Asymptomatic Walled‐Off Pancreatic Necrosis: A Prospective Study of Natural Course and Risk Factors for Intervention

ABSTRACT

Introduction

Walled‐off pancreatic necrosis (WOPN), a complication of acute necrotizing pancreatitis, presents management challenges, especially when asymptomatic. While current guidelines advocate conservative management for asymptomatic WOPN, the natural history of these collections remains unclear. This study aimed to investigate the natural history of asymptomatic WOPN and identify predictors of symptom development or complications necessitating intervention.

Methods

This prospective observational study included consecutive adult patients with asymptomatic WOPN (those tolerating oral nutrition with minimal or no abdominal pain, without infection, pressure symptoms, or GI bleeding) diagnosed via contrast‐enhanced CT or MRI from September 2021 to October 2023. Data on demographics, etiology, imaging findings, and clinical outcomes were collected. Patients were followed for 12 months with monthly assessments for the first 6 months and then every 3 months. MRI abdomen was performed at 6 and 12 months. The primary outcome was the proportion of patients developing symptoms/complications during follow‐up requiring intervention.

Results

Of the 54 patients, 32 (59.2%) developed complications requiring intervention [infection (n = 12), refractory pain (n = 10), obstructive jaundice (n = 2), intracystic hemorrhage (n = 2) and spontaneous rupture (n = 6)]. There was one death (1.9%) secondary to hemorrhage from a splenic artery pseudoaneurysm. Twenty‐two patients (40.7%) remained asymptomatic. Interventions included endoscopic ultrasound‐guided drainage (n = 22), percutaneous drainage (n = 8), and surgical necrosectomy (n = 2). The mean size of WOPN at baseline was significantly higher in patients requiring intervention (9.28 vs. 6.01 cm, p = 0.003). A WOPN size greater than 5.6 cm predicted the need for intervention with 88.5% sensitivity and 54% specificity. Multivariable logistic regression identified WOPN size as an independent predictor of intervention (OR 1.2, p = 0.011).

Conclusion

A significant proportion of patients with asymptomatic WOPN require interventions within 12 months. WOPN size is a key predictor of symptom development and intervention.

Key Summary

• Summarise the established knowledge on this subject

  • ◦Walled‐off pancreatic necrosis (WOPN) is a late complication of acute necrotizing pancreatitis and may persist even after clinical recovery.
  • ◦Current international guidelines recommend conservative management for asymptomatic WOPN, as many collections can remain stable or resolve spontaneously.
  • ◦However, the natural history of asymptomatic WOPN is not well defined, and predictors of progression to symptomatic or complicated disease are poorly understood.
  • ◦Existing evidence is limited to small retrospective series with heterogeneous follow‐up and outcome definitions.

• What are the significant and/or new findings of this study?

  • ◦In this prospective observational study of 54 patients with asymptomatic WOPN, nearly 60% developed symptoms or complications requiring intervention within 1 year.
  • ◦A cut‐off size of > 5.6 cm predicted the need for intervention with 88.5% sensitivity and 54% specificity.
  • ◦WOPN size is a significant predictor of progression to symptomatic disease or need for intervention (OR 1.2, p = 0.011).
  • ◦These findings suggest close monitoring for patients with asymptomatic WOPN exceeding 5–6 cm in size.

1. Introduction

Acute pancreatitis, while often a self‐limiting condition, presents a significant clinical challenge in approximately 20% of cases due to the development of complications such as pancreatic necrosis substantially elevating both morbidity and mortality rates [1]. The revised Atlanta classification introduced the term 'walled‐off pancreatic necrosis' (WOPN) to describe a mature, encapsulated collection of pancreatic and/or peripancreatic necrotic tissue. This collection is characterized by a well‐defined wall and contains liquefied necrosis along with solid tissue fragments [2]. The management of WOPN is contingent on the presence of symptoms. Symptomatic WOPN, typically manifesting as pain, infection, gastric outlet obstruction, or biliary obstruction, necessitates intervention which can be either endoscopic, radiological, surgical drainage procedures or a combination of these procedures, each with its own set of potential complications. Current guidelines strongly advocate for conservative management of asymptomatic necrosis, irrespective of its size or extent [3]. This approach is predicated on the premise that many asymptomatic collections may resolve spontaneously or remain quiescent without causing significant clinical sequelae. However, the data regarding the natural history of these asymptomatic collections remains limited, creating a knowledge gap that impacts clinical decision‐making.

