Gastroenterology Insights 2012; volume 4:e1

The postcholecystectomy bowel syndrome, chronic pancreatitis, and malignancy.5,7 Lasson et al. followed 65 Correspondence: Qiang Cai, Division of Digestive syndrome: a review patients initially diagnosed with PCS and Diseases, Emory University School of Medicine, of etiology and current found 48% with identifiable extrabiliary dis- 1365 Clifton Road, B1262 Atlanta, GA 30322, USA. approaches to management eases during 4-13 years of follow up.8 Similarly, Tel: +1.404.778.4857 - Fax: +1.404.778.2578. Filip et al. found 27 of 80 patients (34%) eval- E-mail: [email protected] uated for PCS actually had non-biliary symp- Robert D. Kung, Amanda W. Cai, Key words: postcholecystectomy syndrome, chole- 9 Jason M. Brown, Anthony M. Gamboa, toms. Others cite gastroparesis, costchondri- cystectomy, etiology. Qiang Cai tis, fibromyalgia, and chronic narcotic use as common causes for PCS pain.10 Thus, the first Received for publication: 9 June 2011. Division of Digestive Diseases, Emory step in evaluating patients with PCS must be a Accepted for publication: 29 August 2011. University, School of Medicine, Atlanta, careful history and evaluation to exclude these GA, USA This work is licensed under a Creative Commons common and often treatable disorders. Given Attribution NonCommercial 3.0 License (CC BY- the number of non-organic pain disorders NC 3.0). included in the differential, referral to a pain specialist may also be appropriate. ©Copyright Robert D. Kung et al., 2012 Abstract Licensee PAGEPress, Italy Organic biliary etiology Gastroenterology Insights 2012; 4:e1 Postcholecystectomy syndrome (PCS) com- doi:10.4081/gi.2012.e1 New biliary disorders may develop after prises a heterogeneous group of symptoms and cholecystectomy, and these must be ruled out disorders in patients who have previously through standard laboratory and radiological undergone cholecystectomy. While it is rela- assessments. Common bile duct stones and of Oddi dyskinesia, referring to a functional tively uncommon, it is defined by chronic cholangiocarcinoma can arise independently abnormality of the sphincter leading to inter- recurring pain, often with no clear source. of cholecystectomy. Obstructive symptoms mittent obstruction, perhaps due to still Recent studies suggest its pathogenesis require relief of the obstruction with prompt unknownonly neuro-hormonal disturbances.13 depends on different factors, but it remains endoscope retrograde cholangiopancreatogra- Stenosis is thought to occur in type 1 SOD, poorly understood and complex to treat. Here, phy (ERCP) or surgical intervention. inferred from its predictable response to we present a brief overview of this syndrome, Malignancy is associated with older age and sphincterotomy, whereas dyskinesia is thought review recent literature regarding its etiology, later presentation. Filip et al. recentlyuse pub- to occur in type 2 and type 3 SOD, which are and present a systematic approach to diagno- lished a cohort study demonstrating endoscop- less understood. sis and management. ic ultrasound was 96.2% sensitive and 88.9% Geenan and Hogan were the first to demon- specific for identifying pancreaticobiliary dis- strate relief of pain after endoscopic biliary eases.9 This approach helped define which sphincterotomy (EBS) in 91% (10 of 11) of patients warranted subsequent ERCP, reducing cholecystectomized patients with elevated Introduction both the number of ERCPs by 51% and the pro- sphincter of Oddi (SO) pressures at 12-month cedure related morbidity associated with this follow up, but no benefit in patients with nor- Cholecystectomy is one of the most com- procedure. Surgically related complications mal sphincter pressures.14 By contrast, two monly performed surgical procedures and is such as strictures and bile duct injuries have recent studies have found only 18-43% of the standard of care in treating symptomatic been described extensively elsewhere and are patients with definite SOD (i.e. proven by 1-4 gallstones. Up to a third of patients undergo- not the focus of this review.11 SOM) had complete resolution of symptoms at ing cholecystectomy will develop recurrent and 12-18 months after EBS.14-15 This suggests a persistent weeks to years after Functional biliary etiology: true pathogenesis which is more complex than 5-6 surgery. In the majority of patients, symp- postcholecystectomy