Acute recurrent pancreatitis

This article was originally presented at the 15th International Course on Therapeutic Endoscopy, hosted by the Wellesley Group, Division of Gastroenterology, St Michael’s Hospital, Toronto, Ontario, October 9-12, 2002 Division of Gastroenterology/Hepatology, Indiana University Medical Center, 550 North University Boulevard, Suite 2300, Indianapolis, Indiana USA Correspondence: Dr GA Lehman, Division of Gastroenterology/Hepatology, Indiana University Medical Center, 550 North University Boulevard, Suite 2300, Indianapolis, Indiana 46202-5250, USA. Telephone 317-274-4821, fax 317-278-0164, e-mail glehman@iupui.edu GA Lehman. Acute recurrent pancreatitis. Can J Gastroenterol 2003;17(6):381-383.

T here are many causes of recurrent pancreatitis (Table 1) (1).Frequently, the diagnosis can be readily determined by a detailed history, physical examination, routine laboratory tests and simple radiological studies.After application of these modalities, plus endoscopic retrograde cholangiopancreatography (ERCP) to reveal structural abnormalities, 10% to 30% of cases remain unexplained (1).Pancreaticobiliary manometry identifies sphincter of Oddi dysfunction (SOD), and reduces the idiopathic group to between 5% and 10% of the total.
It is recommended that ERCP plus sphincter of Oddi manometry be undertaken in cases of idiopathic acute recurrent pancreatitis.Sherman et al (2) evaluated 55 consecutive patients with ERCP, sphincter of Oddi manometry and microscopic examination of the bile for microlithiasis.They identified a potential cause of the illness in 66% of patients, including SOD (33%), microlithiasis (12%), pancreas divisum (PD) (14%), common bile duct stones (5%), choledochocele (4%), pancreatic cancer (4%), pancreatic stricture (2%) and papillary tumour (2%).Endoscopic or surgical therapy was of benefit in 84% of patients during a follow-up period of 17 months, whereas improvement occurred in only seven of the 13 patients (54%) who did not receive a diagnosis.

SOD
Elevated pancreatic and/or biliary basal sphincter pressure can be identified in 15% to 60% of patients with idiopathic pancreatitis (3)(4)(5).Although most patients have elevated pressures in both sphincters, 10% to 20% have abnormalities confined to the pancreatic sphincter (6).Therefore, standard biliary manometry and biliary sphincterotomy alone may miss pancreatic sphincter hypertension and fail to prevent recurrent attacks of pancreatitis.Evaluation of the pancreatic sphincter is recommended.

Pancreas divisum
PD is the most common congenital abnormality of the pancreas, and occurs in 5% to 10% of the general population (7).Even though most individuals with this lesion never experience symptoms, PD has been implicated as a cause of recurrent acute pancreatitis, chronic pancreatitis and chronic abdominal pain without pancreatitis.The mechanism for pancreatitis appears to be obstruction of the flow of pancreatic juice through a small or stenotic minor papilla, resulting in elevated intraductal pressure (8).The most compelling evidence in support of this argument is the prevention of recurrent episodes after pancreatic sphincterotomy (9,10).
Lans et al (11) conducted the first randomized trial of endoscopic therapy for this condition.They prospectively studied 19 patients with PD and acute recurrent pancreatitis, and compared a sham procedure with dilation of the minor papilla (but without sphincterotomy) followed by placement of a stent into the dorsal pancreatic duct.The stent was permanently removed after one year of treatment.During a follow-up period of roughly 30 months, pancreatitis was documented in only one of 10 patients (10%) in the endoscopic group, but occurred seven times in six of the nine control patients (67%).Symptomatic improvement of at least 50% occurred in 90% of the stented patients but in only 11% of control subjects.Ertan (12) reported similar results in an uncontrolled trial of papillary dilation and stent insertion in 25 patients with acute recurrent pancreatitis.
Lehman et al (13) showed that 13 of 17 patients with PD and recurrent acute pancreatitis enjoyed significant reductions in pain scores, frequency of episodes of pancreatitis and hospitalization rate after sphincterotomy of the minor papilla and transpapillary stenting.This technique involves placement of a short 3 to 5 French stent across the minor papilla followed by sphincterotomy using a 3 to 5 mm needle knife.The stent serves to prevent closure of the site by edema.It was then removed or allowed to fall out spontaneously after approximately two weeks.The mean period of follow-up was 1.7 years.
Restenosis is an unresolved problem that occurs in 10% to 25% of patients (10,13), and may be averted by injecting steroids into the sphincterotomy zone.Unlike the situation with recurrent acute pancreatitis, patients with PD and only chronic abdominal pain or chronic pancreatitis have shown minimal or no improvement with endoscopic sphincterotomy and/or stent placement (10,13).

Gallstones and microlithiasis
Gallstones are responsible for 30% to 70% of all cases of acute pancreatitis (3).Many cases of so-called idiopathic pancreatitis are caused by tiny stones (microlithiasis) that cannot be seen at ultrasonography or ERCP, but are visible with the microscopic examination of bile that is aspirated during ERCP (14)(15)(16).In some studies, cholesterol monohydrate or calcium bilirubinate crystals have been documented in 60% of 75% of cases.Other studies, especially those conducted after cholecystectomy, have documented the presence of these crystals only rarely.With modern day ultrasound studies that can readily detect gall bladder stones and sludge, subtle biliary disease is now a less common cause of idiopathic pancreatitis.Patients with liver blood test abnormalities at the onset of pancreatitis should not be classified as 'idiopathic' but more correctly probably biliary.

Neoplasms
Although tumours are often evident with standard imaging studies, ERCP or endoscopic ultrasound may be required to demonstrate the lesion.Neoplasms that can cause pancreatitis include ampullary tumours, cystic pancreatic neoplasms, intraductal mucin-hypersecreting neoplasms and ordinary ductal adenocarcinomas (17).

Drugs
Medications that are shown to cause pancreatitis are listed in Table 2 (1).The clinical value of the drug must be weighed against the potential risk of adverse effects.

CONCLUSIONS
Many patients who are currently thought to have idiopathic recurrent pancreatitis have a detectable cause if carefully evaluated.ERCP will continue to play an important role in the management of patients with recurrent acute pancreatitis, especially those with structural abnormalities.Bile aspiration with microscopic examination for crystals is useful for ruling out microlithiasis.In addition, SOD manometry is essential to identify cases of biliary or pancreatic duct dyskinesia