Arachidonic acid metabolites in hepatobiliary physiology and disease

Arachidonic acid metabolites are involved in a wide spectrum of hepatobiliary physiologic functions and disease. Prostanoids alter hepatic bile flow. Prostaglandins with a C9 ketooxygen stimulate a bicarbonate-rich choleresis and those with a C9 hydroxyloxygen produce a chloride-rich choleresis. Prostaglandin F2 alpha stimulates the release of the potent choleretic glucagon and the stimulatory effect of prostaglandin F2 alpha on bile flow is inhibited by cyclooxygenase inhibitors, suggesting that prostaglandins play a role in the release of choleretic hormones as well as in their action. Prostanoids are involved in gallbladder contraction and water absorption. Prostaglandins produce gallbladder contraction in various species and cause gallbladder relaxation in other species. Prostaglandins also may be mediators of cholecystokinetic hormone action; however, cyclooxygenase inhibitors do not inhibit the effect of cholecystokinetic hormones in all species. Prostanoids alter the normal process of water absorption by gallbladder mucosa and induce net water secretion. The inflamed gallbladder secretes rather than absorbs fluid. The demonstration that prostaglandin E2 inhibits gallbladder fluid absorption has led to subsequent studies that demonstrated that the secretion of fluid into the inflamed gallbladder lumen may be mediated by prostanoids. In cholecystitis, the prostanoids may mediate the distention produced by mucosal fluid secretion and the contraction of the diseased gallbladder. The inflammatory changes produced in various experimental models of cholecystitis can be prevented by cyclooxygenase inhibitors. Cyclooxygenase inhibitors decrease gallbladder prostaglandin formation and are effective in producing relief of the symptoms of gallbladder disease. In experimental cholesterol gallstone formation, prostaglandins are involved in the production of mucin, which acts as a nidus for stone formation, and cyclooxygenase inhibitors prevent the formation of experimental cholesterol gallstones. Prostaglandins have been shown to be cytoprotective in various types of experimental hepatic injury and leukotrienes have been shown to be injurious to hepatocytes and biliary tract tissues. Specific prostanoids and lipoxygenase inhibitors may be valuable in treating patients with various acute hepatic inflammatory disease processes. Continued evaluation of the role of arachidonic acid metabolites in hepatobiliary physiology and disease may lead to important new therapeutic modalities.     

Effect of oral ibuprofen on formation of prostaglandins E and F by human gallbladder muscle and mucosa

In a randomized double-blind trial, the effect of ibuprofen on the pain produced by gallbladder disease and on gallbladder mucosa and muscle wall tissue PGE and PGF production was evaluated to determine if the pain of cholecystitis and prostaglandin formation were altered by administration of a prostaglandin synthetase inhibitor. To ascertain potential differences in extracellular and intracellular prostaglandin production rates, gallbladder mucosal cells and muscle tissues were maintained in tissue culture medium and then subsequently homogenized. PGE and PGF concentrations were measured in culture medium and homogenates utilizing radioimmunoassay. Gallbladder mucosa and muscle tissue produced nanogram per milligram protein amounts of PGE and PGF. As the histological estimation of the degree of inflammation increased, so also did the production of PGE. Increased inflammation was associated with unchanged PGF levels, resulting in an increased ratio of PGE/PGF with increasing inflammation. Oral ibuprofen administration was effective in decreasing PGE production by gallbladder mucosa and muscle and eliminating the significant correlation between PGE levels and the histologic degree of inflammation found in the placebo-treated patients. Ibuprofen significantly decreased the pain of cholecystitis when compared to placebo-treated patients. However, there was poor correlation between pain relief and changes in PGE production by gallbladder mucosa and muscle. PGE may play a mediator role in inflammation associated with cholecystitis. Prostaglandin synthetase inhibition decreases the pain associated with cholecystitis; however, the absence of correlation with decreased PGE formation suggests that other prostanoids may play an important role in producing the symptoms of cholecystitis.     

