Cystic duct anatomical variations and the risk of choledocholithiasis: a systematic review and meta-analysis

Dimosthenis Chrysikos*, Nikolaos Taprantzis*, Amir Shihada, Theodore Troupis

Anatomy Department and Surgical Anatomy Unit, Athens Medical School, National and Kapodistrian University of Athens, Greece (Dimosthenis Chrysikos, Nikolaos Taprantzis, Amir Shihada, Theodore Troupis)

Athens Medical School, National and Kapodistrian University of Athens, Greece

Correspondence to: Nikolaos Taprantzis, Department of Anatomy, Athens Medical School, National and Kapodistrian University of Athens, Mikras Asias 75, Athens, Greece, e-mail: nichostap@gmail.com

* Equal contributions, joint first author

Received 31 January 2026; accepted 5 April 2026; published online 9 July 2026
DOI: https://doi.org/10.20524/aog.2026.1095
© 2026 Hellenic Society of Gastroenterology

Abstract

Background Cystic duct anatomy is clinically significant for surgery and stone formation, yet the literature lacks a systematic analysis linking variations to common bile duct stones. This study investigated their prevalence and risk for choledocholithiasis.

Methods We systematically searched PubMed, Embase, Web of Science and Scopus for studies on cystic duct morphology and choledocholithiasis. Pooled prevalence, risk ratios (RRs), and odds ratios were calculated using R; heterogeneity and bias were assessed via AQUA and Peter’s tests.

Results High (17.2%) and posterior (13.8%) insertions were most prevalent. Factors significantly associated with choledocholithiasis included a long cystic duct (RR 1.50, 95% confidence interval [CI] 1.18-1.90), low insertion (RR 1.46, 95%CI 1.06-1.76), spiral course (RR 1.41, 95%CI 1.06-1.86), and posterior insertion (RR 1.32, 95%CI 1.07-1.60). Lithiasis patients exhibited wider cysto-choledochal angles (47.1° vs. 40.8°). Geographic analysis revealed a high prevalence of low insertion in African populations (21.8%) and spiral ducts in East Asians.

Conclusions Cystic duct variations significantly increase susceptibility to choledocholithiasis and pose surgical challenges. As these complex anatomical courses and configurations are often missed, preoperative imaging is essential. Early identification enables safer surgical planning, reduces biliary injury risk, and can guide tailored strategies to prevent lithiasis in high-risk groups.

Keywords Choledocholithiasis, cystic duct, anatomy, risk factors

Ann Gastroenterol 2026; 39 (5): 543-551

Introduction

The anatomical configuration of the cystic duct plays a critical role in patients’ clinical assessment and management. Its significance is evident, both during surgical procedures involving the extrahepatic biliary tree, and in the pathophysiological development of bile duct stones. The normal, or most commonly reported, anatomical configuration of that structure is a right mid-lateral insertion to the common bile duct, with an approximate length of 2-4 cm [1,2]. Although the existing literature reports the presence of a normal anatomy in 51-72% of all cases, the position of the insertion, the course and the length of the cystic duct show a great degree of variability [3].

An association between the existence of certain cystic duct variations and the development of choledocholithiasis has been proposed by some studies [3,4]. However, no previous meta-analysis or systematic review has aimed to explore that relationship in detail. Accordingly, this study aimed to report the prevalence of the clinically important cystic duct variations, along with their variability across different investigative methods, areas and sexes. Notably, this analysis also calculated the risk ratio (RR) for every available cystic duct variation, quantifying the risk association between anatomy and choledocholithiasis. The clinical interpretation of the results, as well as the surgical challenges of such variations, are discussed below.

Materials and methods

We systematically searched through the PubMed, Embase, Web of Science and Scopus databases—using key words such as “cystic duct variations”, “cystic duct anatomy”, “cystic duct” AND “choledocholithiasis”, “extrahepatic biliary anatomy”, “extrahepatic biliary variations” AND “choledocholithiasis”, “cysto-choledochal angle” AND “choledocholithiasis”, “anatomical study”—in order to collect data that would fit the criteria of our review. The search and study selection process followed the PRISMA guidelines [5] (Supplementary Table 1). Since this paper used only published data, no institutional review board approval or any other consent were needed.

