Outcome In Pancreatic Cancer Patients Research Articles

REEP3 is a potential diagnostic and prognostic biomarker correlated with immune infiltration in pancreatic cancer

Receptor Expression-Enhancing Protein 3 (REEP3) serves as a pivotal enzyme crucial for endoplasmic reticulum (ER) clearance during mitosis and is implicated in the advancement of diverse malignancies. Nonetheless, the biological role and mechanisms of REEP3 in pancreatic cancer patients, along with its interplay with immune infiltration, remain inadequately elucidated. In this study, we initially analyzed the differential expression of REEP3 between pancreatic cancer tissues and normal pancreas tissues using the Cancer Genome Atlas (TCGA), GTEx and Gene Expression Omnibus (GEO) databases. Subsequently, we utilized Kaplan–Meier analysis, Cox regression and ROC curve to determine the predictive value of REEP3 for the clinical outcomes of pancreatic cancer patients. Functional enrichment analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA), were conducted to explore the potential signaling pathways and biological functions associated with pancreatic cancer. Furthermore, we investigated the PPI network, miRNA, RBP and transcription factor interactions of REEP3 using databases such as GeneMania, STRING, StarBase, KnockTK, ENCODE, Jaspar and hTFtarget. Lastly, the “ssGSEA” algorithm and TIMER database were employed to investigate the correlation between REEP3 expression and immune infiltration as well as immune checkpoints. The expression of REEP3 in pancreatic cancer showed a significantly higher level compared to that in normal tissues. ROC curve analysis indicated that REEP3 holds substantial diagnostic potential for pancreatic cancer patients. Elevated REEP3 expression correlated with unfavorable outcomes in terms of both overall survival and relapse-free survival, establishing it as a notable adverse prognostic marker in pancreatic cancer. Moreover, both univariate and multivariate Cox regression analyses demonstrated that REEP3 maintained an independent association with overall survival. Functional enrichment analyses revealed pathways significantly linked to REEP3, including cytoplasmic translation, wound healing, viral processes, regulation of cellular component size and actin filament organization. Additionally, REEP3 expression displayed a significant positive correlation with CD8+ T cells, B cells, natural killer cells, dendritic cells and macrophages. REEP3 is a potential diagnostic, prognostic marker and immunotherapeutic target for pancreatic cancer.

Effect of heart failure on mortality and clinical outcomes in patients hospitalized with pancreatic cancer.

e16367 Background: Pancreatic cancer (PC) is the fourth leading cause of cancer-related death globally. The impact of HF on clinical outcomes in hospitalized patients with PC remains unknown. Considering the poor prognosis associated with PC, we aim to compare clinical outcomes in PC patients with or without HF. Methods: The research utilized the National Inpatient Sample (NIS) database, covering data from 2019 and 2020. Through this dataset, patients hospitalized with a primary discharge diagnosis of PC and a concurrent secondary diagnosis of HF were identified and a multivariate regression analysis was applied. Our primary outcome was mortality in patients with comorbid heart failure in patients diagnosed with pancreatic cancer compared to pancreatic cancer alone and our secondary outcomes were the length of hospitalization, associated hospitalization cost, and the risk of clinical complications or outcomes such as major depressive disorder, atrial fibrillation, acute coronary syndrome, etc. Baseline patient characteristics were found to be comparable in either group and data hence was not specifically adjusted in this regard. Results: A total of 74,585 patients were hospitalized with PC, of which 5,755 had a concurrent diagnosis of HF. The mean age of patients with HF was 74.43 years, while those without heart failure was 67.97 years. Primary and secondary outcomes were calculated. HF was not found to be an independent predictor of mortality (OR 1.17, 95% CI 0.90-1.53, p=0.22), and there was no significant difference in the length of stay in the hospital between the two groups of patients (1.09, 95% CI 0.59-1.60, p<0.001). However, patients with heart failure had an increased total cost of hospitalization ($18,045, 95% CI 5,697-30,392, p=0.00) and increased odds of worse clinical outcomes such as major depressive disorder (OR 1.26, 95% CI 1.02-1.55, p=0.03), p<0.001), atrial fibrillation (OR 4.59, 95% CI 3.85-5.47), acute coronary syndrome (OR 9.96, 95% CI 4.31-23.01, p<0.001), acute respiratory failure (OR 2.69, 95% CI 2.08-3.47, pneumonia (OR 1.66, 95% CI 1.17-2.36 p=0.00), septic shock (OR 1.54, 95% CI 1.09-2.17, p=0.01), p<0.001), invasive mechanical ventilation (OR 2.70, 95% CI 1.96-3.72, p<0.001), ICU admission (OR 2.18, 95% CI 1.67-2.85, p<0.001), acute kidney injury (OR 1.84, 95% CI 1.56-2.18, p<0.001), and cardiovascular accident (CVA) (OR 2.74, 95% CI 1.37-5.47, p=0.004). Conclusions: HF is not an independent predictor of mortality or prolonged length in PC patients, but it is associated with increased hospitalization costs and adverse clinical outcomes. Implementing careful and aggressive management strategies for addressing HF is necessary to optimize patient quality of life, minimize adverse events, and reduce resource utilization to minimize the costs of hospitalization and improve quality of life.

