AIM: To propose a new classification system for sphincter of Oddi dysfunction (SOD) based on clinical data of patients.

METHODS: The clinical data of 305 SOD patients documented over the past decade at our center were analyzed retrospectively, and typical cases were reported.

RESULTS: The new classification with two more types (double-duct, biliary-pancreatic reflux) were set up on the basis of the Milwaukee criteria. There were 229 cases of biliary-type SOD, including 192 (83.8%) cases cured endoscopically, and 29 (12.7%) cured by open abdominal surgery, and the remaining 8 (3.5%) cases observed with unstable outcomes. Eight (50%) patients with pancreatic-type SOD were cured by endoscopic treatment, and the remaining 8 patients were cured after open abdominal surgery. There were 19 cases of double-duct-type SOD, which consisted of 7 (36.8%) patients who were cured endoscopically and 12 (63.2%) who were cured surgically. A total of 41 cases were diagnosed as biliary-pancreatic–reflux-type SOD. Twenty (48.8%) of them were treated endoscopically, 16 (39.0%) were treated by open abdominal surgery, and 5 (12.2%) were under observation.

CONCLUSION: The newly proposed SOD classification system introduced in this study better explains the clinical symptoms of SOD from the anatomical perspective and can guide clinical treatment of this disease.

Sphincter of Oddi dysfunction (SOD) is characterized by a series of clinical pain symptoms caused by abnormalities in sphincter contractility[1]. The sphincter of Oddi (SO), a fibromuscular sheath encircling the distal common bile duct (CBD), pancreatic duct and common channel, controls the flow of bile and pancreatic secretions into the duodenum and prevents reflux of duodenal contents into the pancreaticobiliary system[2]. SO dyskinesia caused by injury or/and inflammation can result in a hypo- or hypertonic sphincter with altered motility, causing an intermittent functional blockage of the sphincter. As it is often difficult to distinguish SO stenosis from dyskinesia, the term “sphincter of Oddi dysfunction” is used to cover both conditions[3]. For SOD, the Milwaukee classification proposed by Hogan and Geenen has been widely accepted; it classifies SOD into two types: the biliary type and the pancreatic type[4-6]. Biliary and pancreatic SOD are each sub-classified as type I, II and III on the basis of symptoms, laboratory tests and radiological imaging[4,5]. This classification explains the clinical manifestations of SOD from the anatomical perspective and reveals the nature of SOD, thus providing a reliable anatomical basis for appropriate clinical treatment. In our long-term clinical practice, however, we have found this classification system somewhat flawed. For instance, the clinical manifestations in some patients with SOD are difficult to be satisfactorily defined using the Milwaukee criteria. Therefore, the existing system is insufficient in guiding the clinical treatment of all SOD patients. In this paper, we introduced a new classification of SOD based on the Milwaukee classification. In the new classification system, SOD is divided into four types according to anatomy, symptoms, endoscopic tests and radiological imaging. These types include not only those already established by the Milwaukee criteria (biliary and pancreatic types), but also two more new types (the double-duct and biliary-pancreatic reflux types) in an attempt to improve the clinical treatment of SOD.

Based on our clinical observations, we added the double-duct type and the biliary-pancreatic reflux type of SOD to the Milwaukee classification, to achieve greater clarity in the SOD clinical symptoms and to guide the clinical treatment of SOD. The therapeutic methods and effects using this new classification are shown in Table 3.

Although the Milwaukee classification system has been widely accepted for the classification of patients with suspected SOD, it has some potential problems. For example, the description of typical biliary or pancreatic pain may be interpreted differently by different doctors, which may lead to inappropriate referrals for SOM. In addition, according to the Milwaukee criteria, a CBD diameter of at least 12 mm is required for the diagnosis of SOD. Most patients being investigated for SOD have had their gallbladder removed, and in the past, it was believed to be normal for a post-cholecystectomy CBD to be dilated by 2-3 mm[10]. Moreover, there is a question of whether patients with both biliary and pancreatic pain should be classified into the biliary type or the pancreatic type. Freeman et al[11] stated that for this group, all patients should undergo biliary sphincterotomy, and 40% should have pancreatic sphincterotomies. How to interpret these clinical data? The Milwaukee classification has some limitations. In our study, there were 60 cases that could not be accurately interpreted by the Milwaukee classification criteria. Our long-term observation of the clinical cases suggests that our new classification based on anatomy, symptoms, endoscopic tests and radiological imaging is superior to the Milwaukee criteria in guiding the treatment of SOD. According to the Milwaukee criteria, the two types of SOD (biliary and pancreatic) can be further classified into three subtypes each, making classification complex. The newly proposed classification of SOD and the clinical characteristics associated with each type are listed in Table 3.