Our search was limited to studies reported in the English language, while additional data were found by screening the references of the articles retrieved. The final set of studies and articles was decided based on the predefined selection criteria, which included studies that reported the presence of different cystic duct variations and/or their association with choledocholithiasis only through the usage of magnetic resonance cholangiopancreatography (MRCP). Additionally, distinct clinically relevant anatomical variations (e.g., posterior and anterior insertion, high or low insertion, medial insertion, parallel or spiral anatomy), as well as their presence in males and females, were recorded so as to calculate and investigate the frequency of these characteristics. Finally, this review did not include animal studies, abstracts from conferences, or any study that did not report the data sufficiently.

Subgroup analyses stratified by geographic area were conducted to explore the variability between different regions. The geographic moderator was categorized as Europe, America, East Asia (Japan, Korea, China), South Asia (India, Pakistan, Sri Lanka), Middle East (Iran, Saudi Arabia, Iraq), West Asia (Turkey, Anatolian populations). Since the 3D rendering ability of MRCP makes it substantially superior to other methods of visualization (e.g., direct surgical view), only studies that utilized MRCP were included in this analysis, in order to avoid any potential bias and provide more clinically relevant data.

Definitions

Low insertion and high insertion referred to joining of the cystic duct into the common bile duct in the lower third and upper third, respectively. Anterior and posterior insertion referred to the front and back end of the common bile duct, respectively. Medial insertion was defined as joining to the left side of the common bile duct. A long cystic duct was defined as one with a length greater than 2 cm, while a short duct was less than 5 mm long. A parallel cystic duct referred to a parallel course along the common hepatic duct. A spiral path referred to a cystic duct that twined around the common hepatic duct before inserting either anteriorly or posteriorly. Finally, the cysto-choledochal angle (CCA) was defined as the angle between the cystic duct and the common bile duct at the site of insertion.

Statistical analysis

We performed a meta-analysis using R (version 4.3.2) and RStudio, employing the ”meta” and ”metafor” packages for statistical analysis. To assess the association between cystic duct anatomical configurations and the risk of choledocholithiasis, RRs were calculated from study-level 2×2 contingency tables for dichotomous variables, while odds ratios (ORs) were used for identifying any differences in prevalence between male and female patients. For these comparative analyses, the Restricted Maximum Likelihood (REML) estimator was utilized to calculate the between-study variance (t2). As far as the pooled prevalences are concerned, we employed the Freeman–Tukey double arcsine (PFT) transformation. The rationale for this transformation was to stabilize the variances of proportions, particularly for rare surgical complications with rates approaching 0 or 1, ensuring appropriate study weighting. For these prevalence estimates, the DerSimonian-Laird (DL) estimator was applied. Given the inherent clinical and methodological heterogeneity expected across observational surgical studies comparing varied patient populations, a random-effects model was chosen a priori and applied to all analyses. Heterogeneity was assessed using Cochran’s Q test and Higgins’ I2 statistic, interpreted as low (0-30%), moderate (30-50%), substantial (50-75%), or considerable (75-100%) heterogeneity. Statistical significance was defined as P<0.05. Publication bias was evaluated with Peters’ test, and sensitivity analyses were performed using leave-one-out methods to assess the robustness of pooled estimates [6].

Data extraction

Two independent reviewers (DC and NT) conducted their literature search across online databases and collected their results into Microsoft Excel files. The extracted data included raw count data artery prevalence. After completing data extraction independently, the reviewers compared their datasets and resolved discrepancies through consensus. No automated tools were used in the data extraction process. The majority of the studies reported just anatomical data, without a comparison between choledocholithiasis-related groups. The RR was calculated only from studies that provided a direct comparison and association between the 2 groups, ensuring a fair evaluation.

Risk of bias assessment

Risk of bias for each included study was assessed using the Anatomical Quality Assurance (AQUA) tool of Henry et al for prevalence studies [7]. Two reviewers (DC and NT) conducted the assessments independently. Each domain of the tool was rated separately, and an overall judgment of risk (low, moderate, or high) was assigned per study. In cases of disagreement, a consensus was reached through discussion. Additionally, to assess the presence of publication bias, Peters’ tests, along with the corresponding plots, were performed for each prevalence analysis [6].

