Pancreatic duct stone management strategies: Advances and clinical practice in chronic pancreatitis

Abstract

Pancreatic duct stones (PDS) are a prevalent and debilitating complication of chronic calcific pancreatitis, primarily driven by etiologies such as alcohol abuse and genetic factors. Their pathogenesis involves pancreatic inflammation, ductal obstruction, and subsequent precipitation of calcium carbonate, leading to ductal hypertension, abdominal pain, pancreatic exocrine/endocrine insufficiency, and recurrent acute exacerbations. Diagnosis relies on a multimodal imaging approach, which plays a pivotal role in not only detecting PDS but also in planning therapeutic strategies. Therapeutic strategies have evolved into a multimodal, stepwise approach. Endoscopic retrograde cholangiopancreatography (ERCP) with sphincterotomy, stone extraction, and stent placement remains a first-line minimally invasive option, demonstrating long-term pain relief in a significant proportion of patients and is applicable even in pediatric populations. For larger or impacted stones, extracorporeal shock wave lithotripsy (ESWL) is a critical adjunct. Evidence shows that ESWL coupled with same-session ERCP yields a higher stone clearance rate. Surgical intervention, including resection and drainage procedures, still plays a pivotal role for complex cases, such as those with large stones (> 0.5 cm) or associated ductal strictures where endoscopic methods may be insufficient. Key advances in clinical practice emphasize a tailored strategy based on stone characteristics (size, density, location) and ductal anatomy. The integration of ESWL with endoscopy, optimized by specialist collaboration and preoperative imaging assessment, enhances outcomes. Furthermore, the management of PDS requires a multidisciplinary framework involving endoscopists, surgeons, and radiologists to construct individualized treatment regimens that effectively alleviate pain, preserve pancreatic function, and improve quality of life.

Key Words: Pancreatic duct stones; Chronic pancreatitis; Endoscopic retrograde cholangiopancreatography; Extracorporeal shock wave lithotripsy; Surgical intervention

Core Tip: This minireview comprehensively addresses pancreatic duct stones, a major complication of chronic pancreatitis. It covers pathogenesis and contemporary diagnostic evaluation, and provides a critical analysis of therapeutic strategies, including endoscopy, lithotripsy, and surgery. By integrating current evidence, it offers a framework for constructing individualized, stepwise treatment regimens to optimize patient management.

INTRODUCTION

Chronic pancreatitis (CP) constitutes a progressive inflammatory condition characterized by irreversible fibrotic changes, intraductal calcification, recurring abdominal distress, and compromised pancreatic function[1,2]. Among the various manifestations of CP, pancreatic duct stones (PDS) emerge as the most frequent and clinically demanding challenge[2,3]. These calculi, primarily composed of calcium carbonate, arise secondary to the disease process and are linked to etiologies such as chronic alcohol abuse, cholelithiasis, genetic predispositions, autoimmune conditions, and tropical fibrocalculous pancreatic diabetes[2,4-7]. Mechanistically, stone formation obstructs the main pancreatic duct (MPD) or its tributaries, inducing ductal hypertension and elevated intraductal and parenchymal pressures. This cascade triggers inflammation and generates the hallmark symptom of CP: Severe epigastric pain radiating dorsally[1-3]. Furthermore, sustained obstruction and inflammatory responses accelerate the depletion of pancreatic parenchyma, resulting in exocrine pancreatic insufficiency (EPI), manifesting as steatorrhea and malnutrition, and endocrine failure[2,8]. PDS also predispose patients to serious complications, including pancreatic pseudocysts, biliary strictures, recurrent acute pancreatitis, pancreaticopleural fistulas, and an elevated risk of pancreatic malignancy[6,9-12].

The therapeutic landscape for PDS has transitioned from predominantly surgical interventions to a multimodal paradigm emphasizing minimally invasive endoscopic techniques, although surgery still plays a pivotal role[2,13]. This evolution has been facilitated by advances in diagnostic imaging and therapeutic capabilities. Precise diagnosis and characterization of PDS remain fundamental in selecting optimal treatment strategies[2,6]. The integration of multimodal imaging with personalized therapeutic strategies significantly refines clinical decision-making. Ultimately, effective management of PDS demands a tailored, multidisciplinary approach involving gastroenterologists, interventional endoscopists, pancreatic surgeons, and radiologists. This collaborative framework must account for individual patient characteristics, operator expertise, and emerging evidence to optimize outcomes related to pain control, preservation of pancreatic function, complication reduction, and overall quality of life[3,12,14].

