Since its introduction, endoscopic retrograde cholangiopancreatography (ERCP) has been an important tool for the confirmation and treatment of acute and chronic pancreatic disease. However, compared with other endoscopic procedures, ERCP carries the highest risk of complications, particularly pancreatitis, which may be fatal. As newer and less-invasive techniques have been introduced, it has evolved into a primarily therapeutic procedure and plays a core role in the management of biliary pancreatitis, idiopathic pancreatitis, chronic pancreatitis, and pancreatic duct leaks. These applications, as well as the important topic of post-ERCP pancreatitis, are explored in this article.
Gallstone Pancreatitis
Biliary stones, along with excess alcohol consumption, account for more than 80% of cases of acute pancreatitis. Biliary pancreatitis is an absolute indication for cholecystectomy, and clearance of persistent bile duct stones either by ERCP or surgery is requisite. Stool analysis from patients with gallstone pancreatitis has led some investigators to propose that small stones that pass spontaneously are to blame for biliary pancreatitis. Other researchers have proposed that obstructing distal bile duct stones may promote the evolution of interstitial pancreatitis to more serious necrotic forms. The role of ERCP in the management of biliary pancreatitis has been the subject of several landmark trials. These publications suggest that early ERCP is primarily beneficial in patients with cholangitis or biliary obstruction ( Fig. 1 ).
Neoptolemos and coworkers randomly assigned 121 patients with gallstone pancreatitis to early ERCP, within 3 days of admission, versus conservative therapy. Patients with jaundice and cholangitis were enrolled in the study. After day 5, those in the conservative arm could undergo ERCP if needed. The researchers reported that fewer complications were seen in the early intervention group; although these findings were primarily found in patients with more severe disease. In another study, Fan and colleagues randomly assigned 195 patients with severe pancreatitis to emergency ERCP within 24 hours or to conservative therapy. Although the study was not limited to gallstone pancreatitis, the authors indicate that biliary pancreatitis was the prevalent form in their Hong Kong population. In the conservatively treated group, ERCP was performed for clinical deterioration. Although there was no significant difference in local or systemic complications of pancreatitis among the groups, no biliary sepsis developed in those treated with emergency ERCP, whereas 9% of those treated conservatively had sepsis. Additionally, the morality rate was somewhat lower in the early ERCP group, 5%, compared with 9% in the conservatively treated group.
The relationship between pancreatitis, cholangitis, and early ERCP was further explored by Folsch and colleagues in a larger series of 238 patients. In this group, enrollment was restricted to patients with gallstone pancreatitis suggested by abnormal imaging or abnormal liver tests. Patients with biliary obstruction or cholangitis with a bilirubin level greater than or equal to 5mg/dL, fever, or persistent biliary pain were excluded. Urgent ERCP was performed in the intervention group within 3 days of admission. In the conservative group, ERCP was performed within the first 3 weeks for clinical deterioration, as defined by fever, an increase in bilirubin level of 3mg/dL, or persistent biliary pain. However, when a trend toward greater mortality was seen, the study was halted by the institutional review board. Fourteen patients in the treatment group died (10 from severe pancreatitis), compared with 7 deaths in the conservative treatment group (4 from severe pancreatitis). Although no overall difference was seen in complications between the groups, more serious complications were seen in the early ERCP group, including respiratory failure.
The explanation for the increased number of cases of severe pancreatitis and mortality in the early ERCP group in the study by Folsch and colleagues is unclear. Worsening pancreatitis caused by ERCP was not measured but may have been a contributing factor. Fan and coworkers noted increased amylase level, compared with amylase level at the time of admission, in 8% of those who underwent urgent ERCP, but in the setting of pancreatitis, interpretation of this information is not simple. The findings by Folsch and colleagues run parallel to findings that both open and laparoscopic cholecystectomy, performed in the setting of moderately severe pancreatitis, are associated with more complications.
Idiopathic Pancreatitis
Although most cases of acute pancreatitis result from gallstones and alcohol consumption, the origin in 10% to 30% of the cases remains unknown after a comprehensive noninvasive workup.
