Duodenal aspiration biopsy for diagnosing pancreatic cystic lesions: a four-case series

Introduction

Background

Endoscopic ultrasound (EUS) combined with fine-needle biopsy (FNB) is regarded as the primary diagnostic approach for patients with pancreatic cystic lesions, considered a risk group for pancreatic cancer (1). Detection of atypical cells, elevation in carcinoembryonic antigen (CEA) levels above 192 ng/mL, and the presence of mutations in genes like KRAS, GNAS, and TP53 in the collected sample are markers of neoplastic rather than benign process in the pancreas, guiding the potential need for surgical intervention (2). However, this diagnostic approach fails to achieve conclusive diagnoses in nearly half of the cases, necessitating repeat examinations and ongoing patient monitoring (1,3). EUS-FNB may not be feasible or reliable in patients with small pancreatic lesions (<10 mm) or those located in anatomically challenging regions of the pancreas (4-6). Additionally, the procedure carries risks of complications such as cystic infection, intracystic bleeding, and potential tumor cell dissemination, limiting its use in some patients (7). Finally, EUS-FNB requires specialized equipment and a high level of expertise from endoscopists, typically available only at high-volume centers, thus restricting access to this diagnostic procedure for many patients. A simpler and less invasive method that addresses these challenges and works alongside standard diagnostic approaches could improve the accessibility and accuracy of pancreatic neoplasm diagnosis.

Rationale and knowledge gap

Pancreatic juice is widely recognized as a uniquely specific substance suitable for a range of diagnostic tests (8-12). However, ongoing challenges remain regarding its collection method, volume, quality, and dilution, leading to inconsistent concentrations of tested markers (8,12). A minimally invasive and simple-to-deploy methodology that allows the collection of large volumes of uncontaminated pancreatic juice without artificial stimulation would address these challenges and could enhance the early detection of pancreatic cancer.

We have developed an effective method of duodenal aspiration biopsy (DAB) involving active aspiration of the mix of pancreatic juice and bile from the lumen of duodenum. Focusing on cases in which standard diagnostic approaches produced inconclusive results or were contraindicated, we aim to demonstrate that DAB is a feasible, minimally invasive diagnostic approach that can complement or replace EUS-FNB in certain cases of pancreatic cystic lesions.

Materials and methods

The DAB uses a novel two-balloon, three-lumen PandiCath^® catheter (Figure 1), previously shown as effective in treating acute pancreatitis and intraluminal gastrointestinal (GI) bleeding (13,14).

Figure 1 Design of PandiCath^® catheter. [1] Channel for balloon inflation (balloons 5 & 8): allows inflation with water or air; [2] channel for gastrointestinal drainage and enteral nutrition: drains stomach and intestine; selectively delivers liquid nutrition; [3] channel for decompressing and collecting biomaterials or delivering medicines: located between balloons 5 & 8, facilitates biomaterial collection or medication delivery; [4] lateral openings in channel 2: aids in stomach drainage, decompression, and selective provision of liquid nutrition; [5, 8] proximal and distal balloons: create an isolated area within a hollow organ; [6] opening of channel 3 into the isolated area between balloons 5 & 8: facilitates access for biomaterial collection or medication delivery; [7] circular elevations surrounding opening 6 of channel 3: prevent blockage by gut mucosa; [9] distal opening of channel 2: facilitates drainage and selective nutrition delivery.

Deployed intranasally via standard endoscopic techniques, PandiCath^® isolates the duodenal segment around the major duodenal papilla. One channel creates controlled negative pressure (60–80 mmHg) to draw out pancreatic juice, while another maintains communication between proximal and distal GI sections, allowing patients to consume liquids during the 2–3-hour procedure and preventing gastric stasis. Unlike secretin-induced methods, this approach stimulates natural secretion without dilution by bicarbonate-rich fluids (8). Up to 300 mL of uncontaminated bile and pancreatic juice can be collected, preserving biomarkers by maintaining inactive enzymes at higher pH. The volume enables multiple analyses and storage for future use. After centrifugation, the solid fraction is used for cytology or genetic testing, and the liquid component for proteomic or biochemical analyses such as CEA measurement.

