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Common bile duct stones are a common clinical disease in hepatobiliary surgery, and their incidence has increased significantly worldwide in recent years with changes in social living standards. According to the different sources of stones, it can be divided into primary and secondary two, primary choledocholiths in East Asian countries are more common than in Western countries, and bile duct stones in Western developed countries are mostly secondary to gallstones.
The main component of primary bile duct stones is bilirubin calcium, which belongs to biliary pigment stones or mixed pigment stones, and the occurrence mechanism is mostly related to bile infection and stasis, as well as nutritional insufficiency, parasitic infection and other factors; Secondary stones are mostly converted from gallbladder stones, and the main component is cholesterol, which is mainly related to excessive cholesterol secretion in the gallbladder, insufficient power of the gallbladder, cholesterol nucleation and crystallization acceleration.
Patients with common bile duct stones may have a variety of clinical symptoms, ranging from asymptomatic to biliary colic, pancreatitis, jaundice, or cholangitis, and can be life-threatening. Most common bile duct stones can be diagnosed by abdominal ultrasound, computed tomography, endoscopic ultrasound, or magnetic resonance cholangiography prior to endoscopic or laparoscopic removal. With the development of minimally invasive technology, its treatment methods are becoming more diversified, and the controversy of different treatment methods continues, this article reviews the epidemiology, etiology, clinical manifestations, diagnosis and treatment of common bile duct stones, focusing on the controversial parts of diagnosis and treatment.
Epidemiology of common bile duct stones
The incidence of cholelithiasis varies around the world, according to statistics, it is about 10%~15% in Western countries, and about 3%~5% in African and Asian countries. Cholelithiasis is more common in women, pregnant women, elderly and hyperlipidemic patients, and the incidence of cholelithiasis has changed significantly in recent years with changes in social living standards. About 60%~80% of cholelithiasis patients have no symptoms and do not need treatment.
People with cholelithiasis are more likely to develop bile duct stones with age. About 5%~15% of patients with symptomatic gallstones are found at the time of surgery, and the probability increases with age and duration of symptoms. It has been reported that the recurrence rate of common bile duct stones after endoscopic lithotomy is 3%~24%, even after cholecystectomy, common bile duct stones will still recur, the recurrence rate is 2%~10%, and the cumulative recurrence rate is 5.8%.
Causes of common bile duct stones
Primary choledocholithiasis has complex etiology, mainly found in East Asian countries, its gallstone type is biliary pigment stones or mixed pigment stones, the main component is bilirubin calcium, the cause is mainly related to parasitic infection, cholestasis, bile infection, malnutrition and other factors, the most important cause is bacterial infection and biliary ascariasis, parasites and bacterial colonies aggregation can be found in gallstones.
The lithogenic mechanism of biliary infection is mainly as follows: bacterial enzymes (such as β-glucuronidase) hydrolyze bilirubin diglucuronic acid to form deconjugated bilirubin, and calcium ions to form unconjugated bilirubin calcium salt, in addition, bacterial phospholipase induces bile phospholipid decomposition, producing water-insoluble free fatty acids and lysophospholipids, bilirubin calcium salt combined with de-bound bile acids, long-chain saturated fatty acids and cholesterol to form stones.
The mechanism of primary intrahepatic cholesterol stones is still unclear, and recent studies have shown that the formation of intrahepatic stones is based on a double defect of up-regulation of hepatic cholesterol synthesis and down-regulation of bile acid synthesis, which may be related to the defect of phospholipid secretion by its tubular transporter multidrug-resistant protein (MDR3).
Secondary bile duct stones, caused by the fall of gallstones through the cystic ducts, are mainly cholesterol stones and have the same etiology as gallstones, which were previously thought to be caused by inflammation of the gallbladder, cholestasis, and absorption of bile salts by the damaged mucosa. However, it is now known to be the result of biliary supersaturation caused by excessive secretion of cholesterol in the gallbladder, insufficient motility of the gallbladder, acceleration of cholesterol nucleation and crystallization, and accumulation of mucin gel.
Clinical manifestations of common bile duct stones
(1) Asymptomatic common bile duct stones
About 5.2%~12% of patients with common bile duct stones do not show obvious symptoms clinically, but most of them are found incidentally during ultrasound examination during physical examination, or found during CT and MRCP examination due to a history of gallstones, or diagnosed by cholangiogram during cholecystectomy. Although asymptomatic common bile duct stones do not have clinical manifestations such as jaundice, cholangitis, pancreatitis, and liver function impairment for the time being, the presence of bile duct stones is a long-term cause of complications such as biliary obstruction and liver function damage in the future.
