The Association between Early-Onset Pancreatic Ductal Adenocarcinoma and Patients Survival: A Systematic Review and Meta-Analysis.

Background: In recent years, the incidence of early-onset pancreatic cancer (EOPC) has increased. Several studies comparing the survival of patients with EOPC to those with average-onset pancreatic cancer (AOPC) have reported mixed results. We aimed, therefore, to perform a meta-analysis summarizing the current evidence. Methods: We searched the MEDLINE and EMBASE databases for relevant articles published through March 2024. Articles comparing the survival of patients with EOPC - defined as pancreatic ductal adenocarcinoma (PDAC) diagnosed at ≤ 50 years of age - and AOPC were included in the present meta-analysis. The primary outcome was the pooled adjusted hazard ratio (aHR), and the risk of bias analysis was performed using the Quality in Prognostic Factor Studies tool. The meta-analysis was performed using a random-effects model. Results: A total of 17 studies were eligible for the primary analysis, the results of which indicated that patients with EOPC had a longer overall survival than those with AOPC (aHR = 0.80; 95% confidence interval [CI], 0.74-0.86; P < 0.001). The rate of distant metastasis was higher in EOPC than AOPC; however, patients with EOPC also received more treatments than those with AOPC. Conclusions: Patients with EOPC had a better prognosis than those with AOPC. Clinicians must ensure that patients with PDAC receive early and appropriate treatment to improve their survival.

Construction and validation of a pancreatic cancer prognostic model based on genes related to the hypoxic tumor microenvironment.

BACKGROUND: Pancreatic cancer is one of the most lethal malignancies, characterized by poor prognosis and low survival rates. Traditional prognostic factors for pancreatic cancer offer inadequate predictive accuracy, often failing to capture the complexity of the disease. The hypoxic tumor microenvironment has been recognized as a significant factor influencing cancer progression and resistance to treatment. This study aims to develop a prognostic model based on key hypoxia-related molecules to enhance prediction accuracy for patient outcomes and to guide more effective treatment strategies in pancreatic cancer. AIM: To develop and validate a prognostic model for predicting outcomes in patients with pancreatic cancer using key hypoxia-related molecules. METHODS: This pancreatic cancer prognostic model was developed based on the expression levels of the hypoxia-associated genes CAPN2, PLAU, and CCNA2. The results were validated in an independent dataset. This study also examined the correlations between the model risk score and various clinical features, components of the immune microenvironment, chemotherapeutic drug sensitivity, and metabolism-related pathways. Real-time quantitative PCR verification was conducted to confirm the differential expression of the target genes in hypoxic and normal pancreatic cancer cell lines. RESULTS: The prognostic model demonstrated significant predictive value, with the risk score showing a strong correlation with clinical features: It was significantly associated with tumor grade (G) (b P < 0.01), moderately associated with tumor stage (T) (a P < 0.05), and significantly correlated with residual tumor (R) status (b P < 0.01). There was also a significant negative correlation between the risk score and the half-maximal inhibitory concentration of some chemotherapeutic drugs. Furthermore, the risk score was linked to the enrichment of metabolism-related pathways in pancreatic cancer. CONCLUSION: The prognostic model based on hypoxia-related genes effectively predicts pancreatic cancer outcomes with improved accuracy over traditional factors and can guide treatment selection based on risk assessment.

Construction of a novel model based on PVT1-MYC duet-related genes for predicting survival and characterization of the tumor microenvironment in pancreatic cancer.

