IntroductionAcute cellular rejection (ACR) is a T cell-driven event in liver transplantation. Current monitoring relies on detecting graft injury, lacking tools for pre-emptive risk assessment based on the patient’s real-time immune status.MethodsWe developed an immunopharmacologic risk model in a retrospective cohort of 98 liver transplant recipients (18 with biopsy-proven ACR). The model integrated peripheral CD4+ T-cell percentage (flow cytometry) and tacrolimus trough level. Firth-penalized logistic regression was used for model development, with internal validation via bootstrapping.ResultsThe parsimonious model, comprising only CD4+ T-cell percentage and tacrolimus level, demonstrated good discrimination (AUC 0.774, 95% CI 0.674-0.874) and calibration. Critically, lead-time analysis revealed the model provided a median warning window of 8 days (IQR: 3.5 days) prior to biochemical injury onset. It offered significant incremental value over monitoring tacrolimus alone (AUC 0.774 vs. 0.694, ΔAUC=0.080, p=0.007) or CD4+ T cells alone (AUC 0.774 vs. 0.733, ΔAUC=0.041, p=0.014).ConclusionWe identify and validate a novel, clinically actionable immunopharmacologic biomarker panel for ACR. This model enables pre-emptive risk stratification by capturing the high-risk confluence of immune activation and subtherapeutic immunosuppression, paving the way for personalized immunotherapy in transplant recipients.

BackgroundPeriampullary cancers frequently induce malnutrition and sarcopenia, which impair treatment tolerance and survival. Current nutritional assessment tools evaluate host status in isolation, ignoring the modifying effect of tumor biology. We developed and validated a simple nutritional risk score integrating host and tumor domains to identify high-risk patients and quantify the extent to which the association between preoperative risk and poor outcomes is mediated through a sequential pathway.MethodsThis dual-center retrospective cohort study included 533 patients who underwent pancreaticoduodenectomy. Using a time-ordered split, patients were assigned to training (n = 261), internal validation (n = 112), and temporal validation (n = 160) sets. Least Absolute Shrinkage and Selection Operator (LASSO)-Cox regression selected predictors for disease-free survival (DFS). The final model was validated internally and temporally, with head-to-head comparisons against 12 established nutritional scores. Formal sequential mediation analysis quantified the pathway from preoperative nutritional risk to postoperative complications, then to adjuvant therapy delay, and ultimately to reduced DFS.ResultsThe cohort had mean age 64.0 ± 9.8 years, 57.8% male. Median follow-up was 23 months. During follow-up, 261 recurrence or death events (49.0%) occurred; 1-year mortality was 55.7% (95%CI 51.5-59.9%). LASSO-Cox identified three independent predictors: total muscle index (TMI, mm2/m2), percent weight loss (>5% vs. ≤ 5%), and tumor type. The model showed good discrimination: C-index 0.783 (training), 0.718 (internal validation), and 0.702 (temporal validation). It significantly outperformed all 12 nutritional scores (all P < 0.001). High-risk patients had worse DFS (log-rank P < 0.0001) and a 3.29-fold higher risk of major complications (95% CI: 1.23–9.46). Complications led to a 22.27-fold higher risk of adjuvant therapy delay (95% CI: 6.70–90.28), which in turn reduced DFS (HR 2.66, 95% CI: 1.39–5.09). Mediation analysis showed that 20.9% (95% CI: 5.1–36.7%) of the total effect of high nutritional risk on DFS was mediated through this complication-to-delay pathway.ConclusionsA simple three-variable score (muscle index, weight loss >5%, tumor type) enables preoperative identification of high-risk periampullary cancer patients. One-fifth of the excess recurrence risk may be mediated through a modifiable cascade of complications leading to adjuvant therapy delays, providing a clear rationale for targeted nutritional prehabilitation and perioperative interventions.

