Effect of sphincter of Oddi dysfunction on the abundance of biliary microbiota (biliary microecology) in patients with common bile duct stones.

Objective: Biliary calculi, a common benign disease of the gastrointestinal tract, are affected by multiple factors, including diet, lifestyle, living environment, and personal and genetic background. Its occurrence is believed to be related to a change in biliary microbiota. Approximately 10%-20% of symptomatic patients with cholecystolithiasis have choledocholithiasis, resulting in infection, abdominal pain, jaundice, and biliary pancreatitis. This study aimed to determine whether a dysfunction in the sphincter of Oddi, which controls the outflow of bile and separates the bile duct from the intestine, leads to a change in biliary microbiota and the occurrence of biliary calculi. Methods: Forty patients with cholecystolithiasis and choledocholithiasis were prospectively recruited. Bile specimens were obtained, and biliary pressure was measured during and after surgery. The collected specimens were analyzed with 16S rRNA gene to characterize the biliary microbiota. The risk factors of common bile duct calculi were analyzed numerically combined with the pressure in the sphincter of Oddi. Results: Different biliary microbiota were found in all cases. Patients with sphincter of Oddi dysfunction had significantly increased biliary microbiota as well as significantly higher level of systemic inflammation than patients with normal sphincter of Oddi. Conclusions: The systemic inflammatory response of patients with sphincter of Oddi dysfunction is more severe, and their microbial community significantly differs from that of patients with normal sphincter of Oddi, which makes biliary tract infection more likely; furthermore, the biliary tract of patients with sphincter of Oddi dysfunction has more gallstone-related bacterial communities.

Cyclic Change of Sphincter of Oddi Motility and Its Relationship with Small Bowel Migrating Motor Complex in Humans.

BACKGROUND: Several animal and human studies have reported that sphincter of Oddi (SO) motility shows cyclical changes during the fasting state. However, to date, the relationship between the SO motility and the migrating motor complex (MMC) of the small bowel (SB) remains unclear in humans. AIMS: We observed SO motility over a long study period and evaluated its relationship with the MMC of the SB in humans using percutaneous long-term manometry. METHODS: Our study included patients with hepatolithiasis who required percutaneous transhepatic catheter placement and subsequently underwent choledochoscopy and stone removal. Long-term percutaneous transhepatic SO manometry was performed after complete stone removal. SO and SB motility were simultaneously recorded. RESULTS: SO motility showed cyclical phasic changes with periodic high-frequency contractions similar to the MMC contractions of the SB. All high-frequency contractions of the SO coincided with phase III contractions of the MMC of the SB. The proportions of phase III contractions of SO and SB were similar, but the proportions of phase I (P = 0.001) and phase II (P = 0.002) contractions were significantly different. The mean basal SO pressure was observed to significantly increase in phase III compared to phase I (P = 0.001) and phase II (P = 0.001) contractions. CONCLUSIONS: SO motility in humans showed cyclical phasic changes closely coordinated with the MMC of the SB in a fasting state; however, the proportion of phases differed between the SO and the SB. The basal pressure significantly increased during physiological high-frequency phase III contractions of the SO.

Sphincter of Oddi dysfunction: sphincter of Oddi dysfunction or discordance? What is the state of the art in 2018?

