Advertisement

Current Treatment Options in Gastroenterology

, Volume 16, Issue 3, pp 333–344 | Cite as

Endoscopic Management of Infected Necrotizing Pancreatitis: an Evidence-Based Approach

  • Lotte Boxhoorn
  • Paul Fockens
  • Marc G. Besselink
  • Marco J. Bruno
  • Jeanin E. van Hooft
  • Robert C. Verdonk
  • Rogier P. VoermansEmail author
  • on behalf of the Dutch Pancreatitis Study Group
Open Access
Endoscopy (P Siersema, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Endoscopy

Abstract

Purpose of Review

Endoscopic management of infected necrotizing pancreatitis has evolved rapidly over the past years and there have been interesting innovations in this field. This review provides an update on the most recently published literature regarding endoscopic management of infected necrotizing pancreatitis.

Recent Findings

A recent randomized trial demonstrated no difference in mortality and major morbidity between endoscopic and surgical step-up treatment of infected necrotizing pancreatitis. However, endoscopic therapy resulted in shorter hospital stay and less pancreatic fistulas. Various innovations have been investigated with the aim to further optimize endoscopic therapy, in particular lumen-apposing metal stents. While major stent-related complications were also reported, findings from recent studies indicated that their use was associated with higher resolution rates of walled-off necrosis compared to double-pigtail stents. Other innovations, such as the multiple gateway technique and dual-modality mode, can be considered for treatment of particular cases. Furthermore, research suggests that irrigation of walled-off necrosis can be performed by using a nasocystic tube and discontinuation of proton-pump inhibitors may be considered.

Summary

Endoscopic treatment should be the preferred treatment modality in patients with infected necrotizing pancreatitis who are eligible for endoscopic drainage. Although data suggests that lumen-apposing metal stents are superior to double-pigtail stents, prospective multicenter studies focusing on safety as well as long-term follow-up are first needed.

Keywords

Endoscopic drainage Endoscopic necrosectomy Infected necrotizing pancreatitis Walled-off necrosis Lumen-apposing metal stent 

Abbreviations

CECT

Contrast-enhanced computed tomography

DEN

Direct endoscopic necrosectomy

DMD

Dual-modality drainage

DPDS

Disconnected pancreatic duct syndrome

DPS

Double-pigtail stents

DPSG

Dutch Pancreatitis Study Group

ERCP

Endoscopic retrograde cholangiopancreatography

EUS

Endoscopic ultrasound

FC-SEMS

Fully covered self-expandable metal stents

FNA

Fine-needle aspiration

H2O2

Hydrogen peroxide

LAMS

Lumen-apposing metal stents

MTGT

Multiple gateway technique

MRCP

Magnetic resonance cholangiopancreatography

PFCs

Pancreatic fluid collections

PPIs

Proton-pump inhibitors

RCT

Randomized controlled trial

VAC

Vacuum-assisted closure system

WON

Walled-off necrosis

Introduction

Acute pancreatitis is the most common gastrointestinal diagnosis requiring hospital admission [1]. Most patients experience a mild clinical course and can be managed with fluid resuscitation and pain control. Approximately 20% of patients develop a severe pancreatitis with necrosis of the (peri)pancreatic tissue [2].

In the majority of cases, (peri)pancreatic necrosis remains sterile and can be treated conservatively. However, about 30% of patients develop infected (peri)pancreatic necrosis [3]. This can be diagnosed by the presence of gas in the necrotic collection on abdominal imaging, a positive culture of a fine-needle aspiration (FNA) or clinical signs of infection (e.g., clinical deterioration despite supportive treatment, fever, increasing inflammatory markers, and/or positive blood cultures) [4].

Infected (peri)pancreatic necrosis is associated with high morbidity and mortality and requires intervention in the majority of cases [5, 6••]. Current guidelines advocate to delay intervention until the necrotic tissue has become walled-off (WON) [7]. It is important to underline that WON is a different entity than a pseudocyst. Especially in older literature, the term pseudocyst is used for WON as well as for real pseudocysts. Per definition, pseudocysts do not contain necrosis and therefore require a different approach. Definitions of pancreatic fluids collections (PFCs) are clearly described in the revised Atlanta classification [8].

The introduction of minimally invasive endoscopic, radiologic, and surgical modalities led to a considerable reduction in morbidity and mortality in comparison with traditional open surgery [9]. The first successful endoscopic drainage of WON was described in 1996 [10]. Subsequently, endoscopic ultrasound (EUS) was integrated, increasing technical success and the safety of the procedure [11, 12].

Endoscopic management of infected necrotizing pancreatitis has evolved rapidly ever since. This review provides an overview of most recently published evidence and innovations in this field.

Evidence for endoscopic management of infected necrotizing pancreatitis

Over the last two decades, there has been a shift in the management of infected necrotizing pancreatitis towards less invasive approaches. Originally, primary open necrosectomy was performed at an early stage of disease, but was associated with high mortality rates [13]. In the past 10 years, minimally invasive surgical treatment within a “step-up” framework showed to reduce mortality and has replaced open surgery as the standard treatment [5].

The step-up approach can also be performed endoscopically. The findings from two randomized controlled trials by the Dutch Pancreatitis Study Group (DPSG) suggest that the endoscopic step-up approach is a potentially less invasive alternative to surgery.

The PENGUIN trial was the first randomized controlled trial (RCT) comparing endoscopic necrosectomy to surgical necrosectomy in 22 patients with infected WON [14]. Findings of the study demonstrated that endoscopic necrosectomy significantly reduced the inflammatory response and the occurrence of new-onset multiorgan failure (0 vs. 50%, P = 0.03).

Subsequently, the TENSION trial was initiated, which compared the endoscopic step-approach with the surgical step-up approach in patients with infected necrotizing pancreatitis [6••]. This trial showed no difference in mortality and major morbidity between both approaches (43% in endoscopic arm vs. 45% in surgical arm, P = 0.88). However, the endoscopic approach resulted in shorter hospital stay (mean 53 vs. 69 days, P = 0.014) and less pancreatic fistulas (5 vs. 32%, P = 0.0011). The endoscopic step-up approach was also superior to the surgical step-up approach in terms of (in)direct medical costs, which was likely due to the shorter length of hospital stay for endoscopically treated patients.

