Endoscopic Management of Biliopancreatic Disease in the Lombardy Pancreas Units

Despite advances in oncological therapies, pancreatic cancer remains one of the leading causes of cancer-related mortality worldwide, with an increasing burden projected over the coming decades. The diagnostic and therapeutic pathway of biliopancreatic malignancies is complex and requires a high level of multidisciplinary expertise, particularly in high-volume referral centers organized as Pancreas Units.

Endoscopic ultrasound (EUS) plays a central role in the diagnostic work-up of biliopancreatic and periampullary lesions, allowing high-resolution morphological assessment and, when indicated, tissue acquisition through fine-needle aspiration (FNA) or fine-needle biopsy (FNB). Accurate histological diagnosis is essential for therapeutic decision-making, including surgical planning, systemic therapy, and molecular profiling.

The Lombardy Region has adopted a Hub-and-Spoke organizational model for Pancreas Units, defining minimum procedural volumes, expertise requirements, and performance benchmarks for referral centers. However, a centralized prospective system for monitoring endoscopic activity, diagnostic performance, and procedural outcomes across these centers is currently lacking.

The GENTLENESS study has been designed to prospectively collect real-world data on EUS procedures performed in Lombardy Pancreas Unit Hub centers, with the primary objective of evaluating the diagnostic accuracy of EUS-guided biopsies. Secondary objectives include assessment of procedural volume, sampling techniques, need for repeat biopsies, complication rates, and time intervals from procedure to definitive diagnosis and initiation of treatment.

The study is observational, does not introduce changes to clinical practice, and reflects routine patient management pathways. Any future analyses beyond the scope of the present registry will require separate Ethics Committee approval.

Primary outcomes

• Diagnostic Accuracy [30 days]: Number of patients with a correct diagnosis obtained through EUS-guided cyto-histological sampling, confirmed by the final diagnosis

Secondary outcomes

• Procedural Volume [6 months]: Number of EUS procedures performed for suspected biliopancreatic neoplasms
• Need of Repeat Sampling [30 days, 60 days]: Need for additional EUS-guided sampling after an initial non-diagnostic procedure
• Sampling Technique [Intraprocedural]: Type of tissue acquisition (FNA vs FNB; ROSE vs MOSE)
• Adverse Events [Intraprocedural, 30 days]: Intra- and post-procedural complications classified according to ASGE criteria
• Time to Diagnosis [30 days, 60 days]: Time from EUS to availability of definitive cyto-histological report
• Time to Treatment [30 days, 60 days]: Time from diagnosis to initiation of disease-specific treatment

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Adults (≥18 years)
* Clinical, biochemical, and/or imaging suspicion of pancreatic neoplasia (adenocarcinoma, neuroendocrine tumors, cystic neoplasms requiring endoscopic, surgical, or oncological treatment) or periampullary neoplasia (distal bile duct, ampulla, duodenum)
* Candidate for EUS according to standard clinical practice
* Ability to understand and sign informed consent

Exclusion Criteria:

* Age <18 years
* Pregnancy or breastfeeding
* Conditions other than those defined in the inclusion criteria
* Inability to provide informed consent
* Refusal to participate in the study

• Paolo Giorgio Arcidiacono, Chief, Principal investigator, IRCCS Ospedale San Raffaele