The mortality of pancreatic cancer in China showed an increasing trend between 2005 and 2020, with significant discrepancies in the burden of pancreatic cancer in provinces.

We analyzed numbers of death, incidence, disability-adjusted life years (DALY) and corresponding age-standardized rates for pancreatic cancer in China using data from the Global Burden of Disease Study 2021. We conducted trend analysis in pancreatic cancer burden over time by age group and gender. Decomposition analysis was used to assess the drivers of change in cancer-related deaths in China due to three explanatory factors: population growth, population ageing and age-specific mortality.

In 2021, the ASMR of pancreatic cancer in China was 5.72/100,000(95%UI: 4.59, 6.91), the age-standardized incidence (ASIR) rate was 5.64/100,000(95%UI: 4.52, 6.84) and the age-standardized DALY rate was 137.23/100,000 (95%UI:108.15, 166.74). From 1990 to 2021, the ASMR of pancreatic cancer in China generally showed an increasing trend (AAPC: 0.56, 95%UI: 0.52, 0.59). The burden of pancreatic cancer was consistently higher in Chinese men compared to women during the study period.Compared with 1990, the number of deaths from pancreatic cancer has increased in all provinces of China in 2021, with the overall number of deaths increasing by 67.49%. Population ageing was the major cause of the increase in deaths from pancreatic cancer in China, accounting for 45.89%.

The burden of pancreatic cancer in China is still at a high level and population ageing is the main reason for the increase in pancreatic cancer deaths.

Pancreatic cancer is recognized as one of the most lethal types of cancer globally, characterized by a high mortality rate and a bleak prognosis, which greatly contributes to cancer-related deaths. Forecasts suggest that by 2030, pancreatic cancer will exceed other cancer types in prevalence. The disease presents considerable difficulties owing to the lack of prominent symptoms in its early stages, restricted options for early detection, rapid progression, and unfavorable outcomes. Presently, traditional methods for diagnosing pancreatic cancer primarily rely on imaging techniques. However, these methods often entail significant costs, require considerable time, and necessitate specialized skills for both operating the equipment and interpreting the resulting images. To overcome these obstacles, the use of biosensors has been proposed as a potentially valuable tool for the early detection of pancreatic cancer. MicroRNAs (miRs), a type of small non-coding RNA molecules, have emerged as highly sensitive molecular diagnostic tools that have the potential to function as precise indicators for a range of diseases, including cancer. Biosensors have been suggested as a potential solution for tackling these challenges, offering a promising approach for the early detection of pancreatic cancer. Small non-coding RNA molecules known as MicroRNAs (miRs) have become recognized as extremely sensitive molecular diagnostic tools and can act as precise biomarkers for different diseases, such as cancer. Moreover, this manuscript presents a thorough summary of the latest innovations in nano-biosensors that have been specifically developed for the identification of non-coding RNAs related to pancreatic cancer.

Studies of the relationship between diabetes medications and pancreatic cancer risk have produced inconclusive results. We aimed to examine associations between classes, subclasses, and individual diabetes medications with pancreatic cancer risk in a population-based retrospective cohort study.

Among British Columbians aged ≥ 35 (1996-2019), prescriptions for diabetes medications were categorised by ever/never use, cumulative duration, and dose. Time-varying Cox proportional hazards models adjusted for demographics were used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for associations between new diabetes medication use and pancreatic cancer. Confounding by indication was explored using active comparator analysis of ever/never associations relative to pioglitazone use.

The cohort consisted of 3,118,538 people (52,088,644 person-years), 7,540 of whom were diagnosed with pancreatic cancer. For every one-year increase in cumulative dose, diabetes medications in the insulin secretagogue class, and glyburide; an individual medication within the class, were associated with 2 % (HR=1.02, 95 % CI=1.02-1.03) and 3 % (HR=1.03, 95 % CI=1.02-1.05) increased risk of pancreatic cancer. For every one-year increase in cumulative dose, medications within the insulins and analogues class and insulin subclasses (basal and bolus insulins) were linked to a 4 % higher risk (HR=1.04, 95 % CI=1.03-1.05) of pancreatic cancer. In the active comparator analysis, elevated risk for basal insulins (HR=1.49, 95 % CI=0.33-6.63) was observed, consistent with the main analysis, although the risk was not statistically significant.

Basal insulins may be associated with higher pancreatic cancer risk. Although confirmatory studies are needed, this finding may be informative for prescribing practices for high-risk populations with diabetes.

We aimed to estimate the incidence and to assess the risk factors associated with pancreatic cancer (PC) in people with HIV (PWH).

We used electronic medical record data from 2009 to 2020 available in the COREVIH Ile-de-France-Est database of PWH treated in Paris public hospitals.

We analyzed data on patient demographics, treatment history, and immunovirologic status. A case-control study was designed; each case (PWH and PC) was matched on age, gender, and duration of HIV infection to 4 controls (PWH without PC).

Twenty-four cases were identified from the database, with an incidence of PC estimated at 28 cases (95% confidence interval: 19 to 43) per 100,000 person-years. The median age was 57 years [interquartile range (IQR) 51-68] at cancer diagnosis. Twenty-one cases (88%) were male. The median CD4 + T-cell count at PC diagnosis was 587/mm 3 (IQR 317-748), and the nadir CD4 + T-cell count was 194 (IQR 98-380). Twenty cases (91%) had a suppressed HIV replication at PC diagnosis. Twelve patients (50%) had metastasis on diagnosis. The median time to death after cancer diagnosis was 11 months (IQR 1-19). Twenty-two cases were matched with 88 controls. There were no statistically significant risk factors of PC identified in our analysis.

PC remains rare in PWH and is associated with a severe prognosis at a relatively young age. Further studies are needed to identify risk factors associated with PC development in PWH.