During the last 2 decades, the optimization of minimally invasive imaging techniques, including magnetic resonance cholangiopancreatography, the advent of endoscopic ultrasound (EUS), and the universality of laparoscopic cholecystectomy have limited the role of ERCP to cases in which therapeutic intervention is needed. The biliary endoscopist has the responsibility to confirm that a comprehensive workup has been completed, including the appropriate history and noninvasive testing, as well as the consideration of EUS. ERCP may then be used appropriately to investigate and treat sources of pancreatitis that may be amenable to endoscopic therapy, including microlithiasis, sphincter of Oddi dysfunction (SOD), pancreas divisum, and other congenital abnormalities.
Initial Evaluation and Endoscopic Ultrasound
Before embarking on a course of interventional endoscopic evaluation, it is imperative to perform a detailed history to assess for alcohol consumption, previous surgery, trauma, toxins, and medications, as well as acquiring a family and past medical history. Extensive family history of pancreatitis warrants testing for hereditary pancreatitis-associated mutations in the cationic trypsinogen, serine protease inhibitor Kazal type 1, and cystic fibrosis genes. In patients with a history of collagen vascular disease, autoimmune pancreatitis should be considered, and testing should include gamma globulin, ANA, and immunoglobulin-4 levels. All patients should undergo transcutaneous sonography to assess for gallstones as well as assesment of calcium, lipid, and liver function. Fluctuating liver test levels, even in the absence of abnormal gallbladder imaging, warrant consideration of an empiric cholecystectomy. A spiral computed tomography scan or magnetic resonance imaging of the pancreas is a consideration in older patients or if there is an increased risk of malignancy.
Given the significant risk of procedure-induced pancreatitis, ERCP is not frequently recommended after a single episode of unexplained pancreatitis. EUS has a significant yield in the setting of both primary and recurrent idiopathic pancreatitis, with a diagnosis achieved in 51% to 92% of cases. Studies suggest that, in patients who have not undergone a cholecystectomy, the most common etiologies are biliary stones or sludge. Among those who have undergone gallbladder resection, the leading etiology is pancreas divisum. Studies vary in their inclusion of chronic pancreatitis; however, it is a leading origin in patients both before and after cholecystectomy when included. Using the yield of endoscopic sphincterotomy as a gold standard, Chak and colleagues reported that EUS has a superior accuracy (97%) to transabdominal ultrasound (83%) and diagnostic ERCP (89%) in the evaluation of bile duct stones. EUS has an excellent correlation with ERCP and secretin testing in those with moderate or severe chronic pancreatitis and is fairly accurate for the diagnosis of pancreas divisum. In their series of patients with idiopathic pancreatitis, Tandon and Topazian report that a diagnosis was confirmed in 68% of patients over a course of 16 months. ERCP was required in the 29% of the cases, and the EUS-based diagnosis changed in 13%. Their findings suggest that patients with idiopathic pancreatitis should undergo EUS before ERCP, given the high yield of the former and potential morbidity of the latter.
Microlithiasis
Microlithiasis and biliary sludge may trigger pancreatitis by occluding the pancreatic duct at the level of the papilla. In a prospective series of patients with idiopathic pancreatitis who had not undergone cholecystectomy or aspiration of bile at time of ERCP or via a duodenal feeding tube, demonstrated biliary sludge as the origin of pancreatitis in more than two-thirds of patients. Biliary sludge and microlithiasis may be diagnosed by microscopy or imaging, and if confirmed, they both merit cholecystectomy.
Biliary sludge is a suspension of cellular debris and biliary crystals. Microscopic analysis of bile is the gold standard for diagnosis of biliary sludge. Bile aspirated from the gallbladder theoretically has the highest yield, followed by bile obtained from the bile duct, and finally, that obtained from the duodenum. In a recent trial using bedside microscopy at the time of ERCP in patients with idiopathic pancreatitis who had not undergone cholecystectomy, bile crystals were found in 50% of patients and were thought to be the primary etiology in 22%. Nonetheless, duodenal bile aspirate at the time of EUS or duodenoscopy has a significant yield, and these procedures are less likely to be associated with complications.
