CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2012;10:12021207

Endotherapy for Organized Pancreatic Necrosis: Perspectives After 20 Years

TODD H. BARON* and RICHARD A. KOZAREK

*Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota; and Digestive Disease Institute, Virginia Mason Medical Center, Seattle, Washington

See related article, van Brunschot S et al, on page 1190 in this issue of CGH.
It has been nearly 20 years since the rst peroral endoscopic necrosectomy was performed for patients with pancreatitis. We have since increased our understanding of pancreatitis, and the nomenclature has changed to dene disease in which necrosis becomes organized (called walled-off). Endoscopic approaches to evaluate and treat pancreatitis have progressed from making small transmural tracts for irrigation to making large tracts, which allow the endoscope to move directly into necrotic cavities and perform endoscopic necrosectomy. The purpose of endoscopic debridement is to irrigate and/or remove areas of necrosis. Collaboration between therapeutic endoscopists and interventional radiologists has led to a combined approach to organized pancreatic necrosis. We discuss the history of peroral endoscopic treatment of organized (walled-off) pancreatic necrosis and current endoscopic approaches to therapy. Keywords: Acute Pancreatitis; Endoscopic Therapy; Minimally Invasive; Complications; Drainage.

linically severe acute pancreatitis is usually due to pancreatic necrosis and can be life-threatening. Fortunately, with early recognition and improvements in critical care, most patients survive the early phase of systemic inammatory response syndrome and multisystem organ failure. These patients, however, often have a prolonged course of sterile necrosis, whereas others develop delayed infection. Mechanical intervention for pancreatic necrosis can take the form of surgical, percutaneous, and endoscopic debridement. Open surgical necrosectomy has given way to minimally invasive approaches1,2 that use exible endoscopic, rigid endoscopic,3 percutaneous, and laparoscopic approaches, alone or in combination.4 However, along with these various interventions for pancreatic necrosis, there is little consensus on optimal timing and type of technique. In this perspectives article, we will share our thoughts on endoscopic intervention of pancreatic necrosis. It has been 16 years since the rst report of endoscopic drainage of pancreatic necrosis was published in Gastroenterology.5 For me (T.H.B.), it was a landmark career moment and an example of how one becomes involved in a specic area of medicine somewhat accidentally. Nearly 20 years ago during the

course of intervening on patients with pancreatic pseudocysts, I had mistakenly diagnosed a patient who had underlying sterile symptomatic pancreatic necrosis as having a pseudocyst. Two 10F stents were endoscopically placed through the gastric wall into the collection. The subsequent infected necrosis (as predicted by Banks group6) required open necrosectomy and a prolonged hospital stay. On the heels of this case, a patient with nearly identical clinical presentation and computed tomography (CT) ndings developed infected necrosis after the same type of intervention. Hoping to avoid the same outcome as the rst patient, I contacted Dick Kozarek, who suggested that irrigation might allow for nonsurgical management. Indeed, placement of a 7F nasocystic irrigation tube resulted in marked clinical improvement and nonsurgical resolution with a 1-week hospital stay.5 The title of the accompanying editorial in Gastroenterology written by Dr Kozarek entitled Endotherapy for Organized Pancreatic Necrosis: Perspectives on Skunk-Poking7 initially burst my bubble. However, as he wisely explained the premise behind the title, it became obvious that intervening on such patients was similar to poking a skunk because the reaction of intervention often leads to a less-than-desirable response. Therefore, what have we learned after nearly 20 years of endoscopic intervention? First, necrosis is not a pseudocyst, although many clinicians and radiologists still confuse the two and use the terms interchangeably, particularly when a concomitant uid component develops. Fortunately, there seems to be improved recognition of the distinction between the 2 types of collections.8,9 Second, it is hard to reinvent the wheel. Our surgical colleagues understood pancreatic necrosis much earlier and had already begun to realize that it is best to delay interventions for selected patients with sterile necrosis and then only when it became well demarcated.10 We coined this demarcation process organized pancreatic necrosis,5,11 now commonly referred to as walled-off pancreatic necrosis (WOPN),9 to distinguish it from early pancreatic necrosis. Third, removal of solid debris is vital to any type of intervention. Fourth, debridement can be mechanical, by irrigation, or a combination of both techniques. The evolution of endoscopic therapy began with small-diameter transmural tracts and placement of 10F stents and a
Abbreviations used in this paper: CT, computed tomography; WOPN, walled-off pancreatic necrosis. 2012 by the AGA Institute 1542-3565/$36.00 http://dx.doi.org/10.1016/j.cgh.2012.07.009