Pancreatic cancer is an extremely malignant tumor. PVT1 and MYC signaling has been considered as a therapeutic target recently. Nonetheless, the prognostic values and critical regulatory networks of PVT1-MYC duet in pancreatic cancer remain unclear. Firstly, we identified PVT1-MYC duet-related genes using public databases. Then we analyzed our Hi-C and ChIP-seq data to confirm PVT1-MYC duet. We performed LASSO regression and multivariate Cox regression analysis to build a prognostic model whose effectiveness and robustness were validated by Cox regression, ROC analysis, calibration curve, and nomogram. Besides, we conducted functional enrichment analyses, mutation profiles analyses and the immune features analyses to compare low- and high-risk group. Functional enrichment analyses revealed that several terms associated with cancer progression were enriched in the high-risk group. Mutation profile analysis showed that high-risk group had higher tumor mutation burden, and immune analysis demonstrated high-risk group had more immunosuppressive tumor microenvironment. Finally, we detected PVT1 expression in pancreatic cancer and paracancer tissues from the PUMCH cohort, which showed that PVT1 was significantly upregulated in pancreatic cancer and associated with invasion, metastasis, and poor prognosis. We further performed transwell and proliferation assays and found that PVT1, CDC6, and COL17A1 could promote migration or proliferation of PDAC cells. This study constructed a prognostic model based on three PVT1-MYC duet-related genes, which had a significant potential in predicting the prognosis and tumor microenvironment of pancreatic cancer. These results suggested that targeting PVT1-MYC duet or its regulatory processes could be a therapeutic option with great interests.

Prognostic Nomograms for Patients With NF-Pan-NET After Pancreatectomy: A Retrospective Analysis Based on SEER Database.

AIMS: Surgical resection is the primary treatment option for patients diagnosed with nonfunctional pancreatic neuroendocrine tumors (NF-Pan-NETs). However, the postoperative prognostic evaluation for NF-Pan-NET patients remains obscure. This study aimed to construct an efficient model to predict the prognosis of NF-Pan-NET patients who have received surgical resection. METHODS: NF-Pan-NET patients after pancreatectomy were retrieved from the SEER database for the period of 2010 to 2019. A total of 2844 patients with NF-Pan-NET from SEER database were included in our study. After careful screening, six clinicopathological variables including age, grade, AJCC T stage, AJCC N stage, AJCC M stage, and chemotherapy were selected to develop nomograms to predict overall survival (OS) and cancer-specific survival (CSS) respectively of the patients. RESULTS: The novel models demonstrated high accuracy and discrimination in prognosticating resected NF-Pan-NET through various validation methods. Furthermore, the risk subgroups classified by the newly developed risk stratification systems based on the nomograms exhibited significant differences in both OS and CSS, surpassing the efficacy of the AJCC 8th TNM staging system. Novel nomograms and corresponding risk classification systems were developed to predict OS and CSS in patients with NF-Pan-NET after pancreatectomy. CONCLUSION: The models demonstrated superior performance compared to traditional staging systems, providing clinicians with more accurate and personalized guidance for postoperative surveillance and treatment.

Prognostic value of neutrophil to lymphocyte ratio in patients with advanced pancreatic ductal adenocarcinoma treated with systemic chemotherapy.

OBJECTIVES: Although systemic chemotherapy for pancreatic ductal adenocarcinoma (PDAC) has made progress, ensuring long-term survival remains difficult. There are several reports on the usefulness of neutrophil-to-lymphocyte ratio (NLR) in predicting the prognosis of PDAC, but few reports in systemic chemotherapy. We hereby investigated the usefulness of NLR in systemic chemotherapy for PDAC. MATERIALS AND METHODS: A retrospective study was conducted on patients with advanced PDAC treated with first-line systemic chemotherapy. Cox regression hazards models were performed to analyze the association between baseline patient characteristics and the initial treatment response, and overall survival (OS). RESULTS: A total of 60 patients with PDAC were enrolled. At baseline, there were significant differences in NLR and carbohydrate antigen 19-9 (CA19-9), as well as the selection rate of combination chemotherapy, between patients with partial response or stable disease and those with progressive disease. Univariate and multivariate analysis showed that NLR < 3.10, combination chemotherapy, and CA19-9 < 1011 U/mL were significant and independent predictive factors of the initial treatment response. Meanwhile, NLR < 3.10 and combination chemotherapy were independently associated with longer OS. Moreover, OS was significantly prolonged in patients with NLR < 3.10, regardless of whether combination chemotherapy or monotherapy. Patients with NLR < 3.10 at baseline had a significantly higher conversion rate to third-line chemotherapy and a longer duration of total chemotherapy. CONCLUSIONS: This study suggests that NLR may be a useful marker for predicting the initial treatment response to first-line chemotherapy and the prognosis for patients with advanced PDAC.