Biliary sludge, as well as microlithiasis, may also be detected radiographically at the time of ERCP. Microlithiasis is defined as bile duct stones that are smaller than 3 mm. In a prospective study of ERCP in patients with recurrent idiopathic pancreatitis and intact gallbladder, 27.5% were found have cholangiographic evidence of microlithiasis. Another approach has been the introduction of 20-MHz intraductal ultrasound probes at the time of ERCP. In a study of the role of this probe in 31 patients with unremarkable diagnostic ERCP findings and idiopathic pancreatitis, intraductal ultrasound scan found a potential etiology in 42%, with most of these having biliary microlithiasis or sludge. However, EUS has been demonstrated to have a 95% sensitivity and high negative predictive value for small gallbladder stones and sludge undetectable by transabdominal ultrasound scan but was not performed in this cohort ( Fig. 2 ).
ERCP may be used to diagnose microlithiasis and biliary sludge, but its use should be reserved for situations in which other testing, including sphincter of Oddi manometry (SOM), is being concurrently performed. Otherwise, less-invasive modalities, such as EUS, should be used. In centers where bedside microscopy is available during ERCP, sphincterotomy is performed on confirmation of biliary crystals. Demonstration of microlithiasis or biliary sludge is an indication for cholecystectomy. Some experts, however, recommend cholecystectomy in patients with idiopathic recurrent pancreatitis and no other detectable etiologies, even if microlithiasis cannot be confirmed.
Sphincter of Oddi Dysfunction and Papillary Stenosis
Among those with idiopathic pancreatitis who have undergone cholecystectomy, SOD is the most frequent diagnosis made after a comprehensive evaluation including ERCP is completed. However, only in the cohort reported by Coyle and colleagues was EUS routinely performed. Consistent with the other series, SOD was the leading etiology confirmed in 31% of patients in this group. It is proposed that dysfunction of the sphincter of Oddi may involve either a fibroinflammatory stenosis or a motility anomaly of the smooth muscle band that surrounds the distal common bile and pancreatic ducts as they pass through the ampulla of Vater. SOD may be confirmed manometrically by measurement of the biliary sphincter, the pancreatic sphincter, or both. Similarly, treatment is sphincterotomy of either sphincter or both. The optimal evaluation and treatment strategies are the subject of several recent series.
SOD is clinically categorized as type 1 (definite) SOD in those with typical pancreaticobiliary pain, abnormal pancreatic or liver enzymes, or dilated or sluggishly emptying bile or pancreatic ducts. Patients with type 2 (probable) SOD have pain accompanied by either abnormal laboratory results or imaging, and type 3 (possible) have only pain. Papillary stenosis represents a subgroup of SOD thought to have a structural origin and is considered similar to SOD type 1 in studies of idiopathic pancreatitis. By definition, those with symptomatic idiopathic pancreatitis have abnormal laboratory values and thus may have type 2 SOD if imaging shows normal ducts.
To confirm the diagnosis of SOD, measurements of the pressures in the distal bile or pancreatic ducts are taken with a manometry catheter. Studies have found that an increased basal pressure (>40 mm Hg) of the bile or pancreatic sphincters correlates best with clinical outcomes and is used to define SOD in most series. Markers of biliary dyskinesia, including high-frequency contractions and preponderant retrograde contractions, are less reliable. SOM has been found more likely to be abnormal in those with type 1 SOD (92.3%) than type 2 (58.2%) or type 3. Given the high correlation, manometry is generally deferred in those with type 1 SOD. Additionally, studies have found nearly universal improvement in patients with type 1 SOD who undergo sphincterotomy, and negative manometry in this group may be misleading.
To minimize intervention of the pancreatic duct, many endoscopists have historically measured only biliary pressures. Eversman and coworkers reported that in a cohort of patients with idiopathic pancreatitis, 25.5% had only pancreatic sphincter abnormalities, 6.4% had only biliary sphincter abnormalities, and 40% had abnormalities of both. It can be argued that if the first sphincter (pancreatic or biliary) exhibits normal manometry, it is then prudent to evaluate the remaining sphincter.
