Sphincter of Oddi Dysfunction: beware danger…

Sphincter of Oddi Dysfunction

Sphincter of Oddi dysfunction (SOD) is the name of a syndrome associating more or less completely biliary or pancreatic pain, disturbance of the liver balance sheet, dilation of the bile duct and corresponding on the motor level to an anomaly comprising at least minimum basal sphincter of Oddi hyperpressure measured by manometry. DSO terminology should replace other inappropriate names such as odditis, biliary dyskinesia, oddian stenosis… DSO is generally diagnosed following a cholecystectomy . Post-cholecystectomy pain is observed in 10 to 20% of operated patients, corresponding in 10 to 50% of cases to OSD according to the diagnostic criterion used. It should be emphasized that the prevalence of oddi dyskinesia is not zero before cholecystectomy in patients with cholelithiasis. It has been estimated at 4% of patients without dilatation of the bile duct or disturbance of hepatic biological tests and at 40% in those with elevated alkaline phosphatase.

The pathophysiology of Oddian dysfunction is complex.Direct sphincter damage by fibrosis is observed in more than half of the cases. Pure motor disorders could be explained by denervation for which liver transplantation practically constitutes an experimental model. This denervation would lead to a breakdown of the non-adrenergic, non-cholinergic inhibitory control of the basal tone of the sphincter of Oddi. This control involves a cascade of neuromediators at CCK, VIP and also NO. Free CCK could then directly excite the muscle fibers of the oddian muscle, explaining the paradoxical response to CCK observed during post-cholecystectomy manometries. Two recent studies have shown the absence of involvement of possible bile microcrystals in the pathogenesis of OSD.

Onset of Sphincter of Oddi Dysfunction

The time to onset between painful crises and cholecystectomy is very variable, ranging from a few months to several years, even more than 20 years.Crises are favored by the intake of codeine or derivatives, found in analgesic or antitussive drugs mainly or by fatty meals, the cholecystokinin released causing a paradoxical contraction of the sphincter of Oddi. Seizures can occur completely unexpectedly, with no triggering factor, with sometimes very violent pain that completely inhibits inspiration. After several months of evolution, the patient develops an apprehension of seizures that ends up being as disabling as the seizures themselves in everyday life. The main differential diagnoses are the existence of a residual lithiasis of the common bile duct, an ampulloma observed in 5% of patients, which requires the systematic performance of a biliary echoendoscopy or, failing that, a biliary-MRI before retaining the diagnosis of OSD. Post-cholecystectomy gastric or duodenojejunal motility disorders, whether or not associated with OSD, have been demonstrated with frequent phase II and III abnormalities of the migrating motor complexes. In some cases, these duodenojejunal motor abnormalities appeared to exist before cholecystectomy. Duodenal sensitivity disorders have recently been demonstrated by barostat in patients who presented with post-cholecystectomy oddi dysfunction.

Oddian dysfunction could also be a cause of  recurrent acute pancreatitis in both adults and children. Moderate hyperamylasemia or hyperlipasemia are frequently associated with painful attacks of OSD. However, no case of  severe acute pancreatitis has been reported in the literature, the manifestations being essentially painful and biological without radiological translation. Hyperpressure on the pancreatic side is seen in one-third to two-thirds of patients with elevated basal odeon pressure. Two-thirds of patients with Sphincter of Oddi dysfunction may have abnormal pancreatic sphincter pressure.

In the presence of post-cholecystectomy biliary-like pain, and after elimination of residual lithiasis or ampullary obstruction, the possibility of having real Oddian dysfunction can be reasonably assessed using  the Milwaukee classification. This includes 4 criteria:

a) biliary pain;

b) elevation of SGOT or alkaline phosphatase to more than twice normal;

c) delay in evacuation of the contrast product after retrograde cholangiography for more than 45 min;

d) diameter of the bile duct greater than 12 mm.

