RESUMEN

Purpose: Due to resistance to gemcitabine (GEM), patients with pancreatic cancer (PC) usually have poor prognosis and low survival rate. The purpose of our research was to explore the impact of exosome PPP3CB on GEM resistance in PC, and concurrently analyze the regulatory role of the miR-298/STAT3 signaling pathway. Methods: Exosomes isolated from PC cells were verified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and western blotting (WB). The interaction between PPP3CB and miR-298 was verified using dual-luciferase reporter gene assay, followed by evaluation of cell growth and death using CCK8 assay, EdU staining, and flow cytometry. Results: Increased PPP3CB expression was observed in GEM-resistant PC cells. Exosomes from PC cells and GEM-resistant PC cells were successfully extracted by ultra-high speed centrifugation. Confocal microscopy showed internalization of fluorescein amide (FAM)-labeled GEM-resistant exosomes by PC cells. PPP3CB enhanced the proliferation of GEM-resistant PC cells and inhibited their apoptosis, whereas down-regulation of PPP3CB promoted the death of PC cells and inhibited the proliferation of GEM-resistant PC cells, and enhance the susceptibility of PC cells to GEM. Additionally, PPP3CB positively regulated STAT3 expression in PC cells by down-regulating miR-298, thus promoting the growth and inhibiting the death of PC cells. Conclusion: PC cell-derived exosome PPP3CB enhances STAT3 expression by downregulating miR-298, stimulating cell growth, and suppressing cell death, thereby increasing the resistance of PC cells to GEM.

RESUMEN

Background: Pancreatic cancer (PC), characterized by its aggressive nature and low patient survival rate, remains a challenging malignancy. Anoikis, a process inhibiting the spread of metastatic cancer cells, is closely linked to cancer progression and metastasis through anoikis-related genes. Nonetheless, the precise mechanism of action of these genes in PC remains unclear. Methods: Study data were acquired from the Cancer Genome Atlas (TCGA) database, with validation data accessed at the Gene Expression Omnibus (GEO) database. Differential expression analysis and univariate Cox analysis were performed to determine prognostically relevant differentially expressed genes (DEGs) associated with anoikis. Unsupervised cluster analysis was then employed to categorize cancer samples. Subsequently, a least absolute shrinkage and selection operator (LASSO) Cox regression analysis was conducted on the identified DEGs to establish a clinical prognostic gene signature. Using risk scores derived from this signature, patients with cancer were stratified into high-risk and low-risk groups, with further assessment conducted via survival analysis, immune infiltration analysis, and mutation analysis. External validation data were employed to confirm the findings, and Western blot and immunohistochemistry were utilized to validate risk genes for the clinical prognostic gene signature. Results: A total of 20 prognostic-related DEGs associated with anoikis were obtained. The TCGA dataset revealed two distinct subgroups: cluster 1 and cluster 2. Utilizing the 20 DEGs, a clinical prognostic gene signature comprising two risk genes (CDKN3 and LAMA3) was constructed. Patients with pancreatic adenocarcinoma (PAAD) were classified into high-risk and low-risk groups per their risk scores, with the latter exhibiting a superior survival rate. Statistically significant variation was noted across immune infiltration and mutation levels between the two groups. Validation cohort results were consistent with the initial findings. Additionally, experimental verification confirmed the high expression of CDKN3 and LAMA3 in tumor samples. Conclusion: Our study addresses the gap in understanding the involvement of genes linked to anoikis in PAAD. The clinical prognostic gene signature developed herein accurately stratifies patients with PAAD, contributing to the advancement of precision medicine for these patients.

RESUMEN

Pancreatic cancer, a highly fatal malignancy, is predicted to rank as the second leading cause of cancer-related death in the next decade. This highlights the urgent need for new insights into personalized diagnosis and treatment. Although molecular subtypes of pancreatic cancer were well established in genomics and transcriptomics, few known molecular classifications are translated to guide clinical strategies and require a paradigm shift. Notably, chronically developing and continuously improving high-throughput technologies and systems serve as an important driving force to further portray the molecular landscape of pancreatic cancer in terms of epigenomics, proteomics, metabonomics, and metagenomics. Therefore, a more comprehensive understanding of molecular classifications at multiple levels using an integrated multi-omics approach holds great promise to exploit more potential therapeutic options. In this review, we recapitulated the molecular spectrum from different omics levels, discussed various subtypes on multi-omics means to move one step forward towards bench-to-beside translation of pancreatic cancer with clinical impact, and proposed some methodological and scientific challenges in store.