In conclusion, these findings suggest that endoscopic treatment should be the preferred treatment modality in patients for whom the infected WON can be reached transluminally.

Recent innovations in endoscopic drainage of infected necrotizing pancreatitis

Endoscopic management of infected necrotizing pancreatitis has evolved rapidly over the past years and there have been interesting innovations in this field (Table 1).
Table 1

Recent innovations regarding endoscopic management of WON

 

Innovation

Available evidence

Level of evidence*

Endoscopic drainage

• Lumen-apposing metal stents

Systematic review of case-controlled studies/cohort studies

2a-3a

• Multiple transluminal gateway technique

Case series

4

• Dual-modality mode

Case series

4

Endoscopic necrosectomy

• Hydrogen peroxide

Case series

Prospective open label study

4

• Nasocystic irrigation

Case series

4

• Discontinuation of proton-pump inhibitors

Case series

4

• Endoscopic vacuum-assisted closure system

Case reports

4

*Grading according to the Oxford Levels of Evidence

Metal stents

Metal stents were proposed as an alternative to the traditionally used double-pigtail stents (DPS) for endoscopic drainage of WON. DPS are limited by a small lumen (7 French) that may result in inadequate drainage. A larger diameter of metal stents would permit spontaneous passage of necrotic tissue into the stomach, improving the success rate of endoscopic drainage.

Although originally designed for biliary strictures, fully covered self-expandable metal stents (FC-SEMS) were the first metal stents assigned for endoscopic drainage. Several case series have described success rates ranging between 80 and 100% when FC-SEMS were used for the endoscopic drainage of WON [15, 16, 17, 18]. However, high rates of stent migration were also reported (15%) [19].

Lumen-apposing metal stents (LAMS) were designed in order to decrease the risk of stent migration. The stents have a saddle-shaped design with anchoring flanges and were originally applied to prevent leakage between the walls of both collections and the stomach (Fig. 1). Its large diameter also permits the spontaneous passage of necrotic tissue into the stomach, which may reduce the need for necrosectomy. LAMS also provide, if necessary, an easy entry port for endoscopic necrosectomy.
Fig. 1

Overview of the available lumen-apposing metal stents

Over 30 retrospective case series, four prospective cohort studies and one interim analysis of a RCT evaluated the efficacy of LAMS for drainage of PFCs (Table 2). A recent review evaluated the endoscopic drainage of WON using DPS versus metal stents from published studies between 1990 and 2016 [20••]. The authors included 41studies, mainly retrospective and non-comparative studies, regarding the use of DPS and metal stents (total of 2213 patients). Only five of the studies included in the meta-analysis compared DPS directly to metal stents (note that the authors excluded four studies due to low total number of patients and disproportion of DPS versus metal stents) [21••, 22•, 23, 24, 25]. Overall, resolution of WON was more likely to occur when using LAMS (91.5%) compared to DPS (80.9%) (OR 2.5, 95% CI 1.4–4.3, P = 0.001). No difference was found in the resolution of WON after the initial endoscopic procedure with LAMS (52.3%) compared to DPS (43.4%) (OR 1.4, 95% CI 0.56–3.6, P = 0.4).
Table 2

Prospective studies about the use of LAMS in the management of WON

Author

Study design

WON (N)

LAMS

Stent removal

Follow-up

Adverse events

Dhir et al. (2017)

Prospective study

Single center

88

NAGI™ stent

Median 3.5 weeks (range 3–17 weeks)

Median 22 months (range 3–46 months)

Mild*

• Post-ERCP pancreatitis following ERCP and ductal stenting (N = 3)

• Stent migration (N = 2)

Moderate*

• Bleeding (N = 1)

Severe*

• Bleeding (N = 2)

• Abscess that required surgery (N = 2)

Fatal*

• Death (cause unknown) (N = 1)

Bang et al. (2016)

Randomized controlled trial

Single center

21

Hot AXIOS™ stent (ø 15 mm)

(Ongoing trial)

(Ongoing trial)

• Bleeding (N = 3)

• Buried LAMS syndrome (N = 2)

• Biliary stricture (N = 1)

Gornals et al. (2016)

Prospective study

Single center

13

AXIOS™/Hot AXIOS™ stent (ø 10 or 15 mm)

Mean 9 ± 3.4 weeks (range 4–16)

Mean 13.3 ± 11.4 months (range 2–36)

Moderate*

• Migration/infection (N = 1)a

• Occlusion/infection (N = 1)b

Severe*

• Bleeding (N = 2)

Walter et al. (2015)

Prospective study

Multicenter

46

AXIOS™ stent (ø 10 or 15 mm)

Median 32 days (range 2–178)

NR

• Infection/occlusion (N = 4)

• Perforation (N = 1)

Shah et al. (2015)

Prospective study

Multicenter

11

AXIOS™ stent (ø 10 or 15 mm)

NR

NR

• Partial occlusion resulting in stent removal (N = 1)

• Dislodgement during DEN resulting in precut and surgical debridement (N = 1)

• Fever with prolonged hospitalization (N = 1)

• Abdominal pain requiring endoscopy (N = 1)

DEN direct endoscopic necrosectomy, ERCP endoscopic retrograde cholangio-pancreatography, LAMS lumen-apposing metal stents

*Grading according to the American Society for Gastrointestinal Endoscopy Lexicon criteria

a Treated with antibiotics and placement of a new LAMS

b Treated with antibiotics and placement of a double pigtail through the AXIOS stent

To date, there are conflicting literature reports with respect to the safety of LAMS in WON drainage. The aforementioned meta-analytical review indicated that the use of LAMS (in the non-comparable studies) was associated with lower bleeding (6.2 vs. 12.6%, P = 0.007) and lower stent occlusion (7.5 versus 17.4%, P = 0.015) [20••]. However, the results of an ongoing randomized controlled trial about endoscopic drainage of WON with LAMS versus DPS have raised concerns [21••]. Stent-related adverse events were observed in 6 of the 12 patients randomized to LAMS: major bleeding (N = 3), buried stent syndrome (N = 2), and biliary stricture (N = 1) were reported [21••]. Interestingly, all adverse events occurred within 6 weeks after stent placement. As a result, the authors changed the study protocol by performing imaging 3 weeks after stent placement in order to remove the LAMS as soon as the necrotic collection was collapsed. These findings suggest that the risk of stent-related adverse events may be related to the timing of LAMS removal. Yet, current literature provides no consensus about the appropriate timing of LAMS retrieval: an interval ranging from 3.5 to 10 weeks after the initial drainage procedure has been described [21••, 26, 27, 28]. Currently, the ESGE guidelines recommend to remove the LAMS after a maximum of 4 weeks [29••]. In order to minimize the risks of bleeding and migration, it has also been suggested to place an additional DPS through the lumen of the LAMS. A single-center retrospective was conducted to compare LAMS alone (N = 21) versus the combination of LAMS and DPS (N = 20) and showed that adverse events were significantly higher in the LAMS group compared to the LAMS combined with DPS group (43 versus 10%, P = 0.04) [30].