Background: Metabolic dysfunction-associated fatty liver disease has been linked to negative outcomes in patients with end-stage liver disease following liver transplantation. However, the influence fl uence of immunosuppressive regimens on it has not been explored. Methods: A retrospective analysis was conducted using the preoperative and postoperative data from patients with end-stage liver disease. The study compared three different groups: tacrolimus-based group, sirolimus-based group, and combined tacrolimus- and sirolimus-based regimens. Binary logistic regression analysis was employed to identify risk factors for metabolic dysfunction-associated fatty liver disease. Results: A total of 171 patients participated in the study, consisting of 127 males and 44 females, with a mean age of 49.6 years. The prevalence of posttransplant metabolic dysfunction-associated fatty liver disease was 29.23%. Among the three groups, there were 111 liver transplant recipients in the tacrolimus-based group, 28 in the sirolimus-based group, and 32 in the combination group. A statistically significant fi cant difference was observed in the incidence of metabolic dysfunction-associated fatty liver disease (P P < 0.05), whereas the other preoperative and postoperative parameters showed no significant fi cant differences. Multivariate analysis revealed that a low-calorie diet (95% confidence fi dence intervals: 0.15-0.90, - 0.90, P = 0.021) and a combination of tacrolimus- and sirolimusbased immunosuppressive regimen (95% confidence fi dence intervals: 1.01-2.77, - 2.77, P = 0.046) were associated with lower risk of posttransplant metabolic dysfunction-associated fatty liver disease. Conclusions: Our study indicates that implementing a low-calorie diet and utilizing a combination of tacrolimus- and sirolimus-based immunosuppressive regimen can effectively lower the risk of posttransplant metabolic dysfunction-associated fatty liver disease following liver transplantation.

Hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) is a major contributor to mortality. We developed a recurrence prediction system for HCC patients before and after LT. Data from patients with HCC who underwent LT were retrospectively collected from three specialist centres in China. Pre- and post-operative variables were selected using support vector machine, random forest, and logistic regression (LR). Then, pre- and post-operative models were developed using three machine learning methods: LR, stacking, and two survival-based approaches. Models were evaluated using seven assessment indices, and patients were classified as either high- or low-risk based on recurrence risk. 466 patients were included and followed for a median of 51.0 months (95% CI 47.8–54.2). The pre-DeepSurv model (pre-DSM) had a C-index of 0.790 ± 0.003 during training, 0.775 ± 0.037 during testing, and 0.765 ± 0.001 and 0.819 ± 0.002 during external validation. After incorporating clinicopathologic variables, the post-DeepSurv model (post-DSM) had a 0.835 ± 0.008 C-index during training, 0.812 ± 0.082 during testing, and 0.839 ± 0.001 and 0.831 ± 0.002 during external validation. The post-DSM outperformed the Milan criteria by more accurately identifying patients at high risk of recurrence. Tumour recurrence predictions also improved significantly with DeepSurv. Both pre- and post-DSMs have the potential to guide personalised surveillance strategies for LT patients with HCC.

B cells possess anti-tumor functions mediated by granzyme B, in addition to their role in antigen presentation and antibody production. However, the variations in granzyme B+ B cells between tumor and non-tumor tissues have been largely unexplored. Therefore, we integrated 25 samples from the Gene Expression Omnibus database and analyzed the tumor immune microenvironment. The findings uncovered significant inter- and intra-tumoral heterogeneity. Notably, single-cell data showed higher proportions of granzyme B+ B cells in tumor samples compared to control samples, and these levels were positively associated with disease-free survival. The elevated levels of granzyme B+ B cells in tumor samples resulted from tumor cell chemotaxis through the MIF- (CD74 + CXCR4) signaling pathway. Furthermore, the anti-tumor function of granzyme B+ B cells in tumor samples was adversely affected, potentially providing an explanation for tumor progression. These findings regarding granzyme B+ B cells were further validated in an independent clinic cohort of 40 liver transplant recipients with intrahepatic cholangiocarcinoma. Our study unveils an interaction between granzyme B+ B cells and intrahepatic cholangiocarcinoma, opening up potential avenues for the development of novel therapeutic strategies against this disease.