Abnormal Duodenal Bile Composition in Patients With Acalculous Chronic Cholecystitis

Objective : Our goal was to characterize biliary lipid composition in patients with the syndrome of chronic biliary pain, absence of gallstones, and inflammation of the gallbladder mucosa (acalculous chronic cholecystitis). Methods : Duodenal bile, obtained from 27 patients with a history of right upper quadrant pain and with negative imaging studies of the biliary tract, was analyzed enzymatically for bile acids, phospholipids, and cholesterol. Fifteen patients were found to have inflammation and/or fibrosis of the gallbladder at cholecystectomy. Results : The 15 patients with abnormal gallbladder histology had more dilute duodenal bile, as indicated by a low bile acid concentration and a lower proportion of phospholipids (   p < 0.01  ) when values were compared with those of duodenal bile samples from postmenopausal women without gallbladder disease or from radiolucent gallstone subjects participating in the National Cooperative Gallstone Study. Cholecystectomy relieved pain in 9 of 14 patients. Conclusions : Some patients with acalculous chronic cholecystitis have duodenal bile samples characterized by a decreased bile acid concentration and a decreased proportion of biliary phospholipids. The low biliary bile acid concentration may result from impaired gallbladder contraction and/or secretion by the biliary tract epithelium. The low proportion of phospholipid may result from posthepatic hydrolysis of luminal phosphatidylcholine followed by absorption of the hydrolysis products. The latter process could be caused by and/or contribute to mucosal inflammation and would also elevate the cholesterol saturation of bile, increasing the risk for cholesterol gallstone formation.     

Chronic Right Upper Quadrant Pain without Gallstones: Does HIDDA Scan Predict Outcome after Cholecystectomy?

Patients with chronic right upper quadrant pain who do not have gallstones on ultrasound or cholecystography are often referred for surgery for presumed acalculous chronic cholecystitis. We followed 26 patients who had cholecystokinin (CCK) cholescintigraphy for evaluation of chronic right upper quadrant pain without demonstrable gallstones on ultrasound who underwent cholecystectomy so that it could be determined whether there was any relation between a low ejection fraction (EF), morphological features of chronic cholecystitis, and clinical outcome. Eighteen patients (69%) were considered therapeutic successes, whereas eight (31%) were failures after an average 2-yr follow-up. Both patient groups had significantly reduced EF: the successful group at 0.39 and the failures at 0.25. Thus, a low EF did not predict clinical outcome, since the failure group had an even lower EF than the success group. Seven gallbladders demonstrated chronic acalculous cholecystitis; the average EF of this group was 0.35. The remaining 19 gallbladders were normal, yet also had an EF of 0.35. Thus, decreased EF does not predict the histologic features of chronic cholecystitis without gallstones. The diagnostic value of cholescintigraphy in patients with acalculous right upper quadrant pain is low, probably because this entity represents a variety of processes, including inflammation, gallbladder dysmotility, and the irritable bowel syndrome.     

Acute acalculous cholecystitis

Acute cholecystitis can develop without gallstones in critically ill or injured patients. However, the development of acute acalculous cholecystitis is not limited to surgical or injured patients, or even to the intensive care unit. Diabetes, malignant disease, abdominal vasculitis, congestive heart failure, cholesterol embolization, and shock or cardiac arrest have been associated with acute acalculous cholecystitis. Children may also be affected, especially after a viral illness. The pathogenesis of acute acalculous cholecystitis is a paradigm of complexity. Ischemia and reperfusion injury, or the effects of eicosanoid proinflammatory mediators, appear to be the central mechanisms, but bile stasis, opioid therapy, positive-pressure ventilation, and total parenteral nutrition have all been implicated. Ultrasound of the gallbladder is the most accurate diagnostic modality in the critically ill patient, with gallbladder wall thickness of 3.5 mm or greater and pericholecystic fluid being the two most reliable criteria. The historical treatment of choice for acute acalculous cholecystitis has been cholecystectomy, but percutaneous cholecystostomy is now the mainstay of therapy, controlling the disease in about 85% of patients. Rapid improvement can be expected when the procedure is performed properly. The mortality rates (historically about 30%) for percutaneous and open cholecystostomy appear to be similar, reflecting the severity of illness, but improved resuscitation and critical care may portend a decreased risk of death. Interval cholecystectomy is usually not indicated after acute acalculous cholecystitis in survivors; if the absence of gallstones is confirmed and the precipitating disorder has been controlled, the cholecystostomy tube can be pulled out after the patient has recovered.     

Human cholecystitis is associated with increased gallbladder prostaglandin I2 and prostaglandin E2 synthesis.