LITERATURE REVIEW

To ensure a comprehensive and evidence-based review of management strategies for PDS, a systematic literature search was conducted in April 2026. Three major databases - PubMed, EMBASE, and the Cochrane Library - were searched for relevant studies. The search strategy combined the following keywords and Medical Subject Headings terms: “pancreatic duct stones”, “pancreaticolithiasis”, “chronic pancreatitis”, “endoscopic retrograde cholangiopancreatography (ERCP)”, “extracorporeal shock wave lithotripsy (ESWL)”, “pancreatic stenting”, “pancreatoscopy”, and “surgery.” Boolean operators (AND, OR) were used to refine the search, and the publication language was restricted to English.

The search was limited to articles published from January 2020 to April 2026. After removing duplicates, titles and abstracts were screened for relevance to PDS in patients with CP. Full-text articles of potentially eligible studies were then assessed against predefined inclusion and exclusion criteria. Inclusion criteria were: (1) Studies involving human subjects with CP and symptomatic PDS; (2) Articles reporting on therapeutic outcomes of endoscopic intervention (e.g., ERCP with sphincterotomy, stenting, pancreatoscopy with electrohydraulic lithotripsy), ESWL, or surgical management; (3) Original research articles, case series, and systematic reviews; and (4) Publications in English. Exclusion criteria were: (1) Studies focusing solely on acute pancreatitis or pancreatic malignancy; (2) Articles that did not provide specific data on treatment modalities or outcomes for PDS; (3) Editorials, letters, conference abstracts, and case reports without sufficient clinical detail; and (4) Non-English publications.

A total of 81 relevant articles were identified from the initial search and met the eligibility criteria. Data from these selected articles were extracted to summarize key findings regarding treatment efficacy, safety profiles, procedural details, and patient outcomes. This methodology ensured that the review was grounded in current, peer-reviewed evidence, providing a solid foundation for the critical evaluation of treatment algorithms presented in the manuscript.

PATHOPHYSIOLOGY AND FORMATION MECHANISMS OF PDS

Biochemical Composition and Classification of Stones

The biochemical makeup of PDS profoundly influences their clinical behavior and therapeutic responsiveness. These calculi primarily consist of calcium carbonate monohydrate. Their inorganic matrix is typically encased within a protein-rich core, which initiates the formation of protein plugs that subsequently promote calcium salt deposition. This pathogenic sequence is intimately linked to alterations in pancreatic juice composition, particularly stasis and increased lithogenic potential[15]. Based on radiological visibility, stones generated through this mechanism can be categorized into two types. Radiopaque (positive) stones, characterized by high calcium content, are readily identifiable on standard plain radiographs. In contrast, radiolucent (negative) stones, possessing lower mineral density or distinct compositional profiles, require cross-sectional imaging modalities such as computed tomography (CT) or magnetic resonance cholangiopancreatography (MRCP) for detection. This distinction carries significant practical implications rather than mere theoretical interest, as it directly informs treatment selection. Specifically, stone hardness and density, dictated by crystal structure and chemical composition, critically influence the choice and efficacy of lithotripsy techniques. For instance, the success rate of ESWL is markedly dependent on these physical properties.

The primary therapeutic approach for pancreatolithiasis is dictated by the physical attributes of the calculus. Subsequent management strategies vary; for instance, rapidly developing radiolucent proteinaceous stones require a conservative regimen centered on dietary modifications to enhance pancreatic fluid secretion and facilitate spontaneous clearance, thereby avoiding repetitive endoscopic interventions[16]. Pancreatic stone protein (PSP), alternatively termed regenerating protein, represents a key constituent of this family. Since its initial link to lithogenesis was established, PSP has served as a valuable point-of-care biomarker for systemic conditions such as sepsis, implying functions extending beyond the local pancreatic environment[17]. Consequently, characterizing stone composition and classification—encompassing both radiological features and biochemical markers like PSP—is imperative for devising effective diagnostic and therapeutic protocols for pancreatic duct stone disease[16].

Promoting factors of stone formation

The genesis of PDS in CP involves alterations in pancreatic juice composition, decreased lithostatic protein levels, alongside genetic predispositions and environmental triggers such as alcohol and tobacco consumption[18]. Among environmental hazards, chronic alcohol abuse and smoking stand out as the most prominent contributors, representing the most frequent etiologies of CP and subsequent pancreatolithiasis[19].