Impact on survival of sarcopenia, systemic inflammatory response and anthropometric factors after pancreatectomy for resectable pancreatic adenocarcinoma.

INTRODUCTION: Pancreatic adenocarcinoma (PDAC) is becoming a public health issue with a 5-years survival rate around 10%. Patients with PDAC are often sarcopenic, which impacts postoperative outcome. At the same time, overweight population is increasing and adipose tissue promotes tumor related-inflammation. With several studies supporting independently these data, we aimed to assess if they held an impact on survival when combined. METHODS: We included 232 patients from two university hospitals (CHU de Lille, Institut Paoli Calmette), from January 2011 to December 2018, who underwent Pancreaticoduodenectomy (PD) for resectable PDAC. Preoperative CT scan was used to measure sarcopenia and visceral fat according to international cut-offs. Neutrophil to lymphocyte (NLR) and platelet to lymphocyte ratios (PLR) were used to measure inflammation. For univariate and multivariate analyses, the Cox proportional-hazard model was used. P-values below 0.05 were considered significant. RESULTS: Sarcopenic patients with visceral obesity were less likely to survive than the others in multivariate analysis (OS, HR 1.65, p= 0.043). Cutaneous obesity did not influence survival. We also observed an influence on survival when we studied sarcopenia with visceral obesity (OS, p= 0.056; PFS, p = 0.014), sarcopenia with cutaneous obesity (PFS, p= 0.005) and sarcopenia with PLR (PFS, p= 0.043). This poor prognosis was also found in sarcopenic obese patients with high PLR (OS, p= 0.05; PFS, p= 0.01). CONCLUSION: Sarcopenic obesity was associated with poor prognosis after PD for PDAC, especially in patients with systemic inflammation. Pre operative management of these factors should be addressed in pancreatic cancer patients.

A novel nomogram based on the number of positive lymph nodes can predict the overall survival of patients with pancreatic head cancer after radical surgery.

BACKGROUND: This study aimed to construct a novel nomogram based on the number of positive lymph nodes to predict the overall survival of patients with pancreatic head cancer after radical surgery. MATERIALS AND METHODS: 2271 and 973 patients in the SEER Database were included in the development set and validation set, respectively. The primary clinical endpoint was OS (overall survival). Univariate and multivariate Cox regression analyses were used to screen independent risk factors of OS, and then independent risk factors were used to construct a novel nomogram. The C-index, calibration curves, and decision analysis curves were used to evaluate the predictive power of the nomogram in the development and validation sets. RESULTS: After multivariate Cox regression analysis, the independent risk factors for OS included age, tumor extent, chemotherapy, tumor size, LN (lymph nodes) examined, and LN positive. A nomogram was constructed by using independent risk factors for OS. The C-index of the nomogram for OS was 0.652 [(95% confidence interval (CI): 0.639-0.666)] and 0.661 (95%CI: 0.641-0.680) in the development and validation sets, respectively. The calibration curves and decision analysis curves proved that the nomogram had good predictive ability. CONCLUSIONS: The nomogram based on the number of positive LN can effectively predict the overall survival of patients with pancreatic head cancer after surgery.