Microsomal prostanoid synthesis was compared in normal gallbladders removed during organ donation and inflamed gallbladders removed at cholecystectomy. Normal human gallbladder microsomes demonstrated low rates of conversion of [14C]arachidonic acid to total labeled prostanoids, which increased during 1 to 30 min of incubation. Normal human gallbladder microsomes converted labeled substrate to all primary prostaglandins without demonstration of a major product. Inflamed human gallbladder microsomes increased the rate of conversion of [14C]arachidonic acid to total labeled prostanoids two or three times over the levels demonstrated by normal gallbladder microsomes at all times of incubation (p < 0.01). The main prostanoids synthesized by the inflamed human gallbladder microsomes were prostaglandin E2 and 6-keto-prostaglandin F1 alpha, which were increased four times over the levels demonstrated by normal gallbladder microsomes (p < 0.01). These data showed that inflammation of the human gallbladder was associated with increased synthesis of gallbladder 6-keto-prostaglandin F1 alpha and prostaglandin E2.     

人体胆囊结石时胆囊组织PGE、PGI2、LTC4的含量

本文测定非结石组（ｎ＝１６）与结石组（ｎ＝４７）人体胆囊粘膜内前列腺素Ｅ（ＰＧＥ）、前列环素（ＰＧＩ２）白三烯０４（ＬＴＣ４）的含量及磷脂酶Ａ２（ＰＬＡ２）的活性，发现结石组四者的水平均非常显著地高于非结石组。提示可能由于脂类代谢紊乱，胆囊组织的ＰＬＡ２活性增加．致使ＰＧｓ、ＬＴｓ水平增高，引起胆囊上皮细胞活化，合成分泌粘蛋白功能亢进，从而参与促进结石的形成。     

Utility and accuracy of ultrasonically measured gallbladder wall as a diagnostic criteria in biliary tract disease

Biliary tract sonography has achieved wide acceptance as a screening test for chronic calculous disease. However, the clinical usefullness of biliary sonography is limited by the inability of this test to identify patients with acalculous cholecystitis or to separate patients with calculous cholecystitis from those with asymptomatic calculi. A prospective blinded study of 106 patients undergoing cholecystectomy was performed to determine if, cholecystosonography could visualize the gallbladder wall accurately and to evaluate gallbladder wall thickening as a predictor of disease. Of these patients, 88 had a sonographically visible gallbladder wall and in 95% of the patients the ultrasonic and direct surgical measurements of the gallbladder wall agreed within 1 mm. To determine the sonographic size range of gallbladder wall thickness in the normal population, the width of the gallbladder wall in the fasting state was measured in 100 patients without biliary tract disease. One percent of the normal population had thickened gallbladder walls, in contrast to 96% of the patients with acute calculous or acalculous cholecystitis. Gallbladder wall thickness appears to be an accurate noninvasive technique for diagnosing patients with acute calculous and acalculous cholecystitis in the absence of other entities which thicken the gallbladder wall such as ascites and hypoproteinemic states.     

Acalculous biliary pain: cholecystectomy alleviates symptoms in patients with abnormal cholescintigraphy

A 45-minute infusion of an octapeptide of cholecystokinin (Kinevac; Squibb Diagnostics, New Brunswick, NJ) was used to measure the gallbladder ejection fraction during cholescintigraphy in 40 normal volunteers. Cholecystokinin cholescintigraphy was shown to be a reproducible test. The maximum mean gallbladder ejection fraction occurred 15 minutes after cholecystokinin infusion and was 74.5% +/- 1.9% (mean +/- SEM). A gallbladder ejection fraction greater than 40% (mean -3SD) was arbitrarily defined to be normal. The gallbladder ejection fraction test was then used to identify patients with acalculous biliary symptoms who may respond to cholecystectomy. A total of 103 patients was tested; 21 had abnormal gallbladder ejection fractions and were randomized into two groups, cholecystectomy or no operation. These patients were followed up symptomatically at 3-month intervals for 13-54 months (mean, 34 months). Of the 11 patients who underwent cholecystectomy, 10 (91%) lost their symptoms and 1 improved. Of the 10 patients in the group that did not undergo surgery, all continued to be symptomatic, 2 of whom requested cholecystectomy after 13 and 24 months, respectively. Of the 13 gallbladders obtained from surgery, 12 showed evidence of chronic cholecystitis, muscle hypertrophy, and/or narrowed cystic duct. A normal gallbladder ejection fraction was recorded in 82 patients, and further treatment was left to the discretion of their referring clinician. On follow-up, 50 patients were asymptomatic and 10 were symptomatic without specific treatment of the biliary tract; 14 underwent cholecystectomy, 8 of whom were asymptomatic. Pathological abnormalities were recorded in 6 of the removed gallbladders. It is concluded that the gallbladder ejection fraction obtained after a 45-minute infusion of cholecystokinin during cholescintigraphy is a reproducible measure of gallbladder emptying, and that cholecystectomy alleviates the biliary-type pain of patients with a reduced gallbladder ejection fraction.     

