Gallstone Formation after Rapid Weight Loss: A Prospective Study in Patients Undergoing Gastric Bypass Surgery for Treatment of Morbid Obesity

The present study evaluated the incidence of gallstone formation in 105 morbidly obese patients undergoing rapid weight loss after proximal gastric bypass surgery. Intraoperative ultrasonography demonstrated gallstones in 20 (19%) and gallbladder sludge in four (4%) patients. Eighty-one patients had a normal gallbladder ultrasound. After bariatric surgery, these patients were followed prospectively with periodic gallbladder ultrasound examinations. At 6 months, gallstones had developed in 36% and gallbladder sludge in 13% of patients. These percentages remained relatively constant at 12 and 18 months. Body weight declined rapidly after surgery from a mean of 132.3 kg to 95.5, 87.0, and 84.0 kg at 6, 12, and 18 months, respectively. Gallstones developed significantly more often in the white race, and in women. No significant differences in age, body weight, percent ideal body weight, percent weight loss, or percent of excess body weight lost existed between patients who developed gallstones or sludge and those who did not. Patients who developed gallbladder sludge had less cholesterol and lower cholesterol saturation (1.25 +/- 0.42) in their gallbladder bile than persons who developed gallstones (2.00 +/- 0.79). Forty percent (13/32) of patients who developed gallstones became symptomatic; nine (28%) underwent elective cholecystectomy. An attempt to prevent gallstone formation during rapid weight loss appears warranted.     

Obesity and the risk and prognosis of gallstone disease and pancreatitis

Obesity is a risk factor for the formation of cholesterol gallstones and exposes patients to increased risk of gallstone-related complications and cholecystectomy. Rapid weight loss achieved by very low calorie diets or bariatric surgery is also a risk factor for cholelithiasis in obese patients, and therapy should take into account the higher prevalence of gallstones, the possibility of more frequent complications and the need for prophylactic treatment with oral ursodeoxycholic acid during weight loss. Obesity is also frequent in children and adolescents, and the burden of cholesterol cholelithiasis is increasing in this population. The chance to develop acute pancreatitis and the severity of the disease are higher in obese subjects because of specific pathogenic factors, including supersaturated bile and crystal formation, rapid weight loss, and visceral obesity. All health policies aimed at reducing the incidence of obesity worldwide will decrease the incidence of gallstones and gallstone-related complications. The pathophysiological scenarios and the therapeutic implications for obesity, gallstone disease, and pancreatitis are discussed.     

Biliary sludge: When should it not be ignored

Opinion statement Biliary sludge is usually seen on transabdominal sonography as low-level echoes that layer in the dependent portion of the gallbladder without acoustic shadowing. Synonyms for biliary sludge include microlithiasis, biliary sand or sediment, pseudolithiasis, and microcrystalline disease. In most patients, biliary sludge is composed of calcium bilirubinate and cholesterol monohydrate crystals. A variety of predisposing factors are associated with biliary sludge formation. In most of these patients, removal of the risk factor can lead to resolution of sludge. In asymptomatic patients, biliary sludge can be managed expectantly. In patients who develop biliary-type pain, cholecystitis, cholangitis, or pancreatitis, the treatment of choice is cholecystectomy for those who can tolerate surgery. In patients who are not operative candidates, endoscopic sphincterotomy can prevent further episodes of cholangitis and pancreatitis, whereas medical therapy with ursodeoxycholic acid can prevent sludge formation and recurrent acute pancreatitis.     

Gallbladder sludge: What is its clinical significance?

Biliary sludge is a mixture of particulate solids that have precipitated from bile. Such sediment consists of cholesterol crystals, calcium bilirubinate pigment, and other calcium salts. Sludge is usually detected on transabdominal ultrasonography. Microscopy of aspirated bile and endoscopic ultrasonography are far more sensitive. Biliary sludge is associated with pregnancy; with rapid weight loss, particularly in the obese; with critical illness involving low or absent oral intake and the use of total parenteral nutrition (TPN); and following gastric surgery. It is also associated with biliary stones with common bile duct obstruction; with certain drugs, such as ceftriaxone and octreotide; and with bone marrow or solid organ transplantation. The clinical course of biliary sludge varies. It often vanishes, particularly if the causative event disappears; other cases wax and wane, and some go on to gallstones. Complications caused by biliary sludge include biliary colic, acute cholangitis, and acute pancreatitis. Asymptomatic patients with sludge or microlithiasis require no therapy. When patients are symptomatic or if complications arise, cholecystectomy is indicated. For the elderly or those at risk from the surgery, endoscopic sphincterotomy can prevent recurrent episodes of pancreatitis. Medical therapy is limited, although some approaches may show promise in the future.     

