Association of education with cholelithiasis and mediating effects of cardiometabolic factors:A Mendelian randomization study

BACKGROUND Education,cognition,and intelligence are associated with cholelithiasis occurrence,yet which one has a prominent effect on cholelithiasis and which cardiometabolic risk factors mediate the causal relationship remain unelucidated.AIM To explore the causal associations between education,cognition,and intelligence and cholelithiasis,and the cardiometabolic risk factors that mediate the associations.METHODS Applying genome-wide association study summary statistics of primarily European individuals,we utilized two-sample multivariable Mendelian randomization to estimate the independent effects of education,intelligence,and cognition on cholelithiasis and cholecystitis(FinnGen study,37041 and 11632 patients,respectively;n=486484 participants)and performed two-step Mendelian randomization to evaluate 21 potential mediators and their mediating effects on the relationships between each exposure and cholelithiasis.RESULTS Inverse variance weighted Mendelian randomization results from the FinnGen consortium showed that genetically higher education,cognition,or intelligence were not independently associated with cholelithiasis and cholecystitis;when adjusted for cholelithiasis,higher education still presented an inverse effect on cholecystitis[odds ratio:0.292(95%CI:0.171-0.501)],which could not be induced by cognition or intelligence.Five out of 21 cardiometabolic risk factors were perceived as mediators of the association between education and cholelithiasis,including body mass index(20.84%),body fat percentage(40.3%),waist circumference(44.4%),waist-to-hip ratio(32.9%),and time spent watching television(41.6%),while time spent watching television was also a mediator from cognition(20.4%)and intelligence to cholelithiasis(28.4%).All results were robust to sensitivity analyses.CONCLUSION Education,cognition,and intelligence all play crucial roles in the development of cholelithiasis,and several cardiometabolic mediators have been identified for prevention of cholelithiasis due to defects in each exposure.

Biliary complications associated with weight loss,cholelithiasis and choledocholithiasis

Biliary complications like cholelithiasis and choledocholithiasis are more common in bariatric surgery patients due to obesity and rapid weight loss.Patients with a body mass index>40 face an eightfold risk of developing cholelithiasis.Postbariatric surgery,especially after laparoscopic Roux-en-Y gastric bypass(LRYGB),30%of patients develop biliary disease due to rapid weight loss.The aim of this review is to analyze the main biliary complications that occur after bariatric surgery and its management.A review of the literature was conducted mainly from 2010 up to 2023 with regard to biliary complications associated with bariatric patients in SciELO,PubMed,and MEDLINE.Patients undergoing LRYGB have a higher incidence(14.5%)of symptomatic calculi post-surgery compared to those undergoing laparoscopic sleeve gastrectomy at 4.1%.Key biliary complications within 6 to 12 months post-surgery include:Cholelithiasis:36%;Biliary colic/dyskinesia:3.86%;Acute cholecystitis:0.98%-18.1%;Chronic cholecystitis:70.2%;Choledocholithiasis:0.2%-5.7%and Pancreatitis:0.46%-9.4%.Surgeons need to be aware of these complications and consider surgical treatments based on patient symptoms to enhance their quality of life.

Analysis of the Effect of Laparoscopic Versus Open Cholecystectomy in Patients with Cholelithiasis and the Effect on CRP and IL-1βLevels

Objective:To evaluate the therapeutic effect of laparoscopic cholecystectomy(LC)and open cholecystectomy(OC)on cholelithiasis.Methods:92 cases of cholelithiasis patients admitted to the hospital in the past 2 years were selected and grouped by random number table;the observation group was treated with LC;the reference group was treated with OC,and the inflammatory factor and other indexes were compared.Results:The total effective rate of the observation group was higher than that of the reference group,and the perioperative indexes were better than that of the reference group(P<0.05).Preoperatively,the C-reactive protein(CRP)and interleukin-1β(IL-1β)levels and immune function indexes of the two groups were compared,and no difference was seen(P>0.05).At 5 days postoperatively,the CRP and IL-1βlevels of the observation group were lower than those of the reference group,and the immune function indicators were higher than those of the reference group(P<0.05).The complication rate of the observation group was lower than that of the reference group(P<0.05).Conclusion:LC can increase the effective rate of cholelithiasis patients,improve their perioperative indexes,reduce the inflammatory response,protect patients’immune function,and ensure higher surgical safety.