Alcohol exerts its detrimental effects through multiple interconnected pathways. Firstly, it directly damages pancreatic acinar cells, leading to the release of intracellular digestive enzymes and triggering autodigestion and recurrent inflammation. Secondly, alcohol alters pancreatic juice composition, increasing its protein content and viscosity. This promotes the formation of proteinaceous plugs within the pancreatic ducts, which serve as the initial nidus for stone formation. Thirdly, alcohol can cause functional dysregulation of the pancreatic duct sphincter (Oddi’s sphincter), leading to increased ductal pressure and pancreatic secretion stasis. This stasis facilitates calcium carbonate precipitation, the principal inorganic component of pancreatic calculi, onto the protein plugs. Finally, chronic alcohol exposure induces oxidative stress and promotes pancreatic fibrosis, which further distorts ductal architecture, creating strictures and areas of obstruction that perpetuate stone formation and growth[19,20].

Smoking is a strong independent and synergistic risk factor with alcohol for the development of CP and its complications. Tobacco smoke contains numerous toxic compounds that induce oxidative stress and inflammatory responses within the pancreatic parenchyma. It accelerates the progression of pancreatic fibrosis, leading to more rapid and severe ductal distortion and obstruction compared with alcohol alone. Furthermore, smoking may directly affect the ionic composition of pancreatic juice, enhancing its lithogenic potential. The combination of smoking and alcohol abuse significantly increases the risk, severity, and speed of PDS formation compared with either factor alone[21].

Persistent inflammation culminates in irreversible fibrosis and scarring within the pancreatic parenchyma and ductal system. A critical precipitating factor is ductal obstruction arising from strictures, anatomical variants like pancreas divisum, or extrinsic compression, all of which induce stasis of pancreatic secretions. Such stagnation promotes calcium carbonate precipitation, the principal component of pancreatic calculi. Ductal anatomy significantly influences the progression from recurrent acute pancreatitis to chronic disease, thereby elevating the risk of intraductal lithiasis[4]. Pseudocysts, particularly those located in the pancreatic head, contribute to the development of significant biliary strictures in CP[10]. PDS, a direct sequela of CP, are observed in approximately 50% of patients, underscoring the clinical significance of pancreatolithiasis[22].

Modifications in pancreatic juice composition serve as major biochemical drivers of calculi formation. A pivotal contributor is the reduced secretion or functional impairment of anti-lithiasis glycoproteins[18], which normally inhibit stone nucleation. Furthermore, alterations in ionic concentrations can precipitate crystallization. These biochemical shifts stem from the chronic inflammation and acinar cell injury characteristic of CP. PDS typically appear radiopaque due to their calcium content; notably, CT Hounsfield unit density predicts therapeutic difficulty, with stones exhibiting a mean density exceeding 1336 HU requiring additional ESWL fragmentation sessions[23]. This combination of biochemical dysregulation and physical stasis fosters the development of ductal calculi.

Genetic susceptibility, environmental exposures, and systemic disorders act as downstream drivers that initiate and perpetuate the chronic inflammatory cascade leading to stone formation. Hereditary factors elevate the risk of developing CP. Among environmental hazards, chronic alcohol abuse and smoking stand out as the most prominent contributors, representing the most frequent etiologies of CP[2,24]. Autoimmune mechanisms, as seen in autoimmune pancreatitis (AIP), offer an alternative pathogenic pathway. Although pancreatic calculi are less common in AIP compared with alcoholic CP, they may emerge during disease relapse[7]. The pathogenesis of pancreatic duct stone formation remains complex, multifactorial, and incompletely elucidated (Figure 1).

Figure 1 Flowchart illustrating the core pathophysiological process of chronic pancreatitis and pancreatic duct stone formation.

DIAGNOSIS AND COMPREHENSIVE ASSESSMENT OF PDS

Functional and clinical assessment

Clinical evaluation must characterize the nature, frequency, and severity of abdominal pain to elucidate the relationship between symptoms and stone-related obstruction. Abdominal pain represents the most prevalent PDS-associated symptom in CP[2]. This discomfort arises from ductal hypertension resulting from the obstruction of pancreatic juice flow within the MPD by stones, strictures, or a combination thereof[2,13]. Pain intensity can be quantified using standardized instruments such as the Izbicki score, which predicts post-surgical pain relief[25]. Assessment should cover pain characteristics (continuous vs sporadic), frequency, intensity, and associations with meals or other triggers. Evidence suggests that a shorter duration of pain prior to surgery predicts better long-term analgesic outcomes[25]. Pancreatic duct obstruction, whether due to stones or strictures, constitutes a primary pain-generating mechanism in CP. However, pain in CP is multifactorial, often involving aberrant central pain processing and psychological comorbidities (e.g., anxiety, depression, pain catastrophizing) that exacerbate patient-reported outcomes regarding pain intensity and quality of life[26]. Therefore, clinical assessment must not only confirm the anatomical link between pain and stone obstruction (via imaging) but also account for these psychosocial factors.

