Biliary microbiome and gallstones: A silent friendship

With increasing evidence,the biliary tract and the gallbladder mucosa are no longer considered sterile environments devoid of bacteria.Rather a profound biofilm of resident bacterial flora is associated with the mucosal surface.The bile too harbors a resident flora.It is when a dysbiotic process ensues,that this bac-terial flora either becomes opportunist or is replaced by a pathogenic one that has a strong ability to survive the challenges of the biliary environment.Although once believed a metabolic problem,recent evidence indicates a complex intera-ction between different species of bacteria and gallbladder mucosa and bile which may culminate in calculus formation.The resident microbiota and its several enzymes dictate the type of gallstone by the mere interplay of the constituting type of bacteria in the biofilm,even without any evidence of infection.Dysbiosis is often mediated by either intestinal dysbiosis or less probably by oral dysbiosis.The gallstones,in turn,provide a haven for the resident microbiota in which they can form their own defined niche enriched with the biofilm that can resist the biliary defense mechanisms and survive the hostile biliary environment in the background of biliary stasis and local infection.However,this process of silent friendship is more complex than said,and further research is needed to define the relationship between the two.

Efficacy of Laparoscopic Cholecystectomy in Treating Patients with Gallstones and Its Effect on Interleukin-6 and Tumor Necrosis Factor-α Levels

Objective:To investigate the efficacy of laparoscopic cholecystectomy in the treatment of patients with gallstones and its effect on the levels of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-a).Methods:A total of 82 patients with gallstones admitted from July 2020 to July 2023 were recruited and allocated into control and observation groups using the random number table method,with 41 cases in each group.The patients were treated with laparoscopic cholecystectomy,with the anterior triangle anatomical approach to the gallbladder in the control group and the posterior triangle anatomical approach to the gallbladder in the observation group.The treatment effect and inflammatory factor levels of both groups were observed and compared.Results:When comparing the clinical outcomes of both patient groups,the key parameters evaluated included time to mobilization,duration of surgery,extubation time,and intraoperative bleeding.The observation group exhibited a significant advantage in these parameters compared to the control group(P<0.05).Regarding the levels of inflammatory factors between the two groups before and after treatment,there was no significant difference in values before treatment.However,following treatment,patients in the observation group showed significantly lower levels of IL-6,TNF-α,and C-reactive protein(CRP)compared to the control group(P<0.05).Conclusion:Patients undergoing laparoscopic cholecystectomy for gallstones can benefit from the implementation of the posterior triangular anatomical approach to the gallbladder,which not only enhances therapeutic efficacy but also offers significant advantages in reducing levels of IL-6,TNF-α,and CRP.Therefore,it is recommended for the widespread adoption of this treatment approach in clinical practice.

Targeted bile acids metabolomics in cholesterol gallbladder polyps and gallstones: From analytical method development towards application to clinical samples

Bile acids(BAs)are synthesized by the liver from cholesterol through several complementary pathways and aberrant cholesterol metabolism plays pivotal roles in the pathogeneses of cholesterol gallbladder polyps(CGP)and cholesterol gallstones(CGS).To date,there is neither systematic study on BAs profile of CGP or CGS,nor the relationship between them.To explore the metabolomics profile of plasma BAs in healthy volunteers,CGP and CGS patients,an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)method was developed and validated for simultaneous determination of 42 free and conjugated BAs in human plasma.The developed method was sensitive and reproducible to be applied for the quantification of BAs in the investigation of plasma samples.The results show that,compared to healthy volunteers,CGP and CGS were both characterized by the significant decrease in plasma BAs pool size,furthermore CGP and CGS shared aberrant BAs metabolic characteristics.Chenodeoxycholic acid,glycochenodeoxycholic acid,l-muricholic acid,deoxycholic acid,and 7-ketolithocholic acid were shared potential markers of these two cholesterol gallbladder diseases.Subsequent analysis showed that clinical characteristics including cysteine,ornithine and body mass index might be closely related to metabolisms of certain BA modules.This work provides metabolomic information for the study of gallbladder diseases and analytical methodologies for clinical target analysis and efficacy evaluation related to BAs in medical institutions.