Given the invasive nature of ERCP with SOM, there have been a number of attempts to develop alternative modalities to assess for SOD. Secretin causes temporary dilatation of the pancreatic duct; prolonged dilatation suggests an abnormal sphincter. Magnetic resonance cholangiopancreatography enhanced with secretin administration has been used to assess for SOD as the origin of idiopathic pancreatitis. Unfortunately, it was found to be insensitive, recognizing only 57.1% of patients who benefited from therapeutic ERCP, although it was 100% specific.
Upon confirmation of SOD, endoscopic sphincterotomy is recommended. In 2 separate trials, patients with suspected SOD were randomly assigned to receive either a sphincterotomy or a sham sphincterotomy. All patients in both arms of each trial received ERCP and SOM. Pain levels were assessed at various points. In both series, patients with manometrically confirmed SOD benefited significantly more from the sphincterotomy compared with those receiving the sham procedure. Also, in both trials, for those patients with normal sphincter pressure, the results from sphincterotomy and sham procedures did not differ. Nonetheless, patients with idiopathic pancreatitis were excluded from one of these trials, and both were primarily focused on those with suspected type 2 biliary SOD. However, cohort studies suggest that at least 70% of those with idiopathic pancreatitis and confirmed SOD remained asymptomatic at a mean follow-up of at least 30 months after sphincterotomy.
Studies suggest that treatment of both the pancreatic and biliary sphincters with dual sphincterotomy, may result in fewer recurrent symptoms and less reintervention for patients with elevated pancreatic sphincter pressure compared with the more historic approach of initiating treatment with a biliary sphincterotomy. This concept also may apply to patients with idiopathic pancreatitis. Wehrmann and coworkers recently reported that relapse occurred in only 29% of those who underwent dual sphincterotomy compared with 92% in those who initially underwent only a biliary or pancreatic sphincterotomy.
Pancreas Divisum and Other Structural Etiologies
Pancreas divisum is the most common congenital anomaly of the pancreas. Because of the failure of the dorsal and ventral pancreatic ducts to fuse during weeks 6 to 8 of gestation, it occurs in 5% to 10% of the population; however, less than 10% of those with pancreas divisum experience symptoms. It is thought that recurrent pancreatitis is caused by increased intraductal pressure, which is caused by outlet obstruction at the level of the minor papilla. Minor papilla cannulation and ductal decompression may be technically challenging. Although decompression appears beneficial, particularly in those with recurrent pancreatitis, long-term treatment strategies are unclear. Additionally, a number of unusual congenital anomalies of the pancreas also present with recurrent pancreatitis and may be amenable to endoscopic therapy.
The primary aim of endoscopic treatment of pancreas divisum is decompression. Highly tapered and needle-tipped catheters often are used for pancreatic duct access, which is frequently difficult. Secretin may be administered to increase flow of bicarbonate as well as widen the pancreatic duct orifice to enhance its visibility. In a double-blind trial, patients with difficult minor papilla cannulation were randomly assigned to receive either secretin or placebo during 2 discrete phases of the procedure. Cannulation was achieved during the placebo phase in 8% versus 81% during the secretin phase. Methylene blue also can be used as a contrast agent to enhance visualization by spraying the minor papilla and by injecting the substance into the major papilla.
Upon cannulation, endoscopic therapy, including papillotomy, stent placement, and balloon dilatation, may be performed ( Fig. 3 ) . Minor papillotomy may be accomplished using a needle knife over a previously placed stent or by performing a pull-type sphincterotomy, with comparable success and complications. Heyries and colleagues treated 16 patients who had recurrent acute pancreatitis and pancreas divisum with stenting (most after papillotomy or papillectomy) for 8 months versus minor papillotomy alone in the remaining 8 patients. The results of this small series suggest that symptomatic recurrence occurred earlier in patients without stents. Another approach has been the placement of stents after balloon dilatation of the minor papilla without papillotomy.