Evaluation of pancreatic exocrine function: Assessing exocrine capacity, specifically regarding fat digestion and absorption, is critical for patients harboring PDS, as CP frequently progresses to EPI. Fecal elastase-1 (FE-1) serves as the predominant non-invasive biomarker for confirming or ruling out EPI[27]. Stool concentrations below 200 µg/g signify EPI, whereas levels under 100 µg/g indicate severe insufficiency[27]. Research demonstrates that EPI severity, quantified via the Pancreatic Exocrine Insufficiency Questionnaire, aligns closely with morphological disease severity observed on imaging, particularly in cases involving pancreatic duct strictures or obstructing intraductal calculi. Furthermore, MPD lithiasis identified through endoscopic ultrasound (EUS) correlates with an elevated risk of developing EPI[28]. Alternative functional assessments include the N-benzoyl-p-aminobenzoic acid test[29] and direct quantification of duodenal secretions following secretin stimulation[30]. Emerging advanced imaging techniques show significant promise; notably, pancreatic T1 relaxation times derived from modified Look-Locker inversion recovery magnetic resonance imaging (MRI) sequences exhibit a significant negative correlation with FE-1 levels, suggesting utility in EPI diagnosis[31]. Additionally, radiomics nomograms constructed from non-contrast T1-weighted MRI data can predict exocrine function, potentially surpassing the accuracy of secretin-enhanced MRCP[32]. In the context of CP, skeletal muscle depletion correlates with diminished exocrine function, malnutrition, parenchymal atrophy, and main duct dilation[33].

Evaluation of endocrine function: Monitoring blood glucose and glycated hemoglobin is essential for diagnosing secondary diabetes. Endocrine pancreatic insufficiency, manifesting as pancreatogenic or type 3c diabetes, represents a frequent and serious complication of CP and PDS[34,35]. Persistent inflammation and fibrosis degrade pancreatic parenchyma and islet cells, leading to functional loss[36,37]. Clinical evaluation typically involves fasting plasma glucose and glycated hemoglobin (HbA1c) measurements, while C-peptide or insulin assays may be employed to assess beta-cell reserve[38]. The prevalence of diabetes within CP cohorts is substantial, with many individuals exhibiting concurrent exocrine and endocrine failure[36]. For example, one investigation reported that 72% of patients suffering from severe EPI also presented with diabetes mellitus[36]. Although new-onset diabetes is more probable in CP patients with existing diabetic conditions compared to those without, mechanisms extending beyond simple islet cell depletion may contribute to this phenomenon[30]. Regarding surgical interventions for CP, procedures such as duodenum-preserving pancreatic head resection result in lower rates of postoperative EPI requiring treatment compared with pancreaticoduodenectomy, while maintaining low incidences of new-onset diabetes[39].

Performance of ERCP: ERCP offers both diagnostic and therapeutic benefits, enabling direct visualization of pancreatic duct morphology, calculi, and strictures, albeit as an invasive modality. It remains a pivotal instrument in managing PDS by providing simultaneous diagnostic insight and therapeutic access. Data obtained regarding stone burden and strictures[13,18] directly informs therapeutic planning. As the primary endoscopic intervention for PDS, ERCP combined with sphincterotomy followed by balloon or basket extraction is the preferred approach for small calculi[2,13]. Conversely, for larger or complex stones, ERCP is typically preceded by ESWL to facilitate fragmentation.

Endoscopic removal has been established as a viable approach[2,23]. The advent of single-operator pancreatoscopy combined with electrohydraulic lithotripsy (EHL) under direct visual guidance has significantly expanded therapeutic capabilities, enabling the management of large and refractory calculi[40,41]. Nevertheless, ERCP remains an invasive procedure associated with notable complications, particularly post-ERCP pancreatitis (PEP)[42], alongside risks of hemorrhage and perforation[43]. Consequently, proceeding with ERCP requires a rigorous assessment of risk vs benefit. In cases involving altered anatomy or failed ERCP attempts, EUS-guided pancreatic duct drainage has emerged as a critical salvage strategy[44].

Imaging diagnostic techniques

Imaging plays a pivotal role in diagnosing PDS, as diverse modalities offer complementary data essential for patient evaluation and treatment planning. Abdominal plain radiography can reveal radiopaque calculi along the pancreatic duct, often serving as an initial, albeit frequently incidental, finding.