Endoscopic drainage with LAMS may be restricted by its high costs. To date, high-quality methodologic studies comparing the cost-effectiveness of the different stents used for endoscopic drainage are lacking. In a recent study from the USA, the costs of endoscopic drainage with LAMS per patient were higher compared to DPS ($20,029 vs. $15,941) [31]. However, more patients achieved successful endoscopic drainage of WON with LAMS (92 vs. 84%). For this reason, the authors described that the incremental cost-effectiveness ratio favored drainage with LAMS.

In contrast, the theoretical benefit of LAMS is not present in the endoscopic drainage of pancreatic pseudocysts. A meta-analysis showed no difference in decrease in PFC size and/or resolution of symptoms between patients with pseudocysts treated with DPS (85%, 95% CI 81–89%) or with metal stents (83%, 95% CI 74–89%) [32]. Although randomized trials are lacking, DPS should be preferred over LAMS when draining pseudocysts given their excellent safety profile and the possibility to leave DPS in for longer periods of time.

To summarize, endoscopic drainage with LAMS seems to result in higher resolution rates of WON when compared with DPS. Therefore, LAMS should be considered in patients with infected WON who are eligible for endoscopic drainage. Nonetheless, the best available evidence originates from only a few prospective studies. Moreover, important questions regarding the safety of LAMS are still unanswered. The current recommendation to remove LAMS after a maximum of 4 weeks is also not based on high-quality evidence [29••]. The suggestion that the placement of DPS within LAMS would minimize the risk of adverse events should be further looked into, although it theoretically conflicts with the proposed drainage advantages associated with the large diameter of LAMS. If a necrotic collection is not fully collapsed, LAMS should be exchanged for DPS, but this may not be easy or even possible in all patients. Finally, it is unclear whether LAMS are cost-effective. In conclusion, these concerns need to be addressed by future multicenter prospective studies before LAMS can be advised for routine use.

We have recently initiated a prospective multicenter clinical study investigating the use of LAMS (Hot AXIOS™) in the management of infected WON (AXIOMA study, NTR7056). With this study, we aim to evaluate the treatment outcomes and safety of LAMS. Furthermore, AXIOMA will test the hypothesis that the use of LAMS is more cost-effective by reducing the need of additional necrosectomies.

Other approaches to optimize endoscopic drainage

Besides the administration of large diameter metal stents, optimization of endoscopic drainage may be achieved by the creation of multiple transluminal tracts into the WON cavity, also called the “multiple transluminal gateway technique” (MTGT).

Three retrospective case series compared MTGT to conventional drainage techniques for the treatment of WON [33, 34, 35]. In total, 39 of 204 patients (19%) were treated with MTGT. MTGT was applied in patients who responded inadequately to the initial endoscopic drainage procedure and in case WON exceeded ≥ 12 cm [33, 35]. A maximum of three transluminal tracts were created. Treatment success between 92 and 100% was reported in patients receiving MTGT compared to 52–70% receiving conventional drainage techniques. One disadvantage of MTGT was a significantly longer median procedural duration in comparison with the conventional drainage technique (37 vs. 22 min, P = 0.017) [35]. However, the introduction of a LAMS allowed a more rapid creation of multiple transluminal tracts (< 10 min) [36].

Transluminal drainage can be combined with percutaneous drainage in particular cases of WON extending to the paracolic gutters. This is also referred to as “dual-modality drainage” (DMD).

Five retrospective studies, which were all initiated in the same hospital, reported on the DMD technique [37, 38, 39, 40, 41]. One of the studies was comparative and described 49 patients that completed DMD versus 45 patients that were only drained percutaneously [37]. It showed that the DMD technique was associated with a shorter length of hospitalization compared to percutaneously draining only (mean 24 vs. 54 days, P < 0.002). Additionally, DMD-treated patients required less drains (1.3 vs. 1.9, P < 0.001). Lastly, a lower number of endoscopic procedures (1.9 vs. 2.7, P < 0.02) and CT scans (7.8 vs. 14.0, P < 0.001) were needed. In another retrospective study, a total of 117 patients underwent DMD for either infected WON (N = 55) or symptomatic sterile WON (N = 62) [38]. Interestingly, none of the 103 patients that completed treatment (88%) needed an additional (surgical) necrosectomy. Furthermore, not a single patient developed a pancreaticocutaneous fistula after treatment with the DMD technique.

In conclusion, evidence suggests that MTGT and DMD are potentially effective approaches for the optimization of endoscopic drainage of WON. Although, these findings were obtained in retrospective studies only and further prospective studies are needed. Therefore, MTGT should only be considered in selected cases of patients who not respond well on the initial endoscopic drainage procedure or in the case of in large WON. Additional percutaneous drainage can be initiated if WON extends to the paracolic gutters.

Recent innovations in endoscopic necrosectomy techniques

Endoscopic necrosectomy remains to be a challenging and time-consuming procedure, especially due to the lack of dedicated endoscopic devices and a standardized approach. Yet, several innovations have been explored in order to simplify the debridement of necrotic tissue.

Hydrogen peroxide

One of the reported innovations is the use of hydrogen peroxide (H2O2) for the irrigation of WON. H2O2 decomposes into water and oxygen when combining with organic tissue and is therefore thought to facilitate the removal of necrotic debris.

