Abstract
Background
This study aimed to evaluate the association between lymph node dissection (LND) and Textbook Outcomes (TO) in patients with intrahepatic cholangiocarcinoma (ICC).
Methods
This retrospective multicenter study was registered in the Research Registry (registration number: researchregistry10392). We included patients treated at four major hospitals between 2011 and 2017. TO was defined as negative surgical margins, no perioperative blood transfusion, no postoperative complications, no prolonged length of stay (LOS ≤ the 50th percentile of the total cohort), no readmission within 30 days after discharge, and no postoperative death within 30 days. A random forest algorithm was used to determine the relative importance of factors associated with TO achievement. Subgroup analyses were conducted to identify patients who may benefit from LND. Adjusted TO was defined as achievement of both the conventional TO criteria and LND.
Results
A total of 376 patients were included in this study. Random forest analysis showed that LND was associated with the likelihood of achieving TO. Patients who underwent LND had higher rates of postoperative complications and longer hospital stays. Further analyses indicated that LND did not adversely affect overall prognosis and may contribute to prognostic stratification.
Conclusions
LND may reduce the rate of achieving TO in the short term; however, its value for long-term prognosis and postoperative treatment planning should not be overlooked.
Supplementary Information
The online version contains supplementary material available at https://doi.org/10.1186/s12876-026-05090-z.
Keywords: Intrahepatic cholangiocarcinoma, Textbook outcome, Survival, Lymph node dissection
Highlights
Innovatively utilizing machine learning methods to analyze the impact of lymph node dissection on textbook outcomes.
A comprehensive survival analysis provides strong support for the conclusion.
Exploring the feasibility of incorporating lymph node dissection into the evaluation criteria for textbook outcomes.
Supplementary Information
The online version contains supplementary material available at https://doi.org/10.1186/s12876-026-05090-z.
Introduction
Intrahepatic cholangiocarcinomais (ICC) an aggressive malignancy that is typically associated with a poor prognosis [1]. Its incidence has increased in recent years [2, 3]. Among available treatment options, surgical resection remains the only potentially curative approach, but it is suitable for only 20%-30% of diagnosed patients [4]. Although long-term prognosis remains a major concern, increasing attention has also been paid to the quality of surgical care and short-term postoperative outcomes [5, 6]. Contemporary clinical assessments predominantly rely on individual postoperative indicators, such as complication rates, mortality, and length of hospital stay. However, these isolated indicators may not fully reflect the overall quality of the surgical procedure [7, 8]. In this context, textbook outcome (TO) has emerged as a composite measure that provides a more comprehensive assessment of surgical quality [9].
For patients with ICC, the significance of lymph node dissection (LND) should not be underestimated [10]. Most contemporary guidelines recommend routine LND in the management of ICC [11, 12]. In addition to its potential impact on postoperative survival, standardized LND has important implications for accurate tumor staging and subsequent decisions regarding adjuvant therapy [13]. Therefore, LND is an important component of standard surgical management. TO is a comprehensive metric that evaluates healthcare quality by incorporating parameters such as negative surgical margins, avoidance of perioperative blood transfusion, absence of postoperative complications, optimized length of hospital stay, no 30-day postoperative mortality, and no readmission within 30 days after discharge. Because these criteria reflect essential surgical principles, achieving TO is generally considered to indicate better surgical quality and prognosis. Previous studies have shown that LND may increase the incidence of surgical complications, prolong operative time, and extend hospital stay [14, 15]. These factors may reduce the rate of TO achievement, even if they do not necessarily improve survival.
Although numerous studies have investigated the application of TO in ICC [8], the impact of LND on TO achievement and prognosis remains unclear. Some investigators have proposed incorporating LND into TO assessment criteria [16]. However, a comprehensive analysis validating this proposal is still lacking. In the present study, we used a random forest algorithm to explore the relationship between LND and TO. We further analyzed the impact of LND on TO achievement and prognosis, and finally assessed the rationale for including LND in the evaluation criteria for TO.
Materials and methods
Patients and data collection
The study was reviewed and approved by the Ethics Committee of the Mengchao Hepatobiliary Hospital of Fujian Medical University, and exempts the requirement of written informed consent (Approval No. 2024_041_01). All relevant procedures were performed in accordance with the World Medical Association Declaration of Helsinki.