Pancreatic cancer is a highly invasive malignant tumor with a complex pathogenesis that makes early diagnosis challenging. The potential association between Helicobacter pylori infection and pancreatic cancer risk has been noted; however, the available results are still highly divergent. The aim of the present study was to systematically evaluate the association between different types of H. pylori infection and pancreatic cancer risk as well as to explore the possible causes. A systematic search was conducted using the PubMed, Embase and Cochrane Library databases up to August 2023. The literature quality was evaluated using the Newcastle-Ottawa Scale. All studies that met the criteria were included in the overall meta-analysis to calculate the odds ratios (ORs) and corresponding 95% confidence intervals (CIs). In addition, subgroup analyses were performed based on factors such as diagnostic criteria for H. pylori infection, study region, type of study design and CagA status. The effect of publication bias on the quantitative synthesis results was assessed using the trim-and-fill analysis, and sensitivity analyses were used to verify the robustness of the quantitative synthesis results. A total of 17 studies involving 67,910 participants, including 64,372 controls and 3,538 patients with pancreatic cancer, were included in the present study. The overall analysis showed that no significant association was observed between H. pylori infection and pancreatic cancer risk (OR, 1.15; 95% CI, 0.93-1.41). Further subgroup analyses, which did not consider the effects of study quality, diagnostic criteria, geographical distribution and the type of study design, did not produce new findings that contradicted the results of the overall analysis. CagA+ H. pylori infection did not significantly affect the risk of pancreatic cancer (OR, 0.95; 95% CI, 0.78-1.16), whereas CagA- H. pylori infection may be a possible risk factor for pancreatic cancer (OR, 1.24; 95% CI, 1.004-1.541). The H. pylori infection did not significantly increase the risk of pancreatic cancer. However, it is noteworthy that CagA- H. pylori infection could be a potential factor that elevated the risk of pancreatic cancer.

Pancreatic neuroendocrine neoplasm (panNEN) is a rare malignancy and the second most common type of pancreatic cancer after pancreatic ductal adenocarcinoma (PDAC), but its etiology is poorly understood. We investigated whether the risk factors of panNEN are concordant with those known for PDAC. We performed the largest case-control study to date on panNENs, comprising 927 sporadic nonfunctional panNEN cases and 1807 frequency-matched controls, using data from the Mayo Clinic Biospecimen Resource for Pancreas Research. We assessed associations for obesity, first-degree family history of pancreatic cancer, cigarette smoking, overall type II diabetes mellitus (T2DM), new-onset T2DM (<1 year before panNEN diagnosis), longstanding T2DM (≥5 years), alcohol intake and aspirin use. Multivariable logistic regression was used to calculate odds ratios and 95% confidence intervals (CIs). Our results show that overall T2DM (OR = 1.71, 95% CI: 1.37-2.14) and new-onset T2DM (OR = 2.65, 95% CI: 1.92-3.69) are associated with higher odds of panNEN, but not longstanding T2DM (OR = 1.29, 95% CI: 0.94-1.75). A non-significant elevated odds of panNEN was observed among participants with a positive family history of pancreatic cancer (OR = 1.44, 95% CI: 0.96-2.14). Alcohol use was inversely related to panNEN (OR = 0.52, 95% CI: 0.42-0.66, ever-vs-never). No association was observed for smoking, obesity or aspirin use. These findings indicate that overall T2DM and new-onset T2DM are associated with higher odds of panNEN. Unlike PDAC, alcohol use was inversely related to panNEN, and we found no associations for cigarette smoking, obesity or aspirin use. These results indicate differences in the risk factor profiles of panNEN and PDAC.

Data on the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on pancreatic cancer incidence are limited and inconsistent. Here we evaluate the association of GLP-1RAs, alone and in combinations, with incident pancreatic cancer risk in a real-world population, stratified by obesity and smoking status.

This retrospective cohort included patients with type 2 diabetes mellitus who were prescribed GLP-1RAs or other nonglucagon-like peptide-1 receptor agonist antidiabetes medications between January 2013 and March 2019 and had no prior diagnosis of pancreatic cancer. The incident (first-time) diagnosis of pancreatic cancer during a 5-year follow-up was compared between propensity-score matched cohorts of patients prescribed GLP-1RAs vs other nonglucagon-like peptide-1 receptor agonist antidiabetes medications. Subgroup analyses were performed in patients stratified by the status of obesity and tobacco use disorder. We also compared GLP-1RA combination therapies with monotherapies. Time-to-first-event analysis was performed using Cox proportional hazards and Kaplan-Meier survival analysis, with the hazard ratio and 95% confidence interval calculated.

The study population comprised 1 636 056 eligible patients including 167 091 prescribed GLP-1RAs and 1 468 965 prescribed other antidiabetes medications. GLP-1RAs were associated with a statistically significant decreased risk for pancreatic cancer incidence compared with each of 6 nonglucagon-like peptide-1 receptor agonist antidiabetes medications with hazard ratios ranging from 0.42 to 0.82. The reduction was greater in patients with obesity and tobacco use disorder than in those without. GLP-1RA combination therapies were associated with lower pancreatic cancer risk compared with monotherapies.

GLP-1RAs were associated with reduced pancreatic cancer incidence in patients with type 2 diabetes mellitus. Further studies and trials are needed to explore mechanisms and confirm causal effects.

Hypertension and diabetes are prevalent among older people and may be associated with cancer. Although several network analyses have been conducted to visualize the associations between diseases and relevant factors, to the best of our knowledge, none have focused on visualizing the associations between cancer and other diseases. We conducted a network analysis to explore the associations between cancer, hypertension, and diabetes. This study used a large-scale clinical dataset of 1,026,305 hospitalized patients aged ≥ 65 years, collected between April 2008 and December 2020. Diseases were categorized using the International Classification of Diseases-10 (2019 version) codes. The analysis focused on diseases with a prevalence of ≥ 1%. A multimorbidity network was constructed for the entire patient cohort, and the same analysis was applied specifically to cancer patients. Hypertension (degree centrality: 58/61) and diabetes (degree centrality: 56/61) were connected to several diseases, indicating significant multimorbidity in the cohort. The associations (observed-to-expected ratio) between digestive system cancers and hypertension and diabetes were relatively stronger than those between the diseases and other cancers. Type 2 diabetes and essential hypertension may be risk factors of cancers at multiple digestive system sites. Early treatment of these conditions could prevent or delay the progression of digestive system cancers.