RESUMEN

Mutations of KRAS, CDKN2A, TP53, and SMAD4 are the four major driver genes for pancreatic ductal adenocarcinoma (PDAC), of which mutations of KRAS and TP53 are the most frequently recognized. However, molecular-targeted therapies for mutations of KRAS and TP53 have not yet been developed. To identify novel molecular targets, we newly established organoids with the Kras mutation (KrasmuOR) and Trp53 loss of function using Cre transduction and CRISPR/Cas9 (Krasmu/p53muOR) from murine epithelia of the pancreatic duct in KrasLSL-G12D mice, and then analyzed the proteomic and metabolomic profiles in both organoids by mass spectrometry. Hyperfunction of the glycolysis pathway was recognized in Krasmu/p53muOR compared with KrasmuOR. Loss of function of triosephosphate isomerase (TPI1), which is involved in glycolysis, induced a reduction of cell proliferation in human PDAC cell lines with the TP53 mutation, but not in PDAC or in human fibroblasts without TP53 mutation. The TP53 mutation is clinically recognized in 70% of patients with PDAC. In the present study, protein expression of TPI1 and nuclear accumulation of p53 were recognized in the same patients with PDAC. TPI1 is a potential candidate therapeutic target for PDAC with the TP53 mutation.

RESUMEN

Targeting checkpoints for immune cell activation has been acknowledged known as one of the most effective way to activate anti-tumor immune responses. Among them, drugs targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) are approved for clinical treatment though several more are in advanced stages of development, which demonstrated durable response rates and manageable safety profile. However, its therapy efficacy is unsatisfactory in pancreatic cancer (PC), which can be limited by the overall condition of patients, the pathological type of PC, the expression level of tumor related genes, etc. To improve clinical efficiency, various researches have been conducted, and the efficacy of combination therapy showed significantly improvement compared to monotherapy. This review analyzed current strategies based on anti-CTLA-4 combination immunotherapy, providing totally new idea for future research.

RESUMEN

The ST6GAL1 sialyltransferase is overexpressed in multiple cancers including pancreatic ductal adenocarcinoma (PDAC). ST6GAL1 adds an α2-6-linked sialic acid to N-glycosylated membrane receptors, which consequently modulates receptor structure and function. While many studies have investigated the effects of ST6GAL1 on cell phenotype, there is a dearth of knowledge regarding mechanisms that regulate ST6GAL1 expression. In the current study, we evaluated the regulation of ST6GAL1 by two pro-inflammatory cytokines, IL-1ß and IL-6, that are abundant within the PDAC tumor microenvironment. Cytokine activity was monitored using the Suit-2 PDAC cell line and two Suit-2-derived metastatic subclones, S2-013 and S2-LM7AA. For all three cell models, treatment with IL-1ß or IL-6 increased the expression of ST6GAL1 protein and mRNA. Specifically, IL-1ß and IL-6 induced expression of the ST6GAL1 YZ mRNA isoform, which is driven by the P3 promoter. The ST6GAL1 H and X isoforms were not detected. Promoter reporter assays confirmed that IL-1ß and IL-6 activated transcription from the P3 promoter. We then examined downstream signaling mechanisms. IL-1ß is known to signal through the NFκB transcription factor, whereas IL-6 signals through the STAT3 transcription factor. CUT&RUN experiments revealed that IL-1ß promoted the binding of NFκB to the ST6GAL1 P3 promoter, and IL-6 induced the binding of STAT3 to the P3 promoter. Finally, we determined that inhibitors of NFκB and STAT3 blocked the upregulation of ST6GAL1 stimulated by IL-1ß and IL-6, respectively. Together, these results highlight a novel molecular pathway by which cytokines within the tumor microenvironment stimulate the upregulation of ST6GAL1 in PDAC cells.

RESUMEN

Pancreatic cancer is highly lethal, and survival chances improve only with early detection at a precancerous stage. However, there remains a significant gap in developing tools for large-scale, rapid screening. To this end, a high-throughput On-Target Array Extraction Platform (OTAEP) by direct sintering of a series of metal-organic frameworks (MOFs) for dual in situ extraction, encompassing both exosomes and their metabolic profiles, is developed. Based on the principle of geometry-dependent photothermal conversion efficiency and standard testing, the appropriate MOF functional unit is identified. This unit enables exosome enrichment within 10 min and metabolic fingerprint extraction in under 1 s of laser irradiation, with over five reuse. To further accelerate and enhance the quality of metabolic profile analysis, the application of Surrogate Variable Analysis to eliminate hidden confounding factors within the profiles is proposed, and five biomarkers demonstrated by MS/MS experiments are identified. These biomarkers enable early diagnosis, risk stratification, and staging of pancreatic cancer simultaneously, with sensitivity of 94.1%, specificity of 98.8%, and precision of 94.9%. This work represents a breakthrough for overcoming throughput challenges in large-scale testing and for addressing confounding factors in big data analysis.

