Codeine has a spasmodic effect on sphincter of Oddi and is suspected to cause acute pancreatitis in patients with a history of cholecystectomy.

To assess the association between codeine use and acute pancreatitis in patients with a previous cholecystectomy.

We conducted a retrospective nested case-control study using the 2005-2015 MarketScan^® Commercial Claims and Encounters Database. The cohort included patients aged 18-64; cohort entry began 365 days after cholecystectomy. Odds ratios (ORs) and 95% CIs for acute pancreatitis hospitalization were estimated comparing use of codeine with non-use of codeine. In a secondary analysis, use of codeine was compared with an active comparator: use of non-steroidal anti-inflammatory drugs (NSAIDs).

Of the 664,083 patients included in the cohort, 1707 patients were hospitalized for acute pancreatitis (incidence 1.1 per 1000 person-years) and were matched to 17,063 controls. Compared with non-use of codeine, use of codeine was associated with an increased risk of acute pancreatitis (OR 2.67; 95% CI 1.63, 4.36), particularly elevated in the first 15 days of codeine use (OR 5.37; 95% CI 2.70, 10.68). Compared with use of NSAIDs, use of codeine was also associated with an increased risk of acute pancreatitis (OR 2.64; 95% CI 1.54, 4.52).

Codeine is associated with an increased risk of acute pancreatitis in patients who have previously undergone cholecystectomy; greater clinician awareness of this association is needed.

This study investigated the changes in echogenicity, as measured by endoscopic ultrasound, and the surface area of the papilla of Vater (PV) and their relationship with postoperative symptoms in a group of 80 patients with symptomatic gallstones before and at 3 and 6 months after cholecystectomy. After cholecystectomy, 50 patients experienced early atypical symptoms characteristic of postcholecystectomy syndrome (PCS) and 30 patients were asymptomatic. The surface area of the PV was larger than normal prior to surgery and increased after surgery. The healthy PV is isoechogenic, but 48% of all patients were anisoechogenic preoperatively, increasing to 61% at 3 months after surgery, and decreasing to 25% at 6 months postsurgery. There was no significant difference between the two patient groups, suggesting that the changes observed in the PV do not explain the presence of the atypical symptoms of PCS.

Effectiveness of medical therapies in chronic pancreatitis has been described in small studies of selected patients.

To describe frequency and perceived effectiveness of non-analgesic medical therapies in chronic pancreatitis patients evaluated at US referral centres.

Using data on 516 chronic pancreatitis patients enrolled prospectively in the NAPS2 Study, we evaluated how often medical therapies [pancreatic enzyme replacement therapy (PERT), vitamins/antioxidants (AO), octreotide, coeliac plexus block (CPB)] were utilized and considered useful by physicians.

Oral PERT was commonly used (70%), more frequently in the presence of exocrine insufficiency (EI) (88% vs. 61%, P < 0.001) and pain (74% vs. 59%, P < 0.002). On multivariable analyses, predictors of PERT usage were EI (OR 5.14, 95% CI 2.87-9.18), constant (OR 3.42, 95% CI 1.93-6.04) or intermittent pain (OR 1.98, 95% CI 1.14-3.45). Efficacy of PERT was predicted only by EI (OR 2.16, 95% CI 1.36-3.42). AO were tried less often (14%) and were more effective in idiopathic and obstructive vs. alcoholic chronic pancreatitis (25% vs. 4%, P = 0.03). Other therapies were infrequently used (CPB - 5%, octreotide - 7%) with efficacy generally <50%.

Pancreatic enzyme replacement therapy is commonly utilized, but is considered useful in only subsets of chronic pancreatitis patients. Other medical therapies are used infrequently and have limited efficacy.

Sphincter of Oddi dysfunction is a benign, functional gastrointestinal disorder for which invasive endoscopic therapy with potential complications is often recommended.

To review the available evidence regarding the diagnostic accuracy of non-invasive methods that have been used to establish the diagnosis and to estimate the long-term outcome after endoscopic sphincterotomy.

A systematic review of English language articles and abstracts containing relevant terms was performed.

