B8. Clinical manifestations of gallstone disease. Laparoscopic cholecystectomy
Gallstone disease
Cholelithiasis refers to the presence of gallstones in the gallbladder, while choledocholithiasis refers to gallstones in the common bile duct. Gallstone disease refers to various clinical manifestations of the presence of gallstones, including:
- Uncomplicated gallstone disease
- Complicated gallstone disease
Complicated gallstone disease refers to the presence of gallstone-related complications, mentioned above. Complicated gallstone disease may present with biliary colic. If biliary colic is present without gallstone-related complications, the condition is called uncomplicated gallstone disease.
The majority of gallstones are asymptomatic (and therefore not considered as gallbladder disease) and are discovered incidentally on imaging. Gallstones exist in 10 – 15% of the Western population, but only 1 – 4% become symptomatic.
Risk factors for gallstone disease
The risk factors for the two different stones are different. For cholesterol stones:
- 6 Fs
- Fat (obesity)
- Female
- Fertile (multiparity or pregnancy)
- Forty (above 40 years of age)
- Fair-skinned (Caucasian)
- Family history
- Gallbladder stasis
For pigment stones:
- Chronic haemolytic anaemias
- Billiary infection
- Gastrointestinal disorders
- Crohn disease
- Ileal resection
- Cystic fibrosis with pancreatic insufficiency.
Pathology
Two types of stones exist. The most common type is the cholesterol stone, which accounts for 80% of all stones in the west. Bile formation is the only significant pathway for the body to eliminate excess cholesterol, either as free cholesterol or as bile salts. Cholesterol is dissolved in bile. The solution gets supersaturated if the cholesterol concentration exceeds the solubilization capacity of the bile.
Cholesterol won’t crystallize out of the solution until there is a nucleus, a “starting point” that it can precipitate onto. This nucleation process is then followed by growth, as more and more cholesterol precipitate into the nucleus, causing the stone to grow in size. Biliary stasis is also essential for the development of a stone.
It should be noted that most cholesterol stones aren’t comprised of only cholesterol. They most commonly also contain some bilirubin-calcium or palmitate-calcium salts. Pure cholesterol stones are rare.
The second type of stone is the pigment stone, which is primarily comprised of bilirubin-calcium salts. These usually occur in association with chronic haemolysis, which increases the production of bilirubin.
Cholesterol stones arise exclusively in the gallbladder and are yellowish. Pigment stones may arise anywhere in the biliary tree and are black or brownish.
Diagnosis and evaluation
Leukocytosis is often present in cholecystitis and cholangitis. An afebrile patient with biliary colic and normal inflammatory parametres likely has uncomplicated gallstone disease. Elevated liver enzymes, bilirubin, or jaundice is suspicious for choledocholithiasis.
Ultrasound is the most sensitive imaging modality for detecting gallbladder stones and evaluating the biliary tree.
Abdominal CT may be used to rule out certain complicated gallstone diseases, like gangrenous cholecystitis, gallbladder perforation, emphysematous cholecystitis, or gallstone ileus. CT cannot visualise the stones themselves well.
Biliary colic
Biliary colic is the clinical manifestation of uncomplicated gallstone disease. It refers to recurrent attacks of severe pain of typical character caused by gallstones. It is not dangerous, but it is bothersome. Treatment involves avoidance of fatty foods and analgesics during attacks. The only definitive treatment is cholecystectomy.
Pathology
Biliary pain occurs because the gallbladder tries to contract to push out a gallstone which is impacted in the gall bladder neck, which increases the pressure in the gallbladder, or because the stones irritate the gall bladder wall during contraction.
Clinical features
Uncomplicated gallstone disease presents with attacks of biliary colic. This pain is intense, dull, constant, and is usually located in the right upper quadrant or epigastrium. The pain may radiate to the back or shoulder. The patient usually feels a strong urge to keep moving, rather than lying still. Worsening after food intake is typical but not always present. Sweating and nausea/vomiting is usually also present. Despite the name, the pain is usually constant rather than colicky. The attack usually lasts a few hours and rarely less than 30 minutes. These attacks often recur.
