Distal pancreatectomy (DP) can worsen pancreatic endocrine function. Effects on glucose metabolism and underlying mechanisms after DP remains a topic of significant interest and not yet fully understood. This study aimed to examine the impact of DP on blood glucose homeostasis with a particular focus on metabolic outcomes and development of postoperative diabetes.

Considered were all patients who underwent DP between 01/2010 and 09/2021 and participated simultaneously in extended blood glucose monitoring with a 12 months follow-up. Blood samples were analyzed for markers of pancreatic endocrine function both fasting and after an oral glucose tolerance test preoperatively and 3 and 12 months after DP.

Included patients (n = 69) were preoperatively categorized into three groups according to American Diabetes Association (ADA) criteria: 17 patients (24.6%) were normoglycemic (NG), 22 (31.9%) had prediabetes (impaired fasting glucose / impaired glucose tolerance - IFG/IGT) and 30 (43.5%) had diabetes mellitus (DM). In the NG subgroup, beta-cell function (HOMA2%B - updated homeostasis model assessment) significantly decreased from 117.4% (101.1-135%) to 66.9% (49.7-102.1%) at 12 months postoperatively (p < 0.05). Insulin sensitivity (HOMA2%S) significantly increased from 48.2% (33.4-66.9%) to 63.5% (49.8-86%) at 12 months postoperatively (p < 0.05). In the IFG/IGT subgroup, there was a non-significant trend of decreased HOMA2%B and increased HOMA2%S postoperatively. Postoperatively, 11.8% of NG patients and 60% of prediabetic patients developed DM.

DP already leads to significant changes in glucose metabolism within a 12 month follow-up period. Patients with preoperative prediabetes are particularly at high risk of developing postoperative DM. Therefore, the indication for DP should be critically evaluated, especially in cases with a relative indication for surgery. If possible parenchymal sparing surgical options should be contemplated.

Not applicable.

Pancreatic cancer is one of the most lethal malignancies worldwide. It is characterized by poor prognosis, high mortality, and recurrence rates. Various modifiable and non-modifiable risk factors are associated with pancreatic cancer incidence. Available treatments for pancreatic cancer include surgery, chemotherapy, radiotherapy, photodynamic therapy, supportive care, targeted therapy, and immunotherapy. However, the survival rates for PC are very low. Regrettably, despite efforts to enhance prognosis, the survival rate of pancreatic cancer remains relatively low. Therefore, it is essential to investigate new approaches to improve pancreatic cancer treatment. By synthesizing current knowledge and identifying existing gaps, this article provides a comprehensive overview of risk factors, pathology, conventional treatments, targeted therapies, and recent advancements in nanocarriers for its treatment, along with various clinical trials and patents that justify the safety and efficacy of innovative carriers for drug delivery systems. Ultimately, this review underscores the potential of these innovative formulations to improve outcomes and contribute significantly to the advancement of Pancreatic Cancer treatment. Together, these insights highlight nano-formulations as a promising frontier for effectively treating Pancreatic Cancer.

We present OmniPRS, a scalable biobank-scale framework that improves genetic risk prediction for complex traits by integrating genome-wide association study (GWAS) summary statistics and functional annotations. It employs a mixed model incorporating tissue-specific genetic variance components from annotations to re-estimate single-nucleotide polymorphism (SNP) effects and constructs tissue-specific polygenic risk scores (PRSs) and aggregates them into the final OmniPRS. Our experiments, encompassing 135 simulation scenarios and 11 representative traits, demonstrate that OmniPRS is flexible and robust, delivering efficient and accurate predictions comparable to ten leading PRS methods. For quantitative (binary) traits, OmniPRS achieved an average improvement of 52.31% (19.83%) versus the clumping and thresholding (C+T) method, 3.92% (1.31%) versus the annotation-integrated PRSs (LDpred-funct), and 8.44% (2.27%) versus the Bayesian-based PRSs (PRScs). Notably, it achieved 35× faster computation than the PRScs. This rapid, precise framework enables efficient polygenic risk scoring with multi-annotation integration for large-scale genomic studies.

Elevated gamma-glutamyl transferase (GGT) levels indicate hepatic dysfunction and have been linked to an increased risk of pancreatobiliary cancers. However, this association, particularly in individuals with diabetes mellitus (DM), requires elucidation. We aimed to examine the association between elevated serum GGT levels and pancreatobiliary cancer risk in patients with diabetes.

Our study included data from the National Health Insurance Service (NHIS) database for 2,459,966 adults aged >20 years diagnosed with DM between 2009 and 2012. We examined the association between serum GGT levels and pancreatobiliary cancer risk, considering DM-related factors. Serum GGT levels were categorized into quartiles, and Cox proportional hazards analysis was performed to evaluate the association between serum GGT levels and pancreatobiliary cancer risk.

Over a median follow-up period of 7.2 years, 21,795 patients (0.89%) were newly diagnosed with pancreatobiliary cancer. The adjusted hazard ratio for pancreatobiliary cancer in quartiles 2-4 compared with that in quartile 1 was 1.091, 1.223, and 1.554, respectively, demonstrating a significant upward trend (p<0.001). This association remained consistent across all cancer types and was independent of the DM duration or treatment regimen.

Elevated serum GGT levels were independently associated with an increased risk of pancreatobiliary cancer, regardless of the duration of DM or the use of oral hypoglycemic agents and insulin. While these findings suggest the potential utility of serum GGT as a biomarker for identifying individuals at higher risk of pancreatobiliary cancer within the diabetic population, further research is needed to validate its clinical applicability.

This study applied machine learning (ML) and explainable artificial intelligence (XAI) to predict changes in HbA1c levels, a critical biomarker for monitoring glycemic control, within 12 months of initiating a new antidiabetic drug in patients diagnosed with type 2 diabetes. It also aimed to identify the predictors associated with these changes.

Electronic health records (EHR) from 10,139 type 2 diabetes patients in North Karelia, Finland, were used to train models integrating randomized controlled trial (RCT)-derived HbA1c change values as predictors, creating offset models that integrate RCT insights with real-world data. Various ML models-including linear regression (LR), multi-layer perceptron (MLP), ridge regression (RR), random forest (RF), and XGBoost (XGB)-were evaluated using R² and RMSE metrics. Baseline models used data at or before drug initiation, while follow-up models included the first post-drug HbA1c measurement, improving performance by incorporating dynamic patient data. Model performance was also compared to expected HbA1c changes from clinical trials.

Results showed that ML models outperform RCT model, while LR, MLP, and RR models had comparable performance, RF and XGB models exhibited overfitting. The follow-up MLP model outperformed the baseline MLP model, with higher R² scores (0.74, 0.65) and lower RMSE values (6.94, 7.62), compared to the baseline model (R²: 0.52, 0.54; RMSE: 9.27, 9.50). Key predictors of HbA1c change included baseline and post-drug initiation HbA1c values, fasting plasma glucose, and HDL cholesterol.