Four retrospective studies and one prospective open label study reported on the use of H2O2 for the debridement of WON [42, 43, 44, 45, 46]. A total of 108 patients underwent endoscopic drainage of WON followed by H2O2 irrigation. Drainage was performed with DPS, FC-SEMS, and LAMS. The reported number of required necrosectomy procedures ranged from 1 to 3. Resolution of WON occurred in 79 to 100% of patients.

Based on this limited set of data, there is currently no supportive evidence to recommend H2O2 in the treatment of WON. Moreover, its safety is questionable because several case series reported that its use may be related to embolic events [47, 48, 49, 50, 51, 52]. In conclusion, irrigation with H2O2 is currently not advised.

Nasocystic irrigation

Irrigation of WON can also be performed by the placement of a nasocystic tube. The tube can be inserted next to DPS or through a deployed metal stent.

To date, prospective studies assessing the duration, type, or volume of irrigation with a nasocystic tube are lacking. In a retrospective comparative study, patients treated with a nasocystic tube reported a decrease in symptoms after 1 month in combination with a minimum of 30% decrease in WON size on imaging (85 vs. 63%, P = 0.03). Furthermore, the addition of a nasocystic tube to placed DPS decreased stent occlusion rates as compared to using the stent alone (13 vs. 33%, P = 0.03) [53].

It is not clear whether irrigation with a nasocystic tube offers any advantages when combined with a LAMS. In a large multicenter retrospective study, 22 of 68 patients with WON were drained via a LAMS with the addition of a nasocystic tube. In this study, there was not a difference in WON resolution in patients drained with or without nasocystic tube (90.9 vs. 95.6%, P = 0.59) [54].

Although data on the irrigation with a nasocystic tube is scarce, its use can be recommended when a significant amount of necrosis is present in the necrotic collection.

Discontinuation of proton-pump inhibitors

The role of gastric acid in the chemical debridement of necrotic tissue has been investigated as well. It is thought that the low pH of gastric acid facilitates the liquefaction of necrosis and prevents bacterial overgrowth. Because proton-pump inhibitors (PPIs) cause a long-lasting reduction of stomach acid production, they could have negative effects on the resolution of WON.

So far, only two studies have focused on the role of PPI and WON resolution [55, 56]. A retrospective multicenter study investigating patients with WON showed that more necrosectomy procedures were required to achieve WON resolution in patients using PPIs (N = 136) in comparison with those (N = 136) who did not use PPIs (median number of procedures of 4.6 vs. 3.2, respectively) [56]. Another retrospective study of 71 patients (54 PPI users and 17 non PPI users) reported a similar trend (mean endoscopic procedures 2 vs. 1.4) [55].

Although this limited set of studies is insufficient to strongly recommend the discontinuation of PPIs in all endoscopically treated patients with WON, this can be considered in particular cases in which there is no strong indication to continue their use.

Endoscopic vacuum-assisted closure system

Vacuum-assisted closure (VAC) is an established treatment method for wounds. The negative pressure of a vacuum-sealed sponge results via several mechanisms into wound closure. Endoscopic vacuum-assisted closure (EVAC) is increasingly being conducted as a new method to repair upper gastrointestinal defects [57]. EVAC might be an effective addition to endoscopic necrosectomy if established endoscopic treatment options have failed.

However, only four case reports described the use of a transluminally placed vacuum-assisted closure system in the management of WON [58, 59, 60, 61]. Moreover, its potential benefits may be limited because the system should often be exchanged, resulting in an added number of endoscopic interventions. Consequently, it is unsure whether EVAC will offer any advantages for the management of WON. Future studies should determine the efficacy of EVAC and address safety endpoints such as the risk of a pancreatic or intestinal fistula.

The role of endoscopy in disconnected pancreatic duct syndrome

Disconnected pancreatic duct syndrome (DPDS) is an important but often overlooked complication in patients with acute necrotizing pancreatitis. Disruption of the main pancreatic duct due to necrosis may cause extraductal leakage of pancreatic fluid, resulting pancreatic fistulas, pseudocysts, ascites, and pleural effusion [62].

Several modalities, such as endoscopic retrograde cholangiopancreatography (ERCP), contrast-enhanced computed tomography (CECT), and magnetic resonance cholangiopancreatography (MRCP), have been conducted in order to diagnose DPDS [63, 64]. To date, it remains unclear which modality visualizes a disrupted pancreatic duct most accurately and should be preferred. The role of EUS was researched in a recent prospective observational study [65]. EUS was used to identify duct disruption in 21 patients during the initial EUS-guided drainage of WON. In all patients, EUS demonstrated the termination of the upstream pancreatic parenchyma and duct into the necrotic collection, thereby suggesting the presence of a duct disruption. These findings were afterwards confirmed by follow-up CECT (100%), ERCP (81%), EUS-pancreatogram (14%), and surgical pathology (5%).

Pancreatic duct disruption and associated fluid collections can be treated surgically, percutaneously, or endoscopically. Currently, endoscopic therapy has become increasingly important in the management of DPSD, especially when a PFC is present.

The current accepted endoscopic strategy for DPDS and associated PFCs (both WON and pseudocysts) is to perform endoscopic drainage with long-term indwelling DPS [29••]. A randomized controlled trial that showed that recurrence of PFCs was less likely if the transmural stents were left in situ (0 vs. 38%, P = 0.013) [66]. Another more recent retrospective study also suggested that recurrence of fluid collections was significantly lower in patients with long-term indwelling transmural stents (0 vs. 21%, P = 0.02) [33].

In contrast, literature is divergent regarding the benefits of transpapillary drainage of DPDS. Theoretically, stenting of the PD across the site of the disruption may direct the pancreatic flow preferentially into the duodenum [67]. A meta-analysis showed that the combination of transmural drainage and transpapillary drainage did not have additional benefit in recurrence of PFCs (OR 1.49, 95% CI 0.53–4.21, P = 0.45) or complications (OR 1.15, 95% 0.61–2.18, P = 0.67) [68]. Thus, combining transluminal drainage with routine stenting of the pancreatic duct is not recommended [29••].

