Introduction

Diabetes mellitus (DM) is a risk factor of pancreatic cancer (PC), but the effect of glycemic control on PC development among patients with long-standing type 2 diabetes (T2D) is not well investigated.

Aims & Methods

We aimed to investigate the benefit effect of optimal glycemic control on PC development in patients with long-standing T2D. In this retrospective cohort study, adults with newly diagnosed T2D between 2001 and 2015 were identified from a territory-wide electronic healthcare database. T2D diagnosis was based on the American Diabetes Association criteria, ICD-9 codes, or use of anti-diabetic medications. Exclusion criteria were prior history of PC, immunoglobulin G4 disease, pancreatectomy and PC cases occurring within three years of T2D diagnosis (to address reverse causality). The primary outcome was PC, while secondary outcome was PC-related mortality. For primary exposure, optimal glycemic control was defined as time-weighted mean hemoglobin A1c (HbA1c) <7%, For secondary exposure, optimal glycemic control was defined as fasting glucose (FG) ≤7mmol/L. Adjusted hazard ratios (aHRs) were derived from propensity score (PS) regression adjustment for 28 covariates including age, sex, smoking, alcohol use, body mass index, diabetes complications, history of pancreatitis and cholangitis, comorbidities, and medications (aspirin, statins, anti-diabetic drugs).

Results

Among 458,331 T2D patients (mean age:60.0±12.1 years; 51.2% male), there were 257,659 and 200,672 patients with optimal and suboptimal glycemic control. Among them, 1,382 (0.3%) developed PC and 922 (0.2%) died from PC over a mean follow-up of 10.8±4.1 years. Optimal glycemic control was associated with lower PC risk – HbA1c <7% (aHR:0.43; 95%CI:0.37-0.48) and FG <7mmol/L (aHR:0.71; 95%CI:0.63-0.80). Optimal control of both HbA1c and FG conferred lowest PC risk (aHR:0.39; 95% CI:0.33-0.46). Optimal control was also associated with lower PC-related mortality – HbA1c <7% (aHR:0.35; 95%CI:0.30-0.41) and FG <7mmol/L (aHR:0.69; 95%CI:0.59-0.79). Every 1% rise in HbA1c and 1mmol/L rise in FG was associated with higher PC risk by 46% (95%:39-35%) and 14% (95% CI:11-17%), respectively. When compared with HbA1c <7.0%, higher HbA1c conferred stepwise increase in PC risk (P_trend<0.001), with aHRs being 1.85 (95% CI:1.59-2.16), 2.52 (95% CI:2.10-3.02), 3.47 (95%CI:2.81-4.29), 3.58 (95% CI:2.76-4.66) and 4.61 (95% CI:3.72-5.70) for HbA1c levels of <7%, 7.0 to <7.5%, 7.5 to <8.0%, 8.0 to <8.5%, 8.5 to <9.0% and ≥9.0%, respectively. When compared with FG <7.0%, higher FG also conferred stepwise increase in PC risk (P_trend<0.001), with aHRs being 1.36 (95% CI:1.20-1.54) and 2.53 (95% CI:1.99-3.22), respectively.

Conclusion

Optimal glycemic control was associated with lower risk of PC risk and PC-related mortality in T2D. Further multicenter cohort studies are warranted to confirm its oncopreventive strategy.

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

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

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

Patients with suspected main-duct intraductal papillary mucinous neoplasms (MD-IPMN) are frequently referred for surgery due to the high risk of malignancy (as high as 40% to 60% in the literature). However, many present with significant comorbidities or concurrent malignancies, complicating the surgical risk-benefit assessment. In such cases, advanced endoscopic procedures may assist in guiding clinical decision-making.

Aims & Methods

This study aimed to evaluate the role of EUS-guided fine-needle biopsy (EUS-FNB) and pancreatoscopy in individualized risk stratification and management decisions for patients with suspected MD-IPMN. We retrospectively analyzed eight patients treated at our center between March 2020 and March 2025. All patients presented with significant comorbidities or active oncologic disease. Data collected included endoscopic findings, biopsy results, complications, and final management decisions.

Results

Eight patients with suspected main-duct IPMN were included (mean age: 67.6 years; 3 females, 37.5%). The mean main pancreatic duct (MPD) diameter was 9.1 mm. All patients were evaluated in a multidisciplinary setting due to clinical complexity, including comorbidities or concurrent malignancies. EUS-guided fine-needle biopsy (EUS-FNB) was performed in 3 patients, and pancreatoscopy in 5. All procedures were technically successful. Biopsy samples were diagnostic in 2 of 3 EUS-FNB cases and 5 of 5 pancreatoscopy cases and contributed directly to management decisions. In 1 EUS-FNB case, the sample was non-diagnostic. Pancreatoscopy revealed mucin extrusion in 4/5 patients, papillary or villous projections in 3/5, and a 'fish egg' appearance in 2/5. These features supported risk assessment and, in several cases, justified a conservative approach in high-risk patients. Three patients underwent surgery following multidisciplinary review. One had concordant findings (high-grade dysplasia), while two had discordant outcomes: one with low-risk pancreatoscopy findings had invasive adenocarcinoma, and one with EUS-FNB showing low-grade atypia had high-grade dysplasia on final pathology. Five patients were managed with active surveillance. One case of mild post-ERCP pancreatitis occurred; no other complications were reported. Endoscopic findings influenced management in 5 of 8 patients (62.5%).

