The last 30 years have seen major developments in the management of gallstone-related disease, which in the United States alone costs over 6 billion dollars per annum to treat. Endoscopic retrograde cholangiopancreatography (ERCP) has become a widely available and routine procedure, whilst open cholecystectomy has largely been replaced by a laparoscopic approach, which may or may not include laparoscopic exploration of the common bile duct (LCBDE). In addition, new imaging techniques such as magnetic resonance cholangiography (MR) and endoscopic ultrasound (EUS) offer the opportunity to accurately visualise the biliary system without instrumentation of the ducts. As a consequence clinicians are now faced with a number of potentially valid options for managing patients with suspected CBDS. It is with this in mind that the following guidelines have been written.

/pdf/guidelines-on-the-management-of-common-bile-duct-stones-cbds-auly7w0tiu.pdf

Guidelines on the management of common bile duct stones (CBDS).

ESGE recommends offering stone extraction to all patients with common bile duct stones, symptomatic or not, who are fit enough to tolerate the intervention. Strong recommendation, low quality evidence. ESGE recommends liver function tests and abdominal ultrasonography as the initial diagnostic steps for suspected common bile duct stones. Combining these tests defines the probability of having common bile duct stones. Strong recommendation, moderate quality evidence. ESGE recommends endoscopic ultrasonography or magnetic resonance cholangiopancreatography to diagnose common bile duct stones in patients with persistent clinical suspicion but insufficient evidence of stones on abdominal ultrasonography. Strong recommendation, moderate quality evidence. ESGE recommends the following timing for biliary drainage, preferably endoscopic, in patients with acute cholangitis, classified according to the 2018 revision of the Tokyo Guidelines: – severe, as soon as possible and within 12 hours for patients with septic shock – moderate, within 48 – 72 hours – mild, elective. Strong recommendation, low quality evidence. ESGE recommends endoscopic placement of a temporary biliary plastic stent in patients with irretrievable biliary stones that warrant biliary drainage. Strong recommendation, moderate quality of evidence. ESGE recommends limited sphincterotomy combined with endoscopic papillary large-balloon dilation as the first-line approach to remove difficult common bile duct stones. Strong recommendation, high quality evidence. ESGE recommends the use of cholangioscopy-assisted intraluminal lithotripsy (electrohydraulic or laser) as an effective and safe treatment of difficult bile duct stones. Strong recommendation, moderate quality evidence. ESGE recommends performing a laparoscopic cholecystectomy within 2 weeks from ERCP for patients treated for choledocholithiasis to reduce the conversion rate and the risk of recurrent biliary events. Strong recommendation, moderate quality evidence.

/pdf/endoscopic-management-of-common-bile-duct-stones-european-1n4upif0zg.pdf

Endoscopic management of common bile duct stones: European Society of Gastrointestinal Endoscopy (ESGE) guideline

