奥迪sphincter dysfunction

　　One, Etiology

　　1. The incidence of SOD after cholecystectomy is 0.88%. In the United States, approximately 700,000 cholecystectomies are performed each year, of which 6,100 cases develop SOD. There are many cases of cholecystectomy for gallstones in China, and it is estimated that the number of SOD cases will not be small either, but there is still a lack of systematic statistical data.

　　2. Secondary to other diseases such as systemic sclerosis, diabetes, or chronic pseudo-obstruction.

　　3. Idiopathic etiology with unknown cause.

　　4. Medications that can increase sphincter tone include cholinergic agonists, alpha-agonists, H1 agonists, and opioid drugs.

　　Two, Pathogenesis

　　SOD includes two types: SO dyskinesia or SO stricture. SO dyskinesia is a primary SO motor abnormality, which can cause decreased sphincter tone, but it is more common for the sphincter tone to be increased. Conversely, SO stricture indicates a change in the sphincter structure, possibly originating from an inflammatory process, and may be accompanied by secondary fibrosis. Because it is often difficult to distinguish between patients with SO dyskinesia and SO stricture in clinical practice, the term SOD is commonly used to refer to both types of patients. In order to facilitate etiological treatment and to determine whether it is necessary to perform SO manometry (SOM), the Hogan-Geenen SOD clinical classification system is often used to classify suspected SOD patients based on clinical history, laboratory tests, and ERCP results.

　　Other terms describing SOD in medical literature, such as nipple stenosis, ampulla stenosis, bile duct motility disorder, and cholecystectomy syndrome, are all inaccurate and less accurate than SOD.

　　The sphincters surrounding the ampulla and the distal bile pancreatic duct are collectively called SO. It consists of four parts: the terminal sphincter of the common bile duct, the terminal sphincter of the main pancreatic duct, the ampulla sphincter located at the nipple, and the longitudinal muscle bundle located in the interval between the pancreatic and bile ducts. The high-pressure area of SO is 4-10mm long, and its function is to regulate the excretion of bile and pancreatic juice, prevent the reflux of duodenal juice, and maintain the sterile environment in the pancreatic and bile ducts. SO has variable basic pressure and phase contraction movement. The former seems to dominate, allowing bile and pancreatic juice to enter the duodenum to aid digestion. Although the phase contraction of SO can help regulate the outflow of bile and pancreatic juice, their main function seems to be to prevent the reflux of duodenal contents into the pancreatic and bile ducts. SO is regulated by different neural and humoral signals. The phase contraction wave activity of the sphincter is closely related to the migrating motor complex (MMC) of the duodenum. It has been reported that the function of the sphincter is protected after liver transplantation, so the neural innervation of the bile duct seems to be unimportant for SO. Although some non-adrenergic, non-cholinergic neurons and nitric oxide can relax SO, the role of cholecystokinin (CCK) and secretin in causing sphincter relaxation seems to be the most important. The role of cholecystectomy in changing these neural pathways needs further confirmation. Luman et al. reported that cholecystectomy, at least in the short term, inhibits the normal inhibitory effect of pharmacological doses of CCK on SO, but the mechanism of action is still unclear.

　　The SO wedge-shaped specimens obtained from SOD patients undergoing SO plastic surgery show that about 60% of patients have evidence of inflammation, muscle hypertrophy, fibrosis, or ectopic endometrium in the nipple area. In the remaining 40% of patients with normal histology, it suggests SO movement disorder. Occasionally, infections such as cytomegalovirus, Cryptosporidium (such as AIDS patients) or Strongyloides (such as Strongyloides) can also cause SOD.

　　How does SOD cause pain? Theoretically, the abnormality of SO can cause high pressure inside the pancreatic and bile ducts by blocking the excretion of bile and pancreatic juice; due to the spasm contraction causing local ischemia; the 'allergy' of the nipple, all of which can cause pain. Although there is no evidence at present, these mechanisms may individually or collectively explain the occurrence of pain.

　　Generally, pain attacks are not accompanied by jaundice, aversion to cold, or fever. Even if jaundice occurs, it is mostly mild conjunctival jaundice, which can completely regress within 1 to 2 days after the pain subsides. Even if there is fever, most of them do not exceed 38℃. Secondly, common symptoms include nausea, vomiting, belching, and diarrhea, etc. Due to chronic pancreatitis, the surgery of incision of the bile duct sphincter is ineffective. These people may have or not have abnormal pancreatic duct造影. Pancreatic juice aspiration after secretin stimulation may be helpful for diagnosis. In some patients with chronic pancreatitis, endoscopic ultrasound can show changes in the parenchyma and pancreatic ducts.

