Pancreatoscopy in the evaluation and management of pancreatic disorders

Abstract

Pancreatoscopy is an advanced endoscopic technique that enables high-resolution imaging of the main pancreatic duct. Its relevance has grown in recent years with the introduction of novel technologies, allowing for both diagnosis and treatment within a single procedure. In therapeutic applications, it facilitates interventions such as stone fragmentation, stone retrieval, and tumor-related obstruction management. In diagnostic applications, it improves the accuracy of biopsies for suspicious lesions, particularly in cases of cystic neoplasms, indeterminate strictures, and pancreatic fistula assessments. The most common complications include post-procedural pancreatitis and self-limited abdominal pain, with their incidence mitigated by prophylactic anti-inflammatory drugs and pancreatic stent placement. Despite being limited by the need for specialized equipment and trained personnel, technological advancements may position pancreatoscopy as a first-line tool in modern clinical practice.

Key Words: Pancreas; Pancreatoscopy; Endoscopy; Pancreatic intraductal neoplasms; Chronic pancreatitis; Pancreatic duct stones

Core Tip: Pancreatoscopy, a minimally invasive and highly specialized technique, enables direct visualization of the pancreatic duct, enhancing the diagnosis and management of conditions such as strictures and intraductal neoplasms. When integrated with therapeutic tools, it provides a powerful approach for complex interventions, significantly improving patient outcomes. Its increasing precision and ability to guide procedures such as stricture dilation and lithotripsy highlight its growing role in advanced pancreatic care.

INTRODUCTION

Pancreatoscopy is an advanced endoscopic technique that provides direct visualization of the main pancreatic duct (MPD), integrating both diagnostic and therapeutic capabilities into a single procedure. This technique is particularly valuable when other diagnostic methods prove inconclusive, such as in the assessment of intraductal papillary mucinous neoplasms (IPMNs) or the biopsy of indeterminate MPD strictures. In therapeutic settings, pancreatoscopy plays a pivotal role in the management of pancreatic lithiasis, both with electrohydraulic or laser lithotripsy and with direct stone extraction[1,2].

While rudimentary pancreatoscopic techniques date back to the 1950s[3], the method was formally introduced in 1975 but faced significant technical limitations. The initial "mother-daughter" system, consisting of a fiber-optic pancreatoscope (daughter) inserted through a duodenoscope (mother), required two operators and lacked essential features such as working channels and irrigation systems, restricting its use to highly specialized centers[4].

In 2015, Boston Scientific launched the SpyGlass™ DS system, marking the first fully digital, singleoperator pancreatoscope[3,5]. This enhanced pancreatoscope enables single-operator control, multidirectional maneuverability, and incorporates enhancements such as narrow-band imaging, digital chromoendoscopy, and high-resolution imaging[3]. It is currently the most widely used pancreatoscope, and its improvements have expanded the accessibility and effectiveness of pancreatoscopy, solidifying its role as a versatile tool in pancreatic disease management[4,5]. Subsequently, the SpyGlass™ DS II, launched in 2019, further increased image resolution and reduced device footprint, improving integration into endoscopy suites[3].

In addition to the SpyGlass™ DS and DS II systems, other pancreatoscopic platforms have emerged—most notably ultraslim endoscopes and repurposed video cholangioscopes. For example, Olympus’s CHFB260 and CHFB290 models, although requiring two operators, deliver superior image quality and also support reusable platforms, potentially reducing long-term costs[6,7]. The CHFB290, Olympus’s most recent offering, features a slightly larger working channel (1.3 mm vs 1.2 mm in the CHFB260), which enhances irrigation and suction capabilities[8]. However, these dualoperator scopes lack the dedicated irrigation ports and intuitive fourquadrant steering mechanisms characteristic of the SpyGlass systems[3,6,7].

Currently, pancreatoscopy is predominantly performed via a peroral approach. Other access methods include transhepatic percutaneous pancreatoscopy—preferred in patients with altered anatomy (e.g., RouxenY hepaticojejunostomy or pancreaticoduodenectomy)[3]—and intraoperative pancreatoscopy, which provides realtime, direct visualization of the MPD during surgery[9].