syndrome sphincter dysmotility alone. Several studies toms are mild and short lived, but 2-5% will have implicated the development of visceral continue to have frequent debilitating pain, a Sphincter of Oddi dysfunction hyperalgesia and somatosensory hypersensi- condition referred to as the postcholecystecto-Non-commercialWhen basic evaluation has ruled out both tivity as a source of PCS which has been over- my syndrome (PCS).5 Rather than being a sin- extrabiliary disorders and gross biliary looked. Desautels et al. reproduced pain symp- gle disorder, this term encompasses a widely obstruction, sphincter of Oddi dysfunction toms in type III SOD patients by distending the varying group of disorders, including extrabil- (SOD) is believed to be the most frequently duodenum.16 Kuruscai et al. demonstrated iary, organic biliary, and functional biliary dis- identifiable cause of PCS. While the estimated increased hypersensitivity of peripheral noci- eases, considered true PCS (Table 1). In many incidence is less than 1% of all cholecystec- ceptive nerve fibers in the right upper quad- cases, no source of PCS can be identified, and tomized patients, SOD may account for 14% of rant of the . Less electrical stimuli symptoms remain unexplained and challeng- pain from PCS.12 Despite the prominence of were needed to illicit sensation in SOD ing to treat. This article is a review of the SOD in the differential diagnosis of PCS, the patients when compared to asymptomatic recent literature regarding the different etiolo- pathogenesis of SOD remains poorly under- cholecystectomized patients, symptomatic gies of PCS, and current diagnostic and thera- stood. Two mechanisms have been proposed: non-SOD patients, and healthy volunteers. It is peutic approaches to its management. sphincter of Oddi stenosis refers to a structur- thought that both peripheral nerve fibers and al abnormality resulting from inflammation central nerve fibers at the level of the spine are Extrabiliary etiology and scarring of the sphincter. Sphincter of hypersensitized, lowering the pain threshold, The most common causes of PCS may be Oddi basal pressures, which can be measured similar to the pathogenesis of other functional extrabiliary diseases, an umbrella classifica- by manometry (SOM) during ERCP, tend to be pain disorders, such as irritable bowel syn- tion including gastroesophageal reflux dis- above 40 mmHg, and do not change after phar- drome.17 Pain associated with injection of con- ease, gastritis, peptic ulcer disease, irritable macological challenge. The second is sphincter trast or saline during ERCP has been common-

[Gastroenterology Insights 2012; 4:e1] [page 1] Review ly reported, but its significance is unknown.18 ical biliary pain follows the Rome III consensus ty of 100%.28,31-33 However, later studies found Linder et al. quantitatively measured symptom criteria for diagnosing functional biliary pain, only a 13% sensitivity despite 95% specifici- improvement in patients with proven SOD who although further studies are needed to prove its ty.34,35 These disparate results have raised ques- underwent EBS compared to those with sus- utility in managing these patients.29 Other tions regarding the reproducibility of scinti- pected SOD with normal SOM.19 At 18-months mechanisms such as visceral hyperalgesia are graphic results. The addition of provo- follow-up, the SOD/EBS group was more likely more likely to be playing a role in this group of cation appeared to increase the sensitivity to to express symptom improvement, but both PCS patients, many of whom are likely misla- 83%, and was associated with 81% specificity.36 groups almost uniformly continued to experi- beled as having SOD.16 Many recent trials have studied how well ence pain, consistent with chronic pain disor- Given the potential morbidity, cost, and lack of secretin-stimulated magnetic resonance cholan- ders and suggesting a multifactorial etiology. availability of SOM, non-invasive strategies to giopancreatography (ss-MRCP) predicts the SOD has been historically classified into 3 evaluate SOD are needed. The morphine- results of SOM. It is to be noted that these stud- types according to the modified Milwaukee prostigmin test (Nardi test) was one of the ear- ies included patients with biliary and pancreatic Criteria, based on the presence or absence of 3 liest methods developed, but has very