Burden of gallstone disease in the United States population:Prepandemic rates and trends

BACKGROUND Gallstone disease is one of the most common digestive disorders in the United States and leads to significant morbidity,mortality,and health care utilization.AIM To expand on earlier findings and investigate prepandemic rates and trends in the gallstone disease burden in the United States using national survey and claims databases.METHODS The National Ambulatory Medical Care Survey,National Inpatient Sample,Nationwide Emergency Department Sample,Nationwide Ambulatory Surgery Sample,Vital Statistics of the United States,Optum Clinformatics®Data Mart,and Centers for Medicare and Medicaid Services Medicare 5%Sample and Medicaid files were used to estimate claims-based prevalence,medical care including cholecystectomy,and mortality with a primary or other gallstone diagnosis.Rates were age-adjusted(for national databases)and shown per 100000 population.RESULTS Gallstone disease prevalence(claims-based,2019)was 0.70%among commercial insurance enrollees,1.03%among Medicaid beneficiaries,and 2.09%among Medicare beneficiaries and rose over the previous decade.Recently,in the United States population,gallstone disease contributed to approximately 2.2 million ambulatory care visits,1.2 million emergency department visits,625000 hospital discharges,and 2000 deaths annually.Women had higher medical care rates with a gallstone disease diagnosis,but mortality rates were higher among men.Hispanics had higher ambulatory care visit and hospital discharge rates compared with Whites,but not mortality rates.Blacks had lower ambulatory care visit and mortality rates,but similar hospital discharge rates compared with whites.During the study period,ambulatory care and emergency department visit rates with a gallstone disease diagnosis rose,while hospital discharge and mortality rates declined.Among commercial insurance enrollees,rates were higher compared with national data for ambulatory care visits and hospitalizations,but lower for emergency department visits.Cholecystectomies performed in the United States included 605000 ambulatory laparoscopic,280000 inpatient laparoscopic,and 49000 inpatient open procedures annually.Among commercial insurance enrollees,rates were higher compared with national data for laparoscopic procedures.CONCLUSION The gallstone disease burden in the United States is substantial and increasing,particularly among women,Hispanics,and older adults with laparoscopic cholecystectomy as the mainstay treatment.Current practice patterns should be monitored for better health care access.

Pathophysiology of severe gallstone pancreatitis:A new paradigm

Severe gallstone pancreatitis(GSP)refractory to maximum conservative therapy has wide clinical variations,and its pathophysiology remains controversial.This Editorial aimed to investigate the pathophysiology of severe disease based on Opie’s theories of obstruction,the common channel,and duodenal reflux and describe its types.Severe GSP might be a hybrid disease with pathology polarized between acute cholangitis with mild pancreatitis(biliary type)and necrotizing pancreatitis uncomplicated with biliary tract disease(pancreatic type),in which hepatobiliary and pancreatic lesion severity is inversely related to the presence or absence of impacted ampullary stones.Severe GSP is caused by stones that are persistently impacted at the ampulla with biliopancreatic obstruction(biliary type),and probably,stones that are either temporarily lodged at the duodenal orifice or passed into the duodenum,thereby permitting reflux of bile or possible duodenal contents into the pancreas(pancreas type).When the status of the stones and the presence or absence of impacted ampullary stones with biliopancreatic obstruction are determined,the clinical course and outcome can be predicted.Gallstones represent the main cause of acute pancreatitis globally,and clinicians are expected to encounter GSP more often.Awareness of the etiology and pathogenesis of severe disease is mandatory.

Comparison of biliary protein spectrum in gallstone patients with obesity and those with normal body weight

Background: Obesity is a common public health issue and is currently deemed a disease. Research has shown that the risk of gallstones in individuals with obesity is elevated. This study aimed to explore the bile proteomics differences between cholelithiasis patients with obesity and normal body weight. Methods: Bile samples from 20 patients(10 with obesity and 10 with normal body weight) who underwent laparoscopic cholecystectomy at our center were subjected to tandem mass tag labeling(TMT) and liquid chromatography-tandem mass spectrometry(LC-MS/MS), followed by further bioinformatic analysis. Results: Among the differentially expressed proteins, 23 were upregulated and 67 were downregulated. Bioinformatic analysis indicated that these differentially expressed proteins were mainly involved in cell development, inflammatory responses, glycerolipid metabolic processes, and protein activation cascades. In addition, the activity of the peroxisome proliferator-activated receptor(PPAR, a subfamily of nuclear receptors) signaling pathway was decreased in the Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis. Two downregulated proteins in the PPAR signaling pathway, APO A-Ⅰ and APO A-Ⅱ, were confirmed using enzyme-linked immunosorbent assay. Conclusions: The PPAR signaling pathway may play a crucial role in the development of cholelithiasis among patients with obesity. Furthermore, biliary proteomics profiling of gallstones patients with obesity is revealed, providing a reference for future research.