Current management of concomitant cholelithiasis and common bile duct stones

The management policy of concomitant cholelithiasis and choledocholithiasis is based on a one-or two-stage procedure.It basically includes either laparoscopic cholecystectomy(LC)with laparoscopic common bile duct(CBD)exploration(LCBDE)in the same operation or LC with preoperative,postoperative and even intraoperative endoscopic retrograde cholangiopancreatography-endoscopic sphincterotomy(ERCP-ES)for stone clearance.The most frequently used worldwide option is preoperative ERCP-ES and stone removal followed by LC,preferably on the next day.In cases where preoperative ERCP-ES is not feasible,the proposed alternative of intraoperative rendezvous ERCP-ES simultaneously with LC has been advocated.The intraoperative extraction of CBD stones is superior to postoperative rendezvous ERCP-ES.However,there is no consensus on the superiority of laparoendoscopic rendezvous.This is equivalent to a traditional two-stage procedure.Endoscopic papillary large balloon dilation reduces recurrence.LCBDE and intraoperative ERCP have similar good outcomes.The risk of recurrence after ERCP-ES is greater than that after LCBDE.Laparoscopic ultrasonography may delineate the anatomy and detect CBD stones.The majority of surgeons prefer the transcductal instead of the transcystic approach for CBDE with or without T-tube drainage,but the transcystic approach must be used where possible.LCBDE is a safe and effective choice when performed by an experienced surgeon.However,the requirement of specific equipment and advanced training are drawbacks.The percutaneous approach is an alternative when ERCP fails.Surgical or endoscopic reintervention for retained stones may be needed.For asymptomatic CBD stones,ERCP clearance is the firstchoice method.Both one-stage and two-stage management are acceptable and can ensure improved quality of life.

Improvement of inflammatory response and gastrointestinal function in perioperative of cholelithiasis by Modified Xiao-Cheng-Qi decoction

BACKGROUND In the perioperative period of biliary surgery,various factors can induce the release of a large number of inflammatory factors,leading to an imbalance in proinflammatory and anti-inflammatory responses and resulting in gastrointestinal(GI)dysfunction.Enhanced Recovery After Surgery protocols in biliary surgery have been shown to reduce the stress response and accelerate postoperative recovery.It is crucial to reduce the inflammatory response and promote the recovery of GI function after biliary surgery,both of which are the basis and key for perioperative care and postoperative recovery.AIM To better understand the effects of Modified Xiao-Cheng-Qi decoction(MXD)on inflammatory response and GI function in the perioperative management of cholelithiasis and their correlation.METHODS This was a prospective randomized placebo-controlled trial,in which 162 patients who received biliary tract surgery were randomly assigned to three groups:MXD group,XD group,and placebo-control group.The observed parameters included frequency of bowel sounds,time of first flatus and defecation,time of diet,and amount of activity after surgery.The serum levels of C-reactive protein(CRP),interleukin(IL)-6,IL-10,serum amyloid A protein(SAA),and substance P were measured by the enzyme-linked immunosorbent assay.Then,the spearman correlation coefficient was used to analyze the relationship between the indicators of GI function and inflammation.RESULTS Compared to the placebo-control,improvements in GI function were observed in the MXD groups including reduced incidence of nausea,vomiting,and bloating;and earlier first exhaust time,first defecation time,and feeding time after surgery(P<0.05).On the 1st and 2nd d after surgery,IL-6,CRP and SAA levels in MXD group were lower than that in placebo control,but substance P level was higher,compared to the control(P<0.05).Functional diarrhea occurred in both MXD and XD groups without any other adverse effects,toxic reactions,and allergic reactions.Diarrhea was relieved after the discontinuation of the investigational remedies.Bowel sounds at 12 h after surgery,the occurring time of the first flatus,first defecation,postoperative liquid diet and semiliquid diet were significantly correlated with levels of IL-6,CRP,SAA and substance P on second day after surgery(P<0.05).CONCLUSION Treatment with MXD can relieve inflammatory response and improve GI function after surgery.Moreover,there are significant correlations between them.Furthermore,it does not cause serious adverse reactions.