Using EHR and ML models allows for the development of more realistic and individualized predictions of HbA1c changes, accounting for more diverse patient populations and their heterogeneous nature, offering more tailored and effective treatment strategies for managing T2D. The use of XAI provided insights into the influence of specific predictors, enhancing model interpretability and clinical relevance. Future research will explore treatment selection models.

Patients with type 2 diabetes mellitus (T2DM) have higher pancreatic cancer (PC) risk. While aspirin has chemopreventive effects on digestive cancers, its effect on PC among patients with T2DM is unclear.

This retrospective cohort study identified newly diagnosed adult patients with T2DM in Hong Kong between 2001 and 2015 from a territory-wide healthcare registry. Exclusion criteria were history of PC, pancreatic cyst, IgG4 disease, or pancreatectomy. To address reverse causality between PC and T2DM, we excluded patients with PC diagnosed within 1 year of T2DM. We also excluded patients with less than 1 year of observation. Primary outcome was PC, and secondary outcomes were PC-related and all-cause mortality. Aspirin use was treated as time-varying variable (≥180 day-use/year) to address immortal-time bias, and multivariable Cox regression model was employed to derive adjusted HR (aHR). Propensity-score (PS) matching was used as secondary analysis.

Among 343 966 newly diagnosed patients with T2DM (median follow-up: 10.5 years; IQR: 7.7-14.5 years), 1224 (0.36%) developed PC. There were 51 151 (14.9%) deaths from any cause, and 787 (0.2%) died from PC. Aspirin use was associated with lower PC risk in both time-dependent (aHR: 0.58; 95% CI 0.49 to 0.69) and PS matching analysis (aHR: 0.61; 95% CI 0.48 to 0.77). An inverse relationship was observed with increasing dose and duration of aspirin use (P trend<0.001). Aspirin was also associated with a lower risk of PC-related mortality (aHR: 0.43; 95% CI 0.34 to 0.53) and all-cause mortality (aHR: 0.78; 95% CI 0.76 to 0.80).

Aspirin use may be an oncopreventive strategy to reduce PC risk in patients with T2DM. Further studies are warranted to validate the study findings.

Despite diabetes mellitus (DM) and pancreatitis being known risk factors for pancreatic cancer, patients with these conditions are not included in pancreatic cancer screening due to the low incidence of pancreatic cancer in these populations. This study aimed to determine the high-risk subgroup of patients with diabetes and pancreatitis that would benefit from pancreatic cancer screening.

A nested case-control study was conducted using data from the National Health Information Database of the Korean National Health Insurance Service. Patients were categorized into the following groups: type 2 diabetes mellitus only (T2DM-only), pancreatitis-only (PAN-only), T2DM followed by pancreatitis (T2DM-PAN), post-pancreatitis diabetes mellitus (PPDM), and no diabetes and no pancreatitis (NDNP). Conditional logistic regression was used to determine significant associations of each group with pancreatic cancer development risk.

The risk of pancreatic cancer was significantly higher in the T2DM-PAN (adjusted odds ratio [AOR], 4.96; 95% confidence interval [CI], 4.48 to 5.49) and PPDM (AOR, 4.71; 95% CI, 4.12 to 5.37) groups than in the NDNP group. Compared to patients in the NDNP group, those with PPDM using insulin had a 17-fold increased risk (AOR, 16.72; 95% CI, 9.50 to 29.43), and individuals with PPDM who had diabetes for less than 3 years had a more than 8-fold increased risk of pancreatic cancer (AOR, 8.83; 95% CI, 5.99 to 13.01).

In patients with post-pancreatitis diabetes, insulin use or shorter duration of diabetes was associated with a higher risk of pancreatic cancer, suggesting that patients in these subgroups may require close monitoring for pancreatic cancer development.

The relationship between diabetes and pancreatic cancer is well documented; however, the effect of preoperative blood glucose levels on prognosis and postoperative complications is currently unclear. The present study aimed to investigate the effect of preoperative blood glucose levels on overall survival (OS) and postoperative complications in patients with pancreatic cancer. This retrospective study included 225 patients with pancreatic cancer treated at The Fourth Hospital of Hebei Medical University from January 2015 to December 2020. Patients were grouped based on preoperative blood glucose levels (normal, ≤6.11 mmol/l; high, >6.11 mmol/l). Data on demographics, clinical history, tumor characteristics, treatment and laboratory results were collected. High preoperative blood glucose levels were associated with reduced OS time [hazard ratio (HR), 1.68; 95% confidence interval (CI), 1.15-2.45; P=0.007] and increased postoperative complications (29.2 vs. 9.8%; χ2=13.658; P<0.001). Median OS time was significantly shorter in the high glucose group (14.2 vs. 20.5 months; HR, 1.96; 95% CI, 1.38-2.77; P<0.001). Elevated CA19-9 levels were also a predictor of poor OS (HR, 1.70; 95% CI, 1.06-2.74; P=0.029). High preoperative blood glucose and elevated CA19-9 levels were independent predictors of poor prognosis in patients with pancreatic cancer. This finding suggests that preoperative blood glucose levels have a greater impact on prognosis compared with a history of diabetes. Elevated preoperative blood glucose levels have poorer OS and a higher incidence of postoperative complications compared to those with lower preoperative glucose levels, underscoring the importance of preoperative glucose management. Effective preoperative blood glucose control may improve outcomes in patients with pancreatic cancer.

Pancreatic cancer is a common and deadly cancer, ranking as the 14th most common cancer worldwide and the 7th leading cause of cancer-related deaths. Advanced pancreatic malignancy frequently presents with biliary and gastric outlet obstruction and palliative open interventions are often required, especially in low-income countries where endoscopic surgical bypass methods are often unavailable. This study aimed to describe the demographic and clinical characteristics of patients undergoing biliodigestive bypass for pancreatic malignancy.

This was a hospital-based retrospective observational study at the tertiary hospital in northern Tanzania. We included 53 patients who underwent double or triple bypass surgery for pancreatic malignancy between January 2019 to December 2022 at Kilimanjaro Christian Medical Centre (KCMC), Tanzania. Data was collected from medical records, analyzing demographics, comorbidities, pre-surgery and surgery details, and post-surgery outcomes. Descriptive statistics were used to summarize continuous variables as mean with standard deviation and categorical variables as percentages.

53 patients were analyzed, with a mean age of 63.2 years and a male to female ratio of 1.03:1. Jaundice was the most common presentation (77.4%). Of the patients, 74.5% had comorbidities, and the majority (81.1%) were uninsured. 50.9% of patients had a length of hospital stay shorter than 5 days, and 88.3% resumed normal oral intake. Palliation failure was observed in 22.6% of patients. The median survival time for the entire cohort of patients was 65 days. Patients with palliation failure had a significantly shorter mean survival time than those without complications (14.17 vs. 90 days, p = 0.001).

