The main symptom is right upper abdominal or epigastric pain, which is often difficult to distinguish from other functional gastrointestinal diseases such as gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS) and functional dyspepsia (FD), as well as from cholecystitis and pancreatitis caused by cholelithiasis. The Rome III Working Group subdivides patients who are eligible for gallbladder and SO dysfunction into gallbladder dysfunction, biliary tract type SO dysfunction and pancreatic type SO dysfunction.
Diagnostic criteria
(6) abdominal pain is not relieved by change of position, (7) abdominal pain is not relieved by antacids, (8) abdominal pain is not relieved by antacids
Exclude other organic diseases that can cause abdominal pain.
The diagnosis of gallbladder and SO dysfunction is supported by one or more of the following features: (1) abdominal pain with nausea and vomiting, (2) pain radiating to the back and/or right subscapular region, and (3) waking up with pain at midnight.
Gallbladder dysfunction
Gallbladder dysfunction is defined as biliary-derived abdominal pain due to abnormalities in metabolism or primary gallbladder dynamics without alterations in bile composition. The diagnosis must meet all of the following conditions: ① meeting the diagnostic criteria for gallbladder and SO dysfunction, ② the presence of the gallbladder, and ③ normal liver enzymes, conjugated bilirubin, blood amylase or lipase tests.
In the opinion of the Rome III Expert Committee, the diagnosis of biliary pain as gallbladder dysfunction must be based on the following conditions: (i) absence of gallbladder stones, biliary sludge and microstones, (ii) gallbladder emptying index <40% after 30 minutes of intravenous octreotide cholecystokinin, and (iii) no recurrence of symptoms 12 months after cholecystectomy.
The Rome III Expert Committee recommended that both symptoms and objective evidence must be present to support the diagnosis of gallbladder dysfunction. The recommendation emphasizes the need for moderate to severe pain of biliary origin with evidence of abnormal gallbladder emptying index (<40%). This recommendation reduces the false positive rate for the diagnosis of functional gallbladder disease.
Diagnostic strategies For patients with biliary-derived abdominal pain, the following strategies are appropriate for the proposed diagnosis of gallbladder dysfunction: (1) liver function, pancreatic enzymes and abdominal ultrasound should be performed first to exclude organic diseases of the gallbladder and biliary tract, and when these tests are normal, upper gastrointestinal endoscopy is feasible; (2) gallbladder dysfunction can be excluded if the above tests are abnormal; (3) gallbladder emptying stimulation by cholecystokinin is feasible when all the above tests are normal If the above tests are normal, cholecystokinin stimulated cholecystokinin emptying test is feasible. If the gallbladder emptying index is <40% and there is no other reason to investigate, gallbladder dysfunction can be diagnosed.
For such patients, cholecystectomy is the most appropriate treatment.
Biliary tract type SO dysfunction
SO dysfunction refers to abdominal pain, elevated liver or pancreatic enzymes, biliary dilation or pancreatitis attacks caused by abnormal SO motility. It can be divided into biliary and pancreatic types depending on the location of the SO motility abnormality. Although SO motility abnormalities can also occur in patients with a gallbladder, the condition is commonly seen in post-cholecystectomy patients.
The biliary tract type of SO dysfunction must meet the following two conditions: (1) meet the diagnostic criteria for gallbladder and SO dysfunction, and (2) have normal amylase or lipase. The diagnosis is supported by the presence of a transient elevation of serum aminotransferase, alkaline phosphatase or conjugated bilirubin associated with at least 2 episodes of abdominal pain.
The Rome III expert committee has revised the clinical staging, and now the diagnosis of biliary SO dysfunction no longer emphasizes the timing of biliary and pancreatic duct drainage to avoid invasive endoscopic retrograde cholangiopancreatography (ERCP) examinations. Although SO manometry has a greater value for diagnosis, it is an invasive test and is only considered when non-invasive tests fail to make a definitive diagnosis and conservative treatment is ineffective.
The new clinical staging of diagnostic strategy stipulates that type I patients should meet the following conditions: (i) biliary abdominal pain, (ii) at least two elevations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin to >2 times normal values, and (iii) abdominal ultrasound showing biliary dilatation with bile duct diameter >8 mm.
The rate of abnormal SO manometry in type I patients is as high as 65% to 95%, which is mainly related to SO stricture. In type II, in addition to biliary abdominal pain, only one abnormality in the above laboratory or imaging tests can be diagnosed, and the rate of abnormal bile duct manometry is 50%-63%. Type III patients have only biliary abdominal pain, and the rate of abnormal bile duct manometry in this type of patients is 12%-59%.
For biliary type I patients with typical symptoms and clinically compatible with the diagnostic criteria, biliary manometry is not required and endoscopic sphincterotomy (EST) can be performed directly. For patients whose clinical presentation meets the diagnosis of biliary type II, SO manometry may be considered, provided that the patient’s benefit is weighed against the risk of possible complications. Type III patients should receive empirical treatment with proton pump inhibitors (PPI), antispasmodics and antipsychotics prior to manometry. EST may be performed for those presenting with abnormal manometry in biliary type II or III patients.