RESUMEN

The increasing availability of patient-derived multimodal biological data for various diseases has opened up avenues for finding the optimal methods for jointly leveraging the information extracted in a customizable and scalable manner. Here, we propose the Proximogram, a graph-based representation that provides a joint construct for embedding independently obtained omics and spatial data. To evaluate the representation, we generated proximograms from 2 distinct biological sources, namely, multiplexed immunofluorescence images and single-cell RNA-seq data obtained from patients across two pancreatic diseases that include normal and chronic Pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC). The generated proximograms were used as inputs to 2 distinct graph deep-learning models. The improved classification results over simpler spatial-data-based input graphs point to the increased discriminatory power obtained by integrating structural information from single-cell ligand-receptor signaling data and the spatial architecture of cells in each disease class, which can help point to markers of high diagnostic significance.

RESUMEN

The massive infiltration of suppressor immune cells within the tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) is a major cause of treatment resistance. Reducing this infiltration may represent a potentially effective therapeutic strategy. Sphingomyelin synthase 2 (SMS2) is a crucial enzyme for sphingomyelin synthesis, contributing significantly to the integrity and function of the plasma membrane. In this study, we developed a self-assembling SMS2 siRNA gene expression plasmid for in vivo delivery. The SMS2 siRNA specifically inhibits SMS2 expression while preserving the expression and activity of SMS1. Administration of the self-assembling SMS2 siRNA suppresses tumor growth in a murine model of Panc02 pancreatic carcinoma, modulates the polarization of tumor-associated macrophages (TAMs), and reduces the infiltration of tumor-associated neutrophils (TANs) by regulating the NF-κB/CXCL5 pathway. Consequently, utilizing SMS2 siRNA to improve the local immunosuppressive microenvironment holds promise for pancreatic cancer therapy.

RESUMEN

INTRODUCTION: The role and impact of preoperative chemotherapy (PC) in pancreatic adenocarcinoma are questions under active investigation. Here we investigate the rate of failure to rescue (FTR) and surgical outcomes in patients undergoing pancreatectomy, with PC within 90 days (d) prior to surgery and without PC. MATERIALS AND METHODS: The National Surgical Quality Improvement Program Targeted Dataset for Pancreatectomy (2014-2020) was queried to identify patients who underwent pancreatectomy for malignant non-neuroendocrine pancreatic tumors. The cohort was divided into those who underwent PC within 90 d and those without. Propensity score analysis was employed to match patients 1:1 based on age, sex, body mass index, hypertension, smoking status, ascites, diabetes, and American Society of Anesthesiology (ASA) score. The primary outcome of interest was FTR, defined as mortality following a major complication (Clavien-Dindo Class III-V). RESULTS: After propensity score matching, 7895 patients with PC were matched to 7895 patients without PC. PC patients exhibited a significantly lower rate of FTR (P = 0.002) despite having higher ASA scores. This benefit was most pronounced in the pancreaticoduodenectomy subgroup (P < 0.009). PC patients demonstrated a lower rate of overall complications compared to those without PC (P < 0.001). Overall, the PC group was more likely to require vascular resection (P < 0.001). CONCLUSIONS: Patients who received chemotherapy within 90 d prior to surgery experienced a lower rate of FTR and overall complications despite higher ASA scores and incidence of vascular resection. This suggests that, when appropriate, the receipt of PC does not negatively impact surgical outcomes.

