Characterization of functional biliary pain and dyspeptic symptoms in patients with sphincter of Oddi dysfunction:Effect of papillotomy

AIM： To characterize functional biliary pain and other gastrointestinal （GI） symptoms in postcholecystectomy syndrome （PCS） patients with and without sphincter of Oddi dysfunction （SOD） proved by endoscopic sphincter of Oddi manometry （ESOM）, and to assess the postendoscopic sphincterotomy （EST） outcome. METHODS： We prospectively investigated 85 cholecystectomized patients referred for ERCP because of PCS and suspected SOD. On admission, all patients completed our questionnaire. Physical examination, laboratory tests, abdominal ultrasound, quantitative hepatobiliary scintigraphy （QHBS）, and ERCP were performed in all patients. Based on clinical and ERCP findings 15 patients had unexpected bile duct stone disease and 15 patients had SOD biliary type Ⅰ. ESOM demonstrated an elevated basal pressure in 25 patients with SOD biliary-type Ⅲ. In the remaining 30 cholecystectomized patients without SOD, the liver function tests, ERCP, QHBS and ESOM were all normal. As a control group, 30 ‘asymptomatic＇ cholecystectomized volunteers （attended to our hospital for general cardiovascular screening） completed our questionnaire, which is consisted of 50 separate questions on GI symptoms and abdominal pain characteristics. Severity of the abdominal pain （frequency and intensity） was assessed with a visual analogue scale （VAS）. In 40 of 80 patients having definite SOD （i.e. patients with SOD biliary type Ⅰ and those with elevated SO basal pressure on ESOM）, an EST was performed just afl：er ERCP. In these patients repeated questionnaires were filled at each follow-up visit （at 3 and 6 too） and a second look QHBS was performed 3 mo after the EST to assess the functional response to EST. RESULTS： The analysis of characteristics of the abdominal pain demonstrated that patients with common bile duct stone and definite SOD had a significantly higher score of symptomatic agreement with previously determined biliary-like pain features than patient groups of PCS without SOD and controls. In contrary, no significant differences were found when the pain severity scores were compared in different groups of PCS patients. In patients with definite SOD, EST induced a significant acceleration of the transpapillary bile flow; and based on the comparison of VASs obtained from the pre-and post-EST questionnaires, the severity scores of abdominal pain were significantly improved, however, only 15 of 35 （43%） patients became completely pain free. Post-EST severity of abdominal pain by VASs was significantly higher in patients with predominant dyspepsia at initial presentation as compared to those without dyspeptic symptoms. CONCLUSION： Persistent GI symptoms and general patient dissatisfaction is a rather common finding after EST in patients with SOD, and correlated with the presence of predominant dyspeptic symptoms at the initial presentation, but does not depend on the technical and functional success of EST.

Sphincter of Oddi dysfunction and pancreatitis

Sphincter of Oddi dysfunction (SOD) is a term used to describe a group of heterogenous pain syndromes caused by abnormalities in sphincter contractility. Biliary and pancreatic SOD are each sub-classified as typeⅠ,Ⅱ or Ⅲ,according to the Milwaukee classification. SOD appears to carry an increased risk of acute pancreatitis as well as rates of post ERCP pancreatitis of over 30%. Various mechanisms have been postulated but the exact role of SOD in the pathophysiology of acute pancreatitis is unknown. There is also an association between SOD and chronic pancreatitis but it is still unclear if this is a cause or effect relationship. Management of SOD is aimed at sphincter ablation,usually by endoscopic sphincterotomy (ES). Patients with typeⅠSOD will benefit from ES in 55%-95% of cases. Sphincter of Oddi manometry is not necessary before ES in typeⅠ SOD. For patients with types Ⅱ and Ⅲ the benefit of ES is lower. These patients should be more thoroughly evaluated before performing ES. Some researchers have found that manometry and ablation of both the biliary and pancreatic sphincters is required to adequately assess and treat SOD. In pancreatic SOD up to 88% of patients will benefit from sphincterotomy. Therefore,there have been calls from some quarters for the current classification system to be scrapped in favour of an overall system encompassing both biliary and pancreatic types. Future work should be aimed at understanding the mechanisms underlying the relationship between SOD and pancreatitis and identifying patient factors that will help predict benefit from endoscopic therapy.