At present, there is a lack of research on the correlation between cumFPG and digestive malignancies, and previous cohort studies have not considered the competitive risk between death and digestive malignancies, which may overestimate the impact of related risk factors. To explore the correlation between cumFPG and malignant tumors of the digestive system. In this study, 53,747 participants who had undergone 3 consecutive physical examinations since 2006 were collected. Finally, a total of 53,747 participants were included in this study. According to the grouping method of previous studies, cumFPG was divided into 4 groups according to the quartile. Cox regression model and competitive risk model were used to assess the risk of new digestive system malignancy. In sensitivity analyses, participants with cancer within 5 years of follow-up were excluded to eliminate the possibility of reverse causation. Subjects taking hypoglycemic drugs were excluded to eliminate the effect of the drug on blood glucose. Restricted cubic splineregresion (RCS) was then used to calculate the relationship between cumFPG and GI cancers. The mean age of participants was 49.02 ± 11.78 years. During a mean follow-up of 10.58 years, 817 new Gastrointestinal cases were identified, and the Cox proportional hazards model suggested that the risk of incidence in the Q2 to Q4 group increased sequentially compared with the lowest Q1 group, even after excluding the diagnosis of digestive malignancy within 5 years, the participants taking hypoglycemic drugs, and the death competition risk model analysis. In site-specific analysis, we observed that this risk was more pronounced in colorectal cancer, liver cancer, and pancreatic cancer, while gastric cancer, small bowel cancer, and bile duct cancer all had a similar trend to the main model but were not statistically significant, while esophageal cancer was U-shaped but not statistically significant. RCS results showed that cumFPG was associated with a similar risk of digestive system tumors, showing an inverted "√" type relationship. High levels of cumFPG are an independent factor in malignancy of the digestive system. cumFPG can provide a new idea for the prevention of Gastrointestinal cancers.

Pancreatic carcinoma has remained one of the leading causes of cancer-related mortality worldwide. Cancer originating in the head of pancreas is often detected early in the disease due to biliary obstruction resulting in jaundice. In contrast, cancer of the pancreatic body and tail remains indolent, presenting late with significantly increased tumor burden and distant metastasis. Unfortunately, a single laboratory screening study is neither sensitive nor specific for early detection of pancreatic cancer. In this report, we present a patient with longstanding diabetes incidentally detected to have pancreatic tail carcinoma while presenting with pulmonary embolism, emphasizing the need for pancreatic cancer screening studies in population with longstanding diabetes.

Pancreatic cancer (PC) is a prevalent gastrointestinal tumour known for its high degree of malignancy, resulting in a mere 10% five-year survival rate for most patients. Over the past decade, a growing body of research has shed light on the intricate bidirectional association between PC and Type 2 diabetes (T2DM). The collection of PC- and T2DM-related articles is derived from two comprehensive databases, namely WOS (Web of Science Core Collection) and CNKI (China National Knowledge Infrastructure). This article discusses the last 10 years of research trends in PC and T2DM and explores their potential regulatory relationship as well as related medications.

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.

Pancreatic ductal adenocarcinoma (PDAC) continues to remain one of the leading causes of cancer-related death. Unlike other malignancies where universal screening is recommended, the same cannot be said for PDAC. The purpose of this study is to review which patients are at high risk of developing PDAC and therefore candidates for screening, methods/frequency of screening, and risk for these groups of patients.

Pancreatic ductal adenocarcinoma (PDAC) is a significant cause of cancer-associated mortality, with a rising global incidence. A paucity of strong predictive risk factors mean screening programmes are difficult to implement. Historically, a lack of identifiable and actionable driver mutations, coupled with a relatively immunosuppressed tumour microenvironment, has led to a reliance on cytotoxic chemotherapy. The NAPOLI-3 trial has reported data supporting consideration of NALIRIFOX as a new first-line standard of care. Kirsten Rat Sarcoma Virus (KRAS) G12D mutations are present in >90% of all PDAC's; exciting breakthroughs in small molecule inhibitors targeting KRAS G12D may open new modalities of treatment, and therapies targeting multiple KRAS mutations are also in early clinical trials. Although immunotherapy strategies to date have been disappointing, combination with chemotherapy and/or small molecule inhibitors hold promise and warrant further exploration.

Pancreatic adenocarcinoma is one of the most lethal types of gastrointestinal cancer despite the latest medical advances. Its incidence has continuously increased in recent years in developed countries. The location of the pancreas can result in the initial symptoms of neoplasia being overlooked, which can lead to a delayed diagnosis and a subsequent reduction in the spectrum of available therapeutic options. The role of modifiable risk factors in pancreatic cancer has been extensively studied in recent years, with smoking and alcohol consumption identified as key contributors. However, the few screening programs that have been developed focus exclusively on genetic factors, without considering the potential impact of modifiable factors on disease occurrence. Thus, fully understanding and detecting the risk factors for pancreatic cancer represents an important step in the prevention and early diagnosis of this type of neoplasia. This review reports the available evidence on different risk factors and identifies the areas that could benefit the most from additional studies.

Cancer is one of the major causes of mortality and is the second leading cause of death. Diabetes mellitus is a serious and growing problem worldwide, and its prevalence continues to grow; it is the 12th leading cause of death. An association between diabetes mellitus and cancer has been suggested for more than 100 years. Diabetes is a common disease diagnosed among patients with cancer, and evidence indicates that approximately 8-18% of patients with cancer have diabetes, with investigations suggesting an association between diabetes and some particular cancers, increasing the risk for developing cancers such as pancreatic, liver, colon, breast, stomach, and a few others. Breast and colorectal cancers have increased from 20% to 30% and there is a 97% increased risk of intrahepatic cholangiocarcinoma or endometrial cancer. On the other hand, a number of cancers and cancer therapies increase the risk of diabetes mellitus. Complications due to diabetes in patients with cancer may influence the choice of cancer therapy. Unfortunately, the mechanisms of the associations between diabetes mellitus and cancer are still unknown. The aim of this review is to summarize the association of diabetes mellitus with selected cancers and update the evidence on the underlying mechanisms of this association.