RESUMEN

BACKGROUND: The incidence of pancreatic cancer is on the rise, and its prognosis remains poor. Recent reports have established a link between the gut and oral microbiome and pancreatic cancer. However, the intricacies of this association within the Japanese population remain unclear. In this study, we investigated the gut and oral microbiomes of Japanese patients with pancreatic cancer, comparing them with those of healthy individuals. METHODS: We recruited 30 patients with untreated pancreatic cancer and 18 healthy controls at Kyoto University Hospital (2018-2022). We performed a comprehensive 16S rRNA gene sequencing to analyze their gut and oral microbiomes. RESULTS: Analysis revealed that the diversity of the gut and oral microbiomes of patients with pancreatic cancer was reduced compared to that of the healthy controls. Specifically, we observed an increase in the genus Streptococcus in both the gut and oral microbiomes and a significant decrease in several butyrate-producing bacteria in fecal samples. Moreover, bacteria such as Streptococcus mitis and Holdemanella biformis were present in pancreatic cancer tissues, suggesting that they might influence the carcinogenesis and progression of pancreatic cancer. CONCLUSIONS: The gut and oral microbiome differed between patients with pancreatic cancer and healthy controls, with a notable decrease in butyrate-producing bacteria in the gut microbiome of the patients. This suggests that there may be a distinct microbial signature associated with pancreatic cancer in the Japanese population. Further studies are required to elucidate the microbiome's causal role in this cancer and help develop prognostic markers or targeted therapies.

RESUMEN

PURPOSE: This review article summarizes the pathophysiological aspects of interleukins (ILs) including IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, and IL-10 in pancreatic cancer (PC). METHODS: Science Direct, PubMed, and Google Scholar were used for the literature review. The search was conducted until August 12, 2024, and particular keywords such as "Pancreatic Cancer," "Interleukins," "Pathophysiological Aspects," "Immunosuppression," "Invasiveness," and "Metastasis" were used. Focusing on interleukins related to pancreatic cancer, 61 original studies were included: 32 studies for human patients, 16 studies for animal models, and 13 studies for both animal models and human patients. All types of PC were considered. The timeframe of 1991 to 2024 was chosen for clinical studies. RESULTS: In epithelial pancreatic tumors, IL-1 is a major inflammation factor. Serum concentrations of soluble interleukin-2-receptor were considerably greater in patients with PC and chronic pancreatitis than in healthy individuals. In comparison to controls, pancreatic cancer patients had considerably greater levels of macrophage colony-stimulating factor and significantly lower levels of stem cell factor and IL-3. The tissues and cells of pancreatic cancer have higher concentrations of IL-4 receptors. IL-5 has a role in the accumulation of pancreatic fibrosis. For individuals with pancreatic ductal adenocarcinoma (PDAC), a high serum level of IL-6 may be a separate risk factor for the development of widespread liver metastases. PDAC patients' peripheral blood mononuclear cells exhibit a substantial upregulation of IL-7 receptor. The role of IL-8 in the growth and spread of PC in humans. The miR-200a/ß-catenin axis may be the mechanism by which IL-9 stimulates the proliferation and metastasis of PC cells. Blocking IL-10 in the local microenvironment appears to result in a significant reversal of tumor-induced immunosuppression. CONCLUSION: The article concludes that interleukins 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10 played significant roles in the pathogenesis of PC.

RESUMEN

Glutathione S-transferase-Pi 1 (GSTP1) is an isozyme that plays a key role in detoxification and antioxidative damage. It also confers resistance to tumor therapy. However, the specific role of GSTP1 in radiotherapy resistance in pancreatic cancer (PC) is not known. In this study, we investigated how GSTP1 imparts radioresistance in PC. The findings of previous studies and this study revealed that ionizing radiation (IR) induces ferroptosis in pancreatic cancer cells, primarily by upregulating the expression of ACSL4. Our results showed that after IR, GSTP1 prolonged the survival of pancreatic cancer cells by inhibiting ferroptosis but did not affect apoptosis. The expression of GSTP1 reduced cellular ferroptosis by decreasing the levels of ACSL4 and increasing the GSH content. These changes increase the resistance of pancreatic cancer cells and xenograft tumors to IR. Our findings indicate that ferroptosis participates in irradiation-induced cell death and that GSTP1 prevents IR-induced death of pancreatic cancer cells by inhibiting ferroptosis.

Asunto(s)

