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Background Laparoendoscopic single-site (LESS) surgery is an evolution of laparoscopic surgery aiming at decreasing the patient’s parietal trauma associated with abdominal operations. LESS has been found so far to be efficient and have the same good results as the standard four-port laparoscopic cholecystectomy. α-Defensins are antimicrobial peptides of the organism. They are the first cell components against pathogens. Cytokines are also mediators in the response to trauma. The aim of this study was to compare the inflammatory reaction in LESS and four-port laparoscopic cholecystectomy. Methods Forty patients with noncomplicated cholelithiasis were randomly assigned into one of two groups. Group A included the patients who would undergo four-port laparoscopic cholecystectomy and group B included the patients who would undergo LESS cholecystectomy. These patients had a BMI < 30, were ASA I or II, and had no previous upper-GI surgery. Blood was taken preoperatively and 6 and 24 h postoperatively. hsCRP (with automated analyzer) and α-defensins (using ELISA) were calculated for each sample. The same postoperative protocol was followed for both groups. Mann-Whitney U test was used to analyze the results. Pain was calculated with a visual analog scale (VAS) for shoulder and abdomen at 6 and 24 h. Hospital stay, nausea, and pain medication needed was noted. Results The α-defensins value was statistically significantly higher in the 24-h samples ( P  < 0.001) for LESS cholecystectomy. No statistically significant difference was shown for hsCRP, even though P  = 0.05 for the 24-h samples with the values of LESS higher. No LESS was converted to a classical laparoscopic cholecystectomy, and none of the patients of either group needed conversion to open cholecystectomy. Pain was statistically significantly less for the LESS group at the 24-h interval ( P  < 0.0001). Less medication was needed for LESS patients after the 6th postoperative hour ( P  = 0.007). Conclusion Higher inflammatory reaction in LESS cholecystectomy could be the result of greater tension on the tissues. More studies are needed to conclude if this has a significant clinical expression.

Background: Rifampicin (RIFA) and ursodeoxycholic acid (UDCA) were found to stimulate different but complementary hepatobiliary detoxification pathways in gallstone patients. Aim: To study whether single drug effects are sustained or even enhanced by combination of both drugs and whether possible effects are mediated by circulating fibroblast growth factor 19 (FGF19), which has recently been identified as a master regulator of bile acid biosynthesis. Methods: 20 patients scheduled for laparoscopic cholecystectomy were randomized to a combination of UDCA (1 g/day during 3 weeks before surgery) and RIFA (600 mg/day during 1 week before surgery), or no treatment. Routine biochemistry, lipids, bile acid synthesis (7α-hydroxy-4-cholesten-3-one, C-4) and FGF19 were measured in serum. Bile acids were analyzed in serum and bile. A wedge liver biopsy was taken for determination of expression of hepatobiliary ABC transporters on mRNA and protein levels and of enzymes and regulatory transcription factors involved in the metabolism of biliary compounds on mRNA levels. Results: Combination treatment with both RIFA and UDCA significantly stimulated bile acid and bilirubin detoxification (CYP3A4, p < 0.001), conjugation (UGT1A1, p < 0.001) and elimination (MRP2, p < 0.05), as well as bile acid synthesis (p < 0.05), as compared to untreated controls. Notably, serum FGF19 levels in RIFA- and UDCA-treated patients did not differ from controls. Conclusion: Combined treatment with RIFA and UDCA preserves the previously observed beneficial effects of single treatment with RIFA, including stimulation of bile acid synthesis. Most notably, the latter effect in humans is not mediated by FGF19.

Cholecystectomy has long been regarded as a safe procedure with no deleterious influence on the body. However, recent studies provide clues that link cholecystectomy to a high risk for metabolic syndrome (MetS). In the present review, we describe the epidemiologic evidence that links cholecystectomy to MetS. Various components of MetS are investigated, including visceral obesity, dyslipidemia, elevated blood pressure, impaired fasting glucose, and insulin resistance. The possible mechanisms that associate cholecystectomy with MetS are discussed on the basis of experimental studies.