Management of gallstones and gallbladder disease in patients undergoing gastric bypass

The appropriate management of gallstones and gallbladder disease in patients undergoing gastric bypass remains unknown.Several therapeutic modalities are used and include performing cholecystectomy on all patients at the time of gastric bypass,performing concomitant cholecystectomy only when patients have gallstones and performing cholecystectomy only in the presence of both symptoms and gallstones.Some groups administer ursodeoxycholic acid for gallstone prevention in the postoperative period.All treatment...     

Gallstone disease: Primary and secondary prevention

Several risk factors for cholesterol gallstone formation in the general population have been identified. There is a strongly increased risk of gallstone disease during prolonged fasting, rapid weight loss, total parenteral nutrition, and somatostatin(-analogue) treatment. The annual risk of biliary colic and gallstone complications in asymptomatic gallstone carriers has been investigated sparsely. In asymptomatic and symptomatic gallstone carriers, treatment with the hydrophilic bile salt ursodeoxycholic acid (UDCA) has been claimed to reduce the risk of biliary colic and gallstone complications such as acute cholecystitis and acute pancreatitis. Also, prophylactic cholecystectomy could be beneficial in certain subgroups of asymptomatic gallstone carriers. However, randomized, double-blind, placebo-controlled trials are lacking. In this review, strategies for the prevention of gallstone formation in the general population and in high-risk conditions are dealt with. Also, strategies for the prevention of biliary colic and gallstone complications in asymptomatic and symptomatic gallstone carriers are discussed.     

Cholesterol cholelithiasis in pregnant women: pathogenesis,prevention and treatment

Epidemiological and clinical studies have found that gallstone prevalence is twice as high in women as in men at all ages in every population studied. Hormonal changes occurring during pregnancy put women at higher risk. The incidence rates of biliary sludge (a precursor to gallstones) and gallstones are up to 30 and 12%, respectively, during pregnancy and postpartum, and 1-3% of pregnant women undergo cholecystectomy due to clinical symptoms or complications within the first year postpartum. Increased estrogen levels during pregnancy induce significant metabolic changes in the hepatobiliary system, including the formation of cholesterol-supersaturated bile and sluggish gallbladder motility, two factors enhancing cholelithogenesis. The therapeutic approaches are conservative during pregnancy because of the controversial frequency of biliary disorders. In the majority of pregnant women, biliary sludge and gallstones tend to dissolve spontaneously after parturition. In some situations, however, the conditions persist and require costly therapeutic interventions. When necessary, invasive procedures such as laparoscopic cholecystectomy are relatively well tolerated, preferably during the second trimester of pregnancy or postpartum. Although laparoscopic operation is recommended for its safety, the use of drugs such as ursodeoxycholic acid (UDCA) and the novel lipid-lowering compound, ezetimibe would also be considered. In this paper, we systematically review the incidence and natural history of pregnancy-related biliary sludge and gallstone formation and carefully discuss the molecular mechanisms underlying the lithogenic effect of estrogen on gallstone formation during pregnancy. We also summarize recent progress in the necessary strategies recommended for the prevention and the treatment of gallstones in pregnant women.     

Gallstone disease: Current therapeutic practice

Opinion statement Most asymptomatic gallstone carriers require no therapy. Laparoscopic cholecystectomy is the best definitive therapy for symptomatic gallstone disease. Selective laparoscopic cholecystectomy can provide secondary prevention of symptoms and complications in certain instances (in a complex clinical setting such as sickle cell disease or to prevent gallbladder carcinoma from developing in those at risk with large [> 3 cm] gallstones or with a calcified gallbladder). Primary prevention is unproven but focuses on early identification and risk alteration to decrease the possibility of developing gallstones. Ursodeoxycholic acid has a limited role for stone dissolution but can prevent stone development in severe obesity during rapid weight reduction with diet or after bariatric surgery. Endoscopic retrograde cholangiopancreatography with endoscopic sphincterotomy represents the therapeutic cornerstone for managing severe pancreatitis and cholangitis.     