Spontaneous biliary peritonitis in acalculous cholecystitis: fact or misdiagnosis?

It is often speculated that an inflamed gallbladder weeps bile to produce bile peritonitis. This may be so, but more likely the problem is a peritoneal effusion in a jaundiced patient which thus resembles bile. So-called "spontaneous or idiopathic biliary peritonitis" in acute acalculous cholecystitis without a proven cause is a further example of this very rare condition. Spontaneous perforations of the extrahepatic biliary ductal system associated with acalculous cholecystitis are uncommon albeit reported in adults. Most patients present with an acute abdomen and are operated upon urgently without diagnostic iter. A recent experience with such a case prompted a thorough review of 27 similar cases previously reported.     

Acute acalculous cholecystitis

Opinion statement Acute acalculous cholecystitis is defined as acute inflammation of the gallbladder in the absence of gallstones. Patients are usually critically ill with atherosclerotic heart disease, recent trauma, burn injury, surgery, or hemodynamic instability. The presentation of acute acalculous cholecystitis may be insidious, characterized by unexplained fever, leukocytosis, hyperamylasemia, or abnormal aminotransferases, and patients often lack right upper quadrant tenderness. Diagnostic evaluation includes ultrasonography, computerized tomography, and cholescintigraphy. Given the high mortality of untreated disease, definitive treatment consists of cholecystectomy or, in poor surgical candidates, cholecystostomy. Endoscopic therapy with nasobiliary drainage and lavage is an effective treatment option in patients unable to tolerate surgery or cholecystostomy.     

Prostanoids and leukotrienes in experimental feline cholecystitis

Current information suggests that arachidonic acid metabolites are involved in the development of cholecystitis. The purpose of this study was to evaluate eicosanoid formation during the development of experimental cholecystitis in cats. Lysophosphatidylcholine is found in the gallbladders of patients with cholecystitis and is known to be a cytolytic, membrane-damaging substance. Anesthetized cats underwent gallbladder perfusion with and without 1.5 mmol/L lysophosphatidylcholine. Additional experiments were performed when calcium ionophore were added to the perfusates and experiments were performed when cats were treated with indomethacin and underwent perfusion with lysophosphatidylcholine. Changes in the gallbladder were determined by evaluating mucosal water transport as measured by determining the changes in concentration in a nonabsorbable marker, by protein secretion and by beta-glucuronidase accumulation in gallbladder tissue as an index of inflammation. Eicosanoid formation was evaluated by measuring perfusate concentrations and gallbladder homogenate concentrations by radioimmunoassay of prostaglandin E, 6 keto prostaglandin F1 alpha, leukotriene B4 and leukotriene C4. Lysophosphatidylcholine perfusion reversed the control patterns of absorption and produced water exsorption, produced an efflux of protein into the perfusate and increased beta-glucuronidase activity. These changes were accompanied by increased production of prostaglandin E and 6 keto prostaglandin F1 alpha in gallbladder perfusate and homogenate. The concentration of leukotriene C4 in gallbladder effusate was increased by lysophosphatidylcholine when compared with control values. Indomethacin inhibited the protein efflux, decreased beta-glucuronidase levels and decreased prostaglandin E and 6 keto prostaglandin F1 alpha formation when compared with values produced by lysophosphatidylcholine alone. Cyclooxygenase inhibition did not alter the secretion of water into the gallbladder or perfusate leukotriene C4 concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dengue fever with acute acalculous cholecystitis

Dengue fever (DF) with acute acalculous cholecystitis is rarely reported. To investigate the incidence, treatment, and prognosis of acute acalculous cholecystitis in DF patients, we retrospectively studied 10 patients with DF and acute acalculous cholecystitis. From October 2001 to July 2002, 131 patients were diagnosed with DF. Ten of 131 DF patients (7.63%) had complications of acute acalculous cholecystitis. Two patients underwent cholecystectomy and one underwent percutaneous transhepatic gallbladder drainage due to poor resolution of acute acalculous cholecystitis. We found acute acalculous cholecystitis in a small proportion of patients with DF. In our experience, closely monitoring vital signs to avoid shock and correct thrombocytopenia to avoid bleeding could be adequate for most patients. In some cases, surgical treatment may be needed for DF fever patients with complications of diffuse peritonitis.     