A study by Wronski et al. provided early insights, revealing that nearly half of patients with asymptomatic WOPN could be successfully managed conservatively [4]. Similarly, a single‐center observational study by Rana et al. further supported this observation, demonstrating that a majority of patients with asymptomatic WOPN could be managed conservatively, with only approximately one‐third eventually requiring intervention during follow‐up [5]. However, both these studies were retrospective with potential bias. Despite these findings, the long‐term burden of persistent retroperitoneal necrotic collections can lead to a syndrome of chronic unwellness, characterized by persistent low‐grade symptoms, poor oral intake, and decreased quality of life [6, 7]. This underscores the potential for even asymptomatic collections to negatively impact patient well‐being over time. While current guidelines provide structured recommendations for symptomatic pancreatic necrosis, the optimal management strategy for asymptomatic WOPN remains an area with limited prospective data. Moreover, since intervention in a sterile WOPN can be associated with a significant risk of infection, it is important to predict and stratify those that would require intervention versus those who can be managed conservatively [8]. Therefore, our study aimed to address this critical knowledge gap by systematically investigating the natural history of asymptomatic WOPN. Specifically, we sought to identify clinical or radiological factors that may predict the eventual need for intervention, such as symptom development or complications.

2. Methods

2.1. Study Population and Setting

This was a prospective observational study of consecutive patients from September 2021 till October 2023 presenting to a tertiary care hospital in Western India. The study was conducted as per Institutional ethics committee approval (EC/OA‐34/2019). Informed consent was obtained from all patients being included in the study.

2.1.1. Inclusion and Exclusion Criteria

Consecutive adult patients over the age of 18 years with a diagnosis of acute necrotizing pancreatitis (ANP) based on the revised Atlanta classification with documented evidence of walled off pancreatic necrosis on cross‐sectional imaging were included [2]. The diagnosis of WOPN was made if all the following conditions were met.

1. Documented evidence of ANP earlier with contrast enhanced computed tomography (CECT) documenting pancreatic/peri‐pancreatic necrosis

2. Encapsulated collection with solid necrotic component as depicted by relative hyperdense content within the hypodense collection on CECT or internal heterogeneity on T2 weighted MRI images or echogenic content on EUS. The presence of necrotic debris was confirmed by the presence of echogenic material on trans‐abdominal ultrasound.

Patients presenting with WOPN within 4–6 weeks of an ANP attack were included. Patients were screened for the development of walled‐off pancreatic necrosis (WOPN) at 4–6 weeks after the index attack, either during the same hospitalization (for those with prolonged hospital stay) or during scheduled outpatient follow‐up visits. Patients with a previous severe course of ANP, including those requiring ICU admission or early interventions during the index hospitalization, were not excluded, provided they were asymptomatic at the time WOPN was identified (i.e., no abdominal pain, fever, gastrointestinal obstruction, or sepsis attributable to the collection). Asymptomatic walled‐off pancreatic necrosis (WON) was defined as the presence of a mature (> 4 weeks) encapsulated necrotic collection in patients who did not exhibit symptoms attributable to the collection. Patients were considered asymptomatic if they had no persistent abdominal pain (VAS score ≤ 3/10), no fever or systemic inflammatory response without an alternative source, and no features of gastric outlet obstruction, biliary obstruction, or clinical deterioration related to the collection [2]. Patients with acute necrotizing pancreatitis with an uneventful clinical course without development of WOPN, imaging evidence of chronic pancreatitis, those with malignant mass lesion (solid or cystic) in the pancreas and pregnant women were excluded.

