Introduction

The aim of this study is to evaluate the volume of biliopancreatic diseases at AUSL Romagna and assess their burden on healthcare system from emergency care to subsequent hospitalization in dedicated departments.

Aims & Methods

We designed a longitudinal, retrospective, descriptive study, considering patients who accessed the Emergency Departments (ED) in all first and second-level centers of AUSL Romagna from January 2018 to December 2024, having blood lipase levels above the upper limit (≥60 U/L). We divided these patients into two groups: the first one (identified as “acute pancreatitis” (AP)) with lipase levels above three times upper limit (≥180 U/L), and the second group (identified as “other biliopancreatic (BP) diseases”) including patients with high lipase level associated to other gastrointestinal conditions, evaluating their care pathways.

Results

The total number of emergency admissions to AUSL Romagna with lipase levels ≥ 60 U/L was 29011, accounting for 1% of annual emergency admissions, with the majority triaged as green (minor urgency). Of these, 9204 patients (32%) were discharged with a diagnosis compatible with AP (13%, N= 3669) or other BP diseases (19%, N= 5535), with consistent rates over the years. Male sex was predominant for BP group with a median age of 63 years, female sex for the AP group and median age of 66 years. Nearly all patients with AP (94%) required subsequent hospitalization, primarily in the gastroenterology department (32%), followed by general medicine (25%) and general surgery (15%). In the other BP diseases group, fewer than half (40%) required subsequent hospitalization. The discharge diagnoses from specialized departments showed an increase in diagnostic accuracy compared to initial assessments, reflecting initial missed diagnoses, appropriate re-evaluations during hospitalization, complications, etc. From an economic perspective, hospital stays in specialized departments lasted an average of 9.5 days, with an average cost of €3,784 per stay. Specifically, hospitalizations in the gastroenterology department for AP had an average duration of 9.3 days, with a total cost of €4129740 for 1181 admissions. For other BP diseases, the costs for a total of 522 hospitalizations amounted to €1808899, with an average stay of 9.3 days. Most hospitalizations ended in discharge to home (84%), with an in-hospital mortality rate of 4%.

Conclusion

Our study provided a detailed roadmap of patients with biliopancreatic diseases in AUSL Romagna (an area covering 1.2 millions of inhabitants), from their admission in ED to their discharge by different departments. BP diseases account for 1% of all ED accesses and most of the cases are characterized by medium-high complexity, with an economic annual burden of €2.8 million. These results may support the healthcare policy towards an optimization of economic and human resources to improve patient’s management and outcomes.

Introduction

The consequences of chronic pancreatitis (CP) may not be exclusively limited to the pancreas or restricted to the gastrointestinal tract but could also be systemic. To date, the relationship between chronic pancreatitis and cardiovascular risk factors has not been studied extensively. We conducted a systematic review and meta-analysis to examine if the combination of chronic inflammatory changes may possibly place CP patients at risk for cardiovascular disease.

Aims & Methods

We systematically searched PubMed, Scopus, and Cochrane Register of Controlled Trials for observational studies that compared major cardiovascular outcomes in patients with chronic pancreatitis. The outcomes explored were: (1) acute coronary disease/myocardial infarction; (2) hypertension; (3) hyperlipidemia; and (4) diabetes mellitus. We computed odds ratio (OR) for binary endpoints, with 95% confidence intervals (CI). Heterogeneity was examined I² statistics; p values less than 0.10 and I² > 25% were considered significant for heterogeneity.

Results

Four observational studies comprising a total of 57,721 patients with chronic pancreatitis were included in this meta-analysis. The most consistent finding across studies was a significantly higher risk of diabetes mellitus in patients with chronic pancreatitis compared to a control group without chronic pancreatitis (OR 4.77; 95% CI 1.32–17.28; p=0.017; I²=100%). In contrast, no statistically significant associations were found between chronic pancreatitis and other cardiovascular outcomes, including cerebrovascular disease (OR 1.59; 95% CI 0.98–2.57; p=0.05; I²=99.4%), acute coronary syndrome/myocardial infarction (OR 1.35; 95% CI 1.00–1.82; p=0.049; I²=95.4%), hypertension (OR 0.52; 95% CI 0.30–7.61; p=0.608; I²=99.9%) or hyperlipidemia (OR 2.60; 95% CI 0.36–18.77; p=0.342; I²=100%).

