Morphological variants of the biliary tree such as periampullary diverticula or papillary stenoses were shown to predispose to a recurrence of gallstones 
. To further study the role of the abnormal biliary course in development of gallstones, we identified and further analysed a subgroup of patients presenting with oblique CBD. In our setting, this variant was found in almost 8% of patients. However, these data were obtained in a tertiary care medical centre and further studies are needed to determine the frequency of OCBD in the general population.
Our findings suggest that OCBD may represent an acquired condition. In support of that, OCBD was observed in older patients and was preferentially seen in subjects who previously underwent a cholecystectomy and/or another intervention on the biliary tree. The fact that OCBD patients more often required an open cholecystectomy further supports the hypothesis of an underlying structural bile duct abnormality. However, OCBD does not seem to be a simple consequence of aging, given that no change in the angle α was seen in a subset of patients undergoing consecutive ERCPs. Therefore, further studies are needed to clarify the etiology (i.e., inherited versus acquired) of OCBD and to find out, what additional hits may contribute to development of clinically apparent condition in these subjects.
We also analysed the consequences of OCBD. Our data indicate that it is associated with (i) development of chronic cholestasis and (ii) chronic pancreatitis; (iii) more severe acute cholangitis; (iv) more difficult gallstone removal and with (v) recurrent gallstone formation. The most likely explanation of these findings is that OCBD subjects experience an impaired bile flow, which represents an established risk factor not only for gallstone development but also for the development of chronic pancreatitis 
. This is further supported by the finding that OCBD subjects had a dilated CBD and the CBD dilation was even more pronounced in patients with severe OCBD. To that end, a dilated CBD represents an established risk factor for gallstone recurrence 
. However, one has to keep in mind that some of the observations may be in part due to the significant age difference between the control and study group. Future studies are needed to overcome this limitation.
A reduced bile flow might be due to a compromised motility of the biliary tract or due to a biliary obstruction. Given that CBD does not significantly contribute to biliary motility, further studies should analyse whether OCBD associates with gallbladder and/or sphincter of Oddi dysfunction, which represent the major reasons for biliary dysmotility 
. With respect to biliary obstruction, although patients with biliary stenosis were not included in our analysis, we cannot exclude a presence of transient/functional stenosis, which might have escaped the detection in ERCP. In any case, the horizontal portion of the CBD seems to be of functional relevance, given that gallstones were typically found in this section (not shown).
The observation that OCBD subjects require multiple ERCPs is of particular clinical relevance. First of all, OCBD subjects need more ERCPs to completely remove all stones, a finding which is likely due to a challenging biliary morphology. In addition to that, “late ERCPs” were more frequent in the OCBD subjects and their frequency was significantly above the data reported in the literature 
. Moreover, several patients required multiple ERCPs during the follow-up. Therefore, a regular surveillance of OCBD patients might be reasonable, especially if they display additional risk factors for stone recurrence such as a dilated bile duct 
. In this respect, patients with multiple bile stone recurrences were previously suggested to benefit from annual ERCPs 
. While a regular screening might be helpful, it remains unclear what might be the best treatment option for OCBD patients with recurrent stones. Given the associated biliary dysmorphism, a surgical treatment might be an option. Choledochojejunostomy was already suggested as a treatment option for recurrent common bile duct stones in previous studies 
. Indeed, five of our OCBD patients with a history of more than five ERCPs underwent a resection of the oblique CBD. A biliodigestive anastomosis with a Roux-en-Y reconstruction and a long loop was performed. These patients were followed up at least one year after surgery and had neither biliary symptoms nor problems due to the surgical treatment. However, one has to keep in mind that the presence of OCBD does not inevitably lead to an incurable disease but merely represents a risk factor for an adverse disease outcome. Only a careful follow-up will tell whether an OCBD patient requires a surgical treatment or whether the OCBD can be managed in a nonsurgical manner.
In summary, OCBD defines a new entity of bile duct abnormality, which is associated with chronic cholestasis, hampers an efficient stone removal and predisposes to recurrence of bile duct stones. Further studies are needed to clarify the pathogenesis of this syndrome and possible treatment strategies. To accurately determine the angle α, these trials should include a magnetic resonance imaging of the bile ducts with a precise three-dimensional reconstruction. Thereby, these studies will enable us to define a cut-off value for angle α which is associated with significant clinical outcomes.