Laparoscopic cholecystectomy (LC) has replaced open cholecystectomy (OC) as the gold standard surgical treatment for symptomatic cholelithiasis and other benign gallbladder disorders, and is one of the most common surgeries performed in the abdomen in the world.[1] Though it is a simple procedure, correct identification of the vascular and biliary structures in the hepatocystic (Calot's) triangle is essential for safe LC.[1]  Misinterpretation of these structures continues to be a significant cause of vasculobiliary injury, especially if they are distended or obstructed by inflammation, adhesions, or congenital anatomic variation.[2] The Critical View of Safety (CVS) approach has thus been adopted as an important method to reduce accidental harm during dissection.[3, 4]

The main blood supply of the gallbladder is the cystic artery, which typically originates from the right hepatic artery and passes through the hepatocystic triangle to the gallbladder.[2] The origin, number, course, position, and relations of it, however, vary greatly with the common hepatic duct and the cystic duct.[5] A recent systematic review and meta-analysis showed that about 85.75% of the cases had a cystic artery arising from the right hepatic artery, and in 88.59% of cases, the artery was a single one, and in 83.83% of cases, it was located in the cystohepatic triangle.[3] The mean length of the cystic artery was about 21.34 mm in the pooled data, indicating that the vascular pedicle is relatively short during the laparoscopic dissection of the gallbladder.[4]

There is variation in the origin of the cystic artery that can be clinically important, such as double or multiple cystic arteries, aberrant origin of the artery, short cystic artery, and unusual relationship of the artery to the cystic duct or common hepatic duct. A large review of over 9800 cases reported that the cystic artery was usually from the right hepatic artery (79.02%), was multiple (8.9%), was short (9.5%), or was located anterior to the common hepatic duct (17.9%). These variations can make it difficult to clearly identify the vascular anatomy before clipping and division, and can obscure the expected anatomy.[6]  Conventional anatomical position of the cystic artery was seen in 86.15% of the 27 studies comprising 9618 patients, while duplicate cystic arteries were noted in 7.18%, and posterior, anterior, and inferior courses of the CA were observed in 14.95%, 10.75%, and 6.23%, respectively.[3]

These variations have clinical implications beyond just anatomical description, as they can be directly related to the difficulty of LC. A prospective observational study comprising 298 patients revealed that anatomical variation was present in 31.9% of patients, with cystic artery variations being the most common identified at 16.8%.[7]  Rarely, abnormal courses of the arteries or other branches may necessitate more extensive dissection, multiple identification of the vascular structures, or changes to the routine of clipping and dividing the vessels.[8] In particular, an unrecognized artery that is not located within the boundaries of Calot's triangle could be confused with a different structure, and multiple or short arteries can make secure control more difficult.[9] Recent evidence highlights the fact that many clinically relevant variants of the cystic artery are found just within the zone of dissection for the vascular-biliary pedicle, and awareness of these variants is an integral part of safe LC.[3]

In spite of the extensive anatomical literature, an important clinical question remains regarding whether these variations are merely anatomical curiosities or whether they are associated with actual operative difficulty during laparoscopic cholecystectomy. When examining the cystic artery, more clinically meaningful data may be obtained than merely the prevalence rate by evaluating against objective operative parameters, including the duration of the surgery, the difficulty of dissection, necessity for further clipping or cauterization, bleeding experienced, the Critical View of Safety achieved, and conversion to open surgery.

This relationship is especially important in routine surgical practice, because sometimes the small arterial variants are not evident in the images obtained before surgery or are not appreciated until the dissection is performed during surgery. The present study was therefore designed to ascertain the prevalence and distribution of cystic artery anatomical variants and to see if there was any difference in the difficulty of the operation between patients with normal and variant anatomy of the cystic artery during laparoscopic cholecystectomy. The results could be useful in enhancing the surgeon's awareness of vascular variants, providing intraoperative anatomical orientation and aiding safer, more standardized dissection of the hepatocystic triangle.