low sensi- type pain, idiopathic pancreatitis, as well those criteria: biliary type abdominal pain; elevation of tivity and specificity for predicting the presence with and without prior cholecystectomy. serum transaminases, alkaline phosphatase, or of SOD.30 Initial studies demonstrated that Prolonged increase in pancreatic duct diameter bilirubin to 1.5 times the upper limit of normal quantitative hepatobiliary scintigraphy (QHBS), after injection of secretin, which relaxes the SO, with normalization between attacks; and bile measuring the hepatic hilum to duodenal transit had previously been shown to correlate well with duct dilatation of more than 12 mm on imag- time of radio-labeled tracer, correlated well with ERCP diagnosis of papillary stenosis, but had not ing.14 Type I is defined as the presence of all 3 elevated SO basal pressures by SOM, the gold been correlated with SOM.37 Overall, the results criteria, Type II as pain plus one other criteria, standard, had a sensitivity of 83% and specifici- have been disappointing (Table 3). Aisen et al. and Type III as pain alone. This classification is useful in identifying the subset of patients with Table 1. Etiologies of postcholecystectomy syndrome. Type I SOD, who have a greater than 90% chance of symptomatic improvement from EBS regard- Extrabiliary Organic biliary Functional Biliary 20-24 less of the results of manometry (Table 2). GERD Choledocholithiasisonly Sphincter of Oddi dysfunction This consistent response suggests that the Gastritis Chronic pancreatitis Biliary microlithiasis underlying pathophysiology of Type I SOD may Gastroparesis Pancreatic cancer Visceral hypersensitivity/hyperalgesia be SO stenosis; however, no studies have proven Somatosensory hyperalgesia this association. It is now common practice to bypass SOM and proceed straight to EBS in this Irritable bowel syndrome Cholangiocarcinomause Remnant cystic duct Retained calculi subset of patients.23-24 The management of Type Neuroma II and Type III SOD is less defined. While ERCP Hyperalgesia is beneficial for Type I, patients with Type II and Peptic ulcer disease III are less likely to have elevated sphincter pres- Nonulcer dyspepsia sures and respond to EBS. This is particularly true for patients with Type III SOD, whose Duodenal motility abnormality response to EBS approaches only 37% even after Narcotic bowel abnormal SOM.25 Given the high risk of ERCP- Duodenal diverticula related pancreatitis, which is 2-9% in unselected Malignancy series and as high as 10-30% in cases of suspect- Abdominal wall pain (associated with Carnett’s sign) ed SOD,26-27 the role of ERCP and SOM in this Chest wall tenderness subset of patients is still a subject of debate. In a Costochondritis recent cohort study, 54% of patients with sus- Fibromylagia pected Type II or III SOD underwent ERCP and SOM and were found to have normal SOM, and Table 2. Response to endoscopic biliary sphincterotomy in sphincter of dysfunction by 12% developed procedure-related pancreatitis.Non-commercial28 Milwaukee classification. Using a symptom scoring survey, Madacsy et al. Sphincter of Oddi dysfunction Likelihood of symptomatic relief showed that this SOD negative PCS group was Milwaukee class Abnormal manometry Normal manometry more likely to complain of atypical abdominal pain; typical abdominal pain experienced by I >90% -- patients with SOD is steady, lasts 15-30 minutes, II 50-70% <30% localized to the epigastrum and right upper III 20-30% <20% quadrant (RUQ), and is exacerbated by fatty Milwaukee class: presence of RUQ pain, transaminitis >1.5 ULN, bile duct >10mm on imaging. Class I: all 3 criteria; Class II: pain + 1 criteri- foods. This delineation between typical and atyp- um; Class III: pain alone.

Table 3. Sensitivity, specificity, positive predictive value, negative predictive value of ss- secretin stimulated magnetic resonance cholan- giopancreatography in the diagnosis of sphincter of Oddi dysfunction; PPV, positive predictive value; NPV, negative predictive value. Trial # of patients # of pts with SOD Prior cholecystectomy (%) Sensitivity Specificity PPV NPV Pereira, 2007 type II 47 27 57 62.5 85 83 65 type II+III --37 85 83 39 Aisen, 2008 30 20 47 10 90 67 33 ss-MRCP, secretin stimulated magnetic resonance cholangiopancreatography; SOD, sphincter of Oddi dysfunction; PPV, positive predictive value; NPV, negative predictive value.