The existing evidence from pre- and post-marketing studies is conflicting on the risk of pancreatic events for anti-diabetic medications.

A retrospective case/non-case study was conducted by using spontaneous reports on pancreatic events for anti-diabetic medications from the FDA Adverse Event Reporting System (FAERS) and VigiBase. Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), and Information Component (IC) were calculated by a disproportionality analysis. Furthermore, PubMed, Google Scholar, Scopus, and ClinicalTrials.gov were systematically searched for randomized controlled trials (RCTs) on anti-diabetic drugs with pancreatic outcomes.

The FAERS data analysis found strong signals on incretin mimetics causing pancreatic events, with sitagliptin having the highest risk [PRR = 24.2, lower bound (LB) ROR = 24.4, IC025 = 4.4 for pancreatitis, and PRR = 15.4, LB ROR = 14.9, IC025 = 3.8 for pancreatic carcinoma]. Empagliflozin was the most pancreatitis-risk sodium-glucose co-transporter-2 inhibitor [PRR = 4.0, LB ROR = 3.5, IC025 = 1.8]. VigiBase reiterated these findings and identified some new signals for novel anti-diabetics. Meta-analysis revealed that the incidence of pancreatitis and pancreatic carcinoma with anti-diabetic medications was insignificant. However, compared to the placebo/active comparator, gliptins had a higher risk of acute pancreatitis (OR 1.44; 95% CI 1.03, 2.01; P = 0.03).

Evidence from the post-marketing safety data analysis identified a strong association between incretin mimetics and pancreatic events. Fewer events in RCTs may justify insignificant meta-analysis results.

To explore the relationship between baseline clinical characteristics and hematological parameters of patients undergoing radical resection for pancreatic ductal adenocarcinoma (PDAC) and their prognosis, and to provide references for stratifying the patients' clinical risks.

We retrospectively collected clinical data from 445 patients who underwent radical surgical treatment for PDAC at West China Hospital, Sichuan University between January 2010 and February 2019. Then, we conducted retrospective clinical analysis with the collected data. Data on patients' basic clinical characteristics, routine blood test results, and tumor indicators were collected to explore their effects on the postoperative overall survival (OS) of PDAC patients. Cox proportional hazards regression was used to identify factors affecting OS. Statistical analysis was performed using the SPSS 23.0 software package.

The postoperative median overall survival (mOS) was 17.0 months (95% CI: 15.0-19.0). The 1, 2, 3, 4, and 5-year survival rates of the patients included in the study were 60.6%, 33.4%, 19.1%, 12.7%, and 9.6%, respectively. The multivariate Cox proportional hazards model analysis demonstrated that a number of factors independently affect postoperative survival in PDAC patients. These factors include tumor location (hazards ratio [HR]=1.574, 95% CI: 1.233-2.011), degree of tumor cell differentiation (HR=0.687, 95% CI: 0.542-0.870), presence of neural invasion (HR=0.686, 95% CI: 0.538-0.876), TNM staging (HR=1.572, 95% CI: 1.252-1.974), postoperative adjuvant therapy (HR=1.799, 95% CI: 1.390-2.328), preoperative drinking history (HR=0.744, 95% CI: 0.588-0.943), and high serum CA199 levels prior to the surgery (HR=0.742, 95% CI: 0.563-0.977).

In PDAC patients, having tumors located in the head of the pancreas, moderate and high degrees of differentiated, being free from local neurovascular invasion, being in TNM stage Ⅰ, undergoing postoperative adjuvant therapy, no history of alcohol consumption prior to the surgery, and preoperative serum CA199 being less than or equal to 37 U/mL are significantly associated with a better prognosis.

Observational data provide invaluable real-world information in medicine, but certain methodological considerations are required to derive causal estimates. In this systematic review, we evaluated the methodology and reporting quality of individual-level patient data meta-analyses (IPD-MAs) conducted with non-randomized exposures, published in 2009, 2014, and 2019 that sought to estimate a causal relationship in medicine. We screened over 16,000 titles and abstracts, reviewed 45 full-text articles out of the 167 deemed potentially eligible, and included 29 into the analysis. Unfortunately, we found that causal methodologies were rarely implemented, and reporting was generally poor across studies. Specifically, only three of the 29 articles used quasi-experimental methods, and no study used G-methods to adjust for time-varying confounding. To address these issues, we propose stronger collaborations between physicians and methodologists to ensure that causal methodologies are properly implemented in IPD-MAs. In addition, we put forward a suggested checklist of reporting guidelines for IPD-MAs that utilize causal methods. This checklist could improve reporting thereby potentially enhancing the quality and trustworthiness of IPD-MAs, which can be considered one of the most valuable sources of evidence for health policy.

The noninvasive detection of pancreatic ductal adenocarcinoma (PDAC) remains an immense challenge. In this study, we proposed a robust, accurate, and noninvasive classifier, namely Multi-Omics Co-training Graph Convolutional Networks (MOCO-GCN). It achieved high accuracy (0.9 ± 0.06), F1 score (0.9± 0.07), and AUROC (0.89± 0.08), surpassing contemporary approaches. The performance of model was validated on an external cohort of German PDAC patients. Additionally, we discovered that the exposome may impact PDAC development through its complex interplay with gut microbiome by mediation analysis. For example, Fusobacterium hwasookii nucleatum, known for its ability to induce inflammatory responses, may serve as a mediator for the impact of rheumatoid arthritis on PDAC. Overall, our study sheds light on how exposome and microbiome in concert could contribute to PDAC development, and enable PDAC diagnosis with high fidelity and interpretability.

