Between step-up and upfront intervention: Risk stratification as the missing link in timing endoscopic necrosectomy

Abstract

The management of walled-off pancreatic necrosis has shifted from surgical debridement to minimally invasive, step-up endoscopic strategies. While lumen-apposing metal stents enable effective drainage in many patients, a substantial proportion still requires direct endoscopic necrosectomy, where the optimal timing of intervention remains debated. Rather than a strict early-vs-delayed paradigm, timing increasingly reflects individualized clinical judgment. The study recently published by Lone et al highlights that clinical, biochemical, and radiologic factors, including necrosis extent, systemic inflammation, nutritional status, and anatomical complexity, can predict failure of passive drainage and the need for direct endoscopic necrosectomy. These findings support a risk-based approach in which patient stratification guides selective upfront or accelerated intervention. Risk stratification thus emerges as the missing link between waiting and acting, enabling more precise and personalized timing of necrosectomy in walled-off pancreatic necrosis management.

Key Words: Walled-off necrosis; Endoscopic necrosectomy; Risk stratification; Endoscopic step-up approach; Passive drainage failure; Personalized intervention

Core Tip: This article highlights the importance of the recently published study by Lone et al, which identifies key clinical, biochemical, and imaging predictors of passive drainage failure in patients with walled-off pancreatic necrosis. By demonstrating that factors such as necrosis extent, persistent inflammation, and poor nutritional reserve can predict the need for direct endoscopic necrosectomy, the study shifts the focus from a time-based step-up protocol toward a risk-based, individualized approach. These findings underscore that in walled-off pancreatic necrosis management, the key question is not when to intervene, but in whom waiting may be riskier than acting.

INTRODUCTION

Although walled-off pancreatic necrosis (WON) is classically framed as a single clinical entity, its behavior is anything but uniform. Some patients stabilize after a single step of transmural drainage, while others deteriorate despite apparently adequate decompression, ultimately requiring direct endoscopic necrosectomy (DEN)[1]. The revised Atlanta classification describes WON as an encapsulated, mature collection developing after 4 weeks, yet this temporal definition does not guarantee clinical stability, homogeneity, or predictability of disease trajectory[2]. Indeed, it is increasingly acknowledged that biological maturity often precedes or lags behind radiologic maturity, suggesting that timing cannot rely solely on chronological thresholds. The traditional assumption that most cases will improve with passive drainage using lumen-apposing metal stents has been challenged by studies indicating that up to one-third of patients develop persistent sepsis, organ dysfunction, or limited cavity collapse despite adequate drainage[1,3]. In this setting, timing is not merely chronological; it is clinical, driven by factors such as persistent sepsis, systemic inflammatory response, organ dysfunction, necrosis burden and failure of cavity collapse despite adequate drainage. The controversy between a sequential step-up strategy and an upfront interventional approach is not about when, but about for whom. Therefore, risk stratification may represent the missing link between waiting and acting, transforming timing into a tailored decision rather than a protocol-driven deadline.

SHIFTING THE FOCUS FROM TEMPORAL THRESHOLDS TO RISK IDENTIFICATION

In this context, the study by Lone et al[4] provides valuable insight into how clinical, laboratory, and imaging variables may help disentangle this decision-making dilemma. Their work reinforces the concept that not all patients are suitable for step-up management; some will benefit from delayed intervention, while others require earlier necrosectomy to prevent progression of sepsis and organ dysfunction. By identifying necrosis extent, systemic inflammatory response syndrome (SIRS), fever, hypoalbuminemia, anemia, and specific anatomical patterns of WON as predictors of the need for necrosectomy, their analysis highlights the importance of early recognition of patients who are unlikely to achieve resolution through drainage alone. Moreover, the excellent discriminative performance of the multivariate predictive model (area under the curve of 0.892) underscores the potential for an integrated, risk-based approach rather than a purely chronological or procedural one. These findings are aligned with previous reports that necrosis burden (> 30%-40%), persistent SIRS, and poor host reserve strongly correlate with drainage failure and need for DEN[5-7]. The concept of “passive drainage failure” has been characterized as a scenario marked by large solid debris, limited collapse of the cavity, and persistent systemic inflammation despite adequate stent placement[8], all markers that Lone et al[4] confirmed as predictive of escalation to DEN.

Rather than confirming the superiority of early or delayed DEN, the study by Lone et al[4] shifts the focus toward selecting the right patients, those in whom postponing intervention may not only delay recovery but also increase morbidity.

STEP-UP VS UPFRONT NECROSECTOMY: THE QUESTION IS NOT WHEN, BUT FOR WHOM

The fundamental limitation of time-based intervention strategies is that they treat all patients with WON as pathophysiologically equivalent. However, WON follows divergent trajectories; some collections liquefy rapidly and respond well to drainage, while others remain highly viscous, compartmentalized, and resistant to collapse even after adequate decompression. For these cases, persistent sepsis or organ dysfunction may signal delayed rescue rather than premature intervention.