PURPOSE OF REVIEW: To review important manuscripts published over the previous 2 years relative to sphincter of Oddi dysfunction (SOD). RECENT FINDINGS: The long-term outcomes of the Evaluating Predictors and Interventions of SOD (EPISOD) trial further substantiated results from the initial EPISOD study, reinforcing that neither endoscopic retrograde cholangiopancreatography-manometry nor endoscopic sphincterotomy are appropriate for SOD type III. Pain management in the latter patients has reverted to neuromodulating agents, and recent studies have suggested a role for duloxetine and potentially acupuncture. The functional role of the sphincter of Oddi has been reiterated with a report demonstrating a higher clinically significant pancreatic fistula rate in distal pancreatectomy patients treated with higher doses of postoperative narcotics. Moreover, the injection of periampullary botulinum toxin preoperatively has been shown to decrease these fistulas in a pilot trial. Additional studies have reinforced that eluxadoline can cause sphincter of Oddi spasm and pancreatitis. In contrast to approaching patients with acute relapsing pancreatitis using endoscopic retrograde cholangiopancreatography and manometry, previous and current studies suggest that endoscopic ultrasound should be done first and the role of SOD in idiopathic acute relapsing pancreatitis remains controversial. Finally, there remain widespread disparities in practice patterns in the approach to patients currently classified as SOD type II. SUMMARY: In contrast to historical manuscripts which stress the classical definitions of three types of SOD and their consequences, more recent manuscripts on this topic have focused on improving surgical outcomes based on the physiologic role of sphincter of Oddi, as well as the pharmacologic causes and treatments of SOD. The simplistic view that SOD, however it has been diagnosed, requires biliary or dual sphincterotomy is just that, simplistic and potentially misguided.

[NERVOUS REGULATION OF BILIARY TRACT MOTILITY].

Aim: The study of mechanisms of regulation of biliary tract motility by divisions of autonomic nervous system (ANS). Material and methods: Experiments were carried out on rabbits, chinchillas weighing 3.5-4 kg using gentle methods of treatment of experimental animals. Electromotor activity of electromotor (EMA) of the gallbladder and sphincter of Oddi was recorded. Irritation of the nerve produces an electrical pulse duration of 2 ms, the amplitude of 1.5-15 V, frequency of 10 Hz. Results: The mechanism of vagal inhibition of sphincter of Oddi motility and unidirectional stimulatory influence of ANS divisions on the motility of the gallbladder and sphincter of Oddi was studied. It was established that in the mechanism of vagal inhibition of sphincter of Oddi motility involved intramural adrenergic neurons synaptically connected with preganglionic parasympathetic fibers. At the stimulatory effect of vagus on biliary tract motility serotonergic intramural neurons are involved transmitting excitation to serotonin receptors of effector tissue.

Effects of thienorphine on contraction of the guinea pig sphincter of Oddi, choledochus and gall bladder.

Opioid analgesics are widely believed to cause spasm of the bile duct sphincter and so impede bile flow. Thienorphine is a partial opioid agonist that is a good candidate for the treatment of opioid dependence; however, to date, no studies have reported the effects of thienorphine on the function of the biliary tract. This study examined the in vivo effects of thienorphine on the guinea pig isolated sphincter of Oddi, choledochus and gall bladder and on bile flow. The area under the curve (AUC) of isolated sphincter of Oddi was not influenced by thienorphine or buprenorphine, whereas morphine increased the AUC of the isolated sphincter of Oddi in a concentration-dependent manner. Thienorphine and buprenorphine concentration-dependently decreased the AUC of isolated choledochus, while morphine increased the AUC of isolated choledochus. Thienorphine had no effect on the contractile amplitude or basal tension of isolated gall bladder muscle strips. In contrast, buprenorphine and morphine increased the contractile basal tension of isolated gall bladder muscle strips in a concentration-dependent manner. Thienorphine (0.01-1.0mg/kg) had no significant inhibitory effect on bile flow. However, morphine (1.0-10mg/kg) and buprenorphine (1.0mg/kg) significantly inhibited bile flow. The maximum inhibition of bile flow by buprenorphine was 63.9±12.9% and by morphine was 74.1±11.3%. In summary, thienorphine has little influence on the guinea pig isolated sphincter of Oddi, choledochus and gall bladder or on bile flow, which may result in a lack of adverse biliary colic effects.

Effects of cholecystectomy on the changes of motility of Beagle dogs' sphincter of Oddi.