This was a comparative cross-sectional study performed over six months from 1st November 2025 to 30th April 2026 in the Department of Surgery, Ayub Teaching Hospital, Abbottabad. The sample size was calculated using the sample size calculator for cross-sectional studies in OpenEpi. The prevalence of a cystic artery anatomical variation was expected to be 16.8%, which was quoted in a previous prospective observational study of 298 patients undergoing laparoscopic cholecystectomy, of whom 16.8% had a cystic artery anatomical variation.[7] With 95% confidence, 5% absolute precision, and an assumed prevalence of 16.8%, the minimum sample size was estimated to be 216 patients. The sample size was expanded to 240 patients in order to make up for the estimated 10% of patients who may be excluded or not have been documented during surgery. This means that 240 patients who had laparoscopic cholecystectomy were chosen for the study. A consecutive non-probability sampling technique was used. Patients who underwent elective laparoscopic cholecystectomy for the presence of gallstones (cholelithiasis), chronic cholecystitis with stones (chronic calculous cholecystitis), gallbladder polyps, and other benign indications of the gallbladder were included. Patients of either sex were eligible. Only cases where the cystic artery could be clearly seen during the operation and where the anatomical course of the artery, the number of the artery, and the relationship of the artery to the duct could be measured were included. Patients with acute complicated cholecystitis requiring emergency laparoscopic cholecystectomy with severe inflammatory distortion, suspected or confirmed gallbladder malignancy, previous major upper abdominal surgery, and hepatobiliary vascular anomalies were excluded; patients in whom laparoscopy could not be used to assess the cystic artery were also excluded. In addition, non-anatomical reasons for conversion to open surgery, such as cardiopulmonary intolerance and equipment failure) were not included in the primary analysis of operative difficulty. Patients in whom the exact identification of the cystic artery was not possible due to complete freezing or a highly distorted hepatocystic triangle were excluded, as accurate classification of the arterial anatomy was not possible. Patients who met the criteria were enrolled prior to surgery with informed consent and institutional ethical approval. A structured data collection proforma was completed for relevant demographic and clinical data, such as age and sex, BMI, indication for surgery, previous episodes of cholecystitis, and relevant comorbidities. Preoperative evaluation and abdominal ultrasound were performed routinely in all patients, as per institutional practice. All the dissection of the hepatocystic triangle was done with regard to the usual surgical rules, and the Critical View of Safety was identified before the division of the cystic artery and duct whenever technically possible. The cystic artery was checked directly with the aid of the laparoscope. Its location, number, origin, and course were recorded, and whether it was joined to the cystic duct and whether it was an accessory or aberrant arterial branch. Anatomical variations were defined as any deviation in origin, number, course, position, or relationship to the cystic duct; the hepatocystic triangle was considered to have normal anatomy if a cystic artery was present and it was the usual right hepatic artery that was present and had the usual course within the hepatocystic triangle. This method was similar to earlier work that recorded the anatomy of the cystic artery during laparoscopic dissection. Operative difficulty was evaluated using predefined intraoperative parameters, such as the duration of surgery, identification and dissection of the cystic artery, difficulty achieving Critical View of Safety, bleeding during surgery, additional clips or cauterization, perforation of the gallbladder, placement of the drain, and conversion to open surgery. Operative time was defined as the time interval between opening the abdomen with the first laparoscopic incision/port and skin closure. The dissection difficulty was noted on a predefined scale according to the surgeon's judgment. Patients were then split into two main groups based on the cystic artery anatomy: normal and cystic artery anatomical variation. The results of the surgeries were then compared between these groups. Data were collected, edited, and analyzed with SPSS version 26. Continuous variables including age, BMI, operating time, and hospital stay were evaluated for normality by the Shapiro-Wilk test. Continuous variables were presented as mean ± standard deviation, and non-normally distributed variables were presented as median with interquartile range. Categorical variables (sex, type of cystic artery variation, Critical View on Safety (CVOS) achievement, intraoperative bleeding, supplementary clipping, drain placement, and conversion to open surgery) were expressed as frequencies and percentages. The incidence and pattern of the individual variations of the cystic artery were established. The Chi-square test and Fisher's exact test were used to compare differences between the categorical variables of patients with normal and variant cystic artery anatomy. An independent-samples t-test was used for data that were normally distributed, while Mann-Whitney U was used for data that were not normally distributed. Operative difficulty was associated with the anatomical variations of the cystic artery as odds ratios (ORs) with 95% confidence intervals (CIs). To assess if the relationship between the presence of a variant cystic artery and the likelihood of a difficult laparoscopic cholecystectomy persisted after adjustment for clinically relevant confounders, including acute/chronic inflammatory status, BMI, sex, age, and previous cholecystitis, binary logistic regression was conducted. A p-value <0.05 on both sides was considered significant.