Research Progress of Ethnic Medicine in the Treatment of Cholelithiasis

In a broad sense, ethnic medicine includes Han traditional Chinese medicine, folk medicine and ethnic minority medicine;ethnic medicine in a narrow sense refers to ethnic minority medicine. It is a medicine developed by ethnic minorities in order to survive and reproduce and in the process of fighting diseases. Culture, based on its own language, life experience and cultural traditions, has its own understanding and theoretical system of disease naming, etiology and pathogenesis, treatment principles and treatment methods, which is a major feature of my country’s medical care. Among them, ethnic medicine has unique advantages and good clinical efficacy in the prevention and treatment of cholelithiasis. Therefore, this paper focuses on summarizing the characteristic theories and diagnosis and treatment experience of Tibetan medicine, Mongolian medicine, Miao medicine, Yao medicine, and Beijing medicine in ethnic medicine by sorting out and summarizing the relevant materials in this regard, so as to provide new ideas for improving the treatment of cholelithiasis and enriching clinical drug selection.

Laparoscopic Surgery and Modified Xiaoyan Lidan Decoction:An Effective Combination for Treating Cholecystitis with Cholelithiasis

Objective:To assess the clinical effects of combining laparoscopic surgery with Modified Xiaoyan Lidan Decoction in patients diagnosed with cholecystitis and cholelithiasis.Methods:Following the guidelines of the double-blind method,86 cases of cholecystitis with cholelithiasis were randomly divided into two groups,each comprising 43 cases.Both groups underwent laparoscopic surgery,with the observation group additionally receiving Modified Xiaoyan Lidan Decoction.A comparative analysis was conducted on clinical treatment effectiveness,general observation indicators,Traditional Chinese Medicine(TCM)syndrome scores,and the occurrence of adverse reactions between the two groups.Results:The observation group demonstrated a significantly higher overall clinical treatment effectiveness compared to the control group(P<0.05).The clinical symptom improvement time and hospitalization time were shorter in the observation group,and the pain score and TCM syndrome score after treatment were lower than those in the control group(P<0.05).No statistically significant difference was observed in the total reaction values(P>0.05).Conclusion:The combined application of laparoscopic surgery and Modified Xiaoyan Lidan Decoction can enhance clinical treatment efficiency for patients with cholecystitis and cholelithiasis.It facilitates a quicker improvement in clinical symptoms without causing serious adverse reactions,suggesting its potential for widespread adoption.

Low phospholipid-associated cholelithiasis syndrome:A rare cause of acute pancreatitis that should not be neglected

