Hidradenitis suppurativa (HS) is a chronic, inflammatory and common skin disease. Observation studies have reported the association between HS and cancers, however no studies reported whether a causal relationship exists between HS and cancers. This study aimed to explore the causal relationship between HS and differential subtypes of cancers by conducting a bidirectional Mendelian randomization (MR) analysis.

Genome-wide association study (GWAS) data related to HS and 16 subtypes of cancers were collected. The inverse variance weighted (IVW) method was primarily applied for our MR analysis, MR-Egger, weighted median, simple mode, and weighted mode methods were used additionally. Heterogeneity, horizontal pleiotropy, and potential outliers were assessed for the MR analysis results. Subsequently, disease-related genes were retrieved from the GeneCards database. To investigate the potential functions of these associated genes, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted.

The results of our MR analysis indicated a causal association between HS and pancreatic cancer (PAC). Specifically, HS was found to elevate the risk of developing PAC (odds ratio (OR), 1.074; 95% confidence interval (CI) 1.015-1.135; p = 0.013). Conversely, reverse MR analysis demonstrated that PAC does not exert a causal effect on HS. Furthermore, our findings did not reveal any significant causal relationships between HS and other types of cancer. No evidence of heterogeneity or pleiotropy was identified in the analysis. Additionally, we identified disease-related genes, and subsequent GO and KEGG enrichment analyses indicated that the genes common to both HS and PAC are implicated in pathways associated with immune and inflammatory processes.

The results of this study offer novel evidence regarding the causal relationship between HA and PAC. Our Mendelian randomization analysis indicates that HS may have a causal influence on PAC, which could inform the development of improved treatment strategies for patients suffering from HS. However, the underlying mechanisms warrant further exploration.

Pancreatic cancer, often diagnosed at advanced stages, has poor survival rates. Effective screening aims to detect the disease early, improving outcomes. Current guidelines recommend screening high-risk groups, including those with a family history or genetic predispositions, using methods like endoscopic ultrasound and MRI. The American Gastroenterological Association and other organizations advise annual surveillance for high-risk individuals, typically starting at the age of 50 or 10 years younger than the youngest affected relative. For certain genetic syndromes, such as Peutz-Jeghers syndrome or hereditary pancreatitis, screening may begin as early as the age of 35 to 40 years.

Pancreatic cancer is a highly lethal malignancy and is predicted to become the second leading cause of cancer-related deaths by 2030. Early detection significantly improves outcomes, but general population screening remains infeasible due to the low prevalence of the disease and lack of specific biomarkers. This review evaluates current recommendations for pancreatic cancer surveillance in high-risk individuals, synthesises evidence from recent studies and explores the sustainability of current imaging-based surveillance programmes. Challenges such as overdiagnosis, economic feasibility and disparities in access highlight the need for targeted, cost-effective strategies. Collaborative initiatives and consortia are needed to advance biomarker research and refine risk stratification. By integrating evidence-based recommendations with sustainable approaches, this review outlines pathways to improve early detection and reduce mortality from pancreatic cancer.

Early-onset pancreatic cancer (EOPC) is usually defined as patients with pancreatic cancer before the age of 50 years, which is relatively rare. However, the research on EOPC is somewhat obscure, and the specific clinical and molecular characteristics of this condition are debated. In this review, we discussed the differences between EOPC and late-onset pancreatic cancer (LOPC) or average-onset pancreatic cancer (AOPC) with a focus on clinical and molecular characteristics, survival outcomes and treatment to promote the diagnosis and treatment of EOPC.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with a five-year survival rate of approximately 13% for advanced stages. While the majority of PDAC cases are sporadic, a significant subset is attributable to hereditary and familial predispositions, accounting for approximately 25% of cases. This article synthesizes recent advancements in the understanding, detection, and management of hereditary pancreatic cancer (PC). Results: Our review highlights the critical role of genetic testing (GT) in identifying high-risk individuals (HRIs), with germline pathogenic variants (PVs) found in up to 20% of hereditary PDAC cases. Since the implementation of next-generation sequencing (NGS) panels in 2014, detection capabilities have been significantly enhanced. HRIs can be included in screening programs that facilitate the early detection of PDAC. Early detection strategies, including the use of microribonucleic acid (miRNAs) signatures and novel imaging techniques like hyperpolarized 13C-magnetic resonance spectroscopy (MRS) have shown promising results. The identification of germline pathogenic variants (PVs) or mutations in homologous recombination (HR) genes plays a predictive role in the response to various treatments, prolonging patient survival. Discussion: Universal germline testing for PDAC, as recommended by the National Comprehensive Cancer Network (NCCN), is now a standard practice, facilitating the identification of at-risk individuals and enabling targeted surveillance and intervention. Multidisciplinary management, integrating genetic counseling, imaging, and gastrointestinal services, is essential for optimizing outcomes. Conclusions: Advances in genetic testing and biomarker research are transforming the landscape of hereditary PC management. Early detection and personalized treatment strategies are pivotal in improving survival rates. Ongoing multi-institutional research efforts are crucial for validating biomarkers and developing preventive measures, ultimately aiming to reduce the burden of this aggressive cancer.

To evaluate in vitro fertilization (IVF) cycles covered by health insurance using a national commercial claims database and validate key clinical events against national IVF registries.

Retrospective cohort study.

US women aged 20-44 years who underwent IVF from 2005-2020 in Optum's deidentified Clinformatics Data Mart Database (CDM).

Undergoing IVF.

In vitro fertilization cycles and rates of pregnancies (inclusive of losses and terminations), live births, and live birth types (e.g., singleton, twin, and triplet or higher-order).