Obesity is a well-established risk factor for various diseases, but the mechanisms through which it influences disease development remain unclear. Using Mendelian randomization (MR) analysis, we examined the causal relationship between BMI, 249 metabolic traits, and cholelithiasis. BMI data were obtained from four sources, and cholelithiasis data were from two distinct datasets. We analyzed the direct effect of BMI on cholelithiasis and identified key metabolic mediators. BMI was found to be positively associated with the risk of cholelithiasis across all datasets analyzed. A total of 176 metabolites were identified to be significantly associated with BMI, including amino acids, cholesterol esters, free cholesterol, triglycerides, and phospholipids. Among these, 49 metabolites were identified as mediators in the BMI-cholelithiasis relationship. Specifically, fatty acid levels, cholesteryl esters, phospholipids, triglycerides, and free cholesterol were key mediators in this relationship, with mediation proportions ranging from − 2.38–7.14%. This study provides robust evidence that BMI significantly impacts metabolic biomarkers, which in turn affect the risk of cholelithiasis. These findings highlight the importance of managing BMI to mitigate metabolic dysfunction and reduce the risk of gallstone formation. Future research should explore the specific metabolic pathways involved to identify potential therapeutic targets.

People with the metabolic syndrome often develop gallstones. Why these two disorders are linked has not been not clear, but now Kahn and his colleagues have shown that lack of insulin signaling in the liver leads to dysregulation of genes that control the transport and synthesis of bile acids, thus altering the proper profile of bile salts and resulting in the formation of gallstones. Despite the well-documented association between gallstones and the metabolic syndrome 1 , 2 , the mechanistic links between these two disorders remain unknown. Here we show that mice solely with hepatic insulin resistance, created by liver-specific disruption of the insulin receptor (LIRKO mice) 3 are markedly predisposed toward cholesterol gallstone formation due to at least two distinct mechanisms. Disinhibition of the forkhead transcription factor FoxO1, increases expression of the biliary cholesterol transporters Abcg5 and Abcg8, resulting in an increase in biliary cholesterol secretion. Hepatic insulin resistance also decreases expression of the bile acid synthetic enzymes, particularly Cyp7b1 , and produces partial resistance to the farnesoid X receptor, leading to a lithogenic bile salt profile. As a result, after twelve weeks on a lithogenic diet, all of the LIRKO mice develop gallstones. Thus, hepatic insulin resistance provides a crucial link between the metabolic syndrome and increased cholesterol gallstone susceptibility.

Telocytes are closely associated with the regulation of tissue smooth muscle dynamics in digestive system disorders. They are widely distributed in the biliary system and exert their influence on biliary motility through mechanisms such as the regulation of CCK and their electrophysiological effects on smooth muscle cells. To investigate the relationship between telocytes and benign biliary diseases,such as gallbladder stone disease and biliary dilation syndrome, we conducted histopathological analysis on tissues affected by these conditions. Additionally, we performed immunohistochemistry and immunofluorescence double staining experiments for telocytes. The results indicate that the quantity of telocytes in the gallbladder and bile duct is significantly lower in pathological conditions compared to the control group. This reveals a close association between the decrease in telocyte quantity and impaired gallbladder motility and biliary fibrosis. Furthermore, further investigations have shown a correlation between telocytes in cholesterol gallstones and cholecystokinin-A receptor (CCK-AR), suggesting that elevated cholesterol levels may impair telocytes, leading to a reduction in the quantity of CCK-AR and ultimately resulting in impaired gallbladder motility.Therefore, we hypothesize that telocytes may play a crucial role in maintaining biliary homeostasis, and their deficiency may be associated with the development of benign biliary diseases, including gallstone disease and biliary dilation.

