To explore the complex interactions between the tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) and the loss of β-cell mass, further elucidating the mechanisms of type 3c diabetes mellitus (T3cDM) onset.

Single-cell RNA sequencing was employed to analyze the PDAC TME, identifying cell interactions and gene expression changes of endocrine cells. Pathological changes and paraneoplastic islets were assessed in the proximal paratumor (PP) and distal paratumor (DP). Fractional β-cell area and islet density were compared among normal pancreas from donors and paraneoplastic tissues from non-diabetes mellitus (NDM) and T3cDM patients. TUNEL staining, RT-qPCR and CCK8 assay were applied to demonstrate the β-cell apoptosis.

Tumor cells, immune cells and fibroblasts could interact with endocrine cells, and apoptotic pathways were activated in endocrine cells of the PP. The PDAC TME was characterized by marked inflammation, sever fibrosis and atrophy. The islets in the PP had lower fractional β-cell area (0.68 ± 0.65% vs. 0.86 ± 1.02%, P = 0.037) and islet density (0.54 ± 0.42 counts/mm2 vs. 0.83 ± 0.90 counts/mm2, P = 0.001) compared to those in the DP. The PDAC TME in T3cDM exerted a more significant impact on the paraneoplastic islets compared to NDM. Moreover, β-cell apoptosis was markedly increased in the PP compared to the DP in PDAC patients without diabetes, particularly in smaller islets. Apoptosis-related genes were highly expressed in INS-1E cells exposed to PANC-1 medium.

Our research revealed that the PDAC TME is usually accompanied by some pathological changes, including inflammation, fibrosis, and atrophy. These pathological changes are related to a reduction in β-cell mass and trigger the development of T3cDM.

Pancreatic ductal adenocarcinoma (PDAC) is recognized as one of the most lethal malignancies, characterized by late-stage diagnosis and limited therapeutic options. Risk stratification has traditionally been performed using epidemiological studies and genetic analyses, through which key risk factors, including smoking, diabetes, chronic pancreatitis, and inherited predispositions, have been identified. However, the multifactorial nature of PDAC has often been insufficiently addressed by these methods, leading to limited precision in individualized risk assessments. Advances in artificial intelligence (AI) have been proposed as a transformative approach, allowing the integration of diverse datasets-spanning genetic, clinical, lifestyle, and imaging data into dynamic models capable of uncovering novel interactions and risk profiles. In this review, the evolution of PDAC risk stratification is explored, with classical epidemiological frameworks compared to AI-driven methodologies. Genetic insights, including genome-wide association studies and polygenic risk scores, are discussed, alongside AI models such as machine learning, radiomics, and deep learning. Strengths and limitations of these approaches are evaluated, with challenges in clinical translation, such as data scarcity, model interpretability, and external validation, addressed. Finally, future directions are proposed for combining classical and AI-driven methodologies to develop scalable, personalized predictive tools for PDAC, with the goal of improving early detection and patient outcomes.

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.

One percent of pancreatic adenocarcinoma (PDAC) patients are diagnosed with new onset diabetes (NOD) over the age of 50 years within 3 years. Therefore, NOD is a major factor for early diagnosis of PDAC. Research has focused on understanding the differences between NOD and type 2 diabetes, particularly in relation to PDAC. However, conflicting data exists regarding their impact on survival outcomes in PDAC patients. We performed this multi-center study to assess the prevalence and influence of NOD on clinical outcomes in patients with PDAC within a community-based hospital system.

We conducted a retrospective cohort study of 138 patients with biopsy-proven PDAC with localized/borderline disease (n=70), and metastatic disease (n=68) at three institutions from 2014 to 2021. NOD group consisted of pts diagnosed with diabetes [hemoglobin A1c (HbA1c) >6.5%] or pre-diabetes (HbA1c 5.7-6.4%) within the 3 years prior to PDAC diagnosis. Primary aim of the study was to determine the impact of NOD on clinical outcomes.

A total of 138 patients were included in the study, from which 30 met the criteria for NOD. No significant differences were noted in the demographic and clinical characteristics comparing patients based on NOD history. Comparing survival outcomes, NOD group was associated with worse overall survival (OS) in both the metastatic cohort [n=68, progression-free survival (PFS) 4.6 vs. 7.1 months, P=0.07; OS 7.1 vs. 13.2 months, P=0.01) and the resected cohort (n=40, PFS 8.4 vs. 19.3 months, P=0.04; OS 24.5 vs. 42.3 months, P=0.04). In multivariate analysis, the impact of NOD remained significant for OS and PFS in the resected cohort. Identifying common features amongst the NOD group, we found the entire cohort had a significant reduction in individual body mass index (BMI) 1 year prior to the NOD diagnosis (P=0.006).

NOD is associated with worse survival outcomes in patients with metastatic and resected PDAC. Reduction of BMI prior to diagnosis of NOD, warrants further investigation to be incorporated into the PDAC screening paradigm.

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.

Currently, those recommended to undergo pancreatic cancer (PC) surveillance include appropriately aged individuals at high risk of PC due to an identifiable genetic susceptibility or those without identifiable genetic susceptibility who nonetheless have a strong family history of PC. With increases in identification of individuals at high risk for PC and increased use of PC surveillance in clinical practice, there has been increasing debate about who should undergo surveillance as well as how surveillance should be performed including use of imaging and blood-based testing. Furthermore, there is increasing interest in the outcomes of PC surveillance in high-risk individuals with some studies demonstrating that surveillance leads to downstaging of PC and improvements in survival. In this review, we summarize the current state of PC surveillance in high-risk individuals, providing an overview of the risk factors associated with PC, selection of high-risk individuals for PC surveillance, and the current, but non-uniform, recommendations for performing PC surveillance. Additionally, we review approaches to apply various imaging and blood-based tests to surveillance and the outcomes of PC surveillance.