We identified more than 3,000 IVF cycles in each year from 2005-2020 within CDM. When comparing our rates of clinical outcomes with external benchmark data, the results were similar across all the years of our study. For example, in 2020, the percentages of pregnancies after first embryo transfer were 62.03% (95% confidence interval [CI], 59.48-64.47) in CDM and 64.96% in data from the Society for Assisted Reproductive Technology (SART). The rates of live birth after first embryo transfer were 44.58% (95% CI, 41.90-47.21) in CDM in 2020 and 46.95% in SART in 2020. The rate of singleton births was 94.17% (95% CI, 92.24-96.10) in CDM in 2020, and this rate was 94.37% in SART in 2020. For twin births, the rates were 5.48% (95% CI, 3.60-7.35) in CDM in 2020 and 5.46% in SART in 2020. The rates of triplet or higher-order births were 0.35% (95% CI, 0.00-0.84) in CDM in 2020 and 0.17% in SART in 2020.

We found that CDM can be used to accurately identify IVF cycles covered by insurance and key clinical outcomes such as rates of pregnancies, live births, and live birth types, and our reported rates were similar to national IVF clinical registry data. Our findings support that CDM is a robust data source to conduct research about IVF insurance coverage and can accurately evaluate clinical outcomes resulting from IVF. Policymakers who are considering insurance coverage for IVF can use CDM to model and measure the impact of new or existing policies for IVF insurance coverage.

The purpose of this study was to synthesize and evaluate the evidence regarding the effects of omega-3 supplementation on the nutritional status of pancreatic cancer patients.

A systematic review of clinical trials was conducted, adhering to the PRISMA Statement. MEDLINE/PubMed, EMBASE, CENTRAL Cochrane, Scopus, and Web of Science databases were searched up to 31 December 2022 without restrictions on the publication date or language. Independent reviewers extracted data and assessed the risk of bias. The internal validity and risk of bias in randomized controlled trials (RCT) were assessed using the revised Cochrane risk of bias tool for randomized trials-RoB2, while the risk of bias in non-randomized intervention studies was evaluated using the ROBINS-I tool.

Eight studies met all the inclusion criteria and were analyzed. Five of them were RCT, with the majority (n = 4) classified as low risk of bias, and the three quasi-experiments were deemed to have a moderate risk of bias. Among the studies investigating the outcome of weight gain/maintenance, six reported statistically significant positive results (p < 0.05).

In conclusion, the presented evidence indicates that omega-3 supplementation in pancreatic cancer patients is safe, well-tolerated, and beneficial, as it contributes to the stabilization or increase in body weight, as well as a reduction in inflammatory biomarkers.

Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease that is the result of an accumulation of sequential genetic alterations. These genetic alterations can either be inherited, such as pathogenic germline variants that are associated with an increased risk of cancer, or acquired, such as somatic mutations that occur during the lifetime of an individual. Understanding the genetic basis of inherited risk of PDAC is essential to advancing patient care and outcomes through improved clinical surveillance, early detection initiatives, and targeted therapies. In this review we discuss factors associated with an increased risk of PDAC, the prevalence of genetic variants associated with an increased risk in patients with PDAC, estimates of PDAC risk in carriers of pathogenic germline variants in genes associated with an increased risk of PDAC. The role of common variants in pancreatic cancer risk will also be discussed.

To evaluate the diagnostic yield of pancreatic cancer screening in individuals at risk (IAR) from familial pancreatic cancer (FPC) families with respect to the presence or absence of pathogenic germline variants predisposing to pancreatic adenocarcinoma (PDAC).

In a 20 years period, IAR from FPC families were enrolled in a prospective screening program of the national case collection for FPC of Germany, including magnet resonance imaging (MRI) and endoscopic ultrasound (EUS). The diagnostic yield was analyzed regarding significant pancreatic lesions such as PDAC, high-grade pancreatic-intraepithelial-neoplasia (PanIN3) and intraductal-papillary-mucinous-neoplasia (IPMN) with high-grade dysplasia. Screening results were compared between carriers of pathogenic variants and variant-negative IAR.

337 IAR, including 74 (22%) variant-carriers and 263 IAR of variant-negative FPC families (mean age 49; standard deviation [SD] + 8.9) were followed 64 (SD + 55) months. IAR underwent 5.1 (SD + 3.9) screening visits with 1733 MRI (5.1,SD + 3.9 per IAR) and 728 EUS (2.2,SD + 1.7 per IAR). In 12 (4%) cases, significant pancreatic lesions were detected, including 4 PDAC, 3 PanIN3 and 5 high-grade IPMN. Three of 4 IAR with PDAC died after a mean of 27 months postoperatively, and one IAR is alive without evidence of disease after 31 months. The diagnostic yield for significant lesions was 13.5% (10/74) for variant carriers compared to 0.8% (2/263) for IAR of variant-negative FPC families (p < 0.001). Logistic regression analysis revealed that a negative variant status was almost always accompanied by the absence of a significant lesion over time with a negative predictive value of 99.2% (95% CI 97.3%-99.9%).

The diagnostic yield seems to justify PDAC screening in IAR of FPC-families with pathogenic germline variants in PDAC predisposing genes, not in IAR of variant-negative families.

Pancreatic cancer is a rare but lethal cancer due to its biologically aggressive nature, advanced stage at the time of diagnosis, and poor response to oncologic therapies. The risk of pancreatic cancer is significantly higher to 5% in certain high-risk individuals with inherited genetic susceptibility. Screening for pancreatic cancer in these individuals from high-risk groups can help with the early detection of pancreatic cancer as well as the detection of precursor lesions leading to early surgical resection and improved overall outcomes. The advancements in radiological imaging as well as advanced endoscopic procedures has made a significant impact on the early diagnosis, surveillance, and staging of pancreatic cancer. There is also a significant advancement in the development of biomarkers for the early detection of pancreatic cancer, which has also led to the development of liquid biopsy, allowing for microRNA detection in serum and circulating tumor cells. Various societies and organizations have provided guidelines for pancreatic cancer screening and surveillance in high-risk individuals. In this review, we aim to discuss the hereditary risk factors for developing pancreatic cancer, summarize the screening recommendations by different societies, and discuss the development of novel biomarkers and areas for future research in pancreatic cancer screening for high-risk individuals.

Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed at an advanced stage, resulting in poor prognosis and low 5-year survival rates. While early evidence suggests increased long-term survival in those with screen-detected resectable cancers, surveillance imaging is currently only recommended for individuals with a lifetime risk of PDAC ≥ 5%. Identification of risk factors for PDAC provides opportunities for early detection, risk reducing interventions, and targeted therapies, thus potentially improving patient outcomes. Here, we summarize modifiable and non-modifiable risk factors for PDAC. We review hereditary cancer syndromes associated with risk for PDAC and their implications for patients and their relatives. In addition, other biologically relevant pathways and environmental and lifestyle risk factors are discussed. Future work may focus on elucidating additional genetic, environmental, and lifestyle risk factors that may modify PDAC risk to continue to identify individuals at increased risk for PDAC who may benefit from surveillance and risk reducing interventions.

Pancreatic cancer is a leading cause of cancer-related death worldwide. Tryptophan plays a vital role in cell growth and maintenance as a building block of protein and coordination of organismal responses to environmental and dietary cues. Animal model study showed that dietary tryptophan improved treatment response in those who received chemotherapy or immune checkpoint inhibitors. Limited data are available assessing the association between tryptophan intake and risk of pancreatic cancer. We aimed to evaluate this association in a case-control study in Vietnam.

We analyzed data from a case-control study, including 3759 cancer cases and 2995 control subjects of whom 37 with pancreatic cancer cases. Tryptophan intake was derived from food frequency questionnaire. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for different levels of tryptophan intake with pancreatic cancer risk.

Overall, tryptophan intake was inversely associated with pancreatic cancer risk in a dose-dependent manner. The ORs and 95% CIs of pancreatic cancer were 0.51 (0.29-0.92) for continuous scale, 0.27 (0.10-0.73) for tertile 2 and 0.34 (0.11-1.06) for tertile 3, compared with tertile 1 (the lowest intake) ( Ptrend = 0.02). In stratified analysis, this inverse association pattern was present among those with BMI < 23 kg/m 2 and ever drinkers.

A diet with a higher intake of tryptophan was significantly associated with a lower incidence of pancreatic cancer among Vietnamese population. These suggest that dietary modification may be an effective strategy for primary prevention of pancreatic cancer development.

With the 12th highest incidence and a common late diagnostic at advanced stages, neoadjuvant therapies for pancreatic cancer are important, but they require a confirmed diagnosis. Being a diagnostic standard, the clarification of the clinical relevance of needle gauges is needed, as larger ones may retrieve more tissue for diagnostics, but may also increase the risk of complications. We performed a meta-analysis to compare the efficiency of the most commonly used 22-G and 25-G needles for EUS guided biopsy in solid pancreatic lesions. The MEDLINE (via PubMed), Embase, Cochrane (CENTRAL), and Scopus databases were searched with "EUS", "needle", "FNA", "pancreas", "prospective", "22G", and "25G" keywords. Mixed effects were assessed in the model, with a mean of 86% and a 95% confidence interval. Fourteen prospective studies that compared the efficiency of 22-G and 25-G biopsy needles in 508 and 524 lesions, respectively, were analyzed, along with 332 specimens biopsied using both needle sizes. The groups did not significantly differ in the outcomes. A low degree of heterogeneity was observed overall, except for specimen adequacy. Moreover, 22-G and 25-G needles have comparable safety and efficacy for focal pancreatic lesion biopsies without a high risk of complications.

Pancreatic cancer is a highly lethal disease with a 5-year survival rate of around 11-12%. Surgery, being the treatment of choice, is only possible in 20% of symptomatic patients. The main reason is that when it becomes symptomatic, IT IS the tumor is usually locally advanced and/or has metastasized to distant organs; thus, early diagnosis is infrequent. The lack of specific early symptoms is an important cause of late diagnosis. Unfortunately, diagnostic tumor markers become positive at a late stage, and there is a lack of early-stage markers. Surgical and non-surgical cases are treated with neoadjuvant and/or adjuvant chemotherapy, and the results are usually poor. However, personalized targeted therapy directed against tumor drivers may improve this situation. Until recently, many pancreatic tumor driver genes/proteins were considered untargetable. Chemical and physical characteristics of mutated KRAS are a formidable challenge to overcome. This situation is slowly changing. For the first time, there are candidate drugs that can target the main driver gene of pancreatic cancer: KRAS. Indeed, KRAS inhibition has been clinically achieved in lung cancer and, at the pre-clinical level, in pancreatic cancer as well. This will probably change the very poor outlook for this disease. This paper reviews the genetic characteristics of sporadic and hereditary predisposition to pancreatic cancer and the possibilities of a personalized treatment according to the genetic signature.

Despite continuous improvement of diagnostic and therapeutic procedures, the number of new pancreatic ductal adenocarcinoma (PDAC) cases diagnosed annually almost equals the number of PDAC-related deaths. Prerequisite for curative treatment is a resectable tumor at the time of diagnosis. Individuals with genetic and/or familial risk profiles should therefore be screened and included in structured surveillance programs.

Description of the status quo and usefulness of current PDAC screening and surveillance concepts.

A selective literature search of current national and international guidelines including underlying literature was performed.

Nearly half of pancreatic cancer cases are missed by currently available surveillance programs, even in high-risk cohorts. Magnetic resonance imaging and endoscopic ultrasound supplemented by CA19‑9 (± HbA1c) are not accurate enough to ensure robust earlier pancreatic cancer detection. Complementary biomarker panels will take on a crucial diagnostic role in the future.

