Association Between Harvesting at Least 15 Lymph Nodes and Survival in Resected Pancreatic Cancer Using a Nationwide Database

Association Between Harvesting at Least 15 Lymph Nodes and Survival in Resected Pancreatic Cancer Using a Nationwide Database | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Association Between Harvesting at Least 15 Lymph Nodes and Survival in Resected Pancreatic Cancer Using a Nationwide Database Chia-Jen Tsai, Pei-Yi Lin, Khaa-Hoo Ong, Chung-Han Ho, Yi-Chen Chen, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8496148/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Introduction Surgical resection plays a pivotal role in the management of pancreatic cancer by achieving complete tumor removal and regional lymphadenectomy. Although most clinical guidelines recommend examining at least 15 lymph nodes (LNY ≥ 15) for accurate staging and better prognostic assessment, the optimal threshold remains uncertain and requires validation across population-based datasets. Methods Using the Taiwan Cancer Registry and National Health Insurance Research Database, 926 patients with pancreatic adenocarcinoma who underwent curative resection between 2013 and 2019 were identified. Cox proportional hazards regression models were used to evaluate the association between lymph node yield (LNY ≥ 15 vs. <15) and overall survival (OS), adjusting for potential confounders. Several sensitivity analyses were performed to assess the robustness of the findings, including a subgroup analysis restricted to patients with pT1–3 pancreatic head tumors who underwent pancreatoduodenectomy. Stratified analyses were additionally performed according to pathological T and N classifications and treatment modalities. Results The median lymph node yield (LNY) was 15, with 496 (53.6%) patients having ≥ 15 nodes retrieved. Patients with adequate LNY were more likely to have tumors in the pancreatic head, undergo pancreatoduodenectomy, and present with advanced pT/N stages and more positive nodes. Although no significant difference in 3-year overall survival (OS) was observed between the ≥ 15 and < 15 groups, a survival benefit appeared in patients with pT1–3 head tumors treated with pancreatoduodenectomy. After adjustment for confounders, multivariable analysis showed that LNY ≥ 15 was not significantly associated with improved 1-year or 3-year OS in the overall cohort or subgroups. Stratified analyses by AJCC stage and treatment revealed no consistent survival advantage, except for patients with pT1–2 disease who demonstrated better 1-year OS. Conclusions: A lymph node yield of ≥ 15 was not independently associated with improved long-term survival in this cohort. Further large-scale studies are warranted to determine the optimal lymph node threshold for accurate prognostic stratification in pancreatic cancer. Biological sciences/Cancer Health sciences/Gastroenterology Health sciences/Oncology pancreatic cancer surgery stage lymph node yield survival Figures Figure 1 Figure 2 Figure 3 1.Introduction Pancreatic cancer remains one of the most aggressive and lethal malignancies, with an estimated 5-year overall survival rate of approximately 5%. 1 The poor prognosis is largely attributed to the fact that the majority of patients present with either distant metastases or locally advanced disease at the time of diagnosis, rendering them unsuitable for curative surgical intervention. 2 Pancreatic ductal adenocarcinoma (PDAC), the predominant histological subtype, exhibits a particularly aggressive biological behavior and high propensity for early local invasion and distant spread. Surgical resection, therefore, represents the cornerstone and only potentially curative treatment modality, offering the best opportunity for durable local control and prolonged survival. Patients who undergo complete resection followed by adjuvant therapy can achieve a 5-year survival rate ranging from 15% to 25%. 3 However, only approximately 20% of patients present with resectable disease at diagnosis, highlighting the urgent need for improved strategies in early detection, surgical selection, and multimodal management to enhance long-term outcomes. Among patients who undergo curative-intent surgery, several clinicopathological factors influence recurrence and survival outcomes. Established prognostic indicators include postoperative serum CA 19 − 9 levels, tumor size, pathological stage, resection margin status, and lymph node involvement. 4 Complete (R0) resection is paramount, as microscopically negative margins are strongly associated with improved local control and long-term survival. In addition, the extent of lymph node dissection and the number of nodes retrieved have emerged as critical indicators of surgical quality and prognostic precision. The total number of lymph nodes examined reflects both the thoroughness of surgical clearance and the adequacy of pathological evaluation, thereby influencing staging accuracy and decisions regarding adjuvant therapy. In other malignancies, such as colorectal and gastric cancer, clinical guidelines recommend harvesting a minimum of 12 and 16 lymph nodes, respectively, for reliable staging. 5 , 6 However, in pancreatic cancer, the optimal lymph node yield for accurate prognostication and quality benchmarking remains a subject of ongoing debate, warranting further investigation. Several expert consensus groups and professional organizations have proposed recommendations for adequate lymph node evaluation in pancreatic cancer. The International Study Group on Pancreatic Surgery (ISGPS) recommends that a standard lymphadenectomy should yield at least 15 lymph nodes to ensure accurate pathological staging. 7 Similarly, the College of American Pathologists (CAP) protocol for pancreatic carcinoma specifies that a minimum of 12 lymph nodes should be examined following pancreatoduodenectomy. 8 The American Joint Committee on Cancer (AJCC) Cancer Staging Manual, 8th Edition, adopts the same threshold to improve nodal staging accuracy, particularly in distinguishing N0 disease. 9 Furthermore, the National Comprehensive Cancer Network (NCCN) guidelines recommend evaluating between 11 and 17 lymph nodes for optimal staging reliability. 10 Consistent with these recommendations, previous studies have proposed a range of adequate lymph node yields, generally between 10 and 21 nodes. 11 – 14 Despite these variations, most evidence and consensus statements converge on a threshold of approximately 15 lymph nodes as the benchmark for adequate lymphadenectomy, serving as an important indicator of surgical and pathological quality in pancreatic cancer management. 13 , 14 The prognostic impact of the number of lymph nodes examined in resected pancreatic cancer remains inconclusive. While inadequate lymph node retrieval may lead to pathological understaging and suboptimal adjuvant treatment decisions, studies have reported conflicting results—some demonstrating improved survival with a higher number of examined nodes, particularly in pathologically node-negative cases whereas others found no significant correlation with overall survival. 15 – 18 These discrepancies may arise from variations in patient characteristics, tumor location, disease stage, and differences in multimodality treatment approaches, such as the use of preoperative chemotherapy or radiotherapy. To clarify these inconsistencies, we analyzed data from the National Taiwan Cancer Registry (TCR) to examine the association between lymph node yield and survival outcomes in patients who underwent curative-intent resection for pancreatic cancer. In particular, this study aimed to re-evaluate whether the commonly recommended threshold of 15 examined lymph nodes remains an appropriate standard, with particular attention to these potential confounding factors. 2.Materials and Methods 2.1Study Design and Participants The clinicopathological data of patients with pancreatic cancer were obtained from the Taiwan Cancer Registry (TCR) and the National Health Insurance Research Database (NHIRD). 19 Established in 1979, the TCR underwent substantial enhancements following the implementation of the Cancer Control Act in 2003. Since then, it has provided a highly comprehensive and reliable nationwide dataset, recognized for its excellent completeness and data quality, comparable to other leading national cancer registries. 20 – 22 Patients diagnosed with pancreatic cancer between January 2013 and December 2019 were identified from the Taiwan Cancer Registry using the International Classification of Diseases for Oncology, Third Edition (ICD-O-3) site codes C25.0, C25.1, C25.2, C25.3, C25.7, C25.8, and C25.9, and histology/behavior codes 8140, 8141, 8255, 8260, 8470, 8471, 8480, 8481, 8490, 8500, 8550, and 8560. Tumor staging was determined according to the 7th edition of the American Joint Committee on Cancer (AJCC) classification system. Follow-up was calculated from the date of pancreatic cancer diagnosis to December 31, 2021. The dataset included comprehensive clinicopathological variables such as age, sex, tumor location, histologic grade, surgical procedure, clinical/pathological stage, margin status, lymph node count, comorbidities, receipt of chemotherapy or radiotherapy, and personal habits. Comorbidity severity was assessed using the Charlson Comorbidity Index (CCI), as previously described. 23 , 24 Patients with incomplete coding, a prior malignancy, or evidence of metastatic disease were excluded. Finally, 926 patients who underwent curative-intent resection for pancreatic cancer were included in the final analysis (Fig. 1 ). 2.2Statistical Analysis This retrospective, population-based study investigated the impact of lymph node (LN) yield on survival among patients with resected pancreatic cancer, comparing groups with ≥ 15 and < 15 retrieved nodes. Overall survival (OS) probabilities were evaluated for patients with a minimum follow-up of 1 year and up to 3 years. Categorical variables were summarized as frequencies with percentages and compared between groups using Pearson’s chi-square test. Diagnosed age and the number of positive lymph node was expressed as the median with interquartile range (IQR) and compared using the Wilcoxon rank-sum test. Cox proportional hazard regression was performed to estimate the relative risk ratio of survival associated with LN yield (≥ 15 vs. <15), adjusted for all potential confounders. 25 The survival rate in the two groups over time was performed using the Kaplan–Meier method with a log-rank test to determine the differences. Several sensitivity analyses were performed to evaluate the robustness of the findings. Because LN yield may be influenced by tumor characteristics, anatomical location, and surgical procedure, a subgroup analysis was included as a sensitivity test. This analysis restricted patient with pT1–3 tumors located in the pancreatic head who underwent pancreatoduodenectomy, which minimize the residual bias. Additional stratified analyses were performed according to pathological T and N classifications and adjuvant treatment status. All statistical analyses were conducted using SAS software, version 9.4 (SAS Institute Inc., Cary, NC, USA) and Stata (15, StataCorp LLC, College Station, TX). A two-sided p-value of < 0.05 was considered statistically significant. 