Relevant data were from patients treated in 4 large-scale Grade A tertiary hospitals in China from 2011 to 2017, including Mengchao Hepatobiliary Hospital of Fujian Medical University, Eastern Hepatobiliary Surgery Hospital, Affiliated Second Hospital of Zhejiang University, Affiliated Hospital of Chuanbei Medical University.
Patients with ICC confirmed by postoperative pathology were included in this study. We evaluated patients with adequate liver reserve and recommended for hepatectomy according to the Barcelona Clinic Liver Cancer (BCLC) staging system. The inclusion criteria were as follows: (1) pathologically confirmed ICC after surgery; and (2) primary ICC treated with initial surgical resection. The exclusion criteria were as follows: (1) receipt of other antitumor treatments before surgery; (2) missing clinical data; and (3) loss to follow-up immediately after discharge. Finally, a total of 376 patients were included.
Follow‑up
According to standard follow-up procedures, the patients were followed up every 3 months for the first 2 years, and then every 3–6 months. During follow-up, routine monitoring included medical record collection, blood test, and imaging. The time between the date of surgery and death for any reason or the last follow-up was defined as overall survival (OS).
Textbook outcome
Textbook outcome (TO) in this analysis was defined according to the following parameters: negative surgical margins, no perioperative blood transfusion, no postoperative complications, no prolonged length of stay (LOS ≤ the 50th percentile of the total cohort), no readmission within 30 days after discharge, and no postoperative death within 30 days. Tumor margins were classified as microscopically negative (R0) or microscopically positive (R1). A positive margin (R1) was defined as a margin width of less than 1 mm or tumor involvement of the margin. Perioperative blood transfusion was defined as blood transfusion during or after surgery. Readmission was defined as admission to any hospital within 30 days after discharge. Mortality was defined as death within 30 days after primary surgery. Patients who met all expected outcomes were considered to have achieved TO.
Adjusted textbook outcome
Patients who met the above criteria and underwent LND were considered to have achieved adjusted TO; otherwise, they were considered not to have achieved adjusted TO.
Surgical procedure and lymph node dissection
During the study period, the indications for laparoscopic surgery, the decision to perform lymph node dissection (LND), surgical techniques, and operative strategies varied across participating centers and were mainly determined by the experience and judgment of the operating surgeons. Both major and minor hepatectomies were included. Non-anatomical liver resection was defined as wedge resection, local resection, or tumor enucleation. Anatomical liver resection was defined as hepatectomy performed after prior control of the first- and/or second-order Glissonean pedicles at the hepatic hilum.
In this study, routine LND was defined as the intentional removal of regional lymphatic tissue from the hepatic hilum to the hepatoduodenal ligament. The mandatory dissection field included the perihilar lymph nodes and lymph nodes within the hepatoduodenal ligament, corresponding mainly to station 12 lymph nodes, including nodes along the proper hepatic artery, portal vein, and common bile duct. Lymph nodes beyond this field, such as common hepatic artery, retropancreatic, or para-aortic lymph nodes, were not routinely required and were removed only when clinically suspicious or technically indicated. Because of the retrospective and multicenter nature of this study, routine LND was defined according to the anatomical dissection field rather than a fixed minimum number of harvested lymph nodes. The actual number of retrieved lymph nodes was recorded based on the pathological report.
Statistical analysis
Propensity score matching was performed to reduce potential baseline imbalance between the LND and non-LND groups. The propensity score was estimated using a logistic regression model including age, sex, Eastern Cooperative Oncology Group performance status, Child-Pugh grade, tumor size, tumor number, carbohydrate antigen 19 − 9, alpha-fetoprotein, carcinoembryonic antigen, total bilirubin, direct bilirubin, tumor differentiation, microvascular invasion, perineural invasion, and postoperative adjuvant therapy. Patients in the LND group were matched with those in the non-LND group using 1:1 nearest-neighbor matching with a caliper value of 0.2.
Variable importance is calculated by the random forest algorithm to determine the significance of each feature variable in classification, enabling the selection of highly correlated variables for modeling. The “importance” function in the randomForest package in R can be used to compute variable importance. The Kaplan Meier method was used to assess OS estimates for the entire study population from the date of surgery to the date of last follow-up or death; Differences in survival were assessed by logarithmic rank test. The Mann–Whitney U test was used to compare continuous variables, and chi-square or Fisher’s exact test were used to compare categorical variables. All data analyses were performed by R software (version4.1.0, http://www.r-project.org).