Bypass surgery remains a treatment of choice for palliating symptoms in patients with advanced pancreatic cancer. This study highlights the importance of prompt diagnosis of pancreatic tumors, especially in low-income countries, to achieve better outcomes.

Understanding the disease trajectories of specific diseases can provide important clinical insights. In this paper, we aimed to discover signature disease trajectories of 3 rare cancer types: pancreatic cancer, soft tissue sarcoma (STS) of the trunk and extremity (STS-TE), and STS of the abdomen and retroperitoneum (STS-AR), leveraging IQVIA Oncology Electronic Medical Record. We identified significant diagnosis pairs in patients with these cancers through matched cohort sampling, statistical computation, right-tailed binomial hypothesis test, and visualized trajectories up to 3 progressions. Results included 266 significant diagnosis pairs for pancreatic cancer, 130 for STS-TE, and 118 for STS-AR. We further found 44 2-hop (i.e., 2-progression) and 136 3-hop trajectories before pancreatic cancer, 36 2-hop and 37 3-hop trajectories before STS-TE, and 17 2-hop and 5 3-hop trajectories before STS-AR. Meanwhile, we found 54 2-hop and 129 3-hop trajectories following pancreatic cancer, 11 2-hop and 17 3-hop trajectories following STS-TE, 5 2-hop and 0 3-hop trajectories following STS-AR. Systematic validation of discovered trajectories with the UTHealth Electronic Health Records confirmed the feasibility and reliability of our method. Our result suggested that some key clinical features can potentially serve as early markers of rare cancers. This approach is generalizable to other disease types and real-world longitudinal patient records.

The pancreas, an organ with dual functions, regulates blood glucose levels through the endocrine system by secreting hormones such as insulin and glucagon. It also aids digestion through the exocrine system by secreting digestive enzymes. Complex interactions and signaling mechanisms between the endocrine and exocrine functions of the pancreas play a crucial role in maintaining metabolic homeostasis and overall health. Compelling evidence indicates direct and indirect crosstalk between the endocrine and exocrine parts, influencing the development of diseases affecting both. From a developmental perspective, the exocrine and endocrine parts share the same origin-the "tip-trunk" domain. In certain circumstances, pancreatic exocrine cells may transdifferentiate into endocrine-like cells, such as insulin-secreting cells. Additionally, several pancreatic diseases, including pancreatic cancer, pancreatitis, and diabetes, exhibit potential relevance to both endocrine and exocrine functions. Endocrine cells may communicate with exocrine cells directly through cytokines or indirectly by regulating the immune microenvironment. This crosstalk affects the onset and progression of these diseases. This review summarizes the history and milestones of findings related to the exocrine and endocrine pancreas, their embryonic development, phenotypic transformations, signaling roles in health and disease, the endocrine-exocrine crosstalk from the perspective of diseases, and potential therapeutic targets. Elucidating the regulatory mechanisms of pancreatic endocrine and exocrine signaling and provide novel insights for the understanding and treatment of diseases.

Although the pancreatic cancer genome has been described, it has not been explored with respect to stages of diagnosis or treatment bottlenecks. We now describe and quantify the genomic features of PDAC in the context of evolutionary metrics and in doing so have identified a novel prognostic biomarker.

Chronic diseases such as diabetes and cancer are the leading causes of mortality worldwide. Receptors for Advanced Glycation End products (RAGEs) are ubiquitous factors that catalyse Advanced Glycation End products (AGEs), proteins, and lipids that become glycated from sugar ingestion. RAGEs are cell surface receptor proteins and play a broad role in mediating the effects of AGEs on cells, contributing to modifying biological macromolecules like proteins and lipids, which can cause Reactive Oxygen Species (ROS) generation, inflammation, and cancer. We targeted RAGE inhibition analysis and screening of United States Food and Drug Administration (FDA) libraries through molecular docking studies that identified the four most suitable FDA compounds: Zytiga, Paliperidone, Targretin, and Irinotecan. We compared them with the control substrate, Carboxymethyllysine, which showed good binding interaction through hydrogen bonding, hydrophobic interactions, and π-stacking at active site residues of the target protein. Following a 100 ns simulation run, the docked complex revealed that the Root Mean Square Deviation (RMSD) values of two drugs, Irinotecan (1.3 ± 0.2 nm) and Paliperidone (1.2 ± 0.3 nm), were relatively stable. Subsequently, the Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) determined that the Paliperidone molecule had a high negative energy of -13.49 kcal/mol, and the Absorption, Distribution, Metabolism, and Excretion (ADME) properties were in control for use in the mentioned cases. We extended this with many in vitro studies, including an immunoblotting assay, which revealed that RAGEs with High Mobility Group Box 1 (HMGB1) showed higher expression, while RAGEs with Paliperidone showed lower expressions. Furthermore, cell proliferation assay and Apoptosis assay (Annexin-V/PI staining) results revealed that Paliperidone was an effective anti-glycation and anti-apoptotic drug-however, more extensive in vivo studies are needed before its use.

Pancreatic cancer poses a significant challenge in individuals with diabetes, prompting a reevaluation of established risk factors beyond conventional glycemic control measures.

To explore the complex interplay of metabolic and psychosocial determinants in pancreatic cancer risk among individuals with diabetes, challenging prevailing perspectives and advocating for a comprehensive approach.

A total of 21,945 UK Biobank participants with baseline diabetes diagnosis were analyzed. Social isolation was assessed through a questionnaire capturing five factors: household size, social activities, friend/family visits, loneliness, and confiding in others. Incident pancreatic cancer was identified using ICD codes. Baseline characteristics, insulin use, and other relevant factors were analyzed. Hazard ratios and mediation analyses were conducted to determine the relationship between social isolation, inflammation, and pancreatic cancer risk.

Individuals with high social isolation were more likely to be male, smokers, non-drinkers, and have shorter sleep duration. They also had an increased risk of pancreatic cancer (HR = 2.65, 95% CI = 1.12-6.24) compared to those with low social isolation. Mediation analyses highlighted inflammation as a crucial mediator, with the proportion mediated by inflammation being 19.44% for insulin use, 10.34% for smoking, and 8.33% for social isolation.

Our findings highlight the importance of psychosocial factors in pancreatic cancer risk and underscore the need for further research to elucidate the underlying mechanisms.