Diagnosis and evaluation
In uncomplicated gallstone disease, there are no elevated inflammatory parametres or signs of cholestasis (elevated ALP/GGT or bilirubin), and no fever. Ultrasound can show the presence of cholelithiasis, but imaging is not necessary for the diagnosis if the clinical features are typical and complicated gallstone is ruled out.
Treatment
Biliary colic itself is not an indication for surgery, unless the patient has many episodes of them. In many cases, patients can live with these attacks if they're rare enough and not that severe (or painkillers have sufficient efficacy).The only definitive way to prevent episodes is cholecystectomy.
Reducing fatty foods in the diet reduces the risk for attacks.
Analgesia during the attacks is important. The first choice is NSAIDs like ketorolac, diclofenac, or ibuprofen, and the second choice is opioids like morphine. Many are reluctant to use morphine as it theoretically contricts the sphincter of Oddi, and alternative opioids which cause less constriction (like buprenorphine or meperidine) are often used instead. However, systematic reviews have found that all opioids cause sphincter constriction, and there is no evidence that morphine is worse than other opioids in this regard.
Peripheral anticholinergics like butylscopolamine/hyoscine (Buscopan®) can reduce the biliary spasm and improve the pain when combined with NSAIDs, but they've not shown to be better than NSAIDs alone.
Choledocholithiasis
Choledocholithiasis is a form of complicated gallstone disease characterised by a gallstone stuck in the common bile duct. It causes cholestasis, and may lead to cholangitis, a severe bacterial infection or acute biliary pancreatitis.
Clinical features
Patients presents with biliary colic-like pain, but choledocholithiasis pain usually lasts longer. Jaundice may be present.
Diagnosis and evaluation
Laboratory investigations show signs of cholestasis, including hyperbilirubinaemia and elevated ALP/GGT. Unlike in cholangitis, there are no laboratory signs of inflammation.
Imaging, usually ultrasound, is indicated to visualise the obstruction.
Treatment
Removal of the obstruction, usually by ERCP, is indicated. Cholecystectomy is indicated to prevent future occurances.
Cholecystitis
Acute calculous cholecystitis is one manifestation of complicated gallstone disease characterised by inflammation of the gallbladder secondary to cystic duct obstruction by a gallstone. It's not necessarily infected by bacteria, but it may be.
Acute calculous cholecystitis may be complicated by gallbladder gangrene, perforation, or emphysema.
Clinical features
Cholecystitis usually presents with right upper quadrant pain which lasts longer than biliary colic, fever, nausea/vomiting, and positive Murphy sign (may be negative in elderly). The patient usually appears ill and may have abnormal vital signs.
Murphy sign refers to the patient abruptly stopping a deep inspiration during palpation of the upper right quadrant due to sudden pain. This occurs because during inspiration, the tender gallbladder is pushed caudally by the expanding lungs, eventually hitting the palpating hand. Note that Murphy sign is not sensitive in elderly.
Diagnosis and evaluation
Laboratory tests show elevated inflammatory parametres. Ultrasound shows gallbladder wall thickening or oedema, and it will likely show gallstones as well. There is usually no evidence of cholestasis, unless there is concomitant choledocholithiasis.
Treatment
Left untreated, most symptoms of cholecystitis are self-limiting. However, the risk of developing complications is high, so treatment is indicated.
Even though the infection is not necessarily bacterial, antibiotics are used in the acute phase (in Norway ampicillin + gentamycin + metronidazole is used). If the patient is really ill or antibiotics are insufficient to clear the infection, we must achieve source control by gallbladder drainage or emergency surgery. Gallbladder drainage can be achieved percutaneously or endoscopically (with ERCP).
The definitive treatment for acute calculous cholecystitis is laparoscopic subtotal cholecystectomy, to prevent both complications and recurrence. There are two approaches to the timing of cholecystectomy, early surgery (during the same hospital admission) and delayed surgery (elective surgery after 6+ weeks).