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Figure 1. Illustration of transgastric drainage of necrosis with nasocystic irrigation.

nasocystic irrigation tube (Figure 1).5 Many of the early patients required adjunctive percutaneous drains, especially to treat paracolic gutter extensions (Figure 2).12 When these percutaneous drains were ushed, the irrigant would pass into the communicating transmural drains, a concept that has been rediscovered over time. A modication of the irrigation approach was placement of a percutaneous endoscopic gastrostomy tube, with irrigation provided by using a jejunal extension tube passed through the percutaneous endoscopic gastrostomy and into the collection through the transmural entry site.13 Larger-diameter transmural dilations were then added to the irrigation approach.12 Although endoscopes had been passed transmurally into organized pancreatic necrosis,11 it was not until Siefert et al14

and subsequently Seewald et al15 introduced direct necrosectomy as a method to remove necrotic tissue (Figure 3A, B; Supplementary Video 1) by using mechanical methods through exible endoscopes that this technique gained some traction. This led to studies showing that direct necrosectomy may be superior to the traditional irrigation method,16 with a signicant decrease in need for adjuvant percutaneous drains, and that it was reproducible.17 In addition to descriptions of placing large-bore (20 to 25-mm diameter) self-expandable metal stents across the gastric wall for maintaining access for direct endoscopic necrosectomy,18 Navarette et al19 and others20,21 have placed large-bore self-expandable metal stents through percutaneous tracts to allow access for direct endoscopic necrosectomy by using ex-

Figure 2. (A) Coronal CT image obtained after transgastric necrosectomy of sterile necrosis; transgastric stent is present within superior portion of cavity (arrow). Left paracolic extension is seen (arrows). The 2 components of the collection communicate. (B) Percutaneous drainage is required to treat the contaminated paracolic gutter collection (arrows from midline to patients left represent feeding tube, transgastric stent, and gutter collection with contrast, respectively).

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Figure 3. Direct endoscopic necrosectomy. (A) Illustration showing direct endoscopic necrosectomy. (B) Endoscopic photo taken from within the necrotic cavity. (C) Gross picture of large volume of necrosis removed during direct endoscopic necrosectomy.

ible endoscopes (Figure 4). This latter approach is similar to video-assisted retroperitoneal debridement as performed by our surgical colleagues who pass rigid endoscopes through percutaneous drain tracts after dilation and/or incision of the tract.3 An overview of the approaches to WOPN by using exible endoscopy is outlined in Table 1. The use of irrigation has come full circle. The Virginia Mason group, historically a percutaneous intervention center based on the pioneering work of interventional radiologist Pat Freeny,22 developed a hybrid technique of percutaneous irriga-

tion combined with internal transmural entry (Figure 5).23 In their experience this hybrid approach is superior to a strictly percutaneous approach, not only in speeding resolution but also in precluding the development of external stulas.24 Varadarajulu et al25 recently reported a multigateway approach, which uses multiple transmural entry sites with placement of nasocystic irrigation catheters so that irrigation enters one site and egresses from another (Figure 6). Many questions remain, however. Where does endoscopic therapy t into the management strategy of pancreatic necrosis? What

Figure 4. (A) Illustration showing right pelvic necrotic collection with self-expandable metal stents in place to perform direct necrosectomy. (B) Radiographic image of endoscope passed through self-expandable metal stents to perform direct necrosectomy of pelvic gutter collection.

