Introduction

The incidence of pancreas cysts is increasing, and the use of EUS-guided through-the-needle-biopsy (EUS-TTNB) is gradually increasing for accurate diagnosis. However, studies including a large number of patients on clinical outcomes and safety of EUS-TTNB for pancreatic cysts are still lacking. In this study, we evaluated the diagnostic yield, adverse events(AE), and risk factors of AE related to EUS-TTNB in a large number of cohorts.

Aims & Methods

We reviewed the prospectively collected EUS-TTNB for pancreatic cysts database at Asan Medical Center, between January 2019 and December 2022. We analyzed technical success rate, diagnostic yield, AE, and risk factors for AE.

Results

A total of 248 patients were analyzed. Technical success could be achieved in 247 patients, except one patient (100%). Among them, 191 patients had a specific histologic diagnosis (diagnostic yield, 77.3%). There was no significant difference in diagnostic yield according to the number of biopsy specimen, the presence of septation in the cysts, the size of cysts, and location of cysts. AE occurred in 41 patients (16%), and there was no serious AE. Acute pancreatitis was the most common AE (12/248, 12%) following cyst hemorrhage (7/247, 3%). In univariate analysis on the risk factors of acute pancreatitis related to EUS-TTNB, male (HR 2.22, 95% CI: 1.02-4.83, P=0.045) and IPMN (HR 3.08, 95% CI: 1.35-7.03, P=0.01) were statistically significant. In multivariate analysis, IPMN (HR 2.75, 95% CI: 1.24-6.11, P=0.01) was the significant risk factor of acute pancreatitis after EUS-TTNB.

Risk factors of acute pancreatitis after TTNB

Conclusion

EUS-TTNB showed a relatively high technical success rate and diagnostic yield. IPMN was the most significant risk factor of AE related to EUS-TTNB.

References

The clinical relevance of the increasing incidence of intraductal papillary mucinous neoplasm, Clin Gastroenterol Hepatol. 2012 May;10(5):555-8
European evidence-based guidelines on pancreatic cystic neoplasms, Gut. 2018 May;67(5):789-804
International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas, Pancreatology 2012;12:183–197.
Diagnosis of pancreatic lesions collected by endoscopic ultrasound-guided fine-needle aspiration using next-generation sequencing, HPB (Oxford). 2015 May; 17(5): 377–386.
Suboptimal accuracy of carcinoembryonic antigen in differentiation of mucinous and nonmucinous pancreatic cysts: results of a large multicenter study, Gastrointest Endosc. 2015 Dec;82(6):1060-9
Efficacy and safety of EUS-guided through-the-needle microforceps biopsy sampling in categorizing the type of pancreatic cystic lesions, Gastrointest Endosc. 2022 Feb;95(2):299-309

Introduction

Pancreatic neuroendocrine tumors (pNETs) are a heterogeneous group of tumors with different treatment options depending on pathological grading, clinical staging, and presence of symptoms related to hormonal secretion. Their classification is made on mitotic count and Ki-67 index.
The current standard for Grading assessment is analysing the material obtained from EUS-guided fine needle aspiration/biopsy (EUS-FNA/FNB). However this technique is not free from adverse events and could be challenging for NETs localization.
The evidence of high grade of fibrosis and microvascular density decrease (MVD) on tumor pathological specimens has led many authors to search for undirected malignant features of pNET extrapolated from non-invasive techniques. The introduction of ancillary techniques, such as second-generation contrast agents (CH-EUS), has improved study of pNET. Particularly, at CH-EUS examination contrast pattern well correlates with behaviour and grading of NETs. However, the use of contrast agents entails a prolongation of procedure time and additional costs. An innovative ultrasound Doppler technique, Detective Flow Imaging EUS (DFI-EUS), involves no additional time or cost as it doesn’t require the administration of contrast agent. There is still no standardisation of this technique and few studies have validated its use.

Aims & Methods

The aim of this study is to evaluate the DFI role in defining NET vascularization and its correlation with CH-EUS. The second aim of the study is to assess DFI role in predicting histological grading.
Single center retrospective analysis on consecutive patients with solid pancreatic lesions who underwent EUS at Therapeutic Digestive Endoscopy Unit of the Fondazione Policlinico Universitario Campus Bio-Medico in Rome.
After activation of DFI, each lesion was observed for at least 30 seconds. Lesions was classified into three grades, according to the degree of vascularisation at DFI: (grade 0 absence of microvascularization of the tumor; grade 1 minimal/isovascularization of the tumor; grade 2 markedly increased microvascularization).
All lesion with final hystological diagnosis of NET were enrolled.
Grading and Ki-67 index of tumors were reported.
Data about lesion’s features and procedure were collected.