Cracking the silent gallstone code:Wait or operate?

The widespread availability of abdominal ultrasound has revealed the common occurrence of asymptomatic gallstones.While the treatment for symptomatic gallstones is clear,the benefits of minimally invasive laparoscopic cholecystectomy have sparked debate about the best approach to managing silent gallstones.The potential for asymptomatic gallstones to become symptomatic or lead to complications complicates the decision-making process regarding surgical intervention,as it's uncertain when or which patients might develop complications.Consequently,risk stratification appears to play a critical role in guiding decisions about silent gallstones.However,there is no definitive evidence to direct management,and a consensus-based on high-quality evidence is yet to be established.

Development and validation of a nomogram model for predicting the risk of gallstone recurrence after gallbladder-preserving surgery

Background:The high incidence of gallstone recurrence was a major concern for laparoscopic gallbladderpreserving surgery.This study aimed to investigate the risk factors for gallstone recurrence after gallbladder-preserving surgery and to establish an individualized nomogram model to predict the risk of gallstone recurrence.Methods:The clinicopathological and follow-up data of 183 patients who were initially diagnosed with gallstones and treated with gallbladder-preserving surgery at our hospital from January 2012 to January 2019 were retrospectively collected.The independent predictive factors for gallstone recurrence following gallbladder-preserving surgery were identified by multivariate logistic regression analysis.A nomogram model for the prediction of gallstone recurrence was constructed based on the selected variables.The C-index,receiver operating characteristic(ROC)curve and calibration curve were used to evaluate the predictive power of the nomogram model for gallstone recurrence.Results:During the follow-up period,a total of 65 patients experienced gallstone recurrence,and the recurrence rate was 35.5%.Multivariate logistic regression analysis revealed that the course of gallstones>2 years[odds ratio(OR)=2.567,95%confidence interval(CI):1.270-5.187,P=0.009],symptomatic gallstones(OR=2.589,95%CI:1.059-6.329,P=0.037),multiple gallstones(OR=2.436,95%CI:1.133-5.237,P=0.023),history of acute cholecystitis(OR=2.778,95%CI:1.178-6.549,P=0.020)and a greasy diet(OR=2.319,95%CI:1.186-4.535,P=0.014)were independent risk factors for gallstone recurrence after gallbladder-preserving surgery.A nomogram model for predicting the recurrence of gallstones was established based on the above five variables.The results showed that the C-index of the nomogram model was 0.692,suggesting it was valuable to predict gallstone recurrence.Moreover,the calibration curve showed good consistency between the predicted probability and actual probability.Conclusions:The nomogram model for the prediction of gallstone recurrence might help clinicians develop a proper treatment strategy for patients with gallstones.Gallbladder-preserving surgery should be cautiously considered for patients with high recurrence risks.

Spilled gallstone mimicking intra-abdominal seeding of gallbladder adenocarcinoma: A case report

BACKGROUND Gallbladder rupture is common in laparoscopic cholecystectomy because the gallbladder is usually in acute or chronic inflammation status.The gallstones may sometime be spilled into the peritoneal cavity,resulting in intra-abdominal ab-scess if the gallstones were not retrieved.The diagnosis of intra-abdominal ab-scess caused by unretrieved gallstone can usually be correctly identified in the routine imaging studies,such as abdominal ultrasonography or computed tomo-graphy(CT).Here we present a case of abscess formation from unretrieved gall-stone following laparoscopic cholecystectomy,which mimics the imaging findings of metastatic gallbladder ade-nocarcinoma.CASE SUMMARY This case described a 78-year-old man who received laparoscopic cholecystectomy and gallbladder adenocarcinoma was diagnosed after surgery.After adjuvant chemotherapy,the following up abdominal CT showed several small nodules at right upper abdomen and peritoneal carcinomatosis is considered.Repeated laparoscopic surgery for the excision of seeding tumor was conducted and the pathological diagnosis of the nodules and mass was inflammatory tissues and gallbladder stone.CONCLUSION Spilled gallstones are a common complication during laparoscopic cholecystectomy and some gallstones fail to be retrieved due to the size or the restricted view of laparoscopic surgery.For spilled gall bladder stones,surgeons may consider regular computerized tomography follow-up,and if necessary,laparoscopic examination can be used as a means of confirming the diagnostic and treatment.