Gallstone disease: Microlithiasis and sludge

'Sludge' is the solid material which results from the slow settling of particles dispersed in a liquid medium. Biliary sludge in the gallbladder can be detected by transabdominal ultrasonography, and the typical echoes derive mainly from pigment precipitates mixed with cholesterol crystals. A portion of biliary sludge contains comparatively large particles (1-3 mm) called microliths, the formation of which is an obligatory intermediate step in the development of all types of gallstone. Microlithiasis and sludge in bile may cause colicky pain, cholecystitis, cholangitis, and acute pancreatitis, and are thus of clinical relevance. In these patients treatment follows the guidelines of symptomatic gallstone disease, and strategies include long-term application of ursodeoxycholic acid, endoscopic papillotomy, or preferably laparoscopic cholecystectomy.     

New strategies for the treatment of gallstone disease

BACKGROUND: Symptomatic gallstones are generally accepted as being the indication for cholecystectomy. Generally, severe abdominal pain in epigastrium and in the right upper abdominal quadrant, and lasting for more than 15 min, is thought to be caused by gallstones. However, many patients with other abdominal complaints undergo cholecystectomy and are satisfied with the outcome of surgery. Possible ways to improve the results of cholecystectomy are discussed. METHODS: Review of previous work by the authors. RESULTS: The introduction of laparoscopic cholecystectomy has even led to an increase in cholecystectomies; in a higher complication rate; and in increased costs of the treatment of gallstone disease. Because of faster recovery, 70% of symptomatic gallstone patients are able and willing to undergo laparoscopic cholecystectomy in day care. Cholecystectomy after sphincterotomy and stone extraction in patients who have stones in the gallbladder was demonstrated to prevent gallstone-related symptoms in at least 40% of patients. If the gallbladder had to be removed later for symptomatic disease, however, this did not result in a higher rate of conversions and complications. Because of shortage in operation capacity in The Netherlands, there is a considerable delay between the diagnosis of symptomatic stones and cholecystectomy. Better selection of patients for cholecystectomy will not only improve the results of cholecystectomy, it will also reduce the number of cholecystectomies and patients on waiting lists. Delay of cholecystectomy is associated with more complications, longer operative times, higher conversion rates to open cholecystectomy and prolonged hospitalization. The efficacy of the bile salt ursodeoxycholic acid in preventing gallstone-related pain attacks and complications in patients with contraindications for operation or waiting to undergo cholecystectomy should be investigated further, since two retrospective studies have demonstrated favourable outcomes for this strategy. CONCLUSION: The results of cholecystectomy are likely to be improved by better selection of patients, prevention of delay of the procedure and possibly treatment with ursodeoxycholic acid.     

Changes in gallbladder bile composition following gallstone formation and weight reduction.

Changes in gallbladder bile composition that occurred in patients who developed gallstones during weight reduction were evaluated. Bile was sampled directly from the gallbladder in 11 morbidly obese patients with no gallstones at the time of gastric bypass surgery and after gallstones had formed at cholecystectomy. Bile salt concentration ([BS]) increased significantly from a mean of 82.7-157.7 mmol/L (P less than 0.05). The concentration of cholesterol in gallbladder bile increased slightly and cholesterol saturation declined slightly with weight reduction and gallstone formation. Gallbladder mucin concentration increased 18-fold from a mean of 62 to 1110 micrograms/mL (P less than 0.001). Both free [Ca2+] and total calcium [Ca] increased 40% from mean values of 1.12 and 5.05 mmol/L at gastric bypass to 1.86 and 8.60 mmol/L after gallstone formation (P less than 0.05). The increase in [Ca2+] observed after gallstone formation was much greater than anticipated from changes in [BS] alone. This excess [Ca2+] in gallbladder bile increased curvilinearly with increasing mucin concentration. These results show that both gallbladder mucin and [Ca2+] increase with gallstone formation in humans and that mucin may modulate [Ca2+] in gallbladder bile.     

