Effect of the extrahepatic bile duct anatomy on choledocholithiasis and its clinical significance

Abstract

BACKGROUND

A comprehensive understanding of the extrahepatic bile duct anatomy is vital to guide surgical procedures and perform endoscopic retrograde cholangiography. Anatomical irregularities within the extrahepatic bile duct may increase susceptibility to bile duct stones.

AIM

To investigate the anatomical risk factors associated with extrahepatic bile ducts in patients diagnosed with choledocholithiasis, with a specific focus on preventing stone recurrence after surgical intervention and endoscopic lithotomy.

METHODS

We retrospectively analyzed the medical records of 124 patients without choledocholithiasis and 108 with confirmed choledocholithiasis who underwent magnetic resonance cholangiopancreatography examinations at our center between January 2022 and October 2022. Logistic regression analyses were conducted to identify the anatomical risk factors influencing the incidence of common bile duct stones.

RESULTS

Multivariate logistic regression analysis revealed that several factors independently contributed to choledocholithiasis risk. Significant independent risk factors for choledocholithiasis were diameter of the common hepatic [adjusted odds ratio (aOR) = 1.43, 95% confidence interval (CI): 1.07-1.92, adjusted P value = 0.016] and common bile (aOR = 1.68, 95%CI: 1.27-2.23, adjusted P value < 0.001) ducts, length of the common hepatic duct (aOR = 0.92, 95%CI: 0.84-0.99, adjusted P value = 0.034), and angle of the common bile duct (aOR = 0.92, 95%CI: 0.89–0.95, adjusted P value < 0.001).

CONCLUSION

The anatomical features of the extrahepatic bile duct were directly associated with choledocholithiasis risk. Key risk factors include an enlarged diameter of the common hepatic and bile ducts, a shorter length of the common hepatic duct, and a reduced angle of the common bile duct.

Key Words: Bile ducts, Extrahepatic, Choledocholithiasis, Cholangiopancreatography, Magnetic resonance, Cholangiopancreatography, Endoscopic retrograde

Core Tip: Comprehensive understanding of the extrahepatic bile duct anatomy is imperative to guide surgical procedures and perform endoscopic retrograde cholangiography. This study aimed to investigate the anatomical risk factors associated with the extrahepatic bile ducts in patients diagnosed with choledocholithiasis, specifically focusing on preventing stone recurrence after surgical intervention and endoscopic lithotomy. Several independent risk factors for choledocholithiasis were identified in our retrospective analysis of medical records. Noteworthy factors include an enlarged diameter of the common hepatic and bile ducts, a shorter length of the common hepatic duct, and a reduced angle of the common bile duct. Our findings underscore the significance of these anatomical features in the incidence of common bile duct stones. Our findings provide valuable insights into the relationship between extrahepatic bile duct anatomy and choledocholithiasis risk.

INTRODUCTION

Cholelithiasis frequently leads to biliary and pancreatic complication-related hospitalizations, with approximately 622000 individuals hospitalized annually in the United States, and approximately 15% of cases are attributed to choledocholithiasis[1,2]. Despite the identification of the various risk factors associated with gallstones, the precise mechanisms underlying their formation remain poorly understood. Significant risk factors, often referred to as the “5 Fs” (Forty years of age, Female, Fatty, Fair, and Fertile), are recognized contributors. Independent studies have implicated type 2 diabetes as an additional risk factor for gallstones[3]. A study by Chen et al[4] further supported this perspective, proposing that lower total cholesterol levels may independently contribute to gallstone formation[3-5]. Furthermore, evidence suggests that abnormalities in the extrahepatic bile duct anatomy may increase the susceptibility to gallstones. A study by Choi et al[6] demonstrated that low cystic duct insertion and the angle of the common bile duct are independent risk factors for the recurrence of common bile duct stones. Similarly, Ji et al[7,8] found that the recurrence rate was the highest in the S-type common bile duct morphology, followed by the polyline and straight-line types.

Anatomically, the extrahepatic bile duct includes the left and right hepatic ducts, common hepatic and bile ducts, gallbladder, and cystic duct[9]. Contributors to the risk of choledocholithiasis recurrence include specific anatomical factors of the extrahepatic bile duct, including the shape and insertion mode of the cystic duct, as well as the diameter, angle, and shape of the common bile duct[6,7,10,11].

Both endoscopic ultrasonography (EUS) and magnetic resonance cholangiopancreatography (MRCP) serve as effective diagnostic methods for choledocholithiasis. Although EUS and MRCP exhibit higher specificity, EUS is notable for its increased sensitivity in the diagnosis of choledocholithiasis[12].