BACKGROUND:There is no reliable means to evaluate the immune status of liver transplant recipients. We proposed a novel score model, namely Mingdao immune cell analysis and Mingdao immune score system, to quantify the immunity.METHODS:Data from those who underwent a single liver transplant between January 2017 and June 2020 at Beijing Chaoyang Hospital, were collected. In addition, healthy volunteers were also enrolled. The score model was based on the immune cell populations determined by flow cytometry.RESULTS:There were a total of 376 healthy controls with 376 tests and 148 liver transplant recipients with 284 tests in this study. Evaluated by Mingdao immune cell analysis and Mingdao immune score system, the mean scores of healthy controls were near zero suggesting a balanced immune system. In contrast, the mean scores of liver transplant recipients were negative both before and after surgery indicating a compromised immune system. When liver transplant recipients were given a reduced or routine first dose according to their preoperative score, they had similar recovery of liver function. Moreover, liver transplant recipients with increased scores ≥ 5 were associated with elevated aspartate transaminase and alanine amiotransferase. Finally, on multivariate analysis the score model was the only significant independent risk factor for clinical acute rejection (P = 0.021; Odds ratio, 0.913; 95% confidence interval, 0.845-0.987).CONCLUSION:The novel score model could be used as an indicator to reflect immunity and to regulate immunosuppressants in liver transplant recipients after surgery.

>Introduction The immune system is the cornerstone of human health, with most diseases and health conditions closely related to immune status. Therefore, immune status management is a core health issue. In recent years, significant research breakthroughs in immunosuppressants, immune cell therapy, and immune checkpoint inhibitors have enabled clinical experts and researchers to effectively modulate immune status and regulate immunity more efficient. Key questions in the field of immunology include: How can immune function be visually assessed?

Background. Managing hepatocellular carcinoma (HCC) presents significant clinical challenges, often necessitating orthotopic liver transplantation (OLT). To mitigate the risk of iatrogenic metastasis during OLT and reduce posttransplantation recurrence (PTR), we introduced the “no-touch” left (NTL) approach for recipient hepatectomy in OLT. Methods. In this retrospective cohort study, our aim was to compare the safety and PTR rates in patients undergoing OLT via either the NTL technique or the conventional approach for recipient hepatectomy. We included 106 patients who met the Hangzhou criteria and exhibited a high tumor burden in the right lobe, with 50 patients assigned to the NTL group and 56 to the conventional group. The primary endpoint was the 1-y PTR rate, whereas secondary endpoints encompassed the safety of the NTL approach, PTR rates at 2 and 5 y, and overall survival. Results. Baseline demographics and clinical characteristics showed no significant differences between the groups. The NTL approach exhibited major surgical outcomes similar to those of the conventional approach. The cumulative PTR rates at 1, 2, and 5 y were 14.0% in the NTL group, compared with 24.5%, 35.8%, and 35.8% in the conventional group (P = 0.013). Cumulative overall survival rates at 1, 2, and 5 y were 94.0%, 91.9%, and 89.7% in the NTL group and 88.7%, 75.5%, and 72.5% in the conventional group (P = 0.03). Conclusions. This innovative surgical technique enhances safety and significantly reduces the risk of PTR, leading to improved long-term survival. Further prospective studies with larger cohorts and longer follow-up periods are needed to validate our findings and establish the NTL approach as a standard practice in OLT.

PurposeWhether the diagnosis of non-alcoholic fatty liver disease or metabolic dysfunction-associated fatty disease has a different impact on liver transplant recipients with hepatocellular carcinoma is not yet clear.MethodsData from a two-center retrospective cohort study were collected to compare and investigate the differences between non-alcoholic fatty liver disease and metabolic dysfunction-associated fatty liver disease in clinicopathologic parameters and prognosis among liver transplant recipients with hepatocellular carcinoma.ResultsA total of 268 liver transplant recipients with hepatocellular carcinoma were included. The prevalence among pre- and post-transplant metabolic dysfunction-associated fatty liver disease was 10.82% and 30.22%, while for non-alcoholic fatty liver disease, it was 7.09% and 26.87%, respectively. The clinicopathological parameters were similar between the two pre-transplant groups. In contrast, the post-transplant group with metabolic dysfunction-associated fatty liver disease exhibited a higher prevalence of diabetes mellitus and a greater body mass index. However, the other parameters were similar between the two post-transplant groups (p > 0.05). Factors such as the largest tumor size > 4 cm, microvascular invasion, lack of tumor capsule, post-transplant metabolic dysfunction-associated fatty liver disease, and decreased post-transplant lymphocyte percentage were related to an increased risk of recurrence.ConclusionIn patients undergone liver transplantation for hepatocellular carcinoma, the diagnosis of metabolic dysfunction-associated fatty disease is more strongly associated with metabolic abnormalities than the diagnosis of non-alcoholic fatty liver disease and is an independent predictor of hepatocellular carcinoma recurrence.

