Ursodeoxycholic acid for the prevention of symptomatic gallstone disease after bariatric surgery (UPGRADE): a multicentre, double-blind, randomised, placebo-controlled superiority trial.

BACKGROUND: Rapid weight loss is a major risk factor for the formation of cholesterol gallstones. Consequently, patients with morbid obesity undergoing bariatric surgery frequently develop symptomatic gallstone disease. This trial assessed the efficacy of ursodeoxycholic acid versus placebo for the prevention of symptomatic gallstone disease after bariatric surgery. METHODS: This multicentre, double-blind, randomised, placebo-controlled superiority trial enrolled patients with an intact gallbladder scheduled for laparoscopic Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy in three hospitals in the Netherlands. Patients were randomly assigned (1:1) by a web-based randomisation module to receive 900 mg ursodeoxycholic acid daily for 6 months or matched placebo. Randomisation was stratified by the presence of asymptomatic gallstones at baseline and type of surgery. Patients, clinicians, and study staff were masked to treatment allocation. The primary endpoint was symptomatic gallstone disease within 24 months, assessed in the modified intention-to-treat population (all randomly assigned eligible patients with any post-randomisation measurement). Prespecified subgroup analyses were done based on the stratification groups. Safety was assessed in all patients who took at least one dose of the study drug. This trial is registered with the Netherlands Trial Register, NL5954. FINDINGS: Between Jan 11, 2017, and Oct 22, 2018, 985 patients were randomly assigned to receive either ursodeoxycholic acid (n=492) or placebo (n=493). 967 patients were included in the modified intention-to-treat population, of whom 959 had data available for primary endpoint assessment. 189 (20%) patients had asymptomatic gallstones at baseline and 78 (8%) received a sleeve gastrectomy. Symptomatic gallstone disease occurred in 31 (6·5%) of 475 patients in the ursodeoxycholic acid group and in 47 (9·7%) of 484 patients in the placebo group (relative risk 0·67, 95% CI 0·43-1·04, p=0·071). Logistic regression showed a significant interaction between ursodeoxycholic acid and the presence of asymptomatic gallstones at baseline (p=0·046), with an effect of ursodeoxycholic acid in patients without (0·47, 0·27-0·84, p=0·0081), and no effect in patients with asymptomatic gallstones at baseline (1·22, 0·61-2·47, p=0·57). The effect was stronger in patients without gallstones at baseline undergoing RYGB (0·37, 0·20-0·71, p=0·0016), whereas the subgroup of patients undergoing sleeve gastrectomy was too small to draw clear conclusions. Adverse events were rare. In the ursodeoxycholic acid group, diarrhoea occurred in four (0·9%) of 444 patients and skin rash in two (0·5%) patients. In the placebo group, diarrhoea occurred in two (0·4%) of 453 patients and skin rash in two (0·4%) patients. The total number of serious adverse events did not significantly differ between the trial groups (75 [17%] in 444 patients in the ursodeoxycholic acid group and 102 [23%] in 453 patients in the placebo group). The most common serious adverse events were abdominal pain and internal hernia. No serious adverse event was attributed to the study drug. INTERPRETATION: Ursodeoxycholic acid prophylaxis did not significantly reduce the occurrence of symptomatic gallstone disease in all patients after bariatric surgery. In patients without gallstones before RYGB surgery, ursodeoxycholic acid treatment reduced the occurrence of symptomatic gallstone disease compared with placebo. Further research is needed to assess the efficacy of ursodeoxycholic acid after sleeve gastrectomy. FUNDING: The Netherlands Organization for Health Research and Development, Zambon Netherlands BV, Foundation for Clinical Research of the Slotervaart Hospital, the Spaarne Gasthuis Academy, and Amsterdam Gastroenterology Endocrinology Metabolism.

Ursodeoxycholic acid for the prevention of symptomatic gallstone disease after bariatric surgery: statistical analysis plan for a randomised controlled trial (UPGRADE trial).