3.Results 3.1Clinicopathological Characteristics Clinicopathological characteristics of patients with resected pancreatic cancer are summarized in Table 1 . Between 2013 and 2019, a total of 926 patients were included, comprising 517 men (55.8%) and 409 women (44.2%). The median age at diagnosis was 64 years (Q1–Q3: 57–71), and the median follow-up duration was 1.30 years (Q1–Q3: 0.79–1.96). Tumors were most frequently located in the pancreatic head (67.9%), followed by the tail (13.3%), body (11.6%), and other sites (7.2%). Overall, 106 patients (11.4%) received neoadjuvant therapy, and 597 (64.5%) underwent adjuvant chemotherapy, with or without radiotherapy. The median number of examined lymph nodes (LNs) was 15 (Q1–Q3: 9–22). Of the entire cohort, 496 patients (53.6%) had ≥ 15 retrieved LNs, whereas 430 (46.4%) had < 15. Compared with patients who had fewer than 15 LNs examined, those with adequate LN yield (≥ 15) were more likely to have tumors located in the pancreatic head, to have undergone pancreatoduodenectomy, and to present with more advanced pathological T/N classifications, higher overall stage (IIB–III), and greater numbers of positive LNs. Table 1 Characteristics of patients with pancreatic cancer undergoing surgery between groups based on the number of LNs removed, n = 926 The number of LNs removed, n (%) < 15, n = 430 ≧ 15, n = 496 P -value Age, years Median (Q1-Q3) 65 (57–73) 64 (57–71) < 65 212 (49.30) 258 (52.02) 0.410 ≧ 65 218 (50.70) 238 (47.98) Sex 0.017 Male 258 (60.00) 259 (52.22) Female 172 (40.00) 237 (47.78) Location < .001 Head 292 (67.91) 417 (84.07) Body 50 (11.63) 27 (5.44) Tail 57 (13.26) 20 (4.03) Others 31 (7.21) 32 (6.45) Grade 0.195 Well 44 (10.23) 33 (6.65) Moderately 300 (69.77) 350 (70.56) Poorly 69 (16.05) 87 (17.54) Not stated 17 (3.95) 26 (5.24) Operation < .001 Pacreatoduodenectomy 313 (72.79) 429 (86.49) Distal pancreatectomy 103 (23.95) 39 (7.86) Total pancreatectomy/ Other 14 (3.26) 28 (5.65) pT classification 0.002 1 20 (4.65) 15 (3.02) 2 105 (24.42) 177 (35.69) 3 291 (67.67) 289 (58.27) 4 14 (3.26) 15 (3.02) pN classification < .001 0 174 (40.47) 128 (25.81) 1 239 (55.58) 289 (58.27) 2 17 (3.95) 79 (15.93) pTNM stage < .001 IA 14 (3.26) 9 (1.81) IB 50 (11.63) 49 (9.88) IIA 104 (24.19) 66 (13.31) IIB 231 (53.72) 280 (56.45) III 31 (7.21) 92 (18.55) Neoadjuvant therapy 54 (12.56) 52 (10.48) 0.323 Adjuvant therapy 262 (60.93) 335 (67.54) 0.036 Margin positive 127 (29.53) 132 (26.61) 0.323 Smoking history 122 (28.37) 128 (25.81) 0.380 Alcohol history 85 (19.77) 101 (20.36) 0.822 CCI score 0.158 0 122 (28.37) 169 (34.07) 1 129 (30.00) 143 (28.83) ≧ 2 179 (41.63) 184 (37.10) Positive Lymph node count Median (Q1-Q3) 1 (0–2) 2 (0–4) < .001 Lymph node ratio < .001 0-0.25 320 (74.42) 431 (86.90) 0.26–0.50 80 (18.60) 54 (10.89) 0.56–0.75 26 (6.05) 8 (1.61) 0.76-1.00 4 (0.93) 3 (0.60) P-value was derived from Pearson’s chi-square test for categorical variables, and Wilcoxon rank sum test for median of continuous variables. 3.2Analysis for LNs on survival Kaplan–Meier survival curves were generated to compare the 3-year OS by different LNs yield ( ≧ 15 and < 15) groups. As shown in Fig. 2 , while there was no significant difference in the overall survival (OS), there was a significant distinction observed in subgroup patients identified by pT1-3 classification, particularly those located at the head and undergoing pancreatoduodenectomy. Log-rank tests confirmed that subgroup patients with 15 or more lymph nodes (LNs) had better survival compared to those with fewer than 15 LNs (p = 0.033). However, after adjustment for confounders (Table 2 ), multivariable analysis indicated that LNs removed more than 15 was not significantly associated with better 1-year and 3-year OS in all patients (adjusted hazard ratio (aHR), 0.91; 95% CI, 0.70–0.1.19; aHR, 0.94; 95% CI, 0.79–1.11) and subgroup patients (aHR, 0.78; 95% CI, 0.57–1.07; aHR, 0.91; 95% CI, 0.75–1.12). Stratified analyses by AJCC pT/pN classification and treatment modality (Figs. 3 and 4) similarly indicated no survival advantage for patients with ≥ 15 retrieved LNs at either 1 or 3 years, except for those with pT1–2 disease, who exhibited better 1-year OS. Table 2 The risk of mortality within 1, and 3 years between groups based on the number of LNs removed in patients with pancreatic adenocarcinoma and the subgroup of patient, classified as pT1-3 classification, located at the head, undergoing pancreatoduodenectomy. Overall, n = 926 Subgroup, n = 666 LNs removed, n (%) Adjusted HR a LNs removed, n (%) Adjusted HR a < 15 (reference) ≧ 15 (95% C.I.) < 15 (reference) ≧ 15 (95% C.I.) Time to death, years 1 - year mortality 132 (30.70) 143 (28.83) 0.91 (0.70–1.19) 98 (35.64) 103 (26.34) 0.78 (0.57–1.07) 3 - years mortality 326 (75.81) 368 (74.19) 0.94 (0.79–1.11) 215 (78.18) 289 (73.91) 0.91 (0.75–1.12) a. The cox proportional hazard regression was used to estimate the relative risk between the number of LNs removed ≧ 15 and < 15 and adjusted the baseline information of patient including, age group, sex, location, grade, pT classification, pN classification, smoking, alcohol, neoadjuvant therapy and adjuvant therapy, margin positive, CCI group, and LNR group. 4.Discussion Surgical resection remains the cornerstone of curative treatment for pancreatic cancer. The pathological stage not only guides the need for adjuvant therapy but is also a critical determinant of patient prognosis. 26 Therefore, obtaining an adequate surgical field and performing sufficient lymph node (LN) dissection are essential to ensure surgical quality and accurate pathological staging. Inadequate lymph node evaluation after curative resection may lead to misclassification of node-positive disease as N0 disease. 27 Most clinical guidelines recommend harvesting a minimum of 15 lymph nodes for accurate staging. 13 , 14 In this nationwide cancer registry–based study, we similarly adopted 15 as the cutoff for analysis. We found that an adequate LN yield (≥ 15) was more frequently achieved in tumors located in the pancreatic head, in patients undergoing pancreatoduodenectomy, and in those with more advanced pT/pN classifications or pathological stages (IIB–III). Additionally, patients with adequate LN evaluation had higher counts of positive nodes, thereby influencing the lymph node ratio. However, no significant association was observed between overall survival and adequate LN harvest. The only subgroup showing a potential improvement in 1-year OS with ≥ 15 resected LNs comprised patients with pathological T1–T2 disease. Our study has several strengths compared with previous single-institution studies or analyses using other national databases. First, the database used for this analysis covers more than 95% of all cancer patients in Taiwan, allowing inclusion of a large patient cohort with comprehensive follow-up data. Moreover, we included patients diagnosed with pancreatic cancer between 2013 and 2019, which makes our findings more representative of current clinical practice. Second, this database provides detailed clinicopathological information, including surgical type, number of lymph nodes retrieved, margin status, neoadjuvant or adjuvant therapy, tumor stage, grade, location, histologic subtype, and number of involved nodes. These data allowed us to perform detailed analyses of the impact of lymph node dissection. Finally, because the database also includes information on comorbidities and subsequent treatments, our analysis was able to assess overall survival with greater precision and clinical relevance. Numerous studies have investigated the prognostic significance and potential survival benefit associated with the number of lymph nodes examined. Showalter et al. conducted a secondary analysis of the RTOG 9704 trial to investigate the relationship between lymph node status and survival. Using 12 and 15 as cutoff values for the number of examined lymph nodes, they found that the total number of nodes examined (TNE) was significantly associated with overall survival. 28 atients with more than 15 examined nodes had longer OS, with a hazard ratio (HR) of 1.47 compared with those with 0–15 examined nodes; similar findings were observed when comparing > 12 versus 0–12 nodes. Slidell et al. also reported that the total number of examined LNs was associated with survival. Using data from the Surveillance, Epidemiology, and End Results (SEER) database, they demonstrated that when LN count was analyzed as a continuous variable, a higher number of examined nodes was correlated with improved survival (HR, 0.99). 29 Moreover, they found that assessment of at least 12 lymph nodes was associated with significantly better survival compared with 0–11 nodes, with this benefit being most pronounced among node-negative patients. 30 Valsangkar et al. reported that an increased number of resected LNs was associated with improved survival in the N0 subgroup. 31 Most of these studies emphasized that the survival advantage likely results from more accurate staging rather than a direct therapeutic benefit. In contrast, our analysis did not demonstrate a significant survival benefit associated with a higher number of examined LNs, except in a small subgroup of patients, leading to conclusions that differ from earlier reports. This discrepancy may be attributed to several factors influencing LN yield, including tumor location, extent of surgical resection, quality of pathological assessment, and the use of neoadjuvant therapy. The total number of resected LNs may also serve as a surrogate marker for surgical quality. While meticulous surgery and precise staging can indirectly affect survival, these outcomes are influenced by multiple factors beyond the absolute number of LNs examined. Our study demonstrated that harvesting more than 15 lymph nodes during surgery was not associated with improved 1-year or 3-year overall survival in the entire cohort (aHR, 0.91 and 0.94, respectively). Consistent with our findings, Masuda et al. investigated the relationship between OS and the number of examined LNs using single-center data including 490 patients. They found that examining more than 15 LNs did not result in better OS compared with fewer than 15 LNs (p = 0.32). 32 Similarly, Yamamoto et al. reported that the number of examined lymph nodes was not a prognostic factor for OS. In their retrospective single-institution analysis, 10 LNs were used as the cutoff value, and only positive surgical margins and a lymph node ratio ≥ 0.2 were associated with poorer survival; examining more than 10 LNs did not confer any survival advantage. 33 Zhan et al. also reported consistent findings, noting that while LN count appeared to be associated with survival in univariate analysis, the association disappeared in multivariate analysis when comparing < 12 versus ≥ 12 examined LNs. 34 Although these studies used different cutoff values for the number of LNs examined, all demonstrated that a higher LN count was not associated with improved survival. Other studies have also reported similar results; however, most of these were retrospective, single-institution analyses that may be limited by variations in surgical technique and pathological assessment among institutions. 35 – 37 Its worthy to be mentioned that our results indicated that examining more than 15 lymph nodes was associated with improved 1-year survival only in patients with pT1–2 pancreatic cancer. A similar observation was reported by Schwarz et al., who analyzed data from the SEER database to evaluate the relationship between the total number of examined LNs and survival. In their subgroup analysis, they identified that adequate LN evaluation—defined as the examination of 10–12 nodes—was a significant cutoff for patients with pT1–2N0 tumors, whereas no meaningful cutoff value was observed for those with pT1–2N1 disease. 14 Although Schwarz et al. reported an overall association between total LN count and survival—contrary to our findings—the observed benefit among patients with pT1–2 tumors was consistent with our results. Other studies have likewise suggested that the number of harvested LNs may influence survival in specific subgroups, particularly among node-negative (pN0) patients; however, our analysis did not demonstrate a similar association. 38 Elshaer et al. conducted a systematic review evaluating the prognostic impact of LN yield and found that most studies did not identify a significant relationship between the number of examined LNs and overall survival, consistent with our findings. 39 As noted earlier, LN yield may be affected by multiple factors—including tumor location, surgical technique, pathological assessment, and the use of neoadjuvant therapy. Further studies are therefore warranted to determine whether LN count represents an independent prognostic factor and to identify patient subgroups that may derive a true survival benefit from more extensive lymph node dissection. 