The sphincter of Oddi comprises a muscular complex encircling the distal part of the common bile duct and the pancreatic duct regulating the outflow from these ducts. Sphincter of Oddi dysfunction refers to the abnormal opening and closing of the muscular valve, which impairs the circulation of bile and pancreatic juices.

To evaluate the benefits and harms of any type of endoscopic sphincterotomy compared with a placebo drug, sham operation, or any pharmaceutical treatment, administered orally or endoscopically, alone or in combination, or a different type of endoscopic sphincterotomy in adults with biliary sphincter of Oddi dysfunction.

We used extensive Cochrane search methods. The latest search date was 16 May 2023.

We included randomised clinical trials assessing any type of endoscopic sphincterotomy versus placebo drug, sham operation, or any pharmaceutical treatment, alone or in combination, or a different type of endoscopic sphincterotomy in adults diagnosed with sphincter of Oddi dysfunction, irrespective of year, language of publication, format, or outcomes reported.

We used standard Cochrane methods and Review Manager to prepare the review. Our primary outcomes were: proportion of participants without successful treatment; proportion of participants with one or more serious adverse events; and health-related quality of life. Our secondary outcomes were: all-cause mortality; proportion of participants with one or more non-serious adverse events; length of hospital stay; and proportion of participants without improvement in liver function tests. We used the outcome data at the longest follow-up and the random-effects model for our primary analyses. We assessed the risk of bias of the included trials using RoB 2 and the certainty of evidence using GRADE. We planned to present the results of time-to-event outcomes as hazard ratios (HR). We presented dichotomous outcomes as risk ratios (RR) and continuous outcomes as mean difference (MD) with their 95% confidence intervals (CI).

We included four randomised clinical trials, including 433 participants. Trials were published between 1989 and 2015. The trial participants had sphincter of Oddi dysfunction. Two trials were conducted in the USA, one in Australia, and one in Japan. One was a multicentre trial conducted in seven US centres, and the remaining three were single-centre trials. One trial used a two-stage randomisation, resulting in two comparisons. The number of participants in the four trials ranged from 47 to 214 (median 86), with a median age of 45 years, and the mean proportion of males was 49%. The follow-up duration ranged from one year to four years after the end of treatment. All trials assessed one or more outcomes of interest to our review. The trials provided data for the comparisons and outcomes below, in conformity with our review protocol. The certainty of evidence for all the outcomes was very low. Endoscopic sphincterotomy versus sham Endoscopic sphincterotomy versus sham may have little to no effect on treatment success (RR 1.05, 95% CI 0.66 to 1.66; 3 trials, 340 participants; follow-up range 1 to 4 years); serious adverse events (RR 0.71, 95% CI 0.34 to 1.46; 1 trial, 214 participants; follow-up 1 year), health-related quality of life (Physical scale) (MD -1.00, 95% CI -3.84 to 1.84; 1 trial, 214 participants; follow-up 1 year), health-related quality of life (Mental scale) (MD -1.00, 95% CI -4.16 to 2.16; 1 trial, 214 participants; follow-up 1 year), and no improvement in liver function test (RR 0.89, 95% CI 0.35 to 2.26; 1 trial, 47 participants; follow-up 1 year), but the evidence is very uncertain. Endoscopic sphincterotomy versus endoscopic papillary balloon dilation Endoscopic sphincterotomy versus endoscopic papillary balloon dilationmay have little to no effect on serious adverse events (RR 0.34, 95% CI 0.04 to 3.15; 1 trial, 91 participants; follow-up 1 year), but the evidence is very uncertain. Endoscopic sphincterotomy versus dual endoscopic sphincterotomy Endoscopic sphincterotomy versus dual endoscopic sphincterotomy may have little to no effect on treatment success (RR 0.65, 95% CI 0.32 to 1.31; 1 trial, 99 participants; follow-up 1 year), but the evidence is very uncertain. Funding One trial did not provide any information on sponsorship; one trial was funded by a foundation (the National Institutes of Diabetes and Digestive and Kidney Diseases, NIDDK), and two trials seemed to be funded by the local health institutes or universities where the investigators worked. We did not identify any ongoing randomised clinical trials.

