Consensus opinion on internal medicine treatment of chronic cholecystitis and gallbladder stones in China (2014)
I. Preface
(I) Background and procedure of this consensus opinion
Clinical symptoms, signs and laboratory tests play an important role in the diagnosis of chronic cholecystitis and gallbladder stones, but they lack specificity. Ultrasonography is usually the first step of imaging examination. At present, no consensus opinion on the diagnosis and treatment of chronic cholecystitis and gallbladder stones supported by evidence-based medical evidence has been developed in domestic gastroenterology.
In order to standardize the diagnosis and treatment of chronic cholecystitis and gallbladder stones, the editorial board of the Chinese Journal of Gastroenterology invited some domestic gastroenterologists and radiologists to form an expert committee for the Consensus Opinion on the Diagnosis and Treatment of Chronic Cholecystitis and Gallbladder Stones in China, based on the epidemiological trends of chronic gallbladder diseases in China, recent research results and evidence-based medicine, and with reference to the Guidelines for the Treatment of Gastrointestinal Diseases (3rd edition) and international guidelines. Based on the epidemiological trend of chronic gallbladder disease in China, recent research results and evidence-based medical evidence, and with reference to the Guidelines for the Treatment of Digestive Diseases (3rd edition) and international guidelines and latest research results, this consensus opinion was formulated.
The aim is to provide a rational and standardized strategy for the medical treatment of chronic cholecystitis and gallbladder stones.
The authors prepared the first draft of the full text, sent it to the expert committee members, and received feedback for revision. At the expert committee meeting, the main points of the full text were discussed collectively, and amendments were proposed and voted by secret ballot (voting options: ① completely agree; ② agree with certain reservations; ③ agree with major reservations; ④ disagree with reservations; ⑤ completely disagree), with the number of people choosing ①+② >80% being approved.
The author will revise the preliminary draft according to the comments made by the expert committee meeting, and further confirm by the expert committee members to become the final draft.
(B) Reference sources and evidence grading of this consensus
The expert committee interpreted and analyzed the literature related to the diagnosis and treatment of chronic cholecystitis and gallbladder stones by searching the databases such as PubMed, Wanfang Data Knowledge Service Platform and China Knowledge Resource IntegratedDatabase (CNKI) by key words, and answered the common problems faced in the diagnosis and treatment of chronic cholecystitis and gallbladder stones in clinical practice.
All consensus opinions are based on evidence-based medical evidence and are marked according to the 2009 Oxford Classification of Evidence and Strength of Recommendation criteria, which are described in detail in the literature. The majority of the treatment strategies covered in this consensus opinion are supported by evidence-based medicine, and all drug doses are targeted to patients with normal liver and kidney function.
Epidemiology
Individual literature reports that the prevalence of chronic cholecystitis and gallbladder stones in China is 16.09%, accounting for 74 and 68% of all benign gallbladder diseases. According to foreign data, chronic cholecystitis accounts for 92.8% of patients who underwent cholecystectomy, with more women than men (79.4% compared to 20.6%), and the peak incidence is around 50 years of age, with the proportion of each age group accounting for 12.1%, 18.0%, 30.7%, 20.4%, and 12.2% in 20-30 years, 30-40 years, 50-60 years, and 60-70 years, respectively. The percentage of gallbladder stones is the most common.
Gallbladder stones are the most common risk factor for chronic cholecystitis, and chronic calculous cholecystitis accounts for 90%-95% of all chronic cholecystitis; chronic non-calculous cholecystitis is less common, accounting for 4.5%-13.0% of all chronic cholecystitis.
The main etiology and pathogenesis
(a) The etiology and pathogenesis of chronic calculous cholecystitis
1, gallbladder stones: stones lead to repeated obstruction of the gallbladder duct and cause damage to the gallbladder mucosa, recurrent inflammatory reaction of the gallbladder wall, scar formation and gallbladder dysfunction. Studies in elderly patients with chronic cholecystitis showed that the severity of inflammatory response was positively correlated with the maximum diameter of stones and negatively correlated with the number of stones and age, and that isolated large stones were a high risk predictor of chronic cholecystitis.