5.Limitations This study has several limitations. First, number of examined lymph nodes was reported by multiple institutions, and no standardized national guideline currently exists in Taiwan regarding the extent of lymphadenectomy during pancreatic surgery. This interinstitutional variability may have contributed to differences in LN yield and potentially influenced the results. Second, several treatment-related variables that could affect overall survival—such as specific neoadjuvant or adjuvant chemotherapy regimens, radiotherapy dose and field, and details of salvage treatments—were unavailable in the registry, possibly leading to residual confounding. Despite these limitations, our study provides important insights into the prognostic value of the total number of examined LNs in pancreatic cancer. The optimal number of LNs required for accurate staging and prognostication likely depends on tumor (T) stage, nodal (N) status, and other clinicopathologic factors; therefore, a single universal cutoff may not be applicable to all patients. Further prospective studies are warranted to define the appropriate extent of LN dissection for different clinical subgroups. . 6.Conclusion By utilizing data from this nationwide cancer registry, we found that evaluating more than 15 lymph nodes (LNs) during curative surgery for pancreatic adenocarcinoma was not associated with improved survival. The only patient subgroup that appeared to benefit from a higher number of examined LNs was those with pathologic stage pT1–2 disease. Further large-scale studies are warranted to clarify the prognostic significance of total LNs examined and to determine whether specific subgroups may derive survival benefit from more extensive LN dissection. Declarations Ethics Approval and Informed Consent The study adhered to the protocol outlined in the Declaration of Helsinki and its subsequent updates. It was approved by the Ethics Committee of the Institutional Review Board of Chi Mei Medical Center (IRB: 11411-008). As this was a retrospective study using a national registry database without personally identifiable information, written informed consent was not required, and all data were analyzed in an anonymized format. Data availability statement: Clinicopathological datasets are available from the corresponding author upon reasonable request. Consent for publication Not applicable. Authorship contribution statement : Study design: CJ Tsai; PY Lin; KH Ong; CH Ho; YC Chen; CF Li; CC Yang; CY Lu. Data analysis: CH Ho; YC Chen; CC Yang. Manuscript writing and editing: CJ Tsai; PY Lin; CH Ho; CC Yang; CY Lu. All authors have read and agreed to the published version of the manuscript. Disclosure statement The authors have no conflicts of interest. Funding The author(s) received no financial support for the research, authorship, and/or publication of this article. Acknowledgements We are grateful to Health Data Science Center, National Cheng Kung University Hospital for providing administrative and technical support. Consent to participate Not applicable References Bengtsson, A., Andersson, R. & Ansari, D. The actual 5-year survivors of pancreatic ductal adenocarcinoma based on real-world data. Sci. Rep. 10 , 16425. https://doi.org:10.1038/s41598-020-73525-y (2020). Lau, S. C. & Cheung, W. Y. Evolving treatment landscape for early and advanced pancreatic cancer. World J. Gastrointest. Oncol. 9 , 281–292. https://doi.org:10.4251/wjgo.v9.i7.281 (2017). Neuzillet, C., Sauvanet, A. & Hammel, P. Prognostic factors for resectable pancreatic adenocarcinoma. J. Visc. Surg. 148 , e232–243. https://doi.org:10.1016/j.jviscsurg.2011.07.007 (2011). Strobel, O. et al. Actual Five-year Survival After Upfront Resection for Pancreatic Ductal Adenocarcinoma: Who Beats the Odds? Ann. Surg. 275 , 962–971. https://doi.org:10.1097/SLA.0000000000004147 (2022). Robinson, T. P. et al. NCCN guideline concordance in colon and rectal cancer patients within a comprehensive health system. Am. J. Surg. 240 , 116114. https://doi.org:10.1016/j.amjsurg.2024.116114 (2025). Ajani, J. A. et al. Gastric Cancer, Version 2.2025, NCCN Clinical Practice Guidelines In Oncology. J. Natl. Compr. Canc Netw. 23 , 169–191. https://doi.org:10.6004/jnccn.2025.0022 (2025). Tol, J. A. et al. Definition of a standard lymphadenectomy in surgery for pancreatic ductal adenocarcinoma: a consensus statement by the International Study Group on Pancreatic Surgery (ISGPS). Surgery 156 , 591–600. https://doi.org:10.1016/j.surg.2014.06.016 (2014). Lamartina, L. et al. 8th edition of the AJCC/TNM staging system of thyroid cancer: what to expect (ITCO#2). Endocr Relat Cancer 25, L7-L11 (2018). https://doi.org:10.1530/ERC-17-0453 Chun, Y. S., Pawlik, T. M. & Vauthey, J. N. 8th Edition of the AJCC Cancer Staging Manual: Pancreas and Hepatobiliary Cancers. Ann. Surg. Oncol. 25 , 845–847. https://doi.org:10.1245/s10434-017-6025-x (2018). Song, C. et al. Elective pelvic versus prostate bed-only salvage radiotherapy following radical prostatectomy: A propensity score-matched analysis. Strahlenther Onkol . 191 , 801–809. https://doi.org:10.1007/s00066-015-0872-9 (2015). Goess, R. et al. Lymph node examination and survival in resected pancreatic ductal adenocarcinoma: retrospective study. BJS Open. 8 https://doi.org:10.1093/bjsopen/zrad125 (2024). Hellan, M. et al. The impact of lymph node number on survival in patients with lymph node-negative pancreatic cancer. Pancreas 37 , 19–24. https://doi.org:10.1097/MPA.0b013e31816074c9 (2008). Tomlinson, J. S. et al. Accuracy of staging node-negative pancreas cancer: a potential quality measure. Arch. Surg. 142 https://doi.org:10.1001/archsurg.142.8.767 (2007). 767 – 723; discussion 773 – 764. Schwarz, R. E. & Smith, D. D. Extent of lymph node retrieval and pancreatic cancer survival: information from a large US population database. Ann. Surg. Oncol. 13 , 1189–1200. https://doi.org:10.1245/s10434-006-9016-x (2006). Ashfaq, A., Pockaj, B. A., Gray, R. J., Halfdanarson, T. R. & Wasif, N. Nodal counts and lymph node ratio impact survival after distal pancreatectomy for pancreatic adenocarcinoma. J. Gastrointest. Surg. 18 , 1929–1935. https://doi.org:10.1007/s11605-014-2566-5 (2014). Huebner, M. et al. Number of lymph nodes evaluated: prognostic value in pancreatic adenocarcinoma. J. Gastrointest. Surg. 16 , 920–926. https://doi.org:10.1007/s11605-012-1853-2 (2012). House, M. G. et al. Prognostic significance of pathologic nodal status in patients with resected pancreatic cancer. J. Gastrointest. Surg. 11 , 1549–1555. https://doi.org:10.1007/s11605-007-0243-7 (2007). Riediger, H. et al. The lymph node ratio is the strongest prognostic factor after resection of pancreatic cancer. J. Gastrointest. Surg. 13 , 1337–1344. https://doi.org:10.1007/s11605-009-0919-2 (2009). Liang, Y. H. et al. Irinotecan and Oxaliplatin Might Provide Equal Benefit as Adjuvant Chemotherapy for Patients with Resectable Synchronous Colon Cancer and Liver-confined Metastases: A Nationwide Database Study. Anticancer Res. 37 , 7095–7104. https://doi.org:10.21873/anticanres.12183 (2017). Bray, F. & Parkin, D. M. Evaluation of data quality in the cancer registry: principles and methods. Part I: comparability, validity and timeliness. Eur. J. Cancer . 45 , 747–755. https://doi.org:10.1016/j.ejca.2008.11.032 (2009). Chiang, C. J. et al. Incidence and survival of adult cancer patients in Taiwan, 2002–2012. J. Formos. Med. Assoc. 115 , 1076–1088. https://doi.org:10.1016/j.jfma.2015.10.011 (2016). Chiang, N. J., Chen, L. T., Tsai, C. R. & Chang, J. S. The epidemiology of gastrointestinal stromal tumors in Taiwan, 1998–2008: a nation-wide cancer registry-based study. BMC Cancer . 14 , 102. https://doi.org:10.1186/1471-2407-14-102 (2014). Huang, Y., Zhang, Y., Li, J. & Liu, G. Charlson comorbidity index for evaluatiomicronn omicronf the outcomes of elderly patients undergoing laparoscopic surgery for colon cancer. J. BUON . 22 , 686–691 (2017). Tian, Y., Xu, B., Yu, G., Li, Y. & Liu, H. Age-adjusted charlson comorbidity index score as predictor of prolonged postoperative ileus in patients with colorectal cancer who underwent surgical resection. Oncotarget 8 , 20794–20801. https://doi.org:10.18632/oncotarget.15285 (2017). DeLong, E. R., DeLong, D. M. & Clarke-Pearson, D. L. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 44 , 837–845 (1988). Malleo, G. et al. Reappraisal of Nodal Staging and Study of Lymph Node Station Involvement in Pancreaticoduodenectomy with the Standard International Study Group of Pancreatic Surgery Definition of Lymphadenectomy for Cancer. J Am Coll Surg 221, 367–379 e364 (2015). https://doi.org:10.1016/j.jamcollsurg.2015.02.019 Eskander, M. F. et al. Evolution and impact of lymph node dissection during pancreaticoduodenectomy for pancreatic cancer. Surgery 161 , 968–976. https://doi.org:10.1016/j.surg.2016.09.032 (2017). Showalter, T. N. et al. The influence of total nodes examined, number of positive nodes, and lymph node ratio on survival after surgical resection and adjuvant chemoradiation for pancreatic cancer: a secondary analysis of RTOG 9704. Int. J. Radiat. Oncol. Biol. Phys. 81 , 1328–1335. https://doi.org:10.1016/j.ijrobp.2010.07.1993 (2011). Fang, C. et al. Proposal and validation of a modified staging system to improve the prognosis predictive performance of the 8th AJCC/UICC pTNM staging system for gastric adenocarcinoma: a multicenter study with external validation. Cancer Commun. (Lond) . 38 , 67. https://doi.org:10.1186/s40880-018-0337-5 (2018). Slidell, M. B. et al. Impact of total lymph node count and lymph node ratio on staging and survival after pancreatectomy for pancreatic adenocarcinoma: a large, population-based analysis. Ann. Surg. Oncol. 15 , 165–174. https://doi.org:10.1245/s10434-007-9587-1 (2008). Valsangkar, N. P. et al. N0/N1, PNL, or LNR? The effect of lymph node number on accurate survival prediction in pancreatic ductal adenocarcinoma. J. Gastrointest. Surg. 17 , 257–266. https://doi.org:10.1007/s11605-012-1974-7 (2013). Masuda, T. et al. A Comprehensive Assessment of Accurate Lymph Node Staging and Preoperative Detection in Resected Pancreatic Cancer. J. Gastrointest. Surg. 22 , 295–302. https://doi.org:10.1007/s11605-017-3607-7 (2018). Yamamoto, Y. et al. The clinical impact of the lymph node ratio as a prognostic factor after resection of pancreatic cancer. Anticancer Res. 34 , 2389–2394 (2014). Zhan, H. X., Xu, J. W., Wang, L., Zhang, G. Y. & Hu, S. Y. Lymph node ratio is an independent prognostic factor for patients after resection of pancreatic cancer. World J. Surg. Oncol. 13 , 105. https://doi.org:10.1186/s12957-015-0510-0 (2015). Bhatti, I. et al. Lymph node ratio versus number of affected lymph nodes as predictors of survival for resected pancreatic adenocarcinoma. World J. Surg. 34 , 768–775. https://doi.org:10.1007/s00268-009-0336-4 (2010). Massucco, P. et al. Prognostic significance of lymph node metastases in pancreatic head cancer treated with extended lymphadenectomy: not just a matter of numbers. Ann. Surg. Oncol. 16 , 3323–3332. https://doi.org:10.1245/s10434-009-0672-5 (2009). John, B. J. et al. Redefining the R1 resection for pancreatic ductal adenocarcinoma: tumour lymph nodal burden and lymph node ratio are the only prognostic factors associated with survival. HPB (Oxford) . 15 , 674–680. https://doi.org:10.1111/hpb.12019 (2013). Pawlik, T. M. et al. Prognostic relevance of lymph node ratio following pancreaticoduodenectomy for pancreatic cancer. Surgery 141 , 610–618. https://doi.org:10.1016/j.surg.2006.12.013 (2007). Elshaer, M., Gravante, G., Kosmin, M., Riaz, A. & Al-Bahrani, A. A systematic review of the prognostic value of lymph node ratio, number of positive nodes and total nodes examined in pancreatic ductal adenocarcinoma. Ann. R Coll. Surg. Engl. 99 , 101–106. https://doi.org:10.1308/rcsann.2016.0340 (2017). Additional Declarations No competing interests reported. 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Hospital","correspondingAuthor":false,"prefix":"","firstName":"Pei-Yi","middleName":"","lastName":"Lin","suffix":""},{"id":572487889,"identity":"a4f0bc81-0f49-43ae-afbe-7aa790164c3d","order_by":2,"name":"Khaa-Hoo Ong","email":"","orcid":"","institution":"CHIMEI (Taiwan)","correspondingAuthor":false,"prefix":"","firstName":"Khaa-Hoo","middleName":"","lastName":"Ong","suffix":""},{"id":572487890,"identity":"838d9711-c1be-48b3-a52c-a5071629c5e7","order_by":3,"name":"Chung-Han Ho","email":"","orcid":"","institution":"CHIMEI (Taiwan)","correspondingAuthor":false,"prefix":"","firstName":"Chung-Han","middleName":"","lastName":"Ho","suffix":""},{"id":572487891,"identity":"4a85c103-a281-49bf-8b06-5b06c7697894","order_by":4,"name":"Yi-Chen Chen","email":"","orcid":"","institution":"CHIMEI 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09:16:46","extension":"html","order_by":13,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":136602,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8496148/v1/23209a7ee33899cc84ee5453.html"},{"id":100366071,"identity":"6456d826-f12e-4d18-aa4b-375b806e3235","added_by":"auto","created_at":"2026-01-16 07:55:54","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":230792,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart of study participant.