Conclusion

The results of our meta-analysis suggest that chronic pancreatitis is not associated with increased risk of cardiovascular disease despite being associated with a higher risk of diabetes mellitus.

Introduction

Chronic pancreatitis (CP) may have differences in causes, presentations and progression related to sex. There are few studies describing the sex related phenotype of CP.

Aims & Methods

We aimed to study sex differences in etiology, complications and treatment of CP in a large, North-European CP cohort. Data were extracted from the Scandinavian Baltic Pancreatic Club (SBPC) database. The collected data included sex, age, etiology, anthropometric measures, data for smoking and alcohol exposures and data on treatment and complications from CP. Differences between sexes were compared with multiple logistic regression models.

Results

We included 1922 patients in the analyses, of whom 1264 were men. Mean age of CP onset was 52.5 (SD 15.0) years in men and 51.5 (SD 16.4) years in women (p=0.2). In univariate analysis alcohol etiology and smoking was associated with male sex, whereas hereditary pancreatitis, efferent duct obstruction, autoimmune pancreatitis were associated to female sex. Numbers of men and women with non-alcoholic etiology were almost equal (461 and 422, respectively). In multivariate analysis including all etiologies, time with disease and age; alcohol etiology remained strongly associated to male sex (OR 2.92 (2.29-3.71), p<0.001), whereas duct obstruction etiology was associated with female sex (OR 0.62 (0.44-0.89), p=0.01).
Significantly more women were underweight (p<0.001), and more men were overweight (p<0.001). Concerning other complications, diabetes mellitus (DM) was strongly associated with men (OR 1.62 (1.27-2.07), p<0.001), whereas osteoporosis was strongly associated with women (OR 0.47 (0.32-0.70), p<0.001). Recurrent acute pancreatitis and exocrine insufficiency were equally distributed between the sexes. There were no differences between sexes for medical, endoscopic or surgical treatment options.

Conclusion

More men than women had alcohol induced CP, but there was almost no difference in absolute numbers of men and women with non-alcoholic CP. Among the CP patients, DM was associated with men, while osteoporosis was associated with women.

Introduction

To assess whether trans papillary drainage is the way to go for pseudocysts complicating patients with chronic pancreatitis. With our previous experience we used the technique of no injecting contrast during ERP in case of leaks complicating chronic pancreatitis causing either pseudocysts, pleural effusions or ascites. Here we are presenting a retrospective analysis of our management of pseudocysts in chronic pancreatitis.

Aims & Methods

We retrospectively analysed all cases of chronic pancreatitis having ascites, effusions and pseudocysts. We performed magnetic resonance cholangiopancreatography (MRCP) followed by therapeutic endoscopic retrograde pancreatography (ERP) without contrast. Results were observed confirming a leak from the MPD, possibility of wire crossing the leak or not and resolution of the pseudocysts. Patients with only pseudocysts were included in this analysis.

Results

We performed ERP in 1522 patients from 2000 till date. Ductal disruptions noted in 509/1522 (33.44%) out of which pseudocyst was observed in 330 cases (64.83%).
311 patients (94.2 %) experienced successful cannulation of PD. In 19 (5.8%) PD could not be cannulated. Non cannulated cases treated with EUS guided transmural drainage 14 (73.7%) and surgery 5(26.3%)
Of these 311, 24 (8.3%) had pancreas divisum and MPD was cannulated from minor papilla.
Leak did not cross but stents put in cyst (236, 75.9 %). Cyst resolution – 228 (96.6%). Cyst Not resolved 8 (3.4%). Leaks were crossed in 75 (24.1 %); Cyst resolution 69 (92%). Cyst not resolved 6 (8%).
Unresolved cysts 14 (4.5%) were treated with EUS Aspiration- 5 (35.7%), EUS Transmural drainage 8 (57.1%), Surgery -2 (14.2%).
Discussion: In chronic pancreatitis the cause of pseudocysts is ductal rupture and very minimal inflammation as compared to acute pancreatitis where the major cause is inflammation with ductal leak and necrosis of the pancreas. There is hardly any necrosis in chronic pancreatitis pseudocysts. Hence the management of both should be individualised. Transpapillary drainage in pseudocysts complicating chronic pancreatitis offers a less morbid and a simpler alternative to transmural drainage or surgery.