Acute cholecystitis and pancreatitis in a patient with biliary sludge associated with the use of ceftriaxone: a rare but potentially severe complication

Ceftriaxone may precipitate in the bile leading to the formation of biliary sludge. Biliary complications, even serious ones, have rarely been described in patients treated with this antibiotic. A 71-year-old woman presented to the emergency room with biliary sludge complicated by acute cholecystitis and pancreatitis after 10 days of treatment with ceftriaxone (2 g, 40 mg/kg per day). There had been no evidence of sludge or gallstones on a transabdominal ultrasonography performed 6 months earlier. The patient underwent open cholecystectomy and recovered fully. Ceftriaxone should be kept in mind as a potential cause of biliary sludge. In most cases, resolution of sludge occurs after interruption of ceftriaxone. Young subjects, patients receiving a prolonged course and a daily dose > or = 40 mg/kg, and subjects with impaired gallbladder emptying have a greater risk of ceftriaxone-associated sludge. Cholecystectomy is the definitive therapy for severe complications.     

Lovastatin alters biliary lipid composition and dissolves gallstones: a long-term study in prairie dogs

Lovastatin, an inhibitor of the rate-limiting enzyme in cholesterol biosynthesis, is widely used to treat hypercholesterolemia. We investigated the long-term effects of lovastatin alone and in combination with ursodeoxycholic acid on biliary lipid composition and gallstone dissolution. Forty-two prairie dogs were fed 1.2% cholesterol diet for 5 weeks, and cholecystectomy was performed on 6 animals to confirm gallstones. The remaining animals were maintained on a 0.4% cholesterol diet and were randomized to receive placebo, lovastatin (3.3 mg/g diet), ursodeoxycholic acid (10 mg/g), or combination of both drugs. After 10 weeks, animals underwent cholecystectomy. Dissolution response to therapy was determined, and serum and biliary lipids were measured. All treatment groups had significant reductions in serum cholesterol. Lovastatin treatment reduced both hepatic and gallbladder bile cholesterol, altered bile acid composition, and induced a 79% total response compared to placebo. Although ursodeoxycholic treatment induced a 44% response, long-term combination treatment elevated both gallbladder bile cholesterol and calcium and failed to produce an augmented response. These data suggest that lovastatin therapy alone may promote gallstone dissolution in humans.     

Small gallstones are associated with increased risk of acute pancreatitis: potential benefits of prophylactic cholecystectomy?

OBJECTIVES: Pancreatitis is a severe complication of gallstone disease with considerable mortality. Small gallstones may increase the risk of pancreatitis. Our aims were to evaluate potential association of small stones with pancreatitis and potential beneficial effects of prophylactic cholecystectomy. METHODS: Stone characteristics were determined in patients with biliary pancreatitis (115), obstructive jaundice due to gallstones (103), acute cholecystitis (79), or uncomplicated gallstone disease (231). Sizes and numbers of gallbladder and bile duct stones were determined by ultrasonography and endoscopic retrograde cholangiopancreatography, respectively. Effects of prophylactic cholecystectomy were assessed by decision analyses with a Markov model and Monte Carlo simulations. RESULTS: Patients with pancreatitis or obstructive jaundice had more and smaller gallbladder stones than those with acute cholecystitis or uncomplicated disease (diameters of smallest stones: 3 +/- 1, 4 +/- 1, 8 +/- 1, and 9 +/- 1 mm, respectively, p < 0.01). Bile duct stones were smaller in case of pancreatitis than in obstructive jaundice (diameters of smallest stones: 4 +/- 1 vs 8 +/- 1, p < 0.01). Multivariate analysis identified old age and small stones as independent risk factors for pancreatitis. Decision analysis in a representative group of patients with small (相似文献   

Gallstones,gallbladder disease,and pancreatitis: cross-sectional and 2-year data from the Swedish Obese Subjects (SOS) and SOS reference studies