Analysis of factors affecting the prognosis of patients with pancreatic cancer patients with obstructive jaundice

Objective: Objective To analyze the relationship between the survival outcomes of pancreatic cancer patients with obstructive jaundice and various clinical and pathological factors. Methods: A case series study was conducted, where clinical data from pancreatic cancer patients with obstructive jaundice, who were admitted to the Cancer Hospital of Tianjin Medical University between March 2022 and May 2023, were retrospectively gathered. Factors potentially affecting patient prognosis were initially analyzed using univariate analysis, followed by multivariate analysis using the Cox regression model for selected factors. A P-value of less than 0.05 was deemed statistically significant. Results: The study included 104 patients, comprising 69 males and 35 females, with a median age of 62 years (ranging from 38 to 85 years). Of these, 76 patients (73.1%) were followed until death, with a median survival time of 8.9 (6.2,11.5) months. The number of deaths versus surviving cases at 6 and 12 months were 20/75 and 64/14, respectively, resulting in estimated survival rates of 79.6% and 22.8%. Univariate analysis identified factors such as weight loss, primary site, TNM stage, liver metastasis, number of organs with tumor, stage at which jaundice appeared, CA19-9 levels, albumin levels, and D-dimer levels as significant in influencing prognosis (all P<0.05). Multivariate analysis revealed TNM stage, number of organs with tumor, method of jaundice treatment, albumin levels, and D-dimer levels as independent prognostic factors (all P<0.05). Conclusion: In pancreatic cancer patients presenting with obstructive jaundice, close monitoring of weight loss, primary site, TNM stage, liver metastasis, number of organs with tumor, the timing of jaundice occurrence, method of jaundice treatment, CA19-9, albumin, and D-dimer levels is crucial, as these factors may significantly impact the patient's survival and prognosis.

Survey of NCI-Designated Cancer Centers on the Utilization of Palliative Care in Pancreatic Cancer Patients.

Recognized as one of the deadliest cancers, pancreatic cancer underscores an urgent need for palliative care. We surveyed palliative care directors at all 65 National Cancer Institute (NCI) cancer centers to assess the utilization and timing of palliative care involvement in pancreatic cancer patients. 1) Does your palliative care team have a policy to get involved with every pancreatic cancer patient? a. Yes b. No 2) When palliative care is involved with pancreatic cancer patients, in what setting are you typically/primarily first asked to be involved? a. Early in the patient's treatment journey (focusing on symptom management) b. Later in the patient's treatment journey (focusing on end-of-life discussions and explaining hospice) All 65 NCI-designated centers responded, achieving 100% of the targeted sample. Among these centers, 64 lacked a policy for palliative care involvement with every pancreatic cancer patient. Additionally, 38 centers initiated intervention early, focusing on symptom management, while 15 centers started palliative care late in the treatment journey, emphasizing end-of-life discussions. Furthermore, 12 centers initiated intervention both early and late when treating pancreatic cancer. There is an increasing recognition among medical centers of palliative care's necessity for pancreatic cancer, with a rising trend toward early integration. Variation in the timing and emphasis of palliative care involvement remains. Future research should explore barriers to accessing palliative care and compare outcomes of early versus late intervention. By addressing these areas, healthcare providers can potentially improve outcomes for pancreatic cancer patients.

Clinicopathologic characteristics and treatment outcomes of pancreatic cancer patients at a tertiary referral hospital in Kenya.

The global incidence of pancreatic cancer (PC) continues to steadily increase whereas its prognosis remains poor. Previous studies have suggested worse outcomes among individuals of African descent. The characteristics of patients with PC in Kenya, and their contemporary management and survival outcomes remain largely unknown. This study aimed to describe the clinical and pathologic characteristics, management, and outcomes of patients diagnosed with PC at Kenyatta National Hospital (KNH), a tertiary referral hospital in Kenya. Records of 242 patients diagnosed with PC at KNH between 1st January 2014 and 30th September 2021 were assessed in this retrospective cohort study. Data on their clinical, histopathologic, and treatment characteristics was presented as mean (± standard deviation) and/or median (interquartile range) for continuous variables and frequency (percentage) for categorical variables. Kaplan-Meier and Cox proportional hazard ratios were used for survival analysis. PC occurred in a young population, the median age being 58.5 years (inter-quartile range 35-88). The majority of tumours (54%) were metastatic at diagnosis, while 28% and 14% were stage III and stage I/II, respectively. Surgical resections with curative intent were performed on 7% overall and 44% of stage I/II cases. The majority of patients with stage I/II disease (52.9%) received chemotherapy whereas the majority with stage III and IV disease received the best supportive care only (62.7% and 64.9%, respectively). Patients who underwent surgical resection (HR for mortality 0.20, 95% CI 0.05-0.83, p = 0.021) and chemotherapy (HR for mortality 0.15, 95% CI 0.08-0.29, p < 0.001) had significantly improved survival, reflecting a more favourable stage of the disease more amenable to aggressive therapies. The median survival time was 3 months and the 1-year survival rate was 32%.