In most cases, we opt for early surgery. In complicated cases, one may opt for delayed surgery. This allows the inflammation to heal, making surgery less risky.
Complications
Gangrenous cholecystitis
Some people (around 20% of cholecystitides) develop gangrenous cholecystitis, which is more severe than "regular" acute cholecystitis and which may cause sepsis.
Gallbladder perforation
10% of cholecystitis cases are complicated by gallbladder perforation, which may form an abscess or cause peritonitis.
Emphysematous cholecystitis
Cholecystitis complicated by secondary infection with gas-forming bacteria like clostridium may cause cholecystitis with gas in the gallbladder wall. This increases the risk for gangrene or perforation. It's difficult to distinguish from "regular" acute cholecystitis, but crepitus in the abdominal wall may be present.
Cholangitis
Cholangitis is a severe bacterial infection and a form of complicated gallstone disease characterised by infection of the biliary tree secondary to stasis secondary to an obstruction of the common bile duct, usually a gallstone, called choledocholithiasis. It's characterised by Charcot's triad of fever, abdominal pain, and jaundice. Urgent treatment with source control and antibiotics is important. It may cause sepsis.
Patients can present with choledocholithiasis which has not yet been complicated by an infection.
Clinical features
Cholangitis usually presents with Charcot’s triad of fever, abdominal pain, and jaundice. Patients are usually ill-looking and may be septic.
Diagnosis and evaluation
Laboratory tests show evidence of cholestasis, especially hyperbilirubinaemia, and elevated inflammatory parametres. Obtaining blood cultures is important.
Imaging (usually ultrasound or MRCP) is indicated to visualise the obstruction, but if the clinical features make the diagnosis obvious one proceeds directly to ERCP, which can both visualise the obstruction and often treat it.
Treatment
Urgent treatment of cholangitis is important and involves antibiotics and source control.
Broad spectrum antibiotics are indicated until culture data is available. In Norway, ampicillin + gentamycin + metronidazole is used.
Source control is achieved by ERCP, which can remove the stone or obstruction, decompress the biliary tree, and place a stent in the common bile duct if necessary. It can also collect samples for culture. Should ERCP fail, one can drain bile pecutaneously.
Following resolution of the acute infection, the underlying cause of the biliary obstruction must be treated. In case of choledocholithiasis, cholecystectomy is indicated to prevent future attacks.
Gallstone ileus
Gallstone ileus is a rare but severe complication of gallstone disease where chronic inflammation of the gallbladder has formed a fistula between the gallbladder and duodenum, through which a gallstone can pass. This gallstone can obstruct the small bowel, causing ileus. These fistulae take a long time to form and are due to long-standing necrosis of the gallbladder wall due to pressure from a gallstone. Gas inside the biliary tract on imaging is diagnostic. The stones are usually larger than 2.5 cm when they cause ileus.
Gallstone ileus requires emergency surgery. An enterotomy is made proximal to the stone, and the stone is then removed. Cholecystectomy and fistula closure should be performed at the same occasion or later.
Cholecystectomy
Cholecystectomy is the surgical removal of the gallbladder. In almost all cases, it's performed laparoscopically. It's a relatively technically simple procedure.
Indications
Cholecystectomy is the definitive treatment for gallstone disease, especially cholecystitis, biliary colic which isn't controlled conservatively, choledocholithiasis, and cholangitis caused by choledocholithiasis.
Timing
There are two approaches to the timing of cholecystectomy in case of cholecystitis, early surgery and delayed surgery. This is to avoid performing surgery on an inflamed organ if possible.
In most cases, we opt for delayed surgery. In that case, the patient is treated conservatively, and if they respond to this the surgery is delayed for 6 – 8 weeks, after the acute inflammation has resolved, which reduces the risk for perioperative complications.
If the patient does not respond to initial conservative therapy, or they have indications for acute surgery like pericholecystic fluid or evidence of gangrene or perforation on imaging, surgery will be performed acutely.