Little is known about the characteristics of early pancreatic cancer. We aimed to identify the characteristics, clues for early detection, and prognostic factors for early pancreatic cancer by analyzing a large number of patients with stage 1 pancreatic cancer.

A clinical data warehouse that includes databases of all the medical records of eight academic institutions was used to select and analyze patients with pancreatic cancer that had been diagnosed from January 2010 to May 2023.

In total, 257 stage 1 pancreatic cancer patients were included. There were 134 men (52%), and the average age was 67.2 ± 9.9 years. Compared to patients with stage 1B pancreatic cancer (2-4 cm), patients with stage 1A pancreatic cancer (≤2 cm) had more tumors in the body and tail than in the head (p = 0.028), more new-onset diabetes and less old diabetes (p = 0.010), less jaundice (p = 0.020), more follow-up of IPMN (intraductal papillary mucinous neoplasm, p = 0.029), and more histories of acute pancreatitis (p = 0.013). The pathological findings showed that stage 1A pancreatic cancer involved more IPMNs (p < 0.001) and lower pancreatic intraepithelial neoplasia (p = 0.004). IPMN was present in all 13 pancreatic tumors that were smaller than 1 cm. In multivariate analysis, positive resection margin (odds ratio [OR] 1.536, p = 0.040), venous invasion (OR 1.710, p = 0.010), and perineural invasion (OR 1.968, p = 0.002) were found to be risk factors affecting disease-free survival, while old diabetes (odds ratio [OS] 1.981, p = 0.003) and perineural invasion (OR 2.270, p = 0.003) were found to be risk factors affecting overall survival.

IPMN is closely associated with early pancreatic cancer and may provide an opportunity for early detection. The presence of perineural invasion was a crucial prognostic factor for both overall and disease-free survival in patients with stage 1 pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is among the leading causes of cancer-related deaths worldwide. Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase often overexpressed in PDAC. FAK has been linked to cell migration, survival, proliferation, angiogenesis and adhesion. This review first highlights the chemoresistant nature of PDAC. Second, the role of FAK in PDAC cancer progression and resistance is carefully described. Additionally, it discusses recent developments of FAK inhibitors as valuable drugs in the treatment of PDAC, with a focus on diamine-substituted-2,4-pyrimidine-based compounds, which represent the most potent class of FAK inhibitors in clinical trials for the treatment of PDAC disease. To conclude, relevant computational studies performed on FAK inhibitors are reported to highlight the key structural features required for interaction with the protein, with the aim of optimizing this novel targeted therapy.

This comprehensive review explores the complexities surrounding pancreatic head cancer, a highly fatal and challenging-to-treat illness with a survival rate of less than five years. Despite being a major contributor to cancer-related deaths, pancreatic head malignancy often eludes early detection due to its posterior location and high metastatic potential. The review delves into the associated symptoms, including gastric outlet obstruction and obstructive jaundice, highlighting the impact on the patient's eligibility for surgery. Examining recent advancements, the article discusses fast-track surgery recovery programs and emerging immunotherapeutic approaches, acknowledging the unique challenges posed by the immunosuppressive environment of pancreatic head cancer. Additionally, the review elucidates the intricate relationship between pancreatic cancer and glucose levels, emphasizing the role of islets of Langerhans in insulin production. The pathogenesis section explores lifestyle and genetic factors contributing to pancreatic head carcinoma, shedding light on risk factors such as smoking, obesity, diabetes, and hereditary predispositions. The extensive analysis of pancreatic cancer diagnosis methods encompasses imaging techniques, biopsies, and biomarkers, emphasizing the challenges posed by late-stage diagnoses. Addressing treatment modalities, the review emphasizes the significance of surgery, chemotherapy, radiotherapy, and targeted therapy. The intricate details of neoadjuvant, immunotherapy, and microbial therapy provide a comprehensive understanding of evolving treatment strategies. The review concludes by highlighting promising areas of research, including oncolytic viral therapy and gene editing technology, aiming to enhance the limited treatment options for this devastating disease.

Human struggle against the deadly disease conditions is continued since ages. The contribution of science and technology in fighting against these diseases cannot be ignored exclusively due to the invention of novel procedure and products, extending their size ranges from micro to nano. Recently nanotechnology has been gaining more consideration for its ability to diagnose and treat different cancers. Different nanoparticles have been used to evade the issues related with conservative anticancer delivery systems, including their nonspecificity, adverse effects and burst release. These nanocarriers including, solid lipid nanoparticles (SLNs), liposomes, nano lipid carriers (NLCs), nano micelles, nanocomposites, polymeric and magnetic nanocarriers, have brought revolutions in antitumor drug delivery. Nanocarriers improved the therapeutic efficacy of anticancer drugs with better accumulation at the specific site with sustained release, improved bioavailability and apoptosis of the cancer cells while bypassing the normal cells. In this review, the cancer targeting techniques and surface modification on nanoparticles are discussed briefly with possible challenges and opportunities. It can be concluded that understanding the role of nanomedicine in tumor treatment is significant, and therefore, the modern progressions in this arena is essential to be considered for a prosperous today and an affluent future of tumor patients.

Pancreatic cancer, notorious for its late diagnosis and aggressive progression, poses a substantial challenge owing to scarce treatment alternatives. This review endeavors to furnish a holistic insight into pancreatic cancer, encompassing its epidemiology, genomic characterization, risk factors, diagnosis, therapeutic strategies, and treatment resistance mechanisms. We delve into identifying risk factors, including genetic predisposition and environmental exposures, and explore recent research advancements in precursor lesions and molecular subtypes of pancreatic cancer. Additionally, we highlight the development and application of multi-omics approaches in pancreatic cancer research and discuss the latest combinations of pancreatic cancer biomarkers and their efficacy. We also dissect the primary mechanisms underlying treatment resistance in this malignancy, illustrating the latest therapeutic options and advancements in the field. Conclusively, we accentuate the urgent demand for more extensive research to enhance the prognosis for pancreatic cancer patients.