Based on very low-certainty evidence from the trials included in this review, we do not know if endoscopic sphincterotomy versus sham or versus dual endoscopic sphincterotomy increases, reduces, or makes no difference to the number of people with treatment success; if endoscopic sphincterotomy versus sham or versus endoscopic papillary balloon dilation increases, reduces, or makes no difference to serious adverse events; or if endoscopic sphincterotomy versus sham improves, worsens, or makes no difference to health-related quality of life and liver function tests in adults with biliary sphincter of Oddi dysfunction. Evidence on the effect of endoscopic sphincterotomy compared with sham, endoscopic papillary balloon dilation,or dual endoscopic sphincterotomyon all-cause mortality, non-serious adverse events, and length of hospital stay is lacking. We found no trials comparing endoscopic sphincterotomy versus a placebo drug or versus any other pharmaceutical treatment, alone or in combination. All four trials were underpowered and lacked trial data on clinically important outcomes. We lack randomised clinical trials assessing clinically and patient-relevant outcomes to demonstrate the effects of endoscopic sphincterotomy in adults with biliary sphincter of Oddi dysfunction.

A retrospective clinical audit was carried out to identify whether relaxation of the sphincter of Oddi (SO) by botulinum toxin (BTX) injection can select patients with episodic functional post-cholecystectomy biliary pain who will benefit from endoscopic sphincterotomy.

Sixty-four patients complaining of functional post-cholecystectomy biliary pain with a frequency of at least four episodes per month had 100 units of BTX injected into their SO muscle in four aliquots. After review patients with a pain free interval following BTX injection of at least 4 weeks were offered biliary endoscopic sphincterotomy and their outcome assessed.

Of the 64 patients 46 (72%) had at least four pain free weeks after BTX therapy and 44 of these 46 patients (96%) went on to experience pain relief following endoscopic sphincterotomy. Of the 64 patients 41 had sphincter of Oddi manometry prior to BTX injection. Every patient with sphincter of Oddi hypertension defined by manometry and at least 4 weeks' pain relief following BTX (24) had pain relief following sphincterotomy. Fifteen (94%) of the 16 patients who did not undergo manometry but reported at least 4 weeks' pain relief after BTX had pain relief after sphincterotomy.

Botulinum toxin relaxation of the SO may be a useful method of predicting the symptom response to endoscopic sphincterotomy in patients who have episodic functional 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.

Functional biliary disorders encompass the conditions of SOD and gallbladder dysmotility, both of which result in clinical pain syndromes. Obtaining objective diagnostic and outcomes data for both disorders has been an ongoing challenge over the last two decades. SOD, although initially believed to be strictly a biliary disorder, has now been implicated in recurrent pancreatitis. The biliary-type classification allows a clinician to stratify patients who would benefit from SOM and endoscopic sphincterotomy. Further study into the impact of endoscopic therapy for recurrent pancreatitis is needed. By the same token, the dilemma of postcholecystectomy abdominal pain, whether classified as biliary or pancreatic type III, remains challenging. The current limitations of knowledge highlight the need for prospective randomized studies to evaluate the clinical significance of SOM abnormalities to facilitate treatment of these patients.

Nifedipine is used to treat sphincter of Oddi dysfunction. Its effects on the biliary system and duodenum in relation to its known vascular actions are unclear. Our aims were to determine the relative tissue sensitivities to dihydropyridine L-type calcium channel antagonism in the sphincter of Oddi, gallbladder, duodenum, and vasculature. For in vivo studies, 23 possums received nifedipine at three different doses with blood pressure and sphincter of Oddi manometry recordings. For in vitro studies, tissues from 28 possums were pretreated with nicardipine (10(-8)-10(-5) M) and cumulative concentrations of agonist were administered (carbachol, norepinephrine at 10(-9)-10(-5) M). In in vivo studies, blood pressure fell significantly at a lower dose than sphincter of Oddi motility. In in vitro studies, the sphincter of Oddi was more sensitive than arterial tissue, with the duodenum especially sensitive. In conclusion, in the possum we found that L-type channel antagonism in vivo was more potent to the vasculature than the sphincter of Oddi but this was not confirmed in vitro.