Adding-on nivolumab to chemotherapy-stabilized patients is associated with improved survival in advanced pancreatic ductal adenocarcinoma.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are rarely used to treat advanced pancreatic ductal adenocarcinoma (PDAC) due to marginal efficacy. PATIENTS AND METHODS: This study included 92 consecutive patients diagnosed with advanced or recurrent PDAC who received nivolumab-based treatment. Univariate and multivariate analyses were used to identify prognostic factors. A control group of 301 patients with PDAC who achieved disease control with palliative chemotherapy but without ICIs was selected for comparison using propensity score matching (PSM). RESULTS: The median overall survival (OS) since nivolumab treatment was 15.8 (95% confidence interval [CI], 12.5-19.0), 2.4 (95% CI 1.2-3.6), and 1.1 (95% CI 1.0-1.2) months in patients who received add-on nivolumab after achieving disease control with chemotherapy, in those who received concomitant nivolumab and chemotherapy without prerequisite confirmation of disease control, and in those who received nivolumab without concomitant chemotherapy, respectively (P < 0.001). After PSM, the median overall survival (OS) since initiation of the concomitant chemotherapy that achieved disease control was significantly longer (P = 0.026) in patients who received add-on nivolumab (19.8 months; 95% CI 14.5-25.1) than in those who received chemotherapy alone (13.8 months; 95% CI 10.8-16.9). The immune profiling of the tumors in resected patients revealed higher scores of CD8+ T cells to Tregs in patients with add-on nivolumab comparing to those who received chemotherapy alone. CONCLUSION: Adding-on nivolumab was associated with improved OS in patients with advanced PDAC who achieved disease control following chemotherapy.

Cytokines and Pancreatic Ductal Adenocarcinoma: Exploring Their Relationship with Molecular Subtypes and Prognosis.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by its poor prognosis. The current challenge remains the absence of predictive biomarkers. Cytokines are crucial factors in the pathogenesis and prognosis of PDAC. Furthermore, there is growing interest in differentiating between molecular subtypes of PDAC. The aim of our study is to evaluate the association between the analyzed cytokines and the molecular subtypes of PDAC and to determine their prognostic value. Cytokine levels were measured in 73 patients, and molecular subtypes were analyzed in 34 of these patients. Transforming Growth Factor Beta 2 (TGF-ß2) levels were independently associated with the basal-like and null subtypes. In patients with locally advanced and metastatic PDAC, elevated levels of interleukin (IL)-1α, IL-1ß, IL-6, IL-8, IL-9, and IL-15 were associated with a higher risk of progression during first-line treatment, and increased levels of IL-1ß, IL-6, IL-8, IL-9, and IL-15 were related to increased mortality. Furthermore, a significant association was observed between higher percentiles of IL-6 and IL-8 and shorter progression-free survival (PFS) during first-line treatment, and between higher percentiles of IL-8 and shorter overall survival (OS). In the multivariate analysis, only elevated levels of IL-8 were independently associated with a higher risk of progression during first-line treatment and mortality. In conclusion, the results of our study suggest that cytokine expression varies according to the molecular subtype of PDAC and that cytokines also play a relevant role in patient prognosis.

Mcl-1 expression is a predictive marker of response to gemcitabine plus nab-paclitaxel for metastatic pancreatic cancer.

Antiapoptotic protein, including Mcl-1, expression is frequently observed in pancreatic cancer. Gemcitabine plus nabpaclitaxel (GnP) is the standard chemotherapy for metastatic pancreatic cancer (MPC); however, predictive markers for its efficacy remain unestablished. This study evaluated the association between GnP's therapeutic effects and Mcl-1 expression in tissue samples obtained using endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for pancreatic tumor or percutaneous ultrasound-guided biopsy for metastatic liver tumor. We retrospectively reviewed 38 patients with histologically diagnosed MPC who received GnP as the first-line chemotherapy at our institute between December 2014 and July 2018. Post-immunohistochemistry analysis for Mcl-1 expression detection, patients were divided to into two groups based on the cell proportion showing Mcl-1 immunoreactivity: positive (> 20%; 23 [60.5%] patients) and negative (≤ 20%; 15 [39.5%] patients) groups. Clinical characteristics did not differ between the two groups. The Mcl-1 positive group showed a significantly higher disease control rate (95.7% vs. 73.3%; P = 0.046), longer progressionfree survival (PFS) (7.2 months vs. 4.9 months; P = 0.018) and longer overall survival (OS) (14.9 months vs. 9.2 months; P = 0.008) than the Mcl-1 negative group. Multivariate analysis showed that Mcl-1 expression was an independent predictive marker for PFS and OS. Mcl-1 expression could be a predictive marker for favorable response to GnP.