The growing interest in this technique stems from its ability to merge diagnostic and therapeutic functions within a single procedure, streamlining interventions and diagnostic workflows that were previously more challenging[4]. This review provides a comprehensive overview of pancreatoscopy, detailing its indications, applications, and emerging role as a critical tool in modern endoscopic practice.

EQUIPMENT

The equipment required for pancreatoscopy includes a connection to a video processor and a standard light source. Two complete setups are necessary: One for the pancreatoscope and another for the duodenoscope, which must have a working channel of at least 4.2 mm[4]. Additionally, a monitor should be available to display images from both the duodenoscope and pancreatoscope, or alternatively, two adjacent monitors can be used[4].

The system is supplied in a sterile package and features a handle allowing four-quadrant navigation of the pancreatoscope's tip. The handle also includes an entry port for the working channel (1.2 mm), while the base houses the pancreatoscope and two Luer Lock connectors for irrigation and aspiration[4]. Compatible accessories for the working channel include biopsy forceps, a Dormia basket, and a polypectomy snare.

TECHNIQUE

The procedure is performed under deep sedation or general anesthesia[4], typically with propofol, midazolam, or fentanyl[10]. Rectal administration of nonsteroidal anti-inflammatory drugs before the procedure is recommended, with indomethacin and diclofenac being the most commonly used agents[11]. Indomethacin has shown variable efficacy, being more effective in high-risk patients for post-procedural pancreatitis[11]. Conversely, diclofenac has demonstrated consistent efficacy across all patient groups, making it the preferred choice at a standard dose of 100 mg administered rectally perioperatively[11].

Antibiotic prophylaxis in pancreatoscopy remains a debated topic due to limited specific evidence. In some cases, the decision is left to the discretion of the endoscopist and anesthesiologist[12,13]. Nevertheless, available data suggest a higher risk of infectious complications—particularly cholangitis—when comparing pancreatoscopy and cholangioscopy to standard endoscopic retrograde cholangiopancreatography (ERCP)[1,12]. Although evidence is limited, studies indicate that antibiotic prophylaxis may reduce the risk of cholangitis and other infectious complications[14,15]. In addition, the European Society of Gastrointestinal Endoscopy and the American Society for Gastrointestinal Endoscopy recommend prophylactic antibiotic use in advanced biliopancreatic endoscopic procedures[16]. While some studies have not shown a statistically significant reduction in cholangitis incidence with antibiotic use[17], the low cost of prophylaxis compared to the potential costs of hospitalization and treatment, along with the favorable safety profile of antibiotics, supports its routine use[14,15]. Therefore, systematic antibiotic prophylaxis is recommended before each pancreatoscopy procedure, with specific regimens varying between centers[1,12,15,16,18,19], although it is important to note that no studies have directly assessed antibiotic prophylaxis in the context of pancreatoscopy.

Before the procedure, the MPD should be evaluated using magnetic resonance cholangiopancreatography or ERCP to assess papillary morphology, pancreatic duct diameter, and lesion location. Additionally, a pancreatogram should be obtained at the beginning of the procedure to guide lesion localization and define ductal anatomy[12] (Figure 1).

Figure 1  Fluoroscopic pancreatogram obtained during pancreatoscopy.

Pancreatic sphincterotomy is typically required prior to pancreatoscope insertion. In specific cases, such as patients with IPMN, an open papilla with evident mucin discharge may not necessitate sphincterotomy, although performing it is generally preferred[1,12]. After sphincterotomy and guidewire placement in the MPD, the pancreatoscope is carefully advanced. Before insertion, irrigation channels should be flushed to avoid introducing air bubbles. Using saline, the duodenal lumen should be irrigated to ensure no air remains in the irrigation channels, preventing air bubbles from entering the pancreatic duct. The optimal protocol involves advancing the pancreatoscope to the pancreatic tail and systematically exploring towards the head, removing the guidewire to optimize aspiration and accessory use (Figure 2).

Figure 2  Normal pancreatic duct.