Sphincter of Oddi dysfunction and bile duct microlithiasis in acute idiopathic pancreatitis

Although there are numerous causes of acute panc-reatitis, 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 Oddi dysfunction: Managing the patient with chronic biliary pain

Sphincter of Oddi dysfunction （SOD） is a syndrome of chronic biliary pain or recurrent pancreatitis due to functional obstruction of pancreaticobiliary flow at the level of the sphincter of Oddi. The Milwaukee classification stratifies patients according to their clinical picture based on elevated liver enzymes, dilated common bile duct and presence of abdominal pain. Type Ⅰ patients have pain as well as abnormal liver enzymes and a dilated common bile duct. Type Ⅱ SOD consists of pain and only one objective finding, and Type Ⅲ consists of biliary pain only. This classification is useful to guide diagnosis and management of sphincter of Oddi dysfunction. The current gold standard for diagnosis is manometry to detect elevated sphincter pressure, which correlates with outcome to sphincterotomy. However, manometry is not widely available and is an invasive procedure with a risk of pancreatitis. Non-invasive testing methods, including fatty meal ultrasonography and scintigraphy, have shown limited correlation with manometric findings but may be useful in predicting outcome to sphincterotomy. Endoscopic injection of botulinum toxin appears to predict subsequent outcome to sphincterotomy, and could be useful in selection of patients for therapy, especially in the setting where manometry is unavailable.

Medical treatment for sphincter of oddi dysfunction:Can it replace endoscopic sphincterotomy?

AIM:To report the results of a medical management of sphincter of oddi dysfunction(SOD) after an intermediate follow-up period.METHODS:A total of 59 patients with SOD(2 men and 57 women,mean age 51 years old) were included in this prospective study.After medical treatment for one year,the patients were clinically re-evaluated after an average period of 30 mo.RESULTS:The distribution of the patients according to the Milwaukee's classification was the following:11 patients were type 1,34 were type 2 and 14 were type 3.Fourteen patients underwent an endoscopic sphincterotomy(ES) after one year of medical treatment.The median intermediate follow-up period was 29.8 ± 3 mo(3-72 mo).The initial effectiveness of the medical treatment was complete,partial and poor among 50.8%,13.5% and 35%,respectively,of the patients.At the end of the follow-up period,37 patients(62.7%) showed more than 50% improvement.The rate of improvement in patients who required ES was not significantly different compared with the patients treated conservatively(64.2% vs 62.2%,respectively).CONCLUSION:Our study confirms that conservative medical treatment could be an alternative to endoscopic sphincterotomy because,after an intermediate follow-up period,the two treatments show the same success rates.

Management of patients with sphincter of Oddi dysfunction based on a new classification

AIM: To propose a new classif ication 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.

Evaluating the efficacy of endoscopic sphincterotomy on biliary-type sphincter of Oddi dysfunction: A retrospective clinical trial

BACKGROUND Although endoscopic sphincterotomy(EST)has a positive therapeutic effect on biliary-type sphincter of Oddi dysfunction(SOD),some patients still have little relief after EST,which implies that other functional abdominal pain may also be present with biliary-type SOD and interfere with the diagnosis and treatment of it.AIM To retrospectively assess EST as a treatment for biliary-type SOD and analyze the importance of functional gastrointestinal disorder(FGID)in guiding endoscopic treatment of SOD.METHODS Clinical data of 79 patients with biliary-type SOD(type I and type II)treated with EST at Affiliated Hospital of Guizhou Medical University from January 2014 to January 2019 were retrospectively collected to evaluate the clinical therapeutic effect of EST.The significance of relationship between FGID and biliary-type SOD was analyzed.RESULTS Seventy-nine patients with biliary-type SOD received EST,including 29 type 1 patients and 50 type 2 patients.The verbal rating scale-5(VRS-5)scores before EST were all 3 or 4 points,and the scores decreased after EST;the difference was statistically significant(P<0.05).After EST,the serum indexes of alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase and total bilirubin in biliary-type SOD were significantly lower than before(P<0.05).After EST,67(84.8%)and 8(10.1%)of the 79 patients with biliary-type SOD had obviously effective(VRS-5=0 points)and effective treatment(VRS-5=1-2 points),with an overall effectiveness rate of 94.9%(75/79).There was no difference in VRS-5 scores between biliary-type SOD patients with or without FGID before EST(P>0.05).Of 12 biliary-type SOD(with FGID)patients,11 had abdominal pain after EST;of 67 biliary-type SOD(without FGID)patients,0 had abdominal pain after EST.The difference was statistically significant(P<0.05).The 11 biliary-type SOD(with FGID)patients with recurrence of symptoms,the recurrence time was about half a year after the EST,and the symptoms were significantly relieved after regular medical treatment.There were 4 cases of postendoscopic retrograde cholangiopancreatography pancreatitis(5.1%),and no cholangitis,bleeding or perforation occurred.Patients were followed up for 1 year to 5 years after EST,with an average follow-up time of 2.34 years,and there were no long-term adverse events such as sphincter of Oddi restenosis or cholangitis caused by intestinal bile reflux during the follow-up.CONCLUSION EST is a safe and effective treatment for SOD.For patients with type I and II SOD combined with FGID,single EST or medical treatment has limited efficacy.It is recommended that EST and medicine be combined to improve the cure rate of such patients.