Prognostic value of ABO blood groups in upfront operated pancreatic ductal adenocarcinomas.

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) has been shown to have a lower incidence in patients with blood group O. It is currently uncertain if patients with group O have a better prognosis after pancreatectomy. This study assessed the overall survival (OS) and disease-free survival (DFS) of PDAC patients who underwent upfront pancreatoduodenectomy based on ABO blood groups. METHODS: A cross-sectional study was performed including patients from two university centers. All consecutive head PDAC patients who underwent upfront pancreatoduodenectomy from 2000 to 2016 were included. OS and DFS were compared between blood groups A, B, AB, and O using Kaplan-Meier curves and log-rank tests. RESULTS: A total of 438 patients were included (215 women, median age 67). Pre- and intraoperative details were comparable between all subgroups. Median OS did not differ between the four blood groups (A: 23 months, 95% CI 18-28; B: 32, 95% CI 20-44; AB: 37, 95% CI 18-56 and O: 26, 95% CI 20-32, p = 0.192). Median DFS were also similar (A: 19 months, 95% CI 15-23; B: 26, 95% CI 19-33; AB: 35, 95% CI 15-55 and O: 22, 95% CI 15-29, p = 0.441). There was no OS difference between O and non-O groups (median: 26 months, 95% CI 20-33 vs. 25 months, 95% CI 20-30, p = 0.773). On multivariable analysis blood groups were not prognostic of OS. Only lymph node involvement, tumor differentiation, and adjuvant chemotherapy were independent prognostic factors. CONCLUSION: OS and DFS were similar between all four blood groups after pancreatoduodenectomy. Independent predictors of OS were associated with tumor characteristics and adjuvant treatment.

Neoadjuvant therapy versus upfront surgery in resectable pancreatic cancer: reconstructed patient-level meta-analysis of randomized clinical trials.

BACKGROUND: Neoadjuvant treatment has shown promising results in patients with borderline resectable pancreatic ductal adenocarcinoma. The potential benefits of neoadjuvant treatment on long-term overall survival in patients with resectable pancreatic ductal adenocarcinoma have not yet been established. The aim of this study was to compare long-term overall survival of patients with resectable pancreatic ductal adenocarcinoma based on whether they received neoadjuvant treatment or underwent upfront surgery. METHODS: A systematic review including randomized clinical trials on the overall survival outcomes between neoadjuvant treatment and upfront surgery in patients with resectable pancreatic ductal adenocarcinoma was conducted up to 1 August 2023 from PubMed, MEDLINE and Web of Science databases. Patient-level survival data was extracted and reconstructed from available Kaplan-Meier curves. A frequentist one-stage meta-analysis was employed, using Cox-based models and a non-parametric method (restricted mean survival time), to assess the difference in overall survival between groups. A Bayesian meta-analysis was also conducted. RESULTS: Five randomized clinical trials comprising 625 patients were included. Among patients with resectable pancreatic ductal adenocarcinoma, neoadjuvant treatment was not significantly associated with a reduction in the hazard of death compared with upfront surgery (shared frailty HR 0.88, 95% c.i. 0.72 to 1.08, P = 0.223); this result was consistent in the non-parametric restricted mean survival time model (+2.41 months, 95% c.i. -1.22 to 6.04, P < 0.194), in the sensitivity analysis that excluded randomized clinical trials with a high risk of bias (shared frailty HR 0.91 (95% c.i. 0.72 to 1.15; P = 0.424)) and in the Bayesian analysis with a posterior shared frailty HR of 0.86 (95% c.i. 0.70 to 1.05). CONCLUSION: Neoadjuvant treatment does not demonstrate a survival advantage over upfront surgery for patients with resectable pancreatic ductal adenocarcinoma.