(2) Biliary colic
Biliary colic is the most common manifestation of common bile duct stones, usually in the right upper abdomen or epigastric region, usually lasting 30 minutes to several hours, and up to 60% of patients experience radiation pain in the back and right shoulder. Biliary colic is generally not relieved by postural changes or bowel movements, and is not related to food intake. Pain is thought to be caused by increased pressure caused by partial or complete blockage of the common bile duct leading to dilation of the common bile duct.
(3) Obstructive jaundice
Partial or complete obstruction of the bile duct can lead to obstructive jaundice, and the severity, occurrence, and duration of jaundice depend on the location, degree, and co-infection of the obstruction, and are characterized by fluctuations. Obstructive jaundice can lead to secondary fatal consequences such as cholangitis, renal dysfunction, cardiovascular dysfunction, and coagulopathy, and chronic obstruction can also lead to secondary biliary cirrhosis and portal hypertension.
(4) Acute cholangitis
Acute cholangitis is a severe purulent infection affecting the bile ducts, usually caused by bacterial infection rising from the duodenum, the most common infectious pathogens are gram-negative bacteria (such as Escherichia coli, enterobacteriaceae, Klebsiella, etc.), less common gram-positive bacteria (such as enterococci, etc.) and mixed anaerobic bacteria (such as bacteroides, clostridial bacillus, etc.).
About 50%~70% of patients present with jaundice, chills, fever and abdominal pain (Charcot's triad). In severe cases, in addition to Charcot's triad, patients may develop altered mental status and shock, known as Raynaud's quint, which can be life-threatening if left untreated.
(5) Acute biliary pancreatitis
4%~8% of patients with cholelithiasis will develop biliolithiasis secondary to migrating gallstones. The main mechanism is ampullary stenosis caused by the fall of common bile duct stones, and the stones can lead to mucosal injury and secondary infection or edema, which worsens the stricture. Ampullary stenosis combined with increased biliary pressure causes bile to flow backwards into the pancreas, activating pancreatic enzymes and causing the pancreas to digest itself, resulting in acute pancreatitis.
So far, choledocholithiasis is still the most common cause of acute pancreatitis, accounting for about 30%~60% of all cases. Smaller stones are more likely to develop gallstone pancreatitis than larger stones. In a study by Venneman, it was found that bile duct stones in patients with gallstone pancreatitis had an average diameter of 4 mm, while those with obstructive jaundice had an average diameter of 9 mm.
Choice of auxiliary test for diagnosis of common bile duct stones
Bile duct stones are usually suspected in patients with jaundice and elevated liver function tests. Common bile duct stones can be diagnosed by abdominal ultrasound, computed tomography, magnetic resonance, endoscopic ultrasonography, or cholangiography, combined with history, symptoms, and laboratory tests. ERCP is also a diagnostic approach for common bile duct stones, but it is an invasive test that may cause associated complications and has been gradually replaced by other tests and selected only when necessary.
Laboratory tests
Laboratory tests are useful in determining the presence of biliary obstruction and in ruling out other differential diagnoses, with liver function tests being the most commonly used as serum bilirubin, alanine aminotransferase, and aspartate aminotransferase, alkaline phosphatase, and γ-glutamyl transpeptidase. Elevated serum alkaline phosphatase and γ-glutamyl transpeptidase were the most common abnormalities in patients with symptomatic choledocholithiasis (elevated in 91% and 94% of cases, respectively).
γ-glutamyl transpeptidase is considered to be the most specific and sensitive index for the diagnosis of common bile duct stones other than jaundice, and γ > 90 U/L of glutamyl transpeptidase often indicates biliary obstruction, especially in the presence of common bile duct stones. Serum aminotransferase activity is markedly elevated in the first 72 hours of biliary obstruction, particularly in the first 72 hours of biliary obstruction, and alkaline phosphatase and bilirubin levels increase gradually if obstruction persists. If liver function is normal in the first 24 hours after the onset of abdominal pain, and if ultrasound does not show bile duct dilation, the likelihood of developing a common bile duct is very low.
With an increase in the duration and severity of biliary obstruction, these indicators of liver function gradually increase. One study showed that serum bilirubin concentrations of at least 1.7 mg/dL (29 micromol/L) predicted 60% specificity for common bile duct stones, while specificity increased to 75% at a cut-off value of 4 mg/dL (68 micromol/L); However, only one-third or fewer patients with choledocholithiasis show significant hyperbilirubinemia. There is still no single biochemical measure or combination that can predict common bile duct stones well. This prediction is compensated for by producing complex risk assessment maps or scoring systems based on various preoperative data.