Update on Sphincter of Oddi Dysfunction: A Review

Sphincter of Oddi dysfunction(SOD)encompasses a spectrum of clinical syndromes that are not fully understood,and various diagnostic and therapeutic methods have had varying results depending on the type of dysfunction.This review explored various mechanisms that might play a role in SOD and methods of diagnosis and management.It is important to rule out other causes of abdominal pain with laboratory testing,imaging studies,and endoscopic procedures.Medications that affect sphincter motility should be identified as well.Manometry is the gold standard for diagnosis but it is not always required.For example,patients with type I SOD may have symptomatic improvement with sphincterotomy without need for a diagnostic manometry.Hepatobiliary scintigraphy and fatty meal sonography may also have diagnostic utility.Sphincterotomy is not always effective for symptomatic improvement in type II and III SOD.Alternate therapies with calcium channel blockers and botulinum toxin have been studied and might be considered as options after discussing the risks and benefits with the patients.

Biliary microlithiasis,sludge,crystals, microcrystallization,and usefulness of assessment of nucleation time

BACKGROUND:The process of microcrystallization,its sequel and the assessment of nucleation time is ignored.This systematic review aimed to highlight the importance of biliary microlithiasis,sludge,and crystals,and their association with gallstones,unexplained biliary pain,idiopathic pancreatitis, and sphincter of Oddi dysfunction.DATA SOURCES:Three reviewers performed a literature search of the PubMed database.Key words used were'biliary microlithiasis','biliary sludge','bile crystals','cholesterol crystallisation','bile microscopy','microcrystal formation of bile','cholesterol monohydrate crystals','nucleation time of cholesterol','gallstone formation','sphincter of Oddi dysfunction'and'idiopathic pancreatitis'.Additional articles were sourced from references within the studies from the PubMed search.RESULTS:We found that biliary microcrystals account for almost all patients with gallstone disease,7%to 79%with idiopathic pancreatitis,83%with unexplained biliary pain, and 25%to 60%with altered biliary and pancreatic sphincter function.Overall,the detection of biliary microcrystals in gallstone disease has a sensitivity ranging from 55%to 87%and a specificity of 100%.In idiopathic pancreatitis,the presence of microcrystals ranges from 47%to 90%.A nucleation time less than 10 days in hepatic bile or ultra-filtered gallbladder bile has a specificity of 100%for cholesterol gallstone disease.CONCLUSIONS:Biliary crystals are associated with gallstone disease,idiopathic pancreatitis,sphincter of Oddi dysfunction, unexplained biliary pain,and post-cholecystectomy biliary pain.Pathways of cholesterol super-saturation,crystallisation, and gallstone formation have been described with scientificsupport.Bile microscopy is a useful method to detect microcrystals and the assessment of nucleation time is a good method of predicting the risk of cholesterol crystallisation.

