The prevalence of gallbladder stones in adults is approximately 5-25% in Western countries, and it is important to understand the outcomes, complications, and proper treatment options associated with gallbladder stones. Kurinchi et al. from the Royal Free Hospital in the United Kingdom conducted a review of advances related to gallbladder stones, which was published in the April 22, 2014 issue of BMJ.
Definition
Gallbladder stones are crystals deposited in the gallbladder with a prevalence of approximately 5-25%, with a higher prevalence in Western populations, women and elderly people. Depending on the composition of the stones, gallbladder stones can be classified as cholesterol stones, bile pigment stones and mixed stones (both cholesterol and bile pigment stones).
In recent years, several new classifications have been introduced based on microscopic analysis of the structure and composition of the stones, although most gallstones are still classified as cholesterol stones (about 37%-86%), bile pigment stones (2%-27%), calcium stones (1%-17%), and mixed stones (4%-16%). Gallbladder stones can be classified according to their causes, prevention methods, imaging and response to lithotropic drugs, but regardless of the classification method, current guidelines for the management of gallbladder stones are applicable to all types.
Predisposed population
The formation of gallbladder stones is associated with a change in the balance between nucleation and inhibition factors in the bile. The causes that contribute to stone formation are: excess cholesterol in the bile, low levels of bile salts, reduced gallbladder motility, and reduced levels of phosphatidylcholine molecules, the latter organizing cholesterol to form crystals.
The main risk factors for cholesterol stones are: female, pregnancy, high estrogen use, aging, race (higher prevalence in Native American Indians and lower prevalence in black Americans and people from China, Japan, India and Thailand), genetics, obesity, high triglyceride levels, low HDL levels, sudden weight loss, high energy diet, refined carbohydrate diet, lack of exercise, cirrhosis of the liver , Crohn’s disease and impaired gallbladder contraction (e.g., post-gastrectomy or post-vagotomy).
Hemolysis and chronic bacterial or parasitic infections are often considered to be the main risk factors for gallstones, but all three of these factors can often be avoided.
Prevention
Although some risk factors associated with gallstones such as obesity, sudden weight loss, high energy diet, refined carbohydrate diet, and lack of exercise can be avoided by lifestyle changes, there is no evidence that lifestyle changes are effective in reducing the incidence of gallstones.
Early detection of sickle cell anemia, so that appropriate measures can be taken to prevent the occurrence of hemolysis, or prophylactic antibiotics for post-splenectomy patients and patients with splenic infarction to prevent infection and thus prevent the occurrence of gallstones.
Another way to prevent gallstones is to remove the gallbladder, for those undergoing bariatric surgery (since sudden weight loss is also a risk factor for gallstone formation) and for patients with symptomatic gallstones. If other major abdominal surgery is required at the same time, the gallbladder can be removed together to avoid further surgery.
There is no evidence to support prophylactic cholecystectomy in patients without stones in the gallbladder, and there is no evidence to suggest that the above methods of gallstone prevention are effective.
Clinical presentation
The most common symptom is biliary colic (pain in the right upper abdomen lasting more than half an hour), usually without fever. If fever is present, it is often indicative of cholecystitis or cholangitis. Other symptoms include epigastric pain and nausea after eating fatty or fried foods, bloating, and frothy and putrid smelling stools.
Complications of gallstones include cholecystitis (0.3%-0.4% per year), acute pancreatitis (0.04%-1.5% per year), obstructive jaundice (0.1%-0.4% per year), and less common complications such as acute cholangitis and intestinal obstruction.
Among them, acute pancreatitis and cholangitis can be life-threatening complications, with a mortality rate of 3%-20% for the first episode of acute pancreatitis and 24% for acute cholangitis.
Other complications can often occur with biliary colic alone, and patients with a history of biliary colic attacks are at higher risk for complications. Although studies have shown an association between gallstones and biliary tract tumors, there is no evidence of a causal relationship, and it is likely that some of the risk factors for these associations are the same.
Related tests
Ultrasound is nowadays the first-line test for the diagnosis of gallstones, and its accuracy is high (sensitivity of 90% and specificity of 88%) even when performed by a non-imaging physician.