Pancreatic cancer (PC) is a devastating malignancy with an extremely high mortality rate and poses significant challenges to healthcare systems worldwide. The prevalence of PC risk factors spiked over the years, leading to a global increase in PC incidence rates. The contribution of different risk factors, however, varied from region to region due to genetic predisposition, environmental, social, and political factors underlying disease prevalence in addition to public health strategies. This comprehensive review aims to provide a thorough analysis of the epidemiology of PC, discussing its incidence, risk factors, screening strategies and socioeconomic burden. We compiled a wide range of seminal studies as well as epidemiological investigations to serve this review as a comprehensive guide for researchers, healthcare professionals, and policymakers keen for a more profound understanding of PC epidemiology. This review highlights the essentiality of persistent research efforts, interdisciplinary collaboration, and public health initiatives to address the expanding burden of this malignancy.

The pancreas is a vital organ with exocrine and endocrine functions. Pancreatitis is an inflammation of the pancreas caused by alcohol consumption and gallstones. This condition can heighten the risk of pancreatic cancer (PC), a challenging disease with a high mortality rate. Genetic and epigenetic factors contribute significantly to PC development, along with other risk factors. Early detection is crucial for improving PC outcomes. Diagnostic methods, including imagining modalities and tissue biopsy, aid in the detection and analysis of PC. In contrast, liquid biopsy (LB) shows promise in early tumor detection by assessing biomarkers in bodily fluids. Understanding the function of the pancreas, associated diseases, risk factors, and available diagnostic methods is essential for effective management and early PC detection. The current clinical examination of PC is challenging due to its asymptomatic early stages and limitations of highly precise diagnostics. Screening is recommended for high-risk populations and individuals with potential benign tumors. Among various PC screening methods, the N-NOSE plus pancreas test stands out with its high AUC of 0.865. Compared to other commercial products, the N-NOSE plus pancreas test offers a cost-effective solution for early detection. However, additional diagnostic tests are required for confirmation. Further research, validation, and the development of non-invasive screening methods and standardized scoring systems are crucial to enhance PC detection and improve patient outcomes. This review outlines the context of pancreatic cancer and the challenges for early detection.

In order to investigate the impact of Treg cell infiltration on the immune response against pancreatic cancer within the tumor microenvironment (TME), and identify crucial mRNA markers associated with Treg cells in pancreatic cancer, our study aims to delve into the role of Treg cells in the anti-tumor immune response of pancreatic cancer.

The ordinary transcriptome data for this study was sourced from the GEO and TCGA databases. It was analyzed using single-cell sequencing analysis and machine learning. To assess the infiltration level of Treg cells in pancreatic cancer tissues, we employed the CIBERSORT method. The identification of genes most closely associated with Treg cells was accomplished through the implementation of weighted gene co-expression network analysis (WGCNA). Our analysis of single-cell sequencing data involved various quality control methods, followed by annotation and advanced analyses such as cell trajectory analysis and cell communication analysis to elucidate the role of Treg cells within the pancreatic cancer microenvironment. Additionally, we categorized the Treg cells into two subsets: Treg1 associated with favorable prognosis, and Treg2 associated with poor prognosis, based on the enrichment scores of the key genes. Employing the hdWGCNA method, we analyzed these two subsets to identify the critical signaling pathways governing their mutual transformation. Finally, we conducted PCR and immunofluorescence staining in vitro to validate the identified key genes.

Based on the results of immune infiltration analysis, we observed significant infiltration of Treg cells in the pancreatic cancer microenvironment. Subsequently, utilizing the WGCNA and machine learning algorithms, we ultimately identified four Treg cell-related genes (TRGs), among which four genes exhibited significant correlations with the occurrence and progression of pancreatic cancer. Among them, CASP4, TOB1, and CLEC2B were associated with poorer prognosis in pancreatic cancer patients, while FYN showed a correlation with better prognosis. Notably, significant differences were found in the HIF-1 signaling pathway between Treg1 and Treg2 cells identified by the four genes. These conclusions were further validated through in vitro experiments.

Treg cells played a crucial role in the pancreatic cancer microenvironment, and their presence held a dual significance. Recognizing this characteristic was vital for understanding the limitations of Treg cell-targeted therapies. CASP4, FYN, TOB1, and CLEC2B exhibited close associations with infiltrating Treg cells in pancreatic cancer, suggesting their involvement in Treg cell functions. Further investigation was warranted to uncover the mechanisms underlying these associations. Notably, the HIF-1 signaling pathway emerged as a significant pathway contributing to the duality of Treg cells. Targeting this pathway could potentially revolutionize the existing treatment approaches for pancreatic cancer.

Pancreatic ductal adenocarcinoma has a very high mortality rate which has been only minimally improved in the last 30 years. This high mortality is closely related to late diagnosis, which is usually made when the tumor is large and has extensively infiltrated neighboring tissues or distant metastases are already present. This is a paradoxical situation for a tumor that requires nearly 15 years to develop since the first founding mutation. Response to chemotherapy under such late circumstances is poor, resistance is frequent, and prolongation of survival is almost negligible. Early surgery has been, and still is, the only approach with a slightly better outcome. Unfortunately, the relapse percentage after surgery is still very high. In fact, early surgery clearly requires early diagnosis. Despite all the advances in diagnostic methods, the available tools for improving these results are scarce. Serum tumor markers permit a late diagnosis, but their contribution to an improved therapeutic result is very limited. On the other hand, effective screening methods for high-risk populations have not been fully developed as yet. This paper discusses the difficulties of early diagnosis, evaluates whether the available diagnostic tools are adequate, and proposes some simple and not-so-simple measures to improve it.

The mechanisms of distant metastasis in pancreatic cancer (PC) have not been elucidated, and this study aimed to explore the risk factors affecting the metastasis and prognosis of metastatic patients and to develop a predictive model.