Objective:To evaluate superior mesenteric artery preferential approach in the borderline resectable pancreatic head cancer.Methods:The clinical and follow-up data of 90 patients with borderline resectable pancreatic head cancer who underwent radical pancreatoduodenectomy at Beijing Chaoyang Hospital,Capital Medical University from Jan 2015 to Dec 2021 were analyzed.Results:After exploring the superior mesenteric artery in the lower colon area to confirm the vascular invasion meet the resection criteria, the blood supply is cut off first, then the tumors were resected en bloc, with the invaded vessels resected and reconstructed or replaced. All 90 patients successfully completed the operation without perioperative death. Pathology established pancreatic ductal adenocarcinoma. The 1-year, 2-year, and 3-year disease-free survival rates of patients in the arterial priority approach group were 68.2%, 60.4%, and 54.3%, while the 1-year, 2-year, and 3-year disease-free survival rates of patients by conventional approach were 58.4%, 26.4%, and 11.7% ( P=0.001). Conclusion:The superior mesenteric artery preferential approach in the inferior colon region can prolong the survival time of patients after surgery, and reduce the recurrence.

Rejection and adverse reactions caused by long-term use of immunosuppressants severely affect the survival rate and quality of life of organ transplant recipients. Immune tolerance induction plays a key role in improving the survival rate and quality of life of organ transplant recipients. In recent years, tremendous progress has been achieved in adoptive re-transfusion of regulatory cells. In this article, research progress in regulatory T cell (Treg), myeloid-derived suppressor cell (MDSC) and regulatory B cell (Breg) in animal experiment and clinical application was reviewed, and the main clinical problems of adoptive re-transfusion of regulatory cells, the application of chimeric antigen receptor Treg and the concept of cell therapy in immune evaluation were summarized, aiming to deepen the understanding of regulatory cell therapy, promote the application of regulatory cells in immune tolerance of organ transplantation, and improve clinical efficacy of organ transplantation and the quality of life of recipients.

Pancreatic cancer (PC) is a stubborn malignancy with high lethality and a low 5-year overall survival (OS) rate. Collagen type VII α1 chain (COL7A1), a major component of the extracellular matrix, serves important roles in numerous physiological processes and various illnesses. COL7A1 protein acts as an anchoring fibril between the external epithelial cells and the underlying stroma, and mutation of COL7A1 could cause recessive dystrophic epidermolysis bullosa. Raw data for PC were acquired from The Cancer Genome Atlas and the Gene Expression Omnibus database, and raw data for the normal pancreas were obtained from the Genotype-Tissue Expression database. COL7A1 mRNA expression in PC tissues was compared with that in either paired (GSE15471 dataset) or unpaired (all other data) normal pancreas tissues. The association between COL7A1 mRNA expression and clinicopathological factors was assessed using logistic regression analysis. Cox analysis and Kaplan-Meier analysis were used to evaluate the role of COL7A1 mRNA expression in prognosis and nomograms were constructed. Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis, Gene Set Enrichment Analysis (GSEA) and single-sample GSEA (ssGSEA) were performed to evaluate the relevant functions of COL7A1 and correlation with immune cell infiltration. Furthermore, reverse transcription-quantitative PCR was used to assess the mRNA expression levels of COL7A1 in PC. The present study demonstrated that COL7A1 mRNA expression was higher in PC tissues compared with in normal pancreas tissues. The Kaplan-Meier survival analysis indicated that patients with PC with high COL7A1 mRNA expression had shorter overall survival (OS), disease-specific survival (DSS) and progression-free interval (PFI) times compared with patients with PC with low COL7A1 mRNA expression. Multivariate analysis demonstrated that COL7A1 mRNA expression was an independent risk factor for OS, DSS and PFI. Nomogram and calibration plots were constructed to predict the prognosis of patients with PC. GSEA demonstrated that high mRNA expression levels of COL7A1 were associated with multiple cancer-related pathways. ssGSEA analysis indicated that COL7A1 expression was positively associated with natural killer CD56bright cells and T helper (Th)2 cells, and negatively associated with Th17 cells and eosinophils. The results of the present study suggested that COL7A1 could be an independent biomarker and an influential moderator of immune infiltration in PC.