However, because proficiency in EUS may not be universal among endoscopists and MRCP has good sensitivity and is noninvasive for suspected biliary tract lesions[13,14], MRCP remains the primary method for clinically diagnosing choledocholithiasis owing to its ability to accurately visualize the bile duct anatomy.

This study aimed to assess the extrahepatic bile duct anatomy through MRCP examinations in patients with suspected choledocholithiasis. Additionally, we sought to explore the relationship between various anatomical characteristics of the extrahepatic bile duct and choledocholithiasis risk. The insights reported in this study are expected to provide valuable guidance for preventing stone recurrence after surgical and endoscopic lithotomy.

MATERIALS AND METHODS

Patients and study design

We collected MRCP data from individuals aged ≥ 18 years hospitalized with suspected choledocholithiasis at our medical center between January 2022 and October 2022. Exclusions were made for patients with chronic liver disease, abnormal liver function tests associated with chronic liver conditions or hemolytic anemia, known hepatobiliary diseases (e.g., choledochal stricture, malignant tumor, or cholecystectomy), suboptimal MRCP imaging, history of biliary surgery, hepatectomy, congenital biliary system abnormalities (such as choledochal cysts), and pregnant women.

Patient records provided information on the following: Demographic details: Age, sex, body mass index (BMI), and history of hypertension, diabetes, and hyperlipidemia; laboratory tests: Alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), γ-glutamyl transferase (GGT), direct bilirubin (DBil), and indirect bilirubin (IBil); MRCP assessment: Anatomical evaluation of the extrahepatic bile duct; and measurement of the length and diameter of the common hepatic, bile, and cystic ducts. Connections between the cystic and bile ducts were noted and divided into anterior, posterior, medial, and lateral sections, whereas those between the left and right hepatic ducts and the common hepatic duct to the ampulla were categorized into upper, middle, and lower segments (Figure 1). The cystic duct route was classified as linear, curved, spiral, or complex (Figure 2). The morphology of the common bile duct, from the connection between the left and right hepatic ducts to the distal common bile duct duodenum, was considered polyline or S type[7] (Figure 3). Additionally, the oblique angle of the common bile duct (i.e., the angle formed between the first bend of the common bile duct and the horizontal line) was recorded[11] (Figure 4). Angulation of the common bile duct (i.e., the first angle between the common bile duct and the ampulla) was also noted[6] (Figure 4).

Figure 1 Cross-section of the bile duct and insertion height of the cystic duct is divided into three equal segments. A: Insertion position of the cystic duct is divided into anterior, posterior, medial, and lateral segments; B: Insertion height of the cystic duct is divided into upper, middle, and lower segments.

Figure 2 Cystic duct typing. I: Linear type; II: Curve type; III: Spiral type; IV: Complex type.

Figure 3 Morphology of the common bile duct. A: Polyline type; B: S type.

Figure 4 Oblique angle of the common bile duct and angle of the common bile duct. α indicates the oblique angle of the common bile duct: Angle between the first bend of the common bile duct and the horizontal line; β indicates the angle of the common bile duct: First angle between the common bile duct and the ampulla.

MRCP anatomical data, demographic features, and laboratory results of patients with and without choledocholithiasis were compared. Given the retrospective and nonintrusive nature of this study, our ethics committee granted approval for the exemption from obtaining written informed consent.

Statistical analysis

Statistical analyses were performed using SPSS version 25.0. Categorical data are shown as frequencies (%), and continuous data as median (range) or mean ± SD. Continuous variables were assessed using Student’s t-test, and categorical variables using Fisher’s exact test or χ² test. Independent risk factors for choledocholithiasis were identified using multivariate logistic regression, with P < 0.05 considered significant.

RESULTS

From January 2022 to October 2022, a thorough assessment of 2239 suspected choledocholithiasis cases was conducted using MRCP. Following stringent exclusion criteria, 232 patients were deemed eligible for the study, including 124 without choledocholithiasis and 108 with confirmed choledocholithiasis.

In the examination of general data, hyperlipidemia, ALT, AST, ALP, GGT, and DBil were associated with the occurrence of choledocholithiasis in both the noncholedocholithiasis and common bile duct stone groups (Table 1). Exploring the anatomical factors of the extrahepatic bile duct revealed various variables linked to the incidence of choledocholithiasis, including the diameter and length of the common hepatic and bile ducts, diameter and diverse insertion points of the cystic duct, and angle and tilt angle of the common bile duct (Table 2).

Table 1 Univariate analysis for general data.