2.2. Etiology of Pancreatitis

The etiology of acute pancreatitis was determined as follows:

1. Alcohol related—If a patient was drinking more than 40 g alcohol per day for > 5 years

2. Idiopathic—If no definite cause of pancreatitis was identified

3. Biliary—Imaging evidence of gallstones or biliary sludge and/or Alanine transferase levels ≥ 150 U/L

4. Others –

   1. Traumatic—If there was a history of definite abdominal trauma followed by acute pancreatitis.

   2. Genetic—Documented mutation in either PRSS1, SPINK1, CFTR or CTRC genes.

   3. Metabolic—If the pancreatitis was caused due to hypertriglyceridemia (serum triglycerides ≥ 1000 mg/dL) or hypercalcemia (serum calcium > 10.5 mg/dL).

   4. Drug induced—If a patient has acute pancreatitis with a temporal association of exposure to a drug implicated in causing pancreatitis [9].

2.3. Definition of Symptoms/Complications Requiring Intervention

1. Infection ‐ clinical and laboratory parameters suggesting sepsis (new‐onset or persistent fever, leukocytosis, or rising CRP) in the absence of any other identifiable source of infection in a patient with WOPN.

2. Refractory pain—Pain as measured by the Visual Analog Scale (VAS) ≥ 3/10.

3. Gastric outlet/biliary obstruction ‐ Extrinsic compression by the WOPN collection resulting in persistent vomiting/inability to tolerate oral intake (Gastric) or a rise in serum bilirubin with dilated bile ducts on imaging (Biliary).

2.4. Intervention and Follow Up

The patients were treated as per the institute's standard management protocol and according to established guidelines for managing acute pancreatitis [3]. After discharge, these patients were followed up monthly for the initial 6 months then every three monthly. On follow up, a detailed clinical assessment was performed. MRI abdomen was done at the end of 6 months, and 12 months follow up. A single radiologist with an experience of over 25 years measured the size of WOPN in three dimensions. The size of WOPN in its longest dimension was measured and recorded. In the event of symptoms or complications (abdominal pain, infected collection, pressure symptoms and/or bleeding into cyst cavity), repeat imaging and appropriate interventions were performed as per standard guidelines. The patients were followed up until spontaneous clinical recovery with resolution of WOPN, need for intervention, mortality and/or till 1 year from recruitment.

2.5. Data Acquisition and Outcome Variables

Demographic details, clinical and data on etiological factors for pancreatitis were noted. Detailed imaging findings including size of WOPN in longest dimension, location and change in size over time were noted. The proportion of patients with asymptomatic WOPN developing symptoms/complications requiring intervention and the nature of intervention was noted.

The primary outcome was the proportion of patients with asymptomatic WOPN developing symptoms/complications that require intervention, which may be endoscopic, percutaneous or surgical drainage. The factors predicting symptoms/complications, time to development of symptoms/complications, adverse events of the intervention, clinical resolution of WOPN and mortality were secondary outcomes.

2.6. Sample Size

This was a prospective observational cohort study, and because asymptomatic WOPN is an uncommon clinical entity, the sample size reflected all consecutive eligible patients presenting during the study period. No formal sample‐size calculation or power analysis was performed, as the primary objective was descriptive—to characterize the natural history and identify potential predictors rather than to test a predefined hypothesis.

2.7. Statistical Analysis

Baseline demographics, clinical characteristics and imaging characteristics were summarized between those managed conservatively and those who required intervention. Continuous variables were expressed as mean ± standard deviation (SD) and categorical variables as percentages. Simple and multiple logistic regression models were used to assess the association between covariates and intervention. Variables included in the final multivariable model were determined using a stepwise selection procedure using significance level (p < 0.05 for entry into the model). Results are presented as odds ratio (OR) and 95% confidence intervals (CI). Predictive accuracy was assessed by area under the receiver operator characteristic curve (AUC). Kaplan‐Meier estimates were plotted for time‐to‐event outcomes (development of symptoms or complications requiring intervention) and the log‐rank test was used to estimate the effect of covariates on outcomes of asymptomatic WOPN. p‐values less than 0.05 were considered statistically significant. Stata version 16.1 (StataCorp) was used for data management and analysis.