BACKGROUND:Metabolic dysfunction-associated fatty liver disease was proposed by international consensus to redefine the metabolic abnormal condition. However, its impact on liver transplant recipients with hepatitis B virus-related hepatocellular carcinoma has not been explored. METHODS:A two-center retrospective cohort study on liver transplant recipients with hepatitis B virus-related hepatocellular carcinoma was performed to analyze the impact of metabolic dysfunction-associated fatty liver disease on the clinicopathologic parameters and prognosis. RESULTS:There were 201 liver transplant recipients enrolled from two hospitals in our study. The pre- and post-transplant prevalences of metabolic dysfunction-associated fatty liver disease were 9.95% and 28.86%, respectively. The clinicopathological parameters revealed a similarity between patients with and without pre-transplant metabolic dysfunction-associated fatty liver disease. In contrast, the group with post-transplant metabolic dysfunction-associated fatty liver disease was linked with older age, a higher hepatitis recurrence rate and incidence of cardiovascular disease, usage of calcineurin inhibitors, a greater body mass index and waist circumference, lower albumin and high-density lipoprotein cholesterol levels, and poorer tumor-free survival and overall survival. The multivariate analysis showed the largest tumor size >4 cm (95% confidence intervals: 0.06~0.63, p = 0.006), microvascular invasion (95% confidence intervals: 1.61~14.92, p = 0.005), post-transplant metabolic dysfunction-associated fatty liver disease (95% confidence intervals: 1.40~10.60, p = 0.009), and calcineurin inhibitors-based regimen (95% confidence intervals: 0.33~0.96, p = 0.036) were the independent risk factors for recurrent hepatocellular carcinoma. CONCLUSIONS:Our study suggests that post-transplant metabolic dysfunction-associated fatty liver disease is more closely to metabolic abnormalities and that it can help identify liver transplant recipients at high risk of recurrent hepatocellular carcinoma.

Abstract Background: Due to the lack of a reliable means to evaluate the immune status, we proposed a novel method, namely Mingdao immune cells analysis and Mingdao immune score system, to quantify the immunity by scores. Methods: Data from healthy controls in addition to liver transplant recipients, who underwent a single liver transplant or were followed up at Beijing Chaoyang Hospital, were retrospectively collected and analyzed between January 2017 and June 2020. Furthermore, peripheral blood was taken for flow cytometric measurement. Results: A total of 376 healthy controls with 376 tests and 148 liver transplant recipients with 284 tests were included in this study. Evaluated by Mingdao immune cells analysis and Mingdao immune score system, the mean values of healthy controls were near zero inspite of different age groups and gender in contrast to negative mean values in liver transplant recipients before and after liver transplantation. The preoperative scores were used to decide the first dose of the immunosuppressants as patients with lower scores (≤ -5) were suggested to give a lower dose in an attempt to reach a balance between over- and under- immunosuppression. Moreover, we found positive scores or increased scores (≥ 5) could reflect immune activation. Finally, the score was defined to be the only significant independent risk factor for clinical acute rejection (odds ratio, 0.913; confidence interval, 0.845-0.987; P = 0.021). Conclusion: The novel method could be used as an indicator to reflect the immunity and to regulate the immunosuppressants.

Little is known about the shift of lymphocytes under the condition of the model for end-stage liver disease score and the follow-up period. Then, we detected the peripheral blood from liver transplant recipients by flow cytometry and compared the results. The model for end-stage liver disease score affected the percentages of T-cell subsets and B cells during the short-term follow-up period, but failed to influence the lymphocyte subsets during the long-term follow-up period. In contrast, the follow-up period not only affected the absolute counts of T-cell subsets and natural killer (NK) cells in patients with the low model for end-stage liver disease scores, but also influenced the percentages and absolute counts of T-cell subsets in patients with the high model for end-stage liver disease scores. In the two-way ANOVA, we further revealed that the model for end-stage liver disease score was associated with the percentages of T cells and CD4+ T cells and the absolute numbers of T-cell subsets and B cells, while the follow-up period was associated with the percentages of T-cell subsets and the absolute numbers of lymphocyte subsets. Therefore, patients with either the low model for end-stage liver disease scores or the long-term follow-up period are in a relatively activated immune condition.