The role of endoscopy in the management of choledocholithiasis

The aim of this article is to review selected aspects of the pathogenesis of cholesterol-rich, gall-bladder stones (GBS)--with emphasis on recent developments in biliary cholesterol saturation, cholesterol microcrystal nucleation, statis within the gall-bladder and, particularly, on the roles of intestinal transit and altered deoxycholic acid (DCA) metabolism, in GBS development. In biliary cholesterol secretion, transport and saturation, recent developments include evidence in humans and animals, that bile lipid secretion is under genetic control. Thus in mice the md-2 gene, and in humans the MDR-3 gene, encodes for a canalicular protein that acts as a 'flippase' transporting phospholipids from the inner to the outer hemi-leaflet of the canalicular membrane. In the absence of this gene, there is virtually no phospholipid or cholesterol secretion into bile. Furthermore, when inbred strains of mice that have 'lith genes' are fed a lithogenic diet, they become susceptible to high rates of GBS formation. The precipitation/nucleation of cholesterol microcrystals from supersaturated bile remains a critical step in gallstone formation. methods of studying this phenomenon have now been refined from the original 'nucleation time' to measurement of cholesterol appearance/detection times, and crystal growth assays. Furthermore, the results of recent studies indicate that, in addition to classical Rhomboid-shape monohydrate crystals, cholesterol can also crystallize, transiently, as needle-, spiral- and tubule-shaped crystals of anhydrous cholesterol. A lengthy list of promoters, and a shorter list of inhibitors, has now been defined. There are many situations where GB stasis in humans is associated with an increased risk of gallstone formation--including iatrogenic stone formation in acromegalic patients treated chronically with octreotide (OT). As well as GB stasis, however, OT-treated patients all have 'bad' bile which is supersaturated with cholesterol, has excess cholesterol in vesicles, rapid microcrystal mulceation times and a two-fold increase in the percentage DCA in bile. This increase in the proportion of DCA seems to be due to OT-induced prolongation of large bowel transit time (LBTT). Thus LBTT is linearly related to (i) the percentage of DCA in serum; (ii) the DCA pool size; and (III) the DCA input or 'synthesis' rate. Furthermore, the intestinal prokinetic, cisapride, counters the adverse effects of OT on intestinal transit, and 'normalizes' the percentage of DCA in serum/bile. Patients with spontaneous gallstone disease also have prolonged LBTTs, more colonic gram-positive anaerobes, increased bile acid metabolizing enzymes and higher intracolonic pH values, than stone-free controls. Together, these changes lead to increased DCA formation, solubilization and absorption, Thus, in addition to the 'lithogenic liver' and 'guilty gall-bladder' one must now add the 'indolent intestine' to the list of culprits in cholesterol gallstone formation.

https://onlinelibrary.wiley.com/doi/pdf/10.1046/j.1365-2036.2000.014s2039.x

Review: pathogenesis of gallstones.

Gallbladder stones (GBS) are found in up to 50% of patients receiving octreotide, but the reported prevalence of cholecystolithiasis in patients treated with octreotide is variable and little is known about gallstone incidence, composition, pathogenetic mechanisms, dissolvability, and primary prevention. Octreotide treatment apart, in industrialised societies most GBS are mixed in composition, cholesterol-rich (arbitrarily greater than 70% cholesterol by weight), radiolucent (70%), and, given a patent cystic duct (70%), dissolvable in bile rendered unsaturated in cholesterol by oral ursodeoxycholic (UDCA) +/- chenodeoxycholic (CDCA) acid treatment. They form when (1) GB bile becomes supersaturated with cholesterol (as the molar ratio of cholesterol to phospholipids in biliary vesicles approaches 1:1, the vesicles become unstable); (2) there is an imbalance between pro- and anti-nucleating factors, which favors cholesterol crystal precipitation; and (3) there is stasis within the GB as a result of altered motor function and/or excess mucus that traps the crystals. These changes may be associated with altered (4) biliary bile acid composition (more DCA and less CDCA than normal), and/or (5) phospholipid fatty acid composition (arachidonyl-rich lecithin acting as a substrate for mucosal prostaglandin synthesis which, in turn, may influence both gallbladder motility, and mucus glycoprotein synthesis and secretion). During octreotide treatment, meal-stimulated cholecystokinin (CCK) release is impaired leading to GB hypomotility, but little is known about the effects of octreotide on biliary cholesterol saturation, crystal nucleation time, mucus glycoprotein concentration, bile acid or phospholipid fatty acid composition. Most, but not all, reports suggest that the prevalence of GBS in octreotide-treated patients is considerably greater than that in age-, sex-, and weight-matched controls, but proof (by pre-treatment and on-treatment ultrasound) that the GBS were absent before, but developed during, therapy is not always available. Furthermore, there are few data on analysis of GBS composition in patients developing stones during treatment, although initial reports suggest that octreotide-associated GBS are also radiolucent, cholesterol-rich, and dissolve with oral bile acid treatment. Maximum GBS attenuation values, measured in Hounsfield Units (HU) by localized computerized tomography scanning of the GB, predict stone composition and dissolvability: GBS with scores of less than 100 HU are cholesterol-rich and dissolve well with oral bile acid treatment. However, preliminary results in 11 acromegalic patients treated with 200 to 600 micrograms octreotide/d for 29 to 68 months show that the HU scores range from 23 to 490 (mean +/- SEM, 116 +/- 41), suggesting that at least four of these 11 patients have non-cholesterol stones.(ABSTRACT TRUNCATED AT 400 WORDS)

Gallstones during octreotide therapy.