According to the conference consensus, acute cholecystitis needs to be suspected when local or systemic inflammatory manifestations are present, such as Murphy’s sign (pressure pain under the right upper abdominal rib cage during deep breathing, 65% sensitivity, 87% specificity), fever, elevated leukocytes or CRP, and the diagnosis can be confirmed by ultrasound, CT, or MRI.
Imaging manifestations of acute cholecystitis include thickening of the gallbladder wall (>4 mm), enlargement of the gallbladder (long diameter >8 cm, short diameter >4 cm), or peribiliary effusion.
Complicated acute pancreatitis should be suspected when there is epigastric pain radiating to the back, which together with total abdominal pain, elevated blood and urine amylase, elevated blood lipase and imaging support, such as pancreatic swelling with peripancreatic exudate helps to confirm the diagnosis.
According to the conference consensus reached by the European Society for Endoscopic Surgery, when obstructive jaundice is present (yellowish skin sclera and darkened urine), concomitant common bile duct stones should be considered and laboratory tests may reveal elevated serum bilirubin and alkaline phosphatase, and the diagnosis is confirmed by MRCP and EUS. If jaundice is combined with fever and chills, one should be alert to cholangitis.
Ultrasonography can be used selectively when the patient presents with symptoms related to gallstones and is in good general condition without manifestations of acute cholecystitis, acute pancreatitis, obstructive jaundice or cholangitis, and is recommended for regular follow-up by their general surgery department. If complications are suspected, immediate surgical consultation is necessary, as early detection and treatment of complications usually have a better prognosis.
The main signs indicating the presence of complications are: fever, chills, hypotension, epigastric pain radiating to the back, darkening of the urine, jaundice, positive Murphy’s sign, total abdominal cramps, and positive urinary bilirubin. According to the clinical manifestations, laboratory tests such as routine blood, CRP, blood and urine amylase, blood and urine lipase, alkaline phosphatase and imaging tests such as ultrasound, CT, MRI, MRCP, EUS should be performed to further confirm the presence or absence of complications.
Treatment
1. Asymptomatic gallstones
Distinguishing asymptomatic from symptomatic gallstones is sometimes difficult because symptoms are sometimes mild and each person has a different level of sensitivity. Although complications of gallstones can be diagnosed by the above criteria, it is difficult to confirm whether symptoms are related to gallstones in patients suspected of having epigastric pain and dyspepsia.
One study showed that 90% of patients with typical biliary colic had relief of symptoms after cholecystectomy, suggesting that biliary colic can reliably indicate the presence of gallstones; 70% of patients with epigastric pain (with no restriction on pain intensity and duration) had relief of symptoms after cholecystectomy; only 55% of dyspeptic patients had relief of symptoms after removal of the gallbladder, suggesting that most patients with suspected epigastric pain and dyspepsia may not be related to gallbladder stones.
There is no evidence that lifestyle changes, such as reducing fat intake and increasing exercise, can reduce or prevent symptoms. Treatment of patients with asymptomatic gallstones (whether cholesterol stones, bile pigment stones, or mixed stones) is not recommended at this time, unless the gallbladder is porcelain (due to its association with gallbladder cancer). Although this remains controversial, surgery is not recommended for patients with asymptomatic gallstones due to the complications that arise after surgical intervention.
If an asymptomatic patient with gallstones happens to require a major abdominal surgery, it seems reasonable to recommend a concomitant cholecystectomy, since the postoperative adhesions will make it difficult to perform a cholecystectomy in the future. However, there is no RCT or systematic evaluation to support the above recommendation.
2. Symptomatic gallstones
Cholecystectomy is the primary treatment for gallbladder stones, and RCTs, systematic evaluations, and cohort studies have shown that extracorporeal shock wave lithotripsy and ursodeoxycholic acid have a low cure rate. 27% of patients treated with ursodeoxycholic acid for gallstones had their stones dissolve, and 55% of carefully selected patients with extracorporeal microwave lithotripsy had their stones disappear.
Although some patients were able to eliminate stones with these methods, the recurrence rate of stones remained high, reaching more than 40% within 4 years. After three months of ursodeoxycholic acid, 26% of patients had no recurrence of biliary colic, compared with 33% in the placebo group. In addition, approximately 2% of patients taking ursodeoxycholic acid developed complications, which is similar to the annual complication rate in patients not taking medication.
