Comparing Upfront Endoscopic Necrosectomy to the Standard Step-Up Endoscopic Approach to Necrotizing Pancreatitis - Article Summary

Summary Author: Shreya Shetty

Brief Summary:

Acute pancreatitis is a common disease that exists on a spectrum, ranging from mild limited episodes managed by supportive care to severe infected necrotizing pancreatitis, which carries a mortality rate of up to 39%. Infected necrosis of the pancreas often requires an interventional procedure. The PANTER trial established the current standard: a “step-up” approach that progresses from conservative treatment to open necrosectomy. This strategy, in use for over a decade, aims to control the infection prior to attempting to remove infected tissue, which minimizes surgical trauma in critically ill patients who are poor surgical candidates. However, this current treatment plan has not considered recent advances in endoscopic surgery which may achieve the same end goal without multiple reinterventions and prolonged hospital stays. The DESTIN trial addresses this possibility by comparing upfront endoscopic necrosectomy to the traditional step-up approach.

Study Design:

The DESTIN trial is a randomized controlled study that enrolled 70 adult patients with infected pancreatic necrosis involving at least 33% of the organ, as confirmed by MRI and CT. Conducted across six hospitals in the U.S. and India, the trial included patients whose necrotic collections were amenable to endoscopic drainage. All patients received standard intravenous antibiotics in addition to procedural interventions. The standard step-up group underwent transgastric or transduodenal metal stent placement for drainage. If there was no clinical improvement, further drainage or endoscopic necrosectomy was performed. The upfront necrosectomy group received immediate endoscopic necrosectomy following metal stent placement. Additional necrosectomies were performed if clinical improvement was inadequate.

Findings:

Primary endpoint = total number of reinterventions required to achieve treatment success, defined as complete symptom relief during admission and disease resolution on CT at 6 months

Secondary endpoints = clinical improvement at 72 hours after index intervention, technical success of procedures, adverse events and hospital readmissions related to disease or procedure, length of hospital stay, development of pancreatic insufficiency, and treatment costs

The upfront necrosectomy group (n = 37, 34 reinterventions) required significantly fewer reinterventions than the step-up group (n = 33, 82 reinterventions), even after adjusting for confounders such as patient demographics and extent of necrosis. Upfront necrosectomy was associated with significantly higher clinical improvement at 72 hours after index intervention, shorter hospital stays, and fewer procedure-related and disease-related adverse effects. Mortality and complication rates were not significantly different between groups.

Limitations:

• The inclusion criteria selected patients who were optimal candidates for endoscopic surgery, limiting generalizability. Unstable patients or those unsuitable for endoscopy may not benefit similarly.

• Enrolled patients had extensive necrosis that likely would not respond to conservative management or minimally invasive drainage alone, biasing results towards early necrosectomy.

• Clinical improvement was defined using more liberal criteria (e.g. resolution of sepsis by SIRS criteria, resolution of organ failure, 25% or greater decrease in the necrotic collection on imaging) compared to prior studies including the PANTER trial.

• Data were pooled from one hospital in India and five in the U.S. Although the investigators attempted protocol standardization, they did not address potential variations in clinical practice and they did not perform subgroup analysis to compare differences by country. 

Conclusions:

Despite certain limitations, the DESTIN trial presents a strong argument for considering upfront endoscopic necrosectomy in clinically stable patients with extensive infected pancreatic necrosis. This approach may reduce the number of necessary reinterventions, accelerate recovery, and shorten hospital stays. Future studies with broader patient populations and standardized international protocols are warranted to validate these findings and refine patient selection criteria.

Main Takeaway

Preliminary evidence suggests that upfront necrosectomy is associated with a significantly lower likelihood of reintervention than the standard step-up approach in stable patients with severe necrotizing pancreatitis that are candidates for endoscopic surgery.

References:

Ji Y, Bang JY, Samarasam I, et al. Upfront endoscopic necrosectomy or step-up endoscopic approach for infected necrotising pancreatitis (DESTIN): a single-blinded, multicentre, randomised trial. Lancet Gastroenterol Hepatol. 2023;8(12): 1062-1071. doi:10.1016/S2468-1253(23)00331-X.

Pavlek G, Romic I, Kekez D, et al. Step-up versus open approach in the treatment of acute necrotizing pancreatitis: a case-matched analysis of clinical outcomes and long-term pancreatic sufficiency. J Clin Med. 2024;13(13): 3766. doi:10.3390/jcm13133766.

Valentin, C., Le Cosquer, G., Tuyeras, G. et al. Step-up approach for the treatment of infected necrotising pancreatitis: real life data from a single-centre experience with long-term follow-up. BMC Gastroenterolgy, 213 (2024). https://doi.org/10.1186/s12876-024-03289-6. 

van Santvoort HC, Besselink MG, Bakker OJ, et al. A step-up approach or open necrosectomy for necrotizing pancreatitis. N Engl J Med. 2010;362(16): 1491-1502. doi:10.1056/NEJMoa0908821.