BACKGROUND Low phospholipid-associated cholelithiasis(LPAC)syndrome is a very particular form of biliary lithiasis with no excess of cholesterol secretion into bile,but a decrease in phosphatidylcholine secretion,which is responsible for stones forming not only in the gallbladder,but also in the liver.LPAC syndrome may be underreported due to a lack of testing resulting from insufficient awareness among clinicians.AIM To describe the clinical and radiological characteristics of patients with LPAC syndrome to better identify and diagnose the disease.METHODS We prospectively evaluated all patients aged over 18 years old who were consulted or hospitalized in two hospitals in Paris,France(Bichat University Hospital and Croix-Saint-Simon Hospital)between January 1,2017 and August 31,2018.All patients whose profiles led to a clinical suspicion of LPAC syndrome underwent a liver ultrasound examination performed by an experienced radiologist to confirm the diagnosis of LPAC syndrome.Twenty-four patients were selected.Data about the patients’general characteristics,their medical history,their symptoms,and their blood tests results were collected during both their initial hospitalization and follow-up.Cytolysis and cholestasis were expressed compared to the normal values(N)of serum aspartate and alanine transaminase activities,and to the normal value of alkaline phosphatase level,respectively.The subjects were systematically reevaluated and asked about their symptoms 6 mo after inclusion in the study through an in-person medical appointment or phone call.Genetic testing was not performed systematically,but according to the decision of each physician.RESULTS Most patients were young(median age of 37 years),male(58%),and not overweight(median body mass index was 24).Many had a personal history of acute pancreatitis(54%)or cholecystectomy(42%),and a family history of gallstones in first-degree relatives(30%).LPAC syndrome was identified primarily in patients with recurring biliary pain(88%)or after a new episode of acute pancreatitis(38%).When present,cytolysis and cholestasis were not severe(2.8N and 1.7N,respectively)and disappeared quickly.Interestingly,four patients from the same family were diagnosed with LPAC syndrome.At ultrasound examination,the most frequent findings in intrahepatic bile ducts were comet-tail artifacts(96%),microlithiasis(83%),and acoustic shadows(71%).Computed tomography scans and magnetic resonance imaging were performed on 15 and three patients,respectively,but microlithiasis was not detected.Complications of LPAC syndrome required hospitalizing 18 patients(75%)in a conventional care unit for a mean duration of 6.8 d.None of them died.Treatment with ursodeoxycholic acid(UDCA)was effective and well-tolerated in almost all patients(94%)with a rapid onset of action(3.4 wk).Twelve patients’(67%)adherence to UDCA treatment was considered“good.”Five patients(36%)underwent cholecystectomy(three of them were treated both by UDCA and cholecystectomy).Despite UDCA efficacy,biliary pain recurred in five patients(28%),three of whom adhered well to treatment guidelines.CONCLUSION LPAC syndrome is easy to diagnose and treat;therefore,it should no longer be overlooked.To increase its detection rate,all patients who experience recurrent biliary symptoms following an episode of acute pancreatitis should undergo an ultrasound examination performed by a radiologist with knowledge of the disease.

Operative treatment for patients with cholelithiasis and liver cirrhosis

BACKGROUND: Liver cirrhosis and cholelithiasis are both familiar diseases in China. However, the rates of operative complications and death are still high in patients with these diseases. This study was designed to determine the operative indications as well as suitable procedures in the treatment of patients with cholelithiasis and liver cirrhosis. METHODS: We studied retrospectively 60 patients with cholelithiasis and liver cirrhosis who had undergone operation from January 2000 to July 2006. We analyzed the loss of blood during operation, postoperative complications and death rate to determine the proper treatment. RESULTS: Fifty patients were cured and 10 (16.7%) died postoperatively, i.e., six patients died from hepatic-renal failure and multisystem organ dysfunction and 4 from massive bleeding in the gallbladder bed. The 10 patients were clearly correlated with the Child-Pugh classification: Child A (8%), Child B (20%) and Child C (30%). Postoperative bleeding occurred in 10 patients (16.7%), intraabdominal in 6 and gastrointestinal in 4. Seven of the 10 patients with bleeding died postoperatively. CONCLUSIONS: The proper perioperative management of patients with cholelithiasis and liver cirrhosis can decrease the mortality. Cholelithiasis should be managed first by emergency operation. It is safe for the patients of Child A to undergo laparoscopy. It is very safe for patients with cirrhosis and cholelithiasis to undergo devascularization and shunt operation followed by biliary tract surgery.