　　Abdominal pain is the most common symptom, usually located in the upper abdomen or right upper quadrant, and can be quite severe, lasting from 30 minutes to several hours. Some patients may experience persistent intermittent exacerbation of abdominal pain, which can radiate to the back or shoulder, accompanied by nausea, vomiting, and the pain may worsen with food or anesthetic drugs. Abdominal pain may start several years after cholecystectomy due to gallbladder motility disorders or stones, and the nature of the pain is similar to the pain caused by the primary disease leading to cholecystectomy. Patients may still have persistent pain that cannot be relieved by cholecystectomy, jaundice, fever, or chills are less common. The Rome II SOD diagnostic criteria are severe pain in the upper abdomen and right upper quadrant, accompanied by the following manifestations: pain-free intervals of 30 minutes or longer after the onset of symptoms; one or more similar episodes within the previous 12 months; persistent pain that often affects daily activities or requires medical consultation; no evidence of structural abnormalities that can explain these symptoms; physical examination findings are typically normal, the most common sign is mild, non-specific abdominal tenderness; trial drug treatment for peptic ulcer or irritable bowel syndrome does not alleviate the abdominal pain of SOD. During typical attacks of abdominal pain, laboratory tests are abnormal in no more than 50% of patients, including transiently elevated liver function; after the initial evaluation, patients are usually classified according to the Hogan-Geenen SOD classification system. SOD patients can present with typical pancreatic pain [radiating to the upper back and/or left upper quadrant] and recurrent pancreatitis.

　　Prevention of奥迪 sphincter dysfunction is targeted at those with clear etiology (such as: after cholecystectomy, certain drugs that can increase sphincter tension) and other prevention measures.

　　Generally, drug therapy is tried first. If drug therapy fails, it is recommended to perform ERCP and pressure measurement assessment. Sphincterotomy is commonly used in symptomatic type I patients and abnormal pressure type II and III patients. Patients who fail initial treatment require a thorough evaluation of the pancreatic sphincter and pancreatic parenchyma. Invasive examinations or treatments have a relatively high incidence of complications and should be comprehensively compared in terms of the risks and benefits they bring to each patient.

　　Some patients have recurrent or persistent elevated serum bilirubin, bile acids, ALP, amino transferases, and amylase, especially commonly elevated ALP, and bile enzymes often increase with the onset of abdominal pain and return to normal with pain relief.

　　1. Morphine-neostigmine stimulation test (Nardi test)

　　Morphine has the effect of causing SO constriction. After intradermal injection of morphine 10mg, intradermal injection of neostigmine 1mg as a cholinergic secretagogue is used. The morphine-neostigmine stimulation test is widely used as a traditional diagnostic method for SOD. If the patient experiences typical abdominal pain accompanied by elevated AST, ALT, AKP, amylase, or lipase by more than 4 times, the test is considered positive. This test predicts the specificity of SOD, but has low sensitivity and poor correlation with the effect prediction after sphincterotomy, so its application is limited and is often replaced by more sensitive tests.

　　2. Ultrasonic examination of the diameter of extrahepatic bile ducts and main pancreatic duct after secretion stimulation

　　After a high-fat meal or the administration of CCK, the gallbladder contracts, and the excretion of bile by liver cells increases, and the SO relaxes, causing bile to enter the duodenum. Similarly, after a high-fat meal or the administration of secretin, stimulation of pancreatic juice secretion, SO relaxes. If SO function is abnormal and causes obstruction, the common bile duct or main pancreatic duct may dilate under the pressure of secretions. It can be monitored by ultrasound. Obstructions of the sphincter and distal biliary pancreatic duct caused by other reasons (stones, tumors, stenosis, etc.) can also cause dilation of the common bile duct or main pancreatic duct and should be ruled out. It should also be noted whether there is pain-induced stimulation. To date, research in this area is limited. These non-invasive tests and comparisons with the effects of SOM or sphincterotomy show only a mild correlation, as intestinal gas often prevents the clear visualization of the pancreatic duct by conventional percutaneous ultrasound. Although endoscopic ultrasound has the advantage of being able to visualize the pancreas, Catalano et al. reported that the sensitivity of endoscopic ultrasound examination after secretin stimulation in SOD diagnosis is only 57%.