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.

This multicenter study analyzed the relationship between preoperative symptoms and postsurgical outcomes utilizing the German national DGAV StuDoQ|Pancreas database.

This retrospective study included 2,643 pancreatic ductal adenocarcinoma patients undergoing pancreatic head resection from 2013-2017 within the German pancreatic surgery registry (DGAV StuDoQ|Pancreas). The association of preoperative symptoms with overall survival was analyzed using Kaplan-Meier and Cox regression analysis.

Preoperative symptoms were common, with 2,380 of 2,643 (90%) patients presenting with any one or more of the following symptoms: jaundice (40%), biliary obstruction treated with biliary stent (41%), pain (37%), weight loss (29%), nausea (18%), diabetes (31%), emesis (6%), and recent onset diabetes (5%). Patients were separated into 3 groups: no symptoms (n = 293), symptoms (n = 2,229), and recent onset diabetes (n = 121). The 3 groups differed in body mass index and nodal staging, where patients with recent onset diabetes had the highest values (body mass index: no symptoms: 24.5 kg/m2, symptoms: 25.1 kg/m2; recent-onset diabetes: 26.3 kg/m2, P = .007), (no symptoms: N1: 55%, N2: 10%; symptoms: N1: 53%, N2: 17%; recent-onset diabetes: N1: 56%, N2: 16%, P = .023). Other pathological characteristics, carbohydrate antigen 19-9 levels, and adjuvant chemotherapy receival did not differ between the groups. Interestingly, recent-onset diabetes was associated with better survival compared with the other groups (Median overall survival: 28 months [no symptoms at all], 22 months [symptoms] versus not reached [recent onset diabetes group], and 5-year overall survival rates of 28%, 11%, and 57%, respectively [log rank, P = .013]). Multivariable analysis revealed that recent-onset diabetes and preoperative symptoms were independently associated with overall survival (recent-onset diabetes, relative risk 0.052 P = .027, >5 symptoms relative risk 3.66, P < .001).

Pancreatic ductal adenocarcinoma symptoms occured in up to 90% of patients with resectable pancreatic ductal adenocarcinoma. In addition, PDAC symptoms were associated with overall survival and might identify unique pancreatic ductal adenocarcinoma subtypes.

Observational data provide invaluable real-world information in medicine, but certain methodological considerations are required to derive causal estimates. In this systematic review, we evaluated the methodology and reporting quality of individual-level patient data meta-analyses (IPD-MAs) published in 2009, 2014, and 2019 that sought to estimate a causal relationship in medicine. We screened over 16,000 titles and abstracts, reviewed 45 full-text articles out of the 167 deemed potentially eligible, and included 29 into the analysis. Unfortunately, we found that causal methodologies were rarely implemented, and reporting was generally poor across studies. Specifically, only three of the 29 articles used quasi-experimental methods, and no study used G-methods to adjust for time-varying confounding. To address these issues, we propose stronger collaborations between physicians and methodologists to ensure that causal methodologies are properly implemented in IPD-MAs. In addition, we put forward a suggested checklist of reporting guidelines for IPD-MAs that utilize causal methods. This checklist could improve reporting thereby potentially enhancing the quality and trustworthiness of IPD-MAs, which can be considered one of the most valuable sources of evidence for health policy.

The single risk factors of pancreatic cancer (PC) has been extensively studied. We aimed to synthesize results from such studies to identify and estimate multiple independent risk factors of PC.

Articles published up to Feb 28, 2020 in English or Chinese reporting risk factors of PC were reviewed. The fixed-effects model with 95% confidence interval (CI) were used to calculate the pooled Odds Ratio (OR). Data were analyzed using RevMan 5.3.

PC was significantly associated with smoking (OR: 1.76, 95% CI: 1.61-1.92, P < 0.00001, I2 = 6%), diabetes (OR: 2.69, 95% CI: 2.52-2.88, P < 0.00001, I2 = 0%), family history of PC (OR: 2.58, 95% CI: 2.13-3.11, P < 0.00001, I2 = 0%), and chronic pancreatitis (OR: 5.84, 95% CI: 3.63-9.41, P < 0.00001, I2 = 0%).

Smoking, diabetes, family history of PC, and chronic pancreatitis were independent risk factors for PC. These independent risk factors have an important role in identifying high-risk groups, which is of great significance to reduce the incidence of PC and improve the quality of life and prognosis of patients.

Cuproptosis is a novel cell death pathway, and the regulatory mechanism in pancreatic cancer (PC) is unclear. The authors aimed to figure out whether cuproptosis-related lncRNAs (CRLs) could predict prognosis in PC and the underlying mechanism. First, the prognostic model based on seven CRLs screened by the least absolute shrinkage and selection operator Cox analysis was constructed. Following this, the risk score was calculated for pancreatic cancer patients and divided patients into high and low-risk groups. In our prognostic model, PC patients with higher risk scores had poorer outcomes. Based on several prognostic features, a predictive nomogram was established. Furthermore, the functional enrichment analysis of differentially expressed genes between risk groups was performed, indicating that endocrine and metabolic pathways were potential regulatory pathways between risk groups. TP53, KRAS, CDKN2A, and SMAD4 were dominant mutated genes in the high-risk group and tumour mutational burden was positively correlated with the risk score. Finally, the tumour immune landscape indicated patients in the high-risk group were more immunosuppressive than that in the low-risk group, with lower infiltration of CD8+ T cells and higher M2 macrophages. Above all, CRLs can be applied to predict PC prognosis, which is closely correlated with the tumour metabolism and immune microenvironment.