Results
Baseline characteristics of patients
A cohort of 376 patients was subjected to the analysis, with their baseline characteristics delineated in Table 1. Among these patients, males constituted a majority at 64.36%, and the most of patients are aged 50 years and above. In total, 133 patients (35.37%) tested positive for hepatitis B surface antigen. The prevalent ECOG (Eastern Cooperative Oncology Group) score ranged score 1. Lymph node dissection (LND) was executed in 116 patients. Post-surgical adjuvant therapy was opted for by a minority, accounting for 20.21%.
Table 1.
Baseline characteristics of patients
| level | Overall | |
|---|---|---|
| n | 376 | |
| Sex(%) | Male | 242 (64.36) |
| Female | 134 (35.64) | |
| Age(%) | ≤ 50 years | 170 (45.21) |
| > 50years | 206 (54.79) | |
| Hepatitis B (%) | Negative | 243 (64.63) |
| Positive | 133 (35.37) | |
| ECOG Score (%) | 0 | 117 (31.12) |
| 1 | 259 (68.88) | |
| Child-Pugh (%) | A | 232 (61.70) |
| B | 144 (38.30) | |
| Tumor size (%) | ≤ 5 cm | 124 (32.98) |
| > 5 cm | 252 (67.02) | |
| Tunmor number(%) | 1 | 258 (68.62) |
| > 1 | 118 (31.38) | |
| CA19-9 (%) | ≤ 200 ng/mL | 322 (85.64) |
| > 200 ng/mL | 54 (14.36) | |
| AFP (%) | ≤ 20 ng/mL | 208 (55.32) |
| > 20 ng/mL | 168 (44.68) | |
| CEA (%) | ≤ 5 ng/mL | 302 (80.32) |
| > 5 ng/mL | 74 (19.68) | |
| Surgical modalities (%) | Anatomic excision | 133 (35.37) |
| Non-anatomical excision | 243 (64.63) | |
| Lymph node dissection (%) | No | 260 (69.15) |
| Yes | 116 (30.85) | |
| Tumor differentiation (%) | Moderate + well | 306 (81.38) |
| Poor | 70 (18.62) | |
| Microvascular invasion (%) | No | 318 (84.57) |
| Yes | 58 (15.43) | |
| Perineural invasion (%) | No | 338 (89.89) |
| Yes | 38 (10.11) | |
| Total bilirubin (%) | ≤ 20µmol/L | 195 (51.86) |
| > 20µmol/L | 181 (48.14) | |
| Direct bilirubin (%) | ≤ 12µmol/L | 259 (68.88) |
| > 12µmol/L | 117 (31.12) | |
| Intraoperative bleeding (%) | ≤ 400mL | 301 (80.05) |
| 400mL-800mL | 56 (14.89) | |
| > 800mL | 19 (5.05) | |
| Adjuvant therapy (%) | No | 300 (79.79) |
| Yes | 76 (20.21) |
ECOG score Eastern Cooperative Oncology Group score, TBIL Total Bilirubin, DBIL Direct Bilirubin, CA19-9 Carbohydrate antigen 19 − 9, AFP Alpha-Fetoprotein, CEA Carcinoembryonic antigen
Risk factors affecting the occurrence of TO
To elucidate the influence of LND on textbook outcomes, we identified 18 factors, LND included. The random forest algorithm was used to analyze the impact of various factors on TO, and the results revealed that LND has a significant influence on achieving TO (Fig. 1). In the entire cohort, 132 patients (35.1%) experienced an extended length of hospital stay. Perioperative blood transfusions were deemed necessary for 12.5%, while an overwhelming 95.21% attained R0 resection. Notably, 3.19% of patients faced either perioperative mortality or were readmitted within a span of 30 days post-surgery, as depicted in Table 2. Statistically significant differences were observed between the LND group and the non-LND group in terms of patient surgical margin status, incidence of complications, and length of hospital stay. Therefore, we further analyzed the impact of hospital stay and complications on survival. The results showed that patients without prolonged hospital stay had better overall survival (OS) and Disease-free survival (DFS) compared to those with prolonged hospital stay. Similarly, patients without postoperative complications showed a trend toward better OS, although the difference was not statistically significant, whereas DFS was significantly better in patients without complications (Fig. 2).
Fig. 1.