　　3. Quantitative hepatobiliary scintigraphy (HBS)

　　When bile excretion into the bile duct is obstructed by sphincter disease, tumor, or stones (and liver parenchymal disease), hepatobiliary scintigraphy estimates the abnormal excretion of radionuclides, and there is still controversy over the clear criteria for positive (i.e., abnormal) results. However, the most widely used criteria are the duodenal arrival time greater than 20min and the time from the porta hepatis to the duodenum greater than 10min. Most studies are flawed in the lack of correlation with the results of SOM or sphincterotomy. However, one study clearly suggests a significant correlation between hepatobiliary scintigraphy and SO basic pressure. In summary, it seems that patients with bile duct dilation and obvious obstruction may have positive scintigraphy results. Esber et al. found that even after CCK stimulation, the scintigraphy results of patients with mild obstruction (Hogan-Geenen classification II and III) are usually normal.

　　Recently, there have been reports of morphine stimulation added to hepatobiliary scintigraphy. Forty-three patients with SOD diagnosed as type II and III underwent hepatobiliary scintigraphy with and without morphine, and later underwent biliary pressure measurement. Standard hepatobiliary scintigraphy cannot differentiate between normal and abnormal SOM patients, however, after morphine stimulation, there are significant differences in the maximum activity time and excretion percentage at 45min and 60min. Using a 15% excretion cutoff at 60min, the sensitivity and specificity of morphine stimulation-enhanced hepatobiliary scintigraphy for detecting elevated SO basic pressure are 83% and 81% respectively.

　　Lacking more definitive data, the conclusion drawn now is that the non-invasive examination methods for SOD have relatively low or unclear sensitivity and specificity. Therefore, they are not recommended for clinical use unless more certain examination methods (such as manometry) are unsuccessful or cannot be checked.

　　Due to the associated risks, invasive ERCP and manometry should only be used for patients with obvious clinical symptoms. Generally speaking, unless the intention is to definitely treat (sphincterotomy), it is not recommended to perform the following invasive evaluations for SOD patients unless there is an abnormality in sphincter function.

　　4. Cholangiography

　　Cholangiography is very important for excluding stones, tumors, or other biliary obstruction diseases with symptoms similar to SOD. Once high-quality cholangiograms exclude these diseases, dilated and (or) slow excretion of bile ducts often suggest obstruction at the sphincter level. Cholangiograms can be obtained by various methods, including percutaneous, intraoperative, or more traditional ERCP. Although there are some controversies, if the diameter of the extrahepatic bile duct is more than 12mm after correction and magnification (after cholecystectomy), it should be considered as dilated, affecting bile excretion and SO sphincter relaxation or contraction. Drugs that can affect the excretion of contrast agents should be avoided to obtain accurate excretion time. Because the common bile duct has an angle from front to back, the patient must be in a supine position to exclude the gravitational effect of the drained fluid through the sphincter. Although there is no good definition of the normal excretion time of contrast agents in the supine position, if the bile ducts cannot empty all the contrast agents within 45 minutes after cholecystectomy, it is usually considered abnormal.

　　Endoscopic examination of the papilla and peripapillary area can provide important information for the diagnosis and treatment of SOD patients. Occasionally, papillary cancer can also be misdiagnosed as SOD. For suspects, papillary biopsy should be performed.

　　In assessing patients with suspected SOD, the pancreatic duct X-ray characteristics are also important. Pancreatic duct dilation (in the head >6mm and in the body >5mm) and prolonged contrast agent excretion time (supine position ≥9min) can provide indirect evidence of the presence of SOD.

　　5. Measurement of SO pressure

　　SOM is the only method that can directly measure the activity of the SO motion, although SOM can be performed intraoperatively and percutaneously, it is most commonly measured during ERCP. Most authorities believe that SOM is the gold standard for evaluating SOD. The measurement of fluid pressure in the Oddi sphincter motility disorder is similar to its application in other parts of the gastrointestinal tract. Unlike other areas of the intestine, SOM requires higher technical requirements and is more dangerous. The question remains whether such a short observation period (2-10 minutes each time of traction) can reflect the '24-hour pathophysiology' of the sphincter. Despite various issues, SOM is still being widely used in clinical practice.