Background: Tolerance is more easily induced in liver transplant models than in other organs; CD8+CD45RClowregulatory T cells (Tregs) have been shown to induce tolerance in heart allografts. Whether CD8+CD45RClowTregs could induce tolerance in a liver transplant model and how dendritic cells (DCs) mediate the CD8+CD45RClowTregs effect remains to be investigated. Methods: A rat liver transplantation model was established and used to test tolerance and acute rejection compared to control groups. Liver function and histopathological changes of allograft were examined by enzymelinked immunosorbent assay (ELISA) and haematoxylin and eosin (H&E) staining, respectively. The distribution and proportion of CD8+CD45RClowTregs and plasmacytoid dendritic cells (pDCs) in the allografts and spleen were determined using flow cytometry. Cytokine secretion levels were determined using ELISA and real-time quantitative PCR (qRT-PCR). Results: The rat liver transplantation model was well established, with a success rate of 93.3% (28/30). The mean survival time of the tolerant and acute-rejection rats were 156 and 14 days, respectively. The proportions of CD8+CD45RClowTegs were higher in the allografts of tolerant rats than in those of acute-rejection rats (33.1 +/- 4.3 and 12.4 +/- 4.6, respectively; P = 0.04). Significant accumulation of pDCs was observed in tolerant liver graft rats compared to that in acute-rejection rats (1.46 +/- 0.23 and 0.80 +/- 0.20, respectively; P = 0.02). Importantly, CD8+CD45RClowTregs were positively associated with the frequency of pDCs (P = 0.001, r2 = 0.775). The protein and mRNA expression of IL-10 and TGF-8 in the allograft group were increased, possibly being responsible for tolerance induction. Conclusion: CD8+CD45RClowT cells interact with pDCs through the induction of IL-10 and TGF-8 expression and are responsible for inducing immune tolerance in rat liver transplantation.

目的 探讨肝移植受者术后发生急性排斥反应时淋巴细胞亚群的变化及意义.方法 选取接受肝移植且发生急性排斥反应的受者作为排斥组(17例),利用倾向评分匹配方法按1:1比例选取肝功能稳定的肝移植受者作为对照组(17例).分析肝移植术后急性排斥反应的发生情况,对比两组受者他克莫司浓度.比较两组受者外周血淋巴细胞亚群的绝对值和比例,采用受试者工作特征(ROC)曲线分析淋巴细胞亚群对肝移植术后急性排斥反应发生的诊断价值.比较排斥组治疗前后淋巴细胞亚群绝对值和比例的变化.结果 排斥组17例受者中,4例在术后28 d内发生急性排斥反应,13例在术后29～180 d发生急性排斥反应.两组他克莫司谷浓度差异无统计学意义(P=0.295).与对照组比较,排斥组受者外周血T细胞、CD4+T细胞、B细胞和自然杀伤(NK)T细胞的比例均上升(均为P<0.05).肝移植术后早期NKT细胞比例升高是肝移植术后发生急性排斥反应的独立危险因素[比值比(OR)1.774,95％可信区间(CI)1.059～2.971,P=0.029].ROC曲线分析结果提示,CD4+T细胞、B细胞和NKT细胞比例的曲线下面积(AUC)分别为0.76、0.73和0.77.联用CD4+T细胞、B细胞和NKT细胞比例的AUC为0.89,当临界值为0.69时,灵敏度为0.706,特异度为0.941.排斥组所有受者治疗后均逐渐恢复,最终肝功能正常,治疗后T细胞、CD4+T细胞、CD8+T细胞和NK细胞比例均降低(均为P<0.05).结论 NKT细胞比例升高提示肝移植术后急性排斥反应发生风险增加,联用CD4+T细胞、B细胞和NKT细胞比例可早期发现和诊断肝移植术后急性排斥反应.