Post-pancreatitis diabetes mellitus, pancreatic cancer-related diabetes, and cystic fibrosis-related diabetes are often underappreciated. As a result, a substantial proportion of people with these sub-types of diabetes receive antidiabetic medications that may be suboptimal, if not harmful, in the context of their underlying disease of the exocrine pancreas. The present article delineates both classical (biguanides, insulin, sulfonylureas, α-glucosidase inhibitors, thiazolidinediones, and meglitinides) and newer (glucagon-like peptide-1 receptor agonists, amylin analogs, dipeptidyl peptidase-4 inhibitors, sodium-glucose co-transporter-2 inhibitors, D2 receptor agonists, bile acid sequestrants, and dual glucagon-like peptide-1 receptor and glucose-dependent insulinotropic polypeptide receptor co-agonists) therapies and provides recommendations for managing people with diabetes of the exocrine pancreas based on the most up-to-date clinical evidence. Also, several emerging directions (lipid-enriched pathways, Y4 receptor agonism, glucagon-like peptide-1 and glucagon receptor co-agonism) are presented with a view to informing the process of new drug discovery and development.

Cancer is currently the second leading cause of death globally. There is much uncertainty regarding the comparative risks of new-onset overall cancer and pre-specified cancer for Type 2 diabetes mellitus (T2DM) patients on sodium-glucose cotransporter 2 inhibitors (SGLT2I) versus DPP4I.

This population-based cohort study patients included patients who were diagnosed with T2DM and administered either SGLT2 or DPP4 inhibitors between 1 January 2015 and 31 December 2020 in public hospitals of Hong Kong.

This study included 60,112 T2DM patients (mean baseline age: 62.1 ± 12.4 years, male: 56.36%), of which 18,167 patients were SGLT2I users and 41,945 patients were dipeptidyl peptidase 4 inhibitor (DPP4I) users. Multivariable Cox regression found that SGLT2I use was associated with lower risks of all-cause mortality (HR: 0.92; 95% CI: 0.84-0.99; p= 0.04), cancer-related mortality (HR: 0.58; 95% CI: 0.42-0.80; p ≤ 0.001) and new diagnoses of any cancer (HR: 0.70; 95% CI: 0.59-0.84; p ≤ 0.001). SGLT2I use was associated with a lower risk of new-onset breast cancer (HR: 0.51; 95% CI: 0.32-0.80; p ≤ 0.001), but not of other malignancies. Subgroup analysis on the type of SGLT2I, dapagliflozin (HR: 0.78; 95% CI: 0.64-0.95; p = 0.01) and ertugliflozin (HR: 0.65; 95% CI: 0.43-0.98; p = 0.04) use was associated with lower risks of new cancer diagnosis. Dapagliflozin use was also linked to lower risks of breast cancer (HR: 0.48; 95% CI: 0.27-0.83; p = 0.001).

Sodium-glucose cotransporter 2 inhibitor use was associated with lower risks of all-cause mortality, cancer-related mortality and new-onset overall cancer compared to DPP4I use after propensity score matching and multivariable adjustment.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease, for which mortality closely parallels incidence. So far, the available techniques for PDAC detection are either too invasive or not sensitive enough. To overcome this limitation, here we present a multiplexed point-of-care test that provides a "risk score" for each subject under investigation, by combining systemic inflammatory response biomarkers, standard laboratory tests, and the most recent nanoparticle-enabled blood (NEB) tests. The former parameters are routinely evaluated in clinical practice, whereas NEB tests have been recently proven as promising tools to assist in PDAC diagnosis. Our results revealed that PDAC patients and healthy subjects can be distinguished accurately (i.e., 88.9% specificity, 93.6% sensitivity) by the presented multiplexed point-of-care test, in a quick, non-invasive, and highly cost-efficient way. Furthermore, the test allows for the definition of a "risk threshold", which can help clinicians to trace the optimal diagnostic and therapeutic care pathway for each patient. For these reasons, we envision that this work may accelerate progress in the early detection of PDAC and contribute to the design of screening programs for high-risk populations.

Metformin and aspirin are commonly co-prescribed to people with diabetes. Metformin may prevent cancer, but in older people (over 70 years), aspirin has been found to increase cancer mortality. This study examined whether metformin reduces cancer mortality and incidence in older people with diabetes; it used randomization to 100 mg aspirin or placebo in the ASPirin in Reducing Events in the Elderly (ASPREE) trial to quantify aspirin's impact on metformin users.

Analysis included community-dwelling ASPREE participants (aged ≥70 years, or ≥65 years for members of US minority populations) with diabetes. Diabetes was defined as a fasting blood glucose level greater than 125 mg/dL, self-report of diabetes, or antidiabetic medication use. Cox proportional hazards regression models were used to analyze the association of metformin and a metformin-aspirin interaction with cancer incidence and mortality, with adjustment for confounders.

Of 2045 participants with diabetes at enrollment, 965 were concurrently using metformin. Metformin was associated with a reduced cancer incidence risk (adjusted hazard ratio [HR] = 0.68, 95% confidence interval [CI] = 0.51 to 0.90), but no conclusive benefit for cancer mortality (adjusted HR = 0.72, 95% CI = 0.43 to 1.19). Metformin users randomized to aspirin had greater risk of cancer mortality compared with placebo (HR = 2.53, 95% CI = 1.18 to 5.43), but no effect was seen for cancer incidence (HR = 1.11, 95% CI = 0.75 to 1.64). The possible effect modification of aspirin on cancer mortality, however, was not statistically significant (interaction P = .11).

In community-dwelling older adults with diabetes, metformin use was associated with reduced cancer incidence. Increased cancer mortality risk in metformin users randomized to aspirin warrants further investigation.

ClinicalTrials.gov ID NCT01038583.

We aim to evaluate the relationship between the use of metformin and the risk of pancreatic cancer in type 2 diabetes patients.

We systematically searched the observational studies on PubMed, Embase, Web of Science, Cochrane Library, clinicalrials.gov, and CNKI databases, extracted relevant data, combined the OR value and 95% CI using the random effect model, and conducted a sensitivity analysis, subgroup analysis, and meta-regression to evaluate the size and stability of this relationship.