The most restrictive criterion is the delay in evacuation of the contrast product because it induces the morbidity of retrograde cholangiography, but it can advantageously be replaced by the isotopic transit time obtained by scintigraphy. Oddian dysfunction is present in 86% of type I (criteria a+b+c+d), in 55% of type II (a+ (b or c or d)) and 28% of type III (a alone).

REad: The Four Stages of Dysphagia

Diagnosis

The main diagnostic argument for Oddian dysfunction is given by biliary manometry. The main criterion used is that of an increase in basal odeon pressure above 40 mm Hg, but accessory criteria may be considered, such as tachycardia (more than 8 phasic contractions / min) or an abnormal frequency of retrograde propagation of contractions phasics. Given the difficulty of performing this gesture and especially the significant risk of  pancreatitis acute post-manometry (6 to 11%), biliary scintigraphy, a completely harmless method, has been developed. It requires IV injection of a derivative of di-imino acetic acid labeled with Tc 99 with recording by gamma camera for 60 min. The most reliable criterion is the measurement of the isotopic transit time between the hilum and the duodenum, which should not exceed 10 min. TTHD is the best correlated with HB and its elongation is considered by some teams as a diagnostic criterion equivalent to that of biliary manometry. However, this fact is not fully supported by the literature, even if biliary scintigraphy is based on recent international standards. Thereby, a recent American study disputed the diagnostic value of TTHD prolongation, but the manometric criteria were not sufficiently restrictive, including abnormalities in phasic contractions or their propagation, which were not validated to establish the diagnosis of OSD. Obviously, this study highlighted a lack of sensitivity of the biliary scintigraphy, the diagnosis of DSO having been carried by excess by the biliary manometry. This is not the case with Cicala’s work et al. which, in addition to a good correlation between the two methods (r = 0.77), show a frequency of OSD consistent with the values ​​established in the literature by biliary manometry (80 to 100% in the case of type I and close to 50% in type II cases). Abnormalities were more frequent in group II for biliary scintigraphy than for biliary manometry (64% vs 36%), suggesting either a greater sensitivity of the scintigraphy or the existence of false positives. Scintigraphic follow-up of patients not treated with SE confirmed good reproducibility of this diagnostic test, with TTHD values ​​remaining unchanged after one year of follow-up. Biliary scintigraphy with measurement of TTHD is therefore a good examination, despite some discrepancies in the literature on the too low sensitivity according to some, or a lack of specificity according to others. It allows a non-invasive approach with sufficient reliability.

In practice, patients are classified according to the Milwaukee classification without taking into account diagnostic cholangiography, the potential risk of which in this indication excludes it from diagnostic means. This makes it possible to globally assess the probability of OSD in the patient. Then, a confirmatory test is performed either by biliary manometry or by biliary scintigraphy. The choice between these two techniques depends on the morbidity accepted by the patient or the clinician, on their availability. Scintigraphy has the advantage of being totally harmless and of easily allowing dynamic or provocation tests to be carried out. Some, however, consider that its diagnostic performance is insufficiently established compared to manometry.

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Treatment for Sphincter of Oddi dysfunction

Medical treatment for Oddi dysfunction proves disappointing although nitrate derivatives or calcium channel blockers have shown in some publications a decrease in basal odeon pressure [23-25]. Nitrates could replace the activity of NO-donating neurons of the non-adrenergic, non-cholinergic axis. Clinical trials evaluating the effect of nifedipine on abdominal pain have been published. The improvement in pain is observed in 75% of cases in two studies, one of which is controlled. Trimebutine and erythromycin seem to modify oddian motricity but their clinical efficacy has not yet been demonstrated. Somatostatin also modifies sphincter activity but in the direction of an increase in the frequency of phasic contractions or the basal odeon pressure. Somatostatin would therefore have no interest in this indication or even as a preventive measure after endoscopic retrograde cholangio-pancreatography. Intra Sphincter injection of botulinum toxin has been tested in humans and in pigs. Botulinum toxin A causes a significant decrease in basal pressure in 50% of cases. Clinically, intrasphincteric injection of botulinum toxin led to an improvement in 55% of patients who suffered from post-cholecystectomy biliary pain without disturbance of liver function tests or dilation of the bile duct. However, 90% of patients who had improved presented a recurrence of symptoms within 6 months. The effect of the toxin is therefore inconstant and transitory.