Variable	Without CBD stones (n = 124)	With CBD stones (n = 108)	P value
Age (yr)	50.88 ± 15.60	55.06 ± 18.00	0.060
Sex, n (%)			0.575
Female	70 (56.45)	57 (52.78)
Male	54 (43.55)	51 (47.22)
BMI (kg/m2)	23.79 ± 3.78	23.62 ± 3.71	0.732
Hypertension, n (%)	19 (15.32)	9 (8.33)	0.103
Diabetes, n (%)	12 (9.68)	5 (4.63)	0.141
Hyperlipidemia, n (%)	23 (18.55)	6 (5.56)	0.003
ALT (U/L)	24.50 (16.00, 45.25)	100.45 (32.00, 216.25)	< 0.001
AST (U/L)	24.00 (19.00, 39.25)	53.00 (26.00, 130.75)	< 0.001
ALP (U/L)	84.50 (70.00, 116.50)	160.80 (104.50, 275.25)	< 0.001
GGT (U/L)	43.00 (23.00, 118.25)	251.50 (121.50, 576.50)	< 0.001
DBil (µmol/L)	4.25 (2.98, 6.60)	10.00 (4.90, 29.48)	< 0.001
IBil (µmol/L)	9.35 (6.47, 13.38)	10.70 (7.50, 15.20)	0.167

BMI: Body mass index; ALT: Alanine transaminase; AST: Aspartate transaminase; ALP: Alkaline phosphatase; GGT: γ-glutamyl transferase; DBil: Direct bilirubin; IBil: Indirect bilirubin; CBD: Common bile duct.

Table 2 Univariate analysis for anatomical factors of the extrahepatic bile duct.

Variable	Without CBD stones (n = 124)	With CBD stones (n = 108)	P value
CHD diameter (mm)	4.10 (3.20, 6.03)	9.40 (6.88, 12.50)	< 0.001
CD diameter (mm)	3.10 (2.40, 4.93)	5.85 (3.70, 8.50)	< 0.001
CBD diameter (mm)	5.00 (3.80, 6.70)	10.35 (8.10, 13.00)	< 0.001
CHD length (mm)	20.51 ± 8.88	25.12 ± 12.58	0.002
CD length (mm)	26.10 ± 12.76	35.83 ± 21.69	< 0.001
CBD length (mm)	50.46 ± 12.87	52.65 ± 13.84	0.212
CBD angulation (°)	138.94 ± 19.19	112.79 ± 19.12	< 0.001
Oblique angle of the CBD (°)	60.12 ± 18.54	47.08 ± 19.85	< 0.001
Insertion position of CD, n (%)
Anterior	15 (12.10)	21 (19.44)	0.123
Posterior	8 (6.45)	33 (30.56)	< 0.001
Lateral	95 (76.61)	50 (46.30)	< 0.001
Medial	6 (4.84)	4 (3.70)	0.920
Upper	85 (68.55)	57 (52.78)	0.014
Middle	38 (30.65)	48 (44.44)	0.030
Lower	1 (0.81)	3 (2.78)	0.519
Route of CD, n (%)
Linear type	15 (12.10)	8 (7.41)	0.233
Curved type	92 (74.19)	80 (74.07)	0.983
Spiral type	8 (6.45)	14 (12.96)	0.091
Complex type	9 (7.26)	6 (5.56)	0.599
Route of CBD, n (%)
Polyline type	118 (95.16)	98 (90.74)	0.185
S type	6 (4.84)	10 (9.26)	0.185

CHD: Common hepatic duct; CD: Cystic duct; CBD: Common bile duct.

Independent risk factors for choledocholithiasis, including the diameter [adjusted odds ratio (aOR) = 1.43, 95% confidence interval (CI): 1.07-1.92, adjusted P value = 0.016] and length (aOR = 0.92, 95%CI: 0.84-0.99, adjusted P value = 0.034) of the common hepatic duct and diameter (aOR = 1.68, 95%CI: 1.27-2.23, adjusted P value < 0.001) and angulation (aOR = 0.92, 95%CI: 0.89-0.95, adjusted P value < 0.001) of the common bile duct, were identified using multivariate logistic regression (Table 3).

Table 3 Independent risk factors for common bile duct stones in multivariate analysis.

Variable	aOR (95%CI)	Adjusted P value
CHD diameter	1.43 (1.07-1.92)	0.016
CBD diameter	1.68 (1.27-2.23)	< 0.001
CHD length	0.92 (0.84-0.99)	0.034
CBD angulation	0.92 (0.89-0.95)	< 0.001

aOR: Adjusted odds ratio; CHD: Common hepatic duct; CBD: Common bile duct.