[page 2] [Gastroenterology Insights 2012; 4:e1] Review found that pancreatic duct measurement statistically significant improvement or res- laparoscopic or open cholecystectomy, and 6 during ss-MRCP was no different in those olution of symptoms in the urso group com- out of 7 patients were found to have retained with normal and elevated sphincter pres- pared to the placebo group. In the second cystic duct calculi on ERCP.47 Symptoms were sures, and fails to predict SOD.38 Pereira et phase of the study, the control group relieved nearly a year after surgical resec- al. found that ss-MRCP had only 63% sensi- switched to urso for six months, and the tion of the remnant, extracorporeal shock- tivity but 85% specificity for diagnosing improvement in symptoms was also statisti- wave lithotripsy (ESWL), or endoscopic bil- manometrically proven Type 2 SOD, with cor- cally significant. This positive response to iary holmium laser lithotripsy. Palanivelu et responding pain relief following BSE. The urso strongly suggests BM as a cause of PCS al. retrospectively analyzed 9,590 patients combined sensitivity in predicting both pain. undergoing laparoscopic cholecystectomy, Types 2 and 3 SOD fell to 37%. The authors A causal relationship between biliary finding an increased incidence of 4% concluded that ss-MRCP may have a role in microlithiasis and SOD has been debated. amongst the group who underwent laparo- selecting patients with suspected Type II Elmi et al. conducted a retrospective study scopic subtotal cholecystectomy.49 All under- SOD who might benefit from sphincteroto- which reviewed 17 Type I SOD patients, who went laparoscopic excision of the remnant my.39 In the absence of better diagnostic underwent ERCP/SOM and EBS with sweep- duct and were pain free and asymptomatic at tools, a recent trial evaluated a strategy to ing of the common bile duct with a basket for 3-months follow up. In that series, ultra- manage SOD without SOM.40 Those with stones. Nine of 17 (53%) patients had con- sound (US) identified these retained calculi Type I SOD and Type II SOD with dilated bile current microlithiasis in their bile, and all with 60% accuracy, while MRCP was 92% ducts on imaging were given the choice of responded similarly well to EBS.13 This study accurate. These findings are consistent with medical therapy with or without sphinctero- speculated that the passing of stones leads earlier series that have highlighted MRCP as tomy, with the possibility of trying the alter- to fibrosis and scarring of the ampulla of the test of choice in this setting.50 native if symptoms persisted beyond 3-6 vater, likely to be part of the pathogenesis of Recommendations on preventing remnant months. Those Type II SOD patients without Type 1 SOD. An earlier and larger prospec- duct calculi at the time of initial surgery dilated bile ducts and all Type III SOD were tive study by Quallich et al. had found only a have been described: milking of the cystic managed with medical therapy alone. The 5% prevalence of microlithiasis in 60 duct before clipping it and routine use of proportion of participants reporting sympto- patients with Type II and Type III SOD with intraoperativeonly cholangiogram have been matic improvement was similar to that previ- both normal and abnormal manometry, proposed. Adoption of these techniques into ously reported in the literature, however, though these results did not meet statistical routine practice would likely reduce the inci- 55% of those enrolled had intact gallblad- significance.44 It is notable that bile sam- dence of this cause of PCS. ders. pling protocols were different between the Cystic duct remnant neuromas are a rare There is insufficient data to determine studies: the former swept the commonuse bile cause of PCS pain. The nerves innervating the existence of SOD in the presence of an duct with a basket, while the latter aspirated the gall bladder are transected during chole- intact gallbladder, since few will be offered from the common bile duct during ERCP. cystectomy and can result in nerve hypertro- SOM prior to cholecystectomy, meaning that These differing conclusions may support the phy with subsequent hyperalgesia or biliary the conclusions of this study cannot be observation that Type 1 SOD is pathological- stricture. This concept was challenged early applied to those with