Routine screening to detect silent but deadly cancers such as pancreatic ductal adenocarcinoma (PDAC) can significantly improve survival, creating an important need for a convenient screening test. High-resolution proton (1H) magnetic resonance spectroscopy (MRS) of plasma identifies circulating metabolites that can allow detection of cancers such as PDAC that have highly dysregulated metabolism.

We first acquired 1H MR spectra of human plasma samples classified as normal, benign pancreatic disease and malignant (PDAC). We next trained a system of artificial neural networks (ANNs) to process and discriminate these three classes using the full spectrum range and resolution of the acquired spectral data. We then identified and ranked spectral regions that played a salient role in the discrimination to provide interpretability of the results. We tested the accuracy of the ANN performance using blinded plasma samples.

We show that our ANN approach yields, in a cross validation-based training of 170 samples, a sensitivity and a specificity of 100% for malignant versus non-malignant (normal and disease combined) discrimination. The trained ANNs achieve a sensitivity and specificity of 87.5% and 93.1% respectively (AUC: ROC = 0.931, P-R = 0.854), with 45 blinded plasma samples. Further, we show that the salient spectral regions of the ANN discrimination correspond to metabolites of known importance for their role in cancers.

Our results demonstrate that the ANN approach presented here can identify PDAC from 1H MR plasma spectra to provide a convenient plasma-based assay for population-level screening of PDAC. The ANN approach can be suitably expanded to detect other cancers with metabolic dysregulation.

Metabolic syndrome represents a pancreatic ductal adenocarcinoma (PDAC) risk factor. Metabolic alterations favor PDAC onset, which occurs early upon dysmetabolism. Pancreatic neoplastic lesions evolve within a dense desmoplastic stroma, consisting in abundant extracellular matrix settled by cancer associated fibroblasts (CAFs). Hereby, dysmetabolism and PDAC association was analyzed focusing on CAF functions.

PDAC development upon dysmetabolic conditions was investigated in: 1) high fat diet fed wild type immunocompetent syngeneic mice by orthotopic transplantation of pancreatic intraepithelial neoplasia (PanIN) organoids; and 2) primary pancreatic CAFs isolated from chemotherapy naïve PDAC patients with/without an history of metabolic syndrome.

The dysmetabolic-associated higher PDAC aggressiveness was paralleled by collagen fibril enrichment due to prolyl 4-hydroxylase subunit alpha 1 (P4HA1) increased function. Upon dysmetabolism, P4HA1 boosts collagen proline hydroxylation, intensifies collagen contraction strength, precluding PDAC infiltration. Noteworthy, semaglutide, an incretin agonist, prevents the higher dysmetabolism-dependent PDAC stromal deposition and allows T lymphocyte infiltration, reducing tumor development.

These results shed light on novel therapeutic options for PDAC patients with metabolic syndrome aimed at PDAC stroma reshape.

Abnormalities of carbohydrate antigen 19 - 9 (CA19-9) are common in patients with type 2 diabetes mellitus (T2DM), and in some patients, CA19-9 returns to normal level after glycemic control. The aim of this study was to investigate the factors associated with CA19-9 levels in patients with T2DM and the associated influences on the degree of reduction of CA19-9 levels after antidiabetic therapy (AT). This study was an observational cross-sectional study. A total of 213 patients with T2DM were enrolled in this study, of whom 105 with abnormal CA19-9 and 108 with normal CA19-9. Socio-demographic information, complete blood counts, biochemical indicators, thyroid function indicators, and CA19-9 level were collected separately for each subject. Levels of glycosylated hemoglobin, type A1C (HbA1c), fasting blood glucose (FBG) were significantly higher in T2DM patients with abnormal CA19-9 compared to patients with normal CA19-9 (both FDR < 0.001). CA19-9 level was significantly and positively correlated with neutrophil/lymphocyte ratio (NLR) (r = 0.16, P = 0.02), monocyte/lymphocyte ratio (MLR) (r = 0.16, P = 0.02), and FBG (r = 0.38, P < 0.001), while significantly and negatively correlated with free triiodothyronine (FT3) (r=-0.22, P = 0.002) and albumin count (r=-0.18, P = 0.007). After AT, the degree of decrease in CA19-9 level in T2DM patients with abnormal CA19-9 was significantly positively correlated with degree of decrease in FBG (r = 0.33, P < 0.001), as well as CA19-9 level before AT (r = 0.73, P < 0.001), NLR (r = 0.20, P = 0.04), and MLR (r = 0.25, P = 0.01). In this study, we investigated the influencing factors associated with CA19-9 level and the factors influencing degree of CA19-9 reduction after AT in T2DM patients with abnormal CA19-9.

Diabetes mellitus has emerged as a global public health issue due to its increasing prevalence and the increased risk of developing cancers. Pancreatic cancer is believed to be both a consequence of pre-existing diabetes and a potential cause of new-onset diabetes.

This study aims to compare the characteristics of patients with pancreatic ductal adenocarcinoma and newly diagnosed or long-standing diabetes mellitus.

A multicentric retrospective study was conducted over 13 years at two university hospitals in Sousse, Tunisia. Included patients had whether a newly diagnosed or a long-standing diabetes mellitus with histologically confirmed pancreatic ductal adenocarcinoma. Statistical analysis using appropriate tests was conducted.

The prevalence of diabetes mellitus was 44.6% among three hundred and seven patients with pancreatic cancer. The male-to-female ratio in patients with pancreatic ductal adenocarcinoma was 2.6:1. Patients' mean age was 63.9 years, with the majority being over 50 years old. Most patients had no family history of diabetes and exhibited significant weight loss, low body mass index, and uncontrolled diabetes. The comparison between individuals with newly diagnosed diabetes and those with long-standing diabetes revealed numerous similarities, apart from significant differences in drinking patterns (p = 0.03), tumor size (p = 0.018), and smoking in the subgroup of males (p = 0.044).

