Choledocholithiasis

Etiology

Choledocholithiasis occurs as a result of either the formation of stones in the common bile duct or the passage of gallstones that are formed in the gallbladder into the CBD. Bile stasis, bactibilia, chemical imbalances, increased bilirubin excretion, pH imbalances, and the formation of sludge are some of the factors which lead to the formation of these stones. Less commonly, stones are formed in the intrahepatic biliary tree, termed primary hepatolithiasis, and may lead to choledocholithiasis. Stones that are too large to pass through the ampulla of Vater remain in the distal common bile duct, causing obstructive jaundice that may lead to pancreatitis, hepatitis, or cholangitis. Gallstones are differentiated by their composition. Cholesterol stones are composed mainly of cholesterol, while black pigment stones are mainly made of pigment, and brown pigment stones are composed of a mix of pigment and bile lipids. Cholesterol stones make up approximately 75% of the secondary common bile duct stones in the United States, while black pigment stones comprise the remainder. Primary common bile duct stones are usually brown pigment stones. Obstruction of the CBD by gallstones leads to symptoms and complications that include pain, jaundice, and sepsis.[4][5]

Epidemiology

Choledocholithiasis has been found in 4.6% to 18.8% of patients undergoing cholecystectomy. The incidence of choledocholithiasis in patients with cholelithiasis increases with age. Cholelithiasis is more common in female patients, pregnant patients, older patients, and those with high serum lipid levels. Cholesterol stones are typically found in obese patients with low physical activity or patients that have recently intentionally lost weight. Black pigment stones are found in patients with cirrhosis, patients receiving total parental nutrition, and in those who have undergone an ileal resection. Nucleating factors, such as bacteria, are the source of the brown pigment primary common bile duct stones.[6][7]

Pathophysiology

Bile made in the liver and stored in the gallbladder can lead to gallstone formation. In some patients with gallstones, the stones will pass from the gallbladder into the cystic duct and then into the common bile duct. Most of the choledocholithiasis cases are secondary to the gallstones passage from the gallbladder into the CBD. Primary choledocholithiasis which is the formation of stones within the common bile duct is seen less commonly. Primary choledocholithiasis occurs in the setting of bile stasis, which results in intraductal stone formation. The size of the bile duct increases with age. Older adults with dilated bile ducts and biliary diverticula are at risk for the formation of primary bile duct stones. Less common sources of choledocholithiasis include complicated Mirizzi syndrome or hepatolithiasis. Bile flow is obstructed by stones within the common bile duct, which leads to obstructive jaundice and possibly hepatitis. The stagnant bile can also lead to bactibilia and ascending cholangitis. Cholangitis and sepsis are more common in patients with choledocholithiasis than other sources of bile duct obstruction because a bacterial biofilm typically covers common bile duct stones. The pancreatic duct joins the common bile duct near the duodenum, and therefore, the pancreas may also become inflamed by the obstruction of pancreatic enzymes. This is termed gallstone pancreatitis.[8]

History and Physical

The treating provider must assess the patient by conducting a thorough history and physical. This includes asking about the onset, timing, and severity of the patient's abdominal pain, in addition to any previous occurrences of similar pain. The pain is colicky, located in the right upper quadrant of the abdomen, and moderate in severity. The pain is intermittent and recurrent. Often, patients will endorse a history of episodes of epigastric, right upper quadrant pain, or epigastric pain. A thorough review of systems will reveal that the patient may have noticed a yellowing of his eyes or skin, experienced pruritus, and possibly nausea or vomiting. Jaundice occurs when the stones obstruct the CBD, and conjugated bilirubin enters the bloodstream. A history including, clay-colored stools and urine turning tea-colored is found in such patients. Jaundice can occur in episodes. A patient with cholangitis also may have a fever, chills, and possibly altered mental status (Charcot triad or Reynolds pentad). Gallstones are responsible for approximately half of all cases of pancreatitis. Pancreatitis is precipitated when CBD obstruction is at the level of the ampulla of Vater. Pancreatic pain is located in the epigastric and midabdominal areas, and is continuous (as compared to colicky in choledocholithiasis), and radiates to the back. Nausea and vomiting are also present. Some patients have intermittent pain, which results due to transient blockage within the common bile duct. Transient blockage occurs when due to floating stones or debris within the bile duct.