PCS. ly different from Types II and III SOD, with on by an autopsy series demonstrating the BM being the missing link. presence of neuromas as common in asymp- Biliary microlithiasis tomatic cholecystectomized patients, sug- Cystic duct remnant: retained calculi and Increasing evidence suggests biliary gesting these are normal post-operative microlithiasis (BM) is another important neuroma changes and may not account for PCS pain.51 cause of PCS. Bile crystals, composed of cho- The cystic duct remnant left behind after However, case series have reported pain lesterol monohydrate crystals (CMC) and cholestectomy has been recognized for many from neuromas without biliary stricture; fur- calcium bilirubinate granules (CBG), are the years to be a potential source of PCS pain. A thermore, others have demonstrated precursors to gallstones. By definition, randomized and blinded trial comparing patients with obstructive due to bil- microlithiasis cannot be directly visualized complete removal of the cystic duct to con- iary strictures arising from the neuro- by conventional trans-abdominal ultrasound ventional cholecystectomy found that 85% of mas.52,53 or CT. Bile from duodenal or bile duct aspi- patients were pain free over an 8-year fol- One case series reported that neuromas rates can be examined for theNon-commercial presence of low-up period compared to 30% in the control can cause pain without stricture formation such microlithiasis. They are considered group.46 Whether or not the cystic duct itself by demonstrating temporary relief of pain positive if 3 or more crystals are present in a is painful is debatable, but both the presence after endoscopic ultrasound (EUS) guided high power view in a polarized microscope. of retained calculi and the development of injection of bupivicaine into the porta Microlithiasis has already been identified as traumatic neuroma have been identified as hepatis.48 All patients then underwent rem- a cause of recurrent idiopathic acute pancre- the underlying pathology in multiple stud- nant duct resection with identification of the atitis in patients with an intact gallbladder, ies.47,48 neuroma on pathology and significant pain presumably due to transient obstruction of By definition, a remnant cystic duct is relief, though recurrence months later was the ampulla or pancreatic duct.41,42 more than 1cm long and believed to be asso- common. Whether or not the size, location, Microlithiasis has also been identified in the ciated with a higher risk of retained calculi. or other characteristics of the neuroma are bile of cholecystectomized patients with Though the incidence is unknown, it associated with the presence and severity of recurrent abdominal pain, although what appears to be growing in the laparoscopic symptoms remain unknown. role they may play in PCS is still not era where higher rates of bile duct and vas- clear.43,44 In a recent randomized trial, 10% cular injuries encourage surgeons to leave of PCS patients had microlithiasis identified behind a longer cystic duct or even part of Diagnostic and therapeutic in their bile.45 Patients were randomized to the gall bladder. Walsh et al. reported approach receive ursodeoxycholic acid (urso) or place- patients developing recurrent biliary type There are currently no widely accepted bo for six months. The results demonstrated pain 14 months to 20 years after either guidelines for evaluating PCS, as PCS com-

[Gastroenterology Insights 2012; 4:e1] [page 3] Review prises many heterogeneous disorders. With multidisciplinary approach with pain manage- administration of vardenafil into the duode- recent suggestions of a diverse and complex ment and psychiatry may be appropriate. SOM num distal to the papilla caused a significant pathogenesis, clinicians should employ a should be performed on patients with Type II decrease in basal sphincter of oddi pressures systematic approach to diagnose and treat a SOD, but generally avoided with Type III SOD on SOM.58 This preliminary study included range of potential etiologies (Figure 1). due to its limited utility and high complication both cholecystectomized patients as well as The first step in the evaluation of a PCS rate. those with intact gallbladders. More SOD-spe- patient should be a thorough history and phys- Few studies have looked at the long-term cific trials are needed