The cases presented here were managed as part of routine clinical practice at different oncological hospitals and were included non-consecutively. In all cases, lesions with worrisome features (2) were initially detected using contrast-enhanced magnetic resonance imaging (MRI) or computed tomography (CT). However, EUS-guided FNB was either inconclusive or not performed due to the risk of serious complications. Therefore, the decision to utilize DAB was based on the need for additional diagnostic information in situations where EUS-FNB alone was either non-diagnostic or contraindicated. We present this article in accordance with the AME Case Series reporting checklist (available at https://apc.amegroups.com/article/view/10.21037/apc-24-23/rc).

Case presentation

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patients for the publication of this case series and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

A comprehensive summary of diagnostic results and subsequent treatment strategies is provided (Table 1).

Patient 1, a 63-year-old female, underwent surgery and adjuvant therapy for colon cancer in 2018. In 2020, a cystic lesion measuring 15 mm × 16 mm was detected in the body of the pancreas on a CT scan (Figure 2).

Figure 2 CT scan of patient 1 showing the size of neoplasia and cystic lesion. CT, computed tomography.

During a routine examination in November 2023, it was discovered that the lesion had increased by 5 mm in each dimension. Due to its proximity to the superior mesenteric artery and the associated risk of vascular injury, percutaneous biopsy and EUS-guided FNB were considered unsafe. However, EUS examination revealed that the lesion corresponded to type 1 intraductal papillary mucinous neoplasm (IPMN-I). DAB was conducted, revealing no atypical cells and a CEA level of 123.94 ng/mL. These findings suggested the lesion had minimal malignant potential, leading to the decision to continue patient observation instead of pursuing distal pancreatic resection initially considered. Twelve months later, a follow-up MRI indicated no clear connection with the main pancreatic duct, as well as absence of lymphadenopathy and signs of contrast accumulation in the lesion.

Patient 2, a 60-year-old male, presented with persistent abdominal pain for months, initially managed as chronic pancreatitis. A 36 mm × 43 mm cystic lesion was identified in the pancreatic head via CT and MRI (Figure 3).

Figure 3 CT scan of patient 2 showing cystic transformation in the head of the pancreas. CT, computed tomography.

Percutaneous biopsy yielded no pathological cells. Subsequent EUS with FNB was performed twice, revealing a hypoechoic lesion measuring 40 mm × 50 mm with hyperechoic walls and solid inclusions, alongside 4 mm dilation of the main pancreatic duct. The first cytological examination of FNB was negative for tumor cells. Due to limited biomaterial, CEA measurements were not conducted initially. Given the inconclusive results from prior tests, DAB was performed, revealing a CEA level of 303 ng/mL and cells with low-grade atypia. This prompted a repeat EUS-FNB procedure, which subsequently detected cells showing high-grade dysplasia consistent with mucinous neoplasia. Despite initial reservations and based on cumulative findings, the decision was made to proceed with pancreaticoduodenal resection. Histological examination confirmed multifocal dysplasia of IPMN of the main pancreatic duct with low and high-grade dysplasia (intestinal type), along with invasive carcinoma, pTis. After 12 months of follow-up, a repeat CT scan showed no signs of progression.

Patient 3, a 60-year-old female, presented with recurrent epigastric pain and was diagnosed with pancreatitis. Imaging with CT and positron emission tomography (PET)-CT suggested an IPMN in the pancreatic head, leading to consideration for pancreaticoduodenal resection. To refine the diagnosis, EUS revealed a 30 mm × 40 mm lesion with increased blood flow, thickened walls, and heterogeneous contents, resembling a post-necrotic pseudocyst (Figure 4).

Figure 4 EUS image of patient 3 showing debris in cystic cavity. EUS, endoscopic ultrasound.

Due to the patient’s coagulopathy (international normalized ratio 3.4), FNB and percutaneous biopsy was deemed unsafe. Instead, DAB indicated a CEA level of 52.73 ng/mL, suggesting a low likelihood of malignancy. Subsequently, transgastric stenting of the cyst was performed, allowing extraction of debris and purulent material, which confirmed its post-necrotic origin following acute pancreatitis. After 8 months, a repeat CT scan showed no residual cystic cavity, and the stent was therefore removed.