In conclusion, DPDS is a serious complication of acute necrotizing pancreatitis and is characterized by the discontinuity of the main pancreatic duct. Long-term indwelling of transluminal DPS is recommended after transluminal WON drainage in case of a proven disconnected pancreatic duct [29••]. Consequently, metal stents should be replaced by DPS in patients with DPDS after approximately 4 weeks. EUS findings of Bang et al. suggest that a disrupted duct may be recognized at the time of initial EUS-guided drainage of WON [65]. In that case, endoscopists should consider transluminal drainage with DPS instead of a metal stent. The combination of transluminal drainage with routine stenting of the pancreatic duct is not recommended [29••].

Conclusion

Over the past decade, endoscopic management of infected necrotizing pancreatitis has evolved rapidly. A recent randomized trial demonstrated no difference in mortality and major morbidity between endoscopic and surgical management step-up approach for infected necrotizing pancreatitis [6••]. Nonetheless, endoscopic therapy resulted in shorter hospital stay and less pancreatic fistulas and should therefore be the preferred treatment modality.

Secondly, there is some evidence that the use of LAMS is superior to the use of DPS for endoscopic drainage of WON. Yet, this needs to be confirmed by multicenter prospective studies, considering the reported safety issues on LAMS. Currently, it is recommended to retrieve LAMS after a maximum of 4 weeks in order to prevent stent-related complications [29••]. In case of a clear disconnected pancreatic duct, DPS should be preferred over LAMS, because DPS can be left in situ permanently. The use of LAMS is also not recommended for the drainage of pancreatic pseudocysts.

MTGT should be considered in patients who do not response well on initial drainage or in case of large WON. If WON extends to the paracolic gutter, the DMD approach can be initiated. Research suggests that irrigation of WON can be performed by using a nasocystic tube and the discontinuation of proton-pump inhibitors should be taken into consideration. To date, there is insufficient evidence that H2O2 and EVAC should be applied in the endoscopic management of WON.