PURPOSE: To observe the effect of cholecystectomy on the changes of motion pattern of Beagle dogs' sphincter of Oddi (SO), and investigate the modulatory role of nitric oxide (NO) and cholecystokinin (CCK) in the regulation of SO. METHODS: Pressure of common bile duct, SO motility, response to bolus injections of cholecystokinin (CCK, 20 ng/kg and 100 ng/kg), basal pressure (BP) and phasic contraction amplitude (PCA) were measured respectively by manometry in six Beagle dogs before and after cholecystectomy. RESULTS: After cholecystectomy, the pressure and diameter of common bile ducts (CBD) was significantly increased (p<0.01); BP and phasic contraction frequency (PCF) were also increased, however, no significant differences were found between the two groups; the SO motilities was not significantly changed. The relaxation responded to physiological dose of CCK (20ng/kg) was decreased, while bolus-dose of CCK (100ng/kg) induced rapid contractions and decreased PCA after cholecystectomy. The regulation pattern of SO pressure modulated by NO and its inhibitor had changed after cholecystectomy. CONCLUSION: After cholecystectomy in Beagle dogs, no obviously change of motion pattern of SO was observed through self-compensation, but these compensations may lead to some changes of regulation pattern of CCK and NO on SO.

Functional MR cholangiography of the cystic duct and sphincter of Oddi using gadoxetate disodium: is a 30-minute delay long enough?

PURPOSE: To determine if excreted contrast is consistently visualized in the gallbladder and duodenum after a 30-minute delay using gadoxetate disodium-enhanced MRI in patients without hepatobiliary disease. MATERIALS AND METHODS: Twenty-two patients without evidence of liver or biliary disease underwent gadoxetate disodium-enhanced magnetic resonance imaging (MRI) from February 17, 2009 through October 3, 2011. The mean age was 45 years (range 25-72). T1-weighted hepatobiliary phase images at 5, 10, 20, and 30 minutes after contrast injection were reviewed in consensus by two radiologists to determine the delay at which enhancement of the gallbladder and duodenum first occurred. RESULTS: Thirteen of 22 (59.1%) patients demonstrated duodenal filling by 20 minutes and 16/22 (72.7%) filled by 30 minutes. The mean time to duodenal enhancement was 19.9 minutes (range 11.4-30.2 min). Seventeen of 22 (77.3%) patients demonstrated gallbladder filling by 20 minutes and 21/22 (95.5%) filled by 30 minutes. The mean time to gallbladder enhancement was 16.5 minutes (range 4.4-30.2 min). CONCLUSION: A significant number of normal patients do not show duodenal filling by 30 minutes, while the majority fill the gallbladder by 30 minutes using functional MR cholangiography (fMRC) with gadoxetate disodium. These findings will guide fMRC protocol design for patients with suspected acute cholecystitis and sphincter of Oddi dysfunction.

The distribution and chemical coding of neurons supplying the sphincter of Oddi in mammals.

The major duodenal papilla (papilla of Vater) is an important structure associated with the biliary tract and, in some species, the pancreas. It usually represents a slight elevation on the intestinal mucosa where the dilated junction (ampulla of Vater) of the commmon bile duct and pancreatic duct enters the duodenum. The ampulla is surrounded by a specifically arranged muscle structure called the sphincter of Oddi (SO) which controls the flow of bile and pancreatic fluid. The function of the sphincter is regulated by a complex system that involves many hormonal and neural factors. The literature in the field contains detailed data on the morphology of the SO in a number of mammalian species. However, the comprehensive information about the anatomy and neurochemistry of the innervation of this structure is very limited. The present review article summarizes the current knowledge on the innervation of the SO in mammals. Special emphasis has been put on the localization and chemical coding of neurons contributing to this nerve supply.

Variabilities of gallbladder contraction indices and a simple regression model for gallbladder and gastric emptying ratio.

