Gallstones are ubiquitous. More than 20 million adults in the U.S. have them, but only 1 to 4 percent of these patients develop symptoms of gallstone disease; of these, only 5 percent develop pancreatitis.
The gallbladder has one purpose only: to store bile, which helps digest fats in the small intestine. But bile can become concentrated and thicken. Eventually, bile salts can combine with cholesterol to form stones; gallstones are composed of a combination of crystallized cholesterol deposits or calcium crystals ionized with bilirubin. These stones can block the flow of bile from the gallbladder; this is typically manifested as pain in the upper right quadrant of the abdomen. Gallstone pancreatitis is caused when a migrating gallstone obstructs the ampulla of Vater. 1
"Acute pancreatitis is a clinical syndrome consisting of epigastric abdominal pain, often radiating to the back; nausea; vomiting (not always present); and a serum amylase or lipase level greater than three to five times normal," writes John Baillie, a professor of medicine at Duke University Medical Center's gastroenterology division.2
Serum amylase and lipase levels are not the only indicators of acute pancreatitis; C-reactive protein, leukocyte elastase, trypsinogen-activating peptides and lactate dehydrogenase are also gauges but are rarely tested by clinicians. A urinary trypsinogen-II assay can be performed at the bedside; the 3-minute dipstick test is "highly sensitive and specific in detecting acute pancreatitis," but it is not currently licensed for use in the United States.2
Risk factors for gallbladder disease besides the "five Fs" (fair, fat, female, fertile and 40-plus years of age) include a larger-diameter cystic duct, a larger-diameter common bile duct, high basal sphincter of Oddi pressure, more pancreatic duct reflux and a common pancreatobiliary channel.1
How prevalent is it?
Gallstone pancreatitis is typically seen in patients described by the five Fs. There are other forms of pancreatitis -- such as alcoholic pancreatitis, which is generally seen in men aged 30 to 45, who have chronic pancreatitis with a "superimposed acute flare-up" of the disease, and idiopathic pancreatitis, which is often related to microlithiasis (caused by gallstones less than 2 mm which are too small to be visualized with imaging techniques).3
How is it caused?
The cause of gallstone pancreatitis is debatable. Reflux of bile into the pancreas by a common channel may contribute; this is a controversial theory, but supported by the fact that there have been gallstones recovered in the feces of 85 to 95 percent of gallstone pancreatitis cases.3
Another hypothesis proposes reflux secondary to an incompetent sphincter of Oddi, which allows duodenal contents (such as lysolecithin, enterokinase or bacterial toxin) to pass into the pancreatic duct. Of note, the sphincter of Oddi may already be incompetent due to an earlier passage of a gallstone. "It is reasonable to assume that the pathogenesis is related to a combination of the above which allows small stones to cause temporary obstruction and flow of infected bile into the pancreas," writes John T. Bjork, Chief of the Department of Internal Medicine at St. Luke's Medical Center in Milwaukee, Wis.
Certain foods have been linked to gallbladder attacks; some physicians believe that undiagnosed food allergies contribute by causing the bile duct to swell and by impairing bile flow.4 Food elimination diets have had some success in reducing symptoms; potentially problematic foods include eggs, pork, onions, poultry, milk, coffee, oranges, corn, beans and nuts.5
How is potential severity assessed?
To predict the severity of acute pancreatitis, Ranson's signs, APACHE II or modified Imrie's score have often been used; other indicators are organ failure, pulmonary disease, renal insufficiency, liver failure or cardiac disease. "However, no special assessment is necessary for a physician to realize that a patient who is hypotensive, hypoxic, oliguric, febrile and confused is seriously ill," notes Baillie.
A study published in the Archives of Surgery concluded that simple admission criteria was superior to the scoring systems in predicting severe complications; specifically, a serum glucose level of 8.3 mmol/L (150 mg/dL) or more was the best predictor, while a white blood cell count of >=14.5 109/L, an APACHE II score of >=5, a modified Imrie score of >=3, and a biliary Ranson score of >=3 were all statistically associated with the development of severe complications.6
Computerized tomography (CT) is one choice for imaging the pancreas. CT allows the identification of pancreatic edema, fluid or cysts, and it allows the severity of pancreatitis to be graded. Later in the disease, it may also be of use in recognizing complications.3
But Baillie states that CT scanning should only be done if the diagnosis is uncertain, if severe pancreatitis is expected, or if the pancreatitis worsens or does not resolve. Transabdominal ultrasonography (TUS) can be used to identify cholelithiasis and dilatation of the extrahepatic biliary tree, but in detecting bile duct stones, it is 95 percent specific and 60 percent sensitive. TUS seldom visualizes the pancreas in patients with acute pancreatitis due to air in the distended loops of the small bowel. If TUS is utilized, the quality of the results relies heavily on the expertise of the technician, who should scan the entire abdomen in case abdominal pain has a nonbiliary, nonpancreatic source.
Other imaging options include ultrasonography and MR cholangiography, which is noninvasive and does not require contrast. "[MR cholangiography] is especially useful for common bile duct stones," Bjork adds. "Endoscopic ultrasound is more accurate than transabdominal ultrasound but is an invasive endoscopic procedure which requires sedation." 3
How can gallstone pancreatitis be treated?