BACKGROUND: Approximately 8-15% of patients undergoing bariatric surgery develop symptomatic gallstone disease within 24 months after surgery. Ursodeoxycholic acid (UDCA) seems to effectively prevent the formation of gallstones detectable by ultrasound after bariatric surgery. The aim of the UPGRADE trial is to provide evidence on the prophylactic use of UDCA in preventing symptomatic gallstone disease postoperatively. METHODS: The UPGRADE trial is designed as a randomised, placebo-controlled, double-blind multicentre trial in patients with morbid obesity undergoing Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG). Patients are randomly assigned to either UDCA 900 mg daily for 6 months or placebo treatment. This paper details the statistical analysis plan (SAP) of this trial and was submitted before outcome data were available. RESULTS: The primary endpoint of this trial is symptomatic gallstone disease within 24 months after bariatric surgery, defined as admission or hospital visit for symptomatic gallstone disease. Secondary outcomes consist of the development of gallstones/sludge on ultrasound at 24 months in the gallstone-negative group at baseline, presence of gallstones/sludge on ultrasound at 24 months, number of cholecystectomies, side effects of UDCA, therapy compliance, quality of life, costs and revenues. Analyses will be completed according to this pre-specified SAP. The main analysis will be performed as a standard ITT analysis using the chi-squared test. DISCUSSION: The UPGRADE trial will show if prophylactic use of UDCA reduces the incidence of symptomatic gallstone disease after bariatric surgery. Unforeseen deviations from the SAP at the time of analysis will be motivated and discussed. TRIAL REGISTRATION: The Netherlands Trial Register NL5954 . Registered on 21 November 2016.

Cholecystectomy during esophagectomy is safe but unnecessary.

Background: Prophylactic cholecystectomy has been proposed as a concomitant procedure during upper gastrointestinal surgery. This study evaluates the safety and the need of concurrent cholecystectomy during esophagectomy for cancer.Methods: All consecutive esophagectomies for esophageal cancer at the Center for Esophageal Diseases in Padova (Italy) between 1992 and 2011 were included. The safety of concurrent cholecystectomy was evaluated by surgical outcomes (length of stay, postoperative mortality and perioperative complications). The need for concurrent cholecystectomy was evaluated by occurrence of biliary duct stones and of cholelithiasis/cholecystitis after esophagectomy.Results: Cholecystectomy was performed during 67 out of 1087 esophagectomies (6.2%). Cirrhosis or chronic liver disease was associated with receiving cholecystectomy during esophagectomy (OR: 1.99, 95%C.I. 1.10-3.56). Patients receiving and those not receiving cholecystectomy showed similar length of stay (median 14 days, p = .87), postoperative mortality (3.0% vs. 2.5%, p = .68), intraoperative complication (4.5% vs. 7.1%, p = .62), early complications (52.2% vs. 44.6%, p = .25) and late complications (20.9% vs. 24.8%, p = .56). Cholelithiasis/cholecystitis after esophagectomy occurred in 61 (6.1%) patients, with only four requiring cholecystectomy during follow-up. The biliary stone occurrence was nil. Only pathologic stage III-IV (OR: 2.17, 95%C.I. 1.19-3.96) was associated with cholelithiasis/cholecystitis after esophagectomy.Conclusion: Routine prophylactic cholecystectomy during esophagectomy could be safe but unnecessary.

Hepatobiliary Complications of Chronic Intestinal Failure.

Intestinal failure-associated liver disease is a multifactorial process that may occur in patients with chronic intestinal failure on long-term home parenteral nutrition. A very short gut, the lack of enteral feeding, recurrent sepsis, and parenteral overfeeding are major risk factors. Histologic changes include steatosis, steatohepatitis, cholestasis, fibrosis, and cirrhosis. Chronic cholestasis is common, but does not always progress to fibrosis and/or cirrhosis. Preventing harmful factors may dramatically decrease the risk of intestinal failure-associated liver disease. Advanced liver disease is an indication for intestinal and/or multivisceral transplantation. Biliary stone formation is frequent and mainly due to a lack of enteral feeding.

[Nutritional intervention in the control of gallstones and renal lithiasis]. / Intervención nutricional en el control de la colelitiasis y la litiasis renal.