to confirm the clinical ical examination to rule out common treatable efficacy of medical therapy for PCS or SOD. An potential of vardenafil in treating SOD. In conditions which may have been previously empirical trial lasting several months of summary, despite the paucity of data for the overlooked. Assessment for H. pylori infection, ursodeoxycholic acid may be reasonable if above treatments, given their relative safety peptic ulcer disease, gastroparesis, amongst patients are not candidates for endoscopy, and the benign course of PCS and SOD, other disorders, should be initiated in the right given the possibility of biliary microlithiasis in experts recommend a trial of medical therapy clinical setting. Signs of extrahepatic obstruc- cholecystectomized patients. Its low cost and prior to SOM and BSE. tion warrant prompt evaluation with func- well tolerated side effect profile make this a Collective understanding of postcholecystec- tion tests and ERCP. EUS may be employed to particularly attractive option even without per- tomy syndrome is still imperfect. Future stud- verify absence of obstruction in patients with forming bile analysis. Two small double-blind, ies are needed to elucidate the pathogenesis of low suspicion for it. placebo controlled, crossover studies have SOD, to develop cost effective and non-inva- The workup for true PCS should begin with shown that nifedipine can reduce the severity sive methods for evaluating SOD, and to pur- differentiating functional pain from biliary and frequency of pain, and need for analgesics sue medical therapies as an adjunct or alterna- pain, and Rome III criteria may be employed in compared to the placebo group.54,56 Nitrates tive to invasive interventions. this process. Having excluded a functional eti- have been shown to reduce the basal sphincter ology, practitioners should evaluate patients pressure in asymptomatic volunteers and for SOD. We propose re-labeling Type I SOD as symptomatic patients with SOD. Octreotide definite SOD and Types II and III as suspected has also been shown to reduce basal sphincter References SOD to avoid mislabeling many with no under- pressures in manometrically proven SOD in a only lying SOD. Patients with definite SOD can be prospective randomized placebo controlled 1. National Institutes of Health Consensus diagnosed with Modified Milwaukee Criteria trial.56 Nitroglycerine, spasmolytics, opiate Development Conference. Statement on with liver function tests and radiography, and analgesics, and corticosteroids have all been gallstones and laparoscopic cholecystecto- should undergo ERCP and EBS. Patients with reported to relieve pain from SOD attacks to my. Am J Surg 1993;165:390-8. suspected SOD should first undergo non-inva- varying degrees.57 Non-steroidal anti-inflam-use2. McPherson K, Wennberg JE, Hovind OB, et sive evaluations, though strategies have not matory drugs were reportedly ineffective.6 al. Small area variations in the use of com- been validated. Biliary scintigraphy has excel- Pancreatic enzyme supplementation has been mon surgical procedures: an international lent specificity for predicting abnormal SOM, reported to reduce dyspeptic symptoms, but comparison of New England, England, and but a negative test does not rule out SOD. have no effect on pain.5 Of note, Cheon et al. Norway. N Eng J Med 1982;307:1310-4. MRCP and EUS can be employed to diagnose recently conducted a randomized controlled 3. Ransohoff DF, Gracie WA. Treatment of pathology involving the cystic duct, such as trial involving cases of suspected SOD: the gallstones. Ann Intern Med 1993;119:606- retained stone. If the workup is negative, a 19. 4. Finan KR, Ruth RW, Bryan MK, et al. Improvement in gastrointestinal symp- toms and quality of life after cholecystecto- my. Am J Surg 2006;192:196-202. 5. Bodvall B. The post cholecystectomy syn- drome. Clin Gastroenterol 1973;2:102-26. 6. Lasson A. The post-cholecystectomy syn- drome: diagnostic and therapeutic strate- gy, Scand J Gastroenterol 1987;22:897-902. Non-commercial 7. Tondelli P, Gyr K, et al. The biliary tract. Part I: Cholecystectomy. Clin Gastroenterol 1979;8:487-505. 8. Lasson A, Fork FT, et al. (1988). The postc- holecystectomy syndrome: bile ducts as pain trigger zone. Scand J Gastroenterol 1988;23:265-71. 9. Filip M, Saftoiu A, et al. Postcho - lecystectomy syndrome - an algorithmic approach. J Gastrointestin Liver Dis 2009;18:67-71. 10. Baillie J. Sphincter of Oddi dysfunction. Curr Gastroenterol Rep 2010;12:130-4. 11. Jaunoo SS, Mohandas S, et al. Postcholecystectomy syndrome (PCS). Int J Surg 2010;8:15-7. Figure 1. Diagnostic and therapeutic approach to postcholecystectomy syndrome. 12. Bar-Meir S, Halpern Z, et al. Frequency of papillary dysfunction among cholecystec-