However, its utility is limited by poor sensitivity; specifically, it fails to identify radiolucent calculi or assess parenchymal alterations and complications like atrophy or pseudocyst formation. Consequently, cross-sectional imaging is indispensable for comprehensive diagnostic evaluation and therapeutic planning. These modalities precisely characterize the quantity, dimensions, and intraductal positioning of stones. CT effectively identifies pancreatic pseudocysts and ductal lithiasis in CP[9]. Notably, non-contrast CT allows quantification of stone density in Hounsfield units, a metric that correlates with endoscopic retrieval success post-lithotripsy. Indeed, lower-density calculi fragment and extract more readily[45]. MRCP aids in diagnosing chronic stone-induced pancreatitis complicated by pancreaticopleural fistulae[11]. Collectively, CT, MRI, and MRCP facilitate the diagnosis of chronic calcific pancreatitis associated with bilateral pancreaticopleural fistulae[11]. By delineating pancreatic ductal architecture—including dilation, obstruction, and communications with pseudocysts or fistulae—these techniques provide an essential “road map” for guiding endoscopic or surgical interventions. While linear EUS can identify anatomical variants such as pancreas divisum, it may struggle to differentiate calcified ductal stones in cases of severe pancreatitis[46]. EUS offers high-resolution visualization of both pancreatic parenchyma and the ductal system, proving vital for the evaluation and management of pancreatitis[47]. Imaging remains paramount for diagnosing PDS, as specific calculi characteristics directly inform clinical decision-making[2]. Furthermore, EUS assesses adjacent vasculature, serving as a critical tool for estimating hemorrhage risk during invasive procedures. Its applications extend to therapeutics; for instance, EUS-guided laser lithotripsy (LL) has been successfully employed for PDS when conventional cannulation fails, as documented in case reports[48]. Similar approaches using EUS-guided LL for refractory stones have also been described[48]. Additionally, EUS facilitates the diagnosis of idiopathic acute and recurrent pancreatitis, as well as AIP via guided fine-needle biopsy[47]. In acute biliary pancreatitis, EUS detects common bile duct stones, thereby optimizing patient management strategies and preventing unnecessary ERCP when findings are negative[49]. Integrating data from CT and MRCP with the high-resolution therapeutic capabilities of EUS fosters a modern, personalized approach to diagnosing and treating PDS.

COMPREHENSIVE MANAGEMENT AND ADJUNCTIVE THERAPY

Pharmacological pain management

Managing pain in CP requires a structured, stepwise approach. While the primary goal for pain due to ductal obstruction is decompression via endoscopic or surgical means, pharmacotherapy is essential for non-obstructive disease and as an adjunct. Initial therapy typically employs non-opioid agents like non-steroidal anti-inflammatory drugs[9]. For severe or refractory pain, especially with a neuropathic component, neuromodulators (e.g., tricyclic antidepressants, pregabalin) are added[50]. Opioid therapy may be initiated for severe pain but requires careful management to mitigate risks of dependence[51]. For refractory cases, interventions like celiac plexus blockade or emerging neuromodulation techniques (e.g., spinal cord stimulation) may be considered[52,53].

Management of pancreatic exocrine insufficiency

Pancreatic exocrine insufficiency is a common complication of CP[54]. Management is centered on optimizing pancreatic enzyme replacement therapy (PERT), with guidelines recommending a minimum lipase dosage of 40000 units per meal taken with food[55]. Concomitant proton pump inhibitors are frequently prescribed to enhance PERT efficacy. Nutritional surveillance is imperative, focusing on identifying and correcting deficiencies in fat-soluble vitamins and other nutrients. Medium-chain triglycerides can provide caloric support independent of pancreatic lipase[56].

Lifestyle intervention and follow-up

Strict, permanent abstinence from alcohol and tobacco is critical to retard disease progression. Dietary management should emphasize low-fat, easily digestible foods consumed in small, frequent portions. A structured follow-up strategy is essential for monitoring disease evolution and therapeutic efficacy. This includes systematic pain evaluation using quantitative scoring systems, close monitoring of blood glucose/HbA1c due to the high risk of diabetes, and serial imaging (e.g., ultrasound, CT, MRCP) to detect complications such as stone recurrence, pseudocysts, or malignancy[57].

ENDOSCOPIC THERAPEUTIC STRATEGIES: STONE EXTRACTION AND DRAINAGE

ERCP for calculus removal

ERCP serves as the primary intervention for PDS. While small stones can be extracted directly, larger calculi require adjunctive ESWL for fragmentation[13]. Short-term pancreatic duct stenting is recommended post-procedure to mitigate the risk of PEP[58].