Prognostic significance of glucose-lipid metabolic index in pancreatic cancer patients with diabetes mellitus.

The incidence of pancreatic cancer (PC) is higher in diabetic patients due to disturbances in glucose and lipid metabolism caused by insulin resistance (IR). However, the effect of diabetes as well as IR on the prognosis of PC patients remains inconclusive. Our study aims to assess the impact of IR on the prognosis of PC patients with diabetes. We conducted a retrospective analysis of 172 PC patients with diabetes in our institute from 2015 to 2021. Prognostic assessment was performed using univariate/multifactorial analysis and survival analysis. The predictive efficacy of metabolic indices was compared using receiver operator characteristic (ROC) curve analysis. One hundred twenty-one of 172 patients died during follow-up, with a median follow-up of 477 days and a median overall survival (OS) of 270 days. Survival analysis showed a significant difference in OS by IR related parameters, which were triglyceride-glucose index (TyG), triglyceride-glucose index-body mass index (TyG-BMI), and triglyceride/high-density lipoprotein cholesterol ratio (TG/HDL-c). The ROC curve indicated that TyG, TyG-BMI, and TG/HDL-c had prognostic efficacy for PC with diabetes. We next optimized TyG-BMI and obtained a new parameter, namely glucose-lipid metabolism index (GLMI), and the patients were classified into GLMI low group and high group based on the calculated cutoff value. The GLMI high group had higher TyG, TyG-BMI, TyG/HDL-c, BMI, TG, total cholesterol (TC), TC/HDL-c, fasting plasma glucose, CA199, and more advanced tumor stage compared to low group. Univariate and multivariate analyses showed that GLMI was an independent prognostic factor. Furthermore, the patients of GLMI high group had worse OS compared to low group and the ROC curves showed GLMI had better predictive ability than TyG and TyG-BMI. IR is associated with the outcome of PC patients with diabetes and higher level of IR indicates worse prognosis. GLMI has a good predictive value for PC with diabetes.

MICAL2 implies immunosuppressive features and acts as an independent and adverse prognostic biomarker in pancreatic cancer

At present, clinical outcomes of pancreatic cancer patients are still poor. New therapeutic targets for pancreatic cancer are urgently needed. Previous studies have indicated that Microtubule Associated Monooxygenase, Calponin and LIM Domain Containing 2 (MICAL2) is highly expressed in many tumors and promotes tumor progression. However, the role played by MICAL2 in pancreatic cancer remains unclear. Based on gene expression and clinical information from multiple datasets, we used comprehensive bioinformatics analysis in combination with tissue microarray to explore the function and clinical value of MICAL2. The results showed that MICAL2 was highly expressed in pancreatic cancer tissue and exhibited potential diagnostic capability. High expression of MICAL2 was also associated with poor prognosis and acted as an independent prognostic factor. MICAL2, mainly expressed in fibroblasts of pancreatic cancer, was closely related to metastasis and immune-related features, such as epithelial-mesenchymal transformation, extracellular cell matrix degradation, and inflammatory response. Furthermore, higher MICAL2 expression in pancreatic cancer was also associated with an increase in cancer-associated fibroblasts as well as M2 macrophage infiltration, and a reduction in CD8 + T cell infiltration, thereby facilitating the formation of an immunosuppressive microenvironment. Our results helped elucidate the clinical value and function in metastasis and immunity of MICAL2 in pancreatic cancer. These findings provided potential clinical strategies for diagnosis, targeted therapy combination immunotherapy, and prognosis in patients with pancreatic cancer.

