Introduction

Diabetes is associated with increased pancreatic cancer (PC) risk. Beta-blockers may mitigate PC risk and progression by inhibiting β-adrenergic receptor-mediated signaling pathways involved in tumor cell proliferation, invasion, and angiogenesis. However, the potential oncopreventive effect of beta-blockers on PC risk in patients with type 2 diabetes (T2D) remains unclear.

Aims & Methods

We aimed to assess the association between beta-blocker use and PC risk in newly diagnosed T2D patients after adjusting for risk factors. This territory-wide retrospective cohort study included adults (≥18 years) newly diagnosed with T2D between 2001 and 2020. Patients with type 1 diabetes, prior PC, immunoglobulin G4-related disease, pancreatectomy, or fewer than two HbA1c results were excluded. To minimize reverse causality between PC and T2D, those diagnosed with PC within 1 year of T2D diagnosis or with <1 year of follow-up were excluded. Primary exposure was beta-blocker use (e.g., acebutotlol, atenolol, bisoprolol, carvedilol, celiprolol, esmolol, labetalol, metoprolol, nadolol, nebivolol, pindolol, propranolol, and sotalol). In the primary (time-fixed) analysis, exposure was defined as ≥90 days of use after T2D diagnosis (i.e. index date). The outcome was incident PC. Patients were followed until PC, pancreatectomy, death, or study end (December 31, 2020). Adjusted hazard ratios (aHRs) were derived from multivariable Cox models adjusting for 31 covariates: age, sex, smoking status, alcohol use disorder, body index mass, glycemic control (in terms of time-weighted mean HbA1c), pancreatitis, cholangitis, colectomy, Charlson’s comorbidity index, metabolic and cardiovascular comorbidities, and concomitant medications (aspirin, non-steroidal anti-inflammatory drugs, statins, and other antidiabetics). Sensitivity analyses included time-dependent analysis (drug use was defined as ≥180 days/year; to address immortal time bias), and multiple propensity score (PS)-based approaches (matching, regression adjustment, weighting, and matching weights). Dose- and duration-response relationships were evaluated.

Results

Among 431,261 T2D patients (mean age: 59.1±11.4 years; male: 52.5%; 61,917 beta-blocker users and 369,344 beta-blocker non-users), 1,303 (0.3%) developed PC during a mean follow-up of 9.4±5.0 years. The 18-year cumulative incidence was 0.68% (95% CI: 0.57%-0.80%) in beta-blocker users and 0.76% (95% CI: 0.70%-0.82%) in non-users (P = 0.02; Figure 1). Beta-blocker use was associated with lowered PC risk in time-fixed analysis (aHR: 0.81; 95% CI: 0.70-0.95), time-dependent analysis (aHR: 0.75; 95% CI: 0.62-0.91), and all PS-based methods (aHR range: 0.83-0.86). A dose- and duration-dependent inverse relationship was observed (P_trend <0.001). Higher cumulative defined daily dose (cDDD) reduced the risk (aHR: 0.84, 95% CI: 0.72-0.98, for <4,000 cDDD; aHR: 0.31, 95% CI: 0.12-0.82, for ≥4,000 cDDD). Longer use also lowered the risk (aHR: 1.12, 95% CI: 0.92-1.37, for <5 years; aHR: 0.70, 95% CI: 0.57-0.87, for 5 to <15 years; aHR: 0.11, 95% CI: 0.04-0.35, for ≥15 years). Each additional 1,000 cDDD and 1-year increase in use was associated with a 21% (aHR: 0.79, 95% CI: 0.72-0.88) and 6% (aHR: 0.94, 95% CI: 0.92-0.96) risk reduction, respectively.

Conclusion

Beta-blocker use was associated with a lowered risk of PC among patients with newly diagnosed T2D, in a dose- and duration-dependent manner.

Introduction

Radioactive phosphorus (³²P) is an innovative therapy for locally advanced pancreatic cancer that is implanted through endoscopic ultrasound (EUS). Pancreatic cancer is the fourth cause of death and is responsible for 7% of all deaths caused by cancer. Nowadays the improvement of chemotherapy and the usage of combination therapies led to a better prognosis and studies showed an improvement of the survival parameters (OS, Free Progression Survival). One of the most innovative therapies is the implantation of radioactive phosphorus-32 which is a type of brachytherapy. It is indicated for the treatment of patients with Locally Advanced Pancreatic Cancer (LAPC) in combination with gemcitabine-based chemotherapy.