[page 4] [Gastroenterology Insights 2012; 4:e1] Review

tomized patients. Hepatology 1984;4:328- 2006;24:237-46. comparison of secretin-stimulated mag- 30. 26. Freeman ML, Guda NM. Prevention of netic resonance cholangiopancreatogra- 13. Elmi F, Silverman WB. Biliary sphincter of post-ERCP pancreatitis: a comprehensive phy with manometry in the diagnosis of Oddi dysfunction type I versus occult bil- review. Gastrointest Endosc 2004;59:845- sphincter of Oddi dysfunction types II and iary microlithiasis in post-cholecystectomy 64. III. Gut 2007;56:809-13. patients: are they both part of the same 27. Freeman ML. Post-ERCP pancreatitis: 40. Kalaitzakis E, Ambrose T, et al. clinical entity? Dig Dis Sci 2010;55:842-6. patient and technique related risk factors. Management of patients with biliary 14. Geenen JE, Hogan WJ, Dodds WJ, et al. JOP 2002;3:169-76. sphincter of Oddi disorder without sphinc- The efficacy of endoscopic sphincterotomy 28. Madacsy L, Middelfart HV, et al. ter of Oddi manometry. BMC Gastroenterol after cholecystectomy in patients with Quantitative hepatobiliary scintigraphy 2010;10:124. sphincter of Oddi dysfunction. N Engl J and endoscopic sphincter of Oddi manom- 41. Ros E, Navarro S, et al. Occult microlithia- Med1989;320:82-7. etry in patients with suspected sphincter sis in idiopathic acute pancreatitis: pre- 15. Madacsy L, Fejes R, et al. Characterization of Oddi dysfunction: assessment of flow- vention of relapses by cholecystectomy or of functional biliary pain and dyspeptic pressure relationship in the biliary tract. ursodeoxycholic acid therapy. Gastro - symptoms in patients with sphincter of Eur J Gastroenterol Hepatol 2000;12:777- enterology 1991;101:1701-9. Oddi dysfunction: effect of papillotomy. 86. 42. Saraswat VA, Sharma BC, et al. Biliary World J Gastroenterol 2006;12:6850-6. 29. Rome Foundation: Rome III diagnostic microlithiasis in patients with idiopathic 16. Desautels SG, Slivka A, et al. Postcho - questionnaires. Available from: http:// acute pancreatitis and unexplained biliary lecystectomy pain syndrome: pathophysiol- www.romecriteria.org/questionnaires/ pain: response to therapy. J Gastroenterol ogy of abdominal pain in sphincter of Oddi 30. Steinberg WM, Salvato RF, et al. The mor- Hepatol 2004;19:1206-11. type III. Gastroenterology 1999;116:900-5. phine-prostigmin provocative test--is it 43. Parasher VK, Roman K, Sukumar R, et al. 17. Kurucsai G, Joo I, et al. Somatosensory useful for making clinical decisions? Is microlithiasis common in postcholecys- hypersensitivity in the referred pain area Gastroenterology 1980;78:728-31. tectomy patients presenting with biliary in patients with chronic biliary pain and a 31. Corazziari E, Cicala M, et al. Hepa - type pain? Am J Gastroenterol 1996;91: sphincter of Oddi dysfunction: new aspects toduodenal bile transit in cholecystec- 1939. of an almost forgotten pathogenetic mech- tomized subjects. Relationship with 44.only Quallich LG, Stern MA, et al. Bile duct crys- anism. Am J Gastroenterol 2008;103:2717- sphincter of Oddi function and diagnostic tals do not contribute to sphincter of Oddi 25. value. Dig Dis Sci 1994;39:1985-93. dysfunction(or pain). Gastrointest Endosc 18. Hastbacka J, Jarvinen H, et al. Results of 32. Cicala M, Habib FI, et al. Outcome of endo- 2002;55:163-6. sphincteroplasty in patients with spastic scopic sphincterotomy in post cholecystec-use 45. Okoro N, Patel A, et al. Ursodeoxycholic sphincter of Oddi. Predictive value of oper- tomy patients with sphincter of Oddi dys- acid treatment for patients with postchole- ative biliary manometry and provocation function as predicted by manometry and cystectomy pain and bile microlithiasis. tests. Scand J Gastroenterol 1986;21:516- quantitative choledochoscintigraphy. Gut Gastrointest Endosc 2008;68:69-74. 20. 2002;50:665-8. 