Clinical data from patients meeting criteria from 1990 to 2019 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database, and two machine learning methods, random forest and support vector machine, combined with logistic regression, were used to explore risk factors influencing distant metastasis and to create nomograms. The performance of the model was validated using calibration curves and ROC curves based on the Shaanxi Provincial People's Hospital cohort. LASSO regression and Cox regression models were used to explore the independent risk factors affecting the prognosis of patients with distant PC metastases.

We found that independent risk factors affecting PC distant metastasis were: age, radiotherapy, chemotherapy, T and N; the independent risk factors for patient prognosis were: age, grade, bone metastasis, brain metastasis, lung metastasis, radiotherapy and chemotherapy.

Together, our study provides a method for risk factors and prognostic assessment for patients with distant PC metastases. The nomogram we developed can be used as a convenient individualized tool to facilitate aid in clinical decision making.

The pancreatic cancer (PC) is the 4th leading cancer-related death, becoming the second one by 2030, with a 5 year survival rate of 8%. Considering its increased incidence in high-risk categories compared to the general population, we aimed to validate a non-contrast MR protocol, to detect PC in its earliest phase, which could be suitable as a screening tool in high-risk patients.

In this retrospective study, we selected 200 patients (> 40 years) from our radiological database, which performed upper abdominal MRI between 2012 and 2017. 100 were negative for pancreatic lesions and 100 positive for pancreatic lesion (< 30 mm). The latter group included: 40 PDAC (pancreatic adenocarcinoma), 42 BD-IPMN (Branch Duct- Intraductal Papillary Mucinous Neoplasm), 10 PNET(pancreatic neuroendocrine tumor), 4 SCN(serous cystic neoplasm), 3 IPS(intrapancreatic spleen), 1 MCN(mucinous cystic neoplasm). Three readers (R1, R2 and R3) with a high, medium and low experience, respectively, analysed, first, the non-contrast MR sequences (single-shot T2w breath-hold, GE T1w FS, DWI and 2D/3D MRCP), and then the standard MR protocol, independently, randomly and anonymously. Readers identified or excluded the presence of pancreatic lesion, in both reading sessions. These results were compared with the histopathological diagnosis, and then divided into 3 different classes of lesions: all lesions, pancreatic adenocarcinoma and solid lesion. Mcnemar's test was used to compare the results. The inter-observer agreement was determined according to the kappa statistic in both protocols, and then the inter-protocol agreement was calculated.

The non-contrast MR protocol has reached statistical parameters values ranging between 83% in SE (sensitivity) by R3 and 99% in NPV (negative predictive value) by R1. The standard MR protocol has reported slight increasing statistical parameters compared to those of the proposed one. However, there are not significant statistical differences between the both protocols. The proposed non-contrast MR protocol has reported the highest NPVs in the PDAC group detection (R1: 99%, R2: 99%, R3: 98%). In all groups of lesions, the agreement between the two protocols was excellent for each Reader ranging from 96 to 98%.

The proposed non-contrast MR protocol showed high PC detection values and a time execution ≤ 20 min. Therefore, it can be proposed as a screening tool in high-risk patients.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers, with five-year survival rates around 10%. The only curative option remains complete surgical resection, but due to the delay in diagnosis, less than 20% of patients are eligible for surgery. Therefore, discovering diagnostic biomarkers for early detection is crucial for improving clinical outcomes. Metabolomics has become a powerful technology for biomarker discovery, and several metabolomic-based panels have been proposed for PDAC diagnosis, but these advances have not yet been translated into the clinic. Therefore, this review focused on summarizing metabolites identified for the early diagnosis of PDAC in the last five years. Bibliographic searches were performed in the PubMed, Scopus and WOS databases, using the terms "Biomarkers, Tumor", "Pancreatic Neoplasms", "Early Diagnosis", "Metabolomics" and "Lipidome" (January 2018-March 2023), and resulted in the selection of fourteen original studies that compared PDAC patients with subjects with other pancreatic diseases. These investigations showed amino acid and lipid metabolic pathways as the most commonly altered, reflecting their potential for biomarker research. Furthermore, other relevant metabolites such as glucose and lactate were detected in the pancreas tissue and body fluids from PDAC patients. Our results suggest that the use of metabolomics remains a robust approach to improve the early diagnosis of PDAC. However, these studies showed heterogeneity with respect to the metabolomics techniques used and further studies will be needed to validate the clinical utility of these biomarkers.

Pancreatic cancer is the seventh most common cause of death in the group of oncological diseases. Due to the asymptomatic course, early diagnosis is difficult. Currently, early detection methods are only used in high-risk groups. A literature review based on the available results of observational studies on patients with pancreatic cancer and people from high-risk groups was used to summarize the knowledge on risk factors. The GLOBOCAN 2020 data were used to assess the epidemiological situation in Europe. A summary of screening recommendations was prepared based on the available documents from medical organizations and associations. Pancreatic cancer risk factors are divided into two main groups: non-modifiable factors, e.g., hereditary factors and age, which increase the risk of developing this disease, and modifiable factors-BMI, smoking, and alcohol consumption. Hereditary factors account for 10% of pancreatic cancer cases. The highly specialized methods of early detection, (MRI, CT, or EUS) are used for screening high-risk populations. Of all the imaging methods, EUS is considered the most sensitive for pancreatic cancer and allows an accurate assessment of the size of even small lesions (<30 mm) and the extent of tumour infiltration into blood vessels. The available studies vary on the level of sensitivity and specificity of these methods for the diagnosis of pancreatic cancer. EUS, MRI, and CT are also expensive procedures and in some patients can be invasive, which is one of the arguments against the introduction of population screening programs based on imaging methods. Therefore, it is important to look for viable solutions that would improve early detection. This is important from the point of view of healthcare systems in Europe, where almost 29% of all global pancreatic cancer cases are reported.