Aims & Methods

The primary goal of this study is to determine the safety of the intra-tumoral implantation of radioactive phosphorus (³²P) through EUS and the complications of the procedure of implantation. The secondary goals are to determine the Local Disease Control Rate (LDCR) at 16 weeks and the effectiveness of the implantation of radioactive phosphorus by measuring Overall Survival (OS), Progression Free Survival (PFS) and Local Progression Free Survival (LPFS). We currently have made the implantation in eight patients with similar clinical and demographic features who suffer from locally advanced pancreatic cancer. They receive gemcitabine-based chemotherapy in combination with an intra-tumoral therapy with radioactive phosphorus (³²P) through a 22-gauge FNA needle guided by EUS. The adverse events of the implantation are evaluated by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The LDCR is evaluated at 16 weeks and the alteration of Tumor Volume every two months for the first year after implantation and every three months the second year after implantation according to RECIST 1.1.

Results

The eight procedures (median age of patients: 68,5 years) were unremarkable and no complication during the procedure was noted. The patients did not have any major adverse events during the day of the procedure. Five out of eight patients (62,5%) revealed mild abdominal pain on the second day which recovered with typical pain killers. The LDCR, for all patients, at 16 weeks, was 100%. Two of the patients had a major reduction in the tumor so it was resectable. The operations were without any complications and the pathology test showed R0 resection. Two patients died after 12 months of follow up (one patient showed progression disease after 10 months from implantation and one patient had stable disease until death) and one patient revealed progression of disease after 12 months and is still alive after 15 months of follow up. Three patients have stable disease after 6 months of follow up, even though a slight reduction of the tumor has been noted. The six patients (including the two that died and not including the two that underwent surgery) have been followed up for 6 to 15 months, depending on time of implantation. The median Progression Free Survival for these six patients is 7 months (max 12 months – min 6 months) and the median Local Progression Free Survival is 6 months (max 12 months – min 6 months).

Conclusion

We must include more patients to conduct more useful results, but the initial results look promising.

References

1.Wungki P, Akhil C, Eileen M. Pancreatic Cancer: A Review. JAMA. 2021 September 07;326(9):851-862.
2.OncoSil System: Instruction for Use
3.Audrey V, Joseph H, Rich S, et al. Pancreatic cancer. Lancet. 2011 August 13; 378(9791): 607-620. doi: 10.1016/S0140-6736(10)62307-0.

Disclosure

​None to report

Introduction

Although the role of radiotherapy in locally advanced pancreatic cancer (LAPC) is still debated, data has demonstrated encouraging results for more precise methods of radiotherapy delivery, including stereotactic body radiation therapy (SBRT) and endoscopic ultrasound (EUS) guided intra-tumoural phosphorus-32 (³²P) microparticle implantation. We compare survival and safety outcomes of patients with SBRT versus EUS-guided ³²P implantation in combination with chemotherapy in patients with LAPC.

Aims & Methods

This is a single-centre retrospective study from March 2015 – April 2025 including all patients with LAPC who underwent combination neoadjuvant chemotherapy with either EUS-guided ³²P microparticle implantation or SBRT. The primary outcome was overall survival from chemotherapy commencement. Secondary outcomes include progression-free survival (PFS), resection rate and rate of adverse effects including grade 3 (CTCAE v. 5) or above adverse effects.

Results

A total of 119 patients (58 ³²P vs. 61 SBRT) were included. Demographics and tumour characteristics were comparable between the groups (Table 1). All ³²P microparticle implantation was successful, with an average volume of 1.6+0.1mL and an estimated 100Gy activity applied to the tumour. The median highest dose of SBRT therapy was 35Gy (IQR 35-40Gy) delivered over 5 fractions. Median overall survival from the date of chemotherapy commencement was significant better with ³²P implantation than SBRT (hazard ratio [HR] 1.98; p=0.004). Compared to SBRT, ³²P implantation was associated with superior local and distant PFS (HR 1.61; p=0.034 and HR 1.71; p=0.019 respectively). Both therapies resulted in significant reduction in serum Ca19.9. Tumour downstaging (15/58 vs. 5/61, P<0.001) and surgery (13/58 vs. 0/61, P<0.001) rates after the therapy were significant higher with ³²P implantation than SBRT. The rate of R0 resection was 77% (10/13) in the ³²P group. The rate of grade 3 adverse events was not significantly different between the groups (6/58 vs. 5/61).

Table 1. Demographics and tumour characteristics

Conclusion

When radiotherapy is used in combined with chemotherapy for LACP, EUS guided intra-tumour ³²P implantation is associated with better clinical outcomes than SBRT, including overall and progression free survival, tumour downstaging and surgical resection. Both forms of radiotherapy have demonstrated a good safety profile. These findings warrant further evaluation with a larger randomized controlled trial.