INTRODUCTION: The objective of this study was to assess the variabilities of gallbladder contraction indices (GBCI) and derive a predictive model for gallbladder and gastric motility. METHODS: The gallbladder volume and gastric antral measurements were obtained from 24 healthy male volunteers in preprandial and post-milk ingestion states. After preprandial measurement of the gallbladder volume and gastric antral area, each subject ingested 157 ml of full cream milk and 30 cl of ion-free water. In supine position, the gallbladder volume and the gastric antral area were obtained every five minutes for 40 minutes. For the gallbladder while only the 5(th), 10(th) and 15(th) measurement of gastric antral area were obtained. Gallbladder contraction indices were calculated and gastric emptying ratio obtained at the fifteenth minute is the indication of gastric motility. Statistical analyses were conducted using SPSS version 16.0 with p < 0.05 as criterion of statistical significance. RESULTS: The GBCIs followed Gaussian response at some stages and did not at some other stages. The least variability occurred at the 35th measurement of GBCI. A cut- off value for the 35th minute GBCI value was established with the mean ± 2 SD (80.79 ± 11.5%). Obvious gallbladder refilling was noted after 35 minutes. A positive relationship was noted between gallbladder and gastric motilities. CONCLUSION: With milk dilution, the variability of gall bladder motility is least at the 35th minute. A significant positive relationship between gastric emptying and gallbladder contraction index was also observed.

Function and dysfunction of the sphincter of Oddi.

In this review, the function of the sphincter of Oddi (SO) is detailed in terms of normal motility, neural and hormonal control of SO function, coordination between gallbladder and SO motility, and correlation of motility of the SO and the duodenum. In addition, SO function tests, such as the morphine Prostigmin test (Nardi test), perfusion manometry, microtransducer manometry, and cholescintigraphy, are explained. Subsequently, the pathophysiology, diagnosis, and treatment of SO dysfunction, including SO stenosis and dyskinesia, are described and discussed in detail. SO manometry and endoscopic sphincterotomy are effective to treat SO dysfunction, but symptoms of the patient must be severe enough to justify these invasive procedures for diagnosis and treatment.

Role of neurocrine somatostatin on sphincter of Oddi contractility and intestinal ischemia reperfusion-induced acute pancreatitis in macaques.

BACKGROUND: Intestinal ischemia-reperfusion (IIR) is implicated in the pathogenesis of severe acute pancreatitis (SAP). This study investigates the impact of neurocrine somatostatin (SST) on the contraction of sphincter of Oddi (SO) during IIR. METHODS: Intestinal ischemia-reperfusion model in macaques was induced by occluding the superior mesenteric artery. Pancreatitis was confirmed by pancreatic histology and serum levels of amylase and lipase. SST and its receptors (SSTRs) in SO were visualized by immunohistochemistry. Effects of SST on the contraction of the isolated SO were recorded in vitro. KEY RESULTS: Inflammatory scores of the pancreas and serum levels of amylase or lipase in the macaques that underwent IIR were significantly higher than those in the control group. The frequency and amplitude of phasic contraction of the circular muscle in SO was increased by SST in a concentration-dependent manner. Compared with the control group, SST innervation or SSTR2 expression in SO of macaques treated with IIR was increased 5.2 fold or 5.6 fold respectively. Prophylactic infusion of SST before IIR significantly reduced SST immunoreactive fibers in SO as compared to those in the IIR group and remarkably alleviated the pathophysiologic changes due to IIR. CONCLUSIONS & INFERENCES: Increased SST innervation in SO during the early phase of IIR associated with the contraction of circular muscle of SO, which might be one of the promoting factors associated with the development of SAP. Prevention of IIR or intervention of SO contraction after occurrence of acute pancreatitis might be beneficial for preventing SAP.

Reduced myoelectric activity in the sphincter of Oddi in a new model of chronic cholangitis in rabbits: an in vivo and in vitro study.