Results

After the completion of our systematic search, 3205 studies were identified from databases and citation searching. Following the removal of duplicates and articles that did not meet the predefined criteria, 1233 studies were assessed for eligibility. Finally, it was decided that 29 studies would be included in the systematic review (Fig. 1). The mean number of patients among the included studies was 321.4 (Table 1).

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Figure 1 PRISMA flow chart

Table 1 Study characteristics

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Low insertion

The overall pooled prevalence of low cystic duct insertion into the common bile duct was 5.6% (95%CI 0.03-0.08). The patient’s sex had no significant effect on choledocholithiasis (OR 1.40, 95%CI 0.70-2.82; P=0.331), whereas low insertion was significantly associated with risk (RR 1.46, 95%CI 1.06-1.76; P<0.001)

High insertion

The pooled prevalence for this variation was 17.2% (95%CI 0.10-0.25). The effect of patients’ sex was not significant (OR 1.02, 95%CI 0.90-1.15; P=0.862). Finally, the association between high insertion and choledocholithiasis was not significant (RR 1.02, 95%CI 0.32-3.29; P=0.729).

Anterior insertion

Pooled prevalence for this variation was calculated to be at 3.6% with (95%CI 0.02-0.05). The effect of patients’ sex was not significant (OR 0.99, 95%CI 0.53-1.82; P=0.879). The association between anterior insertion and the risk of choledocholithiasis was also not significant (RR 1.32, 95%CI 0.82-1.72; P=0.129).

Posterior insertion

Posterior insertion was present in 13.8% of total individuals (95%CI 0.09-0.19). Patients’ sex had a significant effect (OR 1.61, 95%CI 1.13-2.32; P=0.008). However, there was a significant association between this variation and choledocholithiasis (RR 1.32, 95%CI 1.07-1.60; P=0.019).

Medial insertion

A cystic duct with a medial insertion to the common bile duct was present in 10.3% of patients (95%CI 0.05-0.16). Patients’ sex was not significant (OR 0.99, 95%CI 0.23-4.11; P=0.866). Finally, this variation was not significantly associated with choledocholithiasis (RR 0.98, 95%CI 0.82-1.17; P=0.897).

Low medial insertion

Low medial cystic duct insertion is a specific type of anomaly that was reported in most of the included studies. Its prevalence was found to be 4.8% (95%CI 0.03-0.06). Patients’ sex had no significant effect (OR 1.12, 95%CI 0.73-1.72; P=0.580). Nor was there any significant association between this variation and choledocholithiasis (RR 0.70, 95%CI 0.07-6.71; P=0.787).

Parallel

A parallel cystic duct was present in 8.6% of individuals (95%CI 0.04-0.14). The effect of patient’s sex was not significant (OR 1.31, 95%CI 0.78-2.19; P=0.300). This variation had one of the weakest connections with the development of choledocholithiasis (RR 0.90, 95%CI 0.38-2.10; P=0.658).

Spiral

A spiral cystic duct was identified in 11.8% of patients (95%CI 0.06-0.18). A male vs. female sex analysis was not feasible, but this anomaly had a significant association with choledocholithiasis (RR 1.41, 95%CI 1.06-1.86; P=0.015).

Short cystic duct

A short cystic duct was a relatively rare anatomical variation, present in only 2.1% of the total individuals (95%CI 0.01-0.03). The effect of patients’ sex was not significant (OR 1.56, 95%CI 0.72-3.37; P=0.252). The association of this anomaly with choledocholithiasis was very weak (RR 0.46, 95%CI 0.07-2.91; P=0.521).

Long cystic duct

A long cystic duct was identified in 9.1% of the total individuals (95%CI 0.02-0.20) (Table 2). However, there was a highly significant positive association between this variation and choledocholithiasis development (RR 1.50, 95%CI 1.18-1.90; P<0.001).

