Although there are numerous causes of acute pancreatitis, an etiology cannot always be found. Two potential etiologies, microlithiasis and sphincter of Oddi dysfunction, are discussed in this review. Gallbladder microlithiasis, missed on transcutaneous ultrasound, is reported as the cause of idiopathic acute pancreatitis in a wide frequency range of 6%-80%. The best diagnostic technique for gallbladder microlithiasis is endoscopic ultrasound although biliary crystal analysis and empiric cholecystectomy remain as reasonable options. In contrast, in patients who are post-cholecystectomy, bile duct microlithiasis does not appear to have a role in the pathogenesis of acute pancreatitis. Sphincter of Oddi dysfunction is present in 30%-65% of patients with idiopathic acute recurrent pancreatitis in whom other diagnoses have been excluded. It is unclear if this sphincter dysfunction was the original etiology of the first episode of pancreatitis although it appears to have a causative role in recurring episodes since sphincter ablation decreases the frequency of recurrent attacks. Unfortunately, this conclusion is primarily based on small retrospective case series; larger prospective studies of the outcome of pancreatic sphincterotomy for SOD-associated acute pancreatitis are sorely needed. Another problem with this diagnosis and its treatment is the concern over potential procedure related complications from endoscopic retrograde cholangiopancreatography (ERCP), manometry and pancreatic sphincterotomy. For these reasons, patients should have recurrent acute pancreatitis, not a single episode, and have a careful informed consent before assessment of the sphincter of Oddi is undertaken.

Sphincter of dysfunction (SOD) is a benign, noncalculous obstructive disorder that occurs at the level of the sphincter of Oddi (SO) (Figure 1). The pathogenesis of SOD relates either to passive obstruction at the SO caused by fibrosis and/or inflammation or to active obstruction caused by sphincter muscle spasm. These two mechanisms of functional obstruction at the SO are not mutually exclusive.

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Figure 1 Sphincter of Oddi anatomy.

SOD is a possible cause of three clinical conditions: (1) persistent or recurrent biliary pain following cholecystectomy in the absence of structural abnormalities, (2) acute idiopathic pancreatitis, and (3) biliary pain in patients with intact gallbladders but without cholelithiasis (the least studied and most controversial clinical association). SOD also has been described in patients who have had liver transplantation, have the acquired immunodeficiency syndrome, and have hyperlipidemia. This manuscript will discuss only the association of SOD with acute idiopathic pancreatitis (AIP).

Microlithiasis is another possible cause of acute idiopathic pancreatitis. This is best studied in patients with intact gallbladders, and is felt to be one of the most common causes of AIP. Although it seems intuitive that microlithiasis may also occur de novo in the bile duct in patients with prior cholecystectomy, this entity is not well described.

Several studies have demonstrated a high frequency (30%-65%) of sphincter hypertension in patients with acute idiopathic pancreatitis, and a 50% to 87% frequency in those with chronic pancreatitis. Elevated pancreatic sphincter pressure in humans has been shown to correlate to increased intrapancreatic ductal pressure presumably playing a role in the pathogenesis of pancreatitis[16]. Whether this pancreatic duct obstruction causes the initial injury or is the result of prior pancreatic inflammation is unknown. Elevated pancreatic basal SO pressure and concomitant elevated PD pressure also occurs in patients with pain only and no prior evidence of pancreatitis arguing that it is not the sole determinant of pancreatitis. However, since pancreatic sphincter ablation does decrease future attacks of pancreatitis (although studies are primarily retrospective and uncontrolled), it appears that pancreatic SOD plays a role in the pathogenesis of recurrent attacks even if it was not the original cause.

A classification system similar to the three types of suspected biliary SOD has been proposed for possible pancreatic SOD[17]. In the contemporary proposed system, pancreatic typeIpatients have pancreatic-type pain, a serum amylase or lipase level of 1.1 times normal on one occasion, and pancreatic duct dilation (> 6 mm in the head and > 5 mm in the body); pancreatic type II patients have pain and one of the preceding criteria; type III patients have pancreatic-type pain only. This classification system is not widely utilized for several reasons: (1) Few patients with typeIpancreatic SOD are reported, the vast majority of AIP patients have normal pancreatic duct caliber, (2) AIP patients would fit into the pancreatic type II category and are the primary patients of interest, and (3) Pancreatic type pain only is not sufficiently specific to be a widely accepted diagnosis.

The gold standard for making the diagnosis of SOD is SO manometry during ERCP. Water perfused catheters are the most commonly utilized systems although microtransducer manometry is also reported[18]. Although some experts have argued for attention to abnormalities of sphincter manometry other than baseline sphincter pressure, such as phasic wave frequency and propagation direction, only basal pressures are widely used clinically. Abnormal basal sphincter pressures are usually concordant for the pancreatic and bile ducts but may occur in only one portion of the sphincter. It has been shown that increased basal sphincter pressure is more likely to be confined to the pancreas in patients with pancreatitis and more likely confined to the bile duct in persons with elevated levels of serum liver enzymes[19].