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8496148/v1/fc480cdf6a627df076e4a7f7.jpeg"},{"id":100365991,"identity":"94a2ce92-3b8c-41ab-bbd0-00cbd8ed7977","added_by":"auto","created_at":"2026-01-16 07:55:49","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":730648,"visible":true,"origin":"","legend":"\u003cp\u003eProbability of 3-years survival rate between groups based on the number of lymph nodes removed in (A) patients with pancreatic adenocarcinoma and (B) the subgroup of patients, classified as pT1-3 classification, located at the head, undergoing pancreatoduodenectomy.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8496148/v1/18af664b116c8af0882872d6.jpeg"},{"id":100367398,"identity":"66aa4d4b-78b2-49b7-b4fd-f344140f0d1f","added_by":"auto","created_at":"2026-01-16 07:57:02","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":124639,"visible":true,"origin":"","legend":"\u003cp\u003eThe risk of mortality within 1, and 3 years between groups based on the number of LNs removed in patients with pancreatic adenocarcinoma in different (A) pT and (B) pN classification.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8496148/v1/4585ce5a3a972197c025c373.png"},{"id":107133161,"identity":"9d68b7e9-4d82-47c7-bcab-e7ff2c403ee7","added_by":"auto","created_at":"2026-04-17 07:29:00","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1700053,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8496148/v1/1cf1aa6d-d7e3-47ec-84d3-40f9a1e3718a.pdf"},{"id":100367015,"identity":"428a1290-0d08-46dd-834e-306f0b60b6d1","added_by":"auto","created_at":"2026-01-16 07:56:43","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":20292,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarytable.docx","url":"https://assets-eu.researchsquare.com/files/rs-8496148/v1/7c9c8c52d09e382f7817aa07.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Association Between Harvesting at Least 15 Lymph Nodes and Survival in Resected Pancreatic Cancer Using a Nationwide Database","fulltext":[{"header":"1.Introduction","content":"\u003cp\u003ePancreatic cancer remains one of the most aggressive and lethal malignancies, with an estimated 5-year overall survival rate of approximately 5%.\u003csup\u003e1\u003c/sup\u003e The poor prognosis is largely attributed to the fact that the majority of patients present with either distant metastases or locally advanced disease at the time of diagnosis, rendering them unsuitable for curative surgical intervention.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e Pancreatic ductal adenocarcinoma (PDAC), the predominant histological subtype, exhibits a particularly aggressive biological behavior and high propensity for early local invasion and distant spread. Surgical resection, therefore, represents the cornerstone and only potentially curative treatment modality, offering the best opportunity for durable local control and prolonged survival. Patients who undergo complete resection followed by adjuvant therapy can achieve a 5-year survival rate ranging from 15% to 25%.\u003csup\u003e3\u003c/sup\u003e However, only approximately 20% of patients present with resectable disease at diagnosis, highlighting the urgent need for improved strategies in early detection, surgical selection, and multimodal management to enhance long-term outcomes.\u003c/p\u003e \u003cp\u003eAmong patients who undergo curative-intent surgery, several clinicopathological factors influence recurrence and survival outcomes. Established prognostic indicators include postoperative serum CA 19\u0026thinsp;\u0026minus;\u0026thinsp;9 levels, tumor size, pathological stage, resection margin status, and lymph node involvement.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e Complete (R0) resection is paramount, as microscopically negative margins are strongly associated with improved local control and long-term survival. In addition, the extent of lymph node dissection and the number of nodes retrieved have emerged as critical indicators of surgical quality and prognostic precision. The total number of lymph nodes examined reflects both the thoroughness of surgical clearance and the adequacy of pathological evaluation, thereby influencing staging accuracy and decisions regarding adjuvant therapy. In other malignancies, such as colorectal and gastric cancer, clinical guidelines recommend harvesting a minimum of 12 and 16 lymph nodes, respectively, for reliable staging.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e However, in pancreatic cancer, the optimal lymph node yield for accurate prognostication and quality benchmarking remains a subject of ongoing debate, warranting further investigation.\u003c/p\u003e \u003cp\u003eSeveral expert consensus groups and professional organizations have proposed recommendations for adequate lymph node evaluation in pancreatic cancer. The International Study Group on Pancreatic Surgery (ISGPS) recommends that a standard lymphadenectomy should yield at least 15 lymph nodes to ensure accurate pathological staging.\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e Similarly, the College of American Pathologists (CAP) protocol for pancreatic carcinoma specifies that a minimum of 12 lymph nodes should be examined following pancreatoduodenectomy.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e The American Joint Committee on Cancer (AJCC) Cancer Staging Manual, 8th Edition, adopts the same threshold to improve nodal staging accuracy, particularly in distinguishing N0 disease.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e Furthermore, the National Comprehensive Cancer Network (NCCN) guidelines recommend evaluating between 11 and 17 lymph nodes for optimal staging reliability.\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e Consistent with these recommendations, previous studies have proposed a range of adequate lymph node yields, generally between 10 and 21 nodes.\u003csup\u003e\u003cspan additionalcitationids=\"CR12 CR13\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e Despite these variations, most evidence and consensus statements converge on a threshold of approximately 15 lymph nodes as the benchmark for adequate lymphadenectomy, serving as an important indicator of surgical and pathological quality in pancreatic cancer management.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe prognostic impact of the number of lymph nodes examined in resected pancreatic cancer remains inconclusive. While inadequate lymph node retrieval may lead to pathological understaging and suboptimal adjuvant treatment decisions, studies have reported conflicting results\u0026mdash;some demonstrating improved survival with a higher number of examined nodes, particularly in pathologically node-negative cases whereas others found no significant correlation with overall survival.\u003csup\u003e\u003cspan additionalcitationids=\"CR16 CR17\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e These discrepancies may arise from variations in patient characteristics, tumor location, disease stage, and differences in multimodality treatment approaches, such as the use of preoperative chemotherapy or radiotherapy. To clarify these inconsistencies, we analyzed data from the National Taiwan Cancer Registry (TCR) to examine the association between lymph node yield and survival outcomes in patients who underwent curative-intent resection for pancreatic cancer. In particular, this study aimed to re-evaluate whether the commonly recommended threshold of 15 examined lymph nodes remains an appropriate standard, with particular attention to these potential confounding factors.\u003c/p\u003e"},{"header":"2.Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1Study Design and Participants\u003c/h2\u003e \u003cp\u003eThe clinicopathological data of patients with pancreatic cancer were obtained from the Taiwan Cancer Registry (TCR) and the National Health Insurance Research Database (NHIRD).\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e Established in 1979, the TCR underwent substantial enhancements following the implementation of the Cancer Control Act in 2003. Since then, it has provided a highly comprehensive and reliable nationwide dataset, recognized for its excellent completeness and data quality, comparable to other leading national cancer registries.\u003csup\u003e\u003cspan additionalcitationids=\"CR21\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003ePatients diagnosed with pancreatic cancer between January 2013 and December 2019 were identified from the Taiwan Cancer Registry using the International Classification of Diseases for Oncology, Third Edition (ICD-O-3) site codes C25.0, C25.1, C25.2, C25.3, C25.7, C25.8, and C25.9, and histology/behavior codes 8140, 8141, 8255, 8260, 8470, 8471, 8480, 8481, 8490, 8500, 8550, and 8560. Tumor staging was determined according to the 7th edition of the American Joint Committee on Cancer (AJCC) classification system. Follow-up was calculated from the date of pancreatic cancer diagnosis to December 31, 2021. The dataset included comprehensive clinicopathological variables such as age, sex, tumor location, histologic grade, surgical procedure, clinical/pathological stage, margin status, lymph node count, comorbidities, receipt of chemotherapy or radiotherapy, and personal habits. Comorbidity severity was assessed using the Charlson Comorbidity Index (CCI), as previously described.\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e,\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e Patients with incomplete coding, a prior malignancy, or evidence of metastatic disease were excluded. Finally, 926 patients who underwent curative-intent resection for pancreatic cancer were included in the final analysis (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2Statistical Analysis\u003c/h2\u003e \u003cp\u003eThis retrospective, population-based study investigated the impact of lymph node (LN) yield on survival among patients with resected pancreatic cancer, comparing groups with \u0026ge;\u0026thinsp;15 and \u0026lt;\u0026thinsp;15 retrieved nodes. Overall survival (OS) probabilities were evaluated for patients with a minimum follow-up of 1 year and up to 3 years. Categorical variables were summarized as frequencies with percentages and compared between groups using Pearson\u0026rsquo;s chi-square test. Diagnosed age and the number of positive lymph node was expressed as the median with interquartile range (IQR) and compared using the Wilcoxon rank-sum test. Cox proportional hazard regression was performed to estimate the relative risk ratio of survival associated with LN yield (\u0026ge;\u0026thinsp;15 vs. \u0026lt;15), adjusted for all potential confounders.\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e The survival rate in the two groups over time was performed using the Kaplan\u0026ndash;Meier method with a log-rank test to determine the differences. Several sensitivity analyses were performed to evaluate the robustness of the findings. Because LN yield may be influenced by tumor characteristics, anatomical location, and surgical procedure, a subgroup analysis was included as a sensitivity test. This analysis restricted patient with pT1\u0026ndash;3 tumors located in the pancreatic head who underwent pancreatoduodenectomy, which minimize the residual bias. Additional stratified analyses were performed according to pathological T and N classifications and adjuvant treatment status. All statistical analyses were conducted using SAS software, version 9.4 (SAS Institute Inc., Cary, NC, USA) and Stata (15, StataCorp LLC, College Station, TX). A two-sided p-value of \u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"3.Results","content":"\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e3.1Clinicopathological Characteristics\u003c/h2\u003e \u003cp\u003eClinicopathological characteristics of patients with resected pancreatic cancer are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Between 2013 and 2019, a total of 926 patients were included, comprising 517 men (55.8%) and 409 women (44.2%). The median age at diagnosis was 64 years (Q1\u0026ndash;Q3: 57\u0026ndash;71), and the median follow-up duration was 1.30 years (Q1\u0026ndash;Q3: 0.79\u0026ndash;1.96). Tumors were most frequently located in the pancreatic head (67.9%), followed by the tail (13.3%), body (11.6%), and other sites (7.2%). Overall, 106 patients (11.4%) received neoadjuvant therapy, and 597 (64.5%) underwent adjuvant chemotherapy, with or without radiotherapy. The median number of examined lymph nodes (LNs) was 15 (Q1\u0026ndash;Q3: 9\u0026ndash;22). Of the entire cohort, 496 patients (53.6%) had\u0026thinsp;\u0026ge;\u0026thinsp;15 retrieved LNs, whereas 430 (46.4%) had\u0026thinsp;\u0026lt;\u0026thinsp;15. Compared with patients who had fewer than 15 LNs examined, those with adequate LN yield (\u0026ge;\u0026thinsp;15) were more likely to have tumors located in the pancreatic head, to have undergone pancreatoduodenectomy, and to present with more advanced pathological T/N classifications, higher overall stage (IIB\u0026ndash;III), and greater numbers of positive LNs.