Current status of the biliary tract malformation

Abstract

The choledochal cyst (CC) can be better termed as biliary tract malformation because of the close association of embryology and etiology in the causation of CC. Contrary to Babbitt's postulation of reflux, damage and dilatation, reflux was not demonstrable as the causative factor in all varieties of CC. High pressure in the biliary system, otherwise termed ductal hypertension, is put forth as an alternative to explain the evolution of CC. The forme fruste type, which does not find a place in the standard classification, typifies the ductal hypertension hypothesis. Hence a closer, in-depth review would be able to highlight this apt terminology of biliary tract malformation.

Core Tip: The biliary tract malformation has undergone a metamorphosis from its previous nomenclature of choledochal cyst owing to a variety of reasons. The etiology, embryopathology and the current classification require revisiting due to the same. The review looks at the same in detail.

INTRODUCTION

Choledochal cyst (CC) accounts for 1/1000 to 1/150000 live births, with high incidence in Asia, especially Japan. The majority (80%) would present by ten years of age. Less than 1% of the benign biliary tract disorders are due to CC, accounting for the relative rarity in adults. Being a disease of children, CC shares a closer link with embryo pathogenesis[1,2].

The classification of CC into various types considers the dilatation/segment of the biliary tract involved. This may have an etio-pathological association. The old school of thought (Babbitt) is subject to debate as the postulation does not satisfactorily explain the different types of CC. Hence a review of embryology is in order to understand the drift to the current thinking[1,2].

THE OLD THINKING

The traditional concept referred to inflammation as the initiating factor, leading to damage and dilatation. Based on contrast reflux into the pancreatic duct during intraoperative cholangiography, Babbitt suggested that pancreatic enzyme backflow into the bile duct initiates inflammatory damage to the bile duct resulting in progressive dilatation with CC formation. According to this pancreatic reflux-induced etiology, Amylase levels may need to be elevated to justify the presence of reflux[3]. But the cyst Amylase level measurements do not universally show an increase. Rather, what is known, is an inverse co-relation of the CC size with the cyst pressure[4]. Hence, an increase in the intraluminal pressure arising from distal bile duct obstruction was shown as the offending factor in the causation of CC. Relative stenosis of the distal bile duct could be the primary factor which can cause elevation of pressure with resultant intraductal hypertension[5]. Not only does this go against traditional thinking but it also sets up the stage for reconsideration of etiology (Figure 1).

Figure 1.

The traditional Babbitt’s reflux hypothesis and the recent ductal hypertension hypothesis.

NEED FOR RECONSIDERATION

The ductal plate malformation is the embryological basis of Caroli’s disease. At the time of bile duct formation, initial thin plates (single layer) of bile duct around the portal vein get reinforced (double layer), resulting in robust bile ductules after extensive resorption. In case of failure to complete resorption with partial/incomplete retention of the primitive ductal plate can lead to large dilated segments. When this occurs at the level of the segmental ducts or intermediate-size ducts, the resultant insult can be either Caroli’s disease or Caroli’s syndrome, respectively[6].

A different mechanism must be highlighted at this juncture for the evolution of the CC types I/II/IV. The pancreatic duct and common bile duct join together to form a common channel, which is sandwiched between the sphincter of Oddi (entry into D2) and the sphincters of choledochus and pancreaticus. Thus the common channel is usually a short length of ‘uneventful’ passage. Trouble brews when the common channel lengthens for various embryological factors, as the anomalous junction of the biliary and pancreatic with abnormal sphincters lets loose the tight compartmentalization of fluid travel, resulting in reflux of pancreatic contents across into the bile duct. The stage is now set for reflux, inflammation and damage. Thus the presence of a long common channel would lead to a vicious cycle of stasis and dilatation, ultimately evolving into a CC. Should an anomalous proliferation of the biliary epithelium occur during fetal life, this common channel will become longer than the length of the sphincter (which remains constant) with the accompaniment of reflux[7].

ODDITIES FROM THE PREVIOUS CLASSIFICATION

Choledochocele or Type III CC stands apart from the other counterparts due to a different mechanism of pathophysiology. It appears to be a misfit in the Biliary Tract malformation group due to its behaviour and presentation. It has the lowest incidence of malignancy and is associated with divisum pancreas rather than abnormal pancreato biliary malunion, unlike the rest of the Biliary Tract malformations[8,9].

In addition, Caroli’s disease, in view of its familial association and link to hepatic fibrosis, is possibly a separate and different type from the rest of the biliary tract malformation and it may have to stand out as a different entity. Of note embryologically is its relation to ductal plate malformation which pursues another recognizably different pathway[10].

CURRENT UNDERSTANDING

The hallmark of CC, namely gross biliary ductal dilatation, can sometimes not be present but may have clinically significant pain abdomen, as identified in a unique subtype of CC, namely the ‘forme fruste’ type of CC. The presence of marginal dilatation or absent dilatation of the extrahepatic bile duct with malunion of the pancreato-biliary junction is referred to as the ‘forme fruste’ type of CC. The striking relief of symptoms (pain abdomen) post -operatively, after the bile duct is separated from the pancreatic duct during surgical reconstruction (excision of bile duct and roux en y hepatico-jejunostomy) has firmly established the association of ductal hypertension in this subtype[11]. A combination of long common channel with a minimal dilated common bile duct (< 10 mm) noted on an intra-op cholangiogram or Endoscopic Retrograde Cholangio Pancreatography helps in the identification of this condition[12].

Hamada et al[13] considered the dilatation of bile duct by grouping them into two categories, one with biliary dilatation in combination with abnormal pancreato-biliary junction (congenital biliary dilatation or CC) and the other with only abnormal pancreato-biliary junction.

The elaboration of abnormal pancreato-biliary junction or pancreato-biliary malunion is out of scope as it deserves an in-depth and focussed review.

REVISIT CLASSIFICATION?

Todani’s classification of CC dates back to 1977, which attempts to put together the various types as per the understanding of the causation of CC relevant at that point in time. Over a period of time, newer studies have changed the understanding of the etiology of CC, prompting a relook into the traditional classification. Not only the surgical treatment but also the malignancy risk is different among the CC types suggesting a newer regrouping logically agreeable to the etiology as well[14]. A simpler Kings’ college classification which is a management-based classification has been proposed as an alternative[15,16]. But none are widely adopted in current clinical practice.

MORE FOR THE FUTURE-MOLECULAR MECHANISMS

Varied etiology owing to molecular mechanisms has been put forth recently. Analysis of the molecular characteristics has shown that the cystic and fusiform types of CC have different molecular mechanisms of pathogenesis[17]. A higher rate of harmful alleles in genes involved in soft tissue disorders and conditions related to tissue overgrowth may be linked to the formation of the stenotic distal bile duct, ultimately resulting in proximal dilatation and CC[18]. Further studies are required to characterise in detail the genetic polymorphisms involved in the pathogenesis of CC.

CONCLUSION

CC appears to be a misnomer and biliary tract malformation, the current terminology is apt and justifiably in line with the evolving etiopathology. In continuum, the same logic is applicable to the Alonso Lej classification of CC as well, which needs to give way to a system of modified sorting of the various types of Biliary Tract malformation.