RESUMEN

Numerous aspects of cellular signaling are regulated by the kinome-the network of over 500 protein kinases that guides and modulates information transfer throughout the cell. The key role played by both individual kinases and assemblies of kinases organized into functional subnetworks leads to kinome dysregulation driving many diseases, particularly cancer. In the case of pancreatic ductal adenocarcinoma (PDAC), a variety of kinases and associated signaling pathways have been identified for their key role in the establishment of disease as well as its progression. However, the identification of additional relevant therapeutic targets has been slow and is further confounded by interactions between the tumor and the surrounding tumor microenvironment. In this work, we attempt to link the state of the human kinome, or kinotype, with cell viability in treated, patient-derived PDAC tumor and cancer-associated fibroblast cell lines. We applied classification models to independent kinome perturbation and kinase inhibitor cell screen data, and found that the inferred kinotype of a cell has a significant and predictive relationship with cell viability. We further find that models are able to identify a set of kinases whose behavior in response to perturbation drive the majority of viability responses in these cell lines, including the understudied kinases CSNK2A1/3, CAMKK2, and PIP4K2C. We next utilized these models to predict the response of new, clinical kinase inhibitors that were not present in the initial dataset for model devlopment and conducted a validation screen that confirmed the accuracy of the models. These results suggest that characterizing the perturbed state of the human protein kinome provides significant opportunity for better understanding of signaling behavior and downstream cell phenotypes, as well as providing insight into the broader design of potential therapeutic strategies for PDAC.

Asunto(s)

RESUMEN

BACKGROUND: Same-session endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) is an attractive policy for patients with distal malignant biliary obstruction (DMBO) requiring fine-needle biopsy (FNB) and biliary drainage. However, scanty and conflicting data exists regarding safety and efficacy when comparing these two procedures performed in same versus separate sessions. METHODS: Single-center, retrospective, propensity score-matched study including patients with DMBO who underwent EUS-FNB followed by ERCP during the same or separate sessions. The primary outcome was the safety of the procedure [number of patients experiencing adverse events (AEs), overall AEs, its severity, post-ERCP pancreatitis (PEP)]. Secondary outcomes were successful ERCP, use of advanced cannulation techniques, EUS-FNB adequacy, length of hospital stay, overall procedure time, and time to recurrent biliary obstruction. RESULTS: After propensity matching, 87 patients were allocated to each group. AEs developed in 23 (26.4%) vs. 17 (19.5%) patients in the same and separate sessions group, respectively (p = 0.280). The overall number, the severity of AEs, and the rate of PEP were similar in the two groups. Secondary outcome parameters were also comparable in the 2 groups. CONCLUSIONS: Same-session EUS-FNB followed by ERCP with biliary drainage is safe and does not impair technical outcomes of tissue adequacy and biliary cannulation.

RESUMEN

PURPOSE: To clarify the prevalence, risk factors, and clinical implications associated with zinc deficiency in patients undergoing pancreatic surgery. METHODS: The serum zinc levels were measured in 329 patients post-pancreatic surgery between January and April 2021. The postoperative serum zinc levels and clinicopathological variables were retrospectively analyzed. RESULTS: The median serum zinc level was 73 µg/dL (33-218). Zinc deficiency (zinc level < 60 µg/dL) was observed in 52 patients (16%). A total of 329 patients were classified into zinc-deficient (n = 52) and non-deficient (zinc ≥ 60 µg/dL, n = 277) groups. A univariate analysis revealed significant differences in sex, postoperative body mass index, serum albumin, total cholesterol, creatinine, aspartate aminotransferase (AST), HbA1c levels, diabetes, surgical procedures, and operative blood loss. According to a multivariate analysis, male sex [odds ratio (OR) 3.70; 95% confidence interval (CI) 1.67-8.20; p = 0.001], postoperative serum albumin levels < 3.9 g/dL (OR 6.39; 95% CI 3.30-12.37; p < 0.001), postoperative serum AST ≥ 51 U/L (OR, 4.6; 95% CI 0.07-0.29; p < 0.001), and total pancreatectomy (OR 3.68; 95% CI 1.37-9.85; p = 0.009) were found to be independent predictors of zinc deficiency after pancreatic surgery. CONCLUSIONS: Zinc deficiency frequently occurs in patients undergoing pancreatic surgery. Lower postoperative zinc levels could be linked to sex, the serum albumin and AST levels, and surgery type.

RESUMEN

OBJECTIVES: Pancreatic cancer with peritoneal metastasis presents a challenging prognosis, with limited effective treatment options available. This study aims to evaluate the efficacy and safety of combining cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) as a treatment strategy for this patient group. METHODS: A retrospective analysis was conducted on patients with peritoneal metastasis of pancreatic cancer who underwent CRS + HIPEC treatment at Beijing Shijitan Hospital from March 2017 to December 2023. The study focused on assessing clinical features, the incidence of sever adverse events (SAEs), and overall survival (OS). RESULTS: A total of 10 patients were enrolled in this study. The median OS was 24.2 months, suggesting an improvement over traditional therapies. While SAEs were noted, including two cases of severe complications necessitating additional surgical interventions, no perioperative fatalities were recorded. The overall survival time for patients with CC0/1 was not significantly different from that of patients with CC2/3, and no prognostic predictors were identified. CONCLUSIONS: The combination of CRS and HIPEC appears to be a viable and promising treatment modality for patients with peritoneal metastasis of pancreatic cancer, offering an improved survival rate with manageable safety concerns. Further research is needed to refine patient selection criteria and to explore the long-term benefits of this approach.