Internal biliary fistula due to cholelithiasis:A single-centre experience

AIM： To discuss about the perioperative problems encountered in patients with internal biliary fistula （IBF） caused by cholelithiasis.METHODS： In our hospital, 4 130 cholecystectomies were carried out for symptomatic cholelithiasis from January 2000 to March 2004 and only 12 patients were diagnosed with IBF. The perioperative data of these 12 IBF patients were analyzed retrospectively.RESULTS： The incidence of IBF due to cholelithiasis was nearly 0.3%. The mean age was 57 years. Most of the patients presented with non-specific complaints. Only two patients were considered to have IBF when gallstone ileus was observed during the investigations. Nine patients underwent emergency laparotomy with a pre-operative diagnosis of acute abdomen. In the remaining three patients, elective laparoscopic cholecystectomy was converted to open surgery after identification of IBF. Ten patients had cholecystoduodenal fistula and two patients had cholecystocholedochal fistula. The mean hospital stay was 23 d. Two wound infections, three bile leakages and three mortalities were observed.CONCLUSION： Cholecystectomy has to be performed in early stage in the patients who were diagnosed as cholelithiasis to prevent the complications like IBF which is seen rarely. Suspicion of IBF should be kept in mind, especially in the case of difficult dissection during cholecystectomy and attention should be paid in order to prevent iatrogenic injuries.

Pregnane receptor gene polymorphisms,pathogenic bacteria distribution and drug sensitivity,and TCM dyndrome differentiation in patients with cholelithiasis

Objective:To investigate the distribution of pathogens and drug resistance in bile and the association between the pregane X receptor(PXR) gene polymorphisms,traditional Chinese medicine(TCM) syndromes and the risk of cholesterol gallstone disease(CGD).Methods:A total of 392 samples were enrolled in this study from January 2014 to February 2015.among which 192 patients were with CGD.and 200 samples were healthy.Strains were isolated and susceptibility testing was the disk diffusion method susceptibility testing.The patients were divided into hepatochlic hygropyrexia.stagnation of liver-qi.and the accumulation of damp.The PXR gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism.The association between the PXR gene polymorphisms and the risk of CGD was examined by logistic regression analysis.Results:A total of 192 cases were detected in 230 of bile culture pathogens,including Grain-negative bacteria 133(57.83%),Gram-positive bacteria76(33.04%),and fungi 21(9.13%).The top five pathogens were Escherichia coli,Klebsiella pneumoniae.Enterococcus faecalis,Candida albicans,and Enterococcus feces,ot which 110 cases was of single infection.48 cases of mixed infection of two strains,eight cases of mixed infection of three bacteria.Among 59 Escherichia coli,the yield extended-spectrum beta-laetamases had 40(67.80%).The hepatochlic hygropyrexia was the most TCM syndrome,followed by stagnation of liver-qi.and the accumulation of damp was least.Different pathogens and the rs6785049 genotypes distributed differently in cholelithiasis patients with different TCM syndromes(P<0.05).In hepatochlic hygropyrexia patients the Gram-negative bacteria was most.There was significant differences between CGD group and control group in rs6785049(P<0.001).Comparison with wild-type portable GG.GA genotype increased the risk of the occurrence of gallstones(OR=0.40.95%CI:0.16-0.79);likewise,carrying the GA + AA genotype also increased the risk(OR=0.38,95%CI:0.19-0.81).There was no significant differences in rs2276707,rs3814055 site polymorphic loci alleles in CGD group and control group.Conclusions:In the treatment of cholelithiasis,bile samples should be collected for bacterial culture and sensitivity test,and drugs should be strictly chosen based on the results.The rs6785049 polymorphisms in PXR gene may increase the risk of gallstones ontogeny,and gallstones can he early detected and prevented by detecting genotypes.rs6785049 polymorphisms in PXR gene may has relationship with TCM syndromes.

Is intraoperative cholangiography necessary during laparoscopic cholecystectomy for cholelithiasis?