Accuracy of Clinical Staging in Early-Stage Pancreatic Ductal Adenocarcinoma.

This study evaluates the accuracy of clinical staging in early-stage pancreatic ductal adenocarcinoma.

Contribution of Immunoscore to Survival Prediction in Pancreatic Ductal Adenocarcinoma.

BACKGROUND/AIM: The presence of tumor-infiltrating lymphocytes (TILs) has been demonstrated as a prognostic factor in colorectal cancer after surgical resection of malignancy, but knowledge on their role in pancreatic cancer is lacking. The Immunoscore (IS) assesses TILs at the core of the tumor (CT) and invasive margin (IM) and is being evaluated as a new concept in tumor immunity. The aim of this study was to evaluate the relationship between IS and prognosis in PDAC. PATIENTS AND METHODS: The IS was analyzed by immunohistochemistry using surgical tissue blocks from 131 patients with pancreatic ductal adenocarcinoma (PDAC) who underwent surgery to investigate the relationship between immune cell infiltration into the tumor and prognosis in PDAC. RESULTS: A high IS in both CT and IM of the tumor was significantly associated with prolonged overall survival (OS) (p<0.01) and relapse-free survival (RFS) (p<0.01). In multivariate logistic regression models adjusted for clinical pathology data, IS predicted survival and recurrence (p<0.01 and p<0.01, respectively). Moreover, in patients who received preoperative chemotherapy, a high IS was statistically significantly associated with longer OS and RFS (p<0.01 and p<0.01, respectively). CONCLUSION: The immunohistochemically assessed IS might be a useful prognostic marker for patients with PDAC who underwent primary tumor resection.

Modified 5-Item Frailty Index (mFI-5) may predict postoperative outcomes after pancreatoduodenectomy for pancreatic Cancer.

BACKGROUND: Pancreatic Ductal Adenocarcinoma (PDAC) primarily affects older individuals with diminished physiological reserves. The Modified 5-Item Frailty Index (mFI-5) is a novel risk stratification tool proposed to predict postoperative morbidity and mortality. This study aimed to validate the mFI-5 for predicting surgical outcomes in patients undergoing pancreatoduodenectomy (PD) for PDAC. METHODS: Our retrospective PDAC database included patients who underwent PD between 2014 and 2023. Patients were stratified by mFI-5 scores (0 best - 5 worst), which assess preoperative CHF, diabetes mellitus, history of COPD or pneumonia, functional health status, and hypertension requiring medication. Associations between mFI-5 scores and outcomes, including postoperative complications and mortality, were analyzed using logistic regression, Cox proportional hazards models, and Kaplan-Meier survival analysis. RESULTS: Among 250 PDAC patients undergoing PD, 142 (56.8%) had mFI-5 scores ≤ 1, and 25 (10%) had scores ≥ 3. No patients had scores > 4. Higher mFI-5 scores correlated with older age (p < 0.001) and tobacco use (p = 0.036). Multivariate analysis identified age (RR 1.02, p = 0.038), ASA class (ASA III; RR 2.61, p < 0.001; ASA IV; RR 2.63, p = 0.026), and moderate alcohol consumption (RR 0.56, p = 0.038) as frailty predictors. An mFI-5 score > 2 independently associated with higher mortality (HR 2.08, p = 0.026). Median overall survival was significantly lower for patients with mFI-5 scores > 2 than for those with scores ≤ 2 (21.3 vs. 42.1 months, p = 0.022). CONCLUSIONS: The mFI-5 is a valuable tool for predicting postoperative morbidity and mortality in PDAC patients undergoing PD. Integrating frailty assessment into preoperative evaluations can enhance patient selection and surgical outcomes. Future research should focus on incorporating frailty assessments into surgical planning and patient management to improve outcomes in this vulnerable population.