The Effects of Cholecystojejunostomy and Biliary Drainage on Biliary Motor

Summary: Simulating physiological neuronal and hormonal conditions during digestive and interdigestive periods, the study identified the changes of the motility of biliary system including bile duct and sphincter of Oddi (SO) before and after cholecystojejunostomy. Thirty-five rabbits were divided into five groups randomly. The experimental groups received the venous injection of CCK 10 ng/kg, erythromycin 10 mg/kg, atropine 3 μg/kg and L-NAME 10 mg/kg respectively. Each rabbit underwent manometry through introducing a three-lumen catheter via the papilla retrogradely, using the low-compliance papillary infusion system. Then the gallbladder and the upper segment of the jejunum was anastomosed and the manometric procedures repeated after one week. SO basal pressure was increased, contraction amplitude decreased, contraction time shortened after cholecystojejunostomy. L-NAME, CCK and erythromycin could all excite SO. L-NAME could increase basal pressure and contraction amplitude, CCK increase basal pressure contraction amplitude and frequency, and erythromycin increase contraction amplitude, respectively. But comparing with that before cholecystojejunostomy, the increasing extent was decreased. The tensional and spontaneous contractions of the SO were under the control of the neural and hormonal mechanism. The anastomosis of gallbladder and jejunum and the drainage of bile made the tensional contraction stronger, but the spontaneous contraction weakened after the operation due to the decreases of the sensitivity of SO to hormonal factors. The clinical symptoms may not be relieved when the patients with SO dysfunction accepted cholecystojejunostomy.

Review of idiopathic pancreatitis

Recent advances in understanding of pancreatitis and advances in technology have uncovered the veils of idiopathic pancreatitis to a point where a thorough history and judicious use of diagnostic techniques elucidate the cause in over 80% of cases. This review examines the multitude of etiologies of what were once labeled idiopathic pancreatitis and provides the current evidence on each. This review begins with a background review of the current epidemiology of idiopathic pancreatitis prior to discussion of various etiologies. Etiologies of medications,infections,toxins,autoimmune disorders,vascular causes,and anatomic and functional causes are explored in detail. We conclude with management of true idiopathic pancreatitis and a summary of the various etiologic agents. Throughout this review,areas of controversies are highlighted.

Pancreatic ductal system obstruction and acute recurrent pancreatitis

Acute recurrent pancreatitis is a clinical entity largely associated with pancreatic ductal obstruction. This latter includes congenital variants, of which pancreas divisum is the most frequent but also controversial, chronic pancreatitis, tumors of the pancreaticobiliary junction and sphincter of Oddi dysfunction. This review summarizes current knowledge about diagnostic work-up and therapy of these conditions.

Endoscopic therapy in acute recurrent pancreatitis

Endoscopic retrograde cholangiopancreatography (ERCP) has evolved from a largely diagnostic to a largely therapeutic modality. Cross-sectional imaging, such as computed tomography (CT) and magnetic resonance imaging (MRI), and less invasive endoscopy, especially endoscopic ultrasound (EUS), have largely taken over from ERCP for diagnosis. However, ERCP remains the "first line" therapeutic tool in the management of mechanical causes of acute recurrent pancreatitis, including bile duct stones (choledocholithiasis), ampullary masses (benign and malignant), congenital variants of biliary and pancreatic anatomy (e.g. pancreas divisum, choledochoceles), sphincter of Oddi dysfunction (SOD), pancreatic stones and strictures, and parasitic disorders involving the biliary tree and/or pancreatic duct (e.g Ascariasis, Clonorchiasis).

The presence and outcome of biliary sphincter disorders in liver-transplant recipients according to the Rome IV classification

Background Biliary sphincter disorders after liver transplantation(LT)are poorly described.We aim to describe the presence and outcome of patients with papillary stenosis(PS)and functional biliary sphincter disorders(FBSDs)after LT according to the updated Rome IV criteria.Methods We reviewed all endoscopic retrograde cholangiopancreatographies(ERCPs)performed in LT recipients between January 2003 and December 2019.Information on clinical and endoscopic findings was obtained from electronic health records and endoscopy databases.Laboratory and clinical findings were collected at the time of ERCP and 1 month after ERCP.Results Among the 1,307 LT recipients,336 underwent 849 ERCPs.Thirteen(1.0%)patients met the updated Rome IV criteria for PS[former sphincter of Oddi dysfunction(SOD)type I]and 14 patients(1.0%)met the Rome IV criteria for FBSD(former SOD type II).Biliary sphincterotomy was performed in 13 PS and 10 FBSD cases.One month after sphincterotomy,bilirubin,gamma-glutamyl transferase and alkaline phosphatase levels decreased in 85%,61%,and 92%of those in the PS group(P¼0.019,0.087,and 0.003,respectively)and in 50%,70%,and 80%of those in the FBSD group(P¼0.721,0.013,and 0.093,respectively).All the 14 patients initially suspected of having a FBSD turned out to have a different diagnosis during the follow-up.Conclusions PS after LT is uncommon and occurs in only 1%of LT recipients.Our data do not support the presence of an FBSD after LT.Sphincterotomy is a safe and effective procedure in LT recipients with PS.