Notes

Compliance with Ethical Standards

Conflict of Interest

Rogier Voermans reports grants as a consultant for Boston Scientific. Paul Fockens reports grants from Boston Scientific and personal fees from Cook, Ethicon Endosurgery, Fujifilm, Medtronic and Olympus, outside the submitted work. Marco Bruno reports grants industry and investigator initiated studies from Boston Scientific, Cook Medical, Pentax, and 3M; and personal fees from Boston Scientific, Cook Medical, Pentax, 3M outside the submitted work. Jeanin van Hooft reports grants from Cook Medical and Mylan and consultancy fees from Boston Scientific and Metronics, outside the submitted work. Robert Verdonk, Lotte Boxhoom, Marc Besselink declare no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Peery AF, Dellon ES, Lund J, Crockett SD, McGowan CE, Bulsiewicz WJ, et al. Burden of gastrointestinal disease in the United States: 2012 update. Gastroenterology. 2012;143(5):1179–1187.e3.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Banks PA, Freeman ML. Practice guidelines in acute pancreatitis. Am J Gastroenterol. 2006;92(13):2379–400.CrossRefGoogle Scholar
  3. 3.
    Van Santvoort HC, Bakker OJ, Bollen TL, Besselink MG, Ahmed Ali U, Schrijver AM, et al. A conservative and minimally invasive approach to necrotizing pancreatitis improves outcome. Gastroenterology. 2011;141(4):1254–63.CrossRefPubMedGoogle Scholar
  4. 4.
    Van Grinsven J, Van Santvoort HC, Boermeester MA, Dejong CH, Van Eijck CH, Fockens P, et al. Timing of catheter drainage in infected necrotizing pancreatitis. Nat Rev Gastroenterol Hepatol. 2016;13(5):306–12.CrossRefPubMedGoogle Scholar
  5. 5.
    van Santvoort HC, Besselink MG, Bakker OJ, Hofker HS, Boermeester M. a, Dejong CH, et al. A step-up approach or open necrosectomy for necrotizing pancreatitis. N Engl J Med. 2010;362(16):1491–502.CrossRefPubMedGoogle Scholar
  6. 6.
    •• van Brunschot S, van Grinsven J, van Santvoort HC, Bakker OJ, Besselink MG, Boermeester MA, et al. Endoscopic or surgical step-up approach for infected necrotising pancreatitis: a multicentre randomised trial. Lancet. 2017;6736(17):1–8. RCT comparing endoscopic versus surgical step-up management of infected necrotizing pancreatitis.Google Scholar
  7. 7.
    Working Group IAP/APA acute pancreatitis guidelines. IAP/APA evidence-based guidelines for the management of acute pancreatitis. Pancreatology. 2013;13:e1–15.CrossRefGoogle Scholar
  8. 8.
    Banks PA, Bollen TL, Dervenis C, Gooszen HG, Johnson CD, Sarr MG, et al. Classification of acute pancreatitis—2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013;62(1):102–11.CrossRefPubMedGoogle Scholar
  9. 9.
    van Brunschot S, Hollemans RA, Bakker OJ, Besselink MG, Baron TH, Beger HG, et al. Minimally invasive and endoscopic versus open necrosectomy for necrotising pancreatitis: a pooled analysis of individual data for 1980 patients. Gut. 2017;67:697–706.PubMedGoogle Scholar
  10. 10.
    Baron TH, Thaggard WG, Morgan DE, Stanley RJ. Endoscopic therapy for organized pancreatic necrosis. Gastroenterology. 1996;111(3):755–64.CrossRefPubMedGoogle Scholar
  11. 11.
    Park DH, Lee SS, Moon SH, Choi SY, Jung SW, Seo DW, et al. Endoscopic ultrasound-guided versus conventional transmural drainage for pancreatic pseudocysts: a prospective randomized trial. Endoscopy. 2009;41(10):842–8.CrossRefPubMedGoogle Scholar
  12. 12.
    Varadarajulu S, Christein JD, Tamhane A, Drelichman ER, Wilcox CM. Prospective randomized trial comparing EUS and EGD for transmural drainage of pancreatic pseudocysts (with videos). Gastrointest Endosc. 2008;68(6):1102–11.CrossRefPubMedGoogle Scholar
  13. 13.
    Rodriguez JR, Razo AO, Targarona J, Thayer SP, Rattner DW, Warshaw AL, et al. Debridement and closed packing for sterile or infected necrotizing pancreatitis: insights into indications and outcomes in 167 patients. Ann Surg. 2008;247(2):294–9.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Bakker OJ, van Santvoort HC, van Brunschot S, Geskus RB, Besselink MG, Bollen TL, et al. Endoscopic transgastric vs surgical necrosectomy for infected necrotizing pancreatitis. JAMA. 2012;307(10):1053.CrossRefPubMedGoogle Scholar
  15. 15.
    Vazquez-Sequeiros E, Baron TH, Pérez-Miranda M, Sánchez-Yagüe A, Gornals J, Gonzalez-Huix F, et al. Evaluation of the short- and long-term effectiveness and safety of fully covered self-expandable metal stents for drainage of pancreatic fluid collections: results of a Spanish nationwide registry. Gastrointest Endosc. 2016;84(3):450–7.CrossRefPubMedGoogle Scholar
  16. 16.
    Belle S, Collet P, Post S, Kaehler G. Temporary cystogastrostomy with self-expanding metallic stents for pancreatic necrosis. Endoscopy. 2010;42(6):493–5.CrossRefPubMedGoogle Scholar
  17. 17.
    Smith IB, Gutierrez JP, Ramesh J, Wilcox CM, Mönkemüller KE. Endoscopic extra-cavitary drainage of pancreatic necrosis with fully covered self-expanding metal stents (fcSEMS) and staged lavage with a high-flow water jet system. Endosc Int Open. 2015;3(2):E154–60.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Raijman I, Tarnasky PR, Patel S, Fishman DS, Surapaneni SN, Rosenkranz L, et al. Endoscopic drainage of pancreatic fluid collections using a fully covered expandable metal stent with antimigratory fins. Endosc Ultrasound. 2015;4(3):213–8.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Penn DE, Draganov PV, Wagh MS, Forsmark CE, Gupte AR, Chauhan SS. Prospective evaluation of the use of fully covered self-expanding metal stents for EUS-guided transmural drainage of pancreatic pseudocysts. Gastrointest Endosc. 2012;76(3):679–84.CrossRefPubMedGoogle Scholar
  20. 20.
    •• Bazerbachi F, Sawas T, Vargas EJ, Prokop LJ, Chari ST, Gleeson FC, et al. Metal stents versus plastic stents for the management of pancreatic walled-off necrosis: a systematic review and meta-analysis. Gastrointest Endosc. 2018;87(1):30–42. Systematic review and meta-analysis comparing the use of metal versus plastics stents for the management of WON.CrossRefPubMedGoogle Scholar
  21. 21.
    •• Bang JY, Hasan M, Navaneethan U, Hawes R, Varadarajulu S. Lumen-apposing metal stents (LAMS) for pancreatic fluid collection (PFC) drainage: may not be business as usual. Gut. 2016;66(12):2054–6. RCT investigating the use of LAMS for the EUS-guided drainage of WON.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.•