Patients over 50 with newly diagnosed diabetes mellitus, particularly those who consume alcohol occasionally and men who are not heavy smokers, should undergo further evaluation to identify potential early-stage pancreatic ductal adenocarcinoma.

Studies show that new onset diabetes mellitus (DM) (NOD) predates the diagnosis of PDAC by up to 2 years. Two tumor-intrinsic molecular subtypes of PDAC that are prognostic and predictive of chemotherapy response have been described and validated. We hypothesize that patients with NOD may have different molecular subtypes and prognoses.

This is a single-institution study of patients who underwent resection for PDAC from 2009 to 2022 with de-identified samples available for sequencing. Demographic and clinical factors were examined using bivariate and multivariate analysis.

A total of 97 patients met inclusion criteria: 70 with no history of DM, 11 with longstanding DM (> 2 years), and 16 with NOD. The demographics between groups were overall similar. After controlling for age, sex, race, BMI, and tobacco history, NOD was not a significant predictor of PDAC subtype. There were no survival differences between groups. Transcriptomic analysis suggests the upregulation of inflammatory and immune activation and regulation pathways in NOD.

As continued interest in NOD and PDAC mounts, we are the first to examine if NOD may be associated with molecular subtypes and outcomes. Further investigation into the underlying pathophysiology of the NOD group is still needed.

Several studies suggest that new-onset diabetes mellitus is an early manifestation of pancreatic ductal adenocarcinoma (PDAC). Therefore, the International Cancer of the Pancreas Screening Consortium recommends glucose and hemoglobin A1c (HbA1c) monitoring in high-risk individuals (HRIs) undergoing surveillance. However, evidence that such monitoring improves PDAC detection is lacking. Our aim was to investigate the association between serum glucose and HbA1c values and the development of PDAC in HRIs undergoing surveillance.

Participants were recruited from the familial pancreatic cancer surveillance cohort, which follows hereditary predisposed HRIs yearly by magnetic resonance imaging and/or endoscopic ultrasound and blood sampling. Those who underwent fasting glucose and/or HbA1c monitoring at least once were eligible candidates.

Four hundred four HRIs met the inclusion criteria. During a median follow-up of 41 months (range 14-120), 9 individuals developed PDAC and 4 (without PDAC) were diagnosed with new-onset diabetes mellitus. Glucose levels ranged from 3.4 to 10.7 mmol/L (mean 5.6 ± 0.7) and HbA1c levels from 25 to 68 mmol/mol (mean 37.7 ± 4.1). The mean values did not differ significantly between PDAC cases and controls. The percentage of individuals with at least one elevated value were comparable between PDAC cases and controls for glucose (33% and 27%, P = 0.707) and HbA1c (22% and 14%, P = 0.623). No consistent glucose or HbA1c trends over time suggested a correlation with PDAC development.

In this HRI surveillance cohort, measuring glucose and HbA1c values did not contribute to PDAC detection. Larger and longer-term studies are needed to determine the final role of glucose and HbA1c monitoring in PDAC surveillance.

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) often presents as acute pancreatitis (AP). However, data on the clinical outcomes of PDAC initially presenting as AP are limited. We aimed to assess the clinical features of PDAC that manifest as AP.

We reviewed the PDAC database at the Asan Medical Center between 2010-2016. Our study included 77 patients with PDAC who presented with AP (PDAC-AP group) and 154 age-gender-matched PDAC patients as controls (PDAC-other group). Patients' demographics, disease characteristics, and outcomes were compared between both groups.

Acute pancreatitis was an initial symptom in 1.12% of the patients with PDAC (77 of 6,821). Approximately 81.8% of the patients had clinically mild pancreatitis, and 91% were diagnosed with PDAC within two months of presentation with AP. Main tumor size was significantly smaller in the PDAC-AP group than in the PDAC-other group (PDAC-AP: 2.59 ± 1.21 cm vs. PDAC-other: 3.73 ± 1.78 cm, p < 0.01). The PDAC-AP group patients were diagnosed earlier than those in the PDAC-other group (PDAC-AP: stage 1-2, 80.6% vs. PDAC-other: 46.7%, p < 0.01). The proportion of resectable PDAC was significantly higher in the PDAC-AP group (PDAC-AP: 64.9% vs. PDAC-other: 50%, p < 0.01). Overall survival was significantly longer in the PDAC-AP group than in the PDAC-other group (30.2 months vs. 19.9 months, p = 0.03).

In patients who presented with clinical AP, PDAC was identified at an earlier stage, and these patients showed better survival rates. These results suggest that AP may be an early sign of PDAC.

Pancreatic cancer (PC), a highly malignant cancer with a poor diagnosis, may be influenced by diet-related inflammation. This study examined the association between dietary inflammatory index (DII) scores and the incidence and prognosis of PC in Korea.

A total of 55 patients with PC were matched with 280 healthy controls (HCs) by age and sex. We also analyzed the combined effects of DII scores and fasting blood glucose (FBG) levels or smoking status on the risk of PC and performed a survival analysis using the Cox proportional hazards method.

The DII scores were higher in the patients with PC than those in HCs (odds ratio [OR] = 3.36, confidence interval [CI] = 1.16-9.73, p = 0.03), and the effect was larger in women (OR = 6.13, CI = 1.11-33.82, p = 0.04). A high DII score was jointly associated with FBG ≥ 126 mg/dL in raising PC risk [OR = 32.5, relative excess risk due to interaction/synergy (RERI/S) index = 24.2/4.34, p-interaction = 0.04], indicating a multiplicative interaction. A high DII score combined with ex/current smoker status increased PC risk through an additive interaction (RERI/S = 1.01/1.54, p-interaction = 0.76). However, DII scores did not influence disease-free survival.