2. Bacterial infection: Normal bile should be sterile, and when stones become lodged and obstructed in the gallbladder or bile duct, it may lead to retrograde infection with intestinal bacteria. Studies have shown that the positive rate of bile culture in patients with non-gallbladder surgery, acute and chronic cholecystitis is 16%, 72% and 44%, respectively, while the percentage of bacteria found in the bile of patients with jaundice can be as high as 90%, suggesting that incomplete bile duct obstruction is an important risk factor for bacterial infection.
The pathogenic bacteria of chronic cholecystitis mainly originate from retrograde infection of intestinal bacteria, and the species of pathogenic bacteria are basically the same as intestinal bacteria, mainly Gram-negative bacteria, accounting for 74.4%, mainly including Escherichia coli (23.9%), immobile bacilli (32.7%), and Aspergillus chimaericus (19.3%). Recent studies suggest that H, pylori infection may be associated with the development of chronic cholecystitis.
(B) Etiology and pathogenesis of chronic non-lithotripsy cholecystitis
1, abnormal gallbladder dynamics: cholestasis is an important cause of chronic non-lithotripsy cholecystitis. In patients without the presence of stones, if the gallbladder injection fraction (ejection fraction) of cholecystokinin-stimulated scintigraphy (CCK-HIDA) is found to be reduced (<35%), it is highly suggestive of chronic non-lithotripsy cholecystitis. However, this test is rarely performed in China.
2, gallbladder ischemia: common causes are severe diseases such as sepsis, shock, severe trauma, burns, use of vasoconstrictive and elevating drugs, and major non-biliary surgery, which may cause ischemia and local inflammatory reaction and necrosis of the gallbladder mucosa.
3. Other: viral and parasitic infections are one of the few causes of cholecystitis. Dietary factors are also involved in the occurrence of chronic nonstone cholecystitis, such as chronic hunger, overeating, and overnutrition.
IV. Diagnosis and evaluation
(A) Clinical manifestations
1. Abdominal pain: It is the most common symptom of most chronic cholecystitis, with an incidence of 84%. The occurrence of abdominal pain is often associated with a high-fat, high-protein diet. Patients often show episodes of biliary colic, mostly located in the right upper abdomen, or a dull pain that may radiate to the back and last for several hours before relieving.
2, dyspepsia: is a common manifestation of chronic cholecystitis, accounting for 56%, also known as biliary dyspepsia, manifested as warmth, fullness, abdominal distension, nausea and other indigestion symptoms.
3, physical examination: about 34% of patients with chronic cholecystitis can be detected on physical examination with right upper abdominal pressure pain, but most patients may not have any positive signs.
4. common complications: when there is an acute attack of chronic cholecystitis or biliary pancreatitis, the corresponding symptoms and signs of acute cholecystitis and acute pancreatitis can be observed; Mirizzi’s syndrome is similar to common bile duct stones and is non-specific; gallstone intestinal obstruction is dominated by intestinal obstruction.
5, asymptomatic gallbladder stones: with the wide application of ultrasound technology, gallbladder stones can often be detected incidentally during routine health physical examination, and patients have neither obvious symptoms nor positive signs, but some patients may develop symptoms in the future.
(II) Imaging diagnosis
Ultrasonography: It is the most common and valuable test for the diagnosis of chronic cholecystitis and can show thickening of the gallbladder wall, fibrosis, and stones in the gallbladder. A Meta-analysis of 30 studies showed that the sensitivity of gallbladder ultrasound was 97%, specificity was 95%, accuracy was 96%, and positive predictive value was 95%.
The ultrasound features of chronic cholecystitis are mainly thickening of the gallbladder wall (wall thickness ≥3 mm) and grossness; in the case of combined gallbladder stones, there are strong echogenicity and posterior acoustic shadow in the gallbladder, and if there is a laminar distribution of punctate hypoechogenicity in the gallbladder with no posterior acoustic shadow, it is often an image of bile sludge in the gallbladder. If the cholesterol crystals are distinguished from polyps, and if the ultrasound examination shows fixed strong echogenicity in the gallbladder that does not move with body position and no posterior acoustic shadow, it is mostly diagnosed as polyps-like lesions in the gallbladder.