Abstract C018: Spatial profiling of tumor associated cells expressing endoplasmic reticulum stress proteins predicts poor outcomes in pancreatic cancer patients

Abstract The crosstalk between pancreatic cancer (PC) cells and cells of the tumor microenvironment (TME), such as immune cells and cancer associated fibroblasts (CAFs), has important implications for tumor progression. It is evident that the expression of endoplasmic reticulum (ER) stress proteins (e.g., BiP or CHOP) in tumor cells has survival implications for patients. For example, high BiP expression in tumor cells is correlated with poor survival in PC patients. However, the effect of these proteins in TME cells is currently unknown. We have employed quantitative multiplex immunofluorescence on a tumor microarray cohort of 259 treatment naive pancreatic cancer patient samples and 41 normal pancreas samples. We investigated the impact of expression of ER stress proteins BiP or CHOP in CAFS (α-SMA+), immune cells (CD45+), endothelial cells (CD31+) and tumor cells (PanCK+). HALO AI (Indica Labs) was used to conduct cell/tissue classifications and spatial proximity analysis. Notably, the proportion of CAFs and endothelial cells expressing BiP or CHOP was significantly (p&amp;lt;0.01-0.0001) increased in tumor sections compared to non-tumor sections. When considering the tumor sections, increased BiP expression in CAFs and endothelial cells was found to be correlated with vascular invasion (p=0.0388 and p=0.0318 respectively). Interestingly, there was also a positive correlation between the percent of total CAFs and the percent of BiP positive cells (p=0.0037, r=0.293) or CHOP positive cells (p=0.0001, r=0.235), suggesting that ER stress could be associated with activation of CAFs. Spatial analysis was next utilized to explore the distribution of cells expressing BiP or CHOP within the TME. Remarkably, when examining the average distance in a 500 μm radius, our findings showed that immune cells expressing BiP or CHOP were located significantly (p&amp;lt;0.0001) closer to tumor cells compared to non-expressing immune cells. Interestingly, increased distance of CHOP expressing immune cells to tumor cells was negatively correlated (p=0.037, r=-0.137) with tumor size. We next examined these cells within a 20 μm radius of tumor cells, as it represents a physiologically feasible distance for direct cell-cell contact. Increased numbers of CHOP CD45 cells within the 20 μm radius was correlated with poorer overall survival (p=0.0062) and event free survival (p=0.046). Similarly, in CAFS, BiP expressing cells were found on average closer to tumor cells (p&amp;lt;0.0001), although this was not associated with patient survival. The observed correlation between elevated ER stress in TME cells with adverse patient outcomes indicates the importance of BiP or CHOP as potential therapeutic targets. Furthermore, the spatial analysis results provide insights into the organization of TME cells, shedding light on the significance of ER stress in the TME. These findings contribute to our understanding of the complex interplay between ER stress, tumor biology, and patient outcomes in PC. Citation Format: Georgia M. Porter, Murray Norris, Minoti Apte, Angelica Merlot. Spatial profiling of tumor associated cells expressing endoplasmic reticulum stress proteins predicts poor outcomes in pancreatic cancer patients [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr C018.

Effects of Exercise Training on Patient-Specific Outcomes in Pancreatic Cancer Patients: A Scoping Review.

International guidelines have already highlighted the beneficial effects of exercise in common cancer entities. However, specific recommendations for pancreatic cancer are still missing. This scoping review aimed to evaluate the impact of exercise training on patient-specific outcomes in pancreatic cancer patients. A literature search was undertaken using PubMed, Web of Science, and Cochrane Library. We included randomized controlled trials (RCTs) published before August 2023 with structured exercise interventions during or after pancreatic cancer treatment. Seven articles that prescribed home-based or supervised exercise with aerobic or resistance training or both were reviewed. The results indicate that exercise is feasible and safe in pancreatic cancer patients. Furthermore, exercise was associated with improved quality of life, cancer-related fatigue, and muscle strength. Concerning other outcomes, heterogeneous results were reported. We identified a lack of evidence, particularly for patients with advanced pancreatic cancer. Exercise interventions in pancreatic cancer patients are feasible and can lead to improved quality of life, cancer-related fatigue, and muscle strength. However, further studies with larger sample sizes are needed to clarify the potential of exercise in pancreatic cancer, in particular for advanced stages.

Preoperative low skeletal muscle mass index assessed using L3-CT as a prognostic marker of clinical outcomes in pancreatic cancer patients undergoing surgery: A systematic review and meta-analysis.

Reduction in muscle mass can be routinely quantified using computed tomography (CT) of the third lumbar vertebra (L3) during a curative pancreatic cancer (PC) course. This systematic review and meta-analysis aimed to assess the association between preoperative low skeletal muscle index (SMI) measured by L3 CT and postoperative clinical outcomes in PC resectable patients. Three electronic databases (PubMed, Web of Science, and Scopus) were searched for articles published through May 2023. Duplicate titles and abstracts, full-text screening, and data extraction were performed. A meta-analysis was performed for overall survival (OS), recurrence-free survival (RFS), postoperative pancreatic fistula (POPF), morbidity, and postoperative length of stay (P-LOS). The risk of bias was assessed. A total of 2942 patients with PC from 11 studies were identified. Preoperative low SMI was found in 50.9% of PC resectable patients. Preoperative low SMI was significantly associated with adjusted OS (adjusted HR, 1.52; 95% CI 1.25-1.86, P< 0.0001). No significant associations were found between preoperative low SMI and RFS, number of POPF, significant morbidity, and P-LOS (P>0.05). SMI should be evaluated in a timely manner as a predictor of OS in PC resectable patients. Studies assessing nutritional protocols for maintaining/increasing skeletal muscle mass are required to develop a personalized nutritional approach to improve clinical outcomes.