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of patients with pancreatic cancer undergoing surgery between groups based on the number of LNs removed, n\u0026thinsp;=\u0026thinsp;926\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eThe number of LNs removed, n (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;15, n\u0026thinsp;=\u0026thinsp;430\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e≧\u0026thinsp;15, n\u0026thinsp;=\u0026thinsp;496\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, years\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (Q1-Q3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e65 (57\u0026ndash;73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e64 (57\u0026ndash;71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e212 (49.30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e258 (52.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.410\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e≧\u0026thinsp;65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e218 (50.70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e238 (47.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.017\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e258 (60.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e259 (52.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e172 (40.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e237 (47.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLocation\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHead\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e292 (67.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e417 (84.07)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBody\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50 (11.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27 (5.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTail\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e57 (13.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (4.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOthers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31 (7.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32 (6.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGrade\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.195\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWell\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44 (10.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33 (6.65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModerately\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e300 (69.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e350 (70.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePoorly\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e69 (16.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e87 (17.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNot stated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (3.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26 (5.24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOperation\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePacreatoduodenectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e313 (72.79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e429 (86.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDistal pancreatectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e103 (23.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39 (7.86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal pancreatectomy/ Other\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (3.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (5.65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003epT classification\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (4.65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (3.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e105 (24.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e177 (35.69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e291 (67.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e289 (58.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (3.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (3.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003epN classification\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e174 (40.47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e128 (25.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e239 (55.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e289 (58.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (3.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e79 (15.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003epTNM stage\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (3.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (1.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50 (11.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49 (9.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIIA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e104 (24.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66 (13.31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIIB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e231 (53.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e280 (56.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31 (7.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e92 (18.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNeoadjuvant therapy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e54 (12.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52 (10.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.323\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAdjuvant therapy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e262 (60.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e335 (67.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.036\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMargin positive\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e127 (29.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e132 (26.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.323\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSmoking history\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e122 (28.37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e128 (25.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.380\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAlcohol history\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e85 (19.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e101 (20.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.822\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCCI score\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.158\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e122 (28.37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e169 (34.07)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e129 (30.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e143 (28.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e≧\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e179 (41.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e184 (37.10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePositive Lymph node count\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (Q1-Q3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0\u0026ndash;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (0\u0026ndash;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLymph node ratio\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0-0.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e320 (74.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e431 (86.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0.26\u0026ndash;0.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e80 (18.60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54 (10.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0.56\u0026ndash;0.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26 (6.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (1.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0.76-1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (0.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (0.60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eP-value was derived from Pearson\u0026rsquo;s chi-square test for categorical variables, and Wilcoxon rank sum test for median of continuous variables.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e3.2Analysis for LNs on survival\u003c/h2\u003e \u003cp\u003eKaplan\u0026ndash;Meier survival curves were generated to compare the 3-year OS by different LNs yield (\u0026thinsp;≧\u0026thinsp;15 and \u0026lt;\u0026thinsp;15) groups. As shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e2\u003c/span\u003e, while there was no significant difference in the overall survival (OS), there was a significant distinction observed in subgroup patients identified by pT1-3 classification, particularly those located at the head and undergoing pancreatoduodenectomy. Log-rank tests confirmed that subgroup patients with 15 or more lymph nodes (LNs) had better survival compared to those with fewer than 15 LNs (p\u0026thinsp;=\u0026thinsp;0.033). However, after adjustment for confounders (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), multivariable analysis indicated that LNs removed more than 15 was not significantly associated with better 1-year and 3-year OS in all patients (adjusted hazard ratio (aHR), 0.91; 95% CI, 0.70\u0026ndash;0.1.19; aHR, 0.94; 95% CI, 0.79\u0026ndash;1.11) and subgroup patients (aHR, 0.78; 95% CI, 0.57\u0026ndash;1.07; aHR, 0.91; 95% CI, 0.75\u0026ndash;1.12). Stratified analyses by AJCC pT/pN classification and treatment modality (Figs.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e3\u003c/span\u003e and 4) similarly indicated no survival advantage for patients with \u0026ge;\u0026thinsp;15 retrieved LNs at either 1 or 3 years, except for those with pT1\u0026ndash;2 disease, who exhibited better 1-year OS.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe risk of mortality within 1, and 3 years between groups based on the number of LNs removed in patients with pancreatic adenocarcinoma and the subgroup of patient, classified as pT1-3 classification, located at the head, undergoing pancreatoduodenectomy.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eOverall, n\u0026thinsp;=\u0026thinsp;926\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003eSubgroup, n\u0026thinsp;=\u0026thinsp;666\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eLNs removed, n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAdjusted HR\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eLNs removed, n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eAdjusted HR\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;15 (reference)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e≧\u0026thinsp;15\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(95% C.I.)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;15 (reference)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e≧\u0026thinsp;15\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(95% C.I.)