The most robust data regarding the efficacy of endotherapy for pancreas divisum are from the trial of Lans and coworkers. Nineteen patients who had at least 2 episodes of documented pancreatitis in the previous 12 months were randomly assigned to receive either ERCP with placement of pancreatic stent through the minor papilla and stent exchange every 4 months for 1 year or clinical follow-up every 4 months but without therapy for 1 year. Among the 10 patients in the stent group, there were significantly fewer episodes of pancreatitis (1 episode) compared with 7 episodes among the 9 patients randomly assigned to clinical follow-up. In the studies by Heyries and coworkers and Ertan and colleagues, patients had significantly fewer episodes of pancreatitis in the 2 to 3 years after the course of treatment than the period before endoscopic therapy. Although endoscopic therapy has been performed in patients with chronic pancreatitis and abdominal pain, those with acute recurrent pancreatitis appear to have the greatest benefit. Lehman and colleagues reported that at a mean follow-up of 1.7 years after minor papillotomy, the symptoms on patients with acute recurrent pancreatitis were markedly improved in 76.5% versus 27.3% for those with chronic pancreatitis and 26.1% for those with chronic pain. This has been corroborated by additional studies.
Although stent placement may decrease the number of episodes of pancreatitis, particularly for patients with recurrent pancreatitis, it may result in adverse ductal changes. Kozarek and coworkers reported that 36% of those who underwent stent placement for pancreas divisum, SOD, and other indications had de novo pancreatic ductal changes that resembled chronic pancreatitis that did not resolve in some cases. Sherman and colleagues found that parenchymal changes were seen by EUS corresponding to ductal changes after pancreas stent placement and that, in some cases, these changes were persistent.
In addition to pancreas divisum, a number of rare congenital anomalies may present as idiopathic pancreatitis in children as well as in adults. Anomalous pancreaticobiliary union (APBU) is associated with recurrent pancreatitis in children, and these patients may benefit from ERCP with sphincterotomy. APBU manifests either as a biliary type in which the common bile duct inserts into the pancreatic duct (etiologically associated with choledochal cysts), a long-Y type in which there is a long common channel, or a pancreatic type in which the pancreatic duct inserts into the bile duct. Guelrud and colleagues showed in a recent series that a cohort of children with APBU with recurrent pancreatitis all had SOD and benefited from sphincterotomy. It is suspected that the sphincter hypertension may provide the gradient that enables bile to reflux from the low-pressure bile duct into the higher-pressure pancreatic duct driving recurrent pancreatitis.
Choledochocele, or type 3 choledochal cyst, manifests as a cystic dilatation of the intraduodenal segment of the bile duct. It may present as recurrent pancreatitis in adults and may be addressed with endoscopic sphincterotomy. Annular pancreas is a very rare anomaly found in 1 of 20,000 individuals and is caused by faulty rotation of the ventral pancreas. It is associated with pancreas divisum in 30% of cases and most commonly presents with recurrent pancreatitis, although it may also present with bowel obstruction. EUS results show an echogenic ring identical to the pancreatic parenchyma surrounding the duodenum, and ERCP findings often show a looping pancreas duct branch crossing the duodenum. ERCP with pancreatic sphincterotomy may help patients with recurrent pancreatitis, whereas those with bowel obstruction will typically require surgery.
Another anatomic cause of acute recurrent pancreatitis is cystic duct insertion at the papilla ( Fig. 4 ). It is thought that greater reflux of bile into the pancreatic duct is a consequence of this anatomy, and the treatment is cholecystectomy. It has been proposed that juxtapapillary diverticuli may predispose to recurrent pancreatitis. However, a matched-pair analysis of 350 cases found that although the diverticuli were correlated with bile duct stones, they were not correlated with acute or chronic pancreatitis. Chronic pancreatitis with ductal strictures may also cause intermittent recurrent pancreatitis and is the topic of the next section.
Idiopathic Pancreatitis
Although most cases of acute pancreatitis result from gallstones and alcohol consumption, the origin in 10% to 30% of the cases remains unknown after a comprehensive noninvasive workup.