Pancreatoscopy entails greater technical complexity than cholangioscopy, primarily due to anatomical factors such as side branches, ductal tortuosity, and the sharp angle of the pancreatic genu between the head and neck[12]. Depending on the indication, successful MPD visualization is achieved in 70%–80% of cases[1]. Some authors suggest that an MPD diameter greater than 5 mm is required for optimal procedure execution[1].

Irrigation of the MPD should be minimized, and continuous aspiration of perfused fluid should be maintained[15], as excessive irrigation increases the risk of post-procedural pancreatitis[4]. Effective aspiration requires keeping the working channel entry port sealed. Additionally, intermittent fluoroscopic imaging during pancreatoscopy is crucial for confirming scope positioning and ensuring precise lesion localization[12].

After completing the procedure, inserting a plastic pancreatic stent is recommended to prevent complications. Patients should be observed for 24 hours post-procedure[2,4,20,21]. Table 1 summarizes key practical considerations to perform pancreatoscopy.

Table 1 Practical considerations for pancreatoscopy.

Practical considerations
The amount of contrast injected into the pancreatic duct does not interfere with the pancreatoscopy procedure
Intermittent fluoroscopic confirmation of the pancreatoscope's position is recommended
Maintain a collapsed duodenal lumen to reduce the amount of intraductal air
Aspirate intraluminal air to minimize the volume of fluid in the pancreatic duct
Avoid suctioning the pancreatic duct wall
Administer rectal diclofenac at the start of the procedure as prophylaxis for post-pancreatoscopy pancreatitis

INDICATIONS

Pancreatoscopy enables direct visualization of the pancreatic duct and detection of subtle abnormalities[2,12]. Its primary indications involve diagnosing MPD abnormalities when imaging studies yield inconclusive results or when a biopsy is required. These include MPD strictures, MPD dilatation, and suspicious lesions indicative of IPMNs. The primary therapeutic indication for pancreatoscopy is intraductal lithotripsy for pancreatic lithiasis management. Contraindications include active acute cholangitis and an MPD diameter of less than 5 mm[15].

IPMNs

IPMN is a precancerous cystic tumor characterized by the proliferation of neoplastic mucinous cells within the pancreatic duct, leading to ductal dilation[22,23,24]. It is classified into three main subtypes: Main-duct IPMN (MD-IPMN), branch-duct IPMN, and mixed-type IPMN[1]. Among these, MD-IPMN carries the highest malignant potential, with reported malignancy rates of 70%–92%[1,2].

Although imaging modalities such as computed tomography (CT), magnetic resonance imaging (MRI), or endoscopic ultrasound (EUS) are commonly used in the diagnosis of IPMN, certain cases remain challenging to assess with these techniques. This is particularly true when differentiating diffuse MD type IPMN from chronic pancreatitis, identifying branch duct lesions on CT, or evaluating patients who do not present with high-risk stigmata[25,26]. Consequently, some patients may undergo pancreatic surgery for IPMNs or benign lesions that could not be definitively diagnosed using imaging techniques alone[23]. In this context, pancreatoscopy plays a pivotal role by confirming diagnoses when imaging results are inconclusive, even revealing findings not seen on cross-sectional imaging in up to 42% of cases[27]. Furthermore, it facilitates malignancy or high-grade dysplasia evaluation and lesion mapping, enabling more precise surgical resections while reducing unnecessary procedures[23,24].

Pancreatoscopy has demonstrated sensitivity and specificity for diagnosing IPMNs ranging from 64%–100% and 75%–100%, respectively[18,23,27]. A systematic review reported nearly 100% visualization success in 19 of 25 analyzed studies[23]. Additionally, one study reported diagnostic accuracy comparable to that of EUS[28]. However, limitations include inadequate mucosal clearance and MPD strictures, underscoring the continued relevance of histological confirmation[18,23].

Application to branch-duct lesions is limited due to maneuverability restrictions in these areas, even when dilated. Although pancreatic sphincterotomy is generally recommended, it may not be necessary in patients with an open papilla and mucin discharge, as seen in IPMNs[12]. Clearing the pancreatic duct with a balloon to remove as much intraductal mucin as possible is essential before pancreatoscope insertion. Systematic evaluation should begin at the pancreatic tail and progress toward the head.