Results

From April 2024 to February 2025, 17 patients were enrolled (58.8% male; mean age 57±12 years old). The majority of lesion (53%) were localized in the body of the pancreas and the mean lesion’ s size was 28±20 mm. The final histological diagnosis classified 50% lesions as G1, 38.8% G2 and 5.5% G3.
At the CEH-EUS the 70.6% of lesion showed hyper-enhancement. About the DFI evaluation the 17.6% of lesion was hypo-vascular, 17.6% Iso-vascular and 64.7% was hyper-vascular. There was excellent correlation between DFI characterization of the lesion and the CH-EUS (ICC 0.9)
Among the NET G1, 66.7% were Hypervascular at DFI and 33.3% Isovascular. Among the G2, 71.4% were Hypervascular at DFI and 28.6% Hypovascular. The only G3 lesion was Hypovascular.
There was inverse correlation between the NET grade and the DFI grade (Pearson coefficient -0.56; p 0.02).

Conclusion

DFI-EUS can provide a fast evaluation of the micro-vascularization of pNET with excellent correlation with CH-EUS. Hyper-vascular pattern at DFI correlates with low Ki-67 index.

Introduction

Despite advances with chemotherapy regimens, Pancreatic adenocarcinoma (PDAC) is becoming the 2^nd cause of cancer-related death. Personalized medicine will be the game changer, but molecular characterization of pancreatic neoplasms is yet extremely cumbersome and has been performed on surgical samples or few EUS-tissue acquisition (TA) cases, mostly for DNA analysis. Our aim was to evaluate DNA and RNA extracted for research purposes from pancreatic neoplasms employing Endoscopic Ultrasound (EUS) Fine needle aspiration (FNA) and biopsy (FNB) and adequacy to molecular analyses.

Aims & Methods

From Oct 2022, patients with solid pancreatic neoplasms suggestive of either PDAC or neuroendocrine neoplasm (NEN) undergoing diagnostic EUS-TA were considered for enrollment. Employed needles were either FNA, or Franseen, Fork-tip or Three-prong, either 22G or 25G based on operator’s preference, with Rapid on Site Evaluation and, in case of adequacy within the first 2 passes, 1 additional pass with the same needle was performed for molecular analyses. DNA and RNA were then extracted with a new technique and nucleic acids were quantified and evaluated for adequacy for molecular analysis. Mann-Whitney was employed for comparison of continuous variables, and Kruskal-Wallis test for comparison between multiple groups; Logistic regression was applied to determine factors associated with adequacy to molecular tests.

Results

351 patients underwent sampling for molecular analyses, 309 with a definitive diagnosis of PDAC and 42 with NEN. 92,9% of patients were sampled with 25G FNA needles. Median quantity of DNA extracted was significantly lower in PDAC 2048 ng (95%CI: 1470 -3651) compared to NEN 6752 ng (95%CI: 3502-9655)(p<0.0144). Mean quantity of RNA extracted was similar, 312 ng for PDAC, and 444 ng for NEN (p=0.07), with a higher median RIN of 6,4 (95%CI:6,2-6,5) for PDAC versus 4,7 (95%CI:3,9-5) for NEN (p<0.0001). In terms of needle type, concerning DNA extraction, 25G FNA needles retrieved a median of 3384 ng, 25G Franseen needles (4312 ng), 22G Franseen (73864 ng), 25G Fork-tip or Three-prong (3104 ng), with no significant difference. In terms of needle type, concerning RNA extraction, 25G FNA needles retrieved a median of 310 ng (RIN 6,3), 25G Franseen needles 460 ng (RIN 5,5), 22G Franseen 884 ng (RIN 5,9), 25G Fork-tip or Three-prong 301 ng (RIN 5,15), with no significant difference. 295 (95,5%) of PDAC samples and 34 (80,9%) of NEN samples were considered adequate for sequencing. The only factor associated to adequacy for molecular analysis was tumor type, with PDAC having an OR of 5,44 (95%CI 2,06-14,37)(p=0.0006), while the type of employed needle was not

Conclusion

Molecular analysis on EUS-acquired tissue of pancreatic neoplasms will be the mainstay of personalized therapies but how to best perform tissue acquisition and sample handling for this specific purpose is yet to be defined. This is the largest study ever performed on DNA and RNA extraction from EUS-acquired samples, demonstrating superior adequacy for molecular analysis in PDAC compared to NEN. All needle types result similar in terms of performance despite the low number of needles other than 25G FNA needles.