The consumption of an anti-inflammatory diet, coupled with maintaining normal FBG levels and abstaining from smoking, may help reduce the risk of PC by mitigating pancreatic inflammation.

Disturbances in carbohydrate metabolism are suggested to be the early symptoms of pancreatic ductal adenocarcinoma (PDAC). The accumulated data suggests that endocrine function-related biomarkers may represent a breakthrough in the early detection of PDAC. Factors which may predispose one to the development of PDAC are insulin resistance and hyperinsulinemia. Elevated insulin levels induce the onset of carcinogenesis by altering the differentiation and function of islet cells through stimulating growth factors, including insulin-like growth factors (IGFs). Impaired β cell function, along with the impact of PDAC-released factors (e.g., adrenomedullin (ADM), IGF-1, and macrophage inhibitory factor (MIF) on pancreatic islets, may contribute to the induction of diabetes associated with PDAC. Recently, exosomes have attracted worldwide attention due to their role in varied features of cell function, particularly in cancer progression. Exosomes comprise of small extracellular vesicles produced by almost all cells. These vesicles contain a vast array of biomolecules, including proteins and microRNAs. Exosomes participate in cancer growth and promote angiogenesis. They promote tumorigenesis and metastasis, and are associated with the acquisition of cancer cells resistant to chemotherapy. Data have been accumulating recently on the role of exosomes in the rapid recognition, prognosis and potential therapy of pancreatic cancer.

Diabetic ketoacidosis (DKA) is a complication of diabetes mellitus (DM) that can theoretically occur in people of any age. While DKA can typically be the first presentation of type 1 DM in younger people, a first presentation is rare in older adults. Pancreatic cancer often manifests with new DM or hyperglycaemia, but very rarely as DKA. We report a case of an 89-year-old woman who was incidentally diagnosed with DKA during workup for an unwitnessed fall. Her DKA was promptly managed, and she was subsequently diagnosed with metastatic pancreatic cancer. Given the advanced stage of her malignancy, the multidisciplinary team consensus was for a palliative approach. She passed away on day 10 of the admission. To our knowledge, this is the first report of a first DKA presentation as a manifestation of pancreatic cancer in an adult aged over 70 years. To date, there is no effective screening test for pancreatic cancer in the general population. However, new-onset DM in the appropriate context might indicate the need for further evaluation. While it is possible that unresectable tumours are identified, earlier diagnosis of DM with pancreatic cancer may facilitate more timely management, including earlier advanced care planning.

A higher clinical suspicion for pancreatic cancer is required for older adults presenting with diabetic ketoacidosis without a previously diagnosed diabetes mellitus. A bi-directional relationship exists between diabetes and pancreatic cancer. Pancreatic cancer generally has a very poor prognosis due to its advanced stage at diagnosis and the lack of an effective screening test. New-onset diabetes in the appropriate context (such as weight loss) can indicate the need for further evaluation for underlying pancreatic cancer.

In the UK, guidelines recommend pancreatic enzyme replacement therapy (PERT) to all people with unresectable pancreatic cancer. In 2023, we published a national audit of PERT which showed suboptimal prescribing and wide regional variation in England. The aim of this manuscript was to describe how we used the PERT audit to drive improvements in healthcare.

Building on the PERT audit, we deployed an online dashboard which will deliver ongoing updates of the PERT audit. We developed a collaborative intervention with cancer nurse specialists (CNS) to improve care delivered to people with pancreatic cancer. The intervention called Creating a natiOnAL CNS pancrEatic cancer network to Standardise and improve CarE (COALESCE) will use the dashboard to evaluate improvements in prescribing of PERT.

We demonstrated how large databases of electronic healthcare records (EHRs) can be used to improve cancer care. The PERT audit was implemented into a dashboard for tracking the progress of COALESCE. We will measure improvements in PERT prescribing as the intervention with CNS progresses.

Improving healthcare is an ongoing and iterative process. By implementing the PERT dashboard, we created a resource-efficient, automated evaluation method enabling COALESCE to deliver a sustainable change. National-scale databases of EHRs enable rapid cycles of audits, providing regular feedback to interventions, working systematically to deliver change. Here, the focus is on pancreatic cancer. However, this methodology is transferable to other areas of healthcare.

Nurses play a key role in collecting good quality data which are needed in clinical audits to identify shortcomings in healthcare. Nurse-driven interventions can be designed to improve healthcare. In this study, we capitalize on the unique role of CNS coordinating care for every patient with cancer. COALESCE is the first national collaborative study which uses CNS as researchers and change agents.

Background: The early diagnosis of pancreatic cancer (ICD-10 C25) can improve the patient's prognosis. The association between pancreatic cancer and type 2 diabetes (T2D) is known, but not yet fully understood. It is, therefore, necessary to investigate the impact of hemoglobin A1c (HbA1c) serum levels on pancreatic cancer development and the potential intervention options. Methods: In the case-control study, patients from the German IQVIATM Disease Analyzer database aged ≥18 years with a diagnosis of pancreatic cancer (ICD-10 C25) and a diagnosis of T2D (ICD-10: E11) were included. The patients' propensity score matched 1:5 with individuals without pancreatic cancer. Logistic regression models were used to estimate odds ratios (ORs) with 95% confidence intervals (95% CI). Results: An elevated serum HbA1c prior to the index date was found to be significantly associated with an increased risk of a subsequent pancreatic cancer diagnosis for the mean HbA1c values of 6.5-8.4% (OR: 1.38; 95% CI: 1.22-1.57) as well as for mean HbA1c values ≥8.5% (OR: 1.41; 95% CI: 1.16-1.73). The only antihyperglycemic agent negatively associated with the subsequent pancreatic cancer diagnosis was the sodium-glucose cotransporter-2 (SGLT-2) inhibitor, with an odds ratio of 0.80 (95% confidence interval: 0.74-0.87 per year of therapy). This correlation was observed in both age- and sex-stratified subgroups. Conclusions: The data indicate that elevated serum HbA1c levels in patients with T2D are associated with an increased risk of pancreatic cancer development. It is possible that SGLT2 therapy may prove an effective means of reducing the risk of pancreatic cancer, thereby offering a potential avenue for the future reduction in pancreatic cancer incidence in patients with T2D.