Conclusion

Pseudocysts complicating chronic pancreatitis can be managed very effectively using transpapillary drainage in majority of cases and should be attempted before considering transmural or surgical drainage. It saves the patient significant morbidity

Introduction

Biliary stones are a leading cause of acute pancreatitis (AP). Endoscopic Retrograde Cholangiopancreatography (ERCP) is the standard of care when concomitant cholangitis or confirmed choledocholithiasis is present¹. However, spontaneous migration of biliary stones in the latter occurs in approximately 20% of cases², potentially exposing patients to the inherent risks of ERCP without a definitive therapeutic benefit.

Aims & Methods

This study aimed to identify predictors of spontaneous common bile duct stone clearance in patients with acute biliary pancreatitis. We conducted a retrospective cohort study of consecutive patients diagnosed with acute pancreatitis and confirmed choledocholithiasis, who subsequently underwent ERCP. Patients with a prior ERCP or concurrent acute cholangitis were excluded.

Results

Forty-four patients were included, 61.4% female with a mean age of 67±18 years. In 31.8% of cases, no stone was identified at ERCP, suggestive of spontaneous resolution. The median interval from admission to ERCP was 10 days and did not significantly differ between patients with and without stones (p=0.872). Serum levels of total bilirubin (2.5±2.0 vs. 2.3±2.9 mg/dL, p=0.825), AST (160±31 vs. 171±50 U/L, p=0.505), and alkaline phosphatase (267±135 vs. 210±70 U/L, p=0.187) were not significantly different between groups with and without stones at ERCP, respectively. Neither cholecystectomy status (p=0.722), common bile duct dilation on imaging (p=0.955), nor number of stones (p=0.829) correlated with spontaneous clearance. Interestingly, patients without lithiasis at ERCP had significantly smaller common bile duct stones on imaging compared to those with retained stones (5 ± 3 mm vs. 8 ± 5 mm, p=0.025). Stone size was an independent predictor of spontaneous resolution in the multivariate analysis (OR = 1.24; 95% CI: 1.01–1.52; p = 0.036), with a diameter ≥7 mm yielding a sensitivity of 63% and a specificity of 78.6% for predicting the presence of stones at ERCP.

Conclusion

Spontaneous passage of biliary stones is common in the context of acute biliary pancreatitis, particularly when their size is ≤7 mm. These findings support a risk-adapted strategy, in which Endoscopic Ultrasound may be employed to confirm choledocholithiasis immediately prior to ERCP in patients with small biliary stones.

References

1. Manes, G. et al. Endoscopic management of common bile duct stones: European Society of Gastrointestinal Endoscopy (ESGE) guideline. Endoscopy 51, 472–491 (2019).
2. Sperna Weiland, C. J. et al. Suspected common bile duct stones: reduction of unnecessary ERCP by pre-procedural imaging and timing of ERCP. Surg. Endosc. 37, 1194–1202 (2023).

Introduction

Endoscopic ultrasound (EUS) elastography has emerged as a valuable tool for assessing pancreatic tissue stiffness, aiding in the differentiation of normal pancreas, chronic pancreatitis (CP), and solid pancreatic masses, including pancreatic adenocarcinoma (PDAC) and cholangiocarcinoma (CC). The newly developed two-dimensional shear wave elastography (2D-SWE) provides real-time, quantitative elasticity maps with improved reproducibility. This study aims to evaluate the performance of 2D-SWE during EUS for differentiating normal pancreas, CP, and solid pancreatic tumors.