DISCUSSION

In this study, we explored the impact of various risk factors on choledocholithiasis using univariate and multivariate logistic regression analyses.

Contrary to the common consideration of age as a predictor in other studies[15,16], our research did not establish statistical significance in this aspect. However, Govindan et al[17] suggested a potential correlation between age and common bile duct diameter, with an annual expansion rate of 0.07 mm. Nevertheless, the designation of age as an independent contributor to choledocholithiasis may be unreliable. Liver biochemical indicators such as ALT, AST, DBil, and GGT, recognized as choledocholithiasis risk factors, were significant only in the univariate analysis. This discrepancy could be attributed to secondary changes in these indicators after the occurrence of choledocholithiasis, rendering them unsuitable as reliable risk indicators.

Our findings demonstrate no significant variations in the course of the cystic duct. However, Deenitchin et al[10] reported a high incidence of gallstones associated with cystic duct malformations. Currently, a comprehensive understanding of the causes of these abnormalities and their interactions with other factors is lacking. Moreover, due to the absence of long-term follow-up data, our study's single observation does not permit the determination of a causal relationship between cystic duct abnormality and gallstone formation.

In contrast to previous studies[6], our multivariate logistic regression analysis indicated no significant differences in the position, direction, or route of cystic duct insertion. This suggests that cystic duct insertion characteristics may not be a substantial risk factor for choledocholithiasis. Nevertheless, we hypothesize that the development of primary and secondary choledocholithiasis is affected by disparities in the course and position of the cystic duct. For instance, a more twisted and folded cystic duct may impede gallstone entry into the common bile duct, potentially reducing the risk of secondary choledocholithiasis. Further studies are required to validate these hypotheses.

We identified several significant anatomical factors of the extrahepatic bile duct. Additionally, we assessed the common bile duct route, oblique angle, and shape (polyline or S-shaped). Unlike Ji et al's study using endoscopic retrograde cholangiopancreatography (ERCP)[7,8], we categorized bile ducts into polyline and S-shaped and observed no straight-line insertion into the duodenum. This divergence may be attributed to differing presentations of the extrahepatic bile ducts observed on MRCP and ERCP. However, the duct's course and oblique angle showed no statistically significant differences.

Regarding diameters of the common hepatic and bile duct, diameter of the common hepatic duct increased with dilation of the common bile duct. Additionally, gallbladder dilation through the cystic duct can alleviate pressure and reduce dilatation.

No statistically significant relationship was found between low cystic duct insertion and choledocholithiasis risk. However, as the common hepatic duct length increased, choledocholithiasis risk decreased, which is consistent with the findings of Kao et al[18]. Reduced choledocholithiasis risk has been reported with an increased choledochal angle, consistent with the findings related to recurrence risk factors[6,19,20]. This suggests decreased choledocholithiasis risk with an increasing choledochal angle, both in primary and recurrent cases. Furthermore, the biliary tract is not a sterile environment[21,22], and a smaller common bile duct angle may lead to shape distortion, causing a twisted common bile duct. This increases the risk of bile stagnation, bacterial infection, and stone formation.

While ERCP and endoscopic sphincterotomy are widely used to treat choledocholithiasis, the post-treatment recurrence rate remains notably elevated, ranging from 4% to 25%[23]. During ERCP and surgery, potential choledocholithiasis recurrence should be considered in patients with these anatomical characteristics. Further investigations are warranted to explore whether early drug interventions or modifications to the anatomical structure of the extrahepatic bile duct can reduce the occurrence of stones.

The primary limitation of our study lies in the single-time-point assessment of extrahepatic bile duct anatomical changes without long-term patient follow-up. Consequently, we could not ascertain the temporal trends of these changes or their correlations with underlying diseases. Additionally, our two-dimensional measurement method for the extrahepatic bile duct anatomy limits the precise calculation of various anatomical values. It is crucial to note that this was a single-hospital study, potentially introducing limitations specific to the geographical location and population.

CONCLUSION

In conclusion, individuals with a broader diameter of the extrahepatic bile duct, shorter length of the common hepatic duct, and smaller angle of the common bile duct are at an elevated risk of developing choledocholithiasis. Moreover, these patients are more prone to stone recurrence after surgical or endoscopic lithotomy. Thus, vigilance regarding the potential for stone recurrence is crucial in managing such cases.

ACKNOWLEDGEMENTS

We thank all medical staff and technicians of digestive endoscopy center and imaging center for their participation in this study.