INTRODUCTION: Cholelithiasis and kidney stones are frequent pathologies in developed countries. Gallstones can be pigmentary, cholesterol (75%) or mixed. Age, female sex, obesity, rapid weight loss, consumption of refined sugars, saturated fat, iron deficiency, vitamin D and low intake of fiber and vitamin C are factors associated with an increased risk of cholelithiasis. On the other hand, the intake of ω-3 fatty acids, oleic acid, calcium, magnesium, fiber, fruits and vegetables, dairy products, nuts, coffee, moderate consumption of alcohol, vitamin C supplements, physical exercise and a regular diet have a protective paper. The most frequent kidney stones are calcium oxalate followed by mixed ones (oxalate and calcium phosphate), struvite, uric acid and cystine. A high water intake is recommended (> 2.5 l / day), varying the type of recommended or unadvisable food depending on the type of calculus. In oxalic lithiasis it is recommended to reduce the consumption of meat, moderate that of spinach, Swiss chard, asparagus, chocolate and avoid excessive sodium intake. The administration of oxalate-degrading probiotics (Lactobacillus) may reduce intestinal absorption, although further studies are necessary to corroborate these results. In calcium phosphate acidifying diet is recommended and limit the consumption of coffee and tea. The prevention of uric calculus is based on hydration with alkalizing drinks and vegetarian diet, decreasing foods rich in purines (liver, kidney, fish eggs, anchovies, sardines and seafood) and in calculus of cystine diet is recommended alkalizing. Since the formation of struvite calculi is due to urinary infections, pharmacological treatment and the consumption of acidifying diets, moderation of the intake of phosphate-rich foods and limiting the contribution of fats and citrus fruits are necessary. The nutritional intervention is an effective measure in the prevention of biliary and renal lithiasis and prevent its recurrence.

INTRODUCCIÓN: La colelitiasis y litiasis renal son patologías frecuentes en países desarrollados. Los cálculos biliares pueden ser pigmentarios, de colesterol (75%) o mixtos. La edad, el sexo femenino, la obesidad, la pérdida rápida de peso, el consumo de azúcares refinados, la grasa saturada, la deficiencia de hierro y de vitamina D y la baja ingesta de fibra y vitamina C son factores asociados a mayor riesgo de colelitiasis. Por otro lado, la ingesta de ácidos grasos ω-3, ácido oleico, calcio, magnesio, fibra, frutas y verduras, lácteos, frutos secos, café, un consumo moderado de alcohol, suplementos de vitamina C, ejercicio físico y una alimentación regular desempeñan un papel protector. Las litiasis renales más frecuentes son de oxalato cálcico, seguidas de las mixtas (oxalato y fosfato cálcico), estruvita, ácido úrico y cistina. Se aconseja una elevada ingesta hídrica (> 2,5 l/día), variando el tipo de alimentos recomendados o desaconsejados en función del tipo de cálculo. En litiasis oxálica se recomienda reducir el consumo de carne, moderar el de espinacas, acelgas, espárragos, chocolate y evitar el aporte excesivo de sodio. La administración de probióticos degradantes de oxalato (Lactobacillus) podría reducir su absorción intestinal, aunque son necesarios más estudios para corroborar estos resultados. En las de fosfato cálcico se aconseja dieta acidificante y limitar el consumo de café y té. La prevención de cálculos de úrico está basada en la hidratación con bebidas alcalinizantes y dieta vegetariana, disminuyendo los alimentos ricos en purinas (hígado, riñón, huevas de pescado, anchoas, sardinas y mariscos), y en cálculos de cistina se aconseja el consumo de dietas alcalinizantes. Dado que la formación de cálculos de estruvita se debe a infecciones urinarias, es necesario un tratamiento farmacológico y el consumo de dietas acidificantes, moderar la ingesta de alimentos ricos en fosfatos y limitar el aporte de grasas y cítricos. La intervención nutricional es una medida eficaz en la prevención de la litiasis biliar y renal y para evitar su recurrencia.

Effect of oral ursodeoxycholic acid on cholelithiasis following laparoscopic sleeve gastrectomy for morbid obesity.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is a definitive solution for morbid obesity and its related co-morbidities. Cholelithiasis is a postoperative complication of LSG. The use of ursodeoxycholic acid (UDCA) after LSG is a proposed solution to reduce the incidence of cholelithiasis. OBJECTIVE: To evaluate the effect of UDCA prophylaxis on cholelithiasis following LSG in morbidly obese patients. SETTING: Two university hospitals in Egypt, Cairo, and Beni Suef Universities' hospitals. METHODS: This prospective study was conducted between July 2015 and March 2018 and included 200 patients scheduled for LSG. They were randomly divided into 2 groups. The UDCA group received a postoperative prophylaxis regimen for prevention of cholelithiasis in the form of 250 mg twice daily of UDCA for 6 months. The control group did not receive prophylactic treatment. Abdominal ultrasound was done at 3, 6, 9, and 12 months for all patients to detect cholelithiasis. The primary outcome measure was cholelithiasis. RESULTS: Only 6% of the UDCA group developed cholelithiasis compared with 40% in the control group (P < .001). Age, sex, initial body mass index, and excess weight loss at 6 months did not significantly affect cholelithiasis. CONCLUSION: UDCA treatment for 6 months after LSG is effective in the prevention of cholelithiasis.