Pancreatic cancer continues to be a deadly disease because of its delayed diagnosis and aggressive tumor biology. Oncogenes and risk factors are being reported to influence the signaling pathways involved in pancreatic embryogenesis leading to pancreatic cancer genesis. Although studies using rodent models have yielded insightful information, the scarcity of human pancreatic tissue has made it difficult to comprehend how the human pancreas develops. Transcription factors like IPF1/PDX1, HLXB9, PBX1, MEIS, Islet-1, and signaling pathways, including Hedgehog, TGF-β, and Notch, are directing pancreatic organogenesis. Any derangements in the above pathways may lead to pancreatic cancer. TP53: and CDKN2A are tumor suppressor genes, and the mutations in TP53 and somatic loss of CDKN2A are the drivers of pancreatic cancer. This review clarifies the complex signaling mechanism involved in pancreatic cancer, the same signaling pathways in pancreas development, the current therapeutic approach targeting signaling molecules, and the mechanism of action of risk factors in promoting pancreatic cancer.

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.

Individuals with hereditary pancreatic cancer risk include high risk individuals (HRIs) with germline genetic susceptibility to pancreatic cancer (PC) and/or a strong family history of PC. Previously, studies have shown that PC surveillance in HRIs can downstage PC diagnosis and extend survival leading to pancreatic surveillance being recommended for certain HRIs. However, the optimal surveillance strategy remains uncertain, including which modalities should be used for surveillance, how frequently should surveillance be performed, and which sub-groups of HRIs should undergo surveillance. Additionally, in the ideal world PC surveillance should also be cost-effective. Cost-effectiveness analysis is a valuable tool that can consider the costs, potential health benefits, and risks among various PC surveillance strategies. In this review, we summarize the cost-effectiveness of various PC surveillance strategies for HRIs for hereditary pancreatic cancer and provide potential avenues for future work in this field. Additionally, we include cost-effectiveness studies among individuals with new-onset diabetes (NoD), a high-risk group for sporadic PC, as a comparison.

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.

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

Two important questions regarding the genetics of pancreatic adenocarcinoma (PDAC) are 1. Which germline genetic variants influence the incidence of this cancer; and 2. Whether PDAC causally predisposes to associated non-malignant phenotypes, such as type 2 diabetes (T2D) and venous thromboembolism (VTE).

In this study of 8803 patients with PDAC and 67,523 controls, we first performed a large-scale transcriptome-wide association study to investigate the association between genetically determined gene expression in normal pancreas tissue and PDAC risk. Secondly, we used Mendelian Randomization (MR) to analyse the causal relationships among PDAC, T2D (74,124 cases and 824,006 controls) and VTE (30,234 cases and 172,122 controls).

Sixteen genes showed an association with PDAC risk (FDR <0.10), including six genes not yet reported for PDAC risk (PPIP5K2, TFR2, HNF4G, LRRC10B, PRC1 and FBXL20) and ten previously reported genes (INHBA, SMC2, ABO, PDX1, MTMR6, ACOT2, PGAP3, STARD3, GSDMB, ADAM33). MR provided support for a causal effect of PDAC on T2D using genetic instruments in the HNF4G and PDX1 loci, and unidirectional causality of VTE on PDAC involving the ABO locus (OR 2.12, P < 1e-7). No evidence of a causal effect of PDAC on VTE was found.

These analyses identified candidate susceptibility genes and disease relationships for PDAC that warrant further investigation. HNF4G and PDX1 may induce PDAC-associated diabetes, whereas ABO may induce the causative effect of VTE on PDAC.

National Institutes of Health (USA).

Pancreatic surveillance can detect early-stage pancreatic cancer and achieve long-term survival, but currently involves annual endoscopic ultrasound and MRI/MRCP, and is recommended only for individuals who meet familial/genetic risk criteria. To improve upon current approaches to pancreatic cancer early detection and to expand access, more accurate, inexpensive, and safe biomarkers are needed, but finding them has remained elusive. Newer approaches to early detection, such as using gene tests to personalize biomarker interpretation, and the increasing application of artificial intelligence approaches to integrate complex biomarker data, offer promise that clinically useful biomarkers for early pancreatic cancer detection are on the horizon.

New-onset diabetes (NOD) has been identified as a high-risk factor for the early detection of pancreatic ductal adenocarcinoma (PDAC). The role of tumor volume and remnant pancreas volume (RPV) in the progression from normal to NOD in PDAC patients is not fully illustrated yet.

In this cross-sectional study, glycemic metabolism traits of 95 PDAC patients before pancreatic surgery were described and compared with chronic pancreatitis and type 2 diabetes mellitus patients based on the oral glucose tolerance test. The remnant RPV and tumor volume, calculated by three-dimensional reconstruction of radiological images, were included in the ordinal logistic regression models.