If the mechanism of pain in patients with sphincter of Oddi (SO) dysfunction is functional obstruction of the biliary tract, and at least in some patients it results from sphincter smooth muscle hypertrophy, then smooth muscle relaxants should have a theoretic role in the management of these patients. Calcium channel antagonists and other smooth muscle relaxants have been shown in "acute" manometric studies to alter SO motility. However, the effect of these agents on vascular smooth muscle remains a concern and often limits their use. At present the role of medical therapy is somewhat unclear because few well-conducted studies have used manometric criteria for the diagnosis of SO dysfunction and the selection of patients for therapy. The main drawback is that no drugs appear to be specific for the SO, long acting, and free of side effects.

It is well established that prostaglandins (PGs) exert potent pharmacological actions on vascular and nonvascular smooth muscle, although their effects on the sphincter of Oddi (SO) remain to be elucidated. The aim of this study was to investigate the effect of PGE1 on motility of the human SO. Twenty patients appearing for routine endoscopic retrograde cholangiopancreatography (ERCP) examination were studied. Each patient was randomly allocated to receive an intravenous infusion of normal saline (six patients), or alprostadil alfadex, a synthetic PGE1 analog, at a dose of either 0.05 or 0.1 microg/kg/min (seven patients for each condition). Endoscopic biliary manometry was done with a recording of basal SO pressure, amplitude of SO phasic contractions, and phasic contractile frequency before and 5 min after intravenous infusions, using a 4-French microtransducer catheter. There was no significant change in SO motor variables following application of normal saline. Alprostadil alfadex significantly decreased basal SO pressure at a dose of 0.05 microg/kg/min, and significantly decreased all parameters at a dose of 0.1 microg/kg/min. A synthetic PGE1 analog, alprostadil alfadex, effectively inhibits motility of the human SO. This drug may be of clinical application as a SO-relaxing agent.

The case of a 50-year-old man with abdominal pain and abnormal liver test results is described. Endoscopic retrograde cholangiopancreatography with manometric studies showed biliary dilatation, poor ductal drainage, and sphincter of Oddi dysfunction. Clinical and radiographic clues suggested the possibility of an ampullary lesion; a small ampullary adenoma was detected after endoscopic sphincterotomy, and ampullary carcinoma was found in the operative specimen. Malignancy can cause sphincter dysfunction not only in the esophagus (as pseudoachalasia) but in the ampulla of Vater as well.

Because of reduced health care funding it is becoming necessary for surgeons to take a greater interest in the costs of individual operations. This study reports costs directly measurable to the patient, and also the indirect costs of hospital overheads, an operating suite and teaching, which were 37, 10 and 15%, respectively (62%), of hospital budget. A scheme has been developed which could give surgeons a standard to report direct costs. Pre-admission, ward, operating room, recovery, intensive care and post-admission are defined as cost periods and the modalities of staff, equipment (capital, maintenance and replacement), imaging, laboratory and consumables apply to each. This strategy was applied to assess open cholecystectomy (OC) and laparoscopic cholecystectomy (LC) as an example. The direct costs for OC were $3706 and LC $2868, a difference of $838; the indirect and direct costs were OC $6004 and LC $4646, a difference of $1358. Thus indirect cost magnified the difference between the operations. Bed stay, density of nursing and use of disposable instruments were the major influence on direct costs. The individual cost advantage of a shorter bed stay may be countervailed by an increased hospital activity. The main patient benefit of new operations may be improved quality of life and more rapid return to work with prevention of salary losses. A method has been developed to define costs of a particular surgical operation with the purpose of stimulating surgeons' interest in this topic and developing a common style of reporting.(ABSTRACT TRUNCATED AT 250 WORDS)

Several calcium-channel blockers currently in use for the treatment of cardiovascular disorders have recently been tested for their effects on gastrointestinal motility. The rationale for this approach centers on the concept that calcium-channel blockers are at least as potent in inhibiting intestinal smooth muscle as in relaxing vascular smooth muscle. This review will give an outline of the most recent findings on the role of calcium and calcium channels in smooth muscle and neuronal function in the digestive system. It will also consider the mechanisms by which calcium-channel blockers may affect gastrointestinal motility and assess potential clinical applications in gastroenterology. The main goal for researchers in this field will be the development of gut-selective agents, with no cardiovascular side effects.