In patients whose systemic status does not allow cholecystectomy, percutaneous cholecystostomy (temporary drainage of bile outside the body through a catheter under imaging guidance) may play an emergency role, although systematic evaluations have shown that the value of percutaneous cholecystostomy is unclear. Once the patient’s general condition improves, cholecystectomy may be considered.
Some RCTs suggest that cautious observation may avoid surgery for a small proportion of patients without recurrent symptoms, but no one can predict which patients will have recurrent episodes.
3. Pros and cons of cholecystectomy
Although cholecystectomy is a relatively safe operation with few serious complications, there may be long-term complications. Short-term postoperative mortality is 0%-0.3%, and biliary tract injury was previously thought to occur in 0.5% of patients. Data from the Swedish Gallstone Surgery and ERCP Registry on 50,000 patients indicate that biliary tract injury occurred in 1.5% of patients who underwent cholecystectomy between 2005 and 2010, and that 1/5 (0.3%) of these injuries included partial or complete biliary tract dissection. The one-year mortality rate is significantly higher in patients with biliary tract injury than in patients without biliary tract injury.
Cholecystectomy is often performed laparoscopically because of its short hospital stay, minimal pain, early recovery, and minimal scarring. After cholecystectomy, a small percentage of patients may develop fat intolerance and thus a low-fat diet is often recommended for such patients; however, there is no evidence for the exact role of a low-fat diet.
For patients with symptomatic gallstones and common bile duct stones, treatment options include open cholecystectomy + common bile duct exploration, laparoscopic cholecystectomy + common bile duct exploration, and laparoscopic cholecystectomy + endoscopic sphincterotomy (preoperative, intraoperative, and postoperative).
A systematic evaluation showed no difference in stone removal rates between endoscopic sphincterotomy and laparoscopic common bile duct exploration, but the results were inconsistent in comparing the length of stay between the two.
4. Optimal time of surgery
The timing of surgery for different indications is still controversial. In patients with episodes of biliary colic, there is no medical reason to postpone the procedure, although it may be limited by medical resources (some surgeons may also recommend weight loss before surgery in some patients).
An RCT comparing the incidence of complications and length of stay in patients who underwent surgery within 24 hours of admission and those who waited an average of 4 months for surgery showed that the latter had a significantly higher incidence of complications (0% vs 22.5%) and a longer length of stay (the latter averaged 1 day longer than the former).
The optimal timing of cholecystectomy in patients with acute cholecystitis is also controversial. Conventional wisdom suggests that it is best to allow the inflammation to stabilize for at least 6 weeks before performing cholecystectomy. Relevant systematic evaluations have shown that surgical treatment within 1 week from the onset of symptoms prevents the development of more serious complications while waiting for surgery. Early LC reduced the length of hospital stay by an average of 4 days without increasing the incidence of surgical complications (5-6% in each group) or the need for conversion to open surgery (approximately 20% in each group).
Patients awaiting surgery may have prolonged pain, pancreatitis, and obstructive jaundice, although the majority of complications are recurrence or non-remission of acute cholecystitis. An RCT study showed that the complication rate of patients undergoing LC after 7-45 days of attack was 2-3 times higher than that of patients undergoing surgery early, thus surgery is not recommended within this period.
In patients with concurrent mild acute pancreatitis (without organ dysfunction or local complications), a systematic evaluation (including only a small sample size RCT) showed that early surgery (rather than waiting for symptoms to resolve and blood chemistries to return to normal) reduced the length of hospital stay by an average of 1 day.
Some experts say that severe pancreatitis may not show up until 48 hours after the onset of the disease, and that it is harmful to operate on patients with severe pancreatitis within 48 hours. Delaying surgery for 48 hours can resolve this paradox. Early performance of cholecystectomy is not suitable for patients with acute severe pancreatitis and pregnancy, and more research is still needed to find a solution.
Impact of gallstones on health services and society
In 2004, there were 1,800,000 outpatient visits for gallbladder stones in the United States, and more than 500,000 cholecystectomies are performed each year in the United States and 70,000 in the United Kingdom. The cost of cholecystectomy and the time lost from work due to its symptoms and treatment have a significant impact on health services and society.