Background The relationship between physical activity and incident pancreatic cancer is poorly defined, and the evidence to date is inconsistent, largely due to small sample sizes and insufficient incident outcomes. Using the UK Biobank cohort dataset, the association between physical activity levels at recruitment and incident pancreatic ductal adenocarcinoma (PDAC) at follow-up was analysed. Method Physical activity, the key exposure, was quantified using Metabolic Equivalent Task (MET) values and categorised into walking, moderate, and vigorous activity. These categories were each analysed in quartiles. Summed activity was analysed both in quartiles and using International Physical Activity Questionnaire (IPAQ) activity levels (low, moderate, high). Univariate hazard ratios (HRs) and multivariable-adjusted HRs (aHRs) with 95% confidence intervals (CIs) were calculated using Cox regression analyses. Results A total of 542 incident PDAC cases and 2,139 controls (1:4 matching for age and sex) with a median (IQR) follow-up of 6.8 (1.7) years were analysed. No significant association was found in walking, moderate, and vigorous activities. In summed activity, only the 3rd quartile showed a statistically significant inverse association with PDAC risk (aHR 0.67, 95% CI 0.52-0.86, p<0.01). For IPAQ activity, the moderate and high activity groups showed borderline statistically significant associations with incident PDAC (aHR 0.80, 95% CI 0.63-1.00, p=0.05, and aHR 0.80, 95% CI 0.64-1.01, p=0.06, respectively). Conclusion The large UK Biobank cohort study did not show a strong association between physical activity levels and the development of incident PDAC.

In this study, Diels-Alder reaction was performed to sulfolene and endo/exo-diacetate compounds. After a series of reactions, new conduritol A and F analogs containing oxo-bridge and naphthalene rings in their structures were synthesized. To the starting compound, bromination, elimination, singlet oxygen reaction, acetylation, selective oxidation with osmium tetroxide (OsO4), and m-chloroperbenzoic acid (m-CPBA), re-acetylation, and finally hydrolysis of the compounds by NH3(g)/MeOH reactions were carried out. 1H NMR, 13C NMR, IR, and elemental analysis elucidated the structures of all synthesized compounds. The α, β-glucosidase, and α-amylase inhibitory potentials of the new polycyclitols, conduritol A and F analogs, were examined for biological activity. Also, enzyme kinetic studies of well-active compounds were carried out. Compound 30 showed the best inhibition activity against α, β-glucosidase, and α-amylase enzymes. Compound 28a showed the best activity against L929 and Capan-1 cell lines, and compound 22 showed the best activity against the A549 fibroblast cell line. Moreover, hemolysis (ASTM F756 standard) and genotoxicity test results were recorded.

The incidence rate of pancreatic cancer, a fatal illness with a meager 5-year survival rate, has been on the rise in recent times. When individuals accumulate excessive amounts of adipose tissue, the adipose organ becomes dysfunctional due to alterations in the adipose tissue microenvironment associated with inflammation and metabolism. This phenomenon may potentially contribute to the aberrant accumulation of fat that initiates pancreatic carcinogenesis, thereby influencing the disease's progression, resistance to treatment, and metastasis. This review presents a summary of the impact of pancreatic steatosis, visceral fat, cancer-associated adipocytes and lipid diets on the advancement of pancreatic cancer, as well as the reciprocal effects of pancreatic cancer on adipose tissue. Understanding the molecular mechanisms underlying the relationship between dysfunctional adipose tissue and pancreatic cancer better may lead to the discovery of new therapeutic targets for the disease's prevention and individualized treatment. This is especially important given the rising global incidence of obesity, which will improve the pancreatic cancer treatment options that are currently insufficient.

Pancreatic cancer serves as the third leading cause of cancer-associated morbidity and mortality in the United States, with a 5-year survival rate of only 12% with an expected increase in incidence and mortality in the coming years. Pancreatic ductal adenocarcinomas constitute most pancreatic malignancies. Certain genetic syndromes, including Lynch syndrome, hereditary breast and ovarian cancer syndrome, hereditary pancreatitis, familial adenomatous polyposis, Peutz-Jeghers syndrome, familial pancreatic cancer mutation, and ataxia telangiectasia, confer a significantly higher risk. Screening for pancreatic malignancies currently targets patients with germline mutations or those with significant family history. Screening the general population is not currently viable owing to overall low incidence and lack of specific tests. Endoscopic ultrasound (EUS) and its applied advances are increasingly being used for surveillance, diagnosis, and management of pancreatic malignancies and have now become an indispensable tool in their management. For patients with risk factors, EUS in combination with magnetic resonance imaging/magnetic resonance cholangiopancreatography is used for screening. The role of endoscopic modalities has been expanding with the increased utilization of endoscopic retrograde cholangiopancreatography, EUS-directed therapies include EUS-guided fine-needle aspiration and EUS-fine-needle biopsy (FNB). EUS combined with FNB has the highest specificity and sensitivity for detecting pancreatic cancer amongst available modalities. Studies also recognize that artificial intelligence assisted EUS in the early detection of pancreatic cancer. At the same time, surgical resection has been historically considered the only curative treatment for pancreatic cancer, over 80% of patients present with unresectable disease. We also discuss EUS-guided therapies of physicochemicals (radiofrequency ablation, brachytherapy, and intratumor chemotherapy), biological agents (gene therapies and oncolytic viruses), and immunotherapy. We aim to perform a detailed review of the current burden, risk factors, role of screening, diagnosis, and endoscopic advances in the treatment modalities available for pancreatic cancer.

To examine the characteristics of patients with pancreatic cancer with long-term survival.

Although pancreatic cancer is a highly lethal malignancy, a minority of patients experience long-term survival. The characteristics of these patients remain largely unidentified.

An indolent subgroup was established using carbohydrate antigen 19-9 (CA19-9), which is the best-validated biomarker for pancreatic cancer. Of 1558 patients, 13.9% were included in the CA19-9-normal (≤37 U/mL) subgroup.

A normal CA19-9 level was an independent variable for overall survival (median survival, 18.1 vs 9.7 months, hazard ratio = 0.53, P < 0.001). The 5-year survival of patients with stage IV CA19-9-normal cancer was higher than that of patients with stage I-IV CA19-9-high cancer (22.4% vs 6.8%, P = 0.034). The CA19-9-normal subgroup exhibited reduced levels of circulating glucose ( P < 0.001) and increased expression of insulin ( P < 0.001) compared with the CA19-9-high subgroup. Glucose was a substrate for CA19-9 biosynthesis through the hexosamine biosynthesis pathway. In addition, in pancreatic cancer animal models of diabetes, glucose control decreased CA19-9 levels and improved overall survival. In a clinical trial (NCT05306028) of patients before undergoing major anticancer treatments, glucose control decreased CA19-9 levels in 90.9% of the patients.

CA19-9-normal pancreatic cancer is a strikingly indolent subgroup with low glucose and high insulin. Glucose control is a promising therapeutic strategy for pancreatic cancer.

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 cancer (PC) is a malignant tumour with poor prognosis and high mortality, and high fasting plasma glucose (HFPG) is considered to be one of its important risk factors.

PC disease burden data were obtained from the Global Burden of Disease Study 2021 (GBD 2021) database. Annual percent change (APC), average APC (AAPC), and 95% confidence interval (95% CI) were analysed using joinpoint linkpoint regression models to assess the trend of PC burden of disease between 1990 and 2021. An age-period-cohort model was used to estimate the independent effects of age, period, and cohort on PC burden, and data on PC mortality attributable to HFPG in China from 2022 to 2032 were analysed on the basis of a Bayesian age-period-cohort model projection.