BACKGROUND: Chronic cholangitis caused by hepatolithiasis is a common disease in Southeast Asia. Few studies have addressed the effects of chronic cholangitis on cyclic activity of the sphincter of Oddi (SO). In this study, we investigated the changes of myoelectric activity in rabbits with chronic cholangitis in vivo and in vitro. METHODS: Chronic cholangitis was induced in rabbits by initially introducing three pieces of 2-0 silk suture and sequentially injecting E. coli into the choledochus through the tube in ductus cysticus. In in vivo experiments, myoelectric activity of SO was recorded by a circular electrode through the jejunum stump in conscious animals. In in vitro experiments, the SO was completely isolated and the myoelectric activity was recorded by a circular electrode in a 10-mL organ bath filled with Krebs solution, with or without addition of cholecystokinin-8 (CCK-8), KCl, ionomycin or induction of capacitative calcium entry (CCE). KEY RESULTS: In comparison with control and non-infected rabbits, the rabbits with chronic cholangitis showed higher levels of alkaline phosphatase and gamma-glutamyltransferase and significant pathological changes including increased inflammatory infiltration and collagen deposition in mucosae or muscular layer. Cyclic myoelectric activity of SO at phases 2 and 3 of migrating motor complex and the excitatory response to CCK-8 were dramatically decreased in animals with chronic cholangitis. Myoelectric activity of SO was also significantly decreased in vitro with or without agonists or with induction of CCE. CONCLUSIONS & INFERENCES: Myoelectric activity of SO and its response to agonists are decreased in rabbits with chronic cholangitis both in vivo and in vitro.

The feasibility and reliability of using circular electrode for sphincter of Oddi electromyography in anaesthetised rabbits.

Sphincter of Oddi manometry (SOM) is the gold standard for assessing sphincter of Oddi dysfunction (SOD), but is considered a diagnostic sensitivity of 30-80% and associated with significant complications of pancreatitis. Electromyography (EMG) of sphincter of Oddi (SO) using a circular electrode (CE) may be useful in improving diagnostic accuracy and reducing complications. To evaluate the feasibility and reliability of the CE, we record myoelectric activity of SO in rabbits using the CE to compare with the traditional needle electrode (NE). The CE was prepared using a double-channel biogel catheter with two silver rings at the head of the catheter. The CE was then inserted into the lumen of the SO through the duodenal papilla, and myoelectric activity was recorded in the SO in 30 rabbits. An EMG recorded using an NE was performed at the same time, when the SO was in basal state, after injection of cholecystokinin and N-butylscopolamine bromide. Electromyographs recorded by the two methods were then evaluated. Satisfactory SO EMGs were acquired using the CE without any injury. Simultaneous recording revealed a very similar traces and one-to-one correspondence of SO spike bursts (SOSB). Linear regression analysis showed a significant direct correlation between the two methods for SOSB duration and amplitude. The results suggested that CE was comparable with NE in terms of recording efficacy. The CE also has advantages of easy fixation, accurate localisation, broad applicability and ease of achieving satisfactory outcomes without trauma, compared with the NE.

The functional sphincter of Oddi disorder.

The sphincter of Oddi disorder (SOD) has been a controversial subject for many years, about which a lot has been written. However, new findings mainly using Endoscopic Retrograde Cholangiopancreatography (ERCP) and sphincter of Oddi manometry (SOM) demonstrate the fact of this diagnostic. SOD is just a part of a larger pathology, the tfunctional gastrointestinal disorders, which have been reconsidered as an important part of gastrointestinal diseases. For a better understanding, the American Gastroenterology Association Institute created a new classification of The Functional Gastrointestinal Disorders in 2006, Rome III Classification, in which the SOD is grouped in the functional biliary disorders (category E). The term SOD is used to define manometric abnormalities in patients who have signs and symptoms consistent with a biliary or pancreatic ductal origin. Based on the pathogenic mechanism and manometry findings, the SOD is separated into two groups: a group characterized by a stenotic pattern (anatomical abnormality) and a second group with a dyskinetic pattern functional abnormality). The purpose of this article is to construct a short presentation of the main aspects regarding tfunctional SOD (E2 and E3 after Rome III Classificatio).