Background HIV endemic populations are displaying higher incidence of metabolic disorders. HIV and the standard treatment are both associated with altered lipid and cholesterol metabolism, however gallstone disease (a cholesterol related disorder) in Sub-Saharan African populations is rarely investigated. Methods This study sought to evaluate hepatic expression of key genes in cholesterol metabolism ( LDLr , HMGCR , ABCA1 ) and transcriptional regulators of these genes (microRNA-148a, SREBP2 ) in HIV positive patients on antiretroviral therapy presenting with gallstones. Liver biopsies from HIV positive patients (cases: n  = 5) and HIV negative patients (controls: n = 5) were analysed for miR-148a and mRNA expression using quantitative PCR. Results Circulating total cholesterol was elevated in the HIV positive group with significantly elevated LDL-c levels(3.16 ± 0.64 mmol/L) relative to uninfected controls (2.10 ± 0.74 mmol/L; p  = 0.04). A scavenging receptor for LDL-c, LDLr was significantly decreased (0.18-fold) in this group, possibly contributing to higher LDL-c levels. Transcriptional regulator of LDLr , SREBP2 was also significantly lower (0.13-fold) in HIV positive patients. Regulatory microRNA, miR-148a-3p, was reduced in HIV positive patients (0.39-fold) with a concomitant increase in target ABCA1 (1.5-fold), which regulates cholesterol efflux. Conclusions Collectively these results show that HIV patients on antiretroviral therapy display altered hepatic regulation of cholesterol metabolizing genes, reducing cholesterol scavenging, and increasing cholesterol efflux.

Cholelithiasis is a common biliary tract disease. However, the exact mechanism underlying gallstone formation remains unclear. Mucin plays a vital role in the nuclear formation and growth of cholesterol and pigment stones. Excessive mucin secretion can result in cholestasis and decreased gallbladder activity, further facilitating stone formation and growth. Moreover, gallstones may result in inflammation and the secretion of inflammatory factors, which can further increase mucin expression and secretion to promote the growth of gallstones. This review systematically summarises and analyses the role of mucins in gallstone occurrence and development and its related mechanisms to explore new ideas for interventions in stone formation or recurrence.

Background Carcinoma of the gallbladder is the commonest malignancy of the biliary tract in northern India The etiologic relation of specific metals (heavy and trace) and their compounds to neoplasia has been a topic of investigation for some time but not adequately described for carcinoma of the gallbladder. The aim of the present study was to evaluate the relation of heavy and trace metals to this malignancy. Methods The levels of selenium, zinc, copper, manganese, cadmium, chromium, lead, and nickel were estimated in serum, bile, gallstones, and gallbladder tissue using atomic absorption spectrophotometry. The tests were carried out in 30 patients with gallbladder cancer and 30 sex-matched patients with cholelithiasis. Results Selenium and zinc levels were significantly reduced ( p  < 0.001) and copper concentration was found to be significantly higher ( p  < 0.001) in serum, bile, and gallbladder tissue from patients with carcinoma of the gallbladder. Lead, cadmium, chromium, and nickel levels were elevated in serum and bile in patients with carcinoma of the gallbladder. Conclusions The present study demonstrated a significant decrease in serum, biliary, and tissue levels of selenium and zinc but increased copper, lead, cadmium, chromium, and nickel levels in patients with carcinoma of the gallbladder, indicating a strong relation between the concentrations of these metals and gallbladder cancer.

Cholesterol Gallstone Disease (GSD) is a common multifactorial disorder characterized by crystallization and aggregation of biliary cholesterol in the gallbladder. The global prevalence of GSD is ~10–20% in the adult population but rises to 28% in Chile (17% among men and 30% among women). The small intestine may play a role in GSD pathogenesis, but the molecular mechanisms have not been clarified. Our aim was to identify the role of the small intestine in GSD pathogenesis. Duodenal biopsy samples were obtained from patients with GSD and healthy volunteers. GSD status was defined by abdominal ultrasonography. We performed a transcriptome study in a discovery cohort using Illumina HiSeq. 2500, and qPCR, immunohistochemistry and immunofluorescence were used to validate differentially expressed genes among additional case-control cohorts. 548 differentially expressed genes between GSD and control subjects were identified. Enriched biological processes related to cellular response to zinc, and immune and antimicrobial responses were observed in GSD patients. We validated lower transcript levels of metallothionein, NPC1L1 and tight junction genes and higher transcript levels of genes involved in immune and antimicrobial pathways in GSD patients. Interestingly, serum zinc and phytosterol to cholesterol precursor ratios were lower in GSD patients. A significant association was observed between serum zinc and phytosterol levels. Our results support a model where proximal small intestine plays a key role in GSD pathogenesis. Zinc supplementation, modulation of proximal microbiota and/or intestinal barrier may be novel targets for strategies to prevent GSD.