From February 1988 to January 1990, 118 fine-needle diagnostic punctures of the gallbladder (DPG) were performed under continuous ultrasound (US) guidance on symptomatic patients with gallstones. The first attempt at gallbladder puncture and aspiration was successful in every patient with use of a 22-gauge needle and continuous US visualization of the needle tip. The aspirated volume varied between 3 and 88 mL (average +/- standard deviation, 25.0 mL +/- 15.3). Biliary analysis revealed an elevation of the cholesterol saturation index in patients with cholesterol gallstones (attenuation at computed tomographic examination of 50 HU or less) relative to that in patients with pigment stones (attenuation more than 50 HU) (1.3 +/- 0.2 vs 1.0 +/- 0.1, P less than .05). The nucleation time was prolonged in patients with pigment stones (19.3 days +/- 3.5 vs 1.8 days +/- 0.8 for patients with cholesterol stones, P less than .001). All patients remained hospitalized for 24 hours after DPG and were reexamined on an ...

Diagnostic fine-needle puncture of the gallbladder with US guidance.

The effect of ursodeoxycholic acid on recurrence prevention of choledochal calculi after endoscopic sphincterotomy (EPT) was evaluated in 46 patients, whose bile duct stones had been removed endoscopically. 22 patients received 500 mg of ursodeoxycholic acid once a day, 24 patients received placebo. 1 recurrent stone could be detected in the ursodeoxycholic acid treated group 19 months after EPT, whereas 4 recurrent stones occurred in the placebo group about 16 months after EPT. Cholesterol saturation index decreased significantly by the ursodeoxycholic acid treatment 12 and 24 months after EPT (0.93 +/- 0.17 vs. 0.69 +/- 0.12 vs. 0.72 +/- 0.07). The nucleation time increased statistically significant from 9.0 days to 20.4 (12 months) and 17.7 (24 months) days, respectively. Obviously, pharmacological effects of ursodeoxycholic acid exist which modify important processes in the gallstone's pathogenesis.

Preventing the recurrence of common bile duct calculi following endoscopic papillotomy with ursodeoxycholic acid

Within a 2-year period 677 diagnostic fine needle (DFP) and coarse needle punctures (DGP) were performed in 536 patients. In 34 patients (14 women; 20 men; 54 +/- 17.6 years) the abdominal tumour mass was punctured with the fine needle (22 g) as well as with the coarse (18 g) needle. Sensitivity of DGP accounted for 72%, sensitivity of DFP was 82.6%. Specificity was 100%, respectively. Complications could not be observed, neither with the coarse needle nor with the fine needle. Due to the high sensitivity of DFP this method should be employed first in the diagnostic work up of abdominal tumours.

Vergleich ultraschallgezielter Feinnadel- und Grobnadelpunktionen bei umschriebenen Läsionen im Abdomen

In 2 of 12 patients (16.6%) cholesterol monohydrate crystals occurred in duodenal bile samples after a 4 weeks fasting period (452 kcal/day). Cholesterol monohydrate crystals could be observed until recently mainly in patients with cholesterol gallstones. Therefore, this finding indicates increased biliary lithogenicity despite a non statistical decrease in CSI from 1.35 +/- 0.35 to 1.19 +/- 0.64. Presumably the increased lithogenicity may be caused by an increased glycoprotein concentration and an improvement in gallbladder contractility. Short time fasting obviously will be a risk factor for the development of gallstones, if weight and metabolic normalisation cannot be achieved.

[Changes in biliary lithogenicity caused by 4 weeks' weight reduction].

A modified gas chromatographic glass capillary technique for determination of five major bile acids (Cholic acid: CA, Chenodeoxycholic acid: CDCA, Deoxycholic acid: DCA, Lithocholic acid: LCA and Ursodeoxycholic acid: UDCA) has been developed after preliminary extraction with XAD-2 resin. Enzymatic hydrolysis prevents the formation of interferring degradation products. Ether extraction with centrifugation eliminates water soluble interferring substances. Derivatization to hexafluorpropyl- instead of methyl esters results in better separation, shortens analysis time and prolongs the life span of the column.

Determination of bile acids in serum and bile by a modified gas chromatographic glass capillary technique

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