Reviews

Endoscopic therapy of recurrent acute pancreatitis

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ABSTRACTEndoscopic therapy has emerged as an alternative to surgery for the subset of patients with acute recurrent pancreatitis whose disease is due to gallstones or other mechanical processes that obstruct the outflow of the pancreas. In this article, the authors review the specific situations in which endoscopic therapy might be useful in patients with acute recurrent pancreatitis.

KEY POINTS

  • Recurrent attacks of acute pancreatitis can be prevented only by determining and treating the underlying cause.
  • Endoscopic procedures can cause anxiety and carry a risk of bleeding, perforation, and pancreatitis. The risks, benefits, and other treatment options should be discussed with the patient.
  • Endoscopic therapy is now the preferred treatment of sphincter of Oddi dysfunction at centers that have experience with this technique.
  • In patients with pancreas divisum and recurrent acute pancreatitis, surgical and endoscopic minor sphincterotomy are equally effective.


 

References

Endoscopic therapy has become an alternative to surgery for some patients with acute recurrent pancreatitis, ie, those whose disease is caused by gallstones or other mechanical processes that can obstruct the outflow from the pancreas.

In this paper, we review the specific situations in which endoscopic therapy might be useful in patients with acute recurrent pancreatitis.

ACUTE PANCREATITIS IS MANAGED DIFFERENTLY IF IT RECURS

Recurrent acute pancreatitis is defined as more than one episode of acute pancreatitis.1 In clinical practice, it is important to distinguish between the first and recurrent episodes of acute pancreatitis.

Most patients who have one episode of acute pancreatitis never have another one.2,3 Therefore, for patients having an initial attack, we recommend a limited workup that includes a detailed history, laboratory evaluation, and a noninvasive imaging study such as transcutaneous ultrasonography or computed tomography.

On the other hand, people who have a second attack are at higher risk of more recurrences. Therefore, patients having recurrent attacks need a more extensive workup to determine the underlying cause. We recommend referring them to a gastroenterologist for further evaluation.

WHICH CAUSES CAN BE MANAGED ENDOSCOPICALLY?

In the Western world, 70% to 80% of cases of recurrent pancreatitis are due to either alcohol abuse or gallstone disease.2,4 The rest are related to:

  • Autoimmune disorders
  • Cancer, including occult malignancies and premalignant conditions such as intraductal papillary mucinous neoplasm
  • Chronic pancreatitis
  • Drugs
  • Heredity
  • Metabolic abnormalities (hypertriglyceridemia, hypercalcemia)
  • Sphincter of Oddi dysfunction
  • Structural or congenital abnormalities (pancreas divisum)
  • Trauma.

Figure 1.

In this review, we focus on the causes of recurrent acute pancreatitis that can be managed by endoscopic therapy (Figure 1), ie:
  • Gallstone disease, including biliary microlithiasis and sludge (in patients with or without a gallbladder)
  • Sphincter of Oddi dysfunction
  • Pancreas divisum
  • Obstruction to flow of pancreatic juice.

Endoscopy is not completely benign

Although endoscopic procedures are less invasive than surgery, they are not completely benign. They can cause anxiety and are associated with risks such as bleeding, perforation, and pancreatitis.5 The risks, benefits, and alternatives to these procedures should be discussed with the patient, and informed consent should be obtained before any endoscopic procedure.6

STONES (LARGE OR SMALL) OR SLUDGE IN PATIENTS WITH A GALLBLADDER

Gallstones can be large, but small stones (microlithiasis) and sludge are more common and therefore account for more cases of pancreatitis.

Strictly defined, microlithiasis refers to stones smaller than 2 mm in diameter in the biliary tract, whereas sludge is a suspension of biliary crystals, mucin, and cellular debris in the gallbladder or bile ducts.7 The terms are often used interchangeably, since the conditions often coexist and their treatment is similar.

Theories differ as to how microlithiasis or sludge can cause recurrent pancreatitis. According to one theory, the debris blocks the common channel, increasing the pancreatic intraductal pressure and leading to pancreatitis.8 A second theory is that small stones or biliary crystals passing through the sphincter of Oddi cause inflammation, and that repeated inflammation eventually leads to stenosis or dyskinesia of the sphincter, both of which have been associated with pancreatitis.9

Studies suggest that microlithiasis and sludge are common causes of recurrent pancreatitis, accounting for about two-thirds of cases according to estimates by Ros et al10 and Lee et al.11

Detecting small stones and sludge

The diagnosis of microlithiasis and biliary sludge in patients with a gallbladder is based on imaging studies and bile microscopy.12

Transabdominal ultrasonography is the imaging study most often used for diagnosing microlithiasis. The technology and expertise for this test are widely available, and it is relatively inexpensive.

Endoscopic ultrasonography is more sensitive for detecting microlithiasis and can examine the distal common bile duct.

Bile microscopy involves obtaining bile from the second portion of the duodenum (via an endoscope or a duodenal tube) or from the bile ducts (by cannulating the common bile duct and stimulating the gallbladder with cholecystokinin). The bile sample is centrifuged and inspected microscopically under plain light and polarized light (which aids the visualization of biliary crystals). The crystals can be cholesterol monohydrate, calcium bilirubinate, or calcium carbonate.7,13,14

Removing the gallbladder is the treatment of choice for small stones and sludge

Treatments to prevent recurrent attacks of acute pancreatitis due to microlithiasis and sludge include cholecystectomy, biliary sphincterotomy, and ursodioxycholic acid.10,11,15

In prospective observational studies by Ros et al10 and Lee et al,11 about half of the patients with recurrent pancreatitis were treated with cholecystectomy, endoscopic sphincterotomy, or ursodioxycholic acid in a nonrandomized fashion. The choice of therapy was based on the patient’s medical status and the preferences of the patient and the physician. Half the patients received no treatment. In both studies the median follow-up was 4 years. Treated patients had a significantly lower rate of recurrent attacks of pancreatitis during follow-up: less than 20% with therapy compared with more than 60% without therapy. Unfortunately, no published study has compared these three treatments head to head.

Cholecystectomy, however, is the most definitive therapy and is generally considered the treatment of choice.

Biliary sphincterotomy is an endoscopic procedure that involves cutting the sphincter of Oddi to allow the stones and sludge to pass more freely. It is as effective as cholecystectomy in preventing recurrent attacks but does not eliminate the risk of cholecystitis and cholangitis (Figure 1). For this reason, it is usually reserved for patients who cannot tolerate surgery due to comorbidities, those who refuse surgery, or those who are pregnant.16

Ursodeoxycholic acid is a reasonable alternative in patients who cannot tolerate surgical or endoscopic biliary sphincterotomy.1,17–20 The dosage is 10 mg/kg/day, which can be in two or three divided doses. The optimal duration of treatment is not known; however, since this drug works slowly, it may need to be taken for 2 years or more. Ursodeoxycholic acid is more effective in patients with cholesterol-based stones and crystals. It is not effective for large stones (> 1 cm in diameter) or calcified stones.

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