Pancreatic-type SO dysfunction
Pancreatic-type SO dysfunction is most often seen in middle-aged women. Patients often present with intermittent, episodic epigastric pain with episodes of elevated blood amylase or lipase, sometimes with liver enzymatic abnormalities. The exact cause of the patient cannot be found after repeated examinations, and the clinical diagnosis is often idiopathic recurrent pancreatitis. In patients with pancreatic-type SO dysfunction, the incidence of abnormal pancreatic ductal SO manometry is 15% to 72%.
The diagnosis of functional pancreatic SO dysfunction must meet the following two criteria: (1) the characteristics of gallbladder and SO dysfunction, and (2) elevated blood amylase or lipase.
The Rome III Expert Committee recommended that other causes of pancreatitis should be excluded before diagnosis. First, liver and pancreatic enzymatic examination should be performed, abdominal ultrasound or CT examination should be performed to exclude organic diseases, magnetic resonance cholangiopancreatography (MRCP) should be performed to exclude biliary or pancreatic duct diseases, and endoscopic ultrasonography should be performed to exclude microscopic stones in the bile duct. If necessary, SO pressure measurement is performed, but this method may lead to complications such as pancreatitis.
The most effective treatment for pancreatic-type SO dysfunction is pancreatic ductal sphincterotomy, which can be performed either through open surgery or endoscopically. Patients who undergo pancreatic duct sphincterotomy under ERCP often require a short postoperative period of pancreatic duct stenting to prevent the development of postoperative pancreatitis.
The coordinated activity of the gallbladder and SO regulates the discharge of bile from the liver to the duodenum via the bile duct, and the SO plays the same role in regulating the discharge of pancreatic juice to the duodenum, and its dysfunction can cause intermittent epigastric pain, transient elevation of hepatic or pancreatic enzymes, dilatation of the common bile duct, and even pancreatitis.
Case study
The patient was a 48-year-old female with recurrent postprandial right epigastric pain with radiating pain in the right shoulder and right subscapular region for more than 1 year. Each pain lasted for 2-3 hours and was similar in nature to the episodes before cholecystectomy 2 years ago. The pathology report suggested chronic cholecystitis but no stones. The abdominal pain had been attacked 6 times in the past 1 year, 2 of which were severe and relieved by the application of antispasmodic analgesics to the emergency room.
The results of serum biochemical tests, amylase and white blood cell count were normal, while ALT and AST were elevated to >2 times the normal value on two occasions, and bilirubin was only mildly elevated. 2 emergency ultrasound examinations of the upper abdomen indicated that the diameter of the common bile duct was 10 mm. 2 MRCP and ERCP examinations were performed outside the hospital, and no common bile duct stones were seen, but there was stenosis of the lower bile duct. Oral administration of ursodeoxycholic acid and calcium antagonists failed to prevent its onset. Each physical examination was unremarkable.
In patients with recurrent episodes of right upper abdominal pain after cholecystectomy, if liver biochemical tests are abnormal and ultrasonography suggests bile duct dilatation, there is a 50-75% chance that common bile duct stones are present, especially in patients with pre-existing gallbladder stones. If the patient’s biliary colic occurred recently after cholecystectomy, bile leak or intraoperative bile duct injury cannot be excluded. However, in this case, the patient had recurrent attacks with elevated liver enzymes and mild bile duct dilatation starting 1 year after surgery, and no stones were seen on MRCP and ERCP examinations performed outside the hospital.
The initial diagnosis was type I biliary type SO dysfunction, and ERCP angiography was performed again, and no stones were seen in the bile ducts or pancreatic ducts. No manometry was performed, and sphincterotomy was performed directly. The size of the incision was about 0.8 cm, and a short stent of 5 Fr without medial flank was placed in the pancreatic duct. The amylase was elevated at 24 hours postoperatively but asymptomatic, and had returned to normal at 72 hours on recheck. There was no recurrence of right upper abdominal pain symptoms at six months follow-up.
Expert comment
This patient had a history of multiple episodes of typical biliary colic with elevated liver enzymes and bile duct dilatation prior to this admission. Combined with the history of cholecystectomy, common bile duct stones should be considered first. However, both MRCP and ERCP ruled out the possibility of stones, so biliary-type SO dysfunction should be further considered. After attempts of empirical drug treatment failed, papillary sphincterotomy under ERCP was performed. Postoperative symptoms were significantly relieved, further validating the preoperative diagnosis.
The case had undergone 2 ERCP examinations prior to this admission, but no manometry or sphincterotomy was performed. This was considered to be due to a lack of awareness of biliary-type SO dysfunction. Notably, this patient had postoperative hyperamylasemia. It is now well established that the incidence of pancreatitis after ERCP is higher in cases of SO dysfunction, and placement of a short pancreatic duct stent after ERCP is recommended to prevent pancreatitis.