46. Jonson G, Nilsson DM, et al. Cystic duct 19. Linder JD, Klapow JC, et al. Incomplete 33. Cicala M, Scopinaro F, Corazziari E, et al. remnants and biliary symptoms after response to endoscopic sphincterotomy in Quantitative cholescintigraphy in the cholecystectomy. A randomised compari- patients with sphincter of Oddi dysfunc- assessment of choledochoduodenal bile son of two operative techniques. Eur J tion: evidence for a chronic pain disorder. flow. Gastroenterology 1991;100:1106-13. Surg 1991;157:583-6. Am J Gastroenterol 2003;98:1738-43. 34. Craig AG, Peter D, et al. Scintigraphy ver- 47. Walsh RM, Ponsky JL, et al. Retained gall- 20. Toouli J. Sphincter of Oddi: Function, dys- sus manometry in patients with suspected bladder/cystic duct remnant calculi as a function, and its management. J biliary sphincter of Oddi dysfunction. Gut cause of postcholecystectomy pain. Surg Gastroenterol Hepatol 2009;24:S57-62. 2003;52:352-7. Endosc 2002;16:981-4. 21. Toouli J, Roberts-Thomson IC, et al. 35. Toouli J. Biliary scintigraphy versus 48. Topazian M, Salem RR, et al. Painful cystic Manometry based randomised trial of sphincter of Oddi manometry in patients duct remnant diagnosed by endoscopic endoscopic sphincterotomy for sphincter with post-cholecystectomy pain: is it time ultrasound. Am J Gastroenterol 2005;100: of Oddi dysfunction. Gut 2000;46:98-102. to disregard the scan? Curr Gastroenterol 491-5. 22. Rolny P, Geenen JE, et al. Post-cholecystec-Non-commercialRep 2005;7:154-9. 49. Palanivelu C, Rangarajan M, et al. tomy patients with "objective signs" of par- 36. Thomas PD, Turner JG, et al. Use of Laparoscopic management of remnant tial bile outflow obstruction: clinical char- (99m)Tc-DISIDA biliary scanning with cystic duct calculi: a retrospective study. acteristics, sphincter of Oddi manometry morphine provocation for the detection of Ann R Coll Surg Engl 2009;91:25-9. findings, and results of therapy. elevated sphincter of Oddi basal pressure. 50. Shaw C, O'Hanlon DM, et al. Cystic duct Gastrointest Endosc 1993;39:778-81. Gut 2000;46:838-41. remnant and the post-cholecystectomy 23. Thatcher BS, Sivak MV Jr, et al. 37. Matos C, Metens T, et al. Pancreatic duct: syndrome. Hepatogastroenterology 2004; Endoscopic sphincterotomy for suspected morphologic and functional evaluation 51:36-8. dysfunction of the sphincter of Oddi. with dynamic MR pancreatography after 51. Bodner E, Aufschnaiter M, et al. Neuroma Gastrointest Endosc 1987;33:91-5. secretin stimulation. Radiology 1997;203: of the cystic nerve stump. No explanation 24. Corazziari E, Cicala M, et al. Scintigraphic 435-41. for post-cholecystectomy pain. Chirurg assessment of SO dysfunction. Gut 38. Aisen AM, Sherman S, et al. Comparison of 1978;49:424-7. 2003;52:1655-6. secretin-stimulated magnetic resonance 52. Iannelli A, Fabiani P, et al. Traumatic neu- 25. Sgouros SN, Pereira SP. Systematic pancreatography and manometry results roma of the cystic duct with biliary review: sphincter of Oddi dysfunction-- in patients with suspected sphincter of obstruction. Report of a case. Acta non-invasive diagnostic methods and oddi dysfunction. Acad Radiol 2008;15:601- Gastroenterol Belg 2003;66:28-9. long-term outcome after endoscopic 9. 53. Nagafuchi Y, Katuki M, et al. A traumatic sphincterotomy. Aliment Pharmacol Ther 39. Pereira SP, Gillams A, et al. Prospective neuroma associated with obstructive jaun-

[Gastroenterology Insights 2012; 4:e1] [page 5] Review

dice after laparoscopic cholecystectomy. ble-blind, randomized, placebo-controlled, py in a patient with papillary dysfunction." Hepatogastroenterology 1998;45:424-7. cross over trial. Br J Clin Pharmacol Am J Gastroenterol 1983;78:94-5. 54. Sand J, Nordback I, et al. Nifedipine for 1992;33:477-85. 58. Cheon YK, Cho YD, et al. Effects of varde- suspected type II sphincter of Oddi dyski- 56. Fazel A, Li SC, et al. Octreotide relaxes the nafil, a phosphodiesterase type-5 nesia. Am J Gastroenterol 1993;88:530-5. hypertensive sphincter of Oddi: patho- inhibitor, on sphincter of Oddi motility in 55. Khuroo MS, Zargar SA, et al. Efficacy of physiological and therapeutic implica- patients with suspected biliary sphincter nifedipine therapy in patients with sphinc- tions. Am J Gastroenterol 2002;97:612-6. of Oddi dysfunction. Gastrointest Endosc ter of Oddi dysfunction: a prospective, dou- 57. Bar-Meir S, Halpern Z, et al. Nitrate thera- 2009;69:1111-6.

only use

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