    Abu Dayyeh BK, Mukewar S, Majumder S, Zaghlol R, Vargas Valls EJ, Bazerbachi F, et al. Large-caliber metal stents versus plastic stents for the management of pancreatic walled-off necrosis. Gastrointest Endosc. 2016; Retrospective study comparing LAMS, FC-SEMS and DPS in the endoscopic management of WON.Google Scholar
  23. 23.
    Mukai S, Itoi T, Baron TH, Sofuni A, Itokawa F, Kurihara T, et al. Endoscopic ultrasound-guided placement of plastic vs. biflanged metal stents for therapy of walled-off necrosis: a retrospective single-center series. Endoscopy. 2015;47(1):47–55.PubMedGoogle Scholar
  24. 24.
    Siddiqui AA, Kowalski TE, Loren DE, Khalid A, Soomro A, Mazhar SM, et al. Fully covered self-expanding metal stents versus lumen-apposing fully covered self-expanding metal stent versus plastic stents for endoscopic drainage of pancreatic walled-off necrosis: clinical outcomes and success. Gastrointest Endosc. 2017;85(4):758–65.CrossRefPubMedGoogle Scholar
  25. 25.
    Bapaye A, Dubale NA, Sheth KA, Bapaye J, Ramesh J, Gadhikar H, et al. Endoscopic ultrasonography-guided transmural drainage of walled-off pancreatic necrosis: comparison between a specially designed fully covered bi-flanged metal stent and multiple plastic stents. Dig Endosc. 2017;29(1):104–10.CrossRefPubMedGoogle Scholar
  26. 26.
    Dhir V, Adler DG, Dalal A, Aherrao N, Shah R, Maydeo A, et al. Early removal of biflanged metal stents in the management of pancreatic walled-off necrosis: a prospective study. Endoscopy. 2017.Google Scholar
  27. 27.
    Walter D, Will U, Sanchez-Yague A, Brenke D, Hampe J, Wollny H, et al. A novel lumen-apposing metal stent for endoscopic ultrasound-guided drainage of pancreatic fluid collections: a prospective cohort study. Endoscopy. 2015;47(1):63–7.PubMedGoogle Scholar
  28. 28.
    Gornals JB, Consiglieri C, Vida F, Loras C. Endoscopic ultrasound-guided pancreaticogastrostomy using a lumen-apposing metal stents plus a double-pigtail plastic stent. Endoscopy. 2016;48:276–7.CrossRefGoogle Scholar
  29. 29.
    •• Arvanitakis M, Dumonceau J-M, Albert J, Badaoui A, Bali MA, Barthet M, et al. Endoscopic management of acute necrotizing pancreatitis: European Society of Gastrointestinal Endoscopy (ESGE) evidence-based multidisciplinary guidelines. Endoscopy. 2018;50: 524–46. Endoscopic management of acute necrotizing pancreatitis: European Society of Gastrointestinal Endoscopy (ESGE) evidence-based multidisciplinary guidelines.Google Scholar
  30. 30.
    Puga M, Consiglieri CF, Busquets J, Pallarès N, Secanella L, Peláez N, et al. Safety of lumen-apposing stent with or without coaxial plastic stent for endoscopic ultrasound-guided drainage of pancreatic fluid collections: a retrospective study. Endoscopy. 2018.Google Scholar
  31. 31.
    Chen Y-I, Barkun AN, Adam V, Bai G, Singh VK, Bukhari M, et al. Cost-effectiveness analysis comparing lumen-apposing metal stents with plastic stents in the management of pancreatic walled-off necrosis. Gastrointest Endosc. 2018.Google Scholar
  32. 32.
    Bang JY, Hawes R, Bartolucci A, Varadarajulu S. Efficacy of metal and plastic stents for transmural drainage of pancreatic fluid collections: a systematic review. Dig Endosc. 2015;27(4):486–98.CrossRefPubMedGoogle Scholar
  33. 33.
    Bang JY, Wilcox CM, Trevino J, Ramesh J, Peter S, Hasan M, et al. Factors impacting treatment outcomes in the endoscopic management of walled-off pancreatic necrosis. J Gastroenterol Hepatol. 2013;28(11):1725–32.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Mukai S, Itoi T, Sofuni A, Itokawa F, Kurihara T, Tsuchiya T, et al. Novel single transluminal gateway transcystic multiple drainages after EUS-guided drainage for complicated multilocular walled-off necrosis (with videos). Gastrointest Endosc. 2014;79(3):531–5.CrossRefPubMedGoogle Scholar
  35. 35.
    Varadarajulu S, Phadnis MA, Christein JD, Wilcox CM. Multiple transluminal gateway technique for EUS-guided drainage of symptomatic walled-off pancreatic necrosis. YMGE. 2011;74(1):74–80.Google Scholar
  36. 36.
    Bang JY, Varadarajulu S. Management of walled-off necrosis using the multiple transluminal gateway technique with the Hot AXIOS System. 2016;2016.Google Scholar
  37. 37.
    Gluck M, Ross A, Irani S, Lin O, Gan SI, Fotoohi M, et al. Dual modality drainage for symptomatic walled-off pancreatic necrosis reduces length of hospitalization, radiological procedures, and number of endoscopies compared to standard percutaneous drainage. J Gastrointest Surg. 2012;16(2):248–57.CrossRefPubMedGoogle Scholar
  38. 38.
    Ross AS, Irani S, Gan SI, Rocha F, Siegal J, Fotoohi M, et al. Dual-modality drainage of infected and symptomatic walled-off pancreatic necrosis: long-term clinical outcomes. Gastrointest Endosc. 2014;79:929–35.CrossRefPubMedGoogle Scholar
  39. 39.
    Ross A, Gluck M, Irani S, Hauptmann E, Fotoohi M, Siegal J, et al. Combined endoscopic and percutaneous drainage of organized pancreatic necrosis. Gastrointest Endosc. 2010;71(1):79–84.CrossRefPubMedGoogle Scholar
  40. 40.
    Sahar N, Kozarek R, Kanji ZS, Ross AS, Gluck M, Gan SI, et al. Do lumen-apposing metal stents (LAMS) improve treatment outcomes of walled-off pancreatic necrosis over plastic stents using dual-modality drainage? Endosc Int Open. 2017;5(11):E1052–9.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Gluck M, Ross A, Irani S, Lin O, Hauptmann E, Siegal J, et al. Endoscopic and percutaneous drainage of symptomatic walled-off pancreatic necrosis reduces hospital stay and radiographic resources. Clin Gastroenterol Hepatol. 2010;8(12):1083–8.CrossRefPubMedGoogle Scholar
  42. 42.
    Abdelhafez M, Elnegouly M, Hasab Allah MS, Elshazli M, Mikhail HMS, Yosry A. Transluminal retroperitoneal endoscopic necrosectomy with the use of hydrogen peroxide and without external irrigation: a novel approach for the treatment of walled-off pancreatic necrosis. Surg Endosc. 2013;27(10):3911–20.CrossRefPubMedGoogle Scholar
  43. 43.
    Bansal RK, Puri R, Choudhray NS, Bhatia S, Patel N, Patle SK, et al. Endoscopic pancreatic necrosectomy: why scuff when you can flush the muck—make it an easy row to hoe. Endosc Int Open. 2017;5:847–53.CrossRefGoogle Scholar
  44. 44.
    Parra V, Kedia P, Zerbo S, Sharaiha RZ, Kahaleh M. Drainage of infected pancreatic necrosis by using 2 lumen-apposing metal stents, a nasocystic drain, and hydrogen peroxide. Gastrointest Endosc. 2015;81(5):1261.CrossRefPubMedGoogle Scholar
  45. 45.
    Othman MO, Elhanafi S, Saadi M, Yu C, Davis BR. Extended cystogastrostomy with hydrogen peroxide irrigation facilitates endoscopic pancreatic necrosectomy. Diagn Ther Endosc. 2017;2017:1–5.CrossRefGoogle Scholar