Pancreatic cancer (PC) is notorious for its parallel morbidity and mortality rates. Recently, necroptosis, a form of programmed cell necrosis, has gained popularity for its role in tumorigenesis and metastasis. In this study, we explored the expression of necroptosis-related genes in PC and normal pancreatic tissues and identified 52 differentially expressed genes (DEGs). The Cox regression analysis was applied to construct the prognostic risk model, which divided patients into high- and low-risk groups. PC patients in the low-risk group showed a significantly better overall survival (OS) than those in the high-risk group. We further validated the prognostic role in ICGC cohort. Further, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), and tumor microenvironment (TME) analysis were used to explore the underlying mechanisms. Notably, based on the gene signature, we revealed that the risk score was strongly related to the sensitivity of chemotherapy. In conclusion, necroptosis-related genes serve as an important immune mediator, and the risk model could be used to predict the survival and to guide the development of precision drugs for patients with PC.

Superior mesenteric artery‑first approach has been proposed for the surgical treatment of pancreatic head cancer. However, little is known about its effects on resectable pancreatic head cancer. In the present study, data from patients with resectable pancreatic head cancer, who underwent radical pancreatoduodenectomy with or without the superior mesenteric artery‑first approach at from January, 2014 to December, 2019, were retrospectively collected and analyzed. A total of 204 patients were included in the study. The blood loss and blood transfusion of the arterial approach group (n=94) were less than those of the conventional approach group (n=110). Diarrhea occurred in 31 cases (15.2%) of the arterial approach group and in 18 cases (8.8%) of the conventional approach group (P<0.05). A higher rate of R0 resection and a higher number of lymph nodes harvested were achieved in the arterial approach group (P<0.05). The 1‑, 2‑ and 3‑year tumor‑free survival rates of the patients in the arterial approach group were 60.9, 43.2 and 37.9%, respectively, and those of the patients in the conventional approach group were 64.2, 24.9 and 15.6%, respectively (P<0.05). Moreover, the 1‑, 2‑, and 3‑year overall survival rates of the patients in the arterial approach group were 79.5, 49.7 and 36.7%, and those of the patients in the conventional approach group were and 75.9, 38.6 and 18.7%, respectively (P<0.05). On the whole, the present study demonstrates that the superior mesenteric artery‑first approach can reduce intraoperative blood loss and consequent blood transfusion, facilitate the achievement of an R0 resection, and thus prolong the survival of patients, despite resulting in a higher rate of diarrhea.

BACKGROUND:Whether standard lymphadenectomy or extended lymphadenectomy should be performed is still under debate during pancreaticoduodenectomy (PD). We aimed to compare their morbidity and mortality rates among patients with pancreatic head cancer (PHC).METHODS:In this retrospective study, a total of 322 patients were enrolled. According to the scope of intraoperative lymph node dissection, patients were divided into extended lymphadenectomy group (n=120) and standard lymphadenectomy group (n=202). Based on the resectability of the tumor, there were 198 cases of resectable PHC and 124 cases of borderline resectable PHC, respectively, in which further stratified analysis was carried out according to the extent of lymph node dissection.RESULTS:All patients completed the operation successfully, with a perioperative morbidity rate of 27.9% and mortality rate of 0.9%. As for the overall patients, patients in the extended lymphadenectomy group had higher neutrophil-to-lymphocyte ratio (NLR), longer operation time, more intraoperative blood loss, lymph node dissection and patients with borderline resectable pancreatic head cancer (BRPHC) (P<0.05). The 1-, 2- and 3-year overall survival rates of patients with extended lymphadenectomy and standard lymphadenectomy were 71.9%, 50.6%, 30.0% and 70.0%, 32.9%, 21.5%, respectively (P=0.068). With regards to patients with BRPHC, the number of lymph node dissection in the extended lymphadenectomy group was more (P<0.05), and the 1-, 2- and 3-year overall survival rates of patients with extended lymphadenectomy and standard lymphadenectomy were 60.7%, 43.3%, 27.4% and 43.2%, 17.7%, 17.7%, respectively (P=0.007).CONCLUSIONS:Patients with BRPHC tended to have vast lymph node metastasis. Extended lymphadenectomy can improve their long-term survival.