AIM:To determine the efficacy and safety benefits of performing intraoperative cholangiography(IOC)during laparoscopic cholecystectomy(LC)to treat symptomatic cholelithiasis.METHODS:Patients admitted to the Minimally Invasive Surgery Center of Tianjin Nankai Hospital between January2012 and January 2014 for management of symptomaticcholelithiasis were recruited for this prospective randomized trial.Study enrollment was offered to patients with clinical presentation of biliary colic symptoms,radiological findings suggestive of gallstones,and normal serum biochemistry results.Study participants were randomized to receive either routine LC treatment or LC+IOC treatment.The routine LC procedure was carried out using the standard four-port technique;the LC+IOC procedure was carried out with the addition of meglumine diatrizoate(1:1 dilution with normal saline)injection via a catheter introduced through a small incision in the cystic duct made by laparoscopic scissors.Operative data and postoperative outcomes,including operative time,retained common bile duct(CBD)stones,CBD injury,other complications and length of hospital stay,were recorded for comparative analysis.Inter-group differences were statistically assessed by theχ2 test(categorical variables)and Fisher’s exact test(binary variables),with the threshold for statistical significance set at P<0.05.RESULTS:A total of 371 patients were enrolled in the trial(late-adolescent to adult,age range:16-70 years),with 185 assigned to the routine LC group and 186 to the LC+IOC group.The two treatment groups were similar in age,sex,body mass index,duration of symptomology,number and size of gallstones,and clinical symptoms.The two treatment groups also showed no significant differences in the rates of successful LC(98.38%vs97.85%),CBD stone retainment(0.54%vs 0.00%),CBD injury(0.54%vs 0.53%)and other complications(2.16%vs 2.15%),as well as in duration of hospital stay(5.10±1.41 d vs 4.99±1.53 d).However,the LC+IOC treatment group showed significantly longer mean operative time(routine LC group:43.00±4.15 min vs 52.86±4.47 min,P<0.01).There were no cases of fatal complications in either group.At the one-year follow-up assessment,one patient in the routine LC group reported experiencing diarrhea for three months after the LC and one patient in the LC+IOC group reported ongoing intermittent epigastric discomfort,but radiologicalexamination provided no abnormal findings.CONCLUSION:IOC addition to the routine LC treatment of symptomatic cholelithiasis does not improve rates of CBD stone retainment or bile duct injury but lengthens operative time.

Acute transient hepatocellular injury in cholelithiasis and cholecystitis without evidence of choledocholithiasis

AIM： To investigate acute transient hepatocellular injury in patients with cholelithiasis and cholecystitis but no evidence of choledocholithiasis.METHODS： The medical records of patients with cholelithiasis who underwent cholecystectomy between July 2003 and June 2007 were retrospectively reviewed. Imaging studies to detect common bile duct （CBD） stones were performed in 186 patients, who constituted the study population. Biochemical liver tests before and after surgery, and with the presence or absence of CBD stones were analyzed.RESULTS： In 96 patients with cholelithiasis and cholecystitis without evidence of CBD stones, 49 （51.0%） had an alanine aminotransferase level elevated to 2-3 times the upper limit of normal, and 40 （41.2%） had an elevated aspartate aminotransferase level. Similar manifestations of hepatocellular injury were, as would be expected, even more obvious in the 90 patients with CBD stones. These markers of hepatocellular injury resolved almost completely within 2 wk to 1 mo after cholecystectomy. Compared to 59 patients with histologically less severe cholecystitisin the group undergoing urgent surgery （total 74 patients）, the 15 patients with a gangrenous gallbladder had a higher mean level of total bilirubin （2.14 ± 1.27 mg/dL vs 2.66 ± 2.97 mg/dL, P 〈 0.001） and white cell count （9480 ± 4681/μL vs 12840 ± 5273/μL, P = 0.018）.CONCLUSION： Acute hepatocellular injury in cholelithiasis and cholecystitis without choledocholithiasis is mild and transient. Hyperbilirubinemia and leukocytosis may predict severe inflammatory changes in the gallbladder.

Management of cholelithiasis in Italian children:A national multicenter study

AIM:To evaluate the management of Italian children with cholelithiasis observed at Pediatric and Surgical Departments linked to Italian Society of Pediatric Gastroenterology Hepatology and Nutrition. METHODS: One-hundred-eighty children (90 males, median age at diagnosis 7.3 years; range, 0-18 years) with echographic evidence of cholelithiasis were enrolled in the study; the data were collected by an anonymous questionnaire sent to participating centers. RESULTS: One hundred seventeen patients were treated with ursodeoxycholic acid; in 8 children dissolution of gallstones was observed, but the cholelithiasis recurred in 3 of them. Sixty-five percent of symptomatic children treated became asymptomatic. Sixty-four patients were treated with cholecystectomy and in only 2 cases a postoperative complication was reported. Thirty- four children received no treatment and were followed with clinical and echographic controls; in no case thedevelopment of complications was reported. CONCLUSION: The therapeutic strategies were extremely heterogeneous. Ursodeoxycholic acid was ineffective in dissolution of gallstones but it had a positive effect on the symptoms. Laparoscopic cholecystectomy was confirmed to be an efficacy and safe treatment for pediatric gallstones.