Radiomics analysis with three-dimensional and two-dimensional segmentation to predict survival outcomes in pancreatic cancer.

Radiomics can assess prognostic factors in several types of tumors, but considering its prognostic ability in pancreatic cancer has been lacking. To evaluate the performance of two different radiomics software in assessing survival outcomes in pancreatic cancer patients. We retrospectively reviewed pretreatment contrast-enhanced dual-energy computed tomography images from 48 patients with biopsy-confirmed pancreatic ductal adenocarcinoma who later underwent neoadjuvant chemoradiation and surgery. Tumors were segmented using TexRad software for 2-dimensional (2D) analysis and MIM software for 3D analysis, followed by radiomic feature extraction. Cox proportional hazard modeling correlated texture features with overall survival (OS) and progression-free survival (PFS). Cox regression was used to detect differences in OS related to pretreatment tumor size and residual tumor following treatment. The Wilcoxon test was used to show the relationship between tumor volume and the percent of residual tumor. Kaplan-Meier analysis was used to compare survival in patients with different tumor densities in Hounsfield units for both 2D and 3D analysis. 3D analysis showed that higher mean tumor density [hazard ratio (HR) = 0.971, P = 0.041)] and higher median tumor density (HR = 0.970, P = 0.037) correlated with better OS. 2D analysis showed that higher mean tumor density (HR = 0.963, P = 0.014) and higher mean positive pixels (HR = 0.962, P = 0.014) correlated with better OS; higher skewness (HR = 3.067, P = 0.008) and higher kurtosis (HR = 1.176, P = 0.029) correlated with worse OS. Higher entropy correlated with better PFS (HR = 0.056, P = 0.036). Models determined that patients with increased tumor size greater than 1.35 cm were likely to have a higher percentage of residual tumors of over 10%. Several radiomics features can be used as prognostic tools for pancreatic cancer. However, results vary between 2D and 3D analyses. Mean tumor density was the only variable that could reliably predict OS, irrespective of the analysis used.

FOLFIRINOX chemotherapy modulates the peripheral immune landscape in pancreatic cancer: Implications for combination therapies and early response prediction

BackgroundFOLFIRINOX chemotherapy has improved outcomes for pancreatic cancer patients, but poor long-term survival outcomes and high toxicity remain challenges. This study investigates the impact of FOLFIRINOX on plasma proteins and peripheral immune cells to guide immune-based combination therapies and, ideally, to identify a potential biomarker to predict early disease progression during FOLFIRINOX. MethodsBlood samples were collected from 86 pancreatic cancer patients before and two weeks after the first FOLFIRINOX cycle and subjected to comprehensive immune cell and proteome profiling. Principal Component Analysis and Linear Mixed Effect Regression models were used for data analysis. FOLFIRINOX efficacy was radiologically evaluated after the fourth cycle. ResultsOne cycle of FOLFIRINOX diminished tumour-cell-related pathways and enhanced pathways related to immune activation, illustrated by an increase in pro-inflammatory IL–18, IL–15, and TNFRSF4. Similarly, FOLFIRINOX promoted the activation of CD4 + and CD8 + T cells, the proliferation of NK(T), and the activation of antigen-presenting cells. Furthermore, high pre-treatment levels of VEGFA and PRDX3 and an elevation in FCRL3 levels after one cycle predicted early progression under FOLFIRINOX. Finally, patients with progressive disease exhibited high levels of inhibitory markers on B cells and CD8 + T cells, while responding patients exhibited high levels of activation markers on CD4 + and CD8 + T cell subsets. ConclusionFOLFIRINOX has immunomodulatory effects, providing a foundation for clinical trials exploring immune-based combination therapies that harness the immune system to treat pancreatic cancer. In addition, several plasma proteins hold potential as circulating predictive biomarkers for early prediction of FOLFIRINOX response in patients with pancreatic cancer.

Survey of NCI-designated cancer centers on the utilization of palliative care in patients with pancreatic cancer.

