Elsevier

The Lancet

Volume 391, Issue 10115, 6–12 January 2018, Pages 51-58
The Lancet

Articles
Endoscopic or surgical step-up approach for infected necrotising pancreatitis: a multicentre randomised trial

https://doi.org/10.1016/S0140-6736(17)32404-2Get rights and content

Summary

Background

Infected necrotising pancreatitis is a potentially lethal disease and an indication for invasive intervention. The surgical step-up approach is the standard treatment. A promising alternative is the endoscopic step-up approach. We compared both approaches to see whether the endoscopic step-up approach was superior to the surgical step-up approach in terms of clinical and economic outcomes.

Methods

In this multicentre, randomised, superiority trial, we recruited adult patients with infected necrotising pancreatitis and an indication for invasive intervention from 19 hospitals in the Netherlands. Patients were randomly assigned to either the endoscopic or the surgical step-up approach. The endoscopic approach consisted of endoscopic ultrasound-guided transluminal drainage followed, if necessary, by endoscopic necrosectomy. The surgical approach consisted of percutaneous catheter drainage followed, if necessary, by video-assisted retroperitoneal debridement. The primary endpoint was a composite of major complications or death during 6-month follow-up. Analyses were by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN09186711.

Findings

Between Sept 20, 2011, and Jan 29, 2015, we screened 418 patients with pancreatic or extrapancreatic necrosis, of which 98 patients were enrolled and randomly assigned to the endoscopic step-up approach (n=51) or the surgical step-up approach (n=47). The primary endpoint occurred in 22 (43%) of 51 patients in the endoscopy group and in 21 (45%) of 47 patients in the surgery group (risk ratio [RR] 0·97, 95% CI 0·62–1·51; p=0·88). Mortality did not differ between groups (nine [18%] patients in the endoscopy group vs six [13%] patients in the surgery group; RR 1·38, 95% CI 0·53–3·59, p=0·50), nor did any of the major complications included in the primary endpoint.

Interpretation

In patients with infected necrotising pancreatitis, the endoscopic step-up approach was not superior to the surgical step-up approach in reducing major complications or death. The rate of pancreatic fistulas and length of hospital stay were lower in the endoscopy group. The outcome of this trial will probably result in a shift to the endoscopic step-up approach as treatment preference.

Funding

The Dutch Digestive Disease Foundation, Fonds NutsOhra, and the Netherlands Organization for Health Research and Development.

Introduction

Acute pancreatitis is a potentially lethal disease with increasing incidence. Approximately 10–20% of patients develop necrosis of pancreatic parenchyma or extrapancreatic tissues.1, 2 Moreover, about one third of these patients develop infection of the necrotic tissue, which generally requires an invasive intervention.3

In the past 10 years, the surgical step-up approach, consisting of percutaneous catheter drainage followed, if necessary, by minimally invasive necrosectomy, has replaced open surgery as the standard treatment.4, 5 A randomised trial of the surgical step-up approach versus primary open necrosectomy showed that catheter drainage as a first step obviates the need for necrosectomy in 35–50% of patients.4, 6

An endoscopic step-up approach is a potentially less invasive alternative. Endoscopic necrosectomy has shown promising results in reducing complications in several observational studies and one small pilot randomised trial.7, 8 These favourable results were explained by the absence of general anaesthesia and surgical exploration with a reduction of surgical stress and surgery-associated complications such as pancreatic fistulas. The endoscopic approach can also be performed in a step-up fashion, starting with endoscopic transluminal drainage, only to be followed by endoscopic necrosectomy if drainage does not result in clinical improvement.

We did a multicentre randomised trial to investigate whether the endoscopic step-up approach is superior to the surgical step-up approach in patients with infected necrotising pancreatitis.

Research in context

Evidence before this study

Before the start of our trial, we did an extensive literature search using PubMed, Embase, and the Cochrane Library database for studies published between Jan 1, 1980, and Dec 31, 2010. We used the search terms “necrosectomy” and “pancreatitis”. We included only studies with patients with infected necrosis or symptomatic sterile necrosis, published in English. Studies needed to report the results of patients with infected necrosis separately, as well as mortality and complications. We excluded cohorts with fewer than five patients and studies of patients with chronic pancreatitis. We identified one small pilot trial, 13 cohort studies, and two systematic reviews. The pilot trial of 20 patients compared an endoscopic necrosectomy with a surgical necrosectomy in patients with infected necrosis. This trial was not designed or powered for differences in clinically relevant outcomes but the results suggested a reduced pro-inflammatory response and development of new-onset organ failure after endoscopic necrosectomy. Furthermore, this pilot trial did not incorporate the step-up approaches because it only included patients in whom catheter drainage had failed and subsequently required necrosectomy. The other studies had numerous limitations (ie, small number of patients, retrospective study design, no fixed treatment algorithms, and included patients with sterile necrosis) but they all showed promising results in favour of endoscopic necrosectomy by indirect comparison with surgical necrosectomy. The pilot trial showed significant results by direct comparison.

Added value of this study

To our knowledge, our study is the first high-quality trial to compare an endoscopic step-up approach with the current reference standard of a surgical step-up approach in patients with infected necrosis. Our results are the first to provide level 1 evidence for a reduction in hospital stay and pancreatic fistulas in favour of the endoscopic step-up approach.

Implications of all the available evidence

On the basis of the results of this study, we expect that guidelines will shift from minimally invasive surgery towards endoscopic treatment. Furthermore, treatment of infected necrosis should always take a step-up approach, with endoscopic drainage as the first step. In conclusion, an endoscopic step-up approach reduces pancreatic fistula, length of hospital stay, and costs without any evidence for impaired safety; therefore, this approach should be considered the strategy of choice in patients with infected necrosis.

Section snippets

Study design and participants

In this multicentre, randomised, superiority trial, we recruited adult (≥18 years of age) patients from seven university medical centres and 12 teaching hospitals of the Dutch Pancreatitis Study Group with a high suspicion or evidence of infection of pancreatic or extrapancreatic necrotic tissues (ie, infected necrosis) with an indication for invasive intervention, for whom both the endoscopic and surgical step-up approach were deemed feasible by a multidisciplinary expert panel. We defined

Results

Between Sept 20, 2011, and Jan 29, 2015, 418 patients with pancreatic or extrapancreatic necrosis in 19 Dutch hospitals were screened, of which 98 were eligible (figure). 51 patients were randomly assigned to the endoscopic step-up approach and 47 to the surgical step-up approach. In each treatment group, one patient did not undergo any intervention because of spontaneous clinical improvement shortly after randomisation. In two other patients in the endoscopy group, owing to the technical

Discussion

This randomised superiority trial showed that the endoscopic step-up approach was not superior to the surgical step-up approach in reduction of major complications or death in patients with infected necrosis. However, our results showed a benefit in secondary endpoints of endoscopic treatment.

Our results are not in line with a previous small randomised controlled trial,7 a systematic review,8 and observational studies24, 25 suggesting clinical superiority of endoscopy. Several possible

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