Table 2 Area subgroup analysis results

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CCA

The CCA, or the angle between the cystic duct and the common bile duct at the site of insertion, was calculated for patients with and without choledocholithiasis. The CCA was 47.1° in the former group (95%CI 30.52-63.68°) and 40.8° (95%CI 31.87-49.83°) in the latter. Thus, patients with lithiasis in their bile duct tended to have a wider angle of insertion between the cystic duct and the common bile duct.

Other variations

Two other extremely rare variation were also reported in the literature. Specifically, a double cystic duct was found in 0.38% of the population (95%CI 0.00-0.01), while an insertion of the cystic duct to the right hepatic duct was present in 0.5% of the assessed individuals (95%CI 0.00-0.01).

Area subgroups

For the anatomical variations of the cystic duct that presented with a higher RR for choledocholithiasis, additional subgroup analyses were performed in order to determine how their prevalence varied across different geographical areas and ethnic groups.

For low insertion, the African population presented with a significantly higher prevalence (21.8%) compared to the other areas, while Middle Eastern patients were found to have the smallest prevalence (Fig. 2).

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Figure 2 Low insertion of the cystic duct

Regarding the posterior insertion of the cystic duct, studies that were conducted in the western part of Asia were associated with greater numbers for this type of variation (22.3%), while the Middle Eastern population again had the lowest prevalence (3.5%) (Fig. 3).

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Figure 3 Posterior insertion of the cystic duct

Regarding a spiral course of the cystic duct, the Eastern Asian populations presented with the highest prevalence of this type of variation (35.4%), while the European and south Asian individuals had the lowest prevalence (7.1% and 8.6%, respectively).

Finally, a long cystic duct was more common in Eastern Asian and Western Asian populations, with prevalences of 13.5% and 8.9%, respectively. The Middle East area had the lowest prevalence (5.2%) (Table 2).

Risk of bias assessment

Each study that was included in this analysis was assessed using to the AQUA Tool (Supplementary Table 2). Additionally, Peters’ test for funnel plot asymmetry showed no evidence of bias in the prevalence of any of the cystic duct variations assessed (Supplementary Fig. 1-10). In the sensitivity analysis, none of the findings showed any significant change in results or heterogeneity after the omission of each study (Supplementary Table 3).

Discussion

This systematic review with meta-analysis investigated, assessed and presented the prevalence of the most clinically significant anatomical variations of the cystic duct, along with their variation across patient’s sex and geographic regions. Furthermore, this is the first meta-analysis to investigate the risk and association between each anatomical variation and the development of choledocholithiasis. One other systematic review presented the prevalences of each cystic variation, without analyzing its variability through different moderators and factors [36] (Table 3).

Table 3 Comparison of study findings with existing literature

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Several variations showed meaningful associations with choledocholithiasis. Low insertion (RR 1.46, 95%CI 1.06-1.76), posterior insertion (RR 1.32, 95%CI 1.07-1.60), a spiral course (RR 1.41, 95%CI 1.06-1.86), and a long cystic duct (RR 1.50, 95%CI 1.18-1.90) were all positively associated with lithiasis. In contrast, anterior, medial, parallel and low medial insertions showed no significant association, while a short cystic duct demonstrated the weakest relationship (RR 0.46, 95%CI 0.07-2.91). Sex-based analysis did not demonstrate a higher prevalence for either gender, with the exception of posterior insertion, which was more prominent in females. Collectively, these findings indicate that cystic duct anatomical variations can be identified equally in both female and male patients.

As far as the geographical analysis is concerned, the results demonstrated that Middle Eastern populations consistently exhibited the lowest prevalence of cystic duct variations associated with the highest risk of choledocholithiasis. In contrast, both Eastern and Western Asian populations showed a higher overall frequency of these high-risk anatomical variants, suggesting a greater susceptibility to anatomy-related choledocholithiasis in these groups. Finally, special mention needs to be made for the African population, whose low insertion prevalence (21.8%), was more than double the frequency for the American population, which was in second place. Hence, it should also be noted that African patients have a stronger association with this highly significant risk factor for development of bile duct stones.

Thus, based on the findings of the present study, patients exhibiting the aforementioned cystic duct variations, which are associated with an increased risk of choledocholithiasis, may warrant assessment and treatment using more radical means. Patients that belong in the aforesaid high-risk groups have a greater need to undergo imaging evaluation in order to determine the presence of this risk factor, which will help in preoperative and management planning.