CT: With a sensitivity of 79%, a specificity of 99%, and an accuracy of 89%, CT can provide a good visualization of gallbladder wall thickening and possible stones, and can assess dystrophic calcification of the gallbladder and help to exclude other diseases that need to be differentiated.
MRI: It is better than CT in assessing gallbladder wall fibrosis, gallbladder wall ischemia, peri-gallbladder hepatic tissue edema, and peri-gallbladder fat accumulation, and is mainly used to differentiate acute and chronic cholecystitis. In addition, magnetic resonance cholangio-pancreatography (MRCP) can detect small stones in the gallbladder and common bile duct that are not easily detected by ultrasound and CT.
4.Hepatobiliary duct CCK-HIDA: It is the imaging test of choice to assess gallbladder emptying and to identify the presence of gallbladder emptying disorders. In patients with suspected chronic non-lithotripsy cholecystitis, CCK-HIDA can be used to assess changes in gallbladder kinetics, with positive findings of slow bile filling, reduced ejection index (ejection index of 70% in the general population, below 35% is considered low ejection index), and low response to injection of cholecystokinin. After cholecystectomy, most patients with cholecystokinetic disorders are relieved of their symptoms. However, there is a lack of relevant research results in China.
(iii) Diagnostic points
1. Recurrent episodes of right upper abdominal pain, which may radiate to the right subscapular region. The occurrence of abdominal pain may be associated with a high-fat, high-protein diet.
2, may be accompanied by dyspeptic symptoms, and physical examination may or may not be accompanied by right upper abdominal pressure pain.
3, ultrasound and other imaging studies reveal gallbladder stones and/or a low ejection index of the gallbladder (ejection index <35%) as assessed by CCK-HIDA.
4, need to be differentiated from acute cholecystitis, functional dyspepsia, peptic ulcer, liver abscess, acute myocardial infarction and other diseases that may present with right upper abdominal pain.
V. Treatment
For patients with chronic cholecystitis and gallbladder stones, treatment should be individualized according to the presence or absence of symptoms and complications, respectively. The goals of treatment are symptom control, prevention of recurrence, and prevention and control of complications.
(A) Treatment of asymptomatic chronic cholecystitis and gallbladder stones
For patients with asymptomatic chronic cholecystitis and gallbladder stones, the treatment principles are dietary modification, symptomatic treatment with bile when symptoms are present, and continued observation. For some high-risk patients, preventive cholecystectomy can be adopted.
1. Dietary adjustment: The onset of gallbladder stones and chronic calculous cholecystitis is related to diet and obesity. Regular, low-fat, low-calorie diets should be recommended, and a regular diet with a quantitative and regular schedule should be promoted.
2.Biliary treatment.
① Ursodeoxycholic acid is a hydrophilic dihydroxycholic acid with mechanisms of action such as expansion of the bile acid pool, promotion of bile secretion, regulation of immunity, and cytoprotection. (b) In patients with cholelithiasis, the use of ursodeoxycholic acid helps to reduce the risk of biliary pain, avoid acute cholecystitis, and improve gallbladder smooth muscle contractility and inflammatory infiltration.
(ii) Azinomide promotes bile synthesis and secretion, while increasing pancreatic enzyme activity and facilitating absorption of carbohydrates, fats and proteins. The clinically available Compound Azinimide Enteric Tablets, the pancreatic enzymes and cellulase in its composition have the effect of promoting digestion, while dimethicone oil can promote gas discharge in the stomach and improve the symptoms of abdominal distension and discomfort. Therefore, compound azelmette enteric-coated tablets can help improve symptoms such as indigestion while benefiting bile.
③Anisotrisulfide has pro-biliary secretion and mild pro-biliary tract dynamics effect.