Oral medical dissolution of gallstones in patients with gallstone disease

Being the main treatment for cholelithiasis, laparoscopic cholecystectomy does not always solve the problem. It often entails postcholecystectomy syndrome (PCS). Oral medication to dissolve gallstones with bile acids is alternative therapy for some patients. However, lack of efficacy and limited medical indications make it necessary to apply combination treatment tactics. This study was conducted to investigate the dissolution of gallstones during the combined effects of ursodeoxycholic acid (UDCA) and rosuvastatin as well as to assess the results of eradication therapy in the presence of H. pylory as a measure to prevent cholelithiasis in the course of treatment.

Cholesterol cholelithiasis: part of a systemic metabolic disease, prone to primary prevention.

INTRODUCTION: Cholesterol gallstone disease have relationships with various conditions linked with insulin resistance, but also with heart disease, atherosclerosis, and cancer. These associations derive from mechanisms active at a local (i.e. gallbladder, bile) and a systemic level and are involved in inflammation, hormones, nuclear receptors, signaling molecules, epigenetic modulation of gene expression, and gut microbiota. Despite advanced knowledge of these pathways, the available therapeutic options for symptomatic gallstone patients remain limited. Therapy includes oral litholysis by the bile acid ursodeoxycholic acid (UDCA) in a small subgroup of patients at high risk of postdissolution recurrence, or laparoscopic cholecystectomy, which is the therapeutic radical gold standard treatment. Cholecystectomy, however, may not be a neutral event, and potentially generates health problems, including the metabolic syndrome. Areas covered: Several studies on risk factors and pathogenesis of cholesterol gallstone disease, acting at a systemic level have been reviewed through a PubMed search. Authors have focused on primary prevention and novel potential therapeutic strategies. Expert commentary: The ultimate goal appears to target the manageable systemic mechanisms responsible for gallstone occurrence, pointing to primary prevention measures. Changes must target lifestyles, as well as experimenting innovative pharmacological tools in subgroups of patients at high risk of developing gallstones.

Concomitant cholecystectomy during bariatric surgery: The jury is still out.

BACKGROUND: We sought to compare clinical outcomes of concomitant cholecystectomy during four different types of bariatric surgery vs. bariatric surgery alone. DATA SOURCES: A systematic literature search of PubMed and Cochrane databases was conducted in accordance with the PRISMA guidelines. Thirty studies were included in this study, reporting data on 13,675 patients. Our findings suggest a higher rate of anastomotic leak/stricture in the case of concomitant cholecystectomy with gastric bypass compared to those who had gastric bypass alone. The scarcity of data concerning sleeve gastrectomy, adjustable gastric banding and biliopancreatic diversion prevented us from quantifying possible difference of outcomes between the examined treatment groups. CONCLUSIONS: This study highlights the small number and poor quality of available studies referring to the role of simultaneous cholecystectomy during bariatric surgery.

The Cholegas trial: long-term results of prophylactic cholecystectomy during gastrectomy for cancer-a randomized-controlled trial.

BACKGROUND: The incidence of cholelithiasis has been shown to be higher for patients after gastrectomy than for the general population, due to vagal branch damage and gastrointestinal reconstruction. The aim of this trial was to evaluate the need for routine concomitant prophylactic cholecystectomy (PC) during gastrectomy for cancer. METHODS: A multicenter, randomized, controlled trial was conducted between November 2008 and March 2017. Of the total 130 included patients, 65 underwent PC and 65 underwent standard gastric surgery only for curable cancers. The primary endpoint was cholelithiasis-free survival after gastrectomy for gastric adenocarcinoma. Cholelithiasis was detected by ultrasound exam. RESULTS: After a median follow-up of 62 months, eight patients (12.3%) in the control group developed biliary abnormalities (four cases of gallbladder calculi and four cases of biliary sludge), with only three (4.6%) being clinically relevant (two cholecystectomies needed, one acute pancreatitis). One patient in the PC group had asymptomatic biliary dilatation during sonography after surgery. The cholelithiasis-free survival did not show statistical significance between the two groups (P = 0.267). The number needed to treat with PC to avoid reoperation for cholelithiasis was 1:32.5. CONCLUSIONS: Concomitant PC during gastric surgery for malignancies, although reducing the absolute number of biliary abnormalities, has no significant impact on the natural course of patients.