248 Background: Pancreatic cancer, known as one of the deadliest cancers, has a high demand for palliative care. However, there remains a considerable amount of uncertainty regarding the nature of palliative care treatment to this specific patient demographic across the United States. This study aims to assess the utilization of palliative care in pancreatic cancer patients and explore the variations in timing and emphasis of palliative care involvement. Methods: We conducted a survey assessing utilization of palliative care in pancreatic cancer patients. We targeted palliative care directors at all 65 National Cancer Institute (NCI) cancer centers. The physicians were invited to voluntarily participate in the study. Responses were collected by email between May 30, 2023, and June 22, 2023. 1) Does your palliative care and/or oncology team have a policy to get involved with every pancreatic cancer patient (yes or no)? 2) When palliative care is involved with pancreatic cancer patients, in what setting are you typically/primarily first asked to be involved (early in the patient’s treatment journey, focusing more to assist with symptom management, or later in the patient’s treatment journey, focusing more on end-of-life discussions such as explaining hospice)? Results: We received responses from palliative care leaders at 65 NCI-designated palliative care centers, and thus 100% of the targeted population sample. Out of these centers, 64 indicated that there was no established policy for palliative care involvement with every pancreatic cancer patient. Among the respondents, 38 centers started intervention early, primarily focusing on symptom management, while 15 centers started palliative care late in the treatment process, with a focus on end-of-life discussions. Additionally, 12 centers reported that they first intervene both early and late when treating pancreatic cancer. Conclusions: The utilization of palliative care services improves various outcome measures. Pancreatic cancer has one of the lowest survival rates and is associated with significant morbidity. Our findings suggest an increasing recognition among medical centers of the need for palliative care services for pancreatic cancer patients. However, there is variation in the timing and emphasis of palliative care involvement, suggesting a need for further exploration in this area. Notably, there is a growing trend to integrate palliative care at an early stage. Future research should explore barriers to accessing palliative care, distinguish between inpatient and outpatient services, and compare outcomes of early versus late palliative care intervention. By addressing these areas, healthcare providers can enhance the quality of care and improve outcomes for pancreatic cancer patients.

Impact of Neoadjuvant Treatment and Minimally Invasive Surgery on Perioperative Outcomes of Pancreatoduodenectomy: an ACS NSQIP Analysis

BackgroundThere is an increasing use of neoadjuvant treatment (NAT) for pancreatic cancer (PC) followed by minimally invasive pancreatoduodenectomy (MIPD). We evaluate the impact of the surgical approach on 30-day outcomes in PC patients who underwent NAT. MethodsPatients with PC who had NAT followed by MIPD or open pancreatoduodenectomy (OPD) were identified from a pancreatectomy-targeted dataset (2014–2020) of the National Surgical Quality Improvement Program. Comparisons were made between MIPD and OPD within NAT groups. ResultsA total of 5588 patients were analyzed. Of those, 4907 underwent OPD and 476 underwent MIPD. In addition, 3559 patients received neoadjuvant chemotherapy alone and 1830 received neoadjuvant chemoradiation. In the chemotherapy-alone group, the MIPD subgroup had lower rates of any complication (38.2% vs. 45.8%, P = 0.005), but there were no differences in mortality (2.1% for MIPD vs 1.9% for OPD, P=0.8) or serious complication (11.8% for MIPD vs 15% for OPD, P=0.1). On multivariable analysis, MIPD was independently predictive of lower rates of any complication (OR: 0.74, 95% CI 0.6–0.93, P = 0.0009), CR-POPF (OR: 0.58, 95% CI 0.35–0.96, P = 0.04), and shorter LOS (estimate: −1.03, 95% CI −1.73 to −0.32, P = 0.004). In the chemoradiation group, patients undergoing MIPD had higher rates of preoperative diabetes (P < 0.05), but there were no significant differences in any outcomes between the two approaches in this group. ConclusionMIPD is safe and feasible after NAT. Patients having neoadjuvant chemotherapy alone followed by MIPD had lower rates of complications, shorter LOS, and fewer CR-POPFs compared to OPD.

Accelerating artificial intelligence: How federated learning can protect privacy, facilitate collaboration, and improve outcomes.

Cross-institution collaborations are constrained by data-sharing challenges. These challenges hamper innovation, particularly in artificial intelligence, where models require diverse data to ensure strong performance. Federated learning (FL) solves data-sharing challenges. In typical collaborations, data is sent to a central repository where models are trained. With FL, models are sent to participating sites, trained locally, and model weights aggregated to create a master model with improved performance. At the 2021 Radiology Society of North America's (RSNA) conference, a panel was conducted titled "Accelerating AI: How Federated Learning Can Protect Privacy, Facilitate Collaboration and Improve Outcomes." Two groups shared insights: researchers from the EXAM study (EMC CXR AI Model) and members of the National Cancer Institute's Early Detection Research Network's (EDRN) pancreatic cancer working group. EXAM brought together 20 institutions to create a model to predict oxygen requirements of patients seen in the emergency department with COVID-19 symptoms. The EDRN collaboration is focused on improving outcomes for pancreatic cancer patients through earlier detection. This paper describes major insights from the panel, including direct quotes. The panelists described the impetus for FL, the long-term potential vision of FL, challenges faced in FL, and the immediate path forward for FL.