Impact of various factors on Textbook outcome (TO) according to random forest analysis. AFP, alpha-fetoprotein; CA19-9, carbohydrate antigen 19 − 9; CEA, carcinoembryonic antigen; DBIL, direct bilirubin; ECOG, Eastern Cooperative Oncology Group performance status; LND, lymph node dissection; MVI, microvascular invasion; TBIL, total bilirubin; Child-Pugh, Child-Pugh classification
Table 2.
Textbook outcome related variables
| level | Overall | Non-LND | LND | p | |
|---|---|---|---|---|---|
| n | 376 | 260 | 116 | ||
| Perioperative blood transfusions (%) | No | 329 (87.50) | 227 (87.31) | 102 (87.93) | 1 |
| Yes | 47 (12.50) | 33 (12.69) | 14 (12.07) | ||
| Surgical margin(%) | Negative | 358 (95.21) | 255 (98.08) | 103 (88.79) | 0.0003 |
| Postive | 18 (4.79) | 5 (1.92) | 13 (11.21) | ||
| Postoperative complications (%) | No | 297 (78.99) | 219 (84.23) | 78 (67.24) | 0.0003 |
| Yes | 79 (21.01) | 41 (15.77) | 38 (32.76) | ||
| Postoperative death or readmissions within 30-day(%) | No | 364 (96.81) | 251 (96.54) | 113 (97.41) | 0.8978 |
| Yes | 12 (3.19) | 9 (3.46) | 3 (2.59) | ||
| Prolonged length of stay (%) | No | 244 (64.89) | 195 (75.00) | 49 (42.24) | < 0.0001 |
| Yes | 132 (35.11) | 65 (25.00) | 67 (57.76) |
Fig. 2.
Overall survival (OS) and Disease free survival (DFS) of patients stratified by prolonged hospital stay and postoperative complications. A OS of patients with and without prolonged hospital stay. B DFS of patients with and without prolonged hospital stay. C OS of patients with and without complications. D DFS of patients with and without complications
Factors influencing TO in patients undergoing LND
A total of 116 patients with LND were screened. Multivariate logistic regression analysis showed that Carbohydrate antigen 19 − 9 (CA19-9) > 200 ng/mL was the influencing factor of TO in patients with LND (Supplement Table 1). Therefore, we performed survival analysis again, dividing the patients into subgroups based on their CA19-9 levels. The results showed that there was no significant difference in OS between patients with CA19-9 levels above 200 ng/mL and those with CA19-9 levels below 200 ng/mL (Supplement Fig. 1). These results suggest that although CA19-9 may be related to TO achievement among patients undergoing LND, CA19-9 stratification alone does not identify a subgroup with a clear survival difference.
Construction of the adjusted textbook outcomes
We integrated lymph node dissection as a criterion within the textbook outcome assessment, termed as the adjusted textbook outcome. All patients has completed postoperative follow-up. The median follow-up time was 19 months, with a range of 1 to 74 months. The achievement rate of the TO was 52.9%, and the achievement rate of the adjusted-TO decreased to 20.5%. In the adjusted-TO group, except for the increase of patients with negative margin, the number of patients with other evaluation indicators decreased (Fig. 3). To minimize the effect of baseline errors on survival analyses, we performed Propensity Score Matching on the data set (Supplement Table 2). Lastly, a survival analysis based on the adjusted textbook outcome was carried out (Fig. 4A-B). The findings indicated differential survival rates among patients categorized under the adjusted textbook outcome without lymph node metastasis, the adjusted textbook outcome with lymph node metastasis, and those outside of the adjusted textbook outcome parameters. Incorporating LND into the TO framework may provide a complementary perspective by integrating perioperative safety with oncologic adequacy. Nevertheless, adjusted TO should be regarded as an exploratory concept rather than a definitive evaluation standard. Further prospective studies are required to validate its stability and clinical applicability across different tumor stages, surgical procedures, and lymph node dissection strategies.
Fig. 3.
Characteristics of patients who achieved textbook outcome (TO) and adjusted TO
Fig. 4.
Comparison of overall survival among patients according to adjusted textbook outcome status. A One-year overall survival among patients with adjusted TO without lymph node metastasis, adjusted TO with lymph node metastasis, and those outside the adjusted TO group. B Five-year overall survival among patients with adjusted TO without lymph node metastasis, adjusted TO with lymph node metastasis, and those outside the adjusted TO group
Discussion
ICC represents a less frequent yet lethal condition [1]. Surgical resection remains a major therapeutic strategy for ICC [17]. In recent decades, the role of LND in ICC treatment has received increasing attention [18–20]. Previous studies have suggested that LND may increase the risk of complications, prolong operative time, and extend hospitalization [10, 21], thereby making TO achievement more challenging. Based on machine learning interpretability [22], we used a random forest algorithm to confirm that LND was an important factor associated with TO achievement. However, the potential influence of LND on prognosis and its relevance to tumor staging should also be considered [23, 24] .