Serum PCSK9 is a novel serological biomarker for the diagnosis and prognosis of pancreatic cancer.

Background: Although CA19-9 is an essential blood biomarker of pancreatic cancer (PC), its sensitivity and specificity are limited for early detection. Methods: We analyzed the serum proprotein convertase subtilisin/kexin type 9 (sPCSK9) in PC patients, benign disease groups (BDG), and healthy controls (HC) by ELISA. Results: Consistently, sPCSK9 was considerably lower in PC patients than in HC (Z = -2.546, P < 0.05), and sPCSK9 in PC patients was statistically significantly higher than in BDG (Z = -5.457, P < 0.001). sPCSK9 was linked to the invasion of lymph nodes (χ2 = 6.846, P < 0.01). According to ROC curves, combining sPCSK9 with CA19-9 could potentially enhance the diagnostic capability of CA19-9 in early-stage PC patients. Furthermore, the low sPCSK9 group (n = 41) exhibited statistically significantly prolonged overall survival compared to the high sPCSK9 group (n = 15), with median survival times of 27 months (95% CI [17.59-36.41]) and 11 months (95% CI [7.21-14.79]), respectively (P = 0.022). Conclusion: The diagnostic performance of CA19-9 for early-stage PC patients could be improved by combining sPCSK9 with CA19-9. Moreover, the higher sPCSK9 group has a significantly shorter overall survival rate.

Synergistic effects of calcium channel blockers and renin-angiotensin inhibitors with gemcitabine-based chemotherapy on the survival of patients with pancreatic cancer.

PURPOSE: Pancreatic cancer remains a significant public health challenge, with poor long-term outcomes due to the lack of effective treatment options. Repurposing commonly used clinical drugs, such as ACE inhibitors, ARBs, CCBs, and metformin, may enhance the efficacy of chemotherapy and offer a promising therapeutic strategy for improving patient outcomes. METHODS: A retrospective analysis of concomitant treatment with ACE-Is, ARBs, CCBs, and metformin alongside gemcitabine chemotherapy in patients with pancreatic cancer was conducted. Treatment responses were evaluated, with overall survival (OS) estimated using the Kaplan-Meier method. Additionally, the Cox proportional hazards model was employed to assess the impact of these specific agents on patient survival. RESULTS: 4628 patients with various stages of pancreatic cancer were identified in the database between 2007 and 2016. The estimated overall survival (OS) in the analyzed group was 6.9 months (95% CI 6.4-7). The use of any of the analyzed drugs was associated with a significant improvement in mOS of 7.5 months (95% CI 6.8-7.8) vs. 6.7 months (95% CI 6.4-7.0) for patients who did not have additional treatment (p < 0.0001). ARBs, ACE-Is, CCBs, and metformin varied in their effectiveness in prolonging mOS among patients. The longest mOS of 8.9 months (95% CI 7.7-11.6) was observed in patients receiving additional therapy with ARBs, while the shortest mOS of 7.7 months (95% CI 6.5-8.9) was achieved by patients receiving metformin. In the adjusted Cox analysis, metformin was associated with a significantly weaker effect on mOS (p = 0.029). A particularly interesting trend in prolonging 5-year survival was demonstrated by ARBs and CCBs with 14.1% (95% CI 9-22%) and 14.8% (95% CI 11.1-19.6%), respectively, compared to patients not taking these drugs, who achieved a 5-year OS of 3.8% (95% CI 3.2-4.4%). CONCLUSION: Our results demonstrate a significant positive impact of ARBs, ACE inhibitors, and CCBs on survival in patients with pancreatic cancer treated with gemcitabine. The addition of these inexpensive and relatively safe drugs in patients with additional comorbidities may represent a potential therapeutic option in this indication. However, prospective clinical trials to evaluate the optimal patient population and further studies to determine the potential impact of these agents on chemotherapy are necessary.