The prevalence of NOD was high among PDAC patients (38.9%). However, normal glucose tolerance (NGT) or prediabetes mellitus status were present as more than half (24/44) of advanced tumor stage patients. Indexes reflecting beta-cell function but not insulin sensitivity gradually worsened from NGT to NOD patients (all p < 0.05). The remnant pancreas volume (RPV) was identified as a potential protective factor for diabetes secondary to PDAC (odds ratio 0.95, 95% CI [0.92, 0.97], p < 0.001).

Reduced RPV causing beta-cell dysfunction might be one of the mechanisms of NOD secondary to PDAC. Subjects with sufficient pancreas volume could not be detected earlier when regarding patients with NOD as the population at risk for PDAC.

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.

This paper presents an overview of the interconnection between various factors related to both cancer and type 2 diabetes mellitus (T2DM). Hyperglycemia, hyperinsulinemia, chronic inflammation, and obesity are involved in the development and progression of both diseases but, strong evidence for a direct causal relationship between diabetes and cancer, is lacking. Several studies described a relationship between hyperglycemia and cancer at the cellular, tissular and organismic levels but at the same time recent Mendelian randomization studies proved a significant causal relationship only between hyperglycemia and breast cancer. On the other hand, the association between both hyperinsulinemia and obesity and several cancer types appears to be robust as demonstrated by Mendelian randomized studies. Metabolic alterations, including the Warburg effect and excessive glucose consumption by tumors, are discussed, highlighting the potential impact of dietary restrictions, such as fasting and low-carb diets, on tumor growth and inflammation. Recent data indicates that circulating branched-chain amino acids levels, may represent novel biomarkers that may contribute to both better diabetes control and early pancreatic cancer detection. Understanding the underlying mechanisms and shared risk factors between cancer and T2DM can provide valuable insights for cancer prevention, early detection, and management strategies.

Type 3c diabetes mellitus (T3cDM), also known as pancreatogenic or pancreoprivic diabetes, is a specific type of DM that often develops as a result of diseases affecting the exocrine pancreas, exhibiting an array of hormonal and metabolic characteristics. Several pancreatic exocrine diseases and surgical procedures may cause T3cDM. Diagnosing T3cDM remains difficult as the disease characteristics frequently overlap with clinical presentations of type 1 DM (T1DM) or type 2 DM (T2DM). Managing T3cDM is likewise challenging due to numerous confounding metabolic dysfunctions, including pancreatic endocrine and exocrine insufficiencies and poor nutritional status. Treatment of pancreatic exocrine insufficiency is of paramount importance when managing patients with T3cDM. This review aims to consolidate the latest information on surgical etiologies of T3cDM, focusing on partial pancreatic resections, total pancreatectomy, pancreatic cancer and trauma.

Pancreatic cancer is notorious for its persistently poor prognosis and health outcomes, so some of the questions that may be begged are "Why is it mostly diagnosed at end stage?", "What could we possibly do with the advancing technology in today's world to detect early pancreatic cancer and intervene?", and "Are there any implementation of the existing novel imaging technologies?". Well, to start with, this is in part because the majority of patients presented would already have reached a locally advanced or metastatic stage at the time of diagnosis due to its highly aggressive characteristics and lack of symptoms. Due to this striking disparity in survival, advancements in early detection and intervention are likely to significantly increase patients' survival. Presently, screening is frequently used in high-risk individuals in order to obtain an early pancreatic cancer diagnosis. Having a thorough understanding of the pathogenesis and risk factors of pancreatic cancer may enable us to identify individuals at high risk, diagnose the disease early, and begin treatment promptly. In this review, the authors outline the clinical hurdles to early pancreatic cancer detection, describe high-risk populations, and discuss current screening initiatives for high-risk individuals. The ultimate goal of this current review is to study the roles of both traditional and novel imaging modalities for early pancreatic cancer detection. A lot of the novel imaging techniques mentioned seem promising, but they need to be put to the test on a large scale and may need to be combined with other non-invasive biomarkers before they can be widely used.

Pancreatic ductal adenocarcinoma (pancreatic cancer) is often detected at late stages resulting in poor overall survival. To improve survival, more patients need to be diagnosed early when curative surgery is feasible. We aimed to identify circulating metabolites that could be used as early pancreatic cancer biomarkers.

We performed metabolomics by liquid and gas chromatography-mass spectrometry in plasma samples from 82 future pancreatic cancer patients and 82 matched healthy controls within the Northern Sweden Health and Disease Study (NSHDS). Logistic regression was used to assess univariate associations between metabolites and pancreatic cancer risk. Least absolute shrinkage and selection operator (LASSO) logistic regression was used to design a metabolite-based risk score. We used receiver operating characteristic (ROC) analyses to assess the discriminative performance of the metabolite-based risk score.

Among twelve risk-associated metabolites with a nominal P value <0.05, we defined a risk score of three metabolites [indoleacetate, 3-hydroxydecanoate (10:0-OH), and retention index (RI): 2,745.4] using LASSO. A logistic regression model containing these three metabolites, age, sex, body mass index (BMI), smoking status, sample date, fasting status, and carbohydrate antigen 19-9 (CA 19-9) yielded an internal area under curve (AUC) of 0.784 [95% confidence interval (CI): 0.714-0.854] compared to 0.681 (95% CI: 0.597-0.764) for a model without these metabolites (P value =0.007). Seventeen metabolites were significantly associated with pancreatic cancer survival [false discovery rate (FDR) <0.1].

Indoleacetate, 3-hydroxydecanoate (10:0-OH), and RI: 2,745.4 were identified as the top candidate biomarkers for early detection. However, continued efforts are warranted to determine the usefulness of these metabolites as early pancreatic cancer biomarkers.