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Table 1. Flexible Endoscopic Approaches to Organized (Walled-off) Pancreatic Necrosis

Endoscopic approach Single or multiple transmural entry with nasocystic irrigation (Figures 1 and 6) Single entry transmural with PEG-PEJ for irrigation Advantages Technically easy Disadvantages Discomfort of nasal tube

Avoids nasal tube

Technically more difcult than nasocystic irrigation External tube Technically difcult Time-consuming Labor-intensive Requires both interventional radiologist and gastroenterologist External tube Requires both interventional radiologist and gastroenterologist External stent Abdominal wall pain Stent cost

Transmural entry with direct endoscopic necrosectomy (Figure 3)

Avoidance of external drains

Hybrid percutaneous irrigationendoscopic transmural approach (Figure 5)

Minimal endoscopic procedures

Hybrid percutaneousendoscopic direct necrosectomy by using external/internal large-diameter stents (Figure 4)

Allows endoscopic access to areas not accessible transluminally

PEG, percutaneous endoscopic gastrostomy; PEJ, percutaneous endoscopic jejunostomy.

is the optimal type of endoscopic therapy? Who should be performing such therapytertiary care centers only or high-level community care providers? Should there be a more aggressive approach to underlying ductal disruptions to prevent disconnected duct syndrome? Should endotherapy even be performed in patients with sterile pancreatic necrosis, and if so, what is the optimal timing? Can we predict which patients will fail endoscopic drain-

age? Unfortunately, an evidenced-based approach to answer these questions is not possible at the present time. We believe that patients with a prolonged course of sterile necrosis, intractable pain, gastric outlet obstruction, inability to eat, or rapidly enlarging collections present at 4 or more weeks after onset of pancreatitis deserve to be offered an intervention as long as the necrosis is organized (WOPN),

Figure 5. Illustration of hybrid percutaneous endoscopic technique. The percutaneous tube is used to provide irrigation that passes through the internal stents.

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Figure 6. Illustration showing the multigateway approach. Nasocystic irrigation tube (inside endoscope) is passed through 1 of the 2 transluminal entry sites alongside double pigtail stents.

as determined by CT. The belief is that an intervention will return the patient to a normal health status more rapidly than watchful-waiting (supportive care), although without denite proof. The decision to intervene is easier in patients in whom there is a high suspicion for or known infected necrosis, and we have intervened as early as 3 weeks after the onset of acute pancreatitis and in septic patients with acute pancreatitis and documented organized necrosis (as determined by CT). What is clear is that if endoscopic therapy is undertaken, commitment is required by the endoscopist, clinical care team, and most importantly the patient. Endoscopic debridement is a time-consuming, labor-intensive process that is not for the uncommitted26 or faint of heart because adverse events occur more commonly than in any other pancreaticobiliary intervention and have the potential to be fatal.27 Therefore, even more important perhaps is the need for support from a team of intensivists, endoscopists, surgeons, and interventional radiologists to manage these complicated patients. Evidence in favor of endotherapy is evolving with work done by the Dutch Pancreatitis Group4,28 and others.27,29,30 However, patients with pancreatic necrosis remain a heterogeneous group with regard to severity of illness and comorbid medical conditions at the time of intervention, because of surrounding inammatory changes, location and extent of necrosis, and degree of underlying solid debris (necrotic tissue burden). Coupled with variability in intercenter expertise of the various disciplines, this leads us to be skeptical that the approach to these patients will ever be standardized. Perhaps all we can hope for is the ability to tailor the best approach to the individual patient. We do believe, however, there will be unforeseen breakthroughs in endoscopic intervention as technology continues to

evolve. The latter includes new methods and devices to facilitate debridement, to keep tracts into the necrotic cavity open to allow reintervention, and to preclude the long-term consequences of necrosis and a disconnected pancreatic duct to include recurrent uid collections or attacks of relapsing pancreatitis.

Supplementary Material
Note: To access the supplementary material accompanying this article, visit the online version of Clinical Gastroenterology and Hepatology at www.cghjournal.org, and at http:// dx.doi.org/10.1016/j.cgh.2012.07.009. References
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Reprint requests Address requests for reprints to: Todd H. Baron, MD, 200 First Street SW, Rochester, Minnesota 55905. e-mail: baron.todd@mayo.edu; fax: (507) 255-7612. Acknowledgments The authors acknowledge the dedication of family, friends, and colleagues to allow us to passionately pursue our discipline. Conicts of interest The authors disclose no conicts.