Recent advances in understanding and managing cholesterol gallstones.

The high prevalence of cholesterol gallstones, the availability of new information about pathogenesis, and the relevant health costs due to the management of cholelithiasis in both children and adults contribute to a growing interest in this disease. From an epidemiologic point of view, the risk of gallstones has been associated with higher risk of incident ischemic heart disease, total mortality, and disease-specific mortality (including cancer) independently from the presence of traditional risk factors such as body weight, lifestyle, diabetes, and dyslipidemia. This evidence points to the existence of complex pathogenic pathways linking the occurrence of gallstones to altered systemic homeostasis involving multiple organs and dynamics. In fact, the formation of gallstones is secondary to local factors strictly dependent on the gallbladder (that is, impaired smooth muscle function, wall inflammation, and intraluminal mucin accumulation) and bile (that is, supersaturation in cholesterol and precipitation of solid crystals) but also to "extra-gallbladder" features such as gene polymorphism, epigenetic factors, expression and activity of nuclear receptors, hormonal factors (in particular, insulin resistance), multi-level alterations in cholesterol metabolism, altered intestinal motility, and variations in gut microbiota. Of note, the majority of these factors are potentially manageable. Thus, cholelithiasis appears as the expression of systemic unbalances that, besides the classic therapeutic approaches to patients with clinical evidence of symptomatic disease or complications (surgery and, in a small subgroup of subjects, oral litholysis with bile acids), could be managed with tools oriented to primary prevention (changes in diet and lifestyle and pharmacologic prevention in subgroups at high risk), and there could be relevant implications in reducing both prevalence and health costs.

Prophylactic cholecystectomy in short bowel syndrome: Is it being utilized?

INTRODUCTION: Cholelithiasis is common in patients with short bowel syndrome (SBS). Prophylactic cholecystectomy (PC) of the non-diseased gallbladder has been recommended in SBS patients when laparotomy is being undertaken for other reasons. Our aim was to determine if PC is being utilized. METHODS: 500 adults with SBS were seen over a 25 year period. 215 undergoing cholecystectomy prior to SBS were excluded, leaving 285 patients for evaluation. RESULTS: 151 (53%) SBS patients underwent a subsequent laparotomy. 77 underwent cholecystectomy for cholelithiasis at the 1st opportunity. 27 patients underwent a PC at the 1st opportunity. 47 patients did not undergo PC at the 1st opportunity. 17 (36%) of these 47 patients subsequently developed cholelithiasis with 7 undergoing cholecystectomy. Age, gender, diagnosis and initial BMI and need for longterm parenteral nutrition were similar in patients who had PC or did not. PC patients were more likely to have intestinal remnant length <60 cm (59% vs 21%, p < .05). CONCLUSIONS: Overall 10% of SBS patients underwent PC. However, only 36% of eligible patients undergoing laparotomy had a PC.

Exercising the hepatobiliary-gut axis. The impact of physical activity performance.

BACKGROUND: Physical inactivity puts the populations at risk of several health problems, while regular physical activity brings beneficial effects on cardiovascular disease, mortality and other health outcomes, including obesity, glycaemic control and insulin resistance. The hepatobiliary tract is greatly involved in several metabolic aspects which include digestion and absorption of nutrients in concert with intestinal motility, bile acid secretion and flow across the enterohepatic circulation and intestinal microbiota. Several metabolic abnormalities, including nonalcoholic fatty liver as well as cholesterol cholelithiasis, represent two conditions explained by changes of the aforementioned pathways. MATERIALS AND METHODS: This review defines different training modalities and discusses the effects of physical activity in two metabolic disorders, that is nonalcoholic fatty liver disease (NAFLD) and cholelithiasis. Emphasis is given to pathogenic mechanisms involving intestinal bile acids, microbiota and inflammatory status. RESULTS: A full definition of physical activity includes the knowledge of aerobic and endurance exercise, metabolic equivalent tasks, duration, frequency and intensity, beneficial and harmful effects. Physical activity influences the hepatobiliary-gut axis at different levels and brings benefits to fat distribution, liver fat and gallbladder disease while interacting with bile acids as signalling molecules, intestinal microbiota and inflammatory changes in the body. CONCLUSIONS: Several beneficial effects of physical activity are anticipated on metabolic disorders linking liver steatosis, gallstone disease, gut motility, enterohepatic circulation of signalling bile acids in relation to intestinal microbiota and inflammatory changes.