Cholescintigraphy for acute cholecystitis: false positive results caused by chronic cholecystitis

We investigated the effect of the severity of chronic cholecystitis on the incidence of false positive cholescintigrams in the diagnosis of acute cholecystitis. In a 4-year period 66 patients underwent cholescintigraphy (without evidence of significant hepatocellular disease or biliary tract obstruction) followed within 6 days by surgical removal of the gallbladder. At histopathology the gallbladders were categorized as normal, acute cholecystitis, or chronic cholecystitis. In addition, the severity of chronic cholecystitis was graded on a three-point scale. Using nonvisualization of the gallbladder for up to 4 h as the criterion for acute cholecystitis, the sensitivity and specificity for acute cholecystitis were 97 and 66%, respectively. Of the 35 gallbladders without acute cholecystitis, 4 were normal and the rest had various grades of chronic cholecystitis. The incidence of false positive studies increased with the severity of chronic cholecystitis (p less than 0.05). In addition, there were no false positive studies among the normal gallbladders and all gallbladders with grade three chronic cholecystitis gave false positive results. The data suggests that the severity of chronic cholecystitis affects the likelihood of obtaining false positive results with cholescintigraphy in the diagnosis of acute cholecystitis.     

Cholesterol crystal morphology in acalculous gallbladder disease

BACKGROUND: Biliary crystal morphology is best described in patients with gallbladder stones, but most patients undergoing bile collection for microscopy have a clinical diagnosis of acalculous gallbladder disease. We investigated the morphology of biliary crystals in such patients. STUDY: Bile was obtained for polarizing microscopy from fresh cholecystectomy specimens of patients with a clinical diagnosis of acalculous or calculous gallbladder disease. Slides for microscopy were prepared by touch contact with bile in freshly opened gallbladder specimens, and following aspiration of gallbladder bile through a 5-French cannula. RESULTS: Bile was examined from five patients with a clinical diagnosis of acalculous gallbladder disease and five patients with known gallstones. Needle-like cholesterol crystals predominated in most patients without gallstones, whereas plate-like and dot-like crystals were more common in patients with gallstones. All three crystal types were seen in most patients. Crystal morphology was not affected by aspiration of bile through a 5-French cannula. CONCLUSIONS: Birefringent needles and dots should be recognized as cholesterol crystals during bile microscopy. These crystal morphologies may predominate in some patients with a clinical diagnosis of acalculous gallbladder disease.     

Cholecystectomy or gallbladder in situ after endoscopic sphincterotomy and bile duct stone removal in Chinese patients

BACKGROUND & AIMS: In patients with stones in their bile ducts and gallbladders, cholecystectomy is generally recommended after endoscopic sphincterotomy and clearance of bile duct stones. However, only approximately 10% of patients with gallbladders left in situ will return with further biliary complications. Expectant management is alternately advocated. In this study, we compared the treatment strategies of laparoscopic cholecystectomy and gallbladders left in situ. METHODS: We randomized patients (>60 years of age) after endoscopic sphincterotomy and clearance of their bile duct stones to receive early laparoscopic cholecystectomy or expectant management. The primary outcome was further biliary complications. Other outcome measures included adverse events after cholecystectomy and late deaths from all causes. RESULTS: One hundred seventy-eight patients entered into the trial (89 in each group); 82 of 89 patients who were randomized to receive laparoscopic cholecystectomy underwent the procedure. Conversion to open surgery was needed in 16 of 82 patients (20%). Postoperative complications occurred in 8 patients (9%). Analysis was by intention to treat. With a median follow-up of approximately 5 years, 6 patients (7%) in the cholecystectomy group returned with further biliary events (cholangitis, n = 5; biliary pain, n = 1). Among those with gallbladders in situ, 21 (24%) returned with further biliary events (cholangitis, n = 13; acute cholecystitis, n = 5; biliary pain, n = 2; and jaundice, n = 1; log rank, P = .001). Late deaths were similar between groups (cholecystectomy, n = 19; gallbladder in situ, n = 11; P = .12). CONCLUSIONS: In the Chinese, cholecystectomy after endoscopic treatment of bile duct stones reduces recurrent biliary events and should be recommended.     