[Functional recovery of Oddi's sphincter after balloon dilatation of the papilla of Vater. An experimental study in rabbits]. / Recuperación funcional del esfínter de Oddi tras dilatación con balón de la papila de Vater. Estudio experimental en conejos.

INTRODUCTION: Balloon dilatation of the papilla of Vater is used to treat biliary lithiasis. The results and complications rate of this technique are excellent. Published data indicate that this procedure does not significantly alter the physiology of the sphincter of Oddi and that normal function is maintained. Papillary balloon dilatation would therefore provide an advantage over other techniques in which sphincteric function is abolished. The objective of this study was to evaluate the functional status of the sphincter of Oddi after balloon dilatation of the papilla of Vater. MATERIAL AND METHODS: Twenty-four New Zealand albino rabbits were used. All animals underwent laparotomy and duodenotomy with balloon dilatation of the papilla of Vater. Manometric study of the biliary tract and of the sphincter of Oddi was also performed before, shortly after, and 21 days after dilatation. Biliary and sphincter of Oddi pressures and phasic activity of the sphincter (frequency, amplitude and duration of waves) were used as measuring variables for each of the stages of the experiment. RESULTS: Papillary balloon dilatation immediately provoked substantial sphincter relaxation. Comparison of the values of basal biliary and sphincter of Oddi pressures with those found 21 days after dilatation showed no statistically significant differences. No significant differences were found when the variables related to phasic activity of the sphincter (frequency, amplitude and duration) were compared between the distinct phases of the experiment. CONCLUSIONS: The results of the present study suggest complete recovery of sphincter function 21 days after balloon dilatation.

Neurohormonal regulation of the sphincter of Oddi.

The control of sphincter of Oddi (SO) motor activity is complex and involves interactions between the SO smooth muscle with nerves, bioactive agents, and presumably interstitial cells of Cajal. Disturbances in SO motility are known to be related to painful clinical conditions, such as SO dysfunction and acute pancreatitis. Understanding normal SO motility and comparing this to disturbed SO motility patterns may identify mechanisms that could be targeted for future pharmacologic intervention. The effect on SO motility of recently identified neurotransmitters/neuropeptides, such as purines and orexins, is currently being determined. Furthermore, because the control of SO motility is complex, investigations with known bioactive agents, such as cholecystokinin and nitric oxide, are continuing. This review summarizes research investigating SO motility and function performed in 2005 and 2006.

Exogenous adenosine triphosphate and adenosine stimulate proximal sphincter of oddi motility via neural mechanisms in the anesthetized Australian possum.

We aimed to determine if exogenous adenosine triphosphate or adenosine modulated sphincter of Oddi motility and involved neural mechanisms. Sphincter of Oddi motility was recorded in anesthetized possums by manometry. Adenosine triphosphate or adenosine (1 microM-10 mM) was applied topically to the sphincter before and after pretreatment with tetrodotoxin, hexamethonium, atropine, or Nomega-nitro-L-arginine methyl ester. Sphincter contraction amplitude and frequency were quantified. Adenosine triphosphate induced a concentration-dependent increase in proximal sphincter contraction amplitude and frequency (P < 0.05). This response was reduced by tetrodotoxin and atropine but enhanced by hexamethonium and Nomega-nitro-L-arginine methyl ester. Adenosine concentration dependently increased proximal sphincter contraction amplitude (P < 0.05) only. This response was reduced by tetrodotoxin, atropine, and Nomega-nitro-L-arginine methyl ester, whereas hexamethonium had no effect. We conclude that exogenous adenosine triphosphate and adenosine stimulate proximal sphincter of Oddi motility via neural mechanisms, involving cholinergic motor neurons. Adenosine triphosphate may further modulate sphincter motility via nicotinic and nitrergic pathways.