Sphincter of Oddi Disorders

Postcholecystectomy Pain

FBSD is commonly considered in the 10% to 20% of patients who have persistent or recurrent pains after cholecystectomy. Loss of the gall bladder reservoir aggravates the increase in intrabiliary pressure when the sphincter is closed. There is also evidence that sphincter dynamics are altered after cholecystectomy. Animal studies have shown a cholecysto-sphincteric reflex with distention of the gallbladder that results in sphincter relaxation. Interruption of this reflex could affect sphincter behavior by an altered response to cholecystokinin (CCK), or because the loss of innervation unmasks the direct contractile effects of CCK on smooth muscle. Abnormalities in both basal pressure and responsiveness to CCK have also been described in humans.

The simple concept that the pain in these patients is wholly or partly due to increased ductal pressure is now under challenge. Another explanation stems from the concept of nociceptive sensitization. Significant tissue inflammation such as cholecystitis will activate nociceptive neurons acutely and, if it persists, also result in sensitization, and the gain in the entire pain pathway is increased. In most patients with gallbladder disease, cholecystectomy removes the ongoing stimulus and the system reverts back to its normal state. However, in a subset of patients, the “gain” stays at a high level. In such patients, even minor increases in biliary pressure within the physiological range can trigger nociceptive activity and the sensation of pain, a concept called allodynia .

A relevant related phenomenon is cross-sensitization. Many viscera share sensory innervation, and it is difficult to distinguish pain originating in one organ from that in another. Persistent sensitization in one organ can lead to sensitization of the nociceptive pathway from an adjacent organ. Thus, an entire region can be sensitized with innocous stimuli (such as duodenal contraction after a meal) leading to pain that was indistinguishable from that associated with the initial insult. Evidence for this was provided by an important study in which patients with postcholecystectomy pain were found to have duodenal, but not rectal, hyperalgesia. A strong case can be made for nociceptive sensitization to be the principal cause of pain in these patients. Motor phenomena such as sphincter hypertension may still be relevant, but more as a marker for the syndrome rather than the cause.

There are many reasons why patients may have pains after cholecystectomy. The first task is to exclude organic causes. Possibilities include early postoperative complications (such as a bile leak or duct stricture), retained stones or partial gallbladder, other intraabdominal disorders such as pancreatitis, fatty liver disease, peptic ulceration, functional dyspepsia and irritable bowel syndrome, musculoskeletal disorders, and other rare conditions. Nonbiliary findings are more likely when the symptoms are atypical and long-standing, similar to those suffered preoperatively and without a period of relief postoperatively, and when the removed gallbladder did not contain stones. The concept and management of “functional gallbladder disorder” is equally controversial.

Whether the pain appears to be “biliary” is a crucial clinical question because it focuses the approach to diagnosis and treatment. The Rome process has provided a consensus definition of biliary pain, which is unchanged in the IVth iteration( Box 56.1 ). It must be said that few, if any, of the stated criteria are sufficiently based on evidence, and more data would be helpful.

Initial Investigation

When the pain appears to be biliary, and is sufficiently troublesome to warrant investigation, initial testing should include liver and pancreatic enzymes (preferably taken shortly after a pain episode) and transabdominal ultrasound, supplemented with computed tomography (CT) scan or magnetic resonance cholangiopancreatography (MRCP). The goal of imaging is to rule out other pancreatic and biliary pathology and to determine the size of the bile duct. Equivocal findings are best evaluated further by endoscopic ultrasound (EUS). Upper endoscopy is usually performed to rule out mucosal diseases, especially if the pains are meal-related.

How to proceed further will depend on the findings of these initial tests. In the past, patients have been classified into 3 categories.

• Type I: dilated bile duct and elevated liver enzymes

• Type II: dilated duct or elevated liver enzymes, but not both

• Type III: no abnormalities

Rome IV concluded that this classification is now outdated and should be abandoned. Patients with both dilated ducts and elevated liver enzymes have an organic problem (sphincter fibrosis or microlithiasis) rather than functional pathology, and they benefit from biliary sphincterotomy. Thus the term sphincter of Oddi (SOD) I is no longer appropriate; we prefer sphincter of Oddi stenosis. Equally, the term SOD III should be abandoned. The 2014 randomized sham-controlled effect of endoscopic sphincterotomy for suspected sphincter of Oddi dysfunction on pain-related disability following cholecystectomy (EPISOD) trial showed that those patients do not have sphincter dysfunction because the results of sphincterotomy were no better than sham ( Table 56.1 ). The conclusions remained valid in the 99 subjects who were followed for 3 years. Contrary to widespread clinical belief, the EPISOD patients (even those who also had irritable bowel syndrome) had psychosocial profiles no different from population norms. We recognize that these patients are often seriously disabled with pain, but the trial strongly suggests exploring other causes, and less dangerous methods of management.