In this study, patients in the LND group had a higher incidence of complications, a longer hospital stay, and more positive surgical margins. These findings indicate that LND was associated with a lower likelihood of achieving TO in the present cohort. However, this association should be interpreted with caution. Because this was a retrospective study, patients who underwent LND may have had more advanced disease, a higher suspected risk of lymph node metastasis, or more complex surgical conditions. Additionally, margin status and postoperative complications are closely associated with OS and DFS, which is consistent with previous studies [25, 26]. Miyata et al. [27] identified postoperative complications as a risk factor for postoperative survival in patients with ICC; however, these complications were not associated with disease-free survival. After propensity score matching, a multicenter study by Bagante et al. [28] suggested that patients with cirrhosis were more susceptible to complications after LND. Moreover, Littau et al. [29] reported that negative margins were associated with improved overall survival. Postoperative recovery may influence the selection of adjuvant therapy, which is closely related to lymph node status and tumor staging. In conclusion, complications and prolonged hospital stay may affect OS and DFS, but this does not necessarily mean that LND is directly responsible for these outcomes. LND remains important for accurate nodal staging and may guide postoperative treatment decisions [24]. Therefore, the importance of LND in ICC should not be denied.
Further subgroup analysis showed that, among patients undergoing LND, CA19-9 > 200 ng/mL was associated with a lower likelihood of achieving TO. However, survival analysis demonstrated that CA19-9 levels did not significantly affect long-term survival. Previous studieshave suggested that elevated CA19-9 levels may be associated with lymph node metastasis (LNM) [30, 31]. In our analysis, however, no statistically significant difference in prognosis was observed between patients undergoing LND when stratified by CA19-9 levels. Accordingly, CA19-9 should not be used alone to define the population that may benefit from LND. The clinical value of LND should be evaluated using more comprehensive information, including radiological lymph node status, pathological nodal status, tumor burden, extent of lymph node dissection, number of harvested lymph nodes, postoperative treatment, and long-term survival outcomes [32]. Future prospective studies are needed to determine whether specific subgroups of ICC patients may derive greater benefit from LND.
Given the distinctive characteristics of LNM in ICC, as well as the recommendations of the 8th edition of the AJCC guidelines and the NCCN Clinical Practice Guidelines [33, 34], we support the inclusion of LND in TO assessment criteria. TO is an important benchmark of medical quality. However, the criteria used to define TO may vary slightly according to cancer type [41]. Previous studies have confirmed the ability of TO to evaluate short-term postoperative outcomes and its association with long-term prognosis [16, 35]. The main innovation of this study is the incorporation of lymph node dissection LND into the TO framework to establish an adjusted TO for ICC. While conventional TO primarily reflects short-term perioperative quality, adjusted TO integrates both perioperative safety and oncologic adequacy by considering nodal assessment, which is important for tumor staging, prognostic evaluation, and postoperative treatment planning. Therefore, adjusted TO may provide a more comprehensive evaluation of surgical quality, particularly for patients undergoing curative-intent resection in whom lymph node status has clinical relevance [36]. However, adjusted TO should be regarded as a complementary measure rather than a replacement for conventional TO and may be most applicable to resectable ICC patients suitable for curative surgery. Several limitations should be acknowledged, including the retrospective study design, lack of standardized LND practices across centers, incomplete consideration of LND extent and nodal yield, and the possibility that incorporating LND may lower TO achievement rates in patients for whom LND was not clinically indicated. Consequently, adjusted TO should be interpreted within the context of individualized surgical decision-making and requires further external validation.
This study has several limitations. First, because of its retrospective design, inherent selection bias may be present. Second, although the data were derived from multiple centers in China, the sample size should be expanded, and the incorporation of international multicenter data would enhance the credibility and generalizability of the findings. Third, although this study supports the inclusion of LND in TO evaluation, data limitations prevented further analysis of specific factors such as the number and anatomical stations of dissected lymph nodes. Future studies should address these issues. Furthermore, failure to achieve TO does not necessarily indicate poor surgical quality or worse survival. Advances in adjuvant treatments may improve survival outcomes for a broader patient population.
