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Background: The prognosis of pancreatic carcinoma (PC) remains poor and the American Joint Committee on Cancer (AJCC) 8th staging system for survival prediction in PC patients after curative resection is still limited. Thus, the aim of this study is to refine a valuable prognostic model and novel staging system for PC with curative resection. Methods: The data of 3,458 patients used in this study were retrieved from the Surveillance, Epidemiology, and End Results database registry of National Cancer Institute. The prognostic value of lymph node ratio (LNR) was analyzed in the primary cohort and prognostic nomogram based on the LNR was established to create a novel staging system. Then, analyses were conducted to evaluate the application of the formulated nomogram staging system and the AJCC 8th staging system. The predictive performance of model was further validated in the internal validation cohort. Results: Significant positive correlations were found between LNR and all factors except for surgical procedures. The results of univariate and multivariate analyses showed that LNR was identified as an independent prognostic indicator for overall survival (OS) in both primary and validation cohorts (all P < 0.001). A prognostic nomogram based on the LNR was formulated to obtain superior discriminatory abilities. Compared with the AJCC 8th staging system, the formulated nomogram staging system showed higher hazard ratios of stage II, III, and IV disease (reference to stage I disease) that were 1.637, 2.300, and 3.521, respectively, by univariate analyses in the primary cohort and the distinction between stage I, II, and III disease at the beginning or end of the survival curves was more apparent. All these results were further verified in the validation cohort. Conclusion: LNR can be considered as a useful independent prognostic indicator for PC patients after curative resection regardless of the surgical procedures. Compared with the AJCC 8th staging system, the formulated nomogram showed superior predictive accuracy for OS and its novel staging system revealed better risk stratification. [ABSTRACT FROM AUTHOR]

Aim: To identify the risk factors for overall survival (OS) of pancreatic ductal adenocarcinoma patients with no distant metastasis, and formulate a novel nomogram for prognostic prediction.Patients& Methods: Data were obtained from Surveillance, Epidemiology, and End Results database of pancreatic ductal adenocarcinoma patients with no distant metastasis as the primary cohort, and 127 patients at our institution were enrolled as the validation cohort. The prognostic nomogram integrating all independent risk factors for predicting OS was established to achieve superior discriminatory ability.Results: The constructed nomogram showed excellent performance and superior predictive accuracy for OS according to the concordance index and calibration curve.Conclusion: One more advanced and accurate predictive model will be obtained to assist in risk stratification via the constructed nomogram. [ABSTRACT FROM AUTHOR]

Previous fundamental or clinical trials of dendritic cell (DC) vaccine against pancreatic ductal adenocarcinoma (PDAC) revealed the burgeoning neoadjuvant immunotherapy. Microarray studies indicated that multiple ingredients of the transfer growth factor beta (TGF-β) pathway were overexpressed in PDAC, which inhibited the intratumoral immune response. To explore whether the DC volume in tumor microenvironment contributes to the differentiation of T cell cohort and test the hypothesis that combining DC vaccine with TGF-β inhibitors will elevate the anti-tumor immune response, we managed to co-culture T cells in vitro with pancreatic cancer cells and DCs in different concentrations, and combine TGF-β blockage with DC vaccine therapy in a murine model of pancreatic cancer. In in vitro studies, we discovered that CD8+ T cytotoxic cell (Tc) presented a significant advantage and lower volume of CD4+ Thelper cell (Th) existed with a certain elevated DC concentration (p < 0.05), associated with declined interleukin (IL)-10 and increased interferon (IFN)-y, which suggested with the DC volume increasing, the enhancing immune effect may represent a great advantage in such a system (p < 0.05). When interfered with anti-TGF-β antibody or TGF-β cytokine, respectively, in the co-culture system, we found IFN-γ producing was extremely higher and Tcell apoptosis relatively descent with TGF-β blockage (p < 0.05). The murine PDAC model demonstrated a survival advantage treated with anti-TGF-β antibody combined with DC vaccine when compared with monotherapy controls (p < 0.05). Therefore, these findings indicated that, through neutralizing TGF-β associated with DC vaccine, the anti-tumor immunity is highly elevated and this combinational therapy will provide an efficacious prospect. [ABSTRACT FROM AUTHOR]

