Calcium Bilirubinate Granules Research Articles

Clinical profile of patients with cholelithiasis at a tertiary care hospital

Gallstones represent a failure to maintain certain biliary solutes, primarily cholesterol and calcium salts in a solubilized state. An important biliary precipitate in gallstone pathogenesis is biliary sludge, which refers to a mixture of cholesterol crystals, calcium bilirubinate granules, and a mucin gel matrix. The general bio-data of patient regarding his name, age, sex, religion, occupation, socio-economic status and address was collected. A detailed history was taken with special reference to duration of right upper quadrant pain or epigatric pain, its periodicity, its aggravation by fatty meals and relief by oral or parenteral analgesics. 16 patients presented with nausea along with pain abdomen and 78 patients presented with vomiting, whereas 94 patients presented with both. Jaundice was seen in 33 patients.

Tumefactive sludge mimicking gallbladder neoplasm: A case report and review of the literature

Biliary sludge (or very thick bile) is mainly comprised of calcium bilirubinate granules and lesser amounts of cholesterol crystals, and it can produce a layer of low amplitude of echoes in the most dependent part of the gallbladder (GB). In tumefactive biliary sludge, low-amplitude echoes do not form a fluid–fluid level but instead tend to give the appearance of a polypoid mass that is bounded by a smooth margin, round, and lobulated. Differential diagnoses for an echogenic mass in the GB lumen include GB carcinoma, tumefactive sludge, and gangrenous cholecystitis. In this case report, we describe a rare case in which biliary sludge did not form a fluid–fluid level but tended to accumulate and appear as a polypoid mass within the lumen of the GB. The lesion was finally identified as being tumefactive sludge mimicking neoplasm of the GB.

Functional Gallbladder and Sphincter of Oddi Disorders

The functional disorder of the gallbladder (GB) is a motility disorder caused initially either by metabolic abnormalities or by a primary motility alteration. The functional disorders of the sphincter of Oddi (SO) encompass motor abnormalities of either the biliary or the pancreatic SO. Dysfunction of the GB and/or biliary SO produce similar patterns of pain. The pain caused by a dysfunction of the pancreatic SO can be similar to that of acute pancreatitis. The symptom-based diagnostic criteria of motility dysfunction of the GB and biliary SO are episodes of moderate to severe steady pain located in the epigastrium and right upper abdominal quadrant that last at least 30 minutes. GB motility disorder is suspected after gallstones and other structural abnormalities have been excluded. This diagnosis should then be confirmed by a decreased GB ejection fraction induced by cholecystokinin at cholescintigraphy and after disappearance of the recurrent biliary pain after cholecystectomy. Symptoms of biliary SO dysfunction may be accompanied by features of transient biliary obstruction, and those of pancreatic SO dysfunction are associated with elevation of pancreatic enzymes and even pancreatitis. Biliary-type SO dysfunction is more frequently recognized in postcholecystectomy patients. SO manometry is valuable to select patients with sphincter dysfunction; however, because of the high incidence of complications, these patients should be referred to an expert unit for such assessment. Thus invasive tests should be performed only in the presence of compelling clinical evidence and after noninvasive testing has yielded negative findings. The committee recommends that division of the biliary or pancreatic sphincters only be considered when the patient has severe symptoms, meets the required criteria, and other diagnoses are excluded.

Frequency of biliary crystals in patients with suspected sphincter of Oddi dysfunction