3. Results

3.1. Baseline Characteristics

During the study period, 234 patients were admitted with acute necrotizing pancreatitis. Ninety‐three (39.7%) patients developed PFC's of which 58/93 (62.3%) developed acute necrotic collections which were managed conservatively, and 35/93 (37.6%) developed mature WOPN which required intervention. A total of 54 asymptomatic patients with asymptomatic WOPN at baseline (42 male; mean age −37.7 ± 10.2 years) were included in the study and followed up for a period of 12 months. There was no loss to follow up. The etiology of pancreatitis was alcohol in 34 (62.9%), idiopathic in 11 (21.1%), traumatic in 3 (5.77%), gallstones in 2 (3.85%), drug induced in 2 (3.8%), hypertriglyceridemia and PRSS1 mutation in 1 patient each (Figure 1). The median size of the WOPN at baseline in the longest dimension was 7.25 (IQR 4.5–10) cm. The sites of the WOPN were head, body, tail and uncinate processes in 17 (31.4%), 24 (44.4%), 9 (16.6%) and 4 (7.4%), respectively.

FIGURE 1.

Patient inclusion flow‐chart.

3.2. Natural History, Complications and Interventions

Thirty‐two (59.2%) patients developed complications such as infection (n = 12), refractory pain (n = 10), obstructive jaundice (n = 2), and intracystic hemorrhage (n = 2). Spontaneous rupture into the GI tract was seen in 6 (11.1%) patients which required intervention in view of incomplete drainage of the collection. The majority of patients who developed symptoms and/or complications on follow up were successfully treated with EUS guided transmural drainage (n = 22) with fully covered self‐expanding metallic stents or multiple plastic stents. Eight patients were managed with percutaneous drainage alone, whereas two patients required surgical drainage and open necrosectomy. All patients who underwent percutaneous or surgical drainage had signs of infected collection and no access to drain the collection endoscopically. The mean size of WOPN in patients developing symptoms/complications requiring intervention increased from 9.28 ± 3.9 cm at baseline to 12.29 ± 3.5 cm at the time of intervention. Thirteen (40.7%) patients developed signs of infection post drainage. All the cases were managed conservatively. MRI abdomen with MRCP performed after resolution of WOPN demonstrated normal pancreatic duct in 5/32 (15.6%) patients with partial disruption seen in 6 (18.7%) patients. Disconnected pancreatic duct (DPD) was observed in 21/32 (65.6%) patients. In patients with DPD, transmural stents were left in situ with no migration of stents observed at 12 months follow up. Patients with normal pancreatic duct and those with partial disruption who underwent successful transpapillary bridging of the leak remained asymptomatic. There was one mortality secondary to massive bleeding from a splenic artery pseudoaneurysm. The patient was a 34‐year‐old male with a history of recurrent acute pancreatitis secondary to significant alcohol intake, with a WOPN of size 6.2 × 5.1 × 5.8 cm in size, subsequently developed acute onset pain and fever 3 weeks after the diagnosis of WOPN. Imaging was suggestive of hyperdense content within WOPN with a splenic artery pseudoaneurysm of size 2.2 cm. The patient underwent vascular intervention in the form of coiling of the gastroduodenal artery. However, he succumbed to sepsis and multiorgan failure.

Twenty‐two patients (40.7%) of 54 patients did not have any complications during the period of observation of 12 months with WOPN completely resolving in 8 (14.8%) patients. In the remaining 14 patients who did not develop symptoms or complications, the mean size decreased from 7.52 ± 1.3 cm to 3.14 ± 1.9 cm over 12 months. On follow up MRI assessment at 12 months, 2/22 (9.09%) of patients had evidence of dilated MPD. Rest of the patients had a normal pancreatic duct. On comparing patients with and without symptoms/complications versus those without who were managed conservatively, mean size of WOPN on presentation was significantly greater in patients with symptoms/complications requiring intervention (9.28 vs. 6.01 cm, p = 0.003). Table 1 summarizes the baseline findings between those had symptoms/complications versus those who did not. A receiver operating characteristic curve (ROC) for size of WOPN predicting symptoms/complications requiring eventual intervention demonstrated an area under the curve of 0.7081 (95% CI 0.56–0.79) as shown in Figure 2 with size cut‐off of 5.6 cm demonstrating a sensitivity of 88.5% (95% CI 69.8%–97.6%), specificity of 54% (95% CI 27.5%–66.1%), positive predictive value of 60.5% (95% CI 43.4%–76%) and a negative predictive value of 81.2% (54.4%–96%) (Youden Index = 0.420).