The number of Pc deaths due to HFPG continue to rise in China from 1990 to 2021, with age-standardised mortality (ASMR) and age-standardised disability-adjusted life-year rates with increasing AAPC values of 1.12% (95% CI, 0.73-1.52) and 1.00% (95% CI, 0.63-1.37), respectively. Throughout the study, we found that the overall level of PC disease burden was significantly higher in men than that in women. In age-period-cohort analyses, the age effect of PC showed an increasing and then decreasing trend, the period effect showed an overall increasing trend during the study period, and the cohort effect showed an overall slow decreasing trend. In addition, the BAPC model predicted that ASMR is expected to decline significantly in both men and women from 2022 to 2032.

It was found that PC attributable to HFPG was generally on the rise in China from 1990 to 2021 and has been on the decline in recent years, and projections suggest that the country's future PC disease burden will continue to show a downward trend. Age and period of birth are the main factors affecting the disease burden, especially in men and older age groups. Early prevention, regular screening, and research into the pathogenesis of PC have, therefore, become particularly important.

Pancreatic cancer (PC) has one of the highest mortality to incidence ratio of all cancers. Early identification of at-risk individuals should permit early diagnosis. Genome-wide association studies showed the association of several genetic variants with PC risk in multi-ethnic populations. Our objective was to examine the association of these genetic variants with PC in a population sample from Kuwait.

DNA samples from 103 pancreatic ductal adenocarcinoma (PDAC) specimens and 132 healthy controls were used for genotyping ABO rs505922, BCAR1 rs7190458, LINC-PINT rs6971499, HNF1B rs4795218, VDR rs2228570 rs731236, and PRSS1 rs111033565 rs111033568 rs387906698 and rs267606982 using TaqMan genotyping assays, and VDR expression was performed by immunocytochemistry.

ABO rs505922C and VDR rs2228570A were associated with PDAC risk (odds ratio (OR): 1.55, 95% confidence interval (CI): 1.07 - 2.24, P = 0.027; OR: 1.64, 95% CI: 1.09 - 2.48, P = 0.024; respectively). An unweighted polygenic risk score (ABO rs505922, BCAR1 rs7190458, LINC-PINT rs6971499, and HNF1B rs4795218) was significantly associated with PDAC risk (β: -0.11, 95% CI: -0.15 to -0.05, P < 0.001). VDR expression was downregulated or absent in most PDAC specimens regardless of VDR haplotype.

ABO rs505922C and VDR rs2228570A are PDAC genetic risk factors in our population. Ethnicity influences the association of reported genetic PDAC risk factors and should be adjusted for when performing PDAC genetic risk estimations. Investigation of these genetic risk factors in other ethnic populations is a necessity to evaluate their PDAC risk prediction potential.

Background/Objectives: Pancreatic cancer remains one of the deadliest malignancies worldwide with a pressing need for early detection and intervention strategies. Emerging evidence has suggested a potential link between pancreas steatosis, characterized by excessive pancreatic fat accumulation, and an increased risk of pancreatic cancer development. This retrospective imaging study aims to elucidate the association between pancreatic steatosis and the subsequent development of pancreatic cancer. In the study, we aimed to determine the characteristics of pancreatic cancer with pancreatic steatosis. Methods: During the period of January 2022 to December 2022, we conducted a retrospective study, collecting 101 newly diagnosed pancreas cancer cases from the available image datasets. A comprehensive database of retrospective abdominal imaging studies, comprising computed tomography (CT) and magnetic resonance imaging (MRI), was established from a diverse patient population and subsequently analyzed. Inclusion criteria encompassed patients having available baseline imaging data, allowing for the assessment of pancreatic fat content. Pancreatic fat content was quantified using validated radiological techniques, while demographic, clinical, and histopathological data were all collected. The clinical data and patient characteristics were collected from medical records and analyzed. Results: Preliminary analysis revealed a significant correlation between elevated pancreatic fat content and an increased incidence of subsequent pancreatic cancer. Moreover, subgroup analysis based on age, gender, and comorbidities provided valuable insight into potential risk factors associated with this progression. Additionally, the study identified novel radiological markers that may serve as early indicators of pancreatic cancer development in individuals with pancreatic steatosis. Conclusions: In the imaging study, approximately 30% (30/101) of pancreatic cancer patients presented with pancreatic steatosis. Chronic pancreatitis emerged as the primary factor contributing to pancreatic steatosis in these patients. Importantly, pancreatic steatosis did not significantly impact the prognosis of pancreatic cancer. Follow-up data revealed no significant differences in survival duration between patients with or without pancreatic steatosis. Additionally, no association was found between pancreatic steatosis and hepatic steatosis.

Prolonging life is a global trend, and more medical expenditure is being spent on chronic diseases owing to population aging. Diseases commonly seen in middle-aged and elderly people, such as heart disease and diabetes, have slowed mortality improvement in recent years. Diabetes is a common chronic disease and comorbidity of many serious health conditions. The total estimated cost of diabetes in the United States was $327 billion in 2017. However, many people are unaware that diabetes is common, and at least 21.4% of adults do not know that they have diabetes. The number of diabetes-related deaths has been increasing, and diabetes was the 5th cause of death in Taiwan in 2019. In this study, we explore the trend and influence of diabetes in Taiwan and apply mortality models, such as the Lee-Carter and Age-Period-Cohort models, using data from Taiwan's National Insurance to model the incidence and mortality rates of diabetes. We found that the Lee-Carter model provides fairly satisfactory estimates and that people with diabetes regularly taking diabetes medication have lower mortality rates. Moreover, we demonstrate how these results can be used to design diabetes related insurance products and prepare the insured to face the impact of incurring diabetes. In addition, we consider different criteria for judging whether people have diabetes (as there is no consensus on these criteria) and investigate the issue of moral hazard in designing diabetes insurance products.

Glucagon-like peptide-1 receptor agonist (GLP-1RA), a novel hypoglycemic agent for the treatment of type 2 diabetes, has well-known effects such as lowering blood sugar, ameliorating inflammation, reducing weight, and lowering blood lipids. It has also been shown that it can influence the proliferation and survival of cells and has a certain effect on the prognosis of some neoplastic diseases. In this study, the potential effects of GLP-1RAs on the occurrence and development of tumors were reviewed to provide new ideas for the prevention and treatment of tumors in patients.

Aggressive malignancies, such as pancreatic cancer, are increasingly impacting young, female populations. Our investigation centered on whether the observed trends in cancer incidence were unique to pancreatic cancer or indicative of a broader trend across various cancer types. To delve deeper into this phenomenon, we analyzed cancer incidence trends across different age and sex groups. Furthermore, we explored differences in cancer incidence within specific young subgroups aged 18 to 26 and 27 to 34, to better understand the emerging incidence trend among young individuals.