The exact pathophysiological mechanisms underlying the association between cystic duct anatomical variations and choledocholithiasis remain a subject of ongoing debate. Much of the current literature focuses on altered biliary hemodynamics and primary stone formation. Anomalous configurations inherently increase resistance to bile flow, promoting biliary stasis. Zhu et al and Pitt et al. [16,37] postulated that this increased resistance significantly reduces bile flux. According to Poiseuille’s law, this reduction in flow velocity is associated with greater bile viscosity, which creates a highly lithogenic environment and facilitates the precipitation of primary stones [16,38]. Furthermore, a tortuous or abnormal anatomy may subject the cystic duct mucosa to altered shear stress and constant physical collision from bile flow. The resulting cycle of chronic mucosal injury, localized inflammation and subsequent repair can either act directly as a focal point for stone crystallization, or progressively narrow the ductal lumen, thereby exacerbating stasis [37,38].

However, the specific pathophysiology regarding low-inserting cystic ducts presents a more complex paradigm. While a recent study has established a clear clinical correlation between intrapancreatic low insertion and common bile duct stones [39], the exact mechanical etiology remains elusive. Attributing this association solely to stagnation is controversial, as some authors argue that variations in the duct’s course or length are far more likely to cause significant stasis than the insertion site itself [11]. Interestingly, Garg et al [4] highlight that structural variations do not universally guarantee downstream stone progression. They propose that severe flow restriction in an abnormal cystic duct might actually trap forming stones within the cystic duct, preventing their transit into the common bile duct and theoretically decreasing the clinical incidence of choledocholithiasis.

Alternatively, the anatomical association may be driven by a migratory mechanism, where existing secondary stones travel from the gallbladder into the common bile duct. Although direct evidence for this specific pathway is currently limited, Tastemur et al [12] demonstrated that anterior, posterior, and low medial insertions are associated with a significantly higher coexistence of gallbladder and choledochal stones. This finding supports a mechanical theory wherein certain anatomical insertion angles may facilitate the passage and migration of preexisting gallstones into the main biliary tree.

Building upon this theory, another clinically relevant anatomical variation, albeit reported by a limited number of studies, is a large cystic duct diameter. Krisem et al [14] demonstrated a statistically significant relationship (OR 2.22, 95%CI 1.32-3.73) between a dilated cystic duct and choledocholithiasis, suggesting its potential utility as a strong anatomical predictor for stone occurrence. Mechanistically, this aligns with the migratory theory; a case report by Tong et al [40] hypothesizes that an abnormally wide cystic duct offers less physical resistance, thereby facilitating the unobstructed transit of preexisting gallbladder stones directly into the common bile duct.

Given the inherent predisposition to primary choledocholithiasis in patients with specific high-risk cystic duct variations, clinical management should focus on mitigating synergistic risk factors. While anatomical morphology is unalterable, studies consistently demonstrate that primary stone formation is multifactorial [11]. Recent multivariate analyses indicate that, alongside ductal anatomy, advanced age, female sex, and specifically modifiable factors such as an elevated body mass index (≥24 kg/m2), hyperlipidemia and dietary habits are independent risk factors for lithiasis [11,41]. Therefore, when a high-risk anatomical variation (such as a long or low-inserting duct) is identified, clinicians should proactively address these concurrent risks. Advising lifestyle modifications is a critical preventative measure to minimize the cumulative risk of primary bile duct stone development in these susceptible individuals.

All of these variations hold additional significance during surgical operation concerning the gallbladder and the biliary tree. One of the most serious complications during biliary surgery is the failure to accurately identify cystic duct anatomy, resulting in confusion with the common bile duct. In such cases, misidentification may lead to inadvertent transection of the common bile duct [42]. Other variants, such as cystic duct drainage into the right hepatic duct, can distort the hepatocytic triangle, thereby heightening the likelihood of inadvertent biliary injury during dissection. Similarly, the presence of a double cystic duct can lead to significant intraoperative confusion and, if unrecognized, may result in inadequate clipping and postoperative bile leakage [11]. Furthermore, given that low insertion has a relatively high association with stone formation, not identifying such a variation could lead to complications and challenges during endoscopic retrograde cholangiopancreatography.