Aims & Methods

This prospective study included patients undergoing EUS for pancreatic evaluation. All 2D-SWE measurements were made using the Aplio i800 EUS ultrasound machine. Four groups were analyzed: (1) individuals with a normal pancreas, (2) patients with CP (based on Rosemont criteria), (3) patients with PDAC, and (4) patients with CC (all diagnoses confirmed histopathologically). 2D-SWE was performed during EUS using a linear-array echoendoscope. Quantitative elasticity values (kPa) were recorded for the normal pancreas, CP-affected tissue, and tumor lesions. The diagnostic performance of 2D-SWE was assessed using intraclass correlation coefficient (ICC), receiver operating characteristic (ROC) analysis, and pairwise statistical comparisons.

Results

A total of 30 patients were included (6 normal, 5 CP, 17 PDAC, 2 CC). The intra-observer reproducibility of SWE measurements was excellent (ICC = 0.89). Mean elasticity values significantly differed among groups, with PDAC showing the highest variability (mean SWE = 54.1 ± 45.7 kPa, median = 33.1), CC presenting elevated stiffness (mean SWE = 77.4 ± 11.0 kPa), CP showing heterogeneous values (mean SWE = 57.5 ± 52.3 kPa, median = 43.6), and normal pancreas showing the lowest stiffness (mean SWE = 7.5 ± 3.9 kPa, median = 6.2).
ROC analysis for distinguishing malignant solid tumors (PDAC + CC) from normal pancreas showed excellent diagnostic performance (AUC = 0.93). The optimal cutoff of 17.0 kPa yielded a sensitivity of 84.2%, specificity of 100%, positive predictive value (PPV) of 100%, negative predictive value (NPV) of 66.7%, and overall accuracy of 88%.
Pairwise t-tests confirmed a statistically significant difference between PDAC and normal pancreas (p = 0.0007), with trends observed for CC vs normal (p = 0.0605) and CP vs normal (p = 0.099). No statistically significant differences were observed among solid tumor subtypes (PDAC vs CC, PDAC vs CP, CC vs CP).

Conclusion

2D-SWE during EUS provides highly reproducible and quantitative elasticity values that reliably differentiate normal pancreas from solid pancreatic tumors. This method demonstrates excellent diagnostic performance, particularly in identifying PDAC, and shows promising trends for distinguishing CP and CC, supporting its clinical integration in EUS evaluation protocols.

Introduction

Pancreatic ductal adenocarcinoma (PDAC) is a highly desmoplastic tumor that significantly affects its aggressiveness and treatment resistance. Cancer-associated fibroblasts (CAFs) are key components of the desmoplastic stroma and are now recognized as dynamic, heterogeneous cells that contribute to disease progression. While CAFs play a role in creating an immunosuppressive tumor microenvironment (TME), their precise impact on survival and cellular dynamics remains unclear. This study aims to provide an unbiased classification of CAF subtypes and investigate their functional relevance and dynamics in chronic pancreatitis (CP) and PDAC.

Aims & Methods

We conducted single-cell RNA sequencing (scRNA-seq) on 40,000 fibroblasts isolated from resected human CP and PDAC tissues. We clustered the CAFs and examined the driving genes for each subtype. Validating these subtypes involved immunohistochemistry (IHC)-multiplexing on tissue microarrays (TMA) from 126 PDAC and 66 CP patients. Additionally, we performed flow cytometry on human PDAC CAFs and utilized immunocytochemistry (ICC) with our newly identified markers.

Results

Our clustering revealed 11 distinct CAF subtypes. To facilitate future mechanistic experiments, we also analyzed the surface receptor signatures of these enriched subtypes. IHC multiplexing confirmed the existence of these subtypes, with End Stage inflammatory CAFs (iCAFs) (35.7% in PDAC vs. 56.6% in CP) and End Stage myofibroblastic CAFs (myCAFs) (35.3% in PDAC vs. 25.6% in CP) being the most prevalent. Flow cytometry results corroborated IHC findings. Notably, we identified a novel subtype, Lipofibroblast, in both PDAC and CP, with RNA velocity analysis indicating its ability to differentiate into other subtypes, driven by Periostin (POSTN).

Conclusion

The discovery of a novel Lipofibroblast subtype with differentiation potential highlights a new avenue for understanding CAF plasticity and therapeutic targeting in PDAC and CP.