Rat model of cholelithiasis with human gallstones implanted in cholestasis-induced virtual gallbladder

AIM:To facilitate translational research on cholelithiasis,we have developed a rat model of human gallstones by exploiting the unique biliopancreatic features of this species.METHODS:Under anesthesia,16 adult rats of equal genders underwent two times of abdominal surgery.First,their common bile duct(CBD)was ligated to cause cholestasis by total biliary obstruction(TBO).On day 0,1,3,7,14,21 and 28 after TBO,magnetic resonance imaging(MRI)was conducted to monitor the dilatation of the CBD,and blood was sampled to analyze total serum bilirubin(TSB).Secondly,on day 30,the abdomen was re-opened and gallstone(s)collected from human patients were implanted in the dilated CBD asa virtual gallbladder(VGB),which was closed by suture ligation.This rat cholelithiasis model was examined by MRI,clinical observation,microcholangiography and histology.RESULTS:All rats survived two laparotomies.After ligation,the CBD was dilated to a stable size of 4 to30 mm in diameter on day 21-28,which became a VGB.The rats initially showed signs of jaundice that diminished over time,which paralleled with the evolving TSB levels from 0.6±0.3 mg/d L before ligation,through a peak of 10.9±1.9 mg/dL on day 14,until a nearly normalized value after day 28.The dilated CBD with thickened wall allowed an incision for implantation of human gallstones of 1-10 mm in diameter.The rat cholelithiasis was proven by in vivo MRI and postmortem microcholangiography and histomorphology.CONCLUSION:A rat model cholelithiasis with human gallstones has been established,which proves feasible,safe,reliable,nontoxic and cost-effective.Given the gallstones of human origin,applications of this model may be of help in translational research such as optical detection and lysis of gallstones by systemic drug administration.

Acute pain management in symptomatic cholelithiasis

AIM To review the evidence for the use of different nonsteroidal anti-inflammatory drugs(NSAIDs) in the treatment of biliary colic.METHODS The strategies employed included an extensive literature review for articles and studies related to biliary colic from electronic databases including Pub Med,Science Direct,Wiley Inter Science,Medline and Cochrane from last 15 years.Keywords: "Biliary colic","management of biliary colic","non-steroidal anti-inflammatory drugs","cholelithiasis" and "biliary colic management".Six randomized control trials,1 non-randomized trial and 1 meta-analysis were included in this review.The outcomes of these studies and their significance have been reviewed in this paper.RESULTS Current evidence suggests there are no set protocols for biliary colic pain management.NSAIDs are potent in the management of biliary colic,not only in terms of symptom control but in disease progression as well.Apart from the studies on diclofenac and ketorolac,there are studies which have shown that intravenous tenoxicam and injectable flurbiprofen are equally effective in managing biliary colic.The efficacy of NSAIDs is superior in terms of lower number of doses and longer duration of action in comparison to other analgesic agents.CONCLUSION This literature review has found that NSAIDs are safe and effective for pain control in biliary colic,and reduce the likelihood of further complications.