The new classification system presented in this paper is simpler than the initial one, but continues to closely follow the Milwaukee classification criteria. For example, biliary-type SOD patients only have biliary pain, and pancreatic-type SOD patients only have pancreatic pain. The two types are no longer divided into subtypes. MRCP usually shows the distension of bile ducts for biliary SOD and dilation solely of the pancreatic duct for pancreatic-type SOD. With respect to treatment, EST can often yield better results for patients suffering from biliary SOD, and EPS should be a good choice of treatment for patients with pancreatic SOD.

We have paid more attention to the clinical characteristics and significance of the other two types of SOD, i.e. the double-duct and biliary-pancreatic reflux types.

In double duct type of SOD, both the biliary and pancreatic ducts of the sphincter of Oddi are affected. Clinical cases of SOD meeting these criteria have previously been reported but have not been definitively classified[12]. The characteristics of this SOD type include symptoms typical of both biliary- and pancreatic-type SOD that appear simultaneously or alternately, with mobile positions of abdominal pain and radiating pain. Meanwhile, laboratory tests indicate elevated levels of liver-related enzymes and amylase in the blood. These findings usually result in the diagnosis of chronic biliary pancreatitis, manifested as mild abnormal liver function due to edema of the pancreatic head. Imaging exams usually show distension of both the bile and pancreatic ducts and stones in the pancreatic duct. Notably, frequently recurrent pancreatitis and evident distension of the pancreatic duct could mislead surgeons to focus on pancreatitis, thus underestimating the severity of mild bile duct distension, causing the neglect of possible SOD diagnoses, and resulting in unsuccessful treatment. Therefore, it is necessary to outline the double-duct type of SOD so that patients with these symptoms can be effectively treated. Case 1 is a typical SOD of the double-duct type, with mild bile duct distension due to sphincter of Oddi stenosis, and not due to compression by the head of the pancreas. This was proved by the finding that the obstruction in the extremity of the bile duct was not relieved even when the head of the pancreas was resected in the first operation. In patients with the double-duct type SOD, the sphincter of common duct is short, but the inferior stenotic segment of the bile duct is relatively long. Hence, patients with this form of SOD can be treated by surgery rather than EPS.

The anatomical basis for biliary-pancreatic reflux type of SOD is probably as follows: Patients may have a congenital abnormality in the convergence of the biliary and pancreatic systems, i.e. an overlong duct (> 11 mm). Inflammation and stenosis mainly occur in the sphincter of the common duct, whereas the sphincters of the superior bile duct and the pancreatic duct remain relatively normal or only mildly affected. If fibrosis of the ampullary septum causes dysfunction in the anti-reflux valve, reflux between the bile and pancreatic ducts is likely to occur. Repeated reflux of small amounts of bile into the pancreatic duct will usually induce pancreatitis, including recurrent chronic biliary pancreatitis and even severe acute pancreatitis. Although the clinical manifestations of this SOD are quite similar to those of the pancreatic duct type, there are a few differences: (1) As the reciprocal reflux between the fluids in the bile and pancreatic ducts is structurally barrier-free, the pancreatic duct orifice has no evident stenosis or obstruction, and so distension of the pancreatic duct does not occur; (2) Because there was only mild biliary-pancreatic reflux in most cases, the pancreatic duct and gland alveoli in the head of the pancreas near the biliary-pancreatic convergence were usually affected, inducing swelling of the pancreatic head, as indicated by imaging examination. Therefore, these cases are sometimes diagnosed as pancreatitis with a pancreatic head mass. Some authors have reported tumor-like features of chronic pancreatitis, and some of these cases may suffer from biliary-pancreatic reflux[13,14]; (3) In this type of SOD, EST failed to incise the stenotic segment of the sphincter of Oddi due to the slender and tortuous common duct. EST was successful in only 56% of cases with this type of SOD at our center. However, the achievement ratio of incision on the normal ampulla of Vater was nearly 100%[15,16]. Moreover, some patients can only be treated by open abdominal surgery due to failure to incise the stenotic common duct after several attempts by EST; and (4) The amylase levels in bile sampled from the biliary tract during ERCP in biliary-pancreatic-reflux-type SOD patients were about 2-10 times higher than normal.

Although distension does not always occur in the pancreatic duct and is usually slight in the biliary duct in the early stages of biliary-pancreatic reflux SOD, the symptoms of pancreatitis may be more serious than those in the simple pancreatic-type SOD. Because the common duct of the bile and pancreatic ducts is simply a potential duct due to the tension of the sphincter of Oddi, an image of an over long common duct was obtained from ERCP or MRCP in only a few cases. Case 2 mentioned above illustrates that the therapeutic effects of BPD were satisfactory for the biliary-pancreatic-reflux-type SOD patients who failed in EST. This demonstrates the significance of using the biliary-pancreatic reflux type classification for SOD.

In summary, the new classification of SOD proposed in this study demonstrates significant advantages for guiding the diagnosis and treatment of SOD patients in China, as compared with the conventional Milwaukee criteria. Nonetheless, further investigations on the applicability of this quaternary classification system to patients in other regions are needed.