Classification of anatomical morphology of cystic duct and its association with gallstone

BACKGROUND Gallstones are common lesions that often require surgical intervention.Laparo-scopic cholecystectomy is the treatment of choice for symptomatic gallstones.Preoperatively,the anatomical morphology of the cystic duct(CD),needs to be accurately recognized,especially when anatomical variations occur in the CD,which is otherwise prone to bile duct injury.However,at present,there is no optimal classification system for CD morphology applicable in clinical practice,and the relationship between anatomical variations in CDs and gallstones remains to be explored.AIM To create a more comprehensive clinically applicable classification of the morphology of CD and to explore the correlations between anatomic variants of CD and gallstones.METHODS A total of 300 patients were retrospectively enrolled from October 2021 to January 2022.The patients were divided into two groups:The gallstone group and the nongallstone group.Relevant clinical data and anatomical data of the CD based on magnetic resonance cholangiopancreatography(MRCP)were collected and analyzed to propose a morphological classification system of the CD and to explore its relationship with gallstones.Multivariate analysis was performed using logistic regression analyses to identify the independent risk factors using variables that were significant in the univariate analysis.RESULTS Of the 300 patients enrolled in this study,200(66.7%)had gallstones.The mean age was 48.10±13.30 years,142(47.3%)were male,and 158(52.7%)were female.A total of 55.7%of the patients had a body mass index(BMI)≥24 kg/m2.Based on the MRCP,the CD anatomical typology is divided into four types:Type I:Linear,type II:n-shaped,type III:S-shaped,and type IV:W-shaped.Univariate analysis revealed differences between the gallstone and nongallstone groups in relation to sex,BMI,cholesterol,triglycerides,morphology of CD,site of CD insertion into the extrahepatic bile duct,length of CD,and angle between the common hepatic duct and CD.According to the multivariate analysis,female,BMI(≥24 kg/m2),and CD morphology[n-shaped:Odds ratio(OR)=10.97,95%confidence interval(95%CI):5.22-23.07,P<0.001;S-shaped:OR=4.43,95%CI:1.64-11.95,P=0.003;W-shaped:OR=7.74,95%CI:1.88-31.78,P=0.005]were significantly associated with gallstones.CONCLUSION The present study details the morphological variation in the CD and confirms that CD tortuosity is an independent risk factor for gallstones.

Gallstones in patients with liver cirrhosis:Incidence,etiology,clinical and therapeutical aspects

Gallstones occur in about one third of the patients having liver cirrhosis.Pigment gallstones are the most frequent type,while cholesterol stones represent about15%of all stones in cirrhotics.Increased secretion of unconjugated bilirubin,increased hydrolysis of conjugated bilirubin in the bile,reduced secretion of bile acids and phospholipds in bile favor pigment lithogenesis in cirrhotics.Gallbladder hypomotility also contributes to lithogenesis.The most recent data regarding risk factors for gallstones are presented.Gallstone prevalence increases with age,with a ratio male/female higher than in the general population.Chronic alcoholism,viral C cirrhosis,and non-alcoholic fatty liver disease are the underlying liver diseases most often associated with gallstones.Gallstones are often asymptomatic,and discovered incidentally.If asymptomatic,expectant management is recommended,as for asymptomatic gallstones in the general population.However,a closer follow-up of these patients is necessary in order to earlier treat symptoms or complications.For symptomatic stones,laparoscopic cholecystectomy has become the therapy of choice.Child-Pugh class and MELD score are the best predictors of outcome after cholecystectomy.Patients with severe liver disease are at highest surgical risk,therefore gallstone complications should be treated using noninvasive or minimally invasive procedures,until stabilization of the patient condition.