However, these are never really used in clinical practice because they are often too complex or unreliable to use. A continuous study of 1390 cholecystectomy cases showed 60% accuracy with common bile duct stones when based solely on changes in liver function indicators, 69% when liver function indicators were combined with imaging, and 42% when imaging tests alone. In a prospective trial of 1171 cholecystectomy, 42% of patients were found to have elevated liver function values, 20% had a history of acute pancreatitis, and 9% had acute cholecystitis.
The relationship between elevated liver function markers and common bile duct stones was stronger in patients undergoing elective cholecystectomy compared with emergency surgery. However, when alkaline phosphatase and bilirubin are normal, the risk of common bile duct stones is only 6%. A retrospective cohort study based on the ACS-NSQIP database found that important positive predictors of common bile duct stones were female sex, elevated BMI, abnormal bilirubin, aspartate aminotransferase, and alkaline phosphatase. People with cholecystitis with a history of chronic cholecystitis are more likely to have common bile duct stones.
Abdominal ultrasound
Abdominal ultrasound is often used to screen for gallstones, but the sensitivity for diagnosing common bile duct stones is relatively low, especially if the stones do not cause bile duct dilation, which is the case in about half of patients, but can be as sensitive as 80% by experienced operators. Ultrasound evidence of bile duct stones, common bile duct dilation, acute cholangitis, and jaundice is the best predictor for the diagnosis of common bile duct stones. Because of its high specificity, abdominal ultrasound remains an important modality and is often used as the primary imaging modality, along with laboratory tests, as a first-line test for common bile duct stones.
Endoscopic Ultrasonography (EUS)
EUS is an endoscopic method of placing an ultrasound probe inside the duodenum, which provides detailed imaging of the common bile duct, especially distal bile duct, with greater than 90% sensitivity and specificity for common bile duct stone examination. EUS is also a valuable diagnostic modality for detecting gallstones, silt, or micro-bindings, and in identifying the presence of incarcerated stones in the papillary area early in acute biliary pancreatitis.
EUS and MRCP have similar accuracy of 5 mm for common bile duct stone >, but EUS is more cost-effective than MRCP. Meta-analysis showed a sensitivity of 95% and specificity of 97% for EUS and 93% sensitivity and 96% specificity for MRCP. EUS is more sensitive for fine stones (diameter < 3 mm) located distal to the bile duct. However, EUS relies on physician technique and cannot identify stones above the common hepatic duct.
Intraoperative laparoscopic ultrasound
Intraoperative laparoscopic ultrasound has been increasingly used to replace intraoperative cholangiography, which is a safe, rapid, radiation-free and effective technique, and can be applied to pregnant women and patients allergic to contrast agents, and its sensitivity and specificity for diagnosing common bile duct stones are 76%~100% and 96.2%~100%, respectively. Compared with intraoperative cholangiography, intraoperative laparoscopic ultrasound has a lower failure rate (0%~7%) and less time consuming (5-10min increase in operation time).
In addition, when cholecystectomy is performed, intraoperative laparoscopic ultrasound can identify anatomical structures in the presence of severe local inflammation. Currently, the main disadvantages of intraoperative laparoscopic ultrasound are that it is very dependent on operator familiarity, a long learning curve, and the cost of purchasing a probe.
CT
CT has a high sensitivity for common bile duct dilation, and can also judge epigastric pain and other causes of gallstone complications, conventional CT detection of common bile duct stones has a sensitivity of about 80%, specificity of about 90%, oral contrast enhanced CT has a higher sensitivity, 92%.
CT is a common test, especially useful in patients with subtle abdominal symptoms. However, CT is not reasonable as a routine test to diagnose common bile duct stones before cholecystectomy because it has a low positive predictive value and some radiation.
MRCP
MRCP has become a recognized alternative to diagnostic ERCP. In most studies published to date, MRCP has a sensitivity and specificity of 90% or better relative to ERCP, but a few studies have shown MRCP sensitivity to ERCP to be lower than this.
One study showed that MRCP sensitivity decreased from 100% to 71% for stones < 5 mm in diameter. Studies using ERCP as a reference standard confirm that MRCP's ability to diagnose common bile duct stones, while generally good, is affected by stone diameter. MRCP is not dependent on operator technology and provides a complete picture of the intrahepatic and intrahepatic ductal system and pancreatic duct, but is prone to missed smaller stones. Despite its good results, it is not recommended as a routine examination due to its high price, and is not suitable for patients with metal and claustrophobia.
Common bile duct stones found in symptomatic patients have a high complication rate if left in place (about 50% of patients subsequently develop jaundice, cholangitis, biliary colic, or pancreatitis). Patients with asymptomatic bile duct stones may have serious complications such as cholangitis and pancreatitis even if they have no obvious symptoms, and treatment is still recommended, and the main treatment methods for common bile duct stones are endoscopic treatment and surgical treatment, but the best treatment method is still controversial.