Background The passage of gallstones (macro- or microlithiasis) is theorized to play a role in inducing sphincter of Oddi dysfunction. This study examined the frequency at which biliary crystals are found in patients with suspected type II and type III sphincter of Oddi dysfunction. Methods A total of 85 patients (66 women, 19 men; mean age 38 years) with unexplained abdominal pain of suspected pancreatobiliary origin and no prior episode of pancreatitis underwent ERCP with sphincter of Oddi manometry and bile collection for crystal analysis. Eighty-one patients had a gallbladder in situ. No patient had evidence of stones or sludge on prior abdominal imaging. Sphincter of Oddi manometry was performed in standard retrograde fashion by using an aspirating catheter. Patients were classified by sphincter of Oddi dysfunction type by using a modified Hogan-Geenen classification system. Patients with type I sphincter of Oddi dysfunction were excluded. Bile was collected directly from the gallbladder (n = 23) or common bile duct (n = 62) after an infusion of 3.5 μg of cholecystokinin and was examined by light and polarizing microscopy for cholesterol crystals or calcium bilirubinate granules. Results The proportion of patients with crystals was 3.5% (3/85). Thirty-five patients (41%) had elevated biliary and/or pancreatic sphincter pressure (type II, 16; type III, 19), of whom one (3%) had cholesterol crystals. Fifty patients had normal sphincter pressure, of whom two (4%) had cholesterol crystals ( p = 0.6). All 3 patients with cholesterol crystals had a gallbladder in situ. Calcium bilirubinate granules were not found in any patient. Conclusions Microlithiasis appears to be rare in patients suspected to have type II or type III sphincter of Oddi dysfunction. Evaluation of bile for crystals appears unproductive in this group of patients.

Endoscopic Ultrasound-Guided Gallbladder Bile Aspiration in Idiopathic Pancreatitis Carries a Significant Risk of Bile Peritonitis

Background: Direct microscopic examination of bile for the presence of microlithiasis is often performed during the evaluation of patients with idiopathic pancreatitis. Bile sampled from the duodenum and/or the common bile duct may not represent gallbladder bile, and thus may be inadequate for the diagnosis of microlithiasis. Aim: We sought to determine the safety and efficacy of endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) of gallbladder bile in patients with idiopathic pancreatitis. Methods: Patients with idiopathic pancreatitis underwent EUS with a linear echoendoscope. After excluding potential causes of pancreatitis such as common bile duct stones or pancreatic lesions, the gallbladder was identified. The gallbladder lumen was entered using a 22-gauge FNA needle via the duodenal wall. Bile was aspirated and analyzed for the presence of cholesterol monohydrate crystal, calcium bilirubinate granules, calcium carbonate microspheroliths and mucin gel strands. Results: Three patients underwent EUS-guided FNA of gallbladder bile. Two of these patients developed bile peritonitis within one hour of the procedure prompting us to discontinue the study. One patient’s gallbladder bile contained microlithiasis. This patient had bile aspirated from the common bile duct via ERCP 3 weeks prior to EUS. However, analysis of that bile sample failed to show microlithiasis. Conclusion: Unfortunately, transduodenal EUS-guided FNA of gallbladder bile using a 22-gauge needle carries a significant risk of bile peritonitis.

The frequency of bile duct crystals in patients with presumed biliary pancreatitis

Background: Previous studies of biliary microlithiasis in acute pancreatitis of uncertain etiology were conducted a few weeks to months after the acute episode. Bile obtained during urgent ERCP (less than 24 hours after admission) was studied for the presence of microlithiasis during the acute phase of acute pancreatitis of suspected biliary origin. Methods: Fifteen consecutive patients with acute pancreatitis of suspected biliary origin were recruited from a population of 309 patients with acute pancreatitis (5%) treated during the last 4 years. Patients with gallstones on US and/or ERCP and those in whom the etiology of acute pancreatitis was certain were excluded. Results: Microlithiasis (mostly calcium bilirubinate granules) was found in 12 (80%) cases. Despite endoscopic sphincterotomy 3 patients died within 2 weeks because of multisystemic organ failure. Among the 12 remaining patients, 2 (16%) developed gallbladder stones and 1 underwent cholecystectomy for cholecystitis (8%) during follow-up. The average length of follow-up was 30 months. No episodes of acute pancreatitis were noted during follow-up. Conclusions: In the acute phase of acute pancreatitis of suspected biliary origin, biliary microlithiasis was found in most cases. Endoscopic sphincterotomy appears to protect patients from further episodes of acute pancreatitis. (Gastrointest Endosc 2001;54:37-41.)