Prevalence of and risk factors for gallstones in Uighur and Han Chinese

AIM:To perform a single-centre survey of the prevalence of and possible risk factors for gallstones in Uighur and Han Chinese.METHODS:Complete medical data for 9455 patients were collected from the medical centre of our hospital,and the overall prevalence of gallstones as well as the prevalence in different ethnic groups was studied.The risk factors for gallstones in different ethnic groups were identified in a univariate analysis,and variables with statistical significance were analysed by unconditional multiple logistic regression,to primarily explore the similarities and differences in gallstone risk factors between different ethnic groups.RESULTS:The prevalence of gallstones was significantly higher in the Uighur population than in the Hanpopulation(22.87%vs 11.64%,P<0.05).Further analysis of risk factors for gallstones based on the different ethnic areas revealed that age was a risk factor for gallstones in both groups;triglycerides,body-mass index(BMI)and high-density lipoprotein were risk factors for gallstones in the Han population,while total cholesterol(TC),gender and fatty liver were risk factors in the Uighur population.The Uighur patients were older than the Han patients,and had higher BMI,TC,low-density lipoprotein,female rate and fatty liver rate,while the incidence of hypertension was lower than that in the Han patients.CONCLUSION:The prevalence of and risk factors for gallstones differ between the Uighur and Han populations.

Effects of sphincter of Oddi motility on the formation of cholesterol gallstones

AIM: To investigate the mechanisms and effects of sphincter of Oddi(SO) motility on cholesterol gallbladder stone formation in guinea pigs.METHODS: Thirty-four adult male Hartley guinea pigs were divided randomly into two groups, the control group(n = 10) and the cholesterol gallstone group(n = 24), which was sequentially divided into four subgroups with six guinea pigs each according to time of sacrifice. The guinea pigs in the cholesterol gallstone group were fed a cholesterol lithogenic diet and sacrificed after 3, 6, 9, and 12 wk. SO manometry and recording of myoelectric activity were obtained by a multifunctional physiograph at each stage. Cholecystokinin-A receptor(CCKAR) expression levels in SO smooth muscle were detected by quantitative real-time PCR(q RT-PCR) and serum vasoactive intestinal peptide(VIP), gastrin, and cholecystokinin octapeptide(CCK-8) were detected by enzyme-linked immunosorbent assay at each stage in the process of cholesterol gallstone formation.RESULTS: The gallstone formation rate was 0%, 0%, 16.7%, and 83.3% in the 3, 6, 9, and 12 wk groups, respectively. The frequency of myoelectric activity in the 9 wk group, the amplitude of myoelectric activity in the 9 and 12 wk groups, and the amplitude and the frequency of SO in the 9 wk group were all significantly decreased compared to the control group. The SO basal pressure and common bile duct pressure increased markedly in the 12 wk group, and the CCKAR expression levels increased in the 6 and 12 wk groups compared to the control group. Serum VIP was elevated significantly in the 9 and 12 wk groups and gastrin decreased significantly in the 3 and 9 wk groups. There was no difference in serum CCK-8 between the groups.CONCLUSION: A cholesterol gallstone-causing diet can induce SO dysfunction. The increasing tension of the SO along with its decreasing activity may play an important role in cholesterol gallstone formation. Expression changes of CCKAR in SO smooth muscle and serum VIP and CCK-8 may be important causes of SO dysfunction.

Helicobacter pylori infection is associated with gallstones: Epidemiological survey in China

AIM: To elucidate the prevalence and risk factors for gallstones, primarily focusing on Helicobacter pylori(H. pylori) infection. METHODS: A total of 10016 Chinese subjects, who had undergone physical examination, fasting 13 C urea breath test and abdominal ultrasonography, had sufficient blood test data, and had finished a questionnaire, were included in this cross-sectional study. Participants(n = 1122) who had previous eradication of H. pylori were studied separately. RESULTS: Gallstones were discovered in 9.10% of men and 8.58% of women, with no significant sex difference. Multivariate analyses displayed that age, aspartate aminotransferase, total cholesterol, H. pylori infection, hepatitis C virus(HCV) infection, and fattyliver had a significant association with gallstones(P < 0.05). Successive multiple logistic regression analysis including index of odds ratio(OR) and standardized coefficient(β) indicated that older age(OR/β = 1.056/0.055), H. pylori infection(OR/β = 1.454/0.109), HCV infection(OR/β = 1.871/0.123), and fatty liver(OR/β = 1.947/0.189) had a significant positive association with gallstones. After age stratification, H. pylori infection and fatty liver still had a significant positive association with gallstones in any age-specific groups, whereas HCV infection had a significant positive association in patients aged > 40 years. The prevalence of gallstones among H. pylori-positive, H. pylori-eradicated, and H. pylori-negative subjects was 9.47%, 9.02%, and 8.46%, respectively. The matched analysis showed that gallstones among H. pylori eradicated subjects was significantly lower compared with H. pylori-positive subjects(P < 0.05).CONCLUSION: H. pylori infection and fatty liver have a significant positive association with gallstones. H. pylori eradication may lead to prevention of gallstones.