Pancreatic duct stenting and drainage

The principal objective of stenting is decompressive drainage and pain relief. It is utilized when immediate stone clearance is not possible or in the presence of a tight stricture[59]. However, stent placement carries risks of migration and may induce morphological alterations in the ductal architecture with prolonged indwelling times (Table 1)[60].

Table 1 Summary of benefits and risks of endoscopic procedures for pancreatic duct stones.

	Key benefits	Key risks/limitations
ERCP for stone extraction	Primary intervention for PDS; enables direct removal of small stones (≤ 0.5 cm); provides access for fragment removal post-ESWL	Risk of PEP; ineffective for large/impacted stones without prior fragmentation (requiring ESWL); risk of procedure failure (e.g., guidewire placement increasing risk of residual stones)
Pancreatic duct stenting	Achieves decompressive drainage; alleviates pain associated with chronic pancreatitis and ductal obstruction; bridges obstructed segments when immediate stone removal is not feasible	Risk of stent-induced ductal changes (strictures/dilatation); complications include proximal/distal migration, stent occlusion, and rare events like jejunal obstruction; may require subsequent removal procedure

PDS: Pancreatic duct stones; ERCP: Endoscopic retrograde cholangiopancreatography; ESWL: Extracorporeal shock wave lithotripsy; PEP: Post-endoscopic retrograde cholangiopancreatography pancreatitis.

APPLICATION OF ESWL IN PDS

ESWL is a non-invasive technique that uses externally generated high-energy pulses to fragment pancreatic duct calculi[61]. The goal is to reduce stones to fragments ≤ 3 mm for subsequent endoscopic removal[13]. Its efficacy is influenced by stone characteristics; for instance, stones with high CT attenuation may require multiple sessions[23]. The procedure is indicated for symptomatic radiopaque calculi ≥ 5 mm in the MPD[62]. The combination of ESWL with ERCP is a strategic approach to enhance stone clearance (Table 2).

Table 2 Summary of benefits and risks of extracorporeal shock wave lithotripsy for pancreatic duct stones.

Procedure	Key benefits	Key risks/limitations
ESWL	Non-invasive fragmentation of large stones into fragments ≤ 3 mm. High success rate for complete/near-complete fragmentation and clearance. Effective for pain relief by decompressing the obstructed duct. Generally safe with a low incidence of severe adverse events	Incomplete fragmentation can occur; predictors include high stone CT attenuation and large stone volume. May require multiple sessions. Common side effects: Cutaneous ecchymosis, sinus bradycardia. Post-procedural acute pancreatitis occurs in approximately 3.7% of patients. Efficacy is reduced by a concomitant main pancreatic duct stricture

ESWL: Extracorporeal shock wave lithotripsy; CT: Computed tomography.

DIRECT INTRACORPOREAL LITHOTRIPSY TECHNIQUES

Direct intracorporeal lithotripsy techniques, including LL and EHL, are advanced endoscopic strategies for managing complex PDS, particularly those resistant to primary therapies like ESWL.

LL involves the endoscopic placement of a laser fiber directly onto the calculus under direct visualization via peroral pancreatoscopy (POP)[63,64]. It is characterized by high precision and efficacy, with high pooled technical and clinical success rates. However, it presents technical challenges, carries risks such as ductal trauma and PEP, and is limited to specialized centers due to high cost and the need for advanced expertise[65].

EHL employs localized high-pressure shockwaves to fragment calculi under fluoroscopic or direct pancreatoscopic guidance. It is particularly effective for impacted stones, achieving high technical success rates[66]. Its efficacy can be limited by stone characteristics (high density or large size), and it requires meticulous technique to avoid complications like PEP, which is its most frequent adverse event (Table 3)[67].

Table 3 Summary of benefits and risks of direct intracorporeal lithotripsy techniques.

Technique	Key benefits	Key risks/limitations
LL	High-precision, effective strategy for complex or ESWL-resistant stones. Allows fragmentation under direct visualization via POP. High pooled technical (88.1%) and clinical (81.6%) success rates. No ionizing radiation	Technically challenging and requires advanced endoscopic expertise. High cost and limited availability, restricted to specialized centers. Risks include pancreatic duct trauma, perforation, and PEP. Pooled adverse event rate for POP-guided lithotripsy is approximately 12%
EHL & electromechanical lithotripsy	Highly effective for fragmenting impacted main pancreatic duct stones. High technical success rate (e.g., 91.18% for POP-guided intracorporeal lithotripsy). Serves as a robust alternative or adjunct to other lithotripsy modalities	Efficacy is influenced by stone characteristics; high CT attenuation (> 2050 HU) or large diameter (> 12.8 mm) predict incomplete fragmentation. Requires precise electrode placement to avoid ductal wall contact, preventing barotrauma or perforation. Pooled adverse event rate is approximately 14.9%, with PEP being the most frequent complication (approximately 7%)

LL: Laser lithotripsy; ESWL: Extracorporeal shock wave lithotripsy; POP: Peroral pancreatoscopy; PEP: Post-endoscopic retrograde cholangiopancreatography pancreatitis; EHL: Electrohydraulic lithotripsy; CT: Computed tomography.