Malignant characteristics in IPMNs include villous or vegetative projections, mucin presence, visible tumor vessels, friability, and mucosal thickening (Figure 3)[23,29,30]. Additionally, the “fish-mouth papilla” sign (a bulging ampulla extruding mucin) is pathognomonic for IPMN, though its sensitivity ranges from 25%–68%[18,24,30].

Figure 3 Intraductal papillary mucinous neoplasm. A: Villous projections from a main-duct intraductal papillary mucinous neoplasm; B: SpyBite forceps used to perform a direct biopsy of a suspected intraductal papillary mucinous neoplasm; C: Intraductal papillary mucinous neoplasm and pancreatic stones.

When abnormalities are detected, fluoroscopy should be used to precisely localize the lesion. Directed biopsies should be performed, collecting 8–10 samples to cover the largest possible surface area and maximize diagnostic yield. Studies have demonstrated that biopsies obtained via SpyGlass™ DS pancreatoscopy achieve diagnostic accuracy in up to 90.9% of cases, improving upon conventional pancreatic juice cytology[12,30]. Advanced techniques such as narrow-band imaging enhance visualization of vascular patterns and flat lesions, enabling the identification of abnormalities that might be missed even during surgery[18,30,31].

Pancreatoscopy significantly influences treatment planning by improving lesion mapping and detecting lesions that otherwise may be missed with imaging alone. It has a meaningful impact on surgical decision-making, prompting more extensive resections when additional disease is identified, while in other cases, preventing unnecessary procedures and thereby reducing patient morbidity[18,23,29]. A systematic review and meta-analysis by de Jong et al[23] reported that pancreatoscopy contributed to changes in surgical management in 14%–60% of cases, primarily by modifying resection margins (either extending or sparing them), dictating surgery in patients with diffusely dilated MPD, and identifying skip lesions[18,23,30].

Indeterminate pancreatic duct strictures

Pancreatic duct strictures are a frequent finding in chronic pancreatitis due to persistent inflammation, fibrosis, and subsequent disruption of both endocrine and exocrine functions (Figure 4)[18]. These strictures are associated with an increased risk of pancreatic cancer, highlighting the importance of further evaluation through pancreatoscopy or EUS with fine-needle aspiration (EUS-FNA)[2]. Other potential causes for pancreatic duct strictures include recurrent acute pancreatitis, pseudocysts, and surgical complications[3].

Figure 4  Main pancreatic duct stricture due to chronic pancreatitis.

Pancreatoscopy provides a major advantage by allowing direct visualization of the lesion's characteristics, helping to differentiate between benign and malignant strictures. For example, thickened and friable mucosa is commonly observed in malignant strictures, whereas smooth-walled strictures without mucosal irregularities are more indicative of benign conditions[22]. When combined with pancreatoscopy-guided tissue sampling, the sensitivity and specificity for diagnosing ductal pancreatic neoplasms in indeterminate strictures reach 91% and 95%, respectively[32].

To optimize lesion assessment, the pancreatoscope should be advanced as close as possible to the stricture. If necessary, dilation of the stricture using a 4-mm balloon can be performed before further visualization[12]. When irregularities are detected, pancreatoscopic findings should be carefully analyzed in conjunction with imaging modalities such as MRI or EUS to accurately characterize the lesion. Targeted biopsies should be performed, with at least four samples collected to enhance diagnostic yield[12].

In patients with painful chronic pancreatitis, the placement of a single stent with the largest possible diameter is recommended, as it has been associated with greater pain relief compared to the use of multiple stents[33].

Pancreatic duct strictures are often tortuous and asymmetric, making their evaluation and management challenging (Figure 5). These limitations restrict the role of pancreatoscopy to highly specific cases, particularly when prior EUS-FNA or biopsy results are inconclusive[1,18,34].

Figure 5  Fluoroscopy showing a tortuous pancreatic duct in chronic pancreatitis.

Intraductal lithotripsy in pancreatic lithiasis

One of the most debilitating symptoms of chronic pancreatitis is abdominal pain, which can severely impact patients' quality of life[20]. Although the etiology of pain in these patients is multifactorial, pancreatic ductal obstruction caused by stones or strictures is a major contributor. Effective treatment of these obstructions has been associated with substantial pain relief[4].

