Introduction ============ Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease and is the fourth leading cause of cancer-related death.[@b1-cmar-10-3811],[@b2-cmar-10-3811] Curative resection remains the only possibility of long-term survival for patients with PDAC. The rate of positive lymph nodes is an important indicator of the resectability of PDAC; there is a high risk of regional lymphatic metastasis in patients with PDAC.[@b3-cmar-10-3811],[@b4-cmar-10-3811] Thus, some investigators have recommended that all patients with PDAC undergo upfront lymphadenectomy with pancreaticoduodenectomy (PD) to improve survival.[@b3-cmar-10-3811],[@b5-cmar-10-3811] However, routine lymphadenectomy for most PDAC patients is now questionable due to the increasing evidence that does not support this approach.[@b6-cmar-10-3811]--[@b9-cmar-10-3811] Several recent retrospective studies of patients undergoing PD with PDAC have been reported. However, many of these studies have limitations that limit the strength of their findings. First, these studies were not performed at a single center.[@b10-cmar-10-3811] In addition, the authors' decision regarding the resectability criteria for lymphadenectomy and the extent of lymphadenectomy were not uniform.[@b11-cmar-10-3811] Studies that report the outcomes of patients with PDAC must meet the following criteria: (a) patients must have undergone upfront surgery with curative intent, (b) patients must have been pathologically staged as stage I--II disease, and (c) all patients must have been administered standardized adjuvant therapy (SAT).[@b12-cmar-10-3811],[@b13-cmar-10-3811] In this retrospective study, we evaluated the feasibility of lymphadenectomy for patients with PDAC who underwent PD at a single center. The objective of the study was to identify the risk factors for positive nodes and to assess the necessity of lymphadenectomy. Materials and methods ===================== Patients -------- We performed a retrospective analysis of data from patients with PDAC who were admitted to Shanghai General Hospital between October 2007 and October 2013. All these patients underwent PD at Shanghai General Hospital and were diagnosed with PDAC based on histopathological evaluation. All the patients received adjuvant therapy with gemcitabine or fluorouracil or both. None of the patients had received neoadjuvant therapy prior to surgery. The patients were staged according to the 7th edition of the American Joint Committee on Cancer TNM staging system.[@b14-cmar-10-3811] The demographic and clinicopathological data were obtained from the electronic medical records. The patients were divided into two groups based on the presence or absence of lymphadenectomy: the lymphadenectomy (LN) group, which included patients who underwent lymphadenectomy with PD, and the non-LN group, which included patients who did not undergo lymphadenectomy. The patients' age, sex, serum carbohydrate antigen 19-9 level, tumor location, maximum tumor diameter, pancreatic head mass or tail mass, surgical procedure, duration of surgery, and surgical margin were recorded. All of the patients were followed up until November 2017 or the date of death. Written informed consent was obtained from all the patients or their families. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Statistical analyses -------------------- A continuous variable is described as the mean ± SD; categorical variables were analyzed using the *χ*^2^ test. A two-tailed *P*-value of \<0.05 was considered to indicate statistical significance. Statistical analyses were performed using SPSS Statistics version 21.0 (IBM Corporation, Armonk, NY, USA). Results ======= Patient characteristics ----------------------- During the study period, we identified a total of 105 patients with PDAC who underwent PD at Shanghai General Hospital. Among these patients, only 51 were confirmed to have PDAC by histopathological evaluation and all of the patients had an R0 resection. The clinicopathological characteristics are shown in [Table 1](#t1-cmar-10-3811){ref-type="table"}. The median age of the patients was 62 years (range: 26--78 years). A total of 42 (82.3%) patients were female. The histopathological results were divided into four groups: intraductal papillary mucinous neoplasms (IPMNs, n=19); borderline IPMNs, n=4; mucinous adenocarcinomas (MACs), n=4; and other IPMNs, n=19. The patients' characteristics are shown in [Table 2](#t2-cmar-10-3811){ref-type="table"}. Survival analysis ----------------- The median duration of follow-up was 25.8 months (range: 2.6--79.9 months). Two patients had positive lymph nodes and underwent neoadjuvant therapy. Therefore, we excluded them from the survival analysis. In total, 33 patients (64.7%) had pathologically positive lymph nodes; 20 patients (39.2%) had one lymph node involved, 7 (13.7%) had two lymph nodes involved, and 5 (9.8%) had three lymph nodes involved. The details of the patients with positive lymph nodes are summarized in [Table 3](#t3-cmar-10-3811){ref-type="table"}. Of the 51 patients in the study, only 5 (9.8%) patients received upfront lymphadenectomy. Of these patients, 1 (2.0%) patient had positive lymph nodes and underwent upfront lymphadenectomy and 4 (7.8%) patients had positive lymph nodes and did not undergo lymphadenectomy. There was a statistically significant difference between the two groups regarding lymph node involvement (*P*\<0.05) ([Table 4](#t4-cmar-10-3811){ref-type="table"}). In the whole patient population, the median overall survival (OS) was 18 months (range: 0.3--83 months). Five patients (9.8%) were alive at the time of the last follow-up, and these patients survived for 8, 8, 10, 11, and 11 months, respectively. The median relapse-free survival was 5 months (range: 0.3--83 months). Of the 51 patients in this study, 24 patients (47.1%) died during the follow-up period. There was no significant difference in OS between the LN and non-LN groups (*P*\>0.05) ([Figure 1](#f1-cmar-10-39){ref-type="fig"}). Discussion ========== In the present study, we observed a low incidence of positive lymph nodes and a high incidence of nodal micrometastasis in patients with PDAC. In addition, the OS of patients with PDAC after PD was \<3 months. However, the potential benefit of upfront lymphadenectomy in patients with PDAC remains controversial, and it is necessary to evaluate the usefulness of lymphadenectomy for patients with PDAC.[@b2-cmar-10-3811] A major limitation of the study was the retrospective design, and the data regarding the diagnosis of PDAC were based on clinical features and imaging rather than histological evidence. This study showed that lymphadenectomy was associated with an improved OS, and this finding was contrary to the results of other studies, which were performed at different centers.[@b2-cmar-10-3811],[@b3-cmar-10-3811],[@b10-cmar-10-3811],[@b15-cmar-10-3811]--[@b20-cmar-10-3811] However, two recent studies found no survival benefit of lymphadenectomy in patients with PDAC.[@b7-cmar-10-3811],[@b20-cmar-10-3811] This difference might be attributed to different patient numbers. We are aware that the sample size is relatively small, and it is possible that our results were unstable. The present study demonstrated a lack of power of the univariate log-rank test. In the multivariate analysis, lymphadenectomy was a statistically significant prognostic factor for OS in the whole patient population, which included all the patients with PDAC. A low incidence of positive lymph nodes was found, and a low incidence of nodal micrometastasis (positive lymph nodes) was found in patients with PDAC. Many studies have demonstrated the poor survival rates of patients with PDAC.[@b7-cmar-10-3811],[@b21-cmar-10-3811] It is generally accepted that patients with PDAC have a poor prognosis. For example, the median OS in our group was \<3 months (median OS: 18 months). The number of lymph nodes harvested has also been associated with patients' survival. However, we found no significant difference in OS between the LN and non-LN groups, which might be due to the limited number of lymph nodes harvested. In our study, the number of patients undergoing lymphadenectomy was relatively small, and the risk factors for positive nodes were not adequately addressed. Hence, the results presented in this study will not reflect the actual patient population. In a multic