Introduction

The use of contrast-enhanced endoscopic ultrasound (CE-EUS) for characterizing solid pancreatic masses has improved diagnostic capabilities. We aimed to evaluate the performance of an artificial intelligence (AI)-powered system for differential diagnosis of pancreatic adenocarcinoma using CE-EUS.

Aims & Methods

The methodology integrates advanced imaging analysis and machine learning (ML) to develop an automated framework for pancreatic tumor characterization using EUS. A convolutional neural network (CNN) is first trained on labeled non-contrast EUS images to detect and segment the pancreas and tumor regions accurately. Once trained, the CNN is applied to new cases, identifying regions of interest (ROIs) in the non-contrast images, which are subsequently mapped onto the corresponding contrast-enhanced images for further analysis. Time-Intensity Curve (TIC) analysis was performed on the mapped ROIs, extracting a comprehensive set of quantitative parameters describing contrast enhancement dynamics. These parameters include temporal metrics (e.g., time to peak, rise time), intensity measures (e.g., peak intensity, wash-in intensity), slopes (e.g., wash-in and wash-out rates), area-based metrics (e.g., area under the curve), and perfusion-related characteristics (e.g., perfusion index, blood flow). The extracted TIC parameters are then used to train a feedforward neural network (FNN), which learns to differentiate diagnostic categories based on the perfusion characteristics of the lesions. In the final integrated model, the CNN detects pancreas and tumor regions, maps them to contrast-enhanced images, computes TIC parameters, and feeds these into the FNN to provide automated diagnostic predictions.

Results

Retrospective analysis was performed on a prospectively collected dataset of 120 CE-EUS videos obtained from patients with solid pancreatic masses in 3 tertiary referral centers. The dataset included 88 pancreatic adenocarcinomas, 1 lymphoma, 4 metastatic lesions, 10 neuroendocrine neoplasms (G1/G2), 15 cases of chronic pancreatitis, and 2 solid pseudopapillary neoplasms (SPNs). Diagnostic performance was evaluated by calculating sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy. Based on CNN analysis, both precision and recall were also calculated. The AI-powered CE-EUS system achieved high diagnostic performance, with an accuracy of over 95% for the diagnosis of pancreatic adenocarcinoma. Precision and recall were also excellent for differentiating adenocarcinoma from other pancreatic lesions based on CNN analysis.

Conclusion

This novel AI-based approach using CE-EUS reliably distinguished pancreatic adenocarcinoma from other solid pancreatic masses. Real-time analysis of time-intensity curve parameters enhances diagnostic accuracy and offers a promising adjunct to traditional EUS methods. Further prospective validation is warranted to confirm these findings and explore clinical applicability.

References

1. Săftoiu A, Vilmann P, Bhutani MS, Hassan H, Hawes R, Dietrich CF, et al. Enhanced endoscopic ultrasound imaging for pancreatic lesions: A review.
World J Gastrointest Endosc. 2022 Jul 16;14(7):369–84. doi:10.4253/wjge.v14.i7.369 PMID: 35967758; PMCID: PMC9367228.
2. Liang T, Zhang H, Wang Y, Sun Y, Ma K, Liu W, et al. Artificial intelligence-assisted endoscopic ultrasound for detection of pancreatic lesions: A systematic review and meta-analysis. World J Gastroenterol. 2023 Feb 21;29(7):1150–1164. doi:10.3748/wjg.v29.i7.1150 PMID: 36849883; PMCID: PMC10720860.

Introduction

Pancreatic ductal adenocarcinoma (PDAC) represents over 90% of pancreatic cancer cases and remains a highly lethal malignancy with a five-year survival rate below 12%. Although KRAS mutations drive approximately 90% of PDAC cases, the clinical efficacy of direct KRAS inhibitors remains limited, highlighting the critical need for alternative therapeutic targets. Kinases have emerged as promising candidates for PDAC treatment. Through a kinase-focused esiRNA library screen comparing KRAS-mutant and wild-type PDAC cell lines, we identified serine/threonine kinase 31 (STK31) as a KRAS-dependent oncogenic effector that promotes tumor progression by regulating key cell cycle proteins CCNB1 and CDC25C. However, STK31’s kinase activity, downstream signaling mechanisms, and pharmacologically targetable features remain unknown, representing a significant gap in our understanding of its therapeutic potential.

Aims & Methods

This study aims to characterize the molecular mechanisms of STK31’s kinase function and evaluate STK31 inhibitors for PDAC treatment using preclinical models. We employed 4D label-free phosphoproteomics to identify potential STK31 substrates, followed by in vitro kinase assays to validate phosphorylation activity. AlphaFold 3 was utilized for structure-based virtual screening of STK31 inhibitors.

