Introduction

Acute pancreatitis (AP) can be associated with CFTR gene mutations. Several mutations have been described and classified based on the type of protein changes. The CFTR-France database classifies variants in disease-causing (DC), variants of unknown significance (VUS) and no-disease-causing (NDC), according to their clinical consequences. The role of VUS and NDC mutations in AP patients was not clearly defined.

Aims & Methods

The aim of this study is to determine the role of VUS and NDC mutations in patients suffering from AP. We enrolled retrospectively patients with AP observed in our Centre between 2013 and 2020 and tested for CFTR gene mutations. Patients were divided in CFTR wild type, DC, VUS and NDC. We evaluated epidemiological, clinical, and instrumental characteristics at the disease onset and the clinical outcome in terms of progression to chronic pancreatitis, onset of pancreatic calcifications, development of exocrine and endocrine pancreatic insufficiency.

Results

We tested 322 patients (199 males and 123 females, age at onset 35.4±15.8 years). We compared 99 patients with CFTR mutations (65 males and 34 females, age at onset 29±13 years) with 223 wild type patients (134 males and 89 females, age at onset 38.2±15.7 years), showing significant differences in terms of age at onset, BMI, smoking and drinking habits, chronic pancreatitis, and pancreatic calcifications at the onset of the disease. The clinical course of the wild type patients was characterized by an earlier progression to chronic pancreatitis, onset of calcifications and exocrine pancreatic insufficiency. VUS and DC patients had a similar clinical outcome of the disease. NDC group was excluded from the analysis due to the low number of patients.

Conclusion

Patients carrying VUS mutations of the CFTR gene have a clinical outcome similar to patients carrying DC mutations.

Introduction

IPMN are considered a possible cause of acute pancreatitis (AP) due to a transient obstruction of the pancreatic duct by mucin. IPMN-associated-AP is considered a relative indication to surgery for both, prevention of recurrent attacks of pancreatitis and for a hypothesized increased risk of cancer. The published literature is based on surgical series with significant population heterogeneity including MD-IPMN, mixed-type-IPMN and BD-IPMN. No data are available on the clinical features of this particular type of AP, on the risk of recurrent pancreatitis and pancreatic cancer in patients with BD-IPMN-associated-AP.

Aims & Methods

Results

One-hundred-thirty-five patients were included (54.8% males and 45.2% females), with mean age at the first episode of AP of 55.8 ± 12.5 years. Pancreatic necrosis was diagnosed in 15 patients (11.1%) and only 1 patient (0.7%) was admitted in Intensive Care Unit. One-hundred-two (75.6%) had recurrent pancreatitis.
The median size of the largest BD-IPMN was 8 mm (IQR 7). None had mural nodules, thickened cystic walls, or dilated main pancreatic duct ≥ 5 mm. Eighteen patients (13.3%) developed main pancreatic duct dilation ≥ 5 mm. None developed dilation of main pancreatic duct ≥ 10 mm, mural nodules, thickened cystic walls, or jaundice. At Cox unadjusted analysis no BD-IPMN-related features were associated to increased risk of recurrent pancreatitis. Surgical resection was performed in 10 patients (7.4%). None developed pancreatic cancer or signs of chronic pancreatitis during follow-up.

Conclusion

BD-IPMN-associated AP has a benign clinical course. Cystic features are not related to increased risk of recurrence. Cancer risk appears extremely low in patients with BD-IPMN-associated-AP.

Introduction

Branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) are frequently associated with acute (AP) or recurrent pancreatitis (RP), likely due to the mucin-induced obstruction of the main pancreatic duct (MPD). According to the 2024 Kyoto Guidelines, pancreatitis represents an indication for surgical evaluation in IPMN patients. However, pancreatic sphincterotomy (PS) may represent a less invasive alternative for patients who are unfit for surgery or as a bridge to surgery, aiming to reduce the risk of further pancreatitis episodes.

Aims & Methods

This single-center retrospective study aimed to assess the efficacy and safety of PS in patients with BD-IPMN and RP. We included 33 patients who underwent PS between 2016 and 2023, with at least 12 months of follow-up. Patients with other causes of RP or prior pancreatic surgery were excluded. The frequency of pancreatitis episodes before and after PS was compared. Clinical success was defined as complete resolution or ≥50% reduction in pancreatitis episodes. Adverse events, presence of worrisome features (WF), and progression to high-risk stigmata (HRS) were evaluated. Statistical analysis was performed using paired t-test and Fisher’s exact test, with p < 0.05 considered significant.

Results

Among the 33 patients analyzed (39.4% female, 60.6% male, mean age 59 ± 13.9 years) clinical success was achieved in 81.8% of the cases. Specifically, 72.7% of the patients experienced no further AP episodes after PS and 9.1% experienced a reduction in episode frequency, while 18.2% of patients did not respond to treatment. Adverse events occurred in 15% of patients, including: 12% with post-ERCP pancreatitis (all mild) and 3% with intra-procedural bleeding; no perforations were reported. During follow-up WF emerged in 5 patients (15%), while no cases of HRS were identified. Among the 6 non-responders, 3 underwent a second PS, with 2 achieving clinical improvement, and 3 underwent duodenocephalopancreasectomy (DCP), including 1 for a concomitant pancreatic ductal adenocarcinoma (PDAC) unrelated to IPMN progression. Notably, no cases of IPMN degeneration were observed in the series

Conclusion

Pancreatic sphincterotomy appears to be a safe and effective approach for managing recurrent pancreatitis in patients with BD-IPMN, potentially reducing the need for surgery in selected cases.