Can ERCP contrast agents cause pseudomicrolithiasis? Their effect on the final outcome of bile analysis in patients with suspected microlithiasis

Background: Microlithiasis has been implicated in the etiology of idiopathic pancreatitis and biliary-type pain in patients with intact gallbladders. Contrast injection at endoscopic retrograde cholangiopancreatography (ERCP) is used to confirm access into the bile duct and bile is also aspirated to look for microlithiasis. It is not known whether contrast agents contain crystals that could mimic true microlithiasis. Methods: Four mL of 2 contrast agents (Hypaque and Omnipaque) were examined after centrifugation under polarizing microscopy. In the second part of the study, bile aspirated during ERCP with contrast injection was examined for microlithiasis and contrast pseudomicrolithiasis. Results: Contrast agents exhibited pseudomicrolithiasis that mimicked calcium bilirubinate granules. Pathologists participating in the study were not aware of contrast pseudomicrolithiasis. Nine of twelve (75%) patients would have been reported as having microlithiasis and would possibly have undergone an unnecessary cholecystectomy. Conclusion: When bile collected during ERCP is to be examined for microlithiasis, it should be collected without contamination by a contrast agent. If this is not possible, pathologists should be aware that contrast can cause pseudomicrolithiasis. (Gastrointest Endosc 2000;51:401-4.)

Combined Endoscopic Ultrasound and Stimulated Biliary Drainage in Cholecystitis and Microlithiasis - Diagnoses and Outcomes

It is becoming increasingly evident from a number of studies that endoscopic ultrasound (EUS) is much more sensitive in the diagnosis of cholecystitis than transabdominal ultrasound (TUS). The present study was undertaken to further evaluate this relative sensitivity. Sixty-six patients with biliary-type pain and a negative transabdominal ultrasound examination underwent combined endoscopic ultrasound and stimulated biliary drainage (EUS/SBD). Stimulated biliary drainage was obtained following intraduodenal infusion of magnesium sulfate or intravenous sincalide, a CCK analogue. EUS was considered positive if sludge or small stones were seen in the gallbladder. Stimulated biliary drainage was considered positive if calcium bilirubinate granules or cholesterol crystals were seen on microscopic examination of aspirated bile. At operation, 61 of the patients had cholecystitis documented histologically. Fifty-eight of the patients had gallbladder sludge or small stones on EUS. One patient had a negative EUS, but had calcium bilirubinate granules in the bile. Twenty-one patients were followed post-operatively for a period of seven to 17 months, with an average of 10.5 months. Nineteen patients (90.5%) remain free of biliary pain. Combined endoscopic ultrasound and stimulated biliary drainage (EUS/SBD) had a high sensitivity of 92.4% and a positive predictive value of 100% in the diagnosis of cholecystitis when transabdominal ultrasound was negative. A significant majority (90.5%) of patients with positive EUS/SBD who underwent cholecystectomy had resolution of their biliary pain.

Utility of biliary microcrystal analysis in predicting composition of common bile duct stones.

The high failure rate of contact litholytic therapy for common bile duct stones with currently available cholesterol solvents has been attributed to the inclusion of patients with pigment stones, as no pretreatment investigation is undertaken to distinguish the two stone types. In 36 patients with common bile duct stones we prospectively evaluated the utility of microscopic examination of bile collected from the biliary tree in predicting stone composition. The bile, obtained by means of either an endoscopically placed nasobiliary catheter (n = 27) or a surgically placed T-tube (n = 9), was subjected to microscopic examination, and findings were compared with the composition of stones retrieved subsequently. On the basis of quantitative infrared spectroscopy, stones were classified as cholesterol (n = 28) or pigment (n = 8) stones. The presence of cholesterol crystals in bile correctly identified 24 of 28 patients with cholesterol stones (sensitivity, 86%; specificity, 100%; positive predictive value, 100%). Calcium bilirubinate granules, when present alone (without cholesterol crystals), correctly identified all eight patients with pigment stones (sensitivity, 100%; specificity, 89%; positive predictive value, 73%). Thus, microscopic examination of bile from the biliary tree, if used as a pretreatment screening test, may help distinguish between patients with cholesterol and pigment stones and thereby considerably improve the results of litholytic therapy of common bile duct stones with currently available solvents.