Ursodeoxycholic acid combined with percutaneous transhepatic balloon dilation for management of gallstones after elimination of common bile duct stones

AIM To evaluate the effectiveness and safety of combined ursodeoxycholic acid and percutaneous transhepatic balloon dilation for management of gallstones after expulsion of common bile duct(CBD) stones.METHODS From April 2014 to May 2016, 15 consecutive patients(6 men and 9 women) aged 45-86(mean, 69.07 ± 9.91) years suffering from CBD stones associated with gallstones were evaluated. Good gallbladder contraction function was confirmed by type B ultrasonography. Dilation of the CBD and cystic duct was detected. Percutaneous transhepatic balloon dilation of the papilla was performed, ursodeoxycholic acid was administered, and all patients had a high-fat diet. All subjects underwent repeated cholangiography, and percutaneous transhepatic removal was carried out in patients with secondary CBD stones originating from the gallbladder. RESULTS All patients underwent percutaneous transhepatic balloon dilation with a primary success rate of 100%. The combined therapy was successful in 86.7% of patients with concomitant CBD stones and gallstones. No remaining stones were detected in the gallbladder. Transient adverse events include abdominal pain(n = 1), abdominal distension(n = 1), and fever(n = 1). Complications were treated successfully via nonsurgical management without long-term complications. No procedure-related mortality occurred. CONCLUSION For patients with concomitant CBD stones and gallstones, after percutaneous transhepatic removal of primary CBD stones, oral ursodeoxycholic acid and a high-fat diet followed by percutaneous transhepatic removal of secondary CBD stones appear to be a feasible and effective option for management of gallstones.

Spilled gallstones mimicking a retroperitoneal sarcoma following laparoscopic cholecystectomy

Laparoscopic cholecystectomy has become a standard treatment of symptomatic gallstone disease. Although spilled gallstones are considered harmless, unretrieved gallstones can result in intra-abdominal abscess. We report a case of abscess formation due to spilled gallstones after laparoscopic cholecystectomy mimicking a retroperitoneal sarcoma on radiologic imaging. A 59-year-old male with a surgical history of a laparoscopic cholecystectomy complicated by gallstones spillage presented with a 1 mo history of constant right-sided abdominal pain and tenderness. Computed tomography and magnetic resonance imaging demonstrated a retroperitoneal sarcoma at the sub-hepatic space. On open exploration a 5 cm × 5 cm retroperitoneal mass was excised. The mass contained purulent material and gallstones. Final pathology revealed abscess formation and foreign body granuloma. Vigilance concerning the possibility of lost gallstones during laparoscopic cholecystectomy is important. If possible, every spilled gallstone during surgery should be retrieved to prevent this rare complication.

Effect of intestinal transit on the formation of cholesterol gallstones in hamsters

BACKGROUND: The effect of 'intestinal transit' has become a new field of interest in the study of the pathogenesis of cholesterol gallstones. This study was undertaken to further test this notion and ascertain the relationship between impaired intestinal transit function and cholesterol gallstones. METHODS: A total of 64 hamsters were divided into 2 groups, experimental and control. Each was subdivided into 4 subgroups for sacrifice at different time. A high-cholesterol diet and a standard diet were fed to each group. The geometric center, which represents the intestinal transit function was calculated. RESULTS: The growth of all hamsters was normal. Cholesterol gallstones were found in 2 hamsters at the end of the 4th week. The geometric center values for the experimental and control groups were 2.3891 +/- 0.3923 vs. 2.7730 +/- 0.5283, at the end of week 3; 1.8148 +/- 0.4312 vs. 3.2294 +/- 1.1613 at week 4; 1.8451 +/- 0.3700 vs. 2.9075 +/- 0.3756 at week 5; and 1.8025 +/- 0.3413 vs. 3.0920 +/- 0.5622 at week 6. CONCLUSION: A high cholesterol diet can significantly reduce the intestinal transit function and facilitate the formation of cholesterol gallstones.