THE STATUS OF SURGICAL TREATMENT AND SELECTION OF SURGICAL APPROACHES

Surgical intervention is indicated when endoscopic or conservative management is ineffective or unsuitable, such as in cases of failed endoscopic therapy, complex lithiasis, suspected malignancy, or intractable pain. The primary goals are to relieve MPD obstruction, restore drainage, excise diseased tissue, and achieve durable pain relief.

The choice of surgical procedure depends on individual anatomy and pathology. Drainage procedures (e.g., lateral pancreaticojejunostomy) are effective for decompressing a dilated MPD. Local pancreatic head resection combined with drainage (e.g., Beger or Frey procedures) is indicated for disease confined to the pancreatic head with enlargement or concurrent obstruction[68]. Pancreatectomy (pancreaticoduodenectomy or distal pancreatectomy) is reserved for severe localized disease or suspected malignancy[69]. Preoperative imaging is crucial for planning, with an MPD diameter < 8 mm being a notable risk factor for postoperative pancreatic fistula following drainage surgery (Table 4)[25].

Table 4 Summary of surgical approaches for pancreatic duct stones.

Surgical approach	Key benefits	Key risks/limitations
Pancreaticojejunostomy (e.g., Puestow, Frey procedures)	Provides effective decompression of the obstructed MPD. Achieves high rates of long-term pain relief and stone clearance. Aims to restore pancreatic juice flow and reduce intraductal pressure	Risk of postoperative pancreatic fistula, particularly if the MPD diameter is < 8 mm. Primarily indicated for patients with a significantly dilated MPD
Local pancreatic head resection with drainage (e.g., Beger, Frey procedures)	Excises diseased tissue (e.g., inflamed head, stones) while preserving duodenal integrity. Addresses concurrent biliary or duodenal obstruction. Reported long-term success rates for pain relief are high (e.g., approximately 90% for Frey procedure)	Technically more complex than drainage alone. Requires surgical expertise, especially for minimally invasive or robotic approaches
Pancreatectomy (pancreaticoduodenectomy or distal pancreatectomy)	Definitive resection for severe localized disease, suspected malignancy, or when less aggressive options fail. Eliminates the diseased pancreatic segment	Radical procedure with associated morbidity. May lead to endocrine or exocrine insufficiency, and the underlying chronic pancreatitis may progress in the remnant gland

MPD: Main pancreatic duct.

EMERGING TECHNOLOGIES, CHALLENGES, AND FUTURE PROSPECTS

Exploration of novel technologies

The therapeutic landscape for PDS is evolving toward innovative endoscopic and surgical methods to enhance efficacy, safety, and patient comfort. While natural orifice transluminal endoscopic surgery remains experimental, current efforts prioritize refining lithotripsy and drainage techniques. Robotic-assisted endoscopic surgery offers stability for intricate maneuvers but requires further validation for PDS. Nevertheless, recent investigations and clinical practices emphasize advanced lithotripsy methodologies and novel stent architectures. ESWL is first-line therapy for large (> 5 mm), radiopaque, obstructive main PDS, achieving pooled complete clearance rates of approximately 70% and meaningful pain relief[61,62]. Treatment efficacy correlates with factors such as sex, stone diameter, and stone values on CT scans[70,71]. ESWL often requires repeated sessions, followed by ERCP to clear residual fragments; POP enables intracorporeal lithotripsy, serving as an alternative or salvage option, with high success rates for stones refractory to ESWL or ERCP[64,72]. No significant differences in technical success, clinical outcomes, or adverse event rates exist between POP-guided lithotripsy and ESWL[72]. For refractory cases, EUS-guided LL serves as a reliable salvage technique. Novel retrieval instruments, such as the rotating basket catheter (RASEN), demonstrate higher clearance rates for small fragments compared with traditional devices[73,74]; an eight-wire biliary basket catheter effectively retrieves residual microcalculi[75]. Biodegradable pancreatic duct stents are under development to provide transient decompression, avoiding secondary removal and reducing chronic ductal changes. Collectively, these modalities—ranging from non-invasive ESWL and direct visualization via POP to advanced retrieval instruments and next-generation stents—constitute a tailored, minimally invasive algorithm for managing PDS. This approach integrates stone morphology, patient anatomy, and institutional expertise[18].