The incidence of early-onset pancreatic cancer (EOPC) among young population (<50 years) is rising in the last decade, with gender, medical overtreatment, and genetic factors as the risk factors in EOPC. Nevertheless, the role of genetic factors in the development of EOPC needs further exploration since the studies were carried out with small sample size and ambiguous evidence. Notable, the high incidence of pathogenic germline variant (PGV) appears to be involved in EOPC. Compared with average-age-onset pancreatic cancer (AOPC), EOPC patients display a distinctive genomic feature on several well-known tumor suppressor and oncogenic genes including, including SMAD4, RAS wild wild-type, CDKN2A BRCA1, BRCA2 and FOXC2, which is different from the findings of studies with AOPC and LOPC, suggesting the dynamic evolving entity of EOPC. In addition, the potential gender-related incidence found in several countries also suggests the involvement of genetic or socioenvironmental factors in the development of AOPC. Therefore, further prospective epidemiological and molecular studies are warranted to elucidate the shifting epidemiology of this disease and, most importantly, to better exploit the opportunities for the early diagnosis of the disease.

On February 2, 2022, President Biden and First Lady Dr. Biden reignited the Cancer Moonshot, setting a new goal to reduce age-standardized cancer mortality rates by at least 50% over the next 25 years in the United States. We estimated trends in U.S. cancer mortality during 2000 to 2019 for all cancers and the six leading types (lung, colorectum, pancreas, breast, prostate, liver). Cancer death rates overall declined by 1.4% per year from 2000 to 2015, accelerating to 2.3% per year during 2016 to 2019, driven by strong declines in lung cancer mortality (-4.7%/year, 2014 to 2019). Recent declines in colorectal (-2.0%/year, 2010-2019) and breast cancer death rates (-1.2%/year, 2013-2019) also contributed. However, trends for other cancer types were less promising. To achieve the Moonshot goal, progress against lung, colorectal, and breast cancer deaths needs to be maintained and/or accelerated, and new strategies for prostate, liver, pancreatic, and other cancers are needed. We reviewed opportunities to prevent, detect, and treat these common cancers that could further reduce population-level cancer death rates and also reduce disparities.

We reviewed opportunities to prevent, detect, and treat common cancers, and show that to achieve the Moonshot goal, progress against lung, colorectal, and breast cancer deaths needs to be maintained and/or accelerated, and new strategies for prostate, liver, pancreatic, and other cancers are needed. See related commentary by Bertagnolli et al., p. 1049. This article is highlighted in the In This Issue feature, p. 1027.

Epidemiologic data indicate a significant increase in the incidence of colorectal cancer in younger populations in the past three decades. Moreover, recent evidence also demonstrates a similar trend in gastric, pancreatic, and biliary tract cancers. A majority of these early-onset cases are sporadic and lack hereditary or familial background, implying a potential key role for behavioral, lifestyle, nutritional, microbial, and environmental factors. This review explores the current data on early-onset gastrointestinal cancer, exploring the etiology, unique treatment considerations for this population, future challenges, as well as implications for research and practice.

The worrisome trend of an increasing incidence of early-onset gastrointestinal cancers appears to be correlated with nonhereditary etiologies in which behavioral, lifestyle, nutritional, microbial, and environmental factors, as well as host mechanisms, may play a key role. Further epidemiologic and pathogenetic research is urgently needed to better understand the underlying mechanisms and to develop preventive strategies and tailored early detection. Young patients with gastrointestinal cancer face unique challenges and unmet needs. These must be addressed in the future management of the disease to minimize treatment-related somatic morbidity and prevent psychosocial sequelae.

Most patients with pancreatic cancer present with advanced stage, incurable disease. However, patients with high-grade precancerous lesions and many patients with low-stage disease can be cured with surgery, suggesting that early detection has the potential to improve survival. While serum CA19.9 has been a long-standing biomarker used for pancreatic cancer disease monitoring, its low sensitivity and poor specificity have driven investigators to hunt for better diagnostic markers.

This review will cover recent advances in genetics, proteomics, imaging, and artificial intelligence, which offer opportunities for the early detection of curable pancreatic neoplasms.

From exosomes, to circulating tumor DNA, to subtle changes on imaging, we know much more now about the biology and clinical manifestations of early pancreatic neoplasia than we did just five years ago. The overriding challenge, however, remains the development of a practical approach to screen for a relatively rare, but deadly, disease that is often treated with complex surgery. It is our hope that future advances will bring us closer to an effective and financially sound approach for the early detection of pancreatic cancer and its precursors.

Although main pancreatic duct dilatation and pancreatic cysts are risk factors for developing pancreatic cancer, limited data exist regarding these findings in relatives and spouses of pancreatic cancer patients. The frequency of these findings was examined using long-term follow-up data and transabdominal ultrasonography focusing on the pancreas. We prospectively enrolled 184 relatives and spouses of pancreatic cancer patients and performed special pancreatic ultrasonography to detect main pancreatic duct dilatation and pancreatic cysts. First-degree relatives (148 participants) of patients with pancreatic cancer were significantly younger than the spouses (36 participants; 41 vs. 65 years old). The frequency of ultrasonographic findings was significantly different between the relative (8.8%) and spouse (33.3%) groups. Main pancreatic duct dilatation and pancreatic cysts were observed in seven (4.7%) and seven (4.7%) participants in the relative group, and in nine (25.0%) and five (13.9%) participants in the spouse group, respectively. On multivariate analysis, age was an independent risk factor for the ultrasonographic findings. The frequency of ultrasonographic findings was significantly higher in spouses than in first-degree relatives of patients with pancreatic cancer and was strongly influenced by the age gap between the groups. Main pancreatic duct dilatation was frequently observed, especially in the spouse group.