　　SOM is usually performed during ERCP. Before 8-12h of pressure measurement and throughout the pressure measurement period, all relaxing (anticholinergic, nitrates, calcium channel blockers, and glucagon) or stimulating (anesthetics or cholinergic drugs) drugs that affect sphincters should be avoided. Current data suggest that benzodiazepines do not affect sphincter pressure, so they can be used for sedation during SOM. Recent data suggest that pethidine at a dose less than 1mg/kg does not affect the baseline sphincter pressure (although it does have the characteristic of affecting the phase wave), because the baseline sphincter pressure is usually the only pressure standard used to diagnose SOD and determine treatment. Therefore, it is generally recommended that pethidine can be used to assist in analgesia during pressure measurement. If it is necessary to use glucagon to complete the intubation, at least 8-10 minutes are needed to restore the sphincter to its baseline state.

　　Multiple types of three-chamber catheters can be used for pressure measurement. Catheters with long tip heads help to fix the catheter in the bile duct, but they often hinder pancreatic duct pressure measurement. SOM requires selective intubation of the bile duct and (or) pancreatic duct. The inserted catheter can be identified by gentle suction, and the presence of yellow fluid in the endoscopic field indicates entry into the bile duct; clear fluid indicates entry into the pancreatic duct. It is best to have bile duct and pancreatic duct造影 photos taken before SOM, as positive findings (such as common bile duct stones) may avoid SOM. Blaut et al. have recently shown that injecting contrast agent into the biliary tract before SOM does not significantly change sphincter pressure.

　　To ensure accurate pressure measurement, it must be confirmed that the pressure catheter is not blocked by the vessel wall. Once the catheter is inserted into the lumen, it is withdrawn by the定点牵拉法 (each time 1-2mm), and pressure is measured for 30-60s at each point until the catheter is completely withdrawn from SO. Ideally, both pancreatic duct and bile duct pressures should be measured, as it is possible that one sphincter (such as the pancreatic duct sphincter) may be dysfunctional while the other is normal. Raddawi et al. reported that the abnormal baseline pressure of sphincters in patients with pancreatitis is more likely to be confined to the patient's pancreatic duct sphincter; in patients with biliary pain, it is confined to the bile duct sphincter, and liver function tests are abnormal. Usually, the normal baseline pressure of SO is ≤35mmHg, the contraction amplitude ≤220mmHg, the contraction interval ≤8s, the contraction frequency ≤10 times/min, and the reverse contraction ≤50%. Abnormal pressure measurement in SOD patients is manifested as increased baseline pressure, increased contraction amplitude or frequency beyond normal, and reverse contraction beyond 50%, among which increased baseline pressure is the most constant and reliable indicator, often used in determining treatment plans and as a good indicator for predicting the outcome of SO incision.

　　The main complication of SOM is pancreatitis, especially in patients with chronic pancreatitis. Rolny et al. reported that the incidence of pancreatitis after pancreatic duct pressure measurement was 11%; after SOM in patients with chronic pancreatitis, 26% developed pancreatitis. The following methods may reduce the incidence of pancreatitis after pressure measurement:

　　(1) The use of aspiration catheters can continuously drain the fluid into the lumen.

　　(2) Draining the pancreatic duct after pressure measurement.

　　(3) Reducing the lumen perfusion rate to 0.05-0.1 ml/min.

　　(4) Limiting the time of pancreatic duct pressure measurement to less than 2 minutes (or avoiding pancreatic duct pressure measurement).

　　(5) Using a microtransducer system, in a prospective randomized study, Sherman et al. found that the frequency of pancreatitis induced by pancreatic duct pressure measurement was reduced from 31% to 4% by the aspiration catheter.

　　SOM is recommended only for patients with idiopathic pancreatitis or unexplained severe biliary-pancreatic pain. According to the Hogan-Geenen SOD classification system, the indications for SOM are also evolving.