In summary, accumulating evidence underscores the importance of LND in surgery for ICC. TO is a useful metric for evaluating surgical quality and predicting survival. Incorporating LND into the evaluation criteria for TO may enhance its clinical relevance.
Conclusions
LND may reduce the rate of achieving TO. However, considering its potential value for long-term survival and postoperative treatment planning, the significance of LND should not be disregarded. Including LND in the evaluation criteria for TO may help stratify patient prognosis and inform subsequent treatment strategies.
Supplementary Information
Acknowledgements
Not applicable.
Authors’ contributions
Jiangtao Li, Jindong Li, Weipin Zhou and Yongyi Zeng supervised the data collection. Cong Luo, Yongyi Zeng, Tingfeng Huang and Shichuan Tang contributed to the study conception and design. Cong Luo, Ruilin Fan and Heqiang Xu contributed to analysis and interpretation of data. Yongyi Zeng, Tingfeng Huang drafting the manuscript. Yongyi Zeng contributed to revising the article, critical revision, and final approval.
Funding
This study was supported by the Research on the mechanisms underlying cystic dilatation of the bile ducts (TCKY-202401); National Key Research and Development Program (2022YFC2407304); Major Research Project for Middle-Aged and Young Scientists of Fujian Provincial Health Commission(2021ZQNZD013); The National Natural Science Foundation of China (General Program:62275050); Fujian Province Science and Technology Innovation Joint Fund Project(2019Y9108); Major Science and Technology Projects of Fujian Province (2021YZ036017); key Clinical Specialty Discipline Construction Program of Fuzhou (20230101). The funding bodies had no role in the study design, data collection and analysis, interpretation, or in writing the manuscript.
Data availability
The datasets used and analysed during the current study are available from the corresponding author on reasonable request.
Declarations
Ethics approval and consent to participate
The study was reviewed and approved by the Ethics Committee of the Mengchao Hepatobiliary Hospital of Fujian Medical University, and exempts the requirement of written informed consent (Approval No. 2024_041_01). All relevant procedures were performed in accordance with the World Medical Association Declaration of Helsinki.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Cong Luo, Heqiang Xu and Tingfeng Huang are co-first-authors.
Contributor Information
Shichuan Tang, Email: doctortang2022@163.com.
Yongyi Zeng, Email: lampl97311@126.com.
References
- 1.Blechacz B, Cholangiocarcinoma. Current Knowledge and New Developments. Gut Liver. 2017;11(1):13–26. 10.5009/gnl15568. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Saha SK, Zhu AX, Fuchs CS, Brooks GA. Forty-Year Trends in Cholangiocarcinoma Incidence in the U.S.: Intrahepatic Disease on the Rise. Oncologist. 2016;21(5):594–9. 10.1634/theoncologist.2015-0446. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Han B, Zheng R, Zeng H, et al. Cancer incidence and mortality in China, 2022. J Natl Cancer Cent. 2024;4(1):47–53. 10.1016/j.jncc.2024.01.006. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Moris D, Palta M, Kim C, Allen PJ, Morse MA, Lidsky ME. Advances in the treatment of intrahepatic cholangiocarcinoma: An overview of the current and future therapeutic landscape for clinicians. CA Cancer J Clin. 2023;73(2):198–222. 10.3322/caac.21759. [DOI] [PubMed] [Google Scholar]
- 5.Wang SY, Diao YK, Yang YZ, et al. Development and validation of an individualized online calculator for early mortality risk after hepatectomy among patients with hepatocellular carcinoma. iLIVER. 2025;4(4):100201. 10.1016/j.iliver.2025.100201. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Dijs-Elsinga J, Otten W, Versluijs MM, et al. Choosing a hospital for surgery: the importance of information on quality of care. Med Decis Mak. 2010;30(5):544–55. 10.1177/0272989X09357474. [DOI] [PubMed] [Google Scholar]