OBJECTIVES: Obesity and weight loss have been associated with gallstone disease. There is also an association between gallstones and pancreatitis. We investigated cross-sectional relationships between body mass index (BMI), body fat distribution, and prevalence of gallstones, gallbladder disease, and pancreatitis in men and women. Furthermore, 2-yr incidences of these disorders were examined in relation to changes in weight and body fat distribution after surgical and conventional obesity treatment. METHODS: Self-administered questionnaires were used to assess biliary and pancreatic disease. In the cross-sectional investigation, 6328 obese patients and 1135 randomly selected reference individuals were used. Longitudinally, 1422 operated and 1260 conventionally treated patients were examined. RESULTS: Obese subjects had significantly higher prevalence of cholelithiasis, cholecystitis, cholecystectomies, and pancreatitis as compared with the reference population. In women, BMI and waist-hip ratio (WHR) were independently related to an increased biliary disease prevalence. In men, only BMI was independently associated with biliary disease. Compared with conventional treatment, obesity surgery significantly increased the incidence of cholelithiasis, cholecystitis, and cholecystectomies in men. There was no incidence difference among women. In both genders, weight loss, but not change in WHR, was related to an increased incidence of biliary disease. CONCLUSIONS: This study showed an increased prevalence of gallstones, gallbladder disease, and pancreatitis in the obese. Biliary disease was related to BMI and WHR in women, but only to BMI in men. Weight loss, but not change in WHR, increased the risk of biliary disease in both genders.     

Gallstone formation during weight-reduction dieting

We investigated the development of gallstones over an 8-week period from the onset of dieting in 51 obese men and women and 26 nondieting control subjects. Gallbladder examinations were performed by abdominal real-time ultrasonography for the detection of gallstones. Initial sonography was performed prior to dieting and only those subjects in whom initial sonograms showed no gallstones or sludge were included in the study. Repeated sonography was performed at 4-week intervals for 8 weeks while they remained on a 2100-kJ/d diet. Initial weight of subjects prior to dieting averaged 105.9 +/- 3.8 kg (162% of ideal body weight) and decreased to 89.4 +/- 3.2 kg (137.3% of ideal body weight) after 8 weeks of dieting. Sonography performed after 4 weeks of dieting revealed new-onset gallbladder sludge in 1 subject and gallstones in 4 subjects. After 8 weeks of dieting sludge was detected in 3 subjects and gallstones in 13 (25.5%). In contrast, none of the nondieting subjects developed any detectable gallbladder abnormalities. During the dieting period, 1 of 51 subjects developed symptoms of biliary colic, necessitating cholecystectomy. On cessation of dieting with reinstitution of normal feeding, 2 additional subjects with stones developed symptoms severe enough to require cholecystectomy. In all 3 cases, cholesterol gallstones were recovered at the time of surgery. Eleven of the 13 patients with gallstones were followed up for 6 months after discontinuation of the diet. Besides the 3 undergoing cholecystectomy, 4 subjects had gallstones on follow-up ultrasound examination, while sonographically detectable gallstones had disappeared in 4 subjects. We conclude that this form of weight-reduction dieting predisposes to the development of gallstones and that gallstone formation is a risk of this type of prolonged calorie restriction. Dissolution or evacuation of gallstones may occur with resumption of a normal diet.     

Management of gallstone pancreatitis: cholecystectomy or ERCP and endoscopic sphincterotomy

BACKGROUND: Currently, cholecystectomy is recommended for patients with gallstone-induced pancreatitis. ERCP with endoscopic sphincterotomy (ES) within 24 to 48 hours is also suggested for the treatment of acute gallstone pancreatitis. The aim of this study was to determine outcome after cholecystectomy versus ES alone in patients with gallstone pancreatitis. METHODS: One hundred seventeen patients with gallstone pancreatitis were included in this prospective observational study. Inclusion criteria were typical abdominal pain; serum amylase level 3 times or greater than normal; and gallbladder stones and a dilated bile duct, with or without stones, by US, CT, or ERCP. RESULTS: Eighty-three patients (Group A) underwent cholecystectomy after initial evaluation including ERCP in 43 (53%) and ERCP with ES in 38 (47%). The remaining 34 (Group B) underwent successful ERCP with ES alone. Mean follow-up was 33 months for Group A and 34 months for Group B. Recurrent gallstone pancreatitis was noted in 2 patients (2.4%) in Group A (bile duct stone in 2, sludge and papillary stenosis in 1), and in 1 patient (2.9%) in Group B. Ten patients in Group B had follow-up US of the gallbladder that showed disappearance of stones in 3. During follow-up, there was no significant difference in the rates of biliary complications (Group A, 3.6% vs. Group B, 11.6%; p = 0.19) or serious complications (pancreatitis, cholecystitis, cholangitis) (Group A, 3.6% vs. Group B, 5.8%). Also, there was no significant difference in procedure-related complications. CONCLUSIONS: Recurrence of pancreatitis after ERCP with ES alone for gallstone pancreatitis is rare. In patients who have undergone ES alone, cholecystectomy should be considered only if there are overt manifestations of gallbladder disease (e.g., biliary pain, cholecystitis, cystic duct obstruction) and not for prevention of recurrent gallstone pancreatitis. Because treatment by ES alone may be associated with a higher risk of biliary complications during follow-up compared with cholecystectomy, these patients may require close surveillance.     