　　6. As a diagnostic test, stent experiment

　　Although the purpose of placing pancreatic or bile duct stents is to alleviate pain and predict the effectiveness of more certain treatments (i.e., sphincterotomy), this has only been applied to a limited extent, especially in patients with normal pancreatic ducts. If the pancreatic stent is retained for more than a few days, serious pancreatic duct and parenchymal damage may occur. Goff reported on 21 cases of SOD patients with normal bile duct pressure (Type II and III) who had undergone biliary stent placement. If symptoms improved, the 7F stent was retained for at least 2 months; if deemed ineffective, the stent was immediately removed. Predicting pain relief after stent placement can lead to long-term pain relief after bile duct sphincterotomy, unfortunately, 38% of patients developed pancreatitis (14% were severe) due to the high incidence of complications, and the biliary stent trial was strongly discouraged. Rolny et al. also reported on the placement of bile duct stents in 23 patients after cholecystectomy (7 cases of Type II and 16 cases of Type III), as a predictor of the effectiveness of endoscopic sphincterotomy, similar to Goff's study. Regardless of the SO pressure, pain disappearance during at least 12 weeks of stent placement predicts the effectiveness of sphincterotomy, but no complications related to stent placement occurred.

　　1. Postoperative diet should be light and easy to digest, with a focus on high-protein, high-carbohydrate, and low-fat diet.

　　2. Cultivate regular eating habits, with moderate portion sizes for each meal, aiming for comfort after eating, and follow the principle of eating small meals more frequently.

　　First, treatment:

　　The aim of treating SOD patients is to reduce the resistance of bile and (or) pancreatic juice outflow caused by SO. The treatment methods for SOD are being improved. Historically, most emphasis has been placed on treatments with proven efficacy, that is, surgical sphincteroplasty or endoscopic sphincterotomy. This method is suitable for patients with severe obstruction (such as Type I according to the Hogan-Geenen standard). In patients with mild obstruction, clinicians must fully weigh the risks and benefits of invasive treatments before recommending them. Most studies suggest that the incidence of complications from endoscopic sphincterotomy in SOD patients is at least twice as high as that in patients with bile duct stones undergoing endoscopic sphincterotomy.

　　1. Drug Treatment:There are not many studies on drug treatment for diagnosed or suspected SOD. Since SO is a smooth muscle structure, it is reasonable to assume that drugs that relax smooth muscles are effective for the treatment of SOD. Sublingual administration of nifedipine and nitrates has been shown to reduce SO baseline pressure in asymptomatic volunteers and symptomatic SOD patients. Khuroo et al. evaluated the clinical value of nifedipine in a placebo-controlled crossover trial, showing that 75% (21/28) of SOD patients with pressure measurement evidence had a reduction in pain scores, emergency visits, and oral analgesic use in short-term follow-up.

　　In a similar study, Sand et al. found that 75% (9/12) of type II SOD patients (suspected, not done SOM) responded well to nifedipine. In recent years, somatostatin has been found to reduce SO pressure, inhibit SO contraction, and can be used for the treatment of SOD. Although drug therapy may be an attractive treatment method for SOD patients, there are also some drawbacks: first, in 1/3 of patients, side effects of drug therapy may occur. Second, smooth muscle relaxants are unlikely to act on the structural form of SOD (i.e., SO stenosis), and patients with primary motor abnormalities of SO (i.e., SO dyskinesia) may have incomplete responses to drugs. Finally, there are no reports on the long-term follow-up of drug therapy. However, because drug therapy is 'relatively safe' and SOD is benign (although painful), it is advisable to consider drug therapy first before considering invasive sphincterotomy for all type III and mild type II SOD patients.

　　Guelrud et al. have proven that in SOD patients, the method of percutaneous electrical nerve stimulation (TENS) can reduce the sphincter baseline pressure by an average of 38% (but usually not within the normal range), which is related to the increase in serum VIP levels. Electroacupuncture at acupoint 34 (a specific acupuncture point affecting the liver and gallbladder system) shows that the relaxation of SO is related to the increase in plasma CCK levels, but its therapeutic effect in SOD has not been studied.

　　2. Surgical Treatment

　　Surgical surgery is the traditional treatment for SOD. The most common surgical procedures are transduodenal bile duct sphincteroplasty and transampullary septoplasty. Follow-up for 1 to 10 years shows that 67% of patients respond to this treatment, and patients with increased SOM sphincter baseline pressure measured during surgery are more likely to benefit from surgical sphincterotomy than those with normal baseline pressure. Some reports suggest that patients with biliary pain have better outcomes than those with idiopathic pancreatitis; some believe there is no difference. However, most studies have found that for patients with clearly diagnosed chronic pancreatitis, it is relatively rare for a single sphincterotomy surgery to improve symptoms.