A total of 240 patients undergoing laparoscopic cholecystectomy were included in the analysis. The mean age of the study population was 46.8 ± 12.4 years, and the study group comprised more females than males. The inflammatory gallbladder disease was usually chronic, and about one-third of patients had a previous episode of cholecystitis. Demographic and clinical parameters were largely similar in the two groups for both normal and variant cystic artery anatomy, and showed no significant differences in age, sex, BMI, or the occurrence of previous cholecystitis. (Table 1 and Table 3)

In most of the patients, normal anatomy of the cystic artery was observed, while approximately one-sixth were found to have anatomical variation. The most common variations encountered were double cystic arteries, aberrant origin of the arterial supply, short cystic artery, and abnormal course of the artery anterior and posterior to the cystic duct. The majority of the cystic arteries emerged from the right hepatic artery and ran within the hepatocystic triangle. (Table 2)

The operativeness was markedly different in relation to the cystic artery anatomy. Patients with anatomical variations had significantly longer operating times and had more trouble during dissection of the cystic artery, and the Critical View of Safety (CVS) was reached. In addition, patients with variant anatomy had significantly more episodes of intra-operative bleeding and more clips or cauterization needed. Increased frequencies were observed for gallbladder perforation, placement of a drain, and conversion to open surgery in the variant group; however, these differences were not statistically significant. (Table 4)

The difference between the two groups was further confirmed by assessing the operative difficulty. Patients with a variant with respect to the anatomy of the cystic artery had higher operative difficulty scores and longer postoperative hospital stay than the variants with normal anatomy. The non-parametric approach gave a similar result in terms of the distribution of operative time, with the difference still being significant, confirming the robustness of the observed difference. (Table 5)

Anatomical variation of the cystic artery was found to be significantly associated with difficult laparoscopic removal of gallstones in regression analysis. Operative difficulty was also independently associated with the acute inflammatory status after adjustment for age, sex, BMI, and previous cholecystitis (Table 3). Age, male sex, higher BMI, and past history of cholecystitis were not found to be statistically significant in the adjusted model. (Table 6)

Table 1. Demographic and baseline characteristics of patients undergoing

laparoscopic cholecystectomy (n=240)

Table 2. Frequency and pattern of cystic artery anatomical variations

Table 3. Comparison of demographic and clinical characteristics according to cystic artery anatomy

Table 4. Comparison of operative characteristics and difficulty according to cystic artery anatomy

Table 5. Comparison of operative difficulty scores and hospital stay

Table 6. Binary logistic regression analysis of factors associated with difficult laparoscopic cholecystectomy