Cost analysis and risk factors for interval cholecystectomy after bariatric surgery: a national study.

BACKGROUND: Besides rate and extent of weight loss, little is known regarding demographic factors predicting interval cholecystectomy (IC) after bariatric surgery and its incremental costs. OBJECTIVES: We aim to identify risk factors predicting IC after bariatric surgery and quantify its associated costs. SETTING: Nationally representative sampling of acute care hospitals across the United States. METHODS: A retrospective cohort study was performed using the National Readmission Database 2010 to 2014. Cox proportional hazard analyses were used to identify risk factors for IC. Linear regression models were constructed to examine associations between cholecystectomy timing and cumulative hospitalization costs. RESULTS: An estimated national total of 553,658 patients received bariatric surgery during the study period. Of these, 3.3% received concomitant cholecystectomy (CC). After adjusting for bariatric procedure type, age, sex, complication, and length of stay, CC was independently associated with a US$1589 increase in hospitalization cost (95% confidence interval US$1021-2158, P<.01). Of patients that received no CC, only .6% underwent IC during the up to 1-year follow-up. Age<35 (P<.01), female sex (P<.01), and high preoperative body mass index (P = .03) were all risk factors for IC. IC was independently associated with a US$1499 higher cumulative hospitalization cost than CC (P<.01, 95% confidence interval US$844-2154). CONCLUSIONS: Despite the higher absolute cost of IC, its low incidence does not financially justify a routine prophylactic CC approach. In addition, no significant reduction in cholecystectomy-related complications was achieved by performing CC. An individualized approach taking identified risk factors for IC into consideration is recommended when deciding whether to perform prophylactic CC.

Practice Patterns for Cholecystectomy After Endoscopic Retrograde Cholangiopancreatography for Patients With Choledocholithiasis.

BACKGROUND & AIMS: Cholecystectomy (CCY) after an episode of choledocholithiasis requiring endoscopic retrograde cholangiopancreatography (ERCP) with stone extraction reduces recurrent biliary events compared to expectant management. We studied practice patterns for performance of CCY after ERCP for choledocholithiasis using data from 3 large states and evaluated the effects of delaying CCY. METHODS: We conducted a retrospective cohort study using the ambulatory surgery, inpatient, and emergency department databases from the states of California (years 2009-2011), New York (2011-2013), and Florida (2012-2014). We collected data from 4516 patients hospitalized with choledocholithiasis who underwent ERCP. We compared outcomes of patients who underwent CCY at index admission (early CCY), elective CCY within 60 days of discharge (delayed CCY), or did not undergo CCY (no CCY), calculating rate of recurrent biliary events (defined as an emergency department visit or unplanned hospitalization due to symptomatic cholelithiasis, cholecystitis, choledocholithiasis, cholangitis, or biliary pancreatitis), mortality, and cost by CCY cohort. We also evaluated risk factors for not undergoing CCY. The primary outcome measure was the rate of recurrent biliary events in the 365 days after discharge from index admission. RESULTS: Of the patients who underwent ERCP for choledocholithiasis, 41.2% underwent early CCY, 10.9% underwent delayed CCY, and 48.0% underwent no CCY. Early CCY reduced relative risk of recurrent biliary events within 60 days by 92%, compared with delayed or no CCY (P < .001). After 60 days following discharge from index admission, patients with early CCY had an 87% lower risk of recurrent biliary events than patients with no CCY (P < .001) and patients with delayed CCY had an 88% lower risk of recurrent biliary events than patients with no CCY (P < .001). A strategy of delayed CCY performed on an outpatient basis was least costly. Performance of early CCY was inversely associated with low facility volume. Hispanic race, Asian race, Medicaid insurance, and no insurance associated inversely with performance of delayed CCY. CONCLUSIONS: In a retrospective analysis of >4500 patients hospitalized with choledocholithiasis, we found that CCY was not performed after ERCP for almost half of the cases. Although early and delayed CCY equally reduce the risk of subsequent recurrent biliary events, patients are at 10-fold higher risk of recurrent biliary event while waiting for a delayed CCY compared with patients who underwent early CCY. Delayed CCY is a cost-effective strategy that must be balanced against the risk of loss to follow-up, particularly among patients who are ethnic minorities or have little or no health insurance.