Pancreatic lithiasis occurs in approximately 90% of patients with chronic pancreatitis[18]. In addition to pain, ductal obstruction can lead to symptoms of exocrine and endocrine insufficiency, including malabsorption, anorexia, and weight loss[5,18]. Thus, managing these obstructions is a key therapeutic goal, with treatment approaches depending on stone size, location, and associated strictures[2,5].

Conventional ERCP-based techniques, such as stone extraction with balloons or baskets, achieve a limited success rate of about 50%, even in high-volume centers[2,3,20,35]. Mechanical lithotripsy, while effective, has a complication rate nearly three times higher than that observed in biliary lithotripsy, including complications such as basket impaction or breakage[36]. For these reasons, extracorporeal shock wave lithotripsy (ESWL) has been widely used for pancreatic stones, with pain relief reported in approximately two-thirds of patients[37]. However, its availability is limited, and multiple treatment sessions are often required, followed by ERCP to extract the fragmented stones and address any residual strictures[18,20,38].

Intraductal lithotripsy guided by pancreatoscopy combines the advantages of endoscopy and ESWL, enabling simultaneous treatment of stones and strictures (Figure 6)[18,38,39]. This approach employs either electrohydraulic lithotripsy or laser lithotripsy, achieving stone clearance and symptom relief rates of 85%–100%[2,4,5,18,39,40], with comparable efficacy between the two techniques[5,41]. Table 2 compares the two techniques. Complete clearance of the pancreatic duct is achieved in more than 90% of cases, resulting in clinical improvement in up to 90% of patients, including significant pain reduction, decreased opioid use, and fewer hospitalizations[5,19,20,22,33,38]. A key advantage of intraductal lithotripsy over ESWL is the real-time visualization of stone fragmentation, ensuring complete ductal clearance[19].

Figure 6 Stone lithotripsy. A: Laser lithotripsy of a main pancreatic duct stone; B: Pancreatic side-branch stones; C: Electrohydraulic lithotripsy for main pancreatic duct stone fragmentation.

Table 2 Comparison of electrohydraulic lithotripsy and laser lithotripsy.

Feature	Electrohydraulic lithotripsy	Laser lithotripsy
Mechanism	High-pressure shock waves	Laser energy (e.g., holmium)
Efficacy	High fragmentation rate	Higher precision, better control
Tissue injury risk	Higher due to shock waves	Lower due to targeted energy
Preferred for	Hard, larger stones	Smaller, impacted stones

Higher success rates are observed for stones located in the pancreatic head and neck, whereas those in the tail present greater challenges, with a success rate of approximately 70%[18,22]. Similarly, single stones are more amenable to treatment than multiple stones[18]. Reported stone sizes in studies range from 5 mm to 30 mm[35].

The initial treatment strategy for pancreatic stones depends on their size, number, and location. For stones smaller than 4–5 mm, located in the pancreatic head or body, and present in limited numbers, endoscopic extraction is preferred[21,22]. In contrast, for stones larger than 5 mm, ESWL followed by ERCP-assisted retrieval is the first-line approach. Intraductal lithotripsy is typically reserved for cases in which these initial strategies fail[17,19,22,37,40].

For optimal lithotripsy, the most distal stone should be targeted first. The lithotripsy probe should be positioned 2–3 mm away from the pancreatoscope tip to prevent damage. The probe itself should be placed 0.5–2 mm from the stone during treatment, avoiding direct contact to minimize probe damage while maximizing shockwave efficacy[4,15]. Stones should be fragmented as much as possible, with frequent irrigation to improve visualization and maintain appropriate intraductal temperature[15]. The main limitation of this technique is the constrained space within the distal pancreatic duct, which complicates pancreatoscope maneuverability. In such cases, guiding the wire as close as possible to the stone facilitates optimal equipment placement[4,12].

With increasing clinical experience and accumulating evidence supporting its efficacy and safety, intraductal lithotripsy is expected to play a prominent role in pancreatic lithiasis management, given its high success rate and low complication risk[22,38,42].