TABLE 1.

Comparison of patients with and without symptoms/complications requiring intervention.

Variables	No symptoms/complication (n = 22)	Developed symptoms/complication (n = 32)	p‐value
Age (mean ± SD) years	35.15 ± 11.9	39.19 ± 9.1	0.098
Sex‐males (%)	16 (72.7%)	26 (81.2%)	0.348
Etiology n
• Alcohol	14	20	0.254
• Biliary	1	1	0.982
• Idiopathic	4	7	0.741
• Others	3	4	0.444
Size of WOPN at baseline (mean ± SD) cm	6.01 ± 3.09	9.28 ± 3.92	0.003
Location of WOPN
• Head/uncinate process	5	16	0.022
• Body	11	13	0.361
• Tail	5	4	0.903

Note: Bold values indicate significant p‐values.

FIGURE 2.

Receiver operating characteristic (ROC) curve for size predicting complication requiring intervention (Cut off—5.5 cm; sensitivity‐88.5% & specificity of 46%; youden index = 0.392).

The results of the univariate and multivariate logistic regression analysis (adjusted for baseline CTSI score and etiology) are summarized in Table 2. Size of WOPN on presentation was predictive of development of symptoms/complications requiring intervention in univariate analysis [OR 1.23 (1.04–1.46), p = 0.024] which remained significant in multivariable logistic regression analysis [OR 1.2 (1.01–1.4), p = 0.011]. Bootstrapping with 1000 resamples was performed to assess the robustness of the model (Table 3). Kaplan‐Meier survival analysis was performed to estimate the time to symptoms/complication in patients with asymptomatic walled‐off necrosis (WOPN) (Figure 3). The estimated probability of remaining free from complications decreased over time. The median time to complication was 144 days (95% CI 0.35–0.66). The probability of remaining asymptomatic is 60% at 3 months (95% CI 0.45–0.78) and 46% at 6 months (95% CI 0.31–0.60). The timeline of symptom development is summarized in Table 4. Figure 4 shows Kaplan‐Meier plots to show the effect of size distribution on the probability of remaining symptom/complication free. The size categories were defined as shown in Table 5. Patients with smaller size of WOPN at baseline have the lowest rate of developing symptoms/complications and highest probability of remaining asymptomatic throughout the observation period (χ2 = 12.5, p = 0.0029).

TABLE 2.

Univariate and multivariable analysis of factors predicting symptoms/complications requiring intervention in patients with asymptomatic WOPN.

Predictor	OR (95% CI)	p‐value	Adjusted OR (95% CI)	p‐value
Age	1.04 (0.98–1.1)	0.133
Male sex	0.91 (0.23–3.45)	0.897
Etiology
Alcohol	1.2 (0.16–1.55)	0.23
Idiopathic	1.21 (0.32–4.84)	0.780
Biliary	1.46 (0.18–11.7)	0.721
Others	Reference
Size	1.23 (1.02–1.42)	0.024	1.2 (1.01–1.41)	0.011
CTSI	1.25 (0.94–1.68)	0.121	1.18 (0.79–1.75)	0.399
History of recurrent acute pancreatitis	0.47 (0.11–2.15)	0.336
Location
Head/uncinate process	1.6 (0.3–8.36)	0.535	3.11 (0.36–26.93)	0.302
Body	0.46 (0.08–2.43)	0.366
Tail	Reference

Note: Bold values indicate significant p‐values.

TABLE 3.

Bootstrap for variables in the final multivariable logistic regression model.

Parameter	Observed coefficient	Bootstrap standard error	p‐value	Bias corrected 95% CI
Size	0.044	0.018	0.020	0.007–0.081
CTSI	0.039	0.032	0.152	−0.02–0.103
Location—Head/Uncinate	0.2066	0.223	0.518	−0.63–0.32

Note: Bold values indicate significant p‐values.

FIGURE 3.

Kaplan‐Meier estimates of complications in the entire cohort.

TABLE 4.