Twenty-nine studies from twenty-four articles met our inclusion criteria, including more than 2 million subjects. Overall analysis showed that compared with no use of metformin, the use of metformin could reduce the risk of pancreatic cancer in patients with type 2 diabetes (OR = 0.82, 95% CI (0.69, 0.98)). Subgroup analysis showed that compared with the use of hypoglycemic drugs, the use of metformin could reduce the risk of pancreatic cancer in patients with type 2 diabetes (OR = 0.79, 95% CI (0.66, 0.94)). However, compared with no drugs or only diet therapy, metformin users might increase the risk of pancreatic cancer (OR = 2.19, 95% CI (1.08, 4.44)). Sensitivity analysis confirmed the stability of the study, and there was no significant publication bias.

Compared with the no-use of metformin, metformin users with diabetes can reduce the risk of pancreatic cancer. More research is needed to prove it works.

The poor prognosis of pancreatic ductal adenocarcinoma (PDAC) is mainly attributed to late diagnosis. We assessed the predictive performance of our previously reported urine biomarker panel for earlier detection of PDAC (LYVE1, REG1B and TFF1) in prediagnostic samples, alone and in combination with plasma CA19-9. This nested case-control study included 99 PDAC cases with urine samples prospectively collected up to 5 years prior to PDAC diagnosis and 198 matched controls. The samples were obtained from the Shanghai Women's Health Study (SWHS), the Shanghai Men's Health Studies (SMHS) and the Southern Community Cohort Study (SCCS). The urine biomarkers were measured by ELISA. Plasma CA19-9 was quantified by Luminex. Multiple logistic regression and Wilcoxon rank-sum and Mann-Whitney test were used for analysis. The internal validation approach was applied and the validated AUC estimators are reported on. The algorithm of urinary protein panel, urine creatinine and age named PancRISK, displayed similar AUC as CA19-9 up to 1 year before PDAC diagnosis (AUC = 0.79); however, the combination enhanced the AUCs to 0.89, and showed good discriminative ability (AUC = 0.77) up to 2 years. The combination showed sensitivity (SN) of 72% at 90% specificity (SP), and SP of 59% at 90% SN up to 1 year and 60% SN with 80% SP and 53% SP with 80% SN up to 2 years before PDAC diagnosis. Adding the clinical information on BMI value resulted in the overall improvement in performance of the PancRISK score. When combined with CA19-9, the urinary panel reached a workable model for detecting PDAC cases up to 2 years prior to diagnosis.

It remains unclear how pre-existing depression, anxiety, and diabetes of different durations are associated with the risk of pancreatic cancer, its clinical characteristics, treatment modalities, and subsequent survival.

From a register-based random sample of Finns residing in Finland at the end of the period 1987-2007, 6492 patients diagnosed with primary pancreatic cancer in 2000-2014, and 32 460 controls matched for birth cohort and sex, were identified. Pre-existing depression, anxiety, and diabetes were ascertained from the records of prescribed medication purchases. Information on pancreatic cancer outcomes was obtained from the Finnish cancer register. Data were analyzed using logistic and Cox regressions.

The risk of developing pancreatic cancer was found to be associated with long-term anxiety (treatment started 36 + months before the cancer diagnosis) (odds ratio (OR): 1.13, 95% confidence interval (95%CI): 1.04-1.22) and long-term diabetes (OR 1.72, 95%CI 1.55-1.90), as well as with new-onset (treatment started 0-24 months before the cancer diagnosis) depression (OR 1.59, 95%CI 1.34-1.88), anxiety (OR 1.76, 95%CI 1.50-2.07), and diabetes (OR 3.92, 95%CI 3.44-4.48). However, the effects of these new-onset conditions were driven by cases that began treatment within 3 months before the cancer diagnosis (concomitant period). Patients with long-term depression, anxiety and diabetes and those with new-onset anxiety had a higher risk of not receiving standard treatments. Lower survival was found for pancreatic cancer patients with new-onset depression (hazards ratio (HR) 1.38, 95%CI 1.16-1.64). Survival was not associated with pre-existing anxiety or diabetes.

The associations between pancreatic cancer risk and pre-existing depression and anxiety were mostly driven by concomitant effects. Individuals with diabetes, regardless of duration, should be closely monitored for pancreatic cancer. Pancreatic cancer patients with new-onset depression should be targeted to improve their survival.

Pancreatic cancer (PC) is highly fatal, and its incidence is increasing in the United States. Population-based registry studies suggest associations between a few autoimmune conditions and PC risk, albeit based on a relatively small number of cases. We conducted a population-based, nested case-control study to examine the associations between autoimmune conditions and PC risk within the Surveillance, Epidemiology, and End Results Program (SEER)-Medicare population. Incident primary malignant PC cases (n = 80 074) were adults ≥66 years and diagnosed between 1992 and 2015. Controls (n = 320 296) were alive at the time cases were diagnosed and frequency-matched to cases (4:1 ratio) by age, sex, and year of diagnosis. We used multivariable-adjusted, unconditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for 45 autoimmune conditions identified from Medicare claims. Eight autoimmune conditions including ankylosing spondylitis (OR = 1.45; 95% CI: 1.14-1.84), Graves' disease (OR = 1.18; 95% CI: 1.03-1.34), localized scleroderma (OR = 1.27; 95% CI: 1.06-1.52), pernicious anemia (OR = 1.08; 95% CI: 1.02-1.14), primary sclerosing cholangitis (OR = 1.37; 95% CI: 1.18-1.59), pure red cell aplasia (OR = 1.31; 95% CI: 1.16-1.47), type 1 diabetes (OR = 1.11; 95% CI: 1.07-1.15), and ulcerative colitis (OR = 1.18; 95% CI: 1.07-1.31) were associated with increased PC risk (false discovery rate-adjusted P values <.10). In subtype analyses, these conditions were associated with pancreatic ductal adenocarcinoma, whereas only ulcerative colitis was associated with pancreatic neuroendocrine tumors. Our results support the hypothesis that autoimmune conditions may play a role in PC development.