- 7.Dimick JB, Welch HG, Birkmeyer JD. Surgical mortality as an indicator of hospital quality: the problem with small sample size. JAMA. 2004;292(7):847–51. 10.1001/jama.292.7.847. [DOI] [PubMed] [Google Scholar]
- 8.Harrison TG, Ronksley PE, James MT, et al. The Perioperative Surgical Home, Enhanced Recovery After Surgery and how integration of these models may improve care for medically complex patients. Can J Surg. 2021;64(4):E381–90. 10.1503/cjs.002020. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Merath K, Chen Q, Bagante F, et al. A Multi-institutional International Analysis of Textbook Outcomes Among Patients Undergoing Curative-Intent Resection of Intrahepatic Cholangiocarcinoma. JAMA Surg. 2019;154(6):e190571. 10.1001/jamasurg.2019.0571. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Zhang XF, Xue F, Dong DH, et al. Number and Station of Lymph Node Metastasis After Curative-intent Resection of Intrahepatic Cholangiocarcinoma Impact Prognosis. Ann Surg. 2021;274(6):e1187–95. 10.1097/SLA.0000000000003788. [DOI] [PubMed] [Google Scholar]
- 11.Bridgewater J, Galle PR, Khan SA, et al. Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma. J Hepatol. 2014;60(6):1268–89. 10.1016/j.jhep.2014.01.021. [DOI] [PubMed] [Google Scholar]
- 12.Wu J, Lu AD, Zhang LP, Zuo YX, Jia YP. [Study of clinical outcome and prognosis in pediatric core binding factor-acute myeloid leukemia]. Zhonghua Xue Ye Xue Za Zhi. 2019;40(1):52–7. 10.3760/cma.j.issn.0253-2727.2019.01.010. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Sposito C, Ratti F, Cucchetti A, et al. Survival benefit of adequate lymphadenectomy in patients undergoing liver resection for clinically node-negative intrahepatic cholangiocarcinoma. J Hepatol. 2023;78(2):356–63. 10.1016/j.jhep.2022.10.021. [DOI] [PubMed] [Google Scholar]
- 14.Kim DH, Choi DW, Choi SH, Heo JS, Kow AWC. Is there a role for systematic hepatic pedicle lymphadenectomy in intrahepatic cholangiocarcinoma? A review of 17 years of experience in a tertiary institution. Surgery. 2015;157(4):666–75. 10.1016/j.surg.2014.11.006. [DOI] [PubMed] [Google Scholar]
- 15.Zhou R, Lu D, Li W, et al. Is lymph node dissection necessary for resectable intrahepatic cholangiocarcinoma? A systematic review and meta-analysis. HPB (Oxford). 2019;21(7):784–92. 10.1016/j.hpb.2018.12.011. [DOI] [PubMed] [Google Scholar]
- 16.Hobeika C, Cauchy F, Fuks D, et al. Laparoscopic versus open resection of intrahepatic cholangiocarcinoma: nationwide analysis. Br J Surg. 2021;108(4):419–26. 10.1093/bjs/znaa110. [DOI] [PubMed] [Google Scholar]
- 17.Moris D, Palta M, Kim C, Allen PJ, Morse MA, Lidsky ME. Advances in the treatment of intrahepatic cholangiocarcinoma: An overview of the current and future therapeutic landscape for clinicians. CA Cancer J Clin. 2023;73(2):198–222. 10.3322/caac.21759. [DOI] [PubMed] [Google Scholar]
- 18.Kim SH, Han DH, Choi GH, Choi JS, Kim KS. Extent of Lymph Node Dissection for Accurate Staging in Intrahepatic Cholangiocarcinoma. J Gastrointest Surg. 2022;26(1):70–6. 10.1007/s11605-021-05039-5. [DOI] [PubMed] [Google Scholar]
- 19.Zhu J, Liu C, Li H, et al. Adequate lymph node dissection is essential for accurate nodal staging in intrahepatic cholangiocarcinoma: A population-based study. Cancer Med. 2023;12(7):8184–98. 10.1002/cam4.5620. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Kim SH, Han DH, Choi GH, Choi JS, Kim KS. Prognostic impact of the metastatic lymph node number in intrahepatic cholangiocarcinoma. Surgery. 2022;172(1):177–83. 10.1016/j.surg.2021.12.026. [DOI] [PubMed] [Google Scholar]
- 21.Spolverato G, Yakoob MY, Kim Y, et al. Impact of complications on long-term survival after resection of intrahepatic cholangiocarcinoma. Cancer. 2015;121(16):2730–9. 10.1002/cncr.29419. [DOI] [PubMed] [Google Scholar]