Asunto(s)

RESUMEN

Pancreatic ductal adenocarcinoma (PDAC) is frequently detected in late stages, which leads to limited therapeutic options and a dismal overall survival rate. To date, no robust method for the detection of early-stage PDAC that can be used for targeted screening approaches is available. Liquid biopsy allows the minimally invasive collection of body fluids (typically peripheral blood) and the subsequent analysis of circulating tumor cells or tumor-associated molecules such as nucleic acids, proteins, or metabolites that may be useful for the early diagnosis of PDAC. Single biomarkers may lack sensitivity and/or specificity to reliably detect PDAC, while combinations of these circulating biomarkers in multimarker panels may improve the sensitivity and specificity of blood test-based diagnosis. In this narrative review, we present an overview of different liquid biopsy biomarkers for the early diagnosis of PDAC and discuss the validity of multimarker panels.

Asunto(s)

RESUMEN

BACKGROUND: Gastrointestinal (GI) bleeding is a leading cause of intensive care unit (ICU) admission in pancreatic cancer patients. AIMS: To analyze causes, ICU mortality and hemostatic treatment success rates of GI bleeding in pancreatic cancer patients requiring ICU admission. METHODS: Retrospective multicenter cohort study between 2009 and 2021. Patients with a recent pancreatic resection surgery were excluded. RESULTS: Ninety-five patients were included (62 % males, 67 years-old). Fifty-one percent presented hemorrhagic shock, 41 % required mechanical ventilation. Main GI bleeding causes were gastroduodenal tumor invasion (32 %), gastroesophageal varices (21 %) and arterial aneurysm (12 %). Arterial aneurysms were more frequent in patients with previous pancreatic resection (36 % vs 2 %, p < 0.001). Hemostatic procedures included gastroduodenal endoscopy in 81 % patients and arterial embolization in 28 % patients. ICU mortality was 19 %. Multivariate analysis identified four variables associated with mortality: performance status >2 (OR 9.34, p = 0.026), mechanical ventilation (OR 14.14, p = 0.003), treatment success (OR 0.09, p = 0.010), hemorrhagic shock (OR 11.24, p = 0.010). Treatment success was 46 % and was associated with aneurysmal bleeding (OR 29.89, p = 0.005), ongoing chemotherapy (OR 0.22, p = 0.016), and prothrombin time ratio (OR 1.05, p = 0.001). CONCLUSION: In pancreatic cancer patients with severe GI bleeding, early identification of aneurysmal bleeding (particularly in case of previous resection surgery) and coagulopathy management may increase the treatment success and reduce mortality.

RESUMEN

Background: Pancreatic ductal adenocarcinoma (PDAC) remains a lethal and rarely resectable malignancy. Here we explore the outcomes of surgery, as compared to definitive radiotherapy (dRT) or systemic therapy only in PDAC. Methods: Pancreatic surgery and radiotherapy in Southwest Finland have been centralized to Turku University Hospital. Previously validated population-based electronic health records database was searched for all unselected PDAC patients from the years 2009-2019. Main outcome was median overall survival (mOS). Demographics, pathology, surgery, and oncological treatment data were collected. Results: We identified 1006 patients with PDAC, 49% male, median age 71 years and 77% presenting with metastatic disease. In total, 405 patients were treated; 92 resected, 26 dRT without resection and 287 systemic therapy only. mOS was 34.6 months for resected, 26.7 months for dRT, and 7.5 months for systemic therapy patients. Among the 88 patients with locally advanced inoperable PDAC, dRT was independently associated with longer mOS (26.7 months) as compared to systemic therapy only (mOS 10.6 months). Among the 287 patients treated with systemic therapy only, combination chemotherapy was independently associated with longer mOS (11.6 months) as compared to gemcitabine-monotherapy (6.8 months). In patients progressing to second-line systemic treatment after gemcitabine failure, mOS was the same (5.0 months) with single or combination regimens. Conclusion: Surgery remains the only curative approach for PDAC. In locally advanced PDAC, dRT was associated with longer survival as compared to systemic therapy only. Concerning first-line systemic therapy, our results support the use of combination chemotherapy over single-agent therapy.