Background: The prognosis of pancreatic ductal adenocarcinoma (PDAC) remains poor. Open distal pancreatosplenectomy (ODPS) is prevalent in the patients of early PDAC located in pancreatic body or tail. However, the models for relapse or survival prediction in those patients are still limited. Postoperative neutrophil-to-lymphocyte rate (poNLR), a novel inflammation-based score, has been formulated to analyze the prognostic significance in PDAC patients with ODPS. Therefore, this study aims to generate a valuable prognostic nomogram for PDAC following ODPS. Methods: We retrospectively enrolled 97 patients of PDAC undergoing ODPS in this study. The Cox proportional hazards regression methodology was used in univariate and multivariate survival analyses to identify significant independent prognostic factors. The prognostic nomograms integrating poNLR into the American Joint Commission on Cancer (AJCC) staging system (8th edition) for predicting overall survival (OS) and relapse free survival (RFS) were established to achieve superior discriminatory abilities. Further, these prognostic nomograms were verified according to concordance index (C-index), calibrations and decision curve analyses (DCA). Results: The optimal cut-off value of poNLR for assessing OS determined by X-tile program was 14.1. Higher poNLR was associated with higher postoperative neutrophil (poNeutrophil), lower postoperative lymphocyte (poLymphocyte), lower preoperative lymphocyte-to-monocyte rate (preLMR) and higher △NLR (postoperative-preoperative NLR). In the univariate and multivariate analysis, poNLR was identified as an independent prognostic indicator for OS and RFS (P=0.044 and 0.028, respectively) and patients with higher poNLR level were probable to have shorter OS and RFS. Compared with the TNM staging system of the AJCC 8th edition, the nomogram comprising of poNLR and AJCC 8th edition exhibited superior predictive accuracy for OS and RFS. Conclusions: poNLR can be a proven, inexpensive and novel survival predictor of PDAC patients with ODPS. One more advanced and accurate predictive model will be achieved to assist in risk stratification via the incorporation of poNLR into nomograms., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Previous fundamental or clinical trials of dendritic cell (DC) vaccine against pancreatic ductal adenocarcinoma (PDAC) revealed the burgeoning neoadjuvant immunotherapy. Microarray studies indicated that multiple ingredients of the transfer growth factor beta (TGF-β) pathway were overexpressed in PDAC, which inhibited the intratumoral immune response. To explore whether the DC volume in tumor microenvironment contributes to the differentiation of T cell cohort and test the hypothesis that combining DC vaccine with TGF-β inhibitors will elevate the anti-tumor immune response, we managed to co-culture T cells in vitro with pancreatic cancer cells and DCs in different concentrations, and combine TGF-β blockage with DC vaccine therapy in a murine model of pancreatic cancer. In in vitro studies, we discovered that CD8 + T cytotoxic cell (Tc) presented a significant advantage and lower volume of CD4 + T helper cell (Th) existed with a certain elevated DC concentration (p < 0.05), associated with declined interleukin (IL)-10 and increased interferon (IFN)-γ, which suggested with the DC volume increasing, the enhancing immune effect may represent a great advantage in such a system (p < 0.05). When interfered with anti-TGF-β antibody or TGF-β cytokine, respectively, in the co-culture system, we found IFN-γ producing was extremely higher and T cell apoptosis relatively descent with TGF-β blockage (p < 0.05). The murine PDAC model demonstrated a survival advantage treated with anti-TGF-β antibody combined with DC vaccine when compared with monotherapy controls (p < 0.05). Therefore, these findings indicated that, through neutralizing TGF-β associated with DC vaccine, the anti-tumor immunity is highly elevated and this combinational therapy will provide an efficacious prospect., Competing Interests: The authors declare no conflict of interest.

Background : The prognosis of pancreatic ductal adenocarcinoma (PDAC) remains poor and the models for survival prediction in PDAC patients after curative resection are still limited. Preoperative alkaline phosphatase-to-albumin ratio (APAR), an original inflammation-based score, has been established to analyze the prognostic significance in PDAC. Therefore, in this study, we aim to formulate a valuable prognostic nomogram for PDAC following curative resection. Methods : A total of 354 patients with PDAC undergoing curative resection were retrospectively enrolled in this study. The prognostic value of APAR was analyzed in primary cohort containing 220 randomly selected PDAC patients with curative resection and prognostic nomogram incorporating APAR into the American Joint Commission on Cancer (AJCC) 8 th edition was established to obtain superior discriminatory abilities. The predictive performance of APAR was further validated in another independent cohort of 134 PDAC patients. Results : Patients with higher serum APAR level were probable to sustain poorer overall survival (OS). Significant positive correlations were found between APAR and tumor site, and several serum biochemical indexes, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), etc. The results of multivariate analysis showed, APAR was also identified as an independent prognostic indicator for OS in both primary and validation cohorts (P=0.004, P=0.038, respectively). Compared with the AJCC 8 th edition, the nomogram consisting of APAR, pathological differentiation and the TNM staging system of AJCC 8 th edition showed superior predictive accuracy for OS. All these results were further verified in the validation cohort. Conclusions : APAR can be considered as a novel independent prognostic biomarker for PDAC following curative resection. One more accurate and advanced predictive model will be achieved via the incorporation of APAR into nomogram., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.