Pancreatic cancer is a kind of aggressive tumor famous for its lethality and intractability, and pancreatic ductal adenocarcinoma is the most common type. Patients with pancreatic cancer often suffer a rapid loss of weight and abdominal neuropathic pain in their early stages and then go through cachexia in the advanced stage. These features of patients are considered to be related to metabolic reprogramming of pancreatic cancer and abundant nerve innervation responsible for the pain. With increasing literature certifying the relationship between nerves and pancreatic ductal adenocarcinoma (PDAC), more evidence point out that innervation's role is not limited to neuropathic pain but explore its anti/pro-tumor functions in PDAC, especially the neural-metabolic crosstalks. This review aims to unite pancreatic cancer's innervation and metabolic rearrangements with terminated published articles. Hopefully, this article could explore the pathogenesis of PDAC and further promote promising detecting or therapeutic measurements for PDAC according to the lavish innervation in PDAC.

A family history of pancreatic cancer is associated with increased pancreatic cancer risk. However, risk estimates for individuals in kindreds with an aggregation of pancreatic cancer (>1 relative) are imprecise because of small samples sizes or potentially impacted by biases inherent in retrospective data.

The objective of this study is to determine the age-specific pancreatic cancer risk as a function of family history using prospective data.

We compared pancreatic cancer incidence (n = 167) in 21 141 individuals from 4433 families enrolled in the National Familial Pancreatic Cancer Registry with that expected based on Surveillance Epidemiology and End Results data and estimated the cumulative probability of pancreatic cancer using competing risk regression.

Familial pancreatic kindred members (kindreds with pancreatic cancer in 2 first-degree relatives [FDRs] or a pathogenic variant) had a standardized incidence ratio of 4.86 (95% confidence interval [CI] = 4.01 to 5.90), and sporadic kindred members (kindreds not meeting familial criteria) had a standardized incidence ratio of 2.55 (95% CI = 1.95 to 3.34). Risk in familial pancreatic cancer kindreds increased with an increasing number of FDRs with pancreatic cancer, with a standardized incidence ratio of 3.46 (95% CI = 2.52 to 4.76), 5.44 (95% CI = 4.07 to 7.26), and 10.78 (95% CI = 6.87 to 16.89) for 1, 2, and 3 or more FDRs with pancreatic cancer, respectively. Risk was also higher among individuals with a family history of young-onset (aged younger than 50 years) pancreatic cancer.

Pancreatic cancer risk is strongly dependent on family history, including both the degree of relationship(s) and age of onset of pancreatic cancer in relatives. These risk estimates will help inform the design of early detection studies and the risk and benefit analysis of screening trials.

Pancreatic cancer patients usually present at a late stage due to subtle clinical manifestations. One of the most predictive prognostic factors in pancreatic cancer is the pancreatic cancer stage at diagnosis; therefore, early diagnosis is essential. Until now, pancreatic cancer screening has not become a standard practice for the general population due to the low incidence. In current circumstances, targeting individuals with a high risk of pancreatic cancer may be more rational. Several screening modalities for pancreatic cancer have also become debatable topics. Therefore, this article will review current evidence and recommendations regarding pancreatic screening cancer protocol in general and in high-risk populations.

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with poor prognosis. Proteogenomic characterization and integrative proteomic analysis provide a functional context to annotate genomic abnormalities with prognostic value.

We performed an integrated multi-omics analysis, including whole-exome sequencing, RNA-seq, proteomic, and phosphoproteomic analysis of 217 PDAC tumors with paired non-tumor adjacent tissues. In vivo functional experiments were performed to further illustrate the biological events related to PDAC tumorigenesis and progression.

A comprehensive proteogenomic landscape revealed that TP53 mutations upregulated the CDK4-mediated cell proliferation process and led to poor prognosis in younger patients. Integrative multi-omics analysis illustrated the proteomic and phosphoproteomic alteration led by genomic alterations such as KRAS mutations and ADAM9 amplification of PDAC tumorigenesis. Proteogenomic analysis combined with in vivo experiments revealed that the higher amplification frequency of ADAM9 (8p11.22) could drive PDAC metastasis, though downregulating adhesion junction and upregulating WNT signaling pathway. Proteome-based stratification of PDAC revealed three subtypes (S-I, S-II, and S-III) related to different clinical and molecular features. Immune clustering defined a metabolic tumor subset that harbored FH amplicons led to better prognosis. Functional experiments revealed the role of FH in altering tumor glycolysis and in impacting PDAC tumor microenvironments. Experiments utilizing both in vivo and in vitro assay proved that loss of HOGA1 promoted the tumor growth via activating LARP7-CDK1 pathway.

This proteogenomic dataset provided a valuable resource for researchers and clinicians seeking for better understanding and treatment of PDAC.

Recent advancements in surgical and anti-cancer therapies have provided significant hope of long survival in patients with pancreatic cancer (PC). To realize this hope, routine medical checkups of asymptomatic people should be performed to identify operable PCs. In this study, we evaluated the efficacy of medical checkups using abdominal ultrasonography (US). We retrospectively analyzed 374 patients with PC at our institute between 2010 and 2021. We divided these patients into several groups according to the diagnostic approach and compared their background and prognosis. These groups comprised PCs diagnosed through (a) symptoms, 242 cases; (b) US during medical checkup for asymptomatic individuals, 17; and other means. Of the 374 patients, 192 were men (51.3%), and the median age was 74 years (34−105). Tumors were located in the pancreatic tail in 67 patients (17.9%). Excision ratio and 5-year survival rate were significantly better in group (b) than in (a) (58.8% vs. 23.1%, p < 0.01 and 42.2% vs. 9.4%, p < 0.001, respectively). The prognosis of patients diagnosed using US during medical checkup was better than that of patients identified through symptomatic presentation of PC. US for asymptomatic individuals with PC might be one of the useful modalities for promoting better prognosis of PCs.