This study collected cancer incidence data from one of the Surveillance, Epidemiology, and End Results cancer registry databases (SEER22), with 10,183,928 total cases from 2000 to 2020. Data were analyzed through Joinpoint trend analysis approach to evaluate sex- and age-specific trends in cancer incidence. Exposure rates were reported as Average Annual Percentage Changes (AAPCs).

The analysis revealed significant age and sex-specific disparities, particularly among individuals aged 18-26 and 27-34. Pancreatic cancer incidence rates increased more in females aged 18-26 (AAPC, 9.37% [95% CI, 7.36-11.41%]; p < .0001) than in males (4.43% [95% CI, 2.36-6.53%]; p < .0001). Notably, among gender, age, and other malignancies, young females had the highest AAPCs for pancreatic cancer. Additionally, the incidence of gastric cancer, myeloma, and colorectal malignancies also showed higher AAPCs in young females compared to males.

Recognizing emerging risk populations for highly lethal malignancies is crucial for early detection and effective disease management.

New-onset diabetes represent a high-risk cohort to screen for pancreatic cancer.

Develop a machine model to predict pancreatic cancer among patients with new-onset diabetes.

A retrospective cohort of patients with new-onset diabetes was assembled from multiple health care networks in the United States. An XGBoost machine learning model was designed from a portion of this cohort (the training set) and tested on the remaining part of the cohort (the test set). Shapley values were used to explain the XGBoost's model features. Model performance was compared with 2 contemporary models designed to predict pancreatic cancer among patients with new-onset diabetes.

In the test set, the XGBoost model had an area under the curve of 0.80 (0.76 to 0.85) compared with 0.63 and 0.68 for other models. Using cutoffs based on the Youden index, the sensitivity of the XGBoost model was 75%, the specificity was 70%, the accuracy was 70%, the positive predictive value was 1.2%, and the negative predictive value was >99%. The XGBoost model obtained a positive predictive value of at least 2.5% with a sensitivity of 38%. The XGBoost model was the only model that detected at least 50% of patients with cancer one year after the onset of diabetes. All 3 models had similar features that predicted pancreatic cancer, including older age, weight loss, and the rapid destabilization of glucose homeostasis.

Machine learning models isolate a high-risk cohort from those with new-onset diabetes at risk for pancreatic cancer.

Propensity score matching (PSM) was used to investigate the prognostic value of a novel GLUCAR index [Glucose × (C-reactive protein ÷ albumin)] in unresectable locally advanced pancreatic cancer (LA-NPC) patients who received definitive concurrent chemoradiotherapy (CCRT).

The PSM analysis comprised 142 LA-PAC patients subjected to definitive CCRT. Receiver operating characteristic (ROC) curve analysis was utilized to identify relevant pre-CCRT cutoffs that could effectively stratify survival results. The primary and secondary objectives were the correlations between the pre-CCRT GLUCAR measures and overall survival (OS) and progression-free survival (PFS).

The ROC analysis revealed significance at 43.3 for PFS [area under the curve (AUC): 85.1%; sensitivity: 76.8%; specificity: 74.2%; J-index: 0.510)] and 42.8 for OS (AUC: 81.8%; sensitivity: 74.2%; specificity: 71.7%; J-index: 0.459). Given that these cutoff points were close, the standard cutoff point, 42.8, was selected for further analysis. Comparative survival analyses showed that pre-CCRT GLUCAR ≥ 42.8 (n = 71) measures were associated with significantly shorter median PFS (4.7 vs. 15.8 months; p < 0.001) and OS (10.1 vs. 25.4 months; p < 0.001) durations compared to GLUCAR < 42.8 measures (n = 71). The multivariate analysis results confirmed the independent significance of the GLUCAR index on PFS (p < 0.001) and OS (p < 0.001) outcomes.

Elevated pre-CCRT GLUCAR levels are robustly and independently linked to significantly poorer PFS and OS outcomes in unresectable LA-PAC patients treated with definitive CCRT.

The endocrine and exocrine compartments of the pancreas are spatially related but functionally distinct. Multiple diseases affect both compartments, including type 1 diabetes (T1D), pancreatitis, cystic fibrosis, and pancreatic cancer. To better understand how the exocrine pancreas changes with age, obesity, and diabetes, we performed a systematic analysis of well-preserved tissue sections from the pancreatic head, body, and tail of organ donors with T1D (n = 20) or type 2 diabetes (T2D) (n = 25) and donors with no diabetes (ND; n = 74). Among ND donors, we found that the incidence of acinar-to-ductal metaplasia (ADM), angiopathy, and pancreatic adiposity increased with age, and ADM and adiposity incidence also increased with BMI. Compared with age- and sex-matched ND organs, T1D pancreata had greater rates of acinar atrophy and angiopathy, with fewer intralobular adipocytes. T2D pancreata had greater rates of ADM and angiopathy and a higher total number of T lymphocytes, but no difference in adipocyte number, compared with ND organs. Although total pancreatic fibrosis was increased in both T1D and T2D, the patterns were different, with periductal and perivascular fibrosis occurring more frequently in T1D pancreata and lobular and parenchymal fibrosis occurring more frequently in T2D. Thus, the exocrine pancreas undergoes distinct changes as individuals age or develop T1D or T2D.

Type II diabetes is associated with cancer risk in the general population but has not been well studied as a risk factor for subsequent malignancies among cancer survivors. We investigated the association between diabetes and subsequent cancer risk among older (66-84 years), 1-year breast cancer survivors within the linked Surveillance Epidemiology and End Results (SEER)-Medicare database using Cox regression analyses to quantify hazard ratios (HR) and corresponding 95% confidence intervals (95% CI). Among 133 324 women, 29.3% were diagnosed with diabetes before or concurrent with their breast cancer diagnosis, and 10 452 women developed subsequent malignancies over a median follow-up of 4.3 years. Diabetes was statistically significantly associated with liver (HR = 2.35, 95% CI = 1.48 to 3.74), brain (HR = 1.94, 95% CI = 1.26 to 2.96), and thyroid cancer risks (HR = 1.38, 95% CI = 1.01 to 1.89). Future studies are needed to better understand the spectrum of subsequent cancers associated with diabetes and the role of diabetes medications in modifying subsequent cancer risk, alone or in combination with cancer treatments.

GLP-1 RAs are widely used for T2DM treatment due to their cardiorenal and metabolic benefits. This study examines the risk of pancreatic cancer with GLP-1 RA use in patients with T2DM.

We analyzed TriNetX's deidentified research database using the U.S. Collaborative Network comprising 62 healthcare organizations across the U.S.A. Patients with T2DM were split into two cohorts: one receiving GLP-1 RAs, and one not receiving GLP-1 RAs. We excluded patients with known risk factors for pancreatic cancer, including pancreatic cysts, a personal or family history of BRCA1, BRCA2, CDKN2A, KRAS, MEN1, MLH1, MSH2, NOTCH1, PALB2, PMS2, and PRSS1S genes, family history of pancreatic cancer, and VHL syndrome. Using a 1:1 propensity score-matching model based on baseline characteristics and comorbidities, we created comparable cohorts. We then compared the rate of pancreatic cancer between the two cohorts at a 7-year interval.

