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Background: The differential diagnosis of pancreatic ductal adenocarcinoma (PDAC) from chronic pancreatitis (CP) is clinically challenging due to a lack of minimally invasive diagnosis methods. MicroRNAs (miRNAs) derived from small extracellular vesicles (EVs) in the blood have been reported as a promising diagnosis biomarker for various types of cancer. However, blood small EV miRNA signatures and their diagnostic value to differentiate between PDAC and CP remain to be determined. Methods: In this study, 107 patients with PDAC or CP were recruited, and 90 patients were finally enrolled for a training cohort (n = 48) and test cohort (n = 42). Small RNA sequencing was used to assess the expression of blood small EV miRNAs in these patients. Results: The linear model from the differentially expressed blood small EV miR‐95‐3p divided by miR‐26b‐5p showed an average sensitivity of 84.1% and an average specificity of 96.6% to identify PDAC from CP in the training cohort and the test cohort, respectively. When the model was combined with serum carbohydrate antigen 19‐9 (CA19‐9), the average sensitivity increased to 96.5%, and the average specificity remained at 96.4% of both cohorts, which demonstrated the best performance of all the published biomarkers for distinguishing between PDAC and CP. The causal analysis performed using the Bayesian network demonstrated that miR‐95‐3p was associated with a "consequence" of "cancer" and miR‐26b‐5p as a "cause" of "pancreatitis." A subgroup analysis revealed that blood small EV miR‐335‐5p/miR‐340‐5p could predict metastases in both cohorts and was associated with an overall survival (p = 0.020). Conclusions: This study indicated that blood small EV miR‐95‐3p/miR‐26b‐5p and its combination with serum levels of CA19‐9 could separate PDAC from CP, and miR‐335‐5p/miR‐340‐5p was identified to associate with PDAC metastasis and poor prognosis. These results suggested the potentiality of blood small EV miRNAs as differential diagnosis and metastases biomarkers of PDAC. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer is a life-threatening malignant disease with significant diversity among geographic regions and races leading to distinct carcinogenesis and prognosis. Previous studies mainly focused on Western patients, while the genomic landscape of Oriental patients, especially Chinese, remained less investigated. Methods: A total of 408 pancreatic cancer patients were enrolled. A panel containing 436 cancer-related genes was used to detect genetic alterations in tumor samples. Results: We profiled the genomic alteration landscape of pancreatic duct adenocarcinoma (PDAC), intraductal papillary mucinous neoplasm (IPMN), periampullary carcinoma (PVC), and solid-pseudopapillary tumor (SPT). Comparison with a public database revealed specific gene mutations in Oriental PDAC patients including higher mutation rates of DNA damage repair-related genes. Analysis of mutational signatures showed potential heterogenous carcinogenic factors caused by diabetes mellitus. KRAS mutation, especially KRAS G12D mutation, was associated with poor survival, while patients not harboring the 17 significant copy number variations (CNVs) had a better prognosis. We further identified multiple correlations between clinicopathologic variables and genetic mutations, as well as CNVs. Finally, by network-based stratification, three classes of PDAC patients were robustly clustered. Among these, class 1 (characterized by the Fanconi anemia pathway) achieved the best outcome, while class 2 (involved in the platinum drug resistance pathway) suffered from the worst prognosis. Conclusions: In this study, we reported for the first time the genetic alteration landscape of Oriental PDAC patients identifying many Oriental-specific alterations. The relationship between genetic alterations and clinicopathological factors as well as prognosis demonstrated important genomic impact on tumor biology. This study will help to optimize clinical treatment of Oriental PDAC patients and improve their survival. [ABSTRACT FROM AUTHOR]

The study aimed to investigate the potential of tumor–stroma ratio (TSR) on digitalized whole-mount histopathology to predict prognosis in patients with pancreatic ductal adenocarcinoma (PDAC). The effectiveness were evaluated through internal validation. Data were retrospectively collected from consecutive patients who underwent primary pancreatic resection from December 2016 to August 2017 (developing cohort) and from September 2017 to April 2018 (validation cohort). Digitalized whole-mount slide images were used to evaluate TSR by both pathologists and a computerized model based on Conditional Generative Adversarial Model (cGAN), respectively. TSR>1 and ≤ 1 denoted low and high stromal component. Logistic regression analysis revealed intratumoral necrosis and R1 independently associated with low stromal component in the developing cohort. Cox regression analysis revealed tumor–node–metastasis (TNM) stage [II vs. I: hazard ratio (HR), 2.584; 95% CI, 1.386–4.819; P = 0.003; III vs. I: HR, 4.384; 95% CI, 2.285–8.411; P < 0.001], stromal component (low vs. high: HR, 1.876; 95% CI, 1.227–2.870; P = 0.004), tumor grade (G3 vs. G1/2: HR, 2.124; 95% CI, 1.419–3.179; P < 0.001), and perineural invasion (with vs. without: HR, 2.147; 95% CI, 1.187–3.883; P = 0.011) were independent prognostic factors in the developing cohort. Stromal component categories could classify patients into subgroups within TNM stages I, II, and III based on over survival. All results were validated in the validation cohort. The weighted kappa value for categorical assessments between pathologists' evaluation and computer-aided evaluation was 0.804 (95% CI, 0.573–0.951). TSR represents a simple and reliable metric for combining the prognostic value of TNM stage in patients with PDAC. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to explore patterns of the treatment strategies of pancreatic ductal adenocarcinoma based on 2000 consecutive cases of a prospective database since 2012 to obtain new insights for future directions.Methods: Among 2000 patients enrolled in this study, 210 patients were excluded, and 710, 521, and 559 patients were treated between 2012 and 2015 (group 1), between 2016 and 2017 (group 2), and between 2018 and 2019 (group 3), respectively. Patient clinicopathologic and biological factors, and perioperative outcomes were used to assess the prognostic factors.Results: The median survival for all patients with pancreatic ductal adenocarcinoma was 21.7 months (1-year survival, 75.0%; 2-year survival, 43.7%; 5-year survival, 19.7%). Group 3 had a better survival outcome than groups 1 and 2 (median survival time: 23 versus 20.5 and 21.1 months). The proportion of patients younger than 65 gradually increased over time, as did the use of systemic chemotherapy and postoperative adjuvant radiotherapy. The tendency for early diagnosis (lower CA19-9 and CEA levels, smaller size, and earlier N stage), use of chemotherapy and radiotherapy, early recovery (lesser hospital stay and Clavien-Dindo grade <3), absence of abdominal pain, younger age, length of operation ≤3 h, and pathological factors (absence of lymphovascular invasion, peripancreatic fat infiltration and neural invasion, higher differentiation) were related to patients' survival. Multivariable analysis for prognosis revealed that tumor biological factors (increased preoperative serum CA19-9 level, tumor size, tumor differentiation, N stage, and presence of lymphovascular invasion and neural invasion), chemotherapy, radiotherapy, abdomen pain, operation period, length of stay, and length of operation correlated with patients' survival.Conclusions: Systemic therapy, including chemotherapy and radiotherapy, has gradually improved the prognosis after operative resection for pancreatic ductal adenocarcinoma. Neoadjuvant therapy is also beneficial to improve the prognosis to a certain extent. The enhanced recovery after surgery (ERAS) policies and the specific assessment of postoperative pancreatic fistula (POPF) risk may be related to reduced hospital stays and the reduction of serious complications. These advancements show that the concept of systemic therapy has been accepted and actively applied by Chinese medical institutions. [ABSTRACT FROM AUTHOR]