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTime to death, years\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1 - year mortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e132 (30.70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e143 (28.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.91 (0.70\u0026ndash;1.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e98 (35.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e103 (26.34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.78 (0.57\u0026ndash;1.07)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3 - years mortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e326 (75.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e368 (74.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.94 (0.79\u0026ndash;1.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e215 (78.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e289 (73.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.91 (0.75\u0026ndash;1.12)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003ea. The cox proportional hazard regression was used to estimate the relative risk between the number of LNs removed\u0026thinsp;≧\u0026thinsp;15 and \u0026lt;\u0026thinsp;15 and adjusted the baseline information of patient including, age group, sex, location, grade, pT classification, pN classification, smoking, alcohol, neoadjuvant therapy and adjuvant therapy, margin positive, CCI group, and LNR group.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"4.Discussion","content":"\u003cp\u003eSurgical resection remains the cornerstone of curative treatment for pancreatic cancer. The pathological stage not only guides the need for adjuvant therapy but is also a critical determinant of patient prognosis.\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e Therefore, obtaining an adequate surgical field and performing sufficient lymph node (LN) dissection are essential to ensure surgical quality and accurate pathological staging. Inadequate lymph node evaluation after curative resection may lead to misclassification of node-positive disease as N0 disease.\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e Most clinical guidelines recommend harvesting a minimum of 15 lymph nodes for accurate staging.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e In this nationwide cancer registry\u0026ndash;based study, we similarly adopted 15 as the cutoff for analysis. We found that an adequate LN yield (\u0026ge;\u0026thinsp;15) was more frequently achieved in tumors located in the pancreatic head, in patients undergoing pancreatoduodenectomy, and in those with more advanced pT/pN classifications or pathological stages (IIB\u0026ndash;III). Additionally, patients with adequate LN evaluation had higher counts of positive nodes, thereby influencing the lymph node ratio. However, no significant association was observed between overall survival and adequate LN harvest. The only subgroup showing a potential improvement in 1-year OS with \u0026ge;\u0026thinsp;15 resected LNs comprised patients with pathological T1\u0026ndash;T2 disease.\u003c/p\u003e \u003cp\u003eOur study has several strengths compared with previous single-institution studies or analyses using other national databases. First, the database used for this analysis covers more than 95% of all cancer patients in Taiwan, allowing inclusion of a large patient cohort with comprehensive follow-up data. Moreover, we included patients diagnosed with pancreatic cancer between 2013 and 2019, which makes our findings more representative of current clinical practice. Second, this database provides detailed clinicopathological information, including surgical type, number of lymph nodes retrieved, margin status, neoadjuvant or adjuvant therapy, tumor stage, grade, location, histologic subtype, and number of involved nodes. These data allowed us to perform detailed analyses of the impact of lymph node dissection. Finally, because the database also includes information on comorbidities and subsequent treatments, our analysis was able to assess overall survival with greater precision and clinical relevance.\u003c/p\u003e \u003cp\u003eNumerous studies have investigated the prognostic significance and potential survival benefit associated with the number of lymph nodes examined. Showalter et al. conducted a secondary analysis of the RTOG 9704 trial to investigate the relationship between lymph node status and survival. Using 12 and 15 as cutoff values for the number of examined lymph nodes, they found that the total number of nodes examined (TNE) was significantly associated with overall survival.\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e atients with more than 15 examined nodes had longer OS, with a hazard ratio (HR) of 1.47 compared with those with 0\u0026ndash;15 examined nodes; similar findings were observed when comparing\u0026thinsp;\u0026gt;\u0026thinsp;12 versus 0\u0026ndash;12 nodes. Slidell et al. also reported that the total number of examined LNs was associated with survival. Using data from the Surveillance, Epidemiology, and End Results (SEER) database, they demonstrated that when LN count was analyzed as a continuous variable, a higher number of examined nodes was correlated with improved survival (HR, 0.99).\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e Moreover, they found that assessment of at least 12 lymph nodes was associated with significantly better survival compared with 0\u0026ndash;11 nodes, with this benefit being most pronounced among node-negative patients.\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e Valsangkar et al. reported that an increased number of resected LNs was associated with improved survival in the N0 subgroup.\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e Most of these studies emphasized that the survival advantage likely results from more accurate staging rather than a direct therapeutic benefit. In contrast, our analysis did not demonstrate a significant survival benefit associated with a higher number of examined LNs, except in a small subgroup of patients, leading to conclusions that differ from earlier reports. This discrepancy may be attributed to several factors influencing LN yield, including tumor location, extent of surgical resection, quality of pathological assessment, and the use of neoadjuvant therapy. The total number of resected LNs may also serve as a surrogate marker for surgical quality. While meticulous surgery and precise staging can indirectly affect survival, these outcomes are influenced by multiple factors beyond the absolute number of LNs examined.\u003c/p\u003e \u003cp\u003eOur study demonstrated that harvesting more than 15 lymph nodes during surgery was not associated with improved 1-year or 3-year overall survival in the entire cohort (aHR, 0.91 and 0.94, respectively). Consistent with our findings, Masuda et al. investigated the relationship between OS and the number of examined LNs using single-center data including 490 patients. They found that examining more than 15 LNs did not result in better OS compared with fewer than 15 LNs (p\u0026thinsp;=\u0026thinsp;0.32).\u003csup\u003e32\u003c/sup\u003e Similarly, Yamamoto et al. reported that the number of examined lymph nodes was not a prognostic factor for OS. In their retrospective single-institution analysis, 10 LNs were used as the cutoff value, and only positive surgical margins and a lymph node ratio\u0026thinsp;\u0026ge;\u0026thinsp;0.2 were associated with poorer survival; examining more than 10 LNs did not confer any survival advantage.\u003csup\u003e\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e Zhan et al. also reported consistent findings, noting that while LN count appeared to be associated with survival in univariate analysis, the association disappeared in multivariate analysis when comparing\u0026thinsp;\u0026lt;\u0026thinsp;12 versus \u0026ge;\u0026thinsp;12 examined LNs.\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e Although these studies used different cutoff values for the number of LNs examined, all demonstrated that a higher LN count was not associated with improved survival. Other studies have also reported similar results; however, most of these were retrospective, single-institution analyses that may be limited by variations in surgical technique and pathological assessment among institutions.\u003csup\u003e\u003cspan additionalcitationids=\"CR36\" citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eIts worthy to be mentioned that our results indicated that examining more than 15 lymph nodes was associated with improved 1-year survival only in patients with pT1\u0026ndash;2 pancreatic cancer. A similar observation was reported by Schwarz et al., who analyzed data from the SEER database to evaluate the relationship between the total number of examined LNs and survival. In their subgroup analysis, they identified that adequate LN evaluation\u0026mdash;defined as the examination of 10\u0026ndash;12 nodes\u0026mdash;was a significant cutoff for patients with pT1\u0026ndash;2N0 tumors, whereas no meaningful cutoff value was observed for those with pT1\u0026ndash;2N1 disease.\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e Although Schwarz et al. reported an overall association between total LN count and survival\u0026mdash;contrary to our findings\u0026mdash;the observed benefit among patients with pT1\u0026ndash;2 tumors was consistent with our results. Other studies have likewise suggested that the number of harvested LNs may influence survival in specific subgroups, particularly among node-negative (pN0) patients; however, our analysis did not demonstrate a similar association.\u003csup\u003e\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u003c/sup\u003e Elshaer et al. conducted a systematic review evaluating the prognostic impact of LN yield and found that most studies did not identify a significant relationship between the number of examined LNs and overall survival, consistent with our findings.\u003csup\u003e\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e\u003c/sup\u003e As noted earlier, LN yield may be affected by multiple factors\u0026mdash;including tumor location, surgical technique, pathological assessment, and the use of neoadjuvant therapy. Further studies are therefore warranted to determine whether LN count represents an independent prognostic factor and to identify patient subgroups that may derive a true survival benefit from more extensive lymph node dissection.\u003c/p\u003e"},{"header":"5.Limitations","content":"\u003cp\u003eThis study has several limitations. First, number of examined lymph nodes was reported by multiple institutions, and no standardized national guideline currently exists in Taiwan regarding the extent of lymphadenectomy during pancreatic surgery. This interinstitutional variability may have contributed to differences in LN yield and potentially influenced the results. Second, several treatment-related variables that could affect overall survival\u0026mdash;such as specific neoadjuvant or adjuvant chemotherapy regimens, radiotherapy dose and field, and details of salvage treatments\u0026mdash;were unavailable in the registry, possibly leading to residual confounding. Despite these limitations, our study provides important insights into the prognostic value of the total number of examined LNs in pancreatic cancer. The optimal number of LNs required for accurate staging and prognostication likely depends on tumor (T) stage, nodal (N) status, and other clinicopathologic factors; therefore, a single universal cutoff may not be applicable to all patients. Further prospective studies are warranted to define the appropriate extent of LN dissection for different clinical subgroups.\u003c/p\u003e \u003cp\u003e.\u003c/p\u003e"},{"header":"6.Conclusion","content":"\u003cp\u003eBy utilizing data from this nationwide cancer registry, we found that evaluating more than 15 lymph nodes (LNs) during curative surgery for pancreatic adenocarcinoma was not associated with improved survival. The only patient subgroup that appeared to benefit from a higher number of examined LNs was those with pathologic stage pT1\u0026ndash;2 disease. Further large-scale studies are warranted to clarify the prognostic significance of total LNs examined and to determine whether specific subgroups may derive survival benefit from more extensive LN dissection.