Incidence of congenital hemolytic anemias in young cholelithiasis patients

AIM: To clarify the incidence of congenital hemolytic anemias (CHA) in young cholelithiasis patients and to determine a possible screening test based on the results. METHODS: Young cholelithiasis patients (< 35 years) were invited to our outpatient clinic. Participants were asked for comorbidities and family history. The number of gallstones were recorded. Blood samples were obtained to perform a complete blood count, standard Wright-Giemsa staining, reticulocyte count, hemoglobin (Hb) electrophoresis, serum lactate dehydrogenase and bilirubin levels, and lipid profile. RESULTS: Of 3226 cholecystectomy patients, 199 were under 35 years, and 190 with no diagnosis of CHA were invited to take part in the study. Fifty three patients consented to the study. The median age was 29 years (range, 17-35 years), 5 were male and 48 were female. Twelve patients (22.6%) were diagnosed as thalassemia trait and/or ?ron-deficiency anemia. Hblevels were significantly lower (P = 0.046), and mean corpuscular volume (MCV) and hematocrit levels were slightly lower (P = 0.072 and 0.082, respectively) than normal. There was also a significantly lower number of gallstones with the diagnosis (P = 0.007). CONCLUSION: In endemic regions, for young cholelithiasis patients (age under 35) with 2-5 gallstones, the clinician/surgeon should pay attention to MCV and Hb levels as indicative of CHA.

Cholelithiasis associated with haemolytic-uraemic syndrome

Cholelithiasis occurs infrequently in the paediatric age group. Hereditary spherocytosis, sickle cell anaemia and thalassemia are the haemolytic disorders most commonly associated with development of gall stones in paediatric age group. The question is whether an isolated episode of haemolysis can cause gallstones.

Effects of variant UDP-glucuronosyltransferase 1A1 gene, glucose-6-phosphate dehydrogenase deficiency and thalassemia on cholelithiasis

AIM： To test the hypothesis that the variant UDP- glucuronosyltransferase 1A1 （UGT1A1） gene, glucose-6- phosphate dehydrogenase （G6PD） deficiency, and thalassemia influence bilirubin metabolism and play a role in the development of cholelithiasis. METHODS： A total of 372 Taiwan Chinese with cholelithiasis who had undergone cholecystectomy and 293 healthy individuals were divided into case and control groups, respectively. PCR and restriction fragment length polymorphism were used to analyze the promoter area and nucleotides 211, 686, 1 091, and 1 456 of the UGT1A1 gene for all subjects and the gene variants for thalassemia and G6PD deficiency. RESULTS： Variation frequencies for the cholelithiasis patients were 16.1%, 25.8%, 5.4%, and 4.3% for A（TA）6 TAA/A（TA）TTAA （6/7）, heterozygosity within the coding region, compound heterozygosity, and homozygosity of the UGT1A1 gene, respectively. Comparing the case and control groups, a statistically significant difference in frequency was demonstrated for the homozygous variation of the UGT1A1 gene （P = 0.012, Z2 test）, but not for the other variations. Further, no difference was demonstrated in a between-group comparison of the incidence of G6PD deficiency and thalassemia （2.7% vs 2.4% and 5.1% vs 5.1%, respectively）. The bilirubin levels for the cholelithiasis patients with the homozygous variant-UGT1A1 gene were significantly different from the control analog （18.0±6.5 and 12.7±2.9 μmol/L, respectively; P〈0.001, Student＇s ttest）.CONCLUSION： Our results show that the homozygous variation in the UGT1A1 gene is a risk factor for the development of cholelithiasis in Taiwan Chinese. 2005 The WJG Press and Elsevier Inc. All rights reserved

Clinical epidemiological study on intrahepatic cholelithiasis: analysis of 8585 cases

OBJECTIVE: To investigate the clinical epidemiology of intrahepatic cholelithiasis in Guangxi area, China. METHODS: 8585 cases of cholelithiasis proved by surgery in a period of 19 years were analyzed retrospectively. Data were collected and analyzed by computer software package PEMS. RESULTS: Cases of intrahepatic cholelithiasis accounted for more than one third of cases of cholelithiasis treated in the same period. The prevalence of intrahepatic cholelithiasis in farmers increased from 23.4% out of all cases with gallstone in 1981-1985 to 55.8% in 1991-1999. The constituent ratio of intrahepatic cholelithiasis in males was nearly the same in females. The peak prevalence age of patients with intrahepatic cholelithiasis ranged from 31 to 40 years, and the mortality was the highest among all bile stone cases. CONCLUSION: Intrahepatic cholelithiasis is by no means a vanishing disease, especially in rural area.