Moreover, the presence of a long cystic duct can create further challenges for the responsible surgeons. Apart from the great danger of confusing the long cystic duct with the common bile duct and causing a serious iatrogenic injury, an additional risk of transecting or ligating in close proximity to the common bile duct could result in the latter undergoing strictures or narrowing in that area [42]. Patients with a short or absent cystic duct should be carefully assessed during surgery. This group of patients are associated with an unintentional clamping of the common bile and hepatic duct, as the abnormal anatomy of the cystic duct increases the risk of tenting of the 2 aforementioned structures [8].

One procedure that is significantly impacted by the abnormal anatomy of the cystic duct is the endoscopic naso-gallbladder drainage procedure [11]. Such operations rely heavily on the anatomy of the cystic duct, as well as its insertion into the common bile duct. The high failure percentages that several studies have reported seem to be a result of the notably high difficulty of cystic duct cannulation, which is based on the accurate identification of the cystic duct orifice [16,43,44]. However, the high variability of cystic duct insertion into the common bile duct can play a major role in the greater difficulty involved in this procedure. Furthermore, the direction and spatial relativity of the cystic duct compared to the bile duct also play an important role. More precisely, in cases where the cystic duct is located on the left or lower side of the common bile duct, successful wire or catheter cannulation becomes extremely difficult [43].

This analysis is strengthened by a clearly defined and independently executed study selection and data extraction process, which was able to reduce the risk of bias. Another strength was the use of rigorous statistical methodology, including extensive pooled prevalences, subgroup analyses, comprehensive risk of bias and publication bias assessments (AQUA tool, Peters’ test), and sensitivity analyses confirming the robustness of pooled estimates. The transparent use of validated tools and open-source statistical packages further enhances the reproducibility and reliability of the findings.

This systematic review and meta-analysis nevertheless had a few limitations. Specifically, several studies were characterized as Moderate or High Risk according to the AQUA tool. Furthermore, high between-study heterogeneity persisted across most analyses, probably reflecting differences in patient groups, clinical factors, and population characteristics. There were some imbalances in the data distribution regarding the sex, and geographic area analyses, which may affect the generalizability of results. There were some limitations to clinical data reporting, as not all studies reported the association between the presence of any variation and choledocholithiasis. It should be noted that, even though high heterogeneity is expected in anatomy-related analyses, it can limit the precision of a single “global mean”. Thus, readers should interpret the pooled estimates with caution and contextualize these findings within the field of anatomical meta-analysis.

In conclusion, cystic duct anatomy plays a major role during the clinical and surgical assessment of patients. Variations such as low insertion, posterior insertion, spiral course and long cystic ducts demonstrate the strongest associations with stone formation, particularly in certain geographic populations, including Eastern and Western Asians. Awareness of these variations is essential for guiding surgical planning and minimizing the existing risk factors. Future research should focus more on the impact of these variations on the development of choledocholithiasis, by directly comparing the biliary anatomy between the 2 stone-related groups. Additionally, research from diverse geographical areas could also prove to be useful in obtaining a clearer image of the variation trends of cystic duct anatomy.

Summary Box

What is already known:

  • The anatomical configuration of the cystic duct is highly variable, with the standard right mid-lateral insertion present in only 51-72% of individuals

  • While individual studies have hypothesized an association between specific cystic duct variations and choledocholithiasis, there was no previous comprehensive meta-analysis quantifying this exact risk

What the new findings are:

  • Low insertion, posterior insertion, a spiral course and a long cystic duct are statistically associated with a significantly greater risk of developing choledocholithiasis

  • The prevalence of high-risk anatomical variants demonstrates significant geographic variability, highlighted by a notably high frequency of low insertions among African populations and spiral courses in Eastern Asian cohorts

  • Sex-based analysis revealed no significant difference in the overall prevalence of cystic duct variations between male and female patients, with the sole exception of posterior insertion being more prominent in females

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Notes

Conflict of Interest: None