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 damage to the endocrine pancreas among patients with diseases of the exocrine pancreas (DP) leads to reduced glycemic deterioration, ultimately resulting in diabetes of the exocrine pancreas (DEP). The present research aims to investigate the mechanism responsible for glycemic deterioration in DP patients, and to identify useful biomarkers, with the ultimate goal of enhancing clinical practice awareness. Gene expression profiles of patients with DP in this study were acquired from the Gene Expression Omnibus database. The original study defines DP patients to belong in one of three categories: non-diabetic (ND), impaired glucose tolerance (IGT) and DEP, which correspond to normoglycemia, early and late glycemic deterioration, respectively. After ensuring quality control, the discovery cohort included 8 ND, 20 IGT, and 12 DEP, while the validation cohort included 27 ND, 15 IGT, and 20 DEP. Gene set enrichment analysis (GSEA) employed differentially expressed genes (DEGs), while immunocyte infiltration was determined using single sample gene set enrichment analysis (ssGSEA). Additionally, correlation analysis was conducted to establish the link between clinical characteristics and immunocyte infiltration. The least absolute shrinkage and selection operator regression and random forest combined to identify biomarkers indicating glycemic deterioration in DP patients. These biomarkers were further validated through independent cohorts and animal experiments. With glycemic deterioration, biological processes in the pancreatic islets such as nutrient metabolism and complex immune responses are disrupted in DP patients. The expression of ACOT4, B2M, and ACKR2 was upregulated, whereas the expression of CACNA1F was downregulated. Immunocyte infiltration in the islet microenvironment showed a significant positive correlation with the age, body mass index (BMI), HbA1c and glycemia at the 2-h of patients. It was a crucial factor in glycemic deterioration. Additionally, B2M demonstrated a significant positive correlation with immunocyte infiltration and clinical features. Quantitative real-time PCR (qRT-PCR) and western blotting confirmed the upregulation in B2M. Immunofluorescent staining suggested the alteration of B2M was mainly in the alpha cells and beta cells. Overall, the study showed that gradually increased immunocyte infiltration was a significant contributor to glycemic deterioration in patients with DP, and it also highlighted B2M as a biomarker.

Over the last two decades, increased availability of human pancreatic tissues has allowed for major expansions in our understanding of islet biology in health and disease. Indeed, studies of fixed and frozen pancreatic tissues, as well as efforts using viable isolated islets obtained from organ donors, have provided significant insights toward our understanding of diabetes. However, the procedures associated with islet isolation result in distressed cells that have been removed from any surrounding influence. The pancreas tissue slice technology was developed as an in situ approach to overcome certain limitations associated with studies on isolated islets or fixed tissue. In this Perspective, we discuss the value of this novel platform and review how pancreas tissue slices, within a short time, have been integrated in numerous studies of rodent and human islet research. We show that pancreas tissue slices allow for investigations in a less perturbed organ tissue environment, ranging from cellular processes, over peri-islet modulations, to tissue interactions. Finally, we discuss the considerations and limitations of this technology in its future applications. We believe the pancreas tissue slices will help bridge the gap between studies on isolated islets and cells to the systemic conditions by providing new insight into physiological and pathophysiological processes at the organ level.

Human pancreas tissue slices represent a novel platform to study human islet biology in close to physiological conditions. Complementary to established technologies, such as isolated islets, single cells, and histological sections, pancreas tissue slices help bridge our understanding of islet physiology and pathophysiology from single cell to intact organ. Diverse sources of viable human pancreas tissue, each with distinct characteristics to be considered, are available to use in tissue slices for the study of diabetes pathogenesis.

Pancreatic ductal adenocarcinomas (PDACs) are sometimes diagnosed accompanied by rapidly impaired diabetes (PDAC-RID). Although this type of PDAC may have unusual biological features, these features have not been explained.

Patients with PDAC who underwent upfront pancreatectomy between 2010 and 2018 were retrospectively reviewed. PDAC-RID was defined as a glycated hemoglobin (HbA1c) value of ≥ 8.0% of newly diagnosed diabetes, and acute exacerbation of previously diagnosed diabetes. Other patients were classified as PDAC with stable glycometabolism (PDAC-SG). Clinicopathological factors, long-term survival rates, and recurrence patterns were evaluated.

Of the 520 enrolled patients, 104 were classified as PDAC-RID and 416 as PDAC-SG. There was no significant difference regarding TNM staging, resectability, or adjuvant chemotherapy rate between the groups. However, 5-years cancer-specific survival (CSS) was significantly higher in the PDAC-RID group than in the PDAC-SG group (45.3% vs. 31.1%; p = 0.02). This survival difference was highlighted in relatively early-stage PDAC (≤ pT2N1) (CSS: 60.8% vs. 43.6%; p = 0.01), but the difference was not significant for advanced-stage PDAC. A multivariate analysis of early-stage PDAC showed that PDAC-SG was an independent risk factor of shorter CSS (hazard ratio 1.76; p = 0.02). The hematogenous metastatic rate in early-stage PDAC was lower in the PDAC-RID group than in the PDAC-SG group (18.3% vs. 35.8%; p = 0.01).

PDAC-RID showed a favorable long-term survival rate after curative resection with low hematogenous metastases, which may be due to its unique biology.

Postpancreatectomy diabetes can be caused by resection of functioning pancreatic tissue and is associated with postoperative pancreatic islet cell mass loss and subsequent endocrine dysfunction. Diabetes is a well-known risk factor for ischemic heart disease. However, no previous studies have investigated ischemic heart disease in patients with postpancreatectomy diabetes and pancreatic cancer.