Biliary Sludge as a Cause of Acute Pancreatitis

In about 20 to 40 percent of cases of acute pancreatitis, no cause can be found, and these are labeled idiopathic. In this study, we sought to determine the frequency with which patients with acute idiopathic pancreatitis have biliary sludge, a suspension of cholesterol monohydrate crystals or calcium bilirubinate granules that is found predominantly in the gallbladder. Between 1980 and 1988, we prospectively studied 86 patients who had acute pancreatitis. In patients with no known cause of pancreatitis and no ultrasonographic evidence of gallstones or dilatation of the biliary ducts, we determined how often biliary sludge was present and its subsequent fate by repeated microscopical examinations of bile samples and abdominal ultrasonography. The outcome of patients treated by cholecystectomy or papillotomy was compared with that of untreated patients. The pancreatitis was considered idiopathic in 31 of the 86 patients (36 percent), of whom 23 had microscopical evidence of biliary sludge. Biliary sludge was detected by ultrasonography in only 11 of the 23 patients (48 percent). The sludge detected by ultrasonography was composed of calcium bilirubinate granules in 10 and cholesterol monohydrate crystals in 1 (P = 0.003). Calcium bilirubinate granules were found more frequently in men (nine men vs. four women, P less than 0.001). Of the 21 patients in whom biliary sludge was the only finding (2 patients also had dilasted bile ducts when restudied), the 6 treated by cholecystectomy and the 4 treated by papillotomy had fewer recurrences of acute pancreatitis during follow-up (up to seven years) than the 11 untreated patients (P = 0.011). The presence of biliary sludge appeared to increase the likelihood of recurrent attacks of pancreatitis (P = 0.020). Biliary sludge is an underestimated cause of acute idiopathic pancreatitis.

Primary bile duct stones and bacterial activity.

The results of this study suggest that infection with beta-glucuronidase active bacteria is the initial event in the nucleation of primary bile duct stones (PBDS). PBDS from five patients were morphologically fragile and “earthy” with alternating light and dark brown pigment layers with no evidence of a distinct central nucleus that may have been reminiscent of a different structure. Chemically, calcium bilirubinate and calcium palmitate were prominent throughout their structure. All bile duct biles had a positive culture and were always associated with at least one bacterial species which was beta-glucuronidase active. Moreover, fragments of PBDS nuclear areas had positive cultures that were comparable with those present in their individual bile duct bile. Microscopic examination of bile showed abundant precipitation of calcium bilirubinate granules in all samples. Thus, bile duct bile infection with beta-glucuronidase active bacteria (e.g. E. coli, C. perfringens) appears to be a key factor in PBDS pathogenesis, having a precursor role, rather than being a consequence. Bile stasis is likely to be a co-factor which must have a supportive role in subsequent stone growth.

Occult microlithiasis in ‘idiopathic’ acute pancreatitis: Prevention of relapses by cholecystectomy or ursodeoxycholic acid therapy

Gallstone pancreatitis is usually related to small stones, which may not be detected by conventional cholecystographic techniques. In the current study, it was hypothesized that some patients with acute pancreatitis of unknown cause could harbor occult microstones in the gallbladder. Therefore, evidence was sought prospectively of missed gallstones by biliary drainage and microscopic examination of centrifuged duodenal bile in 51 patients recovering from an attack of acute pancreatitis, including 24 patients with relapsing episodes. Clusters of cholesterol monohydrate crystals, calcium bilirubinate granules, and/or CaCo3 microspheroliths were found in 67% of the patients. Biliary drainage showed no abnormal findings in 12 patients convalescing from a bout of known alcoholic pancreatitis. Examination of gallbladder bile at cholecystectomy and/or serial ultrasonography of the gallbladder for up to 12 months showed that 73% of the patients with unexplained pancreatitis had biliary sludge or microlithiasis; the prior finding of biliary crystal/solid markers predicted their existence with both a sensitivity and a specificity of 86% and a predictive value of 94%. The probability of harboring occult gallstones was also associated with age (P = 0.004), prior recurrent pancreatitis (P = 0.024), and altered liver function tests results during an index episode (P = 0.003). In 13 patients with cholesterol monohydrate crystals in bile, ursodeoxycholic acid (10 mg · kg−1 · day−1) eliminated gallbladder microlithiasis within 3–6 months, and subsequent maintenance treatment with a daily dose of 300 mg prevented both gallstone recurrence and further attacks of pancreatitis over a mean follow-up period of 44 months. Cholecystectomy also prevented gallstoneassociated relapses in 17 of 18 patients followed up for a mean postoperative period of 36 months. This study provides firm evidence showing that in most patients with idiopathic acute pancreatitis, the disease is related to microscopic gallstones, as evidenced by the follow-up development of macroscopic stones or sludge and by the prevention of relapses with either cholecystectomy or a cholelitholytic bile acid. Occult gallstones should be strongly suspected when acute pancreatitis of unknown cause occurs in a relapsing manner and in aged patients and when it is associated with altered liver function test results. Biliary microscopy and/or follow-up ultrasonography of the gallbladder provide a simple means of uncovering them to institute appropriate therapy and prevent further attacks.