Endoscopic treatment

Endoscopic treatment by endoscopic sphincterotomy is an effective technique in cases of proven DSO but with heavy morbidity. Predictive criteria of efficacy must therefore be sought. Oddi dysfunction is present in 86% of type I (criteria a+b+c+d), in 55% of type II (a+ (b or c or d)) and 28% of type III (a alone). It has been demonstrated that the therapeutic response to biliary sphincterotomy depends on belonging to this type of classification, with the best responses being observed for type I, then for type II and finally for type III. It seems that the appearance of an anomaly in the liver function immediately following the painful crises is a predictive factor of the response to sphincterotomy, whereas the dilation of the bile duct is not one. A controlled study showed that the response to sphincterotomy did not differ from that of placebo in patients who had no elevated basal odds pressure; it resulted in an improvement in 91% of cases in the event of elevation of the basal odeon pressure. Thus, many patients who belong to type II but especially to type III of the Milwaukee classification actually suffer not from Oddian dysfunction but from sensory or duodenal motricity disorders. The success of biliary endoscopic sphincterotomy in proven OSD was confirmed in a second recent randomized study [35]. The improvement after biliary sphincterotomy was significant (85% vs 38%) only in the group of patients who had basal odeon hypertension but not in the group of patients who presented with biliary dyskinesia or normal manometry. The contribution of biliary scintigraphy seems to predict with good efficiency the clinical success of endoscopic biliary sphincterotomy in types I and II of the Milwaukee classification. The results of long-term endoscopic biliary sphincterotomy are maintained with a 3–5 year follow-up in 60–68% of type II and 8–56% of type III. Classification of the patient according to the type of oddi dysfunction and the establishment of either a measurement of the basal odeon pressure, or its approach by biliary scintigraphy are essential when we know that the risk of complication of endoscopic biliary sphincterotomy in the event of Oddian dysfunction is three times higher than that of the reference population, this risk being significant in the majority of multivariate studies. 

Endoscopic biliary sphincterotomy in case of sphincter of Oddi dysfunction is associated in the literature with a risk close to 25% and an odds ratio close to 5. The placement of a pancreatic prosthesis could reduce the morbidity of biliary endoscopic sphincterotomy, by reducing the risk of this risk being significant in the majority of multivariate studies [39, 40]. Endoscopic biliary sphincterotomy in case of sphincter of Oddi dysfunction is associated in the literature with a risk close to 25% and an odds ratio close to 5. The placement of a pancreatic prosthesis could reduce the morbidity of biliary endoscopic sphincterotomy, by reducing the risk of this risk being significant in the majority of multivariate studies. Endoscopic biliary sphincterotomy in case of sphincter of Oddi dysfunction is associated in the literature with a risk close to 25% and an odds ratio close to 5. The placement of a pancreatic prosthesis could reduce the morbidity of biliary endoscopic sphincterotomy, by reducing the risk of acute pancreatitis  from 27 to 6% in a controlled study. The main thing is anyway to avoid repeated and unsuccessful endoscopic maneuvers to selectively cannulate the bile duct. There is therefore still plenty of room to find a prophylactic medical treatment likely to reduce the risk of acute post-catheterization pancreatitis.

Failure of endoscopic treatment should raise several questions.

The first question must be to question the diagnosis of Oddian dysfunction, especially since it is a type III dysfunction where the actual frequency of Oddian hypertonia does not exceed a quarter of cases. It is then very often a question of disorders of motricity or duodenal sensitivity. The management of such disorders is similar to that of functional digestive disorders in general.

The second possibility is that of an undiagnosed pancreatic condition such as  chronic pancreatitis  or the persistence of hypertonia of the pancreatic sphincter, requiring additional endoscopic or surgical therapy.

The third possibility is the existence of a vaterian tumor, the frequency of which should not be underestimated. Repeated intrapapillary biopsies can confirm diagnosis.

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