Impairment of perioperative activities of daily living is associated with poor prognosis following pancreatectomy for pancreatic cancer.

PURPOSE: It has reported that the prevalence of frailty in patients with pancreatic cancer is 45%. The number of patients with pancreatic cancer is increasing, and within this cohort, patients often suffer from impaired activities of daily living (ADLs). This study aimed to examine the association between perioperative Barthel Index (BI) scores, a validated measure of ADLs, and survival outcomes after pancreatectomy for pancreatic cancer. METHODS: We analyzed the data of 201 patients who underwent pancreatectomy for pancreatic cancer between 2010 and 2020. Preoperative and postoperative ADLs were assessed using the BI (range: 0-100; higher scores indicated greater independence). A preoperative or postoperative BI score ≤ 85 was defined as an impairment of perioperative ADLs. Cox proportional hazards regression was used to calculate the hazard ratios (HRs) after adjusting for potential confounders. RESULTS: Among the 201 patients, 14 (7.0%) had a preoperative BI score ≤ 85 and 50 (25%) had a postoperative BI score ≤ 85. Impairment of perioperative ADLs was independently associated with shorter overall survival (multivariable HR: 2.66, 95% confidence interval [95%CI]: 1.75-4.03, P < 0.001), cancer-specific survival (multivariable HR: 2.64, 95%CI: 1.15-4.25, P < 0.001), and recurrence-free survival (multivariable HR: 1.94, 95%CI: 1.08-3.50, P = 0.021). CONCLUSION: Impairment of perioperative ADLs is associated with poor prognosis following pancreatectomy for pancreatic cancer. The maintenance and improvement of perioperative ADLs could play an important role in providing favorable long-term outcomes in patients with pancreatic cancer.

Revealing a cancer-associated fibroblast-based risk signature for pancreatic adenocarcinoma through single-cell and bulk RNA-seq analysis.

PURPOSE: Proliferation of stromal connective tissue is a hallmark of pancreatic adenocarcinoma (PAAD). The engagement of activated cancer-associated fibroblasts (CAFs) contributes to the progression of PAAD through their involvement in tumor fibrogenesis. However, the prognostic significance of CAF-based risk signature in PAAD has not been explored. METHODS: The single-cell RNA sequencing (scRNA-seq) data sourced from GSE155698 within the Gene Expression Omnibus (GEO) database was supplemented by bulk RNA sequencing data from The Cancer Genome Atlas (TCGA) and microarray data retrieved from the GEO database. The scRNA-seq data underwent processing via the Seurat package to identify distinct CAF clusters utilizing specific CAF markers. Differential gene expression analysis between normal and tumor samples was conducted within the TCGA-PAAD cohort. Univariate Cox regression analysis pinpointed genes associated with CAF clusters, identifying prognostic CAF-related genes. These genes were utilized in LASSO regression to craft a predictive risk signature. Subsequently, integrating clinicopathological traits and the risk signature, a nomogram model was constructed. RESULTS: Our scRNA-seq analysis unveiled four distinct CAF clusters in PAAD, with two linked to PAAD prognosis. Among 207 identified DEGs, 148 exhibited significant correlation with these CAF clusters, forming the basis of a seven-gene risk signature. This signature emerged as an independent predictor in multivariate analysis for PAAD and demonstrated predictive efficacy in immunotherapeutic outcomes. Additionally, a novel nomogram, integrating age and the CAF-based risk signature, exhibited robust predictability and reliability in prognosticating PAAD. Moreover, the risk signature displayed substantial correlations with stromal and immune scores, as well as specific immune cell types. CONCLUSIONS: The prognosis of PAAD can be accurately predicted using the CAF-based risk signature, and a thorough analysis of the PAAD CAF signature may aid in deciphering the patient's immunotherapy response and presenting fresh cancer treatment options.