The present study aimed at assessing both the incidence and the type of anatomic variations of the cystic artery and their association with the difficulty of laparoscopic cholecystectomy. Anatomical variation of the cystic artery was found in 17.1% of 240 patients, and 82.9% of patients had conventional anatomy. The most important finding was that patients with variant anatomy had significantly longer operative times, more difficult dissection of the cystic artery, difficulty achieving Critical View of Safety (CVS), increased bleeding, and increased requirement for additional clips or cauterization. Multivariable analysis showed that the presence of the cystic artery anatomical variation was independently associated with difficult laparoscopic cholecystectomy with an adjusted OR of 4.21 (p<0.001). The results indicated that the variability of the cystic artery is not just an anatomical finding, but could potentially be clinically significant for the technical Management of LC. The present study had cystic artery variation in 17.1% of the cases, which was very close to the report of Kumar et al., who performed a prospective observational study of 298 laparoscopic cholecystectomies and observed 16.8% of cases with cystic artery variation. Their study revealed that the most common anatomical variant was a cystic artery anomaly, and that patients with anatomical variants had significantly more intraoperative complications, including bleeding and open surgery.[7] The parallel in prevalence of their study with the current results supports the findings that clinically significant variants of the cystic artery are present in about 1 in 6 patients who undergo LC in similar surgical populations. The present study, however, specifically took this one step further and looked at the difficulty of the operation as the outcome, not the most common postoperative or intraoperative complications. The results were also similar to those of the Pakistani study performed in 2021 by Fateh et al. It focused on a laparoscopic view of the position of the cystic artery. In that study, it was noted that the position of the cystic artery in relation to the cystic duct is quite variable and that it is important to be aware of these variations to avoid iatrogenic vascular and biliary injury.[10] This observation is more relevant to our results, as we found that abnormal arterial anatomy was associated with difficulties in arterial dissection and in achieving CVS in the present study. It is noteworthy that both studies have been carried out with laparoscopic visualisation, as the appearance of the hepatocystic triangle on laparoscopy is different from the classical anatomical description. This finding was corroborated by the study conducted by Muazzam et al. (2021), which assessed the extrahepatic biliary anatomical variation in patients who underwent LC at CMH and PEMH Rawalpindi. They found an anomaly of the cystic artery in 11% of the patients.[11] This prevalence is a bit lower than that seen in patients in our study (17.1%) and may be related to the different definitions of variation, type of patient population, and the different anatomic parameters that were recorded. Their work confirms, however, that some abnormalities of the cisterna occur with enough frequency in the surgical population to be taken as a precaution during surgery. The current results are also consistent with those of a prospective study by Sproll et al. on vascular and biliary landmarks for safe cholecystectomy that included 500 patients. They found that the commonest pattern was one cystic artery that was placed superomedially to the cystic duct (8%); multiple cystic arteries were seen, and an aberrant right hepatic artery that led to a small cystic artery was found in 2.4%. Importantly, 92.6% of patients achieved CVS.[12] They support our observation that an abnormal arterial pattern can render dissection and identification of the involved structures more challenging. The 2024 cross-sectional study from West Bengal, on 196 patients with LC, is a particularly relevant comparison; this study specifically looked at the role of cyst artery anatomic variations in determining surgical approach. The investigators analyzed intra-operative anatomical findings and determined if there was a correlation between anatomical variation and conversion to open cholecystectomy.[13] There was no significant difference between the groups in the conversion to open surgery (7.3% vs 1.5%, p=0.061), but the trend was comparable. The operative time, the difficulty in vascular dissection, and the achievement of CVS were more frequent and therefore more statistically informative measures of operative complexity, while the lack of statistical significance in our study may have been due to the relatively small number of conversion events. The findings of Perdikakis et al. (2024) provide an important qualitative explanation for our results. They presented a rare case of a cystic artery arising from the middle hepatic artery instead of the right hepatic artery. In LC, careful dissection was needed, and the case was approached in a retrograde manner.[14] This scenario was not typical of our group, but it does show how a seemingly trivial anatomical variation can significantly impact the surgeon's approach and dissection. This is a plausible anatomical explanation for our experience of longer operative time and greater difficulty in obtaining CVS in patients with arterial variants. The findings of the Sudhir et al. (2025) study carried out in Bengaluru also corroborate the need for positional variation. In 100 LC patients, the cystic artery was posteromedial to the cystic duct in 87%, posterolateral in 7%, anterior in 5%, and absent in one patient; in another patient, it was not identified due to necrosis.[15] These results show that variation does not only apply to the origin of the artery or to duplication, but also to the relation of the artery to the artery and the cystic duct. This is especially important for our study, as an abnormal course or position of the artery can necessitate a wider or more careful dissection before the clipping, which will account for the longer and more difficult dissections that were seen in our variation group. The results of Schiewe et al. (2025), who studied anatomical variability of the cystic artery in the context of cholecystectomy, also highlighted the significance of understanding arterial variations for successful surgery.[16] During cholecystectomy, the review pointed out that the following factors were clinically relevant and may differ: origin, course, number, and relationship with other surrounding structures.[16] In the present study, we were able to add a clinical dimension to this anatomical literature, since we found a median operative difficulty score of 4 for patients with variant anatomy and 2 for patients with normal anatomy, this difference being highly significant. The more comprehensive 2025 systematic review and meta-analysis done by Triantafyllou et al. provided a wider picture. Their consensus showed that the right hepatic artery was the origin of the cystic artery in 85.75%, that it was single in 88.59%, and that it was within the cystohepatic triangle in 83.83%. The authors specifically showed that the changed cystic anatomy may lead to confusion, iatrogenic injury, and longer surgical time.