Patient 4, a 75-year-old female, without any clinical manifestations but with a history of chronic pancreatitis and diabetes mellitus. CT and EUS examinations revealed multiple IPMNs resulting in extensive cystic transformation of the pancreatic tissue (Figure 5).

Figure 5 CT scan of patient 4 showing total cystic transformation of the pancreas. CT, computed tomography.

However, it remained unclear which cysts were linked to the main pancreatic duct, complicating the choice of lesions for FNB. Consequently, DAB was performed as an alternative. While no pathological cells were identified, the CEA level exceeded 1,000 ng/mL. Given the connection of the cysts with the main pancreatic duct and the elevated CEA level, a decision was made to proceed with total pancreatectomy. Subsequent histological examination confirmed multifocal IPMNs with a high degree of dysplasia, pTis. After 8 months of follow-up, a CT scan showed no signs of progression.

Discussion

Diagnosing pancreatic cystic lesions remains a substantial clinical challenge. While international guidelines recommend EUS-FNB as the standard diagnostic approach, even in specialized centers FNB often yields inconclusive results or poses procedural risks due to anatomical or patient-specific factors. The limited biomaterial volume obtainable by FNB further restricts diagnostic options.

Key findings

In this case series, we demonstrated that DAB could serve as a feasible alternative or complement to FNB in selected patients. DAB consistently provided sufficient, high-quality samples for cytology and CEA measurement, facilitating clinical decision-making in cases where FNB alone was non-diagnostic or unsafe. Notably, DAB enabled the collection of larger sample volumes, allowing broader laboratory analyses and potentially supporting biomarker discovery efforts.

Strengths and limitations

Our findings confirm that DAB can achieve diagnostic yields comparable to, and in some situations exceeding, those of EUS-FNB. The technique is straightforward, minimally invasive, and can be performed in an outpatient setting with a favorable safety profile. Patients tolerated the procedure well, and sedation requirements were less intensive than for FNB. Nevertheless, potential risks such as duodenal mucosal injury, infection, or sample contamination warrant further evaluation.

Implications and actions needed

These observations suggest that DAB could be integrated into existing diagnostic algorithms as an adjunctive tool when FNB is inconclusive or contraindicated, and potentially as a targeted sampling approach to corroborate findings from imaging or blood based liquid biopsy. However, this study has limitations, including its retrospective design, non-consecutive case inclusion, lack of a control group, and a small sample size, which may limit generalizability. Since 2024, we have initiated a protocol across three inpatient centers focusing on patients with pancreatic cystic neoplasms. The routine application of DAB within this protocol has been implemented alongside the standard EUS-FNB approach, wherever possible (Figure 6), to ensure adherence to the International Consensus Fukuoka Guidelines, 2017 (2).

Figure 6 The proposed clinical workflow integrating DAB alongside the standard approaches in the management of patients with pancreatic cystic lesions. CEA, carcinoembryonic antigen; CT, computed tomography; DAB, duodenal aspiration biopsy; EUS, endoscopic ultrasound; FNB, fine-needle biopsy; MRI, magnetic resonance imaging; PCN, pancreatic cystic neoplasm.

This combined strategy aims to systematically assess the complementary value of DAB in improving diagnostic confidence, particularly in lesions with worrisome features or high-risk stigmata.

Further prospective studies comparing DAB and FNB in well-defined cohorts are needed to better validate its diagnostic accuracy, safety, and impact on clinical outcomes. Additionally, standardized protocols and consensus on indications will be essential to guide broader adoption.

Conclusions

DAB appears to be a promising addition to the diagnostic armamentarium for pancreatic cystic neoplasms, especially in challenging cases where standard methods are limited. Its utility warrants further investigation to better define its role in routine clinical practice.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the AME Case Series reporting checklist. Available at https://apc.amegroups.com/article/view/10.21037/apc-24-23/rc

Peer Review File: Available at https://apc.amegroups.com/article/view/10.21037/apc-24-23/prf

Funding: None.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://apc.amegroups.com/article/view/10.21037/apc-24-23/coif). Both authors are employed by PANDICA LTD., and report patents WO2024033700, WO2021/137739, and WO2023075634. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patients for the publication of this case series and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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