Out of 7,146,015 identified patients with T2DM, 10.3% were on a GLP-1 RA and 89.7% were not. Post-PSM, 721,110 patients were in each group. Patients on GLP-1 RAs had a 0.1% risk compared to a 0.2% risk of pancreatic cancer in the 7-year timeframe.

The use of GLP-1 RAs in patients with type 2 diabetes mellitus (T2DM) does not appear to substantially elevate the risk of pancreatic cancer; in fact, it may potentially exert a protective effect.

To determine the relationship of diabetes with pancreatic cancer incidence among African American and Whites of similar socio-economic status.

Using the Southern Community Cohort Study, we conducted a follow-up during 2002-2015 of pancreatic cancer incidence of 73,378 mostly low-income participants aged 40-79 years; 15,913 reported diabetes at baseline. Multivariable Cox analysis controlling for sex, family history of pancreatic cancer, BMI, smoking status, alcohol consumption, education, income and other important covariates, and with age as the timescale was used.

Totally, 265 incident pancreatic cancer cases were observed. Pancreatic cancer risk was increased among those with diabetes (HR 1.54, CI 1.16-2.05), with similar increases among African Americans (HR 1.51, CI 1.08-2.11) and Whites (HR 1.78, CI 1.00-3.16). No trend in risk was observed for diabetes duration among those with diabetes, with HRs of 1.39 (0.91-2.11), 2.31 (1.51-3.54) and 1.23 (0.80-1.89) for <5, 5-9 and 10+ years duration, respectively. African Americans were at increased risk of pancreatic cancer (HR = 1.40, 95% CI 1.05-1.87), which persisted after adjusting for diabetes (HR 1.36, CI 1.02-1.81). The effect sizes for other pancreatic cancer risk factors with pancreatic cancer were similar by diabetes status, although a stronger association with low BMI was evident among those with diabetes.

Diabetes increases pancreatic cancer risk similarly among African Americans and Whites in this Southern U.S.

The incidence of pancreatitis and pancreatic cancer is on the upswing in the USA. These conditions often lead to higher healthcare costs due to the complex nature of diagnosis and the need for specialized medical interventions, surgical procedures, and prolonged medical management. The economic ramification encompasses direct healthcare expenses and indirect costs related to productivity losses, disability, and potential long-term care requirements. Increasing evidence underscores the importance of a healthy lifestyle in preventing and managing these conditions. Lifestyle medicine employs evidence-based interventions to promote health through six key pillars: embracing a whole-food, plant-predominant dietary pattern; regular physical activity; ensuring restorative sleep; managing stress effectively; removing harmful substances; and fostering positive social connections. This review provides a comprehensive overview of lifestyle interventions for managing and preventing the development of pancreatitis and pancreatic cancer.

Exposure to polycyclic aromatic hydrocarbons (PAHs), byproducts of incomplete combustion, and their effects on the development of cancer are still being evaluated. Recent studies have analyzed the relationship between PAHs and tobacco or dietary intake in the form of processed foods and smoked/well-done meats. This study aims to assess the association of a blood biomarker and metabolite of PAHs, r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (PheT), dietary intake, selected metabolism SNPs, and pancreatic cancer. Demographics, food-frequency data, SNPs, treatment history, and levels of PheT in plasma were determined from 400 participants (202 cases and 198 controls) and evaluated based on pancreatic adenocarcinoma diagnosis. Demographic and dietary variables were selected based on previously published literature indicating association with pancreatic cancer. A multiple regression model combined the significant demographic and food items with SNPs. Final multivariate logistic regression significant factors (p-value < 0.05) associated with pancreatic cancer included: Type 2 Diabetes [OR = 6.26 (95% CI = 2.83, 14.46)], PheT [1.03 (1.02, 1.05)], very well-done red meat [0.90 (0.83, 0.96)], fruit/vegetable servings [1.35 (1.06, 1.73)], recessive (rs12203582) [4.11 (1.77, 9.91)], recessive (rs56679) [0.2 (0.06, 0.85)], overdominant (rs3784605) [3.14 (1.69, 6.01)], and overdominant (rs721430) [0.39 (0.19, 0.76)]. Of note, by design, the level of smoking did not differ between our cases and controls. This study does not provide strong evidence that PheT is a biomarker of pancreatic cancer susceptibility independent of dietary intake and select metabolism SNPs among a nonsmoking population.

Pancreatic cancer (PC) is a common malignant tumor of the digestive system, and its 5-year survival rate is only 4%. N6-methyladenosine (m6A) RNA methylation is the most common post-transcriptional modification and dynamically regulates cancer development, while its role in PC treatment remains unclear.

We treated PC cells with gemcitabine and quantified the overall m6A level with m6A methylation quantification. Real-time quantitative reverse transcription polymerase chain reaction and Western blot analyses were used to detect expression changes of m6A regulators. We verified the m6A modification on the target genes through m6A-immunoprecipitation (IP), and further in vivo experiments and immunofluorescence (IF) assays were applied to verify regulation of gemcitabine on Wilms' tumor 1-associated protein (WTAP) and MYC.

Gemcitabine inhibited the proliferation and migration of PC cells and reduced the overall level of m6A modification. Additionally, the expression of the "writer" WTAP was significantly downregulated after gemcitabine treatment. We knocked down WTAP in cells and found target gene MYC expression was significantly downregulated, m6A-IP also confirmed the m6A modification on MYC. Our experiments showed that m6A-MYC may be recognized by the "reader" IGF2BP1. In vivo experiments revealed gemcitabine inhibited the tumorigenic ability of PC cells. IF analysis also showed that gemcitabine inhibited the expression of WTAP and MYC, which displayed a significant trend of co-expression.

Our study confirmed that gemcitabine interferes with WTAP protein expression in PC, reduces m6A modification on MYC and RNA stability, thereby inhibiting the downstream pathway of MYC, and inhibits the progression of PC.

The unexpected rise in cancer and diabetes statistics has been a significant global threat, inciting ongoing research into various biomarkers that can act as innovative therapeutic targets for their management. The recent discovery of how EZH2-PPARs' regulatory function affects the metabolic and signalling pathways contributing to this disease has posed a significant breakthrough, with the synergistic combination of inhibitors like GSK-126 and bezafibrate for treating these diseases. Nonetheless, no findings on other protein biomarkers involved in the associated side effects have been reported. As a result of this virtual study, we identified the gene-disease association, protein interaction networks between EZH2-PPARs and other protein biomarkers regulating pancreatic cancer and diabetes pathology, ADME/Toxicity profiling, docking simulation and density functional theory of some natural products. The results indicated a correlation between obesity and hypertensive disease for the investigated biomarkers. At the same time, the predicted protein network validates the link to cancer and diabetes, and nine natural products were screened to have versatile binding capacity against the targets. Among all natural products, phytocassane A outperforms the standard drugs' (GSK-126 and bezafibrate) in silico validation for drug-likeness profiles. Hence, these natural products were conclusively proposed for additional experimental screening to complement the results on their utility in drug development for diabetes and cancer therapy against the EZH2-PPARs' new target.