　　SOD surgical treatment has been mostly replaced by endoscopic treatment. Factors favoring endoscopic treatment include patient tolerance, cost of care, complications, mortality, and cosmetically pleasing results. Currently, surgical treatment is only used for patients with recurrence after endoscopic sphincterotomy, and when endoscopic evaluation and (or) treatment are ineffective or technically not feasible. However, in many centers, surgical treatment is still the standard treatment for pancreatic sphincter hypertension.

　　3. Endoscopic treatment

　　(1) Endoscopic sphincterotomy: Currently, endoscopic sphincterotomy is the standard treatment for SOD patients. Most of the information about endoscopic sphincterotomy is related to the sole bile duct sphincterotomy. It has been reported that 55% to 95% of patients showed improvement in clinical symptoms after treatment. The reasons for the differences in these results are the different SOD diagnostic criteria, the degree of obstruction (the results of type I biliary SOD patients seem to be better than those of type II and III), the methods of data collection (retrospective or prospective), and the techniques used to measure the benefits. Rolny et al. studied 17 type I biliary SOD patients after cholecystectomy using SOM. In this study, 65% of SOM were abnormal (although it was not explicitly stated, it seems that only the bile duct sphincter was studied). However, with an average follow-up of 2.3 years, all patients benefited from bile duct sphincterotomy, suggesting that all patients with bile duct type I can benefit from bile duct sphincterotomy, and in this group, SOM is not only unnecessary but may also be misleading. However, the results of this study from another center were ineffective.

　　Although most studies reporting the efficacy of endoscopic treatment for SOD are retrospective, there have been three well-known randomized trials reported. Geenen et al. randomized 47 patients with type II biliary SOD after cholecystectomy into a sphincterotomy group or a sphincterotomy sham surgery group. All patients underwent SOM, but SOM was not used as a randomization criterion. After a 4-year follow-up, 95% of the patients with increased sphincter basal pressure benefited from sphincterotomy. In contrast, only 30% to 40% of the patients in the high sphincter pressure sham surgery group, or those with normal sphincter pressure who underwent sphincterotomy or sham surgery treatment, benefited from it. This study has two important findings: first, SOM predicted the treatment outcome of endoscopic sphincterotomy; second, endoscopic sphincterotomy has a good long-term effect on type II biliary SOD patients.

　　Sherman et al. reported the preliminary results of their randomized study, comparing the conditions of three groups of patients with II and III type biliary SOD with pressure evidence: endoscopic sphincterotomy, surgical sphincterotomy (with or without cholecystectomy), and sphincterotomy sham surgery group. During the 3-year follow-up period, 69% of the patients who underwent endoscopic or surgical sphincterotomy showed improvement, while only 24% of those in the sham sphincterotomy group were effective (P=0.009). The trend is that the effect of sphincterotomy is better for type II patients than for type III patients (13/16, 81% vs. 11/19, 58%; P=0.14). For such patients, pancreatic sphincterotomy combined with endoscopic bile duct sphincterotomy may be more effective.

　　In the third prospective study, patients with biliary pain after cholecystectomy (mainly type II) were randomly assigned to endoscopic bile duct sphincterotomy or sham surgery groups according to the SOM. Two years after endoscopic bile duct sphincterotomy, 85% (11/13) of patients with increased baseline pressure improved, while 38% (13/5) of patients in the sham surgery group improved (P=0.041). Patients with normal SOM were also randomly assigned to sphincterotomy or sham surgery groups, and the results of the two groups were similar (8/13 improved in the sphincterotomy group, 8/19 improved in the sham surgery group, P=0.47).

　　These results clearly suggest that the response rate to sphincterotomy is definitely related to the clinical manifestations of the patients and offsets the high complications reported in SOD endoscopic treatment. However, most studies suggest that the incidence of complications in SOD patients undergoing endoscopic sphincterotomy is 2 to 5 times higher than that in patients with gallstones. Pancreatitis is the most common complication, with an incidence of up to 20%. To reduce these complications, endoscopic techniques are being developed (such as the placement of pancreatic duct stents to reduce the incidence of pancreatitis).

