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

Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) have demonstrated metabolic and cardiovascular benefits in patients with type 2 diabetes (T2D). However, their potential effect on pancreatic cancer (PC) risk remains unclear.

Aims & Methods

We aimed to examine the association between SGLT-2i use and PC risk in T2D patients prescribed metformin. We conducted a retrospective cohort study using a territory-wide electronic healthcare database, retrieving adult patients (≥18 years) with T2D who initiated metformin between 2015 and 2022. The index date was the first metformin prescription during the study period. Patients were observed until PC, pancreatectomy, death, or study end date (December 31, 2022). Exclusion criteria included prior history of PC, IgG4 disease, pancreatectomy, or fewer than two HbA1c measurements during follow-up. The outcome and exposure of interest was PC and SGLT-2i use (including dapagliflozin, empagliflozin, canagliflozin and ertugliflozin), respectively. SGLT-2i exposure was defined as continuous use during 90-day entry period following the index date. Cox proportional hazards model with propensity score (PS) matching (1:2) on 28 covariates – age, sex, smoking, alcohol use, body mass index (BMI), diabetes duration and complications, glycemic control (in terms of time-weighted mean HbA1c), history of pancreatitis and cholangitis, comorbidities, and concomitant medication use (aspirin, statins, and other antidiabetic medications) – were used to estimate hazard ratios (HRs). Sensitivity analysis by treating medication use as time-varying variable was conducted to address immortal time bias.

Results

Among 144,468 matched patients (mean age:59.3±11.2 years; male:58.3%; 48,156 SGLT-2i users and 96,312 SGLT-2i non-users), 441 (0.31%) developed PC during a mean follow-up of 6.6±2.0years. The mean duration of SGLT-2i use was 2.1±1.6 years. SGLT-2i use was associated with lowered PC risk (aHR:0.43; 95% CI:0.34-0.55), irrespective of empagliflozin (aHR0.43; 95%CI: 0.33-0.57) or dapagliflozin use (aHR:0.33; 95% CI:0.22-0.49). When drug use was modelled as time-varying variables, the protective effect remained significant (aHR:0.35; 95% CI:0.15-0.78). Furthermore, a dose- and duration-dependent relationship was observed. The aHR was 0.88 (95% CI:0.84-0.92) per 100-cumulative defined daily dose (cDDD) increase in use, and 0.66 (95% CI:0.59-0.75) per 1-year increase in use. Subgroup analysis showed beneficial effects persistent regardless of age (cutoff of 65 years), sex, BMI (cutoff of 25 kg/m²), diabetes complications, usage of other medications (aspirin, statins, and insulin).

Conclusion

SGLT-2i use was associated with a lower risk of PC in a dose- and duration-dependent manner, which was independent of glycemic control, among T2D patients treated with metformin. These findings provide insights into informing the choice of second-line anti-diabetic drug in lowering PC risk in T2D metformin users.

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

Autoimmune pancreatitis (AIP) is a rare, immune-mediated form of chronic pancreatitis, classified into three subtypes. Type 1 AIP, the pancreatic manifestation of IgG4-related disease, often presents with multisystem involvement and frequent relapse (1,2). Type 2 AIP is pancreas-limited, tends to affect younger individuals, and is commonly associated with inflammatory bowel disease (IBD) (2,3). A third form—checkpoint inhibitor-related pancreatitis (CIP or Type 3 AIP)—has been recently described in patients receiving immune checkpoint inhibitors, typically asymptomatic but may result in pancreatic atrophy (4).
Precise subtyping is critical due to differences in clinical behavior, relapse risk, and treatment response (1,2,3). We present a single-center series comparing clinical, radiologic, and histopathologic characteristics of Type 1 and Type 2 AIP.

Aims & Methods

We retrospectively reviewed 20 patients diagnosed with AIP between 2020–2024 at a tertiary center. Classification followed International Consensus Diagnostic Criteria (1). Diagnostic evaluation included endoscopic ultrasound (EUS), serum IgG4 levels, and contrast-enhanced CT/MRI/MRCP (1,2). EUS-guided fine-needle biopsy (FNB) was performed where malignancy could not be excluded. Histopathology differentiated lymphoplasmacytic sclerosing pancreatitis (LPSP, Type 1) from idiopathic duct-centric pancreatitis (IDCP, Type 2) (2). Data on extra-pancreatic involvement, steroid response, and relapse were collected.

Results

Fifteen patients were diagnosed with Type 1 AIP and five with Type 2. Type 1 patients had a mean age of 63 years and were predominantly male (80%). Obstructive jaundice was the most common presentation. All had elevated serum IgG4. EUS revealed diffusely hyperechoic parenchyma and long-segment ductal narrowing. Histology confirmed LPSP. Extra-pancreatic involvement was observed in 60%, most commonly IgG4 cholangitis. All responded to corticosteroids; 40% relapsed within one year and received rituximab (5).
Type 2 patients had a mean age of 38, with equal gender distribution. Presenting symptoms included abdominal pain and acute pancreatitis. Serum IgG4 was normal in all cases. EUS revealed focal hypoechoic lesions with short-segment narrowing. Histology confirmed IDCP. Two patients (40%) had ulcerative colitis. All achieved remission with steroids, and no relapses were observed (2,3).

Conclusion

This series emphasizes the distinct clinical courses of AIP subtypes. Type 1 AIP represents a systemic IgG4-related disease with high relapse risk, often requiring long-term immunosuppression (5). Type 2 AIP affects younger patients, remains confined to the pancreas, and shows sustained remission after steroid therapy (2,3). Accurate classification using EUS, MRCP, IgG4, and histology is crucial for appropriate management and long-term outcomes (1,2).

References

1. Hart PA, Zen Y, Chari ST. Recent Advances in Autoimmune Pancreatitis. Gastroenterology. 2015;149(1):39–51.

2. de Pretis N, Crinò SF, Amodio A, et al. Type 2 autoimmune pancreatitis: Clinical features and long-term follow-up in an Italian cohort. United European Gastroenterol J. 2024;12(1):50–59.
   

3. Lohr JM, Dominguez-Munoz E, Rosendahl J, et al. United European Gastroenterology evidence-based guidelines for the diagnosis and therapy of chronic pancreatitis (HaPanEU). United European Gastroenterol J.2017;5(2):153–199.

4. Lamarca A, Dhani N, Hubner RA, et al. Immune checkpoint inhibitor-induced autoimmune pancreatitis (Type 3 AIP): Emerging entity with distinct features. Ann Oncol. 2023;34(3):385–393.
   

5. Ghazale A, Chari ST, Zhang L, et al. Treatment of relapsing autoimmune pancreatitis with immunomodulators and rituximab: The Mayo Clinic experience. Clin Gastroenterol Hepatol. 2012;10(6):640–646.