Timeline for symptom development in patients with asymptomatic WOPN.

Time from baseline imaging	Number of patients (%)	Type of symptoms
0–3 months	26 (48.15%)	Refractory pain‐8; infection ‐ 12; obstructive jaundice ‐ 2; spontaneous rupture ‐ 2
3–6 months	6 (11.1%)	Refractory pain ‐ 2; spontaneous rupture ‐ 4
6–12 months	0

FIGURE 4.

Kaplan‐Meier estimates and the effect of size on the probability of remaining asymptomatic. The curves represent the probability of patients remaining asymptomatic without the need for drainage over the follow‐up period. Blue line: mean WOPN size 3.7 ± 1.6 cm. Red line: mean WOPN size 7.2 ± 1.1 cm. Green line: mean WOPN size 12.4 ± 2.5 cm. Analysis Time: Days from the initial detection of a mature walled‐off pancreatic necrosis (WOPN).

TABLE 5.

Distribution according to size category.

Category	Number of patients (n)	Size (mean ± SD) cm
1	18	3.7 ± 1.6
2	20	7.2 ± 1.1
3	16	12.4 ± 2.5

4. Discussion

The asymptomatic WOPN is a therapeutic dilemma because of the lack of availability of reliable information about its natural history. In the current study, 40% of patients remained asymptomatic for a follow up period of 12 months with 60% requiring intervention within a median time of 144 days. Size of the WOPN at baseline was predictive of the development of symptoms/complications requiring intervention with a size cut‐off of 5.6 cm demonstrating a sensitivity of 88.5% and specificity of 54%.

Wronski et al. studied 16 patients with asymptomatic WOPN and found that 44% of patients remained asymptomatic during a median follow up of 17 months (range 7–53.5 months) [4]. Rana et al. had previously reported an intervention rate of 23% over 6 months in a short term follow up study using EUS with WOPN resolving in 11%, and completely liquefied in 40% of patients [10]. Patra et al., in a 6‐month longitudinal analysis of 39 patients with walled‐off necrosis, documented either resolution or sustained asymptomatic presentation in 77% of the cohort, with the remaining 23% requiring interventional procedures [11]. Conversely, another study, spanning three months and including seventy‐six patients with walled‐off necrosis, yielded a significantly higher intervention rate of 70% [12]. The authors posited that this observed disparity in the intervention rate could be attributed to the inclusion of a greater proportion of patients exhibiting organ failure and extensive pancreatic necrosis, indicative of a more severe disease phenotype. Current literature states that more than 50% of individuals with asymptomatic walled‐off necrosis experience spontaneous resolution or a decrease in the size of the necrotic collection during follow‐up, thereby lending support to the prevailing clinical paradigm of meticulous surveillance and non‐interventional, expectant management.

In our study 59.2% of patients with WOPN developed complications with infection being the most common. Similar rates have been previously reported in other observational studies [10, 11]. We also found that most of these complications occur in the first 100 days and thereby stress the need for closed and rigorous surveillance in the initial period after the development of asymptomatic WOPN. In line with previous studies, we demonstrated that majority of the complications could be managed endoscopically. It is important to identify this subset of patients as they require close follow up. The high rate of intervention highlights that “asymptomatic” is often a transient state. The development of complications such as infection, refractory pain, and other issues demonstrates the importance of vigilant monitoring. This study emphasizes that the presence of WOPN, even without initial symptoms, indicates a potential for significant morbidity.

Erosion into the adjacent blood vessel leading to massive life‐threatening hemorrhage is the most dreaded complication of expectant management of pancreatic fluid collections. Unfortunately, one patient developed an arterial pseudoaneurysm leading to massive gastrointestinal bleeding and died. However, the rarity of this complication has been highlighted in prior studies [4, 6]. Also, these vascular complications associated with WOPN in most cases can be successfully managed using a combination of angioembolisation and endoscopic drainage.