- 22.Wang X, Yang J, Zhou B, Tang L, Liang Y. Integrating mixed reality, augmented reality, and artificial intelligence in complex liver surgeries: Enhancing precision, safety, and outcomes. ILIVER. 2025;4(2):100167. 10.1016/j.iliver.2025.100167. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Chen C, Su J, Wu H, et al. Prognostic value of lymphadenectomy in node-negative intrahepatic cholangiocarcinoma: A multicenter, retrospectively study. Eur J Surg Oncol. 2023;49(4):780–7. 10.1016/j.ejso.2022.11.008. [DOI] [PubMed] [Google Scholar]
- 24.Ratti F, Cipriani F, Ingallinella S, Tudisco A, Catena M, Aldrighetti L. Robotic Approach for Lymphadenectomy in Biliary Tumors: The Missing Ring Between the Benefits of Laparoscopic and Reproducibility of Open Approach? Ann Surg. 2023;278(4):e780–8. 10.1097/SLA.0000000000005748. [DOI] [PubMed] [Google Scholar]
- 25.Wang H, Liu W, Tian M, et al. Coagulopathy associated with poor prognosis in intrahepatic cholangiocarcinoma patients after curative resection. Biosci Trends. 2017;11(4):469–74. 10.5582/bst.2017.01080. [DOI] [PubMed] [Google Scholar]
- 26.Adhoute X, Pietri O, Pénaranda G, et al. Intrahepatic Cholangiocarcinoma and Hepatocellular Carcinoma: Real-life Data on Liver Disease, Treatment and Prognosis. J Clin Transl Hepatol. 2023;11(5):1106–17. 10.14218/JCTH.2022.00141. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Miyata T, Yamashita YI, Yamao T, et al. Prognostic impacts of postoperative complications in patients with intrahepatic cholangiocarcinoma after curative operations. Int J Clin Oncol. 2017;22(3):526–32. 10.1007/s10147-017-1099-9. [DOI] [PubMed] [Google Scholar]
- 28.Bagante F, Spolverato G, Weiss M, et al. Surgical Management of Intrahepatic Cholangiocarcinoma in Patients with Cirrhosis: Impact of Lymphadenectomy on Peri-Operative Outcomes. World J Surg. 2018;42(8):2551–60. 10.1007/s00268-017-4453-1. [DOI] [PubMed] [Google Scholar]
- 29.Littau MJ, Kim P, Kulshrestha S, et al. Resectable intrahepatic and hilar cholangiocarcinoma: Is margin status associated with survival? Surgery. 2022;171(3):703–10. 10.1016/j.surg.2021.09.038. [DOI] [PubMed] [Google Scholar]
- 30.Lluís N, Asbun D, Wang JJ, et al. Lymph Node Dissection in Intrahepatic Cholangiocarcinoma: a Critical and Updated Review of the Literature. J Gastrointest Surg. 2023;27(12):3001–13. 10.1007/s11605-023-05696-8. [DOI] [PubMed] [Google Scholar]
- 31.Rhee H, Lim HJ, Han K, et al. A preoperative scoring system to predict lymph node metastasis in intrahepatic cholangiocarcinoma. Hepatol Int. 2023;17(4):942–53. 10.1007/s12072-022-10477-7. [DOI] [PubMed] [Google Scholar]
- 32.Jang HJ, Kim DH, Choi SH, et al. Preoperative Prediction of Microvascular Invasion in Intrahepatic Cholangiocarcinoma and Its Prognostic Implications: A Multicenter Study. Liver Cancer. 2026;15(1):63–76. 10.1159/000547071. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33.Amin MB, Greene FL, Edge SB, et al. The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more personalized approach to cancer staging. CA Cancer J Clin. 2017;67(2):93–9. 10.3322/caac.21388. [DOI] [PubMed] [Google Scholar]
- 34.Benson AB, D’Angelica MI, Abbott DE, et al. Hepatobiliary Cancers, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2021;19(5):541–65. 10.6004/jnccn.2021.0022. [DOI] [PubMed] [Google Scholar]
- 35.Brustia R, Laurent A, Goumard C, et al. Laparoscopic versus open liver resection for intrahepatic cholangiocarcinoma: Report of an international multicenter cohort study with propensity score matching. Surgery. 2022;171(5):1290–302. 10.1016/j.surg.2021.08.015. [DOI] [PubMed] [Google Scholar]
- 36.Li J, Liang YB, Chen XM, et al. Prognostic value of lymphatic vessel density in the capsule of early-stage hepatocellular carcinoma: implications for postoperative recurrence risk. Front Immunol. 2026;17:1714314. 10.3389/fimmu.2026.1714314. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The datasets used and analysed during the current study are available from the corresponding author on reasonable request.