Current challenges

The management of PDS persists as a formidable clinical challenge, primarily due to incomplete stone clearance and inadequate pain relief. Despite successful endoscopic calculus removal and lithotripsy, a substantial proportion of patients continue to suffer from pain. For instance, while ESWL achieves complete clearance in approximately 75% of cases, sustained long-term pain relief is observed in only two-thirds of patients[76]. This discrepancy indicates that CP-associated pain is not solely due to ductal obstruction but involves pancreatic fibrosis, strictures, and multifactorial mechanisms requiring management beyond ductal decompression, including neuropathic components and inflammation[77].

Another significant hurdle is the high rate of stone recurrence following endoscopic intervention. Although ESWL and pancreatoscopy-guided lithotripsy achieve high initial technical success, many patients require retreatment. Recurrence is driven by persistent ductal strictures[22], ongoing inflammation, and metabolic abnormalities. While novel devices like the RASEN catheter can improve clearance rates[74], they do not address the underlying disease process. Consequently, long-term management protocols remain ill-defined, necessitating more durable solutions such as aggressive initial clearance, prolonged pancreatic stenting, and strict etiological control like alcohol cessation.

Certain patient presentations pose particularly difficult management problems: Small stones within non-dilated pancreatic ducts, diffuse parenchymal calcification, and hereditary pancreatitis. Small-duct CP restricts endoscopic access, and the risk of postoperative pancreatic fistula is higher when the pancreatic diameter is ≤ 8 mm[25]. Diffuse pancreatic calcification is prevalent in advanced CP, where stones are diffusely distributed within the parenchyma and side branches, requiring surgical approaches[78]. Hereditary pancreatitis manifests early and demands lifelong management; adult-oriented therapies like ESWL show promise in pediatric populations but remains controversial[79]. Conventional endoscopic algorithms often prove inadequate, necessitating higher-risk surgical interventions[68,80]. The absence of high-level evidence and standardized guidelines for such cases represents a critical gap in current clinical practice.

Future research directions

Future research on PDS focuses on three key areas. First, developing chemical litholytic therapies, such as drug-eluting stents with sustained release litholytic agents (e.g., citric acid), which have shown high efficacy in dissolving calculi in vitro[81]. Future research should prioritize pharmacological strategies to prevent stone formation and recurrence by understanding underlying pathological mechanisms[18].

Second, integrating artificial intelligence (AI) with radiological data holds promise for personalizing the management of pancreatic duct calculi. AI algorithms can be trained to analyze CT features (e.g., stone density, size) to predict treatment difficulty, such as the need for multiple ESWL sessions[23], and to forecast procedural complications like PEP. Consequently, future efforts should focus on developing and validating robust AI models capable of analyzing preprocedural imaging to guide therapeutic decisions, optimize patient selection for endoscopic vs surgical interventions, and tailor treatment strategies.

Third, to advance evidence-based clinical practice, there is an urgent need for high-quality, multicenter randomized controlled trials (RCTs) to rigorously evaluate the long-term efficacy, safety profiles, and cost-effectiveness of therapeutic strategies for PDS. These trials should directly compare endoscopic (e.g., ESWL + ERCP) vs surgical interventions, various lithotripsy techniques, and novel adjunctive therapies[18]. Critical outcome metrics should encompass complete ductal clearance rates, sustained pain relief (> 5 years), quality-of-life indices, incidence of endocrine and exocrine insufficiency, procedural complication rates, stone recurrence, and comprehensive cost-benefit analyses. Data from such investigations are essential to establish clear, individualized treatment algorithms[82].

CONCLUSION

The management of PDS has evolved into a patient-centered, multidisciplinary approach. Endoscopic therapy, particularly the combination of ESWL and ERCP, is the primary modality for most main PDS. However, its success depends on stone characteristics and operator expertise, and it may fail in complex cases with strictures or altered anatomy. Surgical intervention remains indicated for refractory stones or when complications such as pseudocysts or suspected malignancy coexist, with parenchyma-sparing procedures (e.g., Frey, Beger) offering sustained pain relief while preserving organ function. Importantly, complete stone clearance does not always guarantee pain resolution, as pain in CP involves neuropathic and central sensitization mechanisms beyond ductal obstruction. Long-term management requires PERT, nutritional support, and strict abstinence from alcohol and tobacco. Future research should focus on improving lithotripsy technology, preventing stone recurrence, understanding pain pathophysiology, and establishing optimal treatment sequences through RCT trials.