Hereditary liver disease: gallstones

Gallstones are common in Western countries and due to pain and complications pose a substantial burden on health care systems. In general, cholesterol gallstones are distinguished from bilirubin gallstones. Bilirubin gallstones form if the ion product of unconjugated bilirubin and calcium in gallbladder bile exceeds the solubilisation capacities of mixed micelles and vesicles. Cholesterol gallstones develop if the amount of cholesterol in gallbladder bile exceeds the maximum concentration that is soluble at the given concentration of bile salts and phospholipids. In addition, cholesterol gallstone formation requires hypomotility of the gallbladder and a mucin gel as nucleation matrix for monohydrate crystals. The individual risk of gallstone formation is determined by interactions of lithogenic alleles of gallstone susceptibility genes and multiple environmental factors. For asymptomatic gallstones, expectant management is recommended, whereas an episode of gallstone-associated pain substantially increases the risk of complications such as cholecystitis, cholangitis and pancreatitis and therefore necessitates cholecystectomy.     

Usefulness of Gallbladder Ejection Fraction Estimation to Predict the Recurrence of Biliary Pain in Patients with Symptomatic Gallstones Who Did Not Undergo Cholecystectomy

This study was performed to evaluate any predictable factors associated with recurrence of biliary pain in symptomatic gallstone patients who did not undergo cholecystectomy because of operative risk, advanced age, and/or their refusal. The relationships among age, gender, body mass index, frequency of biliary pain before diagnosis, period between the last symptom attack and the hospital visit, size and number of gallstones, gallbladder ejection fraction (GBEF), compliance of ursodeoxycholic acid therapy, and recurrence of biliary pain were examined. The recurrence of biliary pain developed in 15 of 31 patients during the median 29-month follow-up. The cumulative 1-, 2-, and 3-year recurrence rates of biliary pain were 22.8, 40.9, and 53.0% and significantly associated with abnormal GBEF (hazard ratio, 3.12; 95% CI, 1.10-8.87; P = 0.032). In symptomatic gallstone patients with abnormal GBEF, cholecystectomy is strongly advisable because of the high risk of repeated pain attacks.     

Management of patients with symptomatic gallstones: a quantitative analysis

Should persons with symptomatic gallstones (i.e., those that have caused biliary pain) be treated immediately? Or may they be managed expectantly until pain recurs or a biliary complication (i.e., acute cholecystitis or pancreatitis) occurs? To assess the mortality risk of different strategies, we performed a quantitative analysis. For the expectant management strategy that requires surgery only if a biliary complication occurs, the cumulative lifetime probability of gallstone disease death in a 30-year-old man is about 2%, and most deaths occur after age 65. In comparison, elective cholecystectomy has only a 0.1% rate of gallstone disease death, but all deaths occur at age 30. The average amount of life expectancy gained by immediate cholecystectomy compared with expectant management is 52 days, which is reduced to 23 days using 5% discounting. This gain could be increased only slightly by a 100% effective and risk-free therapy such as perfected lithotripsy or medical dissolution. Results are similar for women. The results suggest that, for persons with symptomatic gallstones, the life expectancy gain of immediate cholecystectomy is relatively small and that the potential incremental gain of nonsurgical therapy is also small. For patients and physicians who believe that life expectancy is of primary consideration, the decision about therapy may be made primarily on non-mortality considerations. Some patients and physicians may decide that the risk of symptomatic gallstones is low enough that a policy of expectant management may be acceptable.