During the last 2 decades, the optimization of minimally invasive imaging techniques, including magnetic resonance cholangiopancreatography, the advent of endoscopic ultrasound (EUS), and the universality of laparoscopic cholecystectomy have limited the role of ERCP to cases in which therapeutic intervention is needed. The biliary endoscopist has the responsibility to confirm that a comprehensive workup has been completed, including the appropriate history and noninvasive testing, as well as the consideration of EUS. ERCP may then be used appropriately to investigate and treat sources of pancreatitis that may be amenable to endoscopic therapy, including microlithiasis, sphincter of Oddi dysfunction (SOD), pancreas divisum, and other congenital abnormalities.
Initial Evaluation and Endoscopic Ultrasound
Before embarking on a course of interventional endoscopic evaluation, it is imperative to perform a detailed history to assess for alcohol consumption, previous surgery, trauma, toxins, and medications, as well as acquiring a family and past medical history. Extensive family history of pancreatitis warrants testing for hereditary pancreatitis-associated mutations in the cationic trypsinogen, serine protease inhibitor Kazal type 1, and cystic fibrosis genes. In patients with a history of collagen vascular disease, autoimmune pancreatitis should be considered, and testing should include gamma globulin, ANA, and immunoglobulin-4 levels. All patients should undergo transcutaneous sonography to assess for gallstones as well as assesment of calcium, lipid, and liver function. Fluctuating liver test levels, even in the absence of abnormal gallbladder imaging, warrant consideration of an empiric cholecystectomy. A spiral computed tomography scan or magnetic resonance imaging of the pancreas is a consideration in older patients or if there is an increased risk of malignancy.
Given the significant risk of procedure-induced pancreatitis, ERCP is not frequently recommended after a single episode of unexplained pancreatitis. EUS has a significant yield in the setting of both primary and recurrent idiopathic pancreatitis, with a diagnosis achieved in 51% to 92% of cases. Studies suggest that, in patients who have not undergone a cholecystectomy, the most common etiologies are biliary stones or sludge. Among those who have undergone gallbladder resection, the leading etiology is pancreas divisum. Studies vary in their inclusion of chronic pancreatitis; however, it is a leading origin in patients both before and after cholecystectomy when included. Using the yield of endoscopic sphincterotomy as a gold standard, Chak and colleagues reported that EUS has a superior accuracy (97%) to transabdominal ultrasound (83%) and diagnostic ERCP (89%) in the evaluation of bile duct stones. EUS has an excellent correlation with ERCP and secretin testing in those with moderate or severe chronic pancreatitis and is fairly accurate for the diagnosis of pancreas divisum. In their series of patients with idiopathic pancreatitis, Tandon and Topazian report that a diagnosis was confirmed in 68% of patients over a course of 16 months. ERCP was required in the 29% of the cases, and the EUS-based diagnosis changed in 13%. Their findings suggest that patients with idiopathic pancreatitis should undergo EUS before ERCP, given the high yield of the former and potential morbidity of the latter.
Microlithiasis
Microlithiasis and biliary sludge may trigger pancreatitis by occluding the pancreatic duct at the level of the papilla. In a prospective series of patients with idiopathic pancreatitis who had not undergone cholecystectomy or aspiration of bile at time of ERCP or via a duodenal feeding tube, demonstrated biliary sludge as the origin of pancreatitis in more than two-thirds of patients. Biliary sludge and microlithiasis may be diagnosed by microscopy or imaging, and if confirmed, they both merit cholecystectomy.
Biliary sludge is a suspension of cellular debris and biliary crystals. Microscopic analysis of bile is the gold standard for diagnosis of biliary sludge. Bile aspirated from the gallbladder theoretically has the highest yield, followed by bile obtained from the bile duct, and finally, that obtained from the duodenum. In a recent trial using bedside microscopy at the time of ERCP in patients with idiopathic pancreatitis who had not undergone cholecystectomy, bile crystals were found in 50% of patients and were thought to be the primary etiology in 22%. Nonetheless, duodenal bile aspirate at the time of EUS or duodenoscopy has a significant yield, and these procedures are less likely to be associated with complications.