[3] The findings in this study are direct clinical support for this suggested relationship, as variant anatomy was correlated with an increase in the mean operative time of about 16 minutes and significantly more difficulty with arterial dissection and CVS achievement. Specifically, the latest evidence from the 2026 systematic review and meta-analysis done by Triantafyllou et al. is pertinent to this study. In 27 studies with 9618 patients, conventional cystic artery and duct anatomy was observed in 86.15% of patients. Cystic arteries were duplicated in 7.18% of cases, and posterior, anterior, and inferior courses of the cystic artery to the cystic duct were observed in 14.95%, 10.75%, and 6.23%, respectively. The authors stressed that these variants are often located in the hepatocystic triangle and may affect the identification of the hepatocystic pedicle.[3] The overall rate of variation (17.1%) is consistent with the wide range of reported intraoperative variation in recent literature, but direct numerical comparison must be done with caution as different studies utilize different definitions and classification systems. Likewise, Kothule et al., in a 2026 prospective observational study, analyzed 100 patients with LC and assessed the cystic artery variations of the patients in terms of surgical implications such as the origin, number, location, and position of the cystic artery within Calot's triangle.[17] The study confirms the existing notion that the anatomy of the cystic artery should be considered as an intraoperative variable and not a fixed one. This is significant for our observed result that variation was independently associated with operative difficulty after accounting for age, gender, BMI, and previous cholecystitis and acute inflammatory status. Another important relationship with the concept of CVS is our results. In 2024, a study assessed aberrant anatomy during LC and determined that there was a third anatomical element present in about 15% of cases, most frequently arterial, and heterotopic cystic artery courses were present in 8.6%. Interestingly, these variants were not associated with failure to achieve CVS if they were identified and recognized intraoperatively, the investigators reported.[18] This observation is complementary to our results but not conflicting. In our study, we determined that variant anatomy correlated with increased difficulty in achieving CVS, but this is not a statement that CVS is not safe to achieve. Instead, the presence of an additional or abnormally positioned artery may require more meticulous dissection and greater operative time before CVS can be confidently established. The anatomical variability and bleeding association were most significant in our study. In those with variant anatomy, bleeding was seen in 19.5% of patients, whereas in those with normal anatomy, it was seen in 7.0% of patients (p=0.018). This is in line with the direction of Kumar et al., who reported a 16.8% incidence of hemorrhage in patients with anatomical variations versus 1.9% in those with normal anatomy (p<0.001).[7] In particular, abnormalities of the cystic artery were found to be strongly associated with operative bleeding, as shown by their subgroup analysis. Therefore, the current work reinforces the evidence of the practical vascular implications of anatomical variation of the arteries during LC. Another important finding was the multivariable analysis. In the unadjusted analysis, operative difficulty was associated with both previous cholecystitis and acute inflammatory status, but in the adjusted model only acute inflammatory status and cystic artery anatomical variation remained statistically significant. In these results, there is a strong independent association between the variant anatomy of the cystic artery and the difficult LC, with an adjusted OR of 4.21. This discovery is in keeping with the current surgical literature that emphasizes that operating difficulty is a multi-factor process, inflammation and adhesions are not factors by themselves but are factors in combination with the abnormal hepatocystic anatomy. The literature of recent years also shows abnormal hepatocystic anatomy to be an important factor in difficult LC, along with acute cholecystitis and previous surgery.[19] Overall, the results showed that the cystic artery variation should be considered as an operating variable that may affect the difficulty of the surgery, and not just as an anatomical observation. The findings of our study are consistent with the prevalence as reported in recent observational literature and the significant differences in operative time, arterial dissection, CVS achievement, bleeding, and additional vascular control favour the clinical relevance of systematic intraoperative recognition of the cystic artery anatomy. Concurrently, there are reports in the literature of successful completion of LC despite identification of an unexpected vascular-biliary anatomy if these structures are carefully dissected and deliberately identified, and CVS is obtained. LIMITATIONS There were some limitations to the study. In the first place, the study was carried out at one tertiary-care hospital; thus, the results might not be applicable to other surgical centers and populations. Secondly, the cross-sectional nature of the study enabled the association of anatomical variations of the cystic artery with the difficulty of the operation, but did not prove a causal effect. Thirdly, the surgical difficulty and the extent of the classification of cystic artery anatomy was partly subjective, depending on surgeon judgment and intraoperative visualization, and thus were subject to observer and inter-surgeon variability. Fourth, there were no studies that were specifically developed to detect small cystic artery variations, so some variants may have been detected only during the operation. Third, there were relatively few patients with individual rare arterial variants to make meaningful comparisons of submorphs between groups of anatomical variants.

Anatomical variations of the cystic artery occurred relatively often in patients undergoing laparoscopy and were significantly related to the difficulty of operation. A longer operative time, more difficult arterial dissection and achievement of the Critical View of Safety, more intraoperative bleeding, and more need for additional vascular control were associated with variant anatomy. After controlling for potentially confounding clinical variables, the presence of cystic artery variation was an independent risk factor for difficult laparoscopic cholecystectomy. Therefore, the understanding and careful recognition of the anatomy of the cystic artery during routine surgery may help to dissect the hepatocystic triangle safely and minimize the risk of vascular complications during surgery.