Medical therapy with sphincter relaxing medications has been used in biliary SOD although data is sparse supporting their benefit. There are no trials of medical therapy in the treatment of AIP, although intravenous gabexate[20] and somatostatin[21] given during pancreatic SOM have been shown to either alter phasic wave frequency or lower pancreatic basal sphincter pressure. Endoscopic injection of botulinum toxin in patients with AIP is reported to decrease pancreatitis episodes in 80% of patients[22] although the benefit is not prolonged and there is concern about possible long-term side effects.

Endoscopic sphinctertomy results in clinical benefit for pancreatic SOD in AIP patients although the studies are mostly small case series[132324]. There continues to be disagreement about the type and method of sphincterotomy. Some experts continue to perform biliary sphincterotomy alone as a first line treatment[25]. It is known that this will decrease pancreatic sphincter pressure in some patients and is thought to be a safer first line therapy. It is also a treatment for possible biliary microlithiasis. Other experts direct their endoscopic treatment to the pancreatic sphincter alone when the indication is IAP and pancreatic SOD[17]. This avoids unnecessary biliary sphincterotomy although a small one likely occurs during septotomy. Other experts advocate dual complete sphincterotomies[26]. Current literature supports temporary pancreatic stenting in all of these patients to lower their risk of procedure-induced pancreatitis. There is also some evidence suggesting a lower rate of subsequent pancreatic orifice stenosis and procedure-induced pancreatitis if the pancreatic sphincterotomy is performed with a needle knife over a pancreatic stent instead of a traction type sphincterotome[27].

Surgical sphincteroplasty has also been performed for pancreatic SOD in AIP patients[28]. Although clinical response was reported in 58% of AIP patients in this case series, it is unlikely that the more aggressive surgical approach is warranted unless endoscopic therapy is not feasible due to altered anatomy or in other unusual circumstances.

There are few prospective data and only one controlled trial that address the outcome of endoscopic therapy in patients with IAP. The controlled trial used serial pancreatic stents over 9 mo vs serial ERCP without stent insertion and was performed in patients without sphincter hypertension so it is uncertain if the results pertain to the AIP patients with documented pancreatic SOD. The rate of recurrent pancreatitis was reduced from 53% to 11% over the 3-year study period in the stented group[29]. This positive result in manometrically normal AIP patients highlights our lack of understanding of the sensitivity and specificity of SOM.

Several case series report excellent response to biliary sphincterotomy alone[3031] although Guelrud in an abstract found that patients who underwent dual sphincterotomy fared better (86%) than those treated by biliary sphincterotomy alone (28%)[32]. Most experts believe that treatment of the pancreatic sphincter should occur at the initial therapy although strong evidence is lacking. However, it seems rational to first incise the sphincter that correlates with the presentation of the patient, meaning that pancreatic or dual sphincterotomy should be considered the treatment of choice for AIP patients with documented pancreatic SOD. A rational approach to an AIP patient is to perform EUS to rule out other potential causes of pancreatitis and to proceed to ERCP with manometry if the patient is anxious for treatment and understands that treatment success occurs in only 60%-80% of patients and that the treatment is not without complications[33]. Some experts would limit ERCP with manometry and possible pancreatic sphincterotomy to patients with recurrent AIP since some patients may have only one attack or have attacks separated by many years.

Skeptics continue to point out that there are many problems with endoscopic therapy for AIP[34]. First, there is a variable natural history of AIP patients making it difficult to assess treatment outcome. It is clear that some patients may go years between attacks of pancreatitis making long-term follow up mandatory. Second, endoscopic therapy is not without risks even with prophylactic pancreatic duct stent placement. A prospective randomized controlled trial is needed.

Two potential causes of acute idiopathic pancreatitis are microlithiasis and sphincter of Oddi dysfunction. Microlithiasis is common in patients with an intact gallbladder and acute idiopathic pancreatitis although the reported incidence varies widely. It is best detected by endoscopic ultrasound although empiric cholecystectomy remains a reasonable choice, especially in high incidence centers. Microlithiasis has not been found to be associated with acute idiopathic pancreatitis in post-cholecystectomy patients.

Sphincter of Oddi dysfunction is also common in patients with acute recurrent idiopathic pancreatitis. It remains unclear if SOD is the initial cause of the pancreatitis or is due to prior attacks. Irregardless, sphincter ablation decreases the frequency of subsequent attacks although this conclusion is based on the few available studies that are retrospective and small. Despite this lack of data, it is reasonable to pursue ERCP with manometry and possible pancreatic sphincterotomy in patients with frequent recurrent attacks since there are no other treatment options. However, a careful discussion with the patient of the risks versus benefits of pancreatitic sphincterotomy in acute recurrent pancreatitis is required.