The provider should examine the patient with particular attention to the general appearance, skin, vital signs, and abdomen. Tenderness is noted in the right upper quadrant of the abdomen. Systemic signs such as fever, hypotension, and flushed skin, if present is indicative of infection, or sepsis. Courvoisier sign is the presence of palpable gallbladder on the exam and is seen when gallbladder dilation develops due to the obstruction of the common bile duct. Note should be made for any hyperthermia, diaphoresis, jaundice, scleral icterus, tachycardia, hypotension, tachypnea, or right upper quadrant abdominal tenderness.

Evaluation

The provider should order a white blood cell count, hemoglobin/hematocrit, platelet count, total bilirubin, direct bilirubin, alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase. In a patient with cholelithiasis, total bilirubin of greater than 3 mg/dL to 4 mg/dL, is strongly associated with choledocholithiasis. Gamma-glutamyl transpeptidase is also elevated. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations are elevated in biliary obstruction in a cholestatic pattern, with increases in alkaline phosphatase, serum bilirubin, and gamma-glutamyl transpeptidase (GGT) exceeding the elevations in serum AST and ALT. The positive predictive value of elevated liver tests is poor because liver tests are elevated due to a variety of other etiologies too. Thus, normal levels help in excluding choledocholithiasis. Symptom resolution, coupled with down-trending liver function tests, suggests that a patient has spontaneously passed the gallstone. A lipase should also be checked to assess for gallstone pancreatitis. An INR with prothrombin time can be ordered to assess the intrinsic liver function as well.

A transabdominal ultrasound is the first test that should be ordered for the patient suspected of any biliary disease, including choledocholithiasis. In most cases, an abdominal ultrasound will show a dilated common bile duct (more than 6 mm) and stones within the common bile ducts. The detection of CBD stones is typically impeded by the presence of gas in the duodenum, but ultrasound can identify CBD dilatation accurately with up to 90% accuracy. Abdominal ultrasonography has a sensitivity of 15-40% for detecting CBD stones. If a strong suspicion still exists based on history, physical, and laboratory findings in the face of a negative ultrasound, then a magnetic resonance cholangiopancreatography (MRCP) can be ordered. MRCP is also a noninvasive test with 92% sensitivity and a specificity of 100%. Endoscopic ultrasound also can be used to identify suspected choledocholithiasis, but it is more invasive than a transabdominal ultrasound or MRCP. This entails the introduction of an ultrasonic probe into the duodenum under endoscopic guidance. The sensitivity and specificity of CBD stone detection for MRCP, are reported in the range of 85-100%. Although diagnostic endoscopic retrograde cholangiopancreatography (ERCP) is more sensitive, it is no longer routinely performed given the approximately 10% risk for post-procedure pancreatitis.[9]

If a patient is undergoing laparoscopic or open cholecystectomy, an intraoperative cholangiogram also can be performed to assess for choledocholithiasis. It is performed by inserting a catheter into the cystic duct, followed by injection of contrast material, which outlines the biliary tree. Films are taken to assess for the presence of filling defects, and the flow of contrast into the duodenum. Intraoperative ultrasound or laparoscopic ultrasound will also identify choledocholithiasis. However, this technique is operator-dependent, and not commonly performed by general surgeons.