Laparoscopic cholecystectomy for cholelithiasis in children with sickle cell disease.

Patients with sickle cell disease (SCD) suffer from an increased incidence of gallstone formation due to hemolysis of sickled red blood cells; this leads to an increased level of bilirubin in secreted bile that becomes a nidus for pigment stone formation. Laparoscopic cholecystectomy (LC) is considered a standard operative procedure for gallstone disease mainly due to lower postoperative wound complaints, faster recovery, better postoperative cosmetic results, shorter hospital stay, and earlier return to work. Although numerous studies have been published addressing both the advantages and complications of LC in acute calcular cholecystitis, there is still limited evidence concerning the safety and efficacy of LC for the management of cholelithiasis in pediatric patients with SCD, and controversies remain unresolved. In this review, we aim to comprehensively study the available literature and propose evidence-based practice recommendations for the optimal management of gallstones in pediatric SCD patients. The current practice differs greatly depending on the prevalence of SCD in a particular geographic area. We acknowledge the limited number of patients reported, the lack of randomized control trials addressing the practice of specific recommendations, and the need for further evidence-based studies.

Effect of Inhibition of Intestinal Cholesterol Absorption on the Prevention of Cholesterol Gallstone Formation.

BACKGROUND: Cholesterol cholelithiasis is a multifactorial hepatobiliary disease. METHODS: Interactions between genetic and environmental factors play a critical role in biliary cholesterol homeostasis and its imbalance enhances cholelithogenesis. RESULTS: In patients developing symptoms or complications of gallstone disease, laparoscopic cholecystectomy is recommended for treatment of gallstones. In a subgroup of patients with small, radiolucent pure cholesterol gallstones, the hydrophilic bile acid, ursodeoxycholic acid (UDCA) is still considered the only pharmacological therapy able to induce oral litholysis. Identifying novel and effective pharmacological therapies is being investigated. CONCLUSIONS: We propose that the specific intestinal Niemann-Pick C1-like 1 protein inhibitor ezetimibe is a potential agent for preventing gallstone formation by reducing bioavailability of intestine- derived cholesterol to the liver for biliary secretion and desaturating bile through the inhibition of intestinal absorption of cholesterol.

Evaluation of incidence of cholelithiasis after bariatric surgery in subjects treated or not treated with ursodeoxycholic acid.

BACKGROUND: The use of ursodeoxycholic acid (UDCA) to prevent gallstone formation after gastric bypass (RYGB) is still debated. Furthermore, only 1 study has assessed the effectiveness of UDCA after sleeve gastrectomy (SG) with mitigated results. OBJECTIVES: To compare the incidence of cholelithiasis (CL) between patients treated or not treated with UDCA after RYGB and SG. SETTING: University hospital, France. METHODS: Since January 2008, a postoperative ultrasound monitoring was scheduled for all patients without previous cholecystectomy who underwent bariatric surgery in our institution. Patients who underwent at least 1 ultrasound in the first postoperative year (±6 months) were included. We started to systematically prescribe UDCA (500 mg/d) for 6 months postoperatively, in February 2012 for RYGB (once or twice daily) and in October 2013 for SG (once daily). RESULTS: Mean follow-up was 13.0±3.4 months. The incidence of CL was 32.5% in the 117 nontreated RYGB and 25.5% in the 51 nontreated SG. It was reduced to 2.4% in the 42 SG treated once daily (P = .005), to 5.7% in the 87 RYGB with 250 mg twice daily (P<.001), but only to 18.6% in the 102 RYGB with 500 mg once daily (P = .03). CONCLUSION: UDCA 500 mg once daily for 6 months is efficient to prevent CL 1 year after SG, but the twice-daily doses seem to be more effective after RYGB. The effectiveness of UDCA once daily after SG and the superiority of the twice-daily doses after RYGB should be confirmed with more patients and longer follow-up.