Fatty liver,carotid disease and gallstones:A study of age-related associations

AIM: To evaluate carotid intima-media thickening (IMT) and plaques, gallstone disease (GD) and fatty liver (FL) as a function of age. METHODS: In 449 subjects, FL and carotid disease were assessed ultrasonographically. In a subgroup of 65/449 patients with non-alcoholic fatty liver disease (NAFLD), carotid disease, GD and associated factors were determined. RESULTS: FL of unspecified etiology was more common in younger and GD in older individuals. FL subjects had an increased prevalence of IMT and a decreased prevalence of plaques and manifested carotid disease earlier. Plaques were more common in subjects with GD. Age was an independent predictor of carotid disease outcome and FL was a protective factor for plaques. In NAFLD, there was an inverse correlation between body weight and age and the latter independently predicted carotid findings. CONCLUSION: Cardiovascular risk in patients with FL and NAFLD needs to be assessed as a function of age and body weight.

Overexpression of sterol carrier protein-2 mRNA in patients with cholesterol gallstones

BACKGROUND: Hypersecretion of biliary cholesterol is believed to be one of the important causes of lithogenic bile. Sterol carrier protein-2 ( SCP2 ) participates in choles- terol trafficking and metabolism and may play a key role in cholesterol gallstone formation. This study was undertaken to investigate the expression of liver SCP2 mRNA in pa- tients with cholesterol gallstone and those patients with non-cholesterol gallstone. METHODS: The expression of liver SCP2 mRNA was studi- ed in 36 patients with cholesterol gallstone and 30 patients with non-cholesterol gallstone by reverse transcription-poly- merase chain reaction (RT-PCR). RESULT: The expression of SCP2 mRNA was increased more significantly in patients with cholesterol gallstone than in patients with non-cholesterol gallstone. CONCLUSION: The SCP2 gene was overexpressed in pa- tients with cholesterol gallstone, indicating that SCP2 may be one of the important causes of cholesterol gallstone.

Biliary microbiota and mucin 4 impact the calcification of cholesterol gallstones

Background:Cholesterol gallstones account for over 80%of gallstones,and the pathogenesis of gallstone formation involves genetic and environmental factors.However,data on the evolution of cholesterol gallstones with various densities are limited.This study aimed to determine the roles of microbiota and mucins on the formation of calcified cholesterol gallstones in patients with cholelithiasis.Methods:Paired gallbladder tissues and bile specimens were obtained from cholelithiasis patients who were categorized into the isodense group and calcified group according to the density of gallstones.The relative abundance of microbiota in gallbladder tissues was detected.Immunohistochemistry and enzyme-linked immunosorbent assay were performed to detect the expression levels of MUC1,MUC2,MUC3a,MUC3b,MUC4,MUC5ac and MUC5b in gallbladder tissues and bile.The correlation of microbiota abundance with MUC4 expression was evaluated by linear regression.Results:A total of 23 patients with gallbladder stones were included.The density of gallstones in the isodense group was significantly lower than that of the calcified group(34.20±1.50 vs.109.40±3.84 HU,P<0.0001).Compared to the isodense group,the calcified group showed a higher abundance of gram-positive bacteria at the fundus,in the body and neck of gallbladder tissues.The concentrations of MUC1,MUC2,MUC3a,MUC3b,MUC5ac and MUC5b in the epithelial cells of gallbladder tissues showed no difference between the two groups,while the concentrations of MUC4 were significantly higher in the calcified group than that in the isodense group at the fundus(15.49±0.69 vs.10.23±0.54 ng/mL,P<0.05),in the body(14.54±0.94 vs.11.87±0.85 ng/mL,P<0.05)as well as in the neck(14.77±1.04 vs.10.85±0.72 ng/mL,P<0.05)of gallbladder tissues.Moreover,the abundance of bacteria was positively correlated with the expression of MUC4(r=0.569,P<0.05)in the calcified group.Conclusions:This study showed the potential clinical relevance among biliary microbiota,mucins and calcified gallstones in patients with gallstones.Gram-positive microbiota and MUC4 may be positively associated with the calcification of cholesterol gallstones.