Timing of adjuvant chemoradiation for pancreatic cancer with positive surgical margins

Aims: Impact of adjuvant chemoradiation timing on the outcome of pancreatic cancer patients with positive surgical margins is unknown. The aim of this study was to evaluate the effect of adjuvant chemoradiation timing for margin positive pancreatic cancer patients. Methods: A total of 36 pancreatic adenocarcinoma patients with positive surgical margins and received adjuvant chemoradiation were included in the study. The median radiation dose was 50.4 Gy in 28 fractions. The primary study variable was the timing of chemoradiation, grouped as immediate (after ? 1 cycle of chemotherapy) and delayed (after two or more cycles of chemotherapy) chemoradiation. Gemcitabine (n = 16) and capecitabine (n = 20) were chemotherapy regimens administered with radiation. Results: Median follow-up time was 23.7 months. Thirteen patients (36%) received immediate and 23 (64%) received delayed chemoradiation. For immediate and delayed treatment groups, median overall survival was 13.5 and 42.5 months, and disease-free survival was 6.4 and 18.8 months, respectively. Disease-free survival and overall survival were better with delayed chemoradiation (p = 0.02). However, the two groups did not significantly differ in locoregional control (p = 0.96). Conclusion: Delaying chemoradiation until completion of systemic therapy improves disease-free survival and overall survival without any difference in locoregional failure compared to early chemoradiation in pancreatic cancer patients with positive surgical margins.

Prognostic value of perioperative serum low-density lipoprotein cholesterol level for postoperative prognosis of pancreatic cancer: a retrospective study

BackgroundAs a common malignant tumour, pancreatic cancer (PC) has the worst clinical outcome. Early evaluation of the postoperative prognosis has certain clinical value. Low-density lipoprotein cholesterol (LDL-c), which is mainly composed of cholesteryl esters, phospholipids, and proteins, plays an important role in transporting cholesterol into peripheral tissues. LDL-c has also been reported to be correlated with the occurrence and progression of malignant tumours and can predict postoperative prognosis in various tumours.AimsTo determine correlation between serum LDL-c level and clinical outcome in PC patients after surgery.MethodsData of PC patients that received surgery at our department from January 2015 to December 2021 were retrospectively analysed. Receiver operating characteristic (ROC) curves between perioperative serum LDL-c at different timepoints and survival rate at postoperative 1-year were drawn, and the optimal cut-off value was calculated. Patients were categorized into low and high LDL-c groups, and their clinical data and outcome were compared. Univariate and multivariate analyses were applied to screen out risk markers for poor prognosis of PC patients after surgery.ResultsThe area under the ROC curve of serum LDL-c at 4 weeks after surgery and prognosis was 0.669 (95% CI: 0.581–0.757), and the optimal cut-off value was 1.515 mmol/L. The median disease-free survival (DFS) rates of low and high LDL-c groups were 9 months and 16 months, respectively, and the 1-, 2- and 3-year DFS rates were 42.6%, 21.1% and 11.7% in low LDL-c group, respectively, and, 60.2%, 35.3% and 26.2% in high LDL-c group, respectively (P = 0.005). The median overall survival (OS) rates of low and high LDL-c groups were 12 months and 22 months, respectively, and the 1-, 2- and 3-year OS rates were 46.8%, 22.6% and 15.8% in low LDL-c group, respectively, and 77.9%, 46.8% and 30.4% in high LDL-c group, respectively (P = 0.004). Multivariate analysis confirmed low postoperative 4-week serum LDL-c as independent risk marker for early tumour recrudesce and poor clinical outcome in PC patients.ConclusionHigh postoperative 4-week serum LDL-c is a prognostic marker for prolonged DFS and OS time in PC patients.

High Preoperative Serum D-dimer Predicts Unfavorable Survival Outcomes for Pancreatic Cancer Patients.