As recommended by the European Society of Gastrointestinal Endoscopy[9] and the International Association of Pancreatology/American Pancreatic Association[10] guidelines, the traditional step-up paradigm has undoubtedly improved safety by minimizing unnecessary interventions. However, its universal application may overlook those individuals in whom persistent inflammatory response, extensive necrosis, extra-pancreatic extension, or poor nutritional reserve signal a low likelihood of spontaneous resolution. In such patients, risk escalates not with intervention, but with inaction.

Conversely, though conceptually appealing in high-risk cases, upfront DEN may expose others to over treatment, procedural burden, or avoidable complications[11]. Therefore, the question is not whether step-up or upfront is superior, but which patients are likely to benefit from selective acceleration rather than procedural escalation. European Society of Gastrointestinal Endoscopy guidelines already recognize that persistent sepsis, compartmentalized collections, gastric or biliary obstruction, or failure of cavity collapse despite adequate stent placement represent scenarios where necrosectomy should not be delayed[9,12].

Thus, step-up and upfront interventions should not be considered competing strategies but complementary options with a risk-stratified framework. In this landscape, stratification becomes more than a prognostic exercise; it becomes the clinical compass that guides when waiting becomes riskier than acting.

SAFETY CONSIDERATIONS: BALANCING INTERVENTION AND RISKS

Safety remains a central concern when considering escalation from drainage to DEN. Although DEN is highly effective in achieving cavity resolution, it is also among the most technically demanding and complication-prone procedures in therapeutic endoscopy. Reported adverse events include bleeding, perforation, stent occlusion, infection exacerbation, air embolism, and venous or arterial erosion, with overall complication rates ranging from 15% to 30% in most series[9,13,14]. Bleeding remains the most challenging complication, particularly when necrosis is adherent to major vascular structures or when enzymatic inflammation contributes to vessel wall fragility. Excessive debridement, early intervention in poorly liquefied collections, or use of aggressive instruments may further increase these risks without providing proportional clinical benefit.

However, deferring necrosectomy in patients with persistent infection, evolving SIRS, or high necrotic burden is not necessarily the safer strategy. Prolonged ineffective drainage may contribute to delayed sepsis control, sustained organ failure, fistula formation, and prolonged hospitalization or malnutrition, while also increasing the likelihood that necrosectomy eventually becomes technically more challenging[12,15]. This clinical scenario - termed “passive drainage failure” - is increasingly recognized as a distinct phenotype in which intervention is not premature but rather necessary.

In this context, safety is neither achieved by simply delaying necrosectomy nor by pursuing early intervention but by recognizing when non-intervention becomes riskier than intervention. This requires weighing the procedural risks of DEN, in addition to the clinical risks of prolonged ineffective drainage.

FUTURE DIRECTIONS: PREDICTIVE MODELS AND PERSONALIZED CHRONOLOGY

Looking ahead, the integration of stratification tools into real-world practice may redefine how timing decisions are made in WON management. Rather than relying on single-parameter triggers, composite models combining clinical, biochemical, and radiological indicators, such as necrosis burden, inflammatory markers, and nutritional status, could help identify those patients at highest risk of drainage failure and need for DEN[5,6]. Recent work by Lone et al[4] illustrates the potential of such multifactorial approaches, which outperform isolated variables by capturing the complex interplay between disease severity, host response, and procedural feasibility.

The future may lie in algorithm-driven, preprocedural decision frameworks - similar to those emerging in oncologic surgery, sepsis management, and inflammatory bowel disease care - where timing is individualized not by convention but by risk signature[9]. Artificial intelligence and machine learning may further enhance these algorithms by incorporating longitudinal data, radiomics, and computed necrosis quantification to refine timing decisions[16,17]. Ultimately, personalized timing may help transition from “when to intervene” to “when it is dangerous not to intervene”.

CONCLUSION

The evolving debate between step-up and upfront intervention in WON reflects a broader shift in interventional gastroenterology, from protocol-driven to risk-guided decision-making. Rather than viewing timing as a fixed interval after symptom onset or stent placement, it should be regarded as a dynamic clinical judgment shaped by individual risk trajectories. As the study by Lone et al[4] suggests, decisions regarding necrosectomy may be better informed by stratifying patients based on necrosis extent, inflammatory profile, and overall resilience, rather than simply following time-based milestones. Ultimately, timing is not about how long we wait, but about how much risk waiting carries. When waiting becomes riskier than acting, intervention ceases to be premature; it becomes personalized.