The association between oral microbiota and pancreatic cancer (PC) is increasingly recognized and studied. Yet, contrasting results are seen in current studies. This study aimed to provide systematic review and meta-analysis comparing PC and oral microbiota.

Studies related to the association between oral microbiota and PC were identified through digital databases including PubMed, Medline, EMBASE, COCHRANE, and SCOPUS without limitations on language or publication period. The last identification date was 10 March 2023. Three case-control studies concerning the issue were included. For the meta-analyses, RevMan software version 5.4 was used. The Newcastle-Ottawa scale was used to evaluate articles and measurement of study differences, and publication bias was shown.

Porphyromonas gingivalis in oral bacteria was detected at a comparatively high detection rate in PC patients compared with healthy controls (odds ratio [OR], 1.38; 95 % confidence interval [CI], 1.09-1.74; P = 0.007; I2 = 34 %). The detection rate did not differ significantly between PC patients and healthy control patients for Aggregatibacter actinomycetemcomitans (OR 0.98; 95 % CI 0.75-1.29; P = 0.90; I2 = 76 %); Tannerella forsythiaand (OR 1.12; 95 % CI 0.89-1.42; P = 0.33; I2 = 0 %), or Prevotella intermedia (OR 1.08; 95 % CI 0.84-1.39; P = 0.55; I2 = 0 %).

Oral microbiota were closely related to PC, whereas P. gingivalis was more commonly found in the PC patients than in the healthy controls. For patients with PC, P. gingivalis may play a role in early diagnosis.

The combination of nivolumab + relatlimab is superior to nivolumab alone in the treatment of naive patients and has activity in PD-1 refractory melanoma. We had previously observed a reduced expression of LAG3 in melanoma tissue from patients with type 2 diabetes.

To evaluate the impact of diabetes on oncological outcomes of patients with advanced melanoma treated with nivolumab plus the LAG3 inhibitor relatlimab we performed a retrospective multicenter study.

Overall, 129 patients were included: 88 without diabetes before the treatment, 37 who were diagnosed with type 2 diabetes before the start of treatment, and 4 without diabetes before treatment who developed immune checkpoint inhibitor-induced diabetes (ICI-DM). PFS was 21.71 months (95% CI: 15.61-27.81) in patients without diabetes, 10.23 months (95% CI: 5.81-14.66) in patients with type 2 diabetes, and 50.85 months (95% CI: 23.04-78.65) in patients who developed ICI-DM. OS was 37.94 months (95% CI: 31.02-44.85) in patients without diabetes, 22.12 months (95% CI: 14.41-29.85) in those with type 2 diabetes and 57.64 months (95% CI: 42.29-72.99) in those who developed ICI-DM. Multivariate analysis showed that the presence of diabetes and LDH was correlated with OS and PFS. The mean OS was 64.63 months in subjects with low levels of glucose (< 137 mg/dl) and 36.27 months in those with high levels (hazard ratio 0.16, 95% CI: 0.04-0.58; p = 0.005). The patients whose glucose blood level increased after 3 months of treatment with nivolumab + relatinib compared to baseline (ratio of blood level at baseline/after 3 months > 1.5) had a worse prognosis than those whose glucose level had not increased. This result was observed also in subgroups treated either in first line or further lines. Patients who developed ICI-DM during the study period had better outcomes than the overall population and patients without diabetes.

LAG3 inhibition for treating metastatic or unresectable melanoma has a reduced efficacy in patients with type 2 diabetes, possibly due to a low expression of LAG3 in tumor tissue. Higher level evidence should be obtained.

Adherence to the diabetes risk reduction diet (DRRD) may potentially reduce the risk of developing head and neck cancer (HNC) as the diet includes fruits and limits red and processed meats, known risk factors for HNC. However, there is currently no epidemiological research to investigate this potential association.

The present study utilized data on demographics, lifestyles, medications, and diets of participants from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial to explore the potential association between adherence to DRRD and the risk of HNC. We used a DRRD score to evaluate adherence to the dietary pattern and employed Cox regression analysis to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for HNC risk. Several subgroup analyses were carried out to identify potential effect modifiers, and multiple sensitivity analyses were performed to evaluate the stability of the correlation. The nine components of the DRRD was assessed separately for its association with the risk of HNC.

During a mean follow up of 8.84 years, 279 cases of HNC were observed. DDRD score was found to be inversely associated with the risk of HNC (HR Q4 vs. Q1: 0.582; 95% CI: 0.396, 0.856; p = 0.005 for trend) in a linear dose-response manner (p = 0.211 for non-linearity). Subgroup analysis indicated this inverse correlation was more pronounced among participants who had never smoked (HRQ4 vs. Q1: 0.193; 95% CI: 0.073, 0.511; p < 0.001 for trend) compared to current or former smokers (p = 0.044 for interaction). The primary association of DDRD and HNC risk remained robust after several sensitivity analyses. Regarding the individual components of DRRD, an inverse association was also observed between the risk of HNC and increased intake of cereal fiber and whole fruit (all p < 0.05 for trend).

Our findings provide evidence that following the DRRD pattern may reduce the risk of NHC, especially for non-smokers.

Since the majority of patients with pancreatic cancer (PC) develop insulin resistance and/or diabetes mellitus (DM) prior to PC diagnosis, PC-induced diabetes mellitus (PC-DM) has been a focus for a potential platform for PC detection. In previous studies, the PC-derived exosomes were shown to contain the mediators of PC-DM. In the present study, the response of normal pancreatic islet cells to the PC-derived exosomes was investigated to determine the potential biomarkers for PC-DM, and consequently, for PC. Specifically, changes in microRNA (miRNA) expression were evaluated. The miRNA specimens were prepared from the untreated islet cells as well as the islet cells treated with the PC-derived exosomes (from 50 patients) and the healthy-derived exosomes (from 50 individuals). The specimens were subjected to next-generation sequencing and bioinformatic analysis to determine the differentially expressed miRNAs (DEmiRNAs) only in the specimens treated with the PC-derived exosomes. Consequently, 24 candidate miRNA markers, including IRS1-modulating miRNAs such as hsa-miR-144-5p, hsa-miR-3148, and hsa-miR-3133, were proposed. The proposed miRNAs showed relevance to DM and/or insulin resistance in a literature review and pathway analysis, indicating a potential association with PC-DM. Due to the novel approach used in this study, additional evidence from future studies could corroborate the value of the miRNA markers discovered.