Treatment / Management

The treatment for choledocholithiasis is the removal of the obstructing stones via endoscopic means. An ERCP can be performed under general anesthesia, with the patient in either prone, left lateral, or supine position, though prone is the most common position used. The endoscopist will then place a duodenoscope into the second portion of the duodenum and advance a catheter and guidewire into the common bile duct. A sphincterotome then is used to cut the papilla, using cautery, and enlarge the ampulla of Vater. Often, the stones will be released with this maneuver. A variety of snares and baskets can be used to grasp the stones and remove them if needed. A balloon catheter also can be used to sweep the common bile duct to remove any stones. The endoscopist also can place a stent in the common bile duct, which will serve two purposes. First, any remaining stones will be softened, and potentially easier to remove with a second ERCP. Second, the stent will allow bile drainage to occur, preventing obstructive jaundice. If the stones are large, stuck, or there are many stones within the biliary tree, surgical removal is indicated. A laparoscopic or open common bile duct exploration is needed to remove any stones that can not be removed via endoscopic methods. An elective cholecystectomy is also recommended, during the same hospital admission, to prevent future episodes of choledocholithiasis.[10][11][12] (A1)

Cholecystectomy in patients with choledocholithiasis remains controversial, but most experts recommend it. Arguments can be made against cholecystectomy in patients who cannot tolerate surgery well (eg, due to age, medical problems), as long as the organ is asymptomatic.

Cholecystectomy is not indicated for primary CBD stones. Other surgical options include open choledochotomy, transcystic exploration (a technique to clear the CBD of stones during laparoscopic cholecystectomy), percutaneous extraction, and extracorporeal shock wave lithotripsy. The choice of treatment for choledocholithiasis found during surgery being done for cholelithiasis or cholecystitis includes intraoperative common bile duct exploration, intraoperative ERCP, and postoperative ERCP. The intraoperative procedure can be performed if consent was obtained preoperatively. Otherwise, ERCP is recommended at a later time, but during the same hospitalization. 

There are no medications that will cure choledocholithiasis. However, a one-time dose of 50 mg to 100 mg rectal indomethacin can be used to prevent post-procedure pancreatitis if the pancreatic duct was manipulated during an ERCP. Antibiotics are typically not needed for choledocholithiasis unless the patient also has associated cholecystitis or cholangitis.

Differential Diagnosis

Following are some important differential diagnoses of choledocholithiasis:

• Bile duct cancer
• Klatskin tumor
• Bile duct stricture
• Choledochal cyst
• Peptic ulcer disease
• Acute cholecystitis
• Sphincter of Oddi dysfunction
• Functional gallbladder disorder

Staging

The American Society for Gastrointestinal Endoscopy has proposed the following approach, which helps to stratify patients depending upon their probability of having choledocholithiasis. Following predictors are used for stratification:

Very Strong Predictors

• Serum bilirubin greater than 4 mg/dL
• The presence of a CBD stone on transabdominal ultrasound
• Clinical features of acute cholangitis

Strong Predictors

• Serum bilirubin of 1.8 to 4 mg/dL
• A dilated common bile duct on ultrasound

Moderate Predictors

• Age older than 55 years
• Abnormal liver biochemical test other than bilirubin
• Clinical gallstone pancreatitis
• Using the above predictors, patients are stratified as:

High Risk

• At least one very strong predictor and/or
• Both strong predictors

Intermediate Risk

• One strong predictor and/or
• At least one moderate predictor

Low Risk

• No predictors

Prognosis

The prognosis of choledocholithiasis depends on the presence of complications and their severity. Approximately 45% of patients with choledocholithiasis remain asymptomatic. Of all patients who refuse surgery or are unfit to undergo surgery, only 55% experience varying degrees of complications. Less than 20% of patients experience recurrence of symptoms even after undergoing therapeutic procedures. If treatment is initiated at the right time, the prognosis is deemed favorable under general circumstances.

Complications

Choledocholithiasis and its treatment can lead to several complications, such as:

• Post-ERCP Pancreatitis
• Sepsis
• Wound infection
• Cholangitis
• Retained and impacted stones
• Cholangitis
• Gallstone pancreatitis
• Respiratory insufficiency
• Biliary duct injury
• Renal failure
• Liver failure and cirrhosis
• Hepatic vascular injury