3. Prophylactic cholecystectomy: (1) high-risk groups prone to gallbladder cancer; (2) immunosuppressed patients after organ transplantation; (3) patients with rapidly declining body mass; (4) patients with increased risk of gallbladder cancer due to “porcelain” gallbladder.
(2) Treatment of chronic cholecystitis and gallbladder stones with symptoms
Treatment is mainly to control the symptoms and eliminate the inflammatory reaction.
1, antispasmodic and analgesic: used for biliary colic during acute attacks of chronic cholecystitis. Nitroglycerin 0.6 mg sublingually every 3-4 hours, or atropine 0.5 mg intramuscularly every 4 hours, can be used at the same time isoproterenol 25 mg intramuscularly; analgesic pethidine 50-100 mg intramuscularly, combined with antispasmodics can enhance the analgesic effect (because it may promote the Oddi sphincter spasm and thus increase the pressure in the bile duct, so morphine is generally prohibited).
It should be noted that these drugs do not change the course of the disease and may mask the condition, so they should be discontinued as soon as they are ineffective or if the pain recurs.
2. Relief of biliary dyspepsia symptoms: Inflammatory irritation and chronic fibrosis of the gallbladder wall are common in chronic cholecystitis, which can easily lead to dyspepsia symptoms. For dyspepsia patients with definite gallbladder stones, 10%-33% of the symptoms can be relieved after cholecystectomy.
However, since biliary dyspepsia also has the pathogenesis of extra-biliary digestive system dysfunction (probably related to biliary dynamics and Oddi sphincter tone), it is necessary to apply drugs that can help improve the symptoms of biliary dyspepsia, such as compound azinomide or other pancreatic enzymes, at the early stage of dyspepsia, which can increase the concentration of pancreatic enzymes in the digestive tract, enhance digestive capacity, and improve the symptoms of abdominal distension and nutrition level.
3, anti-infection treatment: according to the bile culture results of patients with chronic cholecystitis, the severity of the patient’s infection, antibiotic resistance and antibacterial spectrum, as well as the patient’s underlying disease, especially for the liver and kidney function is impaired, the rational application of antibiotics in the treatment of biliary tract infection in chronic cholecystitis is of great significance.
The 2010 report of the National Bacterial Drug Resistance Surveillance Network of the former Ministry of Health showed that the resistance rate of Gram-negative bacteria in bile to third- and fourth-generation cephalosporins and fluoroquinolones was as high as 56.6% to 94.1%. Therefore, for chronic cholecystitis and gallbladder stones with acute attacks, piperacillin/tazobactam and cefoperazone/sulbactam should be recommended for treatment, while metronidazoles for anaerobic bacteria also have better results.
In contrast to acute cholecystitis attacks, patients with chronic cholecystitis can wait for bile culture and bacterial drug sensitivity test results to be perfected before choosing to use antibiotics to avoid drug resistance due to blind application.
(iii) The status of surgical treatment in the treatment of chronic cholecystitis and gallbladder stones
Medical treatment is generally preferred for chronic cholecystitis and gallbladder stones, but on the basis of medical treatment, surgical treatment should be considered if the following symptoms and manifestations occur
1, pain without relief or recurrent attacks, affecting life and workers
2, gradual thickening of the gallbladder wall up to 4 mm and above
3, gallbladder stones increase and enlarge year by year, combined with gallbladder dysfunction or impairment.
4. Ceramic-like changes in the gallbladder wall.
(D) Common complications and management principles
In case of acute attack of chronic cholecystitis or complications, such as acute peritonitis, acute gallbladder perforation, severe acute pancreatitis and other acute abdominal conditions, a surgeon should be consulted and dealt with in a timely manner. If surgery is temporarily unsuitable or contraindicated, ultrasound or CT-guided cholecystocentesis and drainage or endoscopic retrograde cholangio-pancreatography (ERCP) can be considered.