Morphological appearance of low-level echoes in the gallbladder. Interpretation with microscopic biliary analysis and clinical correlation.

A total of 743 patients affected by various gastrointestinal disorders were examined by ultrasound. The presence in the gallbladder bile of low-level echoes (LLE) was observed in 56 (7.5%). Twenty-six of these patients had surgery: 24 underwent cholecystectomy for important biliary-like painful symptomatology, and 2 had cephalopancreatectomy for pancreatic head carcinoma. Both macro- and microscopic controls of the bile were carried out in all 26 patients. In 20 cases, only microscopic cholesterol crystals and calcium bilirubinate granules were observed in the bile. The microscopic evidence of these crystals was associated in four cases with macroscopic evidence of so-called "biliary sludge" and in four cases with macroscopic evidence of highly viscous bile. In the other 6 cases these crystals were associated with the presence of cholesterol stones. The authors consider that the observation of LLE in the gallbladder bile is an important index of the presence of cholesterol crystals and/or calcium bilirubinate granules. These LLE can assume polymorphic aspects, described by the authors, which may simulate other pathologies and lead to incorrect echographic diagnosis. The high incidence of LLE in an alithiasic population (5.1%), together with the elevated frequency, according to the authors, of association of these echoes with a painful biliary-like symptomatology (52.6%), underlines the diagnostic importance of an accurate ultrasound investigation in this type of pathology.

The usefulness of microscopic bile examination in patients with suspected microlithiasis: A prospective evaluation

Gallbladder bile collected by duodenal intubation or during surgery was examined microscopically in patients who were free of stones and in patients with proven stones. None of the 16 patients free of stones had cholesterol monohydrate crystals or calcium bilirubinate granules in bile. Among the 17 patients with proven cholelithiasis, 13 with cholesterol stones had cholesterol monohydrate crystals in their bile, but only 2 of the 4 patients with pigment stones had calcium bilirubinate granules. These data confirm that cholesterol monohydrate crystals are sensitive and specific for cholesterol stones, whereas calcium bilirubinate granules lack sensitivity for the diagnosis of pigment stones. From these results, the diagnostic usefulness of microscopic examination of bile collected from the duodenum was studied prospectively in 46 patients with symptoms suggestive of cholelithiasis but in whom stones had not been visualized at cholecystography and ultrasonography. In 15 of them, bile was found to be abnormal: cholesterol monohydrate crystals were seen in 11, cholesterol crystals + calcium bilirubinate granules in 2 and calcium bilirubinate granules in 2. To date, nine of these patients have been operated on: 6 (all with cholesterol monohydrate crystals) had small cholesterol gallstones and 3 (2 with cholesterol monohydrate crystals and 1 with calcium bilirubinate granules) had signs strongly suggestive of the recent migration of gallstones. One patient refused operation, but minute pigment stones were found to be associated with calcium bilirubinate granules at duodenal intubation. In the other 31 patients, bile contained neither cholesterol monohydrate crystals nor calcium bilirubinate granules. They were not operated on and were followed up with repeated investigations for 12 to 24 months.(ABSTRACT TRUNCATED AT 250 WORDS)