　　(2) Balloon dilation and stent: Balloon dilation for gastrointestinal stricture is very common. To minimize invasion and to protect the function of the sphincter as much as possible, this improved treatment technique for SOD has been described. Unfortunately, due to the unacceptable high incidence of complications, mainly pancreatitis, this technique is rarely used for the treatment of SOD. Similarly, although SOD biliary stents may provide short-term symptom improvement and predict the outcome of sphincterotomy for patients, according to existing data, they also have an unacceptable high incidence of complications and are not recommended.

　　(3) Botulinum toxin injection: Botulinum toxin (Botox), a potent inhibitor of acetylcholine released by nerve endings, has been successfully used for gastrointestinal smooth muscle disorders such as achalasia. In preliminary clinical trials, botulinum toxin injection into the SO caused a 50% decrease in baseline sphincter pressure and improved bile excretion, and in some patients, the decrease in pressure was accompanied by an improvement in symptoms. Although further research is needed, botulinum toxin can be used for the experimental treatment of SOD. A recent study has reported that 22 patients with type III SOD after cholecystectomy who had evidence of pressure measurement received botulinum toxin injection into the duodenal sphincter. After botulinum toxin injection, 55% of the patients had symptom relief.

　　(4) No improvement in symptoms after sphincterotomy of the bile duct: The reasons for no improvement in symptoms after sphincterotomy of the bile duct include: residual or recurrent dysfunction of the bile duct sphincter; dysfunction of the pancreatic sphincter (main papilla); chronic pancreatitis; other obstructive biliary and pancreatic diseases (stones, strictures, tumors, pancreatic septa); other non-biliary and pancreatic diseases, especially intestinal motility disorders or irritable bowel syndrome.

　　Firstly, the sphincterotomy of the bile duct may not be sufficient, leading to recurrence of stricture. Although the sphincter of the bile duct is usually not completely incised, Manoukian et al. suggest that clinically significant recurrence of bile duct stricture is rare. If there is no 'incision space' in such patients, 8-10mm balloon dilation can be used, but the long-term results are yet to be observed.

　　Secondly, the importance of pancreatic duct sphincterotomy is gradually being recognized. Eversman et al. found that 90% of patients with persistent pain or pancreatitis after biliary sphincterotomy have abnormal residual pancreatic base pressure. Soffer and Johlin reported that in 26 patients (mainly type II) with ineffective biliary sphincterotomy, 22 had increased pancreatic sphincter pressure, and 2/3 of the patients improved after endoscopic pancreatic duct sphincterotomy. Elton et al. performed pancreatic sphincterotomy in 43 type I and II SOD patients who failed to respond to single biliary sphincterotomy. During the follow-up period, 72% were asymptomatic, and 19% improved partially or temporarily.

　　Third, due to chronic pancreatitis in the patients, the sphincterotomy of the bile duct is ineffective. These people may have or not have pancreatic duct造影 abnormalities. Pancreatic juice aspiration after secretin stimulation may help in diagnosis. In some patients with chronic pancreatitis, endoscopic ultrasound can show changes in the pancreatic parenchyma and pancreatic duct.

　　Fourth, some patients may have pain caused by changes in the motility of the stomach, small intestine, or colon (irritable bowel or pseudo-obstruction). Evidence that upper gastrointestinal motility disorders are misdiagnosed as biliary pain (i.e., intermittent upper abdominal pain) is increasing. Multiple preliminary studies have shown that such patients have duodenal motility disorders, and more research is needed to determine the frequency, significance, and/or coexistence of these motility disorders with SOD. A recent study suggests that type III patients experience duodenal specific visceral hyperalgesia with recurrent pain due to duodenal dilation. Compared with the control group, these patients also have a high level of depression, obsessive-compulsive behavior, and anxiety.

　　Second, prognosis:

　　Techniques for assisting in the diagnosis and treatment of SOD are being improved. Successful endoscopic SOM requires proficient and comprehensive ERCP skills and careful attention to the main details of SOM. If a patient suspected of having type III or mild to moderate pain of type II SOD is generally treated with medication first. If medication fails, ERCP and manometry assessment are recommended. Sphincterotomy is commonly used in type I patients with symptoms and type II and III patients with abnormal pressure. Patients who fail initial treatment require a thorough evaluation of the pancreatic duct sphincter and pancreatic parenchyma. Invasive examinations or treatments have a relatively high incidence of complications, and a comprehensive comparison of the risks and benefits they bring to each patient should be made.