1, acute cholecystitis with acute peritonitis: when acute cholecystitis attacks, it will lead to bile stagnation in the gallbladder and combined with infection, clinical abdominal pain, fever, and abdominal examination may reveal symptoms of peritonitis; if the infection is not controlled in time, gangrene will appear in the gallbladder wall, which may eventually lead to gallbladder perforation, and clinical symptoms of infectious shock may appear and endanger life.
If the inflammatory reaction is early or limited, laparoscopic cholecystectomy can be considered; if the inflammatory reaction is prolonged, the adhesions around the gallbladder are severe or the gallbladder is perforated, cholecystectomy or cholecystostomy is performed by caesarean section.
Non-stone cholecystitis is also often associated with acute cholecystitis attacks due to blood flow disorders, and gangrene of the gallbladder wall often occurs, which also requires surgical resection.
2, biliary pancreatitis: gallstone disease (including biliary microstones), hypertriglyceridemia, ethanol are three common causes of acute pancreatitis, and biliary pancreatitis is still the main cause of acute pancreatitis in China.
For the treatment of patients with acute biliary pancreatitis, in addition to routine fasting, inhibition of pancreatic enzyme secretion, antispasmodic and analgesic and rehydration support therapy, internal medicine also needs to select appropriate antibacterial drug therapy based on the results of blood culture and bile culture ten drug sensitivity test, which can be found in the Chinese guidelines for the diagnosis and treatment of acute pancreatitis. For patients with acute biliary pancreatitis with common bile duct obstruction and cholangitis, ERCP, percutaneous percutaneous hepatobiliary drainage or surgery is recommended.
Mirizzi’s syndrome: The anatomical factors for its formation are that the cystic duct is too long with the common hepatic duct or the confluence of the cystic duct and the common hepatic duct is too low, and the stones near the gallbladder pot belly (Hartmann’s pocket) cause different degrees of obstruction of the common hepatic duct or the common bile duct, and repeated inflammatory reactions lead to the fistula of the common bile duct, the disappearance of the cystic duct, and partial or complete blockage of the common hepatic duct by the stones.
The clinical features are recurrent episodes of cholecystitis and cholangitis with marked obstructive jaundice. Mirizzi’s syndrome accounts for 0.3% to 3.0% of patients undergoing cholecystectomy and increases the risk of bile duct injury during cholecystectomy. The risk of bile duct injury during cholecystectomy is increased (up to 22.2%). For such patients, laparoscopic cholecystectomy is not recommended and open surgery is recommended.
Stone intestinal obstruction: It accounts for 1% of all small bowel obstruction and is caused by the formation of fistulas between the gallbladder injury and the intestine (biliary-duodenal fistulas are the most common, accounting for 68%), as stones enter the intestine through the fistula, mostly causing mechanical obstruction in the narrow ileocecal region. Mild cases often present as incomplete obstruction. Unless the stone is significantly calcified, it is difficult to detect on abdominal X-ray, but CT reveals gas accumulation in the gallbladder, gallbladder shrinkage, and stones at the site of obstruction. Treatment is mainly based on surgical intervention to relieve the obstruction.
(V) Chinese medicine and acupuncture treatment
Traditional Chinese medicine has a long history in the treatment of cholecystitis, and patients can choose biliary herbs according to their clinical manifestations. Acupuncture points commonly used in the treatment of cholecystitis include gallbladder, gallbladder, Yanglingquan, Zhimen, and Feosanli.
Prognosis
Patients with chronic cholecystitis and gallbladder stones generally have a good prognosis, but once symptoms appear or recurrent symptoms occur, especially for patients with biliary colic, they need to be actively treated and, if necessary, undergo surgical operation. The occurrence of gallbladder cancer is related to chronic stony cholecystitis. 65%-90% of gallbladder cancer patients have gallbladder stones, but only 1%-3% of gallbladder stone patients develop into gallbladder cancer.
Studies have confirmed that gallbladder epithelial metaplasia is more closely related to microstones, and if these patients have insidious onset or have mild symptoms for a long time, they need to pay attention and seek surgical consultation promptly if the gallbladder wall is significantly thickened by ultrasound.