Non-invasive diagnostic methods are limited by their low sensitivity and specificity, especially in patients with Type III sphincter of Oddi dysfunction. Secretin-stimulated magnetic resonance cholangiopancreatography appears to be useful in excluding other potential causes of symptoms, and morphine-provocated hepatobiliary scintigraphy also warrants further study. Approximately 85%, 69% and 37%, of patients with biliary Types I, II and III sphincter of Oddi dysfunction, respectively, experience sustained benefit after endoscopic sphincterotomy. In pancreatic sphincter of Oddi dysfunction, approximately 75% of patients report symptomatic improvement after pancreatic sphincterotomy, but the studies have been non-controlled and heterogeneous.

Patients with suspected sphincter of Oddi dysfunction, particularly those with biliary Type III, should be carefully evaluated before considering sphincter of Oddi manometry and endoscopic sphincterotomy. Further controlled trials are needed to justify the invasive management of patients with biliary Type III and pancreatic sphincter of Oddi dysfunction.

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.

The extrahepatic biliary tract is innervated by dense networks of extrinsic and intrinsic nerves that regulates smooth muscle tone and epithelial cell function of extrahepatic biliary tree. Although these ganglia are derived from the same set of precursor neural crest cells that colonize the gut, they exhibit structural, neurochemical, and physiological characteristics that are distinct from the neurons of the enteric nervous system. Gallbladder neurons are relatively inexcitable, and their output is driven by vagal inputs and modulated by hormones, peptides released from sensory fibers, and inflammatory mediators. Gallbladder neurons are cholinergic and they can express a number of other neural active compounds, including substance P, galanin, nitric oxide, and vasoactive intestinal peptide. Sphincter of Oddi (SO) ganglia, which are connected to ganglia of the duodenum, appear to be comprised of distinct populations of excitatory and inhibitory neurons, based on their expression of choline acetyltransferase and substance P or nitric oxide synthase, respectively. While SO neurons likely receive vagal input and their activity is modulated by release of neuropeptides from sensory fibers, a significant source of excitatory synaptic input to these cells arise from the duodenum. This duodenum-SO circuit is likely to play an important role in the coordination of SO tone with gallbladder motility in the process of gallbladder emptying. Now that we have gained a relatively thorough understanding of the innervation of the biliary tree under healthy conditions, the way is paved for future studies of altered neural function in biliary disease.

With the introduction of endoscopic retrograde cholangiopancreatography (ERCP) manometry, the characteristics of sphincter of Oddi (SO) motor activity have been described. SO manometry is the only available method to measure SO motor activity directly and is usually performed at the time of ERCP. SO manometry is considered to be the gold standard for evaluating patients for sphincter dysfunction. This review reports the technique of SO manometry and normal values for SO manometry. SO motility is characterized by prominent phasic contractions superimposed on a tonic pressure. Elevated basal SO pressure is the most consistent and reliable criteria to diagnose SO dysfunction. Basal pressures obtained from the biliary sphincter are similar to the basal pressure obtained from the pancreatic sphincter. Abnormal SO manometric values are shown. Factors that influence SO pressures, and interpretation of SO manometric tracing are discussed. The most common and serious complication of SO manometry is post-manometry pancreatitis. In healthy volunteers with normal sphincter function, pancreatitis is almost never seen. However, in patients with SO dysfunction, the incidence of pancreatitis is high. The use of new nonperfused microtransducers may reduce this complication.

The enteric nervous system is involved in most of the physiological and pathophysiological processes in the gastrointestinal tract. This Minireview is part two of three and describes the role of the enteric nervous system in gastrointestinal functions (motility, exocrine and endocrine secretions, blood flow, and immune processes) in health and some disease states. In this context, the functional importance of the enteric nervous system for food intake, the gall bladder, and pancreas will be addressed. In specific, dysmotility, diarrhoea, constipation, non-occlusive intestinal ischaemia (intestinal angina), inflammation, cholelithiasis, cholecystitis, postcholecystectomy syndrome, and pancreatitis can be treated with neuroactive pharmacological agents. For example, serotonin receptor type four agonists can be used for the treatment of constipation, while nitric oxide synthesis inhibitors can be employed for the treatment of intestinal angina.