With SOD types I and III eliminated as functional sphincter disorders we are left only with patients with postcholecystectomy pain and some objective findings (the prior SOD type II, now called suspected functional biliary sphincter disorder ).

Our main task now is to guide these patients and their advisors through the clinical minefield into optimal management. Additional methodologically rigorous studies are needed to better define the characteristics of patients who may benefit from intervention.

Clinical Predictors of Biliary Sphincter Hypertension

Faced with a symptomatic patient with some evidence for biliary obstruction (a dilated bile duct or elevated liver enzymes) and no other determined cause, the clinician will need to assess the likelihood that the sphincter is the culprit, and that sphincterotomy may be helpful. What are those predictors? Even for bile duct size and liver enzymes, there are devils in the details. To start with, the definition of a dilated duct is arbitrary. It is widely believed that the bile duct enlarges normally after cholecystectomy, and radiologists often report “dilation consistent with prior cholecystectomy.” However, many careful studies have shown no change, and others only a slight increase. There is a gradual increase with age. Regular narcotic use can cause biliary dilation, although usually associated with normal liver enzymes. The main reason why the average size of the duct is bigger after cholecystectomy than the usual norm of 6 to 7 mm is because some of the patients had duct disease at the time of surgery. The original Milwaukee classification of SOD proposed 12 mm as the acceptable upper limit, which seems high; the Rome III panel used 8 mm. The EPISOD study used 9 mm. It would seem likely that a bile duct that is known to have dilated considerably since surgery would be a good sign of obstruction, but that has not been studied. In clinical practice, it is unusual to have access to perioperative imaging to make that assessment in an individual case.

Similar questions arise when considering elevated liver enzymes. Which ones, how high, how often, and when? The standard criteria state that transaminases should be more than twice normal on at least two occasions, and normalize between pain attacks. None of these are firmly evidence-based. Furthermore, as clinicians dealing with many of these patients, we know that these data elements are not always available. Patients are sometimes asked to obtain liver tests shortly after a pain episode, but the evidence that peaking transaminases predict the outcome of sphincterotomy is limited. It is important to remember that elevation of transaminases above the usually accepted normal limits is common in the US population.

There are few data on predictors other than duct size and enzymes. Freeman et al (2007) showed that delayed gastric emptying, daily opioid use, and age less than 40 predicted a poor outcome. They also showed no difference in outcomes between patients classified as SOD types I, II, and III. It has also been reported that patients are more likely to respond if their pain was not continuous, if it was accompanied by nausea and vomiting, and if there had been a pain free interval of at least 1 year after cholecystectomy.

Further research is needed to establish more precisely which clinical features and investigations can best identify those who are likely to respond (or not) to sphincter ablation. Among other possible predictors that have not been investigated fully are: the reason for the cholecystectomy (stones or “gall bladder dyskinesia,” another controversial diagnosis), the response to surgery, the presence of other digestive, functional or psychiatric problems, and details about the pain (classical “biliary” or not, its severity and frequency, whether it is the same as before surgery, and whether it subsided for a while). A survey of 164 members of the American Society of Gastrointestinal Endoscopy (ASGE) showed little consensus about predictors other than duct size and enzyme elevations.

Further Investigation for Suspected FBSD

Further investigation is warranted if there are objective pointers to biliary obstruction, if organic disease has been ruled out as far as possible, and if symptoms are severe enough to move on when simple dietary advice and medications (e.g., antispasmodics) have not been helpful.

We recommend more widespread use of EUS in patients with only a dilated duct. It is the best method to detect and exclude relevant organic causes of pain, especially small stones, tumors and pancreatitis.

Several noninvasive techniques have been developed to assess the drainage dynamics of the bile duct. A major problem with assessing their value is the lack of a gold standard. Manometry was previously believed to be an accurate measure of sphincter function, but the gold is increasingly looking tarnished, as discussed later. One could argue that the only proof that the sphincter is (or was) the cause of the pain is if patients are satisfied by the results of sphincter ablation, albeit recognizing the strong placebo effect of ERCP intervention. There are very few studies with such objective assessments and only small randomized trials. Thus, our comments on the value of these various tests are not based on solid evidence.