  46. 46.
    Siddiqui AA, Easler J, Strongin A, Slivka A, Kowalski TE, Muddana V, et al. Hydrogen peroxide-assisted endoscopic necrosectomy for walled-off pancreatic necrosis: a dual center pilot experience. Dig Dis Sci. 2014;59(3):687–90.CrossRefPubMedGoogle Scholar
  47. 47.
    Beattie C, Harry LE, Hamilton SA, Burke D. Cardiac arrest following hydrogen peroxide irrigation of a breast wound. J Plast Reconstr Aesthetic Surg. 2010;63(3):e253–4.CrossRefGoogle Scholar
  48. 48.
    Huang C, Pik J. Tension pneumocephalus and oxygen emboli from hydrogen peroxide irrigation. J Clin Neurosci. 2014;21(2):323–5.CrossRefPubMedGoogle Scholar
  49. 49.
    Benali ZEA, Abdedaim H, Omari D. Massive gas embolism secondary in the use of intraoperative hydrogen peroxide: still use to lavage with this liquid? Pan Afr Med J. 2013;16:124.PubMedCentralGoogle Scholar
  50. 50.
    Patankar PS, Joshi SS, Choudhari KA. Air-embolism and cerebral ischaemia following epidural hydrogen peroxide irrigation in a closed lumbar cavity. Br J Neurosurg. 2014;28(4):556–8.CrossRefPubMedGoogle Scholar
  51. 51.
    Zhang J, Zhang C, Yan J. Massive cerebral gas embolism under discectomy due to hydrogen peroxide irrigation. Case Rep Neurol Med. 2015;2015(Iv):1–4.Google Scholar
  52. 52.
    Yang Y, Reid C, Nambiar M, Penn D. Hydrogen peroxide in orthopaedic surgery—is it worth the risk? Acta Chir Belg. 2016;116(4):247–50.CrossRefPubMedGoogle Scholar
  53. 53.
    Siddiqui AA, Dewitt JM, Strongin A, Singh H, Jordan S, Loren DE, et al. Outcomes of EUS-guided drainage of debris-containing pancreatic pseudocysts by using combined endoprosthesis and a nasocystic drain. Gastrointest Endosc. 2013;78(4):589–95.CrossRefPubMedGoogle Scholar
  54. 54.
    Siddiqui AA, Adler DG, Nieto J, Shah JN, Binmoeller KF, Kane S, et al. EUS-guided drainage of peripancreatic fluid collections and necrosis by using a novel lumen-apposing stent: a large retrospective, multicenter U.S. experience (with videos). Gastrointest Endosc. 2016;83(4):699–707.CrossRefPubMedGoogle Scholar
  55. 55.
    Cosgrove N, Taunk P, Siddiqui AA, Loren DE, Kowalski TE. Discontinuation of PPIs reduces the number of endoscopic procedures required for resolution of walled-off pancreatic necrosis. Gastrointest Endosc. 2016;83:AB279.CrossRefGoogle Scholar
  56. 56.
    Sharaiha RZ, Yang G, Javia A, Edirisuriya C, Noor A, Mumtaz T, et al. Discontinuation of PPIS reduces the number of endoscopic procedures required for resolution of walled-off pancreatic necrosis. Gastrointest Endosc. 2017;85(5):AB100.CrossRefGoogle Scholar
  57. 57.
    Kuehn F, Loske G, Schiffmann L, Gock M, Klar E. Endoscopic vacuum therapy for various defects of the upper gastrointestinal tract. Surg Endosc. 2017;31(9):3449–58.CrossRefPubMedGoogle Scholar
  58. 58.
    Wedemeyer J, Kubicka S, Lankisch TO, Wirth T, Patecki M, Hiss M, et al. Transgastrically placed endoscopic vacuum-assisted closure system as an addition to transgastric necrosectomy in necrotizing pancreatitis (with video). Gastrointest Endosc. 2012;76(6):1238–41.CrossRefPubMedGoogle Scholar
  59. 59.
    Loske G, Schorsch T, Gobrecht O, Martens E, Rucktäschel F. Transgastric endoscopic vacuum therapy with a new open-pore film drainage device in a case of infective pancreatic necrosis. Endoscopy. 2016;48:E148–9.CrossRefPubMedGoogle Scholar
  60. 60.
    Wallstabe I, Tiedemann A, Schiefke I. Endoscopic vacuum-assisted therapy of infected pancreatic pseudocyst using a coated sponge. Endoscopy. 2012;44:49–50.CrossRefGoogle Scholar
  61. 61.
    Wallstabe I, Tiedemann A, Schiefke I. Endoscopic vacuum-assisted therapy of an infected pancreatic pseudocyst. Endoscopy. 2011;43:E312–3.CrossRefPubMedGoogle Scholar
  62. 62.
    Lawrence C, Howell DA, Stefan AM, Conklin DE, Lukens FJ, Martin RF, et al. Disconnected pancreatic tail syndrome: potential for endoscopic therapy and results of long-term follow-up. Gastrointest Endosc. 2008;67(4):673–9.CrossRefPubMedGoogle Scholar
  63. 63.
    Arvanitakis M, Delhaye M, De Maertelaere V, Bali M, Winant C, Coppens E, et al. Computed tomography and magnetic resonance imaging in the assessment of acute pancreatitis. Gastroenterology. 2004;126(3):715–23.CrossRefPubMedGoogle Scholar
  64. 64.
    Drake LM, Anis M, Lawrence C. Accuracy of magnetic resonance cholangiopancreatography in identifying pancreatic duct disruption. J Clin Gastroenterol. 2012;46(8):696–9.CrossRefPubMedGoogle Scholar
  65. 65.
    Bang JY, Navaneethan U, Hasan MK, Hawes RH, Varadarajulu S. EUS correlates of disconnected pancreatic duct syndrome in walled-off necrosis. Endosc Int Open. 2016;4(8):E883–9.CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Arvanitakis M, Delhaye M, Bali MA, Matos C, De Maertelaer V, Le Moine O, et al. Pancreatic-fluid collections: a randomized controlled trial regarding stent removal after endoscopic transmural drainage. Gastrointest Endosc. 2007;65(4):609–19.CrossRefPubMedGoogle Scholar
  67. 67.
    Yang D, Amin S, Gonzalez S, Mullady D, Hasak S, Gaddam S, et al. Transpapillary drainage has no added benefit on treatment outcomes in patients undergoing EUS-guided transmural drainage of pancreatic pseudocysts: a large multicenter study. Gastrointest Endosc. 2016;83(4):720–9.CrossRefPubMedGoogle Scholar
  68. 68.
    Amin S, Yang D, Lucas AL, Gonzalez S, Dimaio CJ. 208 no advantage to pancreatic duct stenting when performing transmural endoscopic drainage of pancreatic fluid collections: a meta-analysis and review of the literature. Gastrointest Endosc. 2015;81(5):AB123.CrossRefGoogle Scholar

Copyright information

© The Author(s) 2018

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Authors and Affiliations

  • Lotte Boxhoorn
    • 1
  • Paul Fockens
    • 1
  • Marc G. Besselink
    • 2
  • Marco J. Bruno
    • 3
  • Jeanin E. van Hooft
    • 1
  • Robert C. Verdonk
    • 4
  • Rogier P. Voermans
    • 1
    Email author
  • on behalf of the Dutch Pancreatitis Study Group
  1. 1.Department of Gastroenterology & Hepatology, Amsterdam Gastroenterology and MetabolismAmsterdam UMC, University of AmsterdamAmsterdamthe Netherlands
  2. 2.Department of Surgery, Amsterdam Gastroenterology and MetabolismAmsterdam UMC, University of AmsterdamAmsterdamthe Netherlands
  3. 3.Department of Gastroenterology & HepatologyErasmus MC University Medical CenterRotterdamthe Netherlands
  4. 4.Department of Gastroenterology & HepatologySt. Antonius HospitalNieuwegeinthe Netherlands

Personalised recommendations