Biliary sludge, as well as microlithiasis, may also be detected radiographically at the time of ERCP. Microlithiasis is defined as bile duct stones that are smaller than 3 mm. In a prospective study of ERCP in patients with recurrent idiopathic pancreatitis and intact gallbladder, 27.5% were found have cholangiographic evidence of microlithiasis. Another approach has been the introduction of 20-MHz intraductal ultrasound probes at the time of ERCP. In a study of the role of this probe in 31 patients with unremarkable diagnostic ERCP findings and idiopathic pancreatitis, intraductal ultrasound scan found a potential etiology in 42%, with most of these having biliary microlithiasis or sludge. However, EUS has been demonstrated to have a 95% sensitivity and high negative predictive value for small gallbladder stones and sludge undetectable by transabdominal ultrasound scan but was not performed in this cohort ( Fig. 2 ).
ERCP may be used to diagnose microlithiasis and biliary sludge, but its use should be reserved for situations in which other testing, including sphincter of Oddi manometry (SOM), is being concurrently performed. Otherwise, less-invasive modalities, such as EUS, should be used. In centers where bedside microscopy is available during ERCP, sphincterotomy is performed on confirmation of biliary crystals. Demonstration of microlithiasis or biliary sludge is an indication for cholecystectomy. Some experts, however, recommend cholecystectomy in patients with idiopathic recurrent pancreatitis and no other detectable etiologies, even if microlithiasis cannot be confirmed.
Sphincter of Oddi Dysfunction and Papillary Stenosis
Among those with idiopathic pancreatitis who have undergone cholecystectomy, SOD is the most frequent diagnosis made after a comprehensive evaluation including ERCP is completed. However, only in the cohort reported by Coyle and colleagues was EUS routinely performed. Consistent with the other series, SOD was the leading etiology confirmed in 31% of patients in this group. It is proposed that dysfunction of the sphincter of Oddi may involve either a fibroinflammatory stenosis or a motility anomaly of the smooth muscle band that surrounds the distal common bile and pancreatic ducts as they pass through the ampulla of Vater. SOD may be confirmed manometrically by measurement of the biliary sphincter, the pancreatic sphincter, or both. Similarly, treatment is sphincterotomy of either sphincter or both. The optimal evaluation and treatment strategies are the subject of several recent series.
SOD is clinically categorized as type 1 (definite) SOD in those with typical pancreaticobiliary pain, abnormal pancreatic or liver enzymes, or dilated or sluggishly emptying bile or pancreatic ducts. Patients with type 2 (probable) SOD have pain accompanied by either abnormal laboratory results or imaging, and type 3 (possible) have only pain. Papillary stenosis represents a subgroup of SOD thought to have a structural origin and is considered similar to SOD type 1 in studies of idiopathic pancreatitis. By definition, those with symptomatic idiopathic pancreatitis have abnormal laboratory values and thus may have type 2 SOD if imaging shows normal ducts.
To confirm the diagnosis of SOD, measurements of the pressures in the distal bile or pancreatic ducts are taken with a manometry catheter. Studies have found that an increased basal pressure (>40 mm Hg) of the bile or pancreatic sphincters correlates best with clinical outcomes and is used to define SOD in most series. Markers of biliary dyskinesia, including high-frequency contractions and preponderant retrograde contractions, are less reliable. SOM has been found more likely to be abnormal in those with type 1 SOD (92.3%) than type 2 (58.2%) or type 3. Given the high correlation, manometry is generally deferred in those with type 1 SOD. Additionally, studies have found nearly universal improvement in patients with type 1 SOD who undergo sphincterotomy, and negative manometry in this group may be misleading.
To minimize intervention of the pancreatic duct, many endoscopists have historically measured only biliary pressures. Eversman and coworkers reported that in a cohort of patients with idiopathic pancreatitis, 25.5% had only pancreatic sphincter abnormalities, 6.4% had only biliary sphincter abnormalities, and 40% had abnormalities of both. It can be argued that if the first sphincter (pancreatic or biliary) exhibits normal manometry, it is then prudent to evaluate the remaining sphincter.