Experimental study on the pathogenesis of acute acalculous cholecystitis, with special reference to the roles of microcirculatory disturbances, free radicals and membrane-bound phospholipase A2.

To elucidate the pathogenesis of acute acalculous cholecystitis, the gallbladder was subjected to ischemia-reperfusion by simultaneously occluding the middle hepatic artery and the superior mesenteric vein in dogs, and the degree of inflammation and biochemical changes in the gallbladder mucosa were studied by varying the duration of ischemia or reperfusion. Ischemia alone did not induce cholecystitis either macroscopically and histologically, although it increased phospholipase A2 (PLA2) activity, content of lipid peroxide, and superoxide dismutase (SOD) activity in the mucosa with prolongation of the ischemic time. Cholecystitis was produced in all animals by 45-min ischemia followed by 90-min reperfusion as the shortest ischemia and reperfusion times. In this model, prolongation of the ischemic time increased the area of mucosal inflammation horizontally with increases of the PLA2 activity, content of lipid peroxide, and SOD activity, whereas by prolonging the reperfusion time the inflammation area spread deeper vertically toward the serosal side with significant increase in the mucosal PLA2 activity, content of lipid peroxide, and SOD activity. These results revealed that ischemia-reperfusion plays an important role in the pathogenesis of acute acalculous cholecystitis, causing the generation of free radicals and the activation of membrane-bound PLA2.     

Influence of cholecystitis state on pharmacological response to cholecystokinin of isolated human gallbladder with gallstones

We studied the influence of the inflammatory state of the gallbladder with gallstones on its response to cholecystokinin (CCK). Responses to CCK were evaluated in isolated human gallbladder strips incubated with pharmacological antagonists. Gallbladders from patients with gallstones were classified as having mild and severe chronic cholecystitis. Healthy gallbladders were collected from liver donors. In donor gallbladders, the CCK contraction was abolished with the CCK-A receptor antagonist, L-364718, and significantly reduced by indomethacin. In gallbladders with gallstones, only mild cholecystitis showed a decreased contraction to CCK. In gallbladders with gallstones, no involvement of prostaglandins in the CCK response was observed. In severe cholecystitis, CCK contractile effect was reduced by the serotonin receptor antagonist methysergide. In healthy gallbladder, the contraction provoked by CCK is mediated by CCK-A receptors and modulated by prostaglandins. The presence of gallstones in the gallbladder is correlated with a loss of prostaglandins-modulated CCK contraction. However, the excessive release of serotonin in advanced cholecystitis normalizes the contraction to CCK, suggesting that the state of cholecystitis affects the pool of inflammatory mediators responsible for gallbladder CCK-altered motility.     

The Microscopic Examination of Bile in Patients with Biliary Pain and Negative Imaging Tests

We describe a 5-yr retrospective analysis of the accuracy of the microscopic examination of bile in the detection of biliary tract disease in patients with episodic upper abdominal pain who had negative imaging procedures. In 182 patients, 189 studies of bile were performed using duodenal intubation and sincalide stimulation for gallbladder contraction. The presence of cholesterol crystals, leukocytes (greater than or equal to 5/hpf) or the absence of "B" bile constituted a "positive" study. Bilirubinate sludge alone, was defined as "suspicious." Eighty-three patients underwent cholecystectomy. Among the acalculous patients who underwent cholecystectomy, 28/28 with bilirubinate sludge had symptomatic improvement as compared with the negative group of which only five of 10 improved (p less than 0.005). The sensitivity of this test for the presence of gallstones in these imaging-negative patients was 87%, while the specificity was 16%. We conclude that a single microscopic examination of bile cannot accurately predict the pathological findings or the presence of gallstones in image-negative patients with biliary pain. The presence of bilirubinate sludge may predict symptomatic improvement in those patients with acalculous gallbladder disease undergoing cholecystectomy.