnosis, prognosis, and therapy of cancer. Thus, the present review focuses on the diverse role of FXR in different cancers and its agonists and antagonists.

CHOLELITHIASIS IN PEOPLE WITH NORMAL SERUM CHOLESTEROL: ROLE OF SERUM IRON

INTRODUCTION: The old axiom that a typical gallstone patient is a fat, fertile female of forty is only partially true, as the disease has been found in women soon after their first delivery and also in underweight and thin people. So while searching the literature for different factors, the Iron deficiency was found to be a new and interesting etiological factor in the formation of gall stones. Although the cause is still unclear, cholesterol Gallstones develop most commonly in multiparous women. This patient population is also prone to chronic iron deficiency anemia (IDA). Previous studies claimed a cause-effect relationship between iron deficiency and cholesterol gallstones. AIM - To assess the association between Serum Iron and Bile Cholesterol levels in people with normal serum cholesterol levels, which reflects the effect of Serum Iron levels in the formation of Gallstones. MATERIALS AND METHODS – The study was conducted in the Department of General Surgery, G.S.L Medical College, and General Hospital over 18 months. A total of 49 patients with cholelithiasis and normal Serum Cholesterol levels were included in the study. Serum iron and Bile cholesterol contents were analyzed. RESULTS – It is observed that there is a significant association between increased incidence of Cholelithiasis and Low Serum Iron levels among people with normal levels of serum cholesterol. CONCLUSION – Low Serum Iron was associated with increased Bile Cholesterol concentration, indicating a possible role of Serum iron in forming gallstones.

Bile cholesterol and viscosity, the keys to discriminating adenomatous polyps from cholesterol polyps by a novel predictive scoring model.

Background: Adenomatous gallbladder polyps, premalignant lesions of the gallbladder, have fatal outcomes, whereas cholesterol polyps have benign features. Herein, we proposed a novel, predictive scoring model of adenomatous polyps to distinguish them from cholesterol polyps, by analyzing bile components and bile viscosity. Methods: Patients with gallbladder polyp pathologically confirmed after cholecystectomies were analyzed. After dividing patients into two groups (adenomatous or cholesterol polyps), the clinicopathologic profiles and bile nature, including components and viscosity were compared and a predictive scoring model for adenomatous polyps was assessed. Results: 11 adenomatous polyps and 96 cholesterol polyps were analyzed. The variables significantly associated with adenomatous polyps were age>55years (OR=23.550, p=0.020 ), bile viscosity<7.5sec -1 (OR=22.539, p=0.012 ), and bile cholesterol<414.5mg/dl (OR=10.004, p=0.023 ) and the points for each variable in the predictive scoring model were allocated as 3, 3, and 2, respectively. Final scores ranged from 0 to 8 points and the best performance of model at a cutoff of ≥6 points had 90.9% of sensitivity and 80.2% of specificity. Conclusions: Bile viscosity and bile cholesterol accompanied by age were revealed as significant predictors of adenomatous polyps, distinguishing them from cholesterol polyps of gallbladder. It can be the cornerstone for creating accurate guidelines for preoperatively determining treatment strategies of gallbladder polyps.

Bile cholesterol and viscosity, the keys to discriminating adenomatous polyps from cholesterol polyps by a novel predictive scoring model.

Background: Adenomatous gallbladder polyps, premalignant lesions of the gallbladder, have fatal outcomes, whereas cholesterol polyps have benign features. Herein, we proposed a novel, predictive scoring model of adenomatous polyps to distinguish them from cholesterol polyps, by analyzing bile components and bile viscosity. Methods: Patients with gallbladder polyp pathologically confirmed after cholecystectomies were analyzed. After dividing patients into two groups (adenomatous or cholesterol polyps), the clinicopathologic profiles and bile nature, including components and viscosity were compared and a predictive scoring model for adenomatous polyps was assessed. Results: 11 adenomatous polyps and 96 cholesterol polyps were analyzed. The variables significantly associated with adenomatous polyps were age>55years (OR=23.550, p=0.020 ), bile viscosity<7.5sec -1 (OR=22.539, p=0.012 ), and bile cholesterol<414.5mg/dl (OR=10.004, p=0.023 ) and the points for each variable in the predictive scoring model were allocated as 3, 3, and 2, respectively. Final scores ranged from 0 to 8 points and the best performance of model at a cutoff of ≥6 points had 90.9% of sensitivity and 80.2% of specificity. Conclusions: Bile viscosity and bile cholesterol accompanied by age were revealed as significant predictors of adenomatous polyps, distinguishing them from cholesterol polyps of gallbladder. It can be the cornerstone for creating accurate guidelines for preoperatively determining treatment strategies of gallbladder polyps.

Correlation between Serum Iron, Serum Ferritin and Bile Cholesterol Level in Gallstone Disease

Introduction: The cholesterol stones are formed by super-saturation of the bile with cholesterol. Iron deficiency alters activity of several hepatic enzymes, leading to increased cholesterol saturation of bile in gall bladder thus promoting cholesterol crystallisation. Iron has a role in gallstone pathogenesis and ferritin is the most specific marker for iron levels in the body, but there are less studies which depict correlation between serum iron, serum ferritin and bile cholesterol. Aim: To study the correlation between serum iron, serum ferritin and bile cholesterol level in gallstone patients. Materials and Methods: The observational study was conducted in the Department of Surgery. The study population was 45 patients with gallstone disease. Serum iron, Serum ferritin and Bile cholesterol contents were analysed. Serum cholesterol levels were estimated using Folch method and estimation of bile cholesterol was done by Enzopak kit.Statistical analysis was done by using descriptive and inferential statistics using chi square test and software used in the analysis were SPSS 24.0 version and p<0.05 was considered as level of significance. Results: A positive but negligible correlation between serum iron and serum ferritin was observed (Pearson’s correlation coefficient of 0.247). Negative correlation between serum iron vs serum cholesterol and serum ferritin vs serum cholesterol was observed. Conclusion: It can be concluded that a low value of serum iron and serum ferritin is a risk factor for cholelithiasis, whereas, if the value of bile cholesterol increases then there is a high probability of cholelithiasis.

The Effect of Polyphenols on Hypercholesterolemia through Inhibiting the Transport and Expression of Niemann–Pick C1-Like 1

The Niemann–Pick C1-like 1 (NPC1L1) protein is a cholesterol transporter that is expressed in the small intestine. This report describes the discovery of NPC1L1, its transport properties, and the inhibitory effects of polyphenols on NPC1L1. NPC1L1 was identified in 2004 while searching for ezetimibe molecular targets. Excessive synthesis of cholesterol results in hyperlipidemia, which increases the amount of bile cholesterol excreted into the duodenum. The inhibition of NPC1L1 decreases blood cholesterol because food and bile cholesterol are also absorbed from NPC1L1 in the intestine. Some polyphenols, particularly luteolin, have been reported as NPC1L1-mediated anti-dyslipidemia constituents. Luteolin affects NPC1L1 through two mechanisms. Luteolin directly inhibits NPC1L1 by binding to it, which occurs in a short timeframe similar to that for ezetimibe. The other mechanism is the inhibition of NPC1L1 expression. Luteolin reduced the binding of Sterol-regulatory element-binding protein 2 (SREBP2) in the promoter region of the NPC1L1 gene and decreased mRNA levels of SREBP2 and hepatocyte nuclear factor 4α. These data suggest that luteolin decreases the expression of NPC1L1 through regulation of transcription factors. This review also explores the effect of other polyphenols on NPC1L1 and hypercholesterolemia.