ADVERSE EVENTS

The most common complication of pancreatoscopy is post-procedural pancreatitis, with an incidence ranging from 4% to 17%, depending on patient characteristics and pancreatic pathology[4,5,22,23,31,43]. One study found an inverse relationship between the diameter of the MPD and the risk of pancreatitis, suggesting that a smaller-caliber MPD is associated with a higher risk and greater severity[44]. In patients with chronic pancreatitis undergoing pancreatoscopy for pancreatic lithiasis treatment, the risk of complications is estimated to be below 5%-10%[45]. However, when pancreatoscopy is used to evaluate pancreatic tumors, the risk increases up to 12%[4,23]. Additionally, a history of post-ERCP pancreatitis is associated with an increased risk of post-procedural pancreatitis, emphasizing the need for individualized risk assessment in these patients[44].

As for the severity of post-procedural pancreatitis, it has been reported as mild to moderate in 91.2% of cases, with some studies reporting no cases of pancreatitis and only one report of death due to severe pancreatitis[5,23,44].

The increase in intraductal pressure, combined with the injection of saline into the pancreatic duct, are the primary causes in the pathophysiology of post-procedural pancreatitis. Proper control of saline volume and effective aspiration significantly contribute to the prevention of complications[22]. Additionally, performing pancreatic sphincterotomy at the start of the procedure and placing a pancreatic stent at the end ensures optimal drainage, reducing the risk of complications[4].

Other complications include bleeding (3.4%), perforation (4.3%), fever and infectious complications like cholangitis (3.7%), MPD wall injury[46], and mechanical complications such as basket or guidewire entrapment[47]. ERCP, in comparison, presents a lower overall complication rate. Meta-analyses have reported post-ERCP pancreatitis rates ranging from 3.5%-9.7%[16]. Interestingly, in high-risk patients, the incidence of post-ERCP pancreatitis may reach up to 14.7%, approaching rates observed with pancreatoscopy[16,48]. Additionally, complications such as cholangitis occurs in 0.5%-3.0% of cases, bleeding in 0.3%-9.6%, and perforation in 0.08% to 0.6%[16]. Moreover, the majority of ERCP-related adverse events are sedation-related (2%-26%) and are typically transient, without clinical consequences after 48 hours[49,50]. Table 3 provides a comparison of the adverse event rates associated with pancreatoscopy and ERCP.

Table 3 Comparison of adverse events in pancreatoscopy and endoscopic retrograde cholangiopancreatography.

Adverse event	Pancreatoscopy	Endoscopic retrograde cholangiopancreatography
Post-procedural pancreatitis	4%-17%	3.5%-9.7%
Cholangitis	3.7%	0.5%-3.0%
Bleeding	3.4%	0.3%-9.6%
Perforation	4.3%	0.08%-0.6%
Sedation-related adverse events	Not reported	2%-26%

Although pancreatoscopy is a valuable diagnostic and therapeutic tool, its use should be carefully individualized, as it is not free of potential complications and carries higher risks than procedures such as ERCP.

CONCLUSION

Pancreatoscopy has emerged as a valuable tool for both the diagnosis and treatment of complex pancreatic disorders. Its ability to provide direct intraductal visualization, obtain targeted biopsies, and perform therapeutic interventions—such as lithotripsy—makes it particularly useful in cases where conventional imaging techniques yield inconclusive results. In the evaluation of IPMNs, indeterminate strictures, and pancreatic duct stones, pancreatoscopy not only enhances diagnostic precision but also directly informs surgical decision-making, potentially reducing unnecessary procedures. While complications such as post-procedural pancreatitis remain a concern, adherence to established preventive strategies and proper technique has significantly mitigated these risks. Ongoing technological advancements, including higher-resolution digital imaging, enhanced maneuverability, and integration with artificial intelligence, are expected to further refine the diagnostic accuracy and clinical utility of pancreatoscopy. Miniaturization of devices may expand its use in smaller ducts and branch lesions, while AI-assisted interpretation could support real-time differentiation of benign vs malignant features, solidifying its role as a first-line tool in advanced pancreatic care.