Conclusion

In this real-world case series, EUS-FNB and pancreatoscopy contributed meaningfully to individualized decision-making in patients with suspected MD-IPMN. However, discordance between endoscopic impressions and final pathology in two cases highlights the limitations of visual and cytologic assessment. These findings reinforce the need for integrating endoscopic data with imaging, clinical context, and multidisciplinary input when evaluating main-duct IPMN.

References

1. Salvia R, Fernández-del Castillo C, Bassi C, Thayer SP, Falconi M, Mantovani W, Pederzoli P, Warshaw AL. Main-duct intraductal papillary mucinous neoplasms of the pancreas: clinical predictors of malignancy and long-term survival following resection. Ann Surg. 2004 May;239(5):678-85; discussion 685-7. doi: 10.1097/01.sla.0000124386.54496.15. PMID: 15082972; PMCID: PMC1356276.
2. Sohn TA, Yeo CJ, Cameron JL, Hruban RH, Fukushima N, Campbell KA, Lillemoe KD. Intraductal papillary mucinous neoplasms of the pancreas: an updated experience. Ann Surg. 2004 Jun;239(6):788-97; discussion 797-9. doi: 10.1097/01.sla.0000128306.90650.aa. PMID: 15166958; PMCID: PMC1356287.

Introduction

Pancreatic calcification is the most frequent structural change in chronic pancreatitis (CP), but the factors associated with its development are not well understood.

Aims & Methods

We aimed to investigate the risk factors of calcification development in patients with chronic pancreatitis. The study protocol was registered on PROSPERO (CRD42024591837). On September 18, 2024, we conducted a systematic search across three databases (PubMed, EMBASE, and CENTRAL) for studies reporting factors associated with calcification in chronic pancreatitis (CP). Pooled proportions and odds ratios (OR) with 95% confidence intervals (CI) were calculated using a random effects model.

Results

The systematic search resulted in 10,893 articles, from which 85 eligible studies were identified, covering a total of 34568 participants. The odds of calcification were 45% higher in alcoholic compared to idiopathic CP (OR=1.45, CI: 1.00–2.11). Alcohol consumption (OR=2.31, CI: 1.8–2.98) and smoking (OR=2.22, CI: 1.61–3.06) were associated with a two times higher risk of calcification in CP, when compared to non-smokers and non-drinkers. In contrast, the presence of CFTR mutations did not increase the risk of calcification in CP (OR=0.43, CI: 0.11–1.66) compared to patients without CFTR mutations.

Conclusion

Alcohol consumption and smoking were significantly associated with the presence of calcification in CP, making it essential to identify these risk factors and incorporate smoking cessation and alcohol reduction programs into standard care.

Introduction

Pancreatic steatosis (PS) is linked to metabolic dysregulation. Magnetic resonance imaging (MRI)-derived proton density fat fraction (PDFF) provides a reliable assessment of intrapancreatic fat. This study investigates the relationship between pancreatic fat, assessed by ultrasound and MRI, and metabolic parameters from the oral glucose tolerance test (OGTT).

Aims & Methods

We analyzed 40 non-diabetic patients with increased pancreatic echogenicity, of whom 29 completed the study (mean age: 54 ± 10.4 years; BMI: 34.8 kg/m²; waist circumference: 93.8 ± 11.3 cm). Participants underwent OGTT, with assessment of β-cell function indices (Disposition Index, Insulinogenic Index) and insulin sensitivity indices (Matsuda Index, HOMA-IR, Stumvoll Index). Pancreatic fat was evaluated using ultrasound, MRI-PDFF, and two-dimensional shear wave elastography.

Results

The mean pancreatic fat fraction was 13.75 ± 11.22% (median: 7.633%), and mean pancreatic stiffness was 8.1 ± 3.2 kPa. After OGTT, 27.5% of patients exhibited impaired glucose tolerance (IGT). PDFF positively correlated with weight (r = 0.520, p = 0.004), BMI (r = 0.505, p = 0.005), and body surface area (r = 0.509, p = 0.005), but not with liver enzymes, metabolic parameters, or β-cell function. A significant negative correlation was found between pancreatic stiffness and the Potentiation Factor (PFR1), indicating reduced β-cell responsiveness with increasing pancreatic stiffness. Stratification by glucose tolerance status revealed that increased pancreatic fat was associated with greater insulin resistance and compensatory hyperinsulinemia.

Conclusion

In conclusion, our study confirms that increased intrapancreatic fat is an indicator of ectopic lipid accumulation and is correlated with general adiposity. Our study identifies pancreatic fat infiltration as a marker of early metabolic dysfunction, where increasing pancreatic fat triggers β-cell compensatory mechanisms. This underscores the importance of determining a pancreatic fat threshold below which glucose homeostasis may still be restored. Targeted interventions to reduce pancreatic fat are crucial to preventing the progression to irreversible β-cell dysfunction.