Given the invasive nature of ERCP with SOM, there have been a number of attempts to develop alternative modalities to assess for SOD. Secretin causes temporary dilatation of the pancreatic duct; prolonged dilatation suggests an abnormal sphincter. Magnetic resonance cholangiopancreatography enhanced with secretin administration has been used to assess for SOD as the origin of idiopathic pancreatitis. Unfortunately, it was found to be insensitive, recognizing only 57.1% of patients who benefited from therapeutic ERCP, although it was 100% specific.
Upon confirmation of SOD, endoscopic sphincterotomy is recommended. In 2 separate trials, patients with suspected SOD were randomly assigned to receive either a sphincterotomy or a sham sphincterotomy. All patients in both arms of each trial received ERCP and SOM. Pain levels were assessed at various points. In both series, patients with manometrically confirmed SOD benefited significantly more from the sphincterotomy compared with those receiving the sham procedure. Also, in both trials, for those patients with normal sphincter pressure, the results from sphincterotomy and sham procedures did not differ. Nonetheless, patients with idiopathic pancreatitis were excluded from one of these trials, and both were primarily focused on those with suspected type 2 biliary SOD. However, cohort studies suggest that at least 70% of those with idiopathic pancreatitis and confirmed SOD remained asymptomatic at a mean follow-up of at least 30 months after sphincterotomy.
Studies suggest that treatment of both the pancreatic and biliary sphincters with dual sphincterotomy, may result in fewer recurrent symptoms and less reintervention for patients with elevated pancreatic sphincter pressure compared with the more historic approach of initiating treatment with a biliary sphincterotomy. This concept also may apply to patients with idiopathic pancreatitis. Wehrmann and coworkers recently reported that relapse occurred in only 29% of those who underwent dual sphincterotomy compared with 92% in those who initially underwent only a biliary or pancreatic sphincterotomy.
Pancreas Divisum and Other Structural Etiologies
Pancreas divisum is the most common congenital anomaly of the pancreas. Because of the failure of the dorsal and ventral pancreatic ducts to fuse during weeks 6 to 8 of gestation, it occurs in 5% to 10% of the population; however, less than 10% of those with pancreas divisum experience symptoms. It is thought that recurrent pancreatitis is caused by increased intraductal pressure, which is caused by outlet obstruction at the level of the minor papilla. Minor papilla cannulation and ductal decompression may be technically challenging. Although decompression appears beneficial, particularly in those with recurrent pancreatitis, long-term treatment strategies are unclear. Additionally, a number of unusual congenital anomalies of the pancreas also present with recurrent pancreatitis and may be amenable to endoscopic therapy.
The primary aim of endoscopic treatment of pancreas divisum is decompression. Highly tapered and needle-tipped catheters often are used for pancreatic duct access, which is frequently difficult. Secretin may be administered to increase flow of bicarbonate as well as widen the pancreatic duct orifice to enhance its visibility. In a double-blind trial, patients with difficult minor papilla cannulation were randomly assigned to receive either secretin or placebo during 2 discrete phases of the procedure. Cannulation was achieved during the placebo phase in 8% versus 81% during the secretin phase. Methylene blue also can be used as a contrast agent to enhance visualization by spraying the minor papilla and by injecting the substance into the major papilla.
Upon cannulation, endoscopic therapy, including papillotomy, stent placement, and balloon dilatation, may be performed ( Fig. 3 ) . Minor papillotomy may be accomplished using a needle knife over a previously placed stent or by performing a pull-type sphincterotomy, with comparable success and complications. Heyries and colleagues treated 16 patients who had recurrent acute pancreatitis and pancreas divisum with stenting (most after papillotomy or papillectomy) for 8 months versus minor papillotomy alone in the remaining 8 patients. The results of this small series suggest that symptomatic recurrence occurred earlier in patients without stents. Another approach has been the placement of stents after balloon dilatation of the minor papilla without papillotomy.
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