The use of ERCP in patients with gallstone pancreatitis is controversial. The literature indicates that in patients without biliary obstruction, ERCP does not benefit them and may even produce complications that make the disease worse. Overall, Baillie says, experts recommend urgent ERCP for biliary compression only for patients with progressive biliary obstruction (who have progressive jaundice with or without cholangitis).
It is not necessary to perform preoperative ERCP in all patients undergoing laparoscopic cholecystectomy; the surgeon should, alternatively, perform intraoperative cholangiography, with ERCP incorporated if bile duct stones are found. However, patients with a suspected or known surgical reconstruction of the gut should undergo preoperative ERCP, which may help the surgeon plan her approach.
Preoperative ERCP should also be performed in patients with persistent or progressive biliary obstruction (regardless of choledocholithiasis); surgery should then follow the bile duct clearing to prevent any additional migration of stones from the gallbladder.2 "Because ERCP and sphincterotomy combined are associated with much higher morbidity and mortality than is laparoscopic cholecystectomy -- partly owing to the large number (more than 500,000) of cholecystectomy procedures performed annually in the U.S. alone -- endoscopists performing ERCP prior to laparoscopic cholecystectomy must consider the medicolegal consequences in the event of a severe complication (usually severe pancreatitis) related to the procedure," writes Baillie.
Typically, if gallstones are confirmed but are not symptomatic, removal of the gallbladder is not recommended. Diabetic patients are an exception to the "wait and see" theory; they may be better candidates for surgical removal of the gallbladder because they can lack "clear-cut pain signals" and therefore may not recognize a gallbladder attack.5
Diagnostic endoscopic retrograde cholangiopancreatography (ERCP) does increase morbidity in severe pancreatitis patients and is contraindicated "unless expertise is available for therapeutic options," Bjork says. "The therapeutic ERCP with endoscopic sphincterotomy and drainage of the bile duct with extraction of gallstones is of primary importance in the therapy of cholangitis. Even though pancreatitis may occur with endoscopic sphincterotomy, the procedure does not exacerbate the pancreatitis or have a higher incidence of perforation or hemorrhage in patients with gallstone pancreatitis. If drainage is not possible by therapeutic ERCP or the patient is unable to be sedated, percutaneous transhepatic cholangiography is a possible consideration, especially with dilated intrahepatic ducts."3
The gold standard for treatment is laparoscopic cholecystectomy, according to many physicians.4 Richard A. Kozarek, a physician at Virginia Mason Medical Center in Seattle, expresses concern over potential overuse of ERCP and recommends laparoscopic cholecystectomy and mandatory intraoperative cholangiography for patients who have mild gallstone pancreatitis. In his response to a study published in the American Journal of Gastroenterology, Kozarek writes that ERCP and other actions that have traditionally been to treat pancreatitis should be reserved only for patients with severe forms of the malady, not utilized in those with milder forms.7
Overall, both procedures (ERCP and laparoscopic cholecystectomy) are safe and effective when they are clinically indicated, says Bjork; ERCP, when performed selectively (not routinely) before laparoscopic cholecystectomy is cost-effective. Endoscopic sphincterotomy can shorten the hospital stay and allow laparoscopic cholecystectomy earlier.
"The management of gallstone pancreatitis is variable. Laparoscopic cholecystectomy is considered the procedure of choice to prevent recurrent pancreatitis and to evaluate the bile duct," reports Bjork. "An early therapeutic ERCP may prevent recurrence of pancreatitis or prevent the complications of cholangitis and necrotizing pancreatitis. Routine preoperative ERCP is not indicated since gallstone pancreatitis usually responds to conservative therapy and subsequent laparoscopic cholecystectomy."
"Gallstone pancreatitis usually responds to conservative medical therapy, but it is important to identify those patients who require urgent endoscopic therapy in order to shorten the course of the disease and prevent pancreatic complications. The majority of patients require laparoscopic cholecystectomy to prevent a recurrence of the pancreatitis," he concludes.
What products are used for patients?
Only patients with predicted severe acute pancreatitis should be given prophylactic antibiotic therapy; imipenem is the preferred antibiotic. This is the only medication shown to reduce morbidity and mortality in cases of pancreatic necrosis.2
Some "natural" remedies have value as preventive medicine. Extra doses of vitamin C may help the body to digest dietary fat and thus lower the risk of gallstones.4 One study published in the Archives of Internal Medicine demonstrated protection from vitamin C against known gallbladder disease and undetected gallstones. Deficiencies in vitamins C and E have been associated with gallstone formation in animals. Other supplements may have use in preventing gallstone formation, such as:
- Lipotropic factor combination (which includes choline, methionine, folic acid and vitamin B12)
- Cholagogues and choleretics (such as milk thistle and dandelion)
- Lecithin (insufficient levels have been linked to gallstones)
- Psyllium (which binds to cholesterol in bile and prevents gallstone formation, and prevents constipation, which also contributes to gallstones)
- Peppermint oil (which stimulates the flow of bile and is a terpene, which may help dissolve gallstones)
Patients can reduce their risk of gallstones by sticking to a high-fiber, low-fat, low-sugar diet, by drinking plenty of water and by maintaining a healthy weight. Exercise, regular bowel movements and a diet that includes fish rich in omega-3 oil also help.
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