Pancreatic cancer cells release certain tissue factors into the bloodstream. It is well known that pancreatic cancer progresses with thrombus formation. Because we routinely measure serum D-dimer levels in preoperative patients as a screening marker of deep venous thrombosis, we examined its association with high serum D-dimer in our cohort of pancreatic cancer resected cases. We examined 315 patients with pancreatic ductal adenocarcinoma who underwent surgical resection in our department from January 2012 to July 2021. All cases were divided into high D-dimer cases (n=118) and low D-dimer cases (n=197) using the cut-off value of 1.0 μg/ml, an institutional upper limit. Clinicohistological characteristics and postoperative survival outcomes were evaluated. Preoperative high D-dimer cases showed significantly worse progression-free survival (PFS) (p=0.021) and overall survival (OS) (p=0.027) than low D-dimer cases; median PFS was 13.9 months versus 21.4 months, and that of OS was 33.4 months versus 68.0 months. Clinicohistological characteristics of high D-dimer cases were age over 70 years (p<0.001), pathological portal vein invasion (p=0.003), and initially borderline resectable or unresectable cases (p=0.027). Multivariate analysis indicated that preoperative high D-dimer was a significant prognostic factor of PFS (hazard ratio=1.42, p=0.025) and OS (hazard ratio=1.51, p=0.036). Preoperative high serum D-dimer over 1.0 μg/ml was associated with pathological portal vein invasion and could be an unfavorable prognostic marker of PFS and OS after surgery, typically due to distant metastasis.

Post-operative mortality and recurrence patterns in pancreatic cancer according to KRAS mutation and CDKN2A, p53, and SMAD4 expression.

Alterations in KRAS, CDKN2A (p16), TP53, and SMAD4 genes have been major drivers of pancreatic carcinogenesis. The clinical course of patients with pancreatic cancer in relation to these driver alterations has not been fully characterised in large populations. We hypothesised that pancreatic carcinomas with different combinations of KRAS mutation and aberrant expression of CDKN2A, p53, and SMAD4 might show distinctive recurrence patterns and post-operative survival outcomes. To test this hypothesis, we utilised a multi-institutional cohort of 1,146 resected pancreatic carcinomas and assessed KRAS mutations by droplet digital polymerase chain reaction and CDKN2A, p53, and SMAD4 expression by immunohistochemistry. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for disease-free survival (DFS) and overall survival (OS) were computed according to each molecular alteration and the number of altered genes using the Cox regression models. Multivariable competing risks regression analyses were conducted to assess the associations of the number of altered genes with specific patterns of recurrence. Loss of SMAD4 expression was associated with short DFS (multivariable HR, 1.24; 95% CI, 1.09-1.43) and OS times (multivariable HR, 1.27; 95% CI, 1.10-1.46). Compared to cases with 0-2 altered genes, cases with three and four altered genes had multivariable HRs for OS of 1.28 (95% CI, 1.09-1.51) and 1.47 (95% CI, 1.22-1.78), respectively (ptrend < 0.001). Patients with an increasing number of altered genes were more likely to have short DFS time (ptrend = 0.003) and to develop liver metastasis (ptrend = 0.006) rather than recurrence at local or other distant sites. In conclusion, loss of SMAD4 expression and an increasing number of altered genes were associated with unfavourable outcomes in pancreatic cancer patients. This study suggests that the accumulation of the four major driver alterations can confer a high metastatic potential to the liver, thereby impairing post-operative survival among patients with pancreatic cancer.

Efficacy of adjuvant chemoradiotherapy in patients with pancreatic ductal adenocarcinoma after surgery: A real-world study in high-volume pancreatic cancer center.

e16308 Background: Whether adjuvant chemoradiotherapy provides survival benefit for pancreatic ductal adenocarcinoma (PDAC) patients remains unknown. Methods: This prospective real-world study recruited PDAC patients receiving surgical treatment in Zhongshan Hospital Fudan University, Shanghai, China from June 2020 to December 2021. Patients with carcinoma in situ, distant metastases, synchronous cancers within 5 years, and receiving neoadjuvant therapy were excluded. Patients were then categorized into three groups according to their adjuvant treatment: C- (without adjuvant chemotherapy), C+R- (with adjuvant chemotherapy only), and C+R+ (with adjuvant chemoradiotherapy). Overall survival (OS) and disease free survival (DFS) were compared between groups. Results: A total of 216 patients were included in the final analyses. Median follow time for three groups ranged from 18 to 21.9 months. OS and DFS were significantly different between groups (OS, p value = 0.0088; DFS, p value = 0.0037). Median OS (mOS) for C- and C+R- were 24.3 (95% confidence interval [CI], 18 - not available [NA]) and 29.5 (24.9 – NA). Patients in C+R+ groups did not reach mOS (27.2 - NA). Median DFS (mDFS) for C-, C+R-, and C+R+ were 8.42 (5.72 - NA), 16.9 (13.91 - NA) and 19.66 (16.83 - NA), respectively. Conclusions: Adjuvant treatment significantly increased survival outcomes of pancreatic cancer patients after surgical treatment. In order to find out whom might benefit from additional radiotherapy and which is the best therapy combination, more detail information, including chemotherapy regimen, staging, resection margin, etc., were needed to include in the survival analyses. Clinical trial information: NCT04737551 . [Table: see text]