Results

Our preliminary data demonstrate that STK31 exhibits intrinsic kinase activity and phosphorylates mTORC2, potentially regulating CCNB1 and CDC25C expression through STAT1 phosphorylation. AI-driven molecular docking identified ciclopirox as a putative STK31 inhibitor, which was subsequently validated in functional assays. Ciclopirox effectively suppressed PDAC cell growth, with enhanced potency in KRAS-mutant cell lines.

Conclusion

Based on these findings, we propose that STK31 drives PDAC progression via the mTORC2-STAT1-CCNB1/CDC25C axis and that pharmacological inhibition of STK31 represents a viable therapeutic strategy.

Introduction

Acute pancreatitis (AP) is closely intricately linked to electrolyte disturbances. Such imbalances can exacerbate the instability of the intracellular environment, subsequently accelerating the progression of AP. This study aimed primarily to develop a simplified electrolyte scoring system (CC score) to determine AP exacerbation.

Aims & Methods

A new CC score was established in this study using the Medical Information Mart for Intensive Care IV (MIMIC-IV) v3.1 database, and it was validated using the digestive department database of the First Affiliated Hospital of Nanchang University. The primary endpoint considered was the exacerbation of the disease post-admission in AP patients. Receiver operating characteristic (ROC) curves and decision curve analysis (DCA) plots were used to assess the predictive value and clinical applicability of the new CC score. Improvements were implemented on the acute physiology and chronic health evaluation II (APACHE II) and systemic inflammatory response syndrome (SIRS) scoring systems, and their performance was compared with that of traditional predictive scoring systems.

Results

This study incorporates data from 1413 AP patients drawn from the MIMIC-IV database, supplemented by a further 1040 AP patients in an external validation group. Of these, 178 and 70 AP patients were respectively transferred to the Intensive Care Unit (ICU). The multivariate adjustment model indicates that a significant negative correlation between serum Ca²⁺ levels and severe progression in AP patients, while serum Cl^- levels showed a J-shaped association with severe progression. Through node analysis of the restricted cubic splines (RCS) model, combined with the clinical grading standards for hyperchloremia and hypocalcemia, the critical values for Cl^- and Ca²⁺ were determined to be 110 mmol/L and 1.77 and 2.1 mmol/L, respectively. Based on these findings, we established a new CC score and optimized the APACHE II and SIRS scoring systems. The results indicated that the predictive power of the optimized APACHE II score (AUC=0.83) and SIRS score (AUC=0.87) for severe progression in AP patients surpassed that of the original APACHE II score (AUC=0.74) and SIRS score (AUC=0.71).

Conclusion

The new CC score not only effectively predicts the risk of severe progression in AP patients but also enhances the predictive performance of both SIRS and APACHE II scores for assessing severe progression risk in these patients.

Introduction

Pancreatic pseudocysts (PPs), common complications of acute or chronic pancreatitis, are often managed with endoscopic ultrasound-guided double pigtail stent (EUS-DPS) drainage. However, the relationship between stent indwelling duration and PPs recurrence remains poorly defined.

Aims & Methods

We aimed to investigate whether shorter stent dwelling duration is associated with a higher risk of PPs recurrence. Patients diagnosed with PPs who underwent EUS-DPS drainage at Peking Union Medical College Hospital between June 2006 and December 2024 were retrospectively reviewed. Clinical outcomes including technical success, clinical success, postoperative complications, and recurrence were analyzed. Furtherly, the stent indwelling duration-recurrence relationship and risk factors were evaluated.

Results

A total of 116 patients were included (84 males, 72.4%), with a mean age of 48.29±13.56 years. The most common etiologies were biliary pancreatitis (28.4%) and alcoholic pancreatitis (25.9%). PPs were primarily located in the pancreatic body and tail (78.4%), with a mean diameter of 10.23±4.17 cm. Regarding drainage success, technical success was achieved in 106 cases (91.4%), and clinical success in 81 cases (69.8%). Postoperative adverse events occurred in 33.6% of patients, including infections (n=31), bleeding (n=3), perforation (n=2), and cardiopulmonary events (n=3). Patients with clinical success were stratified by stent indwelling duration (0-2 months, 2-6 months, >6 months), while PPs recurrence was significantly higher in the short-duration group compared to the intermediate- and long-duration groups (p-value < 0.05). No postoperative adverse events occurred beyond 30 days in any group, suggesting that prolonged stent indwelling duration does not increase the risk of long-term complications. Meanwhile, multivariate regression analysis identified longer stent dwelling duration and elevated high-sensitivity C-reactive protein as independent protective factors for clinical success.

Conclusion

EUS-DPS placement represents a safe and effective modality for internal drainage and therapeutic approach for PPs. Our findings support that maintaining stent placement for more than six months to significantly reduce recurrence risk and improve long-term clinical outcomes, with manageable adverse events.