Pancreatic cancer (PC) is a highly malignant and aggressive tumor. Despite medical advancement, the silent nature of PC results in only 20% of all cases considered resectable at the time of diagnosis. It is projected to become the second leading cause in 2030. Most pancreatic cancer cases are diagnosed in the advanced stages. Such cases are typically unresectable and are associated with a 5-year survival of less than 10%. Although there is no guideline consensus regarding recommendations for screening for pancreatic cancer, early detection has been associated with better outcomes. In addition to continued utilization of imaging and conventional tumor markers, clinicians should be aware of novel testing modalities that may be effective for early detection of pancreatic cancer in individuals with high-risk factors. The pathogenesis of PC is not well understood; however, various modifiable and non-modifiable factors have been implicated in pancreatic oncogenesis. PC detection in the earlier stages is associated with better outcomes; nevertheless, most oncological societies do not recommend universal screening as it may result in a high false-positive rate. Therefore, targeted screening for high-risk individuals represents a reasonable option. In this review, we aimed to summarize the pathogenesis, genetic risk factors, high-risk population, and screening modalities for PC.

Bone metastasis (BM) is rare in patients with pancreatic cancer (PC), but often neglected at the initial diagnosis and treatment. Bone metastasis is associated with a worse prognosis. This study was aimed to perform a large data analysis to determine the predictors and prognostic factors of BM in PC patients and to develop two nomograms to quantify the risks of BM and the prognosis of PC patients with BM. In the present study, we reviewed and collected the data of patients who were diagnosed as PC from 2010 to 2015 in the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate logistic regression analyses were used together to screen and validate the risk factors for BM in PC patients. The independent prognostic factors for PC patients with BM were identified by Cox regression analysis. Finally, two nomograms were established via calibration curves, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA). This study included 16,474 PC patients from the SEER database, and 226 of them were diagnosed with BM. The risk factors of BM for PC patients covered age, grade, T stage, N stage, tumor size, and primary site. The independent prognostic factors for PC patients with BM included age, race, grade, surgery, and lung metastasis. The AUC of the diagnostic nomogram was 0.728 in the training set and 0.690 in the testing set. In the prognostic nomogram, the AUC values of 6/12/18 month were 0.781/0.833/0.849 in the training set and 0.738/0.781/0.772 in the testing set. The calibration curve and DCA furtherly indicated the satisfactory clinical consistency of the nomograms. These nomograms could be accurate and personalized tools to predict the incidence of BM in PC patients and the prognosis of PC patients with BM. The nomograms can help clinicians make more personalized and effective treatment choices.

Pancreatic cancer is one of the most lethal cancers in the world; it is a silent disease in which symptoms do not present until advanced stages, thereby reducing the 5-year survival rate to 10%. The global burden of pancreatic cancer has doubled over the past 25 years despite advancements in medicine. This review aims to discuss the global trends and disparities in pancreatic cancer, as well as the up-to-date literature on the known risk factors. A better understanding of these risk factors will reduce mortality by providing opportunities to screen these patients as well as counseling on lifestyle modifications.

Hepatic, pancreatic, and biliary (HPB) cancers, including hepatocellular carcinoma (HCC), pancreatic ductal adenocarcinoma (PDAC), and cholangiocarcinoma (CCA) cause a disproportionate amount of the global cancer-related mortality. Despite advances in surgical technique and improved systemic therapies, overall 5-year survival remains dismal, especially for patients with pancreatic and biliary cancer. Historically, systemic therapies for patients with HPB cancers were administered in a "one-size-fits-all" approach due to limited reliable data on efficacy for specific patient populations. However, recent advances in genetic testing techniques have greatly improved our understanding of HPB oncogenesis, shedding light on specific genetic mutations responsible for progression from physiologic cellular regulation to uninhibited cellular replication and invasive cancer. Investigations into the oncogenesis of HPB cancers have revealed multiple actionable genetic variants, as well as increased susceptibilities to currently available systemic therapies. For example, patients with PDAC and a known BRCA mutation are more likely to benefit from FOLFIRINOX or gemcitabine plus cisplatin. While patients with CCA and a IDH1 mutation may benefit from ivosidenib. As a result, many national and societal guidelines now recommend some form of genetic testing in the workup of patients with HPB cancers. We herein review the role of genetic testing in these aggressive cancers including DNA sequencing techniques, clinically relevant mutations, therapeutic implications, and current clinical recommendations.

Individuals at increased risk of developing pancreatic cancer, including those with a significant family history of the disease and those with pancreatic cancer susceptibility gene variants, can benefit from pancreas surveillance. Most pancreatic cancers diagnosed during surveillance are early-stage and such patients can achieve long-term survival. Determining who should undergo pancreas surveillance is still a work-in-progress, but the main tools clinicians use to estimate an individual's risk of pancreatic cancer are patient's age, the extent of their family history of pancreatic cancer, and whether or not they have a pancreatic cancer susceptibility gene mutation.

Current guidelines limit pancreatic cancer screening to those BRCA1/2 patients who have a family history of pancreatic cancer. We aimed to assess the association between family history and risk of pancreatic neoplasms in BRCA1/2 patients.

We reviewed medical records of BRCA1/2 patients followed at our institution between 1995 and 2020. Family history was defined as those with a first-degree relative with pancreatic cancer. We compared the incidence and prevalence of pancreatic neoplasms between patients with and without family history of pancreatic cancer.

We identified 56 BRCA1/2 patients with family history and 238 without family history of pancreatic cancer. No difference between these groups was noted in age, race, or sex. Mean follow-up interval for BRCA1/2 patients was 4.6 years (range, 0-19.7 years). There was no significant difference in prevalence (19.6% vs 12.6; P = 0.3) or incidence (29% vs 14.1%; P = 0.08) of branch-duct intraductal papillary mucinous neoplasm between the 2 groups. No association between family history and pancreatic cancer risk was noted. Only 1 of 10 BRCA1/2 patients with pancreatic cancer had a family history.

Our results do not support using family history to determine eligibility for pancreatic cancer screening.