Rates of patients with diabetes diagnosed with pancreatic cancer who underwent pancreatectomy between 2002 and 2019 in South Korea were obtained from the Korean National Health Insurance Service database. Patient-level propensity score matching was conducted to reduce the possibility of selection bias, and multivariate Cox proportional hazards models were used to determine the association between postpancreatectomy diabetes and ischemic heart disease. In total, 30 242 patients were initially enrolled in the study. After applying exclusion criteria and propensity score matching, 2952 patients were included in the comparative analysis between the postpancreatectomy group with diabetes and the group without diabetes. Patients in the postpancreatectomy group with diabetes had significantly higher rates of ischemic heart disease than those in the group without diabetes. In total, 3432 patients were included in the comparison between the postpancreatectomy and prepancreatectomy groups with diabetes. There was no significant difference in the risk of ischemic heart disease between the postpancreatectomy and prepancreatectomy groups with diabetes.

Patients who developed diabetes after pancreatectomy had a higher risk of ischemic heart disease than patients who did not develop diabetes after pancreatectomy, and the rate of ischemic heart disease in these patients was similar to that in patients preoperatively diagnosed with diabetes.

Diabetes mellitus (DM) is a prominent risk factor for malignant and non-malignant pancreatic diseases. Furthermore, the presence of DM predicts an unfavourable outcome in people with pancreatic cancer. This retrospective observational study investigated 370 patients who underwent pancreatic resection surgery for various indications (84.3% in malignant indication) in a single surgery centre in Graz, Austria. The preoperative and postoperative diabetes statuses were evaluated according to surgery method and disease entity and predictors for diabetes development after surgery, as well as outcomes (survival and cancer recurrence) according to diabetes status, were analysed. In the entire cohort, the postoperative diabetes (postopDM) incidence was 29%. PostopDM occurred significantly more frequently in malignoma patients than in those with benign diseases (31.3% vs. 16.7%; p = 0.040, OR = 2.28). In the malignoma population, BMI, longer surgery duration, and prolonged ICU and hospital stay were significant predictors of diabetes development. The 1- and 2-year follow-ups showed a significantly increased mortality of people with postopDM in comparison to people without diabetes (HR 1-year = 2.02, p = 0.014 and HR 2-years = 1.56, p = 0.034). Local cancer recurrence was not influenced by the diabetes status. Postoperative new-onset diabetes seems to be associated with higher mortality of patients with pancreatic malignoma undergoing pancreatobiliary surgery.

The George E Palade Prize is the highest honour awarded by the International Association of Pancreatology, that recognises an individual who has made outstanding contributions to the understanding of the pancreas and pancreatic diseases. The 2023 Palade Prize was awarded to Professor Minoti Apte, University of New South Wales Sydney on September 16, 2023 during the Joint Meeting of the International Association of Pancreatology and the Indian Pancreas Club, held in Delhi, India. This paper summarises her Palade lecture wherein she reflects on her journey as a medical graduate, an academic and a researcher, with a particular focus on her team's pioneering work on pancreatic stellate cell biology and the role of these cells in health and disease. While there has been much progress in this field with the efforts of researchers worldwide, there is much still to be learned; thus it is a topic with ample scope for innovative research with the potential to translate into better outcomes for patients with pancreatic disease.

Obesity has been recognized to be increasing globally and is designated a disease with adverse consequences requiring early detection and appropriate care. In addition to being related to metabolic syndrome disorders such as type 2 diabetes, hypertension, stroke, and premature coronary artery disease. Obesity is also etiologically linked to several cancers. The non-gastrointestinal cancers are breast, uterus, kidneys, ovaries, thyroid, meningioma, and thyroid. Gastrointestinal (GI) cancers are adenocarcinoma of the esophagus, liver, pancreas, gallbladder, and colorectal. The brighter side of the problem is that being overweight and obese and cigarette smoking are mostly preventable causes of cancers. Epidemiology and clinical studies have revealed that obesity is heterogeneous in clinical manifestations. In clinical practice, BMI is calculated by dividing a person's weight in kilograms by the square of the person's height in square meters (kg/m2). A BMI above 30 kg/m2 (defining obesity in many guidelines) is considered obesity. However, obesity is heterogeneous. There are subdivisions for obesity, and not all obesities are equally pathogenic. Adipose tissue, in particular, visceral adipose tissue (VAT), is endocrine and abdominal obesity (a surrogate for VAT) is evaluated by waist-hip measurements or just waist measures. Visceral Obesity, through several hormonal mechanisms, induces a low-grade chronic inflammatory state, insulin resistance, components of metabolic syndrome, and cancers. Metabolically obese, normal-weight (MONW) individuals in several Asian countries may have BMI below normal levels to diagnose obesity but suffer from many obesity-related complications. Conversely, some people have high BMI but are generally healthy with no features of metabolic syndrome. Many clinicians advise weight loss by dieting and exercise to metabolically healthy obese with large body habitus than to individuals with metabolic obesity but normal BMI. The GI cancers (esophagus, pancreas, gallbladder, liver, and colorectal) are individually discussed, emphasizing the incidence, possible pathogenesis, and preventive measures. From 2005 to 2014, most cancers associated with overweight and Obesity increased in the United States, while cancers related to other factors decreased. The standard recommendation is to offer or refer adults with a body mass index (BMI) of 30 or more to intensive, multicomponent behavioral interventions. However, the clinicians have to go beyond. They should critically evaluate BMI with due consideration for ethnicity, body habitus, and other factors that influence the type of obesity and obesity-related risks. In 2001, the Surgeon General's ``Call to Action to Prevent and Decrease Overweight and Obesity'' identified obesity as a critical public health priority for the United States. At government levels reducing obesity requires policy changes that improve the food and physical activity for all. However, implementing some policies with the most significant potential benefit to public health is politically tricky. The primary care physician, as well as subspecialists, should identify overweight and Obesity based on all the variable factors in the diagnosis. The medical community should address the prevention of overweight and Obesity as an essential part of medical care as much as vaccination in preventing infectious diseases at all levels- from childhood, to adolescence, and adults.