The current literature on the size of WOPN predicting the development of symptoms/complications is contentious. While Rana et al. demonstrated that size was not different in patients developing complications, a study by Jagielski et al. showed that patients with complications had larger WOPN size (12.19 ± 2.5 cm vs. 9.08 ± 2.5 cm, p < 0.01) [5, 13]. A recent similar study by Kumar et al. of 30 patients with asymptomatic WOPN demonstrated that the mean size of the collection was significantly higher in those who developed infection compared to those who remained asymptomatic on follow up [14]. Results of our study demonstrate a size cut off greater than 5.6 cm predicting risk of complications with high sensitivity, which should prompt close follow up of these patients. Moreover, the greater proportion of patients requiring intervention in our study may be explained by the fact that two‐thirds of our patients had WOPN size of more than 6 cm at presentation.

To the best of our knowledge, this is the only prospective study that evaluated the natural history of asymptomatic WOPN in patients with acute pancreatitis. The strengths of our study were the stringent inclusion criteria and meticulous follow‐up of patients for the development of symptoms. Change in size of collection could also be studied in addition to the development of symptoms. We have reported a cut‐off for risk of complication as 5.6 cm with high sensitivity to have a lower threshold for surveillance in patients. However, our study has some limitations. First, a single center design may limit the generalizability of findings. Second, the definition of asymptomatic relied on patient‐reported symptoms, which may be subject to variability. A more objective assessment of symptom burden could have been beneficial. Third, the lack of a comparison group makes it difficult to assess the need and benefit of early intervention. Fourth, the predominant cause of pancreatitis in our cohort was alcohol (65%) which may not be representative of the general population which limits generalizability of our findings. Fifth, although in our study the presence of solid necrotic debris within the WOPN was noted in imaging reports, detailed quantitative assessment was not performed systematically. Internal necrotic debris is a recognized contributor to symptoms and future studies should incorporate standardized methods of quantifying the necrotic burden to clarify the influence of this factor on the outcome of asymptomatic WOPN. Sixth, due to the small sample size, the study may be underpowered for clearly defining the predictive factors for intervention. Finally, the specificity of our model for predicting intervention is low. This may be due to the lack of objective assessment of symptoms that require intervention leading to heterogeneity in outcomes. However, we have selected a size cut off with sufficiently high sensitivity to warrant close observation in such cases. Moreover, the cut off provides a good screening tool for identifying patients who are at low risk of developing a complication and in such patients, a less intensive surveillance regimen may be followed.

In conclusion, this study contributes valuable data to the ongoing discussion regarding the management of asymptomatic walled‐off necrosis, whereas a notable proportion of patients (40%) remained asymptomatic over a 12‐month period, a significant majority (60%) required intervention, highlighting the dynamic nature of this condition. Our findings, consistent with some but divergent from other published data, emphasize the importance of vigilant surveillance, particularly during the early phase following WOPN development. We propose a selective risk‐based strategy of clinical assessments at 2, 4 and 6 weeks and then monthly for 6 months with imaging assessment at 2 and 6 weeks after initial detection followed by 3 monthly assessement in those with large collection (≥ 5.6 cm). For small stable collections (< 5.6 cm), clinical evaluation every 3 months with imaging is suggested only if symptoms develop or if there is clinical suspicion of progression.

Despite the study's limitations, it provides crucial insights into the natural history of asymptomatic WOPN. Future large‐scale, multicenter prospective studies are warranted to refine management strategies, establish optimal intervention timing, and develop objective criteria for predicting disease progression, ultimately improving patient outcomes in this challenging clinical scenario.

Author Contributions

All authors contributed to the study conception and design. Study conceptualization and visualization were done by Sidharth Harindranath, Sridhar Sundaram and Akash Shukla. Material preparation, data collection and analysis were performed by Sidharth Harindranath and Sridhar Sundaram. The first draft of the manuscript was written by Sidharth Harindranath and was critically reviewed by Sridhar Sundaram and Akash Shukla. All authors have read and approved the final manuscript.

Funding

The authors have nothing to report.

Ethics Statement

This study was approved by the institutional ethical review committee EC/OA‐34/2019. Human ethics: This study has been carried out in compliance with the Helsinki Declaration of 1975, as revised in 2008.

Consent

All subjects have provided informed consent prior to participating in this study. The subject details included in the study are anonymised and give consent for publication.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

Access to the dataset will be provided with reasonable request to the corresponding author.