Around 10% to 30% patients with acute pancreatitis (AP) do not have a cause after the routine investigations, and are considered as having idiopathic acute pancreatitis (IAP). Establishing the etiology in such patients will prevent recurrences and evolution to chronic pancreatitis. Endoscopic ultrasonography (EUS) and magnetic resonance cholangiopancreatography (MRCP) characteristically are used to diagnose IAP when routine methods fail, but their exact role is not determined.

This prospective study was undertaken in a tertiary care hospital, in which patients admitted initially with diagnosis of IAP were evaluated. These patients underwent MRCP and EUS at least 4 weeks after an attack of AP. The results of EUS and MRCP were compared and analyzed with various clinical variables using suitable statistical tests.

A total of 31 patients with IAP were included. EUS and/or MRCP was able to establish at least one etiology in 17 patients (54.8%). The diagnoses revealed were gallbladder (GB) microlithiasis, GB sludge, choledocholithiasis, pancreatobiliary ductal anomalies, pancreatic adenocarcinoma, and intraductal papillary mucinous neoplasm. Comparing the diagnostic accuracy of both the modalities, EUS (14/31) was able to diagnose more cases than MRCP (8/31). The diagnostic capability of EUS was lower in patients who had a cholecystectomy (12.5% vs. 56.5%; p = 0.03).

EUS and MRCP are useful modalities in the etiological diagnosis of IAP and should be used in conjunction. EUS is better for establishing a possible biliary etiology and MRCP for an anatomical alteration in pancreatobiliary ducts.

The terms biliary sludge and cholesterol microlithiasis (hereafter referred to as microlithiasis) were originated from different diagnostic techniques and may represent different stages of cholesterol gallstone disease. Although the pathogenesis of biliary sludge and microlithiasis may be similar, microlithiasis could be preceded by biliary sludge, followed by persistent precipitation and aggregation of solid cholesterol crystals, and eventually, gallstone formation. Many clinical conditions are clearly associated with the formation of biliary sludge and microlithiasis, including total parenteral nutrition, rapid weight loss, pregnancy, organ transplantation, administration of certain medications, and a variety of acute and chronic illnesses. Numerous studies have demonstrated complete resolution of biliary sludge in approximately 40% of patients, a cyclic pattern of disappearing and reappearing in about 40%, and progression to gallstones in nearly 20%. Although only a minority of patients with ultrasonographic demonstration of biliary sludge develop gallstones, it is still a matter of controversy whether microlithiasis could eventually evolve to cholesterol gallstones. Biliary sludge and microlithiasis are asymptomatic in the vast majority of patients; however, they can cause biliary colic, acute cholecystitis, and acute pancreatitis. Biliary sludge and microlithiasis are most often diagnosed ultrasonographically and bile microscopy is considered the gold standard for their diagnosis. Specific measures to prevent the development of biliary sludge are not practical or cost-effective in the general population. Laparoscopic cholecystectomy offers the most definitive therapy on biliary sludge. Endoscopic sphincterotomy or surgical intervention is effective for microlithiasis-induced pancreatitis. Ursodeoxycholic acid can effectively prevent the recurrence of solid cholesterol crystals and significantly reduce the risk of recurrent pancreatitis.

In approximately 20% of patients with acute pancreatitis, a cause is not established by history, physical examination, routine laboratory testing, and abdominal imaging. For those with a single unexplained attack, the role of invasive evaluation with endoscopic retrograde cholangiopancreatography is unsettled but has been generally limited to those patients with suspected bile duct stones or malignancy. Recent studies suggest that microlithiasis is causative in up to 75% of patients with an unexplained attack and gallbladder in situ, whereas sphincter of Oddi dysfunction is most prevalent in those with recurrent attacks who have previously undergone cholecystectomy. EUS has been shown to be highly accurate for the identification of gallbladder sludge, common bile duct stones, and pancreatic diseases. Given this apparent diagnostic utility, an EUS-based strategy may be a reasonable approach to evaluate patients with a single idiopathic attack. ERCP and sphincter of Oddi manometry should generally be reserved for patients with multiple unexplained attacks and negative EUS results, especially for those patients who have previously undergone cholecystectomy.

Microlithiasis has been suspected to cause acute pancreatitis and biliary pain. We studied the frequency of microlithiasis and response to treatment in recurrent idiopathic acute pancreatitis (RIAP) and unexplained biliary pain.

Gallbladder bile was examined microscopically for cholesterol monohydrate crystals (CMC) and calcium bilirubinate granules (CBG) in patients with RAIP (n = 24; mean age 36 years, range 18-56 years; 14 men), unexplained biliary pain (n = 12; mean age 32 years, range 22-55 years; six men), gallstones (n = 22; mean age 40 years, range 30-58 years; 12 men) and patients without clinical or imaging evidence of gallstone disease (n = 12; mean age 32 years, range 14-54 years; six men). The presence of a single CMC or >25 CBG/slide was considered abnormal.

Bile microscopy was abnormal in 75% patients with RAIP (18/24; CMC in 10, CBG in six, CMC and CBG in two), 83.3% patients with unexplained biliary pain (10/12; CMC in seven, CBG in one, CMC and CBG in two) and 95.4% patients with gallstones (21/22; CMC in 12, CBG in one, CMC and CBG in eight). None of the controls without gallstone disease had CMC while three patients had low counts of CBG. Twenty-eight patients with RAIP and biliary pain having microlithiasis agreed to be treated with cholecystectomy (n = 2), endoscopic sphincterotomy (n = 21) or ursodeoxycholic acid (UDCA; n = 5). The 23 patients treated with cholecystectomy or sphincterotomy remained asymptomatic during follow up (mean 23 months, range 6-48 months). Four of five patients treated with UDCA remained asymptomatic for a follow-up period of 9, 10, 11 and 18 months, respectively. One patient who had refused cholecystectomy or sphincterotomy continued to experience pain at the same frequency as before during a follow-up period of 12 months. One patient, who was asymptomatic on UDCA for 9 months, agreed to undergo sphincterotomy and remained asymptomatic over a follow-up period of 14 months.

Microlithiasis is a common cause for idiopathic acute pancreatitis and unexplained biliary pain. Lasting relief is obtained in most patients after treatment with UDCA, cholecystectomy or sphincterotomy.

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.

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.

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.

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.

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 gallstone-associated 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.

Duodenal bile crystal analysis for the detection of gallstones was assessed in 26 patients with acute pancreatitis of known aetiology (11 attributable to gallstones and 15 to alcohol) and in 37 patients without a history of acute pancreatitis (21 with gallstones and 16 without). The sensitivity was 64-67 per cent and the specificity was 94-100 per cent in these groups. Analysis of duodenal bile from 14 patients with 'idiopathic' pancreatitis revealed calcium bilirubinate crystals (but not cholesterol crystals) in 5 patients (36 per cent). Gallstones were confirmed at cholecystectomy in three of these patients and also in one other patient who had a gallstone on a 'late' ultrasound examination but was negative for crystals. Thus 29 per cent of the original 'idiopathic' group had gallstones confirmed. Gallstone analysis showed that pigment stones were present in 7 of 31 (23 per cent) non-pancreatitis controls compared with 9 of 13 (69 per cent) pancreatitis patients (P = 0.0048). These results suggest that duodenal bile crystal analysis (involving both calcium bilirubinate and cholesterol crystals) may be a useful technique for the investigation of patients with 'idiopathic' pancreatitis.