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics Approval and Informed Consent\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study adhered to the protocol outlined in the Declaration of Helsinki and its subsequent updates. It was approved by the Ethics Committee of the Institutional Review Board of Chi Mei Medical Center (IRB: 11411-008). As this was a retrospective study using a national registry database without personally identifiable information, written informed consent was not required, and all data were analyzed in an anonymized format.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement:\u0026nbsp;\u003c/strong\u003eClinicopathological datasets are available from the\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ecorresponding author upon reasonable request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthorship contribution statement\u003c/strong\u003e\u003cstrong\u003e:\u0026nbsp;\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eStudy design: CJ Tsai; PY Lin; KH Ong; CH Ho; YC Chen; CF Li; CC Yang; CY Lu. Data analysis: CH Ho; YC Chen; CC Yang. Manuscript writing and editing: CJ Tsai; PY Lin; CH Ho; CC Yang; CY Lu. All authors have read and agreed to the published version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDisclosure statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe author(s) received no financial support for the research, authorship, and/or publication of this article.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe are grateful to Health Data Science Center, National Cheng Kung University Hospital for providing administrative and technical support.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBengtsson, A., Andersson, R. \u0026amp; Ansari, D. The actual 5-year survivors of pancreatic ductal adenocarcinoma based on real-world data. \u003cem\u003eSci. Rep.\u003c/em\u003e \u003cb\u003e10\u003c/b\u003e, 16425. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org:10.1038/s41598-020-73525-y\u003c/span\u003e\u003cspan address=\"https://doi.org:10.1038/s41598-020-73525-y\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLau, S. C. \u0026amp; Cheung, W. Y. Evolving treatment landscape for early and advanced pancreatic cancer. \u003cem\u003eWorld J. Gastrointest. Oncol.\u003c/em\u003e \u003cb\u003e9\u003c/b\u003e, 281\u0026ndash;292. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org:10.4251/wjgo.v9.i7.281\u003c/span\u003e\u003cspan address=\"https://doi.org:10.4251/wjgo.v9.i7.281\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2017).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNeuzillet, C., Sauvanet, A. \u0026amp; Hammel, P. Prognostic factors for resectable pancreatic adenocarcinoma. \u003cem\u003eJ. Visc. Surg.\u003c/em\u003e \u003cb\u003e148\u003c/b\u003e, e232\u0026ndash;243. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org:10.1016/j.jviscsurg.2011.07.007\u003c/span\u003e\u003cspan address=\"https://doi.org:10.1016/j.jviscsurg.2011.07.007\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2011).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStrobel, O. et al. Actual Five-year Survival After Upfront Resection for Pancreatic Ductal Adenocarcinoma: Who Beats the Odds? \u003cem\u003eAnn. Surg.\u003c/em\u003e \u003cb\u003e275\u003c/b\u003e, 962\u0026ndash;971. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org:10.1097/SLA.0000000000004147\u003c/span\u003e\u003cspan address=\"https://doi.org:10.1097/SLA.0000000000004147\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRobinson, T. P. et al. NCCN guideline concordance in colon and rectal cancer patients within a comprehensive health system. \u003cem\u003eAm. J. Surg.\u003c/em\u003e \u003cb\u003e240\u003c/b\u003e, 116114. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org:10.1016/j.amjsurg.2024.116114\u003c/span\u003e\u003cspan address=\"https://doi.org:10.1016/j.amjsurg.2024.116114\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2025).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAjani, J. A. et al. Gastric Cancer, Version 2.2025, NCCN Clinical Practice Guidelines In Oncology. \u003cem\u003eJ. Natl. Compr. Canc Netw.\u003c/em\u003e \u003cb\u003e23\u003c/b\u003e, 169\u0026ndash;191. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org:10.6004/jnccn.2025.0022\u003c/span\u003e\u003cspan address=\"https://doi.org:10.6004/jnccn.2025.0022\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2025).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTol, J. A. et al. Definition of a standard lymphadenectomy in surgery for pancreatic ductal adenocarcinoma: a consensus statement by the International Study Group on Pancreatic Surgery (ISGPS). \u003cem\u003eSurgery\u003c/em\u003e \u003cb\u003e156\u003c/b\u003e, 591\u0026ndash;600. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org:10.1016/j.surg.2014.06.016\u003c/span\u003e\u003cspan address=\"https://doi.org:10.1016/j.surg.2014.06.016\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2014).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLamartina, L. et al. 8th edition of the AJCC/TNM staging system of thyroid cancer: what to expect (ITCO#2). \u003cem\u003eEndocr Relat Cancer\u003c/em\u003e 25, L7-L11 (2018). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org:10.1530/ERC-17-0453\u003c/span\u003e\u003cspan address=\"https://doi.org:10.1530/ERC-17-0453\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChun, Y. S., Pawlik, T. M. \u0026amp; Vauthey, J. N. 8th Edition of the AJCC Cancer Staging Manual: Pancreas and Hepatobiliary Cancers. \u003cem\u003eAnn. Surg. Oncol.\u003c/em\u003e \u003cb\u003e25\u003c/b\u003e, 845\u0026ndash;847. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org:10.1245/s10434-017-6025-x\u003c/span\u003e\u003cspan address=\"https://doi.org:10.1245/s10434-017-6025-x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2018).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSong, C. et al. Elective pelvic versus prostate bed-only salvage radiotherapy following radical prostatectomy: A propensity score-matched analysis. \u003cem\u003eStrahlenther Onkol\u003c/em\u003e. \u003cb\u003e191\u003c/b\u003e, 801\u0026ndash;809. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org:10.1007/s00066-015-0872-9\u003c/span\u003e\u003cspan address=\"https://doi.org:10.1007/s00066-015-0872-9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2015).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGoess, R. et al. Lymph node examination and survival in resected pancreatic ductal adenocarcinoma: retrospective study. \u003cem\u003eBJS Open.\u003c/em\u003e \u003cb\u003e8\u003c/b\u003e \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org:10.1093/bjsopen/zrad125\u003c/span\u003e\u003cspan address=\"https://doi.org:10.1093/bjsopen/zrad125\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2024).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHellan, M. et al. The impact of lymph node number on survival in patients with lymph node-negative pancreatic cancer. \u003cem\u003ePancreas\u003c/em\u003e \u003cb\u003e37\u003c/b\u003e, 19\u0026ndash;24. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org:10.1097/MPA.0b013e31816074c9\u003c/span\u003e\u003cspan address=\"https://doi.org:10.1097/MPA.0b013e31816074c9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2008).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTomlinson, J. S. et al. Accuracy of staging node-negative pancreas cancer: a potential quality measure. \u003cem\u003eArch. Surg.\u003c/em\u003e \u003cb\u003e142\u003c/b\u003e \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org:10.1001/archsurg.142.8.767\u003c/span\u003e\u003cspan address=\"https://doi.org:10.1001/archsurg.142.8.767\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2007). 767\u0026thinsp;\u0026ndash;\u0026thinsp;723; discussion 773\u0026thinsp;\u0026ndash;\u0026thinsp;764.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchwarz, R. E. \u0026amp; Smith, D. D. Extent of lymph node retrieval and pancreatic cancer survival: information from a large US population database. \u003cem\u003eAnn. Surg. Oncol.\u003c/em\u003e \u003cb\u003e13\u003c/b\u003e, 1189\u0026ndash;1200. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org:10.1245/s10434-006-9016-x\u003c/span\u003e\u003cspan address=\"https://doi.org:10.1245/s10434-006-9016-x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2006).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAshfaq, A., Pockaj, B. A., Gray, R. J., Halfdanarson, T. R. \u0026amp; Wasif, N. Nodal counts and lymph node ratio impact survival after distal pancreatectomy for pancreatic adenocarcinoma. \u003cem\u003eJ. Gastrointest. Surg.\u003c/em\u003e \u003cb\u003e18\u003c/b\u003e, 1929\u0026ndash;1935. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org:10.1007/s11605-014-2566-5\u003c/span\u003e\u003cspan address=\"https://doi.org:10.1007/s11605-014-2566-5\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2014).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuebner, M. et al. Number of lymph nodes evaluated: prognostic value in pancreatic adenocarcinoma. \u003cem\u003eJ. Gastrointest. Surg.\u003c/em\u003e \u003cb\u003e16\u003c/b\u003e, 920\u0026ndash;926. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org:10.1007/s11605-012-1853-2\u003c/span\u003e\u003cspan address=\"https://doi.org:10.1007/s11605-012-1853-2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2012).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHouse, M. G. et al. Prognostic significance of pathologic nodal status in patients with resected pancreatic cancer. \u003cem\u003eJ. Gastrointest. Surg.\u003c/em\u003e \u003cb\u003e11\u003c/b\u003e, 1549\u0026ndash;1555. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org:10.1007/s11605-007-0243-7\u003c/span\u003e\u003cspan address=\"https://doi.org:10.1007/s11605-007-0243-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2007).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRiediger, H. et al. The lymph node ratio is the strongest prognostic factor after resection of pancreatic cancer. \u003cem\u003eJ. Gastrointest. Surg.\u003c/em\u003e \u003cb\u003e13\u003c/b\u003e, 1337\u0026ndash;1344. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org:10.1007/s11605-009-0919-2\u003c/span\u003e\u003cspan address=\"https://doi.org:10.1007/s11605-009-0919-2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2009).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiang, Y. H. et al. Irinotecan and Oxaliplatin Might Provide Equal Benefit as Adjuvant Chemotherapy for Patients with Resectable Synchronous Colon Cancer and Liver-confined Metastases: A Nationwide Database Study. \u003cem\u003eAnticancer Res.\u003c/em\u003e \u003cb\u003e37\u003c/b\u003e, 7095\u0026ndash;7104. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org:10.21873/anticanres.12183\u003c/span\u003e\u003cspan address=\"https://doi.org:10.21873/anticanres.12183\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2017).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBray, F. \u0026amp; Parkin, D. M. Evaluation of data quality in the cancer registry: principles and methods. Part I: comparability, validity and timeliness. \u003cem\u003eEur. J. Cancer\u003c/em\u003e. \u003cb\u003e45\u003c/b\u003e, 747\u0026ndash;755. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org:10.1016/j.ejca.2008.11.032\u003c/span\u003e\u003cspan address=\"https://doi.org:10.1016/j.ejca.2008.11.032\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2009).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChiang, C. J. et al. Incidence and survival of adult cancer patients in Taiwan, 2002\u0026ndash;2012. \u003cem\u003eJ. Formos. Med. Assoc.\u003c/em\u003e \u003cb\u003e115\u003c/b\u003e, 1076\u0026ndash;1088. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org:10.1016/j.jfma.2015.10.011\u003c/span\u003e\u003cspan address=\"https://doi.org:10.1016/j.jfma.2015.10.011\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2016).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChiang, N. J., Chen, L. T., Tsai, C. R. \u0026amp; Chang, J. S. The epidemiology of gastrointestinal stromal tumors in Taiwan, 1998\u0026ndash;2008: a nation-wide cancer registry-based study. \u003cem\u003eBMC Cancer\u003c/em\u003e. \u003cb\u003e14\u003c/b\u003e, 102. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org:10.1186/1471-2407-14-102\u003c/span\u003e\u003cspan address=\"https://doi.org:10.1186/1471-2407-14-102\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2014).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuang, Y., Zhang, Y., Li, J. \u0026amp; Liu, G. Charlson comorbidity index for evaluatiomicronn omicronf the outcomes of elderly patients undergoing laparoscopic surgery for colon cancer. \u003cem\u003eJ. BUON\u003c/em\u003e. \u003cb\u003e22\u003c/b\u003e, 686\u0026ndash;691 (2017).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTian, Y., Xu, B., Yu, G., Li, Y. \u0026amp; Liu, H. Age-adjusted charlson comorbidity index score as predictor of prolonged postoperative ileus in patients with colorectal cancer who underwent surgical resection. \u003cem\u003eOncotarget\u003c/em\u003e \u003cb\u003e8\u003c/b\u003e, 20794\u0026ndash;20801. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org:10.18632/oncotarget.15285\u003c/span\u003e\u003cspan address=\"https://doi.org:10.18632/oncotarget.15285\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2017).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDeLong, E. R., DeLong, D. M. \u0026amp; Clarke-Pearson, D. L. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. \u003cem\u003eBiometrics\u003c/em\u003e \u003cb\u003e44\u003c/b\u003e, 837\u0026ndash;845 (1988).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMalleo, G. et al. Reappraisal of Nodal Staging and Study of Lymph Node Station Involvement in Pancreaticoduodenectomy with the Standard International Study Group of Pancreatic Surgery Definition of Lymphadenectomy for Cancer. \u003cem\u003eJ Am Coll Surg\u003c/em\u003e 221, 367\u0026ndash;379 e364 (2015). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org:10.1016/j.jamcollsurg.2015.02.019\u003c/span\u003e\u003cspan address=\"https://doi.org:10.1016/j.jamcollsurg.2015.02.019\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEskander, M. F. et al. Evolution and impact of lymph node dissection during pancreaticoduodenectomy for pancreatic cancer. \u003cem\u003eSurgery\u003c/em\u003e \u003cb\u003e161\u003c/b\u003e, 968\u0026ndash;976. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org:10.1016/j.surg.2016.09.032\u003c/span\u003e\u003cspan address=\"https://doi.org:10.1016/j.surg.2016.09.032\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2017).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShowalter, T. N. et al. The influence of total nodes examined, number of positive nodes, and lymph node ratio on survival after surgical resection and adjuvant chemoradiation for pancreatic cancer: a secondary analysis of RTOG 9704. \u003cem\u003eInt. J. Radiat. Oncol. Biol. Phys.\u003c/em\u003e \u003cb\u003e81\u003c/b\u003e, 1328\u0026ndash;1335. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org:10.1016/j.ijrobp.2010.07.1993\u003c/span\u003e\u003cspan address=\"https://doi.org:10.1016/j.ijrobp.2010.07.1993\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2011).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFang, C. et al. Proposal and validation of a modified staging system to improve the prognosis predictive performance of the 8th AJCC/UICC pTNM staging system for gastric adenocarcinoma: a multicenter study with external validation. \u003cem\u003eCancer Commun. (Lond)\u003c/em\u003e. \u003cb\u003e38\u003c/b\u003e, 67. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org:10.1186/s40880-018-0337-5\u003c/span\u003e\u003cspan address=\"https://doi.org:10.1186/s40880-018-0337-5\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2018).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSlidell, M. B. et al. Impact of total lymph node count and lymph node ratio on staging and survival after pancreatectomy for pancreatic adenocarcinoma: a large, population-based analysis. \u003cem\u003eAnn. Surg. Oncol.\u003c/em\u003e \u003cb\u003e15\u003c/b\u003e, 165\u0026ndash;174. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org:10.1245/s10434-007-9587-1\u003c/span\u003e\u003cspan address=\"https://doi.org:10.1245/s10434-007-9587-1\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2008).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eValsangkar, N. P. et al. N0/N1, PNL, or LNR? The effect of lymph node number on accurate survival prediction in pancreatic ductal adenocarcinoma. \u003cem\u003eJ. Gastrointest. Surg.\u003c/em\u003e \u003cb\u003e17\u003c/b\u003e, 257\u0026ndash;266. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org:10.1007/s11605-012-1974-7\u003c/span\u003e\u003cspan address=\"https://doi.org:10.1007/s11605-012-1974-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2013).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMasuda, T. et al. A Comprehensive Assessment of Accurate Lymph Node Staging and Preoperative Detection in Resected Pancreatic Cancer. \u003cem\u003eJ. Gastrointest. Surg.\u003c/em\u003e \u003cb\u003e22\u003c/b\u003e, 295\u0026ndash;302. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org:10.1007/s11605-017-3607-7\u003c/span\u003e\u003cspan address=\"https://doi.org:10.1007/s11605-017-3607-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2018).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYamamoto, Y. et al. The clinical impact of the lymph node ratio as a prognostic factor after resection of pancreatic cancer. \u003cem\u003eAnticancer Res.\u003c/em\u003e \u003cb\u003e34\u003c/b\u003e, 2389\u0026ndash;2394 (2014).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhan, H. X., Xu, J. W., Wang, L., Zhang, G. Y. \u0026amp; Hu, S. Y. Lymph node ratio is an independent prognostic factor for patients after resection of pancreatic cancer. \u003cem\u003eWorld J. Surg. Oncol.\u003c/em\u003e \u003cb\u003e13\u003c/b\u003e, 105. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org:10.1186/s12957-015-0510-0\u003c/span\u003e\u003cspan address=\"https://doi.org:10.1186/s12957-015-0510-0\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2015).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBhatti, I. et al. Lymph node ratio versus number of affected lymph nodes as predictors of survival for resected pancreatic adenocarcinoma. \u003cem\u003eWorld J. Surg.\u003c/em\u003e \u003cb\u003e34\u003c/b\u003e, 768\u0026ndash;775. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org:10.1007/s00268-009-0336-4\u003c/span\u003e\u003cspan address=\"https://doi.org:10.1007/s00268-009-0336-4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2010).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMassucco, P. et al. Prognostic significance of lymph node metastases in pancreatic head cancer treated with extended lymphadenectomy: not just a matter of numbers. \u003cem\u003eAnn. Surg. Oncol.\u003c/em\u003e \u003cb\u003e16\u003c/b\u003e, 3323\u0026ndash;3332. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org:10.1245/s10434-009-0672-5\u003c/span\u003e\u003cspan address=\"https://doi.org:10.1245/s10434-009-0672-5\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2009).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJohn, B. J. et al. Redefining the R1 resection for pancreatic ductal adenocarcinoma: tumour lymph nodal burden and lymph node ratio are the only prognostic factors associated with survival. \u003cem\u003eHPB (Oxford)\u003c/em\u003e. \u003cb\u003e15\u003c/b\u003e, 674\u0026ndash;680. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org:10.1111/hpb.12019\u003c/span\u003e\u003cspan address=\"https://doi.org:10.1111/hpb.12019\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2013).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePawlik, T. M. et al. Prognostic relevance of lymph node ratio following pancreaticoduodenectomy for pancreatic cancer. \u003cem\u003eSurgery\u003c/em\u003e \u003cb\u003e141\u003c/b\u003e, 610\u0026ndash;618. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org:10.1016/j.surg.2006.12.013\u003c/span\u003e\u003cspan address=\"https://doi.org:10.1016/j.surg.2006.12.013\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2007).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eElshaer, M., Gravante, G., Kosmin, M., Riaz, A. \u0026amp; Al-Bahrani, A. A systematic review of the prognostic value of lymph node ratio, number of positive nodes and total nodes examined in pancreatic ductal adenocarcinoma. \u003cem\u003eAnn. R Coll. Surg. Engl.\u003c/em\u003e \u003cb\u003e99\u003c/b\u003e, 101\u0026ndash;106. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org:10.1308/rcsann.2016.0340\u003c/span\u003e\u003cspan address=\"https://doi.org:10.1308/rcsann.2016.0340\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2017).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"pancreatic cancer, surgery, stage, lymph node yield, survival","lastPublishedDoi":"10.21203/rs.3.rs-8496148/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8496148/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eIntroduction\u003c/h2\u003e \u003cp\u003eSurgical resection plays a pivotal role in the management of pancreatic cancer by achieving complete tumor removal and regional lymphadenectomy. Although most clinical guidelines recommend examining at least 15 lymph nodes (LNY\u0026thinsp;\u0026ge;\u0026thinsp;15) for accurate staging and better prognostic assessment, the optimal threshold remains uncertain and requires validation across population-based datasets.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eUsing the Taiwan Cancer Registry and National Health Insurance Research Database, 926 patients with pancreatic adenocarcinoma who underwent curative resection between 2013 and 2019 were identified. Cox proportional hazards regression models were used to evaluate the association between lymph node yield (LNY\u0026thinsp;\u0026ge;\u0026thinsp;15 vs. \u0026lt;15) and overall survival (OS), adjusting for potential confounders. Several sensitivity analyses were performed to assess the robustness of the findings, including a subgroup analysis restricted to patients with pT1\u0026ndash;3 pancreatic head tumors who underwent pancreatoduodenectomy. Stratified analyses were additionally performed according to pathological T and N classifications and treatment modalities.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe median lymph node yield (LNY) was 15, with 496 (53.6%) patients having\u0026thinsp;\u0026ge;\u0026thinsp;15 nodes retrieved. Patients with adequate LNY were more likely to have tumors in the pancreatic head, undergo pancreatoduodenectomy, and present with advanced pT/N stages and more positive nodes. Although no significant difference in 3-year overall survival (OS) was observed between the \u0026ge;\u0026thinsp;15 and \u0026lt;\u0026thinsp;15 groups, a survival benefit appeared in patients with pT1\u0026ndash;3 head tumors treated with pancreatoduodenectomy. After adjustment for confounders, multivariable analysis showed that LNY\u0026thinsp;\u0026ge;\u0026thinsp;15 was not significantly associated with improved 1-year or 3-year OS in the overall cohort or subgroups. Stratified analyses by AJCC stage and treatment revealed no consistent survival advantage, except for patients with pT1\u0026ndash;2 disease who demonstrated better 1-year OS.\u003c/p\u003e\u003ch2\u003eConclusions:\u003c/h2\u003e \u003cp\u003eA lymph node yield of \u0026ge;\u0026thinsp;15 was not independently associated with improved long-term survival in this cohort. Further large-scale studies are warranted to determine the optimal lymph node threshold for accurate prognostic stratification in pancreatic cancer.\u003c/p\u003e","manuscriptTitle":"Association Between Harvesting at Least 15 Lymph Nodes and Survival in Resected Pancreatic Cancer Using a Nationwide Database","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-13 09:16:39","doi":"10.21203/rs.3.rs-8496148/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a1fb93b9-332c-46d9-bbda-16a16314a76a","owner":[],"postedDate":"January 13th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":60921877,"name":"Biological sciences/Cancer"},{"id":60921878,"name":"Health sciences/Gastroenterology"},{"id":60921879,"name":"Health sciences/Oncology"}],"tags":[],"updatedAt":"2026-04-17T07:28:40+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-13 09:16:39","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8496148","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8496148","identity":"rs-8496148","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}